Space shuttle booster Data Management System (DMS) requirements analysis. Volume 2: Detail requirements

Space shuttle subsystem interface description, subsystem computational requirements, and analysis program - Vol.

A 10B-based neutron detector with stacked Multiwire Proportional Counters and macrostructured cathodes

We present the results of the measurements of the detection efficiency for a 4.7 \r{A} neutron beam incident upon a detector incorporating a stack of up to five MultiWire Proportional Counters (MWPC) with Boron-coated cathodes. The cathodes were made of Aluminum and had a surface exhibiting millimeter-deep V-shaped grooves of 45{\deg}, upon which the thin Boron film was deposited by DC magnetron sputtering. The incident neutrons interacting with the converter layer deposited on the sidewalls of the grooves have a higher capture probability, owing to the larger effective absorption film thickness. This leads to a higher overall detection efficiency for the grooved cathode when compared to a cathode with a flat surface. Both the experimental results and the predictions of the GEANT4 model suggests that a 5-counter detector stack with coated grooved cathodes has the same efficiency as a 7-counter stack with flat cathodes. The reduction in the number of counters in the stack without altering the detection efficiency will prove highly beneficial for large-area position-sensitive detectors for neutron scattering applications, for which the cost-effective manufacturing of the detector and associated readout electronics is an important objective. The proposed detector concept could be a technological option for one of the new chopper spectrometers and other instruments planned to be built at the future European Spallation Source in Sweden. These results with macrostructured cathodes generally apply not just to MWPCs but to other gaseous detectors as well.Comment: 14 pages, 9 figure

Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury

IMPORTANCE: Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury. OBJECTIVE: To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury. DESIGN, SETTINGS, AND PARTICIPANTS: A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid. RESULTS: A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05). CONCLUSIONS AND RELEVANCE: Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy

Knowledge management infrastructure to support quality improvement: A qualitative study of maternity services in four European hospitals

The influence of multilevel healthcare system interactions on clinical quality improvement (QI) is still largely unexplored. Through the lens of knowledge management (KM) theory, this study explores how hospital managers can enhance the conditions for clinical QI given the specific multilevel and professional interactions in various healthcare systems. The research used an in-depth multilevel analysis in maternity departments in four purposively sampled European hospitals (Portugal, England, Norway and Sweden). The study combines analysis of macro-level policy documents and regulations with semi-structured interviews (96) and non-participant observations (193 hours) of hospital and clinical managers and clinical staff in maternity departments. There are four main conclusions: First, the unique multilevel configuration of national healthcare policy, hospital management and clinical professionals influence the development of clinical QI efforts. Second, these different configurations provide various and often insufficient support and guidance which affect professionals’ action strategies in QI efforts. Third, hospital managers’ opportunities and capabilities for developing a consistent KM infrastructure with reinforcing enabling conditions which merge national policies and guidelines with clinical reality is crucial for clinical QI. Fourth, understanding these interrelationships provides an opportunity for improvement of the KM infrastructure for hospital managers through tailored interventions

Interactions in vivo between the Vif protein of HIV-1 and the precursor (Pr55GAG) of the virion nucleocapsid proteins

The abnormality of viral core structure seen in vif-defective HIV-1 grown in PBMCs has suggested a role for Vif in viral morphogenesis. Using an in vivo mammalian two-hybrid assay, the interaction between Vif and the precursor (Pr55GAG) of the virion nucleocapsid proteins has been analysed. This revealed the amino-terminal (aa 1–22) and central (aa 70–100) regions of Vif to be essential for its interaction with Pr55GAG, but deletion of the carboxy-terminal (aa 158–192) region of the protein had only a minor effect on its interaction. Initial deletion studies carried out on Pr55GAG showed that a 35-amino-acid region of the protein bridging the MA(p17)–CA(p24) junction was essential for its ability to interact with Vif. Site-directed mutagenesis of a conserved tryptophan (Trp21) near the amino terminus of Vif showed it to be important for the interaction with Pr55GAG. By contrast, mutagenesis of the highly conserved YLAL residues forming part of the BC-box motif, shown to be important in Vif promoting degradation of APOBEC3G/3F, had little or no effect on the Vif–Pr55GAG interaction

Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis

Common fragile sites (cfs) are specific regions in the human genome that are particularly prone to genomic instability under conditions of replicative stress. Several investigations support the view that common fragile sites play a role in carcinogenesis. We discuss a genome-wide approach based on graph theory and Gene Ontology vocabulary for the functional characterization of common fragile sites and for the identification of genes that contribute to tumour cell biology. CFS were assembled in a network based on a simple measure of correlation among common fragile site patterns of expression. By applying robust measurements to capture in quantitative terms the non triviality of the network, we identified several topological features clearly indicating departure from the Erdos-Renyi random graph model. The most important outcome was the presence of an unexpected large connected component far below the percolation threshold. Most of the best characterized common fragile sites belonged to this connected component. By filtering this connected component with Gene Ontology, statistically significant shared functional features were detected. Common fragile sites were found to be enriched for genes associated to the immune response and to mechanisms involved in tumour progression such as extracellular space remodeling and angiogenesis. Our results support the hypothesis that fragile sites serve a function; we propose that fragility is linked to a coordinated regulation of fragile genes expression.Comment: 18 pages, accepted for publication in BMC Bioinformatic

Alzheimer-associated cerebrospinal fluid fragments of neurogranin are generated by Calpain-1 and prolyl endopeptidase

BACKGROUND: Neurogranin (Ng) is a small 7.6 kDa postsynaptic protein that has been detected at elevated concentrations in cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD), both as a full-length molecule and as fragments from its C-terminal half. Ng is involved in postsynaptic calcium (Ca) signal transduction and memory formation via binding to calmodulin in a Ca-dependent manner. The mechanism of Ng secretion from neurons to CSF is currently unknown, but enzymatic cleavage of Ng may be of relevance. Therefore, the aim of the study was to identify the enzymes responsible for the cleavage of Ng, yielding the Ng fragment pattern of C-terminal fragments detectable and increased in CSF of AD patients. METHODS: Fluorigenic quenched FRET probes containing sequences of Ng were utilized to identify Ng cleaving activities among enzymes known to have increased activity in AD and in chromatographically fractionated mouse brain extracts. RESULTS: Human Calpain-1 and prolyl endopeptidase were identified as the candidate enzymes involved in the formation of endogenous Ng peptides present in CSF, cleaving mainly in the central region of Ng, and between amino acids 75_76 in the Ng sequence, respectively. The cleavage by Calpain-1 affects the IQ domain of Ng, which may deactivate or change the function of Ng in Ca2+/calmodulin -dependent signaling for synaptic plasticity. While shorter Ng fragments were readily cleaved in vitro by prolyl endopeptidase, the efficiency of cleavage on larger Ng fragments was much lower. CONCLUSIONS: Calpain-1 and prolyl endopeptidase cleave Ng in the IQ domain and near the C-terminus, respectively, yielding specific fragments of Ng in CSF. These fragments may give clues to the roles of increased activities of these enzymes in the pathophysiology of AD, and provide possible targets for pharmacologic intervention

Exponential distribution of long heart beat intervals during atrial fibrillation and their relevance for white noise behaviour in power spectrum

The statistical properties of heart beat intervals of 130 long-term surface electrocardiogram recordings during atrial fibrillation (AF) are investigated. We find that the distribution of interbeat intervals exhibits a characteristic exponential tail, which is absent during sinus rhythm, as tested in a corresponding control study with 72 healthy persons. The rate of the exponential decay lies in the range 3-12 Hz and shows diurnal variations. It equals, up to statistical uncertainties, the level of the previously uncovered white noise part in the power spectrum, which is also characteristic for AF. The overall statistical features can be described by decomposing the intervals into two statistically independent times, where the first one is associated with a correlated process with 1/f noise characteristics, while the second one belongs to an uncorrelated process and is responsible for the exponential tail. It is suggested to use the rate of the exponential decay as a further parameter for a better classification of AF and for the medical diagnosis. The relevance of the findings with respect to a general understanding of AF is pointed out

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

We previously cloned human G protein gamma 7 (GNG7) and demonstrated that it was downregulated in gastrointestinal cancer. The significance of GNG7 expression in oesophageal cancer is unknown. TaqMan quantitative real-time PCR was performed to determine the clinical significance of GNG7 expression in 55 cases of oesophageal cancer. Furthermore, GNG7-transfected oesophageal cancer cells were analysed in laboratory studies at genomic and epigenetic levels. Twenty-seven patients with low GNG7 expression showed significantly poorer survival than did 28 patients with high expression (P<0.05). Tumours with low GNG7 expression invaded deeper than those with high GNG7 expression (P<0.05), both in vivo and in vitro. Eight tumours retained GNG7 expression, and they did not show either promoter hypermethylation or loss of heterozygosity (LOH). In 38 tumours with GNG7 suppression, 22 (57%) showed either LOH or promoter hypermethylation. In addition, GNG7 expression was significantly associated with the presence of miR328 in oesophageal cancer cell lines, which suggests that this microRNA might be a regulator of GNG7 expression. GNG7 suppression represents a new prognostic indicator in cases of oesophageal cancer. GNG7 might be suppressed by LOH and promoter hypermethylation or by microRNA

Interface Controlled Thermal Resistances of Ultra-Thin Chalcogenide-Based Phase Change Memory Devices

Phase change memory (PCM) is a rapidly growing technology that not only offers advancements in storage-class memories but also enables in-memory data processing to overcome the von Neumann bottleneck. In PCMs, data storage is driven by thermal excitation. However, there is limited research regarding PCM thermal properties at length scales close to the memory cell dimensions. Our work presents a new paradigm to manage thermal transport in memory cells by manipulating the interfacial thermal resistance between the phase change unit and the electrodes without incorporating additional insulating layers. Experimental measurements show a substantial change in interfacial thermal resistance as GST transitions from cubic to hexagonal crystal structure, resulting in a factor of 4 reduction in the effective thermal conductivity. Simulations reveal that interfacial resistance between PCM and its adjacent layer can reduce the reset current for 20 and 120 nm diameter devices by up to ~ 40% and ~ 50%, respectively. These thermal insights present a new opportunity to reduce power and operating currents in PCMs