dev Development of a novel mammalian display system for selection of antibodies against membrane proteins [Immunology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies. Full Article
dev Carnosine synthase deficiency is compatible with normal skeletal muscle and olfactory function but causes reduced olfactory sensitivity in aging mice [Developmental Biology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) are abundant peptides in the nervous system and skeletal muscle of many vertebrates. Many in vitro and in vivo studies demonstrated that exogenously added carnosine can improve muscle contraction, has antioxidant activity, and can quench various reactive aldehydes. Some of these functions likely contribute to the proposed anti-aging activity of carnosine. However, the physiological role of carnosine and related histidine-containing dipeptides (HCDs) is not clear. In this study, we generated a mouse line deficient in carnosine synthase (Carns1). HCDs were undetectable in the primary olfactory system and skeletal muscle of Carns1-deficient mice. Skeletal muscle contraction in these mice, however, was unaltered, and there was no evidence for reduced pH-buffering capacity in the skeletal muscle. Olfactory tests did not reveal any deterioration in 8-month-old mice lacking carnosine. In contrast, aging (18–24-month-old) Carns1-deficient mice exhibited olfactory sensitivity impairments that correlated with an age-dependent reduction in the number of olfactory receptor neurons. Whereas we found no evidence for elevated levels of lipoxidation and glycation end products in the primary olfactory system, protein carbonylation was increased in the olfactory bulb of aged Carns1-deficient mice. Taken together, these results suggest that carnosine in the olfactory system is not essential for information processing in the olfactory signaling pathway but does have a role in the long-term protection of olfactory receptor neurons, possibly through its antioxidant activity. Full Article
dev ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit [Developmental Biology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Distinct cell types emerge from embryonic stem cells through a precise and coordinated execution of gene expression programs during lineage commitment. This is established by the action of lineage specific transcription factors along with chromatin complexes. Numerous studies have focused on epigenetic factors that affect embryonic stem cells (ESC) self-renewal and pluripotency. However, the contribution of chromatin to lineage decisions at the exit from pluripotency has not been as extensively studied. Using a pooled epigenetic shRNA screen strategy, we identified chromatin-related factors critical for differentiation toward mesodermal and endodermal lineages. Here we reveal a critical role for the chromatin protein, ARID4B. Arid4b-deficient mESCs are similar to WT mESCs in the expression of pluripotency factors and their self-renewal. However, ARID4B loss results in defects in up-regulation of the meso/endodermal gene expression program. It was previously shown that Arid4b resides in a complex with SIN3A and HDACS 1 and 2. We identified a physical and functional interaction of ARID4B with HDAC1 rather than HDAC2, suggesting functionally distinct Sin3a subcomplexes might regulate cell fate decisions Finally, we observed that ARID4B deficiency leads to increased H3K27me3 and a reduced H3K27Ac level in key developmental gene loci, whereas a subset of genomic regions gain H3K27Ac marks. Our results demonstrate that epigenetic control through ARID4B plays a key role in the execution of lineage-specific gene expression programs at pluripotency exit. Full Article
dev Importance of endothelial Hey1 expression for thoracic great vessel development and its distal enhancer for Notch-dependent endothelial transcription [Gene Regulation] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre–mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic fourth PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large-caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help in understanding the significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation. Full Article
dev Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood [Microbiology] By www.jbc.org Published On :: 2018-11-09T03:40:54-08:00 The life cycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is known about the enzymes involved in the synthesis of these phospholipids, and recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug screening have provided new perspectives on the importance of some of these enzymes in parasite development and sexual differentiation and have identified targets for the development of new antimalarial drugs. This Minireview focuses on two phospholipid biosynthesis enzymes of P. falciparum that catalyze phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss our current understanding of the biochemical, structural, and biological functions of these enzymes and highlight efforts to use them as antimalarial drug targets. Full Article
dev A new vision for African agency in sustainable development By www.chathamhouse.org Published On :: Tue, 18 Oct 2022 15:00:01 +0000 A new vision for African agency in sustainable development Expert comment LJefferson 18 October 2022 Change is necessary not only in global economic structures and attitudes – but in African governance too. The conventional notion that Africa is mostly a consumer of norms and practices designed by the Global North has been repeatedly challenged and is increasingly being debunked. Increased African agency in international affairs is today a well-established and documented reality. But Africa’s influence still does not match the scale of the challenges that it faces on its pathway to sustainable development. Pushing for African agency in sustainable development also warrants a critical assessment of how ‘sustainable development’ should be defined, and how it can be achieved in terms of actual poverty reduction and real improvement in the lives of local poor Africans. Sustainable development has been a political catchphrase for over 30 years – but a genuine transition towards sustainability has yet to begin. African agency today Historically, there have been structural limitations on the agency of African stakeholders to shape development pathways. Chief among them, donor-recipient power dynamics have persistently promoted dependency and sustained institutional corruption. Many African countries are also challenged by economic incentives and infrastructure that have favoured the market demands and supply chains of former colonial powers, which largely remain reliant on natural resource extraction, and are marked by limited investment in value-addition activities and technology development. Donor-recipient power dynamics have persistently promoted dependency and sustained institutional corruption. Today, however, African agency is being exerted in a more assertive fashion. The African Union (AU), individual African states, civil society, the private sector and eminent and ordinary persons are all displaying Africa’s agency in steering global sustainable development priorities, namely by proposing their own development agenda, The African Union Agenda 2063, adopted in 2013. This was followed by the UN Sustainable Development Goals (Agenda 2030), which in many ways mirror Agenda 2063 – a clear demonstration of the influence of Africa in the global arena. Agenda 2063 is a strategic roadmap for Africa ‘to build an integrated, prosperous and peaceful Africa, driven and managed by its own citizens and development goals representing a dynamic force in the international arena’. Prepared following a broad-based participatory consultation, it advocates for inclusion and empowerment and provides an excellent vision for African countries and African people. The SDGs address several of the key shortcomings of their predecessor – the MDGs – and incorporate a broader and more transformative agenda that more adequately reflects the complex challenges of the 21st century and the need for structural reforms in the global economy and governance norms. In international forums on sustainable development, African countries are increasingly using their collective voice to change the discourse on how development can and should be done. For instance, by championing innovative solutions for carbon markets, African policy leaders are enabling access to climate finance for development while preserving Africa’s natural wealth. In the post-COVID era, championing investments in and leadership of Africa’s global health architecture demonstrates a desire that in the next pandemic, Africa CDC, AMA and continental manufacturers will play leading roles in determining Africa’s public health strategy and implementation. In trade, building on the groundwork led by the regional economic commissions, the AfCFTA will catalyse and scale regional integration, trade and cooperation, leading to promising new modes of supply chain and self-sufficiency. Encouraging signs, but persistent shortcomings Encouraging signs that African agency is gaining momentum cannot disguise the fact that Africa has yet to move from rhetoric to implementation in the realm of sustainable development. Continental visions often fail to go beyond declarations of intent, and have only limited influence on governance systems or national structural transformation, and African states remain vulnerable to economic shocks emanating from the global system. African agency should not be only seen as emanating from government, but also as being exerted by independent civil society organizations and committed ordinary individuals. Change will require governance systems that are coordinated, transparent, efficient, and inclusive, as well as tools, processes, and means (material, technical, and human) for successful implementation. There is an urgent need for a new governance paradigm in Africa and internationally, dealing with long-term social change. Notably, African agency should not be only seen as emanating from government, but also as being exerted by independent civil society organizations and committed ordinary individuals. Effective agency needs to be multi-faceted and multi-actor, and depends on the inclusiveness of African governments and their willingness to work with civil society in their strategic engagements with external partners. Both Agenda 2063 and the SDGs hold the potential for transformation, but implementation will depend on continued advocacy to hold authorities to account and change the dominant discourse, logic and rules of engagement at global, regional, national, and local levels. There is a need for a dynamic new model of African ‘development’. Time for a new vision Africa’s economic landscape is changing rapidly, with new regional and local value chains, and integrated regional economic corridors to link countries, minimize the burden of high-cost production and logistics, and boost real incomes and international competitiveness. But Africa continues to face structural challenges, including the need for large investment projects – at a time when Africa remains a net exporter of capital. Donors and development partners must reflect upon their prior modes of engagement and commit to genuine and equitable relationships with African states. Such partnerships must reflect mutual respect of ideas and accountability, and commit to making space in international forums and multi-lateral arrangements for African people and countries to realize their own visions for progress. More resources should be channelled to actors engaging closest to communities and people, who can better understand and communicate local needs. But African leaders and actors must also recognize that with the advent of resources and agency comes responsibility for results and outcomes, notably the need to improve governance. Gaps in accountability, widespread corruption, and lack of successful implementation and sustainability of projects must be addressed. Full Article
dev Quantitative proteomics reveal neuron projection development genes ARF4, KIF5B and RAB8A associated with Hirschsprung disease By www.mcponline.org Published On :: 2020-11-17 Qin ZhangNov 17, 2020; 0:RA120.002325v1-mcp.RA120.002325Research Full Article
dev Transcription factor NF-{kappa}B promotes acute lung inȷury via microRNA-99b-mediated PRDM1 down-regulation [Developmental Biology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Acute lung injury (ALI), is a rapidly progressing heterogenous pulmonary disorder that possesses a high risk of mortality. Accumulating evidence has implicated the activation of the p65 subunit of NF-κB [NF-κB(p65)] activation in the pathological process of ALI. microRNAs (miRNAs), a group of small RNA molecules, have emerged as major governors due to their post-transcriptional regulation of gene expression in a wide array of pathological processes, including ALI. The dysregulation of miRNAs and NF-κB activation has been implicated in human diseases. In the current study, we set out to decipher the convergence of miR-99b and p65 NF-κB activation in ALI pathology. We measured the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) in bronchoalveolar lavage fluid using ELISA. MH-S cells were cultured and their viability were detected with cell counting kit 8 (CCK8) assays. The results showed that miR-99b was up-regulated, while PRDM1 was down-regulated in a lipopolysaccharide (LPS)-induced murine model of ALI. Mechanistic investigations showed that NF-κB(p65) was enriched at the miR-99b promoter region, and further promoted its transcriptional activity. Furthermore, miR-99b targeted PRDM1 by binding to its 3'UTR, causing its down-regulation. This in-creased lung injury, as evidenced by increased wet/dry ratio of mouse lung, myeloperoxidase activity and pro-inflammatory cytokine secretion, and enhanced infiltration of inflammatory cells in lung tissues. Together, our findings indicate that NF-κB(p65) promotion of miR-99b can aggravate ALI in mice by down-regulating the expression of PRDM1. Full Article
dev Developing a vaccine against Zika By www.bmj.com Published On :: Thursday, November 10, 2016 - 16:26 Full Article
dev Developments in Mass Spectrometry for Glycosaminoglycan Analysis: A Review [Review] By www.mcponline.org Published On :: 2020-09-16T09:35:59-07:00 This review covers recent developments in glycosaminoglycan (GAG) analysis via mass spectrometry (MS). GAGs participate in a variety of biological functions, including cellular communication, wound healing, and anticoagulation, and are important targets for structural characterization. GAGs exhibit a diverse range of structural features due to the variety of O- and N-sulfation modifications and uronic acid C-5 epimerization that can occur, making their analysis a challenging target. Mass spectrometry approaches to the structure assignment of GAGs have been widely investigated, and new methodologies remain the subject of development. Advances in sample preparation, tandem MS techniques (MS/MS), on-line separations and automated analysis software have advanced the field of GAG analysis. These recent developments have led to remarkable improvements in the precision and time efficiency for the structural characterization of GAGs. Full Article
dev Integrated glycoproteomics identifies a role of N-glycosylation and galectin-1 on myogenesis and muscle development [Research] By www.mcponline.org Published On :: 2020-09-16T09:35:59-07:00 Many cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signaling. Aberrant protein glycosylation has been associated with the development of several muscular diseases suggesting essential glycan- and lectin-mediated functions in myogenesis and muscle development but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during a time-course of myogenesis in cell culture. We observed wide-spread changes in the abundance of several important lectins and enzymes facilitating glycan biosynthesis. Glycomics-based quantification of released N-linked glycans confirmed remodeling of the glycome consistent with the regulation of glycosyltransferases and glycosidases responsible for their formation including a previously unknown di-galactose-to-sialic acid switch supporting a functional role of these glycoepitopes in myogenesis. Furthermore, dynamic quantitative glycoproteomic analysis with multiplexed stable isotope labelling and analysis of enriched glycopeptides with multiple fragmentation approaches identified glycoproteins modified by these regulated glycans including several integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins most notably the up-regulation of galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early functional role of galectin-1 in the myogenic program. Importantly, similar changes in N-glycosylation and the up-regulation of galectin-1 during postnatal skeletal muscle development were observed in mice. Treatment of new-born mice with recombinant adeno-associated viruses to overexpress galectin-1 in the musculature resulted in enhanced muscle mass. Our data form a valuable resource to further understand the glycobiology of myogenesis and will aid the development of intervention strategies to promote healthy muscle development or regeneration. Full Article
dev Quantitative proteomics reveal neuron projection development genes ARF4, KIF5B and RAB8A associated with Hirschsprung disease [Research] By www.mcponline.org Published On :: 2020-11-17T10:35:13-08:00 Hirschsprung disease (HSCR) is a heterogeneous group of neurocristopathy characterized by the absence of the enteric ganglia along a variable length of the intestine. Genetic defects play a major role in the pathogenesis of HSCR while family studies of pathogenic variants in all the known genes (loci) only demonstrate incomplete penetrance and variable expressivity for unknown reasons. Here, we applied large-scale, quantitative proteomics of human colon tissues from 21 patients using iTRAQ method followed by bioinformatics analysis. Selected findings were confirmed by parallel reaction monitoring (PRM) verification. At last the interesting differentially expressed proteins were confirmed by western blot. A total of 5341 proteins in human colon tissues were identified. Among them, 664 proteins with >1.2-fold difference were identified in 6 groups: groups A1 and A2 pooled protein from the ganglionic and aganglionic colon of male, long-segment HSCR patients (L-HSCR, n=7); groups B1 and B2 pooled protein from the ganglionic and aganglionic colon of male, short-segment HSCR patients (S-HSCR, n=7); and groups C1 and C2 pooled protein from the ganglionic and aganglionic colon of female, S-HSCR patients (n=7). Based on these analyses, 49 proteins from 5 pathways were selected for PRM verification, including ribosome, endocytosis, spliceosome, oxidative phosphorylation and cell adhesion. The downregulation of three neuron projection development genes ARF4, KIF5B and RAB8A in the aganglionic part of the colon were verified in 15 paired colon samples using WB. The findings of this study will shed new light on the pathogenesis of HSCR and facilitate the development of therapeutic targets. Full Article
