702 research outputs found

    Scheduling issues on IBM p690: Performance Analysis with the PARbench Environment

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    Training report: Diagnostic procedures for PPR

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    Socioeconomic consequences of the COVID‐19 pandemic for people who use drugs

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    The COVID-19 pandemic triggered widespread socioeconomic hardship, disproportionately impacting disadvantaged populations. People who use illicit drugs are more likely to experience unemployment, homelessness, criminal justice involvement and poorer health outcomes than the general community, yet little is known about the socioeconomic impacts of the pandemic on their lives. To address this gap in the literature, we conducted in-depth interviews with 76 participants from two cohort studies of people who use illicit drugs (people who inject drugs and/or use methamphetamine) in Victoria, Australia. Findings support claims that pandemic-related Social Security supplementary payments and initiatives to reduce homelessness, although not systemically transforming people's lives, produced temporary relief from chronic socioeconomic hardship. Results also indicate how temporary interruptions to drug supply chains inflated illicit drug prices and produced adverse consequences such as financial and emotional stress, which was exacerbated by drug withdrawal symptoms for many participants. Furthermore, increased community demand for emergency food and housing support during the pandemic appeared to reduce participants' access to these services. Our findings about the unintended consequences of pandemic responses on the socioeconomic lives of a group of people who use illicit drugs provide insights into and opportunities for policy reform to redress their entrenched disadvantage

    Biochemistry and functional aspects of human glandular kallikreins

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    Human urinary kallikrein was purified by gel filtration on Sephacryl S-200 and affinity chromatography on aprotinin-Sepharose, followed by ion exchange chromatography on DEAE-Sepharose. In dodecylsulfate gel electrophoresis two protein bands with molecular weights of 41,000 and 34,000 were separated. The amino acid composition and the carbohydrate content of the kallikrein preparation were determined; isoleucine was identified as the only aminoterminal amino acid. The bimolecular velocity constant for the inhibition by diisopropyl fluorophosphate was determined as 9±2 l mol–1 min–1. The hydrolysis of a number of substrates was investigated and AcPheArgOEt was found to be the most sensitive substrate for human urinary kallikrein. Using this substrate an assay method for kallikrein in human urine was developed. It was shown by radioimmunoassay that pig pancreatic kallikrein can be absorbed in the rat intestinal tract. Furthermore, in dogs the renal excretion of glandular kallikrein from blood was demonstrated by radioimmunological methods

    Coherent photo-thermal noise cancellation in a dual-wavelength optical cavity for narrow-linewidth laser frequency stabilisation

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    Optical resonators are used for the realisation of ultra-stable frequency lasers. The use of high reflectivity multi-band coatings allows the frequency locking of several lasers of different wavelengths to a single cavity. While the noise processes for single wavelength cavities are well known, the correlation caused by multi-stack coatings has as yet not been analysed experimentally. In our work, we stabilise the frequency of a 729 nm and a 1069 nm laser to one mirror pair and determine the residual-amplitude modulation (RAM) and photo-thermal noise (PTN). We find correlations in PTN between the two lasers and observe coherent cancellation of PTN for the 1069 nm coating. We show that the fractional frequency instability of the 729 nm laser is limited by RAM at 1 × 10−14. The instability of the 1069 nm laser is at 3 × 10−15 close to the thermal noise limit of 1.5 × 10−1

    Coherent photo-thermal noise cancellation in a dual-wavelength optical cavity for narrow-linewidth laser frequency stabilisation

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    Optical resonators are used for the realisation of ultra-stable frequency lasers. The use of high reflectivity multi-band coatings allows the frequency locking of several lasers of different wavelengths to a single cavity. While the noise processes for single wavelength cavities are well known, the correlation caused by multi-stack coatings has as yet not been analysed experimentally. In our work, we stabilise the frequency of a 729729\,nm and a 10691069\,nm laser to one mirror pair and determine the residual-amplitude modulation (RAM) and photo-thermal noise (PTN). We find correlations in PTN between the two lasers and observe coherent cancellation of PTN for the 10691069\,nm coating. We show that the fractional frequency instability of the 729729\,nm laser is limited by RAM at 1×10141\times10^{-14}. The instability of the 10691069\,nm laser is at 3×10153\times10^{-15} close to the thermal noise limit of 1.5×10151.5\times10^{-15}.Comment: 17 pages, 5 figure

    Suppression of p53 function in normal human mammary epithelial cells increases sensitivity to extracellular matrix–induced apoptosis

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    Little is known about the fate of normal human mammary epithelial cells (HMECs) that lose p53 function in the context of extracellular matrix (ECM)–derived growth and polarity signals. Retrovirally mediated expression of human papillomavirus type 16 (HPV-16) E6 and antisense oligodeoxynucleotides (ODNs) were used to suppress p53 function in HMECs as a model of early breast cancer. p53+ HMEC vector controls grew exponentially in reconstituted ECM (rECM) until day 6 and then underwent growth arrest on day 7. Ultrastructural examination of day 7 vector controls revealed acinus-like structures characteristic of normal mammary epithelium. In contrast, early passage p53− HMEC cells proliferated in rECM until day 6 but then underwent apoptosis on day 7. p53− HMEC-E6 passaged in non-rECM culture rapidly (8–10 passages), lost sensitivity to both rECM-induced growth arrest and polarity, and also developed resistance to rECM-induced apoptosis. Resistance was associated with altered expression of α3-integrin. Treatment of early passage p53− HMEC-E6 cells with either α3- or β1-integrin function-blocking antibodies inhibited rECM-mediated growth arrest and induction of apoptosis. Our results indicate that suppression of p53 expression in HMECs by HPV-16 E6 and ODNs may sensitize cells to rECM-induced apoptosis and suggest a role for the α3/β1-heterodimer in mediating apoptosis in HMECs grown in contact with rECM

    Metabolic Remodeling of Human Skeletal Myocytes by Cocultured Adipocytes Depends on the Lipolytic State of the System

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    Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines. This investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism. Interactions between these two tissues were modeled using a coculture system composed of primary human adipocytes and human skeletal myotubes derived from lean or obese donors. Metabolic analysis of myocytes was performed after coculture with lipolytically silent or activated adipocytes and included transcript and metabolite profiling along with assessment of substrate selection and insulin action. Cocultured adipocytes increased myotube mRNA expression of genes involved in oxidative metabolism, regardless of the donor and degree of lipolytic activity. Adipocytes in the basal state sequestered free fatty acids, thereby forcing neighboring myotubes to rely more heavily on glucose fuel. Under this condition, insulin action was enhanced in myotubes from lean but not obese donors. In contrast, when exposed to lipolytically active adipocytes, cocultured myotubes shifted substrate use in favor of fatty acids, which was accompanied by intracellular accumulation of triacylglycerol and even-chain acylcarnitines, decreased glucose oxidation, and modest attenuation of insulin signaling. The effects of cocultured adipocytes on myocyte substrate selection and insulin action depended on the metabolic state of the system. These findings are relevant to understanding the metabolic consequences of intermuscular adipogenesis
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