Small-Scale Fluctuations in Cosmic X-ray Background : A Power Spectrum Approach

Equations to investigate fluctuations in cosmic X-ray background radiation due to point-like sources at high-redshift are formulated in a systematic way. The angular power spectrum of X-ray background fluctuations is investigated from large-scales to small-scales in various cosmological models such as open universe models and models with the cosmological constant, assuming a simple evolution model of the sources. The effect of epoch-dependent bias is demonstrated for small-angle fluctuations. The contribution from shot noise fluctuations is also discussed.Comment: 12 pages, 4 figures, Phys.Rev.D in pres

Data processing for direct marketing through Big Data

Traditional marketing performs promotion through various channels such as news in newspapers, radio, etc., but those promotions are aimed at all people, whether or not interested in the product or service being promoted. This method usually leads to high expenses and a low response rate by potential customers. That is why, nowadays, because there is a very competitive market, mass marketing is not safe, hence specialists are focusing efforts on direct marketing. This method studies the characteristics, needs and also selects a group of customers as a target for the promotion. Direct marketing uses predictive modeling from customer data, with the aim of selecting the most likely to respond to promotions. This research proposes a platform for the processing of data flows for target customer selection processes and the construction of required predictive response models

Autism and Fragile X: Is There a Neurochemical Link?

BACKGROUND:Autism and Fragile X syndrome are intertwined. This study aimed at assessing Serotonin, Glutamate, and Gama Amino Butyric Acid (GABA) in autism and Fragile X syndrome patients and to detect possible neurochemical similarities between the 2 disorders that can be used as metabolic biomarkers.DESIGN AND METHODS: Eighty subjects divided into four groups, two diseased groups (20 male patients with Autism and 20 males with Fragile X syndrome) and two control groups (20 neurotypical male controls and 20 Down syndrome male patients) were included. Estimation of Serotonin, Glutamate and GABA were done using Enzyme linked Immunosorbent Assay (ELISA), Tandem Mass Spectrometry and high-pressure liquid chromatography (HPLC), respectively.RESULTS: Serotonin was, exclusively, significantly low in autistic children. GABA was significantly high in both autistic and Fragile X children only, but not in Down syndrome children. Glutamate was significantly high in children with autism, Fragile X and Down syndrome Children.CONCLUSIONS: Autism and Fragile X syndrome share some neurochemical similarities with regards of high Glutamate and GABA levels while Serotonin was significantly different in the 2 disorders and may be used a unique biomarker for autism

Hybrid cloud computing architecture based on open source technology

The advance of technologies such as distributed computing, Internetand grid computing, have enabled Cloud Computing to become part of a new model of computing and business. Cloud Computing is transforming the traditional ways in which companies use and acquire Information Technology (IT) resources. After an initial boom in Public Cloud, companies begun to mount hybrid Clouds that offer the advantages of Cloud Computing in addition to the privacy of data they consider strategic. A hybrid Cloud solution allows the integration of both systems. Leading companies in cloud solutions have understood this evolution and begun to offer hybrid solutions. Moreover, many of these companies are taking the next step by offering solutions based on open source standards that allow a high degree of interoperability and portability

Synthesis, physicochemical characterization, toxicity and efficacy of a PEG conjugate and a hybrid PEG conjugate nanoparticle formulation of the antibiotic moxifloxacin

Antibiotic resistance is increasing at such an alarming rate that it is now one of the greatest global health challenges. Undesirable toxic side-effects of the drugs lead to high rates of non-completion of treatment regimens which in turn leads to the development of drug resistance. We report on the development of delivery systems that enable antibiotics to be toxic against bacterial cells while sparing human cells. The broad-spectrum fluoroquinolone antibiotic moxifloxacin (Mox) was successfully conjugated to poly(ethylene glycol) (PEG) which was further encapsulated into the hydrophobic poly(3- caprolactone) (PCL) nanoparticles (NPs) with high efficiency, average particle size of 241.8 4 nm and negative zeta potential. Toxicity against erythrocytes and MDBK cell lines and drug release in human plasma were evaluated. Hemocompatibility and reduced cytotoxicity of the PEG–Mox and PCL(PEG– Mox) NPs were demonstrated in comparison to free Mox. Antimicrobial activity was assessed against drug sensitive and resistant: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The antibacterial activity of Mox was largely maintained after conjugation. Our data shows that the toxicity of Mox can be effectively attenuated while, in the case of PEG–Mox, retaining significant antibacterial activity. At the conditions employed in this study for antimicrobial activity the encapsulated conjugate (PCL(PEG–Mox) NPs) did not demonstrate, conclusively, significant antibacterial activity. These systems do, however, hold promise if further developed for improved treatment of bacterial infections.The National Research Foundation of South Africa and the Ministry of Higher Education and Scientific Research, Egypt.http://pubs.rsc.org/en/journals/journalissues/raam2021Chemistr

Dark matter and structure formation a review

This paper provides a review of the variants of dark matter which are thought to be fundamental components of the universe and their role in origin and evolution of structures and some new original results concerning improvements to the spherical collapse model. In particular, I show how the spherical collapse model is modified when we take into account dynamical friction and tidal torques

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Characterization and mitigation of gene expression burden in mammalian cells

Despite recent advances in circuit engineering, the design of genetic networks in mammalian cells is still painstakingly slow and fraught with inexplicable failures. Here, we demonstrate that transiently expressed genes in mammalian cells compete for limited transcriptional and translational resources. This competition results in the coupling of otherwise independent exogenous and endogenous genes, creating a divergence between intended and actual function. Guided by a resource-aware mathematical model, we identify and engineer natural and synthetic miRNA-based incoherent feedforward loop (iFFL) circuits that mitigate gene expression burden. The implementation of these circuits features the use of endogenous miRNAs as elementary components of the engineered iFFL device, a versatile hybrid design that allows burden mitigation to be achieved across different cell-lines with minimal resource requirements. This study establishes the foundations for context-aware prediction and improvement of in vivo synthetic circuit performance, paving the way towards more rational synthetic construct design in mammalian cells

Ligand-induced sequestering of branchpoint sequence allows conditional control of splicing

<p>Abstract</p> <p>Background</p> <p>Despite tremendous progress in understanding the mechanisms of constitutive and alternative splicing, an important and widespread step along the gene expression pathway, our ability to deliberately regulate gene expression at this step remains rudimentary. The present study was performed to investigate whether a theophylline-dependent "splice switch" that sequesters the branchpoint sequence (BPS) within RNA-theophylline complex can regulate alternative splicing.</p> <p>Results</p> <p>We constructed a series of pre-mRNAs in which the BPS was inserted within theophylline aptamer. We show that theophylline-induced sequestering of BPS inhibits pre-mRNA splicing both in vitro and in vivo in a dose-dependent manner. Several lines of evidence suggest that theophylline-dependent inhibition of splicing is highly specific, and thermodynamic stability of RNA-theophylline complex as well as the location of BPS within this complex affects the efficiency of splicing inhibition. Finally, we have constructed an alternative splicing model pre-mRNA substrate in which theophylline caused exon skipping both in vitro and in vivo, suggesting that a small molecule-RNA interaction can modulate alternative splicing.</p> <p>Conclusion</p> <p>These findings provide the ability to control splicing pattern at will and should have important implications for basic, biotechnological, and biomedical research.</p

Staphylococcus aureus Protein A Binds to Osteoblasts and Triggers Signals That Weaken Bone in Osteomyelitis

Osteomyelitis is a debilitating infectious disease of the bone. It is predominantly caused by S. aureus and is associated with significant morbidity and mortality. It is characterised by weakened bones associated with progressive bone loss. Currently the mechanism through which either bone loss or bone destruction occurs in osteomyelitis patients is poorly understood. We describe here for the first time that the major virulence factor of S. aureus, protein A (SpA) binds directly to osteoblasts. This interaction prevents proliferation, induces apoptosis and inhibits mineralisation of cultured osteoblasts. Infected osteoblasts also increase the expression of RANKL, a key protein involved in initiating bone resorption. None of these effects was seen in a mutant of S. aureus lacking SpA. Complementing the SpA-defective mutant with a plasmid expressing spa or using purified protein A resulted in attachment to osteoblasts, inhibited proliferation and induced apoptosis to a similar extent as wildtype S. aureus. These events demonstrate mechanisms through which loss of bone formation and bone weakening may occur in osteomyelitis patients. This new information may pave the way for the development of new and improved therapeutic agents to treat this disease