Fault-tolerant computer study

A set of building block circuits is described which can be used with commercially available microprocessors and memories to implement fault tolerant distributed computer systems. Each building block circuit is intended for VLSI implementation as a single chip. Several building blocks and associated processor and memory chips form a self checking computer module with self contained input output and interfaces to redundant communications buses. Fault tolerance is achieved by connecting self checking computer modules into a redundant network in which backup buses and computer modules are provided to circumvent failures. The requirements and design methodology which led to the definition of the building block circuits are discussed

Organsko-geohemijska korelacija nekih nafti depresije Drmno (južni deo panonskog basena, Jugoslavija)

The results of an investigation of crude oils originating from the Sirakovo and Bradarac-Maljurevac localities (southern part of the Pannonian Basin) are reported in this paper. The aim was to estimate the organic geochemical similarity of the crude oils fi om the DI mno (Kostolac) depression oil fields. The nine selected samples originated from reservoir. rocks of various depths. Reliable source and organic geochemical maturation parameters served as the basis for the correlation studies. The similar origin of the investigated DI mno depression crude oils was corroborated, characterized by a significant participation of terrestrial precursor biomass. They were shown to be of relatively low maturity and to have been formed during the earlier stages of the diagenet- ic-catagenetic sequence of processes leading to the formation of crude oils, most probably in source rocks of Tertiary age, corresponding to vitrinite reflectances between Ro = 0.70 % and Ro = 0.80%. The crude oils from Bradarac-Maljurevac seemed to be somewhat less homogeneous with respect to organic geochemical parameters compared to Sirakovo crude oils.U ovom radu ispitivani su uzorci sirovih nafti depresije Drmno (Kostolac) sa lokaliteta Sirakovo i Bradarac-Maljurevac. Cilj rada bio je da se proceni organsko-geohemijska ujednačenost nafti naftnih polja depresije Drmno. Izabrani su uzorci koji potiču iz rezervoarskih stena sa različitih dubina i u njima su određeni grupni i specifični izvorni i maturacioni organsko-geohemijski parametri. Potvrđeno je da ispitivani uzorci depresije Drmno imaju slično poreklo koje karakteriše veći udeo terestrijalne prekursorske biomase. Ispitivane nafte su nešto nižeg stepena maturisanosti i nastale su u ranijim fazama dijagenetsko-katagenetske sekvencije formiranja nafte kojima odgovaraju vrednosti refleksije vitrinita između Ro = 0,70 % i Ro = 0,80 %. Najverovatnije su nastale u izvornim stenama tercijarne starosti. Nafte sa lokaliteta Bradarac-Maljurevac karakteriše nešto niži nivo organsko-geohemijske homogenosti nego nafte sa lokaliteta Sirakovo

Fast Quantum Modular Exponentiation

We present a detailed analysis of the impact on modular exponentiation of architectural features and possible concurrent gate execution. Various arithmetic algorithms are evaluated for execution time, potential concurrency, and space tradeoffs. We find that, to exponentiate an n-bit number, for storage space 100n (twenty times the minimum 5n), we can execute modular exponentiation two hundred to seven hundred times faster than optimized versions of the basic algorithms, depending on architecture, for n=128. Addition on a neighbor-only architecture is limited to O(n) time when non-neighbor architectures can reach O(log n), demonstrating that physical characteristics of a computing device have an important impact on both real-world running time and asymptotic behavior. Our results will help guide experimental implementations of quantum algorithms and devices.Comment: to appear in PRA 71(5); RevTeX, 12 pages, 12 figures; v2 revision is substantial, with new algorithmic variants, much shorter and clearer text, and revised equation formattin

GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu

Deletion polymorphism of glutathione S-transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end-stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether GSTM1-null genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol-binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein (CRP), angiogenin, dickkopf-1 (Dkk-1), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). In accordance with these findings, the levels of serum ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) were increased in ESRD patients lacking GSTM1, in comparison with patients with the GSTM1-active genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD

A combination of urinary biomarker panel and PancRISK score for earlier detection of pancreatic cancer: A case–control study

