2,103 research outputs found
Specialization at an expanding front
As a population grows, spreading to new environments may favor
specialization. In this paper, we introduce and explore a model for
specialization at the front of a colony expanding synchronously into new
territory. We show through numerical simulations that, by gaining fitness
through accumulating mutations, progeny of the initial seed population can
differentiate into distinct specialists. With competition and selection limited
to the growth front, the emerging specialists first segregate into sectors,
which then expand to dominate the entire population. We quantify the scaling of
the fixation time with the size of the population and observe different
behaviors corresponding to distinct universality classes: unbounded and bounded
gains in fitness lead to superdiffusive () and diffusive ()
stochastic wanderings of the sector boundaries, respectively.Comment: 6+3 pages, 3+3 figure
Learning-Based Distributed Detection-Estimation in Sensor Networks with Unknown Sensor Defects
We consider the problem of distributed estimation of an unknown deterministic
scalar parameter (the target signal) in a wireless sensor network (WSN), where
each sensor receives a single snapshot of the field. We assume that the
observation at each node randomly falls into one of two modes: a valid or an
invalid observation mode. Specifically, mode one corresponds to the desired
signal plus noise observation mode (\emph{valid}), and mode two corresponds to
the pure noise mode (\emph{invalid}) due to node defect or damage. With no
prior information on such local sensing modes, we introduce a learning-based
distributed procedure, called the mixed detection-estimation (MDE) algorithm,
based on iterative closed-loop interactions between mode learning (detection)
and target estimation. The online learning step re-assesses the validity of the
local observations at each iteration, thus refining the ongoing estimation
update process. The convergence of the MDE algorithm is established
analytically. Asymptotic analysis shows that, in the high signal-to-noise ratio
(SNR) regime, the MDE estimation error converges to that of an ideal
(centralized) estimator with perfect information about the node sensing modes.
This is in contrast to the estimation performance of a naive average consensus
based distributed estimator (without mode learning), whose estimation error
blows up with an increasing SNR.Comment: 15 pages, 2 figures, submitted to TS
Genome-Wide Comparison of PU.1 and Spi-B Binding Sites in a Mouse B Lymphoma Cell Line
Background
Spi-B and PU.1 are highly related members of the E26-transformation-specific (ETS) family of transcription factors that have similar, but not identical, roles in B cell development. PU.1 and Spi-B are both expressed in B cells, and have been demonstrated to redundantly activate transcription of genes required for B cell differentiation and function. It was hypothesized that Spi-B and PU.1 occupy a similar set of regions within the genome of a B lymphoma cell line.
Results
To compare binding regions of Spi-B and PU.1, murine WEHI-279 lymphoma cells were infected with retroviral vectors encoding 3XFLAG-tagged PU.1 or Spi-B. Anti-FLAG chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) was performed. Analysis for high-stringency enriched genomic regions demonstrated that PU.1 occupied 4528 regions and Spi-B occupied 3360 regions. The majority of regions occupied by Spi-B were also occupied by PU.1. Regions bound by Spi-B and PU.1 were frequently located immediately upstream of genes associated with immune response and activation of B cells. Motif-finding revealed that both transcription factors were predominantly located at the ETS core domain (GGAA), however, other unique motifs were identified when examining regions associated with only one of the two factors. Motifs associated with unique PU.1 binding included POU2F2, while unique motifs in the Spi-B regions contained a combined ETS-IRF motif.
Conclusions
Our results suggest that complementary biological functions of PU.1 and Spi-B may be explained by their interaction with a similar set of regions in the genome of B cells. However, sites uniquely occupied by PU.1 or Spi-B provide insight into their unique functions
Reversible temperature-controlled gelation in mixtures of pNIPAM microgels and non-ionic polymer surfactant
Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene
An ability to precisely regulate the quantity and location of molecular flux
is of value in applications such as nanoscale 3D printing, catalysis, and
sensor design. Barrier materials containing pores with molecular dimensions
have previously been used to manipulate molecular compositions in the gas
phase, but have so far been unable to offer controlled gas transport through
individual pores. Here, we show that gas flux through discrete angstrom-sized
pores in monolayer graphene can be detected and then controlled using
nanometer-sized gold clusters, which are formed on the surface of the graphene
and can migrate and partially block a pore. In samples without gold clusters,
we observe stochastic switching of the magnitude of the gas permeance, which we
attribute to molecular rearrangements of the pore. Our molecular valves could
be used, for example, to develop unique approaches to molecular synthesis that
are based on the controllable switching of a molecular gas flux, reminiscent of
ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog
A dynamic network approach for the study of human phenotypes
The use of networks to integrate different genetic, proteomic, and metabolic
datasets has been proposed as a viable path toward elucidating the origins of
specific diseases. Here we introduce a new phenotypic database summarizing
correlations obtained from the disease history of more than 30 million patients
in a Phenotypic Disease Network (PDN). We present evidence that the structure
of the PDN is relevant to the understanding of illness progression by showing
that (1) patients develop diseases close in the network to those they already
have; (2) the progression of disease along the links of the network is
different for patients of different genders and ethnicities; (3) patients
diagnosed with diseases which are more highly connected in the PDN tend to die
sooner than those affected by less connected diseases; and (4) diseases that
tend to be preceded by others in the PDN tend to be more connected than
diseases that precede other illnesses, and are associated with higher degrees
of mortality. Our findings show that disease progression can be represented and
studied using network methods, offering the potential to enhance our
understanding of the origin and evolution of human diseases. The dataset
introduced here, released concurrently with this publication, represents the
largest relational phenotypic resource publicly available to the research
community.Comment: 28 pages (double space), 6 figure
Development, Validation, and Assessment of an Ischemic Stroke or Transient Ischemic Attack-Specific Prediction Tool for Obstructive Sleep Apnea
BACKGROUND:
Screening instruments for obstructive sleep apnea (OSA), as used routinely to guide clinicians regarding patient referral for polysomnography (PSG), rely heavily on symptomatology. We sought to develop and validate a cerebrovascular disease-specific OSA prediction model less reliant on symptomatology, and to compare its performance with commonly used screening instruments within a population with ischemic stroke or transient ischemic attack (TIA).
METHODS:
Using data on demographic factors, anthropometric measurements, medical history, stroke severity, sleep questionnaires, and PSG from 2 independently derived, multisite, randomized trials that enrolled patients with stroke or TIA, we developed and validated a model to predict the presence of OSA (i.e., Apnea-Hypopnea Index ≥5 events per hour). Model performance was compared with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score.
RESULTS:
The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck, weight [in Pounds], Insulin resistance/diabetes, and National Institutes of Health Stroke Scale) performed modestly better than other instruments in identifying patients with OSA, showing reasonable discrimination in the development (c-statistic .732) and validation (c-statistic .731) study populations, and having the highest negative predictive value of all in struments.
CONCLUSIONS:
Clinicians should be aware of these limitations in OSA screening instruments when making decisions about referral for PSG. The high negative predictive value of the SLEEP INventory may be useful in determining and prioritizing patients with stroke or TIA least in need of overnight PSG
Inhalation of Ultrafine Particles Alters Blood Leukocyte Expression of Adhesion Molecules in Humans
Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter ~ 25 nm, geometric standard deviation ~ 1.6), for 2 hr, in three separate protocols: 10 μg/m(3) at rest, 10 and 25 μg/m(3) with exercise, and 50 μg/m(3) with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 μg/m(3) UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 μg/m(3) UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4(+) T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed
Evidence of Glycolysis Up-Regulation and Pyruvate Mitochondrial Oxidation Mismatch During Mechanical Unloading of the Failing Human Heart: Implications for Cardiac Reloading and Conditioning
This study sought to investigate the effects of mechanical unloading on myocardial energetics and the metabolic perturbation of heart failure (HF) in an effort to identify potential new therapeutic targets that could enhance the unloading-induced cardiac recovery. The authors prospectively examined paired human myocardial tissue procured from 31 advanced HF patients at left ventricular assist device (LVAD) implant and at heart transplant plus tissue from 11 normal donors. They identified increased post-LVAD glycolytic metabolites without a coordinate increase in early, tricarboxylic acid (TCA) cycle intermediates. The increased pyruvate was not directed toward the mitochondria and the TCA cycle for complete oxidation, but instead, was mainly converted to cytosolic lactate. Increased nucleotide concentrations were present, potentially indicating increased flux through the pentose phosphate pathway. Evaluation of mitochondrial function and structure revealed a lack of post-LVAD improvement in mitochondrial oxidative functional capacity, mitochondrial volume density, and deoxyribonucleic acid content. Finally, post-LVAD unloading, amino acid levels were found to be increased and could represent a compensatory mechanism and an alternative energy source that could fuel the TCA cycle by anaplerosis. In summary, the authors report evidence that LVAD unloading induces glycolysis in concert with pyruvate mitochondrial oxidation mismatch, most likely as a result of persistent mitochondrial dysfunction. These findings suggest that interventions known to improve mitochondrial biogenesis, structure, and function, such as controlled cardiac reloading and conditioning, warrant further investigation to enhance unloading-induced reverse remodeling and cardiac recovery
Infarct Location and Sleep Apnea: Evaluating the Potential Association in Acute Ischemic Stroke.
Background: The literature about the relationship between obstructive sleep apnea (OSA) and stroke location is conflicting with some studies finding an association and others demonstrating no relationship. Among acute ischemic stroke patients, we sought to examine the relationship between stroke location and the prevalence of OSA; OSA severity based on apnea-hypopnea index (AHI), arousal frequency, and measure of hypoxia; and number of central and obstructive respiratory events. Methods: Data were obtained from patients who participated in a randomized controlled trial (NCT01446913) that evaluated the effectiveness of a strategy of diagnosing and treating OSA among patients with acute ischemic stroke and transient ischemic attack. Stroke location was classified by brain imaging reports into subdivisions of lobes, subcortical areas, brainstem, cerebellum, and vascular territory. The association between acute stroke location and polysomnographic findings was evaluated using logistic regression for OSA presence and negative binomial regression for AHI. Results: Among 73 patients with complete polysomnography and stroke location data, 58 (79%) had OSA. In unadjusted models, no stroke location variable was associated with the prevalence or severity of OSA. Similarly, in multivariable modeling, groupings of stroke location were also not associated with OSA presence. Conclusions: These results indicate that OSA is present in the majority of stroke patients and imply that stroke location cannot be used to identify a group with higher risk of OSA. The results also suggest that OSA likely predated the stroke. Given this high overall prevalence, strong consideration should be given to obtaining polysomnography for all ischemic stroke patients
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