Gas-phase spin relaxation of 129Xe

Journal ArticleWe have completed an extensive study of 129Xe longitudinal spin relaxation in the gas phase, involving both intrinsic and extrinsic mechanisms. The dominant intrinsic relaxation is mediated by the formation of persistent Xe2 van der Waals dimers. The dependence of this relaxation on applied magnetic field yields the relative contributions of the spin-rotation and chemical-shift-anisotropy interactions; the former dominates at magnetic fields below a few tesla. This relaxation also shows an inverse quadratic dependence on temperature T; the maximum low-field intrinsic relaxation for pure xenon at room temperature (measured here to be 4.6 h, in agreement with previous work) increases by ~60% for T=100 °C. The dominant extrinsic relaxation is mediated by collisions with the walls of the glass container. Wall relaxation was studied in silicone-coated alkali-metal-free cells, which showed long (many hours or more) and robust relaxation times, even at the low magnetic fields typical for spin-exchange optical pumping (~3 mT). The further suppression of wall relaxation for magnetic fields above a few tesla is consistent with the interaction of 129Xe with paramagnetic spins on or inside the surface coating. At 14.1 T and sufficiently low xenon density, we measured a relaxation time T1 =99 h, with an inferred wall-relaxation time of 174 h. A prototype large storage cell (12 cm diameter) was constructed to take advantage of the apparent increase in wall-relaxation time for cells with a smaller surfaceto- volume ratio. The measured relaxation time in this cell at 3 mT and 100 °C was 5.75 h. Such a cell (or one even larger) could be used to store many liters of hyperpolarized 129Xe produced by a flow-through polarizer and accumulator for up to three times longer than currently implemented schemes involving freezing xenon in liquid nitrogen

Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes

DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono-and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes

Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes

DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono-and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes

THI safety system

International audienceFor several years, GANIL has been allowed to reach a maximum beam power of six kilowatts (400W in normal mode) thanks to the THI system (High Intensity Transport System). Three modes of running are necessary to accelerate a THI beam ("Injector" mode, "tuning" mode and "surveillance" mode). The "surveillance" mode requires a safety system to protect equipment against beam losses. Inside cyclotrons, diagnostics measure beam-loss currents at the injection and extraction devices. Along beam lines, diaphragms measure beam-loss currents at the input and output of dipoles. Current transformers are used for beam transmission measurements through beam lines and the cyclotrons. The safety system controls beam losses and quickly cuts the beam with a chopper if losses exceed thresholds. These thresholds can be seen and changed by software

Association of Pesticide Exposure with Neurologic Dysfunction and Disease

Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neuro-toxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease

Expert perceptions of game-changing innovations towards net zero

Current technological improvements are yet to put the world on track to net-zero, which will require the uptake of transformative low-carbon innovations to supplement mitigation efforts. However, the role of such innovations is not yet fully understood; some of these ‘miracles’ are considered indispensable to Paris Agreement-compliant mitigation, but their limitations, availability, and potential remain a source of debate. We evaluate such potentially game-changing innovations from the experts' perspective, aiming to support the design of realistic decarbonisation scenarios and better-informed net-zero policy strategies. In a worldwide survey, 260 climate and energy experts assessed transformative innovations against their mitigation potential, at-scale availability and/or widescale adoption, and risk of delayed diffusion. Hierarchical clustering and multi-criteria decision-making revealed differences in perceptions of core technological innovations, with next-generation energy storage, alternative building materials, iron-ore electrolysis, and hydrogen in steelmaking emerging as top priorities. Instead, technologies highly represented in well-below-2°C scenarios seemingly feature considerable and impactful delays, hinting at the need to re-evaluate their role in future pathways. Experts' assessments appear to converge more on the potential role of other disruptive innovations, including lifestyle shifts and alternative economic models, indicating the importance of scenarios including non-technological and demand-side innovations. To provide insights for expert elicitation processes, we finally note caveats related to the level of representativeness among the 260 engaged experts, the level of their expertise that may have varied across the examined innovations, and the potential for subjective interpretation to which the employed linguistic scales may be prone to

Studying Health Outcomes in Farmworker Populations Exposed to Pesticides

A major goal of studying farmworkers is to better understand how their work environment, including exposure to pesticides, affects their health. Although a number of health conditions have been associated with pesticide exposure, clear linkages have yet to be made between exposure and health effects except in cases of acute pesticide exposure. In this article, we review the most common health end points that have been studied and describe the epidemiologic challenges encountered in studying these health effects of pesticides among farmworkers, including the difficulties in accessing the population and challenges associated with obtaining health end point data. The assessment of neurobehavioral health effects serves as one of the most common and best examples of an approach used to study health outcomes in farmworkers and other populations exposed to pesticides. We review the current limitations in neurobehavioral assessment and strategies to improve these analytical methods. Emerging techniques to improve our assessment of health effects associated with pesticide exposure are reviewed. These techniques, which in most cases have not been applied to farmworker populations, hold promise in our ability to study and understand the relationship between pesticide exposure and a variety of health effects in this population

Recent developments for beam intensity increase operation

International audienceThe aim of the beam intensity increase operation (THI project) is to multiply the present intensities for lightest ions by a factor of fifteen in order to reach maximum power of six kilowatts [1]. The main objective is the production of large amounts of rare isotopes, either with SISSI (device intended for producing radioactive beams), or with SPIRAL (production and acceleration of radioactive ion beams). As part of this THI project, new developments have been required such as spiral scanners, for beanl profile measurements, and safety system to protect equipments against beam losses. Other developments are being carried on to improve the high intensity beam operation

Patterns of medical management of overactive bladder (OAB) and benign prostatic hyperplasia (BPH) in the United States

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142147/1/nau23276.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142147/2/nau23276_am.pd