On the formalization of termination techniques based on multiset orderings

Multiset orderings are a key ingredient in certain termination techniques like the recursive path ordering and a variant of size-change termination. In order to integrate these techniques in a certifier for termination proofs, we have added them to the Isabelle Formalization of Rewriting. To this end, it was required to extend the existing formalization on multiset orderings towards a generalized multiset ordering. Afterwards, the soundness proofs of both techniques have been established, although only after fixing some definitions. Concerning efficiency, it is known that the search for suitable parameters for both techniques is NP-hard. We show that checking the correct application of the techniques-where all parameters are provided-is also NP-hard, since the problem of deciding the generalized multiset ordering is NP-hard. © René Thiemann, Guillaume Allais, and JulianNagele

Rescaled mean spherical approximation for colloidal mixtures

In this work, the rescaled mean spherical approximation (RMSA) for colloidal mixtures interacting via a DLVO-type potential is developed, and its application to suspensions of highly charged macroions is illustrated. For this purpose we introduce a simple scheme to solve the mean spherical approximation (MSA) for Yukawa mixtures with factorized coupling parameters. This scheme consists of the mapping of the Yukawa system onto a corresponding primitive model system. Such a correspondence is used as a device for the calculation of the static structure functions of the original Yukawa mixture. Within this scheme, a straightforward implementation of the rescaling procedure is performed, which allows for the calculation of partial structure factors in strongly interacting mixtures. The rescaling procedure we use is an extension of that introduced by Hansen and Hayter for monodisperse suspensions. The structure factors obtained with the rescaled mean spherical approximation compare well with computer simulation results. The advantages and limitations of the RMSA are also discussed in some detail.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28352/1/0000113.pd

Cops and CoCoWeb: Infrastructure for Confluence Tools

In this paper we describe the infrastructure supporting confluence tools and competitions: Cops, the confluence problems database, and CoCoWeb, a convenient web interface for tools that participate in the annual confluence competition

Antibodies in the Diagnosis, Prognosis, and Prediction of Psychotic Disorders.

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a top-down approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging bottom-up or omics approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the antibody repertoire. Here we review the evidence for antibodies (to self-antigens as well as infectious organism and dietary antigens) as biomarkers of diagnosis, prognosis, and treatment response in psychotic disorders. Neuronal autoantibodies have current, and increasing, clinical utility in the diagnosis of organic or atypical psychosis syndromes. Antibodies to selected infectious agents show some promise in predicting cognitive impairment and possibly other symptom domains (eg, suicidality) within psychotic disorders. Finally, infectious antibodies and neuronal and other autoantibodies have recently emerged as potential biomarkers of response to anti-infective therapies, immunotherapies, or other novel therapeutic strategies in psychotic disorders, and have a clear role in stratifying patients for future clinical trials. As in nonpsychiatric disorders, combining biomarkers and large-scale use of bottom-up approaches to biomarker identification are likely to maximize the eventual clinical utility of antibody biomarkers in psychotic disorders

Diagnosis of Alzheimer's Disease Based on Disease-Specific Autoantibody Profiles in Human Sera

After decades of Alzheimer's disease (AD) research, the development of a definitive diagnostic test for this disease has remained elusive. The discovery of blood-borne biomarkers yielding an accurate and relatively non-invasive test has been a primary goal. Using human protein microarrays to characterize the differential expression of serum autoantibodies in AD and non-demented control (NDC) groups, we identified potential diagnostic biomarkers for AD. The differential significance of each biomarker was evaluated, resulting in the selection of only 10 autoantibody biomarkers that can effectively differentiate AD sera from NDC sera with a sensitivity of 96.0% and specificity of 92.5%. AD sera were also distinguishable from sera obtained from patients with Parkinson's disease and breast cancer with accuracies of 86% and 92%, respectively. Results demonstrate that serum autoantibodies can be used effectively as highly-specific and accurate biomarkers to diagnose AD throughout the course of the disease

Atrial fibrillation and treatment changes in cryptogenic stroke patients with an implantable loop recorder for continuous cardiac rhythm monitoring

