Should We Learn Probabilistic Models for Model Checking? A New Approach and An Empirical Study

Many automated system analysis techniques (e.g., model checking, model-based testing) rely on first obtaining a model of the system under analysis. System modeling is often done manually, which is often considered as a hindrance to adopt model-based system analysis and development techniques. To overcome this problem, researchers have proposed to automatically "learn" models based on sample system executions and shown that the learned models can be useful sometimes. There are however many questions to be answered. For instance, how much shall we generalize from the observed samples and how fast would learning converge? Or, would the analysis result based on the learned model be more accurate than the estimation we could have obtained by sampling many system executions within the same amount of time? In this work, we investigate existing algorithms for learning probabilistic models for model checking, propose an evolution-based approach for better controlling the degree of generalization and conduct an empirical study in order to answer the questions. One of our findings is that the effectiveness of learning may sometimes be limited.Comment: 15 pages, plus 2 reference pages, accepted by FASE 2017 in ETAP

Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.Fil: Goncearenco, Alexander. National Institutes of Health; Estados UnidosFil: Li, Minghui. Soochow University; China. National Institutes of Health; Estados UnidosFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Shoemaker, Benjamin A. National Institutes of Health; Estados UnidosFil: Panchenko, Anna R. National Institutes of Health; Estados Unido

Multifocal multi-organ ischaemia and infarction in a preterm baby due to maternal intravenous cocaine use: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although the adverse effects of cocaine use in pregnancy are well recognised, we believe this case highlights the importance of considering the route of administration, and suggests the possibility of multifocal damage relating to intravenous use.</p> <p>Case presentation</p> <p>A Caucasian female baby of 29-weeks' gestation was spontaneously delivered and subsequently developed multi-organ failure considered unrelated to simple prematurity. Intensive care was re-orientated following the development of massive intraventricular haemorrhage.</p> <p>Conclusion</p> <p>This case illustrates the need for regular cranial ultrasound in babies of pregnancies at risk due to intravenous cocaine use and also the necessity of counselling women who misuse cocaine in the antenatal period. As such, this article will be of most interest to paediatric and obstetric staff.</p

«Prozessintelligenz» : Gegenstand und Ziele der Studie

«Intelligente Prozesse, «intelligentes Prozessmanagement», «iBPM» sind Schlagworte, die in erster Linie eingesetzt werden, um Technologien zu vermarkten. Die Begriffe lassen viel Raum für Interpretation und Assoziationen. Können Unternehmen den Hype ignorieren oder bietet «Prozessintelligenz» die Chance, das Prozessmanagement aus einem anderen Blickwinkel zu betrachten und weiterzuentwickeln? Doch was ist Prozessintelligenz? Welche Lösungsansätze, Erfahrungen und Erfolgsmuster gibt es bereits in Unternehmen? Welche Methoden und Werkzeuge kommen zum Einsatz, um Prozesse «intelligenter» zu machen? Diesen Fragen hat sich die Business-Process-Management-Studie 2015 gestellt, mit der das Institut für Wirtschaftsinformatik der Zürcher Hochschule für Angewandte Wissenschaften School of Management and Law seit 2011 regelmässig Status quo und Best Practices im deutschsprachigen Raum erhebt

Complement C3 Deficiency Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension in Mice

Background: Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension. Methodology/Principal Findings: Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice. Conclusions: Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans. © 2011 Bauer et al

BASS. XXXV. The MBH-σ* Relation of 105 Month Swift-BAT Type 1 AGNs

We present two independent measurements of stellar velocity dispersions (sigma(star)) from the Ca II H+K lambda 3969, 3934 and Mg I b lambda 5183, 5172, 5167 region (3880-5550 angstrom) and the calcium triplet region (8350-8750 angstrom) for 173 hard X-ray-selected Type 1 active galactic nuclei (AGNs; z &lt;= 0.08) from the 105 month Swift-BAT catalog. We construct one of the largest samples of local Type 1 AGNs that have both single-epoch virial black hole mass (M-BH) estimates and sigma(star) measurements obtained from high spectral resolution data, allowing us to test the usage of such methods for supermassive black hole studies. We find that the two independent sigma(star) measurements are highly consistent with each other, with an average offset of only 0.002 +/- 0.001 dex. Comparing M-BH estimates based on broad emission lines and stellar velocity dispersion measurements, we find that the former is systematically lower by approximate to 0.12 dex. Consequently, Eddington ratios estimated through broad-line MBH determinations are similarly biased (but in the opposite way). We argue that the discrepancy is driven by extinction in the broad-line region. We also find an anticorrelation between the offset from the M-BH-sigma(star) relation and the Eddington ratio. Our sample of Type 1 AGNs shows a shallower M-BH-sigma(star) relation (with a power-law exponent of approximate to 3.5) compared with that of inactive galaxies (with a power-law exponent of approximate to 4.5), confirming earlier results obtained from smaller samples

Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results: In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.Bernhard T Baune, Carsten Konrad, Dominik Grotegerd, Thomas Suslow, Eva Birosova, Patricia Ohrmann, Jochen Bauer, Volker Arolt, Walter Heindel, Katharina Domschke, Sonja Schöning, Astrid V Rauch, Christina Uhlmann, Harald Kugel and Udo Dannlowsk

Functional Dichotomy between NKG2D and CD28-Mediated Co-Stimulation in Human CD8+ T Cells

Both CD28 and NKG2D can function as co-stimulatory receptors in human CD8+ T cells. However, their independent functional contributions in distinct CD8+ T cell subsets are not well understood. In this study, CD8+ T cells in human peripheral blood- and lung-derived lymphocytes were analyzed for CD28 and NKG2D expression and function. We found a higher level of CD28 expression in PBMC-derived naïve (CD45RA+CD27+) and memory (CD45RA−CD27+) CD8+ T cells (CD28Hi), while its expression was significantly lower in effector (CD45RA+CD27−) CD8+ T cells (CD28Lo). Irrespective of the differences in the CD28 levels, NKG2D expression was comparable in all three CD8+ T cell subsets. CD28 and NKG2D expressions followed similar patterns in human lung-resident GILGFVFTL/HLA-A2-pentamer positive CD8+ T cells. Co-stimulation of CD28Lo effector T cells via NKG2D significantly increased IFN-γ and TNF-α levels. On the contrary, irrespective of its comparable levels, NKG2D-mediated co-stimulation failed to augment IFN-γ and TNF-α production in CD28Hi naïve/memory T cells. Additionally, CD28-mediated co-stimulation was obligatory for IL-2 generation and thereby its production was limited only to the CD28Hi naïve/memory subsets. MICA, a ligand for NKG2D was abundantly expressed in the tracheal epithelial cells, validating the use of NKG2D as the major co-stimulatory receptor by tissue-resident CD8+ effector T cells. Based on these findings, we conclude that NKG2D may provide an expanded level of co-stimulation to tissue-residing effector CD8+ T cells. Thus, incorporation of co-stimulation via NKG2D in addition to CD28 is essential to activate tumor or tissue-infiltrating effector CD8+ T cells. However, boosting a recall immune response via memory CD8+ T cells or vaccination to stimulate naïve CD8+ T cells would require CD28-mediated co-stimulation

Supported by science?: what canadian naturopaths advertise to the public

<p>Abstract</p> <p>Background</p> <p>The increasing popularity of complementary and alternative medicines in Canada has led to regulatory reforms in Ontario and British Columbia. Yet the evidence for efficacy of these therapies is still a source of debate. Those who are supportive of naturopathic medicine often support the field by claiming that the naturopathic treatments are supported by science and scientific research.</p> <p>Methods</p> <p>To compare provinces that are regulated and unregulated, we examined the websites of 53 naturopathic clinics in Alberta and British Columbia to gain a sense of the degree to which the services advertised by naturopaths are science based.</p> <p>Results</p> <p>There were very few differences between the provinces in terms of the types of services offered and conditions treated. Many of the most common treatments--such as homeopathy, chelation and colon cleanses--are viewed by the scientific community to be of questionable value and have no scientific evidence of efficacy beyond placebo.</p> <p>Conclusions</p> <p>A review of the therapies advertised on the websites of clinics offering naturopathic treatments does not support the proposition that naturopathic medicine is a science and evidence-based practice.</p