Absolute-Magnitude Distributions and Light Curves of Stripped-Envelope Supernovae

The absolute visual magnitudes of three Type IIb, 11 Type Ib and 13 Type Ic supernovae (collectively known as stripped-envelope supernovae) are studied by collecting data on the apparent magnitude, distance, and interstellar extinction of each event. Weighted and unweighted mean absolute magnitudes of the combined sample as well as various subsets of the sample are reported. The limited sample size and the considerable uncertainties, especially those associated with extinction in the host galaxies, prevent firm conclusions regarding differences between the absolute magnitudes of supernovae of Type Ib and Ic, and regarding the existence of separate groups of overluminous and normal-luminosity stripped-envelope supernovae. The spectroscopic characteristics of the events of the sample are considered. Three of the four overluminous events are known to have had unusual spectra. Most but not all of the normal luminosity events had typical spectra. Light curves of stripped-envelope supernovae are collected and compared. Because SN 1994I in M51 was very well observed it often is regarded as the prototypical Type Ic supernova, but it has the fastest light curve in the sample. Light curves are modeled by means of a simple analytical technique that, combined with a constraint on E/M from spectroscopy, yields internally consistent values of ejected mass, kinetic energy, and nickel mass.Comment: 39 pages, 14 figures, 7 tables; Accepted to A

The rainbow cohort: 96 week follow-up of saquinavir-containing regimens in previously antiretroviral therapy (ART)-naïve and pre-treated but protease inhibitor (PI)- naïve hiv-infected patients

<p>Abstract</p> <p>Objective</p> <p>We have previously reported data from the German cohort of the multinational observational prospective RAINBOW survey which assessed the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r)-containing regimens over 48 weeks in routine clinical practice. This analysis presents data from antiretroviral (ART)-naïve and pretreated but protease inhibitor (PI)-naïve patients treated in a long-term one line (96 weeks) follow-up of the initial study.</p> <p>Methods</p> <p>All ART-and PI-naïve patients from the initial RAINBOW cohort who had recorded data to one line 96 weeks of treatment were eligible for inclusion in the current analysis. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 96. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 96. For evaluation of efficacy, intent-to-treat analysis, in which missing values were recorded as failure (ITT), and last-observation-carried-forward (LOCF) analysis were used. Metabolic parameters were assessed using LOCF analysis.</p> <p>Results</p> <p>The analysis included 175 ART-naïve and 109 pretreated but PI-naïve patients. After 96 weeks, a similar proportion of patients in the ART-naïve and in the pretreated but Pi-naïve group had HIV-1 RNA levels < 400 copies/mL (68.0% and 70.6% [ITT], respectively; 96.6% and 90.8% [LOCF], respectively). The proportion of patients with HIV RNA < 50 copies/mL was higher in the ART-naïve group compared with the pretreated but PI-naïve group (61.1% and 56.9% [ITT], respectively; 84.0% and 75.2% [LOCF], respectively). Median change in CD4 cell count from baseline to week 96 was'+263 cells/mm³(IQR 170; 384. LOCF; p < 0.0001) in the ART-naïve group, and one line +181 cells/mm³(IQR 60; 309. LOCF; p < 0.0001) in the pretreated but PI-naïve group. Treatment was well tolerated, with only 2.5% of patients withdrawing from treatment due to side effects. There were no clinically relevant changes in liver enzyme levels. Overall total cholesterol, triglyceride, and low-and high-density lipoprotein levels increased to week 96, although levels remained within normal ranges in the majority of ART-naïve and pretreated patients.</p> <p>Conclusions</p> <p>This follow-up analysis confirms the long term efficacy and tolerability of SQV/r in ART-naïve and pretreated but PI-naïve patients in the real-life clinical setting.</p

Science and Film-making

The essay reviews the literature, mostly historical, on the relationship between science and film-making, with a focus on the science documentary. It then discusses the circumstances of the emergence of the wildlife making-of documentary genre. The thesis examined here is that since the early days of cinema, film-making has evolved from being subordinate to science, to being an equal partner in the production of knowledge, controlled by non-scientists

Lobster Fishery Management in the Marine Ecosystem Approach at Simeulue Island Waters (Wpp-nri 572)

The lobster fishery is one of the leading fisheries commodity on Simeulue Regency so that local government must manage wisely in order to maintain the sustainability of the lobster fishery. Aceh Government Regulation namely Qanun Aceh No. 7 of 2010 concerning fisheries already in effect. However, the institutional system has not functioned optimally in the management of lobster fisheries. The purpose this study is to examine the domain of fishing techniques, socio-economic and institutional management of lobster fisheries with ecosystem approaches in Simeulue waters. Research method using qualitative research. The method of data collection is survey method which is done by purposive sampling approach that is by doing depth responder interview which is considered informative and wide knowledge about the institute. Data analysis using EAFM analysis done with Flag Modeling technique. Based on the results of the study that the assessment of the fishing domain techniques and economic domains in aggregate showed bad category. Meanwhile, social domains and institutional domains show moderate categories so aggregate composites overall show fewer categories. It is therefore necessary to make a tactical decision from the bad to be better in accordance with the category of each EAFM domain

A mathematical framework for contact detection between quadric and superquadric surfaces