dev Dance of the Trillions: Developing Countries and Global Finance By www.chathamhouse.org Published On :: Fri, 06 Jul 2018 10:50:25 +0000 Dance of the Trillions: Developing Countries and Global Finance Book sysadmin 6 July 2018 David Lubin tells the story of what makes money flow from high-income countries to lower-income ones; what makes it flow out again; and how developing countries have sought protection against the volatility of international capital flows. Selected by the Financial Times as one of the best economics books of 2018, Dance of the Trillions traces an arc from the 1970s, when developing countries first gained access to international financial markets, to the present day. Underlying this story is a discussion of how the relationship between developing countries and global finance appears to be moving from one governed by the ‘Washington Consensus’ to one more likely to be shaped by Beijing. This book is part of the Insights series. Praise for Dance of the Trillions This brilliant, well-written book shows how the destinies of developing countries have been shaped by the capricious flows of trillions of US dollars in international capital. When the funds gushed in, many emerging markets flourished but were just as quickly left stricken when the tides of international capital deserted them. James Kynge, emerging markets editor, Financial Times and author of China Shakes the World About the author David Lubin is managing director and head of emerging markets economics at Citi, an American bank, where he is responsible for a team of more than 30 economists in 15 locations globally. Purchase UK (via Amazon) Rest of world (via Brookings Institution Press) Students (via Browns Books) Full Article
dev Business Development in Madagascar: How to Enable Entrepreneurialism By www.chathamhouse.org Published On :: Thu, 09 Nov 2017 10:30:00 +0000 Business Development in Madagascar: How to Enable Entrepreneurialism 15 November 2017 — 12:00PM TO 1:00PM Anonymous (not verified) 9 November 2017 Chatham House, London Madagascar’s business environment has improved in a period of stability ushered in with elections in 2013, which brought an end to the political crisis that had started in 2009. SME development has been constrained by poor access to credit and financial services, weak definition of property titles, and skills gaps and human capital shortfalls that have impeded the development of a managerial talent pool. However, the government has prioritized reform for company creation, granting construction permits and cross-border trade, in support of entrepreneurialism and business development. At this event, Erick Rajaonary, the CEO of the GuanoMad Group and president of the association of the Madagascar entrepreneurs, will discuss the how to create space for entrepreneurialism and prospects for broad based business development in Madagascar. Full Article
dev Water, Energy and Development in Angola: From Ambition to Actuality By www.chathamhouse.org Published On :: Wed, 28 Nov 2018 16:05:01 +0000 Water, Energy and Development in Angola: From Ambition to Actuality 13 December 2018 — 5:00PM TO 6:00PM Anonymous (not verified) 28 November 2018 Chatham House, London Many Angolans continue to face severe difficulties in accessing the country’s water and energy supplies, with over two-thirds of the population currently unable to connect to the national grid and two-fifths lacking access to drinking water. This already unequal picture is further amplified by the overwhelming concentration of power consumption in the capital: Luanda currently accounts for 70-75 per cent of consumption but supply remains patchy and marred by power cuts. At the core of the government response is an increased engagement with the private sector – including in the construction and modernization of dams and several projects to improve water infrastructure – and progress has been evident in installed power generation capacity which increased by 500MW between 2002 and 2012. Ultimately, a more equitable distribution of energy and water can provide significant benefits for Angola’s economy and citizens. At this event, HE João Baptista Borges will discuss progress made and challenges faced by Angola’s government in pursuit of water and energy provision and the priorities and prospects for the delivery of targeted improvements in future. Attendance at this event is by invitation only. Full Article
dev Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study By www.bmj.com Published On :: Thursday, January 18, 2018 - 16:21 Full Article
dev Can rhetoric match reality? Britain’s international development future By www.chathamhouse.org Published On :: Wed, 12 Apr 2023 09:07:13 +0000 Can rhetoric match reality? Britain’s international development future 27 April 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 12 April 2023 Chatham House and Online In conversation with Andrew Mitchell, minister of state, UK Foreign, Commonwealth and Development Office. Last month’s updated Integrated Review positioned international development as a key pillar of British foreign policy which sets out the importance of the UK’s efforts to shape the ‘global strategic environment’. Focusing heavily on Africa and the Indo-Pacific, international development will be central to the ambition of a ‘Global Britain’. The Integrated Review outlines seven priority areas to revitalize the drive to meet the Global Goals, with a climate security strategy at its heart, while seeking to go beyond official development assistance (ODA). However, there are major challenges ahead. Since 2021, the UK’s ODA has been cut from 0.7 per cent to 