Quasi-molecular lines in Lyman wings of cool DA white dwarfs; Application to FUSE observations of G231-40

We present new theoretical calculations of the total line profiles of Lyman alpha and Lyman beta which include perturbations by both neutral hydrogen AND protons and all possible quasi-molecular states of H_2 and H_2^+. They are used to improve theoretical modeling of synthetic spectra for cool DA white dwarfs. We compare them with FUSE observation of G231-40. The appearance of the line wings between Lyman alpha and Lyman beta is shown to be sensitive to the relative abundance of hydrogen ions and neutral atoms, and thereby to provide a temperature diagnostic for stellar atmospheres and laboratory plasmas.Comment: 6 pages, 4 figures, accepted for publication in Astronomy and Astrophysic

Corrigendum to “Counting adolescents in: the development of an adolescent health indicator framework for population-based settings”

The authors were recently made aware of an oversight such that parts of the text in the Introduction and Methods sections, which describe shortcomings in the existing literature and the methods in this work to identify frameworks and indicators, were missing attribution to published work cited elsewhere in the manuscript. To clarify, we adjust the relevant sections to fully attribute the prior work in three areas, as described below. Underlined text is additional to the original: While both school- and community-based modalities can provide nationally representative data among eligible adolescents, several shortcomings in adolescent health measurement in LMICs were noted by the GAMA Advisory Group (Reference 13 as in the original paper). First, these measurements do not equally cover all adolescent subgroups, with evidence gaps being largest for males, younger adolescents aged 10–14 years, adolescents of diverse genders, ethnicities, and religions, as well as those out of school and migrants. Second, age-disaggregated data are often lacking—due in part to incomplete age coverage—limiting their use for program planning. Third, several aspects of adolescent health are inadequately covered including mental health, substance use, injury, sexual and reproductive health among unmarried adolescents, and positive aspects of adolescent health and well-being. Fourth, the definitions and assessment methods used across adolescent health indicator frameworks are inconsistent. For example, adolescent overweight and obesity—a major cause of non-communicable diseases and a public health risk for future and intergeneration health—is inconsistently captured across indicator frameworks and strikingly absent from the SDGs (Reference 13 as in the original paper). Additional shortcomings include, current adolescent health data systems often lack intersectoral coordination beyond health (e.g., with education, water and sanitation, and social protection systems) and suffer from irregularities in coverage and timing (Reference 6 as in the original paper). Broadly, these indicator frameworks and strategy documents captured disease burden, health risks, and prominent social determinants of health during adolescence. To be congruent with the existing global recommendations and guidelines (References 3–7 as in the original paper) and global measurement efforts (References 10 and 16 as in the original paper), the indicator framework documents had to meet three inclusion criteria, as laid out by the GAMA Advisory Group (Reference 14 as in the original paper): (1) provide recommendations about the measurement of adolescents' health and well-being; (2) include indicators for “adolescents” covering the adolescent age range (10–19 years) in the whole or part; and (3) be global or regional in scope. Using the GAMA's approach (Reference 13 as in the original paper), the recommendations of Lancet Adolescent Health Commission (Reference 6 as in the original paper), and several other guidelines (References 7, 9, 12, 17–19 as in the original paper), we selected adolescent health and well-being domains based on four key aspects of adolescents in LMICs: a) population trends; b) disease burden; c) drivers of health inequality; and d) opportunity for interventions

Counting adolescents in: the development of an adolescent health indicator framework for population-based settings

Changing realities in low- and middle-income countries (LMICs) in terms of inequalities, urbanization, globalization, migration, and economic adversity shape adolescent development and health, as well as successful transitions between adolescence and young adulthood. It is estimated that 90% of adolescents live in LMICs in 2019, but inadequate data exist to inform evidence-based and concerted policies and programs tailored to address the distinctive developmental and health needs of adolescents. Population-based data surveillance such as Health and Demographic Surveillance Systems (HDSS) and school-based surveys provide access to a well-defined population and provide cost-effective opportunities to fill in data gaps about adolescent health and well-being by collecting population-representative longitudinal data. The Africa Research Implementation Science and Education (ARISE) Network, therefore, systematically developed adolescent health and well-being indicators and a questionnaire for measuring these indicators that can be used in population-based LMIC settings. We conducted a multistage collaborative and iterative process led by network members alongside consultation with health-domain and adolescent health experts globally. Seven key domains emerged from this process: socio-demographics, health awareness and behaviors; nutrition; mental health; sexual and reproductive health; substance use; and healthcare utilization. For each domain, we generated a clear definition; rationale for inclusion; sub-domain descriptions, and a set of questions for measurement. The ARISE Network will implement the questionnaire longitudinally (i.e., at two time-points one year apart) at ten sites in seven countries in sub-Saharan Africa and two countries in Asia. Integrating the questionnaire within established population-based data collection platforms such as HDSS and school settings can provide measured experiences of young people to inform policy and program planning and evaluation in LMICs and improve adolescent health and well-being

Vibrational Excitations in Weakly Coupled Single-Molecule Junctions: A Computational Analysis

In bulk systems, molecules are routinely identified by their vibrational spectrum using Raman or infrared spectroscopy. In recent years, vibrational excitation lines have been observed in low-temperature conductance measurements on single molecule junctions and they can provide a similar means of identification. We present a method to efficiently calculate these excitation lines in weakly coupled, gateable single-molecule junctions, using a combination of ab initio density functional theory and rate equations. Our method takes transitions from excited to excited vibrational state into account by evaluating the Franck-Condon factors for an arbitrary number of vibrational quanta, and is therefore able to predict qualitatively different behaviour from calculations limited to transitions from ground state to excited vibrational state. We find that the vibrational spectrum is sensitive to the molecular contact geometry and the charge state, and that it is generally necessary to take more than one vibrational quantum into account. Quantitative comparison to previously reported measurements on pi-conjugated molecules reveals that our method is able to characterize the vibrational excitations and can be used to identify single molecules in a junction. The method is computationally feasible on commodity hardware.Comment: 9 pages, 7 figure

Genome-wide association reveals genetic effects on human Aβ₄₂and τ protein levels in cerebrospinal fluids: a case control study

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is common and highly heritable with many genes and gene variants associated with AD in one or more studies, including APOE ε2/ε3/ε4. However, the genetic backgrounds for normal cognition, mild cognitive impairment (MCI) and AD in terms of changes in cerebrospinal fluid (CSF) levels of Aβ_1-42, T-tau, and P-tau_181P, have not been clearly delineated. We carried out a genome-wide association study (GWAS) in order to better define the genetic backgrounds to these three states in relation to CSF levels.</p> <p>Methods</p> <p>Subjects were participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The GWAS dataset consisted of 818 participants (mainly Caucasian) genotyped using the Illumina Human Genome 610 Quad BeadChips. This sample included 410 subjects (119 Normal, 115 MCI and 176 AD) with measurements of CSF Aβ_1-42, T-tau, and P-tau_181PLevels. We used PLINK to find genetic associations with the three CSF biomarker levels. Association of each of the 498,205 SNPs was tested using additive, dominant, and general association models while considering APOE genotype and age. Finally, an effort was made to better identify relevant biochemical pathways for associated genes using the ALIGATOR software.</p> <p>Results</p> <p>We found that there were some associations with APOE genotype although CSF levels were about the same for each subject group; CSF Aβ_1-42levels decreased with APOE gene dose for each subject group. T-tau levels tended to be higher among AD cases than among normal subjects. From adjusted result using APOE genotype and age as covariates, no SNP was associated with CSF levels among AD subjects. <it>CYP19A1 </it>'aromatase' (rs2899472), <it>NCAM2</it>, and multiple SNPs located on chromosome 10 near the <it>ARL5B </it>gene demonstrated the strongest associations with Aβ_1-42in normal subjects. Two genes found to be near the top SNPs, <it>CYP19A1 </it>(rs2899472, p = 1.90 × 10^-7) and <it>NCAM2 </it>(rs1022442, p = 2.75 × 10^-7) have been reported as genetic factors related to the progression of AD from previous studies. In AD subjects, APOE ε2/ε3 and ε2/ε4 genotypes were associated with elevated T-tau levels and ε4/ε4 genotype was associated with elevated T-tau and P-tau_181Plevels. Pathway analysis detected several biological pathways implicated in Normal with CSF β-amyloid peptide (Aβ_1-42).</p> <p>Conclusions</p> <p>Our genome-wide association analysis identified several SNPs as important factors for CSF biomarker. We also provide new evidence for additional candidate genetic risk factors from pathway analysis that can be tested in further studies.</p

