Genetic analysis of posterior medial barrel subfield (PMBSF) size in somatosensory cortex (SI) in recombinant inbred strains of mice

<p>Abstract</p> <p>Background</p> <p>Quantitative trait locus (QTL) mapping is an important tool for identifying potential candidate genes linked to complex traits. QTL mapping has been used to identify genes associated with cytoarchitecture, cell number, brain size, and brain volume. Previously, QTL mapping was utilized to examine variation of barrel field size in the somatosensory cortex in a limited number of recombinant inbred (RI) strains of mice. In order to further elucidate the underlying natural variation in mouse primary somatosensory cortex, we measured the size of the posterior medial barrel subfield (PMBSF), associated with the representation of the large mystacial vibrissae, in an expanded sample set that included 42 BXD RI strains, two parental strains (C57BL/6J and DBA/2J), and one F1 strain (B6D2F1). Cytochrome oxidase labeling was used to visualize barrels within the PMBSF.</p> <p>Results</p> <p>We observed a 33% difference between the largest and smallest BXD RI strains with continuous variation in-between. Using QTL linkage analysis from WebQTL, we generated linkage maps of raw total PMBSF and brain weight adjusted total PMBSF areas. After removing the effects of brain weight, we detected a suggestive QTL (likelihood ratio statistic [LRS]: 14.20) on the proximal arm of chromosome 4. Candidate genes under the suggestive QTL peak for PMBSF area were selected based on the number of single nucleotide polymorphisms (SNPs) present and the biological relevance of each gene. Among the candidate genes are <it>Car8 </it>and <it>Rab2</it>. More importantly, mRNA expression profiles obtained using GeneNetwork indicated a strong correlation between total PMBSF area and two genes (<it>Adcy1 </it>and <it>Gap43</it>) known to be important in mouse cortex development. GAP43 has been shown to be critical during neurodevelopment of the somatosensory cortex, while knockout <it>Adcy1 </it>mice have disrupted barrel field patterns.</p> <p>Conclusion</p> <p>We detected a novel suggestive QTL on chromosome 4 that is linked to PMBSF size. The present study is an important step towards identifying genes underlying the size and possible development of cortical structures.</p

Enclosing the behavior of a hybrid automaton up to and beyond a Zeno point

Even simple hybrid automata like the classic bouncing ball can exhibit Zeno behavior. The existence of this type of behavior has so far forced a large class of simulators to either ignore some events or risk looping indefinitely. This in turn forces modelers to either insert ad-hoc restrictions to circumvent Zeno behavior or to abandon hybrid automata. To address this problem, we take a fresh look at event detection and localization. A key insight that emerges from this investigation is that an enclosure for a given time interval can be valid independent of the occurrence of a given event. Such an event can then even occur an unbounded number of times. This insight makes it possible to handle some types of Zeno behavior. If the post-Zeno state is defined explicitly in the given model of the hybrid automaton, the computed enclosure covers the corresponding trajectory that starts from the Zeno point through a restarted evolution

Improvement in word recognition following treatment failure for sudden sensorineural hearing loss

AbstractObjectivesPatients with sudden sensorineural hearing loss (SSNHL) may have word recognition scores (WRS) that correlate with pure tone average (PTA). We hypothesize that there is a subset of patients with SSNHL who have improved WRS despite stable PTA.MethodsRetrospective case review at a tertiary otolaryngology practice.ResultsWe identified 13 of 113 patients with SSNHL whose WRS increased despite overall stable pure tone averages. There was an observed average improvement in WRS by 23.8 points in this patient cohort at follow-up, with mean initial PTA in the affected ear at 48.7 dB.ConclusionsWe identify a novel cohort of SSNHL patients that have failed treatment as measured by PTA, but who have increased WRS over time. These data have implications for patient counseling and lend insight into the pathophysiology of SSNHL

Improvement in word recognition following treatment failure for sudden sensorineural hearing loss

