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Science® Microsoft 



Digitized by the Internet Archive 

in 2013 


© 2012 Microsoft Corporation. All rights reserved. 

Except where otherwise noted, content in this publication is licensed under the Creative Commons 

Attribution 3.0 United States license, available at 

ISBN 978-0-9825442-1-1 

Printed in the United States of America 

The information, findings, views, and opinions contained in this publication are those of the authors 

and do not necessarily reflect the views of Microsoft Corporation or Microsoft Research. Microsoft 

Corporation does not guarantee the accuracy of any information provided herein. 

Microsoft Research 





Chief Research and Strategy Officer 
Microsoft Corporation 


IN THE 20 YEARS since its founding, Microsoft 
Research has grown from a small group of 
researchers to more than 800 computer scientists and 
researchers at labs on four continents. Throughout 
this growth, the mission of Microsoft Research has 
remained consistent: to advance the state of the art 
in computer science and software engineering, and to 
take these technology advances to the public through 
our products. 

As in many areas of research, the eventual 
applications and impact of computer-science 
research are challenging to predict and frequently 
different than originally envisioned. Over the years, 
we have seen many instances where Microsoft 
researchers have made advances that are at first 
incorporated into our products and technologies, 
but subsequently found to be uniquely impactful 
for an unrelated purpose in a very different field. 
Research at Microsoft helps drive forward the entire 
frontier of computing — and thus enables scientists 
to make significant progress on some of the major 
challenges facing society. That's why we collaborate 
with leading academic researchers around the world 
on a broad range of issues related to health, the 
environment, education, and many other disciplines. 
By working on these non-computer-science projects 
we often discover new ways to hone and improve our 
own technologies — these are powerfully symbiotic 

This collection of Science@Microsoft vignettes 
illustrates some of the progress researchers have 

been making in a number of disciplines — from 
neurology and immunology to astronomy and climate 
change — and describes the technologies that have 
been deployed to gain these insights. We see our 
collaborative ventures and blue-sky research yielding 
returns both in the broader social arena and in 
improved products and services. It's a classic case of 
"doing well by doing good." 

These stories also reveal interesting ways in which 
Microsoft and academic researchers are effectively 
applying computer science and technical computing 
research to fields far removed from computer science. 
With such multidisciplinary research collaborations, 
Microsoft Research is helping researchers reduce 
their time to new insights and accelerate the pace of 
scientific discovery. Microsoft's unparalleled corporate 
support of basic research is fundamental to our 
long-term vision of transforming society through 

We have seen research on spam filters with machine 
learning lead to a new approach to develop an HIV 
vaccine. We have seen fundamental advances in 
computer vision and speech processing research 
lead to the Kinect hands-free controller. What will 
be the next breakthrough discovery, or cool new 
product? Who can say? That's the beauty of doing 
basic research: you're never certain where the results 
might lead, but you can be sure the journey will be 
worthwhile and full of surprises. 

Chief Research and Strategy Officer 


Table of Contents 

Genomics and Machine Learning 

/t Using Model-Based Machine Learning to 
Understand Childhood Asthma 

Understanding childhood asthma 

/* Understanding the Genetic Causes of Human 

How researchers are untangling the complexity of human diseases 

20 Algorithms that Can Handle the "Omics" 

New developments in data analysis help address significant 
problems in biological research 

22 Identifying Genetic Factors in Disease with Big Data 

Analysis of large datasets helps researchers understand 
connections between heredity and disease 

Earth and Environment 

26 Amassing Global Data on Carbon and Climate 

Enabling scientists to investigate the biological implications of 
persistent weather events 

2c? Simulating the Breathing of the Biosphere 

Scientists address both the science and computational challenges 

so Data Deluge and Digital Watersheds 

Using data to restore habitat for endangered fish 

.32 Improving Fuel Refining Technologies 

How computer vision research can transform MRI 

jf Transforming the Science of Behavioral Ecology 

Exploring novel ways of investigating wildlife species 

Health and Computer Vision 

jc? Understanding the Immune Response to HIV 

Natural-killer cells play a direct role in fighting HIV 

so Medical Sensing via a Contact Lens 

How this noninvasive technology monitors blood sugar levels 

42 Improving Echocardiography 

How scientists are improving the efficacy of echocardiography 

// Searching the Human Body 

How researchers are untangling the complexity of human diseases 

Computer Science and Technology 

4# SenseCam 

This device can aid those with debilitating memory impairment 

so Technology to Combat Counterfeit Products 

How science is protecting consumers from purchasing fraudulent 

S2 Clinical Studies and Data Collection and Reuse 

How software can help make clinical studies more effective 

s? Microsoft TerraServer: an Imagery Scalability Story 

Online, high-resolution maps 

Table of contents continued next page ... 



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* 7.1 

Table of Contents 

Physics and AstrDriDmy 

ss Worldwide Telescope and Seamless Astronomy 

How scientists are interacting with the universe 

fro SkyServer: the Universe at Your Fingertips 

How software can help make clinical studies more effective 

62 Topological Quantum Computation 

Faster, more powerful, more versatile computing 

Biology and Life Sciences 

66 Coevolution of Viruses and the Immune System 

Understanding the human body's response to disease-causing 

<f<? Software Verification Meets Biology 

Biological models are bettering our understanding of biological 

70 Programming Life 

Using genetic devices to reprogram cell behavior and improve health, 
agriculture, and energy 

72 How Many Species Are There? 

Scientists are using expertise, tools, and technologies to find out 

Citizen Science 

7* GalaxyZoo 

How volunteers are assisting professional astronomers to classify 


Anyone in the world can run a regional climate model 

so Rosetta@Home 

Computer power — citizen participants help predict and design the 
three-dimensional structures 

Scientific Tools 

&t Chemistry Add-in for Word 

Modify and share chemical information 

sfr NodeXL 

NodeXL helps analyze and visualize its influence on individuals and 

<?<? Scientific Workflow Workbench 

Modify and share chemical information 

Genomics and 
Machine Learning 

Genomics and Machine Learning 

Using Model-Based Machine Learning 
to Understand Childhood Asthma 


Distinguished Scientist 
Machine Learning and 
Perception Group 

Professor of Allergy 
Head, Respiratory 
Research Group 

ASTHMA AND ALLERGIES rank among the most 
common chronic disorders in children — and their 
incidence is on the rise. The question is why. 
Understanding the underlying causes of asthma 
might lead to prevention in susceptible children 
and better treatment for adults. 

Although evidence from twin studies suggests 
a strong genetic component in asthma and 
allergies, few of these studies have identified the 
same genetic associations. Moreover, the role 
of the environment in asthma and allergies is 
evidenced by the rapid increase in the prevalence 
of these disorders over the last four to five 
decades, a time frame too short to be attributable 
to genetic factors alone. And indeed, various 
environmental exposures have been associated 
with the development of asthma and allergies. 
However, as with genetics, the data on the role of 
environmental factors are inconsistent, with the 
same environmental exposure showing increased 
risk, protection, or no effect, depending on the 

The conflicting evidence on the effects of genetic 
variants and environmental exposures may be 
due in part to these factors having largely been 
studied separately. By contrast, this research 
seeks to model genetic and environmental factors 
jointly. The researchers view asthma as a complex 
disease that takes multiple forms, and therefore 
a central goal is to discover these underlying 
"phenotypes." To do so, they are using a Bayesian 
model-based machine-learning approach, which, 
unlike conventional statistical analyses and black- 

box machine-learning methods, easily allows 
the incorporation of rich, hierarchical structure 
derived from clinical background knowledge. 

The project is a collaboration between Microsoft 
Research and the University of Manchester. 
Microsoft Research provides the machine- 
learning expertise through its team of Chris 
Bishop, John Winn, Markus Svensen, and Nevena 
Lazic in the Machine Learning and Perception 
group, and has contributed Infer.NET, a new 
framework that allows rapid construction of 
complex Bayesian models and performs efficient 
inference within those models. The University of 
Manchester brings world-class clinical expertise 
through Iain Buchan, Adnan Custovic, and Angela 
Simpson, along with a high-quality dataset 
collected by the Manchester Asthma and Allergies 

Together, the researchers hope to build complex 
models that represent a broad range of important 
variables associated with asthma. And while the 
immediate goal is to study the development 
of asthma, a successful outcome can highlight 
the benefits of a model-based approach to the 
analysis of clinical data generally, which could 
have much broader applicability. 

This work significantly contributed to the 
development of Infer.NET by providing real-world 
testing of its scalability and capabilities, and led 
to the first paper published using this technology. 
Improvements to Infer.NET resulting from this 
project have helped prepare the framework to 
enhance a range of Microsoft products. 

Microsoft Research Cambridge University of Manchester 


"It is very exciting to take ideas from a 
technology context and apply them to such 
an important societal problem. At the same 
time, the challenges of modeling a disease as 
complex as asthma are pushing us to develop 
the machine-learning techniques in new 
directions." — chris bishop 

"With Microsoft Research, we have created a 
multi-disciplinary collaborative partnership 
which will combine our world-leading expertise 
in birth cohorts and health informatics 
research with innovative computational 
statistical methods. We will work together to 
apply newly developed state-of-the-art data 
analysis techniques (of Bayesian inference 
and machine learning) to build complex models 
to describe different types of 'asthma' and 
investigate risk factors (both genetic and 
environment) for each asthma subtype. In 
doing so. we hope to underst ' ' 

nechanisms that u 
different asthmas, and to identify molecules 
which may be targets for future drug 
therapies." — adnan custovic 

Genomics and Machine Learning 

Understanding the Genetic 
Causes of Human Disease 


Senior Researcher 
Machine Learning and 
Perception Group 
Microsoft Research Cambridge 


Joint Head of Human 


Wellcome Trust Sanger 


cardiovascular disease, cancer, and various 
psychiatric illnesses, arise from complex 
interactions between a person's genetics and all 
the environmental influences he or she encounters 
over a lifetime. Untangling these factors and 
determining the underlying causes might lead 
to better prevention, diagnosis, and treatment 
of the diseases. Physicians might even develop 
individualized treatments that are based on a 
patient's genetic make-up. 

But analyzing multiple genetic and environmental 
factors is complicated, to say the least. Researchers 
have developed enormous genomics datasets but 
need statistical methods that can represent the 
complexity of human disease. In other words, they 
need both rich data about the behavior of human 
cells in various environmental contexts along with 
complex statistical models to analyze the resultant 

Impossible? Hardly, thanks to the work of the 
Machine Learning and Perception group at 
Microsoft Research Cambridge and the Wellcome 
Trust Sanger Institute. Senior Researcher John Winn 
and his colleagues have developed Infer.NET, 
an advanced machine-learning framework for 
modeling and understanding very complex 
systems. Infer.NET allows the team to represent the 
complexity of human diseases in a way previously 
unachievable. The team at the Wellcome Trust 
Sanger Institute, led by Joint Head of Human 
Genetics Richard Durbin, brings world-class 
expertise in large-scale genomic sequencing and 
analysis of genomic data. 

The project requires analyzing four types of data: 

• Genetic data— All or key parts of the DNA 
sequence of an individual. 

• Functional genomic data — Measurements, 
such as gene expression, that indicate the 
activity of individual genes in various body 

• Environmental data — Information about an 
individual's environmental exposures, such as 
smoking or sunbathing. 

• Disease data — Physiological measurements 
and information about known diseases or 
symptoms that an individual has experienced. 

This data is brought together in a single statistical 
model, so as to discover associations between the 
genome, cell function, environmental factors, and 

The researchers' analysis is identifying 
correlations between genetics and the activity of 
genes in different tissues and the symptoms or 
characteristics of the individuals from whom the 
samples come. This is shedding new light on how 
variations in genetic makeup can make individuals 
susceptible to different diseases, giving 
researchers deeper understanding than ever 
before on the genetic causes of human disease. 

The application of Infer.NET to bioinformatics 
led to the first parallel version of the framework, 
driving improvements to the design and 
implementation of this key technology. By 
pushing the scalability of Infer.NET, this project 
directly helped make this machine-learning 
framework ready to use in a number of Microsoft 


"New, large-scale functional genomics 
datasets have the potential to tell us a 
huge amount about the underlying causes 
of many diseases. But data alone cannot 
achieve this-we need new statistical 
methods that are capable of representing 
the realistic complexity of human disease. I 
am very excited to play a part in developing 
such methods because they are the key to 
unlocking the secrets contained in these 
exciting new datasets and to making new 
inroads in understanding and treating 
disease." — john winn 

"The scale and complexity of genomic 
datasets is increasing exponentially with 
the recent revolution in DNA sequencing and 
related technologies. Working with Microsoft 
Research enables us to bring state-of-the- 
art ideas and methods in machine learning 
research to bear on these data sets, letting 
us shed light on key interactions involved in 
complex disease." — richard durbin 

Genomics and Machine Learning 

Algorithms that Can Handle 
the "Omics" 

Theoretical Physics 
Politecnico di Torino 


Distinguished Scientist 
Managing Director 
Microsoft Research 
New England 


Deputy Managing Director 
Microsoft Research 
New England 

IMAGINE TWO NEANDERTHAL proto-scientists, 
standing before an enormous pile of rocks — big 
rocks, small rocks, smooth rocks, rocks with jagged 

"Well," remarks one of the Stone Age researchers, 
"this is a lot of data here." 

"Yes," replies his colleague, "if only we had some 
way to make sense of it all, I bet we could achieve 
a breakthrough in rock utilization." 

Today, biological researchers are confronting 
a similar dilemma: a wealth of data but an 
inadequate analytical toolkit. Increasingly, 
biologists are using genomic methods, such as 
expression profiling, next-generation sequencing, 
and RNAi screens, together with proteomic 
and metabolomic technologies, to discover the 
molecular basis of changes in living systems. 
Collectively, these methods are often referred to as 

Unfortunately, these advances in experimental 
technologies have, in many cases, outpaced the 
development of the bioinformatics tools that 
are needed to analyze the data. In other words, 
optimal analysis of large quantities of experimental 
data often require the solution of hard problems 
that are intractable by conventional computational 
tools. Fortunately, collaborative efforts between 
the Massachusetts Institute of Technology and 
Microsoft Research have resulted in new algorithms 
that often do quite well in analyzing these types of 

These methods, which extend ideas from statistical 
physics of disordered systems to problems in 
computer science, have provided novel distributive 
algorithmic schemes for solving large-scale 
optimization and inference tasks. Among the 
features of these new algorithms are computational 
efficiency, parallelizability, and flexibility to include 
heterogeneous prior knowledge and to integrate 
diverse data sources. The spectrum of applications 
ranges from constraint satisfaction and stochastic 
optimization problems over networks to graphical 
games and statistical inference problems. 

The collaboration aims to apply these new 
algorithmic techniques to significant problems in 
biological research. Preliminary results have already 
led to the discovery of new functional genes, the 
prediction of protein contacts from sequence data, 
and the discovery of a new algorithm for message 
passing. These developments have the potential for 
broad application across computer science and to 
improve future Microsoft products. 

The researchers' current focus is on cancer 
genomics. In collaboration with the Memorial 
Sloan-Kettering Cancer Center, they are working 
on the integration of different types of molecular 
data to reveal complex response pathways of 
relevance in cancer development. They hope that 
this work leads to not only advances in general 
algorithmic techniques for biological research 
but also to the development of drug targets for 
specific cancers. 


"Using insights from the statistical physics of 
disordered systems, we have developed highly 
parallel algorithmic techniques for addressing 
a host of combinatorial optimization problems. 
The applications range from more conventional 
computer science problems like multicasting 
to problems of biological significance, including 
in particular an understanding of human gene 
regulatory networks— which, hopefully, will 
lead to the development of drug targets for 
various cancers. Jennifer chayPs 



"Current biological research is generating a 
vast amount of data relevant to prol ' 
human disease— from cancer to Alzheimer's. 
But algorithmic techniques have not kept 
pace with the increase in experimental data. 
Dur research with Riccardo Zecchina and his 
group in Turin is focused on closing this gap 
by developing new algorithmic techniques 
originating in statistical physics with domain- 

specific methods developed by computational 

biologists." -christian borgs 

"We are filling an existing methodological gap 
between advanced algorithmic schemes that 
have their origin in statistical physics and the 
huge amount of molecular and evolutionary 
data made available by experimental 
technologies. We are developing computational 
tools which are intrinsically parallel and can 
be applied to large-scale inverse problems of 
biological interest and of clinical relevance in 
cancer genomics." —riccardo zecchina 


• i 3~.Tr 

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Genomics and Machine Learning 

Identifying Genetic Factors 
Disease with Big Data 



eScience Group 
Microsoft Research 


Microsoft Distinguished Scientist 

Senior Director 

eScience Group 

Microsoft Research Connections 



Max Planck Institutes for 
Developmental Biology and for 
Intelligent Systems 

many serious diseases — including heart disease, 
asthma, and many forms of cancer — are hereditary. 
Until fairly recently, however, there was no easy 
way to identify the particular genes that are 
associated with a given malady. Now, researchers 
can conduct genome-wide association studies — by 
sequencing the DNA of human subjects — enabling 
them to statistically correlate specific genes to 
particular diseases. 

In order to study the genetics of a particular 
disease, researchers need a large sample of people 
who have the disorder, which means that some 
of these people are likely to be related to one 
another — even if it's a distant relationship. This 
skews research results because certain positive 
associations between specific genes and the 
disease are false positives — the result of two 
people sharing a common ancestor. In other 
words, the research sample is not truly random, 
and researchers must statistically correct for the 
"confounding" that was caused by the shared 
ancestry of the subjects. 

This is not an insurmountable statistical problem: 
there are so-called linear mixed models (LMMs) 
that can eliminate the confounding. However, 
an inordinately large amount of computer run 
time and memory are required to run LMMs to 
account for the relatedness among thousands of 

research subjects. When working with the large 
datasets that offer the most promise for finding 
the connections between genetics and disease, the 
cost of the computer time and memory that these 
models require can quickly become prohibitive. 

To address this problem, the Microsoft Research 
team developed Factored Spectrally Transformed 
Linear Mixed Model (FaST-LMM), an algorithm 
for genome-wide association studies that scale 
linearly in the number of individuals in both run 
time and memory use. FaST-LMM can analyze 
data for 120,000 individuals in just a few hours 
(whereas the current algorithms fail to run at all 
with data for just 20,000 individuals). The outcome: 
large datasets that are indispensable to genome- 
wide association studies are now computationally 
manageable from a memory and run-time 

FaST-LMM will enable researchers to analyze 
hundreds of thousands of individuals to find 
relationships between their DNA and their traits, 
identifying not only which diseases a given patient 
may get, but also which drugs will work best for 
that patient. FaST-LMM takes us one step closer to 
the day when physicians can provide their patients 
with personalized assessments of their risk of 
developing certain diseases and devise prevention 
and treatment protocols that are attuned to their 
unique hereditary makeup. 


"Dne of the greatest challenges in uncovering 
the genetic causes of disease is that 
hidden artifacts can confound statistical 
analyses, leading to seemingly real yet false 
causes. With FaST-LMM, we break down the 
computational barriers that have hindered the 
analysis of genome-wide datasets, opening 
the door to new understandings of heredity 
and disease." — david heckerman 

"High-throughput genetic studies are 
producing incredible amounts of data, about 
which people are scratching their heads 
wondering how to deal with it. But it's only 
with large amounts of data that we can infer 
confounders from the data itself, enabling 
accurate analysis. FaST-LMM allows us to 
infer and incorporate these confounders 
in a manageable way for extremely large 
datasets." —Jennifer listgarten 

"As the rate at which data is being generated 
in genomics is already outgrowing Moore's 
law by far, it won't be sufficient to just throw 
more and more computing power at the 
data analysis. We also need highly efficient 
algorithms and software tools like FaST-LMM 
to keep up with the growing demands of that 
task." — christoph lippert 

Earth and 


Earth and Environment 

Amassing Global Data on 
Carbon and Climate 



Senior Scientist 


Departmental Head, Advanced 


Computing for Science 

University of California, 

Lawrence Berkeley National 




AS CONCERNS OVER climate change mount, hard 
data on the interactions between the atmosphere 
and biosphere have become vital. Fortunately, over 
the past two decades, scientists have deployed 
sensor collections at several hundred locations 
worldwide, gathering continuous, long-term data 
on carbon balance across different climate zones 
and vegetative land covers. These records enable 
scientists to investigate the implications of fires 
and other disturbances and to study the impact of 
land-management approaches such as fertilization, 
grazing, and irrigation. They also let scientists 
examine the biological implications of persistent 
weather events, such as drought, or episodic 
events, such as major storms. 

Sitting atop these sensor collections is FLUXNET, 
a "network of networks." Through FLUXNET, 
independent regional networks and individual 
field scientists come together to pursue synthesis 
science — crossing disciplines, data sources, 
and national boundaries. The FLUXNET dataset 
consists of more than 960 site-years of sensor 
data from more than 253 sites, as well as more 
than 100 related non-sensor field measurements. 
Contributions are ongoing and the data-processing 
algorithms are continually improved through 

Managing FLUXNET's living dataset presents 
several computing challenges, which are shared 
by Dario Papale of the University of Tuscia in 

Italy and Markus Reichstein (Max Planck Institute, 
Germany), working with Deb Agarwal (Lawrence 
Berkeley Laboratory, United States), Dennis 
Baldocchi (University of California, United States), 
Marty Humphrey (University of Virginia, United 
States), and Catharine van Ingen (Microsoft 
Research, United States). The team has constructed 
an advanced data server that is based on Microsoft 
SQL Server technologies and a collaboration portal 
that is based on Microsoft SharePoint. Sensor data 
can be rapidly browsed over the Internet from 
the scientist's desktop, and the portal enables 
communication among scientists via a private social 
networking site. 

The ability to share data at this scale and diversity 
enables new insights, can reduce the uncertainty 
of existing model predictions, and has been 
the basis for landmark papers that challenge 
conventional wisdom. One such paper suggests that 
the availability of water may be more important 
than temperature for carbon fixation by plants, 
a conclusion that poses questions about existing 
predictions of ecosystem changes — such as tropical 
forest decline — in response to temperature change. 

The project team designed a database for storing 
environmental data and explored how SQL 
databases, SQL Analysis Services data cubes, and 
Microsoft SharePoint can manipulate such data. Five 
other science projects in the field of climate change 
study have already used the database design. 




"Enabling the more than I2D global groups 
studying the carbon cycle through 
is helping us to better understand what 
cyber infrastructure is needed to further the 
science." —deb agarwal 

"Dur goal is to produce a data system that 
enables us to produce computations of 
ecosystem photosynthesis and evaporation 
'everywhere and all of the time.' The 
computational demands of such a product 
are far beyond the capacity of the PCs in my 
lab. Working with Microsoft and the cloud 
computing system has enabled us to take ideas 
that were expressed on a classroom chalk 



Earth and Environment 

Simulating the Breathing 
of the Biosphere 


Assistant Professor 
Environmental Ecology 
Seoul National University 


Associate Professor 

Department of Computer 


University of Virginia 

THE BIOSPHERE AND and atmosphere interact. 
Climatic variables, including temperature, humidity, 
wind, and precipitation, affect individual plants 
and plant communities, while the type and 
diversity of plant cover influence the atmosphere. 
Understanding the breathing of the biosphere — the 
fluxes of carbon dioxide, water vapor, and trace 
gases between plants and the atmosphere — is a 
challenging task, involving numerous coupled, 
non-linear, biophysical processes. 

At the regional to global scale, the computational 
demands require at least daily merging of 
several remote-sensing datasets. Scaling such a 
computation means scaling the science as well; for 
example, the science algorithm must encompass 
rainforests as well as croplands. 

The Breathing Earth System Simulator (BESS) 
computation on the MODISAzure cloud addresses 
both the science and computational challenges. 
BESS scientists Youngryel Ryu and Dennis 
Baldocchi developed the science computation, 
which synthesizes data from satellite imagery, 
global climate models, and ground-based sensors. 
MODISAzure computer scientists, Marty Humphrey, 
Jie Li, You-Wei Cheah, and Catharine van Ingen 
addressed the computational challenges by 
building a four-stage data processing pipeline on 
Windows Azure. 

Cloud computing addresses three barriers to such 
a computation: 

• Access to sufficient resources — The BESS 
computation used more than 500,000 CPU 

hours, ingesting 14 terabytes of data from 
NASA and generating 1.5 terabytes of results. 
MODISAzure scales from 5 to 240 deployed 
virtual machines in the cloud. 

• Tedium — The global-scale science computation 
breaks into more than 70,000 tasks and 
consumes 500,000 input files. MODISAzure 
marshals the right input files for each task and 
handles synchronization and error recovery. 

• Complexity — The bulk of the input files were 
the result of preprocessing approximately 
800,000 initial NASA satellite files into 
"sinusoidal" files that contain the daytime 
aggregate value at fixed, equal-sized pixels. 

Computations like BESS enable researchers 
to examine complex climate changes globally 
and locally. Global-scale fluctuations can be 
simulated with climate models, extending their 
understanding of complex climate change 

The results can also be combined with local 
observations to address specific questions, such 
the implications of rice farming in the Sacramento 
Delta region. 

This was one of the first applications to use 
Windows Azure as a large computational platform. 
It provided the Windows Azure team with 
feedback and input that could be useful for future 
refinements to the cloud platform. It also proved 
how scientists can broaden their work from one 
PC to large-scale computations. 


"The Microsoft cloud service. Azure, Enabled 
me to study land-atmosphere interactions from 
I kilometer to a global scale. I learned how 
collaboration across disciplines can advance the 
science." — youngryel ryu 

"We have been very excited to participate in 
the MDDISAzure project seeing first-hand what 
capabilities Windows Azure might be able to 
provide to eScience activities now and in the 
future. We really think this can enable a new 
generation of data-first explorations-we have 
been amazed at the results that Windows Azure 
has enabled the BESS scientists to achieve!" 


Earth and Environment 

Data Deluge and Digital 


Partner Architect 
eScience Group 
Microsoft Research 


Civil and Environmental 


University of California, Berkeley 

COMMODITY SENSORS AND Internet connectivity 
have created a veritable data deluge. Yet it remains 
a challenge to find, access, clean, and reuse data. 
That is particularly true when data from different 
sources is needed for synthesis science — bringing 
many diverse observations together to create a 
larger, holistic view. 

Scientists at the Berkeley Water Center, led by 
James Hunt, worked with the National Marine 
Fisheries Service on a synthesis challenge in the 
Russian River area. The watershed is the breeding 
ground for several species of fish, but wine-grape 
farming, urbanization, gravel mining, and other 
factors have affected the river. As a result, the fish 
have become endangered, and habitat restoration 
is critical. 

To enable such studies, Microsoft Research's 
Catharine van Ingen and Lawrence Berkeley 
National Laboratory researcher Deb Agarwal built a 
digital watershed. Constructed on a Microsoft SQL 
Server database and SQL Server Analysis Services 
data cube, the digital watershed enables simple 
interactive browsing of the assembled diverse 

sensor and field observations. Data updates 
are automatically harvested from available 
government websites and are ingested from 
smaller spreadsheets or other sources. Some of 
the data are historic, dating back more than 100 
years. Others are real-time measurements with 
only transient availability over the Internet. 

Among the questions examined with the digital 
watershed was the impact of "frost dips." During 
the season when wine-grape buds are setting, 
local farmers use sprinklers to avoid frost 
damage. Pumping from the river to supply the 
sprinklers causes transient dips in the river water 
level. Such dips can strand small hatchling fish, 
making them susceptible to predators or oxygen 

This research led to a fundamental change in 
how hydrologists get timely answers to their 
questions by using advanced computing methods. 
It established a model for how scientists can use 
technologies to help them solve problems with 
data processing so that they can remain focused 
on their sciences. 


"The Turkish proverb, 'Small keys unlock big 
doors,' characterizes much environmental data. 
Remote sensing, ground-based sensors, direct 
measurements in the field, and historic events 
such as fires and floods all play a part." 


"Dur collaborative research with Microsoft and 
LBNL [Lawrence Berkeley National Laboratory] 
was essential in utilizing the extensive and 
widely distributed data to help environmental 
managers resolve fishery habitat questions 
in altered watersheds. Within environmental 
science, data on the state of water, air, land, 
and ecological resources are essential in 
understanding current conditions and providing 
a base for assessing future conditions. Modeling 
at multiple levels of complexity is a secondary 
component that is heavily dependent on data 
synthesis efforts at different spatial and 
temporal scales." — james hunt 


*?. ^ 





■ ' •■-- •- • ■ 

'*¥ y - ' 



- • 

Earth and Environment 

Improving Fuel Refining Technologies 

CLIMATE CHANGE IS a hot topic these days, with 
great attention focused on the need to reduce 
atmospheric carbon dioxide (C0 2 ) concentrations to 
slow the process of global warming. Such reduction 
will rely, in part, on developing better quality — that 
is, lower emission — automotive fuels, and among 
the most promising approaches to improving fuel 
quality is the use of gas-to-liquid (GTL) refining 

But making GTL competitive with conventional oil 
refining technology will require improved design in 
trickle-bed reactors (TBRs). TBRs are essentially a 


Pro- Vice-Chancellor 

for Research 

Shell Professor 

of Chemical Engineering 

University of Cambridge 


Microsoft Distinguished Scientist 

Managing Director 

Microsoft Research Cambridge 

column filled with catalyst particles, through which 
gas and liquid flow downward. Improved design and 
operation of TBRs could reduce C0 2 emissions by 
400 million metric tons a year, or about 2 percent of 
global C0 2 emissions. 

TBRs are currently designed by using imprecise 
empirical correlations, which leads to significantly 
oversized reactors and higher operating and 
capital costs, thereby putting TBR technology 
at a competitive disadvantage. The best way to 
improve TBR design is to enhance understanding 
and modeling of the reactors through new 
phenomenological models and better closure laws 
for computational fluid dynamics simulations. Both 
of these require measurements of the velocity of 
the liquid and gas inside the reactor, as this will 
determine the overall performance of the reactor. 

The only technique that can provide these 
measurements is magnetic resonance imaging (MRI), 
but the signal-to-noise ratio of conventional gas 
phase imaging is too low to achieve the required 
resolution. Collaboration between the Magnetic 
Resonance Research Centre at the University of 
Cambridge and Microsoft Research has produced 
a compressed sensing algorithm that enables gas 
phase velocity mapping at a resolution an order 
of magnitude greater than in the past. These 
measurements are of sufficiently high resolution to 
enable characterization of the interfacial velocity 
between the liquid and gas, which is critical to 
improved understanding of the reactor's behavior 
and prospective design improvements. 

In addition to its potential for helping to reduce 
atmospheric C0 2 emissions, the compressed 
sensing algorithm could lead to greater use of 
MRI as a means for testing hypotheses about 
the process under study. A particular target is 
to reduce data acquisition times by an order of 

magnitude; this opens up new opportunities for 
studying chemical engineering processes, as well as 
enabling the implementation of magnetic resonance 
measurements with low magnetic field hardware, 
which would enable the use of on-site MRI as a 
process analytics tool. 

Most recently, the researchers have been looking at 
radical techniques that avoid, altogether, the need 
to produce an image in order to perform a particular 
analysis. Producing an intermediate image is very 
costly in terms of the amount of data required 
and may be unnecessary when what is needed is a 
simple decision or an estimate of the value of a few 
parameters. An example is estimating the density 
and shape distribution of bubbles in a reactor. They 
have shown that this can be done directly, without 
any intermediate image, resulting in much shorter 
acquisition times and tolerance to noise. Ultimately, 
this could allow the use of more compact MRI 
machines, avoiding the need for strong magnetic 
fields and thus avoiding the need for supercooling. 
This would simplify the machinery in terms of 
both weight and cost, and allow certain kinds of 
measurements that were previously impossible. The 
resulting machines could have an impact in chemical 
engineering and, potentially, medical diagnosis. 

In an increasingly data-driven world, where big data 
and real-time analytics become more prevalent with 
technologies like Streamlnsight, Windows Azure, 
and Hadoop, probabilistic techniques, such as the 
compressed sensing algorithm developed during this 
research, can produce step changes to improve how 
researchers understand and use data competitively. 
The algorithm exemplifies the extensive expertise 
that Microsoft Research applies to developing a wide 
range of applications, which is vital to Microsoft's 
development of more sophisticated analytical and 
data management tools. 


"The opportunity to develop technologies based 
on probabilistic inference that may change 
the nature of magnetic resonance imaging 
machines has been exciting. The results that 
we've been able to achieve together show how 
multidisciplinary research can create step 
changes in science." — andrew blake 

"The project with Microsoft Research has 
enabled us to make significant advances in 
magnetic resonance imaging, which we have 
used in medical MRI as well as our main 
activity in chemical engineering. It has been 
possible to reduce imaging acquisition times 
by more than an order of magnitude and. in 
so doing, enabled us to study phenomena 
in multi-phase hydrodynamics that have 
not been studied previously using magnetic 
resonance or, indeed, any other experimental 
technique." — lynn gladden 

Earth and Environment 

Transforming the Science 
of Behavioral Ecology 


Computational Ecology 
crosoft Research Cambridge 


Professor of Animal 

Department of Zoology 
University of Oxford 

UNDERSTANDING HOW THE behavior of species 
changes over time is vital to knowing how to protect 
and preserve key species. This is critical for those 
species that are vulnerable to changes in the envi- 
ronment, such as the response of global ecosystems 
to climate change and human activity. In particular, 
understanding the movement and spatial dynamics 
of individual species, between individuals and their 
environment, and spatial locations and patterns that 
are important for species survival, is vital. However, 
established techniques for studying the movement 
and behavior of individual animals are typically lim- 
ited, inefficient, time consuming, and expensive. 

The two most commonly used approaches to 
observing species are far from perfect. The first 
approach is a scientist spending years observing mi- 
gratory behavior, for example, which tells only when 
animals depart and when they return (if at all), but 
nothing about what they do when, where, and why 
they migrate. The second approach includes track- 
ing technologies, which are expensive, inflexible, 
inappropriate (in size, range, functionality, or weight, 
for example), and labor intensive, limiting both the 
applicability and scale of ecological and behavioral 
studies. In addition, even when data are collected, 
few if any computational and software tools exist to 
analyze the data easily and accurately or to enable 
the development and testing of predictive mod- 
els that use the data. As a consequence, scientists 
understand remarkably little about the behavior of 
most key species, and less still about how their be- 
havior is or will change as the environment changes. 

Robin Freeman, a zoologist in the Computational 
Ecology and Environmental Sciences group at 
Microsoft Research, has developed an open, recon- 
figurable, flexible, wirelessly-enabled, and low-cosi 
tracking technology and set of software tools that 
address almost all of these problems. These tech- 
nologies enable Freeman, his collaborators Tim 
Guilford, Ben Dean, and Holly Kirk at the University 
of Oxford, and now, other researchers worldwide, to 
undertake previously impossible scientific studies 
collecting novel types of data and employing new 
kinds of analyses. These studies are initially focused 
on the migratory and foraging behavior of pelagic 
seabirds. The new platform is an open design with 
open software, so researchers can choose to modify 
the existing designs as their projects require. Micro- 
soft Research has provided a number of solutions for 
most common tracking problems. 

Furthermore, the group's software tools for data 
analysis, modeling, and visualization enable Robin 
and his colleagues to analyze these new data to 
form a fundamentally better understanding of the 
movement and behavior of individuals, groups, and 
populations of important species, including the 
Manx shearwater, Hutton shearwater, black petrel, 
puffins, and guillemots. This project exemplifies how 
targeted research can help scientists understand so- 
cial behavior and spatial dynamics at different levels. 
The rapid growth of personal devices that include 
sensors, such as smartphones, creates potential 
applications for the techniques used here to investi- 
gate how people interact in society. 


"Dur collaboration with Microsoft Research 
is very exciting and has allowed us to explore 
ideas that would have been impossible in a 
normal university setting. In particular, the 
development of this new device is opening 
a whole area of possibilities that we would 
not normally have been able to consider. Dur 
'' on the spatial ecology of highly pelagic 


the creation of protected areas and habitats. 
Dur truly interdisciplinary team is allowing us 
to explore novels ways of investigating these 
species. Conducting such interdisciplinary 
research can be complex and challenging bu 
is also extremely rewarding and, I believe, hi 
enormous future potential." 

"Understanding the movement and behavior 
of wild animals is fundamental to preserving 
some of our most important endangered, and 
engaging species. Leading this project has 
been immensely exciting, and the involvement 
of our collaborators at Oxford has been very 
rewarding and stimulating. These projects are 
often complex, and it's amazing to be working 
with such a wonderful group of researchers." 



Health and 
Computer Vision 

Health and Computer Vision 

Understanding the Immune 
Response to HIV 


Director, Program for Innate 


Partners AIDS Research Center 


Microsoft Distinguished 
Senior Director 
eScience Group 
Microsoft Research 


Principal Research Software 
Design Engineer 
eScience Group 
Microsoft Research 

ACCORDING TO THE UNAIDS Report on the Global 
AIDS Epidemic 2010 by the Joint United Nations 
Programme on HIV/AIDS, HIV killed 260,000 
children in 2009 with a disproportionate number 
of deaths in sub-Saharan Africa. Even in the 
United States, while no longer a death sentence, 
HIV requires expensive, life-long treatment. In 
2011, investigators from the Ragon Institute of 
Massachusetts General Hospital, Massachusetts 
Institute of Technology, and Harvard University; 
Imperial College London; the National Cancer 
Research Institute; and Microsoft Research showed, 
for the first time, that the immune system's natural 
killer (NK) cells play a direct role in fighting HIV 
This knowledge opens a new path of research into 
ways to beat the virus. 

Scientists have long known that NK cells play an 
important role in the control of viral infections, 
mounting short-lived but highly toxic assaults on 
infected cells. It's logical to expect that NK cells 
would play a role in the control of HIV infections, 
and, in fact, various in-vitro and epidemiological 
studies suggest that NK cells do just that. However, 
it remained unknown whether NK cells directly 

mediate anti-HIV immune pressure inside the 
human body. 

The first tell-tale signs that NK cells were affecting 
HIV were found by using a sophisticated software 
tool that was developed at Microsoft Research. The 
tool used almost a CPU-year of computation to sift 
through millions of possible clues as to how our 
immune system interacts with this deadly virus. 

Subsequent clinical and laboratory work that was 
performed by instructional collaborators resulted 
in evidence that the virus mutates in response 
to NK cell activity— by inference, confirming that 
NK cells play a direct role in fighting HIV. This 
knowledge opens a new path of research into ways 
to beat the virus, helping physicians in their long- 
running battle with HIV and AIDS. 

Multiple Microsoft .NET and Windows HPC 
Server-based Microsoft technologies are being 
used in this effort to facilitate efficient software 
development and computing. In addition, the 
knowledge gained from working with scientists 
on the complex computational scenarios in this 
project has helped Microsoft make improvements 
to Windows HPC Server. 


"This study suggests for the first time that 
NK cells can impose immune pressure on 
HIV. something that had previously been 
described only for T cells and antibodies, 
adding an additional cell to the repertoire of 
those with anti-HIV activity. The results of 
this study raise a number of interesting new 
questions. We need to better understand the 
molecular mechanisms that allow NK cells to 
recognize HIV-infected cells and learn how to 
manipulate these cells in humans for therapy 
or prevention." — marcus altfeld 

"Using the full breadth of Microsoft tools, 
including .NET and Windows HPC Server, 
allowed us to quickly code our algorithms. The 
big one-CPU-year run then finished in just over 
a day." —carl kadie 

"Dur study provides hope that a greater 
appreciation of the NK-cell-mediated immune 
insBS to HIV can lead to therapies that 

thereby giving physicians another weapon 
in their long-running battle with HIV and 

Health and Computer Vision 

Medical Sensing via 
a Contact Lens 

McMorrow Innovation 
Associate Professor 
Electrical Engineering 
University of Washington 

Sen/or Researcher 
Computational User Experiences 
Microsoft Research 

HAVING SUCCEEDED IN making computers faster, 
smaller, and cheaper, technologists are now 
focused on making computing more accessible — 
more effortlessly integrated into the user's life — 
enabling more people to do more interesting 
things. Over the last few years, Microsoft has been 
working on creating natural user interfaces (NUIs) 
that make interacting with computers seamless, 
so that people can focus on completing their 
everyday tasks, building better relationships, and 
living better lives, even — or especially — when 
they're on the go. 

The Functional Contact Lens project is one such 
NUI endeavor. A collaboration between Babak 
Parviz and his Bio-Nanotechnology group at the 
University of Washington and Desney Tan and 
his Computational User Experiences group at 
Microsoft Research, the project aims to build a 
contact lens that provides the wearer with a fully 
configurable display of digital information. 

In the initial phases of this project, the team 
designed and built prototype contact lenses that 
included an embedded LED display, a wireless data 
communication link, and a power harvesting unit. 
While difficult problems remain — for example, 
adequately focusing the light and dealing with the 
jitter of the contact lenses— this proof-of-concept 
is highly encouraging. 

Recently, the team took advantage of the fact that 
the lens comes into contact with bodily fluid- 

tears, to be precise — to explore applicability of 
the lens for continuous medical sensing. Tests 
show that blood-glucose levels can be measured 
via special sensors embedded into the lens. This 
could be a boon to patients with type 1 diabetes, 
allowing them to monitor their blood-glucose 
levels without having to jab their fingertips several 
times a day. Moreover, the lens would monitor 
glucose levels continuously, a major improvement 
over the snapshot readings from periodic finger- 
stick blood draws. 

Initially, the lens would record information on 
blood-glucose levels for review by patients and 
their physicians. Ideally, however, the lens will 
be perfected to automatically display alerts of 
abnormal glucose levels directly in the wearer's 
view. Such alerts would prompt the patient to 
inject insulin or eat a high-glucose snack — and 
would fulfill the NUI goal of providing seamless 
computing interaction that improves quality of life. 

While the project team continues to explore 
uses of a fundamentally new type of natural user 
interface based on the functional contact lens, 
they have developed a number of novel methods 
for building devices such as sensors, radios, and 
antennas and integrating them onto a thin, flexible 
substrate. These methods are of significant interest 
to researchers in the fields of augmented reality, 
continuous health, and activity monitoring, and 
provide inspiration to Microsoft engineers who are 
developing future NUI technologies. 


"A lot of people considered the functional 
contact lens science fiction. Desney Tan and 
Microsoft Research were actually, very early on, 
convinced that this was perhaps a worthy cause. 
They were willing to work with us and support us. 
And I'm very grateful they did." — babak parviz 

"The project challenges our imaginations. We 
can now imagine a world in which the virtual 
and the real are truly fused, without technology 
getting in the way. Imagine your contact lens 
overlaying appropriate digital content on the 
real world wherever you go. Imagine continuous 
medical sensing to monitor your health. It's a 
brave new (or NUI) world." —desney tan 

/ € 


#• » 

Health and Computer Vision 

Improving Echocardiography 



Technikos Professor of 

Microsoft Distinguished Scientist 

Biomedical Engineering 

Managing Director 

Department of Engineering 

Microsoft Research Cambridge 


Oxford University 



important tool for diagnosing heart defects 
and diseases. However, its usefulness has been 
hampered by difficulties in quickly and accurately 
identifying the myocardium (heart muscle) in 
echocardiograms. Unfortunately, echocardiography 
images are of relatively low quality, with only 
about 40 percent of the clinical data considered 
of sufficient quality for automated analysis. 
This problem is particularly pronounced in 3-D 
echocardiography, where the large number 
of tissues that have similar appearance to the 
myocardium, including adjacent muscles and 
bright vessel walls, complicate the discrimination 
even more. Finally, the sheer amount of the data 
contained in a 3-D echocardiography study should 
be processed in a matter of a few seconds — ideally 
in real time — to be optimally useful in clinical 
practice. Most, if not all, current methods fail to 
meet this timeliness criterion. 

The University of Oxford collaborated with 
Microsoft Research Cambridge to investigate 
automated methods for segmenting 3-D 
echocardiography to assist cardiologists in 
assessing heart performance. The initial plan was 
to combine the graph-cuts framework developed 
at Microsoft Research with 3-D echocardiographic 
fusion, a technique for improving image quality 
being developed by Oxford. This plan quickly 
led to the idea of applying random forests to 

ultrasound image segmentation. (Random forests 
are discriminative classifiers developed recently in 
the machine-learning community.) The idea was t< 
investigate whether the power of machine learning 
and training can lead to good segmentation results 
on medium-to-low quality data without the need 
for image fusion. 

Recently, researchers have focused on using the 
temporal features, rather than just the intensity 
information, in a 3-D random forests framework 
to improve segmentation accuracy. They are 
also looking to establish efficient ways to train 
random forests for 3-D analysis. The project has 
demonstrated that the use of random forests 
allows scientists to obtain accurate delineations 
for the entire 3-D cardiac volume in a matter of 
seconds on a central processing unit (CPU), or 
even in real-time on a graphics processing unit 
(GPU). This class of techniques was also used by 
Andrew Blake and the team at Microsoft Research 
to produce the Kinect skeletal tracking technology. 
It is an example of how fundamental machine- 
learning research has widespread applications, 
ranging from medical imaging to consumer 

The improvement in the efficacy of 
echocardiography — a non-invasive diagnosis 
technique with no known risks or side effects — has 
major applications in the diagnosis of congenital 
heart disease and other cardiac conditions. 

"The Oxford-Microsoft collaboration has 
provided a very effective way to combine the 
strengths of Microsoft in machine learning 
applied in computer vision with my group's 
expertise in cardiovascular image analysis to 
provide new insight into how to analyze the quite 
challenging images of varying quality we meet 
in 3-D echocardiography. We published one of 
the first early papers in this area, and this has 
generated interest from a number of other 
groups around the world, as well as seeded a 
number of further projects in my laboratory 
looking at both other application domains, as 
well as methodological extensions suitable for 
3-D and 4-D biomedical image analysis. This 
has been a great experience of translating 
research ideas from one research domain to 
another." — alison noble 

"Alison Noble and her team have collaborated 
with us to apply ideas in machine learning to 
make a difference in medical imaging. It's an 
example of how computer science underpins 
many of the advanced technologies that are 
becoming commonplace in hospitals around the 


Health and Computer Vision 

Searching the Human Body 

Senior Researcher 
Computer Vision Group 
Microsoft Research 

IN RECENT YEARS, great advances in medical 
technology have improved the accuracy by 
which medical professionals can diagnose and 
treat a myriad of ailments. With the ability to 
literally see inside a patient's body — by using 
technologies such as magnetic resonance (MR), 
computed tomography (CT), and positron emission 
tomography (PET) — doctors now have a plethora of 
image information to help them address patients' 
conditions. However, while the technology for 
image acquisition has improved enormously, 
deciphering the information buried in the pixels 
is a time-consuming process that is subject to the 
individual clinician's experience and skill level. 

Antonio Criminisi and his team at Microsoft 
Research Cambridge are addressing new challenges 
and opportunities in clinical routines. Through a 
project entitled InnerEye, Criminisi is combining 
medical expertise and machine-learning theory 
to design a system that makes computer-aided 
diagnoses from medical imagery. By working 
directly with clinicians, such as those from 
Addenbrooke's Hospital in Cambridge, the team 
has been able to design the system for practical 
use from the ground up. 

Given a CT or MR scan, a clinician's key challenge 
is the identification of different body organs. 
Doctors typically view slices through the scan 
data, displayed in grey levels, and try to manually 
inspect different organs. By applying state-of-the- 
art machine-learning techniques, it is now possible 

for the computer to automatically identify dozens 
of key body organs, as well as their size and 
location. In effect, the system extracts semantic 
information about the presence and position of 
organs from the image pixels. This information 
can be stored in conventional text files and is 
searchable. Thus, a doctor can quickly retrieve 
information about, for example, all patients with an 
enlarged spleen, or patients with kidney stones. 

