pwc-archive/papers-with-abstracts huggingface dataset:
Quantitative Molecular Scaling Theory of Protein Amino Acid Sequences, Structure, and Functionality
Date: 2016-10-13 00:00:00
Tasks: Articles

Here we review the development of protein scaling theory, starting from
backgrounds in mathematics and statistical mechanics, and leading to biomedical
applications. Evolution has organized each protein family in different ways,
but scaling theory is both simple and effective in providing readily
transferable dynamical insights complementary for many proteins represented in
the 90 thousand static structures contained in the online Protein Data Base
(PDB). Scaling theory is a simplifying magic wand that enables one to search
the hundreds of millions of protein articles in the Web of Science, and
identify those proteins that present new cost-effective methods for early
detection and/or treatment of disease through individual protein sequences
(personalized medicine). Critical point theory is general, and recently it has
proved to be the most effective way of describing protein networks that have
evolved towards nearly perfect functionality in given environments
(self-organized criticality). Evolutionary patterns are governed by common
scaling principles, which can be quantified using scales that have been
developed bioinformatically by studying thousands of PDB structures. The most
effective scales involve either hydropathic globular sculpting interactions
averaged over length scales centered on membrane dimensions, or exposed beta
strand propensities associated with aggregative (strong) protein-protein
interactions.
Ionic channels in biological membranes. Electrostatic analysis of a natural nanotube
Date: 2016-10-14 00:00:00

A simple theory of ion permeation through a channel is presented, in which
diffusion occurs according to Fick's law and drift according to Ohm's law, in
the electric field determined by all the charges present. This theory accounts
for permeation in the channels studied to date in a wide range of solutions.
Interestingly, the theory works because the shape of the electric field is a
sensitive function of experimental conditions, e.g., ion concentration. Rate
constants for flux are sensitive functions of ionic concentration because the
fixed charge of the channel protein is shielded by the ions in an near it. Such
shielding effects are not included in traditional theories of ionic channels,
or other proteins, for that matter.
Mind Control as a Guide for the Mind
Date: 2017-04-25 00:00:00
Tasks: Ethics

The human brain is a complex network that supports mental function. The
nascent field of network neuroscience applies tools from mathematics to
neuroimaging data in the hopes of shedding light on cognitive function. A
critical question arising from these empirical studies is how to modulate a
human brain network to treat cognitive deficits or enhance mental abilities.
While historically a number of tools have been employed to modulate mental
states (such as cognitive behavioral therapy and brain stimulation),
theoretical frameworks to guide these interventions - and to optimize them for
clinical use - are fundamentally lacking. One promising and as-yet
underexplored approach lies in a sub-discipline of engineering known as network
control theory. Here, we posit that network control fundamentally relates to
mind control, and that this relationship highlights important areas for future
empirical research and opportunities to translate knowledge in practical
domains. We clarify the conceptual intersection between neuroanatomy,
cognition, and control engineering in the context of network neuroscience.
Finally, we discuss the challenges, ethics, and promises of mind control.
Pan-genome Analysis of the Genus Serratia
Date: 2016-10-13 00:00:00

Pan-genome analysis is a standard procedure to decipher genome heterogeneity
and diversification of bacterial species. Specie evolution is traced by
defining and comparing the core (conserved), accessory (dispensable) and unique
(strain-specific) gene pool with other strains of interest. Here, we present
pan-genome analysis of the genus Serratia, comprising of a dataset of 100
genomes. The isolates have clinical to environmental origin and consist of ten
different species from the genus, along with two subspecies of the
representative strain Serratia marcescens. Out of 19430 non-redundant coding
DNA sequences (CDS) from the dataset, 972 (5%) belonged to the core genome.
Majority of these genes were linked to metabolic function, followed by cellular
processes/signalling, information storage/processing while rest of them were
poorly characterized. 10,135 CDSs (52.16%) were associated with dispensible
genome while 8,321 CDSs (42.82%) were singletons or strain specific. The
Pan-genome orthologs indicated a positive correlation to the number of genomes
whereas negative correlation was obtained for core genome. Genomes were aligned
to obtain information about synteny, insertion/inversion, deletion and
duplications. This study provides insights into variation of Serratia species
and paves way for pan-genome analysis of other bacterial species at genus
level.
Parallel ICA reveals linked patterns of structural damage and fMRI language task activation in chronic post-stroke aphasia
Date: 2016-10-13 00:00:00

