Reductive Decomposition of A Diazonium Intermediate by Dithiothreitol Affects The Determination of NOS Turnover Rates

Accurate determination of nitrite either as such or as the breakdown product of nitric oxide (NO) is critical in a host of enzymatic reactions in various settings addressing structure–function relationships, as well as mechanisms and kinetics of molecular operation of enzymes. The most common way to quantify nitrite, for instance in nitric oxide synthase (NOS) mechanistic investigations, is the spectrophotometric assay based on the Griess reaction through external standard calibration. This assay is based on a two-step diazotization reaction, in which a cationic diazonium derivative of sulfanilamide is formed as intermediate before the final absorbing azo-product. We show that this intermediate is very sensitive to reducing agents that may be transferred from the reaction media under investigation. The interaction of this vital intermediate with the reducing agent, dithiothreitol (DTT), which is widely used in NOS reactions, is characterized by both electrochemical and spectroscopic means. The effect of DTT on the performance of external calibration, both in sample recovery studies and in actual NOS reactions, is presented. Finally an alternative method of standard additions, which partially compensates for the accuracy and sensitivity problems of external calibration, is proposed and discussed

Lowering of ground state induced by core-shell structure in strontium titanate

International audienc

A Pitfall in the Diagnosis of Unresectable Liver Metastases: Multiple Bile Duct Hamartomas (von Meyenburg Complexes)

Von Meyenburg complexes (VMC) are a cluster of benign liver malformations including biliary cystic lesions, with congenital fibrocollagenous stroma. This rare entity can mimick multiple secondary hepatic lesions. We report a case of a 56-year-old woman who had multiples liver lesions 12 years after operation for breast cancer. Biopsy of the hepatic lesion confirmed the diagnosis of VMC. Preoperative discovery of multiple gray-white nodular lesions scattered on the surface of the liver should not always contraindicate curative liver resection. The diagnosis of VMC should be known and confirmed with liver biopsy

International Space Station Research for the Next Decade: International Coordination and Research Accomplishments

During 2011, the International Space Station reached an important milestone in the completion of assembly and the shift to the focus on a full and continuous utilization mission in space. The ISS partnership itself has also met a milestone in the coordination and cooperation of utilization activities including research, technology development and education. We plan and track all ISS utilization activities jointly and have structures in place to cooperate on common goals by sharing ISS assets and resources, and extend the impacts and efficiency of utilization activities. The basic utilization areas on the ISS include research, technology development and testing, and education/outreach. Research can be categorized as applied research for future exploration, basic research taking advantage of the microgravity and open space environment, and Industrial R&D / commercial research focused at industrial product development and improvement. Technology development activities range from testing of new spacecraft systems and materials to the use of ISS as an analogue for future exploration missions to destinations beyond Earth orbit. This presentation, made jointly by all ISS international partners, will highlight the ways that international cooperation in all of these areas is achieved, and the overall accomplishments that have come as well as future perspectives from the cooperation. Recently, the partnership has made special efforts to increase the coordination and impact of ISS utilization that has humanitarian benefits. In this context the paper will highlight tentative ISS utilization developments in the areas of Earth remote sensing, medical technology transfer, and education/outreach

International Space Station Benefits for Humanity

The ISS partnership has seen a substantial increase in research accomplished, crew efforts devoted to research, and results of ongoing research and technology development. The ISS laboratory is providing a unique environment for research and international collaboration that benefits humankind. Benefits come from the engineering development, the international partnership, and from the research results. Benefits can be of three different types: scientific discovery, applications to life on Earth, and applications to future exploration. Working across all ISS partners, we identified key themes where the activities on the ISS improve the lives of people on Earth--not only within the partner nations, but also in other nations of the world. Three major themes of benefits to life on earth emerged from our review: benefits to human health, education, and Earth observation and disaster response. Other themes are growing as use of the ISS continues. Benefits to human health range from advancements in surgical technology, improved telemedicine, and new treatments for disease. Earth observations from the ISS provide a wide range of observations that include: marine vessel tracking, disaster monitoring and climate change. The ISS participates in a number of educational activities aimed to inspire students of all ages to learn about science, technology, engineering and mathematics. To date over 63 countries have directly participated in some aspect of ISS research or education. In summarizing these benefits and accomplishments, ISS partners are also identifying ways to further extend the benefits to people in developing countries for the benefits of humankind

International Space Station Accomplishments Update: Scientific Discovery, Advancing Future Exploration, and Benefits Brought Home to Earth

Throughout the history of the International Space Station (ISS), crews on board have conducted a variety of scientific research and educational activities. Well into the second year of full utilization of the ISS laboratory, the trend of scientific accomplishments and educational opportunities continues to grow. More than 1500 investigations have been conducted on the ISS since the first module launched in 1998, with over 700 scientific publications. The ISS provides a unique environment for research, international collaboration and educational activities that benefit humankind. This paper will provide an up to date summary of key investigations, facilities, publications, and benefits from ISS research that have developed over the past year. Discoveries in human physiology and nutrition have enabled astronauts to return from ISS with little bone loss, even as scientists seek to better understand the new puzzle of "ocular syndrome" affecting the vision of up to half of astronauts. The geneLAB campaign will unify life sciences investigations to seek genomic, proteomic, and metabolomics of the effect of microgravity on life as a whole. Combustion scientists identified a new "cold flame" phenomenon that has the potential to improve models of efficient combustion back on Earth. A significant number of instruments in Earth remote sensing and astrophysics are providing new access to data or nearing completion for launch, making ISS a significant platform for understanding of the Earth system and the universe. In addition to multidisciplinary research, the ISS partnership conducts a myriad of student led research investigations and educational activities aimed at increasing student interest in science, technology, engineering and mathematics (STEM). Over the past year, the ISS partnership compiled new statistics of the educational impact of the ISS on students around the world. More than 43 million students, from kindergarten to graduate school, with more than 28 million teachers located in 49 countries have participated in some aspect of ISS educational activities. These activities include student-developed investigations, education competitions, and classroom versions of ISS investigations, participating in ISS investigator experiments, ISS hardware development, educational demonstrations, and cultural activities. Through the many inquiry-based educational activities, students and teachers are encouraged to participate in the ISS program thus motivating the next generation of students to pursue careers in STEM

Genome-Wide Association Study in a Lebanese Cohort Confirms PHACTR1 as a Major Determinant of Coronary Artery Stenosis

The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10−5). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10−6), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10−10). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD

International Research Results and Accomplishments From the International Space Station

No abstract availabl

Large Scale Association Analysis Identifies Three Susceptibility Loci for Coronary Artery Disease

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR = 0.68, p = 0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR = 1.33, p = 0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries