Aero-Thermal Calibration of the NASA Glenn Icing Research Tunnel (2004 and 2005 Tests)

A full aero-thermal calibration of the NASA Glenn Icing Research Tunnel was completed in 2004 following the replacement of the inlet guide vanes upstream of the tunnel drive system and improvement to the facility total temperature instrumentation. This calibration test provided data used to fully document the aero-thermal flow quality in the IRT test section and to construct calibration curves for the operation of the IRT. The 2004 test was also the first to use the 2-D RTD array, an improved total temperature calibration measurement platform

Efficacy of Cognitive and Metacognitive Interventions on Executive Functioning Post Traumatic Brain Injury to Enhance Occupational Performance

Cognitive rehabilitation (CR) is proposed as an effective intervention for individuals post Traumatic Brain Injury (TBI), by addressing cognitive function through remediating skills and practicing new compensatory skills. While there is considerable research, including systematic reviews that explore cognitive interventions post TBI, more research is needed in which occupational performance is the primary outcome of cognitive intervention. This current systematic review aims to synthesize the current body of evidence available on how using CR techniques to address executive functioning impact occupational performance in individuals who sustained a mild or moderate TBI

A Needs and Resource Assessment of Continuing Medical Education in Haiti

Background: Haiti has a chronic physician shortage, and the country has been facing an increased disease burden since the 2010 earthquake and the subsequent introduction of cholera. In such resource-challenged settings, access to postgraduate medical education often is limited due to inadequate financial, structural, and academic resources. A crucial component to improved health in Haiti is the expansion of continuing medical education (CME). To our knowledge there have been no previous studies investigating the continuing professional development needs of Haitian physicians working in this context. Objective: The objectives of this study are to describe the educational resources available to Haitian physicians and to understand their continuing professional development needs. Methods: We performed a needs and resource assessment of CME available to Haitian physicians using surveys and focus groups. We surveyed 62 physicians and led 3 focus groups. Questions gathered data on physicians’ access to educational resources. Descriptive statistics were calculated from surveys, and focus group transcripts were manually reviewed for themes. Findings: In all, 82 conference attendees were invited to participate. Of these, 62 physicians completed the needs and resource assessment survey. Of the participants, 16% had a medical library at work and 31% had access to a computer at work. Educational conferences were available at work for 27% of participants, and 50% attended conferences outside of work. Less than half (45%) identified a clinical mentor. Focus group participants described inadequate tangible and reference resources, lack of colleague support, and lack of avenues for specialty training and employment. Conclusions: In this needs assessment, Haitian physicians identified lack of support for clinical decision making, poor access to CME activities, limited professional development, and absence of employment opportunities as key areas of need in support of their clinical and professional work

FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Smith, J. A., Curry, E. G., Blue, R. E., Roden, C., Dundon, S. E. R., Rodríguez-Vargas, A., Jordan, D. C., Chen, X., Lyons, S. M., Crutchley, J., Anderson, P., Horb, M. E., Gladfelter, A. S., & Giudice, J. FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells. Journal of Cell Biology, 219(4), (2020): e201911129, doi: 10.1083/jcb.201911129.Fragile-X mental retardation autosomal homologue-1 (FXR1) is a muscle-enriched RNA-binding protein. FXR1 depletion is perinatally lethal in mice, Xenopus, and zebrafish; however, the mechanisms driving these phenotypes remain unclear. The FXR1 gene undergoes alternative splicing, producing multiple protein isoforms and mis-splicing has been implicated in disease. Furthermore, mutations that cause frameshifts in muscle-specific isoforms result in congenital multi-minicore myopathy. We observed that FXR1 alternative splicing is pronounced in the serine- and arginine-rich intrinsically disordered domain; these domains are known to promote biomolecular condensation. Here, we show that tissue-specific splicing of fxr1 is required for Xenopus development and alters the disordered domain of FXR1. FXR1 isoforms vary in the formation of RNA-dependent biomolecular condensates in cells and in vitro. This work shows that regulation of tissue-specific splicing can influence FXR1 condensates in muscle development and how mis-splicing promotes disease.We thank the A.S. Gladfelter and J. Giudice laboratories, Nancy Kedersha, and Silvia Ramos for critical discussions; Eunice Y. Lee for technical help; Dr. Stephanie Gupton (University of North Carolina at Chapel Hill, Chapel Hill, NC) for donation of WT C57BL/6J mouse embryos; and Marcin Wlizla and National Xenopus Resource (RRID:SCR_013731) for their help in maintaining adult frogs and other important technical support. This work has been funded by a University of North Carolina at Chapel Hill Junior Faculty Development Award (to J. Giudice); a Nutrition and Obesity Research Center, University of North Carolina at Chapel Hill, Pilot & Feasibility Research grant (P30DK056350 to J. Giudice); University of North Carolina at Chapel Hill startup funds (to J. Giudice); the March of Dimes Foundation (5-FY18-36, Basil O’Connor Starter Scholar Award to J. Giudice); and NCTraCs Pilot Grant (550KR181805) from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002489 (to J. Giudice), National Institutes of Health National Institute of General Medical Sciences grants (R01-GM130866 to J. Giudice, R01-GM081506 to A.S. Gladfelter, R35-GM126901 to P. Anderson, K99-GM124458 to S.M. Lyons, R25-GM089569 and 2R25-GM055336-20 to E.G. Curry); Howard Hughes Medical Institute Faculty Scholars program (A.S. Gladfelter), and National Institute of Health grants R01-HD084409 and P40-OD010997 (to M.E. Horb). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.2020-09-1

