Embedded expert system for space shuttle main engine maintenance

The SPARTA Embedded Expert System (SEES) is an intelligent health monitoring system that directs analysis by placing confidence factors on possible engine status and then recommends a course of action to an engineer or engine controller. The technique can prevent catastropic failures or costly rocket engine down time because of false alarms. Further, the SEES has potential as an on-board flight monitor for reusable rocket engine systems. The SEES methodology synergistically integrates vibration analysis, pattern recognition and communications theory techniques with an artificial intelligence technique - the Embedded Expert System (EES)

The cost of work-related stress to society: a systematic review

Objective. A global and systematic review of the available evidence examining the cost of work-related stress would yield important insights into the magnitude and nature of this social phenomenon. The objective of this systematic review was to collate, extract, review, and synthesize economic evaluations of the cost of work-related stress to society. Method. A research protocol was developed outlining the search strategy. Included cost-of-illness (COI) studies estimated the cost of work-related stress at a societal level, and were published in English, French or German. Searches were carried out in ingenta connect, EBSCO, JSTOR, Science Direct, Web of Knowledge, Google and Google scholar. Included studies were assessed against ten COI quality assessment criteria. Results. Fifteen COI studies met the inclusion criteria and were reviewed. These originated from Australia, Canada, Denmark, France, Sweden, Switzerland, the United Kingdom, the United States, and the EU-15. At a national and pan-European level, the total estimated cost of work-related stress in 2014 was observed to be considerable and ranged substantially from US $221.13 million to$187 billion. Productivity related losses were observed to proportionally contribute the majority of the total cost of work-related stress (between 70 to 90%), with healthcare and medical costs constituting the remaining 10% to 30%. Conclusion. The evidence reviewed here suggests a sizeable financial burden imposed by work-related stress on society. The observed range of cost estimates across studies was understood to be attributable to variations in definitions of work-related stress; the number and type of costs estimated; and, in how production loss was estimated. It is postulated that the cost estimates identified by this review are likely conservative due to narrow definitions of work - related stress (WRS) and the exclusion of diverse range of cost components

Aberrant Promoter CpG Methylation Is a Mechanism for Impaired PHD3 Expression in a Diverse Set of Malignant Cells

The prolyl-hydroxylase domain family of enzymes (PHD1-3) plays an important role in the cellular response to hypoxia by negatively regulating HIF-α proteins. Disruption of this process can lead to up-regulation of factors that promote tumorigenesis. We observed decreased basal expression of PHD3 in prostate cancer tissue and tumor cell lines representing diverse tissues of origin. Furthermore, some cancer lines displayed a failure of PHD3 mRNA induction when introduced to a hypoxic environment. This study explores the mechanism by which malignancies neither basally express PHD3 nor induce PHD3 under hypoxic conditions.Using bisulfite sequencing and methylated DNA enrichment procedures, we identified human PHD3 promoter hypermethylation in prostate, breast, melanoma and renal carcinoma cell lines. In contrast, non-transformed human prostate and breast epithelial cell lines contained PHD3 CpG islands that were unmethylated and responded normally to hypoxia by upregulating PHD3 mRNA. Only treatment of cells lines containing PHD3 promoter hypermethylation with the demethylating drug 5-aza-2'-deoxycytidine significantly increased the expression of PHD3.We conclude that expression of PHD3 is silenced by aberrant CpG methylation of the PHD3 promoter in a subset of human carcinoma cell lines of diverse origin and that this aberrant cytosine methylation status is the mechanism by which these cancer cell lines fail to upregulate PHD3 mRNA. We further show that a loss of PHD3 expression does not correlate with an increase in HIF-1α protein levels or an increase in the transcriptional activity of HIF, suggesting that loss of PHD3 may convey a selective advantage in some cancers by affecting pathway(s) other than HIF

Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis

Chondrocytes are mesenchymally derived cells that reportedly acquire some epithelial characteristics; however, whether this is a progression through a mesenchymal to epithelial transition (MET) during chondrosarcoma development is still a matter of investigation. We observed that chondrosarcoma cells acquired the expression of four epithelial markers, E-cadherin,desmocollin 3, maspin, and 14-3-3σ, all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of both maspin and 14-3-3σ in chondrosarcomas. In contrast, chondrocyte cells were negative for maspin and 14-3-3σ and displayed nearly complete DNA methylation. Robust activation of these genes was also observed in chondrocyte cells following 5-aza-dC treatment. We also examined the transcription factor snail which has been reported to be an important mediator of epithelial to mesenchymal transitions (EMTs). In chondrosarcoma cells snail is downregulated suggesting a role for loss of snail expression in lineage maintenance. Taken together, these results document an epigenetic switch associated with an MET-like phenomenon that accompanies chondrosarcoma progression