Funder: Pancreatic Cancer Research Fund; funder-id: http://dx.doi.org/10.13039/100011704Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with around 9% of patients surviving >5 years. Asymptomatic in its initial stages, PDAC is mostly diagnosed late, when already a locally advanced or metastatic disease, as there are no useful biomarkers for detection in its early stages, when surgery can be curative. We have previously described a promising biomarker panel (LYVE1, REG1A, and TFF1) for earlier detection of PDAC in urine. Here, we aimed to establish the accuracy of an improved panel, including REG1B instead of REG1A, and an algorithm for data interpretation, the PancRISK score, in additional retrospectively collected urine specimens. We also assessed the complementarity of this panel with CA19-9 and explored the daily variation and stability of the biomarkers and their performance in common urinary tract cancers. Methods and findings: Clinical specimens were obtained from multiple centres: Barts Pancreas Tissue Bank, University College London, University of Liverpool, Spanish National Cancer Research Center, Cambridge University Hospital, and University of Belgrade. The biomarker panel was assayed on 590 urine specimens: 183 control samples, 208 benign hepatobiliary disease samples (of which 119 were chronic pancreatitis), and 199 PDAC samples (102 stage I–II and 97 stage III–IV); 50.7% were from female individuals. PDAC samples were collected from patients before treatment. The samples were assayed using commercially available ELISAs. Statistical analyses were performed using non-parametric Kruskal–Wallis tests adjusted for multiple comparisons, and multiple logistic regression. Training and validation datasets for controls and PDAC samples were obtained after random division of the whole available dataset in a 1:1 ratio. The substitution of REG1A with REG1B enhanced the performance of the panel to detect resectable PDAC. In a comparison of controls and PDAC stage I–II samples, the areas under the receiver operating characteristic curve (AUCs) increased from 0.900 (95% CI 0.843–0.957) and 0.926 (95% CI 0.843–1.000) in the training (50% of the dataset) and validation sets, respectively, to 0.936 in both the training (95% CI 0.903–0.969) and the validation (95% CI 0.888–0.984) datasets for the new panel including REG1B. This improved panel showed both sensitivity (SN) and specificity (SP) to be >85%. Plasma CA19-9 enhanced the performance of this panel in discriminating PDAC I–II patients from controls, with AUC = 0.992 (95% CI 0.983–1.000), SN = 0.963 (95% CI 0.913–1.000), and SP = 0.967 (95% CI 0.924–1.000). We demonstrate that the biomarkers do not show significant daily variation, and that they are stable for up to 5 days at room temperature. The main limitation of our study is the low number of stage I–IIA PDAC samples (n = 27) and lack of samples from individuals with hereditary predisposition to PDAC, for which specimens collected from control individuals were used as a proxy. Conclusions: We have successfully validated our urinary biomarker panel, which was improved by substituting REG1A with REG1B. At a pre-selected cutoff of >80% SN and SP for the affiliated PancRISK score, we demonstrate a clinically applicable risk stratification tool with a binary output for risk of developing PDAC (‘elevated’ or ‘normal’). PancRISK provides a step towards precision surveillance for PDAC patients, which we will test in a prospective clinical study, UroPanc

Placing the library at the heart of plagiarism prevention: The University of Bradford experience.

yesPlagiarism is a vexed issue for Higher Education, affecting student transition, retention and attainment. This paper reports on two initiatives from the University of Bradford library aimed at reducing student plagiarism. The first initiative is an intensive course for students who have contravened plagiarism regulations. The second course introduces new students to the concepts surrounding plagiarism with the aim to prevent plagiarism breaches. Since the Plagiarism Avoidance for New Students course was introduced there has been a significant drop in students referred to the disciplinary programme. This paper discusses the background to both courses and the challenges of implementation

BMP axis in cancer cachexia

BACKGROUND Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although cancer cachexia is responsible for about 25% of cancer deaths, no effective therapies are available, and the underlying mechanisms have not been fully elucidated. Its occurrence complicates patients’ management, reduces tolerance to treatments and negatively affects patient quality of life. Muscle wasting, mainly due to increased protein breakdown rates, is one of the most prominent features of cachexia. Blocking muscle loss in cachexia mouse models dramatically prolongs survival even of animals in which tumor growth is not inhibited. Recent observations showed that bone morphogenetic protein (BMP) signaling, acting through Smad1, Smad5 and Smad8 (Smad1/5/8), is a master regulator of muscle homeostasis. BMP-Smad1/5/8 axis negatively regulates a novel ubiquitin ligase (MUSA1) required for muscle loss induced by denervation. MATERIALS AND METHODS First aim of the present work was to test if alterations of the BMP signaling pathway occur in cancer-induced muscle wasting in patients. For this purpose we checked the state of activation of the BMP pathway in muscle of cachectic vs non–cachectic patients affected by colon, pancreatic and esophagus cancer and in control subjects. We checked by Western Blot the phosphorylation levels of Smad1/5/8 and of Smad3 and by quantitative Real-Time PCR (qRT-PCR) the expression levels of different atrophy-related genes The second aim was to evaluate the degree of muscle atrophy and distribution of muscle fibers in patients and control subjects using morphometric and immunohistochemical analyses. We also performed analysis on distribution of NCAM positive muscle fibers to assess the effect of denervation on muscle tropism. RESULTS From December 2014 we collected 95 rectus abdominis muscle biopsies of cancer patients and 11 from control subjects. In line with the results we obtained in C26 mice model (a well-established cancer cachexia experimental model) Smad1/5/8 phosphorylation, readout of the state of activation of the BMP pathway, was nearly completely abrogated in the muscles of cancer cachectic patients compared to cancer non-cachectic ones. Interestingly, the level of phosphorylation of Smad3 was not significantly affected suggesting specific effects of cancer growth on BMP pathway. The expression levels of different atrophy-related genes including MUSA1 were induced in the cachectic muscles. Interestingly, several BMP related genes are also changing the expression during cancer growth. We also found a correlation between suppression of BMP pathway, expression of atrophy related genes and Noggin, known to block BMP pathway. Morphometric analysis shown that patients with cancer cachexia have smaller myofiber diameter (in particular fast type fibers) in comparison to age-matched controls. In skeletal muscle from cancer patients (either cachectic or non-cachectic) we detected a prevalence of flat shaped, angulated and severely atrophic myofibers (i.e. morphological features of denervated myofibers), big fiber-type grouping (i.e. typical hallmark of denervation/reinnervation events) and numerous NCAM positive myofibers (i.e. specific marker of denervation). CONCLUSIONS These findings are consistent with the hypothesis that BMP inhibition is permissive to cachexia onset. Since the reactivation of the BMP-dependent signaling and MUSA1 suppression was sufficient to prevent tumor-induced muscle atrophy in our C26 mouse model (data not shown), the present data suggest that the BMP axis can be an effective target for therapeutic approaches to counteract cachexia also in cancer patients. The results of morphometric and immunohistochemical studies collected till now may suggest that denervation contributes to myofiber atrophy in cancer cachexia