89 research outputs found
Background Studies for the Neutral Current Detector Array in the Sudbury Neutrino Observatory
An array of 3He-filled proportional counters will be used in the Sudbury
Neutrino Observatory to measure the neutral-current interaction of neutrinos
and deuterium. We describe the backgrounds to this detection method.Comment: Accepted for publication in the proceedings of TAUP99. 2 page
Development of Microstrip Gas Chambers
This research was sponsored by the National Science Foundation Grant NSF PHY-931478
Gravitational Lensing at Millimeter Wavelengths
With today's millimeter and submillimeter instruments observers use
gravitational lensing mostly as a tool to boost the sensitivity when observing
distant objects. This is evident through the dominance of gravitationally
lensed objects among those detected in CO rotational lines at z>1. It is also
evident in the use of lensing magnification by galaxy clusters in order to
reach faint submm/mm continuum sources. There are, however, a few cases where
millimeter lines have been directly involved in understanding lensing
configurations. Future mm/submm instruments, such as the ALMA interferometer,
will have both the sensitivity and the angular resolution to allow detailed
observations of gravitational lenses. The almost constant sensitivity to dust
emission over the redshift range z=1-10 means that the likelihood for strong
lensing of dust continuum sources is much higher than for optically selected
sources. A large number of new strong lenses are therefore likely to be
discovered with ALMA, allowing a direct assessment of cosmological parameters
through lens statistics. Combined with an angular resolution <0.1", ALMA will
also be efficient for probing the gravitational potential of galaxy clusters,
where we will be able to study both the sources and the lenses themselves, free
of obscuration and extinction corrections, derive rotation curves for the
lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on
"Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be
published by Springer-Verlag 2002. Paper with full resolution figures can be
found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g
A secreted PD-L1 splice variant that covalently dimerizes and mediates immunosuppression
Targeting immune checkpoint pathways, such as programmed death ligand-1 (PD-L1, also known as CD274 or B7-H1) or its receptor programmed cell death-1 (PD-1) has shown improved survival for patients with numerous types of cancers, not limited to lung cancer, melanoma, renal cell carcinoma, and Hodgkin lymphoma. PD-L1 is a co-inhibitory molecule whose expression on the surface of tumor cells is associated with worse prognosis in many tumors. Here we describe a splice variant (secPD-L1) that does not splice into the transmembrane domain, but instead produces a secreted form of PD-L1 that has a unique 18 amino acid tail containing a cysteine that allows it to homodimerize and more effectively inhibit lymphocyte function than monomeric soluble PD-L1. We show that recombinant secPD-L1 can dimerize and inhibit T-cell proliferation and IFN-gamma production in vitro. The secPD-L1 variant is expressed by malignant cells in vitro that also express high levels of full-length PD-L1. Transcriptomic analysis of gene expression across The Cancer Genome Atlas found the strongest association of secPD-L1 with full-length PD-L1, but also with subsets of immunologic genes, such as in myeloid-derived suppressor cells. Moreover, the splice variant is also expressed in normal tissues and within normal peripheral blood cells it is preferentially expressed in activated myeloid cells. This is the first report of a form of secreted PD-L1 that homodimerizes and is functionally active. SecPD-L1 may function as a paracrine negative immune regulator within the tumor, since secPD-L1 does not require a cell-to-cell interaction to mediate its inhibitory effect
Analysis of Severe Illness after Postvaccination COVID-19 Breakthrough among Adults with and Without HIV in the US
Importance: Understanding the severity of postvaccination SARS-CoV-2 (ie, COVID-19) breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations. Objective: To estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection. Design, Setting, and Participants: In this cohort study, the Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration included adults (aged ≥18 years) with HIV who were receiving care and were fully vaccinated by June 30, 2021, along with PWoH matched according to date fully vaccinated, age group, race, ethnicity, and sex from 4 US integrated health systems and academic centers. Those with postvaccination COVID-19 breakthrough before December 31, 2021, were eligible. Exposures: HIV infection. Main Outcomes and Measures: The main outcome was severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Discrete time proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% CIs of severe breakthrough illness within 28 days of breakthrough COVID-19 by HIV status adjusting for demographic variables, COVID-19 vaccine type, and clinical factors. The proportion of patients who received mechanical ventilation or died was compared by HIV status. Results: Among 3649 patients with breakthrough COVID-19 (1241 PWH and 2408 PWoH), most were aged 55 years or older (2182 patients [59.8%]) and male (3244 patients [88.9%]). The cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs 6.7%; risk difference, -0.67%; 95% CI, -2.58% to 1.23%). The risk of severe breakthrough illness was 59% higher in PWH with CD4 cell counts less than 350 cells/μL compared with PWoH (aHR, 1.59; 95% CI, 0.99 to 2.46; P =.049). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 cell count were associated with increased risk of severe breakthrough illness, whereas previous COVID-19 was associated with reduced risk. Among 249 hospitalized patients, 24 (9.6%) were mechanically ventilated and 20 (8.0%) died, with no difference by HIV status. Conclusions and Relevance: In this cohort study, the risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. PWH with moderate or severe immune suppression had a higher risk of severe breakthrough infection and should be included in groups prioritized for additional vaccine doses and risk-reduction strategies
Exome sequencing identifies variants in infants with sacral agenesis
Background: Sacral agenesis (SA) consists of partial or complete absence of the caudal end of the spine and often presents with additional birth defects. Several studies have examined gene variants for syndromic forms of SA, but only one has examined exomes of children with non-syndromic SA. Methods: Using buccal cell specimens from families of children with non-syndromic SA, exomes of 28 child–parent trios (eight with and 20 without a maternal diagnosis of pregestational diabetes) and two child–father duos (neither with diagnosis of maternal pregestational diabetes) were exome sequenced. Results: Three children had heterozygous missense variants in ID1 (Inhibitor of DNA Binding 1), with CADD scores >20 (top 1% of deleterious variants in the genome); two children inherited the variant from their fathers and one from the child's mother. Rare missense variants were also detected in PDZD2 (PDZ Domain Containing 2; N = 1) and SPTBN5 (Spectrin Beta, Non-erythrocytic 5; N = 2), two genes previously suggested to be associated with SA etiology. Examination of variants with autosomal recessive and X-linked recessive inheritance identified five and two missense variants, respectively. Compound heterozygous variants were identified in several genes. In addition, 12 de novo variants were identified, all in different genes in different children. Conclusions: To our knowledge, this is the first study reporting a possible association between ID1 and non-syndromic SA. Although maternal pregestational diabetes has been strongly associated with SA, the missense variants in ID1 identified in two of three children were paternally inherited. These findings add to the knowledge of gene variants associated with non-syndromic SA and provide data for future studies
The Sudbury Neutrino Observatory
The Sudbury Neutrino Observatory is a second generation water Cherenkov
detector designed to determine whether the currently observed solar neutrino
deficit is a result of neutrino oscillations. The detector is unique in its use
of D2O as a detection medium, permitting it to make a solar model-independent
test of the neutrino oscillation hypothesis by comparison of the charged- and
neutral-current interaction rates. In this paper the physical properties,
construction, and preliminary operation of the Sudbury Neutrino Observatory are
described. Data and predicted operating parameters are provided whenever
possible.Comment: 58 pages, 12 figures, submitted to Nucl. Inst. Meth. Uses elsart and
epsf style files. For additional information about SNO see
http://www.sno.phy.queensu.ca . This version has some new reference
Measurement of the νe and total 8B solar neutrino fluxes with the Sudbury Neutrino Observatory phase-III data set
This paper details the solar neutrino analysis of the 385.17-day phase-III data set acquired by the Sudbury Neutrino Observatory (SNO). An array of 3He proportional counters was installed in the heavy-water target to measure precisely the rate of neutrino-deuteron neutral-current interactions. This technique to determine the total active 8B solar neutrino flux was largely independent of the methods employed in previous phases. The total flux of active neutrinos was measured to be 5.54-0.31+0.33(stat.)-0.34+0.36(syst.)×106 cm-2 s-1, consistent with previous measurements and standard solar models. A global analysis of solar and reactor neutrino mixing parameters yielded the best-fit values of Δm2=7.59-0.21+0.19×10 -5eV2 and θ=34.4-1.2+1.3degrees
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