Induction of Akt Activity by Chemotherapy Confers Acquired Resistance

[[abstract]]Resistance to chemotherapy is a major cause of treatment failure in human cancer. Accumulating evidence has indicated that the acquisition of resistance to chemotherapeutic drugs involves the activation of the PI3K/Akt pathway, modulating Akt activity ill response to chemotherapy has been observed often ill chemoresistant cancers. The potential molecular mechanisms by which chemotherapeutic agents activate the PI3K/Akt pathway arc emerging. Activation of this pathway evades the cytotoxic effects of chemotherpeutic agents via regulation of essential cellular functions such as protien synthesis, antiapoptosis, survival and proliferation in cancer flow chemotherapeutic agents induce Akt activation and how activated Akt confers chemoresistance through regulation of signaling networks are discussed in this review. Combining PI3K/Akt inhibitors with standard chemotherapy has been successful in increasing the efficacy of chemotherapeutic agents both in vivo and in vitro. Several small molecules have been developed to specifically target PI3K/Akt and other components of this pathway, which in combination with chemotherapy may be a valid approach mechanisms Of signaling networks for maintenance, of the Akt activity for cell survival. These regulatory mechanisms may limit the efficacy Of PI3K/Akt-targeted therapy; therefore, disruption of these mechanisms may be an effective strategy for development of novel anti-cancer therapies

Reliability of 95% confidence interval revealed by expected quality-of-life scores: an example of nasopharyngeal carcinoma patients after radiotherapy using EORTC QLQ-C 30

<p>Abstract</p> <p>Background</p> <p>Many researchers use observed questionnaire scores to evaluate score reliability and to make conclusions and inferences regarding quality-of-life outcomes. The amount of false alarms from medical diagnoses that would be avoided if observed scores were substituted with expected scores is interesting, and understanding these differences is important for the care of cancer patients. Using expected scores to estimate the reliability of 95% confidence intervals (CIs) is rarely reported in published papers. We investigated the reliability of patient responses to a quality-of-life questionnaire and made recommendations for future studies of the quality of life of patients.</p> <p>Methods</p> <p>A total of 115 patients completed the EORTC core questionnaire QLQ-C30 (version 3) after radiotherapy. The observed response scores, assumed to be one-dimensional, were summed and transformed into expected scores using the Rasch rating scale model with WINSTEPS software. A series of simulations was performed using a unified bootstrap procedure after manipulating scenarios with different questionnaire lengths and patient numbers to estimate the reliability at 95% confidence intervals. Skewness analyses of the 95% CIs were compared to detect different effects between groups according to the two data sets of observed and expected response scores.</p> <p>Results</p> <p>We found that (1) it is necessary to report CIs for reliability and skewness coefficients in papers; (2) data derived from expected response scores are preferable to making inferences; and (3) visual representations displaying the 95% CIs of skewness values applied to item-by-item analyses can provide a useful interpretation of quality-of-life outcomes.</p> <p>Conclusion</p> <p>Reliability coefficients can be reported with 95% CIs by statistical software to evaluate the internal consistency of respondent scores on questionnaire items. The SPSS syntax procedures for estimating the reliability of the 95% CI, expected score generation and visual skewness analyses are demonstrated in this study. We recommend that effect sizes such as a 95% CI be reported along with <it>p </it>values reporting significant differences in quality-of-life studies.</p

Chlamydial infection among patients attending STD and genitourinary clinics in Taiwan

<p>Abstract</p> <p>Background</p> <p>The main objective of this study is to examine the epidemiology of <it>Chlamydia trachomatis </it>(CT) infection amongst patients (473 men, 180 women) seen two hospitals in Taiwan.</p> <p>Methods</p> <p>Between July 2004 and June 2005, a total of 653 patients provided first-void urine samples for examination of CT using PCR assay.</p> <p>Results</p> <p>The overall prevalence of CT infection was 18.4% (95% confidence interval [CI] 17.3–19.5). Prevalence for men and women were 16.7 % (95% CI 15.3–18.0%) and 22.8% (95% CI 17.5–28.1%), respectively. Age group-specific prevalence was 25.7% (95% CI 22.5–28.9%) in < 20 year olds, 23.5% (95% CI 20.3–26.7%) in 20–24 year olds, 22.3% (95% CI 18.9–25.7%) in 25–30 year olds, and 11.5% (95% CI 10.3–12.7%) in > 30 year olds. Independent risk factors for chlamydial infection included younger age (aged ≤ 30 years) (adjusted odds ratio [AOR] = 2.44; 95% CI 1.52–3.84; <it>p </it>< 0.001), inconsistent condom use (AOR = 2.01; 95% CI 1.32–3.06; <it>p </it>< 0.001), being symptomatic (dysuria, urethral discharge) at the time of testing (AOR = 1.84; 95% CI 1.21–2.80; <it>p </it>< 0.001), and having <it>N. gonorrhoeae </it>infection (AOR = 3.82; 95% CI 2.20–6.58; <it>p </it>< 0.001).</p> <p>Conclusion</p> <p>Genital chlamydial infection is an important sexually transmitted disease in Taiwan. Young Taiwanese persons attending a STD clinic should be screened for CT infection and counselled on condom use.</p

First-principles design and subsequent synthesis of a material to search for the permanent electric dipole moment of the electron

We describe the first-principles design and subsequent synthesis of a new material with the specific functionalities required for a solid-state-based search for the permanent electric dipole moment of the electron. We show computationally that perovskite-structure europium barium titanate should exhibit the required large and pressure-dependent ferroelectric polarization, local magnetic moments, and absence of magnetic ordering even at liquid helium temperature. Subsequent synthesis and characterization of Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ ceramics confirm the predicted desirable properties.Comment: Nature Materials, in pres

Applying the revised Chinese Job Content Questionnaire to assess psychosocial work conditions among Taiwan's hospital workers

<p>Abstract</p> <p>Background</p> <p>For hospital accreditation and health promotion reasons, we examined whether the 22-item Job Content Questionnaire (JCQ) could be applied to evaluate job strain of individual hospital employees and to determine the number of factors extracted from JCQ. Additionally, we developed an Excel module of self-evaluation diagnostic system for consultation with experts.</p> <p>Methods</p> <p>To develop an Excel-based self-evaluation diagnostic system for consultation to experts to make job strain assessment easier and quicker than ever, Rasch rating scale model was used to analyze data from 1,644 hospital employees who enrolled in 2008 for a job strain survey. We determined whether the 22-item Job Content Questionnaire (JCQ) could evaluate job strain of individual employees in work sites. The respective item responding to specific groups' occupational hazards causing job stress was investigated by using skewness coefficient with its 95% CI through item-by-item analyses.</p> <p>Results</p> <p>Each of those 22 items on the questionnaire was examined to have five factors. The prevalence rate of Chinese hospital workers with high job strain was 16.5%.</p> <p>Conclusions</p> <p>Graphical representations of four quadrants, item-by-item bar chart plots and skewness 95% CI comparison generated in Excel can help employers and consultants of an organization focusing on a small number of key areas of concern for each worker in job strain.</p

Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM

<p>Abstract</p> <p>Background</p> <p>Hemophilia A represents the most common and severe inherited hemorrhagic disorder. It is caused by mutations in the F8 gene, which leads to a deficiency or dysfunctional factor VIII protein, an essential cofactor in the factor X activation complex.</p> <p>Methods</p> <p>We used long-distance polymerase chain reaction and denaturing high performance liquid chromatography for mutation scanning of the F8 gene. We designed the competitive multiplex PCR to identify the carrier with exonal deletions. In order to facilitate throughput and minimize the cost of mutation scanning, we also evaluated a new mutation scanning technique, high resolution melting analysis (HRM), as an alternative screening method.</p> <p>Results</p> <p>We presented the results of detailed screening of 122 Taiwanese families with hemophilia A and reported twenty-nine novel mutations. There was one family identified with whole exons deletion, and the carriers were successfully recognized by multiplex PCR. By HRM, the different melting curve patterns were easily identified in 25 out of 28 cases (89%) and 15 out of 15 (100%) carriers. The sensitivity was 93 % (40/43). The overall mutation detection rate of hemophilia A was 100% in this study.</p> <p>Conclusion</p> <p>We proposed a diagnostic strategy for hemophilia A genetic diagnosis. We consider HRM as a powerful screening tool that would provide us with a more cost-effective protocol for hemophilia A mutation identification.</p

