Interference of billing and scheduling strategies for energy and cost savings in modern data centers

The high energy consumption of HPC systems is an obstacle for evergrowing systems. Unfortunately, energy consumption does not decrease linearly with reduced workload; therefore, energy conservation techniques have been deployed on various levels which steer the overall system. While the overall saving of energy is useful, the price of energy is not necessarily proportional to the consumption. Particularly with renewable energies, there are occasions in which the price is significantly lower. The potential of saving energy costs when using smart contracts with energy providers is lacking research. In this paper, we conduct an analysis of the potential savings when applying cost-aware schedulers to data center workloads while considering power contracts that allow for dynamic (hourly) pricing. The contributions of this paper are twofold: 1) the theoretic assessment of cost savings; 2) the development of a simulator to replay batch scheduler traces which supports flexible energy cost models and various cost-aware scheduling algorithms. This allows to approximate the energy costs savings of data centers for various scenarios including off-peak and hourly budgeted energy prices as provided by the energy spot market. An evaluation is conducted with four annual job traces from the German Climate Computing Center (DKRZ) and Leibniz Supercomputing Centre (LRZ)

Pkhd1

Autosomal-recessive polycystic kidney disease (ARPKD; MIM #263200) is a severe, hereditary, hepato-renal fibrocystic disorder that causes early childhood morbidity and mortality. Mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene, which encodes the protein fibrocystin/polyductin complex (FPC), cause all typical forms of ARPKD. Several mouse lines carrying diverse, genetically engineered disruptions in the orthologous Pkhd1 gene have been generated, but none expresses the classic ARPKD renal phenotype. In the current study, we characterized a spontaneous mouse Pkhd1 mutation that is transmitted as a recessive trait and causes cysticliver (cyli), similar to the hepato-biliary disease in ARPKD, but which is exacerbated by age, sex, and parity. We mapped the mutation to Chromosome 1 and determined that an insertion/deletion mutation causes a frameshift within Pkhd1 exon 48, which is predicted to result in a premature termination codon (UGA). Pkhd

Heavy-quark mass effects in Higgs boson production at the LHC

We study the impact of heavy-quark masses in Higgs boson production through gluon fusion at the LHC. We extend previous computations of the fully differential cross section and of the transverse momentum spectrum of the Higgs boson by taking into account the finite top- and bottom-quark masses up to O(alpha_S^3). We also discuss the issues arising when the heavy-quark mass is much smaller than the Higgs mass. Our results are implemented in updated versions of the HNNLO and HRes numerical programs.Comment: Minor modifications, results unchanged. Discussion on uncertainties added. Version published on JHE

Exosome loaded immunomodulatory biomaterials alleviate local immune response in immunocompetent diabetic mice post islet xenotransplantation

Foreign body response (FBR) to biomaterials compromises the function of implants and leads to medical complications. Here, we report a hybrid alginate microcapsule (AlgXO) that attenuated the immune response after implantation, through releasing exosomes derived from human Umbilical Cord Mesenchymal Stem Cells (XOs). Upon release, XOs suppress the local immune microenvironment, where xenotransplantation of rat islets encapsulated in AlgXO led to >170 days euglycemia in immunocompetent mouse model of Type 1 Diabetes. In vitro analyses revealed that XOs suppressed the proliferation of CD3/CD28 activated splenocytes and CD3+ T cells. Comparing suppressive potency of XOs in purified CD3+ T cells versus splenocytes, we found XOs more profoundly suppressed T cells in the splenocytes co-culture, where a heterogenous cell population is present. XOs also suppressed CD3/CD28 activated human peripheral blood mononuclear cells (PBMCs) and reduced their cytokine secretion including IL-2, IL-6, IL-12p70, IL-22, and TNFα. We further demonstrate that XOs mechanism of action is likely mediated via myeloid cells and XOs suppress both murine and human macrophages partly by interfering with NFκB pathway. We propose that through controlled release of XOs, AlgXO provide a promising new platform that could alleviate the local immune response to implantable biomaterials

Sleep disruption due to nocturnal heartburn: a review of the evidence and clinical implications

Nocturnal heartburn (NHB) is a symptom that affects up to 25% of the general population and has been shown to cause sleep disruption that adversely affects quality of life and psychomotor performance. Few studies have evaluated the association between occasional NHB and sleep disturbances; therefore, this connection may be underappreciated and left untreated by the primary care provider and patient, with potentially significant negative clinical consequences and effects on quality of life. This review sought to describe what is currently known about the interplay between occasional NHB and sleep disruption, and identify whether acid suppression therapy can improve symptoms of occasional NHB and associated sleep disruptions. The pathophysiology of heartburn-induced sleep disruption appears to follow a bidirectional cycle due to the normal physiologic changes that occur in the upper gastrointestinal tract during sleep and due to the potential for heartburn symptoms to cause sleep arousal. The majority of the identified studies suggested that pharmacologic interventions for acid reduction, including proton pump inhibitors or histamine type-2 receptor antagonists (H2RAs), improved objective and/or subjective sleep outcomes among individuals with gastroesophageal reflux disease (GERD) and NHB. Several studies specific to famotidine demonstrated that treatment with 10 mg or 20 mg reduced nighttime awakenings due to NHB. In conclusion, NHB symptoms can cause sleep dysfunction that can have a profound adverse downstream effect on quality of life, next-day functioning, and health-related outcomes. The current approach to managing occasional NHB is similar to that associated with GERD, highlighting the need for studies specific to the occasional heartburn population. Health care providers should investigate NHB as one of the potential causes of sleep complaints, and patients with heartburn should be questioned about sleep quality, recalled arousals, next-day vitality, early fatigue, and next-day functioning

The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance

BACKGROUND: Klinefelter syndrome (KS), caused by XXY karyotype, is characterized by low testosterone, infertility, cognitive deficits, and increased prevalence of health problems including obesity and diabetes. It has been difficult to separate direct genetic effects from hormonal effects in human studies or in mouse models of KS because low testosterone levels are confounded with sex chromosome complement. METHODS: In this study, we present the Sex Chromosome Trisomy (SCT) mouse model that produces XXY, XYY, XY, and XX mice in the same litters, each genotype with either testes or ovaries. The independence of sex chromosome complement and gonadal type allows for improved recognition of sex chromosome effects that are not dependent on levels of gonadal hormones. All mice were gonadectomized and treated with testosterone for 3 weeks. Body weight, body composition, and motor function were measured. RESULTS: Before hormonal manipulation, XXY mice of both sexes had significantly greater body weight and relative fat mass compared to XY mice. After gonadectomy and testosterone replacement, XXY mice (both sexes) still had significantly greater body weight and relative fat mass, but less relative lean mass compared to XY mice. Liver, gonadal fat pad, and inguinal fat pad weights were also higher in XXY mice, independent of gonadal sex. In several of these measures, XX mice also differed from XY mice, and gonadal males and females differed significantly on almost every metabolic measure. The sex chromosome effects (except for testis size) were also seen in gonadally female mice before and after ovariectomy and testosterone treatment, indicating that they do not reflect group differences in levels of testicular secretions. XYY mice were similar to XY mice on body weight and metabolic variables but performed worse on motor tasks compared to other groups. CONCLUSIONS: We find that the new SCT mouse model for XXY and XYY recapitulates features found in humans with these aneuploidies. We illustrate that this model has significant promise for unveiling the role of genetic effects compared to hormonal effects in these syndromes, because many phenotypes are different in XXY vs. XY gonadal female mice which have never been exposed to testicular secretions

High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism

Reducing AD-Like Pathology in 3xTg-AD Mouse Model by DNA Epitope Vaccine — A Novel Immunotherapeutic Strategy

BACKGROUND: The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42) (Abeta(1-11)) , a non-self T helper cell epitope (PADRE), and macrophage-derived chemokine (MDC/CCL22) as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype. METHODS AND FINDINGS: We generated pMDC-3Abeta(1-11)-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages. CONCLUSIONS: Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials