475 research outputs found
Recycled Pulsars Discovered at High Radio Frequency
We present the timing parameters of nine pulsars discovered in a survey of
intermediate Galactic latitudes at 1400 MHz with the Parkes radio telescope.
Eight of these pulsars possess small pulse periods and period derivatives
thought to be indicative of ``recycling''. Six of the pulsars are in circular
binary systems, including two with relatively massive white dwarf companions.
We discuss the implications of these new systems for theories of binary
formation and evolution. One long-period pulsar (J1410-7404) has a moderately
weak magnetic field and an exceedingly narrow average pulse profile, similar to
other recycled pulsars.Comment: 9 pages, 4 figures. Accepted for publication in Ap
QUARTERLY PROGRESS REPORT JANUARY, FEBRUARY, MARCH, 1968 REACTOR FUELS AND MATERIALS DEVELOPMENT PROGRAMS FOR FUELS AND MATERIALS BRANCH OF USAEC DIVISION OF REACTOR DEVELOPMENT AND TECHNOLOGY
Progress is reported in these areas: nuclear graphite; fuel development for gas-cooled reactors; HTGR graphite studies; nuclear ceramics; fast-reactor nitrides research; non-destructive testing; metallic fuels; basic swelling studies; ATR gas and water loop operation and maintenance; reactor fuels and materials; fast reactor dosimetry and damage analysis; and irradiation damage to reactor metals
High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor
The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al
Concentration Dependence of Superconductivity and Order-Disorder Transition in the Hexagonal Rubidium Tungsten Bronze RbxWO3. Interfacial and bulk properties
We revisited the problem of the stability of the superconducting state in
RbxWO3 and identified the main causes of the contradictory data previously
published. We have shown that the ordering of the Rb vacancies in the
nonstoichiometric compounds have a major detrimental effect on the
superconducting temperature Tc.The order-disorder transition is first order
only near x = 0.25, where it cannot be quenched effectively and Tc is reduced
below 1K. We found that the high Tc's which were sometimes deduced from
resistivity measurements, and attributed to compounds with .25 < x < .30, are
to be ascribed to interfacial superconductivity which generates spectacular
non-linear effects. We also clarified the effect of acid etching and set more
precisely the low-rubidium-content boundary of the hexagonal phase.This work
makes clear that Tc would increase continuously (from 2 K to 5.5 K) as we
approach this boundary (x = 0.20), if no ordering would take place - as its is
approximately the case in CsxWO3. This behaviour is reminiscent of the
tetragonal tungsten bronze NaxWO3 and asks the same question : what mechanism
is responsible for this large increase of Tc despite the considerable
associated reduction of the electron density of state ? By reviewing the other
available data on these bronzes we conclude that the theoretical models which
are able to answer this question are probably those where the instability of
the lattice plays a major role and, particularly, the model which call upon
local structural excitations (LSE), associated with the missing alkali atoms.Comment: To be published in Physical Review
Expanded molecular diversity generation during directed evolution by trinucleotide exchange (TriNEx)
Trinucleotide exchange (TriNEx) is a method for generating novel molecular diversity during directed evolution by random substitution of one contiguous trinucleotide sequence for another. Single trinucleotide sequences were deleted at random positions in a target gene using the engineered transposon MuDel that were subsequently replaced with a randomized trinucleotide sequence donated by the DNA cassette termed SubSeqNNN. The bla gene encoding TEM-1 β-lactamase was used as a model to demonstrate the effectiveness of TriNEx. Sequence analysis revealed that the mutations were distributed throughout bla, with variants containing single, double and triple nucleotide changes. Many of the resulting amino acid substitutions had significant effects on the in vivo activity of TEM-1, including up to a 64-fold increased activity toward ceftazidime and up to an 8-fold increased resistance to the inhibitor clavulanate. Many of the observed amino acid substitutions were only accessible by exchanging at least two nucleotides per codon, including charge-switch (R164D) and aromatic substitution (W165Y) mutations. TriNEx can therefore generate a diverse range of protein variants with altered properties by combining the power of site-directed saturation mutagenesis with the capacity of whole-gene mutagenesis to randomly introduce mutations throughout a gene
Evaluation of bone texture imaging parameters on panoramic radiographs of patients with Sheehan’s syndrome: a STROBE-compliant case-control study
Summary
Sheehan’s syndrome (SHS) is a rare condition related to the risk of osteoporosis and evaluation of bone texture imaging features on panoramic radiographs would be suitable for this condition, which was the aim of the present study. Fractal dimension, lacunarity, and trabecular morphologic aspects were significantly altered in these patients.
Introduction
SHS is an important public health problem particularly in developing countries. It is characterized as postpartum hypopituitarism secondary to obstetric complications-related ischemic pituitary necrosis that shows significant systemic metabolic repercussions. Thus, this study aimed to evaluate bone texture parameters in digital panoramic radiographs of patients with SHS.
Methods
A case-control study was conducted with 30 SHS patients from an Endocrinology and Diabetology Service of reference in Brazil, and 30 age- and sex-matched healthy controls. A custom computer program measured fractal dimension, lacunarity, and some morphologic features in the following mandibular regions of interest (50 × 50 pixels): below the mental foramen (F1), between the first and second molars (M1), and at the center of the mandibular ramus (R1).
Results
The fractal analysis showed a statistically significant difference between the studied groups in all regions of interest. The fractal dimension in F1 (p = 0.016), M1 (p = 0.043), and R1 (p = 0.028) was significantly lower in SHS group, as well as lacunarity in R1 (p = 0.008). Additionally, several morphologic features were statistically significant in the SHS group (p < 0.05).
Conclusion
Therefore, individuals with SHS showed altered imaging texture parameters on panoramic radiographs, which reflect a smaller spatial organization of the bone trabeculae and, possibly, a state of reduced mineral bone density
Dual ankyrinG and subpial autoantibodies in a man with well-controlled HIV infection with steroid-responsive meningoencephalitis: A case report
Neuroinvasive infection is the most common cause of meningoencephalitis in people living with human immunodeficiency virus (HIV), but autoimmune etiologies have been reported. We present the case of a 51-year-old man living with HIV infection with steroid-responsive meningoencephalitis whose comprehensive pathogen testing was non-diagnostic. Subsequent tissue-based immunofluorescence with acute-phase cerebrospinal fluid revealed anti-neural antibodies localizing to the axon initial segment (AIS), the node of Ranvier (NoR), and the subpial space. Phage display immunoprecipitation sequencing identified ankyrinG (AnkG) as the leading candidate autoantigen. A synthetic blocking peptide encoding the PhIP-Seq-identified AnkG epitope neutralized CSF IgG binding to the AIS and NoR, thereby confirming a monoepitopic AnkG antibody response. However, subpial immunostaining persisted, indicating the presence of additional autoantibodies. Review of archival tissue-based staining identified candidate AnkG autoantibodies in a 60-year-old woman with metastatic ovarian cancer and seizures that were subsequently validated by cell-based assay. AnkG antibodies were not detected by tissue-based assay and/or PhIP-Seq in control CSF (N = 39), HIV CSF (N = 79), or other suspected and confirmed neuroinflammatory CSF cases (N = 1,236). Therefore, AnkG autoantibodies in CSF are rare but extend the catalog of AIS and NoR autoantibodies associated with neurological autoimmunity
Genetic Variants of Wnt Transcription Factor TCF-4 (TCF7L2) Putative Promoter Region Are Associated with Small Intestinal Crohn's Disease
Reduced expression of Paneth cell antimicrobial α-defensins, human defensin (HD)-5 and -6, characterizes Crohn's disease (CD) of the ileum. TCF-4 (also named TCF7L2), a Wnt signalling pathway transcription factor, orchestrates Paneth cell differentiation, directly regulates the expression of HD-5 and -6, and was previously associated with the decrease of these antimicrobial peptides in a subset of ileal CD. To investigate a potential genetic association of TCF-4 with ileal CD, we sequenced 2.1 kb of the 5′ flanking region of TCF-4 in a small group of ileal CD patients and controls (n = 10 each). We identified eight single nucleotide polymorphisms (SNPs), of which three (rs3814570, rs10885394, rs10885395) were in linkage disequilibrium and found more frequently in patients; one (rs3814570) was thereby located in a predicted regulatory region. We carried out high-throughput analysis of this SNP in three cohorts of inflammatory bowel disease (IBD) patients and controls. Overall 1399 healthy individuals, 785 ulcerative colitis (UC) patients, 225 CD patients with colonic disease only and 784 CD patients with ileal involvement were used to determine frequency distributions. We found an association of rs3814570 with ileal CD but neither with colonic CD or UC, in a combined analysis (allele positivity: OR 1.27, 95% CI 1.07 to 1.52, p = 0.00737), which was the strongest in ileal CD patients with stricturing behaviour (allele frequency: OR 1.32, 95% CI 1.08 to1.62, p = 0.00686) or an additional involvement of the upper GIT (allele frequency: OR 1.38, 95% CI 1.03 to1.84, p = 0.02882). The newly identified genetic association of TCF-4 with ileal CD provides evidence that the decrease in Paneth cell α-defensins is a primary factor in disease pathogenesis
High-Precision Timing of 5 Millisecond Pulsars: Space Velocities, Binary Evolution and Equivalence Principles
We present high-precision timing of five millisecond pulsars (MSPs) carried
out for more than seven years; four pulsars are in binary systems and one is
isolated. We are able to measure the pulsars' proper motions and derive an
estimate for their space velocities. The measured two-dimensional velocities
are in the range 70-210 km/s, consistent with those measured for other MSPs. We
also use all the available proper motion information for isolated and binary
MSPs to update the known velocity distribution for these populations. As found
by earlier works, we find that the velocity distribution of binary and isolated
MSPs are indistinguishable with the current data. Four of the pulsars in our
observing program are highly recycled with low-mass white dwarf companions and
we are able to derive accurate binary parameters for these systems. For three
of these binary systems we are able to place initial constraints on the pulsar
masses with best-fit values in the range 1.0-1.6 M_sun. The implications of the
results presented here to our understanding of binary pulsar evolution are
discussed. The updated parameters for the binary systems studied here, together
with recently discovered similar systems, allowed us to update previous limits
on the the violation of the strong equivalence principle through the parameter
|Delta| to 4.6x10^-3 (95% confidence) and the violation of
Lorentz-invariance/momentum-conservation through the parameter |hat{alpha}_3|
to 5.5x10^-20 (95% confidence).Comment: 24 pages, 8 figures; accepted for publication in The Astrophysical
Journa
Host Genes Related to Paneth Cells and Xenobiotic Metabolism Are Associated with Shifts in Human Ileum-Associated Microbial Composition
The aim of this study was to integrate human clinical, genotype, mRNA microarray and 16 S rRNA sequence data collected on 84 subjects with ileal Crohn’s disease, ulcerative colitis or control patients without inflammatory bowel diseases in order to interrogate how host-microbial interactions are perturbed in inflammatory bowel diseases (IBD). Ex-vivo ileal mucosal biopsies were collected from the disease unaffected proximal margin of the ileum resected from patients who were undergoing initial intestinal surgery. Both RNA and DNA were extracted from the mucosal biopsy samples. Patients were genotyped for the three major NOD2 variants (Leufs1007, R702W, and G908R) and the ATG16L1T300A variant. Whole human genome mRNA expression profiles were generated using Agilent microarrays. Microbial composition profiles were determined by 454 pyrosequencing of the V3–V5 hypervariable region of the bacterial 16 S rRNA gene. The results of permutation based multivariate analysis of variance and covariance (MANCOVA) support the hypothesis that host mucosal Paneth cell and xenobiotic metabolism genes play an important role in host microbial interactions
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