Toward the Static Detection of Deadlock in Java Software

Concurrency is the source of many real-world software reliability and security problems. Concurrency defects are difficult to detect because they defy conventional software testing techniques due to their non-local and non-deterministic nature. We focus on one important aspect of this problem: static detection of the possibility of deadlock - a situation in which two or more processes are prevented from continuing while each waits for resources to be freed by the continuation of the other. This thesis proposes a flow-insensitive interprocedural static analysis that detects the possibility that a program can deadlock at runtime. Our analysis proceeds in two steps. The first extracts the real call graph decorated with acquired locks from the target program. The second analysis this decorated graph to report how a possible deadlock may occur at runtime. We demonstrate our analysis via a prototype implementation that detects deadlock conditions within two small Java programs. The two principle limitations of our analysis are on the target program: (1) we need its real call graph and (2) its overall size is limited. Construction of the real call graph requires perfect aliasing information. The program\u27s size our technique is able to analyze is roughly 35 kSLOC

Using Reputation Based Trust to Overcome Malfunctions and Malicious Failures in Electric Power Protection Systems

This dissertation advocates the use of reputation-based trust in conjunction with a trust management framework based on network flow techniques to form a trust management toolkit (TMT) for the defense of future Smart Grid enabled electric power grid from both malicious and non-malicious malfunctions. Increases in energy demand have prompted the implementation of Smart Grid technologies within the power grid. Smart Grid technologies enable Internet based communication capabilities within the power grid, but also increase the grid\u27s vulnerability to cyber attacks. The benefits of TMT augmented electric power protection systems include: improved response times, added resilience to malicious and non-malicious malfunctions, and increased reliability due to the successful mitigation of detected faults. In one simulated test case, there was a 99% improvement in fault mitigation response time. Additional simulations demonstrated the TMT\u27s ability to determine which nodes were compromised and to work around the faulty devices when responding to transient instabilities. This added resilience prevents outages and minimizes equipment damage from network based attacks, which also improves system\u27s reliability. The benefits of the TMT have been demonstrated using computer simulations of dynamic power systems in the context of backup protection systems and special protection systems

Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases

In parallel to our better understanding of the role of the immune system in neurologic diseases, there has been an increased availability in therapeutic options for autoimmune neurologic diseases such as multiple sclerosis, myasthenia gravis, polyneuropathies, central nervous system vasculitides and neurosarcoidosis. In many cases, the purported benefits of this class of therapy are anecdotal and not the result of good controlled clinical trials. Nonetheless, their potential efficacy is better known than their adverse event profile. A rationale therapeutic decision by the clinician will depend on a comprehensive understanding of the ratio between efficacy and toxicity. In this review, we outline the most commonly used immune suppressive medications in neurologic disease: cytotoxic chemotherapy, nucleoside analogues, calcineurin inhibitors, monoclonal antibodies and miscellaneous immune suppressants. A discussion of their mechanisms of action and related toxicity is highlighted, with the goal that the reader will be able to recognize the most commonly associated toxicities and identify strategies to prevent and manage problems that are expected to arise with their use

A Machine Learning Classifier Trained on Cancer Transcriptomes Detects NF1 Inactivation Signal in Glioblastoma

We have identified molecules that exhibit synthetic lethality in cells with loss of the neurofibromin 1 (NF1) tumor suppressor gene. However, recognizing tumors that have inactivation of the NF1 tumor suppressor function is challenging because the loss may occur via mechanisms that do not involve mutation of the genomic locus. Degradation of the NF1 protein, independent of NF1 mutation status, phenocopies inactivating mutations to drive tumors in human glioma cell lines. NF1 inactivation may alter the transcriptional landscape of a tumor and allow a machine learning classifier to detect which tumors will benefit from synthetic lethal molecules. We developed a strategy to predict tumors with low NF1 activity and hence tumors that may respond to treatments that target cells lacking NF1. Using RNAseq data from The Cancer Genome Atlas (TCGA), we trained an ensemble of 500 logistic regression classifiers that integrates mutation status with whole transcriptomes to predict NF1 inactivation in glioblastoma (GBM)

Análise da correção atmosférica de imagens Landsat em estudo multitemporal na região de Mata Atlântica, Estado do Rio de Janeiro.

Multitemporal, remotely sensed data applied to land use land cover dynamic studies require radiometric correction of images, in addition to geometric correction. This allow the analysis of temporal variation of targets without the influence of others factors such as the atmospheric effects. This study aims to apply the dark-object subtraction technique to correct atmospheric effects and to analyze the results on multitemporal images of rivers Macacu and Caceribu watersheds, in Rio de Janeiro state, in Atlantic Forest region. Images without clouds from sensors TM/Landsat-5 and ETM+/Landsat-7 were selected for analysis of land use land cover dynamic of two periods: 1997 to 2002 and 2002 to 2007. The results indicated that the correction method did not reduce the atmospheric effects in a satisfactory manner. These effects continued to influence in any significant way in the spectral response of the targets. The major differences between the levels of gray of the corrected images were among the images of different sensors, indicating likely influence of the response of the sensors on the final results. o objetivo do presente trabalho é analisar o efeito da correção atmosférica aplicando método de subtração de nível de ci nza em imagens multitemporais da região das bacias hidrográficas dos rios Macacu e Caceribu, no Estado do Rio de Janeiro, em região de Mata Atlântica

