285 research outputs found
CODE-1 : moored array and large-scale data report
The Coastal Ocean Dynamics Experiment
(CODE) was undertaken to identify and study
the important dynamical processes which
govern the wind-driven motion of coastal
water over the continental shelf. The
initial effort in this multi-year, multi-institutional
research program was to obtain
high-quality data sets of all the
relevant physical variables needed to construct
accurate kinematic and dynamic descriptions
of the response of shelf water
to strong wind forcing in the 2 to 10 day
band. A series of two small-scale, densely-instrumented
field experiments of approximately
four months duration (called CODE-1
and CODE-2) were designed to explore and
to determine the kinematics and momentum
and heat balances of the local wind-driven
flow over a region of the northern California shelf which is characterized by both
relatively simple bottom topography and
large wind stress events in both winter
and summer. A more lightly instrumented,
long-term, large-scale component was designed
to help separate the local wind-driven
response in the region of the small-scale
experiments from motions generated either offshore by the California Current
system or in some distant region along the
coast, and also to help determine the seasonal
cycles of the atmospheric forcing,
water structure, and coastal currents over
the northern California shelf.
The first small-scale experiment
(CODE-1) was conducted between April and
August, 1981 as a pilot study in which
primary emphasis was placed on characterizing
the wind-driven "signal" and the
"noise" from which this signal must be
extracted. In particular, CODE-1 was
designed to identify the key features of
the circulation and its variability over
the northern California shelf and to
determine the important time and length
scales of the wind-driven response. This
report presents a basic description of the
moored array data and some other Eulerian
data collected during CODE-1. A brief
description of the CODE-1 field program is
presented first, followed by a description
of the common data analysis procedures used
to produce the various data sets presented
here. Then basic descriptions of the following
data sets are presented: (a) the
coastal and moored meteorological measurements,
(b) the moored current measurements,
(c) the moored temperature and conductivity
observations, (d) the bottom pressure measurements,
and (e) the wind and adjusted
coastal sea level observations obtained as
part of the CODE-1 large-scale component.Prepared for the National Science
Foundation under Grant OCE 80-14941
Evidence of Natural Bluetongue Virus Infection among African Carnivores
Bluetongue is an International Office of Epizootics List A disease described as the century\u27s most economically devastating affliction of sheep. Bluetongue (BLU) viruses were thought to infect only ruminants, shrews, and some rodents, but recently, inadvertent administration of BLU virus-contaminated vaccine resulted in mortality and abortion among domestic dogs. We present evidence of natural BLU virus infection among African carnivores that dramatically widens the spectrum of susceptible hosts. We hypothesize that such infection occurred after ingestion of meat and organs from BLU virus infected prey species. The effect of BLU virus on endangered carnivores such as the cheetah and African wild dog requires urgent investigation. Also, the role of carnivores in the epizootiology of this disease needs elucidation
NOTCH3 Expression Is Linked to Breast Cancer Seeding and Distant Metastasis
Background: Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive.
Methods: We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERñ+) MCF-7 breast cancer cells with constitutive active Raf-1/mitogen-associated protein kinase (MAPK) signaling (vMCF-7Raf-1) and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The critical role of NOTCH3 in inducing an invasive phenotype and poor outcome was corroborated in unique TNBC cells resulting from a patient-derived brain metastasis (TNBC-M25) and in publicly available claudin-low breast tumor specimens collected from participants in the Molecular Taxonomy of Breast Cancer International Consortium database.
Results: In this study, we identified an association between NOTCH3 expression and development of metastases in ERñ+ and TNBC models. ERñ+ breast tumor xenografts with a constitutive active Raf-1/MAPK signaling developed spontaneous lung metastases through the clonal expansion of cancer cells expressing a NOTCH3 reprogramming network. Abrogation of NOTCH3 expression significantly reduced the self-renewal and invasive capacity of ex vivo breast cancer cells, restoring a luminal CD44low/CD24high/ERñhigh phenotype. Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype. Likewise, pharmacologic inhibition of NOTCH signaling also impaired TNBC cell seeding and metastatic growth. Significantly, the role of aberrant NOTCH3 expression in promoting tumor self-renewal, invasiveness, and poor outcome was corroborated in unique TNBC cells from a patient-derived brain metastasis and in publicly available claudin-low breast tumor specimens.
Conclusions: These findings demonstrate the key role of NOTCH3 oncogenic signaling in the genesis of breast cancer metastasis and provide a compelling preclinical rationale for the design of novel therapeutic strategies that will selectively target NOTCH3 to halt metastatic seeding and to improve the clinical outcomes of patients with breast cancer
Status of Muon Collider Research and Development and Future Plans
The status of the research on muon colliders is discussed and plans are
outlined for future theoretical and experimental studies. Besides continued
work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy
collider, many studies are now concentrating on a machine near 0.1 TeV (CoM)
that could be a factory for the s-channel production of Higgs particles. We
discuss the research on the various components in such muon colliders, starting
from the proton accelerator needed to generate pions from a heavy-Z target and
proceeding through the phase rotation and decay ()
channel, muon cooling, acceleration, storage in a collider ring and the
collider detector. We also present theoretical and experimental R & D plans for
the next several years that should lead to a better understanding of the design
and feasibility issues for all of the components. This report is an update of
the progress on the R & D since the Feasibility Study of Muon Colliders
presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A.
Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics
(Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics,
Accelerators and Beam
An Outcome Assessment of a Single Institution\u27s Longitudinal Experience with Uveal Melanoma Patients with Liver Metastasis.
There is no FDA-approved treatment for metastatic uveal melanoma (UM) and overall outcomes are generally poor for those who develop liver metastasis. We performed a retrospective single-institution chart review on consecutive series of UM patients with liver metastasis who were treated at Thomas Jefferson University Hospital between 1971â1993 (Cohort 1, n = 80), 1998â2007 (Cohort 2, n = 198), and 2008â2017 (Cohort 3, n = 452). In total, 70% of patients in Cohort 1 received only systemic therapies as their treatment modality for liver metastasis, while 98% of patients in Cohort 2 and Cohort 3 received liver-directed treatment either alone or with systemic therapy. Median Mets-to-Death OS was shortest in Cohort 1 (5.3 months, 95% CI: 4.2â7.0), longer in Cohort 2 (13.6 months, 95% CI: 12.2â16.6) and longest in Cohort 3 (17.8 months, 95% CI: 16.6â19.4). Median Eye Tx-to-Death OS was shortest in Cohort 1 (40.8 months, 95% CI: 37.1â56.9), and similar in Cohort 2 (62.6 months, 95% CI: 54.6â71.5) and Cohort 3 (59.4 months, 95% CI: 56.2â64.7). It is speculated that this could be due to the shift of treatment modalities from DTIC-based chemotherapy to liverdirected therapies. Combination of liver-directed and newly developed systemic treatments may further improve the survival of these patients
Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England
The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1â42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0â5) and 5 (95%CI 3â6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0â23) hospitalisations with epilepsy and 4 (95%CI 0â6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection
Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1â28âdays following adenovirus (ChAdOx1, nâ=â20,615,911) or messenger RNA-based (BNT162b2, nâ=â16,993,389; mRNA-1273, nâ=â1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (nâ=â3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1â28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1âmillion people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28âdays following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1âmillion vaccinated in the 28âdays after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1âmillion patients in the 28âdays following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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