Miracle-dz/UniFAR-FTUs huggingface dataset:
Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells

Significance Ca2+- and voltage-regulated K+ channels (termed BK channels) are expressed in a diverse variety of cells, playing distinct physiological roles often defined by cell-specific regulatory subunits. Here, genetic deletion of one particular regulatory subunit, LRRC26, reveals that LRRC26-containing BK channels are found, perhaps exclusively, in secretory epithelial cells, including salivary glands, airways, and gastrointestinal tract. Such cells mediate fluid, peptide, and mucus secretion, influencing digestion, airway function, gut resistance to infection, and lactation. The absence of LRRC26 in secretory epithelial cells renders BK channels inactive during normal physiological conditions and alters ion efflux from salivary gland. LRRC26-containing BK channels are critical for normal ionic flux in secretory epithelial cells, likely impacting on a variety of epithelial cell pathologies. Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca2+- and voltage-dependent BK-type K+ channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca2+, suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KO mice with a β-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons. We establish the presence of LRRC26 protein in eight secretory tissues or tissues with significant secretory epithelium and show that LRRC26 protein coassembles with the pore-forming BK α-subunit in at least three tissues: lacrimal gland, parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar cells, LRRC26 KO shifts BK gating to be like α-subunit-only BK channels. Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K+] in saliva. LRRC26-containing BK channels are competent to contribute to resting K+ efflux at normal cell membrane potentials with resting cytosolic Ca2+ concentrations and likely play a critical physiological role in supporting normal secretory function in all secretory epithelial cells.
Development of Bead Modelling for Distortion Analysis Induced by Wire Arc Additive Manufacturing using FEM and Experiment

In this research, Wire Arc Additive Manufacturing is modelled and simulated to determine the most suitable bead modelling strategy. This analysis is aimed to predict distortion by means of thermomechanical Finite Element Method (FEM). The product model with wire as feedstock on plate as substrate and process simulation are designed in form of multi-layered beads and single string using MSC Marc/Mentat. This research begins with finding suitable WAAM parameters which takes into account the bead quality. This is done by using robotic welding system with 01.2mm filler wire (AWS A5.28 : ER80SNi1), shielding gas (80% Ar/ 20% CO2) and 6mm-thick low carbon steel as base plate. Further, modelling as well as simulation are to be conducted with regards to bead spreading of each layers. Two different geometrical modelling regarding the weld bead are modelled which are arc and rectangular shape. Equivalent material properties from database and previous researches are implemented into simulation to ensure a realistic resemblance. It is shown that bead modelling with rectangular shape exhibits faster computational time with less error percentage on distortion result compared to arc shape. Moreover, by using the rectangular shape, the element and meshing are much easier to be designed rather than arc shape bead.
Evolution of cooperation in evolutionary games for Sanitation Boards

In a group of individuals that come together to produce a good or provide a service, the cooperators (who pay to produce the good) are often exploited by those who receive the benet without paying the cost. Models were developed over time using incentives (reward or punishment) and the option of abandoning the initiative to promote and stabilize the cooperation. In this paper we analyze several models based on the evolutionary game theory and public good games. We compare and organize them in a taxonomic table following their main characteristics to select the most suitable for a specic problem. The analyzed models are compared by using a public good problem in community projects for water supply. We have reasonable assurance that phenomena that appear on models also occurs in these community projects. Therefore, we propose that evolutionary game theory can be a useful tool for policy-makers in order to improve cooperation and discourage defection in sanitation boards.
Early glycogen synthase kinase‐3β and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway

Abnormal tau phosphorylation (p‐tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p‐tau is controlled by Glycogen Synthase Kinase (GSK)‐3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This study assessed the effects of global brain ischaemia/reperfusion on the immediate status of p‐tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser396 and Ser262after 2 min of ischaemia, which did not recover during the first two hours of reperfusion, while the tau phosphorylation at GSK‐3β sensitive but AMPK insensitive residues, Ser202/Thr205 (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK‐3β and PP2A during similar episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischaemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p‐AMPK, in ischaemic/reperfusion groups. This suggests the involvement of AMPK in changing the p‐tau levels, indicating that tau dephosphorylation following ischaemia is not dependent on GSK‐3β or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction in AMPK activity is a possible early mechanism responsible for tau dephosphorylation.
High-Affinity Internalizing Human scFv-Fc Antibody for Targeting FGFR1-Overexpressing Lung Cancer

Targeted delivery of anticancer drugs using antibodies specific for tumor-associated antigens represents one of the most important approaches in current immuno-oncology research. Fibroblast growth factor receptor 1 (FGFR1) has been demonstrated to be a high-frequency targetable oncogene specific for smoking-associated lung cancers, present in over 20% of lung squamous cell carcinoma cases. This report describes the generation of a potent, fully human antibody fragment in scFv-Fc format efficiently targeting FGFR1. Antibody phage display was used to select high-affinity scFv antibody fragments against the extracellular domain of FGFR1(IIIc). Enzyme immunoassay (ELISA) and surface plasmon resonance (SPR) analysis were used for antibody screening and characterization. The best binder (named D2) was cloned to diabody and Fc fusion formats. All D2 antibodies demonstrated high affinity for FGFR1 with dissociation constants of 18 nmol/L (scFvD2), 0.82 nmol/L (scFvD2 diabody), and 0.59 nmol/L (scFvD2-Fc). scFvD2 was found to be exquisitely selective for FGFR1 versus other FGFR family members and bound FGFR1 even in the presence of its natural ligand FGF2, as shown by competitive analysis. Confocal microscopy revealed that scFvD2-Fc was specifically and rapidly internalized by a panel of cell lines overexpressing FGFR1. Finally, it was demonstrated that scFvD2-Fc mediated specific delivery of a cytotoxic payload into lung cancer cells harboring oncogenic FGFR1 gene amplifications. Implications: This study reports a highly specific internalizing antibody fragment that can serve as a therapeutic targeting agent for efficient delivery of cytotoxic drugs into FGFR1-positive lung cancer cells. Mol Cancer Res; 15(8); 1040–50. ©2017 AACR.
The Course of Esophageal Varices in Patients with Hepatitis C Cirrhosis Responding to Interferon/ Ribavirin Therapy

Background Gastrointestinal haemorrhage from ruptured esophageal varices (EV) is a significant cause of morbidity and mortality in patients with HCV-related cirrhosis. The risk of developing EV and bleeding is influenced by hepatitis severity, which can be attenuated by successful interferon (IFN) therapy. Our aim was to prospectively assess whether a successful IFN therapy modifies development and/or progression of EV in patients with HCV-related compensated cirrhosis. Methods Child–Pugh A patients with either no or small (F1) EV underwent surveillance with repeated endoscopy during and after completion of IFN-based therapy. Results A total of 127 patients (59 years, 79 males, 65 HCV-1/4 and 17 F1 EV) received weight-based ribavirin (RBV) combined with either IFN-α2b 3 MU three times per week (n=36), weekly pegylated (PEG)-IFN-α2b 1.5 μg/kg (n=68) or weekly PEG-IFN-α2a 180 μg (n=23). Patients were followed-up for 18–108 months after treatment completion with a median endoscopic follow-up of 68 months for the 62 patients with a sustained virological response (SVR) and 57 months for the 65 non-SVR patients (P=0.3). De novo EV developed in 10 (9.1%) patients including 2/57 SVR and 8/53 non-SVR (3.5% versus 15.1%; P=0.047), whereas EV progressed in size in 3 patients, including 1/5 SVR and 2/12 non-SVR (P=0.87). Two non-SVR patients bled from EV and one died. Conclusions A successful IFN therapy prevents or delays the de novo onset of EV in patients with compensated cirrhosis due to HCV, but does not abrogate the need for continued endoscopic surveillance.
Development and Initial Validation of the Alcohol Expectancy Task

BACKGROUND Although studies have shown that alcohol expectancies are prominent predictors of alcohol initiation and subsequent drinking levels, the questionnaires used to assess these expectancies among young adolescents have been criticized as being time-intensive, biased, and inappropriate. METHODS In response, we developed the Alcohol Expectancy Task (AET), in which 8 scenarios featuring adults in everyday situations and in different emotional states, accompanied by photographs of a range of beverages (4 alcoholic, 8 nonalcoholic), are displayed on a tablet screen, and participants are then asked to tap on the beverage they think the given person had been drinking. RESULTS In a first study among 184 adults (75.1% women; mean age = 37.8, SD = 12.2), results from a repeated-measures analysis of variance revealed a strong correspondence between the emotions depicted in the scenarios and how the participants interpreted them. In a second study, this time among 283 third and fourth graders (50.2% girls; mean age = 10.6, SD = 0.69), a confirmatory factor analysis confirmed the 4-factor structure of the AET. The results from a logistic regression analysis showed that the more often young adolescents assigned alcohol to the adults in an arousal-positive mood than to those in a sedation-negative mood, the more likely they were to have already consumed alcohol more than twice. Questionnaire-assessed expectancies were unrelated to adolescents' drinking and did not affect the associations of the AET. CONCLUSIONS The AET has the advantage of being time-efficient and convenient and could overcome certain limitations associated with questionnaire-based assessments of alcohol expectancy.
Discrepancy Models in the Identification of Learning Disability. Executive Summary.

On April 6, 1963, Samuel A. Kirk told a parent advocacy group that “Recently, I have used the term ‘learning disability’ to describe a group of children who have disorders in development, in language, speech, reading, and associated communication skills needed for social interaction” (Kirk, 1975, p. 9). By 1968, “specific learning disability” (LD) became a federally designated category of special education (U.S. Office of Education, 1968). The formal definition offered at the time has not changed substantively and was reaffirmed in the 1997 reauthorization of the Individuals With Disabilities Education Act [IDEA] (Public Law 105-17) as follows:
Agonist E-6837 and antagonist SB-271046 of 5-HT6 receptors both reverse the depressive-like effect induced in mice by subchronic ketamine administration

Major depression is one of the most common affective disorders caused by schizophrenia. The administration of N-methyl-D-aspartate receptor antagonists, such as ketamine, can reproduce the negative and affective symptoms of this disorder in animals. Preclinical studies have shown that 5-HT6 receptor (5-HT6R) agonists and antagonists have a considerable antipsychotic response. The aim of the present study was to evaluate the effect of an acute treatment with an agonist, E-6837, and an antagonist, SB-271046, of 5-HT6R on the immobility induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day, intraperitoneal). Repeated ketamine administration alone increased the immobility time in the forced-swimming test and the tail-suspension test. E-6837 at 10 and 20 mg/kg caused a significant reduction of immobility in the tail-suspension test and forced-swimming test, respectively. Interestingly, SB-271046 (10 mg/kg) also elicited an antidepressant-like effect in both tests. The current findings suggest an important role for these 5-HT6R ligands as mood modulators. However, it is necessary to explore the physiological mechanisms involved in this process in greater detail.
Rapid characterisation and identification of compounds in Saposhnikoviae Radix by high-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry

Abstract Saposhnikoviae Radix (SR), the dried root of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae), is commonly used as a traditional Chinese medicine. In this study, a rapid and accurate method was firstly, developed for the qualitative analysis of SR by high-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry (HPLC-ESI-Q-TOF-MS/MS). A total of 45 compounds were identified or tentatively characterised, including 13 chromones, 28 coumarins and four others. Among them, 16 compounds were identified from SR for the first time. In addition, six chromones reference standards, including two isolated compounds of 3′-O-angeloylhamaudol and norcimifugin from the extraction of SR, were used to study the fragmentation pathways of chromones. The developed method was effective for characterising the compounds of SR, and the results of the study enriched the understanding of the chemical connotation.
Congenital Bleeding Disorders in Karachi, Pakistan

Objective: To determine the frequency of inherited bleeding disorders, its complications, and treatment modalities available for its treatment. Design: Cross-sectional study. Patients and Methods: Patients with a history of bleeding tendency were tested for confirmation of the diagnosis. History and clinical findings were recorded. Laboratory analysis included prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time (BT), and fibrinogen assay. Patients with prolonged APTT were tested for factors VIII (FVIII) and IX (FIX). If FVIII was low, von Willebrand factor: antigen (vWF:Ag) and von Willebrand factor:ristocetin cofactor (vWF:RCo) were performed. When PT and APTT both were prolonged, FV, FX, and FII were tested. Platelet aggregation studies were done when there was isolated prolonged BT. Urea clot solubility test was done when all coagulation tests were normal. All patients with hemophilia A and B were evaluated for inhibitors. Results: Of the 376 patients, inherited bleeding disorder was diagnosed in 318 (85%) cases. Median age of patients was 16.4years. Hemophilia A was the commonest inherited bleeding disorder that was observed in 140 (37.2%) followed by vWD 68 (18.0%), platelet function disorders 48 (12.8%), and hemophilia B in 33 (8.8%) cases. We also found rare congenital factor deficiencies in 13 (3.4%), low VWF in 11 (3.0%) participants and 5 (1.3%) in female hemophilia carriers. Hemarthrosis was the most frequent symptom in hemophilia A and B (79.7%) involving knee joint. Inhibitor was detected in 21 (15%) cases. Fresh frozen plasma/cryoprecipitate were the most common modality of treatment. In 58 patients, no abnormality was detected in coagulation profile. Conclusion: Hemophilia A and vWD are the most common congenital bleeding disorders in this study. Hemarthrosis involving knee joint was the most common complication. Inhibitor was detected in a significant number of patients. Plasma is still the most common modality of treatment.
Parenting Stress in Parents of Infants With Congenital Heart Disease and Parents of Healthy Infants: The First Year of Life

ABSTRACT While we know that the parents of infants with congenital heart disease (CHD), the most prevalent group of congenital anomalies, experience increased parenting stress, the stress levels throughout infancy have yet to be studied. Stress experienced by parents beyond the normative stress of parenting can interfere with parenting processes, and bear adverse family outcomes. This prospective cohort study was conducted to describe and compare parenting stress levels during infancy between parents of infants with complex CHD and parents of healthy infants. The Parenting Stress Index-Long Form was distributed to parents of infants with complex CHD and parents of healthy infants (N = 129). T-tests were used to compare stress between groups at 3, 6, 9, and 12 months of age. Parents of infants with complex CHD had higher parenting stress than parents of healthy infants on multiple subscales on the Child and Parent Domains, at 3 months of age. The stress remained higher on the demandingness subscale throughout infancy. Parents of CHD infants also demonstrated significantly higher stress scores on the life stress subscale at 12 months of age. Findings highlight stressful periods related to parenting infants with CHD, which may increase existing psycho-social risk for parents of infants with CHD. Early family intervention may promote parental adaptation to the illness, and help establishing healthy parenting practices.
A Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease.

To the Editor: In reporting on the Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis (LEVANT) 2 trial, Rosenfield et al. (July 9 issue)1 suggest that angioplasty with a paclitaxel-coated balloon, as compared with angioplasty with a standard balloon, provided superior vessel patency in patients with femoropopliteal disease at 12 months. Although these results are encouraging, it is unclear whether superior vessel patency translates into improvements in more clinically appropriate end points such as ambulatory function and quality of life.2 The majority of the patients in the trial (92%) had moderate intermittent claudication (Rutherford stage 2) or severe intermittent claudication (Rutherford stage 3) (the Rutherford scale ranges from 0 to 6, with higher numbers indicating worse disease), with single, short lesions of the superficial femoral artery. Yet, the primary end point of freedom from binary restenosis or targetlesion revascularization occurred in only 65% of the intervention cohort and 53% of controls. The clinical significance of this difference is unclear, and this lack of clarity highlights the need to design trials that are powered to show the effectiveness of endovascular interventions for the clinical outcomes of femoropopliteal disease, such as improvements in symptoms of claudication.3 In the meantime, enthusiasm for techniques such as this one must be curbed.
Oxygen-Inducible Conversion of Lactate to Acetate in Heterofermentative Lactobacillus brevis ATCC 367

ABSTRACT Lactobacillus brevis is an obligatory heterofermentative lactic acid bacterium that produces high levels of acetate, which improve the aerobic stability of silages against deterioration caused by yeasts and molds. However, the mechanism involved in acetate accumulation has yet to be elucidated. Here, experimental evidence indicated that aerobiosis resulted in the conversion of lactate to acetate after glucose exhaustion in L. brevis ATCC 367 (GenBank accession number NC_008497 ). To elucidate the conversion pathway, in silico analysis showed that lactate was first converted to pyruvate by the reverse catalytic reaction of lactate dehydrogenase (LDH); subsequently, pyruvate conversion to acetate might be mediated by pyruvate dehydrogenase (PDH) or pyruvate oxidase (POX). Transcriptional analysis indicated that the pdh and pox genes of L. brevis ATCC 367 were upregulated 37.92- and 18.32-fold, respectively, by oxygen and glucose exhaustion, corresponding to 5.32- and 2.35-fold increases in the respective enzyme activities. Compared with the wild-type strain, the transcription and enzymatic activity of PDH remained stable in the Δpox mutant, while those of POX increased significantly in the Δpdh mutant. More lactate but less acetate was produced in the Δpdh mutant than in the wild-type and Δpox mutant strains, and more H2O2 (a product of the POX pathway) was produced in the Δpdh mutant. We speculated that the high levels of aerobic acetate accumulation in L. brevis ATCC 367 originated mainly from the reuse of lactate to produce pyruvate, which was further converted to acetate by the predominant and secondary functions of PDH and POX, respectively. IMPORTANCE PDH and POX are two possible key enzymes involved in aerobic acetate accumulation in lactic acid bacteria (LAB). It is currently thought that POX plays the major role in aerobic growth in homofermentative LAB and some heterofermentative LAB, while the impact of PDH remains unclear. In this study, we reported that both PDH and POX worked in the aerobic conversion of lactate to acetate in L. brevis ATCC 367, in dominant and secondary roles, respectively. Our findings will further develop the theory of aerobic metabolism by LAB.
Opportunities and challenges of mobile learning for promoting mathematical literacy

Mathematical literacy plays an important role in supporting individuals to fulfil their professional roles in modern society. The affordances of mobile technologies as well as the emergence of new theories in mobile learning have the potential to promote mathematical literacy. However, implementation of mobile learning in Indonesian society faces challenges related to perceived ethical and learning issues in curriculum-based educational settings. This study aims to investigate the preparedness of teachers in integrating mathematics subject content with mobile technologies, especially in promoting mathematical literacy. An exploratory study has been conducted using mixed methods by performing questionnaire survey and semi-structured interviews to understand teacher's knowledge towards mathematical literacy and identifying opportunities and challenges of mobile learning within instruction. Findings indicate that teachers mostly do not know about mathematical literacy, indicating that the concept of mathematical literacy needs to be promoted. Further, most schools prohibit the use of mobile devices in classrooms as they are wary of inappropriate use of mobile devices which may harm students' mental health and distract them from learning. Study finds this to be the most common cause for teachers' reluctance in using mobile learning.