How important is public procurement to the public sector? Many contracting bodies incur more expenditure each year on externally provided works, services and supplies than they do on their own workforce, but focus typicall...

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Members of the #TotalShutdownAlex movement said they wouldn’t allow City of Joburg to relocate families Stjwetla informal settlement the majority of them are not South Africans.

"Realty Expo Korea 2018 to Unveil in Sept. This Year   Organized by Korea’s No.1 Business News Provider Korea Economic Daily FIABCI KOREA to Sponsor Jointly... Interest of 67 Member Countries Heightened REK 2018 Organizers Start Taking Applications... Foreign Exhibitors to Get Additional Discounts   Realty Expo Korea (REK), the global festival for real estate professionals in the Age of the Fourth Industrial Revolution, will be with you for three days between September 19th and 2...

Reopening Virginia Phase 1: Haircuts? Yes. Dining inside? No. North Carolina says Outer Banks renters are due refunds. Many find red tape instead. Norfolk students won’t be graded for work done from home during pandemic Virginia beaches could...

Check and lubricate all chains and sprockets, grease all the necessary points. Then later check and grease all the bearings, writes Denis Bbosa

[Dalsan Radio] Security officers have arrested a man linked with the hand grenade attack in which a police officer was killed.

“Today we live in a water-stressed world. It’s not just Africa and India that are suffering from a shortage of water – it is all over the world.”

“Wow, your shirt is really see-through. Are you wearing matching underwear?” the man says lewdly.It’s a virtual reality simulation – but it’s enough to shock 23-year-old Elizabeth Lee into silence as the scene plays out on her headset.The VR technology is part of the Girl, Talk project which is aimed at helping women fight back against harassment in Singapore.“I would think that I would respond in a more confrontational way,” Lee admits. “It felt very physically close … it was just really…

Hong Kong doctors have performed Asia’s first heart transplant using a new technology invented in the United States that keeps the organ warm, beating and supplied with blood during the transfer, in a medical breakthrough that will enable more life-saving operations across borders.Dr Timmy Au Wing-kuk – chief of Queen Mary Hospital’s cardiothoracic surgery department, which carried out the medical procedure – hailed the Organ Care System as a success story that could not only allow up to five…

Vidya Balan, in a recent interview, shed light on the many realisations she has been having during the lockdown

The poor and middle class are struggling to find affordable housing across the region, but there are some basic steps cities can take to improve the situation.

NEW DELHI: Builders are scrambling to acquire cheap land and technology for low-cost housing after the government and central bank announced incentives for affordable housing, including cheaper loans to developers and buyers. Real estate companies including Tata Housing, ATS Infrastructure, Bhartiya Group and Anantraj Industries are busy sewing up land deals for projects in the Rs 5-20 lakh home segment. There is unlimited demand for homes in this segment, say experts. “There is a large market for such homes but a big supply constraint as well,” said Shailesh Pathak, executive director of the Bhartiya Group, which is planning to build 10,000 low-cost homes over the next two-three years on a […]

The Central Government has approved around 93 percent of the total planned housing units under the Pradhan Mantri Awas Yojana-Urban (PMAY-U). By far, as many as 1.03 crore housing units have been sanctioned across the country under the said scheme. To provide affordable pucca houses to the homeless population of the country, the Central Government has approved over 1 crore houses in urban parts of the country under the Pradhan Mantri Awas Yojana – Urban (PMAY-U). Against the humongous target of 1.2 crore units, the Government has sanctioned nearly 1.03 crore units across the States and Union Territories (UTs). Of the approved units, approximately 61 lakh units are under-construction and nearly […]

radeep Sharma Tribune News Service Chandigarh, January 23 The group-housing societies, residential colonies of employers and commercial-cum-residential complexes of developers will be supplied power on single-point (bulk supply) system by the electricity department from April 1. While the electricity bills for February/March would be issued as per the existing practice, the bills from April onwards would be issued as per the single-point metering system, according to an order issued by the Chief General Manager (Commercial), Uttar Haryana Bijli Vitran Nigam (UHBVN). The new system would be implemented in housing colonies having 20 or more houses. The order said on the basis of the reading of April 1, the bills of […]

The Chandigarh Housing Board (CHB) has terminated its housing scheme, which was announced last year, amid poor response. Applicants who were picked on the basis of a demand survey will get their paid amounts refunded while a new scheme is framed. The housing scheme in Chandigarh, which would have offered homes in Sector 53, has reportedly been scrapped by the housing board, CHB. Officials have been asked by the government to frame a new, which would be more affordable. The scheme was criticised for being so expensive. For 492 flats, Chandigarh Housing Scheme received only 178 applications despite the board reducing the prices of the flats twice and also extending the […]

Due to the global COVID-19 pandemic, engineers and scientists are finding themselves suddenly working from home or other remote locations. We’d like to help you continue to use MATLAB and Simulink productively. We hope this brief collection of resources will help you access MATLAB, collaborate and connect with others, and... read more >>

One day after saying that the White House COVID-19 task force would be winding down, President Donald Trump said Wednesday it would continue indefinitely but focus more on rebooting the economy.

Tata Value Homes Limited (TVHL), a 100% subsidiary of Tata Housing Development Company Limited, today strengthened its presence in South India by developing Spanish themed residential township at Sriperumbudur, near Chennai. The company plans to Invest around Rs 300 crore in setting up this township. Inspired by Spanish living, Santorini is designed by architects F+A. The township is spread across lush greenery at Sriperumbudur, one of the fastest growing corridors in Chennai. Speaking on the project Brotin Banerjee, MD & CEO, Tata Housing Development Co. Ltd., said, with rapid urbanisation and influx of global lifestyle trends more and more affluent home buyers are looking for homes to reflect the financial […]

NEW DELHI: Realty firm Ambience today said it will invest about Rs 1,950 crore over the next four years to develop two luxury housing projects in Gurgaon and Noida. The Delhi-based company will develop over 1,030 apartments in these two projects launched today. Ambience has presence in Delhi and Gurgaon property markets. It is developing a 150-acre project ‘Ambience Island’ in Gurgaon that comprises premium homes, ‘Leela Ambience’ hotel with over 400 keys and a huge shopping mall. In Delhi, it has a ‘Kempinski Ambience’ hotel comprising 480 keys and a shopping mall at Vasant Kunj. “We are coming up two new projects in Noida and Gurgaon. We are entering […]

SAMRH71 Using ICC and ECC for Efficient Memory Scrubbing

AN3401 - Using Microchip I2C EERAMs with MPLAB X and MPLAB Code Configurator

AN3380 - Driving a Metronome Using a PIC Microcontroller

AN3453 - Sensored 3-Phase BLDC Motor Control Using Sinusoidal Drive

AN3433 - Touchpad With Built-In Surface Gesture Recognition Using Peripheral Touch Controller

NEW DELHI: Low-cost housing, which found several mentions in BJP’s 2014 election manifesto, is likely to get infrastructure status, making it easier for real-estate developers to get finance from banks and for longer tenures, and eventually increasing the supply of houses. While developers are in favour of an infrastructure tag to the housing sector as a whole, the government is likely to grant it only to the low-cost segment, said a senior government official, who did not wish to be named. According to government definition, low-cost houses are those with an area of up to 40 sq metres. BJP’s manifesto talks about rolling out a massive low-cost housing programme to […]

Join Michael De Podesta as he explains how he made the world’s most precise thermometer – and demonstrates its principle live on stage

This Pi Day, try calculating everyone’s favourite mathematical constant using balls and a cardboard tube, thanks to a mathematical trick involving the balls’ masses

Climate change is leading to lower numbers of marine life towards the equator – including mammals, birds, fish and plankton – while populations nearer the poles increase

Title: Selenium Helped Cells 'Reboot' After Exposure to Cancer-Causing Chemicals
Category: Health News
Created: 4/27/2010 2:10:00 PM
Last Editorial Review: 4/28/2010 12:00:00 AM

Title: Many Ivy League Students Admit Using ADHD Drugs for Better Grades: Study
Category: Health News
Created: 5/2/2014 12:36:00 PM
Last Editorial Review: 5/2/2014 12:00:00 AM

Title: COVID-19 May Be Causing Kawasaki Disease Heart Condition in Kids
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

A large-scale update of the file names used for articles available via the PMC FTP service for bulk download was undertaken in early January 2017. The new file naming convention is PMCID-based (e.g., PMC4855680.tar.gz) rather than being built from article citation data (i.e., journal abbreviation_pub date_volume_issue_page). This update was made following user reports that the previous naming convention was resulting in missing contents in cases where citation data was duplicated across multiple articles. The new convention will ensure that file names are unique and that the corpus available via the FTP service is complete.

Title: Using Pot to Help You Sleep? It Could Backfire
Category: Health News
Created: 4/14/2020 12:00:00 AM
Last Editorial Review: 4/15/2020 12:00:00 AM

This article describes the development of medical competencies for oral medicine specialty training in the UK and Ireland by a collaborative working group using a modified Delphi technique. The current specialty training curriculum for oral medicine (OM) in the UK was developed by a working group including members of the British Society for Oral Medicine (BSOM) and members of the Specialty Advisory Committee for Additional Dental Specialties (SACADS) and adopted by the UK General Dental Council (GDC) in 2010. When the curriculum was developed, the entry requirements for specialty training in OM included undergraduate degrees in both dentistry and medicine. At the time of adoption, the requirement for a medical degree was removed. Medical competencies were assumed to have been delivered in medical undergraduate and postgraduate training. Accordingly, there was a need to define the medical competencies for OM specialty training to benefit trainees, trainers, and assessors. In 2018, a group comprising specialty trainers, recent former specialty trainees, and current specialty trainees in OM held face-to-face meetings in addition to email discussions and developed an updated curriculum document to better reflect the medical competencies required in specialty training. A collaborative modified Delphi approach was used to evaluate medical foundation competencies and to include only those that were considered relevant to OM specialty training. A list of relevant and achievable medical competencies was determined that has been approved by SACADS and will be incorporated into a revised OM curriculum from the UK GDC. The newly agreed-upon document for medical competencies in OM specialty training will serve as a reference for trainees, trainers, and assessors and reflects a successful use of a modified Delphi approach.

The aims of this study were to qualitatively assess dental public health (DPH) residents’ perspectives on teaching methods for DPH competencies and to develop and implement a case-based simulation to address those competencies, constructed on the basis of the qualitative assessment. Focus group discussions were conducted with 18 DPH residents enrolled in two university-based DPH programs. Topic areas discussed in the two focus groups were perceived value of DPH competencies, ways to acquire new DPH skills/abilities, and additional skills/abilities needed by DPH residents. The focus groups’ responses showed that the residents felt competent in the analytical thinking competencies such as research methodology and critiquing literature. They emphasized the importance of learning leadership skills and reported feeling somewhat uncertain about their mastery of the policy and advocacy and system evaluation competencies. Of the two distinct categories of DPH skills and competencies— analytical/critical thinking and practical competencies—these residents reported that a greater proportion of time needed to be devoted to integrating the practical competencies into their education. Based on the residents’ feedback, the authors developed a structured seminar series taking a case-based approach to simulate real-world DPH problems, using real and semi-hypothetical planning projects to meet the residents’ perceived needs and covering gaps between didactic learning and practice.

ABSTRACT

The luminous marine Gram-negative bacterium Vibrio (Aliivibrio) fischeri is the natural light organ symbiont of several squid species, including the Hawaiian bobtail squid, Euprymna scolopes, and the Japanese bobtail squid, Euprymna morsei. Work with E. scolopes has shown how the bacteria establish their niche in the light organ of the newly hatched host. Two types of V. fischeri strains have been distinguished based upon their behavior in cocolonization competition assays in juvenile E. scolopes, i.e., (i) niche-sharing or (ii) niche-dominant behavior. This study aimed to determine whether these behaviors are observed with other V. fischeri strains or whether they are specific to those isolated from E. scolopes light organs. Cocolonization competition assays between V. fischeri strains isolated from the congeneric squid E. morsei or from other marine animals revealed the same sharing or dominant behaviors. In addition, whole-genome sequencing of these strains showed that the dominant behavior is polyphyletic and not associated with the presence or absence of a single gene or genes. Comparative genomics of 44 squid light organ isolates from around the globe led to the identification of symbiosis-specific candidates in the genomes of these strains. Colonization assays using genetic derivatives with deletions of these candidates established the importance of two such genes in colonization. This study has allowed us to expand the concept of distinct colonization behaviors to strains isolated from a number of squid and fish hosts.

IMPORTANCE There is an increasing recognition of the importance of strain differences in the ecology of a symbiotic bacterial species and, in particular, how these differences underlie crucial interactions with their host. Nevertheless, little is known about the genetic bases for these differences, how they manifest themselves in specific behaviors, and their distribution among symbionts of different host species. In this study, we sequenced the genomes of Vibrio fischeri isolated from the tissues of squids and fishes and applied comparative genomics approaches to look for patterns between symbiont lineages and host colonization behavior. In addition, we identified the only two genes that were exclusively present in all V. fischeri strains isolated from the light organs of sepiolid squid species. Mutational studies of these genes indicated that they both played a role in colonization of the squid light organ, emphasizing the value of applying a comparative genomics approach in the study of symbioses.

ABSTRACT

Clostridioides difficile is an important nosocomial pathogen that causes approximately 500,000 cases of C. difficile infection (CDI) and 29,000 deaths annually in the United States. Antibiotic use is a major risk factor for CDI because broad-spectrum antimicrobials disrupt the indigenous gut microbiota, decreasing colonization resistance against C. difficile. Vancomycin is the standard of care for the treatment of CDI, likely contributing to the high recurrence rates due to the continued disruption of the gut microbiota. Thus, there is an urgent need for the development of novel therapeutics that can prevent and treat CDI and precisely target the pathogen without disrupting the gut microbiota. Here, we show that the endogenous type I-B CRISPR-Cas system in C. difficile can be repurposed as an antimicrobial agent by the expression of a self-targeting CRISPR that redirects endogenous CRISPR-Cas3 activity against the bacterial chromosome. We demonstrate that a recombinant bacteriophage expressing bacterial genome-targeting CRISPR RNAs is significantly more effective than its wild-type parent bacteriophage at killing C. difficile both in vitro and in a mouse model of CDI. We also report that conversion of the phage from temperate to obligately lytic is feasible and contributes to the therapeutic suitability of intrinsic C. difficile phages, despite the specific challenges encountered in the disease phenotypes of phage-treated animals. Our findings suggest that phage-delivered programmable CRISPR therapeutics have the potential to leverage the specificity and apparent safety of phage therapies and improve their potency and reliability for eradicating specific bacterial species within complex communities, offering a novel mechanism to treat pathogenic and/or multidrug-resistant organisms.

IMPORTANCE Clostridioides difficile is a bacterial pathogen responsible for significant morbidity and mortality across the globe. Current therapies based on broad-spectrum antibiotics have some clinical success, but approximately 30% of patients have relapses, presumably due to the continued perturbation to the gut microbiota. Here, we show that phages can be engineered with type I CRISPR-Cas systems and modified to reduce lysogeny and to enable the specific and efficient targeting and killing of C. difficile in vitro and in vivo. Additional genetic engineering to disrupt phage modulation of toxin expression by lysogeny or other mechanisms would be required to advance a CRISPR-enhanced phage antimicrobial for C. difficile toward clinical application. These findings provide evidence into how phage can be combined with CRISPR-based targeting to develop novel therapies and modulate microbiomes associated with health and disease.

ABSTRACT

Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris.

IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

Congenital myopathies are clinically and genetically heterogeneous, resulting from mutations in at least 30 different genes.¹ The classical presentation is neonatal hypotonia and nonprogressive weakness with normal creatine phosphokinase, although there is a broad range in terms of age at onset and clinical presentation. Historically, congenital myopathies have been defined and diagnosed based on muscle biopsy. However, with advances in genomics, genetics have taken primacy in the diagnostic pathway.²

The World Health Organization (WHO) has listed moxifloxacin and linezolid among the preferred "group A" drugs in the treatment of multidrug-resistant (MDR)-tuberculosis (TB) [1]. Therapeutic drug monitoring (TDM) could potentially optimise MDR-TB therapy, since moxifloxacin and linezolid show large pharmacokinetic variability [1–4]. TDM of moxifloxacin focuses on identifying patients with low drug exposure who are at risk of treatment failure and acquired fluoroquinolone resistance [5, 6]. Alternatively, TDM of linezolid strives to reduce toxicity while ensuring an adequate drug exposure because of its narrow therapeutic index [1, 3, 7].