Structural and functional MRI studies of patients with post-stroke language
deficits have contributed substantially to our understanding of how
cognitive-behavioral impairments relate to the location of structural damage
and to the activation of surviving brain regions during language processing,
respectively. However, very little is known about how inter-patient variability
in language task activation relates to variability in the structures affected
by stroke. Here, we used parallel independent component analysis (pICA) to
characterize links between patterns of structural damage and patterns of
functional MRI activation during semantic decisions. The pICA analysis revealed
a significant association between a lesion component featuring damage to left
posterior temporo-parietal cortex and the underlying deep white matter and an
fMRI component featuring (1) heightened activation in a primarily right
hemispheric network of frontal, temporal, and parietal regions, and (2) reduced
activation in areas associated with the semantic network activated by healthy
controls. Stronger loading parameters on both the lesion and fMRI activation
components were associated with poorer language test performance. Fiber
tracking suggests that lesions affecting the left posterior temporo-parietal
cortex and deep white matter may lead to the simultaneous disruption of
multiple long-range structural pathways connecting distal language areas.
Damage to the left posterior temporo-parietal cortex and underlying white
matter may (1) impede the language task-driven recruitment of canonical left
hemispheric language and other areas (e.g. the right anterior temporal lobe and
default mode regions) that likely support residual language function after
stroke, and (2) lead to the compensatory recruitment of right hemispheric
fronto-temporo-parietal networks for tasks requiring semantic processing.
The Influence of Streamlined Music on Cognition and Mood
Date: 2016-10-13 00:00:00
Tasks: Form

Recent advances in sound engineering have led to the development of so-called
streamlined music designed to reduce exogenous attention and improve endogenous
attention. Although anecdotal reports suggest that streamlined music does
indeed improve focus on daily work tasks and may improve mood, the specific
influences of streamlined music on cognition and mood have yet to be examined.
In this paper, we report the results of a series of online experiments that
examined the impact of one form of streamlined music on cognition and mood. The
tested form of streamlined music, which was tested primarily by listeners who
felt they benefited from this type of music, significantly outperformed plain
music on measures of perceived focus, task persistence, precognition, and
creative thinking, with borderline effects on mood. In contrast, this same form
of streamlined music did not significantly influence measures assessing visual
attention, verbal memory, logical thinking, self-efficacy, perceived stress, or
self-transcendence. We also found that improvements in perceived focus over a
2-month period were correlated with improvements in emotional state, including
mood. Overall the results suggest that at least for individuals who enjoy using
streamlined music as a focus tool, streamlined music can have a beneficial
impact on cognition without any obvious costs, while at the same time it may
potentially boost mood.
Different roles for inhibition in the rhythm-generating respiratory network
Date: 2017-06-12 00:00:00
Tasks: Rhythm

Unraveling the interplay of excitation and inhibition within
rhythm-generating networks remains a fundamental issue in neuroscience. We use
a biophysical model to investigate the different roles of local and long-range
inhibition in the respiratory network, a key component of which is the
pre-B\"otzinger complex inspiratory microcircuit. Increasing inhibition within
the microcircuit results in a limited number of out-of-phase neurons before
rhythmicity and synchrony degenerate. Thus, unstructured local inhibition is
destabilizing and cannot support the generation of more than one rhythm. A
two-phase rhythm requires restructuring the network into two microcircuits
coupled by long-range inhibition in the manner of a half-center. In this
context, inhibition leads to greater stability of the two out-of-phase rhythms.
We support our computational results with in vitro recordings from mouse
pre-B\"otzinger complex. Partial excitation block leads to increased rhythmic
variability, but this recovers following blockade of inhibition. Our results
support the idea that local inhibition in the pre-B\"otzinger complex is
present to allow for descending control of synchrony or robustness to adverse
conditions like hypoxia. We conclude that the balance of inhibition and
excitation determines the stability of rhythmogenesis, but with opposite roles
within and between areas. These different inhibitory roles may apply to a
variety of rhythmic behaviors that emerge in widespread pattern generating
circuits of the nervous system.
Unfolding knots by proteasome-like systems: simulations of the behaviour of folded and neurotoxic proteins
Date: 2016-10-13 00:00:00

Knots in proteins have been proposed to resist proteasomal degradation. Ample
evidence associates proteasomal degradation with neurodegeneration. One
interesting possibility is that indeed knotted conformers stall this machinery
leading to toxicity. However, although the proteasome is known to unfold
mechanically its substrates, at present there are no experimental methods to
emulate this particular traction geometry. Here, we consider several dynamical
models of the proteasome in which the complex is represented by an effective
potential with an added pulling force. This force is meant to induce
translocation of a protein or a polypeptide into the catalytic chamber. The
force is either constant or applied periodically. The translocated proteins are
modelled in a coarse-grained fashion. We do comparative analysis of several
knotted globular proteins and the transiently knotted polyglutamine tracts of
length 60 alone and fused in exon 1 of the huntingtin protein. Huntingtin is
associated with Huntington disease, a well-known genetically-determined
neurodegenerative disease. We show that the presence of a knot hinders and
sometimes even jams translocation. We demonstrate that the probability to do so
depends on the protein, the model of the proteasome, the magnitude of the
pulling force, and the choice of the pulled terminus. In any case, the net
effect would be a hindrance in the proteasomal degradation process in the cell.
This would then yield toxicity \textit{via} two different mechanisms: one
through toxic monomers compromising degradation and another by the formation of
toxic oligomers. Our work paves the way to the mechanistic investigation of the
mechanical unfolding of knotted structures by the proteasome and its relation
to toxicity and disease.
Time-Varying Comovement of Foreign Exchange Markets
Date: 2016-10-14 00:00:00

A time-varying cointegration model for foreign exchange rates is presented.
Unlike previous studies, we allow the loading matrix in the vector error
correction (VEC) model to be varying over time. Because the loading matrix in
the VEC model is associated with the speed at which deviations from the
long-run relationship disappear, we propose a new degree of market comovement\
based on the time-varying loading matrix to measure the strength or robustness
of the long-run relationship over time. Since exchange rates are determined by
macrovariables, cointegration among exchange rates implies those macroeconomic
variables share common stochastic trends. Therefore, the proposed degree
measures the degree of market comovement. Our main finding is that the market
comovement has become stronger over the past quarter century, but the rate at
which market comovement strengthens is decreasing with two major turning
points: one in 1995 and the other one in 2008.
A singular mutation in the hemagglutinin of the 1918 pandemic virus
Date: 2016-10-14 00:00:00

The influenza pandemic of 1918-1919 killed at least 50 million people. The
reasons why this pandemic was so deadly remain largely unknown. However, It has
been shown that the 1918 viral hemagglutinin allows to reproduce the hallmarks
of the illness observed during the original pandemic. Thanks to the wealth of
hemagglutinin sequences accumulated over the last decades, amino-acid
substitutions that are found in the 1918-1919 sequences but rare otherwise can
be identified with high confidence. Such an analysis reveals that Gly188, which
is located within a key motif of the receptor binding site, is so rarely found
in hemagglutinin sequences that, taken alone, it is likely to be deleterious.
Monitoring this singular mutation in viral sequences may help prevent another
dramatic pandemic.
Symmetric Private Information Retrieval For MDS Coded Distributed Storage
Authors: Wang Qiwen, Skoglund Mikael
Date: 2016-10-14 00:00:00
Tasks: Information Retrieval, Retrieval

A user wants to retrieve a file from a database without revealing the
identity of the file retrieved at the database, which is known as the problem
of private information retrieval (PIR). If it is further required that the user
obtains no information about the database other than the desired file, the
concept of symmetric private information retrieval (SPIR) is introduced to
guarantee privacy for both parties. In this paper, the problem of SPIR is
studied for a database stored among $N$ nodes in a distributed way, by using an
$(N,M)$-MDS storage code. The information-theoretic capacity of SPIR, defined
as the maximum number of symbols of the desired file retrieved per downloaded
symbol, for the coded database is derived. It is shown that the SPIR capacity
for coded database is $1-\frac{M}{N}$, when the amount of the shared common
randomness of distributed nodes (unavailable at the user) is at least
$\frac{M}{N-M}$ times the file size. Otherwise, the SPIR capacity for the coded
database equals zero.
The Robustness and the Doubly-Preferential Attachment Simulation of the Consensus Connectome Dynamics of the Human Brain
Date: 2016-10-14 00:00:00
Tasks: Diffusion  MRI

The increasing quantity and quality of the publicly available human cerebral
diffusion MRI data make possible the study of the brain as it was unimaginable
before. The Consensus Connectome Dynamics (CCD) is a remarkable phenomenon that
was discovered by continuously decreasing the minimum confidence-parameter at
the graphical interface of the Budapest Reference Connectome Server
(\url{http://connectome.pitgroup.org}). The Budapest Reference Connectome
Server depicts the cerebral connections of $n=418$ subjects with a
frequency-parameter $k$: For any $k=1,2,...,n$ one can view the graph of the
edges that are present in at least $k$ connectomes. If parameter $k$ is
decreased one-by-one from $k=n$ through $k=1$ then more and more edges appear
in the graph, since the inclusion condition is relaxed. The surprising
observation is that the appearance of the edges is far from random: it
resembles a growing, complex structure, like a tree or a shrub (visualized on
\url{https://www.youtube.com/watch?v=yxlyudPaVUE}). Here we examine the
robustness of the CCD phenomenon, and we show that it is almost independent of
the particular choice of the set of underlying individual connectomes, yielding
the CCD phenomenon. This result shows that the CCD phenomenon is very likely a
biological property of the human brain and not just a property of the data sets
examined. We also present a simulation that well-describes the growth of the
CCD structure: in our random graph model a doubly-preferential attachment
distribution is found to mimic the CCD: a new edge appear with a probability
proportional to the sum of the degrees of the endpoints of the new edge.
Giant Hub Src and Syk Tyrosine Kinase Thermodynamic Profiles Recapitulate Evolution
Date: 2016-10-14 00:00:00

Thermodynamic scaling theory, previously applied mainly to small proteins,
here analyzes quantitative evolution of the titled functional network giant hub
enzymes. The broad domain structure identified homologically is confirmed
hydropathically using amino acid sequences only. The most surprising results
concern the evolution of the tyrosine kinase globular surface roughness from
avian to mammals, which is first order, compared to the evolution within
mammals from rodents to humans, which is second order. The mystery of the
unique amide terminal region of proto oncogene tyrosine protein kinase is
resolved by the discovery there of a septad targeting cluster, which is
paralleled by an octad catalytic cluster in tyrosine kinase in humans and a few
other species. These results, which go far towards explaining why these
proteins are among the largest giant hubs in protein interaction networks, use
no adjustable parameters.
A model with Darwinian dynamics on a rugged landscape
Date: 2016-10-15 00:00:00

We discuss the population dynamics with selection and random diffusion,
keeping the total population constant, in a fitness landscape associated with
Constraint Satisfaction, a paradigm for difficult optimization problems. We
obtain a phase diagram in terms of the size of the population and the diffusion
rate, with a glass phase inside which the dynamics keeps searching for better
configurations, and outside which deleterious `mutations' spoil the
performance. The phase diagram is analogous to that of dense active matter in
terms of temperature and drive.
Three-dimensional contact of TITH cartilage layers, a closed-form solution
Date: 2016-10-15 00:00:00
Tasks: Form

Inhomogeneity and anisotropy play a crucial role in attributing articular
cartilage its properties. The frictionless contact model constructed here
consists in two thin biphasic transversely isotropic transversely homogeneous
(TITH) cartilage layers firmly attached onto rigid substrates and shaped as
elliptic paraboloids of different radii. Using asymptotic techniques, a
solution to the deformation problem of such material has been recently obtained
extending previous ones referred to homogeneous materials. The layer itself is
thin in comparison with the size of the contact area and the observed time is
shorter than the hydrogel characteristic time. The emerging three-dimensional
contact problem is solved in closed-form and numerical benchmarks for constant
and oscillating loads are given. The results are shown in terms of contact
pressure and approach of the bones. The latter is derived to be directly
proportional to the contact area. Existing experimental data are reinterpreted
in view of the current model formulation. Comparisons are made with existing
solutions for homogeneous biphasic materials in order to underline the
functional importance of inhomogeneity in spreading the contact pressure
distribution across the contact area. Particular attention is paid to the
applicability of the retrieved formulas for interpreting measurements of in
vivo experiments. Future directions are also prospected.
A System Level Approach to Controller Synthesis
Date: 2019-06-12 00:00:00

Biological and advanced cyberphysical control systems often have limited,
sparse, uncertain, and distributed communication and computing in addition to
sensing and actuation. Fortunately, the corresponding plants and performance
requirements are also sparse and structured, and this must be exploited to make
constrained controller design feasible and tractable. We introduce a new
"system level" (SL) approach involving three complementary SL elements. System
Level Parameterizations (SLPs) generalize state space and Youla
parameterizations of all stabilizing controllers and the responses they
achieve, and combine with System Level Constraints (SLCs) to parameterize the
largest known class of constrained stabilizing controllers that admit a convex
characterization, generalizing quadratic invariance (QI). SLPs also lead to a
generalization of detectability and stabilizability, suggesting the existence
of a rich separation structure, that when combined with SLCs, is naturally
applicable to structurally constrained controllers and systems. We further
provide a catalog of useful SLCs, most importantly including sparsity, delay,
and locality constraints on both communication and computing internal to the
controller, and external system performance. The resulting System Level
Synthesis (SLS) problems that arise define the broadest known class of
constrained optimal control problems that can be solved using convex
programming. An example illustrates how this system level approach can
systematically explore tradeoffs in controller performance, robustness, and
synthesis/implementation complexity.
Strength and stability of active ligand-receptor bonds: a microtubule attached to a wall by molecular motor tethers
Date: 2017-08-20 00:00:00

We develop a stochastic kinetic model of a pre-formed attachment of a
mictrotuble (MT) with a cell cortex, in which the MT is tethered to the cell by
a group of active motor proteins. Such an attachment is a particularly unique
case of ligand-receptor bonds: The MT ligand changes its length (and thus
binding sites) with time by polymerization-depolymerization kinetics, while
multiple motor receptors tend to walk actively along the MT length. These
processes, combined with force-mediated unbinding of the motors, result in an
elaborate behavior of the MT connection to the cell cortex. We present results
for the strength and lifetime of the system through the well-established
force-clamp and force-ramp protocols when external tension is applied to the
MT. The simulation results reveal that the MT-cell attachment behaves as a
catch-bond or slip-bond depending on system parameters. We provide analytical
approximations of the lifetime and discuss implications of our results on
in-vitro experiments.