Advances in Architectures and Tools for FPGAs and their Impact on the Design of Complex Systems for Particle Physics

The continual improvement of semiconductor technology has provided rapid advancements in device frequency and density. Designers of electronics systems for high-energy physics (HEP) have benefited from these advancements, transitioning many designs from fixed-function ASICs to more flexible FPGA-based platforms. Today’s FPGA devices provide a significantly higher amount of resources than those available during the initial Large Hadron Collider design phase. To take advantage of the capabilities of future FPGAs in the next generation of HEP experiments, designers must not only anticipate further improvements in FPGA hardware, but must also adopt design tools and methodologies that can scale along with that hardware. In this paper, we outline the major trends in FPGA hardware, describe the design challenges these trends will present to developers of HEP electronics, and discuss a range of techniques that can be adopted to overcome these challenges

The Stronger Downregulation of in vitro and in vivo Innate Antiviral Responses by a Very Virulent Strain of Infectious Bursal Disease Virus (IBDV), Compared to a Classical Strain, Is Mediated, in Part, by the VP4 Protein

IBDV is economically important to the poultry industry. Very virulent (vv) strains cause higher mortality rates than other strains for reasons that remain poorly understood. In order to provide more information on IBDV disease outcome, groups of chickens (n = 18) were inoculated with the vv strain, UK661, or the classical strain, F52/70. Birds infected with UK661 had a lower survival rate (50%) compared to F52/70 (80%). There was no difference in peak viral replication in the bursa of Fabricius (BF), but the expression of chicken IFNα, IFNβ, MX1, and IL-8 was significantly lower in the BF of birds infected with UK661 compared to F52/70 (p < 0.05) as quantified by RTqPCR, and this trend was also observed in DT40 cells infected with UK661 or F52/70 (p < 0.05). The induction of expression of type I IFN in DF-1 cells stimulated with polyI:C (measured by an IFN-β luciferase reporter assay) was significantly reduced in cells expressing ectopic VP4 from UK661 (p < 0.05), but was higher in cells expressing ectopic VP4 from F52/70. Cells infected with a chimeric recombinant IBDV carrying the UK661-VP4 gene in the background of PBG98, an attenuated vaccine strain that induces high levels of innate responses (PBG98-VP4UK661) also showed a reduced level of IFNα and IL-8 compared to cells infected with a chimeric virus carrying the F52/70-VP4 gene (PBG98-VP4F52/70) (p < 0.01), and birds infected with PBG98-VP4UK661 also had a reduced expression of IFNα in the BF compared to birds infected with PBG98-VP4F52/70 (p < 0.05). Taken together, these data demonstrate that UK661 induced the expression of lower levels of anti-viral type I IFN and proinflammatory genes than the classical strain in vitro and in vivo and this was, in part, due to strain-dependent differences in the VP4 protein

Germ-line DICER1 mutations do not make a major contribution to the etiology of familial testicular germ cell tumours.

BACKGROUND: The RNase III enzyme DICER1 plays a central role in maturation of microRNAs. Identification of neoplasia-associated germ-line and somatic mutations in DICER1 indicates that mis-expression of miRNAs in cancer may result from defects in their processing. As part of a recent study of DICER1 RNase III domains in 96 testicular germ cell tumors, a single RNase IIIb domain mutation was identified in a seminoma. To further explore the importance of DICER1 mutations in the etiology of testicular germ cell tumors (TGCT), we studied germ-line DNA samples from 43 probands diagnosed with familial TGCT. FINDINGS: We carried out High Resolution Melting Curve Analysis of DICER1 exons 2-12, 14-19, 21 and 24-27. All questionable melt curves were subjected to confirmatory Sanger sequencing.Sanger sequencing was used for exons 13, 20, 22 and 23. Intron-exon boundaries were included in all analyses. We identified 12 previously reported single nucleotide polymorphisms and two novel single nucleotide variants. No likely deleterious variants were identified; notably no mutations that were predicted to truncate the protein were identified. CONCLUSIONS: Taken together with previous studies, the findings reported here suggest a very limited role for either germ-line or somatic DICER1 mutations in the etiology of TGCT.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

An Ar-rahnu Shop Acceptance Model (ARSAM)

The objective of this study is to examine the factors affect the local people of Labuan to accept ar-Rahnu shop (Islamic-based pawnshop). Considering this objective, the current study tends to develop a model, a theoretical framework to explain the factors influencing consumers’ acceptance of Islamic-based pawnshop. The model was tested with a survey sample (N = 384). The model labeled as an ARSAM (ar-Rahnu Shop Acceptance Model). Findings are useful for the local authorities or businesses to take initiative to develop an ar-Rahnu shop in order to promote Islamic-based economy among women as well as men minority. It is also treated as an eye-opener about the importance of having that system in Labuan. Totally, the study renders an overview of the ar-Rahnu shop acceptance among the Labuan local people, thus creating a chance to suggest a policy either to introduce an ar-Rahnu shop or to make the existing conventional pawnshops introduce window for ar-Rahnu

What Do Program Directors Look for in an Applicant?

Program directors (PDs) are faced with an increasing number of applicants to emergency medicine (EM) and a limited number of positions. This article will provide candidates with insight to what PDs look for in an applicant. We will elaborate on the performance in the emergency medicine clerkship, interview, clinical rotations (apart from EM), board scores, Alpha Omega Alpha membership, letters of recommendation, Medical Student Performance Evaluation or dean’s letter, extracurricular activities, Gold Humanism Society membership, medical school attended, research and scholarly projects, personal statement, and commitment to EM. We stress the National Resident Matching Program process and how, ultimately, selection of a residency is equally dependent on an applicant’s selection process

Gravitational wave probes of dark matter: challenges and opportunities

In this white paper, we discuss the prospects for characterizing and identifying dark matter using gravitational waves, covering a wide range of dark matter candidate types and signals. We argue that present and upcoming gravitational wave probes offer unprecedented opportunities for unraveling the nature of dark matter and we identify the most urgent challenges and open problems with the aim of encouraging a strong community effort at the interface between these two exciting fields of research.Comment: 17 pages, 2 figures. Comments welcome. v2: Added references and minor correction

Mitochondrial dysfunction and mitophagy blockade contribute to renal osteodystrophy in chronic kidney disease-mineral bone disorder

Chronic kidney disease–mineral and bone disorder (CKD-MBD) presents with extra-skeletal calcification and renal osteodystrophy (ROD). The origins of ROD likely lie with elevated uremic toxins and/or an altered hormonal profile but the cellular events responsible remain unclear. Here, we report that stalled mitophagy contributes to mitochondrial dysfunction in bones of a CKD-MBD mouse model, and also human CKD-MBD patients. RNA-seq analysis exposed an altered expression of genes associated with mitophagy and mitochondrial function in tibia of CKD-MBD mice. The accumulation of damaged osteocyte mitochondria and the expression of mitophagy regulators, p62/SQSTM1, ATG7 and LC3 was inconsistent with functional mitophagy, and in mito-QC reporter mice with CKD-MBD, there was a 2.3-fold increase in osteocyte mitolysosomes. Altered expression of mitophagy regulators in human CKD-MBD bones was also observed. To determine if uremic toxins were possibly responsible for these observations, indoxyl sulfate treatment of osteoblasts revealed mitochondria with distorted morphology and whose membrane potential and oxidative phosphorylation were decreased, and oxygen-free radical production increased. The altered p62/SQSTM1 and LC3-II expression was consistent with impaired mitophagy machinery and the effects of indoxyl sulfate were reversible by rapamycin. In conclusion, mitolysosome accumulation from impaired clearance of damaged mitochondria may contribute to the skeletal complications, characteristic of ROD. Targeting mitochondria and the mitophagy process may therefore offer novel routes for intervention to preserve bone health in patients with ROD. Such approaches would be timely as our current armamentarium of anti-fracture medications has not been developed for, or adequately studied in, patients with severe CKD-MBD