Temperature Profile Of the Brain During Suspended Animation

In most cases of serious truncal injuries, cardiac arrest occurs within minutes due the severe blood loss. Although many of these injuries are potentially repairable, death is often resulted from fatal brain damage due to insufficient supply of blood. Suspended animation (SA) is a way to preserve the whole organism by lowering brain temperature during prolonged cardiac arrest (often over one hour). A hypothermic flush of cold saline solution is administered through blood vessels to the brain. By lowering the rate of cerebral metabolic activity, damage to the brain is reduced and the brain can be preserved for later cerebral resuscitation. Current studies have focused on animals but no experiment has been implemented on humans yet. In our project, we use GAMBIT and FIDAP to model the temperature profile of the brain during suspended animation. A suitable model of saline flow through blood vessels in the brain is developed to determine how temperature in the outer brain region changes at any given time. From our model, the temperature in the outer brain quickly drops to 8?C after flushing a saline solution of 4?C. While saline is very effective in reducing outer brain temperature, the decrease in brain temperature can be adjusted by using saline solutions of different temperatures

Directionality in translator training. Contrastive evaluation of L1 and L2 translations using the PIE method (Preselected Items Evaluation) and the ATA Framework for Standardized Error Marking

This paper illustrates the results of an experiment conducted in translator training in which thirty students translated a text from their L1 (Dutch) into their L2 (English). The students completed a questionnaire on their acquisition of the L1, the perceived difficulty of each translation direction and the main difficulties encountered. The translations were analysed and scored by means of PIE (Preselected Items Evaluation), and the errors identified were categorised using the error categories of the ATA Framework for Standardized Error Marking. While the students scored slightly higher into their L2, the scores and main error categories were similar in the two translation directions. The students whose L1 is not Dutch obtained similar scores to those whose L1 is Dutch. The students’ perceived main difficulties were confirmed in the error categorisation. Finally, the perceived overall difficulty was higher than the item difficulty measured by means of PIE

Poly(sulfur-random-(1,3-diisopropenylbenzene)) Based Mid-Wavelength Infrared Polarizer: Optical Property Experimental and Theoretical Analysis

Development of polymer based mid-wavelength infrared (MWIR) optics has been limited mainly due to high optical loss of organic polymers used in general optical components. In this study, a MWIR polarization grating based on a sulfuric polymer poly(sulfur-random-(1,3-diisopropenylbenzene)) with a low loss in the MWIR range was fabricated using a simple two-step process: imprint and metal deposition. Fourier-transform infrared (FTIR) spectroscopy measurement showed that this polymeric MWIR polarizer selectively transmitted the polarized IR in transverse magnetic (TM) mode over the transverse electric (TE) mode at normal incidence. The measured extinction ratios (  = The ratio of transmissions in TM and TE) were 208, 176, and 212 at the wavelength of 3, 4, and 5 μm, respectively. The computational simulation and analytical model confirmed that the enhanced TM transmission efficiency and followed a Fabry-Pérot (FP) resonance mode within the created sulfuric polymer film. This polymeric MWIR polarizer demonstrated a great potential for broader applications in IR photonics to realize low-cost and durable optical components

Negative correlation of single-cell PAX3:FOXO1 expression with tumorigenicity in rhabdomyosarcoma

Rhabdomyosarcomas (RMS) are phenotypically and functionally heterogeneous. Both primary human RMS cultures and low-passage Myf6Cre,Pax3:Foxo1,p53 mouse RMS cell lines, which express the fusion oncoprotein Pax3:Foxo1 and lack the tumor suppressor Tp53 (Myf6Cre,Pax3:Foxo1,p53), exhibit marked heterogeneity in PAX3:FOXO1 (P3F) expression at the single cell level. In mouse RMS cells, P3F expression is directed by the Pax3 promoter and coupled to eYFP. YFPlow/P3Flow mouse RMS cells included 87% G0/G1 cells and reorganized their actin cytoskeleton to produce a cellular phenotype characterized by more efficient adhesion and migration. This translated into higher tumor-propagating cell frequencies of YFPlow/P3Flow compared with YFPhigh/P3Fhigh cells. Both YFPlow/P3Flow and YFPhigh/P3Fhigh cells gave rise to mixed clones in vitro, consistent with fluctuations in P3F expression over time. Exposure to the anti-tropomyosin compound TR100 disrupted the cytoskeleton and reversed enhanced migration and adhesion of YFPlow/P3Flow RMS cells. Heterogeneous expression of PAX3:FOXO1 at the single cell level may provide a critical advantage during tumor progression

Sox2 Cooperates with Inflammation-Mediated Stat3 Activation in the Malignant Transformation of Foregut Basal Progenitor Cells

SummarySox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment-activated Stat3 is required for Sox2-driven tumorigenesis

Constraining emissions of volatile organic compounds from western US wildfires with WE-CAN and FIREX-AQ airborne observations

The impact of biomass burning (BB) on the atmospheric burden of volatile organic compounds (VOCs) is highly uncertain. Here we apply the GEOS-Chem chemical transport model (CTM) to constrain BB emissions in the western US at ~25 km resolution. Across three BB emission inventories widely used in CTMs, the total of 14 modeled BB VOC emissions in the western US agree with each other within 30&ndash;40 %. However, emissions for individual VOC differ by up to a factor of 5 (i.e., lumped &ge; C4 alkanes), driven by the regionally averaged emission ratios (ERs) among inventories. We further evaluate GEOS-Chem simulations with aircraft observations made during WE-CAN (Western Wildfire Experiment for Cloud Chemistry, Aerosol Absorption, and Nitrogen) and FIREX-AQ (Fire Influence on Regional to Global Environments and Air Quality) field campaigns. Despite being driven by different global BB inventories or applying various injection height assumptions, GEOS-Chem simulations underpredict observed vertical profiles by a factor of 3&ndash;7. The model shows small-to-no bias for most species in low/no smoke conditions. We thus attribute the negative model biases mostly to underestimated BB emissions in these inventories. Tripling BB emissions in the model reproduces observed vertical profiles for primary compounds, i.e., CO, propane, benzene, and toluene. However, it shows no-to-less significant improvements for oxygenated VOCs, particularly formaldehyde, formic acid, acetic acid, and lumped &ge; C3 aldehydes, suggesting the model is missing secondary sources of these compounds in BB-impacted environments. The underestimation of primary BB emissions in inventories is likely attributable to underpredicted amounts of effective dry matter burned, rather than errors in fire detection, injection height, or ERs. We cannot rule out potential sub-grid uncertainties (i.e., not being able to fully resolve fire plumes) in the nested GEOS-Chem which could explain the model negative bias partially, though the back-of-the-envelope calculation and evaluation using longer-term ground measurements help increase the argument of the dry matter burned underestimation. The ERs of the 14 BB VOCs implemented in GEOS-Chem account for about half of the total 161 measured VOCs (~75 versus 150 ppb ppm-1). This reveals a significant amount of missing reactive organic carbon in widely-used BB emission inventories. Considering both uncertainties in effective dry matter burned and unmodeled VOCs, we infer that BB contributed up to 10 % in 2019 and 45 % in 2018 (240 and 2040 GgC) of the total VOC primary emission flux in the western US during these two fire seasons, compared to only 1&ndash;10 % in the standard GEOS-Chem.</p

Independent optical excitation of distinct neural populations

Optogenetic tools enable examination of how specific cell types contribute to brain circuit functions. A long-standing question is whether it is possible to independently activate two distinct neural populations in mammalian brain tissue. Such a capability would enable the study of how different synapses or pathways interact to encode information in the brain. Here we describe two channelrhodopsins, Chronos and Chrimson, discovered through sequencing and physiological characterization of opsins from over 100 species of alga. Chrimson's excitation spectrum is red shifted by 45 nm relative to previous channelrhodopsins and can enable experiments in which red light is preferred. We show minimal visual system–mediated behavioral interference when using Chrimson in neurobehavioral studies in Drosophila melanogaster. Chronos has faster kinetics than previous channelrhodopsins yet is effectively more light sensitive. Together these two reagents enable two-color activation of neural spiking and downstream synaptic transmission in independent neural populations without detectable cross-talk in mouse brain slice.PostprintPeer reviewe

Evaluation of medical student self-rated preparedness to care for limited english proficiency patients

<p>Abstract</p> <p>Background</p> <p>Patients with limited English proficiency (LEP) represent a growing proportion of the US population and are at risk of receiving suboptimal care due to difficulty communicating with healthcare providers who do not speak their language. Medical school curricula are required to prepare students to care for all patients, including those with LEP, but little is known about how well they achieve this goal. We used data from a survey of medical students' cross-cultural preparedness, skills, and training to specifically explore their self-rated preparedness to care for LEP patients.</p> <p>Methods</p> <p>We electronically surveyed students at one northeastern US medical school. We used bivariate analyses to identify factors associated with student self-rated preparedness to care for LEP patients including gender, training year, first language, race/ethnicity, percent LEP and minority patients seen, and skill with interpreters. We used multivariate logistic regression to examine the independent effect of each factor on LEP preparedness. In a secondary analysis, we explored the association between year in medical school and self-perceived skill level in working with an interpreter.</p> <p>Results</p> <p>Of 651 students, 416 completed questionnaires (63.9% response rate). Twenty percent of medical students reported being very well or well-prepared to care for LEP patients. Of these, 40% were in their fourth year of training. Skill level working with interpreters, prevalence of LEP patients seen, and training year were correlated (p < 0.001) with LEP preparedness. Using multivariate logistic regression, only student race/ethnicity and self-rated skill with interpreters remained statistically significant. Students in third and fourth years were more likely to feel skilled with interpreters (p < 0.001).</p> <p>Conclusions</p> <p>Increasingly, medical students will need to be prepared to care for LEP patients. Our study supports two strategies to improve student preparedness: training students to work effectively with interpreters and increasing student diversity to better reflect the changing US demographics.</p

Increased Memory Conversion of Naïve CD8 T Cells Activated during Late Phases of Acute Virus Infection Due to Decreased Cumulative Antigen Exposure

Background: Memory CD8 T cells form an essential part of protective immunity against viral infections. Antigenic load, costimulation, CD4-help, cytokines and chemokines fluctuate during the course of an antiviral immune response thus affecting CD8 T cell activation and memory conversion. Methodology/Principal Findings: In the present study, naïve TCR transgenic LCMV-specific P14 CD8 T cells engaged at a late stage during the acute antiviral LCMV response showed reduced expansion kinetics but greater memory conversion in the spleen. Such late activated cells displayed a memory precursor effector phenotype already at the peak of the systemic antiviral response, suggesting that the environment determined their fate during antigen encounter. In the spleen, the majority of late transferred cells exhibited a central memory phenotype compared to the effector memory displayed by the early transferred cells. Increasing the inflammatory response by exogenous administration of IFNc, PolyI:C or CpG did not affect memory conversion in the late transferred group, suggesting that the diverging antigen load early versus later during acute infection had determined their fate. In agreement, reduction in the LCMV antigenic load after ribavirin treatment enhanced the contribution of early transferred cells to the long lasting memory pool. Conclusions/Significance: Our results show that naïve CD8 cells, exposed to reduced duration or concentration of antigen during viral infection convert into memory more efficiently, an observation that could have significant implications fo