Characterization of an isolated lactase enzyme produced by Bacillus licheniformis ALSZ2 as a potential pharmaceutical supplement for lactose intolerance

IntroductionLactose intolerance is a widespread problem that affects people of many different races all over the world. The following pharmacological supplements can improve the lives of those who suffer from this issue.MethodsThis work focused on lactase producer isolation and statistical design (Plackett–Burman, and BOX–Behnken) to maximize the effectiveness of environmental factors. A lactase-producing bacterium was chosen from a discovery of 100 strains in soil that had previously been polluted with dairy products. Plackett-Burman investigated fifteen variables.ResultsThe most critical variables that lead to increased lactase synthesis are glucose, peptone, and magnesium sulfate (MgSO4). The ideal process conditions for the creation of lactase yield among the stated variables were then determined using a BOX-Benken design. To establish a polynomial quadratic relationship between the three variables and lactase activity, the Box–Behnken design level was used. The EXCEL-solver nonlinear optimization technique was used to predict the best form for lactase production. The ideal temperature and pH levels have been determined, both before and after the lactase purification process, to achieve the highest performance of isolated lactase.ConclusionAccording to this study, Bacillus licheniformis is a perfect supply of the lactase enzyme (β -Galactosidase), It can be used as a product to assist people who have health issues due to lactose intolerance

Risk Analysis of Prostate Cancer in PRACTICAL Consortium--Response.

D.F. Easton was recipient of the CR-UK grant C1287/A10118. R.A. Eeles was recipient of the CR-UK grant C5047/A10692.This is the author accepted manuscript. The final version is available from the American Association for Cancer Research via http://dx.doi.org/10.1158/1055-9965.EPI-15-100

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application

A recurrent truncating germline mutation in the BRIP1/FANCJ gene and susceptibility to prostate cancer

Although prostate cancer (PrCa) is one of the most common cancers in men in Western countries, little is known about the inherited factors that influence PrCa risk. On the basis of the fact that BRIP1/FANCJ interacts with BRCA1 and functions as a regulator of DNA double-strand break repair pathways, and that germline mutations within the BRIP1/FANCJ gene predispose to breast cancer, we chose this gene as a candidate for mutation screening in familial and young-onset PrCa cases. We identified a truncating mutation, R798X, in the BRIP1/FANCJ gene in 4 out of 2714 UK PrCa cases enriched for familial (2 out of 641; 0.3%) and young-onset cases (2 out of 2073; 0.1%). On screening 2045 controls from the UK population, we found one R798X sequence alteration (0.05%; odds ratio 2.4 (95% CI 0.25–23.4)). In addition, using our data from a genome-wide association study, we analysed 25 SNPs in the genomic region of the BRIP1/FANCJ gene. Two SNPs showed evidence of association with familial and young-onset PrCa (rs6504074; Ptrend=0.04 and rs8076727; Ptrend=0.01). These results suggest that truncating mutations in BRIP1/FANCJ might confer an increased risk of PrCa and common SNPs might also contribute to the alteration of risk, but larger case–control series will be required to confirm or refute this association

Real Time Simulation of Power Grid Disruptions

DOE-OE and DOE-SC workshops (Reference 1-3) identified the key power grid problem that requires insight addressable by the next generation of exascale computing is coupling of real-time data streams (1-2 TB per hour) as the streams are ingested to dynamic models. These models would then identify predicted disruptions in time (2-4 seconds) to trigger the smart grid s self healing functions. This project attempted to establish the feasibility of this approach and defined the scientific issues, and demonstrated example solutions to important smart grid simulation problems. These objectives were accomplished by 1) using the existing frequency recorders on the national grid to establish a representative and scalable real-time data stream; 2) invoking ORNL signature identification algorithms; 3) modeling dynamically a representative region of the Eastern interconnect using an institutional cluster, measuring the scalability and computational benchmarks for a national capability; and 4) constructing a prototype simulation for the system s concept of smart grid deployment. The delivered ORNL enduring capability included: 1) data processing and simulation metrics to design a national capability justifying exascale applications; 2) Software and intellectual property built around the example solutions; 3) demonstrated dynamic models to design few second self-healing

Cybersecurity through Real-Time Distributed Control Systems

Critical infrastructure sites and facilities are becoming increasingly dependent on interconnected physical and cyber-based real-time distributed control systems (RTDCSs). A mounting cybersecurity threat results from the nature of these ubiquitous and sometimes unrestrained communications interconnections. Much work is under way in numerous organizations to characterize the cyber threat, determine means to minimize risk, and develop mitigation strategies to address potential consequences. While it seems natural that a simple application of cyber-protection methods derived from corporate business information technology (IT) domain would lead to an acceptable solution, the reality is that the characteristics of RTDCSs make many of those methods inadequate and unsatisfactory or even harmful. A solution lies in developing a defense-in-depth approach that ranges from protection at communications interconnect levels ultimately to the control system s functional characteristics that are designed to maintain control in the face of malicious intrusion. This paper summarizes the nature of RTDCSs from a cybersecurity perspec tive and discusses issues, vulnerabilities, candidate mitigation approaches, and metrics