Miracle-dz/UniFAR-FTUs huggingface dataset:
SFRP 5 inhibits gastric epithelial cell migration induced by macrophage-derived Wnt 5 a

Secreted frizzled-related protein 5 (SFRP5) is frequently found downregulated in gastric cancer due to SFRP5 gene hypermethylation, and there is a great necessity to elucidate the role of its downregulation in gastric cancer. By binding Wnt molecules, SFRP5 is generally supposed to exert negative effects on Wnt signal pathways widely linked to human cancers. This study found that macrophages over-produced Wnt5a under the stimulation of Lipopolysaccharide (LPS) or Helicobacter pylori, the most common infectious agent in human stomach. Wnt5a-conditioned medium from macrophages enhanced cell migration and CXCR4 expression in either SFRP5-negative gastric epithelial cells (GEC) harboring SFRP5 methylation or SFRP5-positive cells treated with SFRP5 small interfering RNA (siRNA). However, such induced effect was remarkably eliminated by either Wnt5a siRNA in macrophages or treatment with recombinant SFRP5. We also found that Wnt5a-conditioned medium stimulated phosphorylation of c-jun N-terminal kinase (JNK) and c-Jun, and JNK inhibitor SP600125 blocked Wnt5a-induced CXCR4 expression and cell migration in SFRP5-negative cells. Taken together, these findings suggest that epithelium-derived SFRP5 may play a probable defensive role in impeding gastric cancer progression, characteristically by inhibiting GEC migration induced by macrophage-derived Wnt5a via JNK signaling activation.
Discrepancy between one-stage and chromogenic factor VIII activity assay results can lead to misdiagnosis of haemophilia A phenotype

Summary Severity of bleeding phenotype in hemophilia A (HA) depends on the underlying mutation in the F8 gene and, ultimately, on the concentration and functional integrity of the factor VIII (FVIII) protein in circulating plasma. Initial diagnosis for HA and monitoring of treatment is typically performed by measuring of FVIII activity by either one-stage assay or chromogenic assay. We review evidence for why both types of assay do not give comparable results in a significant proportion of patients with non-severe haemophilia A and why the discrepancy in results between both methods segregates with distinct subclasses of known missense mutations causing haemophilia A. The current understanding of the mechanistic basis for how FVIII:C assay discrepancies arise are discussed. Conclusion We propose that both methods should be used in initial patient diagnosis along with follow-up genetic analysis to avoid potential misdiagnosis and to optimize treatment monitoring of patients with HA phenotypes.
Editor’s Highlight: PlacentalDisposition and Effects of Crizotinib An Ex Vivo Study in the Isolated Dual-Side Perfused Human Cotyledon

Tyrosine kinase inhibitors (TKIs) play an important role in cancer pharmacotherapy, yet there is limited data on their use during pregnancy. We studied placental disposition and placental toxicity of crizotinib, a TKI used to treat nonsmall cell lung cancer. Term placentas were perfused for 3 h with crizotinib (1 µM) using the ex vivo dual-side cotyledon perfusion technique. Interference of TKIs with trophoblast viability was studied using BeWo cells. Expression of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) in placental tissue was assessed by immunohistochemistry and inhibition of these transporters was determined in vitro by transport studies with membrane vesicles overexpressing human P-gp or BCRP. We found that crizotinib rapidly and strongly accumulates in cotyledon perfusion experiments, reaching a concentration of 3.1 ± 0.4 µM in placental tissue. Final drug concentrations in the maternal and foetal reservoirs were 0.2 ± 0.05 and 0.08 ± 0.01 µM, respectively. Furthermore, crizotinib inhibited BeWo cell viability (IC50: 234 nM, 95% CI: 167-328 nM) 10 times more potently than other TKIs tested. In vitro transport studies revealed that crizotinib is a potent inhibitor of the transport activities of BCRP (IC50: 5.7 µM, 95% CI: 2.7-11.8 µM) and P-gp (IC50: 7.8 µM, 95% CI: 3.4-18.0 µM). In conclusion, crizotinib strongly accumulated in placental tissue at clinically relevant concentrations. IC50 values for transporter inhibition and trophoblast cell viability were similar to the tissue concentrations reached, suggesting that crizotinib can inhibit placental BCRP and P-gp function and possibly affect trophoblast viability.
Cytogenetic study in lung carcinoma of north coastal andhra pradesh, india

Tobacco smoking is the principal risk factor for the cause of lung cancer in South Asian countries. In India, males are more prone to risk than the females. Besides smoking, occupational exposure to industrialization and second-hand smoking are of minor causes. The change in cell metabolism and its function due to exposure of carcinogens that lead to structural abnormalities which are known as chromosomal aberrations. The present study is focused on the cytotoxicity and genotoxicity of the cells in lung cancer patients. Micronucleus assay (MN) was performed to assess the genotoxicity and cytotoxicity of the cells damaged in lung cancer cases and compared it with the control group. A sample size of 20 cases and 20 controls were taken. Males showed statistically high risk towards DNA damage than females. The mean age in the study is 50. 5Â±13.642. The frequency of chromosomal aberrations showed significant in cases than the control groups.
Market formation as transitive closure: The evolving pattern of trade in music

Abstract Where do new markets come from? I construct a network model in which national markets are nodes and flows of recorded music between them are links and conduct a longitudinal analysis of the global pattern of trade in the period 1976–2010. I hypothesize that new export markets are developed through a process of transitive closure in the network of international trade. When two countries' markets experience the same social influences, it brings them close enough together for new homophilous ties to be formed. The implication is that consumption of foreign products helps, not hurts, home-market producers develop overseas markets, but only in those countries that have a history of consuming the same foreign products that were consumed in the home market. Selling in a market changes what is valued in that market, and new market formation is a consequence of having social influences in common.
Presynaptic CRF1 Receptors Mediate the Ethanol Enhancement of GABAergic Transmission in the Mouse Central Amygdala

Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide involved in stress responses initiated from several brain areas, including the amygdala formation. Research shows a strong relationship between stress, brain CRF, and excessive alcohol consumption. Behavioral studies suggest that the central amygdala (CeA) is significantly involved in alcohol reward and dependence. We recently reported that the ethanol augmentation of GABAergic synaptic transmission in rat CeA involves CRF1 receptors, because both CRF and ethanol significantly enhanced the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs) in CeA neurons from wild-type (WT) and CRF2 knockout (KO) mice, but not in neurons of CRF1 KO mice. The present study extends these findings using selective CRF receptor ligands, gene KO models, and miniature IPSC (mIPSC) analysis to assess further a presynaptic role for the CRF receptors in mediating ethanol effects in the CeA. In whole-cell patch recordings of pharmacologically isolated GABAAergic IPSCs from slices of mouse CeA, both CRF and ethanol augmented evoked IPSCs in a concentration-dependent manner, with low EC50s. A CRF1 (but not CRF2) KO construct and the CRF1-selective nonpeptide antagonist NIH-3 (LWH-63) blocked the augmenting effect of both CRF and ethanol on evoked IPSCs. Furthermore, the new selective CRF1 agonist stressin1, but not the CRF2 agonist urocortin 3, also increased evoked IPSC amplitudes. Both CRF and ethanol decreased paired-pulse facilitation (PPF) of evoked IPSCs and significantly enhanced the frequency, but not the amplitude, of spontaneous miniature GABAergic mIPSCs in CeA neurons of WT mice, suggesting a presynaptic site of action. The PPF effect of ethanol was abolished in CeA neurons of CRF1 KO mice. The CRF1 antagonist NIH-3 blocked the CRF- and ethanol-induced enhancement of mIPSC frequency in CeA neurons. These data indicate that presynaptic CRF1 receptors play a critical role in permitting or mediating ethanol enhancement of GABAergic synaptic transmission in CeA, via increased vesicular GABA release, and thus may be a rational target for the treatment of alcohol abuse and alcoholism.
A New Phase Space Density for Quantum Expectations

We introduce a new density for the representation of quantum states on phase space. It is constructed as a weighted difference of two smooth probability densities using the Husimi function and first-order Hermite spectrograms. In contrast to the Wigner function, it is accessible by sampling strategies for positive densities. In the semiclassical regime, the new density allows to approximate expectation values to second order with respect to the high frequency parameter and is thus more accurate than the uncorrected Husimi function. As an application, we combine the new phase space density with Egorov's theorem for the numerical simulation of time-evolved quantum expectations by an ensemble of classical trajectories. We present supporting numerical experiments in different settings and dimensions.
Perioperative Management of Pregnant Women With Idiopathic Pulmonary Arterial Hypertension: An Observational Case Series Study From China.

OBJECTIVES The mortality of pregnant women with idiopathic pulmonary arterial hypertension (PAH) is very high. There are limited data on the management of idiopathic PAH during pregnancy. The authors aimed to examine systematically the characteristics of parturient women with idiopathic PAH, to explore the adverse effects of idiopathic PAH on pregnancy outcomes, and to report the multidisciplinary perioperative management strategy from the largest comprehensive cardiac hospital in China. DESIGN Observational case series study. SETTING Tertiary referral acute care hospital in Beijing, China. PARTICIPANTS The cases of 17 consecutive pregnant idiopathic PAH patients undergoing abortion or parturition at Anzhen Hospital were reviewed retrospectively. INTERVENTIONS Preoperative characteristics, anesthesia method, intensive care management, PAH-specific therapy, and maternal and neonatal outcomes were analyzed in this case series study. MEASURES AND MAIN RESULTS Maternal and neonatal outcomes were the main measures. The mean ages of the 17 parturient women with idiopathic PAH were 28.3 ± 5.4 years, and the mean systolic pulmonary arterial pressure was 97.9 ± 18.6 mmHg. Fifteen patients (88.2%) received PAH-specific therapy before delivery, including sildenafil, iloprost, and treprostinil. All except 1 parturient received epidural anesthesia for surgery due to an emergency Caesarean section. Three patients experienced pulmonary hypertension crisis that necessitated conversion to general anesthesia. Ten parturients underwent Caesarean delivery at a median gestational age of 31 weeks. Three patients developed acute pulmonary hypertensive crisis intraoperatively. Two patients underwent cardiopulmonary resuscitation and extracorporeal membrane oxygenation support. The maternal mortality was 17.6% (3/17). Of the 10 delivered neonates, 9 (90.0%) survived. CONCLUSIONS The maternal mortality of the idiopathic PAH parturient was high in this case series from China. The authors applied epidural anesthesia, early management with multidisciplinary approaches, PAH-specific therapy, avoidance of oxytocin, and timely delivery or pregnancy termination to improve maternal and neonatal outcomes.
Inhibitors of Helicobacter pylori Protease HtrA Found by ‘Virtual Ligand’ Screening Combat Bacterial Invasion of Epithelia

Background The human pathogen Helicobacter pylori (H. pylori) is a main cause for gastric inflammation and cancer. Increasing bacterial resistance against antibiotics demands for innovative strategies for therapeutic intervention. Methodology/Principal Findings We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. Pharmacophoric features of the map are clustered and transformed in a correlation vector (‘virtual ligand’) for rapid virtual screening of compound databases. This computer-based technique was validated for 18 different targets of pharmaceutical interest in a retrospective screening experiment. Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. Among 22 tested compounds six block E-cadherin cleavage by HtrA in vitro and result in reduced scattering and wound healing of gastric epithelial cells, thereby preventing bacterial infiltration of the epithelium. Conclusions/Significance This study demonstrates that receptor-based virtual screening with a permissive (‘fuzzy’) pharmacophore model can help identify small bioactive agents for combating bacterial infection.
Antidyslipidemic potential of a novel farnesoid X receptor antagonist in a hamster model of dyslipidemia: Comparative studies of other nonstatin agents

We attempted to clarify the therapeutic capability of antagonists of the farnesoid X receptor (FXR), a nuclear receptor that regulates lipid and bile acid metabolism. Herein, we report the antidyslipidemic effects of a novel synthesized FXR antagonist, compound‐T1, utilizing a dyslipidemic hamster model. Compound‐T1 selectively inhibited chenodeoxycholic acid‐induced FXR activation (IC50, 2.1 nmol·L−1). A hamster model of diet‐induced hyperlipidemia was prepared to investigate the antidyslipidemic effects of compound‐T1 through comparative studies of the nonstatin lipid‐modulating agents ezetimibe, cholestyramine, and torcetrapib. In the hamster model, compound‐T1 (6 mg·kg−1·day−1, p.o.) increased the level of plasma high‐density lipoprotein (HDL)‐cholesterol (+22.2%) and decreased the levels of plasma non‐HDL‐cholesterol (−43.6%) and triglycerides (−31.1%). Compound‐T1 also increased hepatic cholesterol 7α‐hydroxylase expression and fecal bile acid excretion, and decreased hepatic cholesterol content. Moreover, the hamster model could reflect clinical results of other nonstatin agents. Torcetrapib especially increased large HDL particles compared with compound‐T1. Additionally, in the human hepatoma Huh‐7 cells, compound‐T1 enhanced apolipoprotein A‐I secretion at a concentration close to its IC50 value for FXR. Our results indicated the usefulness of the hamster model in evaluating FXR antagonists and nonstatin agents. Notably, compound‐T1 exhibited beneficial effects on both blood non‐HDL‐cholesterol and HDL‐cholesterol, which are thought to involve enhancement of cholesterol catabolism and apolipoprotein A‐I production. These findings aid the understanding of the antidyslipidemic potential of FXR antagonists with a unique lipid and bile acid modulation.
HäirIÖ: Human Hair as Interactive Material

Human hair is a cultural material, with a rich history displaying individuality, cultural expression and group identity. It is malleable in length, color and style, highly visible, and embedded in a range of personal and group interactions. As wearable technologies move ever closer to the body, and embodied interactions become more common and desirable, hair presents a unique and little-explored site for novel interactions. In this paper, we present an exploration and working prototype of hair as a site for novel interaction, leveraging its position as something both public and private, social and personal, malleable and permanent. We develop applications and interactions around this new material in HäirIÖ: a novel integration of hair-based technologies and braids that combine capacitive touch input and dynamic output through color and shape change. Finally, we evaluate this hair-based interactive technology with users, including the integration of HäirIÖ within the landscape of existing wearable and mobile technologies.
Bidirectional power flow control of a power converter using passive Hamiltonian techniques

A controller able to achieve bidirectional power flow for a boost‐like full‐bridge rectifier is presented. It is shown that no single output yields a stable zero dynamics for power flowing both ways. The controller is computed using port Hamiltonian passivity techniques for a suitable generalized state space averaging truncation of the system, which transforms the control objectives, namely specified output mean value of the voltage dc‐bus and unity input power factor in the ac side, into a regulation problem. Simulation and experimental results for the full system confirm the correctness of the simplifications introduced to obtain the controller. Copyright © 2007 John Wiley & Sons, Ltd.
Parental work characteristics and diet quality among pre-school children in dual-parent households: results from a population-based cohort in Taiwan

Abstract Objective To examine the relationship between parental work characteristics and diet quality among pre-school children in dual-parent households. Design Cross-sectional study. Parental work characteristics were measured by the types of combined parental work schedules and work hours. The main outcome variables included meal eating habits as well as ‘health-conscious food’ and ‘unhealthy non-core food’ dietary patterns derived by using principal component analysis. Sociodemographic covariates were considered to reduce confounding and selection biases. Setting The Taiwan Birth Cohort Study, Taiwan. Subjects A population-based sample of 18 046 children. Results Multiple regression analyses indicated that compared with having both parents working standard schedules, having at least one parent who worked non-standard schedules was significantly associated with a lower likelihood of a child eating breakfast every day and a higher consumption of unhealthy non-core foods. If only one parent was employed and worked standard schedules, the children demonstrated greater odds of having home-prepared dinner most of the time. The mother’s working long hours was associated with lower odds of eating breakfast every day, more frequent consumption of unhealthy non-core foods and a lower frequency of healthy food consumption. Conclusions The findings raise concern that parents’ non-standard work schedules and mother’s long working hours have negative effects on diet quality of pre-school children. Policy implications include the need for a multifaceted approach to supporting working parents so as to create healthier food environments.
A Test of the Psychometric Characteristics of the BIS-Brief Among Three Groups of Youth

The Barratt Impulsiveness Scale (BIS-11) is the most widely administered trait impulsiveness questionnaire. Recently a shorter, unidimensional version of the instrument was developed for adults (BIS-Brief). While psychometric characteristics of the BIS-Brief support its use among adults, it also may be more appropriate for youth samples than the complete BIS-11 because it less burdensome and omits items about activities not usually encountered by children and adolescents. This article describes a test of psychometric characteristics of the BIS-Brief among youth. To measure a sufficiently wide range of scores, analyses were conducted based on secondary data analysis of data sets pooled from 3 distinct youth cohorts aged 10–17: healthy controls (Control; n = 356); those who had a family history of substance use disorder (FH+; n = 302); and psychiatric inpatients (Patients; n = 322). Model fit for the BIS-Brief was good but varied somewhat depending on the respondent cohort. There was a strong correlation between test and re-test BIS-Brief both within a single day and at 6 months, and also a strong correlation between BIS-Brief and BIS-11 scores. Concurrent validity was supported by correlation with questionnaire measures, which tended to be more robustly associated with BIS-Brief than behavioral measures. Both BIS-Brief and BIS-11 forms were similarly associated with other convergent measures. In conclusion, the BIS-Brief is a shorter version of the BIS-11 that reduces participant burden and with psychometric properties that support its use among youth populations.
Structural Disorder in Eukaryotes

Based on early bioinformatic studies on a handful of species, the frequency of structural disorder of proteins is generally thought to be much higher in eukaryotes than in prokaryotes. To refine this view, we present here a comparative prediction study and analysis of 194 fully described eukaryotic proteomes and 87 reference prokaryotes for structural disorder. We found that structural disorder does distinguish eukaryotes from prokaryotes, but its frequency spans a very wide range in the two superkingdoms that largely overlap. The number of disordered binding regions and different Pfam domain types also contribute to distinguish eukaryotes from prokaryotes. Unexpectedly, the highest levels – and highest variability – of predicted disorder is found in protists, i.e. single-celled eukaryotes, often surpassing more complex eukaryote organisms, plants and animals. This trend contrasts with that of the number of domain types, which increases rather monotonously toward more complex organisms. The level of structural disorder appears to be strongly correlated with lifestyle, because some obligate intracellular parasites and endosymbionts have the lowest levels, whereas host-changing parasites have the highest level of predicted disorder. We conclude that protists have been the evolutionary hot-bed of experimentation with structural disorder, in a period when structural disorder was actively invented and the major functional classes of disordered proteins established.
Explanation Generation for a Math Word Problem Solver

This paper proposes a math operation (e.g., Summation, Addition, Subtraction, Multiplication, Division, etc.) oriented approach to explain how the answers are obtained for math word problems. Based on the reasoning chain given by the inference engine, we search each math operator involved. For each math operator, we generate one sentence. Since explaining math operation does not require complicated syntax, we adopt a specific template to generate the text for each kind of math operator. To the best of our knowledge, this is the first explanation generation that is specifically tailored to solving the math word problem.