MBI BioSciences Problem-Solving Workshop (PSW@MBI)

(July 16,2012 - July 20,2012 )

Organizers


Jonathan Bell
Department of Mathematics & Statistics, University of Maryland Baltimore County
Chris Breward
Mathematical Institute, University of Oxford
Helen Byrne
Centre for Mathematical Medicine and Biology, University of Nottingham
Huaxiong Huang
Mathematics and Statistics, York University
Donald Schwendeman
Mathematical Sciences, Rensselaer Polytechnic Institute
Siv Sivaloganathan
Applied Mathematics, University of Waterloo

PSW@MBI is a week-long workshop where participating mathematical modelers tackle questions proposed by life science researchers. Similar workshops have provided fresh perspectives and new ideas to proposed questions and established new interdisciplinary collaborations between theoreticians and life scientists. The workshop gives the opportunity to practitioners and researchers in medicine and the biosciences who present problems to exploit the expertise of applied mathematical faculty, postdoctoral fellows, and graduate students in working toward solutions to their problems. Workshop Format Participants will include between 50-60 applied mathematicians, statisticians and domain experts. Problems will be presented on the first day and participants will divide into teams of 6-10 self-selected people each. The teams will collaborate and brain-storm on their problems, and present their solution on the final day of the workshop. Problem presenters have domain knowledge, which is needed throughout the workshop and will be available during the workshop to provide background information. Deliverables The teams will prepare reports for the problem sponsors shortly after the end of the workshop. Cost Accepted participants will receive partial travel support, hotel, and a small per diem.

Accepted Speakers

Richard Braun
Department of Mathematical Sciences, University of Delaware
Matthew Doyle
Department of Mechanical and Industrial Engineering, University of Toronto
Martin Frasch
Centre de recherche en reproduction animale, CHU Sainte-Justine
Ewen King-Smith
College of Optometry, The Ohio State University
Nicanor Moldovan
Internal Medicine, Disease Pathways, LLC
Thomas Rosal
Veterinary Biosciences, The Ohio State University
Masami Tatsuno
Neuroscience, University of Lethbridge
Monday, July 16, 2012
Time Session
09:45 AM
10:15 AM
Martin Frasch - Online detection of physiological fetal distress pattern during birth
This proposal is derived from our studies on changes of fetal brain electrical activity
(electroenkephalogram, EEG) and heart rate (FHR) which we recorded during simulated labour
in fetal sheep model of human pregnancy and fetal development.

The goal is to develop mathematical models allowing online detection of physiological
patterns alarming of incipient fetal distress in clinical conditions of labour.

There are two major aspects of the problem:

1. A pattern of time correlated changes in EEG and FHR is now known to occur during
conditions of deteriorated blood supply to the fetus as it may occur during labour. This pattern is
an early predictor of immanent severe drop in fetal pH. Fetal pH under 7.00 (severe acidemia) is
associated with increased risk of brain injury and sustained neurological deficits. In obstetrical
care, an urgent need exists for technologies allowing the detection of such severe acidemia in
fetus. We describe the phenomenon in detail in Frasch et al (2011).

Question 1: Can we create a mathematical model of this phenomenon robust enough to be
capable of capturing the onset of the pattern online despite varying EEG/FHR signal
characteristics?

2. Certain properties of FHR variability (FHRV, higher order fluctuations in FHR on millisecond
time scale) can also be used for early detection of the onset of severe acidemia.
FHRV can be calculated in different signal property domains (linear, nonlinear, time and
frequency or both). Different measures of FHRV are known to reflect somewhat different
aspects of underlying physiological activities and probably carry a predictive value variable in
time. A group of FHRV measures is likely to provide a higher positive predictive value of fetal
acidemia than one particular FHRV measure alone. Please see also Frasch (2011).

Question 2: Can we develop a mathematical model to allow us to 1) identify the FHRV
measures that would perform best together to detect the pathophysiological mechanism of
incipient acidemia and 2) incorporate such FHRV measures into the model that captures the
correlated changes in EEG and FHR?

