Managing Dynamic Enterprise and Urgent Workloads on Clouds Using Layered Queuing and Historical Performance Models

The automatic allocation of enterprise workload to resources can be enhanced by being able to make what-if response time predictions whilst different allocations are being considered. We experimentally investigate an historical and a layered queuing performance model and show how they can provide a good level of support for a dynamic-urgent cloud environment. Using this we define, implement and experimentally investigate the effectiveness of a prediction-based cloud workload and resource management algorithm. Based on these experimental analyses we: i.) comparatively evaluate the layered queuing and historical techniques; ii.) evaluate the effectiveness of the management algorithm in different operating scenarios; and iii.) provide guidance on using prediction-based workload and resource management

Micro-cogeneration versus conventional technologies: Considering model uncertainties in assessing the energy benefits

Fuel cells with nominal outputs of approximately 1kW AC are emerging as a prime-mover of a micro-cogeneration system potentially well-suited to compete, on an energy basis, with conventional methods for satisfying occupant electrical and thermal demands in a residential application. As the energy benefits of these systems can be incremental when compared to efficient conventional methods, it is especially important to consider the uncertainties of the models on which simulation results are based. However, researchers have yet to take this aspect into account.This article makes a contribution by demonstrating how these model uncertainties may be propagated to the simulation results of a micro-cogeneration system for comparison to a reference scenario using a case study. This case study compares the energy performance of a fuel-cell based micro-cogeneration system serving only domestic hot water demands to an efficient reference scenario where the conventional methods for providing electrical and thermal demands are considered to be a central gas-fired combined-cycle plant and a condensing tankless water heater respectively. The simulation results demonstrated that if model uncertainties were ignored, it would have been possible to demonstrate that the considered micro-cogeneration system was more efficient than the reference scenario for average consumption levels of domestic hot water. However, when model uncertainties were considered, the efficiency of the considered micro-cogeneration system could not reliably exceed that of the reference scenario by serving the domestic hot water needs of a single-family home

Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells

Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally, somatic deletion in RMCs of the Wnt ligand transporter Wntless results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching

Placing high-redshift quasars in perspective: A catalog of spectroscopic properties from the gemini near infrared spectrograph-distant quasar survey

We present spectroscopic measurements for 226 sources from the Gemini Near Infrared Spectrograph-Distant Quasar Survey (GNIRS-DQS). Being the largest uniform, homogeneous survey of its kind, it represents a fluxlimited sample (mi≤19.0 mag, H≤16.5 mag) of Sloan Digital Sky Survey (SDSS) quasars at 1.5 ≤ z ≤ 3.5 with a monochromatic luminosity (λLλ) at 5100 Å in the range of 1044-1046 erg s-1. A combination of the GNIRS and SDSS spectra covers principal quasar diagnostic features, chiefly the C IV λ1549, Mg II λλ2798, 2803, Hβ λ4861, and [O III] λλ4959, 5007 emission lines, in each source. The spectral inventory will be utilized primarily to develop prescriptions for obtaining more accurate and precise redshifts, black hole masses, and accretion rates for all quasars. Additionally, the measurements will facilitate an understanding of the dependence of rest-frame ultraviolet-optical spectral properties of quasars on redshift, luminosity, and Eddington ratio, and test whether the physical properties of the quasar central engine evolve over cosmic time.Fil: Matthews, Brandon M.. University of North Texas; Estados UnidosFil: Shemmer, Ohad. University of North Texas; Estados UnidosFil: Dix, Cooper. University of North Texas; Estados UnidosFil: Brotherton, Michael S.. University of Wyoming; Estados UnidosFil: Myers, Adam D.. University of Wyoming; Estados UnidosFil: Andruchow, Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Brandt, W.N.. State University of Pennsylvania; Estados UnidosFil: Ferrero, Gabriel A.. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Gallagher, S.C.. The University Of Western Ontario; CanadáFil: Green, Richard. University of Arizona; Estados UnidosFil: Lira, Paulina. Universidad de Chile.; ChileFil: Plotkin, Richard M.. University of Nevada. Deparment of Physics; Estados UnidosFil: Richards, Gordon T.. Drexel University; Estados UnidosFil: Runnoe, Jessie C.. Vanderbilt University; Estados UnidosFil: Schneider, Donald P.. State University of Pennsylvania; Estados UnidosFil: Shen, Yue. University of Illinois at Urbana; Estados UnidosFil: Strauss, Michael A.. University of Princeton; Estados UnidosFil: Wills, Beverley J.. University of Texas at Austin; Estados Unido

Exploring the blueprint of photoprotection in Mycosporine-like Amino Acids

Microorganisms require protection against the potentially damaging effects of ultraviolet radiation exposure. Photoprotection is, in part, provided by mycosporine-like amino acids (MAAs). Previous reports have proposed that nonradiative decay mediates the impressive photoprotection abilities of MAAs. In this letter, we present the first ultrafast dynamics study of two MAAs, shinorine and porphyra-334. We demonstrate that, in aqueous solution, these MAAs relax along their S1 coordinates toward the S1/S0 conical intersection within a few hundred femtoseconds after photoexcitation and then traverse the conical intersection and vibrationally cool in approximately 1 ps through heat transfer to the solvent. This new insight allows a quintessential component of microbial life to be unraveled and informs the development of molecular photon-to-heat converters for a myriad of applications

Effect of secular trends on age-related trajectories of cardiovascular risk factors: the Whitehall II longitudinal study 1985-2009

BACKGROUND:: Secular trends in cardiovascular risk factors have been described, but few studies have examined simultaneously the effects of both ageing and secular trends within the same cohort. METHODS:: Development of cardiovascular risk factors over the past three decades was analysed using serial measurements from 10 308 participants aged from 35 to 80 years over 25 years of follow-up from five clinical examination phases of the Whitehall II study. Changes of body mass index, waist circumference, blood pressure and total and high-density lipoprotein cholesterol distribution characteristics were analysed with quantile regression models in the 57-61 age group. Age-related trajectories of risk factors were assessed by fitting mixed-effects models with adjustment for year of birth to reveal secular trends. RESULTS:: Average body mass index and waist circumference increased faster with age in women than in men, but the unfavourable secular trend was more marked in men. Distributions showed a fattening of the right tail in each consecutive phase, meaning a stronger increase in higher percentiles. Despite the higher obesity levels in younger birth cohorts, total cholesterol decreased markedly in the 57-61 age group along the entire distribution rather than in higher extremes only. CONCLUSION:: The past three decades brought strong and heterogeneous changes in cardiovascular risk factor distributions. Secular trends appear to modify age-related trajectories of cardiovascular risk factors, which may be a source of bias in longitudinal analyses

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™).

BACKGROUND: The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for nanosafety screening. However, conflicting outcomes are often observed when in vitro and in vivo study results are compared, suggesting more physiologically representative in vitro models are required to minimise reliance on animal testing. METHOD: BASF Levasil® silica nanoparticles (16 and 85 nm) were used to adapt the 3D reconstructed skin micronucleus (RSMN) assay for nanomaterials administered topically or into the growth medium. 3D dose-responses were compared to a 2D micronucleus assay using monocultured human B cells (TK6) after standardising dose between 2D / 3D assays by total nanoparticle mass to cell number. Cryogenic vitrification, scanning electron microscopy and dynamic light scattering techniques were applied to characterise in-medium and air-liquid interface exposures. Advanced transmission electron microscopy imaging modes (high angle annular dark field) and X-ray spectrometry were used to define nanoparticle penetration / cellular uptake in the intact 3D models and 2D monocultured cells. RESULTS: For all 2D exposures, significant (p < 0.002) increases in genotoxicity were observed (≥100 μg/mL) alongside cell viability decreases (p < 0.015) at doses ≥200 μg/mL (16 nm-SiO2) and ≥100 μg/mL (85 nm-SiO2). In contrast, 2D-equivalent exposures to the 3D models (≤300 μg/mL) caused no significant DNA damage or impact on cell viability. Further increasing dose to the 3D models led to probable air-liquid interface suffocation. Nanoparticle penetration / cell uptake analysis revealed no exposure to the live cells of the 3D model occurred due to the protective nature of the skin model's 3D cellular microarchitecture (topical exposures) and confounding barrier effects of the collagen cell attachment layer (in-medium exposures). 2D monocultured cells meanwhile showed extensive internalisation of both silica particles causing (geno)toxicity. CONCLUSIONS: The results establish the importance of tissue microarchitecture in defining nanomaterial exposure, and suggest 3D in vitro models could play a role in bridging the gap between in vitro and in vivo outcomes in nanotoxicology. Robust exposure characterisation and uptake assessment methods (as demonstrated) are essential to interpret nano(geno)toxicity studies successfully

Tauopathic Changes in the Striatum of A53T α-Synuclein Mutant Mouse Model of Parkinson's Disease

Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn) A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of tauopathy in striata of the A53T α-Syn mutant mice, suggesting that tauopathy is a common feature of synucleinopathies