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The Cherenkov Telescope Array (CTA) is the next-generation atmospheric Cherenkov gamma-ray observatory. The Observation Execution System (OES) team within the CTA project is designing and prototyping the software to execute the observations and to handle the acquisition of scientific data at GB/s rates. In this contribution we show the OES system as it is being designed using the Unified Modeling Language (UML) and Systems Modeling (SysML) formalisms. In addition, we present the status of the associated prototyping activities.

The Cherenkov Telescope Array (CTA), as the next generation ground-based very high-energy gamma-ray observatory, is defining new areas beyond those related to physics. It is also creating new demands on the control and data acquisition system. CTA will consist of two installations, one in each hemisphere, containing tens of telescopes of different sizes. The ACTL (array control and data acquisition) system will consist of the hardware and software that is necessary to control and monitor the CTA array, as well as to time-stamp, read-out, filter and store the scientific data at aggregated rates of a few GB s. The ACTL system must implement a flexible software architecture to permit the simultaneous automatic operation of multiple sub-arrays of telescopes with a minimum personnel effort on site. In addition ACTL must be able to modify the observation schedule on timescales of a few tens of seconds, to account for changing environmental conditions or to prioritize incoming scientific alerts from time-critical transient phenomena such as gamma-ray bursts. This contribution summarizes the status of the development of the software architecture and the main design choices and plans.

Many practitioners - especially those in small and medium enterprises -work in organizations that don't yet implement dedicated requirements engineering methods. Furthermore, these organizations often lack the appropriate knowledge and tools for implementing RE. For this target group of practitioners, we propose patterns as a format for RE knowledge transfer, which can provide guidance by offering easy access to proven methods and tools. As an example, we provide four patterns for basic RE activities.

This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to gaγ ∼ 1.5 × 10-11 GeV-1, and masses up to ma ∼ 0.25 eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups.

BabyIAXO is the intermediate stage of the International Axion Observatory (IAXO) to be hosted at DESY. Its primary goal is the detection of solar axions following the axion helioscope technique. Axions are converted into photons in a large magnet that is pointing to the sun. The resulting X-rays are focused by appropriate X-ray optics and detected by sensitive low-background detectors placed at the focal spot. The aim of this article is to provide an accurate quantitative description of the different components (such as the magnet, optics, and X-ray detectors) involved in the detection of axions. Our efforts have focused on developing robust and integrated software tools to model these helioscope components, enabling future assessments of modifications or upgrades to any part of the IAXO axion helioscope and evaluating the potential impact on the experiment's sensitivity. In this manuscript, we demonstrate the application of these tools by presenting a precise signal calculation and response analysis of BabyIAXO's sensitivity to the axion-photon coupling. Though focusing on the Primakoff solar flux component, our virtual helioscope model can be used to test different production mechanisms, allowing for direct comparisons within a unified framework.

This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to \\(g_{a\\gamma} \\sim 1.5 \\times 10^{-11}\\) GeV\\(^{-1}\\), and masses up to \\(m_a\\sim 0.25\\) eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups.

T cell receptors (TCRs) encode the history of antigenic challenge within an individual and have the potential to serve as molecular markers of infection. In addition to peptide antigens bound to highly polymorphic MHC molecules, T cells have also evolved to recognize bacterial lipids when bound to non-polymorphic CD1 molecules. One such subset, germline-encoded, mycolyl lipid-reactive (GEM) T cells, recognizes mycobacterial cell wall lipids and expresses a conserved TCR-ɑ chain that is shared among genetically unrelated individuals. We developed a quantitative PCR assay to determine expression of the GEM TCR-ɑ nucleotide sequence in human tissues and blood. This assay was validated on plasmids and T cell lines. We tested blood samples from South African subjects with or without tuberculin reactivity or with active tuberculosis disease. We were able to detect GEM TCR-ɑ above the limit of detection in 92% of donors but found no difference in GEM TCR-ɑ expression among the three groups after normalizing for total TCR-ɑ expression. In a cohort of leprosy patients from Nepal, we successfully detected GEM TCR-ɑ in 100% of skin biopsies with histologically confirmed tuberculoid and lepromatous leprosy. Thus, GEM T cells constitute part of the T cell repertoire in the skin. However, GEM TCR-ɑ expression was not different between leprosy patients and control subjects after normalization. Further, these results reveal the feasibility of developing a simple, field deployable molecular diagnostic based on mycobacterial lipid antigen-specific TCR sequences that are readily detectable in human tissues and blood independent of genetic background.

Erythema nodosum leprosum (ENL) is a severe multisystem immune mediated complication of borderline lepromatous leprosy and lepromatous leprosy. ENL is associated with skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. The treatment of ENL requires immunosuppression, which is often required for prolonged periods of time and may lead to serious adverse effects. ENL and its treatment is associated with increased mortality and economic hardship. Improved, evidence-based treatments for ENL are needed; however, defining the severity of ENL and outcome measures for treatment studies is difficult because of the multiple organ systems involved. A cross-sectional study was performed, by the members of the Erythema Nodosum Leprosum International STudy (ENLIST) Group, of patients with ENL attending seven leprosy referral centres in Brazil, Ethiopia, India, Nepal, the Philippines and the United Kingdom. We systematically documented the clinical features and type of ENL, its severity and the drugs used to treat it. Patients with chronic ENL were more likely to be assessed as having severe ENL. Pain, the most frequent symptom, assessed using a semi-quantitative scale was significantly worse in individuals with \"severe\" ENL. Our findings will determine the items to be included in a severity scale of ENL which we are developing and validating. The study also provides data on the clinical features of ENL, which can be incorporated into a definition of ENL and used for outcome measures in treatment studies.

Virus-like particles are an emerging class of nano-biotechnology with the Tobacco Mosaic Virus (TMV) having found a wide range of applications in imaging, drug delivery, and vaccine development. TMV is typically produced in planta , and, as an RNA virus, is highly susceptible to natural mutation that may impact its properties. Over the course of 2 years, from 2018 until 2020, our laboratory followed a spontaneous point mutation in the TMV coat protein—first observed as a 30 Da difference in electrospray ionization mass spectrometry (ESI–MS). The mutation would have been difficult to notice by electrophoretic mobility in agarose or SDS-PAGE and does not alter viral morphology as assessed by transmission electron microscopy. The mutation responsible for the 30 Da difference between the wild-type (wTMV) and mutant (mTMV) coat proteins was identified by a bottom-up proteomic approach as a change from glycine to serine at position 155 based on collision-induced dissociation data. Since residue 155 is located on the outer surface of the TMV rod, it is feasible that the mutation alters TMV surface chemistry. However, enzyme-linked immunosorbent assays found no difference in binding between mTMV and wTMV. Functionalization of a nearby residue, tyrosine 139, with diazonium salt, also appears unaffected. Overall, this study highlights the necessity of standard workflows to quality-control viral stocks. We suggest that ESI–MS is a straightforward and low-cost way to identify emerging mutants in coat proteins.

IntroductionErythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the ‘MTX and prednisolone study in ENL’ (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL.Methods and analysisMaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients’ reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events.Ethics and disseminationResults will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.