HES1 in immunity and cancer

Hairy and enhancer of split homolog-1 (HES1) is a part of an extensive family of basic helix-loop-helix (bHLH) proteins and plays a crucial role in the control and regulation of cell cycle, proliferation, cell differentiation, survival and apoptosis in neuronal, endocrine, T-lymphocyte progenitors as well as various cancers. HES1 is a transcription factor which is regulated by the NOTCH, Hedgehog and Wnt signalling pathways. Aberrant expression of these pathways is a common feature of cancerous cells. There appears to be a fine and complicated crosstalk at the molecular level between the various signalling pathways and HES1, which contributes to its effects on the immune response and cancers such as leukaemia. Several mechanisms have been proposed, including an enhanced invasiveness and metastasis by inducing epithelial mesenchymal transition (EMT), in addition to its strict requirement for tumour cell survival. In this review, we summarize the current biology and molecular mechanisms as well as its use as a clinical target in cancer therapeutics

Temperature calibration of Mg/Ca ratios in the intermediate water benthic foraminifer Hyalinea balthica

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 12 (2011): Q04003, doi:10.1029/2010GC003333.Core top samples from Indonesian and northeast Atlantic depth transects were used to calibrate Mg/Ca and δ18O in tests of the calcitic benthic foraminifer Hyalinea balthica to bottom water temperature between 4°C and 13°C. This shallow infaunal species is primarily abundant in neritic to upper bathyal sediments (<600 m). Both linear and exponential calibrations suggest a temperature sensitivity of ~12% per °C that is ~4 times higher than observed in other species of deep-sea benthic foraminifera. Culture experiments support the core top calibration. We find no discernible effect of salinity and saturation on Mg/Ca. Comparison between the measured benthic foraminiferal δ18O and predicted equilibrium values suggests that on average H. balthica δ18O is 0.64‰ ± 0.13‰ lower than predicted from the equilibrium composition. To test the reliability of using paired H. balthica Mg/Ca and δ18O measurements for reconstructing seawater δ18Osw and salinity, we apply this calibration to another depth transect from Cape Ghir off NW Africa, which was not included in the calibration. Based on error analysis of the calibration data and this validation test, we show that the uncertainty of reconstructing bottom water temperature and salinity from paired Mg/Ca and δ18O measurements of H. balthica is better than ±0.7°C and ±0.69 practical salinity scale, respectively. The small uncertainties allow for the reconstruction of seawater density to better than 0.3σθ units, which is precise enough for the identification of specific water masses and reconstruction of changes in their properties. We propose that the relatively high Mg content and temperature sensitivity of H. balthica might be due to minor, biologically mediated contribution of high-Mg calcite to the primarily low Mg calcite test, which is influenced by the ambient temperature. This hypothesis, if correct, suggests that benthic species with relatively high Mg/Ca may be better suited for deepwater temperature reconstructions than species that have thus far been more commonly used.This project was funded by NSF Awards OCE 02‐20922 and 09‐02977 to YR, OCE 09‐28607 to MK, OCE02‐20776 to DWO, and DFG priority program INTERDYNAMIK to AM

Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management

Fetal Demise and Failed Antibody Therapy During Zika Virus Infection of Pregnant Macaques

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management

International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended