Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of hr‐IL2 treatment on intestinal P‐glycoprotein expression and activity in Caco‐2 cells

Caco‐2 cells were used to investigate the effect of human recombinant interleukin‐2 (IL2) on intestinal P‐glycoprotein (P‐gp) transporter activity in‐vitro. More specifically the efflux function of P‐gp was studied by measuring the transepithelial transport of rhodamine‐123, a fluorescent substrate of P‐gp. Its transport was completely inhibited by two specific P‐gp inhibitors, ciclosporin A and GG918, in our experiments. Conversely, these two specific P‐gp inhibitors inhibited only 50% of transepithelial transport when [3H]vincristine was used as substrate. After Caco‐2 cells were treated with 100 IU mL−1 (6.1 ng mL−1) IL2 for 24 h, a significant diminution (21%) of P‐gp transporter function was observed with rhodamine‐123 substrate. This effect was also confirmed after 48 and 72 h of exposure to IL2. However, for higher concentrations of IL2 (1000 and 5000 IU mL−1), diminution of P‐gp function only occurred after a longer treatment period (48 h and more). The inhibitory effect of IL2 on P‐gp activity was found to be independent of tight junction function as demonstrated by constant transepithelial electrical resistance (TEER) measurements for all experimental conditions encountered in this study (time and concentration of IL2 exposure). Furthermore, the MDR1 mRNA level was found to be strongly repressed in Caco‐2 cells exposed with 1000 IU mL−1 IL2 for 72 h while the amount of MRP1 mRNA remained unchanged. In conclusion, acute incubation of Caco‐2 cells with IL2 induced a decrease of P‐gp transporter expression and activity.
Importance of cysteine residues for the stability and catalytic activity of human pancreatic beta cell glucokinase.

The low-affinity glucose phosphorylating enzyme glucokinase has the function of a physiological glucose sensor in pancreatic beta cells and in liver. In contrast to the high-affinity hexokinase types I-III glucokinase shows extraordinary sensitivity toward SH group oxidizing compounds. To characterize the function of sulfhydryl groups cysteine residues in the vicinity of the sugar binding site (Cys 213, Cys 220, Cys 230, Cys 233, and Cys 252) as well as cysteine residues a distance from the active site (Cys 364, Cys 371, and Cys 382), they were replaced in human beta cell glucokinase by serine through site-directed mutagenesis. Controlled proteolysis of wild-type glucokinase by proteinase K revealed that the SH group oxidizing agent alloxan can induce the formation of multiple intramolecular disulfide bridges corresponding to a double-band pattern of glucokinase protein in nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The formation of intramolecular disulfide bridges altered the mobility of the protein. None of the cysteine mutations could prevent the formation of the 49-kDa glucokinase conformation after alloxan treatment. The cysteine mutants Cys 233, Cys 252, and Cys 382 showed nearly complete loss of catalytic activity, whereas the V(max) values of the Cys 213, Cys 220, Cys 364, and Cys 371 mutants were decreased by 30-60%. Only the Cys 230 mutant showed kinetic characteristics comparable to those of wild-type glucokinase. The sensitivity of the Cys 213, Cys 230, Cys 364, and Cys 371 mutants toward alloxan-induced inhibition of enzyme activity was up to 10-fold lower compared with wild-type glucokinase. d-Glucose and dithiotreitol provided protection against alloxan-induced inhibition of wild-type glucokinase and all catalytically active cysteine mutants. Conclusively our data demonstrate the functional significance of the cysteine residues of beta cell glucokinase for both structural instability of the enzyme and catalytic function. Knowledge of sensitive cysteine targets may help to develop strategies that improve glucokinase enzyme function under conditions of oxidative stress.
External validation and clinical evaluation of the International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET‐thrombosis) in a large cohort of Chinese patients

In patients with essential thrombocythemia (ET), vascular complications contribute to both morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score of thrombosis for ET (IPSET‐thrombosis) was recently developed. We hereby presented an external validation and analysis of this model in a large Cohort of Chinese Patients.
Online survey on subjective and objective competency in clinical pharmacology skills among final year Australian medical students: a pilot study

