A Generic Blade-Element Simulation Library Based On The Genhel Model: Final Report On The BERMADA Rotor Model Project

Report on a project to design and construct a set of reusable mathematical routines which amount to a general-purpose library to implement blade-element rotor math models for helicopters

Discovery and Identification of Dimethylsilanediol as a Contaminant in ISS Potable Water

In September 2010, analysis of ISS potable water samples was undertaken to determine the contaminant(s) responsible for a rise of total organic carbon (TOC) in the Water Processor Assembly (WPA) product water. As analysis of the routine target list of organic compounds did not reveal the contaminant, efforts to look for unknown compounds were initiated, resulting in discovery of an unknown peak in the gas chromatography/mass spectrometry (GC/MS) analysis for glycols. A mass spectrum of the contaminant was then generated by concentrating one of the samples and analyzing it by GC/MS in full-scan mode. Although a computer match of the compound identity could not be obtained with the instrument database, a search with a more up-to-date mass spectral library yielded a good match with dimethylsilanediol (DMSD). Inductively coupled plasma/mass spectrometry (ICP/MS) analyses showed abnormally high silicon levels in the samples, confirming that the unknown compound(s) contained silicon. DMSD was then synthesized to confirm the identification and provide a standard to develop a calibration curve. Further confirmation was provided by external direct analysis in real time time of flight (DART TOF) mass spectrometry. To routinely test for DMSD in the future, a quantitative method was needed. A preliminary GC/MS method was developed and archived samples from various locations on ISS were analyzed to determine the extent of the contamination and provide data for troubleshooting. This paper describes these events in more detail as well as problems encountered in routine GC/MS analyses and the subsequent development of high performance liquid chromatography and LC/MS/MS methods for measuring DMSD

Discovery and Identification of Dimethylsilanediol as a Contaminant in ISS Potable Water

In September of 2010, analysis of ISS potable water samples was undertaken to determine the contaminant responsible for a rise in total organic carbon (TOC). As analysis of the routine target list of organic compounds did not reveal the contaminant, efforts to look for unknown compounds was initiated, resulting in an unknown peak being discovered in the gas chromatography/mass spectrometry (GC/MS) analysis for glycols. A mass spectrum of the contaminant was then generated by concentrating one of the samples by evaporation and analyzing by GC/MS in full-scan mode. Although a computer match of the compound s identity could not be obtained with the instrument s database, a search with a more up to date mass spectral library yielded a good match with dimethylsilanediol (DMSD). Inductively Coupled Plasma/Mass Spectrometry (ICP/MS) analyses showed abnormally high silicon levels in the samples, confirming that the unknown contained silicon. DMSD was then synthesized to confirm the identification and provide a standard to develop a calibration curve. Further confirmation was provided by external Direct Analysis in Real Time (DART) GC/MS analysis. A preliminary GC/MS method was then developed and archived samples from various locations on ISS were analyzed to determine the extent of the contamination and provide data for troubleshooting. This paper describes these events in more detail as well as problems encountered in routine GC/MS analyses and the subsequent development of high performance liquid chromatography and LC/MS/MS methods for quantitation of DMSD

Deterministic evolution and stringent selection during preneoplasia

The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over 2 years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single-cell sequencing of TP53-deficient gastric organoids similarly indicates progression towards malignant transcriptional programmes. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programmes repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference and a marked degree of phenotypic convergence in premalignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and show evolutionary constraints and barriers to malignant transformation, with implications for earlier detection and interception of aggressive, genome-instable tumours

Sensitivity of Air Pollution-Induced Premature Mortality to Precursor Emissions under the Influence of Climate Change

The relative contributions of PM2.5 and ozone precursor emissions to air pollution-related premature mortality modulated by climate change are estimated for the U.S. using sensitivities of air pollutants to precursor emissions and health outcomes for 2001 and 2050. Result suggests that states with high emission rates and significant premature mortality increases induced by PM2.5 will substantially benefit in the future from SO2, anthropogenic NOX and NH3 emissions reductions while states with premature mortality increases induced by O3 will benefit mainly from anthropogenic NOX emissions reduction. Much of the increase in premature mortality expected from climate change-induced pollutant increases can be offset by targeting a specific precursor emission in most states based on the modeling approach followed here

Do short birth intervals have long-term implications for parental health? Results from analyses of complete cohort Norwegian register data.

