Rapid single- and multiple-scattering EXAFS Debye-Waller factor calculations on active sites of metalloproteins

This paper describes recent results using our approach to calculating self-consistently single (SS) and multiple-scattering (MS) Debye- Waller factors (DWF) on active sites of metalloproteins. The calculation of MS DWF, together with the Feff7 program allows us to simulate ab-initio EXAFS spectra for a given temperature systems with no adjustable parameters. In our latest report (Dimakis N., and Bunker G., 1998) we calculate, using density functional and semiempirical approaches, the SS and MS DWF for small molecules and compared them to Raman, infrared and EXAFS spectra. In this report calculation of DWFs is done for tetrahedral Zn imidazole, a complex containing thirty two atoms that is similar in certain respects to active sites of many metalloproteins. Ab-initio calculation, although it is a more accurate and reliable scheme, it is not at present practical on desktop computers; computation times are weeks. Therefore as an alternative we have tried the semiempirical MNDO Hamiltonian, which is at least three orders of magnitude faster than ab-initio, and can be expected to be of reasonable accuracy because it is parameterized for organic compounds. Our approaches take advantage of commercially available molecular orbital programs. We have written additional programs which, using normal mode calculations, calculate the MS paths, and transparently interface with Fef-f\u27/to produce the EXAFS spectra. Results are in very good agreement with experimental data tested

NiO-Nanofillers Embedded in Graphite/PVA-Polymer Matrix for efficient Electromagnetic Radiation Shielding

In this study, we report on the preparation of NiO/graphite sheets nanofillers in PVA-polymer matrix using a simple cost-effective hydrothermal process for EM shielding effectiveness applications. The careful optimization of the growth conditions and NiO/G/PVA relative ratios have resulted in NiO nanoparticles formation with homogeneous density. In this nanocomposite, the NiO nanoparticles and graphite sheets were incorporated into a polymer to enhance the electromagnetic shielding effectiveness. The morphological, structural, and chemical analysis have been conducted by SEM, EDX and XRD techniques. EDX and XRD analysis confirmed the exact chemical composition with high purity. SEM images showed the best morphology with homogenous NiO-nanoparticles distribution on graphite sheets for 15 wt% NiO relative ratio NiO/G/PVA nanocomposite. The nanocomposite was tested in different environments and shielding chambers that contained relatively high-level exposure to electromagnetic radiation. The shielding effectiveness (SE) measurements of NiO/G/PVA showed a significant increase of shielding effectiveness of about 17 dB compared to the commercial shielding paint. This can be ascribed to the homogenous distribution of NiO-NPs over the entire graphite sheets and the strong interaction of the incident electromagnetic radiation with the magnetic and electric dipoles in the nanocomposite. These finding is promising for enhanced flexible and cost-effective EMI shielding applications

PathogenMip Assay: A Multiplex Pathogen Detection Assay

The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer progression. Probe construction was based on a novel, cost-effective, ligase-based protocol. The assay was validated by performing pyrosequencing and Microarray chip detection in parallel experiments. HPV plasmids were used to validate sensitivity and selectivity of the assay. In addition, 20 genomic DNA extracts from primary tumors were genotyped with the PathogenMip Assay results and were in 100% agreement with conventional sequencing using an L1-based HPV genotyping protocol. The PathogenMip Assay is a widely accessible protocol for producing and using highly discriminating probes, with experimentally validated results in pathogen genotyping, which could potentially be applied to the detection and characterization of any microbe

Fine Mapping of Genetic Variants in BIN1, CLU, CR1 and PICALM for Association with Cerebrospinal Fluid Biomarkers for Alzheimer's Disease

Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ42) and tau phosphorylated at threonine 181 (ptau181), have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ42 or ptau181 levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ42 or ptau181

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Radiations and male fertility

During recent years, an increasing percentage of male infertility has to be attributed to an array of environmental, health and lifestyle factors. Male infertility is likely to be affected by the intense exposure to heat and extreme exposure to pesticides, radiations, radioactivity and other hazardous substances. We are surrounded by several types of ionizing and non-ionizing radiations and both have recognized causative effects on spermatogenesis. Since it is impossible to cover all types of radiation sources and their biological effects under a single title, this review is focusing on radiation deriving from cell phones, laptops, Wi-Fi and microwave ovens, as these are the most common sources of non-ionizing radiations, which may contribute to the cause of infertility by exploring the effect of exposure to radiofrequency radiations on the male fertility pattern. From currently available studies it is clear that radiofrequency electromagnetic fields (RF-EMF) have deleterious effects on sperm parameters (like sperm count, morphology, motility), affects the role of kinases in cellular metabolism and the endocrine system, and produces genotoxicity, genomic instability and oxidative stress. This is followed with protective measures for these radiations and future recommendations. The study concludes that the RF-EMF may induce oxidative stress with an increased level of reactive oxygen species, which may lead to infertility. This has been concluded based on available evidences from in vitro and in vivo studies suggesting that RF-EMF exposure negatively affects sperm quality

Ac electrical properties of polystyrene/ferroelectric barium stannate titanate Ba(Ti_{0.9}Sn_{0.1})O₃ ceramic composite

A composite of polystyrene (PS)/ferroelectric barium stannate titanate (BST) with different BST concentration was prepared. The dielectric properties were measured using HP low impedance frequency analyzer. It is found that samples behaved as an RC network. Composites become more capacitive than resistive with increasing frequency while resistance decreases with increasing BST ceramic concentration. Temperature effects were monitored throughout the annealing process. It is found that the capacity and the ac conductivity increased after annealing while the bulk resistance decreased. Our results suggest that, the obtained material is expected to be a promising candidate for electronic ceramics. The study provides a better understanding of the relationship among these parameters

Empirical Evaluation of Noise Influence on Supervised Machine Learning Algorithms Using Intrusion Detection Datasets

Optimizing the detection of intrusions is becoming more crucial due to the continuously rising rates and ferocity of cyber threats and attacks. One of the popular methods to optimize the accuracy of intrusion detection systems (IDSs) is by employing machine learning (ML) techniques. However, there are many factors that affect the accuracy of the ML-based IDSs. One of these factors is noise, which can be in the form of mislabelled instances, outliers, or extreme values. Determining the extent effect of noise helps to design and build more robust ML-based IDSs. This paper empirically examines the extent effect of noise on the accuracy of the ML-based IDSs by conducting a wide set of different experiments. The used ML algorithms are decision tree (DT), random forest (RF), support vector machine (SVM), artificial neural networks (ANNs), and Naïve Bayes (NB). In addition, the experiments are conducted on two widely used intrusion datasets, which are NSL-KDD and UNSW-NB15. Moreover, the paper also investigates the use of these ML algorithms as base classifiers with two ensembles of classifiers learning methods, which are bagging and boosting. The detailed results and findings are illustrated and discussed in this paper

Evaluation of Half-Cell Potential Measurements for Reinforced Concrete Corrosion

The evaluation of half-cell potential measurements in reinforced concrete (RC) members can be a key issue for civil engineers. The primary reason for this is that the interpretation of half-cell potential measurements based on the available standards provides information related only to the possibility of corrosion in concrete, but it does not provide a clear perception of the influence of corrosion on the capacity of the RC members. The objective of this study is two-fold: (1) to explore the influence of corrosion level on the flexural capacity of RC members; and (2) to provide engineers with a better understanding of the correlation between half-cell potential measurements and flexural capacity of RC members. To establish this, twelve RC beams were cast and then exposed to accelerated corrosion utilizing an impressed current. After that, half-cell potential tests were performed on the entire surface of the beams. Next, a four-point loading test was performed on the beams to determine their flexural behavior. The analysis of measurements showed that there is a high positive correlation between the half-cell potential measurements and the flexural capacity of the tested beams which demonstrates the potential of half-cell measurements to predict the capacity degradation level of the RC beams due to corrosion