Objectives: Patients with sudden sensorineural hearing loss (SSNHL) may have word recognition scores (WRS) that correlate with pure tone average (PTA). We hypothesize that there is a subset of patients with SSNHL who have improved WRS despite stable PTA. Methods: Retrospective case review at a tertiary otolaryngology practice. Results: We identified 13 of 113 patients with SSNHL whose WRS increased despite overall stable pure tone averages. There was an observed average improvement in WRS by 23.8 points in this patient cohort at follow-up, with mean initial PTA in the affected ear at 48.7 dB. Conclusions: We identify a novel cohort of SSNHL patients that have failed treatment as measured by PTA, but who have increased WRS over time. These data have implications for patient counseling and lend insight into the pathophysiology of SSNHL

Project ATLANTA (ATlanta Land-use ANalysis: Temperature and Air quality): A Study of how the Urban Landscape Affects Meteorology and Air Quality Through Time

It is our intent through this investigation to help facilitate measures that can be Project ATLANTA (ATlanta Land-use ANalysis: applied to mitigate climatological or air quality Temperature and Air-quality) is a NASA Earth degradation, or to design alternate measures to sustain Observing System (EOS) Interdisciplinary Science or improve the overall urban environment in the future. investigation that seeks to observe, measure, model, and analyze how the rapid growth of the Atlanta. The primary objectives for this research effort are: 1) To In the last half of the 20th century, Atlanta, investigate and model the relationship between Atlanta Georgia has risen as the premier commercial, urban growth, land cover change, and the development industrial, and transportation urban area of the of the urban heat island phenomenon through time at southeastern United States. The rapid growth of the nested spatial scales from local to regional; 2) To Atlanta area, particularly within the last 25 years, has investigate and model the relationship between Atlanta made Atlanta one of the fastest growing metropolitan urban growth and land cover change on air quality areas in the United States. The population of the through time at nested spatial scales from local to Atlanta metropolitan area increased 27% between 1970 regional; and 3) To model the overall effects of urban and 1980, and 33% between 1980-1990 (Research development on surface energy budget characteristics Atlanta, Inc., 1993). Concomitant with this high rate of across the Atlanta urban landscape through time at population growth, has been an explosive growth in nested spatial scales from local to regional. Our key retail, industrial, commercial, and transportation goal is to derive a better scientific understanding of how services within the Atlanta region. This has resulted in land cover changes associated with urbanization in the tremendous land cover change dynamics within the Atlanta area, principally in transforming forest lands to metropolitan region, wherein urbanization has urban land covers through time, has, and will, effect consumed vast acreas of land adjacent to the city local and regional climate, surface energy flux, and air proper and has pushed the rural/urban fringe farther quality characteristics. Allied with this goal is the and farther away from the original Atlanta urban core. prospect that the results from this research can be An enormous transition of land from forest and applied by urban planners, environmental managers agriculture to urban land uses has occurred in the and other decision-makers, for determining how Atlanta area in the last 25 years, along with subsequent urbanization has impacted the climate and overal

BRAVE-NET: Fully Automated Arterial Brain Vessel Segmentation in Patients With Cerebrovascular Disease

Introduction: Arterial brain vessel assessment is crucial for the diagnostic process in patients with cerebrovascular disease. Non-invasive neuroimaging techniques, such as time-of-flight (TOF) magnetic resonance angiography (MRA) imaging are applied in the clinical routine to depict arteries. They are, however, only visually assessed. Fully automated vessel segmentation integrated into the clinical routine could facilitate the time-critical diagnosis of vessel abnormalities and might facilitate the identification of valuable biomarkers for cerebrovascular events. In the present work, we developed and validated a new deep learning model for vessel segmentation, coined BRAVE-NET, on a large aggregated dataset of patients with cerebrovascular diseases. Methods: BRAVE-NET is a multiscale 3-D convolutional neural network (CNN) model developed on a dataset of 264 patients from three different studies enrolling patients with cerebrovascular diseases. A context path, dually capturing high- and low-resolution volumes, and deep supervision were implemented. The BRAVE-NET model was compared to a baseline Unet model and variants with only context paths and deep supervision, respectively. The models were developed and validated using high-quality manual labels as ground truth. Next to precision and recall, the performance was assessed quantitatively by Dice coefficient (DSC); average Hausdorff distance (AVD); 95-percentile Hausdorff distance (95HD); and via visual qualitative rating. Results: The BRAVE-NET performance surpassed the other models for arterial brain vessel segmentation with a DSC = 0.931, AVD = 0.165, and 95HD = 29.153. The BRAVE-NET model was also the most resistant toward false labelings as revealed by the visual analysis. The performance improvement is primarily attributed to the integration Hilbert et al. Fully-Automated Arterial Brain Vessel Segmentation of the multiscaling context path into the 3-D Unet and to a lesser extent to the deep supervision architectural component. Discussion: We present a new state-of-the-art of arterial brain vessel segmentation tailored to cerebrovascular pathology. We provide an extensive experimental validation of the model using a large aggregated dataset encompassing a large variability of cerebrovascular disease and an external set of healthy volunteers. The framework provides the technological foundation for improving the clinical workflow and can serve as a biomarker extraction tool in cerebrovascular diseases

Acumen : an open-source testbed for cyber-physical systems research

Developing Cyber-Physical Systems requires methods and tools to support simulation and verification of hybrid (both continuous and discrete) models. The Acumen modeling and simulation language is an open source testbed for exploring the design space of what rigorousbut- practical next-generation tools can deliver to developers of Cyber- Physical Systems. Like verification tools, a design goal for Acumen is to provide rigorous results. Like simulation tools, it aims to be intuitive, practical, and scalable. However, it is far from evident whether these two goals can be achieved simultaneously. This paper explains the primary design goals for Acumen, the core challenges that must be addressed in order to achieve these goals, the “agile research method” taken by the project, the steps taken to realize these goals, the key lessons learned, and the emerging language design

Immunomodulatory factors in cervicovaginal secretions from pregnant and non-pregnant women: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Pregnant women are at an increased risk for HIV infection due to unknown biological causes. Given the strong effect of sex-hormones on the expression of immunomuodulatory factors, the central role of mucosal immunity in HIV pathogenesis and the lack of previous studies, we here tested for differences in immunomuodulatory factors in cervico-vaginal secretions between pregnant and non-pregnant women.</p> <p>Methods</p> <p>We compared concentrations of 39 immunomodulatory factors in cervicovaginal lavages (CVL) from 21 pregnant women to those of 24 non-pregnant healthy women from the US. We used Bonferroni correction to correct for multiple testing and linear regression modeling to adjust for possible confounding by plasma cytokine concentration, cervical ectopy, total protein concentration, and other possible confounders. Cervical ectopy was determined by planimetry. Concentration of immunomodulatory factors were measured by a multiplex assay, protein concentration by the Bradford Method.</p> <p>Results</p> <p>Twenty six (66%) of the 39 measured immunomodulatory factors were detectable in at least half of the CVL samples included in the study. Pregnant women had threefold lower CVL concentration of CCL22 (geometric mean: 29.6 pg/ml versus 89.7 pg/ml, p = 0.0011) than non-pregnant women. CVL CCL22 concentration additionally correlated negatively with gestational age (Spearman correlation coefficient [R_S]: -0.49, p = 0.0006). These associations remained significant when corrected for multiple testing.</p> <p>CCL22 concentration in CVL was positively correlated with age and negatively correlated with time since last coitus and the size of cervical ectopy. However, none of these associations could explain the difference of CCL22 concentration between pregnant and non-pregnant women in this study, which remained significant in adjusted analysis.</p> <p>Conclusions</p> <p>In this study population, pregnancy is associated with reduced concentrations of CCL22 in cervicovaginal secretions. The role of CCL22 on HIV transmission should now be investigated in prospective studies.</p