105 research outputs found
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Reducing cache misses due to frequent context switching using a cache context store
No full textComputer system performance has been pushed further and further for decades, and hence the complexity of the designs has been increasing as well. This is true for both hardware and software. Problems at the interface of hardware and software are particularly interesting, as are solutions which include interaction between hardware and software. Cache misses due to frequent context switching is one such problem and the solution proposed in this thesis is to save the cache context of processes in a memory called a Cache Context Store (CCS). The CCS is designed as a byte-addressable memory close to the processor capable of holding multiple cache contexts. Speedup achievable by such a system is calculated analytically using experimental data from running SPEC CPU2006 benchmarks on a real system.Electrical and Computer Engineerin
Evaluating the neutralizing antibody response to HIV-1 membrane proximal external regional; Implications for vaccine design
No full textIncludes bibliographical references.Inducing broadly neutralizing antibodies targeting the HIV-1 envelope is thought to be crucial for developing an effective vaccine. The Membrane Proximal External Region (MPER) within the HIV- 1 gp41 envelope is a promising vaccine target. The MPER is highly conserved, functionally constrained, facilitates virus fusion and is targeted by broadly neutralizing monoclonal antibodies. The objectives of this research were 1) To evaluate the neutralization breadth of antibodies induced by epitopes within the MPER compared to the PG9/16-site in chronically HIV-1-infected individuals, 2) to identify neutralization resistant HIV-1 isolates (using plasma samples infected with the same subtype) and to characterize their sensitivity to anti-MPER antibodies and 3) to determine the accessibility of the MPER to HIV-1 induced polyclonal anti-MPER antibodies in a highly neutralization resistant virus (253-11; CRF02_AG subtype)
A lowcost concurrent error detection technique for processor control logic
No full textThis paper presents a concurrent error detection tech-nique targeted towards control logic in a processor with em-phasis on low area overhead. Rather than detect all mod-eled transient faults, the technique selects faults which have a high probability of causing damage to the architectural state of the processor and protects the circuit against these faults. Fault detection is achieved through a series of asser-tions. Each assertion is an implication from inputs to the outputs of a combinational circuit. Fault simulation exper-iments performed on control logic modules of an industrial processor suggest that high reduction in damage causing faults can be achieved with a low overhead.
Nutritional status and various morbidities among school children of a coastal area in South India
No full textBackground: Malnutrition and poor health among school children is the common cause of low school enrolment, high absenteeism, early dropout and poor classroom performance. This study was conducted to assess the various morbidities and nutritional status among school children.Methods: This descriptive study was conducted during year 2013 in a higher secondary school located in a coastal area of Puducherry. A total of 714 students were interviewed and examined. A pre-designed and pre-tested questionnaire was used to interview and examine all the participated students. Body weight and height were measured using standardized procedures. WHO criteria for classification of nutritional status was used. Visual acuity and colour vision was assessed using Snellen’s chart and Ishihara’s pseudo isochromatic chart respectively. Mean scores and proportions were calculated and chi-square test was applied. P value of <0.05 was considered as statistically significant.Results: Among 714 student, 369 (51.4%) were males and 345 (48.6%) were females. The mean age of children was 10.2 ± 3.1 years. Among all age groups and both sexes, the observed BMI was lower as compared to the reference values. The prevalence of underweight among children of 5-9 years was (30.7%) and (1.1%) were severely underweight. The prevalence of stunting was 10.4%, including 0.1% of severely stunted children. A total of 30.7% children were thin (low BMI for age). Pallor (39.5%), myopia (34.9%) and dental caries (14.7%) were the common morbidities observed among children. The pallor was observed more commonly among girls and this difference was statistically significant (p value <0.05).Conclusion: Under-nutrition is a prevalent condition among school children. Apart from various nutritional programmes, health education to parents, community and school teachers are quite important to address this problem.
The HIV-1 accessory proteins Nef and Vpu downregulate total and cell surface CD28 in CD4+ T cells
No full textAbstract Background The HIV-1 accessory proteins Nef and Vpu alter cell surface levels of multiple host proteins to modify the immune response and increase viral persistence. Nef and Vpu can downregulate cell surface levels of the co-stimulatory molecule CD28, however the mechanism of this function has not been completely elucidated. Results Here, we provide evidence that Nef and Vpu decrease cell surface and total cellular levels of CD28. Moreover, using inhibitors we implicate the cellular degradation machinery in the downregulation of CD28. We shed light on the mechanisms of CD28 downregulation by implicating the Nef LL165 and DD175 motifs in decreasing cell surface CD28 and Nef DD175 in decreasing total cellular CD28. Moreover, the Vpu LV64 and S52/56 motifs were required for cell surface CD28 downregulation, while, unlike for CD4 downregulation, Vpu W22 was dispensable. The Vpu S52/56 motif was also critical for Vpu-mediated decreases in total CD28 protein level. Finally, the ability of Vpu to downregulate CD28 is conserved between multiple group M Vpu proteins and infection with viruses encoding or lacking Nef and Vpu have differential effects on activation upon stimulation. Conclusions We report that Nef and Vpu downregulate cell surface and total cellular CD28 levels. We identified inhibitors and mutations within Nef and Vpu that disrupt downregulation, shedding light on the mechanisms utilized to downregulate CD28. The conservation and redundancy between the abilities of two HIV-1 proteins to downregulate CD28 highlight the importance of this function, which may contribute to the development of latently infected cells
Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2
No full textNumerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such as microRNAs (miRNAs), which are involved in the regulation of 60% of human gene activity, remains poorly explored. Similar to research we have previously undertaken with other viruses such as Ebola and HIV, in this study we investigated the miRNA profile of lung epithelial cells following infection with SARS-CoV-2. At the 24 and 72 h post-infection time points, SARS-CoV-2 did not drastically alter the miRNome. About 90% of the miRNAs remained non-differentially expressed. The results revealed that miR-1246, miR-1290 and miR-4728-5p were the most upregulated over time. miR-196b-5p and miR-196a-5p were the most downregulated at 24 h, whereas at 72 h, miR-3924, miR-30e-5p and miR-145-3p showed the highest level of downregulation. In the top significantly enriched KEGG pathways of genes targeted by differentially expressed miRNAs we found, among others, MAPK, RAS, P13K-Akt and renin secretion signaling pathways. Using RT-qPCR, we also showed that SARS-CoV-2 may regulate several predicted host mRNA targets involved in the entry of the virus into host cells (ACE2, TMPRSS2, ADAM17, FURIN), renin–angiotensin system (RAS) (Renin, Angiotensinogen, ACE), innate immune response (IL-6, IFN1β, CXCL10, SOCS4) and fundamental cellular processes (AKT, NOTCH, WNT). Finally, we demonstrated by dual-luciferase assay a direct interaction between miR-1246 and ACE-2 mRNA. This study highlights the modulatory role of miRNAs in the pathogenesis of SARS-CoV-2
Emerg Infect Dis
No full textIsolating and characterizing emerging SARS-CoV-2 variants is key to understanding virus pathogenesis. In this study, we isolated samples of the SARS-CoV-2 R.1 lineage, categorized as a variant under monitoring by the World Health Organization, and evaluated their sensitivity to neutralizing antibodies and type I interferons. We used convalescent serum samples from persons in Canada infected either with ancestral virus (wave 1) or the B.1.1.7 (Alpha) variant of concern (wave 3) for testing neutralization sensitivity. The R.1 isolates were potently neutralized by both the wave 1 and wave 3 convalescent serum samples, unlike the B.1.351 (Beta) variant of concern. Of note, the R.1 variant was significantly more resistant to type I interferons (IFN-\u3b1/\u3b2) than was the ancestral isolate. Our study demonstrates that the R.1 variant retained sensitivity to neutralizing antibodies but evolved resistance to type I interferons. This critical driving force will influence the trajectory of the pandemic.439999/CIHRCanada
Cancer mortality in India: a nationally representative survey.
No full textBACKGROUND: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. METHODS: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. FINDINGS: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). INTERPRETATION: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health
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