In a broader sense, we hope that such approach would help create a novel paradigm for
context-specific generation of mathematical models for online detection of complex
physiological patterns. Ideally, this new paradigm should go beyond a purely statistical or data
mining framework. For example, can we build a model that incorporates physiological
mechanisms into a standard data mining approach?

In order to facilitate the discussion and modeling building exercise, relevant data will be
provided for workshop participants.
10:15 AM
10:45 AM
Ewen King-Smith - The structure of the lipid layer of the tear film
Dry eye disorders affect about 15% of older Americans and are poorly understood.  Increased
evaporation is an important contributing factor.  The superficial lipid layer of the tear film is normally an
excellent barrier to evaporation but its effectiveness is often reduced in dry eye disorders.  This lipid,
called meibum, is secreted from meibomian glands in the lids.

The main components of meibum are wax esters and cholesteryl esters with smaller quantities of polar
and other lipids.  Also, surfactant proteins probably play an important role.  The esters often contain a
proportion of long, saturated hydrocarbon chains which are thought to help increase resistance to
evaporation.  Another important characteristic of the lipid layer is its ability to withstand the blink cycle
which causes compression to a small fraction of the original area, followed by expansion.   Lipids with
long, saturated hydrocarbon chains often do not re€?spread to their original state after compression and
expansion, so the inclusion of unsaturated hydrocarbon chains in meibum may aid in respreading after a
blink.

The molecular organization of the lipid layer is poorly understood.   The team will be asked to consider
and propose models of molecular structure of the lipid layer, and to evaluate their consistency with
observed properties which will be presented.   
11:00 AM
11:30 AM
Thomas Rosal - Mathematical model of blood ionized calcium concentration
The blood ionized calcium concentration (Ca2+, iCa) is tightly regulated in animals
ranging from the most primitive fishes and nonvertebrates to humans. This is because
iCa is utilized by diverse cell types as a transcellular and intracellular signaling
molecule, such as in the nervous system, cardiac and skeletal muscle, epithelial cells,
endocrine cells, blood cells, among others. The blood ionized calcium concentration is
approximately 1.5 mM in all animals. If the concentration changes by as little as 10-20%
dysregulation of body systems (such as the neuromuscular system) will result and can
be fatal. Therefore, there are multiple, redundant regulatory systems that exist to
maintain blood calcium in a narrow biological range.

Terrestrial animals live in a calcium poor environment and are dependent upon calcium
absorption from the gastrointestinal tract to provide calcium as a regulatory ion and
component of bones. In contrast, sea animals live in a calcium rich environment (since
seawater has 10 mM calcium) and excretion of calcium is important.
11:30 AM
12:00 PM
Matthew Doyle - Development of a mathematical model for microindentation of aortic valve leaflets to aid in the determination of local micromechanical properties
Calcific aortic valve disease (CAVD) is the most common heart valve disease, affecting over
25% of the population in developed countries. The hallmark of early CAVD is focal changes in
the mechanical properties of the extracellular matrix (ECM) in the valve leaflets. In particular,
proteoglycan-rich lesions begin to form on the surface of the fibrosa layer of these leaflets.
Maladaptive remodeling of the ECM is hypothesized to negatively influence valve cell function,
ultimately resulting in stiffened leaflets that do not function properly. To date, the local
micromechanical properties of healthy and diseased valve leaflets have not been characterized.
The objectives of the present study are to measure local micromechanical properties of the three
layers of porcine aortic valve leaflets (fibrosa, spongiosa, and ventricularis), and of these
proteoglycan-rich lesions, and to develop material models for these layers and the lesions that
take into account material non-linearity and heterogeneity. Leaflets will be obtained from
healthy swine as well as those with early stage CAVD; comparison between the material models
developed for the two cases will help identify changes in the local micromechanical properties of
the aortic valve leaflets during the onset of CAVD.

To obtain the experimental data, a microindenter will be used to deform the surface of the
leaflets. From these experiments, we will obtain the indenter depth and the corresponding force.
We will also know the shape and size of the indenter and the shape and size of the tissue region
deformed by the indentation.
12:00 PM
12:30 PM
Masami Tatsuno - Information geometric analysis for multi-neuronal spike trains - Estimation of directional interaction and direct/indirect synaptic connections
Understanding how the brain works is one of the most challenging questions of modern science. It is
important not only for expanding the frontier of our scientific knowledge, but also for developing a
more effective treatment for neuronal diseases.
The brain is composed of a large number of neurons. Most neurons interact with other neurons via
action potentials (spikes), and have the tendency to form cell-assemblies (1) that can be organized
dynamically through information processing in the brain. To
study these group dynamics and their role in cognitive
functions, it is important to record simultaneously from as
many neurons as possible from behaving animals (2). Due to
recent technological developments, multi-electrode recordings
have become an increasingly widespread tool in
electrophysiology, enabling the recording of spiking activity
from tens to hundreds of neurons simultaneously
Tuesday, July 17, 2012
Time Session
Wednesday, July 18, 2012
Time Session
Thursday, July 19, 2012
Time Session
Friday, July 20, 2012
Time Session
09:10 AM
09:35 AM
Ewen King-Smith - The structure of the lipid layer of the tear film
Dry eye disorders affect about 15% of older Americans and are poorly understood.  Increased
evaporation is an important contributing factor.  The superficial lipid layer of the tear film is normally an
excellent barrier to evaporation but its effectiveness is often reduced in dry eye disorders.  This lipid,
called meibum, is secreted from meibomian glands in the lids.

The main components of meibum are wax esters and cholesteryl esters with smaller quantities of polar
and other lipids.  Also, surfactant proteins probably play an important role.  The esters often contain a
proportion of long, saturated hydrocarbon chains which are thought to help increase resistance to
evaporation.  Another important characteristic of the lipid layer is its ability to withstand the blink cycle
which causes compression to a small fraction of the original area, followed by expansion.   Lipids with
long, saturated hydrocarbon chains often do not re€?spread to their original state after compression and
expansion, so the inclusion of unsaturated hydrocarbon chains in meibum may aid in respreading after a
blink.

The molecular organization of the lipid layer is poorly understood.   The team will be asked to consider
and propose models of molecular structure of the lipid layer, and to evaluate their consistency with
observed properties which will be presented.   
09:35 AM
10:00 AM
Thomas Rosal - Mathematical model of blood ionized calcium concentration
The blood ionized calcium concentration (Ca2+, iCa) is tightly regulated in animals
ranging from the most primitive fishes and nonvertebrates to humans. This is because
iCa is utilized by diverse cell types as a transcellular and intracellular signaling
molecule, such as in the nervous system, cardiac and skeletal muscle, epithelial cells,
endocrine cells, blood cells, among others. The blood ionized calcium concentration is
approximately 1.5 mM in all animals. If the concentration changes by as little as 10-20%
dysregulation of body systems (such as the neuromuscular system) will result and can
be fatal. Therefore, there are multiple, redundant regulatory systems that exist to
maintain blood calcium in a narrow biological range.

Terrestrial animals live in a calcium poor environment and are dependent upon calcium
absorption from the gastrointestinal tract to provide calcium as a regulatory ion and
component of bones. In contrast, sea animals live in a calcium rich environment (since
seawater has 10 mM calcium) and excretion of calcium is important.
10:00 AM
10:25 AM
Masami Tatsuno - Information geometric analysis for multi-neuronal spike trains - Estimation of directional interaction and direct/indirect synaptic connections
Understanding how the brain works is one of the most challenging questions of modern science. It is
important not only for expanding the frontier of our scientific knowledge, but also for developing a
more effective treatment for neuronal diseases.
The brain is composed of a large number of neurons. Most neurons interact with other neurons via
action potentials (spikes), and have the tendency to form cell-assemblies (1) that can be organized
dynamically through information processing in the brain. To
study these group dynamics and their role in cognitive
functions, it is important to record simultaneously from as
many neurons as possible from behaving animals (2). Due to
recent technological developments, multi-electrode recordings
have become an increasingly widespread tool in
electrophysiology, enabling the recording of spiking activity
from tens to hundreds of neurons simultaneously
10:40 AM
11:05 AM
Martin Frasch - Online detection of physiological fetal distress pattern during birth
This proposal is derived from our studies on changes of fetal brain electrical activity
(electroenkephalogram, EEG) and heart rate (FHR) which we recorded during simulated labour
in fetal sheep model of human pregnancy and fetal development.

The goal is to develop mathematical models allowing online detection of physiological
patterns alarming of incipient fetal distress in clinical conditions of labour.

There are two major aspects of the problem:

1. A pattern of time correlated changes in EEG and FHR is now known to occur during
conditions of deteriorated blood supply to the fetus as it may occur during labour. This pattern is
an early predictor of immanent severe drop in fetal pH. Fetal pH under 7.00 (severe acidemia) is
associated with increased risk of brain injury and sustained neurological deficits. In obstetrical
care, an urgent need exists for technologies allowing the detection of such severe acidemia in
fetus. We describe the phenomenon in detail in Frasch et al (2011).

Question 1: Can we create a mathematical model of this phenomenon robust enough to be
capable of capturing the onset of the pattern online despite varying EEG/FHR signal
characteristics?

2. Certain properties of FHR variability (FHRV, higher order fluctuations in FHR on millisecond
time scale) can also be used for early detection of the onset of severe acidemia.
FHRV can be calculated in different signal property domains (linear, nonlinear, time and
frequency or both). Different measures of FHRV are known to reflect somewhat different
aspects of underlying physiological activities and probably carry a predictive value variable in
time. A group of FHRV measures is likely to provide a higher positive predictive value of fetal
acidemia than one particular FHRV measure alone. Please see also Frasch (2011).

Question 2: Can we develop a mathematical model to allow us to 1) identify the FHRV
measures that would perform best together to detect the pathophysiological mechanism of
incipient acidemia and 2) incorporate such FHRV measures into the model that captures the
correlated changes in EEG and FHR?

In a broader sense, we hope that such approach would help create a novel paradigm for
context-specific generation of mathematical models for online detection of complex
physiological patterns. Ideally, this new paradigm should go beyond a purely statistical or data
mining framework. For example, can we build a model that incorporates physiological
mechanisms into a standard data mining approach?

In order to facilitate the discussion and modeling building exercise, relevant data will be
provided for workshop participants.
11:05 AM
11:30 AM
Matthew Doyle - Development of a mathematical model for microindentation of aortic valve leaflets to aid in the determination of local micromechanical properties
Calcific aortic valve disease (CAVD) is the most common heart valve disease, affecting over
25% of the population in developed countries. The hallmark of early CAVD is focal changes in
the mechanical properties of the extracellular matrix (ECM) in the valve leaflets. In particular,
proteoglycan-rich lesions begin to form on the surface of the fibrosa layer of these leaflets.
Maladaptive remodeling of the ECM is hypothesized to negatively influence valve cell function,
ultimately resulting in stiffened leaflets that do not function properly. To date, the local
micromechanical properties of healthy and diseased valve leaflets have not been characterized.
The objectives of the present study are to measure local micromechanical properties of the three
layers of porcine aortic valve leaflets (fibrosa, spongiosa, and ventricularis), and of these
proteoglycan-rich lesions, and to develop material models for these layers and the lesions that
take into account material non-linearity and heterogeneity. Leaflets will be obtained from
healthy swine as well as those with early stage CAVD; comparison between the material models
developed for the two cases will help identify changes in the local micromechanical properties of
the aortic valve leaflets during the onset of CAVD.

To obtain the experimental data, a microindenter will be used to deform the surface of the
leaflets. From these experiments, we will obtain the indenter depth and the corresponding force.
We will also know the shape and size of the indenter and the shape and size of the tissue region
deformed by the indentation.
11:30 AM
11:55 AM
Nicanor Moldovan - Using magnetic force to colonize fibrillar scaffolds with stem/progenitor cells (report)
Summary Report for Using magnetic force to colonize fibrillar scaffolds with stem/progenitor cells
Name Email Affiliation
Bell, Jonathan jbell@math.umbc.edu Department of Mathematics & Statistics, University of Maryland Baltimore County
Bohun, Sean sean.bohun@uoit.ca Science, University of Ontario Institute of Technology
Braun, Richard braun@math.udel.edu Department of Mathematical Sciences, University of Delaware
Breward, Chris breward@maths.ox.ac.uk Mathematical Institute, University of Oxford
Byrne, Helen helen.byrne@nottingham.ac.uk Centre for Mathematical Medicine and Biology, University of Nottingham
Chou, Thomas tomchou@ucla.edu Biomathematics, University of California, Los Angeles
Chugunova, Marina chugunom@math.utoronto.ca Mathematics, University of Toronto
Cui, Kai kc52@stat.duke.edu Statistical Science, Duke University
Cytrynbaum, Eric cytryn@math.ubc.ca Mathematics, University of British Columbia
Doyle, Matthew mg.doyle@utoronto.ca Department of Mechanical and Industrial Engineering, University of Toronto
Fok, Pak-Wing pakwing@udel.edu Mathematical Sciences, University of Delaware
Frasch, Martin mg.frasch@umontreal.ca Centre de recherche en reproduction animale, CHU Sainte-Justine
Gevertz, Jana gevertz@tcnj.edu Mathematics and Statistics, The College of New Jersey
Gewecke, Nicholas ngewecke@math.udel.edu Department of Mathematical Sciences, University of Delaware
Hinkelmann, Franziska fhinkel@vt.edu MBI, The Ohio State University
Huang, Huaxiong hhuang@yorku.ca Mathematics and Statistics, York University
King-Smith, Ewen EKing-smith@optometry.osu.edu College of Optometry, The Ohio State University
Ledder, Glenn gledder@math.unl.edu Mathematics, University of Nebraska
Lewis, Gregory greg.lewis@uoit.ca Faculty of Science, UOIT
Louzoun, Yoram louzouy@math.biu.ac.il
Matamba Messi, Leopold lmatamba@gmail.com Department of Mathematics, University of Georgia
Miakonkana, Guy-vanie gmm0006@auburn.edu Mathematics and Statistics, Auburn University
Moldovan, Nicanor moldovan.6@osu.edu Internal Medicine, Disease Pathways, LLC
Moulton, Derek moulton@maths.ox.ac.uk OCCAM, Mathematical Institute, University of Oxford
Newby, Jay newby@maths.ox.ac.uk Mathematics, University of Oxford
O'Keeffe, Stephen stephen.okeeffe@hertford.ox.ac.uk OCCAM, Mathematical Institute, University of Oxford
Peercy, Bradford bpeercy@umbc.edu Mathematics and Statistics, University of Maryland Baltimore County
Pugh, Mary mpugh@math.utoronto.ca Mathematics, University of Toronto
Radunskaya, Ami aradunskaya@pomona.edu Mathematics, Pomona College
Roberts, Paul paul.roberts@univ.ox.ac.uk Mathematics Department and Computer Science Department, University of Oxford
Rosol, Thomas rosol.1@osu.edu Veterinary Biosciences, The Ohio State University
Schwendeman, Donald schwed@rpi.edu Mathematical Sciences, Rensselaer Polytechnic Institute
Shipley, Rebecca rebecca.shipley@ucl.ac.uk Department of Mechanical Engineering, University College London
Siggers, Jennifer j.siggers@imperial.ac.uk Department of Bioengineering,
Sivaloganathan, Siv ssivalog@math.uwaterloo.ca Applied Mathematics, University of Waterloo
Solomon, Bill billsolo@sbcglobal.net Blue Valley High School
Stamper, Johanna jstamper@uab.edu Physics, University of Alabama at Birmingham
Stepien, Tracy tls52@pitt.edu Mathematics, University of Pittsburgh
Strawbridge, Eva emstrawbridge@gmail.com Mathematics, University of Chicago
Tatsuno, Masami tatsuno@uleth.ca Neuroscience, University of Lethbridge
Tseng, Yu-Hau yhtseng@math.nctu.edu.tw DEPARTMENT OF MATHEMATICS AND STATISTICS, York University
Vandiver, Becky vandiver@stolaf.edu Mathematics and Computer Science, St. Olaf College
Vats, Divyanshu dvats@ima.umn.edu Institute for Mathematics and its Applications, University of Minnesota
Wang, Steven stevenw@mathstat.yorku.ca Mathematics and Statistics, York University
Ward, John John.Ward@lboro.ac.uk Mathematical Sciences,
Washington, Talitha talitha.washington@howard.edu Mathematics, Howard University
Wattis, Jonathan Jonathan.Wattis@nottingham.ac.uk School of Mathematical Sciences, University of Nottingham
Witelski, Thomas witelski@math.duke.edu Mathematics, Duke University
Development of a mathematical model for microindentation of aortic valve leaflets to aid in the determination of local micromechanical properties
Calcific aortic valve disease (CAVD) is the most common heart valve disease, affecting over
25% of the population in developed countries. The hallmark of early CAVD is focal changes in
the mechanical properties of the extracellular matrix (ECM) in the valve leaflets. In particular,
proteoglycan-rich lesions begin to form on the surface of the fibrosa layer of these leaflets.
Maladaptive remodeling of the ECM is hypothesized to negatively influence valve cell function,
ultimately resulting in stiffened leaflets that do not function properly. To date, the local
micromechanical properties of healthy and diseased valve leaflets have not been characterized.
The objectives of the present study are to measure local micromechanical properties of the three
layers of porcine aortic valve leaflets (fibrosa, spongiosa, and ventricularis), and of these
proteoglycan-rich lesions, and to develop material models for these layers and the lesions that
take into account material non-linearity and heterogeneity. Leaflets will be obtained from
healthy swine as well as those with early stage CAVD; comparison between the material models
developed for the two cases will help identify changes in the local micromechanical properties of
the aortic valve leaflets during the onset of CAVD.