Clinicopathological characteristics and treatment strategies in early gastric cancer: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Both endoscopic and surgical approaches are employed in the treatment of early gastric cancer (EGC). The aim of this study was to establish appropriate treatment strategies for early gastric cancer.</p> <p>Methods</p> <p>We retrospectively examined clinicopathological data of EGC patients who had undergone surgery.</p> <p>Results</p> <p>A total of 327 patients (204 males and 123 females, mean age 63.2 years) were eligible for inclusion in the study. The median follow-up period was 31 months. Of 161 mucosal (pT1a) tumors, 87 were mainly undifferentiated and 110 had an undifferentiated component. Four patients with pT1a tumors had lymph node metastases; all these tumors were signet-ring cell carcinomas and were macroscopic type 0-IIc with ulceration, and only one of them had lymphatic invasion. Among patients with submucosal tumors, four of 43 patients with pT1b1 tumors and 37 of 123 patients with pT1b2 tumors had nodal metastases. Lymph node metastases were significantly higher in mixed undifferentiated type group than differentiated type group for both groups, pT1a-pT1b1 (p = 0.0251) and pT1b2 (p = 0.0430) subgroups. Only four of 45 patients with nodal metastases were diagnosed preoperatively by computed tomography (sensitivity 8.9%, specificity 96.2%). Nine patients with pT1b tumors had recurrence after surgery, and died. The sites of initial recurrence were liver, bone, peritoneum, distant nodes, and the surgical anastomosis.</p> <p>Conclusions</p> <p>The incidence of nodal metastases was approximately 5% in undifferentiated type mucosal (pT1a) tumors, and higher in submucosal (pT1b) tumors. The sensitivity of preoperative diagnosis of nodal metastases in EGC using computed tomography was relatively low in this study. Therefore at present surgery with adequate lymphadenectomy should be performed as curative treatment for undifferentiated type EGC.</p

Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes

peer-reviewedBackground: About forty human diseases are caused by repeat instability mutations. A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation is also apparent in human poly-Q encoding genes from normal individuals. As these coding sequence repeats are subject to selection in mammals, it has been suggested that normal variations in some of these typically highly conserved genes are implicated in morphological differences between species and phenotypic variations within species. At present, poly-Q encoding genes in non-human mammalian species are poorly documented, as are their functions and propensities for polymorphic variation. Results: The current investigation identified 178 bovine poly-Q encoding genes (Q ≥ 5) and within this group, 26 genes with orthologs in both human and mouse that did not contain poly-Q repeats. The bovine poly-Q encoding genes typically had ubiquitous expression patterns although there was bias towards expression in epithelia, brain and testes. They were also characterised by unusually large sizes. Analysis of gene ontology terms revealed that the encoded proteins were strongly enriched for functions associated with transcriptional regulation and many contributed to physical interaction networks in the nucleus where they presumably act cooperatively in transcriptional regulatory complexes. In addition, the coding sequence CAG repeats in some bovine genes impacted mRNA splicing thereby generating unusual transcriptional diversity, which in at least one instance was tissue-specific. The poly-Q encoding genes were prioritised using multiple criteria for their likelihood of being polymorphic and then the highest ranking group was experimentally tested for polymorphic variation within a cattle diversity panel. Extensive and meiotically stable variation was identified. Conclusions: Transcriptional diversity can potentially be generated in poly-Q encoding genes by the impact of CAG repeat tracts on mRNA alternative splicing. This effect, combined with the physical interactions of the encoded proteins in large transcriptional regulatory complexes suggests that polymorphic variations of proteins in these complexes have strong potential to affect phenotype.Dairy Australia (through the Innovative Dairy Cooperative Research Center

Separation of DNA Replication from the Assembly of Break-Competent Meiotic Chromosomes

The meiotic cell division reduces the chromosome number from diploid to haploid to form gametes for sexual reproduction. Although much progress has been made in understanding meiotic recombination and the two meiotic divisions, the processes leading up to recombination, including the prolonged pre-meiotic S phase (meiS) and the assembly of meiotic chromosome axes, remain poorly defined. We have used genome-wide approaches in Saccharomyces cerevisiae to measure the kinetics of pre-meiotic DNA replication and to investigate the interdependencies between replication and axis formation. We found that replication initiation was delayed for a large number of origins in meiS compared to mitosis and that meiotic cells were far more sensitive to replication inhibition, most likely due to the starvation conditions required for meiotic induction. Moreover, replication initiation was delayed even in the absence of chromosome axes, indicating replication timing is independent of the process of axis assembly. Finally, we found that cells were able to install axis components and initiate recombination on unreplicated DNA. Thus, although pre-meiotic DNA replication and meiotic chromosome axis formation occur concurrently, they are not strictly coupled. The functional separation of these processes reveals a modular method of building meiotic chromosomes and predicts that any crosstalk between these modules must occur through superimposed regulatory mechanisms

Rivastigmine Lowers Aβ and Increases sAPPα Levels, Which Parallel Elevated Synaptic Markers and Metabolic Activity in Degenerating Primary Rat Neurons

Overproduction of amyloid-β (Aβ) protein in the brain has been hypothesized as the primary toxic insult that, via numerous mechanisms, produces cognitive deficits in Alzheimer's disease (AD). Cholinesterase inhibition is a primary strategy for treatment of AD, and specific compounds of this class have previously been demonstrated to influence Aβ precursor protein (APP) processing and Aβ production. However, little information is available on the effects of rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, on APP processing. As this drug is currently used to treat AD, characterization of its various activities is important to optimize its clinical utility. We have previously shown that rivastigmine can preserve or enhance neuronal and synaptic terminal markers in degenerating primary embryonic cerebrocortical cultures. Given previous reports on the effects of APP and Aβ on synapses, regulation of APP processing represents a plausible mechanism for the synaptic effects of rivastigmine. To test this hypothesis, we treated degenerating primary cultures with rivastigmine and measured secreted APP (sAPP) and Aβ. Rivastigmine treatment increased metabolic activity in these cultured cells, and elevated APP secretion. Analysis of the two major forms of APP secreted by these cultures, attributed to neurons or glia based on molecular weight showed that rivastigmine treatment significantly increased neuronal relative to glial secreted APP. Furthermore, rivastigmine treatment increased α-secretase cleaved sAPPα and decreased Aβ secretion, suggesting a therapeutic mechanism wherein rivastigmine alters the relative activities of the secretase pathways. Assessment of sAPP levels in rodent CSF following once daily rivastigmine administration for 21 days confirmed that elevated levels of APP in cell culture translated in vivo. Taken together, rivastigmine treatment enhances neuronal sAPP and shifts APP processing toward the α-secretase pathway in degenerating neuronal cultures, which mirrors the trend of synaptic proteins, and metabolic activity