Almost Linear B\"uchi Automata

We introduce a new fragment of Linear temporal logic (LTL) called LIO and a new class of Buechi automata (BA) called Almost linear Buechi automata (ALBA). We provide effective translations between LIO and ALBA showing that the two formalisms are expressively equivalent. While standard translations of LTL into BA use some intermediate formalisms, the presented translation of LIO into ALBA is direct. As we expect applications of ALBA in model checking, we compare the expressiveness of ALBA with other classes of Buechi automata studied in this context and we indicate possible applications

Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis

BACKGROUND: Psychosis is a severe mental condition that is characterized by a loss of contact with reality and is typically associated with hallucinations and delusional beliefs. There are numerous psychiatric conditions that present with psychotic symptoms, most importantly schizophrenia, bipolar affective disorder, and some forms of severe depression referred to as psychotic depression. The pathological mechanisms resulting in psychotic symptoms are not understood, nor is it understood whether the various psychotic illnesses are the result of similar biochemical disturbances. The identification of biological markers (so-called biomarkers) of psychosis is a fundamental step towards a better understanding of the pathogenesis of psychosis and holds the potential for more objective testing methods. METHODS AND FINDINGS: Surface-enhanced laser desorption ionization mass spectrometry was employed to profile proteins and peptides in a total of 179 cerebrospinal fluid samples (58 schizophrenia patients, 16 patients with depression, five patients with obsessive-compulsive disorder, ten patients with Alzheimer disease, and 90 controls). Our results show a highly significant differential distribution of samples from healthy volunteers away from drug-naïve patients with first-onset paranoid schizophrenia. The key alterations were the up-regulation of a 40-amino acid VGF-derived peptide, the down-regulation of transthyretin at approximately 4 kDa, and a peptide cluster at approximately 6,800-7,300 Da (which is likely to be influenced by the doubly charged ions of the transthyretin protein cluster). These schizophrenia-specific protein/peptide changes were replicated in an independent sample set. Both experiments achieved a specificity of 95% and a sensitivity of 80% or 88% in the initial study and in a subsequent validation study, respectively. CONCLUSIONS: Our results suggest that the application of modern proteomics techniques, particularly mass spectrometric approaches, holds the potential to advance the understanding of the biochemical basis of psychiatric disorders and may in turn allow for the development of diagnostics and improved therapeutics. Further studies are required to validate the clinical effectiveness and disease specificity of the identified biomarkers

Political Leadership and Global Governance: Structural Power Versus Custodial Stewardship

This article examines the role of political leadership within the realm of global governance. Drawing upon relevant theories of political agency, particular attention is given to addressing the relationship between leadership and collective action. A two-level analysis of institution building in relation to maritime security and economic trade and investment reveals both strengths and weaknesses in practice. A review of the Law of the Sea Convention and the Multilateral Investment Agreement provides a salutary reminder that material power does not translate easily into dominating the rules of international conduct. The cases of the Asia Pacific Economic Cooperation Forum and the Trans-Pacific Partnership further highlight the importance of mixed sources of political leadership in responding to economic challenges at the regional level. The policy implication for both the United States and China is that taking the lead in Global Governance, either jointly or multilaterally, will require a renewed focus upon custodial stewardship that aims to realign interests with long-term goals

Venting of a separate CO2-rich gas phase from submarine arc volcanoes: Examples from the Mariana and Tonga-Kermadec arcs

Submersible dives on 22 active submarine volcanoes on the Mariana and Tonga-Kermadec arcs have discovered systems on six of these volcanoes that, in addition to discharging hot vent fluid, are also venting a separate CO2-rich phase either in the form of gas bubbles or liquid CO2 droplets. One of the most impressive is the Champagne vent site on NW Eifuku in the northern Mariana Arc, which is discharging cold droplets of liquid CO2 at an estimated rate of 23 mol CO2/s, about 0.1% of the global mid-ocean ridge (MOR) carbon flux. Three other Mariana Arc submarine volcanoes (NW Rota-1, Nikko, and Daikoku), and two volcanoes on the Tonga-Kermadec Arc (Giggenbach and Volcano-1) also have vent fields discharging CO2-rich gas bubbles. The vent fluids at these volcanoes have very high CO2 concentrations and elevated C/3He and δ 13C (CO2) ratios compared to MOR systems, indicating a contribution to the carbon flux from subducted marine carbonates and organic material. Analysis of the CO2 concentrations shows that most of the fluids are undersaturated with CO2. This deviation from equilibrium would not be expected for pressure release degassing of an ascending fluid saturated with CO2. Mechanisms to produce a separate CO2-rich gas phase at the seafloor require direct injection of magmatic CO2-rich gas. The ascending CO2-rich gas could then partially dissolve into seawater circulating within the volcano edifice without reaching equilibrium. Alternatively, an ascending high-temperature, CO2-rich aqueous fluid could boil to produce a CO2-rich gas phase and a CO2-depleted liquid. These findings indicate that carbon fluxes from submarine arcs may be higher than previously estimated, and that experiments to estimate carbon fluxes at submarine arc volcanoes are merited. Hydrothermal sites such as these with a separate gas phase are valuable natural laboratories for studying the effects of high CO2 concentrations on marine ecosystems

In Vitro Efficacy of Myxococcus fulvus ANSM068 to Biotransform Aflatoxin B1

Aflatoxin B1 (AFB1) is commonly found in cereals and animal feeds and causes a significant threat to the food industry and animal production. Several microbial isolates with high AFB1 transformation ability have been identified in our previous studies. The aim of this research was to characterize one of those isolates, Myxococcus fulvus ANSM068, and to explore its biotransformation mechanism. The bacterial isolate of M. fulvus ANSM068, isolated from deer feces, was able to transform AFB1 by 80.7% in liquid VY/2 medium after incubation at 30 °C for 72 h. The supernatant of the bacterial culture was more effective in transforming AFB1 as compared to the cells alone and the cell extract. The transformation activity was significantly reduced and eradicated after the culture supernatant was treated with proteinase K, proteinase K plus SDS and heating. Culture conditions, including nitrogen source, initial pH and incubation temperature were evaluated for an optimal AFB1 transformation. Liquid chromatography mass spectrometry (LCMS) analyses showed that AFB1 was transformed to a structurally different compound. Infrared analysis (IR) indicated that the lactone ring on the AFB1 molecule was modified by the culture supernatant. Chromatographies on DEAE-Ion exchange and Sephadex-Molecular sieve and SDS-PAGE electrophoresis were used to determine active components from the culture supernatant, indicating that enzyme(s) were responsible for the AFB1 biotransformation. This is the first report on AFB1 transformation by a strain of myxobacteria through enzymatic reaction(s)

Cross-Reactivity of Herpesvirus-Specific CD8 T Cell Lines Toward Allogeneic Class I MHC Molecules

Although association between persistent viral infection and allograft rejection is well characterized, few examples of T-cell cross-reactivity between self-MHC/viral and allogeneic HLA molecules have been documented so far. We appraised in this study the alloreactivity of CD8 T cell lines specific for immunodominant epitopes from human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). CD8 T cell lines were generated after sorting with immunomagnetic beads coated with either pp65495–503/A*0201, BMLF1259–267/A*0201, or BZLF154–64/B*3501 multimeric complexes. Alloreactivity of the CD8 T cell lines against allogeneic class I MHC alleles was assessed by screening of (i) TNF-α production against COS-7 cells transfected with as many as 39 individual HLA class I-encoding cDNA, and (ii) cytotoxicity activity toward a large panel of HLA-typed EBV-transformed B lymphoblastoid cell lines. We identified several cross-reactive pp65/A*0201-specific T cell lines toward allogeneic HLA-A*3001, A*3101, or A*3201. Moreover, we described here cross-recognition of HLA-Cw*0602 by BZLF1/B*3501-specific T cells. It is noteworthy that these alloreactive CD8 T cell lines showed efficient recognition of endothelial cells expressing the relevant HLA class I allele, with high level TNF-α production and cytotoxicity activity. Taken together, our data support the notion that herpes virus-specific T cells recognizing allo-HLA alleles may promote solid organ rejection

A roadmap to improve the quality of atrial fibrillation management:proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference

At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF