132 research outputs found
Expected geoneutrino signal at JUNO
Constraints on the Earth's composition and on its radiogenic energy budget
come from the detection of geoneutrinos. The KamLAND and Borexino experiments
recently reported the geoneutrino flux, which reflects the amount and
distribution of U and Th inside the Earth. The KamLAND and Borexino experiments
recently reported the geoneutrino flux, which reflects the amount and
distribution of U and Th inside the Earth. The JUNO neutrino experiment,
designed as a 20 kton liquid scintillator detector, will be built in an
underground laboratory in South China about 53 km from the Yangjiang and
Taishan nuclear power plants. Given the large detector mass and the intense
reactor antineutrino flux, JUNO aims to collect high statistics antineutrino
signals from reactors but also to address the challenge of discriminating the
geoneutrino signal from the reactor background.The predicted geoneutrino signal
at JUNO is 39.7 TNU, based on the existing reference Earth
model, with the dominant source of uncertainty coming from the modeling of the
compositional variability in the local upper crust that surrounds (out to
500 km) the detector. A special focus is dedicated to the 6{\deg} x
4{\deg} Local Crust surrounding the detector which is estimated to contribute
for the 44% of the signal. On the base of a worldwide reference model for
reactor antineutrinos, the ratio between reactor antineutrino and geoneutrino
signals in the geoneutrino energy window is estimated to be 0.7 considering
reactors operating in year 2013 and reaches a value of 8.9 by adding the
contribution of the future nuclear power plants. In order to extract useful
information about the mantle's composition, a refinement of the abundance and
distribution of U and Th in the Local Crust is required, with particular
attention to the geochemical characterization of the accessible upper crust.Comment: Slight changes and improvements in the text,22 pages, 4 Figures, 3
Tables. Prog. in Earth and Planet. Sci. (2015
Functional Effects of the TMEM43 Ser358Leu Mutation in the Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy
Background: The Ser358Leu mutation in TMEM43, encoding an inner nuclear membrane protein, has been implicated in arrhythmogenic right ventricular cardiomyopathy (ARVC). The pathogenetic mechanisms of this mutation are poorly understood. Methods: To determine the frequency of TMEM43 mutations as a cause of ARVC, we screened 11 ARVC families for mutations in TMEM43 and five desmosomal genes previously implicated in the disease. Functional studies were performed in COS-7 cells transfected with wildtype, mutant, and 1:2 wildtype:mutant TMEM43 to determine the effect of the Ser358Leu mutation on the stability and cellular localization of TMEM43 and other nuclear envelope and desmosomal proteins, assessed by solubility assays and immunofluorescence imaging. mRNA expression was assessed of genes potentially affected by dysfunction of the nuclear lamina. Results: Three novel mutations in previously documented desmosomal genes, but no mutations in TMEM43, were identified. COS-7 cells transfected with mutant TMEM43 exhibited no change in desmosomal stability. Stability and nuclear membrane localization of mutant TMEM43 and of lamin B and emerin were normal. Mutant TMEM43 did not alter the expression of genes located on chromosome 13, previously implicated in nuclear envelope protein mutations leading to skeletal muscular dystrophies. Conclusions: Mutant TMEM43 exhibits normal cellular localization and does not disrupt integrity and localization of other nuclear envelope and desmosomal proteins. The pathogenetic role of TMEM43 mutations in ARVC remains uncertain
Sleep Disturbance, Symptoms, Psychological Distress, and Health-Related Quality of Life in Pulmonary Arterial Hypertension
Background:
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by elevated pulmonary pressures that lead to right heart failure and premature mortality. Patients experience multiple symptoms including dyspnea, fatigue and chest pain, but little is known about sleep disturbance, PAH symptoms, psychological distress and health-related quality of life (HRQOL) in PAH.
Aim:
The purpose of this study was to describe the occurrence of sleep disturbance and compare PAH symptoms, psychological distress, and HRQOL across severity of sleep disturbance.
Methods:
One hundred and ninety-one participants completed a socio-demographic and clinical data form, PAH Symptom Severity Scale, Profile of Mood States (POMS) short form and the Medical Outcomes Short Form-36 (SF-36). Descriptive statistics were used to describe sleep disturbances; analysis of variance models were used to quantify differences in PAH symptoms, psychological distress and HRQOL by sleep disturbance groups.
Results:
The majority of participants (n=162, 85%) were women with a mean age of 53 years. Sixty-five (34%) reported no sleep disturbance; 54 (28%) mild sleep disturbance; 41 (22%) moderate sleep disturbance; and 31 (16%) severe sleep disturbance. Those reporting higher sleep disturbance severity reported worse PAH symptoms, psychological distress, and HRQOL.
Conclusions:
Sleep disturbance is a significant finding in PAH. Increasing levels of sleep disturbance are associated with worse PAH symptoms, psychological states, and health-related quality of life. Interventions that decrease sleep disturbances may improve symptoms and HRQOL
The relationship of the knowledge of letter names and reading achievement in grade one.
Thesis (Ed.M.)--Boston Universit
Living Machines: A study of atypical animacy
This paper proposes a new approach to animacy detection, the task of determining whether an entity is represented as animate in a text. In particular, this work is focused on atypical animacy and examines the scenario in which typically inanimate objects, specifically machines, are given animate attributes. To address it, we have created the first dataset for atypical animacy detection, based on nineteenth-century sentences in English, with machines represented as either animate or inanimate. Our method builds on recent innovations in language modeling, specifically BERT contextualized word embeddings, to better capture fine-grained contextual properties of words. We present a fully unsupervised pipeline, which can be easily adapted to different contexts, and report its performance on an established animacy dataset and our newly introduced resource. We show that our method provides a substantially more accurate characterization of atypical animacy, especially when applied to highly complex forms of language use
THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage
Background and Purpose A ruptured intracranial aneurysm (IA) is the leading cause of a subarachnoid hemorrhage (SAH). This study seeks to define a specific gene whose mutation leads to disease. Methods More than 500 IA probands and 100 affected families were enrolled and clinically characterized. Whole exome sequencing was performed on a large family, revealing a segregating THSD1 mutation. THSD1 was sequenced in other probands and controls. Thsd1 loss-of-function studies in zebrafish and mice were used for in vivo analyses, and functional studies performed using an in vitro endothelial cell model. Results A nonsense mutation in THSD1 (thrombospondin type-1 domain-containing protein 1) was identified that segregated with the 9 affected (3 suffered SAH; 6 had unruptured IA) and 13 unaffected family members (LOD score 4.69). Targeted THSD1 sequencing identified mutations in 8 of 507 unrelated IA probands, including 3 who had suffered SAH (1.6% [95% CI, 0.8%–3.1%]). These THSD1 mutations/rare variants were highly enriched in our IA patient cohort relative to 89,040 chromosomes in ExAC database (p\u3c0.0001). In zebrafish and mice, Thsd1 loss-of-function caused cerebral bleeding (which localized to the subarachnoid space in mice) and increased mortality. Mechanistically, THSD1 loss impaired endothelial cell focal adhesion to the basement membrane. These adhesion defects could be rescued by expression of wild-type THSD1 but not THSD1 mutants identified in IA patients. Conclusions This report identifies THSD1 mutations in familial and sporadic IA patients, and shows that THSD1 loss results in cerebral bleeding in two animal models. This finding provides new insight into IA and SAH pathogenesis and provides new understanding of THSD1 function, which includes endothelial cell to extracellular matrix adhesion
Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?
Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure
Damaging variants in FOXI3 cause microtia and craniofacial microsomia
Q1Q1Pacientes con Microtia y MicrosomÃa craneofacialPurpose:
Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown.
Methods:
We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro.
Results:
We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3.
Conclusion:
Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.https://orcid.org/0000-0003-3822-7780https://orcid.org/0000-0002-0729-6866Revista Internacional - IndexadaA1N
Gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL) and 1,4 butanediol (1,4-BD; BDO) : a literature review with a focus on UK fatalities related to non-medical use
Misuse of gamma hydroxybutrate (GHB) and gamma butyrolactone (GBL) has increased greatly since the early 1990s, being implicated in a rising number of deaths. This paper reviews knowledge on GHB and derivatives, and explores the largest series of deaths associated with their non-medical use. Descriptive analyses of cases associated with GHB/GBL and 1,4 butanediol (1,4-BD) use extracted from the UK’s National Programme on Substance Abuse Deaths database. From 1995 to September 2013, 159 GHB/GBL-associated fatalities were reported. Typical victims: White (92%), young (mean age 32 years); male (82%); with a drug misuse history (70%). Most deaths (79%) were accidental or related to drug use, the remainder (potential) suicides. GHB/GBL alone was implicated in 37%; alcohol 14%; other drugs 28%; other drugs and alcohol 15%. Its endogenous nature and rapid elimination limit toxicological detection. Post-mortem blood levels: mean 482 (range 0 - 6500; S.D. 758) mg/L. Results suggest significant caution is needed when ingesting GHB/GBL, particularly with alcohol, benzodiazepines, opiates, stimulants, and ketamine. More awareness is needed about risks associated with consumption.Peer reviewe
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