Methotrexate Encephalopathy: Two Cases in Adult Cancer Patients, Who Recovered with Pathophysiologically Based Therapy

Background/Objectives: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. Results: Case 1 : A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2 : A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high- dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery. Conclusions: These two cases suggest that N -methyl d -aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity

Steroid-Induced Sigmoid Diverticular Perforation in a Patient with Temporal Arteritis: A Rare Clinical Pathology

Corticosteroids are used in the treatment of many rheumatological diseases including temporal arteritis. The gastrointestinal perforation during corticosteroid treatment is a serious complication. Colon perforation after steroid use was first reported by Beck et al in 1950.1 Although the pathophysiological mechanism is not understood clearly, it is claimed that steroids probably by disturbing the intestinal mucosal barrier, facilitate the intestinal perforation. The long term treatment with corticosteroids increases the risk of colon perforation. We are presenting a patient who was taking corticosteroid due to temporal arteritis for two years and operated with sigmoid diverticular perforation

Temozolomide in aggressive pituitary adenomas and carcinomas

Temozolomide is an alkylating agent used in the treatment of gliomas and, more recently, aggressive pituitary adenomas and carcinomas. Temozolomide methylates DNA and, thereby, has antitumor effects. O6-methylguanine-DNA methyltransferase, a DNA repair enzyme, removes the alkylating adducts that are induced by temozolomide, thereby counteracting its effects. A Medline search for all of the available publications regarding the use of temozolomide for the treatment of pituitary tumors was performed. To date, 46 cases of adenohypophysial tumors that were treated with temozolomide, including 30 adenomas and 16 carcinomas, have been reported. Eighteen of the 30 (60%) adenomas and 11 of the 16 (69%) carcinomas responded favorably to treatment. One patient with multiple endocrine neoplasia type 1 and an aggressive prolactin-producing adenoma was also treated and demonstrated a good response. No significant complications have been attributed to temozolomide therapy. Thus, temozolomide is an effective treatment for the majority of aggressive adenomas and carcinomas. Evidence indicates that there is an inverse correlation between levels of O6-methylguanine-DNA methyltransferase immunoexpression and therapeutic response. Alternatively, high-level O6-methylguanine-DNA methyltransferase immunoexpression correlates with an unfavorable response. Here, we review the use of temozolomide for treating pituitary neoplasms

NDRG2 Expression Correlates with Neurofibrillary Tangles and Microglial Pathology in the Ageing Brain.

Astrocytes play a major role in the pathogenesis of a range of neurodegenerative diseases, including Alzheimer's disease (AD), undergoing dramatic morphological and molecular changes that can cause potentially both beneficial and detrimental effects. They comprise a heterogeneous population, requiring a panel of specific phenotype markers to identify astrocyte subtypes, changes in function and their relation to pathology. This study aimed to characterise expression of the astrocyte marker N-myc downstream regulated gene 2 (NDRG2) in the ageing brain, investigate the relationship between NDRG2 and a panel of astrocyte markers, and relate NDRG2 expression to pathology. NDRG2 specifically immunolabelled the cell body and radiating processes of astrocytes in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) neuropathology cohort. Expression of NDRG2 did not correlate with other astrocyte markers, including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 2 (EAAT2) and glutamine synthetase (GS). NDRG2 showed a relationship to AT8+ neurofibrillary tangles (p = 0.001) and CD68+ microglia (p = 0.047), but not β-amyloid plaques or astrocyte nuclear γH2AX immunoreactivity, a marker of DNA damage response. These findings provide new insight into the astrocyte response to pathology in the ageing brain, and suggest NDRG2 may be a potential target to modulate this response

Transcriptomic Analysis of Age-Associated Periventricular Lesions Reveals Dysregulation of the Immune Response.

White matter lesions (WML) are a common feature of the ageing brain associated with cognitive impairment. The gene expression profiles of periventricular lesions (PVL, n = 7) and radiologically-normal-appearing (control) periventricular white matter cases (n = 11) obtained from the Cognitive Function and Ageing Study (CFAS) neuropathology cohort were interrogated using microarray analysis and NanoString to identify novel mechanisms potentially underlying their formation. Histological characterisation of control white matter cases identified a subgroup (n = 4) which contained high levels of MHC-II immunoreactive microglia, and were classified as "pre-lesional." Microarray analysis identified 2256 significantly differentially-expressed genes (p ≤ 0.05, FC ≥ 1.2) in PVL compared to non-lesional control white matter (1378 upregulated and 878 downregulated); 2649 significantly differentially-expressed genes in "pre-lesional" cases compared to PVL (1390 upregulated and 1259 downregulated); and 2398 significantly differentially-expressed genes in "pre-lesional" versus non-lesional control cases (1527 upregulated and 871 downregulated). Whilst histological evaluation of a single marker (MHC-II) implicates immune-activated microglia in lesion pathology, transcriptomic analysis indicates significant downregulation of a number of activated microglial markers and suggests established PVL are part of a continuous spectrum of white matter injury. The gene expression profile of "pre-lesional" periventricular white matter suggests upregulation of several signalling pathways may be a neuroprotective response to prevent the pathogenesis of PVL