First detection of methanol towards a post-AGB object, HD101584

The circumstellar environments of objects on the asymptotic giant branch and beyond are rich in molecular species. Nevertheless, methanol has never been detected in such an object, and is therefore often taken as a clear signpost for a young stellar object. However, we report the first detection of CH3OH in a post-AGB object, HD101584, using ALMA. Its emission, together with emissions from CO, SiO, SO, CS, and H2CO, comes from two extreme velocity spots on either side of the object where a high-velocity outflow appears to interact with the surrounding medium. We have derived molecular abundances, and propose that the detected molecular species are the effect of a post-shock chemistry where circumstellar grains play a role. We further provide evidence that HD101584 was a low-mass, M-type AGB star

Ground-state ammonia and water in absorption towards Sgr B2

Context. Observations of transitions to the ground-state of a molecule are essential to obtain a complete picture of its excitation and chemistry in the interstellar medium, especially in diffuse and/or cold environments. For the important interstellar molecules H₂O and NH₃, these ground-state transitions are heavily absorbed by the terrestrial atmosphere, hence not observable from the ground. Aims: We attempt to understand the chemistry of nitrogen, oxygen, and their important molecular forms, NH₃ and H₂O in the interstellar medium of the Galaxy. Methods: We have used the Odin* submillimetre-wave satellite telescope to observe the ground state transitions of ortho-ammonia and ortho-water, including their ¹⁵N, ¹⁸O, and ¹⁷O isotopologues, towards Sgr B2. The extensive simultaneous velocity coverage of the observations, >500 km s^-1, ensures that we can probe the conditions of both the warm, dense gas of the molecular cloud Sgr B2 near the Galactic centre, and the more diffuse gas in the Galactic disk clouds along the line-of-sight. Results: We present ground-state NH₃ absorption in seven distinct velocity features along the line-of-sight towards Sgr B2. We find a nearly linear correlation between the column densities of NH₃ and CS, and a square-root relation to N₂H⁺. The ammonia abundance in these diffuse Galactic disk clouds is estimated to be about 0.5–1 × 10^-8, similar to that observed for diffuse clouds in the outer Galaxy. On the basis of the detection of H_218O absorption in the 3 kpc arm, and the absence of such a feature in the H_217O spectrum, we conclude that the water abundance is around 10-7, compared to ~10-8 for NH3. The Sgr B2 molecular cloud itself is seen in absorption in NH₃, 15NH₃, H₂O, H_218O, and H_217O, with emission superimposed on the absorption in the main isotopologues. The non-LTE excitation of NH3 in the environment of Sgr B2 can be explained without invoking an unusually hot (500 K) molecular layer. A hot layer is similarly not required to explain the line profiles of the 11,0≥ts10,1 transition from H2O and its isotopologues. The relatively weak 15NH3 absorption in the Sgr B2 molecular cloud indicates a high [ 14N/15N] isotopic ratio >600. The abundance ratio of H_218O and H_217O is found to be relatively low, 2.5–3. These results together indicate that the dominant nucleosynthesis process in the Galactic centre is CNO hydrogen burning. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), and the centre National d'Études Spatiales (CNES, France). The Swedish Space Corporation (SSC) was the industrial prime contractor and is also responsible for the satellite operation

Carbon-Based Nanoelectromechanical Devices

Carbon-based nanoelectromechanical devices are approaching applications in electronics. Switches based on individual carbon nanotubes deliver record low off-state leakage currents. Arrays of vertically aligned carbon nanotubes or nanofibers can be fabricated to constitute varactors. Very porous, low density arrays of quasi-vertically aligned arrays of carbon nanotubes behave mechanically as a single unit with very unusual material properties

Variation in amount of wild-type transthyretin in different fibril and tissue types in ATTR amyloidosis

Familial transthyretin (TTR) amyloidosis is caused by a mutation in the TTR gene, although wild-type (wt) TTR is also incorporated into the amyloid fibrils. Liver transplantation (LT) is the prevailing treatment of the disease and is performed in order to eliminate the mutant TTR from plasma. The outcome of the procedure is varied; especially problematic is a progressive cardiomyopathy seen in some patients, presumably caused by continued incorporation of wtTTR. What determines the discrepancy in outcome is not clear. We have previously shown that two structurally distinct amyloid fibrils (with or without fragmented ATTR) are found among ATTRV30M patients. In this study, we investigated the proportion of wtATTR in cardiac and adipose amyloid from patients having either fibril type. It was found that cardiac amyloid more easily incorporates wtTTR than adipose amyloid, offering a potential explanation for the vulnerability of cardiac tissue for continued amyloidosis after LT. In cardiac tissue, fibrils with fragmented ATTR contained a higher wt proportion than fibrils without, suggesting that continued incorporation of wtTTR after LT, perhaps, can take place more easily in these patients. In adipose tissue, a rapid increase in wt proportion after LT indicates that a rather fast turnover of the deposits must occur. A difference in wt proportion between the fibril types was seen post-LT but not pre-LT, possibly caused by differences in turnover rate. Conclusively, this study further establishes the basic dissimilarities between the two fibril types and demonstrates that their role in LT outcome needs to be further investigated