Criminisi's team is also developing an efficient 
algorithm for the automatic detection and 
delineation of brain tumors and the identification 
of their constituent regions, such as the actively 
proliferating cells or the necrotic region. This task 
enables clinicians to better diagnose the tumor 
type and determine the best course of treatment. 

One of the key algorithms used in this work is 
called decision forests. This algorithm can "learn" 
discriminative features about human organs 
or tumors from vast amounts of example data. 
Interestingly, this technique is also the engine of 
the Microsoft Kinect skeletal tracking capability, 
exemplifying how fundamental machine- 
learning research has uses in both medicine 
and entertainment. Many of the technologies in 
the InnerEye project have now been integrated 
into the Microsoft Amalga health care platform, 
enabling doctors to more effectively work with 
patients; by automating some of the most difficult 
tasks, doctors have more time to focus on patient 


Consultant Clinical Oncologist 
Cambridge University Hospitals 
NHS Foundation Trust 


"I work with a team that looks after patients with 
the most aggressive forms of brain cancer. We 
rely heavily on image information from CT and 
MRI scans to build up a picture of the tumor, 
where it is located, how it is growing, and how 
it is affecting the surrounding healthy brain 
tissue. We know that different treatments such 
as surgery, radiotherapy, and chemotherapy can 
target different areas of the tumor, which is why 
we tend to use these treatments in combination. 
Tracking these different areas of tumor through 
the course of a patient's cancer treatment 
in order to determine the effectiveness of 
treatment is a non-trivial exercise. Whilst 
automated techniques have been developed to 
track the anatomy of the healthy brain, none of 
these techniques have been able to identify the 
different areas that make up a brain tumor. The 
exciting prospect of the InnerEye project is that 
machine-learning techniques might be able to 
accelerate, if not fully automate, the process 
of tumor tracking, allowing us as clinicians to 
make meaningful and objective assessments of 
treatments in the clinic for the immediate benefit 
of our patients." — rajjena 

"Working on the InnerEye project is a fantastic 
opportunity to do interesting research with a 
direct impact on people's lives. It is refreshing to 
see how modern machine-learning technology is 
now being employed by doctors to deliver better 
health care, more promptly. At the same time, 
medical needs are helping advance the state of 
the art in machine learning and computer vision 



Computer Science 
and Technology 

Computer Science and Technology 



Principal Hardware Engineer 
Sensors and Devices Group 
Microsoft Research Cambridge 

IMAGINE LIFE WITHOUT daily memories. Not 
recalling what you did yesterday or the day before. 
Many victims of Alzheimer's disease and brain 
infections don't have to imagine this memory- 
deficient existence— they live it. Anything that 
can help these sufferers retain memories is a 
godsend, which is why memory researchers 
greeted Microsoft Research's SenseCam with such 

A small digital camera that is typically worn 
suspended from a neck strap, SenseCam 
automatically takes approximately two or three 
digital pictures every minute, in response to built- 
in sensors and a user-programmable timer. The 
camera easily stores a day's worth of images on its 
internal memory card; these images can then be 
downloaded to a PC for viewing. 

What has amazed memory researchers is the 
impact of the pictures. They don't just jog the 
patient's memory — studies indicate that they 
actually help in memory formation and retention. 
As one neuropsychologist working with the device 
observed, "Not only does it allow people to recall 
memories while they are looking at the images — 
which in itself is wonderful — but after an initial 
period of consolidation, it appears to lead to long- 
term retention of memories over many months, 
without the need to view the images repeatedly." 
Moreover, with improved memory recall, patients 
exhibit greater confidence and higher self-esteem. 

Initially developed in 1999, SenseCam was 
originally conceived as a general-purpose tool 

that would aid in capturing visual data. Microsoft 
Researchers, however, quickly realized it had 
potential in helping patients with memory 
impairment and began collaboration with 
Addenbrooke's Hospital in Cambridge, England, a 
facility renowned for its work with memory-loss 

The initial results at Addenbrooke's led to a 
host of clinical studies funded by Microsoft 
Research, including research on SenseCam's 
value in treating patients with epileptic amnesia, 
Alzheimer's, and severe brain injuries, as well 
exploring the effect of SenseCam images on 
memory in healthy people. 

This research project was so successful that it 
led to Microsoft licensing the technology to 
Vicon, which now distributes it as a product 
called Revue. As well as being used in the study 
of memory impairment, the device also has 
many other possible applications, which include 
market research, documentary filmmaking, art 
projects, and classroom instruction. There is now 
a burgeoning international SenseCam research 
community comprising academics, clinicians, 
and practitioners from a variety of fields. More 
than 100 workshop, conference, and journal 
papers report on how SenseCam is being used, 
and there is an annual SenseCam Symposium 
where the community gathers to exchange ideas 
and results. It is a compelling example of how 
a research project has led to a commercially 
available product that is used in a wide variety of 
applications that benefit society. 

Senior Lecturer 
Cognitive Neuropsychology 
University of Leeds 


"SenseCam has been a really inspiring project 
for me to be involved in. It's amazing to see the 
technology get picked up by so many different 
researchers and clinicians all around the world. 
With so many different applications, it's gone 
far beyond what we ever imagined. And in some 

incredibly rewarding." — steve hodges 

"If SenseCam only gave you memories for 
things in the pictures, there would be no 
surprises, no magic, and no benefit to our 
research. What continues to amaze me, in my 

we've made for others in the course of our 
research, is that SenseCam recovers memories 
for events, feelings, and details not captured in 
the lens and displayed on the screen. It's not so 
much an aide-memoire as a powerful cue for 
unlocking memories that you ma 
were lost." 

"For the memory researcher, it is going to 
be an invaluable tool for rehabilitation and 
measurement. The most important memory 
to someone is for their daily lives and events. 
It has been difficult tD measure, observe, and 
rehabilitate these, because the psychologist 
can't follow the person around. SenseCam 
can go anywhere with the person and thus 
provides the researcher or clinician with 
a set of materials fit for rehabilitation and 
research." — chris moulin 

Computer Science and Technology 

Technology to Combat 
Counterfeit Products 



School of Electrical and 
Computer Engineering 
Georgia Institute of Technology 


Senior Researcher 

Machine Learning and Applied 


Microsoft Research 

problem for legitimate manufacturers and their 
customers. A flood of sham products bedevil the 
software, computer hardware, pharmaceutical, 
entertainment, and fashion industries — everything 
from fake designer jeans to phony prescription 
drugs. The losses to the legitimate producers are 
substantial, as are the risks to consumers who 
unknowingly purchase fraudulent goods. 

Sometimes buyers know they're not getting the 
real deal — a Rolex for $100 just can't be real. But 
all too often, buyers pay full market price for 
a forgery, thinking they're getting the genuine 
item. The latter instances are what we call true 
counterfeits, and these represent the gravest 
threats to legitimate manufacturers and the buying 

A group of scientists, Darko Kirovski and Gerald 
DeJean at Microsoft and Manos Tentzeris, Vasileios 
Lakafosis, Anya Traille, Hoseon Lee, and Edward 
Gebara at the Georgia Institute of Technology 
(Georgia Tech), proposed the development of 
a technologically sophisticated certificate of 
authenticity (COA), an anti-counterfeiting device 
whose "signature" is extremely hard to copy 
but easy and convenient to authenticate. The 
proposed COA is a digitally signed physical object 
of fixed dimensions that has a random unique 
structure. Key among its requirements is that the 
COA be inexpensive to make and authenticate, 
but prohibitively expensive to replicate. Using 
radio-frequency electromagnetic "fingerprints" of 
dielectric and conductive resonators in the near- 

field is the technological basis of the proposed 

The proposed technology, referred to as RF-DNA, 
would satisfy the key COA requirements. Each 
instance of the COA would cost less than one cent, 
and the COA reader is projected to cost around 
US$100 in mass production. Because of the COA's 
complex topology and interdependent fingerprint 
components, it would be extremely difficult and 
costly to reproduce illegally. Moreover, it would 
be resistant to wear and tear, as the fingerprint 
readout is contactless. 

Gray-market piracy (high-quality counterfeits 
and illegal distribution of copies of software) 
costs Microsoft approximately US$l-5 billion in 
losses annually. Piracy of other goods constitutes 
approximately 5 percent of all world trade annually, 
resulting in a serious threat to public safety, equity, 
job markets, as well as tax losses around the world. 

RF-DNA offers a potential means of protecting 
producers and consumers from counterfeit 
goods — easily and at a low cost that is comparable 
with the costs of current, ineffective antipiracy 
features. Use of the COA could be extended to 
protect currency, checks, money orders, credit 
cards, licenses, passports, and a myriad of 
other legal documents. The anti-counterfeiting 
technology with cryptographically strong security 
could save Microsoft and worldwide resellers 
billions of dollars of revenue annually. Of course, 
it won't help you if you buy a $10 pair of Armani 
sunglasses— sometimes you just have to remember 
caveat emptor. 


ped RF-DNA system features 
unprecedented anti-counterfeiting capabilities, 
effectively equivalent tD 'security keys' of 
thousands of bits, by combining inkjet-printing 
ideas, ultra-low-cost 'green' materials, and 
near-field RFID technologies. It is a wonderful 
example of a very successful synergy between 
GT [Georgia Tech] and Microsoft Research, 
and it could set the foundation for near- 
ubiquitous anti-counterfeiting solutions in future 
Internet of Things or High-Speed Computing/ 
Telecommunication/WSN Systems." 

"RF-DNA comes to market with claims that 
are unparalleled in the world of anti- 
counterfeiting. What makes out a real challenge 
is to explore deployment scenarios as the 
business and operational landscape is excitingly 

Computer Science and Technology 

Clinical Studies and Data 
Collection and Reuse 

CLINICAL STUDIES DRIVE medical research, but 
they're complex and costly affairs. In order to 
be scientifically useful, they must record large 
amounts of data on the health and treatment 
regimens of a carefully selected group of test 
subjects. The IT infrastructure to collect this 
valuable dataset is often created from scratch 
for each study, a time-consuming and expensive 
process that leads to non-standard systems that 
compile data in non-standard ways. 

Could standardized software increase the 
effectiveness and reduce the cost of clinical 
studies, and thereby accelerate medical research? 
Together with colleagues from the CancerGrid 
project in the United Kingdom, researchers at 
Microsoft decided to find out. 

Building on the work of CancerGrid, which set 
out to improve information management for 
large-scale phase III clinical trials, researchers 
employed a semantics-driven approach and 
developed models, standards, and software for 
collecting medical research data. They broadened 
the scope of the work to include early-phase 
(phase I and II) studies, in which many more 
observations — including detailed molecular and 
imaging data — are made, but in a smaller number 
of subjects. Despite the importance of early-phase, 
experimental medicine in the development of new 
therapies, data from these studies is rarely reused 

or combined. The researchers aimed to show how 
appropriate information systems support can be 
rapidly provided, facilitating study management and 
data reuse, at little or no cost to the researchers. 

Their project focused on early-phase experimental 
studies in cancer, but the technology has proven 
to be widely applicable and is now deployed in 
institutes around the world. For example, it is being 
used to support a clinical study on the effectiveness 
of different ways of administering pneumonia 
vaccines to children in Nepal. Aside from allowing 
the trial to be run more cost-effectively, their 
system is collecting the data in a standardized 
way that will allow it to be easily reused in future 

The storage of clinical trials data required 
the creation of a robust and highly flexible 
IT infrastructure that would permit rapid 
reconfiguration to support different studies 
while maintaining the consistent data definitions 
needed to ensure that the data can be reused. 
Microsoft SharePoint and Microsoft InfoPath 
provided the needed robustness and configurability, 
demonstrating the value that these standard 
business technologies can bring to scientific 
research. The academic researchers shared their 
experiences with Microsoft product development 
teams, contributing to the design process for the 
next generation of Microsoft Office tools. 



Software Engineering 

University of Oxford 



Health and Wellbeing 

Microsoft Research Connections 


"The CancerGrid project is just one example of 
the value standard Microsoft tools can bring to 
basic scientific research." — simon mercer 

■as had a huge impact on our productivity. Dur 
Dllaboration has made us more effective and 
e connected researchers. We've been able 
to develop the tools and technologies that our 
medical colleagues need." — jim davies 

Computer Science and Technology 

Microsoft TerraServer: 

an Imagery Scalability Story 

TODAY, ONLINE MAPPING websites enable PC 
and smartphone users to view traditional maps, 
aerial or satellite imagery, or "street view" images 
of their neighborhood, place of work, or vacation 
destination practically anywhere in the world. These 
applications did not exist until the late 1990s. 
Researchers led by database legend James Gray 
at Microsoft Research's Bay Area Research Center 
in San Francisco, California, pioneered the early 
work of building a massively large image database 
of aerial and satellite imagery that standard web 
browsers can access without the need for special 
plug-ins or other applications. 



Product and Services Lead 


US Geological Survey 


Development Manager 
Bing Search 


The original motivation for the project was to test 
the scalability of a new version of the Microsoft 
SQL Server relational database management 
system (RDBMS). Working with the SQL Server 
team, the research project was to build a single 
database instance that was big (1 terabyte 
or larger); public (accessible on the Internet); 
interesting; accessible via standard web browsers 
(no plug-ins required); real (had a commercial 
purpose); fast; and easy to use, build, and deploy. 
Finding an interesting, real, and large dataset that 
wasn't already widely available was a challenge. In 
researching potential datasets, the research team 
met with researchers at the University of California, 
Santa Barbara (UCSB), who were building an 
online digital corpus of geospatial information. 
Collaborating with UCSB, the team developed 
the Microsoft TerraServer database and web. At 
the time, circa 1996, the geographic information 
system (GIS) community was able to store and 
display street and world maps through web 
browsers. But the industry had not been able to 
build and deploy high-resolution imagery such as 
that found today on sites like Bing Maps or Google 

The website then known as Microsoft TerraServer 
and now known as Microsoft Research Maps 
initially stored 2.3 TB of U.S. Geological Survey 
(USGS) grayscale "digital orthophoto quadrangle" 
(DOQ) imagery and 1 TB of declassified Russian 
military satellite data that were provided by 
Sovinformsputnik's US partner, Aerial Images, 
Inc. The Microsoft TerraServer researcher's novel 
approach was to take the very large images — 
varying from 25 MB to 200 MB each — and tile them 
into very small, 200 x 200 pixel JPEG compressed 
"tiles" that ranged from 6 KB to 36 KB, depending 

on the image content. The pixels were selected 
from the source imagery such that a "seamless 
mosaic" of large expanses of Earth would appear 
to the user as a single, large image. The tiles were 
formatted to HTML tables of 3 x 2, 4 x 3, or 5 x 4 
(in other words, the tiles were cut into 6, 12, or 20 
pieces). Clickable arrows and zoom-in/out images 
placed around the table of images enabled users 
to pan and zoom around each logical collection 
of seamless tiles. In the conterminous United 
States, there were 10 logical images enabling a 
user to continuously pan north to south from 
Albuquerque, New Mexico, to Montana, or east 
to west from San Francisco, California, to Reno, 
Nevada, without changing logical seamless images 

The Microsoft TerraServer tiling and mosaic 
scheme proved to be a breakthrough in the GIS 
industry. The Microsoft TerraServer tiling approach 
is used by all major high-resolution imagery sites, 
including Google Earth, Google Maps, MapQuest, 
and Yahoo Maps. Microsoft TerraServer / Microsoft 
Research Maps are available to end users and 
researchers. Today, the site exclusively stores 
USGS original grayscale DOQ imagery, scanned 
USGS topographic maps (digital raster graphic, 
or DRG), and color imagery of major US cities 
photographed by the National GeoSpatial Agency 
(NGA) after 9/11. Microsoft continues to provide 
free and unencumbered access to this data via an 
HTML user interface, a SOAP/XML web service, and 
an OpenGIS Consortia compliant web map server. 
The site enables consumers as well as commercial 
and academic users to have both interactive and 
programmatic access to a total of 4.3 terabytes of 

TerraServer was the first mapping service on 
the Internet with programmatic interfaces. At its 
release, it was the largest data collection accessible 
via web services. The TerraServer project generated 
a significant amount of feedback to the Microsoft 
SQL team on how to scale databases to large 
datasets. SQL Server was the foundation for the 
Virtual Earth technology. 

"The TerraServer was the world's largest public 
repository of high-resolution aerial, satellite, 
and topographic data. It was designed to be 
accessed by thousands of simultaneous users 
using Internet protocols 1 ' 


"Drthoimagery is one of the most cost-effective 
methods for producing current maps, and it has 
been my dream that orthophotomaps be readily 
available to everyone. Today, orthoimagery is 
used in GIS systems at all levels of government 
and throughout the geospatial community. More 
importantly, it is readily available to the general 
public. Microsoft TerraServer and the technology 
behind it were the beginning steps toward 
making that dream a reality." -george lee 

Physics and 

Physics and Astronomy 

Worldwide Telescope and 
Seamless Astronomy 

THE SEAMLESS ASTRONOMY project, led by Alyssa 
Goodman at Harvard University, aims to apply new 
technologies, as they are imagined or developed, 
to the research environment that astronomy 
researchers find themselves in every day. Microsoft 
Research Worldwide Telescope (WWT) provides 
a fantastic set of linkages between data archives, 
data visualization, and online resources, including 
the refereed literature. By collaborating closely 
with other leaders of the NASA/NSF-sponsored 
Virtual Astronomical Observatory (VAO) program 
and researchers at Microsoft, participants in the 
Seamless Astronomy effort are working toward 
a "seamless" research environment in which 
researchers use their favorite tools to retrieve 
data, which is then used to conduct literature 
searches. Researchers then use other tools in 




Principal Researcher 


eScience Group 

Harvard University 

Microsoft Research Connections 



that environment to analyze, model, and simulate 
with the data in a freeform effort. The goal is for 
researchers to be able to focus on their research 
without being concerned about the various 
programs and services they use to help them with 
their work. 

Worldwide Telescope is a free, interactive, virtual 
learning environment that combines terabytes of 
high-resolution images from ground- and space- 
based telescopes, astronomical data, and guided 
tours, enabling users to experience a seamless 
exploration of the universe. "Anybody who's looked 
up at the sky has wondered about the nature of 
what they are seeing," says Curtis Wong, a principal 
researcher at Microsoft Research who worked to 
bring Turing Award winner Jim Gray's WWT vision 
to reality. "I think it's a fundamental thing for 
people to be curious about the universe." 

WWT provides a unique opportunity to see 
and hear guided tours about the universe from 
astronomers and educators within the context 
of the sky. Students are able to pause a tour to 
get more in-depth information about any object 
from multiple sources on the web, examine other 
multispectral imagery of that object, or jump 
to a different tour that is related to that object. 
WWT makes this unprecedented level of data and 
imagery easy to access so that users of all ages can 
explore the universe. 

As Goodman describes, the WWT technology, 
though still evolving, is just one example of new 
ways to interact with the large datasets that 
are accumulated by projects that are affiliated 
with the research labs, such as the Dataverse, 
Seamless Astronomy, and High Dimensional Data 
Visualization and Interaction. While in the past, 
data has typically been displayed in charts and 
graphs, in recent years, technology has enabled 
the collection of such large volumes of data that 
traditional display methods are inadequate. By 
displaying the data in three dimensions (with time 
as a fourth) or by interacting with it graphically, 
WWT enables researchers to not only better 
visualize and explain what they've found but 
also understand it better themselves, Goodman 
observes. "WWT is also one of the most extensive 
and powerful astronomical data environments 
that are accessible to the public for education," 
she notes. 

Through this research effort, Microsoft has gained 
valuable insight into geo-spatial visualization 
technologies. Researchers envision the data 
deluge extending beyond the sciences and into 
the business world. With information feeds and 
large volumes of streaming data, visualization 
techniques like the WWT will be valuable not only 
for research but also for the broader community of 
knowledge workers and data analysts. 

"WorldWide Telescope is an example of where 
science and science education should be going; 
it is the best interpretation of the 'virtual 
observatory' concept." — alyssa goodman 

"WorldWide Telescope provides a multitude 
of astronomical image and data sources 
seamlessly integrated into a vast virtual 
universe that can serve as research 
environment for astronomers as well 
as an educational exploration, content 
creation, and presentation platform for 

kids." —CURTIS WONG 

Physics and Astronomy 


the Universe at Your Fingertips 



Astrophysics and Computer 


Johns Hopkins University 


Distinguished Engineer 
eScience Group 
Microsoft Research 

SKYSERVER IS THE multi-terabyte astronomy 
archive, containing the data of the Sloan Digital 
Sky Survey (SDSS) project, a collaborative effort 
among public and private organizations to 
create the most complete map of the northern 
sky. It presents the SDSS data as a web- 
accessible database, along with visual tools to 
analyze the data. The result is an SQL database 
with approximately 3 billion rows describing 
approximately 400 million celestial objects and 1 
million spectra. It gives full graphical user interface 
(GUI) and SQL access to the SDSS data, allowing 
everyone the chance to use one of the world's best 
telescopes. SkyServer includes 200 hours of online 
instruction to teach astronomy and computational 
science by using this data. 

The ability to pose questions in a few hours and 
get answers in a few minutes changes the way 
scientists view the data; they can experiment 
interactively. When queries take three days and 
hundreds of lines of code, scientists ask fewer 
questions and so get far fewer answers. This and 
similar experiences prove that interactive access 
to scientific data and data mining tools can 

dramatically improve productivity. 

The SkyServer is also an educational tool. Several 
interactive astronomy projects, from elementary 
to graduate level, have been developed in three 
languages (English, Japanese, and German). The 
SkyServer design has been cloned by several other 
observatories: Royal Observatory, Edinburgh, 
Cornell Arecibo Pulsar Search, Caltech Quest, Space 
Telescope Science Institute for Hubble and Galex 
datasets, and the National Optical Astronomical 
Observatories at Tucson. Also, SkyServer's 
framework has been used as the template for 
radiation oncology and environmental sensing 

SkyServer was one of the earliest projects that 
used web services to access and serve large 
datasets and image files. With many terabytes 
of data and imagery, the application explored 
the scaling capability of Microsoft SQL Server 
database technology. The project also inspired a 
new generation of astro-informaticians to take 
advantage of the power of relational database 


"SkyServer is a goad example of information 
at your fingertips for astronomers-letting 
scientists work in new, more productive ways. 
An astronomer can ask complex questions and 
see results almost instantly. It allows them to 
explore the data from desktops anywhere in the 
world." —JIM GRAY 

"With so much information in so many databases 
around the world, we cannot move all the data 
to where the analysis is being done; rather, 
we need to bring the analysis to the data 
by dividing the computation up among the 
archives." —Alexander s. szalay 

Physics and Astronomy 

Topological Quantum 

WITH THE GROWING demand for faster, more 
powerful, more versatile computing, and limitations 
on how small circuits can be built within the 
current paradigm, scientists inevitably must turn 
to a new era of intelligent computational devices. 
Researchers are reaching the limit of how fast and 
small they can make conventional microprocessors 
and urgently need to look to possible alternatives. 

Quantum computers are one exciting avenue to 
explore. Research in quantum computing has 
offered many important new physical insights, as 
well as the potential of exponentially increasing 
the computational power that can be harnessed 
to solve important problems in energy, medicine, 
computer science, physics, mathematics, and 
material science. Quantum computing promises, 
quite literally, a quantum leap in the ability to 
execute complex quantum simulations across a wide 
range of applications. 

Microsoft is working with universities around the 
world to develop the first quantum computer — a 
topological quantum computer. Since 2005, 
Microsoft's collaboration with universities has 
driven a resurgence in condensed-matter physics, 
in the area of topological phases and materials. 
The unique basis of this approach to quantum 
computation is to use topological materials that by 

their nature limit errors. These are exotic, low- 
temperature systems that possess degrees of 
freedom that are immune to the action of local 
operators. By their topological nature, individual 
qubits and quantum gates are protected from 
errors. Examples of topological materials include 
fractional quantum Hall effect (FQHE) systems, 
Ising superconductor-topological insulator 
heterostructures (ISH), and ID nanowires. 

Among the ongoing external collaborators, 
Charles Marcus and the Marcus Lab at Harvard 
University have made great strides in fabricating 
and studying ID quantum nanowires and FQHE 
systems. They aim to manipulate non-Abelian 
anyons — strange quantum quasi-particles that 
appear in two-dimensional systems — for use in 
quantum information processing, and ultimately 
for building a full-scale quantum computer. 
Microsoft's collaboration with the Marcus Lab 
has revealed beautiful, intricate physics and a 
path toward building a topological quantum 

This project demonstrates the strong 
commitment at Microsoft Research to explore 
new computing paradigms that have great 
potential to influence the future of computing as 
well as the future of Microsoft. 




Harvard University 


"The mathematicians and theoretical physicists 
at Microsoft Station Q have created a vision of 
computation that completely reconsiders how 
information is processed and stored, intrinsically 
rooted in the laws of quantum mechanics, which 
appears poised to bring revolutionary change to 
technology and physical science. The challenges 
created for the experimentalists involved in this 
project are thrilling: first, discover a new class 
of particle, expected to exist in nature but not yet 
found; learn to create these particles on demand, 
move them, store them, wrap them around each 
other, and read out their states; then build a 
computer out of them. Perhaps this kind of vision 
is to be expected. After all, these are topologists- 
the notion "off on the horizon" means nothing 
to these people; the whole problem sits before 
them, all challenges equidistant. What compels 
the experimentalist to try is something different. 
Remarkably, each piece of the puzzle seems within 
reach, hard for sure, but not impossible. So, one 
step at time, we proceed, occasionally getting the 
theoreticians to meet us half way between here 
and the horizon." — charles m. marcus 

The Bloch Sphere 

"We believe that topological materials, arguably 
among the most enigmatic objects in nature, 
appear to be essential to quantum information 
processing. Dur challenge on the topological 
road is to physically realize the mathematically 
known topological phases of matter, and then to 
develop a scalable quantum device. If we can build 
it, we will be able to provide new answers to new 
questions and revolutionize our understanding of 
computation. Topological quantum computation is 
hard to resist." — michael freedman 

Biology and Life 

Biology and Life Sciences 

Coevolution of Viruses and 
the Immune System 



Institute for Immunology and 
Infectious Diseases 
Murdoch University 



Staff Scientist 

Principal Researcher 

Vaccine and Infectious 

eScience Group 

Disease Division 

Microsoft Research 

Fred Hutchinson Cancer 

Research Center 



INSIDE THE HUMAN body, a battle rages 
between the immune system and disease-causing 
pathogens. Striving for an advantage, pathogens 
constantly evolve to evade detection by the 
immune system. 

In 2010, Microsoft researchers — together with 
colleagues from Murdoch University in Western 
Australia, the University of Western Australia, and 
Fundacion Ciencia para la Vida in Chile — explored 
this evolutionary struggle. Their study focused on 
human leukocyte antigen (HLA) molecules, which 
sample cellular proteins and present them on the 
cellular surface for examination by the immune 

When viruses infect a cell, they bring their own 
genetic material into the cell and use cellular 
resources to propagate. As a result, HLA molecules 
present viral proteins on the infected cell's surface, 
spurring an immune attack on the "odd" cells. 
However, viruses often mutate to evade detection, 
altering the protein segments that HLA molecules 
are most likely to present. 

On the other side, the distribution of the 
thousands of HLA variants present in human 
populations can change over many generations. 
This sets up an evolutionary game: viruses on 
one side, the immune system on the other. To 
analyze this contest, the researchers quantified 
HLA-binding preferences according to targeting 
efficiency, a novel measure that captures the 
correlation between HLA-binding affinities and 
the genetic conservation in the targeted regions. 
In theory, HLA molecules should draw attention to 

protein segments that are shared across related 
viral species, as such regions should be functionally 
important and thus immutable. 

Analysis of targeting efficiencies indicated 
that HLA molecules do indeed prefer to target 
such conserved regions. The magnitude of this 
preference varies in a way that shows evidence of 
target splitting, where two different HLA loci focus 
on different viral families. This phenomenon is 
consistent with theoretical biology predictions for 
predator-prey models and indicates that targeting 
efficiency as a measure of the HLA-virus links will 
be useful in analyzing viral evolution. Furthermore, 
in many cases the host's total targeting efficiency 
scores for various viruses correlate with clinical 
outcomes, offering a potentially useful system 
of measures for analyzing infection outcomes in 
individual patients or entire human populations 
under different conditions, such as post- 
vaccination or following a previous viral infection. 

This work was possible only by combining 
machine-learning techniques with large numbers of 
viral sequences. It illustrates that a computational 
approach can be just as important to biology as 
"wet lab" work for both formulating and testing 
new hypotheses. Several new fields of inquiry have 
stemmed from this work, including research on 
"correlation sifting," a method for feature selection 
that improves upon standard LASSO approaches to 
a variety of tasks beyond biology, and which may 
be used to improve future Microsoft products that 
currently utilize LASSO or similar feature-selection 

"The findings are fascinating and of fundamental 
importance. We showed that the immune system 
focuses its attack on the segments of viruses 
that are most critical for their function. In 
response, different viruses have had to find 
different ways to survive our ability to detect 
and eliminate foreign forms of life within us. 
Some viruses have even been able to redirect 
our immune system attack in a way that 
enhances their survival." -simon mallal 

"This is one of the first large-scale analyses that 
use HLA binding prediction methods for studying 
host-pathogen co-evolution. The ability to scan 
a large number of viral genomes and to do this 
in parallel for a large number of HLA alleles 
provided compelling evidence that the immune 
system has evolved to focus surveillance on 
conserved regions of the pathogens with which 
it is co-evolving. We found that different HLA 
alleles have evolved to preferentially target 
specific viral families, showing additional 
evidence for the ongoing process of the 
adaptation of our immune system to the 
pathogens it encounters." — tomer hertz 

"In this study, we sought to identify possible 
commonalities in HLA (human leukocyte 
antigen) binding preferences that would reveal 
patterns of optimization of this component of 
the immune system in response to the variation 
in pathogens. What we found was fascinating. 
For example, for the first time, we saw that 
sequence variation patterns in very different 
viral families show mutual dependencies 
that can only be detected when these are 
observed through the prism of our immune 
responses." — nebojsa jojic 

Biology and Life Sciences 

Software Verification 
Meets Biology 


Principal Researcher 
Programming Principles and 
Tools Group 
Microsoft Research 



Programming Principles and 
Tools Group 
Microsoft Research 



Department of Computer 


University of Leicester 

schoolchild learns it: question, hypothesis, 
experiment, data analysis, and conclusions. Critical 
to this process is the construction of models whose 
predictions can be compared to the real universe, 
and vice versa. In biology, for example, scientists 
deal with models of the mechanisms by which 
embryonic cells differentiate to become one type 
of cell in the course of cell division. They want to 
know whether the absence of a particular protein 
or gene in the cell determines which type of cell 
the embryonic cell becomes. The problem is that 
models of biological systems are so complex that it 
is difficult to extract useful predications from them. 

Is there a way to answer queries about intractably 
large models of biological systems automatically? 
This is the problem a group of researchers set 
out to solve at Microsoft Research. They have 
developed an approach called executable biology, 
which takes advantage of Microsoft's strength in 
automatic software proving and formal methods. 
Executable biology takes analytical tools developed 
to study reasoning about computer systems 
and uses them to model and analyze biological 
systems. Their solution adapts recently discovered 
automatic-program verification techniques that 
were originally developed for the analysis of high- 
performance concurrent software. In particular, 
they have applied techniques for proving 
termination of these systems. Many biological 
models can be viewed as concurrent systems with 
far more concurrently executing threads than 
would be found in an average software system. 

Nonetheless, with some adaptation, the techniques 
have shown great scalability. 

