810 research outputs found
The Developing Methodology for Analyzing Privacy Torts
The authors assert the need for a common method of analyzing privacy situations that can be applied consistently by practitioners, juries and courts. They contend that confusion exists as to the legal basis of privacy torts because the right of privacy, as originally conceived by Warren and Brandeis, was never adequately defined. Prosser\u27s analysis of privacy torts departs from the Warren and Brandeis formulation and, according to the authors, also can be criticized for lack of definition. The authors present a new methodology that analyzes privacy torts based upon the scope of consent standard. They maintain that the result will be the protection of the right of privacy as originally conceived by Warren and Brandeis
Retention in the British National Health Service of medical graduates trained in Britain: cohort studies
Objective To report the percentage of graduates from British medical schools who eventually practise medicine in the British NHS
Loss of the Histone Pre-mRNA Processing Factor Stem-Loop Binding Protein in Drosophila Causes Genomic Instability and Impaired Cellular Proliferation
BACKGROUND:Metazoan replication-dependent histone mRNAs terminate in a conserved stem-loop structure rather than a polyA tail. Formation of this unique mRNA 3' end requires Stem-loop Binding Protein (SLBP), which directly binds histone pre-mRNA and stimulates 3' end processing. The 3' end stem-loop is necessary for all aspects of histone mRNA metabolism, including replication coupling, but its importance to organism fitness and genome maintenance in vivo have not been characterized. METHODOLOGY/PRINCIPAL FINDINGS:In Drosophila, disruption of the Slbp gene prevents normal histone pre-mRNA processing and causes histone pre-mRNAs to utilize the canonical 3' end processing pathway, resulting in polyadenylated histone mRNAs that are no longer properly regulated. Here we show that Slbp mutants display genomic instability, including loss of heterozygosity (LOH), increased presence of chromosome breaks, tetraploidy, and changes in position effect variegation (PEV). During imaginal disc growth, Slbp mutant cells show defects in S phase and proliferate more slowly than control cells. CONCLUSIONS/SIGNIFICANCE:These data are consistent with a model in which changing the 3' end of histone mRNA disrupts normal replication-coupled histone mRNA biosynthesis and alters chromatin assembly, resulting in genomic instability, inhibition of cell proliferation, and impaired development
Angular versus radial correlation effects on momentum distributions of light two-electron ions
We investigate different correlation mechanisms for two-electron systems and
compare their respective effects on various electron distributions. The
simplicity of the wave functions used allows for the derivation of closed-form
analytical expressions for all electron distributions. Among other features, it
is shown that angular and radial correlation mechanisms have opposite effects
on Compton profiles at small momenta.Comment: 22 pages, 5 figures, 3 tabl
Lightest-neutralino decays in R_p-violating models with dominant lambda^{prime} and lambda couplings
Decays of the lightest neutralino are studied in R_p-violating models with
operators lambda^{prime} L Q D^c and lambda L L E^c involving third-generation
matter fields and with dominant lambda^{prime} and lambda couplings.
Generalizations to decays of the lightest neutralino induced by subdominant
lambda^{prime} and lambda couplings are straightforward. Decays with the
top-quark among the particles produced are considered, in addition to those
with an almost massless final state. Phenomenological analyses for examples of
both classes of decays are presented. No specific assumption on the composition
of the lightest neutralino is made, and the formulae listed here can be easily
generalized to study decays of heavier neutralinos. It has been recently
pointed out that, for a sizable coupling lambda^{prime}_{333}, tau-sleptons may
be copiously produced at the LHC as single supersymmetric particles, in
association with top- and bottom-quark pairs. This analysis of neutralino
decays is, therefore, a first step towards the reconstruction of the complete
final state produced in this case.Comment: 40 pages, 11 figures, version to appear in JHE
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.
It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases6-8. This includes muscle biopsies from patients with undiagnosed rare muscle disorders6,9, and cultured fibroblasts from patients with mitochondrial disorders7. However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution
Upper gastrointestinal Crohn's disease
Symptomatic gastroduodenal manifestations of Crohn's disease are rare, with less than 4% of patients being clinically symptomatic. Gastroduodenal involvement may, however, be found endoscopically in 20% and in up to 40% of cases histologically, most frequently as Helicobacter pylori-negative focal gastritis, usually in patients with concomitant distal ileal disease. In practice, the activity of concomitant distal Crohn's disease usually determines the indication for therapy, except in the presence of obstructive gastroduodenal symptoms. With the few data available, it seems correct to say that localized gastroduodenal disease should be treated with standard medical therapy used for more distal disease, with the exception of the galenic formulation of sulfasalazine and mesalazine with pH-dependent release. The presence of symptoms of obstruction needs aggressive therapy. If medical therapy with steroids and immunomodulatory drugs does not alleviate the symptoms, balloon dilation and surgery are the options to consider. [Ed.]]]>
oai:serval.unil.ch:BIB_5E8B8CEC2A7F
2022-05-07T01:18:50Z
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Agniṣṭoma and the nature of sacrifice
Bronkhorst, Johannes
info:eu-repo/semantics/bookPart
incollection
2016
On Meaning and Mantras: Essays in Honor of Frits Staal, pp. 79-99
Thompson, George (ed.)
