lab

Collaboration on the gridiron: an interview with Fred Bowen and James Ransome

Sports are important to young people on many levels. When participating, they experience teamwork, self-discipline, following rules, and just plain fun. Often, children see role models in professional athletes. But professional sports can provide an introduction to history, depicting the times in which they are played. Also like the world we live in, games have evolved over time to respond to events and social changes.





lab

Engaging, Explicit, and Elaborated: An Initial Trial of Media-Enhanced Preschool Vocabulary Instruction

Children from backgrounds of poverty often lag behind more advantaged peers in early language skills, including breadth and depth of vocabulary knowledge. We report the results of a pilot study of an explicit and elaborated vocabulary intervention in preschool classrooms serving children from lower-income backgrounds. The intervention used multimodal instruction, including segments from public television children's programs and interactive games, to build children's knowledge of and semantic connections for 128 words across 18 weeks of daily lessons.




lab

K2 will not be made available for Joomla 4/5 - change of course

The writing's on the wall. Joomla 4 and 5 are failed CMS releases.

They account for around 0.3% of ALL Joomla sites according to W3Techs (https://w3techs.com/technologies/details/cm-joomla).

Joomla's official stats (which were introduced near the end of life of Joomla 3 - https://developer.joomla.org/about/stats.html) are far less accurate obviously (e.g. they don't account for Joomla 1.5 > 2.5 sites or older Joomla 3 releases) but still show around 10% of sites use Joomla 4/5, after 3 years of their release. And these stats can be disabled by users of Joomla sites (most do).

This means adoption for these versions is close to non-existent. A sad reality, but an understandable one (read my posts on May 30th at https://x.com/joomlaworks for additional context).

There is literally nothing to say about how things have evolved for Joomla.

At this rate, it will probably be a dead software project within the next couple of years.

It's not just the users that are de-motivated, it's the developers too (the Joomla core developers). Few people will enjoy working on Joomla if no one uses it. It just makes sense.

As such, and given that we're strongly invested in Joomla 3 (in some of the largest news/media site implementations worldwide with Joomla), we don't plan on giving up on K2 (or Joomla 3). In fact, our goal is to pivot and work on a possible fork, unless a miracle happens and the Joomla core team gets their shit together and works on a true/seamless Joomla 3 to Joomla 5 (or 6?) upgrade.

The fork is a reasonable path for us for many reasons but I'd list the following ones here (for now):

  • It'll be exciting to go from K2 (a "half" CMS so to speak) to a full CMS. Any crap that didn't work or half-worked on J3 will be fixed.
  • Sky's the limit. Really. No stupid politics, irrelevant conventions, idiotic patterns to follow. We have a clear goal for K2 (and Joomla) and that's what we're gonna work on. That goal is a fast, reliable. modern CMS that leaves people asking "why WordPress?"
  • Some will nag Joomla 3 uses old code. No it doesn't. It uses a certain design that was popular at the time it was introduced. The only change that is required is for it to be updated so it catches up with PHP's latest versions (for the record, we actively run sites with Joomla 3 / K2 on PHP 8.2). It's a mature code base that can be gradually improved.
  • The fork could be introduced in 2 phases. Phase 1: A re-branding for existing sites to move over their content from com_content to K2 (far less work than switching to Joomla 4/5) and existing Joomla/K2 sites to freshen up their backend. Phase 2: This would be the part we lighten up the core. This means com_content & components like banners, newsfeeds, messages etc., their respective modules and plugins and generally other accumulated crap (like User Notes) that literally noone ever used will be stripped off Joomla. Either way K2 can reproduce most of these stuff far better.
  • Any design changes will be subtle and NOT affect existing Joomla extensions that respected the Joomla UI design. It will also certainly NOT affect extensions that brought in their own design/MVC and so on (think AcyMailing, page builders etc. etc.).
  • If our friend Ryan provides his blessing, we would also love to swap the current Joomla WYSIWYG editor with JCE Core. If not, it's always available either way. We will just upgrade TinyMCE and still install our beloved JCE. This would also be a good time to standardize things like "editor xtd" buttons in a way that they better integrate with the WYSIWYG editor...
  • Features and custom extensions we've used for large scale projects could be integrated in the new CMS, if it makes sense for most users to have. E.g. fast search powered by Elasticsearch is a no-brainer (and we can throw that Smart Search crap out for good).