BACKGROUND: Short and very long interbirth intervals are associated with worse perinatal, infant and immediate maternal outcomes. Accumulated physiological, mental, social and economic stresses arising from raising children close in age may also mean that interbirth intervals have longer term implications for the health of mothers and fathers, but few previous studies have investigated this. METHODS: Discrete-time hazards models were estimated to analyse associations between interbirth intervals and mortality risks for the period 1980-2008 in complete cohorts of Norwegian men and women born during 1935-1968 who had had two to four children. Associations between interbirth intervals and use of medication during 2004-2008 were also analysed using ordinary least-squares regression. Covariates included age, year, education, age at first birth, parity and change in coparent since the previous birth. RESULTS: Mothers and fathers of two to three children with intervals between singleton births of less than 18 months, and mothers of twins, had raised mortality risks in midlife and early old age relative to parents with interbirth intervals of 30-41 months. For parents with three or four children, longer average interbirth intervals were associated with lower mortality. Short intervals between first and second births were also positively associated with medication use. Very long intervals were not associated with raised mortality or medication use when change of coparent since the previous birth was controlled. CONCLUSIONS: Closely spaced and multiple births may have adverse long-term implications for parental health. Delayed entry to parenthood and increased use of fertility treatments mean that both are increasing, making this a public health issue which needs further investigation

How to diagnose and treat hepatitis B virus antiviral drug resistance in the liver transplant setting

Key Points 1 Hepatitis B virus variants with antiviral drug–resistant mutations and/or hepatitis B immune globulin–resistant mutations are the main cause of hepatitis B virus reinfections post–liver transplant. 2 Early diagnosis of antiviral drug resistance and prompt initiation of rescue therapy are important in preventing hepatitis flares and hepatic decompensation. 3 Virologic breakthrough is the first indication of antiviral drug resistance. 4 Genotypic resistance testing should be performed when possible to avoid unnecessary modification of treatment in patients who do not have confirmed antiviral drug resistance and to permit appropriate selection of rescue therapy in those who have confirmed antiviral drug resistance. 5 Choice of rescue therapy requires knowledge of the past history of hepatitis B virus treatments and virologic response to those treatments, patterns of mutations detected at the time of virologic breakthrough, and in vitro cross-resistance data. 6 Occurrence of antiviral drug resistance can be reduced by the use of the most potent nucleos(t)ide analogue(s) with the highest genetic barrier to resistance, emphasis of medication compliance, and close monitoring of virologic response. Liver Transpl 14:S8–S14, 2008. © 2008 AASLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61245/1/21616_ftp.pd

The Hubble Constant

I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give $H_0$ values of around 72-74km/s/Mpc , with typical errors of 2-3km/s/Mpc. This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67-68km/s/Mpc and typical errors of 1-2km/s/Mpc. The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.Comment: Extensively revised and updated since the 2007 version: accepted by Living Reviews in Relativity as a major (2014) update of LRR 10, 4, 200

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

Multiple foci of spatial attention in multimodal working memory

The maintenance of sensory information in working memory (WM) is mediated by the attentional activation of stimulus representations that are stored in perceptual brain regions.Using event-related potentials (ERPs), we measured tactile and visual contralateral delay activity (tCDA / CDA components) in a bimodal WM task to concurrently track the attention-based maintenance of information stored in anatomically segregated (somatosensory and visual) brain areas. Participants received tactile and visual sample stimuli on both sides, and in different blocks, memorized these samples on the same side or on opposite sides. After a retention delay, memory was unpredictably tested for touch or vision. In same side blocks, tCDA and CDA components simultaneously emerged over the same hemisphere, contralateral to the memorized tactile / visual sample set. In opposite side blocks, these two components emerged over different hemispheres, but had the same sizes and onset latencies as in the same side condition. This finding indicates that distinct foci of tactile and visual spatial attention were concurrently maintained on task-relevant stimulus representations in WM. The independence of spatially-specific biasing mechanisms for tactile and visual WM content suggests that multimodal information is stored in distributed perceptual brain areas that are subject to modality-specific control processes, which can operate simultaneously and largely independently of each other