700 research outputs found
On-Orbit Calibration of Photodiodes for Attitude Determination
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140645/1/1.g000175.pd
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Long-Term Follow-up of Reduced Intensity Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia: Prognostic Model to Predict Outcome
CLL remains incurable with chemoimmunotherapy, and allogeneic hematopoietic stem cell transplantation (HSCT) offers potential for cure. We assessed the outcomes of 108 CLL patients undergoing first allogeneic HSCTs, 76 with reduced intensity (RIC) and 32 with myeloablative (MAC) conditioning between 1998 and 2009 at Dana-Farber Cancer Institute. With median follow-up 5.9 years in surviving patients, the 5 year OS for the entire cohort is 63% for RIC regimens and 49% for MAC regimens (p=0.18). The risk of death declined significantly starting in 2004 and we found that 5 year OS for HSCT between 2004â2009 was 83% for RIC regimens compared to 47% for MAC regimens (p=0.003). For RIC transplantation, we developed a prognostic model based on predictors of PFS, specifically remission status, LDH, comorbidity score and lymphocyte count, and found 5-year PFS 83% for score 0, 63% for score 1, 24% for score 2, and 6% for score >= 3 (p<0.0001). We conclude that RIC HSCT for CLL in the current era is associated with excellent long-term PFS and OS, and, as potentially curative therapy, should be considered early in the disease course of relapsed high-risk CLL patients
Looking ahead: forecasting and planning for the longer-range future, April 1, 2, and 3, 2005
This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's spring Conference that took place during April 1, 2, and 3, 2005.The conference allowed for many highly esteemed scholars and professionals from a broad range of fields to come together to discuss strategies designed for the 21st century and beyond. The speakers and discussants covered a broad range of subjects including: long-term policy analysis, forecasting for business and investment, the National Intelligence Council Global Trends 2020 report, Europeâs transition from the Marshal plan to the EU, forecasting global transitions, foreign policy planning, and forecasting for defense
The Samurai Project: verifying the consistency of black-hole-binary waveforms for gravitational-wave detection
We quantify the consistency of numerical-relativity black-hole-binary
waveforms for use in gravitational-wave (GW) searches with current and planned
ground-based detectors. We compare previously published results for the
mode of the gravitational waves from an equal-mass
nonspinning binary, calculated by five numerical codes. We focus on the 1000M
(about six orbits, or 12 GW cycles) before the peak of the GW amplitude and the
subsequent ringdown. We find that the phase and amplitude agree within each
code's uncertainty estimates. The mismatch between the modes
is better than for binary masses above with respect to
the Enhanced LIGO detector noise curve, and for masses above
with respect to Advanced LIGO, Virgo and Advanced Virgo. Between the waveforms
with the best agreement, the mismatch is below . We find that
the waveforms would be indistinguishable in all ground-based detectors (and for
the masses we consider) if detected with a signal-to-noise ratio of less than
, or less than in the best cases.Comment: 17 pages, 9 figures. Version accepted by PR
The Mock LISA Data Challenges: from Challenge 3 to Challenge 4
The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis
capabilities and to encourage their development. Each round of challenges
consists of one or more datasets containing simulated instrument noise and
gravitational waves from sources of undisclosed parameters. Participants
analyze the datasets and report best-fit solutions for the source parameters.
Here we present the results of the third challenge, issued in Apr 2008, which
demonstrated the positive recovery of signals from chirping Galactic binaries,
from spinning supermassive--black-hole binaries (with optimal SNRs between ~ 10
and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from
cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud
isotropic background with Omega_gw(f) ~ 10^-11, slightly below the LISA
instrument noise.Comment: 12 pages, 2 figures, proceedings of the 8th Edoardo Amaldi Conference
on Gravitational Waves, New York, June 21-26, 200
Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome
Biliary atresia (BA) is the most common cause of endâstage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations â a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patientâparent trios, from the NIDDKâsupported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a preâspecified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious biâallelic variants in polycystin 1âlike 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other nonâcholestatic diseases. Conclusion WES identified biâallelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyteâexpressed candidate gene for the BASM syndrome
Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection
<p>Abstract</p> <p>Background</p> <p>Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis.</p> <p>Methods</p> <p>Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups.</p> <p>Results</p> <p>Seven individual protein spots were identified as either significantly increased (α<sub>2</sub>-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α<sub>2</sub>-macroglobulin, are included in existing non-invasive serum marker panels.</p> <p>Conclusion</p> <p>Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.</p
Natural Variation in Interleukin-2 Sensitivity Influences Regulatory T-Cell Frequency and Function in Individuals With Long-standing Type 1 Diabetes.
