A modular, programmable measurement system for physiological and spaceflight applications

The NASA-Ames Sensors 2000! Program has developed a small, compact, modular, programmable, sensor signal conditioning and measurement system, initially targeted for Life Sciences Spaceflight Programs. The system consists of a twelve-slot, multi-layer, distributed function backplane, a digital microcontroller/memory subsystem, conditioned and isolated power supplies, and six application-specific, physiological signal conditioners. Each signal condition is capable of being programmed for gains, offsets, calibration and operate modes, and, in some cases, selectable outputs and functional modes. Presently, the system has the capability for measuring ECG, EMG, EEG, Temperature, Respiration, Pressure, Force, and Acceleration parameters, in physiological ranges. The measurement system makes heavy use of surface-mount packaging technology, resulting in plug in modules sized 125x55 mm. The complete 12-slot system is contained within a volume of 220x150x70mm. The system's capabilities extend well beyond the specific objectives of NASA programs. Indeed, the potential commercial uses of the technology are virtually limitless. In addition to applications in medical and biomedical sensing, the system might also be used in process control situations, in clinical or research environments, in general instrumentation systems, factory processing, or any other applications where high quality measurements are required

Is there Really a When-Issued Premium?

We use a unique set of equities in the when-issued market to provide new tests of the law of one price in financial markets. We compare the prices of when-issued and regular-way shares of publicly-traded subsidiaries and their parents around the time the subsidiaries are fully divested. In contrast to prior analyses of when-issued trading in equity markets, we find that the when-issued shares of the subsidiary trade at a discount. Some of the pricing differences stem from measurement factors such as exchange location and bid-ask clustering that bias the observed when-issued pricing differential away from zero. The remaining difference between the when-issued and regular-way prices is due to asymmetric movements in bid and ask quotes in the two markets. We also find evidence of temporary price pressures on the date of execution of the spinoff of the subsidiary firms that bear resemblance to the pricing in the when-issued market. We interpret the evidence as consistent with the law of one price in the presence of transaction costs.Law of One Price; Market Efficiency; Market Microstructure

First results of the XI Groups Project: Studying an unbiased sample of galaxy groups

X-ray observations of hot, intergalactic gas in galaxy groups provide a useful means of characterizing the global properties of groups. However, X-ray studies of large group samples have typically involved very shallow X-ray exposures or have been based on rather heterogeneous samples. Here we present the first results of the XI (XMM/IMACS) Groups Project, a study targeting, for the first time, a redshift-selected, statistically unbiased sample of galaxy groups using deep X-ray data. Combining this with radio observations of cold gas and optical imaging and spectroscopy of the galaxy population, the project aims to advance the understanding of how the properties and dynamics of group galaxies relate to global group properties. Here, X-ray and optical data of the first four galaxy groups observed as part of the project are presented. In two of the groups we detect diffuse emission with a luminosity of L_X ~ 10^41 erg/s, among the lowest found for any X-ray detected group thus far, with a comparable upper limit for the other two. Compared to typical X-ray selected groups of similar velocity dispersion, these four systems are all surprisingly X-ray faint. We discuss possible explanations for the lack of significant X-ray emission in the groups, concluding that these systems are most likely collapsing for the first time. Our results strongly suggest that, unlike our current optically selected sample, previous X-ray selected group samples represented a biased picture of the group population. This underlines the necessity of a study of this kind, if one is to reach an unbiased census of the properties of galaxy groups and the distribution of baryons in the Universe.Comment: 14 pages, 8 figures, accepted for publication in MNRA

Perceptual fluency can be used as a cue for categorization decisions.

Learning in the prototype distortion task is thought to involve perceptual learning in which category members experience an enhanced visual response (Ashby & Maddox. Annual Review of Psychology, 56, 149-178, 2005). This response likely leads to more-efficient processing, which in turn may result in a feeling of perceptual fluency for category members. We examined the perceptual-fluency hypothesis by manipulating fluency independently from category membership. We predicted that when perceptual fluency was induced using subliminal priming, this fluency would be misattributed to category membership and would affect categorization decisions. In a prototype distortion task, the participants were more likely to judge stimuli that were not members of the category as category members when the nonmembers were made perceptually fluent with a matching subliminal prime. This result suggests that perceptual fluency can be used as a cue during some categorization decisions. In addition, the results provided converging evidence that some types of categorization are based on perceptual learning

Continuous executive function disruption interferes with application of an information integration categorization strategy.

Category learning is often characterized as being supported by two separate learning systems. A verbal system learns rule-defined (RD) categories that can be described using a verbal rule and relies on executive functions (EFs) to learn via hypothesis testing. A nonverbal system learns non-rule-defined (NRD) categories that cannot be described by a verbal rule and uses automatic, procedural learning. The verbal system is dominant in that adults tend to use it during initial learning but may switch to the nonverbal system when the verbal system is unsuccessful. The nonverbal system has traditionally been thought to operate independently of EFs, but recent studies suggest that EFs may play a role in the nonverbal system-specifically, to facilitate the transition away from the verbal system. Accordingly, continuously interfering with EFs during the categorization process, so that EFs are never fully available to facilitate the transition, may be more detrimental to the nonverbal system than is temporary EF interference. Participants learned an NRD or an RD category while EFs were untaxed, taxed temporarily, or taxed continuously. When EFs were continuously taxed during NRD categorization, participants were less likely to use a nonverbal categorization strategy than when EFs were temporarily taxed, suggesting that when EFs were unavailable, the transition to the nonverbal system was hindered. For the verbal system, temporary and continuous interference had similar effects on categorization performance and on strategy use, illustrating that EFs play an important but different role in each of the category-learning systems

The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

Immune drug discovery from venoms

This review catalogues recent advances in knowledge on venoms as standalone therapeutic agents or as blueprints for drug design, with an emphasis on venom-derived compounds that affects the immune system. We discuss venoms and venom-derived compounds that affect total immune cell numbers, immune cell proliferation, immune cell migration, immune cell phenotype and cytokine secretion. Identifying novel compounds that 'tune' the system, up-regulating the immune response during infectious disease and cancer and down-regulating the immune response during autoimmunity, will greatly expand the tool kit of human immunotherapeutics. Targeting these pathways may also open therapeutic options that alleviate symptoms of envenomation. Finally, combining recent advances in venomics with progress in low cost, high-throughput screening platforms will no doubt yield hundreds of prototype immune modulating compounds in the coming years

A high-resolution mass spectrometry based proteomic dataset of human regulatory T cells

Regulatory T cells (Tregs) play a core role in maintaining immune tolerance, homeostasis, and host health. High-resolution analysis of the Treg proteome is required to identify enriched biological processes and pathways distinct to this important immune cell lineage. We present a comprehensive proteomic dataset of Tregs paired with conventional CD4+ (Conv CD4+) T cells in healthy individuals. Tregs and Conv CD4+ T cells were sorted to high purity using dual magnetic bead-based and flow cytometry-based methodologies. Proteins were trypsin-digested and analysed using label-free data-dependent acquisition mass spectrometry (DDA-MS) followed by label free quantitation (LFQ) proteomics analysis using MaxQuant software. Approximately 4,000 T cell proteins were identified with a 1% false discovery rate, of which approximately 2,800 proteins were consistently identified and quantified in all the samples. Finally, flow cytometry with a monoclonal antibody was used to validate the elevated abundance of the protein phosphatase CD148 in Tregs. This proteomic dataset serves as a reference point for future mechanistic and clinical T cell immunology and identifies receptors, processes, and pathways distinct to Tregs. Collectively, these data will lead to a better understanding of Treg immunophysiology and potentially reveal novel leads for therapeutics seeking Treg regulation

Dual molecular mechanisms govern escape at immunodominant HLA A2-restricted HIV epitope

Serial accumulation of mutations to fixation in the SLYNTVATL (SL9) immunodominant, HIV p17 Gag-derived, HLA A2-restricted CTL epitope produce the SLFNTIAVL triple mutant ‘ultimate’ escape variant. These mutations in solvent-exposed residues are believed to interfere with TCR recognition, although confirmation has awaited structural verification. Here, we solved a TCR co-complex structure with SL9 and the triple escape mutant to determine the mechanism of immune escape in this eminent system. We show that, in contrast to prevailing hypotheses, the main TCR contact residue is 4N and the dominant mechanism of escape is not via lack of TCR engagement. Instead, mutation of solvent exposed residues in the peptide destabilize the peptide-HLA and reduce peptide density at the cell surface. These results highlight the extraordinary lengths that HIV employs to evade detection by high-affinity TCRs with a broad peptide-binding footprint and necessitate reevaluation of this exemplar model of HIV TCR escape