Patterns-based Evaluation of Open Source BPM Systems: The Cases of jBPM, OpenWFE, and Enhydra Shark

In keeping with the proliferation of free software development initiatives and the increased interest in the business process management domain, many open source workflow and business process management systems have appeared during the last few years and are now under active development. This upsurge gives rise to two important questions: what are the capabilities of these systems? and how do they compare to each other and to their closed source counterparts? i.e. in other words what is the state-of-the-art in the area?. To gain an insight into the area, we have conducted an in-depth analysis of three of the major open source workflow management systems - jBPM, OpenWFE and Enhydra Shark, the results of which are reported here. This analysis is based on the workflow patterns framework and provides a continuation of the series of evaluations performed using the same framework on closed source systems, business process modeling languages and web-service composition standards. The results from evaluations of the three open source systems are compared with each other and also with the results from evaluations of three representative closed source systems - Staffware, WebSphere MQ and Oracle BPEL PM, documented in earlier works. The overall conclusion is that open source systems are targeted more toward developers rather than business analysts. They generally provide less support for the patterns than closed source systems, particularly with respect to the resource perspective which describes the various ways in which work is distributed amongst business users and managed through to completion

SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801

All known recently emerged human coronaviruses probably originated in bats1. Here we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats harbour endogenous coronaviruses capable of direct transmission into humans. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Acute SARS-CoV-2 infection was highly cytopathic and induced a robust and sustained type I interferon and inflammatory cytokine/chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for coronavirus infection. Our results show that therapeutic and prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II–III clinical trials, dramatically inhibited SARS-CoV-2 replication in vivo and thus has significant potential for the prevention and treatment of COVID-19

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Socio-demographic, medical and social-cognitive correlates of physical activity behavior among older adults (45-70 years): a cross-sectional study

BACKGROUND: Present study aimed to identify socio-demographic, medical and social-cognitive correlates of physical activity among Dutch older individuals. METHODS: A systematic random sample of 2,568 Dutch participants aged 45–70 years filled out the validated modified Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire on physical activity. Socio-demographic and social-cognitive correlates were measured with validated instruments; medical correlates were checked by a general practitioner. The study had a cross-sectional design and the data collection ran from March 2005 until August 2006. Linear regression analyses were conducted to identify correlates of PA. We separated the findings for men from those for women to explore potential gender-specific associations. RESULTS: Being female, living in North Limburg or North-Brabant, having a higher educational level, a higher perceived behavioral control, more knowledge about PA advantages, a stronger habitual PA behavior, having more action plans and a stronger intention to engage in PA were significantly associated with higher PA levels. Being older, being a smoker, having a higher body mass index (BMI), having a paid job, observing others being physically active and overestimating one's PA level were associated with being less physically active. Socio-demographic and medical correlates significantly explained 20% of the variance of PA behavior while social-cognitive correlates as attitude explained an additional 4% and intention together with actual control explained another 1% of the variance of PA behavior. CONCLUSION: There may be stable individual differences that influence PA in view of the fact that several socio-demographic and medical factors were not completely mediated by the socio-cognitive factors. The current study may help to focus PA interventions for individuals aged 45–70 years on influential socio-demographic, medical and social-cognitive correlates. Physical activity was significantly associated with age, gender, education, BMI, work situation, region of residence, smoking, awareness, advantages, descriptive norm, perceived behavioral control, habit, action plans and intention

Expression of APOBEC family members as regulators of endogenous retroelements and malignant transformation in systemic autoimmunity

Objective: To explore whether APOBEC family members are involved in the response to inappropriate expression of L1 retroelements in primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), as well as in SS related lymphomagenesis. Methods: Minor salivary glands (MSG) and kidney biopsy (KB) specimens were obtained from 41 SS patients (10 with lymphoma) and 23 patients with SLE, respectively. PBMC and sera were also collected from 73 SLE patients. Full-length L1 transcripts, members of the APOBEC and IFN family were quantitated by real time PCR. Type I IFN activity was assessed in lupus plasma by a cell assay. Results: APOBEC3A was increased in SS MSG, SLE KB and PBMC and correlated with L1. AID and APOBEC3G were particularly overexpressed in MSG tissues derived from SS lymphoma patients. Conclusion: These data reveal a previously unappreciated role of APOBEC family proteins in the pathogenesis of systemic autoimmunity and SS related lymphomagenesis. © 202

New constraints on the kinematic, relativistic and evolutionary properties of the PSR J1757−1854 double neutron star system

PSR J1757$-$1854 is one of the most relativistic double neutron star binary systems known in our Galaxy, with an orbital period of $P_\text{b}=4.4\,\text{hr}$ and an orbital eccentricity of $e=0.61$. As such, it has promised to be an outstanding laboratory for conducting tests of relativistic gravity. We present the results of a 6-yr campaign with the 100-m Green Bank and 64-m Parkes radio telescopes, designed to capitalise on this potential. We identify secular changes in the profile morphology and polarisation of PSR J1757$-$1854, confirming the presence of geodetic precession and allowing the constraint of viewing geometry solutions consistent with General Relativity. We also update PSR J1757$-$1854's timing, including new constraints of the pulsar's proper motion, post-Keplerian parameters and component masses. We conclude that the radiative test of gravity provided by PSR J1757$-$1854 is fundamentally limited to a precision of 0.3 per cent due to the pulsar's unknown distance. A search for pulsations from the companion neutron star is also described, with negative results. We provide an updated evaluation of the system's evolutionary history, finding strong support for a large kick velocity of $w\ge280\,\text{km s}^{-1}$ following the second progenitor supernova. Finally, we reassess PSR J1757$-$1854's potential to provide new relativistic tests of gravity. We conclude that a 3-$\sigma$ constraint of the change in the projected semi-major axis ($\dot{x}$) associated with Lense-Thirring precession is expected no earlier than 2031. Meanwhile, we anticipate a 3-$\sigma$ measurement of the relativistic orbital deformation parameter $\delta_\theta$ as soon as 2026.PSR J1757−1854 is one of the most relativistic double neutron star binary systems known in our Galaxy, with an orbital period of Pb=4.4hr and an orbital eccentricity of e=0.61. As such, it has promised to be an outstanding laboratory for conducting tests of relativistic gravity. We present the results of a 6-yr campaign with the 100-m Green Bank and 64-m Parkes radio telescopes, designed to capitalise on this potential. We identify secular changes in the profile morphology and polarisation of PSR J1757−1854, confirming the presence of geodetic precession and allowing the constraint of viewing geometry solutions consistent with General Relativity. We also update PSR J1757−1854's timing, including new constraints of the pulsar's proper motion, post-Keplerian parameters and component masses. We conclude that the radiative test of gravity provided by PSR J1757−1854 is fundamentally limited to a precision of 0.3 per cent due to the pulsar's unknown distance. A search for pulsations from the companion neutron star is also described, with negative results. We provide an updated evaluation of the system's evolutionary history, finding strong support for a large kick velocity of w≥280km s−1 following the second progenitor supernova. Finally, we reassess PSR J1757−1854's potential to provide new relativistic tests of gravity. We conclude that a 3-σ constraint of the change in the projected semi-major axis (x˙) associated with Lense-Thirring precession is expected no earlier than 2031. Meanwhile, we anticipate a 3-σ measurement of the relativistic orbital deformation parameter δθ as soon as 2026

Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: Macrophage harbingers of disease severity

Objective Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that targets salivary and lacrimal glands and may be accompanied by multiorgan systemic manifestations. To further the understanding of immunopathology associated with SS and identify potential therapeutic targets, we undertook the present study comparing the gene expression profiles of salivary glands with severe inflammation versus those of salivary glands with mild or no disease. Methods Using microarray profiling of salivary gland tissue from patients with SS and control subjects, we identified target genes, which were further characterized in tissue, serum, and cultured cell populations by real-time polymerase chain reaction and protein analysis. Results Among the most highly expressed SS genes were those associated with myeloid cells, including members of the mammalian chitinase family, which had not previously been shown to be associated with exocrinopathies. Both chitinase 3-like protein 1 and chitinase 1, highly conserved chitinase-like glycoproteins (one with enzymatic activity and one lacking enzymatic activity), were evident at the transcriptome level and were detected within inflamed tissue. Chitinases were expressed during monocyte-to-macrophage differentiation and their levels augmented by stimulation with cytokines, including interferon-α (IFNα). Conclusion Because elevated expression of these and other macrophage-derived molecules corresponded with more severe SS, the present observations suggest that macrophages have potential immunopathologic involvement in SS and that the tissue macrophage transcription profile reflects multiple genes induced by IFNα. Copyright © 2011 by the American College of Rheumatology

Determination of the Cytosolic NADPH/NADP Ratio in Saccharomyces cerevisiae using Shikimate Dehydrogenase as Sensor Reaction

Eukaryotic metabolism is organised in complex networks of enzyme catalysed reactions which are distributed over different organelles. To quantify the compartmentalised reactions, quantitative measurements of relevant physiological variables in different compartments are needed, especially of cofactors. NADP(H) are critical components in cellular redox metabolism. Currently, available metabolite measurement methods allow whole cell measurements. Here a metabolite sensor based on a fast equilibrium reaction is introduced to monitor the cytosolic NADPH/NADP ratio in Saccharomyces cerevisiae:. The cytosolic NADPH/NADP ratio was determined by measuring the shikimate and dehydroshikimate concentrations (by GC-MS/MS). The cytosolic NADPH/NADP ratio was determined under batch and chemostat (aerobic, glucose-limited, D\u89=\u890.1\u89h '1) conditions, to be 22.0\u89±\u892.6 and 15.6\u89±\u890.6, respectively. These ratios were much higher than the whole cell NADPH/NADP ratio (1.05\u89±\u890.08). In response to a glucose pulse, the cytosolic NADPH/NADP ratio first increased very rapidly and restored the steady state ratio after 3 minutes. In contrast to this dynamic observation, the whole cell NADPH/NADP ratio remained nearly constant. The novel cytosol NADPH/NADP measurements provide new insights into the thermodynamic driving forces for NADP(H)-dependent reactions, like amino acid synthesis, product pathways like fatty acid production or the mevalonate pathway.BT/BiotechnologyApplied Science

Hydroxychloroquine in the primary thrombosis prophylaxis of antiphospholipid antibody positive patients without systemic autoimmune disease

Objective: The objective of this study was to determine the efficacy of hydroxychloroquine (HCQ) in the primary thrombosis prevention of antiphospholipid antibody (aPL)-positive patients with no other systemic autoimmune diseases. Methods: Under the auspices of Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, a multicenter, international, randomized controlled trial (RCT) was initiated, in which persistently aPL-positive but thrombosis-free patients without systemic autoimmune diseases were randomized to receive HCQ or no treatment in addition to their standard regimen. The primary objective was the efficacy of HCQ in preventing the first thrombosis. The secondary objectives were the thrombosis incidence rate, and the effects of HCQ on aPL profile and mortality rate. Patients were risk-stratified based on antiplatelet agent use. The goal was to follow patients every 6 months for 5 years. Results: We recruited 20 persistently aPL-positive patients (female: 19, mean age: 46.6 ± 9.9 years, and baseline antiplatelet medication: 14); 9/20 were randomized to HCQ. During the mean follow-up of 1.7 years, no patients developed thrombosis or a serious adverse event. The study was terminated early due to the low recruitment rate, exacerbated by the prolonged manufacturing shortage and significant price increase of HCQ in the United States. Conclusion: Given that a small number of patients with a relatively short follow-up were enrolled in our RCT, and no patients developed thrombosis, we cannot accurately assess the effectiveness of HCQ for primary thrombosis prevention in persistently aPL-positive patients with no other systemic autoimmune diseases. Our experience suggests that conducting an international RCT, especially without pharmaceutical support, is an extremely challenging undertaking. © 2017, © The Author(s) 2017