Many complex human traits exhibit differences between sexes. While numerous factors likely contribute to this phenomenon, growing evidence from genome-wide studies suggest a partial explanation: that males and females from the same population possess differing genetic architectures. Despite this, mapping gene-by-sex (GxS) interactions remains a challenge likely because the magnitude of such an interaction is typically and exceedingly small; traditional genome-wide association techniques may be underpowered to detect such events, due partly to the burden of multiple test correction. Here, we developed a local Bayesian regression (LBR) method to estimate sex-specific SNP marker effects after fully accounting for local linkage-disequilibrium (LD) patterns. This enabled us to infer sex-specific effects and GxS interactions either at the single SNP level, or by aggregating the effects of multiple SNPs to make inferences at the level of small LD-based regions. Using simulations in which there was imperfect LD between SNPs and causal variants, we showed that aggregating sex-specific marker effects with LBR provides improved power and resolution to detect GxS interactions over traditional single-SNP-based tests. When using LBR to analyze traits from the UK Biobank, we detected a relatively large GxS interaction impacting bone mineral density within ABO, and replicated many previously detected large-magnitude GxS interactions impacting waist-to-hip ratio. We also discovered many new GxS interactions impacting such traits as height and body mass index (BMI) within regions of the genome where both male- and female-specific effects explain a small proportion of phenotypic variance (R² < 1 x 10^–4), but are enriched in known expression quantitative trait loci.

Age-at-onset is one of the critical traits in cohort studies of age-related diseases. Large-scale genome-wide association studies (GWAS) of age-at-onset traits can provide more insights into genetic effects on disease progression and transitions between stages. Moreover, proportional hazards (or Cox) regression models can achieve higher statistical power in a cohort study than a case-control trait using logistic regression. Although mixed-effects models are widely used in GWAS to correct for sample dependence, application of Cox mixed-effects models (CMEMs) to large-scale GWAS is so far hindered by intractable computational cost. In this work, we propose COXMEG, an efficient R package for conducting GWAS of age-at-onset traits using CMEMs. COXMEG introduces fast estimation algorithms for general sparse relatedness matrices including, but not limited to, block-diagonal pedigree-based matrices. COXMEG also introduces a fast and powerful score test for dense relatedness matrices, accounting for both population stratification and family structure. In addition, COXMEG generalizes existing algorithms to support positive semidefinite relatedness matrices, which are common in twin and family studies. Our simulation studies suggest that COXMEG, depending on the structure of the relatedness matrix, is orders of magnitude computationally more efficient than coxme and coxph with frailty for GWAS. We found that using sparse approximation of relatedness matrices yielded highly comparable results in controlling false-positive rate and retaining statistical power for an ethnically homogeneous family-based sample. By applying COXMEG to a study of Alzheimer’s disease (AD) with a Late-Onset Alzheimer’s Disease Family Study from the National Institute on Aging sample comprising 3456 non-Hispanic whites and 287 African Americans, we identified the APOE 4 variant with strong statistical power (P = 1e–101), far more significant than that reported in a previous study using a transformed variable and a marginal Cox model. Furthermore, we identified novel SNP rs36051450 (P = 2e–9) near GRAMD1B, the minor allele of which significantly reduced the hazards of AD in both genders. These results demonstrated that COXMEG greatly facilitates the application of CMEMs in GWAS of age-at-onset traits.

Toward the goal of increasing the throughput of high-resolution mass characterization of intact antibodies, we developed a RapidFire–mass spectrometry (MS) assay using electrospray ionization. We achieved unprecedented screening throughput as fast as 15 s/sample, which is an order of magnitude improvement over conventional liquid chromatography (LC)-MS approaches. The screening enabled...

Cowen et al. (1) leverage modern gains in data science to describe impressive cross-cultural similarities in the perception of musical affect and do so in unprecedented detail. Their approach is innovative and fundamentally empirical. As such, it should have important applications for prediction in the field of affective computing, which...

Christopher T. Richards and Enrico A. Eberhard

Muscle force-length dynamics are governed by intrinsic contractile properties, motor stimulation and mechanical load. Although intrinsic properties are well-characterised, physiologists lack in vitro instrumentation accounting for combined effects of limb inertia, musculoskeletal architecture and contractile dynamics. We introduce in vitro virtual-reality (in vitro-VR) which enables in vitro muscle tissue to drive a musculoskeletal jumping simulation. In hardware, muscle force from a frog plantaris was transmitted to a software model where joint torques, inertia and ground reaction forces were computed to advance the simulation at 1 kHz. To close the loop, simulated muscle strain was returned to update in vitro length. We manipulated 1) stimulation timing and, 2) the virtual muscle's anatomical origin. This influenced interactions among muscular, inertial, gravitational and contact forces dictating limb kinematics and jump performance. We propose that in vitro-VR can be used to illustrate how neuromuscular control and musculoskeletal anatomy influence muscle dynamics and biomechanical performance.