Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution of Hole Trapping in the Oxynitride Gate p-MOSFET Subjected to Negative-Bias Temperature Stressing

We present experimental evidence of a thermally activated transformation of negative-bias-temperature-stress-induced transient hole trapping at preexisting oxide traps into more permanent trapped holes in the ultrathin oxynitride gate p-MOSFET. The transformation is also shown to correlate with the generation of stress-induced leakage current, indicating that it is one of the key mechanisms of bulk trap generation. A similar observation (reported elsewhere) applies to the HfO2 gate p-MOSFET, implying that the observed hole-trap transformation is a common mechanism for bulk trap generation across different gate oxide technologies. The results further imply that preexisting oxide defects, usually deemed irrelevant to negative-bias temperature instability, have a definite role on long-term device parametric drifts.
Autoimmune Pancreatitis in Young Patients

Goals To examine whether there is a difference in the autoimmune pancreatitis (AIP) seen in young and elderly patients. Background AIP has a preponderance for elderly males, although the reason is unknown. Study A total of 64 patients with AIP were divided into a young (<40 y old) group and a middle-aged or elderly group (≥40 y old) according to the age at diagnosis. The clinical findings of each group were compared. Results The young group consisted of 6 patients (3 men, 3 women) with a mean age of 33.0 (range, 28 to 37) years. In the middle-aged or elderly group, there were 58 patients with a mean age of 66.4 (range, 46 to 83) years; males predominated (79%). Abdominal pain as the presenting symptom was significantly more frequent in the young group than in the middle-aged or elderly group (100% vs. 43%, P<0.05). Obstructive jaundice was detected in only 17% (1/6) of patients in the young group compared with 59% (34/58) of patients in the middle-aged or elderly group. Serum amylase elevations were detected more frequently in the young group than in the middle-aged or elderly group (83% vs. 40%, P<0.05). One young patient also had ulcerative colitis. Conclusions Although rare in Japan, young patients with AIP show different clinical features from middle-aged or elderly patients with AIP; young patients are more likely to have abdominal pain and serum amylase elevations.
Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients

We retrospectively analysed the data of 1519 antiphospholipid antibody (APLA) positive patients between 1986 and 1999. Among them 637 were considered to have antiphospholipid syndrome (APS) based on the 1999 preliminary classification criteria, while 704 patients had no clinical signs of the syndrome. Our aim was to compare the autoantibody profile and clinical characteristics of primary and secondary APS, moreover to evaluate the associations between different APLA and specific symptoms attributable to APS. In our results, the APLA profiles for primary and SLE-associated secondary APS were similar. Among the evaluated clinical symptoms, cerebrovascular thrombosis was found to be more frequent in the SLE-associated, than in the primary APS group (P = 0.04). We identified important differences in the clinical profile of patient populations with various types of APLA. Venous thrombosis occurred more frequently in subjects with lupus anticoagulant (LA), than in those with IgG or IgM type ACLA (P < 0.0001), while coronary, carotid and peripheral artery thrombosis occurred more often in subjects with IgG or IgM ACLA (P < 0.0001). These findings may support the role of antibodies to cardiolipin or its cofactor, b2glycoprotein I (b2-GPI) in the initiation and progression of atherosclerosis. Cerebrovascular thrombosis was detected in larger proportion of LA or IgG ACLA-positive patients compared with to IgM ACLA-positive subjects, while the occurrence of foetal loss was similar in all three groups.
The Increase of Energy Consumption and Carbon Dioxide (CO2) Emission in Indonesia

In the last decade, the increase of energy consumption that has multiplied carbondioxide emissions becomes world problems, especially in the developing countries undergoing industrialization to be developed ones like Indonesia. This aim of this study was to analyze the effect of fossil energy consumption, population growth, and consumption of renewable energy on carbon dioxide emission. The method used was multiple linear regression analysis with Ordinary Least Square approach using time series in the period of 1990 - 2014. The result showed that fossil energy consumption and population growth have a positive influence on carbon dioxide emission in Indonesia. Meanwhile, the consumption variable of renewable energy has a negative effect on the level of carbon dioxide emissions produced.
Expression of CD40 and CD40 Ligand among Cell Populations within Rheumatoid Synovial Compartment

Augmented and prolonged expression of CD40 ligand (CD40L) was recently reported in lymphoid cells from human lupus patients, suggesting that CD40/CD40L pathway was involved in the pathogenesis of systemic autoimmune diseases. This study was thus designed to study the expression of CD40 and CD40L among cell populations within inflammatory joints of patients with rheumatoid arthritis (RA). The result showed that most B cells and monocytes in synovial fluids (SF) expressed CD40. Cultured synovial fibroblasts also stained positive for CD40. Regarding CD40L, we found that T cells as well as B cells could express CD40L. Compared with normal controls, RA patients had higher levels of CD40L+ T cells (8.71 ± 17.69 % vs 1.74 ± 2.30 %, P± 0.05) and CD40L+ B cells (7.71 ± 7.64 % vs 1.12 ± 1.59 % P < 0.05). After in vitro stimulation, T cells from RA patients had higher and longer CD40L expression than T cells from normal peripheral blood. For investigating the effect of CD40 expressed on synovial fibroblasts on TNF-a production in joint compartment, we used anti-CD40 antibody to bind CD40 on fibroblasts for one hour and then co-cultured with synovial fluid mononuclear cells. We found that the levels of TNF-a decreased in the presence of anti-CD40 antibody. We concluded that there was an intrinsic hyperexpression of CD40L on lymphoid cells within rheumatoid joints, and synovial fibroblasts could contribute to articular inflammation through surface CD40 molecule.
Characterization of the DNA-binding properties of herpes simplex virus regulatory protein ICP4

ICP4 is a herpesvirus-encoded protein that is expressed during the immediate-early phase of productive infection and is required for efficient transcription of viral genes during the early and late phases of infection. Previous studies have shown that ICP4 is a component of specific protein-DNA complexes but have not revealed whether native ICP4 directly recognizes specific nucleotide sequences. Using DNA affinity chromatography, we have purified ICP4 to near homogeneity. The purified preparation consists primarily of dimeric and tetrameric forms of ICP4. As shown by DNase protection experiments, purified ICP4 binds directly to specific sequences in viral DNA. The stability of ICP4-DNA complexes is increased over 100-fold by shifting the temperature from 23 to 4 degrees C. The equilibrium dissociation constant of ICP4-DNA complexes formed at 4 degrees C in the presence of 100 mM NaCl was determined to be approximately 1.1 nM.
How Does Genotype Influence Disease Phenotype in Inflammatory Bowel Disease?

Abstract:Inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) are chronic immunologically mediated diseases of the gut. Advances in genetics have revolutionized our understanding of the pathogenesis of these conditions with 163 risk loci identified, encompassing a variety of immunologic functions. There is substantial heterogeneity in the natural history of these diseases with respect to disease onset, course, and progression to complications. There are also significant variations in response to therapies and susceptibility to therapy-related and disease-related complications. An important need in the field is to identify predictors of disease course, complications, and likelihood of response and adverse events to allow for targeted therapeutic decision making. The genotype of an individual in constant and non-modifiable, and thus could potentially fulfill the role of important predictors of these outcomes. In this review, we discuss the existing literature on the prediction of various disease phenotypes in Crohn’s disease and ulcerative colitis using underlying genotype. We also identify gaps in the literature and suggest future directions for research. There is need for large, multi-institutional, and international collaborative consortia with efficient and detailed cohort accrual, phenotypic definition, genotyping, and dynamic assessments of external (e.g., diet) and internal (microbiome) environment to allow us to progress toward personalized and precision medicine in the management of these complex diseases.
DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma

Esophageal cancer is ranked as the eighth most common cancer and the sixth leading cause of cancer deaths worldwide. To identify candidate tumor suppressor genes related to esophageal squamous cell carcinoma (ESCC) development, a cDNA microarray analysis was performed using paired tumor and nontumor tissue samples from ESCC patients. Differentially expressed in squamous cell carcinoma 1 (DESC1), which belongs to the Type II transmembrane serine protease family, was frequently downregulated in ESCC. This study aims to elucidate the molecular mechanism for the tumor suppressive function of DESC1 in ESCC. We show that DESC1 reduced cell viability and sensitized cells to apoptosis, when cells were under apoptotic stimuli. The proapoptotic effect of DESC1 was mediated through downregulating AKT1 activation and the restoration of AKT activation by the introduction of the constitutively active AKT, myr‐AKT, abolished the apoptosis‐sensitizing effect of DESC1. DESC1 also reduced EGFR protein level, which was abrogated when the proteolytic function of DESC1 was lost, suggesting that DESC1 cleaved EGFR and downregulated the EGFR/AKT pathway to favor apoptosis. The transmembrane localization and the structural domains provide an opportunity for DESC1 to interact with the extracellular environment. The importance of such interaction was highlighted by the finding that DESC1 reduced cell colony formation ability in three‐dimensional culture. In line with this, DESC1 reduced tumor growth kinetics in the in vivo orthotopic tumorigenesis assay. Taken together, our novel findings suggest how DESC1 may suppress ESCC development by sensitizing cells to apoptosis under an apoptotic stimulus through downregulating the EGFR/AKT signaling pathway.
Hippocampal Shape Modeling Based on a Progressive Template Surface Deformation and its Verification

Accurately recovering the hippocampal shapes against rough and noisy segmentations is as challenging as achieving good anatomical correspondence between the individual shapes. To address these issues, we propose a mesh-to-volume registration approach, characterized by a progressive model deformation. Our model implements flexible weighting scheme for model rigidity under a multi-level neighborhood for vertex connectivity. This method induces a large-to-small scale deformation of a template surface to build the pairwise correspondence by minimizing geometric distortion while robustly restoring the individuals' shape characteristics. We evaluated the proposed method's 1) accuracy and robustness in smooth surface reconstruction, 2) sensitivity in detecting significant shape differences between healthy control and disease groups (mild cognitive impairment and Alzheimer's disease), 3) robustness in constructing the anatomical correspondence between individual shape models, and 4) applicability in identifying subtle shape changes in relation to cognitive abilities in a healthy population. We compared the performance of the proposed method with other well-known methods-SPHARM-PDM, ShapeWorks and LDDMM volume registration with template injection-using various metrics of shape similarity, surface roughness, volume, and shape deformity. The experimental results showed that the proposed method generated smooth surfaces with less volume differences and better shape similarity to input volumes than others. The statistical analyses with clinical variables also showed that it was sensitive in detecting subtle shape changes of hippocampus.
Cefuroxime pharmacokinetics in pediatric cardiovascular surgery patients undergoing cardiopulmonary bypass.

OBJECTIVES The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. DESIGN A prospective study. SETTING A tertiary pediatric teaching hospital. PARTICIPANTS Infants and children undergoing CPB were enrolled in the study. INTERVENTION An initial dose (mean, 24.2 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined by a validated high-performance liquid chromatography method. A 2-compartment pharmacokinetic model was fitted to the data using maximum a priori-Bayesian estimation, with weight as a covariate. Monte Carlo simulations of a single-dose (25 mg/kg pre-CPB) approach and a 2-dose (25 mg/kg pre- and 12.5-mg/kg prime solution dose) approach were performed. MEASUREMENTS AND MAIN RESULTS Fifteen subjects (9 males/6 females) were enrolled in the study, with median (range) age and weight of 11 (3-34) months and 9.5 (4.5-15.4) kg, respectively. The median (range) duration of CPB was 136 (71-243) minutes. Median and range cefuroxime pharmacokinetic parameters were as follows: maximum concentration (Cmax) dose, 1: 328 (150-512) μg/mL; systemic clearance, 0.050 (0.041-0.058) L/h/kg; steady-state volume of distribution, 0.213 (0.081-0.423) L/kg; volume of distribution in the central compartment, 0.081 (0.046-0.162) L/kg; and elimination half-life, 3.76 (1.03-6.81) hours. The median 8-hour post-dose-simulated cefuroxime concentrations were 26.5 and 16.0 mg/L for the 2-dose and single-dose regimens, respectively. CONCLUSION Manufacturers recommend that pediatric doses of cefuroxime (25-50 mg/kg) can be used in infants and children undergoing CPB to maintain adequate serum concentrations for surgical-site infection prophylaxis. A second intraoperative dose, administered through the CPB circuit, provides no additional prophylactic advantage.
Knowledge and acceptance of telemedicine in surgery: a survey

A questionnaire was sent to the chief surgeons at 141 Swiss hospitals to evaluate their knowledge and acceptance of telemedicine in surgery. The response rate was 69%. Ninety-three per cent of all surgical departments used computer technology, 85% regularly used the Web and 88% had an internal hospital network. ISDN lines were used in 58% of the participants' hospitals. While 35% of respondents had participated at least once in networking, only 8% regularly used telemedicine. The opinion was that access to therapeutic advice (87%) was a better use of telemedicine than was obtaining a primary diagnosis (24%), although the majority accepted the principle of making (91%) and receiving (94%) a remote diagnosis. The survey suggested that surgeons are interested in telemedicine and open to its development, although their experience and knowledge are limited. Therefore, telemedicine in surgery may be advanced by creating surgical networks for teleconsultation and tele-education.
Foreign and Domestic Investment in Global Bond Markets

Gauging foreign (domestic) biases as the deviation of foreign (domestic) investors’ actual portfolio allocation of a bond market from the same bond market’s weight in global bond market, we investigate the determinants of foreign and domestic investment biases in 41 global bond markets. We find that foreign investors significantly overweigh markets that offer better risk–return profiles. In addition, greater market openness and sound macroeconomic outlook attract foreign investment. Such return driven behavior of foreign investors is especially pronounced in emerging bond markets. Meanwhile, home bias is higher in smaller bond markets. Our evidence sheds some light on the role of regional financial integration on broadening investor base and improving investor profile in emerging markets.
LPA4/GPR23 Is a Lysophosphatidic Acid (LPA) Receptor Utilizing Gs-, Gq/Gi-mediated Calcium Signaling and G12/13-mediated Rho Activation*

Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that signals through G protein-coupled receptors (GPCRs) to produce a range of biological responses. A recently reported fourth receptor, LPA4/GPR23, was notable for its low homology to the previously identified receptors LPA1–3 and for its ability to increase intracellular concentrations of cAMP and calcium. However, the signaling pathways leading to LPA4-mediated induction of cAMP and calcium levels have not been reported. Using epitope-tagged LPA4, pharmacological intervention, and G protein mini-genes, we provide independent confirmatory evidence that supports LPA4 as a fourth LPA receptor, including LPA concentration-dependent responses and specific membrane binding. Importantly, we further demonstrate new LPA-dependent activities of LPA4 that include the following: receptor internalization; G12/13- and Rho-mediated neurite retraction and stress fiber formation; Gq protein and pertussis toxin-sensitive calcium mobilization and activation of a nonselective cation conductance; and cAMP increases mediated by Gs. The receptor is broadly expressed in embryonic tissues, including brain, as determined by Northern blot and reverse transcription-PCR analysis. Adult tissues have increased expression in skin, heart, and to a lesser extent, thymus. These data confirm the identification and extend the functionality of LPA4 as an LPA receptor, bringing the number of independently verified LPA receptors to five, with both overlapping and distinct signaling properties and tissue expression.
Pharmacokinetics of antofloxacin hydrochloride in healthy male subjects after multiple intravenous dose administration

The purpose of the study was to evaluate pharmacokinetic characteristics of antofloxacin hydrochloride, a new fluoroquinolone antibiotic, during a multiple, intravenous dosing regimen. Twelve healthy, Chinese male volunteer subjects were each given 300 mg of antofloxacin by intravenous infusion once daily for 7 days. Blood and urine samples were taken at designated time points for analysis of antofloxacin concentration by high-performance liquid chromatography (HPLC). Safety and tolerability were assessed by evaluation of subject complaints, vital signs, electrocardiograms, electroencephalograms, clinical chemistry parameters, haematology and urinalysis and prothrombin time. The serum steady concentration of antofloxacin was obtained in 96 h after the administration of a daily intravenous dose of 300 mg of the drug. In the present study, the following pharmacokinetic parameters after 7 days of treatment with antofloxacin were determined to be: Cmax 3.81 ± 0.66 mg/L, Cmin 0.85 ± 0.19 mg/L, AUC0–24 60.51 ± 8.30 mg/L·h, Cav 2.52 ± 0.35 mg/L, PTF 87.45 ± 3.37%, t1/2β 20.34 ± 1.88 h. The Cmax and AUC0–24 after 7-day treatment were both higher than after the first dose (by 43% and 110%, respectively). The cumulative urinary elimination of antofloxacin within 96 h after the last dose was about 56%. During the study, there were neither subject complaints nor significant adverse clinical findings. Antofloxacin, administered intravenously as a single, daily 300 mg dose for 7 days, demonstrated favourable pharmacokinetic characteristics and tolerability. The results of this study indicate that antofloxacin hydrochloride is suitable for further clinical study.
Psychological effects of diagnosis and treatment of cervical intraepithelial neoplasia: a systematic review

Background Treatment of cervical intraepithelial neoplasia (CIN) is a common minor surgical procedure to prevent uterine cervical cancer. However, news of an abnormality detected at screening for cancer might cause the woman to worry. Objectives To investigate the psychological consequences of CIN diagnosis and treatment in a systematic review. Data sources We searched PubMed using Medical Subject Headings (MeSH) terms for articles published from January 1990 to February 2013. We also examined the reference lists of retrieved articles. Selection criteria Quantitative studies measuring psychological outcomes in women with a histological diagnosis or treatment of CIN, and in women having an outcome other than CIN at cervical screening. Data collection and analysis We abstracted the data using a pre-specified list of study characteristics and measured outcomes. For studies not reporting statistical testing, we estimated the statistical significance of the differences between the compared groups using unpaired t tests. Main results From 5099 retrieved abstracts, 16 studies were included. Diagnosis and treatment of CIN were associated with worse psychological outcomes than normal cytology test results, but the impact decreased over time. In several but not all studies, CIN appeared to have similar psychological consequences to abnormal smears. No study showed a difference in psychological outcomes between CIN and cervical cancer diagnosis when these were measured some years after diagnosis. Conclusions The studies suggested that CIN diagnosis and treatment have a negative psychological impact. However, this conclusion should be viewed in the context of a paucity of rigorously designed studies.
Comparison of Cerebral Blood Flow in Computed Tomographic Hypodense Areas of the Brain in Head-injured Patients

OBJECTIVEHypodense lesions identified on computed tomographic (CT) scans are often assumed to indicate ischemia. The purpose of this study was to investigate regional cerebral blood flow (rCBF) in hypodense areas of the brain after severe traumatic brain injury. METHODSCBF was measured by stable xenon-enhanced CT scans. Hypodense areas were identified, and rCBF values as well as CT density were averaged for the region. RESULTSThirty (60%) of the 50 patients had a total of 45 hypodense regions, which were associated with either contusion (n = 30) or areas of infarction (n = 15). rCBF in the hypodense regions was variable, ranging from a low of 3.3 to a high of 72.5 ml/100 g/min. The cause of the lesion was the major factor associated with the level of rCBF. Although the average decrease in CT density was similar for the two types of lesions, the average rCBF was significantly lower and the difference in rCBF between the lesion and the contralateral side was greater when the hypodense lesion was associated with a contusion. A critical reduction in rCBF (<20 ml/100 g/min) was found in 19 (63%) of the hypodense regions associated with contusions but in only 4 (27%) of those from areas of infarction. CONCLUSIONHypodensity on plain CT scans does not always indicate reduction in CBF. This association was found more commonly when the low-density area was associated with a contusion. In hypodense areas associated with infarction, rCBF was variable and not commonly in the ischemic range at the time the CBF measurement was obtained.