Miracle-dz/UniFAR-FTUs huggingface dataset:
On the Implication of NTC versus Dark Silicon on Emerging Scale-Out Workloads: The Multi-Core Architecture Perspective

The end of Dennard's scaling poses computer systems, especially the datacenters, in front of both power and utilization walls. One possible solution to combat the power and utilization walls is dark silicon where transistors are under-utilized in the chip, but this will result in a diminishing performance. Another solution is Near-Threshold Voltage Computing (NTC) which operates transistors in the near-threshold region and provides much more flexible tradeoffs between power and performance. However, prior efforts largely focus on a specific design option based on the legacy desktop applications, therefore, lacking comprehensive analysis of emerging scale-out applications with multiple design options when dark silicon and/or NTC are/is applied. In this paper, we characterize different perspectives including performance, energy efficiency and reliability in the context of NTC/dark silicon cloud processors running emerging scale-out workloads on various architecture designs. We find NTC is generally an effective way to alleviate the power challenge over scale-out applications compared with dark silicon, it can improve performance by 1.6X, energy efficiency by 50 percent and the reliability problem can be relieved by ECC. Meanwhile, we also observe tiled-OoO architecture improves the performance by 20∼370 percent and energy efficiency by 40 ∼ 600 percent over alternative architecture designs, making it a preferable design paradigm for scale-out workloads. We believe that our observations will provide insights for the design of cloud processors under dark silicon and/or NTC .
Disparity in frequency of normal coronary artery in black and white patients undergoing cardiac catheterization.

BACKGROUND Normal epicardial coronary arteries (NCA) based on angiography have been reported to occur more frequently in Blacks than in Whites, but these studies have suffered from the limitation of being retrospective, reporting on relatively small numbers of subjects, or lacking a systematic angiogram interpretation. METHODS AND RESULTS Angiograms of 560 consecutive patients (226 Black and 334 White) enrolled in the Harlem-Bassett Study were reviewed. The presence of coronary artery disease risk factors was documented. A coronary artery was defined as normal if no segment contained a luminal diameter stenosis > 24%. Overall, NCA were found in 39.1% of patients (Blacks 42.9% and Whites 36.5%) and were present most frequently in White women (53.7%). Black men were two times more likely than White men to have NCA (odds ratio [OR] 2.09, P < .002). More Blacks than Whites with NCA were hypertensive (OR 3.30, P < .001) and cigarette smokers (OR 5.18, P < .001), whereas more Whites had hypercholesterolemia (OR .29, P < .001). CONCLUSION Significant racial differences exist between the Black and White populations in regard to the presence of NCA. The traditional risk factors of age, diabetes, cigarette smoking, and hypercholesterolemia are present in both groups. However, a racial disparity exists in the frequency of some risk factors (hypertension, cigarette smoking, hypercholesterolemia) in patients with NCA.
XIAP Overexpression in Islet β‐Cells Enhances Engraftment and Minimizes Hypoxia–Reperfusion Injury

Recent advances in clinical islet transplantation have allowed patients with type 1 diabetes to become insulin independent, but the procedure is limited since islets from two donors per recipient are typically required. This limitation arises because within a few days of the islets being embolized into the portal circulation, at least half of the transplanted β‐cells have undergone apoptotic cell death triggered by hypoxic and chemokine/cytokine‐mediated stress. We hypothesized that the survival of β‐cells in the early post‐transplant period would be enhanced if naturally occurring inhibitor of apoptosis proteins (IAPs) were transiently overexpressed in the grafts. In the present study, we used a growth‐regulatable β‐cell line (βTC‐Tet) as a model for β‐cells within islets, and examined whether adenovirally delivered XIAP (X‐linked IAP—a highly potent IAP) could enhance β‐cell survival. In vitro , XIAP‐expressing βTC‐Tet cells were markedly resistant to apoptosis in an ischemia‐reperfusion injury model system and following exposure to cytokines. When Ad‐XIAP transduced βTC‐Tet cells were transplanted subcutaneously into immunodeficient mice, the grafts were able to reverse diabetes in 3 days, vs. 21 days for Ad‐βGal transduced cells. This approach may allow more efficient use of the limited existing supply of human islets.
Phosphorylation‐dependent degradation of the cyclin‐dependent kinase inhibitor p27Kip1

The p27Kip1 protein associates with G1‐specific cyclin–CDK complexes and inhibits their catalytic activity. p27Kip1 is regulated at various levels, including translation, degradation by the ubiquitin/proteasome pathway and non‐covalent sequestration. Here, we describe point mutants of p27 deficient in their interaction with either cyclins (p27c−), CDKs (p27k−) or both (p27ck−), and demonstrate that each contact is critical for kinase inhibition and induction of G1 arrest. Through its intact cyclin contact, p27k− associated with active cyclin E–CDK2 and, unlike wild type p27, p27c− or p27ck−, was efficiently phosphorylated by CDK2 on a conserved C‐terminal CDK target site (TPKK). Retrovirally expressed p27k− was rapidly degraded through the proteasome in Rat1 cells, but was stabilized by secondary mutation of the TPKK site to VPKK. In this experimental setting, exogenous wild‐type p27 formed inactive ternary complexes with cellular cyclin E–CDK2, was not degraded through the proteasome, and was not further stabilized by the VPKK mutation. p27ck−, which was not recruited to cyclin E–CDK2, also remained stable in vivo. Thus, selective degradation of p27k− depended upon association with active cyclin E–CDK2 and subsequent phosphorylation. Altogether, these data show that p27 must be phosphorylated by CDK2 on the TPKK site in order to be degraded by the proteasome. We propose that cellular p27 must also exist transiently in a cyclin‐bound non‐inhibitory conformation in vivo.
GR SUMOylation and formation of an SUMO-SMRT/NCoR1-HDAC3 repressing complex is mandatory for GC-induced IR nGRE-mediated transrepression

Significance Glucocorticoids (GCs), acting through binding to the GC receptor (GR), are peripheral effectors of circadian and stress-related homeostatic functions fundamental for survival throughout vertebrate life span. They are widely used to combat inflammatory and allergic disorders, and their therapeutic effects have been mainly ascribed to their capacity to suppress the production of proinflammatory cytokines. The present study unveils, at the molecular level, the mechanisms that underlie the GC-induced GR direct transrepression function mediated by the evolutionary conserved inverted repeated negative response element. This knowledge paves the way to the elucidation of the functions of the GR at the submolecular levels and to the future educated design and screening of drugs, which could be devoid of undesirable debilitating effects on prolonged GC therapy. Unique among the nuclear receptor superfamily, the glucocorticoid (GC) receptor (GR) can exert three distinct transcriptional regulatory functions on binding of a single natural (cortisol in human and corticosterone in mice) and synthetic [e.g., dexamethasone (Dex)] hormone. The molecular mechanisms underlying GC-induced positive GC response element [(+)GRE]-mediated activation of transcription are partially understood. In contrast, these mechanisms remain elusive for GC-induced evolutionary conserved inverted repeated negative GC response element (IR nGRE)-mediated direct transrepression and for tethered indirect transrepression that is mediated by DNA-bound NF-κB/activator protein 1 (AP1)/STAT3 activators and instrumental in GC-induced anti-inflammatory activity. We demonstrate here that SUMOylation of lysine K293 (mouse K310) located within an evolutionary conserved sequence in the human GR N-terminal domain allows the formation of a GR-small ubiquitin-related modifiers (SUMOs)-NCoR1/SMRT-HDAC3 repressing complex mandatory for GC-induced IR nGRE-mediated direct repression in vitro, but does not affect transactivation. Importantly, these results were validated in vivo: in K310R mutant mice and in mice ablated selectively for nuclear receptor corepressor 1 (NCoR1)/silencing mediator for retinoid or thyroid-hormone receptors (SMRT) corepressors in skin keratinocytes, Dex-induced direct repression and the formation of repressing complexes on IR nGREs were impaired, whereas transactivation was unaffected. In mice selectively ablated for histone deacetylase 3 (HDAC3) in skin keratinocytes, GC-induced direct repression, but not bindings of GR and of corepressors NCoR1/SMRT, was abolished, indicating that HDAC3 is instrumental in IR nGRE-mediated repression. Moreover, we demonstrate that the binding of HDAC3 to IR nGREs in vivo is mediated through interaction with SMRT/NCoR1. We also show that the GR ligand binding domain (LBD) is not required for SMRT-mediated repression, which can be mediated by a LBD-truncated GR, whereas it is mandatory for NCoR1-mediated repression through an interaction with K579 in the LBD.
Ethnic differences in interleukin 6 (IL‐6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels

Preterm birth (PTB) is a significant neonatal health problem that is more common in African‐Americans (AA) than in European‐Americans (EA). Part of this disparity is likely to result from the differing genetic architectures of EA and AA. To begin assessing the role of these differences, patterns of genetic variation in two previously proposed candidate genes, encoding interleukin 6 (IL6) and its receptor (IL6R), were analyzed in mothers and fetuses from 496 EA birth‐events (149 cases and 347 controls) and 397 birth‐events in AA (76 cases and 321 controls). IL‐6 levels in amniotic fluid (AF) samples were determined in a subset of these pregnancies. Case‐control comparisons revealed a single SNP in IL6R associated with PTB (p=0.04 for allelic and p=0.05 for genotype association). In addition, all of the SNPs studied showed significant frequency differences between AA and EA in at least one comparison, significantly in excess of that expected from general population databases. Higher IL‐6 concentrations were associated with the IL6 SNP ‐661 in EA preterm samples (p=0.0056), and this result seems to be driven by microbial invasion of the amniotic cavity, indicating a gene by infection interaction. These findings indicate that, as a function of IL6 genotype, EA and AA women respond differently to infection with respect to their expression of IL‐6. Our data support differential genetic control of levels of IL‐6 in amniotic fluid between EA and AA.
Combination of DNA methylation inhibitor 5‐azacytidine and arsenic trioxide has synergistic activity in myeloma

XAF1 is a newly identified candidate tumour‐suppressor gene that can antagonise XIAP and sensitise cells to cell death triggers. This study was undertaken to study the effect of 5‐azacytidine (AZA) on XAF1 expression in myeloma cells and efficacy of 5‐AZA and arsenic trioxide (ATO) combination treatment in myeloma in vivo and in vitro. XAF1 expression was analysed by semi‐quantitative PCR and western blotting. Methylation specific PCR was used to detect methylation status of XAF1 promoter CpG islands. RPMI 8226 and XG‐7 cells were treated with various concentrations of 5‐AZA and ATO. Expression of XAF1 mRNA variants were confirmed by gel electrophoresis and sequencing. Untreated RPMI 8226 cell expresses two variants of XAF1 mRNA. Untreated XG‐7 cell has no expression of XAF1. Hypermethylation of XAF1 promoter CpG islands was detected in both cell lines. Both cell lines express full‐length XAF1 transcript after treated with 2.5 μmol/L 5‐AZA for 72 h. Our studies demonstrated that 5‐AZA exhibits anti‐myeloma synergy with ATO. In addition, ATO alone, 5‐AZA alone, or combination of 5‐AZA and ATO was effective in slowing myeloma growth and prolonging survival of myeloma‐loaded nude mice. The findings suggested that 5‐AZA and ATO may be an effective combination in the therapy of myeloma patients.
The G‐Allele of the PSMA6−8C>G polymorphism is associated with poor outcome in multiple myeloma independently of circulating proteasome serum levels

Introduction: The proteasome system plays a crucial role in several malignant disorders, especially in multiple myeloma (MM). The G‐allele of a single nucleotide polymorphism (SNP) −8C>G in the gene PSMA6, one of seven α‐subunit genes of the 20S proteasome, was associated with myocardial infarction. Moreover, PSMA6 mRNA expression in human B‐cell lines depended on genotypes. We investigated a potential role of this novel SNP in patients with MM. Methods: PSMA6 genotypes of 116 patients with MM were associated with survival. Circulating proteasome levels (CPL) dependent on −8C>G genotypes of 70 newly diagnosed patients were studied using an anti‐20S proteasome enzyme‐linked immunoabsorbant assay (ELISA). Results: Genotype distribution (69 CC, 44 CG, 3 GG) was compatible with Hardy–Weinberg equilibrium. Kaplan–Meier curves revealed a significant association of PSMA6−8C>G with 5‐yr survival (P = 0.014). Median survival time was 43 months for the GG genotype and 50 months for the CG genotype. It was not reached within follow‐up by the CC genotype (CC 5‐yr survival rate 61.2%). Following hazard ratio (HR) for overall survival was calculated: G‐allele vs. CC genotype: 2.038, 95% CI 1.14–3.65, P = 0.017. In multivariate analysis the G‐allele was an independent prognostic factor (HR 2.1, P = 0.014). CPL were not significantly different between genotypes [mean CPL: CC 284.9 ng/mL vs. 303.3 ng/mL G‐allele carriers (P = 0.709)]. Conclusions: These results suggest the G‐allele of the PSMA6−8C>G polymorphism as a possible survival prognosticator.
Performance of English stop smoking services in first 10 years: analysis of service monitoring data

Objectives To analyse the performance of the English Stop Smoking Services from 2001/02 to 2010/11. Design Analysis of national service monitoring data. Setting England. Participants Smokers recorded as having been treated by English stop smoking services between April 2001 and March 2011. Main outcome measures Annual figures for the number of quit dates set (throughput), the percentage of these that led to biochemically verified abstinence after four weeks (four week quit rate), and the “impact” in terms of the number of four week quitters beyond those who it is estimated would have stopped with only a prescription for smoking cessation treatment; characteristics of smokers being treated, medication used, and mode of delivery (for example, one to one, group based); variability across local services in throughput, four week quit rates, and impact for 2010/11. Results Throughput rose from 227 335 in 2001/02 to 787 527 (8% of all smokers) in 2010/11. The percentage of four week quitters declined slightly from 35% to 34%. Impact rose from 22 933 four week quitters created in 2001/02 to 72 411 in 2010/11 (corresponding to an estimated 21 723 12 month quitters). The services were successful in reaching disadvantaged smokers; 54% (n=425 684) were in receipt of free prescriptions in 2010/11. Substantial variation existed across local services in throughput, success rates, and impact. Conclusions The English stop smoking services have had an increasing impact in helping smokers to stop in their first 10 years of operation and have successfully reached disadvantaged groups. However, performance across local services has varied considerably.
Variable degree of growth hormone (GH) and insulin-like growth factor (IGF) sensitivity in children with idiopathic short stature compared with GH-deficient patients: evidence from an IGF-based dosing study of short children.

CONTEXT We recently showed that, in IGF-based GH therapy, the IGF-I target chosen affects GH dose requirements, and higher IGF-I targets are associated with more robust growth parameters. OBJECTIVE The objective of the study was to compare the response of GH-deficient (GHD) vs. idiopathic short-stature (ISS) children to IGF-based GH therapy. DESIGN This was a 2-yr, open-label, randomized trial. SETTING The setting was multicenter and outpatient. PATIENTS Prepubertal short children [height sd score (SDS) < -2] with low IGF-I levels (<or=-1 SDS), subclassified based on the peak stimulated serum GH concentration at baseline, into two subgroups: GHD (n = 63, GH < 7 ng/ml) and ISS (n = 102, GH >or= 7 ng/ml). INTERVENTIONS Patients were randomized 2:2:1 to three treatment groups: IGF-I target of 0 SDS (IGF0T), 2 SDS (IGF2T), or a conventional weight-based GH dosing of 40 microg/kg x d (Conv). MAIN OUTCOME MEASURES Change in (Delta) height SDS, IGF-I SDS, and GH dose was measured. RESULTS ISS subjects required higher GH doses than GHD patients in the IGF2T (but not IGF0T) arm (medians 119 and 65 microg/kg x d, respectively), indicating that ISS represents a partial GH-insensitive state that manifests during treatment with higher doses of GH. GHD children grew more than those with ISS in both IGF-targeted dosage groups despite similar IGF-I levels (suggesting a degree of IGF insensitivity in ISS subjects): Delta height SDS of 2.04 +/- 0.17 for GHD and 1.33 +/- 0.09 for ISS groups in IGF2T, 1.41 +/- 0.13 for children with GHD, and 0.84 +/- 0.07 for those with ISS in IGF0T. CONCLUSION IGF-based GH dosing is clinically feasible in both GHD and ISS patients, although GH dose requirements and auxological outcomes are distinct between these groups. This suggests a degree of both GH and IGF insensitivity in subjects with ISS that requires specific management strategies to optimize growth during GH therapy.
Cyberbullying In Cyprus - Associated Parenting Style and Psychopathology

In this paper we present data from a cross-sectional study on cyberbullying experiences and cyberbullying perpetration in the Republic of Cyprus. Data were collected from a representative sample of the adolescent student population of the first and fourth grades of high school. Total sample was 2684 students, 48.5% of them male and 51.5% female. Research material included extended demographics, a detailed questionnaire on Internet activities, the Parental Bonding Index (PBI) and the Strengths and Difficulties Questionnaire (SDQ). We compared the results on psychometry for those students who did not report being bullied or having bullied others with those who were bullied, those who bullied others and those who were both sufferers and perpetrators of cyberbullying. Those students who reported being both victims and perpetrators tended to show similar or higher dysfunction than those students who only perpetrated cyberbullying. High maternal and paternal protection in combination with low maternal and paternal care ('affectionless control' parenting style) was associated with perpetrating cyberbullying, either with or without any experience of oneself being bullied as well. Results support a hypothesis that the perpetration of cyberbullying is associated with inefficient parenting styles. They also point to the existence of significant emotional symptoms for the involved adolescents and also general conduct problems, hyperactivity, peer problems and antisocial tendencies. It is important to note that perpetrators of cyberbullying were in most cases victims themselves at some point in time.
Low‐intensity pulsed ultrasound accelerates fracture healing by stimulation of recruitment of both local and circulating osteogenic progenitors

We investigated the effect of low‐intensity pulsed ultrasound (LIPUS) on the homing of circulating osteogenic progenitors to the fracture site. Parabiotic animals were formed by surgically conjoining a green fluorescent protein (GFP) mouse and a syngeneic wild‐type mouse. A transverse femoral fracture was made in the contralateral hind limb of the wild‐type partner. The fracture site was exposed to daily LIPUS in the treatment group. Animals without LIPUS treatment served as the control group. Radiological assessment showed that the hard callus area was significantly greater in the LIPUS group than in the control group at 2 and 4 weeks post‐fracture. Histomorphometric analysis at the fracture site showed a significant increase of GFP cells in the LIPUS group after 2 weeks (7.5%), compared to the control group (2.4%) (p < 0.05). The LIPUS group exhibited a significantly higher percentage of GFP cells expressing alkaline phosphatase (GFP/AP) than the control group at 2 weeks post‐fracture (5.9%, 0.3%, respectively, p < 0.05). There was no significant difference in the percentage of GFP/AP cells between the LIPUS group (2.0%) and the control group (1.4%) at 4 weeks post‐fracture. Stromal cell derived factor‐1 and CXCR4 were immunohistochemically identified at the fracture site in the LIPUS group. These data indicate that LIPUS induced the homing of circulating osteogenic progenitors to the fracture site for possible contribution to new bone formation. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1516–1521, 2012
Cell Cycle Regulators in Bladder Cancer: Relationship to Schistosomiasis

Dysregulation of cell cycle control may lead to genomic instability, neoplastic transformation and tumor progression. In terms of the particular roles in regulation of the cell‐cycle, p21(WAF1) causes growth arrest through inhibition of cyclin‐dependant kinases required for G1/S transition. P16 (INK4A) and p15 (INK4B) are thought to act as tumor suppressors, since their inactivation and/or deletion are observable in various types of malignancies. Cyclin D1 is hypothesized to control cell cycle progression through the G1‐S check point. The present study evaluated p21 expression, p16 and p15 gene deletion and cylin D1 expression in bladder carcinoma among Egyptian patients, in relation to different clinicopathological features of the tumors and presence or absence of bilharziasis. Tissue specimens were obtained from 132 patients with bladder carcinoma and 50 normal tissue samples from the same patients served as control. P21 was determined by Western blot (WB) and enzyme immunoassay (EIA), p16 and p15 gene deletions were examined by polymerase chain reaction (PCR) and Cyclin D1 was detected by WB. Levels of p21 were lower in malignant tumors than in normal tissues. Lower expression of p21 was evident in lymph node positive, well differentiated tumors and squamous cell carcinoma (SCC) than in lymph node negative, poorly differentiated tumors and transitional cell carcinoma (TCC). In all normal samples, p15 and p16 genes were detected while cyclin D1 was not detected. P16 and p15 genes were deleted in 38.7% (41/106) and 30.2% (32/106) of bladder tumors respectively. The deletion of both genes was associated with poor differentiation grade and presence of bilharziasis. P16 deletion was also correlated to advancing tumor stage. Cyclin D1 was expressed in 57.5% of bladder tumors (69/120), where its expression was correlated to early stage, well differentiation grade, schistomiasis, and low levels of p21. Cell cycle is dysregulated in bladder carcinoma. This was evident from the increased expression of cyclin D1, the decreased levels of p21 and the deletion of p15 and p16 genes. Moreover, p16 and p15 gene deletion was related to tumor progression and might have a role in bilharzial bladder carcinogenesis. Cyclin D1 over‐expression appears to be an early event in bladder cancer and might explain bilharzial associated bladder carcinogenesis. IUBMB Life, 56: 557‐564, 2004