Molecular cloning and characterization of novel genes HEPN1, hepaCAM and HEPT3 that are altered in human hepatocellular carcinoma

Ph.DDOCTOR OF PHILOSOPH

Functional significance of the hepaCAM gene in bladder cancer

<p>Abstract</p> <p>Background</p> <p>The hepaCAM gene encodes a new immunoglobulin-like cell adhesion molecule, and its expression is suppressed in a variety of human cancers. Additionally, hepaCAM possesses properties often observed in tumor suppressor genes. However, the expression and biological function of hepaCAM has not been investigated in bladder cancer. Therefore we sought to examine hepaCAM expression and the relationship between its structure and function in human transitional cell carcinoma of bladder (TCCB).</p> <p>Materials and methods</p> <p>HepaCAM expression was evaluated in 28 normal and 34 TCCB bladder specimens and 2 TCCB cell lines using semi-quantitative RT-PCR. The wild-type hepaCAM and the extracellular domain-truncated mutant gene were transfected into the TCCB cell line T24, and the biological properties of both the wild-type gene and the domain-truncated mutant were then assessed.</p> <p>Results</p> <p>HepaCAM expression was down-regulated in 82% (28/34) of TCCB specimens and undetectable in the 2 TCCB cell lines tested. The localization of hepaCAM appeared to be dependent on cell density in T24 cells. In widely spread cells, hepaCAM accumulated on the perinuclear membrane and the cell surface protrusions, whereas in confluent cells, hepaCAM was predominantly localized at the sites of cell-cell contacts on the cell membrane. Functionally, hepaCAM expressed not only increased cell spreading, delayed cell detachment, enhanced wound healing and increased cell invasion; it also inhibited cell growth (P < 0.01). When the extracellular domain was deleted, the localization of hepaCAM was significantly altered, and it lost both its adhesive function and its influence on cell growth.</p> <p>Conclusions</p> <p>HepaCAM is involved in cell adhesion and growth control, and its expression is frequently silenced in TCCB. The extracellular domain of hepaCAM is essential to its physiological and biological functions.</p

Chemical analysis on the honey of Heterotrigona itama and Tetrigona binghami from Sarawak, Malaysia

This study aims to compare the chemical composition of honey samples produced by Heterotrigona itama and Tetrigona binghami which originated from Sarawak, Malaysia. One hundred and six (106) honey samples were collected from local bee farms and analysed in terms of their chemical profiles. The chemical analysis conducted includes physicochemical composition such as moisture, total phenolic content, sugar, 5-hydroxymethylfurfural (5-HMF), pH and organic acids and proximate analysis which included ash, protein, carbohydrates and energy. Independent T-test was used as a statistical tool to investigate the significant difference between the composition of both honey samples. The results showed that honey samples of Heterotrigona itama and Tetrigona binghami possessed significant difference (p<0.05) in moisture, total phenolic content, fructose, glucose, pH, protein, gluconic acid, acetic acid, ash, carbohydrates and energy. The honey samples of Heterotrigona itama exhibited significantly higher fructose and glucose at the average of 22.00 ± 3.48 g/ 100 g and 23.45 ± 3.23 g/100 g, respectively. Besides, the honey samples also possessed higher pH value, gluconic acid, ash, carbohydrates and energy. Meanwhile, Tetrigona binghami honey samples possessed significantly (p< 0.05) higher moisture content, total phenolic content, protein and acetic acid compared to the Heterotrigona itama’s honey samples. To conclude, the geographical and floral origins of honey are the two important quality parameters which fundamentally affect the physical-chemical properties as well as biological activities of honey samples

Power Analysis and Optimization Techniques for Energy Efficient Computer Systems

Reducing power consumption has become a major challenge in the design and operation of to-day’s computer systems. This chapter describes different techniques addressing this challenge at different levels of system hardware, such as CPU, memory, and internal interconnection network, as well as at different levels of software components, such as compiler, operating system and user applications. These techniques can be broadly categorized into two types: Design time power analysis versus run-time dynamic power management. Mechanisms in the first category use ana-lytical energy models that are integrated into existing simulators to measure the system’s power consumption and thus help engineers to test power-conscious hardware and software during de-sign time. On the other hand, dynamic power management techniques are applied during run-time, and are used to monitor system workload and adapt the system’s behavior dynamically to save energy

Enzymatic Determination of Diglyceride Using an Iridium Nano-Particle Based Single Use, Disposable Biosensor

A single use, disposable iridium-nano particle contained biosensor had been developed for the determination of diglyceride (DG). In this study hydrogen peroxide, formed through the enzymatic breakdown of DG via lipase, glycerol kinase and glycerol 3-phosphate oxidase, was electrochemically oxidized at an applied potential of +0.5 V versus the Ag/AgCl reference electrode. The oxidation current was then used to quantify the diglyceride concentration. Optimum enzyme concentrations and the surfactant loading used were established for successful sensor response. Good linear performance was observed over a DG concentration range of 0 to 25 μM in phosphate buffer and bovine serum media

Prostate-Specific Antigen, Digital Rectal Examination and Transrectal Ultrasonography: A Meta-Analysis for This Diagnostic Triad of Prostate Cancer in Symptomatic Korean Men

We conducted a meta-analysis using results from the Korean literature to determine whether prostate-specific antigen (PSA) or digital rectal examination (DRE) or transrectal ultrasonography (TRUS) provides a better diagnostic outcome for possible prostate cancer patients. An extensive literature search of MedRIC database et al. (1980 to 2003) was performed using the medical subject headings "PSA", "DRE", "TRUS" and "prostate cancer". Of the 108 articles that we retrieved, 13 studies (2,029 subjects) were selected for this meta-analysis. The criteria for quality evaluation were as follows: the study subjects must have been compared clinically for suspected prostate cancer, and the articles must have included individual data about sensitivity and specificity for this diagnostic triad based on the biopsy results as a reference standard. For the quantitative meta-analysis process the Hasselblad method was utilized. The pooled sensitivity and specificity for a PSA level greater than 4 ng/mL were 91.3% and 35.9%, respectively; and those for a PSA level greater than 10 ng/mL were 77.3% and 67.5%, respectively; and those for DRE were 68.4% and 71.5%, respectively; and those for TRUS were 73.6% and 61.3%, respectively. According to the results in a fixed effect model for PSA criteria, the estimates of d for PSA4 and PSA10 were 0.8517 [95% confidence interval (CI): 0.6694, 1.0340] and 1.0996 (95% CI: 0.9459, 1.2534), respectively. Also, according to the results using a random effect model for both DRE and TRUS criteria, the estimates of d for DRE and TRUS were 0.8398 (95% CI: 0.7169, 0.9627) and 0.8002 (95% CI: 0.6714, 0.9289), respectively. The detection rate for combination testing of PSA, DRE and TRUS for the diagnosis of prostate cancer jumped further to 68.3% or to 76.8%. In conclusion, this study suggests that this diagnostic triad for prostate cancer was noneffective when they were used separately. Therefore, we recommend that the urologists should use PSA together with DRE and TRUS for the primary diagnosis of prostate cancer in men with lower urological symptoms

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030