Introduction: This interim analysis evaluates the risk profile and incidence of atrial fibrillation (AF) in patients who underwent continuous monitoring with an implantable loop recorder (ILR) for cryptogenic (unexplained) stroke or transient ischemic attack (TIA). Methods: The observational INSIGHT XT study prospectively enrolled patients who received an ILR with dedicated diagnostics for atrial fibrillation, irrespective of the clinical indication. Of 1002 patients enrolled in the study between Aug 2008 and Jan 2012, 121 received the ILR to evaluate cryptogenic stroke or TIA. The definition of cryptogenic stroke/TIA was at the investigators' appraisal and no unified approach to patient work-up was required. This analysis includes 74 patients with cryptogenic stroke or TIA for whom at least one follow-up visit was available at the time of interim analysis. Results: The mean age was 63±12 (50% female). Stroke was the index event in 46 of 74 (62%) of patients. 61% had hypertension, 14% diabetes, and none had heart failure. The mean CHADS2 score was 3.0±0.8 and the mean CHA2DS2VASc score 4.0±1.2. Most patients (72%) had no prior symptoms or cardiac rhythm disturbances, whereas 18% had a history of prior palpitations. Sixty-seven patients were taking antiplatelet medication and four were on oral anticoagulation (OAC) at enrollment. During a median follow up of 12 months (IQR 7 to 18) AF was reported in 17 patients (23%) and two patients were started on OAC and 10 patients were converted from antiplatelets to OAC. Five patients experienced a stroke or TIA (median time to event 1.2 months), of which one patient died. Three of the patients with stroke or TIA had AF detected prior to the recurrent event. Conclusion: Continuous monitoring with an ILR in patients with cryptogenic stroke of TIA detects a high proportion of AF; this can be attributed to longer continuous monitoring in this study. These patients have high CHADS2/CHA2DS2VASc scores; documenting AF in these cases may therefore be clinically relevant in order to decide appropriate treatment

A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier

Schizophrenia (SZ) is one of the most severe forms of mental illness, yet mechanisms remain unclear. A widely established brain finding in SZ is hippocampal atrophy, and a coherent explanation similarly is lacking. Epidemiological evidence suggests increased cerebrovascular and cardiovascular complications in SZ independent of lifestyle and medication, pointing to disease-specific pathology. Endothelial cell contributions to blood-brain barrier (BBB) compromise may influence neurovascular unit and peripheral vascular function, and we hypothesize that downstream functional and structural abnormalities may be explained by impaired BBB

Lipopolysaccharide (LPS) potentiates hydrogen peroxide toxicity in T98G astrocytoma cells by suppression of anti-oxidative and growth factor gene expression

<p>Abstract</p> <p>Background</p> <p>Lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria with proved role in pathogenesis of sepsis. Brain injury was observed with both patients dead from sepsis and animal septic models. However, <it>in vitro </it>administration of LPS has not shown obvious cell damage to astrocytes and other relative cell lines while it does cause endothelial cell death <it>in vitro</it>. These observations make it difficult to understand the role of LPS in brain parenchymal injury.</p> <p>Results</p> <p>To test the hypothesis that LPS may cause biological changes in astrocytes and make the cells to become vulnerable to reactive oxygen species, a recently developed highly sensitive and highly specific system for large-scale gene expression profiling was used to examine the gene expression profile of a group of 1,135 selected genes in a cell line, T98G, a derivative of human glioblastoma of astrocytic origin. By pre-treating T98G cells with different dose of LPS, it was found that LPS treatment caused a broad alteration in gene expression profile, but did not cause obvious cell death. However, after short exposure to H₂O₂, cell death was dramatically increased in the LPS pretreated samples. Interestingly, cell death was highly correlated with down-regulated expression of antioxidant genes such as cytochrome b561, glutathione s-transferase a4 and protein kinase C-epsilon. On the other hand, expression of genes encoding growth factors was significantly suppressed. These changes indicate that LPS treatment may suppress the anti-oxidative machinery, decrease the viability of the T98G cells and make the cells more sensitive to H₂O₂stress.</p> <p>Conclusion</p> <p>These results provide very meaningful clue for further exploring and understanding the mechanism underlying astrocyte injury in sepsis <it>in vivo</it>, and insight for why LPS could cause astrocyte injury <it>in vivo</it>, but not <it>in vitro</it>. It will also shed light on the therapeutic strategy of sepsis.</p