Internal ribosomal entry sites (IRESs) recruit the ribosome to promote translation, typically in an m7G cap-independent manner. Although IRESs are well-documented in viral genomes, they have also been reported in mammalian transcriptomes, where they have been proposed to mediate cap-independent translation of mRNAs. However, subsequent studies have challenged the idea of these "cellular" IRESs. Current methods for screening and discovering IRES activity rely on a bicistronic reporter assay, which is prone to producing false positive signals if the putative IRES sequence has a cryptic promoter or cryptic splicing sites. Here, we report an assay for screening IRES activity using a genetically encoded circular RNA comprising a split nanoluciferase (nLuc) reporter. The circular split nLuc reporter is less susceptible to the various sources of false positives that adversely affect the bicistronic IRES reporter assay and provides a streamlined method for screening IRES activity. Using the circular split nLuc reporter, we find that nine reported cellular IRESs have minimal IRES activity. Overall, the circular split nLuc reporter offers a simplified approach for identifying and validating IRESs and exhibits reduced propensity for producing the types of false positives that can occur with the bicistronic reporter assay.

ABSTRACTToxicological emergencies present a significant health challenge in Nepal. Despite the high burden, the country has inadequate formal toxicology training, medical toxicology expertise, and adequate poison control infrastructure. In recognition of this need, the Nepal Poison Information Center (PIC) was established as a collaborative effort involving local and international partners. Through a comprehensive partnership framework, the Nepal PIC provides 24 hours a day, 7 days a week expert guidance to health care workers, conducts educational webinars, and engages in research. Initial data from the pilot phase indicate successful consultation delivery. Challenges include bureaucratic hurdles and the need for sustainable funding. Despite these challenges, the Nepal PIC demonstrates early feasibility and potential for expansion into a comprehensive toxicology center, contributing to the advancement of clinical toxicology in Nepal. Long-term sustainability relies on governmental support and continued advocacy efforts.

In nuclear medicine, estimating the number of radioactive decays that occur in a source organ per unit administered activity of a radiopharmaceutical (i.e., the time-integrated activity coefficient [TIAC]) is an essential task within the internal dosimetry workflow. TIAC estimation is commonly derived by least-squares fitting of various exponential models to organ time–activity data (radiopharmaceutical biodistribution). Rarely, however, are methods used to objectively determine the model that best characterizes the data. Additionally, the uncertainty associated with the resultant TIAC is generally not evaluated. As part of the MIRDsoft initiative, MIRDfit has been developed to offer a biodistribution fitting software solution that provides the following essential features and advantages for internal dose assessment: nuclear medicine–appropriate fit functions; objective metrics for guiding best-fit selection; TIAC uncertainty calculation; quality control and data archiving; integration with MIRDcalc software for dose calculation; and a user-friendly Excel-based interface. For demonstration and comparative validation of MIRDfit’s performance, TIACs were derived from serial imaging studies involving ¹⁸F-FDG and ¹⁷⁷Lu-DOTATATE using MIRDfit. These TIACs were then compared with TIAC estimates obtained using other software. In most cases, the TIACs agreed within approximately 10% between MIRDfit and the other software. MIRDfit has been endorsed by the MIRD Committee of the Society of Nuclear Medicine and Molecular Imaging and has been integrated into the MIRDsoft suite of free dosimetry software; it is available for download at no user cost (https://mirdsoft.org/).

The class F of G protein-coupled receptors (GPCRs) consists of 10 Frizzleds (FZD_1–10) and Smoothened (SMO). FZDs bind and are activated by secreted lipoglycoproteins of the Wingless/Int-1 (WNT) family, and SMO is indirectly activated by the Hedgehog (Hh) family of morphogens acting on the transmembrane protein Patched. The advance of our understanding of FZDs and SMO as dynamic transmembrane receptors and molecular machines, which emerged during the past 14 years since the first-class F GPCR IUPHAR nomenclature report, justifies an update. This article focuses on the advances in molecular pharmacology and structural biology providing new mechanistic insight into ligand recognition, receptor activation mechanisms, signal initiation, and signal specification. Furthermore, class F GPCRs continue to develop as drug targets, and novel technologies and tools such as genetically encoded biosensors and CRISP/Cas9 edited cell systems have contributed to refined functional analysis of these receptors. Also, advances in crystal structure analysis and cryogenic electron microscopy contribute to the rapid development of our knowledge about structure-function relationships, providing a great starting point for drug development. Despite the progress, questions and challenges remain to fully understand the complexity of the WNT/FZD and Hh/SMO signaling systems.

As the International Space Station comes to the end of its life, we should recognise its biggest achievement – showing that a better world is possible

From artificial retinas to ageing mice, here are five of the most promising results from research performed on the ISS – and what they might mean for humans on Earth and in space

AlphaProof, an AI from Google DeepMind, came close to matching the top participants in a prestigious competition for young mathematicians

Credit the franchise's popularity, sure—but also its ludicrous file sizes.

In Episode 606 of The TouchArcade Show we kick things off talking about my plans for this weekend, which has …

Continue reading "Back When AOL WAS the Internet – The TouchArcade Show #606"

An internal report on workplace racism and harassment at the highest levels of the federal public service shows that not even the federal government’s top executives are immune from the problem.

THIS footage of the US Open winner’s wife’s short skirt was far too long or not long enough depending on who you ask.

Pesky leaks on the International Space Station aren’t the most serious issue facing U.S. human spaceflight

In July 2024, internet personality Bobby Saputra posted a video of himself living it up at what appeared to be the star-studded, ultra-lavish wedding of Radhika Merchant and Anant Ambani, the youngest child of Indian billionaire and Asia's richest man, Mukesh Ambani. The video featured clips of Saputra dancing, feasting and soaking up the "completely crazy" celebrations. He gushes in the voiceover: "It was like watching a Bollywood production." The video quickly went viral, racking up 6.6 million views on Instagram, 5.1 million on TikTok, and another 2.2 million on YouTube. Thousands left comments, including some celebrities who claimed they spotted him there. Except… he never set foot in the party. As it turns out, he had pieced together clips from a wedding he attended a few months prior — complete with him in full Indian attire, dancing with friends — and spliced in shots from the Ambani wedding that he found online. The result? Social media magic.

Aug 8, 2023

When states use moral language in a dispute, they reduce the possibility of compromise. The possibility of military escalation, meanwhile, rises in response to moral language when states’ domestic audiences accuse their governments of hypocrisy for their willingness to compromise. The Falkland Islands/Islas Malvinas case explores the theory.

Jun 18, 2024

The rise of political populism and economic protectionism are serious barriers impeding efforts to combat global climate change. Robert Lawrence, the Albert Williams Professor of International Trade and Investment at Harvard Kennedy School, expressed those concerns in the latest episode of “Environmental Insights: Discussions on Policy and Practice from the Harvard Environmental Economics Program.”

Apr 9, 2024

On April 2, the study group met for the second time to evaluate the role of international humanitarian groups in shaping political and social outcomes in Africa. The group examined how these organizations deal with emergencies, crises, and conflict situations across the continent, and scrutinized their influence on policy decisions and discuss the potential benefits and drawbacks of their involvement. Discussions covered the expanding influence of organizations like the United Nations High Commissioner for Refugees (UNHCR), Médecins Sans Frontières (Doctors Without Borders), and the International Rescue Committee (ICR). The study group counted with the presence of external expert guest Professor Sabs K. Quereshi, a senior-level leader with 17+ years of experience in global health, gender equality, health policy and equity, national security, humanitarian response, and government and multilateral affairs sectors in the U.S., with the UN, and worldwide.

Jun 14, 2024

Dr. Gloria Ayee led a study group over the course of five sessions during the Spring of 2024, exploring the current pivotal moment on the African continent. Participants of the study group were invited to reflect on the role that international cooperation must play in supporting inclusive, sustainable development in Africa, as well as to move beyond outdated perspectives and learn about Africa’s profound transformation through trade, investments in clean energy and health, and youth empowerment initiatives.

Jun 21, 2024

Dr. Gloria Ayee led a study group over the course of five sessions during the Spring of 2024, exploring the current pivotal moment on the African continent. Reflecting back, Dr. Ayee highlights the key takeaways from the study group.

Redefining the American Auto Industry. - The Growing Impact of International Automakers on the U.S. Economy.

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The London Look International Contest With Rita Ora Teaser

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XCMG Apprentice Program introduces latest technologies and Chinese culture to international apprentices.

Altimetrik defines future of the Enterprise Internet of Things

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The Hear the World Foundation wants you to make listening safe in celebration of the World Health Organization�s International Ear Care Day in 2015

Chief Executive Officer Susan Docherty invites you to experience debut Canyon Ranch international resort: Canyon Ranch Wellness Resort at Kaplankaya in Turkey

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Download Direct Tax Laws & International Taxation (DT) Question Papers New Course Nov 2024 in PDF. For older question papers of CA final May 2024, Nov 2023, May 2023, Nov 2022, May 2022, Dec 2021, July 2021, Nov 2020, Nov 2019, May 2019, Nov 2018,CA final May 2018, Nov 2017, May 2017, CA final may 2016, CA final Nov 2016 check similar section. Previous years CA final Financial Reporting FR question papers can also be downloaded using Search. You can also search and download may 2015 IPCC & IPC question papers here. We are providing ca final question papers of may 2016 for Financial Reporting FR, Advanced Financial Management AFM, Advanced Auditing, Assurance And Professional Ethics, Direct Tax Laws DT, Indirect Tax Laws IDT,Integrated Business Solutions (Multidisciplinary Case Study with Strategic Management) and IPCC/IPC Nov 2023 question papers for Accounting, Business, Law, Ethics & Communications , Cost Accounting & Financial Management CAFM, Taxation, Advanced Accounting , Auditing & Assurance, Information Technology & Strategic Management ITSM.

Poachers, when caught stealing content from our website, always blamed the theft on an “intern” or “freelancer.” We always pretended to believe them.

The post Ah yes, the famous “intern did it” syndrome appeared first on Zeldman on Web and Interaction Design.

Chinese technology giant ByteDance denied reports that the incident caused more than $10m of damage.

"He could be the next great" - meet the 14-year-old international goalkeeper hoping to one day make it in the Premier League.

The International Monetary Fund has collated information on the tax and non-tax policy responses of some 193 jurisdictions to COVID-19.

US Trade Representative Robert Lighthizer told a congressional hearing on June 17, 2020, that the US Government has withdrawn from international negotiations on new global tax rules for digital companies at the OECD.

US Trade Representative Robert Lighthizer told a congressional hearing on June 17, 2020, that the US Government has withdrawn from international negotiations on new global tax rules for digital companies at the OECD.

The OECD has said 131 countries and jurisdictions have put their name to an international agreement on an overhaul to tax rules for the digitalized economy and for large multinational businesses.

The International Nurses Day 2021 is being observed amid the ongoing second wave in India and it highlights the contribution of nurses in the entire healthcare system.

A strong nursing sector is an important building block of a strong healthcare sector. Nurses are the foundation of hospitals and the heart and the soul

IWMI Pakistan and Khwaja Fareed University of Engineering and Information Technology (KFUEIT), RYK join hands to organize an international workshop on Water, Energy, Food and Ecosystem (WEFE) Nexus for Indus Basin

The post International workshop on Water, Energy, Food and Ecosystem Nexus for Indus Basin first appeared on International Water Management Institute (IWMI).

Use of medlinkArtificial Intelligence/medlink (AI) for self-diagnosis and prescription may put human life at risk, warn healthcare experts. On