Japan is blessed with a growing number of artisan bakeries around the city that can fill that pain de campagne-sized hole in our diets.

TIMERGARA: Equipment has been delivered to set up a coronavirus testing laboratory in Lower Dir district, officials said.“We have received PCR machine and its safety units and a team of the KMU would reach soon to set up Dir Public Health Laboratory at DHQ Hospital Timergara. They would also...

Gourmet takeaway delivered by a butler in a black sedan – Thailand’s super-rich have not forgone luxury during a pandemic which has locked the country down, crushed the economy and left millions unemployed.Thailand is one of the most unequal nations in the world and the chasm between rich and poor is widening as the coronavirus eviscerates jobs, leaving 22 million registering for a government cash handout.Hundreds line up daily for food donations across Bangkok, a grim sign of an economic…

Microchip Solves Interoperability Challenges of Delivering up to 90 Watts of Power Over Ethernet Wiring

ADB has a vacancy for the position of Intern - Solutions Delivery Division, OIST - 2012 in the Office of Information Systems and Technology. The deadline for submitting applications is on 15 September 2019.

The unique challenges of financing and building a climate-resilient port in a tiny Pacific country required ADB to develop and deploy innovative approaches to ensure the project’s design, governance, and monitoring were efficient and effective.

Microchip Delivers 50 Millionth MOST® Technology 50 Mbps Automotive Intelligent Network Interface Controller

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The unique challenges of financing and building a climate-resilient port in a tiny Pacific country required ADB to develop and deploy innovative approaches to ensure the project’s design, governance, and monitoring were efficient and effective.

AN3265 - UPD301A USB Power Delivery Operation

NEW DELHI: Builders in Noida are unable to hand over more than 30,000 completed homes to their buyers, because of a National Green Tribunal order forbidding the Noida Authority from giving completion certificates to projects within a 10-kilometre radius of the Okhla bird sanctuary. Developers in Noida say they have in the past seven months since the tribunal’s order lost close to Rs 1,000 crore as they have been holding on the flats, paying interest on their loans as well as penalty to home buyers. “Everyone is bleeding,” said Vineet Gupta, director of the Ajnara group, which has around 1,500 apartments waiting to be handed over to buyers. Projects of […]

Huemen, HARMAN’s in-house design agency, brings home 25 iF World Design Awards

STAMFORD, CT – September 14, 2016 –HARMAN International Industries, Incorporated (NYSE:HAR), the premier connected technologies company for automotive, consumer and enterprise markets, announced it will showcase additional sensor functionality for the...

Stamford, CT – 12 March, 2020 – HARMAN International, a wholly-owned subsidiary of Samsung Electronics Co. Ltd., focused on connected technologies for automotive, consumer and enterprise markets, and its Huemen design team have received 25 iF Design...

A pizza chain in northern Russia begins to deliver pizza by Russian-made drones. Elly Park reports.

Companies across the globe are focused on delivering voice-enabled products to their customers. However, voice technology is a nascent, complicated one that few companies can develop internally, without any collaboration. Enter, HARMAN Embedded Audio. A...

CES 2020, LAS VEGAS – JANUARY 6, 2020 – Harman International, a wholly-owned subsidiary of Samsung Electronics Co., Ltd. focused on connected technologies for automotive, consumer and enterprise markets, today announced its EV Plus+ Solutions, a new...

Shanghai Auto Show 2019 – SHANGHAI – April 16, 2019 – HARMAN , a wholly-owned subsidiary of Samsung Electronics Co., Ltd., focused on connected technologies for automotive, consumer and enterprise markets, today announced a continued partnership with the...

CES 2020 – LAS VEGAS, Nev. – January 6, 2020 – HARMAN, a wholly-owned subsidiary of Samsung Electronics Co. Ltd., focused on connected technologies for automotive, consumer and enterprise markets, today launched the HARMAN Ignite Marketplace, an...

Priest Don Giuseppe Castelvecchio hasn't been able to conduct services in his San Fiorano church for two months. In the town where restrictions are easing, his sermons delivered from a loud speaker in a car are a welcome relief. Joe Davies reports.

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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.

Multiple births are increasing in frequency related to advanced maternal age and fertility treatments, and they have an increased risk for congenital anomalies compared to singleton births. However, twins have the same congenital anomalies <15% of the time. Thus, having multiple births with discordant anomalies is a growing challenge for neonatologists. Although external anomalies can often be spotted quickly at delivery or sex differences between multiples can rapidly identify those with internal anomalies described on prenatal ultrasound, we present a case of male multiples, who would optimally receive different initial resuscitation strategies on the basis of the presence or absence of an internal anomaly. The similar size of 4 extremely preterm quadruplets raises concern for whether accurate, immediate identification of 1 neonate with a congenital diaphragmatic hernia will be reliable in the delivery room. Clinicians discuss the ethical considerations of an "all for one" approach to this resuscitation.

Human adenoviruses have many attractive features for gene therapy applications. However, the high prevalence of preexisting immunity against these viruses in general populations worldwide has greatly limited their clinical utility. In addition, the most commonly used human adenovirus, human adenovirus subgroup C serotype 5 (HAd5), when systemically administered, triggers systemic inflammation and toxicity, with the liver being the most severely affected organ. Here, we evaluated the utility and safety of a new low-seroprevalence gorilla adenovirus (GAd; GC46) as a gene transfer vector in mice. Biodistribution studies revealed that systemically administered GAd had a selective and robust lung endothelial cell (EC) tropism with minimal vector expression throughout many other organs and tissues. Administration of a high dose of GAd accomplished extensive transgene expression in the lung yet elicited no detectable inflammatory histopathology in this organ. Furthermore, GAd, unlike HAd5, did not exhibit hepatotropism or induce liver inflammatory toxicity in mice, demonstrating the exceptional safety profile of the vector vis-à-vis systemic utility. We further demonstrated that the GAd capsid fiber shared the flexibility of the HAd5 equivalent for permitting genetic modification; GAd with the pan-EC-targeting ligand myeloid cell-binding peptide (MBP) incorporated in the capsid displayed a reduced lung tropism and efficiently retargeted gene expression to vascular beds in other organs.

IMPORTANCE In the aggregate, our mouse studies suggest that GAd is a promising gene therapy vector that utilizes lung ECs as a source of therapeutic payload production and a highly desirable toxicity profile. Further genetic engineering of the GAd capsid holds the promise of in vivo vector tropism modification and targeting.

PURPOSE

Although cesarean delivery is the most common surgical procedure in the United States, postoperative opioid prescribing varies greatly. We hypothesized that patient characteristics, procedural characteristics, or both would be associated with high vs low opioid use after discharge. This information could help individualize prescriptions.

Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II IFNs. To explore PD-1/PD-L1 signaling as a direct target in tumor tissue, we developed a novel immunotherapeutic herpes simplex virus (HSV), OVH-aMPD-1, that expressed a single-chain variable fragment (scFv) against PD-1 (aMPD-1 scFv). The virus was designed to locally deliver aMPD-1 scFv in the TME to achieve enhanced antitumor effects. This virus effectively modified the TME by releasing damage-associated molecular patterns, promoting antigen cross-presentation by dendritic cells, and enhancing the infiltration of activated T cells; these alterations resulted in antitumor T-cell activity that led to reduced tumor burdens in a liver cancer model. Compared with OVH, OVH-aMPD-1 promoted the infiltration of myeloid-derived suppressor cells (MDSC), resulting in significantly higher percentages of CD155⁺ granulocytic-MDSCs (G-MDSC) and monocytic-MDSCs (M-MDSC) in tumors. In combination with TIGIT blockade, this virus enhanced tumor-specific immune responses in mice with implanted subcutaneous tumors or invasive tumors. These findings highlighted that intratumoral immunomodulation with an OV expressing aMPD-1 scFv could be an effective stand-alone strategy to treat cancers or drive maximal efficacy of a combination therapy with other immune checkpoint inhibitors.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, causing progressive decline in lung function leading to premature death. Acute exacerbations in COPD patients are predominantly associated with respiratory viruses. Ribavirin is a generic broad-spectrum antiviral agent that could be used for treatment of viral respiratory infections in COPD. Using the Particle Replication In Nonwetting Templates (PRINT) technology, which produces dry-powder particles of uniform shape and size, two new inhaled formulations of ribavirin (ribavirin-PRINT-CFI and ribavirin-PRINT-IP) were developed for efficient delivery to the lung and to minimize bystander exposure. Ribavirin-PRINT-CFI was well tolerated in healthy participants after single dosing and ribavirin-PRINT-IP was well tolerated in healthy and COPD participants after single and repeat dosing. Ribavirin-PRINT-CFI was replaced with ribavirin-PRINT-IP since the latter formulation was found to have improved physicochemical properties and it had a higher ratio of active drug to excipient per unit dose. Ribavirin concentrations were measured in lung epithelial lining fluid in both healthy and COPD participants and achieved target concentrations. Both formulations were rapidly absorbed with approximately dose proportional pharmacokinetics in plasma. Exposure to bystanders was negligible based on both the plasma and airborne ribavirin concentrations with the ribavirin-PRINT-IP formulation. Thus, ribavirin-PRINT-IP allowed for an efficient and convenient delivery of ribavirin to the lungs while minimizing systemic exposure. Further clinical investigations would be required to demonstrate ribavirin-PRINT-IP antiviral characteristics and impact on COPD viral-induced exacerbations. (The clinical trials discussed in this study have been registered at ClinicalTrials.gov under identifiers NCT03243760 and NCT03235726.)

BACKGROUND AND PURPOSE:

Conventional nonadhesive liquid embolic agents currently are the criterion standard for endovascular embolization of cerebral AVMs. However, inadequate distal penetration into the nidus and unstable proximal plug formation are the major limitations of this approach and of the currently available embolic materials. The aim of this study was to evaluate the hypothetic efficacy of combining liquid embolic agents with different properties and viscosities for use in endovascular embolization of cerebral AVMs.

It delivers almost all the functionality Apple promised, with a steep Apple-like price tag to match.

A military exercise in Australia demonstrates how small drones can airdrop critical medical supplies to soldiers in combat

Platform sandals meet 40-denier tights as rock’n’roll goes bourgeois at Paris fashion week

At his Celine catwalk show on Friday night, the designer Hedi Slimane distilled what looks to be the most compelling trend of this season of fashion shows. Working title: rock’n’roll bourgeois.

Slim knee-length dresses were worn with slinky chain belts; towering platform sandals with sensible 40-denier semi-sheer tights; slim bootcut velvet trousers worn with Princess-line above-the-knee coats. This was a masterclass in Parisian allure: take one part Avenue Montaigne privilege, and mix with one part backstage pass. Shaken, not stirred.

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The Duke and Duchess of Sussex spent the Easter weekend helping deliver meals to vulnerable and housebound people in Los Angeles.

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Hospital leaders have criticised the Government after a shipment which contained vital equipment for NHS staff was delayed.

An NHS dentist is spending her time away from the frontline co-ordinating food donation packages for fellow heathcare staff during the coronavirus pandemic.

The CEO of the NHS Confederation said the supply could have been enough to 'avert an absolute crisis'