Monitoring the Large Proper Motions of Radio Sources in the Orion BN/KL Region

We present absolute astrometry of four radio sources in the Becklin-Neugebauer/Kleinman-Low (BN/KL) region, derived from archival data (taken in 1991, 1995, and 2000) as well as from new observations (taken in 2006). All data consist of 3.6 cm continuum emission and were taken with the Very Large Array in its highest angular resolution A configuration. We confirm the large proper motions of the BN object, the radio source I (GMR I) and the radio counterpart of the infrared source n (Orion-n), with values from 15 to 26 km/s. The three sources are receding from a point between them from where they seem to have been ejected about 500 years ago, probably via the disintegration of a multiple stellar system. We present simulations of very compact stellar groups that provide a plausible dynamical scenario for the observations. The radio source Orion-n appeared as a double in the first three epochs, but as single in 2006. We discuss this morphological change. The fourth source in the region, GMR D, shows no statistically significant proper motions. We also present new, accurate relative astrometry between BN and radio source I that restrict possible dynamical scenarios for the region. During the 2006 observations, the radio source GMR A, located about 1' to the NW of the BN/KL region, exhibited an increase in its flux density of a factor of ~3.5 over a timescale of one hour. This rapid variability at cm wavelengths is similar to that previously found during a flare at millimeter wavelengths that took place in 2003.Comment: Accepted for publication in Ap

Dissection of a Complex Disease Susceptibility Region Using a Bayesian Stochastic Search Approach to Fine Mapping.

Identification of candidate causal variants in regions associated with risk of common diseases is complicated by linkage disequilibrium (LD) and multiple association signals. Nonetheless, accurate maps of these variants are needed, both to fully exploit detailed cell specific chromatin annotation data to highlight disease causal mechanisms and cells, and for design of the functional studies that will ultimately be required to confirm causal mechanisms. We adapted a Bayesian evolutionary stochastic search algorithm to the fine mapping problem, and demonstrated its improved performance over conventional stepwise and regularised regression through simulation studies. We then applied it to fine map the established multiple sclerosis (MS) and type 1 diabetes (T1D) associations in the IL-2RA (CD25) gene region. For T1D, both stepwise and stochastic search approaches identified four T1D association signals, with the major effect tagged by the single nucleotide polymorphism, rs12722496. In contrast, for MS, the stochastic search found two distinct competing models: a single candidate causal variant, tagged by rs2104286 and reported previously using stepwise analysis; and a more complex model with two association signals, one of which was tagged by the major T1D associated rs12722496 and the other by rs56382813. There is low to moderate LD between rs2104286 and both rs12722496 and rs56382813 (r2 ≃ 0:3) and our two SNP model could not be recovered through a forward stepwise search after conditioning on rs2104286. Both signals in the two variant model for MS affect CD25 expression on distinct subpopulations of CD4+ T cells, which are key cells in the autoimmune process. The results support a shared causal variant for T1D and MS. Our study illustrates the benefit of using a purposely designed model search strategy for fine mapping and the advantage of combining disease and protein expression data.We acknowledge use of DNA from The UK Blood Services collection of Common Controls (UKBS-CC collection), which is funded by the Wellcome Trust grant 076113/C/04/Z and by the USA National Institute for Health Research program grant to the National Health Service Blood and Transplant (RP-PG-0310-1002). We acknowledge the use of DNA from the British 1958 Birth Cohort collection, which is funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. This research utilized resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Human Genome Research Institute, the National Institute of Child Health and Human Development and the JDRF and is supported by the USA National Institutes of Health grant U01-DK062418. The JDRF/Wellcome Trust Diabetes and Inflammation Laboratory is funded by the JDRF (9-2011-253), the Wellcome Trust (091157) and the National Institute for Health Research Cambridge Biomedical Centre. The research leading to these results has received funding from the European Union's 7th Framework Programme (FP7/2007-2013) under grant agreement no.241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). CW is supported by the Wellcome Trust (089989). We acknowledge the National Institute for Health Research Cambridge Biomedical Research Centre for funding.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pgen.100527

