Precision metering of microliter volumes of biological fluids in micro-gravity

Concepts were demonstrated and investigated for transferring accurately known and reproducible microliter volumes of biological fluids from sample container onto dry chemistry slides in microgravity environment. Specific liquid transfer tip designs were compared. Information was obtained for design of a liquid sample handling system to enable clinical chemical analysis in microgravity. Disposable pipet tips and pipet devices that were designed to transfer microliter volumes of biological fluid from a (test tube) sample container in 1-G environment were used during microgravity periods of parabolic trajectories of the KC-135 aircraft. The transfer process was recorded using charge coupled device camera and video cassette equipment. Metering behavior of water, a synthetic aqueous protein solution, and anticoagulated human blood was compared. Transfer of these liquids to 2 substrate materials representative of rapidly wettable and slowly wettable dry chemistry slide surface was compared

The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods

A recent workshop entitled The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods was held in Paris in December 2010, sponsored by the French National Centre for Scientific Research (CNRS) and by the journal Human Biology. This workshop was intended to foster a debate on questions related to the family names and to compare different multidisciplinary approaches involving geneticists, historians, geographers, sociologists and social anthropologists. This collective paper presents a collection of selected communications

Equatorial Pacific pCO2 Interannual Variability in CMIP6 Models

The El Niño-Southern Oscillation (ENSO) in the equatorial Pacific is the dominant mode of global air-sea carbon dioxide (CO2) flux interannual variability (IAV). Air-sea CO2 fluxes are driven by the difference between atmospheric and surface ocean pCO2, with variability of the latter driving flux variability. Previous studies found that models in Coupled Model Intercomparison Project Phase 5 (CMIP5) failed to reproduce the observed ENSO-related pattern of CO2 fluxes and had weak pCO2 IAV, which were explained by both weak upwelling IAV and weak mean vertical dissolved inorganic carbon (DIC) gradients. We assess whether the latest generation of CMIP6 models can reproduce equatorial Pacific pCO2 IAV by validating models against observations-based data products. We decompose pCO2 IAV into thermally and non-thermally driven anomalies to examine the balance between these competing anomalies, which explain the total pCO2 IAV. The majority of CMIP6 models underestimate pCO2 IAV, while they overestimate sea surface temperature IAV. Insufficient compensation of non-thermal pCO2 to thermal pCO2 IAV in models results in weak total pCO2 IAV. We compare the relative strengths of the vertical transport of temperature and DIC and evaluate their contributions to thermal and non-thermal pCO2 anomalies. Model-to-observations-based product comparisons reveal that modeled mean vertical DIC gradients are biased weak relative to their mean vertical temperature gradients, but upwelling acting on these gradients is insufficient to explain the relative magnitudes of thermal and non-thermal pCO2 anomalies

Blood Purification by Non-Selective Hemoadsorption Prevents Death after Traumatic Brain Injury and Hemorrhagic Shock in Rats

Background Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS. Methods Male Sprague Dawley rats were subjected to a combined injury of a controlled cortical impact (CCI) to their brain and pressure-controlled hemorrhagic shock (HS). Animals were subsequently instrumented with an extracorporeal blood circuit that passed through a cartridge for sham or experimental treatment. In experimental animals, the treatment cartridge was filled with proprietary beads (Cytosorbents; Monmouth Junction, NJ) that removed circulating molecules between 5 KDa and 60 KDa. Sham rats had equivalent circulation but no blood purification. Serial blood samples were analyzed with multiplex technology to quantify changes in a trauma-relevant panel of immunologic mediators. The primary outcome was survival to 96hr post-injury. Results HA improved survival from 47% in sham treated rats to 86% in HA treated rats. There were no treatment-related changes in histologic appearance. HA affected biomarker concentrations both during the treatment and over the ensuing four days after injury. Distinct changes in biomarker concentrations were also measured in survivor and non-survivor rats from the entire cohort of rats indicating biomarker patterns associated with survival and death after injury. Conclusions Blood purification by non-selective HA is an effective intervention to prevent death in a combined TBI/HS rat model. HA changed circulating concentrations of multiple inmmunologically active mediators during the treatment time frame and after treatment. HA has been safely implemented in human patients with sepsis and may be a treatment option after injury

Contract Aware Components, 10 years after

The notion of contract aware components has been published roughly ten years ago and is now becoming mainstream in several fields where the usage of software components is seen as critical. The goal of this paper is to survey domains such as Embedded Systems or Service Oriented Architecture where the notion of contract aware components has been influential. For each of these domains we briefly describe what has been done with this idea and we discuss the remaining challenges.Comment: In Proceedings WCSI 2010, arXiv:1010.233

Promiscuous binding of extracellular peptides to cell surface class I MHC protein

Algorithms derived from measurements of short-peptide (8–10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K[superscript b], can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide–MHC complexes that form on cells exposed to extracellular (exogenous) peptides.Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra

Neuroenhancement in Military Personnel::Conceptual and Methodological Promises and Challenges

Military personnel face harsh conditions that strain their physical and mental well-being, depleting resources necessary for sustained operational performance. Future operations will impose even greater demands on soldiers in austere environments with limited support, and new training and technological approaches are essential. This report highlights the progress in cognitive neuroenhancement research, exploring techniques such as neuromodulation and neurofeedback, and emphasizes the inherent challenges and future directions in the field of cognitive neuroenhancement for selection, training, operations, and recovery

The Spectral Energy Distribution of Powerful Starburst Galaxies I : Modelling the Radio Continuum

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2018 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.We have acquired radio-continuum data between 70MHz and 48 GHz for a sample of 19 southern starburst galaxies at moderate redshifts (0.067 < z < 0.227) with the aim of separating synchrotron and free-free emission components. Using a Bayesian framework, we find the radio continuum is rarely characterized well by a single power law, instead often exhibiting lowfrequency turnovers below 500 MHz, steepening at mid to high frequencies, and a flattening at high frequencies where free-free emission begins to dominate over the synchrotron emission. These higher order curvature components may be attributed to free-free absorption across multiple regions of star formation with varying optical depths. The decomposed synchrotron and free-free emission components in our sample of galaxies form strong correlations with the total-infrared bolometric luminosities. Finally, we find that without accounting for free-free absorption with turnovers between 90 and 500MHz the radio continuum at low frequency (v < 200 MHz) could be overestimated by upwards of a factor of 12 if a simple power-law extrapolation is used from higher frequencies. The mean synchrotron spectral index of our sample is constrained to be α = -1.06, which is steeper than the canonical value of -0.8 for normal galaxies. We suggest this may be caused by an intrinsically steeper cosmic ray distribution.Peer reviewe

Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning

Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35–86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65–86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35–54) and middle-aged (aged 55–64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification