The neutron-capture reaction plays a critical role in the synthesis of the elements in stars and is important for societal applications including nuclear power generation and stockpile-stewardship ...science. However, it is difficult-if not impossible-to directly measure neutron capture cross sections for the exotic, short-lived nuclei that participate in these processes. In this Letter we demonstrate a new technique which can be used to indirectly determine neutron-capture cross sections for exotic systems. This technique makes use of the (d,p) transfer reaction, which has long been used as a tool to study the structure of nuclei. Recent advances in reaction theory, together with data collected using this reaction, enable the determination of neutron-capture cross sections for short-lived nuclei. A benchmark study of the ^{95}Mo(d,p) reaction is presented, which illustrates the approach and provides guidance for future applications of the method with short-lived isotopes produced at rare isotope accelerators.
We describe a simple scheme, truncated-channel injection, to inject electrons directly into the wakefield driven by a high-intensity laser pulse guided in an all-optical plasma channel. We use this ...approach to generate dark-current-free 1.2 GeV, 4.5% relative energy spread electron bunches with 120 TW laser pulses guided in a 110 mm-long hydrodynamic optical-field-ionized plasma channel. Our experiments and particle-in-cell simulations show that high-quality electron bunches were only obtained when the drive pulse was closely aligned with the channel axis, and was focused close to the density down ramp formed at the channel entrance. Start-to-end simulations of the channel formation, and electron injection and acceleration show that increasing the channel length to 410 mm would yield 3.65 GeV bunches, with a slice energy spread ∼5×10^{-4}.
Summary
Synthetic biology requires the design and implementation of novel enzymes, genetic circuits or even entire cells, which can be controlled by the user. RNA‐based regulatory elements have many ...important functional properties in this regard, such as their modular nature and their ability to respond to specific external stimuli. These properties have led to the widespread exploration of their use as gene regulation devices in synthetic biology. In this review, we focus on two major types of RNA elements: riboswitches and RNA thermometers (RNATs). We describe their general structure and function, before discussing their potential uses in synthetic biology (e.g. in the production of biofuels and biodegradable plastics). We also discuss their limitations, and novel strategies to implement RNA‐based regulatory devices in biotechnological applications. We close with a description of some common model organisms used in synthetic biology, with a focus on the current applications and limitations of RNA‐based regulation.
The imminent threat of viral epidemics and pandemics dictates a need for therapeutic approaches that target viral pathology irrespective of the infecting strain. Reactive oxygen species are ancient ...processes that protect plants, fungi and animals against invading pathogens including bacteria. However, in mammals reactive oxygen species production paradoxically promotes virus pathogenicity by mechanisms not yet defined. Here we identify that the primary enzymatic source of reactive oxygen species, NOX2 oxidase, is activated by single stranded RNA and DNA viruses in endocytic compartments resulting in endosomal hydrogen peroxide generation, which suppresses antiviral and humoral signaling networks via modification of a unique, highly conserved cysteine residue (Cys98) on Toll-like receptor-7. Accordingly, targeted inhibition of endosomal reactive oxygen species production abrogates influenza A virus pathogenicity. We conclude that endosomal reactive oxygen species promote fundamental molecular mechanisms of viral pathogenicity, and the specific targeting of this pathogenic process with endosomal-targeted reactive oxygen species inhibitors has implications for the treatment of viral disease.Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.
There is a pressing need for a holistic characterisation of people with incurable cancer. In this group, where quality of life and improvement of symptoms are therapeutic priorities, the physical and ...biochemical manifestations of cancer are often studied separately, giving an incomplete picture. In order to improve care, spur therapeutic innovation, provide meaningful endpoints for trials and set priorities for future research, work must be done to explore how the tumour influences the clinical phenotype. Characterisation of the host-tumour interaction may also provide information regarding prognosis, allowing appropriate planning of investigations, treatment and referral to palliative medicine services.
Routine EValuatiOn of people LivIng with caNcer (REVOLUTION) is a prospective observational study that aims to characterise people with incurable cancer around five key areas, namely body composition, physical activity, systemic inflammatory response, symptoms, and quality of life by developing a bio-repository. Participants will initially be recruited from a single centre in the UK and will have assessments of body composition (bio-impedance analysis BIA and computed tomography CT), assessment of physical activity using a physical activity monitor, measurement of simple markers of inflammation and plasma cytokine proteins and three symptom and quality of life questionnaires.
This study aims to create a comprehensive biochemical and clinical characterisation of people with incurable cancer. Data in this study can be used to give a better understanding of the 'symptom phenotype' and quality of life determinants, development of a profile of the systemic inflammatory response and a detailed characterisation of body composition.
We present two wide-field catalogues of photometrically selected emission line galaxies (ELGs) at z ... 0.8 covering about 2800 deg super( 2) over the south galactic cap. The catalogues were obtained ...using a Fisher discriminant technique described in a companion paper. The two catalogues differ by the imaging used to define the Fisher discriminant: the first catalogue includes imaging from the Sloan Digital Sky Survey and the Wide-field Infrared Survey Explorer, the second also includes information from the South Galactic Cap U-band Sky Survey. Containing respectively 560 045 and 615 601 objects, they represent the largest ELG catalogues available today and were designed for the ELG programme of the extended Baryon Oscillation Spectroscopic Survey (eBOSS). We study potential sources of systematic variation in the angular distribution of the selected ELGs due to fluctuations of the observational parameters. We model the influence of the observational parameters using a multivariate regression and implement a weighting scheme which allows effective removal of all of the systematic errors induced by the observational parameters. We show that fluctuations in the imaging zero-points of the photometric bands have minor impact on the angular distribution of objects in our catalogues. We compute the angular clustering of both catalogues and show that our weighting procedure effectively removes spurious clustering on large scales. We fit a model to the small-scale angular clustering, showing that the selections have similar biases of 1.35/D sub( a)(z) and 1.28/D sub( a)(z). Both catalogues are publicly available. (ProQuest: ... denotes formulae/symbols omitted.)
We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by ...optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.
Modern treatment strategies have increased life expectancy in multiple myeloma, but little is known about the endocrine, metabolic and nutritional status of long-term survivors. We performed ...endocrine, metabolic, bone, body composition and nutritional evaluations in 32 patients with intensively-treated, advanced but stable, myeloma a median duration of 6 years from diagnosis and three lines of intensive treatment, including at least one haematopoietic SCT procedure. All patients were off active treatment. There was a high prevalence of endocrine dysfunction: hypothyroidism (9%), hypogonadism (65% males) and elevated prolactin (19%). Adrenocortical function was preserved despite large cumulative corticosteroid pretreatment. Biochemical markers were consistent with postmenopausal status in all females and infertility in males. Nutritionally, 59% were vitamin D insufficient/deficient, reduced serum folate in 25% and vitamin B12 in 6%. Total body DEXA scanning confirmed 'sarcopenic-obesity' in 65%, but reduced bone density was seen in a minority. We conclude that potentially correctable endocrine, metabolic and nutritional abnormalities are prevalent in heavily-treated patients with stable multiple myeloma. Preservation of bone supports the efficacy of bisphosphonate treatment from diagnosis, but sarcopenic-obesity may contribute to frailty. Ultimately, multi-system screening and appropriate interventions may optimise quality of long-term survival and further studies are warranted.
Context:
Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot ...replace the cortisol circadian rhythm.
Objectives:
The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration.
Design, Setting, and Patients:
Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology.
Main Outcome Measures:
The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP).
Results:
In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700–1500 h; P = .002), and afternoon (1500–2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700–1500 h; P = .02) 17-OHP AUC.
Conclusions:
Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH.
Local and international research has identified rural origin as an important reason why healthcare professionals (HCPs) work in rural areas, and in South Africa (SA) considerable effort has gone into ...recruiting and training rural-origin students. However, there is little information in the SA literature on where graduates supported by these initiatives work, and whether they contribute to the rural workforce long term.
To determine the number of years that rural-origin Umthombo Youth Development Foundation (UYDF)-supported graduates of different disciplines worked at rural public healthcare facilities (PHCFs).
A retrospective descriptive study reviewed work record data of 405 UYDF graduates, to calculate the number of years they worked at a rural PHCF. Data were analysed descriptively and presented in tables with totals and percentages.
Ninety percent (363/405) of UYDF-supported graduates returned to work at a rural PHCF. High percentages of social workers (85%), optometrists (80%), speech therapists, nurses (72%) and dental therapists (70%) worked for ≥5 years at a rural PHCF, while only 13% of audiologists, 14% of doctors, 29% of pharmacists, and 28% of dentists and occupational therapists worked at a rural PHCF for ≥5 years. Ten percent (42/405) of graduates did not work at a rural PHCF at all. A total of 110/124 (89%) of doctors supported by UYDF had worked at a rural PHCF, with 32% (40/124) working at a rural PHCF for ≥3 years. Overall, 54% of UYDF-supported graduates (219/405) worked for ≥3 years at a rural PHCF, and 38.5% (157/405) worked for ≥5 years at rural PHCFs. The majority of UYDF graduates had contributed towards long-term staffing of rural PHCFs. Lack of professional development opportunities at rural PHCFs as well as the reduced number of funded posts at rural PHCFs reduced the effectiveness of the UYDF initiative.
The UYDF Scholarship Scheme has shown that investment in rural students through a bonded scholarship can contribute to staffing rural PHCFs, as >90% of graduates worked at rural PHCFs, and for some disciplines >70% of graduates worked for ≥5 years at a rural PHCF. Allied HCPs worked on average for longer periods at rural PHCFs than doctors.
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