Modeling the Emergence of Whisker Direction Maps in Rat Barrel Cortex

Based on measuring responses to rat whiskers as they are mechanically stimulated, one recent study suggests that barrel-related areas in layer 2/3 rat primary somatosensory cortex (S1) contain a pinwheel map of whisker motion directions. Because this map is reminiscent of topographic organization for visual direction in primary visual cortex (V1) of higher mammals, we asked whether the S1 pinwheels could be explained by an input-driven developmental process as is often suggested for V1. We developed a computational model to capture how whisker stimuli are conveyed to supragranular S1, and simulate lateral cortical interactions using an established self-organizing algorithm. Inputs to the model each represent the deflection of a subset of 25 whiskers as they are contacted by a moving stimulus object. The subset of deflected whiskers corresponds with the shape of the stimulus, and the deflection direction corresponds with the movement direction of the stimulus. If these two features of the inputs are correlated during the training of the model, a somatotopically aligned map of direction emerges for each whisker in S1. Predictions of the model that are immediately testable include (1) that somatotopic pinwheel maps of whisker direction exist in adult layer 2/3 barrel cortex for every large whisker on the rat's face, even peripheral whiskers; and (2) in the adult, neurons with similar directional tuning are interconnected by a network of horizontal connections, spanning distances of many whisker representations. We also propose specific experiments for testing the predictions of the model by manipulating patterns of whisker inputs experienced during early development. The results suggest that similar intracortical mechanisms guide the development of primate V1 and rat S1

VLA/Realfast Detection of a Burst from FRB 180916.J0158+65 and Tests for Periodic Activity

We report on the detection of a burst from FRB 180916 by realfast/Very Large Array and present software for interpreting fast radio bursts (FRB) periodicity. We demonstrate a range of periodicity analyses with bursts from FRB 180916, FRB 121102 and FRB 180814. Our results for FRB 180916 and FRB 121102 are consistent with published results. For FRB 180814, we did not detect any significant periodic episodes. The realfast-detected and other high-frequency bursts for FRB 180916 tend to lie at the beginning of the activity window, indicating a possible phase-frequency relation. The python package frbpa can be used to reproduce and expand on this analysis to test models for repeating FRBs

VLA/Realfast Detection of a Burst from FRB180916.J0158+65 and Tests for Periodic Activity

We report on the detection of a burst from FRB180916 by realfast/VLA and present software for interpreting fast radio bursts (FRB) periodicity. We demonstrate a range of periodicity analyses with bursts from FRB180916, FRB121102 and FRB180814. Our results for FRB180916 and FRB121102 are consistent with published results. For FRB180814, we did not detect any significant periodic episodes. The realfast-detected and other high-frequency bursts for FRB180916 tend to lie at the beginning of the activity window, indicating a possible phase-frequency relation. The python package $\texttt{frbpa}$ can be used to reproduce and expand on this analysis to test models for repeating FRBs.Comment: Published in Research Notes of the AA

Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures

Aspergillus fumigatus is a filamentous fungus that produces abundant pigmented conidia. Several fungal components have been identified as virulence factors, including melanin; however, the impact of these factors in a repeated exposure model resembling natural environmental exposures remains unknown. This study examined the role of fungal melanin in the stimulation of pulmonary immune responses using immunocompetent BALB/c mice in a multiple exposure model. It compared conidia from wild-type A. fumigatus to two melanin mutants of the same strain, Δarp2 (tan) or Δalb1 (white). Mass spectrometry-based analysis of conidial extracts demonstrated that there was little difference in the protein fingerprint profiles between the three strains. Field emission scanning electron microscopy demonstrated that the immunologically inert Rodlet A layer remained intact in melanin-deficient conidia. Thus, the primary difference between the strains was the extent of melanization. Histopathology indicated that each A. fumigatus strain induced lung inflammation, regardless of the extent of melanization. In mice exposed to Δalb1 conidia, an increase in airway eosinophils and a decrease in neutrophils and CD8(+) IL-17(+) (Tc17) cells were observed. Additionally, it was shown that melanin mutant conidia were more rapidly cleared from the lungs than wild-type conidia. These data suggest that the presence of fungal melanin may modulate the pulmonary immune response in a mouse model of repeated exposures to A. fumigatus conidia

Sites of vulnerability in HCV E1E2 identified by comprehensive functional screening

The E1 and E2 envelope proteins of hepatitis C virus (HCV) form a heterodimer that drives virus-host membrane fusion. Here, we analyze the role of each amino acid in E1E2 function, expressing 545 individual alanine mutants of E1E2 in human cells, incorporating them into infectious viral pseudoparticles, and testing them against 37 different monoclonal antibodies (MAbs) to ascertain full-length translation, folding, heterodimer assembly, CD81 binding, viral pseudoparticle incorporation, and infectivity. We propose a model describing the role of each critical residue in E1E2 functionality and use it to examine how MAbs neutralize infection by exploiting functionally critical sites of vulnerability on E1E2. Our results suggest that E1E2 is a surprisingly fragile protein complex where even a single alanine mutation at 92% of positions disrupts its function. The amino-acid-level targets identified are highly conserved and functionally critical and can be exploited for improved therapies and vaccines

Critical adsorption on curved objects

A systematic fieldtheoretic description of critical adsorption on curved objects such as spherical or rodlike colloidal particles immersed in a fluid near criticality is presented. The temperature dependence of the corresponding order parameter profiles and of the excess adsorption are calculated explicitly. Critical adsorption on elongated rods is substantially more pronounced than on spherical particles. It turns out that, within the context of critical phenomena in confined geometries, critical adsorption on a microscopically thin `needle' represents a distinct universality class of its own. Under favorable conditions the results are relevant for the flocculation of colloidal particles.Comment: 52 pages, 10 figure

A new mild hyperthermia device to treat vascular involvement in cancer surgery

Abstract Surgical margin status in cancer surgery represents an important oncologic parameter affecting overall prognosis. The risk of disease recurrence is minimized and survival often prolonged if margin-negative resection can be accomplished during cancer surgery. Unfortunately, negative margins are not always surgically achievable due to tumor invasion into adjacent tissues or involvement of critical vasculature. Herein, we present a novel intra-operative device created to facilitate a uniform and mild heating profile to cause hyperthermic destruction of vessel-encasing tumors while safeguarding the encased vessel. We use pancreatic ductal adenocarcinoma as an in vitro and an in vivo cancer model for these studies as it is a representative model of a tumor that commonly involves major mesenteric vessels. In vitro data suggests that mild hyperthermia (41–46 °C for ten minutes) is an optimal thermal dose to induce high levels of cancer cell death, alter cancer cell’s proteomic profiles and eliminate cancer stem cells while preserving non-malignant cells. In vivo and in silico data supports the well-known phenomena of a vascular heat sink effect that causes high temperature differentials through tissues undergoing hyperthermia, however temperatures can be predicted and used as a tool for the surgeon to adjust thermal doses delivered for various tumor margins

Cardiorespiratory fitness is associated with physical literacy in a large sample of Canadian children aged 8 to 12 years

Background The associations between cardiorespiratory fitness (CRF) and physical literacy in children are largely unknown. The aim of this study was to assess the relationships between CRF, measured using the 20-m shuttle run test (20mSRT), and components of physical literacy among Canadian children aged 8–12 years. Methods A total of 9393 (49.9% girls) children, with a mean (SD) age of 10.1 (±1.2) years, from a cross-sectional surveillance study were included for this analysis. The SRT was evaluated using a standardized 15 m or 20 m protocol. All 15 m SRTs were converted to 20mSRT values using a standardized formula. The four domains of physical literacy (Physical Competence, Daily Behaviour, Motivation and Confidence, and Knowledge and Understanding) were measured using the Canadian Assessment of Physical Literacy. Tertiles were identified for 20mSRT laps, representing low, medium, and high CRF for each age and gender group. Cohen’s d was used to calculate the effect size between the low and high CRF groups. Results CRF was strongly and favourably associated with all components of physical literacy among school-aged Canadian children. The effect size between low and high CRF tertile groups was large for the Physical Competence domain (Cohen’s d range: 1.11–1.94) across age and gender groups, followed by moderate to large effect sizes for Motivation and Confidence (Cohen’s d range: 0.54–1.18), small to moderate effect sizes for Daily Behaviour (Cohen’s d range: 0.25–0.81), and marginal to moderate effect sizes for Knowledge and Understanding (Cohen’s d range: 0.08–0.70). Conclusions This study identified strong favourable associations between CRF and physical literacy and its constituent components in children aged 8–12 years. Future research should investigate the sensitivity and specificity of the 20mSRT in screening those with low physical literacy levels