The point is to do something that's fun, while professional at the same time.

Backward compatibility will be our holy grail. Anyone that tells it can't are either lazy or just plain bad programmers (hell, we've maintained K2 for Joomla 1.5 to 3 for 15 damn years).

We're already in touch with partners to finance this move. On the long term, all we need is a couple of devs, working full time.

The next big phase will be infrastructure as required for any modern CMS. That means rebuilding something like the JED, working on documenting use and code etc. At the same time, it's practical to keep everything to a minimum. E.g. there is no reason to use our own forum, but probably go for something like GitHub so we can have everything in a single place: code and discussion, coupled with solid anti-spam (cause let's face it, that's what forums suffer from these days).

By keeping things lean and simple, we will work less on infrastructure and more on the CMS's code and features.

If you ask "why now", I can respond with 2 things:

1) There's been plenty of time for people to switch to Joomla 4/5. Very few did.

2) It's MUCH worse waiting things out to chart their predefined course than actually fucking doing something about it, even if it fails or doesn't work out.

Follow up blog posts will provide more insight into how things will play out in the coming months and how others can join this effort.

 

P.S.

If you have any questions, please use Twitter/X to communicate these to us (@joomlaworks).




lab

Beyond Labels and Agendas: Research Teachers need to Know about Phonics and Phonological Awareness

This article describes the current findings on phonics and phonological awareness instruction. It uses a question & answer format to explore 10 common questions that teachers ask about teaching phonics and phonemic awareness. Here are a few key questions addressed in the article: What are phonics and phonemic awareness? Should phonemic awareness be paired with print and taught together? Should phonological awareness be coordinated with phonics instruction? What is the best sequence for teaching phonics?




lab

AI labs – Learning unsupervised learning through Robotics

We are launching an AI lab. The goal is to learn unsupervised learning through Robotics (Cobots) Long seen as a poor cousin to supervised learning -  with Variational autoencoders, Reinforcement learning and  Generative-Adversarial networks , unsupervised learning techniques have moved beyond the limitations of autoencoders. From Oct 2018 to March 2019 , we are running a [...]




lab

AI labs – a club for #AI research and a chance to gain hands-on experience with AI

  We have been working on this idea over the summer and have now launched the next stage of the AI labs in London Here are some more details. Think of AI labs – as a club for AI research AI labs addresses three problems a)  Today, even if you are working on Machine Learning [...]




lab

Testimony before the North Dakota Senate Industry, Business and Labor Committee

Chairman Klein and members of the Senate Industry, Business and Labor Committee- My name is David Heinemeier Hansson, and I’m the CTO and co-founder of Basecamp, a small internet company from Chicago that sells project-management software and email services. I first testified on the topic of big tech monopolies at the House Antitrust Subcommittee’s field… keep reading




lab

Labour Party Conference – International affairs networking brunch

Labour Party Conference – International affairs networking brunch 24 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) Labour – Grace 1 Suite, Hilton Hotel, Liverpool

Hosted by Sir Simon Fraser, Chairman of Chatham House.

This event is taking place at the Hilton Hotel, Grace 1 Suite, Liverpool.

You are warmly invited to join us for an exclusive networking brunch at the 2024 Labour Party Conference.

Sir Simon Fraser, Chairman of Chatham House, and Olivia O’Sullivan, Director of Chatham House’s UK in the World Programme, will deliver opening remarks, followed by an interactive networking session where you will have the chance to engage with a wide range of stakeholders. Join us to connect with key senior parliamentary, corporate and media attendees at the Labour Party Conference.

