TDRSS/user satellite timing study

A timing analysis for data readout through the Tracking and Data Relay Satellite System (TDRSS) was presented. Various time tagging approaches were considered and the resulting accuracies delineated. The TDRSS was also defined and described in detail

X-Ray Crystal Analysis of Acid Salts, and Tris-Ethyl-Sulphonyl Methane: Development of Related Computer Programs

The phase problem of X-ray crystallography is stated, some of the methods available for its solution are surveyed and their theoretical background is outlined. ' Three computer programs written by the author, are described. These are a program for scanning three-dimensional density maps, which automatically produces interpolated coordinates for every peak in the map; a program for sorting crystallographic reflexion data into order by the Miller indices; and a program which supplies a suitable weighting-scheme for structure-factor-least-squares refinement. The "ASS" system of crystallographic computer programs is then described with special reference to the method of storing the crystallographic data, and the features which enable it, in some cases, to obtain the positions of all the light atoms automatically, given the position of only the heavy-atom. The crystal structure analysis of tris (ethyl sulphonyl) methane is described, and the structure obtained is compared to that of tris (methyl sulphonyl) methane. A description is given of the course of the structure analyses of three acid salts, potassium hydrogen dianisate, potassium hydrogen dicrotonate and rubidium hydrogen dicrotonate, and their structures, which all contain short hydrogen bonds, are discussed

Making a difference - the appropriate use of web technology

Much has been written elsewhere about how, different Information Technology tools, can in principle be used by groups or communities to make their web sites more effective for Continued Professional Development. In practice, complex use is not often the case. In particular, three sites were studied in Scotland, which provided web facilities for the over 60s. The sites, and the communities they served, used only simple Information Technology. Nevertheless, they enabled their communities to participate effectively, on the 'right side', of the European population's 'digital divide'

Development of semiconductor detectors for fast neutron radiography

A high-energy neutron detector has been developed using a semiconductor diode fabricated from bulk gallium arsenide wafers with a polyethylene neutron converter layer. Typical thickness of the diode layer is 250 to 300 μm with bias voltages of 30 to 150 volts. Converter thicknesses up to 2030 μm have been tested. GaAs neutron detectors offer many advantages over existing detectors including positional information, directional dependence, gamma discrimination, radiation hardness, and spectral tailoring. Polyethylene-coated detectors have been shown to detect 14 MeV neutrons directly from a D-T neutron generator without interference from gamma rays or scattered neutrons. An array of small diode detectors can be assembled to perform fast neutron radiography with direct digital readout and real-time display of the image produced. In addition, because the detectors are insensitive to gamma rays and low energy neutrons, highly radioactive samples (such as spent nuclear fuel or transuranic waste drums) could be radiographed. © 2001 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87673/2/1118_1.pd

The Black-Hole Mass in M87 from Gemini/NIFS Adaptive Optics Observations

We present the stellar kinematics in the central 2" of the luminous elliptical galaxy M87 (NGC 4486), using laser adaptive optics to feed the Gemini telescope integral-field spectrograph, NIFS. The velocity dispersion rises to 480 km/s at 0.2". We combine these data with extensive stellar kinematics out to large radii to derive a black-hole mass equal to (6.6+-0.4)x10^9 Msun, using orbit-based axisymmetric models and including only the NIFS data in the central region. Including previously-reported ground-based data in the central region drops the uncertainty to 0.25x10^9 Msun with no change in the best-fit mass; however, we rely on the values derived from the NIFS-only data in the central region in order to limit systematic differences. The best-fit model shows a significant increase in the tangential velocity anisotropy of stars orbiting in the central region with decreasing radius; similar to that seen in the centers of other core galaxies. The black-hole mass is insensitive to the inclusion of a dark halo in the models --- the high angular-resolution provided by the adaptive optics breaks the degeneracy between black-hole mass and stellar mass-to-light ratio. The present black-hole mass is in excellent agreement with the Gebhardt & Thomas value, implying that the dark halo must be included when the kinematic influence of the black hole is poorly resolved. This degeneracy implies that the black-hole masses of luminous core galaxies, where this effect is important, may need to be re-evaluated. The present value exceeds the prediction of the black hole-dispersion and black hole-luminosity relations, both of which predict about 1x10^9 Msun for M87, by close to twice the intrinsic scatter in the relations. The high-end of the black hole correlations may be poorly determined at present.Comment: 12 pages, accepted for publication in the Astrophysical Journa

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Synergism/complementarity of recombinant adenoviral vectors and other vaccination platforms during induction of protective immunity against malaria

The lack of immunogenicity of most malaria antigens and the complex immune responses required for achieving protective immunity against this infectious disease have traditionally hampered the development of an efficient human malaria vaccine. The current boom in development of recombinant viral vectors and their use in prime-boost protocols that result in enhanced immune outcomes have increased the number of malaria vaccine candidates that access pre-clinical and clinical trials. In the frontline, adenoviruses and poxviruses seem to be giving the best immunization results in experimental animals and their mutual combination, or their combination with recombinant proteins (formulated in adjuvants and given in sequence or being given as protein/virus admixtures), has been shown to reach unprecedented levels of anti-malaria immunity that predictably will be somehow reproduced in the human setting. However, all this optimism was previously seen in the malaria vaccine development field without many real applicable results to date. We describe here the current state-of-the-art in the field of recombinant adenovirus research for malaria vaccine development, in particular referring to their use in combination with other immunogens in heterologous prime-boost protocols, while trying to simultaneously show our contributions and point of view on this subject

Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines

Five endometrial cancer risk loci identified through genome-wide association analysis.

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.I.T. is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. T.H.T.C. is supported by the Rhodes Trust and the Nuffield Department of Medicine. Funding for iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565), the US National Institutes of Health (R01 CA128978, U19 CA148537, U19 CA148065 and U19 CA148112), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Susan G. Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund. SEARCH recruitment was funded by a programme grant from Cancer Research UK (C490/A10124). Stage 1 and stage 2 case genotyping was supported by the NHMRC (552402 and 1031333). Control data were generated by the WTCCC, and a full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by UK Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02; funding for this project was provided by the Wellcome Trust under award 085475. NSECG was supported by the European Union's Framework Programme 7 CHIBCHA grant and Wellcome Trust Centre for Human Genetics Core Grant 090532/Z/09Z, and CORGI was funded by Cancer Research UK. BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014). OCAC is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07) and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.356