In collaboration with Nir Piterman at the University 
of Leicester, an expert with unique experience in 
using formal methods in biological modeling, the 
researchers are developing an efficient procedure 
for proving stabilization of biological systems 
modeled as qualitative networks or genetic 
regulatory networks. For scalability, their procedure 
uses modular proof techniques, where state-space 
exploration is applied only locally to small pieces 
of the system, rather than the system as a whole. 
It exploits the observation that, in practice, the 
form of modular proofs can be restricted to a very 
limited set. For completeness, their technique falls 
back on a non-compositional counterexample 

By using this procedure, they have analyzed a 
number of challenging examples, including a 3-D 
model of mammalian epidermis and a model of 
metabolic networks operating in type 2 diabetes. 
In cases where previous stabilization-proving 
techniques were known to succeed, this technique 
attained results far faster, and it obtained new 
results in cases where tools had previously failed. 
Biologists can now ask much deeper questions 
about their models and expect to have tools 
that automatically answer them. By applying 
Microsoft Research's software analysis expertise 
and tools to a biological scenario, this project is 
helping to create new business opportunities and 
partnerships in areas such as biotechnology and 
health care. 


P8.p P7.p P6.p PS.p p 4 p 

„ P8 p P7.p 



"The intersection between purely mechanistic 
questions in cell biology and theories from 
software engineering is extremely powerful for 
both disciplines. Dn the biology side, this kind 
of work allows us to ask and address questions 
about dynamicity that we couldn't have asked 
before; and on the computer science side, well, 
I think there's no doubt in anyone's mind that 
the complexity observed in living systems is 
orders of magnitude more complex than any 
man-made engineered system, which means 
that the languages, analysis methods, and the 
tools all need to adapt, scale up, and be specially 
designed to cope both with the complexity 
and the new end users, who are biologists 
(non-professional programmers). Extremely 
challenging!" —jasmin fisher 

"Unlike software, which is custom designed 
with a (usually) sensible architecture, 
nature's natural selection process gives 
rise to some outrageously byzantine 
svstems." -byron cook 

"Biological systems are fascinating to model. 
We are forced to take a fresh view on our 
techniques as we have to adapt them to systems 
that are both like and unlike the artifacts we are 
used to working on. At the same time, biologists 
are learning to use our tools and get a hang of 
the advantages that this kind of modeling and 
automation enables." — nir piterman 


Biology and Life Sciences 

Programming Life 


Head of Biological 
Computation Group 
Microsoft Research Cambridge 


Plant Biologist 

Department of Plant Sciences 

University of Cambridge 

EACH ONE OF the 10 17 cells that make up an 
individual, each cell that makes up a plant, each 
stem cell, and even a "simple" bacterium or 
a white blood cell, is a remarkable biological 
"machine." At the heart of these biological 
machines is a molecular "program" governing 
sophisticated biological computation, 
information processing, and decision making — 
from energy production and consumption, to 
effective response to attack and malfunction, 
to what actions need to be taken in response 
to changes in the environment. It's a program 
that determines, for example, plant growth and 
agricultural yield, which in turn affects global 
carbon cycling. When this program malfunctions, 
it can lead to autoimmune disease, cancer, and 
viral infections. 

What if it were possible to program cells? 
Scientists could address some of the greatest 
challenges facing humanity. For instance, it might 
be possible to program human cells or even the 
entire immune system to prevent or tackle disease 
in new ways that would transform medicine. 
Plant cells could be programmed to improve 
crop yields, to solve a problem for which there is 
currently no viable solution: how to feed a global 
population of 9 billion people. It might even be 
possible to design and program artificial cells to 

cheaply generate sustainable, global sources of 
energy, for example, by artificial photosynthesis. 

This isn't science fiction, but, until very recently, 
nor has it been "science fact." While the current 
state of the art has shown how bacteria can 
be modified to attack specific types of cancer 
cells, how yeast can be modified to make the 
world's most effective antimalarial drug, and how 
bacteria can be engineered to convert sunlight 
into electricity, there is a major barrier to making 
progress: designing cellular behavior currently 
involves complex, laborious, and highly error-prone 
methods, often based on trial and error. 

This work has not only pushed the boundaries of 
biological computing, it has also helped Microsoft 
refine Microsoft Visual Studio products. In the 
process of building a visual tool for scientists, the 
research team used Microsoft Automatic Graph 
Layout (MSAGL), which provides an essential part 
of the tool's user interface, and is part of Visual 
Studio. With scenarios that pushed the limits 
of MSAGL's capabilities, the researchers helped 
the Visual Studio team expand its capabilities — 
and also provided direct input into making it 
more robust. This teamwork between Microsoft 
researchers and product development groups 
simultaneously helps advance science and 
improvements to Visual Studio technology. 


"All of the technologies that we need to feed 
ourselves, to clothe ourselves, to provide 
materials for the modern world derive from 
nonrenewable sources. We need to move 
towards renewable sources and to use 
sustainable technologies. And. largely, they are 
biologically based. It's the way of the future. 
We anticipate that in the next 5, ID, 2D years' 
time, the scale of circuits that we will certainly 
be able to produce, and will want to produce, 
is far beyond the ability of humans to model, 
and that will clearly require this kind of 
technology. We're do a trajectory here, with 
a close integration between software 
design and modeling and biological 
assembly." — jim haseloff 

"It is tremendously exciting working with Jim 
Haseloff and others to be able to see our 
programs running in living cells, and it gives 
us hope that our dream can be realized in the 


Biology and Life Sciences 

How Many Species Are There? 


Doris Duke Chair of 

Conservation Ecology 

Nicholas School of the 


Duke University 



Computational Ecology and 
Environmental Science Group 
Microsoft Research Cambridge 

HOW MANY SPECIES are there? While the question 
has an almost childlike simplicity, the answer has 
proven elusive. Biologists agree that the list of 
known species — numbering about 2 million — is 
woefully incomplete. Estimates of how many 
more species exist range from 5 to 50 million, a 
practically meaningless span. 

Biologists have long sought to identify areas where 
effective conservation could save the most species. 
Biodiversity hotspots — places with extreme rates of 
habitat loss as well as unusually high numbers of 
endemic species — are priorities. But with so many 
species as yet unknown, one has to wonder: could 
and would their discovery change those priorities? 

Moreover, those unknown species are likely to have 
small geographic ranges and to be rare within their 
habitats, and thus they would be prime candidates 
for extinction. So by figuring out how many species 
are "missing" from the record, Lucas Joppa, an 
ecologist in the Computational Science Laboratory 
at Microsoft Research — together with Stuart Pimm, 
a world-leading expert in conservation ecology at 
Duke University, and David Roberts at University 
of Kent — are providing quantitative estimates for 
how many more species might be threatened and 

The unique insight that the team brings is the 
acknowledgment of an inherent social dimension 
to the process of species description. People 
(taxonomists) describe species, so the number 
of species described must surely depend on the 
number of people actively describing them. By 
incorporating human effort into their statistical 

model, the researchers can predict, with measured 
confidence, the numbers of species remaining to 
be discovered. 

Pimm and Joppa defined and refined the species 
model from a quantitative viewpoint, providing 
deep insight into how one might potentially 
account for unknown species by using a novel 
proxy parameterization around the number of 
taxonomists in a given field. Then, by using new 
scientific software tools and technologies being 
developed by Microsoft's Computational Science 
Laboratory, they are taking massive amounts of 
hugely dispersed data, bringing them together in 
a computationally powerful manner, and applying 
statistical models to make predictive assessments 
of the total number of species. 

The new approach to conservation science 
is helping to push the boundaries of current 
spatial database technology. The project uses 
Microsoft SQL Server in novel ways that change 
how scientists think about analyzing spatial data, 
helping to bring new insights across a range of 
application scenarios. The researchers are working 
with the product team to push the limits of SQL 
Server's capabilities, while their feedback is 
contributing to the development process for future 
versions, including SQL Azure. 

The future of human life depends upon the 
consequences of the massive extinction crisis 
currently facing humanity. The unknown-species 
estimates present quantitative evidence that 
can improve the effectiveness of environmental 
regulation and conservation — and help the planet. 


"We know we have an incomplete catalogue 
f life. If we don't know how many species 
are, we may be underestimating or 
i estimating how fast species are becoming 
reatened or extinct, and if we don't know 
where they live, then how can we prioritize 
places and policy for conservation? What if 
the places we are ignoring now turn out to be 
amongst those with the most unknown species? 
'ying to answer these great unknowns keeps 
b excited about the work I do. because it is not 
only hugely challenging intellectually, but the 
answers we are seeking are so important for 
addressing some of the most dire environmental 
problems of our generation." — lucas jo 

"Understanding biodiversity-how much there 
is, where it is, how fast we are losing it (and 
what we can do to prevent that lass) — is a major 
environmental challenge for this new century. 
What we know already constitutes a vast amount 
of information, data stream in from around the 
globe daily, and yet we know we must make 
decisions on incomplete data, while modeling 
where the data gaps lie. Microsoft's commitment 
to handling, visualizing, and modeling 
environmental data makes it a leading player in 
this effort." — stuart pimm 


Citizen Science 

Citizen Science 


ONE OF THE most successful citizen-science 
efforts, Galaxy Zoo enlists individuals worldwide 
to assist in the classification of galaxies. It 
represents the world's largest astronomical 
collaboration, bringing professional astronomers 
together with hundreds of thousands of 
volunteers. Independent assessments show that 
classifications provided by Galaxy Zoo volunteers 
are as accurate as those from professional 
astronomers. The results have informed research 
into the formation of elliptical galaxies and 
provided a sample of merging galaxies of 
unprecedented breadth and fidelity. Some 
classifications have highlighted the dominance 
in some environments of red spirals, in which 

star formation has been rapidly and mysteriously 

The influence of Galaxy Zoo stretches beyond 
the band of astronomers who seek to understand 
the evolution of the universe. The Zooniverse, 
which grew out of Galaxy Zoo, now hosts 10 
projects inviting volunteers to do everything 
from transcribing ancient papyri to searching for 
planets around other stars. Meanwhile, the rich 
datasets that citizen science of this sort provides 
also inspire new approaches to machine learning- 
something that will be essential to enable 
automated and human classifiers to cope with the 
next generation of surveys, which will produce 
terabytes of data every night. 





Department of Physics 

Citizen Science 

University of Oxford 

Adler Planetarium 


"Galaxy Zdd's initial success took us by 
surprise, stretching our server capacity 
and overwhelming the science team. 
Collaboration with Microsoft Research helped 
us understand how to make the most of the 
project's potential." — chris lintott 


> \ 

Citizen Science 

EVIDENCE OF GLOBAL climate change is now 
unequivocal, but what does that mean for the 
weather where you live? Will damaging weather 
events increase, or might your weather become 
less extreme? To answer these questions, has partnered with the 
Met Office (the United Kingdom's national 
weather service) to create, an 
international project that is open to anyone with a 
computer and Internet access. 

With support from Microsoft Research, will enable anyone in the 
world to download and run a regional climate 
model on their home computer. The model is 
initially available for three target regions: Europe, 
the western United States, and southern Africa. 
Participants produce simulations that will enable 
scientists to estimate how often heat waves, floods, 

and hurricanes will strike in the next few decades. 
The initiative will also indicate how much of 
the blame for these events can be attributed to 
greenhouse gas emissions caused by humans. 

The model has been developed by the Met Office, 
and results from different regions are being 
used directly by scientists who specialize in the 
climates of those regions. The European region is 
being analyzed by the Met Office and by Oxford, 
Edinburgh, and Leeds universities; southern 
Africa by the University of Cape Town; and the 
western United States by Oregon State University. 
Results are also made available to scientists who 
are interested in climate impacts in the various 

The first results from the 
experiment were recently published in the journal, 
Geophysical Research Letters (February 2012). 



Research Scientists & Joint 



College of Oceanic and 

Atmospheric Sciences 
Oregon State University 


"The support that 
has recEived from Microsoft Research for 
developing the weatherathome project has been 
invaluable and is very gratefully acknowledged. 
Microsoft's support has been vital in enabling 
a whole new modeling capability that will much 
more accurately inform decision-making 
processes in the face of uncertain future 
changes to weather-and in particular, extr. 
weather patterns." — suzanne rosier 

"Many scientists and decision makers, seeking 
to understand the consequences of global 
climate change, have used climate modeli 
results to describe future climates. Previi 
descriptions of future climates have had to 
choose between a fairly high number (100+) of 
simulations using global models with coarse 
spatial resolution (IDD+km) missing important 
features like mountain ranges, or finer spatial 
resolution from regional models but only one 
or two simulations, which is not enough to 
describe the probability of different future 
climates. For instance, one model might suggest 
an increase in winter precipitation of ID percent 
and another suggests a decrease of 5 percent. offers an ideal way to 
achieve both the fine spatial resolution and the 
high number of simulations that scientists and 
decision makers desire. In addition to Microsoft 
Research, the western US part of the project is 
jointly supported by both science- and decision- 
oriented agencies: US Geological Survey, Bureau 
of Land Management, and the California Energy 
Commission." — philip w. mote 

Citizen Science 


University of Washington 


Partner Group Program 


Mi< i osoft Server and Tools 


allow volunteers to observe the work that their 
computer is performing on behalf of the project, 
there has been no mechanism to visually present 
the overall results and the aggregate contributions 
of individual volunteers or teams. Thanks to a 
first-of-its-kind feedback system collaboratively 
developed by Microsoft Research and the 
University of Washington (UW), that's no longer 
the case. 

The system was created for the UW's Rosetta@ 
Home project, which uses the distributed 
computing power of citizen participants to 
help predict and design the three-dimensional 
structures of natural and synthetic proteins by 
using minimum energy calculations. In Rosetta@ 
Home, an individual computational run generates 
a folded protein conformation, along with two key 
metrics: energy (Rosetta score of the computed 
protein structure, which is analogous to free 
energy) and RMSD (root mean square deviation 
from the experimentally determined structure). A 
typical experiment consists of generating a large 
number of conformations in an effort to find the 

lowest energy structure, which, ideally, should 
also have the lowest RMSD. 

By using Microsoft SQL Server, the researchers 
created an Internet-based feedback report that 
illustrates the contributions of individuals or 
teams, displayed in the context of overall results. 
A SQL Server relational database tracks individual 
results and processes reporting queries on 
demand, and its associated reporting services 
render plots from query results — graphics 
that can be fully integrated with the project's 
public website. The feedback reports have been 
extremely popular with participants, who find 
it reinforcing to see the actual impact of their 
contribution. Moreover, the reporting system 
has also proven to be useful to investigators 
inside the UW lab, allowing them to monitor the 
progress of experiments and view results quickly. 

Because user engagement is critical to the 
success of community computing projects like 
Rosetta@Home, there's every reason to believe 
that this reporting solution can encourage 
participation in a variety of citizen-science 


"The incorporation of SQL Server into RosettaS 
Home has provided an invaluable and unique 
way in which the general public can directly see 
the results of their contributions to biomedical 
research." — david baker 

"David Baker's team had introduced 
breakthroughs in applying massive scale, 
distributed community computing solutions to 
the problem of predicting protein structure. 
Microsoft had just released a version of 
SQL Server that offered easy-to-use data 
integration and visualization tools, and we 
realized that it was now simple to harness 
the high volume data that resulted from 
his distributed computing experiments into 
graphical images that helped experimenters 
see progress 'at a glance' and keep the 
community engaged-without having to become 
database administrators or SQL experts in the 



.' K -4 

Scientific Tools 

Scientific Tools 

Chemistry Add-in for Word 



Unilever Center for Molecular 
Science Informatics 
University of Cambridge 

THIS POWERFUL TOOL simplifies the authoring 
of chemical information in Microsoft Word. The 
Chemistry Add-in for Word project was developed 
in collaboration with Peter Murray-Rust and Joe 
Townsend from the University of Cambridge's Unilever 
Centre for Molecular Science Informatics. 

The add-in harnesses a chemistry-specific extensible 
markup language (XML) — Chemical Markup Language 
(CML) — that allows scientific information to be 
captured and expressed more easily at the authoring 
stage. The Chemistry Add-in for Word enables the 
scientific and academic research community to author 
chemical content, represent it in a variety of ways, 
and include the data behind those structures — right 

in a Word document. The add-in makes chemistry 
documents open, readable, and easily accessible to 
humans and computers. 

Scientists, researchers, and students can use the 
Chemistry Add-in for Word to insert chemical 
structures directly into Word documents; render print- 
ready, two-dimensional diagrams; contribute to simpler 
pre-publication processes and richer information 
discovery scenarios; preserve chemical information 
for archival purposes; and store and expose chemical 
information in a semantically rich manner. 

The Chemistry Add-in for Word is available to 
scientists, researchers, students, and the general public 
to facilitate the sharing of scientific information. 




Scientific Tools 


I l Chief Social Scientist 
Connected Action 
Consulting Group 

NODEXL IS A POWERFUL and easy-to-use 
interactive network visualization and analysis tool 
that uses Microsoft Excel for representing generic 
graph data, performing advanced network analysis, 
and visual exploration of networks. NodeXL 
supports multiple social network data providers 
that import graph data (nodes and edge lists) into 
Excel. The import features of NodeXL explore social 
media by pulling data from personal email indexes 
on the desktop, Twitter, Flicker, YouTube, Facebook, 
and web hyperlinks. 

NodeXL allows non-programmers to generate 

useful network statistics and metrics quickly and 
create visualizations of network graphs. Filtering 
and display attributes can be used to highlight 
important structures in the network. 

NodeXL is a project from the Social Media 
Research Foundation with support from Microsoft 
Research Connections and Microsoft Research 
Cambridge, with additional contributions from 
researchers at the University of Porto, University of 
Maryland, Connected Action Consulting, Stanford 
University, Oxford University, Australian National 
University, and Illinois Institute of Technology. 



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"NodeXL has been downloaded more than 
75.DDD times and is becoming the easiest 
path to getting insights from network 
data. If you can make a pie chart in a 
spreadsheet, you can now make a network 
visualization." —marc smith 

□ □ 

Scientific Tools 

Scientific Workflow Workbench 



Data to Insight Center 

Indiana University 

PROJECT TRIDENT: Scientific Workflow 
Workbench is an open-source toolkit based 
on the Windows Workflow Foundation that 
addresses scientists' need for a flexible, powerful 
way to analyze large, diverse datasets. It includes 
graphical tools for creating, running, managing, 
and sharing workflows. 

As part of Vortex2, a project funded by the 
National Science Foundation to study tornados, 
Project Trident was used by Indiana University to 
invoke and manage hourly workflows. By using a 
512-core HPC super computer at the university, 
the workflow automatically obtained current 
weather data and then generated a short-term 
forecast, ultimately producing 240 forecasts and 
more than 9,000 weather images for researchers 
to access by their smartphones in the field. 







Proc e 











"WDrkflDW systems have proven valuable in 
eScience. Their use will be as varied as are the 
science domains themselves. Finding the optimum 
use in different domains is an exciting challenge, 
and Trident has strengths that make it suitable 
across a range of uses." — beth plale 


^^^ ' CHRIS BISHOP is a distinguished scientist at Microsoft Research Cambridge, 
jk ) where he leads the Machine Learning and Perception group. He is also vice 
^k Iw president of the Royal Institution of Great Britain and professor of computer 

]^L ^^ science at the University of Edinburgh. He is a fellow of the Royal Academy of 
■M I Engineering, a fellow of the Royal Society of Edinburgh, and a fellow of Darwin 

College Cambridge. His research interests include machine learning and its applications. 

ADNAN CUSTOVIC is a professor of allergy and a head of the Respiratory 
Research Group at the School of Translational Medicine at the University of 
Manchester. He is a world-leading authority on the primary prevention of 
allergic diseases, and he focuses on the relationship between allergic disease 
and the environment and primary prevention of asthma and allergic diseases. 
He is currently secretary of the British Society for Allergy and Clinical Immunology and 
president of the European Academy of Allergy and Clinical Immunology. 


JOHN WINN is a senior researcher in the Machine Learning and Perception 
group at Microsoft Research Cambridge and co-creator of the Infer.NET 
inference framework. His main research interests are in machine learning, 
machine vision, and computational biology. 

9 RICHARD DURBIN is joint head of human genetics at the Wellcome Trust 
Sanger Institute and leader of the Genome Informatics group. He leads a 
team of researchers that has worked on evolutionary probabilistic methods 
and is interested in population genome sequencing. He is involved in projects 
ranging from SGRP yeast sequence variation and the TreeFarm database of 
animal gene families to new methods for handling genetic variation data and the ACEDB 
genome database. 

JENNIFER CHAYES is distinguished scientist and managing director of 
Microsoft Research New England in Cambridge, Massachusetts, which she 
co-founded in July 2008. Before this, she was research area manager for 
mathematics, theoretical computer science, and cryptography at Microsoft 
Research Redmond. She joined Microsoft Research in 1997, when she co- 
founded the Theory Group. Her research areas include phase transitions in discrete 
mathematics and computer science, structural and dynamical properties of self-engineered 
networks, and algorithmic game theory. 

CHRISTIAN BORGS is deputy managing director of the Microsoft Research New 
England lab in Cambridge, Massachusetts. He is also an affiliate professor of 
mathematics at the University of Washington. Since joining Microsoft in 1997, 
he has become one of the world leaders in the study in phase transitions in 
combinatorial optimization, and more generally, in the application of methods 
from statistical physics and probability theory to address problems of interest to computer 
science and technology. He is one of the top researchers in the modeling and analysis of 
self-organized networks, such as the Internet, the World Wide Web, and social networks. 

RICCARDO ZECCHINA is professor of theoretical physics at the Politecnico di 
Torino in Italy. His interests are in topics at the interface between statistical 
physics and computer science. His current research activity is focused on 
combinatorial and stochastic optimization, probabilistic and message- 
passing algorithms, and interdisciplinary applications of statistical physics (in 
computational biology, graphical games, and statistical inference). 

^^^. I DAVID HECKERMAN is a Microsoft distinguished scientist and senior director 
M of the eScience group at Microsoft Research, His research interest is focused on 

I learning from data. The models and methods he uses are inspired by work in 
I the fields of statistics and data analysis, machine learning, probability theory, 
_^fl WLM decision theory, decision analysis, and artificial intelligence. His recent work ha: 
concentrated on using graphical models for data analysis and visualization in biology and 
medicine with a special focus on the design of HIV vaccines. 

JENNIFER LISTGARTEN is a researcher in the eScience group at Microsoft 
Research. Her work focuses on the development and application of statistical and 
machine-learning methods for the analysis of high-throughput, biologically-baseci 

jm CHRISTOPH LIPPERT is a graduate student at the Max Planck Institutes for 

f I Developmental Biology and for Intelligent Systems in Tubingen, Germany. 

' *• -^' In summer 2012, he will join the eScience group at Microsoft Research. His 

research focuses on the development of probabilistic models in genomics. He 
has contributed analysis tools that assist biologists with their research in genetic 
mapping of human diseases and the analysis of genetic and phenotypic variation in plants 
and other model organisms. 

DEB AGARWAL is a senior scientist, Advanced Computing for Science 
departmental head, and the Data Intensive Systems group lead at the Lawrence 
Berkeley National Laboratory. She is also working with the Berkeley Water Center 
at the University of California, Berkeley, where she has been leading the team 
developing advanced cyber infrastructure for geosciences since 2005. Her projects 
involve research, development, and deployment of computing technologies to support 
collaborative scientific research. Her current research focus is on the development of data 
server infrastructure to significantly enhance data browsing and analysis capabilities. 

DENNIS BALDOCCHI is a professor of biometeorology at the University of 
California, Berkeley. His research focuses on the physical, biological, and chemical 
processes that control the exchange of trace gases between ecosystems and the 
atmosphere. His current projects include a long-term study on carbon dioxide, 
water vapor, and energy exchange of an oak savanna and annual grassland in the 

foothills of California, and measurements of methane exchange from rice, a drained peatland, 

and a restored wetland in the Sacramento-San Joaquin Delta. 

MARTY HUMPHREY is an associate professor in the Department of Computer 
Science at the University of Virginia. He has been on the faculty of the University 
of Virginia since 1988. His research interests include the use of cloud computing 

I for cancer research and for environmental research, such as using Windows Azure 

.i to model and manage large watershed systems. 

YOUNGRYEL RYU is assistant professor of environmental ecology at Seoul 
National University. He was a main contributor to the project that simulated the 
~| breathing of the biosphere by using BESS computations on the MODISAzure cloud 
while he was an intern working with Catharine van Ingen at Microsoft Research in 
i\M 2010. His current research topics include land-atmosphere interactions and the 
application of computing resources for data-intensive science. 

CATHARINE VAN INGEN is partner architect in the Microsoft Research eScience 
group. Her research explores how commercial software and tools can be used to 
enable synthesis science in environmental research science. A key challenge in 
such studies is addressing not only very large datasets from satellites and ground 
sensors, but also the small, irregular, ancillary, and categorical data that are 
necessary for scientific understanding. 



JAMES HUNT is professor of civil and environmental engineering at University 
of California, Berkeley. A fundamental challenge in all instances of his research 
topics is how to deal with vast and widely distributed data. 

LYNN GLADDEN is pro-vice-chancellor for research for the University of 
Cambridge. She is the Shell Professor of Chemical Engineering, and head of the 
Department of Chemical Engineering and Biotechnology, where she leads the 
activities in the Magnetic Resonance Research Centre. She is a fellow of both the 
Royal Society and Royal Academy of Engineering, and was appointed Commander 

of the Order of the British Empire (CBE) in 2009. She is a member of the council of the 

Engineering and Physical Sciences Research Council. 

ANDREW BLAKE is a Microsoft distinguished scientist and managing director 
of Microsoft Research Cambridge. He is a fellow of the Royal Academy of 
Engineering, the Royal Society, and the IEEE. He received the Royal Academy of 
Engineering Silver Medal in 2006, the IET Mountbatten Medal in 2007, and the 
Royal Academy of Engineering MacRobert Award in 2011 with his colleagues for 
their machine-learning contribution to Microsoft Kinect human motion capture. His research 
interests include probabilistic principles of computer vision software, with applications to 
motion capture, user interface, image editing, remote collaboration, and medical imaging. 

TIM GUILFORD leads the Oxford Navigation Group in animal behavior at the 
Department of Zoology, Oxford University. His research explores the mechanisms 
and processes of animal navigation and movement, principally in avian systems. 
I He has pioneered a number of techniques for understanding avian navigation, 
leading to new insights and understanding. Recently, he has developed a variety 

of methods for investigating highly pelagic seabirds, including endangered and vulnerable 


ROBIN FREEMAN is a researcher in computational ecology at Microsoft Research 
Cambridge and a research fellow in CoMPLEX (the Centre for Mathematics and 
Physics in the Life Sciences and Experimental Biology) at University College 
London. He is also a research associate with the Animal Behaviour group at 
Oxford University. His research focuses on topics at the interface between 
behavior, ecology, and computation. He is particularly interested in the application of 
computational techniques for analyzing animal behavior, from systems to autonomously 
record the behavior of animals in the wild to the development and application of machine- 
learning techniques to analyze these data. 

MARCUS ALTFELD is the director of the Program for Innate Immunity at the 
Partners AIDS Research Center (PARC) and the Division of Infectious Diseases at 
the Massachusetts General Hospital in Boston, and he is an associate professor at 
Harvard Medical School. 

CARL KADIE is principal research software design engineer in the eScience group 
at Microsoft Research. He is also an affiliate of the Machine Learning and Applied 
Statistics (MLAS) and Adaptive Systems and Interaction (ASI) groups at Microsoft 
Research. His research interests include creating practical machine learning 
I algorithms for recommendation, spam detection, and, most recently, biology. 

BABAK PARVIZ is the McMorrow Innovation Associate Professor in the Electrical 
Engineering Department and the associate director of the Micro-Scale Life 
Sciences Center at the University of Washington. His research at the interface 
between biology and electrical engineering has led to a rewarding collaboration 
with Microsoft Research to develop functional contact lenses by using novel 
in computer science and engineering. 

I DESNEY TAN is a senior researcher at Microsoft Research, where he manages 
the Computational User Experiences group in Redmond, Washington, as well as 
the Human-Computer Interaction group in Beijing, China. He was honored as 
one of MIT Technology Review's 2007 list of 35 innovators under 35 for his work 
on brain-computer interfaces, and he was named one of SciFi Channel's Young 

Visionaries at TED 2009, as well as one of Forbes' Revolutionaries — radical thinkers and their 

world-changing ideas — for his work on whole body computing. 

ALISON NOBLE is the Technikos Professor of Biomedical Engineering in the 
Oxford University Department of Engineering Science and a fellow of St Hilda's 
College, Oxford. She is a director of the Biomedical Image Analysis (BioMedIA) 
Laboratory, a multi-disciplinary research group working in the area of biomedical 
imaging and image analysis. She is a senior member of the IEEE, a fellow of the 
IET, and a fellow of the Royal Academy of Engineering (FREng). 

ANTONIO CRIMINISI is a senior researcher in the Computer Vision group at 
Microsoft Research Cambridge. His current research interests are in the area of 
'^T. visual metrology and 3-D reconstruction from single and multiple images with 

J application to computer vision, visual arts, and art history. 

RAJ JENA is a consultant clinical oncologist for Cambridge University Hospitals 
NHS Foundation Trust, visiting fellow in the Faculty of Engineering and Physical 
Science at the University of Surrey, and a visiting scientist at the European Centre 
for Nuclear Research (CERN). His research interests are in the application of 
advanced imaging techniques and radiotherapy treatment to improve outcomes 
for patients with central nervous system tumors. 

STEVE HODGES leads the Sensors and Devices group at Microsoft Research 
Cambridge, which applies its skills across both hardware and software layers to 
deliver compelling new user experiences. The ultimate goal of the group is to 
better understand how advances in technology will impact traditional computing 
'• and the ways in which people use and interact with computing devices. His 

personal research focuses around sensing, ubiquitous computing, and new technologies for 

display and interaction. 

CHRIS MOULIN is a senior lecturer in cognitive neuropsychology at the 
University of Leeds, United Kingdom. His current research interests focus on 
neuropsychological impairments of memory. In particular, he is interested in the 
nteraction of executive function and long-term memory. 


MANOS M. TENTZERIS is a professor with the Georgia Tech School of Electrical 
and Computer Engineering (GT-ECE). Currently, he is the head of GT-ECE 
Electromagnetics Technical Interest Group. Also, he is the head of the ATHENA 
(Agile Technologies for High-performance Electromagnetic Novel Applications) 
research group and has established academic programs about highly integrated/ 
multilayer packaging for RF and wireless applications that use ceramic and organic flexible 
materials, plastic/paper-based RFIDs and sensors, inkjet-printed electronics and antennas, RF 
nanostructures, SOP-integrated (ultrawideband, multiband, conformal) antennas, "green" RF 
electronics, wearable RF, power scavenging, wireless power transfer and RF biomonitoring, 
and implantable devices. 

DARKO KIROVSKI has been a researcher at Microsoft Research since 2000, first in 
the Crypto and Anti-Piracy group and now in the Machine Learning and Applied 
Statistics group. His research interests include: intellectual property protection 
and embedded system design, in particular, code compression for embedded 
processors, debugging using combined emulation-simulation, engineering 
change, symbolic debugging, design watermarking, and forensic engineering. 

more biographies ... 




a JIM DAVIES is a professor of software engineering in the Department of 
Computer Science at the University of Oxford, and he directs a program of 
advanced, professional education in software engineering, teaching advanced 
techniques to people working full-time in the industry. He is leading the 
development of semantics-driven technology for medical research and electronic 
governance and a related program of work into the automatic generation of systems from 
reusable models of structure and functionality. 

SIMON MERCER is the director of the Health and Wellbeing group for Microsoft 
Research Connections. He has a background in zoology and worked as director 
of software engineering at Gene Codes Corporation before moving to Microsoft 
Research in 2005. In his current role at Microsoft Research, he manages a range 
of collaborations between Microsoft and academia in the area of health care 

research. His interests include bioinformatics, synthetic biology, translational medicine, and 

the management of scientific data. 

TOM BARCLAY is partner architect and development manager of Bing Imagery 
Technologies and the Bing Search team at Microsoft. He has been the lead 
researcher on Microsoft TerraServer since 1996. His interests include database 
design, scientific computing, and data mining. 

GEORGE LEE is the US Geological Survey (USGS) product and services lead for 
orthoimagery. His use of the orthoimagery method during his collaboration with 
Microsoft Research to develop Microsoft TerraServer exemplifies the successful 
use of real-world scenarios to challenge and advance computing technologies. 

ALYSSA GOODMAN is professor of astronomy at Harvard University and a 
research associate of the Smithsonian Institution. With her research group at 
the Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts, 
* she studies the dense gas between the stars. She has worked with Microsoft 
Research for several years on the Worldwide Telescope project. Her innovative 
use of WWT in research (such as with the Seamless Astronomy project) and science education 
(for example, the Worldwide Telescope Ambassadors Program) has significantly helped the 
Microsoft Research team expand the capabilities of WWT to assist researchers and educators 
with their work. 

CURTIS WONG is principal researcher with Microsoft Research Connections, 
focusing on interaction, media, and visualization technologies. He has received 
more than 25 patents in areas such as interactive television, media browsing, 
visualization, search, gaming and learning. An amateur astronomer since 
childhood, he was the driving force in bringing the Worldwide Telescope project 
to reality. He gives credit to colleague and Turing Award winner Jim Gray, who encouraged 
him to build his dream of creating an environment for scientific research as well as public 
education in astronomy. He is particularly proud that millions of people from every continent 
on the earth are using Worldwide Telescope. 

JIM GRAY was a distinguished engineer in the Microsoft Research Bay Area 
eScience group. His long career with Microsoft, Digital Equipment, Tandem 
Computers, and IBM produced seminal work in relational database management 
systems, transaction processing systems, and the sciences. His vision and work 
on applying computing technologies to data-intensive sciences inspired the 
collection of insightful essays in The Fourth Paradigm: Data-Intensive Scientific Discovery. 


ALEXANDER S. SZALAY is professor of astrophysics and computer science at the 
Johns Hopkins University. He is a cosmologist whose work spans a broad area from 
astrophysics to statistics and computer science. He collaborated with Jim Gray 
to extend the ideas from the SkyServer to the Virtual Observatory and to other 
scientific disciplines. He currently works on building large scientific databases and 
data-intensive computing. 

I CHARLES M. MARCUS is a professor of physics at Harvard University and former 
r scientific director of the Center for Nanoscale Systems. His main research interest is 
experimental condensed matter physics, including solid-state quantum information 
processing, nanofabrication of electronic devices, and electron transport. Much of 
his ongoing research has focused on clean, ballistic semiconductor structures, such 
as chaotic quantum dots, with more recent work emphasizing novel fabrication approaches 
and systems, effects of electron spin, measurements of electron decoherence, and potential 
applications of nanostructures to quantum information and quantum computing. 

MICHAEL FREEDMAN is the director of Microsoft Station Q and a technical 
fellow at Microsoft. His main research interest is topological states of matter and 
the construction of mathematical models which illuminate these. He leads the 
Microsoft Station Q team, which is the Microsoft Research group that is working on 
topological quantum computing by combining research from math, physics, and 
computer science. He received the Fields Medal, the highest honor in mathematics, for solving 
the long-standing Poincare conjecture in four dimensions. He has also received numerous 
other awards including the Oswald Veblen Prize in Geometry, a MacArthur Fellowship, and the 
National Medal of Science. 

SIMON MALLAL is director of the Institute for Immunology and Infectious Diseases 
at Murdoch University and a clinical immunologist and immunopathologist at 
Royal Perth Hospital. He has had a longstanding research interest in the major 
histocompatibility complex (MHC) and genetic influences on clinical outcomes in 
HIV and other diseases. More recently, he has focused on viral adaptation to HLA- 
restricted immune responses and the implications of this for HIV vaccine immunogen design. 

TOMER HERTZ is currently a staff scientist in the Vaccine and Infectious Disease 
Division at the Fred Hutchinson Cancer Research Center in Seattle, Washington, 
■ working on computational immunology. His general research interests are in 

machine learning and computational immunology. He was a main contributor to this 
1 research project during his postdoctoral training in the Microsoft Research eScience 
group, working with Nebojsa Jojic. 

NEBOJSA JOJIC is a principal researcher in the eScience group at Microsoft 
Research. He is interested in machine-learning approaches to building compact 
representations of natural signals that reveal patterns of scientific and practical 
importance. His interest in computational immunology was spurred by similarities 
»^ that he found between types of data and inference tools used in biology and 

JASMIN FISHER is a researcher in the Programming Principles and Tools group at 
Microsoft Research. She is one of the founders of the field of executable biology 
and a leader in the area of formal methods in biology. 

BYRON COOK is a principal researcher in the Programming Principles and Tools 
group at Microsoft Research. He is a leader in automatic program verification. He 
pioneered the research on practical proofs of termination of programs making 
termination proofs a useful and practical tool. 

NIR PITERMAN is a lecturer in the Department of Computer Science at 
University of Leicester. He worked with the team to develop the analysis 
techniques, in particular suggesting an important enhancement that further 
accelerated the performance of the analysis. 

ANDREW PHILLIPS is head of the Biological Computation Group in the 
Computational Sciences Laboratory at Microsoft Research Cambridge. His 
f research is in developing visual programming languages and tools for 
simulating and analyzing complex models of biological systems. He was 
recipient of a prestigious MIT Technology Review TR35 award in 2011. 

JIM HASELOFF is a plant biologist working at the Department of Plant 
Sciences, University of Cambridge, where he leads a synthetic biology lab. His 
scientific interests are focused on the engineering of plant morphogenesis 
by using microscopy, molecular genetics, and computational and synthetic 
biology techniques. 

LUCAS JOPPA is a scientist in the Computational Ecology and Environmental 
Science group in the Computational Science Lab at Microsoft Research 
Cambridge. He leads the conservation research unit, which develops and 
accelerates better, predictive, actionable, and systemic conservation science, 
tools, and technologies in areas of societal importance His research covers all 
aspects of the conservation spectrum, from gathering the next-generation data necessary 
for better scientific understanding to developing new predictive methods and models. 

STUART PIMM is Doris Duke Chair of Conservation Ecology at the Nicholas 
School of the Environment at Duke University and one of the most cited 
scientists working in the field of conservation biology. He was the recipient of 
the Dr. A. H. Heineken Prize from the Royal Netherlands Academy of Arts and 
Sciences in 2006 and the Tyler Prize for Environmental Achievement in 2010. 

ARFON SMITH is the director of citizen science at the Adler Planetarium in 
Chicago and technical lead of the Zooniverse. Before joining the Zooniverse, 
he earned his doctorate in astrochemistry from the University of Nottingham 
n 2006 and then worked as a senior developer in the production software 
group at the Wellcome Trust Sanger Institute in Cambridge. 

CHRIS LINTOTT is a researcher in the Department of Physics at the University 
of Oxford, where he leads a team of scientists, educators, and developers 
in the development of citizen science projects. Passionately committed to 
scientific outreach, he is best known as co-presenter of the BBC's long-running 
Sky at Night series. 

SUZANNE ROSIER is a research scientist, joint coordinator of, and coordinating author of the associated project. She helped launch climateprediction. net's first 
regional modeling initiative, "weatherathome," which is modeling limited 
areas of the world in sufficient detail to enable scientists to deduce future 
changes in extreme weather patterns. She is now helping to develop this experiment for 
the Australia/New Zealand region — due for launch in mid-2012 — and will be analyzing the 
results as they become available. 

PHILIP W. MOTE is a professor in the College of Oceanic and Atmospheric 
Sciences at Oregon State University, director of the Oregon Climate Change 
Research Institute for the Oregon University system, and director of the 
Oregon Climate Service. His current research interests include scenario 
development, regional climate modeling with a superensemble generated by 
volunteers' personal computers, and adaptation to climate change. 

DAVID BAKER is a professor at the University of Washington, an investigator of 
the Howard Hughes Medical Institute, and a member of the National Academy 
of Sciences. He is a world leader in protein structure prediction and design. He 
eads the Baker Laboratory with a research focus on the prediction and design of 
protein structures and protein-protein interactions. 

STUART OZER currently leads a team in the Microsoft Server and Tools business, 
working with the largest-scale and most demanding data-intensive workloads on 
SQL Server and Windows Azure. He is a veteran of Microsoft Research's eScience 
team, where he worked on academic collaboration efforts to apply modern 
database-centered technologies and workflows to diverse problems in biological 
sequence analysis, protein structure, and environmental sensor networks. 

PETER MURRAY-RUST is a researcher at the Unilever Center for Molecular Science 
Informatics in the Department of Chemistry at the University of Cambridge, 
England. His research in molecular informatics brings tools from computer 
science to chemistry, biosciences, and Earth sciences, integrating humans and 
machines in managing information. He is one of the creators of the Chemical 
Markup Language (CML), an expanding XML representation of molecular science including 
molecules, spectra, reactions, computational chemistry, and solid state. He campaigns for 
open data in science, and is on the advisory board of the Open Knowledge Foundation and a 
co-author of the Panton Principles for Open Data. 

MARC SMITH is a sociologist specializing in the social organization of online 
I communities and computer-mediated interaction. He founded and managed the 
Community Technologies Group at Microsoft Research in Redmond, Washington, 
and led the development of social media reporting and analysis tools for Telligent 
Systems. He is the chief social scientist of Connected Action consulting group and 
lives and works in Silicon Valley, California. He is a co-founder of the Social Media Research 
Foundation, which is dedicated to open tools, open data, and open scholarship related to 
social media. 

BETH PLALE is director of the Data to Insight Center, which is associated with 
the Indiana University Pervasive Technology Institute. She is an experimental 
computer scientist whose research interests include data management, data- 
driven computing, and the preservation of scientific and scholarly data sets. She 
is a professor in the School of Informatics and Computing at Indiana University. 




This book contains a collection of vignettes on a variety 
of scientific research projects that either use state-of- 
the-art Microsoft technologies and research, or have 
led to pioneering new Microsoft technology concepts. 
As described, the use of advanced computer science 
technologies — as well as the use of robust product 
software — has led to a wide range of new scientific 
insights. Along the way, the application of Microsoft 
technologies to emerging scientific problems has 
significantly enhanced research, development, and 

In the mid-1990s, Jim Gray of Microsoft Research 
recognized that the next "big data" challenges for 
database technology would come from science and 
not from commerce. He also identified the technical 
challenges that such data-intensive phenomena would 
pose for scientists, as well as the key role that IT and 
computer science could play to enable future scientific 
discoveries. Gray called this new mode of data-intensive 
scientific discovery the "fourth paradigm," and contrasted 
it with traditional methodologies of experiment, theory, 
and computer simulation. In designating this new mode, 
he promoted the need for computer scientists to work 
collaboratively as equals with scientists in other fields 
to develop the necessary tools and technologies for this 
new type of scientific exploration — but not to replace 
the first three paradigms (experimental, theoretical, and 
computational). The book, The Fourth Paradigm: Data- 
Intensive Scientific Discovery, contains a collection of 
essays that expand on Gray's vision for this new, fourth 
paradigm. Written by scientists from various fields, 
the essays explore the future impact of the explosion 
of scientific data to research areas such as earth, 

environment, health, and wellbeing, as well as the scientific 
infrastructure that is required to support data-intensive 
science. Many of the projects in this book demonstrate the 
fourth paradigm in practice. 

In 2005, Stephen Emmott of Microsoft Research assembled 
an international group of computer scientists and scientific 
researchers at a meeting in Venice to discuss the evolution 
and potential impact of computer science and computing 
on scientific research in the next fifteen years. The 
outcome was a manifesto: Towards 2020 Science, which 
described both the challenges and the opportunities 
arising from the increasing symbiosis of computing, 
computer science, and the sciences. In the short time since 
that document was published, many new research activities 
have emerged from a broad range of science disciplines 
spanning genomics and proteomics, Earth sciences and 
climatology, nano-materials, chemistry, and physics. 
The "2020 science" vision inspired some of the projects 
described in this book. 

Also in 2005, Microsoft Chief Research and Strategy 
Officer Craig Mundie started the Technical Computing 
Initiative at Microsoft, a program that enabled computer 
scientists at Microsoft Research to work with scientists at 
universities. As described in this book, these collaborative 
science projects put the visions of "fourth paradigm" 
and "2020 science" into practice. The success of these 
projects constitutes a set of examples of how computer 
scientists can collaborate with scientists in other fields to 
advance computing technologies and sciences to solve 
major scientific challenges together. As Mundie says in 
his introduction, this is genuinely a case of "doing well by 
doing good!" 

Senior editors: Stephen Emmott, David Heckerman, Tony Hey 
Editors: Kenji Takeda, Yan Xu 

Artist Interpretations 

Molecular science inspired these abstract works by Tessa Coe 



An amazing molecule called hsp60 assists wrongly folded proteins to achieve their correct 
shape. This large molecule is classed as one of the so-called molecular chaperones. Within its 
barrel-shaped center, hsp60 can isolate a protein from counterproductive chance interactions 
and even guide a misshapen protein to fold up into its correct final form. Unless proteins are 
exactly the "right" shape, the process within the body for which they were intended will not 
happen properly. 


I chose a small molecule called insulin to look at when I first became interested in proteins 
and the processes by which they fold up into their correct shape. Insulin comprises just two 
short chains of small molecules. One chain has a couple of short spirals in it; the other just 
loops, and that's all. Within this small structure, as in the other globular proteins, powerful 
hydrophobic interactions help determine the molecule's final folded shape. 


Protein chains usually fold up spontaneously into complex structures. One of the main 
driving forces in the folding process is the need for all the hydrophobic molecules within the 
protein — those molecules that are not "happy" being surrounded by water — to be hidden 
away at the center of the protein. In contrast, charged and ionic hydrophilic regions of the 
molecule are edged to the surface of the protein, where they can be surrounded by water. 
These opposing tendencies begin the protein's drive towards a final self-formed shape. 


Originally trained as a physicist at Imperial College in London, Tessa Coe 
worked for some years as a research scientist before an interlude in industry. 
Her research interests were biological, however, centered on trying to 
understand how and why molecules cross the outer surfaces of cells. Biology 
has flourished since those days, but she has maintained a keen interest in 
the amazing discoveries related to cells, genes, and proteins It is these 
astonishing stories that she draws upon in her most recent work. 

Coe has always loved to draw, but her serious interest in art began when 
she was a student. The physics department at Imperial College is across 
the street from the Royal College of Art and quite close to the Victoria and 
Albert Museum. Because Imperial was an all science and engineering college, 
Coe considers herself lucky to have had such ready access to these great 
art institutions. During her undergraduate years, she enjoyed wonderful 
lunchtime art history lectures, after which she could explore the galleries 
and museums of London and consolidate what she had learned. 

At various stages in her life, Coe has attended courses in drawing, painting, 
and art history, most notably, at Winchester School of Art, the Tower Arts 
Centre in in Winchester, and at the Juno Studio in Braishfield, in Hampshire. 
She has been a full-time painter and exhibitor for the last 15 years. 



The editors would like to thank all of the university researchers who kindly 
agreed to be interviewed for this collection. They were extremely patient 
with our requests and without their input, this book would not have been 
possible. We are grateful to the Microsoft researchers who participated 
in these projects and to Andrew Herbert, former director of the Microsoft 
Research Cambridge laboratory, for his invaluable support of computational 
science and the UK-based projects. We also would like to thank Dan Fay, 
Simon Mercer, and Jim Pinkelman of Microsoft Research Connections 
for their constructive input throughout the course of putting this book 
together. We would like to express our gratitude to Alyssa Felda of Microsoft 
Research Connections and her team of proofreaders and art designers; and 
to Kimberley Lane of Microsoft Research Connections for her support of 
putting together a Creative Commons license for this book. Finally, we thank 
Rick Rashid, chief research officer at Microsoft Research, for his support and 
guidance, and Craig Mundie, Microsoft chief research and strategy officer, for 
the inspiration behind Microsoft's Technical Computing Initiative. 



David Heckerman, Kenji Takeda, Stephen Emmott, Tony Hey, Yan Xu 


Chris Towey, Director of Photography for: Medical Sensing via a 
Contact Lens; Understanding the Immune Response to HIV, Clinical 
Studies and Data Collection and Reuse 
Stock Photos: Dreamstime, IStockphoto, Getty Images 

© 2012 Microsoft Corporation. All rights reserved. 

ift provides this material solely for informational and marketing purposes. 






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