Payne, Richard K. (ed.)
info:eu-repo/semantics/altIdentifier/isbn/978-1-886439-64-1
eng
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oai:serval.unil.ch:BIB_5E8C17A3E220
2022-05-07T01:18:50Z
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Selective regulation of acid-sensing ion channel 1 by serine proteases.
info:doi:10.1074/jbc.M407381200
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M407381200
info:eu-repo/semantics/altIdentifier/pmid/15247234
Poirot, O.
Vukicevic, M.
Boesch, A.
Kellenberger, S.
info:eu-repo/semantics/article
article
2004
Journal of Biological Chemistry, vol. 279, no. 37, pp. 38448-38457
info:eu-repo/semantics/altIdentifier/pissn/0021-9258[print], 0021-9258[linking]
<![CDATA[Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that belong to the epithelial Na(+) channel/degenerin family. ASICs are transiently activated by a rapid drop in extracellular pH. Conditions of low extracellular pH, such as ischemia and inflammation in which ASICs are thought to be active, are accompanied by increased protease activity. We show here that serine proteases modulate the function of ASIC1a and ASIC1b but not of ASIC2a and ASIC3. We show that protease exposure shifts the pH dependence of ASIC1a activation and steady-state inactivation to more acidic pH. As a consequence, protease exposure leads to a decrease in current response if ASIC1a is activated by a pH drop from pH 7.4. If, however, acidification occurs from a basal pH of approximately 7, protease-exposed ASIC1a shows higher activity than untreated ASIC1a. We provide evidence that this bi-directional regulation of ASIC1a function also occurs in neurons. Thus, we have identified a mechanism that modulates ASIC function and may allow ASIC1a to adapt its gating to situations of persistent extracellular acidification
Variegate porphyria in South Africa, 1688 - 1996 - new developments in an old disease
Variegate porphyria, an autosomal dominant inherited trait resulting in decreased activity of protoporphyrinogen oxidase, the penuttimate haem biosynthetic enzyme, is characterised clinically by photosensitive skin disease and a propensity to acute neurovisceral crises. The disease has an exceptionally high frequency in South Africa,owing to a founder effect. The specific mutation in the protoporphynnogen oxidase gene sequence which represents this founder gene has been identified. Genetic diagnosis is therefore now possible in families in whom the gene defect is known. However, the exact nature and degree of activity of the porphyria can only be determined by detailed quantitative biochemical analysis of excreted porphyrins. The relative contributions of the acute attack and the skin disease to the total disease burden of patients with variegate porphyria is not static, and in South Africa there have been significant changes over the past 25 years, with fewer patients presenting with acute attacks, leaving a greater proportion to present with skin disease or to remain asymptomatic with the diagnosis being made in the laboratory. The most common precipitating cause of the acute attack of VP is administration of porphyrinogenic drugs. Specific suppression of haem synthesis with intravenous haem arginate is the most useful treatment of a moderate or severe acute attack. Although cutaneous lesions are limited to the sun-exposed areas, management of the skin disease of VP remains inadequate
Is leptogenesis falsifiable at LHC?
It is well known that the leptogenesis mechanism offers an attractive
possibility to explain the baryon asymmetry of the universe. Its particular
robustness however comes with one major difficulty: it will be very hard if not
impossible to test experimentally in a foreseeable future, as most of the
mechanics typically takes place at high energy or results from suppressed
interactions, without unavoidable low-energy implications. An alternate
approach is taken by asking: can it be at least falsified? We show that
possible discoveries at current and future colliders, most notably that of
right-handed gauge interactions, would indeed forbid at least the "canonical"
leptogenesis mechanisms, namely those based on right-handed neutrino decay.
General lower bounds for successful leptogenesis on the mass of the
right-handed gauge boson W_R are given. Other possibilities to falsify
leptogenesis, including from the observation of a Z', are also considered.Comment: 22 pages ; v3: discussion about resonant leptogenesis case added ;
matches JHEP published versio
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