A fast time-domain EM-TCAD coupled simulation framework via matrix exponential

We present a fast time-domain multiphysics simulation framework that combines full-wave electromagnetism (EM) and carrier transport in semiconductor devices (TCAD). The proposed framework features a division of linear and nonlinear components in the EM-TCAD coupled system. The former is extracted and handled independently with high efficiency by a matrix exponential approach assisted with Krylov subspace method. The latter is treated by ordinary Newton's method yet with a much sparser Jacobian matrix that leads to substantial speedup in solving the linear system of equations. More convenient error management and adaptive control are also available through the linear and nonlinear decoupling. © 2012 ACM.published_or_final_versio

Plasma high sensitivity troponin T levels in adult survivors of childhood leukaemias: determinants and associations with cardiac function

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Nasopharyngeal carcinoma: time lapse before diagnosis and treatment

This is a descriptive study of 168 patients with nasopharyngeal carcinoma who were referred to public oncology departments for primary treatment between July and September 1996. The mean duration from the onset of the symptoms to histological diagnosis was 5.0 months; the duration ranged from 6.1 months (for patients presenting with nasal symptoms) to 1.8 months (for those with cranial nerve dysfunction). The mean period between the onset of symptoms and the seeking of medical advice was 2.9months. For 54% of the patients, there was a further delay of up to 2.4 months between the initial medical consultation and referral to the appropriate specialist. The majority (84%) of patients attended public institutions for histological confirmation. The mean total time taken from the onset of symptoms to the commencement of radiotherapy was 6.5 months (range, 1.3-74.0 months)---45% of the delay was attributed to the patient, 20% to initial consultations, 14% to diagnostic arrangement, and 21% to preparation for radiotherapy. Concerted efforts are needed to minimise further the time between the onset of symptoms and treatment. A substantial reduction in this delay can be achieved if both public and primary care doctors were made more aware of the significance of relevant symptoms.published_or_final_versio

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Estimating Incidence Curves of Several Infections Using Symptom Surveillance Data

We introduce a method for estimating incidence curves of several co-circulating infectious pathogens, where each infection has its own probabilities of particular symptom profiles. Our deconvolution method utilizes weekly surveillance data on symptoms from a defined population as well as additional data on symptoms from a sample of virologically confirmed infectious episodes. We illustrate this method by numerical simulations and by using data from a survey conducted on the University of Michigan campus. Last, we describe the data needs to make such estimates accurate

Emerging strengths in Asia Pacific bioinformatics

The 2008 annual conference of the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation set up in 1998, was organized as the 7th International Conference on Bioinformatics (InCoB), jointly with the Bioinformatics and Systems Biology in Taiwan (BIT 2008) Conference, Oct. 20–23, 2008 at Taipei, Taiwan. Besides bringing together scientists from the field of bioinformatics in this region, InCoB is actively involving researchers from the area of systems biology, to facilitate greater synergy between these two groups. Marking the 10th Anniversary of APBioNet, this InCoB 2008 meeting followed on from a series of successful annual events in Bangkok (Thailand), Penang (Malaysia), Auckland (New Zealand), Busan (South Korea), New Delhi (India) and Hong Kong. Additionally, tutorials and the Workshop on Education in Bioinformatics and Computational Biology (WEBCB) immediately prior to the 20th Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Taipei Conference provided ample opportunity for inducting mainstream biochemists and molecular biologists from the region into a greater level of awareness of the importance of bioinformatics in their craft. In this editorial, we provide a brief overview of the peer-reviewed manuscripts accepted for publication herein, grouped into thematic areas. As the regional research expertise in bioinformatics matures, the papers fall into thematic areas, illustrating the specific contributions made by APBioNet to global bioinformatics efforts

Proline-Rich Tyrosine Kinase 2 (Pyk2) Promotes Cell Motility of Hepatocellular Carcinoma through Induction of Epithelial to Mesenchymal Transition

Aims: Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. Methodology/Principal Findings: We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. Conclusion: These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT. © 2011 Sun et al.published_or_final_versio

Triptolide Inhibits the Proliferation of Prostate Cancer Cells and Down-Regulates SUMO-Specific Protease 1 Expression

Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa

Clinical and prognostic analysis of hepatitis B virus infection in diffuse large B-cell lymphoma

<p>Abstract</p> <p>Background</p> <p>Hepatitis B virus (HBV) infection in diffuse large B-cell lymphoma (DLBCL) patients is a common complication in China. However, the clinical relevance of HBV infection with respect to DLBCL disease stages and patient survival remains unclear. The main objective of the current study was to analyze the clinical features and to evaluate the prognostic factors of HBV infection in DLBCL patients.</p> <p>Methods</p> <p>In this retrospective study, DLBCL patients were divided into two groups as HBsAg-positive (n = 81) and HBsAg-negative (n = 181) patients. The HBsAg-positive patients were further divided into two subgroups based on their hepatic function during chemotherapy. Various statistical analyses were used to determine the significance of the relevant clinical parameters.</p> <p>Results</p> <p>Compared with the HBsAg-negative group, the HBsAg-positive DLBCL group displayed a younger median onset age (46 year vs 51), more advanced stage at grade III/IV (58% vs 42%, p = 0.016), and more frequent hepatic dysfunction before (21% vs 5.5%, p < 0.001) and during (49.4% vs 16.6%, p < 0.001) chemotherapy. Female DLBCL patients exhibited a higher frequency of HBsAg positivity (p = 0.006). However, in both groups the median overall survival (OS) duration (55.8 vs 66.8 months) and response rates (91% vs 90.4%) were similar. In the HBsAg-positive DLBCL group, the poor prognostic factors were advanced stage (p < 0.001) and hepatic dysfunction during chemotherapy (p = 0.02). The OS of HBsAg-positive patients with hepatic dysfunction during chemotherapy was significantly shorter than those without liver dysfunction (p = 0.016), and the OS rates at 3 years were 48% and 72%, respectively. The use of rituximab did not increase the rates of liver dysfunction in HBsAg-positive DLBCL patients.</p> <p>Conclusion</p> <p>Compared with HBsAg-negative patients, the HBsAg-positive DLBCL patients had earlier onset and more advanced stage. The disease stage and hepatic dysfunction during chemotherapy and were two significant prognostic factors in the HBsAg-positive DLBCL patients. This study suggests that prophylactic treatment of HBV may be of great importance in the cases of HBsAg-positive patients.</p