Aged-senescent cells contribute to impaired heart regeneration

Aging leads to increased cellular senescence and is associated with decreased potency of tissue-specific stem/progenitor cells. Here, we have done an extensive analysis of cardiac progenitor cells (CPCs) isolated from human subjects with cardiovascular disease, aged 32-86 years. In aged subjects (>70 years old), over half of CPCs are senescent (p16INK4A , SA-β-gal, DNA damage γH2AX, telomere length, senescence-associated secretory phenotype [SASP]), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. SASP factors secreted by senescent CPCs renders otherwise healthy CPCs to senescence. Elimination of senescent CPCs using senolytics abrogates the SASP and its debilitative effect in vitro. Global elimination of senescent cells in aged mice (INK-ATTAC or wild-type mice treated with D + Q senolytics) in vivo activates resident CPCs and increased the number of small Ki67-, EdU-positive cardiomyocytes. Therapeutic approaches that eliminate senescent cells may alleviate cardiac deterioration with aging and restore the regenerative capacity of the heart

Current status of acute hepatopancreatic necrosis disease (AHPND) of farmed shrimp in Malaysia

A report about a disease problem in cultured whiteleg shrimp (Penaeus vannamei) was first received by the National Fish Health Research Center (NaFisH) in 2011 from Perak State showing signs of white feces and slow death leading to serious mortality rate. Later, in September of the same year, the Malaysian Shrimp Farmers Association (MSFA) reported to Department of Fisheries (DOF) severe mortalities in almost all of the whiteleg shrimp farms throughout Peninsular Malaysia. Sampling of shrimps for disease diagnosis was then conducted by NaFisH. The bacteriological and histopathological examinations revealed respectively the isolation of V. parahemolyticus and massive sloughing of hepatopancreatic epithelial cells. The disease was subsequently identified as acute hepatopancreatic necrosis disease (AHPND). From our 3-year study, the annual prevalence rates of AHPND were 50%, 26% and 73% in 2011, 2012 and 2013, respectively. At present, AHPND still persists in Malaysia but at a lower prevalence. The risk factors associated with the disease were studied, however, varied environmental and management data analyzed were inconclusive to relate any one parameter directly to the disease. To help ensure the early detection of AHPND, an experimental observation study on `gut scorecard was carried out and this was confirmed by PCR and histopathology. Validation of this technique has yet to be carried out to ensure its reliability. We also examined the potential use of some commercial products such as probiotics and disinfectants available in the market but unfortunately results showed that they were not effective in controlling AHPND. Control measures applied by the farmers such as the use of probiotics were also verified but data generated likewise appeared to be inconclusive. On the contrary, our preliminary study on the antibacterial property of the plant extracts, i.e. betel and lemongrass, incorporated in the feed showed some prophylactic and chemotherapeutic potential against AHPND. However, comprehensive in vitro and in vivo trials are still currently being undertaken to elucidate its efficacy and practical applications. To ensure the shrimp industry s sustainability in Malaysia, results of our ongoing and future studies aimed at preventing and controlling unwarranted outbreaks of AHPND and other emerging transboundary diseases of penaeid shrimps will be continually disseminated to shrimp farmers and pertinent stakeholders

En bloc resection of bladder tumour: the rebirth of past through reminiscence

Purpose: To learn about the history and development of en bloc resection of bladder tumour (ERBT), and to discuss its future directions in managing bladder cancer. / Methods: In this narrative review, we summarised the history and early development of ERBT, previous attempts in overcoming the tumour size limitation, consolidative effort in standardising the ERBT procedure, emerging evidence in ERBT, evolving concepts in treating large bladder tumours, and the future directions of ERBT. / Results: Since the first report on ERBT in 1980, there has been tremendous advancement in terms of its technique, energy modalities and tumour retrieval methods. In 2020, the international consensus statement on ERBT has been developed and it serves as a standard reference for urologists to practise ERBT. Recently, high-quality evidence on ERBT has been emerging. Of note, the EB-StaR study showed that ERBT led to a reduction in 1-year recurrence rate from 38.1 to 28.5%. An individual patient data meta-analysis is currently underway, and it will be instrumental in defining the true value of ERBT in treating non-muscle-invasive bladder cancer. For large bladder tumours, modified approaches of ERBT should be accepted, as the quality of resection is more important than a mere removal of tumour in one piece. The global ERBT registry has been launched to study the value of ERBT in a real-world setting. / Conclusion: ERBT is a promising surgical technique in treating bladder cancer and it has gained increasing interest globally. It is about time for us to embrace this technique in our clinical practice

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13