To obtain the experimental data, a microindenter will be used to deform the surface of the
leaflets. From these experiments, we will obtain the indenter depth and the corresponding force.
We will also know the shape and size of the indenter and the shape and size of the tissue region
deformed by the indentation.
Development of a mathematical model for microindentation of aortic valve leaflets to aid in the determination of local micromechanical properties (report)
Summary Report for Development of a mathematical model for microindentation of aortic valve leaflets to aid in the determination of local micromechanical properties
Online detection of physiological fetal distress pattern during birth
This proposal is derived from our studies on changes of fetal brain electrical activity
(electroenkephalogram, EEG) and heart rate (FHR) which we recorded during simulated labour
in fetal sheep model of human pregnancy and fetal development.

The goal is to develop mathematical models allowing online detection of physiological
patterns alarming of incipient fetal distress in clinical conditions of labour.

There are two major aspects of the problem:

1. A pattern of time correlated changes in EEG and FHR is now known to occur during
conditions of deteriorated blood supply to the fetus as it may occur during labour. This pattern is
an early predictor of immanent severe drop in fetal pH. Fetal pH under 7.00 (severe acidemia) is
associated with increased risk of brain injury and sustained neurological deficits. In obstetrical
care, an urgent need exists for technologies allowing the detection of such severe acidemia in
fetus. We describe the phenomenon in detail in Frasch et al (2011).

Question 1: Can we create a mathematical model of this phenomenon robust enough to be
capable of capturing the onset of the pattern online despite varying EEG/FHR signal
characteristics?

2. Certain properties of FHR variability (FHRV, higher order fluctuations in FHR on millisecond
time scale) can also be used for early detection of the onset of severe acidemia.
FHRV can be calculated in different signal property domains (linear, nonlinear, time and
frequency or both). Different measures of FHRV are known to reflect somewhat different
aspects of underlying physiological activities and probably carry a predictive value variable in
time. A group of FHRV measures is likely to provide a higher positive predictive value of fetal
acidemia than one particular FHRV measure alone. Please see also Frasch (2011).

Question 2: Can we develop a mathematical model to allow us to 1) identify the FHRV
measures that would perform best together to detect the pathophysiological mechanism of
incipient acidemia and 2) incorporate such FHRV measures into the model that captures the
correlated changes in EEG and FHR?

In a broader sense, we hope that such approach would help create a novel paradigm for
context-specific generation of mathematical models for online detection of complex
physiological patterns. Ideally, this new paradigm should go beyond a purely statistical or data
mining framework. For example, can we build a model that incorporates physiological
mechanisms into a standard data mining approach?

In order to facilitate the discussion and modeling building exercise, relevant data will be
provided for workshop participants.
Online detection of physiological fetal distress pattern during birth (report)
Summary Report for Online detection of physiological fetal distress pattern during birth
The structure of the lipid layer of the tear film
Dry eye disorders affect about 15% of older Americans and are poorly understood.  Increased
evaporation is an important contributing factor.  The superficial lipid layer of the tear film is normally an
excellent barrier to evaporation but its effectiveness is often reduced in dry eye disorders.  This lipid,
called meibum, is secreted from meibomian glands in the lids.

The main components of meibum are wax esters and cholesteryl esters with smaller quantities of polar
and other lipids.  Also, surfactant proteins probably play an important role.  The esters often contain a
proportion of long, saturated hydrocarbon chains which are thought to help increase resistance to
evaporation.  Another important characteristic of the lipid layer is its ability to withstand the blink cycle
which causes compression to a small fraction of the original area, followed by expansion.   Lipids with
long, saturated hydrocarbon chains often do not re�spread to their original state after compression and
expansion, so the inclusion of unsaturated hydrocarbon chains in meibum may aid in respreading after a
blink.

The molecular organization of the lipid layer is poorly understood.   The team will be asked to consider
and propose models of molecular structure of the lipid layer, and to evaluate their consistency with
observed properties which will be presented.   
The structure of the lipid layer of the tear film (report)
Summary Report from The structure of the lipid layer of the tear film problem solving workshop
Using magnetic force to colonize fibrillar scaffolds with stem/progenitor cells (report)
Summary Report for Using magnetic force to colonize fibrillar scaffolds with stem/progenitor cells
Mathematical model of blood ionized calcium concentration
The blood ionized calcium concentration (Ca2+, iCa) is tightly regulated in animals
ranging from the most primitive fishes and nonvertebrates to humans. This is because
iCa is utilized by diverse cell types as a transcellular and intracellular signaling
molecule, such as in the nervous system, cardiac and skeletal muscle, epithelial cells,
endocrine cells, blood cells, among others. The blood ionized calcium concentration is
approximately 1.5 mM in all animals. If the concentration changes by as little as 10-20%
dysregulation of body systems (such as the neuromuscular system) will result and can
be fatal. Therefore, there are multiple, redundant regulatory systems that exist to
maintain blood calcium in a narrow biological range.

Terrestrial animals live in a calcium poor environment and are dependent upon calcium
absorption from the gastrointestinal tract to provide calcium as a regulatory ion and
component of bones. In contrast, sea animals live in a calcium rich environment (since
seawater has 10 mM calcium) and excretion of calcium is important.
Mathematical model of blood ionized calcium concentration (report)
Summary Report on Mathematical model of blood ionized calcium concentration
Information geometric analysis for multi-neuronal spike trains - Estimation of directional interaction and direct/indirect synaptic connections
Understanding how the brain works is one of the most challenging questions of modern science. It is
important not only for expanding the frontier of our scientific knowledge, but also for developing a
more effective treatment for neuronal diseases.
The brain is composed of a large number of neurons. Most neurons interact with other neurons via
action potentials (spikes), and have the tendency to form cell-assemblies (1) that can be organized
dynamically through information processing in the brain. To
study these group dynamics and their role in cognitive
functions, it is important to record simultaneously from as
many neurons as possible from behaving animals (2). Due to
recent technological developments, multi-electrode recordings
have become an increasingly widespread tool in
electrophysiology, enabling the recording of spiking activity
from tens to hundreds of neurons simultaneously
Information geometric analysis for multi-neuronal spike trains - Estimation of directional interaction and direct/indirect synaptic connections (report)
Summary Report for Information geometric analysis for multi-neuronal spike trains - Estimation of directional interaction and direct/indirect synaptic connections