Berkovich Nanoindentation on AlN Thin Films

Berkovich nanoindentation-induced mechanical deformation mechanisms of AlN thin films have been investigated by using atomic force microscopy (AFM) and cross-sectional transmission electron microscopy (XTEM) techniques. AlN thin films are deposited on the metal-organic chemical-vapor deposition (MOCVD) derived Si-doped (2 × 1017 cm−3) GaN template by using the helicon sputtering system. The XTEM samples were prepared by means of focused ion beam (FIB) milling to accurately position the cross-section of the nanoindented area. The hardness and Young’s modulus of AlN thin films were measured by a Berkovich nanoindenter operated with the continuous contact stiffness measurements (CSM) option. The obtained values of the hardness and Young’s modulus are 22 and 332 GPa, respectively. The XTEM images taken in the vicinity regions just underneath the indenter tip revealed that the multiple “pop-ins” observed in the load–displacement curve during loading are due primarily to the activities of dislocation nucleation and propagation. The absence of discontinuities in the unloading segments of load–displacement curve suggests that no pressure-induced phase transition was involved. Results obtained in this study may also have technological implications for estimating possible mechanical damages induced by the fabrication processes of making the AlN-based devices

Unravelling the effects of age, period and cohort on metabolic syndrome components in a Taiwanese population using partial least squares regression

<p>Abstract</p> <p>Background</p> <p>We investigate whether the changing environment caused by rapid economic growth yielded differential effects for successive Taiwanese generations on 8 components of metabolic syndrome (MetS): body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TG), high-density lipoprotein (HDL), Low-density lipoproteins (LDL) and uric acid (UA).</p> <p>Methods</p> <p>To assess the impact of age, birth year and year of examination on MetS components, we used partial least squares regression to analyze data collected by Mei-Jaw clinics in Taiwan in years 1996 and 2006. Confounders, such as the number of years in formal education, alcohol intake, smoking history status, and betel-nut chewing were adjusted for.</p> <p>Results</p> <p>As the age of individuals increased, the values of components generally increased except for UA. Men born after 1970 had lower FPG, lower BMI, lower DBP, lower TG, Lower LDL and greater HDL; women born after 1970 had lower BMI, lower DBP, lower TG, Lower LDL and greater HDL and UA. There is a similar pattern between the trend in levels of metabolic syndrome components against birth year of birth and economic growth in Taiwan.</p> <p>Conclusions</p> <p>We found cohort effects in some MetS components, suggesting associations between the changing environment and health outcomes in later life. This ecological association is worthy of further investigation.</p

A tryptophan-rich peptide acts as a transcription activation domain

<p>Abstract</p> <p>Background</p> <p>Eukaryotic transcription activators normally consist of a sequence-specific DNA-binding domain (DBD) and a transcription activation domain (AD). While many sequence patterns and motifs have been defined for DBDs, ADs do not share easily recognizable motifs or structures.</p> <p>Results</p> <p>We report herein that the N-terminal domain of yeast valyl-tRNA synthetase can function as an AD when fused to a DNA-binding protein, LexA, and turn on reporter genes with distinct LexA-responsive promoters. The transcriptional activity was mainly attributed to a five-residue peptide, WYDWW, near the C-terminus of the N domain. Remarkably, the pentapeptide <it>per se </it>retained much of the transcriptional activity. Mutations which substituted tryptophan residues for both of the non-tryptophan residues in the pentapeptide (resulting in W₅) significantly enhanced its activity (~1.8-fold), while mutations which substituted aromatic residues with alanine residues severely impaired its activity. Accordingly, a much more active peptide, pentatryptophan (W₇), was produced, which elicited ~3-fold higher activity than that of the native pentapeptide and the N domain. Further study indicated that W₇mediates transcription activation through interacting with the general transcription factor, TFIIB.</p> <p>Conclusions</p> <p>Since W₇shares no sequence homology or features with any known transcription activators, it may represent a novel class of AD.</p