Orbits for eighteen visual binaries and two double-line spectroscopic binaries observed with HRCAM on the CTIO SOAR 4m telescope, using a new Bayesian orbit code based on Markov Chain Monte Carlo

We present orbital elements and mass sums for eighteen visual binary stars of spectral types B to K (five of which are new orbits) with periods ranging from 20 to more than 500 yr. For two double-line spectroscopic binaries with no previous orbits, the individual component masses, using combined astrometric and radial velocity data, have a formal uncertainty of ~0.1 MSun. Adopting published photometry, and trigonometric parallaxes, plus our own measurements, we place these objects on an H-R diagram, and discuss their evolutionary status. These objects are part of a survey to characterize the binary population of stars in the Southern Hemisphere, using the SOAR 4m telescope+HRCAM at CTIO. Orbital elements are computed using a newly developed Markov Chain Monte Carlo algorithm that delivers maximum likelihood estimates of the parameters, as well as posterior probability density functions that allow us to evaluate the uncertainty of our derived parameters in a robust way. For spectroscopic binaries, using our approach, it is possible to derive a self-consistent parallax for the system from the combined astrometric plus radial velocity data ("orbital parallax"), which compares well with the trigonometric parallaxes. We also present a mathematical formalism that allows a dimensionality reduction of the feature space from seven to three search parameters (or from ten to seven dimensions - including parallax - in the case of spectroscopic binaries with astrometric data), which makes it possible to explore a smaller number of parameters in each case, improving the computational efficiency of our Markov Chain Monte Carlo code.Comment: 32 pages, 9 figures, 6 tables. Detailed Appendix with methodology. Accepted by The Astronomical Journa

Rescuing compound bioactivity in a secondary cell-based screening by using gamma-cyclodextrin as a molecular carrier

In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones) against a protein target results in the discovery of lead com- pounds that must be tested in cell-based efficacy secondary screenings. Very often lead com- pounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly accord- ing to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that prob- lem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction with the target, some of the compounds were not able to inhibit viral replication in cell assays. In order to overcome this obstacle and potentially improve cellular internalization three of these compounds were complexed with gamma-cyclodextrin. Two of them showed a five- and 16-fold activity increase, compared to their activity when delivered as free compounds in solution (while gamma-cyclodextrin did not show antiviral activity by itself ). The most remarkable result came from a third compound that showed no antiviral activity in cell assays when delivered free in solu- tion, but its gamma-cyclodextrin complex exhibited a 50% effective concentration of 5 micromoles. Thus, the antiviral activity of these compounds can be significantly improved, even completely rescued, using gamma-cyclodextrin as carrier molecule

Headache of recent onset in adults: a prospective population-based study

One hundred consecutive adult patients with headache of recent onset were prospectively studied. Every patient was examined by craneal CT scan. Their mean age was 46 years (range 17-82). Neurological examination was normal in 80 patients. Organic headache represented 39% of the entire group, and 26% of them had a normal neurological examination. The yield of CT scan in patients with headaches and a normal neurological examination was 22.5% (95% IC: 14%-33%); of which we encountered the following pathologies: intracranial tumors (13), hydrocephalus (2), arachnoid cyst (l), toxoplasmic abscess (1) and parenchymal hemorrhage (1). The clinical characteristics of the headache on their own was insufficient to rule out the possibility of an intracranial tumor. Neuroimaging studies should be performed in all adult patients with non-vascular headache of recent onset, I and previously headache-free individual

The Identification of Heavy Metal Accumulator Ferns in Abandoned Mines in the Philippines With Applications to Mine Rehabilitation and Metal Recovery

This paper focuses on the identification of some plant accumulators of heavy metals that can facilitate mine remediation and rehabilitation in the Philippines and metal recovery or phytomining. Most of these hyperaccumulators are ferns that thrive very well in different terrains and of particular interest are Pityrogramma calomelanos, Pteris vittata, and Pteris melanocaulon that are abundant in abandoned CueAu mining areas. The amounts of Cu and As in the soil and in the aboveground (AG) and belowground (BG) components of the accumulator ferns were determined and the Bioaccumulation Factor (BF) and the Translocation Factor (TF) were derived. Efforts to propagate the accumulator ferns identified from spores were successful, thus providing the opportunity of using them for various experiments on mine rehabilitation and metal recovery. The results of these experiments indicated that these hyperaccumulator ferns have the greatest potential for the remediation of metal contaminated soils, the rehabilitation of abandoned mines, and phytomining

Dual Pharmacological Targeting of HDACs and PDE5 Inhibits Liver Disease Progression in a Mouse Model of Biliary Inflammation and Fibrosis

Liver fibrosis, a common hallmark of chronic liver disease (CLD), is characterized by the accumulation of extracellular matrix secreted by activated hepatic fibroblasts and stellate cells (HSC). Fibrogenesis involves multiple cellular and molecular processes and is intimately linked to chronic hepatic inflammation. Importantly, it has been shown to promote the loss of liver function and liver carcinogenesis. No effective therapies for liver fibrosis are currently available. We examined the anti-fibrogenic potential of a new drug (CM414) that simultaneously inhibits histone deacetylases (HDACs), more precisely HDAC1, 2, and 3 (Class I) and HDAC6 (Class II) and stimulates the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway activity through phosphodiesterase 5 (PDE5) inhibition, two mechanisms independently involved in liver fibrosis. To this end, we treated Mdr2-KO mice, a clinically relevant model of liver inflammation and fibrosis, with our dual HDAC/PDE5 inhibitor CM414. We observed a decrease in the expression of fibrogenic markers and collagen deposition, together with a marked reduction in inflammation. No signs of hepatic or systemic toxicity were recorded. Mechanistic studies in cultured human HSC and cholangiocytes (LX2 and H69 cell lines, respectively) demonstrated that CM414 inhibited pro-fibrogenic and inflammatory responses, including those triggered by transforming growth factor β (TGFβ). Our study supports the notion that simultaneous targeting of pro-inflammatory and fibrogenic mechanisms controlled by HDACs and PDE5 with a single molecule, such as CM414, can be a new disease-modifying strateg

Which DSM validated tools for diagnosing depression are usable in primary care research? A systematic literature review

IntroductionDepression occurs frequently in primary care. Its broad clinical variability makes it difficult to diagnose. This makes it essential that family practitioner (FP) researchers have validated tools to minimize bias in studies of everyday practice. Which tools validated against psychiatric examination, according to the major depression criteria of DSM-IV or 5, can be used for research purposes

Evaluación de los implantes cocleares bilaterales en niños: criterios de indicación de los implantes cocleares en niños y adultos

Implants coclears; Avaluació; Infants; Cochlear Implants; Evaluation; Childrens; Implantes Cocleares; Evaluación; NiñosL’Agència d’Informació, Avaluació i Qualitat en Salut (AIAQS, abans Agència d’Avaluació de Tecnologia i Recerca Mèdiques), va elaborar l’any 2006, per encàrrec del Departament de Salut de la Generalitat de Catalunya, una consulta tècnica (informe d’avaluació breu) sobre els implants coclears (IC), que tenia com a objectius descriure les indicacions clíniques dels IC en adults i nens, així com avaluar la seva seguretat i eficàcia sobre la base de l’evidència científica disponible. Al final del 2009, l’AIAQS va rebre l’encàrrec de la Comissió de Terciarisme del CatSalut d’actualitzar aquesta consulta tècnica analitzant el coneixement científic disponible sobre l’eficàcia/efectivitat i seguretat dels implants coclears bilaterals (ICB) i els criteris d’indicació dels IC en adults i nens

The brazilian Amaryllidaceae as a source of acetylcholinesterase inhibitory alkaloids

Nine Brazilian Amaryllidaceae species were studied for their alkaloid composition and acetylcholinesterase (AChE) inhibitory activity via GC-MS and a modified Ellman assay, respectively. A total of thirty-six alkaloids were identified in these plants, of which Hippeastrum papilio and H. glau-cescens exhibited the highest galanthamine content and the best IC50 values against AChE. Furthermore, Hippeastrum vittatum and Rhodophiala bifida also showed notable AChE inhibitory effects. X-ray crys-tallographic data for four galanthamine-type com-pounds revealed significant differences in the orientation of theN-methyl group, which are shown to be related to AChE inhibition

Epigenetic mechanisms and metabolic reprogramming in fibrogenesis: dual targeting of G9a and DNMT1 for the inhibition of liver fibrosis

OBJECTIVE: Hepatic stellate cells (HSC) transdifferentiation into myofibroblasts is central to fibrogenesis. Epigenetic mechanisms, including histone and DNA methylation, play a key role in this process. Concerted action between histone and DNA-mehyltransferases like G9a and DNMT1 is a common theme in gene expression regulation. We aimed to study the efficacy of CM272, a first-in-class dual and reversible G9a/DNMT1 inhibitor, in halting fibrogenesis. DESIGN: G9a and DNMT1 were analysed in cirrhotic human livers, mouse models of liver fibrosis and cultured mouse HSC. G9a and DNMT1 expression was knocked down or inhibited with CM272 in human HSC (hHSC), and transcriptomic responses to transforming growth factor-β1 (TGFβ1) were examined. Glycolytic metabolism and mitochondrial function were analysed with Seahorse-XF technology. Gene expression regulation was analysed by chromatin immunoprecipitation and methylation-specific PCR. Antifibrogenic activity and safety of CM272 were studied in mouse chronic CCl4 administration and bile duct ligation (BDL), and in human precision-cut liver slices (PCLSs) in a new bioreactor technology. RESULTS: G9a and DNMT1 were detected in stromal cells in areas of active fibrosis in human and mouse livers. G9a and DNMT1 expression was induced during mouse HSC activation, and TGFβ1 triggered their chromatin recruitment in hHSC. G9a/DNMT1 knockdown and CM272 inhibited TGFβ1 fibrogenic responses in hHSC. TGFβ1-mediated profibrogenic metabolic reprogramming was abrogated by CM272, which restored gluconeogenic gene expression and mitochondrial function through on-target epigenetic effects. CM272 inhibited fibrogenesis in mice and PCLSs without toxicity. CONCLUSIONS: Dual G9a/DNMT1 inhibition by compounds like CM272 may be a novel therapeutic strategy for treating liver fibrosis