The calculation of the minimum distance between surfaces plays an important role in computational mechanics, namely, in the study of constrained multibody systems where contact forces take part. In this paper, a general rigid contact detection methodology for non-conformal bodies, described by ellipsoidal and superellipsoidal surfaces, is presented. The mathematical framework relies on simple algebraic and differential geometry, vector calculus, and on the C2 continuous implicit representations of the surfaces. The proposed methodology establishes a set of collinear and orthogonal constraints between vectors defining the contacting surfaces that, allied with loci constraints, which are specific to the type of surface being used, formulate the contact problem. This set of non-linear equations is solved numerically with the Newton-Raphson method with Jacobian matrices calculated analytically. The method outputs the coordinates of the pair of points with common normal vector directions and, consequently, the minimum distance between both surfaces. Contrary to other contact detection methodologies, the proposed mathematical framework does not rely on polygonal-based geometries neither on complex non-linear optimization formulations. Furthermore, the methodology is extendable to other surfaces that are (strictly) convex, interact in a non-conformal fashion, present an implicit representation, and that are at least C2 continuous. Two distinct methods for calculating the tangent and binormal vectors to the implicit surfaces are introduced: (i) a method based on the Householder reflection matrix; and (ii) a method based on a square plate rotation mechanism. The first provides a base of three orthogonal vectors, in which one of them is collinear to the surface normal. For the latter, it is shown that, by means of an analogy to the referred mechanism, at least two non-collinear vectors to the normal vector can be determined. Complementarily, several mathematical and computational aspects, regarding the rigid contact detection methodology, are described. The proposed methodology is applied to several case tests involving the contact between different (super)ellipsoidal contact pairs. Numerical results show that the implemented methodology is highly efficient and accurate for ellipsoids and superellipsoids.Fundação para a Ciência e a Tecnologia (FCT

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

Translation of mouse model to human gives insights into periodontitis etiology

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10-4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10-5) and RNASE2 (rs2771342, P = 2.84×10-5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10-14) and HLA-DPA1 (rs17214512, P = 5.14×10-5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease

Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma : preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and primates

Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D (KLAKLAK)2-containing class of agents. BMTP-78 was validated in cells from patients with acute myeloid leukemia and in a panel of human leukemia and lymphoma cell lines, where it induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro efficacy of BMTP-78, we performed formal good laboratory practice toxicology studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and rhesus monkeys). These analyses represent required steps towards an IND application of BMTP-78 for theranostic first-in-human clinical trials.Peer reviewe

Gastrointestinal stromal tumour of the duodenum in childhood: a rare case report

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumours (GISTs) are uncommon primary mesenchymal tumours of the gastrointestinal tract mostly observed in the adults. Duodenal GISTs are relatively rare in adults and it should be regarded as exceptional in childhood. In young patients duodenal GISTs may be a source of potentially lethal haemorrhage and this adds diagnostic and therapeutic dilemmas to the concern about the long-term outcome.</p> <p>Case presentation</p> <p>A 14-year-old boy was referred to our hospital with severe anaemia due to recurrent episodes of upper gastrointestinal haemorrhage. Endoscopy, small bowel series, scintigraphy and video capsule endoscopy previously done elsewhere were negative. Shortly after the admission, the patient underwent emergency surgery for severe recurrence of the bleeding. At surgery, a 4 cm solid mass arising from the wall of the fourth portion of the duodenum was identified. The invasion and the erosion of the duodenal mucosa was confirmed by intra-operative pushed duodenoscopy. The mass was resected by a full-thickness duodenal wall excision with adequate grossly free margins. Immunohistochemical analysis of the specimen revealed to be positive for CD117 (c-KIT protein) consistent with a diagnosis of GIST. The number of mitoses was < 5/50 HPF. Mutational analysis for c-KIT/PDGFRA tyrosine kinase receptor genes resulted in a wildtype pattern. The patient had an uneventful course and he has remained disease-free during two years of follow-up.</p> <p>Conclusion</p> <p>Duodenal GISTs in children are very rare and may present with massive bleeding. Cure can be achieved by complete surgical resection, but even in the low-aggressive tumours the long-term outcome may be unpredictable.</p

Mechanisms of c-Myc Degradation by Nickel Compounds and Hypoxia

Nickel (Ni) compounds have been found to cause cancer in humans and animal models and to transform cells in culture. At least part of this effect is mediated by stabilization of hypoxia inducible factor (HIF1a) and activating its downstream signaling. Recent studies reported that hypoxia signaling might either antagonize or enhance c-myc activity depending on cell context. We investigated the effect of nickel on c-myc levels, and demonstrated that nickel, hypoxia, and other hypoxia mimetics degraded c-myc protein in a number of cancer cells (A549, MCF-7, MDA-453, and BT-474). The degradation of the c-Myc protein was mediated by the 26S proteosome. Interestingly, knockdown of both HIF-1α and HIF-2α attenuated c-Myc degradation induced by Nickel and hypoxia, suggesting the functional HIF-1α and HIF-2α was required for c-myc degradation. Further studies revealed two potential pathways mediated nickel and hypoxia induced c-myc degradation. Phosphorylation of c-myc at T58 was significantly increased in cells exposed to nickel or hypoxia, leading to increased ubiquitination through Fbw7 ubiquitin ligase. In addition, nickel and hypoxia exposure decreased USP28, a c-myc de-ubiquitinating enzyme, contributing to a higher steady state level of c-myc ubiquitination and promoting c-myc degradation. Furthermore, the reduction of USP28 protein by hypoxia signaling is due to both protein degradation and transcriptional repression. Nickel and hypoxia exposure significantly increased the levels of dimethylated H3 lysine 9 at the USP28 promoter and repressed its expression. Our study demonstrated that Nickel and hypoxia exposure increased c-myc T58 phosphorylation and decreased USP28 protein levels in cancer cells, which both lead to enhanced c-myc ubiquitination and proteasomal degradation