This event will be taking place outside of the secure zone.




lab

Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work

Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work Research paper sysadmin 29 June 2016

A new paper sets out the factors that have made previous cross-border projects in South Asia successful, arguing that cooperation around water is feasible despite the region’s political differences and economic assymetries.

Indian people walk in the Ganga riverbed in Allahabad on 1 September 2015. Photo: Getty images.

  • The countries of South Asia share some of the world’s major river basins – the Ganga (or Ganges), the Brahmaputra and the Indus. These rivers and their tributaries flow through seven countries, support more than 1 billion people, irrigate millions of hectares of land and are of cultural importance to many of those who rely on them.
  • River management presents common challenges across the region. These include physical factors such as droughts, flooding, cyclones and climate change, as well political and institutional factors impeding the development of solutions and policies to improve resource management and reduce vulnerability. Water is increasingly seen as a source of competition, with population growth, industrialization and urbanization exacerbating the pressures on supply.
  • Although South Asian examples of regional cooperation in general are limited, there is a clear positive trend. In areas such as disaster response and cross-border power trading, regional and bilateral engagement is beginning to take place. Multilateral official arrangements exist for trade and other economic issues, but there is none on water or ecosystems. However, as the benefits from cooperation become proven, its desirability is likely to gradually enter mainstream policy thinking on water issues.
  • This research paper sets out the factors that have enabled cooperation, and the processes adopted, in previous successful cross-border projects. It focuses on four categories of cooperation: development of early-warning systems for natural disasters, in particular floods; protection of cross-border ecosystems; sharing of learning, through the showcasing of innovative approaches in one country that can be adopted by others; and power trading, in particular the development of hydropower in Bhutan and its export to India.
  • The paper argues that cooperation around water in South Asia is feasible despite political differences and economic asymmetries. Different forms of collective action, and common understanding of both the threats and the shared benefits from cooperation, are required to foster more partnerships within the river basin states.




lab

Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun Proteomics

William M. Old
Oct 1, 2005; 4:1487-1502
Research




lab

Accurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ

Jürgen Cox
Sep 1, 2014; 13:2513-2526
Technological Innovation and Resources




lab

Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics

Shao-En Ong
May 1, 2002; 1:376-386
Research




lab

Undercurrents: Episode 17 - Alastair Campbell on New Labour and Brexit, Alistair Darling on the Financial Crisis




lab

Indo-UK Collaboration: Opportunities and Challenges




lab

A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent

M el-Saadani
Apr 1, 1989; 30:627-630
Articles




lab

Co-crystal structures of HIV TAR RNA bound to lab-evolved proteins show key roles for arginine relevant to the design of cyclic peptide TAR inhibitors [Molecular Biophysics]

RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction.




lab

Guidance and best practices for nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic: An Information Statement from ASNC and SNMMI




lab

Theranostics for Meningioma on the Rise: New EANM/EANO/RANO/SNMMI Guidelines Pave the Way to Improved Patient Outcomes Using Radiolabeled Somatostatin Receptor Ligands




lab

Bioavailability and spatial distribution of fatty acids in the rat retina after dietary omega-3 supplementation

Elisa Vidal
Dec 1, 2020; 61:1733-1746
Research Articles




lab

Problem Notes for SAS®9 - 66539: A new calculated variable that you create in the Edit Value dialog box is not available for selection in SAS Customer Intelligence Studio

In SAS Customer Intelligence Studio, you can choose to create a new calculated variable in the Edit Value dialog box when you populate a treatment custom detail. Following creation of the new calculated




lab

Harmonized procedures lead to comparable quantification of total oxylipins across laboratories [Research Articles]

Oxylipins are potent lipid mediators involved in a variety of physiological processes. Their profiling has the potential to provide a wealth of information regarding human health and disease and is a promising technology for translation into clinical applications. However, results generated by independent groups are rarely comparable, which increases the need for the implementation of internationally agreed upon protocols. We performed an interlaboratory comparison for the MS-based quantitative analysis of total oxylipins. Five independent laboratories assessed the technical variability and comparability of 133 oxylipins using a harmonized and standardized protocol, common biological materials (i.e., seven quality control plasmas), standard calibration series, and analytical methods. The quantitative analysis was based on a standard calibration series with isotopically labeled internal standards. Using the standardized protocol, the technical variance was within ±15% for 73% of oxylipins; however, most epoxy fatty acids were identified as critical analytes due to high variabilities in concentrations. The comparability of concentrations determined by the laboratories was examined using consensus value estimates and unsupervised/supervised multivariate analysis (i.e., principal component analysis and partial least squares discriminant analysis). Interlaboratory variability was limited and did not interfere with our ability to distinguish the different plasmas. Moreover, all laboratories were able to identify similar differences between plasmas. In summary, we show that by using a standardized protocol for sample preparation, low technical variability can be achieved. Harmonization of all oxylipin extraction and analysis steps led to reliable, reproducible, and comparable oxylipin concentrations in independent laboratories, allowing the generation of biologically meaningful oxylipin patterns.




lab

Bioavailability and spatial distribution of fatty acids in the rat retina after dietary omega-3 supplementation [Research Articles]

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined by LC coupled to MS/MS and MALDI coupled to MS imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that PLs as well as TGs are good omega-3 carriers for retina. However, a significant increase in DHA content in retina was observed, especially molecular species as di-DHA-containing PC and PE, as well as an increase in very long chain PUFAs (more than 28 carbons) following PL-EPA and TG-DHA diets only. All supplemented diets triggered spatial organization changes of DHA in the photoreceptor layer around the optic nerve. Taken together, these findings suggest that dietary omega-3 supplementation can modify the content of FAs in the rat retina.




lab

MSstatsTMT: Statistical Detection of Differentially Abundant Proteins in Experiments with Isobaric Labeling and Multiple Mixtures [Technological Innovation and Resources]

Tandem mass tag (TMT) is a multiplexing technology widely-used in proteomic research. It enables relative quantification of proteins from multiple biological samples in a single MS run with high efficiency and high throughput. However, experiments often require more biological replicates or conditions than can be accommodated by a single run, and involve multiple TMT mixtures and multiple runs. Such larger-scale experiments combine sources of biological and technical variation in patterns that are complex, unique to TMT-based workflows, and challenging for the downstream statistical analysis. These patterns cannot be adequately characterized by statistical methods designed for other technologies, such as label-free proteomics or transcriptomics. This manuscript proposes a general statistical approach for relative protein quantification in MS- based experiments with TMT labeling. It is applicable to experiments with multiple conditions, multiple biological replicate runs and multiple technical replicate runs, and unbalanced designs. It is based on a flexible family of linear mixed-effects models that handle complex patterns of technical artifacts and missing values. The approach is implemented in MSstatsTMT, a freely available open-source R/Bioconductor package compatible with data processing tools such as Proteome Discoverer, MaxQuant, OpenMS, and SpectroMine. Evaluation on a controlled mixture, simulated datasets, and three biological investigations with diverse designs demonstrated that MSstatsTMT balanced the sensitivity and the specificity of detecting differentially abundant proteins, in large-scale experiments with multiple biological mixtures.




lab

The Chatham House Sustainable Laboratories Initiative: Prior Assessment Tool

The Chatham House Sustainable Laboratories Initiative: Prior Assessment Tool Other resource sysadmin 14 June 2019

Laboratories are critical for supporting effective infectious disease surveillance and outbreak response. This tool is meant to help structure a conversation between funding partners and recipient countries on how to most effectively establish or repurpose laboratories in low-resource environments.

Copyright: Getty Images/ER Productions Limited

Introduction

Laboratories are critical for supporting effective infectious disease surveillance and outbreak response, and lack of adequate laboratory capacity is a global challenge. As part of global health security initiatives, cooperative threat reduction efforts and international development programmes, sophisticated laboratories have been provided to mitigate biological threats and bolster a country’s capacity for detection, diagnosis and storage of high-consequence pathogens. Very often, these use the assumptions, standards and templates applied in high-income countries. However, it can be difficult or even impossible to sustain these facilities in low-resource environments. There can sometimes be limited local technical capacity and capability, which can result in a high reliance on imported expertise, skills, equipment and other resources. Sustainability can therefore be hard to achieve. In addition, when a funding partner withdraws, the laboratories can become disused, foundering without the trained personnel and financial resources to sustain them.

To help address this situation, a proposal gaining increasing support internationally is to adopt an approach based on a local risk assessment, whereby laboratories are appropriately and optimally tailored to the local risks and to the resources available, both in the short and longer term, without compromising biosafety and biosecurity.

A Chatham House workshop was convened in Abuja, Nigeria, in 2018 to explore what West African countries would find most appropriate in terms of building laboratory capacity, what the main challenges have been so far, and what needs to be done to improve the sustainability of laboratories in the region. It emerged that there was a need for a more structured conversation between the funding partner and recipient country early in the process – prior to embarking on the detailed planning phase for the establishment or repurposing of a laboratory. This should involve careful consideration and an assessment of existing and planned capacity, needs and contextual issues, together with proposals for how to address the issues revealed, so that any ensuing laboratory demonstrably supports the national strategy and therefore flourishes.

The purpose of this tool

This tool aims to provide a structure for such a conversation. Developed in close collaboration with international experts and West African stakeholders, it seeks to increase local ownership and help partners ensure they have given due attention to all the relevant aspects, including risks and benefits, that need to be considered at an early stage. It should provide clarity on what is needed and improve the sustainability of any laboratory project that might result from the discussions. The tool can be applied when a new laboratory is being considered, or when an existing laboratory is to be repurposed or strengthened. It is also appropriate for use with public health, veterinary and environmental laboratories. Although the tool was developed in the context of high-consequence pathogens in Africa, it is anticipated that it will find global application.

It should support recipient countries to take stock of their capacities and capabilities, identify gaps, conduct an analysis of their needs and to develop the business case that can assist in seeking the necessary political and financial support for the laboratory. Meanwhile, it should facilitate the process of due diligence for the funding partner and provide a better understanding of what the recipient country perspective and realities are, and what the scale and nature of any investment might be.




lab

The Justice Laboratory: International Law in Africa

The Justice Laboratory: International Law in Africa Book dora.popova 30 March 2022

The Justice Laboratory is the first major study of the institutions created to enforce international criminal justice standards in Sub-Saharan Africa, including the UN tribunal for the Rwandan genocide.

Since the Second World War, the United Nations and other international actors have created laws, treaties, and institutions to punish perpetrators of genocide, war crimes, and crimes against humanity. But international criminal justice now seems to be a declining force — its energy sapped by long delays in prosecutions, lagging public attention, and a globally rising authoritarianism that disregards legal niceties.

The Justice Laboratory reviews five examples of international criminal justice as they have been applied across Africa, where brutal civil conflicts in recent decades resulted in varying degrees of global attention and action.

Written in an accessible style, the book explores the connections between politics and the doctrine of international criminal law. Highlighting little-known institutional examples and under-discussed political situations, the book contributes to a broader international understanding of African politics and international criminal justice, and the lessons African experiences can offer to other countries.

This book is part of the Insights series.

 

Praise for The Justice Laboratory

Integrating legal and political analysis, Kerstin Bree Carlson provides a highly accessible and provocative examination of the promises and pitfalls of seeking accountability in a range of contemporary international criminal justice interventions in Africa.

Victor Peskin, School of Politics and Global Studies, Arizona State University

About the author

Kerstin Bree Carlson is associate professor of international law at the Department of Social Science and Business, Roskilde University, where she teaches topics in law and society, global studies, international politics, and Nordic migration.

Purchase




lab

Get ready to watch: MLB.TV available for 2019

Spring Training is imminent, Opening Day is within sight and the big league season isn't complete for fans without a subscription to MLB.TV. The most comprehensive streaming service in professional sports is now available for the 2019 season.




lab

Challenges in diabetes and obesity: five minutes with . . . Jonathan Valabhji




lab

GLP-1 shortages will not resolve this year, EMA warns, amid concern over off-label use




lab

Helen Salisbury: Weight loss treatment—available in theory but not in practice




lab

What is Labour’s foreign policy?

What is Labour’s foreign policy? 24 January 2023 — 12:00PM TO 1:00PM Anonymous (not verified) 3 January 2023 Chatham House and Online

In conversation with David Lammy, the UK shadow foreign secretary.

David Lammy MP, shadow secretary of state for foreign, commonwealth and development affairs, outlines Labour’s plan for UK foreign policy if elected to government.

He addresses the UK’s strengths and opportunities in a world that has become more divided, more dangerous, and more unpredictable. He also offers a critique of the current UK government’s approach to foreign policy, particularly at strained relationships with allies and Britain’s economic woes.

The shadow foreign secretary explores the following key questions:

  • What would a future Labour government do to modernize Britain’s diplomacy and rebuild alliances to improve Britain’s global influence?

  • In a new age of warfare in Europe, how would Labour pursue security cooperation with allies?

  • How would Labour address high energy costs, energy security, and the climate crisis?

  • As Britain’s economy falters, how can foreign policy drive prosperity at home?

  • What is Labour’s plan for international development, following the UK government’s abandonment of the 0.7% commitment?

As with all members events, questions from the audience drive the conversation.

Read a transcript




lab

Design, Synthesis, and Preclinical Evaluation of a High-Affinity 18F-Labeled Radioligand for Myocardial Growth Hormone Secretagogue Receptor Before and After Myocardial Infarction

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with 18F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with 18F a quinazolinone derivative ([18F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [18F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [18F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [13N]NH3 PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [18F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [18F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [18F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [18F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.




lab

Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Methods: Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with 111In to allow SPECT imaging. 111In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non–p53-specific 111In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. Results: In vivo SPECT imaging showed enhanced uptake of 111In-anti-p53-TAT, versus 111In-mIgG-TAT, in high-expression p53R175H and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse–derived pancreatic ductal adenocarcinoma tumors. Imaging with 111In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53R172H pancreatic ductal adenocarcinoma tumors. Conclusion: We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.




lab

Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177Lu-Labeled Radiohapten

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic - and β-emitting isotope 177Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [177Lu]Lu-Gemini was prepared with no-carrier-added 177LuCl3 to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-177Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [177Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [177Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([177Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [177Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [177Lu]Lu-Gemini behaved similarly to [177Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [177Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor–to–normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [177Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [177Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [177Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [177Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [177Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered 177Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).




lab

Five additional monkeys from S.C. research lab recovered; 13 remain at large

An additional five rhesus macaque monkeys that escaped from a South Carolina research facility last week have been recovered, meaning about a dozen of the rhesus macaque primates remain at large.




lab

Costco recalls nearly 80,000 pounds of butter due to possible mislabeling

Costco voluntarily recalled 79,200 pounds of two types of its store-brand butter over the past month because their labels may not have said the products contain milk.




lab

Supermicro Introduces JBOF Storage Platform Powered by NVIDIA BlueField-3 for Scalable AI and HPC

SAN JOSE, Calif., Oct. 16, 2024 — Supermicro, Inc. is launching a new optimized storage system for high performance AI training, inference and HPC workloads. This JBOF (Just a Bunch […]

The post Supermicro Introduces JBOF Storage Platform Powered by NVIDIA BlueField-3 for Scalable AI and HPC appeared first on HPCwire.




lab

Xsight Labs Launches E1 SoC Built on TSMC’s 5nm Tech for AI Workloads

Oct. 16, 2024 — Xsight Labs, a leading fabless semiconductor company providing end-to-end connectivity solutions for next-generation hyperscale, edge, and AI data center networks, has announced the tape-out of the […]

The post Xsight Labs Launches E1 SoC Built on TSMC’s 5nm Tech for AI Workloads appeared first on HPCwire.




lab

PNNL-Microsoft Collaborate on Cloud Computing for Chemistry, More to Come

RICHLAND, Wash.—Some computing challenges are so big that it’s necessary to go all in. That’s the approach a diverse team of scientists and computing experts led by the Department of Energy’s […]

The post PNNL-Microsoft Collaborate on Cloud Computing for Chemistry, More to Come appeared first on HPCwire.



  • Features
  • Pacific Northwest National Laboratory

lab

Ethernet Alliance to Feature Cross-Industry Collaboration at ECOC 2024 Exhibit

BEAVERTON, Ore., Sept. 10, 2024 — The Ethernet Alliance, a global consortium dedicated to the continued success and advancement of Ethernet technologies, today announced details of its exhibit at stand #A3 […]

The post Ethernet Alliance to Feature Cross-Industry Collaboration at ECOC 2024 Exhibit appeared first on HPCwire.




lab

TSMC Collaborates with Ansys and Microsoft to Accelerate Photonic Simulations

PITTSBURGH, Sept. 24, 2024 — Ansys and TSMC today announced a successful pilot with Microsoft that significantly speeds-up the simulation and analysis of silicon photonic components. Together, the companies achieved […]

The post TSMC Collaborates with Ansys and Microsoft to Accelerate Photonic Simulations appeared first on HPCwire.




lab

Alphawave Semi and TSMC Collaborate on 3nm UCIe Die-to-Die Subsystem for AI and HPC

LONDON and TORONTO, Sept. 30, 2024 — Alphawave Semi, a global leader in high-speed connectivity and compute silicon for the world’s technology infrastructure, has unveiled the availability of the industry’s […]

The post Alphawave Semi and TSMC Collaborate on 3nm UCIe Die-to-Die Subsystem for AI and HPC appeared first on HPCwire.





lab

Watch: Loose wallaby caught on Kentucky security camera

A wallaby on the loose in Kentucky was caught on security camera during a nighttime visit to a Perry County family's front yard.




lab

NSF Issues Next Solicitation and More Detail on National Quantum Virtual Laboratory

After percolating for roughly a year, NSF has issued the next solicitation for the National Quantum Virtual Lab program — this one focused on design and implementation phases of the […]

The post NSF Issues Next Solicitation and More Detail on National Quantum Virtual Laboratory appeared first on HPCwire.





lab

Sylabs Highlights Confidential Computing in HPC at SC24 BoF Session

ATLANTA, Nov. 12, 2024 — Sylabs, in collaboration with Sandia National Laboratories, will host a Birds of a Feather (BoF) session at SC24 titled Integrating Confidential Computing into High-Performance Cloud Workflows. […]

The post Sylabs Highlights Confidential Computing in HPC at SC24 BoF Session appeared first on HPCwire.




lab

Costco recalls nearly 80,000 pounds of butter due to possible mislabeling

Costco voluntarily recalled 79,200 pounds of two types of its store-brand butter over the past month because their labels may not have said the products contain milk.




lab

Research Insights, HPC Expertise, Meaningful Collaborations Abound at TACCSTER 2024

It’s a wrap! The Texas Advanced Computing Center (TACC) at UT Austin welcomed more than 100 participants for the 7th annual TACC Symposium for Texas Researchers (TACCSTER). The event exists […]

The post Research Insights, HPC Expertise, Meaningful Collaborations Abound at TACCSTER 2024 appeared first on HPCwire.