Defective immune homeostasis in the balance between FOXP3+ regulatory T cells (Tregs) and effector T cells is a likely contributing factor in the loss of self-tolerance observed in type 1 diabetes (T1D). Given the importance of interleukin-2 (IL-2) signaling in the generation and function of Tregs, observations that polymorphisms in genes in the IL-2 pathway associate with T1D and that some individuals with T1D exhibit reduced IL-2 signaling indicate that impairment of this pathway may play a role in Treg dysfunction and the pathogenesis of T1D. Here, we have examined IL-2 sensitivity in CD4+ T-cell subsets in 70 individuals with long-standing T1D, allowing us to investigate the effect of low IL-2 sensitivity on Treg frequency and function. IL-2 responsiveness, measured by STAT5a phosphorylation, was a very stable phenotype within individuals but exhibited considerable interindividual variation and was influenced by T1D-associated PTPN2 gene polymorphisms. Tregs from individuals with lower IL-2 signaling were reduced in frequency, were less able to maintain expression of FOXP3 under limiting concentrations of IL-2, and displayed reduced suppressor function. These results suggest that reduced IL-2 signaling may be used to identify patients with the highest Treg dysfunction and who may benefit most from IL-2 immunotherapy.This work was supported by the JDRF UK Centre for Diabetes Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003), the Wellcome Trust (WT061858/091157) and the NIHR Cambridge Biomedical Research Centre (CBRC). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140).This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db15-051
Observational Limit on Gravitational Waves from Binary Neutron Stars in the Galaxy
Using optimal matched filtering, we search 25 hours of data from the LIGO
40-meter prototype laser interferometric gravitational-wave detector for
gravitational-wave chirps emitted by coalescing binary systems within our
Galaxy. This is the first test of this filtering technique on real
interferometric data. An upper limit on the rate R of neutron star binary
inspirals in our Galaxy is obtained: with 90% confidence, R< 0.5/hour. Similar
experiments with LIGO interferometers will provide constraints on the
population of tight binary neutron star systems in the Universe.Comment: RevTeX, minor revisions, exactly as published in PRL 83 (1999) p1498,
4 pages, 2 figures include
IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients.
AIMS/HYPOTHESIS: Type 1 diabetes results from the autoimmune destruction of insulin-secreting pancreatic beta cells by T cells. Despite the established role of T cells in the pathogenesis of the disease, to date, with the exception of the identification of islet-specific T effector (Teff) cells, studies have mostly failed to identify reproducible alterations in the frequency or function of T cell subsets in peripheral blood from patients with type 1 diabetes. METHODS: We assessed the production of the proinflammatory cytokines IL-21, IFN-Îł and IL-17 in peripheral blood mononuclear cells from 69 patients with type 1 diabetes and 61 healthy donors. In an additional cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. IL-21 and IL-17 production was also measured in peripheral blood mononuclear cells (PBMCs) from a subset of 46 of the 62 donors immunophenotyped for Tfh. RESULTS: We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 Ă 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). Consistent with this finding, we found a 14.9% increase in circulating Tfh cells in the patients (95% CI 2.9, 26.9; p = 0.016). CONCLUSIONS/INTERPRETATION: These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.This work was supported by the JDRF UK Centre for
Diabetes - Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003) in collaboration with M. Peakman and T. Tree at Kingâs College
London, the JDRF, the Wellcome Trust (WT; WT061858/091157 and
083650/Z/07/Z) and the National Institute for Health Research
Cambridge Biomedical Research Centre (CBRC). The Cambridge
Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust
Strategic Award (100140). RCF is funded by a JDRF post-doctoral fellowship
(3-2011-374). CW is funded by the Wellcome Trust (088998).
The funding organisations had no involvement with the design and
conduct of the study; collection,management, analysis, and interpretation
of the data; and preparation, review, or approval of the manuscript.This is the final published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00125-015-3509-8
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