0.5 per cent gross national income (GNI). Some are concerned that since being subsumed by the UK Foreign Office, the UK Foreign, Commonwealth and Development Office has diluted the effectiveness of UK international development. Then there is the question of the strength of British public support for development assistance at a time of domestic economic hardship. Can rhetoric match reality? This event tackles questions including: What does the UK’s vision for international development mean in practice? Will aid and development help push Britain’s influence around the world? Can policymakers and politicians garner domestic support for international aid in times of economic uncertainty, and if so, how? Can the UK rebuild its reputation in the world while it doesn’t meet its 0.7 per cent GNI target? This event will be balloted for in-person attendance. Register your interest to join and a confirmation email will be sent to you on Tuesday 25 May at 12:00 BST to confirm your place at the event. As with all member events, questions from the audience drive the conversation. A coffee reception will immediately follow this event. Full Article
dev Development of 18F-Fluoromisonidazole Hypoxia PET/CT Diagnostic Interpretation Criteria and Validation of Interreader Reliability, Reproducibility, and Performance By jnm.snmjournals.org Published On :: 2024-10-01T04:08:08-07:00 Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with 18F-fluoromisonidazole (18F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret 18F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus–positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 18F-FDG PET/CT and 134 18F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no 18F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of 18F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if 18F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUVmax was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement ( = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement ( = 0.86). Quantitative assessment with an estimated best SUVmax ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement ( = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement ( = 0.86). Conclusion: Nuclear medicine physicians without 18F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria. Full Article
dev Watch: British daredevil dragged behind motorcycle at 159 mph By www.upi.com Published On :: Wed, 06 Nov 2024 16:28:30 -0500 A British daredevil was intentionally dragged behind his motorcycle at a speed of 159.52 mph to break a Guinness World Record. Full Article
dev EPB Offers Commercial Quantum Network for Quantum Developers By www.hpcwire.com Published On :: Tue, 10 Oct 2023 13:44:45 +0000 We hear a lot about quantum computers – sometimes too much – but not as much about quantum networking which will also be a critical component in making widespread use […] The post EPB Offers Commercial Quantum Network for Quantum Developers appeared first on HPCwire. Full Article Features EPB Quantum Network
dev What’s New with Chapel? Nine Questions for the Development Team By www.hpcwire.com Published On :: Wed, 04 Sep 2024 16:30:47 +0000 HPC news headlines often highlight the latest hardware speeds and feeds. While advances on the hardware front are important, improving the ability to write software for advanced systems is equally […] The post What’s New with Chapel? Nine Questions for the Development Team appeared first on HPCwire. Full Article Features c Chapel Fortan Python
dev IBM Develops New Quantum Benchmarking Tool — Benchpress By www.hpcwire.com Published On :: Thu, 26 Sep 2024 18:14:56 +0000 Benchmarking is an important topic in quantum computing. There’s consensus it’s needed but opinions vary widely on how to go about it. Last week, IBM introduced a new tool — […] The post IBM Develops New Quantum Benchmarking Tool — Benchpress appeared first on HPCwire. Full Article Short Takes
dev IBM Quantum Summit Evolves into Developer Conference By www.hpcwire.com Published On :: Wed, 02 Oct 2024 16:12:02 +0000 Instead of its usual quantum summit this year, IBM will hold its first IBM Quantum Developer Conference which the company is calling, “an exclusive, first-of-its-kind.” It’s planned as an in-person […] The post IBM Quantum Summit Evolves into Developer Conference appeared first on HPCwire. Full Article Short Takes IBM Quantum
dev Fujitsu and Carnegie Mellon University Develop AI-powered Social Digital Twin Tech with Traffic Data from Pittsburgh By www.hpcwire.com Published On :: Thu, 07 Mar 2024 21:23:29 +0000 TOKYO, March 7, 2024 — Fujitsu Limited and Carnegie Mellon University today announced the development of a new technology to visualize traffic situations, including people and vehicles, as part of […] The post Fujitsu and Carnegie Mellon University Develop AI-powered Social Digital Twin Tech with Traffic Data from Pittsburgh appeared first on HPCwire. Full Article
dev ORNL Develops Solution to Residual Stress Challenges in 3D-Printed Metal Structures By www.hpcwire.com Published On :: Tue, 26 Mar 2024 21:42:30 +0000 March 26, 2024 — Scientists at the Department of Energy’s Oak Ridge National Laboratory have determined how to avoid costly and potentially irreparable damage to large metallic parts fabricated through […] The post ORNL Develops Solution to Residual Stress Challenges in 3D-Printed Metal Structures appeared first on HPCwire. Full Article
dev BSC Develops AI Model to Predict Stroke Risk Using Mobile Devices By www.hpcwire.com Published On :: Fri, 08 Nov 2024 14:26:21 +0000 Nov. 8, 2024 — Barcelona Supercomputing Center‘s Innostroke project aims to transform the prevention and monitoring of stroke, one of the leading causes of death and disability worldwide, through artificial […] The post BSC Develops AI Model to Predict Stroke Risk Using Mobile Devices appeared first on HPCwire. Full Article
dev Preclinical research and development of a herbal antipyretic drug based on leaves of Ceiba pentandra (Malvaceae) By resources.medipacademy.com Published On :: 30 July 2022 11:32:03 Background: Faced with the limits of synthetic antipyretic substances, in particular their involvement in the occurrence of numerous and often serious adverse effects; the challenge is in search of new antipyretics especially from the African traditional pharmacopoeia. The objective of this study was to evaluate the antipyretic activity of an aqueous extract and a formulation of Ceiba pentandra, with a view to designing an herbal antipyretic drug. Methods: Trials of formulation of an antipyretic syrup with leaves extract of Ceiba pentandra were carried out. The antipyretic activity was investigated by the bewer's yeast induced pyrexia. Physicochemical and microbiological stability tests were carried out on the syrup. Results: It was found with the extract an antipyretic activity at doses of 125 mg/kg and 150 mg/kg. The effect was greater for the 125 mg/kg dose with inhibition percentages ranging from 27.58% to 71.25%. This antipyretic activity was early (from 30 minutes) and was preserved during the four hours of the experiment. The syrup dosed at 125 mg/kg gave an activity similar to that of the extract by significantly reducing the hyperthermia in the rats. Regarding the stability tests, the syrup remained stable both physico-chemically and microbiologically throughout the study period (28 days) both when exposed to low temperature (5 °±3 ° C) and at high temperature (40°±2° C). Conclusions: Ceiba pentandra leaves have antipyretic activity and could be used for the development of an herbal antipyretic drug. Full Article
dev Watch: Disney+ teases 'Alien: Earth,' 'Andor' S2, 'Daredevil: Born Again' in 2025 preview By www.upi.com Published On :: Tue, 12 Nov 2024 11:53:02 -0500 "Alien: Earth," "Andor" Season 2, "The Bear" Season 4, "Daredevil: Born Again" and other Disney+ and Hulu series will premiere in 2025. Full Article
dev Beyond Hallucinations, This Could Be Schizophrenia’s Most Devastating Symptom (M) By www.spring.org.uk Published On :: Mon, 04 Nov 2024 18:00:15 +0000 A surprising brain defect could hold the key to schizophrenia’s toughest symptoms. Full Article Neuroscience Schizophrenia subscribers-only
dev DeVos: Give Religious Groups Equal Consideration for Education Grants By blogs.edweek.org Published On :: Fri, 07 Aug 2020 00:00:00 +0000 The new U.S. Department of Education guidance creates a federal process for individuals and organizations to file complaints under the federal Religious Freedom Restoration Act. Full Article Montana
dev Coronavirus Squeezes Supply of Chromebooks, iPads, and Other Digital Learning Devices By www.edweek.org Published On :: Wed, 01 Apr 2020 00:00:00 +0000 School districts are competing against each other for purchases of digital devices as remote learning expands to schools across the country. Full Article Massachusetts
dev Deval Patrick, Obama Education Ally, Announces Presidential Run By blogs.edweek.org Published On :: Thu, 14 Nov 2019 00:00:00 +0000 A businessman, Patrick served two terms as governor of Massachusetts and has credited education with his own dramatic rise to success. Full Article Massachusetts
dev DeVos Visits Kentucky School Recovering From Shooting By blogs.edweek.org Published On :: Wed, 17 Apr 2019 00:00:00 +0000 U.S. Secretary of Education Betsy DeVos on Wednesday visited a Kentucky high school that is recovering from a 2018 shooting to award additional grant money meant to aid its recovery efforts. Full Article Kentucky
dev Betsy DeVos Greenlights ESSA Plans for Nebraska and North Carolina By blogs.edweek.org Published On :: Tue, 05 Jun 2018 00:00:00 +0000 U.S. Ed Secretary DeVos has approved plans for 46 states, plus the District of Columbia and Puerto Rico. Still waiting: California, Florida, Oklahoma, and Utah. Full Article North_Carolina
dev Betsy DeVos Approves Vermont and Maine ESSA Plans By blogs.edweek.org Published On :: Thu, 31 Aug 2017 00:00:00 +0000 The latest approvals mean 12 of the 17 state plans submitted so far for Every Student Succeeds Act implementation have been given the federal go-ahead. Full Article Maine
dev Betsy DeVos Greenlights ESSA Plans for Nebraska and North Carolina By blogs.edweek.org Published On :: Tue, 05 Jun 2018 00:00:00 +0000 U.S. Ed Secretary DeVos has approved plans for 46 states, plus the District of Columbia and Puerto Rico. Still waiting: California, Florida, Oklahoma, and Utah. Full Article Nebraska
dev DeVos says free college amounts to a 'socialist takeover' By www.edweek.org Published On :: 2020-12-02T08:39:40-05:00 Full Article Education
dev Betsy DeVos OKs ESSA Plans for California, Utah By blogs.edweek.org Published On :: Thu, 12 Jul 2018 00:00:00 +0000 U.S. Secretary of Education Betsy DeVos green-lighted California and Utah's plans to implement the Every Student Succeed Act. That means just one state is still waiting: Florida. Full Article Utah
dev Betsy DeVos OKs ESSA Plans for South Carolina and Virginia By blogs.edweek.org Published On :: Thu, 03 May 2018 00:00:00 +0000 U.S. Secretary of Education Betsy DeVos has greenlighted two more Every Student Succeeds Act plans from Virginia and South Carolina. That brings the grand total of states with approved plans to 39, plus the District of Columbia and Puerto Rico. Full Article South_Carolina
dev Betsy DeVos to Visit Manufacturer Where Hundreds of Teachers Work Second Jobs By blogs.edweek.org Published On :: Wed, 17 Jul 2019 00:00:00 +0000 U.S. Secretary of Education Betsy DeVos will hold a workforce event at a South Carolina drug manufacturer that employs hundreds of cash-strapped teachers in second jobs. Full Article South_Carolina
dev Schools Handed Out Millions of Digital Devices Under COVID-19. Now, Thousands Are Missing By www.edweek.org Published On :: Thu, 23 Jul 2020 00:00:00 +0000 Some districts are scrambling to account for thousands of devices—a task made more urgent by the uncertainty over when students will be able to return to school buildings full-time. Full Article South_Carolina
dev Betsy DeVos Greenlights Florida's ESSA Plan. Now All 50 States Have Been Approved. By blogs.edweek.org Published On :: Wed, 26 Sep 2018 00:00:00 +0000 Education Secretary Betsy DeVos has finally OK'd Florida's plan to implement the Every Student Succeeds Act. That means that single state, plus Puerto Rico and the District of Columbia, has gotten the go-ahead for its plan. Full Article Florida
dev Betsy DeVos Gave a State Charter School Grants. Lawmakers Have Said No Thanks, Twice By blogs.edweek.org Published On :: Wed, 15 Jan 2020 00:00:00 +0000 It's pretty obvious by now that many Democrats are growing increasingly uncomfortable supporting charter schools. But New Hampshire lawmakers have taken the unusual step of rejecting federal charter school grant money. Full Article New_Hampshire
dev Betsy DeVos Approves ESSA Plans for Alaska and Iowa By blogs.edweek.org Published On :: Wed, 16 May 2018 00:00:00 +0000 That brings the number of states with approved plans to 44, plus the District of Columbia and Puerto Rico. Still awaiting the OK: California, Florida, Nebraska, North Carolina, Oklahoma, and Utah Full Article Iowa
dev Betsy DeVos OKs ESSA Plans for Minnesota, West Virginia By blogs.edweek.org Published On :: Wed, 10 Jan 2018 00:00:00 +0000 Minnesota and West Virginia are the first two states that submitted plans in the fall to win federal approval. Full Article Minnesota
dev Spencer Knight looks to continue strong return to NHL, will start against visiting Devils By sports.yahoo.com Published On :: Tue, 12 Nov 2024 16:48:29 GMT Knight receives a more traditional start, at home, with days off ahead of the game Full Article article Sports
dev Former Devils Goalie Lands With New Team By sports.yahoo.com Published On :: Tue, 12 Nov 2024 20:32:15 GMT The former New Jersey Devils goalie finds themselves playing for a new Western Conference team. Full Article article Sports
dev 4 Former Devils Expected To Be In Panthers Lineup By sports.yahoo.com Published On :: Tue, 12 Nov 2024 23:30:00 GMT The New Jersey Devils will face former teammates Tomas Nosek, Jesper Boqvist, AJ Greer, and Dmitry Kulikov on Tuesday night in their game against the Florida Panthers. Full Article article Sports
dev Devils defeat Panthers, 4-1, to snap Florida's seven-game winning streak By sports.yahoo.com Published On :: Wed, 13 Nov 2024 03:27:13 GMT Timo Meier scored the go-ahead goal late in the second period, Jacob Markstrom made 33 saves and the New Jersey Devils snapped Florida’s seven-game winning streak by beating the Panthers 4-1 on Tuesday night. Full Article article Sports
dev Betsy DeVos Approves ESSA Plans for Alaska and Iowa By blogs.edweek.org Published On :: Wed, 16 May 2018 00:00:00 +0000 That brings the number of states with approved plans to 44, plus the District of Columbia and Puerto Rico. Still awaiting the OK: California, Florida, Nebraska, North Carolina, Oklahoma, and Utah Full Article Alaska