The technical assistance (TA) will support the Kingdom of Cambodia in building resilience within, and improving the competitiveness of the country's private sector by enhancing the capacity of state institutions to support adoption of digital technologies and to foster innovation and diversification in micro-, small- and medium-sized enterprises (MSMEs), where women entrepreneurs and workers are traditionally prevalent.

The proposed SMEDP2-Phase 2 will consist of a $100 million concessional loan from ADB's ordinary capital resources and an attached technical assistance of $950,000 in aggregate from TASF-7 and Financial Sector Development Partnership Special Fund. It will finance the continuation and expansion of activities financed under the SMEDP2 project by increasing the number and size of commercially viable cottage, micro, small and medium enterprises (CMSMEs), as well as supporting employment in the CMSME sector.

The natural motors that power tail-like appendages in bacteria seem to have a single evolutionary origin, allowing parts from different species to be combined to create a tiny new engine

A new technique uses glowing molecules, laser light and microscopes to measure distances as minuscule as 0.1 nanometres – the width of a typical atom

An arm bone from an ancient human that lived 700,000 years ago on the island of Flores is the smallest ever found from an adult hominin, adding a new piece to the puzzle of Homo floresiensis

Title: Cosmetic Eye Procedure May Ease Migraines, Small Study Says
Category: Health News
Created: 8/22/2014 12:36:00 PM
Last Editorial Review: 8/25/2014 12:00:00 AM

Title: Antiviral Drug May Prevent Ebola, Small Study Suggests
Category: Health News
Created: 8/25/2015 12:00:00 AM
Last Editorial Review: 8/26/2015 12:00:00 AM

Title: U.S. Opioid Deaths Take a Small Dip, as Fentanyl Leaves Deadly Mark
Category: Health News
Created: 8/29/2019 12:00:00 AM
Last Editorial Review: 8/30/2019 12:00:00 AM

Title: Nerve Block Plus Lidocaine Clears Psoriasis in Small Study
Category: Health News
Created: 8/15/2022 12:00:00 AM
Last Editorial Review: 8/16/2022 12:00:00 AM

Title: SIBO (Small Intestinal Bacterial Overgrowth)
Category: Diseases and Conditions
Created: 10/28/2005 12:00:00 AM
Last Editorial Review: 8/8/2022 12:00:00 AM

Vault RNAs (vtRNAs) are evolutionarily conserved small noncoding RNAs transcribed by RNA polymerase III. Vault RNAs were initially described as components of the vault particle, but have since been assigned multiple vault-independent functions, including regulation of PKR activity, apoptosis, autophagy, lysosome biogenesis, and viral particle trafficking. The full-length transcript has also been described as a noncanonical source of miRNAs, which are processed in a DICER-dependent manner. As central molecules in vault-dependent and independent processes, vtRNAs have been attributed numerous biological roles, including regulation of cell proliferation and survival, response to viral infections, drug resistance, and animal development. Yet, their impact to mammalian physiology remains largely unexplored. To study vault RNAs in vivo, we generated a mouse line with a conditional Vaultrc5 loss-of-function allele. Because Vaultrc5 is the sole murine vtRNA, this allele enables the characterization of the physiological requirements of this conserved class of small regulatory RNAs in mammals. Using this strain, we show that mice constitutively null for Vaultrc5 are viable and histologically normal but have a slight reduction in platelet counts, pointing to a potential role for vtRNAs in hematopoiesis. This work paves the way for further in vivo characterizations of this abundant but mysterious RNA molecule. Specifically, it enables the study of the biological consequences of constitutive or lineage-specific Vaultrc5 deletion and of the physiological requirements for an intact Vaultrc5 during normal hematopoiesis or in response to cellular stresses such as oncogene expression, viral infection, or drug treatment.

Antifolates are important for chemotherapy in non–small cell lung cancer (NSCLC). They mainly rely on reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) to enter cells. PCFT is supposed to be the dominant transporter of the two in tumors, as it operates optimally at acidic pH and has limited transport activity at physiological pH, whereas RFC operates optimally at neutral pH. In this study, we found RFC showed a slightly pH-dependent uptake of antifolates, with similar affinity values at pH 7.4 and 6.5. PCFT showed a highly pH-dependent uptake of antifolates, with an optimum pH of 6.0 for pemetrexed and 5.5 for methotrexate. The Michaelis-Menten constant (K_m) value of PCFT for pemetrexed at pH 7.4 was more than 10 times higher than that at pH 6.5. Interestingly, we found that antifolate accumulations mediated by PCFT at acidic pH were significantly affected by the efflux transporter, breast cancer resistance protein (BCRP). The highest pemetrexed concentration was observed at pH 7.0–7.4 after a 60-minute accumulation in PCFT-expressing cells, which was further evidenced by the cytotoxicity of pemetrexed, with the IC₅₀ value of pemetrexed at pH 7.4 being one-third of that at pH 6.5. In addition, the in vivo study indicated that increasing PCFT and RFC expression significantly enhanced the antitumor efficacy of pemetrexed despite the high expression of BCRP. These results suggest that both RFC and PCFT are important for antifolates accumulation in NSCLC, although there is an acidic microenvironment and high BCRP expression in tumors.

In this study, the nonclinical pharmacokinetics of OLX702A-075-16, an RNA interference therapeutic currently in development, were investigated. OLX702A-075-16 is a novel N-acetylgalactosamine conjugated asymmetric small-interfering RNA (GalNAc-asiRNA) used for the treatment of an undisclosed liver disease. Its unique 16/21-mer asymmetric structure reduces nonspecific off-target effects without compromising efficacy. We investigated the plasma concentration, tissue distribution, metabolism, and renal excretion of OLX702A-075-16 following a subcutaneous administration in mice and rats. For bioanalysis, high-performance liquid chromatography with fluorescence detection was used. The results showed rapid clearance from plasma (0.5 to 1.5 hours of half-life) and predominant distribution to the liver and/or kidney. Less than 1% of the liver concentration of OLX702A-075-16 was detected in the other tissues. Metabolite profiling using liquid chromatography coupled with high-resolution mass spectrometry revealed that the intact duplex OLX702A-075-16 was the major compound in plasma. The GalNAc moiety was predominantly metabolized from the sense strand in the liver, with the unconjugated sense strand of OLX702A-075-16 accounting for more than 95% of the total exposure in the rat liver. Meanwhile, the antisense strand was metabolized by the sequential loss of nucleotides from the 3'-terminus by exonuclease, with the rat liver samples yielding the most diverse truncated forms of metabolites. Urinary excretion over 96 hours was less than 1% of the administered dose in rats. High plasma protein binding of OLX702A-075-16 likely inhibited its clearance through renal filtration.

Early detection of drug-drug interactions (DDIs) can facilitate timely drug development decisions, prevent unnecessary restrictions on patient enrollment, resulting in clinical study populations that are not representative of the indicated study population, and allow for appropriate dose adjustments to ensure safety in clinical trials. All of these factors contribute to a streamlined drug approval process and enhanced patient safety. Here we describe a new approach for early prediction of the magnitude of change in exposure for cytochrome P450 (P450) CYP3A4-related DDIs of small-molecule anticancer drugs based on the model-based extrapolation of human-CYP3A4-transgenic mice pharmacokinetics to humans. Victim drugs brigatinib and lorlatinib were evaluated with the new approach in combination with the perpetrator drugs itraconazole and rifampicin. Predictions of the magnitude of change in exposure deviated at most 0.99- to 1.31-fold from clinical trial results for inhibition with itraconazole, whereas exposure predictions for the induction with rifampicin were less accurate, with deviations of 0.22- to 0.48-fold. Results for the early prediction of DDIs and their clinical impact appear promising for CYP3A4 inhibition, but validation with more victim and perpetrator drugs is essential to evaluate the performance of the new method.

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.

Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership.

It's just the core trio this week, as Chris tosses a coin to his hunting horn partner Kelley, and Anna Marie rolls her eyes as Chris cracks terrible jokes about what the Vita really means. We all consider MiHoYo's bottom line, as well as whether we're classified as normies.

The post RPG Cast – Episode 580: “Marshmallow Is Canon” appeared first on RPGamer.

A newly spotted asteroid named 2024 RW1 burned up in the atmosphere over the South Pacific, creating a spectacular bright flash in the sky over the Philippines just hours after first being detected

A single dose of a smallpox vaccine seems to lower the risk of catching mpox by around 60 per cent, and two doses would probably be even better

The appointment of a political outsider like Musk could help Trump cut regulations and rein in government bureaucracy, even if the moves are unpopular

An inquiry found abuse, torture and neglect of some 200,000 people in state care over 70 years. People with disabilities or from Maori and Pacific Islander communities were especially vulnerable.

Speaking with CBC News’s Eli Glasner, Cillian Murphy discusses ‘imploding emotionally’ in his role in Small Things Like These, his partnership with Matt Damon and Ben Affleck and how his experience on Oppenheimer influenced this film. CORRECTION: A previous version of this video interview includes reference to communities in Canada 'still finding bodies of Indigenous children in the ground' at 1:24. We have removed this portion of the interview. Searches at the sites of former residential schools using ground-penetrating radar have found evidence of possible unmarked graves.

Researchers at Rice University have developed a magnetoelectric material that converts a magnetic field into an electric field. The material can be formulated such that it can be injected into the body, near a neuron, and then an alternating magnetic field can be applied to the area from outside the body. Magnetic fields are very […]

Neurogene’s Rett syndrome gene therapy has preliminary data supporting safety and efficacy of the one-time treatment. But a late-breaking report of a serious complication in a patient who received the high dose sent shares of the biotech downward.

The post Neurogene Gene Therapy Shows Signs of Efficacy in Small Study, But an Adverse Event Spooks Investors appeared first on MedCity News.

Edmunds.com�s roundup of new vehicles at the 2014 LA Auto Show

2016 IIHS TOP SAFETY PICKS

The New KitchenAid� Artisan� Mini Stand Mixer: Small Yet Mighty

When traveling, the hotel becomes Sword & Plough�s mobile office, and Holiday Inn� hotels have become an integral extension of their team while on the road.

Kala Gibson, Head of Business Banking at Fifth Third Bank, discusses the importance of small businesses to our economy and communities

Get a sneak peak at the industry�s smallest and smartest bone conduction sound processor. Now the first hearing implant with Made for iPhone� technology.

In this article, we explore the key reasons why LLPs are increasingly favoured, focusing on the advantages of LLPs for small business owners.

Väike-kirjurähn on Euroopa väikseim rähn, olles kõigest varblase mõõtu. The Lesser Spotted Woodpecker is the smallest woodpecker in Europe, being only the size of a sparrow.

I've spent a month doing my best to help my community and prepare my household for Covid-19.