Computational studies on the factors influencing stabilities of collagen-like peptides

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.Includes bibliographical references (leaf 26).In this study, thermodynamic integration and molecular dynamics methods were used to elucidate the factors affecting stabilities of collagen-like peptides. We proposed to investigate three specific aspects: (1) the stabilizing effect of hydroxyproline (Hyp), (2) the destabilizing effect of replacing Gly, and (3) the role of water mediated hydrogen bonds. A better understanding of the origins of the stabilities of collagens will help in the design of new biomaterials and the treatment of collagen-related diseases.by Nai-yuan Chang.S.M

Surface scattering mechanisms of tantalum nitride thin film resistor

In this letter, we utilize an electrical analysis method to develop a TaN thin film resistor with a stricter spec and near-zero temperature coefficient of resistance (TCR) for car-used electronic applications. Simultaneously, we also propose a physical mechanism mode to explain the origin of near-zero TCR for the TaN thin film resistor (TFR). Through current fitting, the carrier conduction mechanism of the TaN TFR changes from hopping to surface scattering and finally to ohmic conduction for different TaN TFRs with different TaN microstructures. Experimental data of current–voltage measurement under successive increasing temperature confirm the conduction mechanism transition. A model of TaN grain boundary isolation ability is eventually proposed to influence the carrier transport in the TaN thin film resistor, which causes different current conduction mechanisms

Mutation and Lineage Analysis of DNMT3A in BCR-ABL1-negative Chronic Myeloproliferative Neoplasms

SummaryIn addition to the JAK2 V617F mutation, somatic mutation in DNMT3A has been described in BCL-ABL1-negative myeloproliferative neoplasms (MPNs). We have screened for DNMT3A exon 23 mutations in 130 adult Taiwanese patients with chronic phase myeloproliferative neoplasms. Only one somatic DNMT3A R882H mutation was identified in one JAK2 V617F mutation-positive essential thrombocythemia patient (1/91, 1%). Both mutations were detected in the CD34+-, CD19+-, peripheral blood mononuclear cell- and granulocyte-enriched fractions, but were not detected in the CD3+-enriched fraction by lineage analysis. Our findings suggest that DNMT3A mutation is not prevalent in MPNs, and further study is needed to clarify its role in the molecular pathogenesis of myeloproliferative neoplasms

Duration of Antibody Responses after Severe Acute Respiratory Syndrome

Among 176 patients who had had severe acute respiratory syndrome (SARS), SARS-specific antibodies were maintained for an average of 2 years, and significant reduction of immunoglobulin G–positive percentage and titers occurred in the third year. Thus, SARS patients might be susceptible to reinfection >3 years after initial exposure

B5, a thioredoxin reductase inhibitor, induces apoptosis in human cervical cancer cells by suppressing the thioredoxin system, disrupting mitochondrion-dependent pathways and triggering autophagy

published_or_final_versio

Potassium channel dysfunction in human neuronal models of Angelman syndrome

Disruptions in the ubiquitin protein ligase E3A (UBE3A) gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remains unclear. Using human neurons and brain organoids, we demonstrate that UBE3A suppresses neuronal hyperexcitability via ubiquitin-mediated degradation of calcium- and voltage-dependent big potassium (BK) channels. We provide evidence that augmented BK channel activity manifests as increased intrinsic excitability in individual neurons and subsequent network synchronization. BK antagonists normalized neuronal excitability in both human and mouse neurons and ameliorated seizure susceptibility in an AS mouse model. Our findings suggest that BK channelopathy underlies epilepsy in AS and support the use of human cells to model human developmental diseases

Single Nucleotide Polymorphisms of 8 Inflammation-related Genes and their Associations with Smoking-related Cancers

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers. © 2010 UICC

Magnetic resonance imaging for lung cancer detection: Experience in a population of more than 10,000 healthy individuals

<p>Abstract</p> <p>Background</p> <p>Recent refinements of lung MRI techniques have reduced the examination time and improved diagnostic sensitivity and specificity. We conducted a study to assess the feasibility of MRI for the detection of primary lung cancer in asymptomatic individuals.</p> <p>Methods</p> <p>A retrospective chart review was performed on images of lung parenchyma, which were extracted from whole-body MRI examinations between October 2000 and December 2007. 11,766 consecutive healthy individuals (mean age, 50.4 years; 56.8% male) were scanned using one of two 1.5-T scanners (Sonata and Sonata Maestro, Siemens Medical Solutions, Erlangen, Germany). The standard protocol included a quick whole-lung survey with T2-weighted 2-dimensional half Fourier acquisition single shot turbo spin echo (HASTE) and 3-dimensional volumetric interpolated breath-hold examination (VIBE). Total examination time was less than 10 minutes, and scanning time was only 5 minutes. Prompt referrals and follow-ups were arranged in cases of suspicious lung nodules.</p> <p>Results</p> <p>A total of 559 individuals (4.8%) had suspicious lung nodules. A total of 49 primary lung cancers were diagnosed in 46 individuals: 41 prevalence cancers and 8 incidence cancers. The overall detection rate of primary lung cancers was 0.4%. For smokers aged 51 to 70 years, the detection rate was 1.4%. TNM stage I disease accounted for 37 (75.5%). The mean size of detected lung cancers was 1.98 cm (median, 1.5 cm; range, 0.5-8.2 cm). The most histological types were adenocarcinoma in 38 (77.6%).</p> <p>Conclusion</p> <p>Rapid zero-dose MRI can be used for lung cancer detection in a healthy population.</p

Epidemiology of Schistosomiasis in the People’s Republic of China, 2004

Although the number of human infections decreased, human prevalence increased from 4.9% in 1995 to 5.1% in 2004