“They can do whatever they want”: Meanings of receiving psychiatric care based on a common staff approach

This study deepens our understanding of how patients, when cared for in a psychiatric ward, experience situations that involve being handled according to a common staff approach. Interviews with nine former psychiatric in-patients were analyzed using a phenomenological–hermeneutic method to illuminate the lived experience of receiving care based on a common staff approach. The results revealed several meanings: discovering that you are as subjected to a common staff approach, becoming aware that no one cares, becoming aware that your freedom is restricted, being afflicted, becoming aware that a common staff approach is not applied by all staff, and feeling safe because someone else is responsible. The comprehensive understanding was that the patient's understanding of being cared for according to a common staff approach was to be seen and treated in accordance with others' beliefs and valuations, not in line with the patients' own self-image, while experiencing feelings of affliction

A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants in Relation to Risk of Type 1 Diabetes

BACKGROUND: The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes. METHODOLOGY/ PRINCIPAL FINDINGS: The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p'-DDE (OR 0.56, 95% CI 0.29, 1.08). CONCLUSIONS: The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes

Effects of chirality on the intracellular localization of binuclear ruthenium(II) polypyridyl complexes

Interest in binuclear ruthenium(II) polypyridyl complexes as luminescent cellular imaging agents and for biomedical applications is increasing rapidly. We have investigated the cellular localization, uptake, and biomolecular interactions of the pure enantiomers of two structural isomers of [μ-bipb(phen)4Ru2]4+ (bipb is bis(imidazo[4,5-f]-1,10-phenanthrolin-2-yl)benzene and phen is 1,10-phenanthroline) using confocal laser scanning microscopy, emission spectroscopy, and linear dichroism. Both complexes display distinct enantiomeric differences in the staining pattern of fixed cells, which are concluded to arise from chiral discrimination in the binding to intracellular components. Uptake of complexes in live cells is efficient and nontoxic at 5 μM, and occurs through an energy-dependent mechanism. No differences in uptake are observed between the structural isomers or the enantiomers, suggesting that the interactions triggering uptake are rather insensitive to structural variations. Altogether, these findings show that the complexes investigated are promising for future applications as cellular imaging probes. In addition, linear dichroism shows that the complexes exhibit DNA-condensing properties, making them interesting as potential gene delivery vectors

Isosteviol Has Beneficial Effects on Palmitate-Induced α-Cell Dysfunction and Gene Expression

BACKGROUND: Long-term exposure to high levels of fatty acids impairs insulin secretion and exaggerates glucagon secretion. The aim of this study was to explore if the antihyperglycemic agent, Isosteviol (ISV), is able to counteract palmitate-induced α-cell dysfunction and to influence α-cell gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Long-term incubation studies with clonal α-TC1-6 cells were performed in the presence of 0.5 mM palmitate with or without ISV. We investigated effects on glucagon secretion, glucagon content, cellular triglyceride (TG) content, cell proliferation, and expression of genes involved in controlling glucagon synthesis, fatty acid metabolism, and insulin signal transduction. Furthermore, we studied effects of ISV on palmitate-induced glucagon secretion from isolated mouse islets. Culturing α-cells for 72-h with 0.5 mM palmitate in the presence of 18 mM glucose resulted in a 56% (p<0.01) increase in glucagon secretion. Concomitantly, the TG content of α-cells increased by 78% (p<0.01) and cell proliferation decreased by 19% (p<0.05). At 18 mM glucose, ISV (10(-8) and 10(-6) M) reduced palmitate-stimulated glucagon release by 27% (p<0.05) and 27% (p<0.05), respectively. ISV (10(-6) M) also counteracted the palmitate-induced hypersecretion of glucagon in mouse islets. ISV (10(-6) M) reduced α-TC1-6 cell proliferation rate by 25% (p<0.05), but ISV (10(-8) and 10(-6) M) had no effect on TG content in the presence of palmitate. Palmitate (0.5 mM) increased Pcsk2 (p<0.001), Irs2 (p<0.001), Fasn (p<0.001), Srebf2 (p<0.001), Acaca (p<0.01), Pax6 (p<0.05) and Gcg mRNA expression (p<0.05). ISV significantly (p<0.05) up-regulated Insr, Irs1, Irs2, Pik3r1 and Akt1 gene expression in the presence of palmitate. CONCLUSIONS/SIGNIFICANCE: ISV counteracts α-cell hypersecretion and apparently contributes to changes in expression of key genes resulting from long-term exposure to palmitate. ISV apparently acts as a glucagonostatic drug with potential as a new anti-diabetic drug for the treatment of type 2 diabetes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation