Miracle-dz/UniFAR-FTUs huggingface dataset:
CHARSTAR: Clock hierarchy aware resource scaling in tiled architectures

High-performance architectures are over-provisioned with resources to extract the maximum achievable performance out of applications. Two sources of avoidable power dissipation are the leakage power from underutilized resources, along with clock power from the clock hierarchy that feeds these resources. Most reconfiguration mechanisms either focus solely on power gating execution resources alone or in addition, simply turn off the immediate clock tree segment which supplied the clock to those resources. These proposals neither attempt to gate further up the clock hierarchy nor do they involve the clock hierarchy in influencing the reconfiguration decisions. The primary contribution of CHARSTAR is optimizing reconfiguration mechanisms to become clock hierarchy aware. Resource gating decisions are cognizant of the power consumed by each node in the clock hierarchy and additionally, entire branches of the clock tree are greedily shut down whenever possible. The CHARSTAR design is further optimized for balanced spatio-temporal reconfiguration and also enables efficient joint control of resource and frequency scaling. The proposal is implemented by leveraging the inherent advantages of spatial architectures, utilizing a control mechanism driven by a lightweight offline trained neural predictor. CHARSTAR, when deployed on the CRIB tiled microarchitecture, improves processor energy efficiency by 20–25%, with efficiency improvements of roughly 2x in comparison to a naive power gating mechanism. Alternatively, it improves performance by 10–20% under varying power and energy constraints.
Effectiveness Analysis of Agricultural Protection Policy on Food Supply, Export and Farmer-Welfare in Nigeria: Generalized Method of Moment Approach

This study examined the effectiveness of agricultural protection policy and other macroeconomic variables on food supply, agricultural export, and farmers welfare in Nigeria, from 1980-2016 with a special interest in their relationship with the political economy. The specific objectives were to (i) estimate the degrees of agricultural protection, domestic agricultural food supply and economic welfare to farmers in Nigeria, (ii) determine the effectiveness of agricultural protection on food self-supply, agricultural export; and farmer-welfare. Data were obtained from secondary sources. Descriptive statistics and generalized method of moment (GMM) were used. Nigeria’s self-food supply was slightly above 50% while the rest of the consumption depended on importation. The welfare measure to farmers was relatively poor and not good enough to motivate them. There was a positive and significant relationship between export and agricultural protection. A significant and positive relationship also exists between farmer-welfare and protection in the sector.
Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that causes progressive cognitive impairment. The initiation and progression of AD has been linked to cholesterol metabolism and inflammation, processes that can be modulated by liver x receptors (LXRs). We show here that endogenous LXR signaling impacts the development of AD-related pathology. Genetic loss of either Lxrα or Lxrβ in APP/PS1 transgenic mice results in increased amyloid plaque load. LXRs regulate basal and inducible expression of key cholesterol homeostatic genes in the brain and act as potent inhibitors of inflammatory gene expression. Ligand activation of LXRs attenuates the inflammatory response of primary mixed glial cultures to fibrillar amyloid β peptide (fAβ) in a receptor-dependent manner. Furthermore, LXRs promote the capacity of microglia to maintain fAβ-stimulated phagocytosis in the setting of inflammation. These results identify endogenous LXR signaling as an important determinant of AD pathogenesis in mice. We propose that LXRs may be tractable targets for the treatment of AD due to their ability to modulate both lipid metabolic and inflammatory gene expression in the brain.
Doxorubicin‐based chemotherapy for diffuse large B‐cell lymphoma in elderly patients

Although many studies of elderly patients with non‐Hodgkin lymphoma have focused on the dose intensity of chemotherapy, few studies have restricted the histologic inclusion criteria such that only patients with diffuse large B‐cell lymphoma (DLCL) are considered. In the current study, treatment outcomes for elderly patients (age ≥ 60 years) were analyzed, with emphasis on the dose intensity of doxorubicin.
The role of oxytocin in psychiatric disorders: a review of biological and therapeutic research findings.