Adequate training in clinical pharmacology (CP) is considered essential to produce medical graduates who can provide safe and effective prescribing. National and international curriculums for CP teaching generally cover the following domains: knowledge and principles of CP, skills and attitudes [Orme et al. 2002; ASCEPT, 2011; CIOMS, 2012]. Two main approaches have been used by medical schools to objectively assess CP and prescribing competency: a list of core drugs, known as a student formulary, that students must know; and a list of common clinical conditions that students must be able to manage [Orme et al. 2002].
Basal Core Promoter and Precore Mutations in the Hepatitis B Virus Genome Enhance Replication Efficacy of Lamivudine-Resistant Mutants

ABSTRACT During chronic hepatitis B virus (HBV) infection, mutations in the precore (PC) or basal core promoter (BCP) region affecting HBV e antigen (HBeAg) expression occur commonly and represent the predominant virus species in patients with HBeAg-negative chronic hepatitis B. The PC mutation (G1896A+C1858T) creates a translational stop codon resulting in absent HBeAg expression, whereas BCP mutations (A1762T/G1764A) reduce HBeAg expression by transcriptional mechanisms. Treatment of chronic HBV infection with lamivudine (LMV) often selects drug-resistant strains with single (rtM204I) or double (rtL180M+rtM204V) point mutations in the YMDD motif of HBV reverse transcriptase. We cloned replication-competent HBV vectors (genotype A, adw2) combining mutations in the core (wild type [wt], PC, and BCP) and polymerase gene (wt, rtM204I, and rtL180M/M204V) and analyzed virus replication and drug sensitivity in vitro. Resistance to LMV (rtM204I/rtL180M+rtM204V) was accompanied by a reduced replication efficacy as evidenced by reduced pregenomic RNA, encapsidated progeny DNA, polymerase activity, and virion release. PC mutations alone did not alter virus replication but restored replication efficacy of the LMV-resistant mutants without affecting drug resistance. BCP mutants had higher replication capacities than did the wt, also in combination with LMV resistance mutations. All nine HBV constructs showed similar sensitivities to adefovir. In conclusion, BCP-PC mutations directly impact the replication capacity of LMV-resistant mutants. PC mutations compensated for replication inefficiency of LMV-resistant mutants, whereas BCP mutations increased viral replication levels to above the wt baseline values, even in LMV-resistant mutants, without affecting drug sensitivity in vitro. Adefovir may be an effective treatment when combinations of core and polymerase mutations occur.
Adjustment of children and adolescents to parental cancer: Parents' and children's perspectives

Little empirical evidence exists to address the impact of a diagnosis of cancer of a father or mother on his or her children. Previous studies have found inconsistencies in the levels of distress reported for children of a parent with cancer, which may be a function of who (parent or child) was reporting on the child's symptoms and when the reports were taken (near diagnosis or months or years later).
Synergism between dipyridamole and cisplatin in human breast cancer cells in vitro

Cisplatin is very effective in the treatment of metastatic breast cancer. However, the development of cellular resistance is a serious problem in cisplatin chemotherapy. In the present work, the effects of dipyridamole (DPM) on the cellular accumulation and cytotoxicity of cisplatin was studied in cisplatinsensitive (MDA/S) and cisplatinresistant (MDA/R) human breast cancer cells. In the presence of 30 µM DPM, the IC50 of cisplatin was reduced by 39% for both cell lines. Combination index analysis revealed that cisplatin and dipyridamole interact synergistically in MDA/R cells. In the MDA/S cells, the cellular accumulation of cisplatin increased by 57 ± 8% in the presence of 30 µM DPM. In the MDA/R cells, the cellular accumulation of cisplatin remained the same with or without 30 µM DPM. The results suggest that the enhancement of cisplatin cytotoxicity by DPM in MDA/S cells may be related to a DPM-induced increase in cisplatin accumulation, but the enhanced cytotoxicity in MDA/R cells employs a mechanism that does not involve an increase in the cellular accumulation of cisplatin.
First trimester prediction of growth discordance in twin gestations.

OBJECTIVE The purpose of this study was to determine whether first trimester ultrasound scanning can identify twin gestations that are at risk for subsequent growth discordance. STUDY DESIGN Ultrasound examinations of dichorionic twin pregnancies between 11 and 14 weeks of gestation were evaluated for growth discordance with crown-rump length. Pregnancies that were complicated by fetal death or anomalies were excluded from the analysis. Birth weight discordance was defined as >or=20% difference in birth weight, relative to the larger twin. Fisher's exact, Mann Whitney U, and Spearman rho tests were used for statistical analysis. RESULTS Of 130 twin pregnancies, 16 pregnancies (12.3%) had discordant birth weight. Crown-rump length disparity was correlated positively with birth weight discordance (r=0.31; P<.001). Of pregnancies with a discrepancy of <or=3 days in estimated gestational age, only 9.2% were discordant at birth compared with 45.5% of pregnancies with >3 days discrepancy (P=.004), which resulted in a likelihood ratio of 5.9 for having discordant birth weight. CONCLUSION Twins who are ultimately discordant at birth may exhibit differences in growth as early as 11 to 14 weeks of gestation.
Age-related differences in recall for words using semantics and prosody

ABSTRACT The positivity effect is a developmental shift seen in older adults to be increasingly influenced by positive information in areas such as memory, attention, and decision-making. This study is the first to examine the age-related differences of the positivity effect for emotional prosody. Participants heard a factorial combination of words that were semantically positive or negative said with either positive or negative intonation. Results showed a semantic positivity effect for older adults, and a prosody positivity effect for younger adults. Additionally, older adults showed a significant decrease in recall for semantically negative words said in an incongruent prosodically positive tone.
Using the 12-item General Health Questionnaire (GHQ-12) to Assess the Psychological Health of Malaysian College Students

The primary objective of this study was to assess the psychological health of students at a local university in Malaysia using General Health Questionnaire (GHQ-12). Additionally, the study was carried out to determine the reliability and factor structure of the GHQ-12. Sample comprised 386 students (female=177, male=209) who were selected using multistage cluster sampling. A self-administered questionnaire was used to collect the data required. Results showed that slightly more than half (52.9%) of the respondents scored low on the GHQ-12, and a substantial proportion (47.1%) of them scored high, indicating an unhealthy psychological state. Nevertheless, no differences were observed between the genders. Reliability analysis showed satisfactory results, with a Cronbach’s alpha of 0.70. Meanwhile, factor analysis revealed that GHQ-12 was a measure of psychological distress, with a three-factor structure (Psychological Distress, Social and Emotional Dysfunction and Cognitive Disorder), which jointly accounted for 51.9% of the variance. The findings of the study therefore affirm that the GHQ-12 is a good measure for assessing the overall psychological well-being of students in Malaysia.
Underactuated ships follow smooth paths with Integral actions and without velocity measurements for feedback: theory and experiments

Steering a ship along a desired path with a prescribed forward speed is a vitally important issue in many offshore applications. This paper presents a global controller that forces a ship without a sway actuator to follow a reference path and without velocity measurements for feedback. Nonlinear damping terms are also included to cover both low- and high-speed applications. Integral actions are added to the controller to compensate for a constant bias of environmental disturbances. Experimental results on a model ship illustrate the effectiveness of the proposed method.
Grain physical characteristics and bread-making quality of alternative cereals towards common and durum wheat.

The present study is aimed at explaining the physical characteristics and bread-making quality of Khorasanwheat (BGR 40365, BGR 12389), einkorn (B2E0417) and emmer (B2000528). Here we will compare theaforementioned grains to both, common wheat (cv. Enola and Sadovo 1) and durum wheat (cv. Progres andDenitza). The physico-chemical characteristics (i.e thousand kernel weight, gluten content and Pelshenkevalue), are known to differ significantly among the wheat species, however, few studies have examined thesecharacteristics in ancient grains. The highest thousand kernel weight and test weight were observed in BGR40365. The highest wet gluten content was found in BGR 12389 (34.02%). One variety of einkorn (B2E0417)was determined to be ? gluten free'. Emmer (B2000528) was characterized by high content of wet gluten(30.13%). The best balance between gluten quantity and quality was observed in two varieties of Khorasanwheat (BGR12389, BGR 40365). PC-analysis was applied to group varieties according to their similarity on thebasis of ten traits. Three sub-groups could be identified where the first one composed by the hexaploid wheatcultivar Sadovo 1 and cultivar Enola. The second sub-group included cultivar Progres and BGR 40365, whilecultivar Denitza, BGR 12389 and B2000528 constituted the heterogeneous third sub-group.
Trust-Assuring Arguments in B2C E-commerce: Impact of Content, Source, and Price on Trust

The research question examined in this paper is whether or not product price can be used as a proxy to predict how customers' trust will be influenced by different trust-assuring arguments displayed on a business-to-consumer e-commerce Web site. Drawing from the elaboration likelihood model (ELM) and Toulmin's model of argumentation, we examine the effects on consumer trust of two levels of source and two levels of content factors, under two levels of product price, in a laboratory experiment with 128 subjects. Product price was predicted as a moderating factor that would influence the customer's motivation to scrutinize more closely the content of the trust-assuring arguments. The results suggest that customers are more influenced by the content of trust-assuring arguments when the price of a product is relatively high than when it is relatively low. Presumably, Internet stores employ a third party's trust-assuring arguments because customers are less likely to trust an unknown Internet store's own trust-assuring arguments. However, the results paradoxically may imply that when customers have more at stake (e.g., buying a high-price product), they do not necessarily have to rely only on an independent third-party source to form high trust beliefs about the store. When customers purchase a high-price product, they seem to form trusting beliefs by scrutinizing argument content rather than by depending on heuristic cues (e.g., an independent party's opinion) as the ELM would predict.
Detecting Anomalous Online Reviewers: An Unsupervised Approach Using Mixture Models

Abstract Online reviews play a significant role in influencing decisions made by users in day-to-day life. The presence of reviewers who deliberately post fake reviews for financial or other gains, however, negatively impacts both users and businesses. Unfortunately, automatically detecting such reviewers is a challenging problem since fake reviews do not seem out-of-place next to genuine reviews. In this paper, we present a fully unsupervised approach to detect anomalous behavior in online reviewers. We propose a novel hierarchical approach for this task in which we (1) derive distributions for key features that define reviewer behavior, and (2) combine these distributions into a finite mixture model. Our approach is highly generalizable and it allows us to seamlessly combine both univariate and multivariate distributions into a unified anomaly detection system. Most importantly, it requires no explicit labeling (spam/not spam) of the data. Our newly developed approach outperforms prior state-of-the-art unsupervised anomaly detection approaches.
Coherent amygdalocortical theta promotes fear memory consolidation during paradoxical sleep

Brain activity in sleep plays a crucial role in memory consolidation, an offline process that determines the long-term strength of memory traces. Consolidation efficacy differs across individuals, but the brain activity dynamics underlying these differences remain unknown. Here, we studied how interindividual variability in fear memory consolidation relates to neural activity in brain structures that participate in Pavlovian fear learning. From the end of training to testing 24 h later, some rats showed increased and others decreased conditioned fear responses. We found that overnight bidirectional changes in fear memory were selectively correlated with modifications in theta coherence between the amygdala, medial prefrontal cortex, and hippocampus during paradoxical sleep. Thus, our results suggest that theta coordination in the limbic system may influence interindividual differences in memory consolidation of aversive experiences.
Effect of CZT System Characteristics on Compton Scatter Event Recovery

Improving 511 keV photon detection sensitivity is a common goal for positron emission tomography (PET) system designers. One attractive approach to increase sensitivity is recovering events that are normally rejected. The kinematics of Compton scattering can be used to recover the line of response through direction difference angle (DDA). The uncertainty of DDA is determined by the energy and spatial resolution of a system. In this paper, we evaluated the performance of small animal cadmium zinc telluride-based PET systems with energy resolution of 1%, 4%, and 6% and different spatial resolution based on prior work for guiding new design efforts. Designs with energy resolution limited by counting statistics and by electronic noise were considered. The influence of modifying the conventional energy window and uncertainty of DDA was investigated. For a system with 4% energy resolution and limited by electronic noise, the figure of merit of noise equivalent count increases by 65% as the lower energy bound increases from 471 to 493 keV. If the system-wide energy resolution becomes worse than 4% of the full width half maximum at 511 keV, going to a pixel size finer than 1 mm has very limited effect in reducing total angular uncertainty. For a system with 1% energy resolution, as the spatial resolution improves from 1 mm to 0.5 mm, the contrast-to-noise ratio increases by 9%.
Points of View Examining Basal Avian Divergences with Mitochondrial Sequences: Model Complexity, Taxon Sampling, and Sequence Length

Traditional avian classications have generally indicated that the paleognathous birds (ratites and tinamous) represent the earliest divergence within the extant birds and the perching birds (Passeriformes) represent one of the most recently derived lineages (reviewed by Sibley and Ahlquist, 1990; Feduccia, 1995; see Fig. 1A). However, the conclusions of several recent studies using complete mitochondrial genome sequences from birds have challenged these classications (Mindell et al., 1997, 1999; Härlid and Arnason, 1999; Haring et al., 2001; but see Paton et al., 2002). In particular, these studies have suggested that the passeriforms are one of the most ancient groups of extant birds and that the paleognaths are derived. This conclusion has profound implications for avian evolution. An ancient origin of passerines could explain the remarkable diversity of this group, which represents over half of modern avian species, without invoking different rates of cladogenesis and/or extinction in the passerines and other groups of birds. Likewise, a derived position of paleognaths would require a neotenous origin of paleognath morphological characters (Härlid and Arnason, 1999) and a different model of avian sex chromosome evolution (Ellegren and Carmichael, 2001). Although complete avian mitochondrial sequences provide a large number of sites, it seems unlikely that mitochondrial data have provided an accurate picture of avian
Detection of SV40 DNA sequences in malignant mesothelioma specimens from the United States, but not from Turkey

The incidence of malignant mesothelioma (MM) shows a strong epidemiological association with exposure to asbestos fibers. Recently, simian virus 40 (SV40) DNA sequences have been reported in MM tumor specimens from the United States and several European countries, and the SV40 tumor virus has been implicated as a potential co‐factor in the etiology of this disease. However, several large studies from the US, Finland, and Turkey did not detect SV40 sequences in MM samples. To address this discrepancy, MM specimens from Turkey and the US were analyzed in the same laboratory under identical conditions to detect the presence of SV40 DNA. We detected SV40 sequences in 4 of 11 specimens from the United States, but in none of the 9 Turkish samples examined. These findings suggest that geographical differences exist with regard to the involvement of SV40 in human tumors. J. Cell. Biochem. 84: 455–459, 2002. © 2001 Wiley‐Liss, Inc.
Weaning Mass Affects Changes in Body Composition and Food Intake in Harbour Seal Pups during the First Month of Independence

In phocid seals, the transition to nutritional independence is abrupt, with females abandoning their offspring after weaning and returning to sea. We hypothesized that body size at weaning may play an important role in the nature of this transition. We studied the changes in body composition and water flux of newly weaning harbour seals over the first 4–6 wk postweaning. Thirty‐three pups were dosed with deuterium oxide to estimate total body water (TBW) and a subset of 24 was dosed twice to estimate changes in body composition and water flux. All pups lost body mass over the study period, but TBW increased during the period of mass loss, indicating continued lean tissue growth. Combined data from this and our early study indicated that heavy (>median mass) pups were relatively fatter (41.0% vs. 37.1%) and had significantly greater total body energy at weaning than did light (≤ median mass) pups. Percentage TBW declined linearly over time in light pups but was constant in heavy pups for the first 19 d postweaning and then declined linearly. Both the temporal pattern and composition of mass loss differed between light and heavy pups. Estimated food intake increased in the second 2 wk of study compared to the first 2 wk, in both light and heavy pups, reflecting increased foraging success but at levels still insufficient to meet daily expenditures of most individuals.