Technology adoption of enhanced manual on fire safety and protection management

The study was conducted at Cebu Technological University Pinamungajan Extension Campus, Cebu, in order to Implement Fire Safety Management Procedure and determine its acceptability and effectiveness of the Technology Adoption of Enhanced Manual on Fire Safety and Protection Management during academic year 2019-2020. The Fire Safety and Protection Management Manual for School Maintenance was evaluated on the acceptability of its Effectiveness, Awareness, Safety and Health. Quasi-experiment method particularly survey research was employed on this study. Questionnaires were given to 10 professors/instructors and 180 students, 30 Faculty, 15 Fire Brigade Personnel, 15 Admin Personnel and 15 Safety Maintenance Personnel in Danao City, Cebu for evaluation. Gathered data were treated using total weighted points, weighted mean, and t-test. Based on the findings and after a careful analysis and interpretation of the study, it is concluded that the Technology Adoption of Enhanced Manual on Fire Safety and Protection Management meets the fire safety standards for school campuses. It was found out that the Technology Adoption of Enhanced Manual on Fire Safety and Protection Management Manual was highly acceptable in terms of acceptability of its Effectiveness, Awareness, Safety and Health. It is recommended that the Fire Safety Management Manual be adopted and practice for safety of the end users

The imperative usage of an innovated Biscuit-Shaped Tenon Groove Machine towards Technology Model for interior design technology program in technical education

This study was conducted in order to create and effectively use an Innovated Biscuit-Shaped Tenon Groove Machine towards Technology Model for Interior Design technology program in Technical education so that the creative learners could use it to support instruction in school, the study was conducted at Cebu Technological University- Pinamungajan Campus, Pinamungajan, Cebu. The output of this study was regarded as an alternative technology tool of CTU- Pinamungajan Campus, Pinamungajan, Cebu where the study is being done. This study used quasi-experimental techniques, specifically survey research. 90 students and 5 professors/instructors were given questionnaires to complete for evaluation. Weighted mean and t-test were used to analyze the collected data. Based on the results and following a careful analysis, it is concluded that Innovative Biscuit-Shaped Tenon Groove Machine meets campus needs and standards

Novel variation and <i>de novo </i>mutation rates in population-wide <i>de novo</i> assembled Danish trios

Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e−8 and 1.5e−9 per nucleotide per generation for SNVs and indels, respectively

A Plasmonic Biosensor Based on Light-Diffusing Fibers Functionalized with Molecularly Imprinted Nanoparticles for Ultralow Sensing of Proteins

Plasmonic bio/chemical sensing based on optical fibers combined with molecularly imprinted nanoparticles (nanoMIPs), which are polymeric receptors prepared by a template-assisted synthesis, has been demonstrated as a powerful method to attain ultra-low detection limits, particularly when exploiting soft nanoMIPs, which are known to deform upon analyte binding. This work presents the development of a surface plasmon resonance (SPR) sensor in silica light-diffusing fibers (LDFs) functionalized with a specific nanoMIP receptor, entailed for the recognition of the protein human serum transferrin (HTR). Despite their great versatility, to date only SPR-LFDs functionalized with antibodies have been reported. Here, the innovative combination of an SPR-LFD platform and nanoMIPs led to the development of a sensor with an ultra-low limit of detection (LOD), equal to about 4 fM, and selective for its target analyte HTR. It is worth noting that the SPR-LDF-nanoMIP sensor was mounted within a specially designed 3D-printed holder yielding a measurement cell suitable for a rapid and reliable setup, and easy for the scaling up of the measurements. Moreover, the fabrication process to realize the SPR platform is minimal, requiring only a metal deposition step

The technological innovation of wood lamination: a hydraulic “A” metal frame structure for educational design and purpose

This study aimed to develop and assess its acceptability and effectiveness of Technological Innovated Wood Lamination: A Hydraulic “A” Metal Structure for Educational Design and Purpose at Cebu Technological University- Pinamungajan Campus in Pinamungajan, Cebu, Philippines. The research utilized a quasi-experimental approach with a survey research design, where questionnaires were distributed to 40 BIT-IDT students, 10 MAVED students, and 10 instructors for evaluation. The data gathered were analyzed using total weighted points, weighted mean, and t-test. The study concluded that the Technological Innovated Wood Lamination: A Hydraulic “A” Metal Structure for Technology Instruction met the standards and performed each function accurately and effectively in construction instruction. The design, ergonomics, and safety features were highly acceptable, according to the survey responses. The study recommends the adoption and implementation of the Technological Innovated Wood Lamination: A Hydraulic “A” Metal Structure for Educational Design and Purpose. Furthermore, the study suggests the use of the User’s Manual to ensure the safety of the end-users. Overall, this study highlights the potential of the Technological Innovated Wood Lamination technology in enhancing construction technology instruction and promoting safety in the construction industry

Proteostasis and ALS: Protocol for a phase II, randomised, double-blind, placebo-controlled, multicentre clinical trial for colchicine in ALS (Co-ALS)

Introduction: Disruptions of proteasome and autophagy systems are central events in amyotrophic lateral sclerosis (ALS) and support the urgent need to find therapeutic compounds targeting these processes. The heat shock protein B8 (HSPB8) recognises and promotes the autophagy-mediated removal of misfolded mutant SOD1 and TDP-43 fragments from ALS motor neurons (MNs), as well as aggregating species of dipeptides produced in C9ORF72-related diseases. In ALS-SOD1 mice and in human ALS autopsy specimens, HSPB8 is highly expressed in spinal cord MNs that survive at the end stage of disease. Moreover, the HSPB8-BAG3-HSP70 complex maintains granulostasis, which avoids conversion of dynamic stress granules (SGs) into aggregation-prone assemblies. We will perform a randomised clinical trial (RCT) with colchicine, which enhances the expression of HSPB8 and of several autophagy players, blocking TDP-43 accumulation and exerting crucial activities for MNs function. Methods and analysis: Colchicine in amyotrophic lateral sclerosis (Co-ALS) is a double-blind, placebo-controlled, multicentre, phase II RCT. ALS patients will be enrolled in three groups (placebo, colchicine 0.01 mg/day and colchicine 0.005 mg/day) of 18 subjects treated with riluzole; treatment will last 30 weeks, and follow-up will last 24 weeks. The primary aim is to assess whether colchicine decreases disease progression as measured by ALS Functional Rating Scale - Revised (ALSFRS-R) at baseline and at treatment end. Secondary aims include assessment of (1) safety and tolerability of Colchicine in patiets with ALS; (2) changes in cellular activity (autophagy, protein aggregation, and SG and exosome secretion) and in biomarkers of disease progression (neurofilaments); (3) survival and respiratory function and (4) quality of life. Preclinical studies with a full assessment of autophagy and neuroinflammation biomarkers in fibroblasts, peripheral blood mononuclear cells and lymphoblasts will be conducted in parallel with clinic assessment to optimise time and resources. Ethics and dissemination: The study protocol was approved by the Ethics Committee of Area Vasta Emilia Nord and by Agenzia Italiana del Farmaco (EUDRACT N.2017-004459-21) based on the Declaration of Helsinki. This research protocol was written without patient involvement. Patients' association will be involved in disseminating the study design and results. Results: will be presented during scientific symposia or published in scientific journals

Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2

The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25- naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense. We also observed an IL-8-producing memory T cell subpopulation coexpressing CR1 and CR2 and with a gene expression signature resembling that of RTEs. The functions of CR1 and CR2 on T cells remain to be determined, but we note that CR2 is the receptor for Epstein-Barr virus, which is a cause of T cell lymphomas and a candidate environmental factor in autoimmune disease