LEARNING OBJECTIVES After participating in this educational activity, the physician should be better able to 1. Identify the biological role of oxytocin in forming attachments. 2. Evaluate the relationship between various neuropsychiatric disorders and oxytocin. 3. Identify clinical implications of using oxytocin to treat various neuropsychiatric disorders. Oxytocin is a peptide hormone integral in parturition, milk letdown, and maternal behaviors that has been demonstrated in animal studies to be important in the formation of pair bonds and in social behaviors. This hormone is increasingly recognized as an important regulator of human social behaviors, including social decision making, evaluating and responding to social stimuli, mediating social interactions, and forming social memories. In addition, oxytocin is intricately involved in a broad array of neuropsychiatric functions and may be a common factor important in multiple psychiatric disorders such as autism, schizophrenia, and mood and anxiety disorders. This review article examines the extant literature on the evidence for oxytocin dysfunction in a variety of psychiatric disorders and highlights the need for further research to understand the complex role of the oxytocin system in psychiatric disease and thus pave the way for developing new therapeutic modalities. Articles were selected that involved human participants with various psychiatric disorders and that either compared oxytocin biology to healthy controls or examined the effects of exogenous oxytocin administration.
Impact and Costs of Incentives to Reduce Attrition in Online Trials: Two Randomized Controlled Trials

Background Attrition from follow-up is a major methodological challenge in randomized trials. Incentives are known to improve response rates in cross-sectional postal and online surveys, yet few studies have investigated whether they can reduce attrition from follow-up in online trials, which are particularly vulnerable to low follow-up rates. Objectives Our objective was to determine the impact of incentives on follow-up rates in an online trial. Methods Two randomized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption (the Down Your Drink randomized controlled trial, DYD-RCT). Participants were those in the DYD pilot trial eligible for 3-month follow-up (study 1) and those eligible for 12-month follow-up in the DYD main trial (study 2). Participants in both studies were randomly allocated to receive an offer of an incentive or to receive no offer of an incentive. In study 1, participants in the incentive arm were randomly offered a £5 Amazon.co.uk gift voucher, a £5 charity donation to Cancer Research UK, or entry in a prize draw for £250. In study 2, participants in the incentive arm were offered a £10 Amazon.co.uk gift voucher. The primary outcome was the proportion of participants who completed follow-up questionnaires in the incentive arm(s) compared with the no incentive arm. Results In study 1 (n = 1226), there was no significant difference in response rates between those participants offered an incentive (175/615, 29%) and those with no offer (162/611, 27%) (difference = 2%, 95% confidence interval [CI] –3% to 7%). There was no significant difference in response rates among the three different incentives offered. In study 2 (n = 2591), response rates were 9% higher in the group offered an incentive (476/1296, 37%) than in the group not offered an incentive (364/1295, 28%) (difference = 9%, 95% CI 5% to 12%, P < .001). The incremental cost per extra successful follow-up in the incentive arm was £110 in study 1 and £52 in study 2. Conclusion Whereas an offer of a £10 Amazon.co.uk gift voucher can increase follow-up rates in online trials, an offer of a lower incentive may not. The marginal costs involved require careful consideration. Trial registration ISRCTN31070347; http://www.controlled-trials.com/ISRCTN31070347 (Archived by WebCite at http://www.webcitation.org/5wgr5pl3s)
Normal T-Cell Turnover in Sooty Mangabeys Harboring Active Simian Immunodeficiency Virus Infection

ABSTRACT Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) remain healthy though they harbor viral loads comparable to those in rhesus macaques that progress to AIDS. To assess the immunologic basis of disease resistance in mangabeys, we compared the effect of SIV infection on T-cell regeneration in both monkey species. Measurement of the proliferation marker Ki-67 by flow cytometry showed that mangabeys harbored proliferating T cells at a level of 3 to 4% in peripheral blood irrespective of their infection status. In contrast, rhesus macaques demonstrated a naturally high fraction of proliferating T cells (7%) that increased two- to threefold following SIV infection. Ki-67+ T cells were predominantly CD45RA−, indicating increased proliferation of memory cells in macaques. Quantitation of an episomal DNA product of T-cell receptor α rearrangement (termed α1 circle) showed that the concentration of recent thymic emigrants in blood decreased with age over a 2-log unit range in both monkey species, consistent with age-related thymic involution. SIV infection caused a limited decrease of α1 circle numbers in mangabeys as well as in macaques. Dilution of α1 circles by T-cell proliferation likely contributed to this decrease, since α1 circle numbers and Ki-67+ fractions correlated negatively. These findings are compatible with immune exhaustion mediated by abnormal T-cell proliferation, rather than with early thymic failure, in SIV-infected macaques. Normal T-cell turnover in SIV-infected mangabeys provides an explanation for the long-term maintenance of a functional immune system in these hosts.
Cardiovascular Risk of Young Growth-Hormone-Deficient Adolescents

Objective: To determine whether postprandial lipids, coagulation factors and homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD) adolescents. Methods: Fifteen GHD adolescents on GH replacement were studied. Ten untreated GHD adolescents and 15 healthy subjects served as controls. Fasting lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1, homocysteine, folate and vitamin B12 levels were measured. Cholesterol and triglycerides were measured 4 h after a high fat meal. Results: Fasting and postprandial triglycerides and homocysteine levels of untreated GHD patients were increased compared to those of GH-treated GHD subjects and healthy controls; fibrinogen concentrations were elevated in both treated and untreated adolescents. Conclusions: GHD adolescents present an abnormal fasting and postprandial lipid profile. In addition, the increased fibrinogen and homocysteine levels are suggestive of the accumulation of cardiovascular risk factors early on in life.
Divalent cations regulate acidity within the lumen and tubulovesicle compartment of gastric parietal cells.

BACKGROUND & AIMS Until recently, it has not been possible to evaluate factors that regulate the acidity of the microenvironment within the tubulovesicles and luminal (TV/L) spaces of the gastric gland. The goal of this study was to develop a method for monitoring the mechanisms that regulate acidity in the TV/L compartment. METHODS Isolated rabbit gastric glands (intact or permeabilized with S. aureus alpha-toxin) were loaded with a recently characterized fluorescent dye, LysoSensor Yellow-Blue DND 160 (Molecular Probes, Eugene, OR), which localizes to highly acidic compartments and can be used to monitor acidity ratiometrically. RESULTS In resting glands, the pH of the TV/L compartment was approximately 3.4. Moderate alkalizations ( approximately 0.5 to 1.0 pH unit alkalization) were observed during exposure to inhibitors of the apical H(+)/K(+) ATPase (omeprazole and SCH28080), thereby unmasking a stable, low-level leak of H(+) ions from the TV/L compartment. Similar changes were observed in alpha-toxin permeabilized glands following depletion of ATP in the cytoplasm. In intact and permeabilized glands, we used the cell-permeant, divalent cation chelator, tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) to probe the effects of lowering divalent cation content of the TV/L compartment. Exposure to relatively low concentrations (20 micromol/L, 50 micromol/L) of TPEN reversibly promoted H(+) leakage. At these concentrations, simultaneous inhibition using SCH28080 led to marked enhancement of the rate of alkalization. CONCLUSIONS The effects of low-dose TPEN suggests that acidity within the TV/L compartment of the gastric gland may be regulated, at least in part, by its content of divalent cations such as Zn(2+), for which TPEN has high affinity.
Undiagnosed impaired fasting glucose and diabetes mellitus amongst inpatients receiving antipsychotic drugs

The associations between psychosis, antipsychotic drugs and diabetes mellitus have not been precisely defined but it has been repeatedly suggested that atypical antipsychotics are more likely to give rise to diabetes than are conventional drugs. This belief is largely based on healthcare database analyses which, in part, rely on the assumption that all cases of diabetes are identified in practice. We examined records of 606 hospitalized patients receiving antipsychotic treatment and found an apparent prevalence of diabetes and impaired fasting glucose of 6.4%. From this sample of patients, we investigated 166 patients (fasting blood samples) who were not known to have any disorder of glucose homeostasis and identified 10 cases of impaired fasting glucose and nine cases of diabetes mellitus (11.4% of those tested). Nine of these cases had documented evidence of previous testing for diabetes. Apparent prevalence of diabetes and impaired fasting glucose was 16.9% in those tested in practice or the study. Diagnosis was significantly associated with age [odds ratio (OR) 1.02] and treatment duration with current drug (OR 1.01). Adjusted ORs of diagnosis were not significantly different for any atypical antipsychotic compared with conventional drugs. It is concluded that there was a clinically significant prevalence of undiagnosed diabetes and impaired fasting glucose in those individuals receiving antipsychotics. Importantly, database analyses may underestimate the true prevalence of diabetes in similar populations and erroneously ascribe increased risk to certain drug treatments.
Vancomycin Tolerance Induced by Erythromycin but Not by Loss of vncRS, vex3, or pep27 Function in Streptococcus pneumoniae

ABSTRACT Vancomycin-tolerant Streptococcus pneumoniae is a growing problem among drug-resistant human pathogens. Some vancomycin-tolerant pneumococci have been reported to carry mutations in loci encoding a two-component regulatory system designated VncRS or in a proximal ABC transporter, Vex. A model was advanced proposing that the tolerance phenotype resulted from the inability of a vncS mutant to respond to the Vex-transported Pep27 “death peptide” signal and dephosphorylate VncR, thereby preventing relief of repression of autolytic and other cell death functions in response to antibiotics. To explore this hypothesis, we constructed mutations in vncS, vncR, vex3, and pep27 in S. pneumoniae strain R6 and two additional genetic backgrounds. The lytic responses of the isogenic ΔvncS, Δvex3, ΔvncR, and Δpep27 mutants, but not a ΔlytA strain, to vancomycin were indistinguishable from that of the parent strain. ΔvncS strains also failed to exhibit tolerance to vancomycin at various doses in multiple media and showed wild-type sensitivity to other classes of autolysis-inducing antibiotics. In contrast, addition of subinhibitory levels of the antibiotic erythromycin led to tolerance to vancomycin during late, but not early, exponential-phase growth in a ΔvncS strain, in the parent strain R6, and in two other strains bearing erythromycin resistance markers, namely, a ΔvncR strain and an unrelated ΔcomD strain that is defective in competence-quorum sensing. Thus, this tolerance effect resulted from changes in cell growth or other erythromycin-dependent phenomena and not inactivation of vncS per se. Consistent with these results, and in contrast to a previous report, we found that a synthetic form of Pep27 did not elicit lytic or nonlytic killing of pneumococci. Finally, microarray transcriptional analysis and β-galactosidase reporter assays revealed VncS-dependent regulation of the vex123 gene cluster but did not support a role for VncRS in the regulation of autolytic or other putative cell death loci. Based on these findings, we propose that vancomycin tolerance in S. pneumoniae does not result from loss of vncS function alone.
Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure.

BACKGROUND The risk of developing nervous system tumors following exposure to ionizing radiation is not well quantified. We characterized the incidence of nervous system tumors among atomic bomb survivors as a function of radiation dose. METHODS Tumors of the nervous system and pituitary gland diagnosed between 1958 and 1995 among 80 160 atomic bomb survivors were ascertained using the Hiroshima and Nagasaki tumor registries, medical records, and death certificates. Pathologists reviewed slides and medical records to provide histologic diagnoses. Poisson regression analyses were used to characterize radiation effects on tumor incidence, which are expressed as excess relative risk per sievert (ERR(Sv)). All statistical tests were two-sided. RESULTS A statistically significant dose-related excess of nervous system tumors was observed in the cohort (ERR(Sv) = 1.2, 95% confidence interval [CI] = 0.6 to 2.1). The highest ERR(Sv) was seen for schwannoma (4.5, 95% CI = 1.9 to 9.2). The risk for all other nervous system tumors as a group is also statistically significantly elevated (ERR(Sv) = 0.6, 95% CI = 0.1 to 1.3). Risk increases, although not statistically significant, were seen for meningiomas (ERR(Sv) = 0.6, 95% CI = -0.01 to 1.8), gliomas (ERR(Sv) = 0.6, 95% CI = -0.2 to 2.0), other nervous system tumors (ERR(Sv) = 0.5, 95% CI = <-0.2 to 2.2), and pituitary tumors (ERR(Sv) = 1.0, 95% CI = <-0.2 to 3.5). The dose-response relationships were linear. For nervous system tumors other than schwannoma, excess risks were higher for men than for women and for those exposed during childhood than for those exposed during adulthood. CONCLUSIONS A statistically significant dose response was observed for all nervous system tumors combined and for schwannoma considered separately, indicating that exposure to even moderate doses (i.e., <1 Sv) of radiation is associated with an elevated incidence of nervous system tumors.
Aortic balloon valvuloplasty: is there still a role in high-risk patients in the era of percutaneous aortic valve replacement?

OBJECTIVES To assess procedural and clinical outcomes in adults with severe aortic stenosis (AS) undergoing percutaneous aortic balloon valvuloplasty (PABV), who are considered unsuitable on initial assessment for surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI). BACKGROUND Surgical valve replacement provides better outcomes than conservative treatment for patients with severe symptomatic AS; however, patients with multiple comorbidities or hemodynamic instability carry a high operative risk. While TAVI offers an alternative to surgery, not all patients are suitable. This study looks at medium-term outcomes in a series of high-risk patients undergoing PABV. METHODS Pre- and postprocedure aortic valve gradients were measured by catheterization and echocardiography. Patients were assessed for symptomatic benefit and clinical outcomes. RESULTS Over 4 years, 42 patients underwent PABV. Mean clinical follow-up was 8 +/- 5.8 months and survival was 63%. Mean echocardiographic aortic valve gradient fell from 84.6 +/- 27 mmHg to 51.3 +/- 16 mmHg (p < 0.05). In 29% (12/42) patients, PABV was performed as a bridge to definitive AVR. Four had surgical AVR and six had TAVI. Two had successful noncardiac surgery. Four patients died in the periprocedural period and all were in cardiogenic shock. Patients were in New York Heart Association (NYHA) class IV decreased from 60% to 5% postprocedure (p < 0.05). CONCLUSION PABV is useful as a palliation or bridge to definitive therapy for treatment of patients with severe AS unsuitable for surgery. It is associated with good medium-term cardiac outcomes and enables some patients to receive definitive therapy.
Altered Innate Immune Development in HIV-Exposed Uninfected Infants

Background:Early in life, HIV-exposed uninfected (HEU) infants are at an increased risk of morbidity and mortality from infectious disease compared with HIV-unexposed (UE) infants. To improve our understanding of the mechanisms underlying their increased risk, we contrasted innate immune development between HEU and UE infants in a developing world setting, where early life infectious disease risk is exceptionally high. Methods:A prospective longitudinal cohort of HEU and UE newborns was established, and the most detailed characterization to date of HEU infant immune development was performed. Single-cell cytokine production was analyzed by flow cytometry after stimulation of whole blood with pathogen-associated molecular patterns (PAMPs). Results:Monocyte, classical dendritic cell, and plasmacytoid dendritic cell composition was similar between HEU and UE infants throughout the first year of life. However, HEU mononuclear cells mounted an enhanced pro-inflammatory response to PAMP stimulation, both in quantity of cytokine produced per cell and in proportion of responder cells. Significant differences in cytokine production were detected on the single-cell level in a PAMP-specific pattern, but only at 2 and 6 weeks of age; all differences normalized by 12 months of age. Conclusions:This time course of innate immune deviation early in life corresponds to the clinical window of vulnerability to infections in HEU infants and may be at least partially responsible for their increased morbidity and mortality from infectious disease.