Miracle-dz/UniFAR-FTUs huggingface dataset:
Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease

Cystic fibrosis is caused by impaired ion transport due to mutated cystic fibrosis transmembrane conductance regulator, accompanied by elevated activity of the amiloride-sensitive epithelial Na+ channel (ENaC). Here we show that knockout of the ubiquitin ligase Nedd4L (Nedd4-2) specifically in lung epithelia (surfactant protein C-expressing type II and Clara cells) causes cystic fibrosis-like lung disease, with airway mucus obstruction, goblet cell hyperplasia, massive inflammation, fibrosis, and death by three weeks of age. These effects of Nedd4L loss are likely caused by enhanced ENaC function, as reflected by increased ENaC protein levels, increased lung dryness at birth, amiloride-sensitive dehydration of lung explants, and elevated ENaC currents in primary alveolar type II cells analyzed by patch clamp recordings. Moreover, the lung defects were rescued with administration of amiloride into the lungs of young knockout pups via nasal instillation. Our results therefore suggest that the ubiquitin ligase Nedd4L can suppress the onset of cystic fibrosis symptoms by inhibiting ENaC in lung epithelia.
Default Prediction Using Piotroski’s F-score

This article is an attempt to explore the usefulness of a model that uses the Piotroski’s F-score and its individual components for predicting the risk of default for a sample of Indian firms. The study uses logistic regression as the prediction technique. The Piotroski’s F-score is found to be statistically significant in predicting defaults. Higher values of the score are associated with lower probability of default. Among the individual components of the score, change in leverage is found to be statistically significant in predicting defaults. Increases in leverage are associated with higher probability of default. The model using the individual components of the score is found to have better prediction accuracy as compared to the model using the aggregate score. The findings of the study hold important implications for investment and lending decisions. The study contributes to the existing literature on default prediction by making available yet another measure which has so far not been explicitly used for distress prediction.
Epidemiology of Helicobacter pylori Infection

Medline and PubMed databases were searched on epidemiology of Helicobacter pylori for the period of April 2013–March 2014. Several studies have shown that the prevalence of H. pylori is still high in most countries. In north European and North American populations, about one‐third of adults are still infected, whereas in south and east Europe, South America, and Asia, the prevalence of H. pylori is often higher than 50%. H. pylori remains highly prevalent in immigrants coming from countries with high prevalence of H. pylori. However, the lower prevalence of infection in the younger generations suggests a further decline of H. pylori prevalence in the coming decades. Low socioeconomic conditions in childhood are confirmed to be the most important risk factors for H. pylori infection. Although the way the infection is transmitted is still unclear, interpersonal transmission appears to be the main route. Finally, H. pylori recurrence after successful eradication can still occur, but seems to be an infrequent event.
Regional Profile of Developmental Changes in the Sensitivity of the N‐Methyl‐D‐Aspartate Receptor to Polyamines

Abstract: The NMDA receptor exhibits increased sensitivity to stimulation during early development compared with the adult. In this study, we examined modulation of the NMDA receptor by polyamines during development to see if it correlates with differences in the functional responsiveness of the NMDA receptor. [3H]MK‐801 binding was measured in discrete brain regions in the presence and absence of polyamines in 3‐, 7‐, 15‐, 25‐, and 60‐day‐old Sprague‐Dawley rats. [3H]MK‐801 binding increased between postnatal days 3 and 15, with adult levels of binding being reached between days 15 and 25. Spermidine (75 μM) caused maximal stimulation of [3H]MK‐801 binding during early development, ranging from 250% in the thalamus to 450% in the caudate putamen at postnatal day 3. This effect gradually declined to levels seen in the adult by postnatal days 15–25. During all developmental stages, the stimulation seen was greater in the caudate putamen compared with the hippocampus. Diethylenetriamine (1 μM) exhibited similar developmental and regional heterogeneity in its effects on [3H]MK‐801 binding, producing substantial stimulation of binding in the neonate, but not in the adult. The EC50 and Emax values for the stimulatory effect of spermidine were significantly higher at day 7 compared with the adult. Unlike spermidine and diethylenetriamine, there was no regional variation in the effects of the putative “polyamine site” inverse agonist 1,10‐diaminodecane at any age and only a slightly attenuated inhibition at postnatal day 3 compared with the adult. This lack of complementarity in the regional and developmental profiles of spermidine and diethylenetriamine, on the one hand, and 1,10‐diaminodecane, on the other, suggests that their effects on [3H]MK‐801 binding are mediated at different sites. The altered sensitivity of the NMDA receptor to polyamines during development could reflect the expression of molecular variants with different sensitivities to modulation by polyamines.
How Has the Relevance of Institutional Brokerage Changed?

Institutional brokerage rates have been in decline. We investigate whether this reduction has coincided with a fall in benefits provided by brokers to institutional asset managers. We use trade packages from both active and passive equity funds from 1995 to 2001 and active equity funds from 2002 to 2010. We find that later period active funds recoup a combined 1.75 basis point benefit (from price impact cost recovery and short-term alpha) per basis point of brokerage cost. Later period active investors saw improved trade price impact and shorter-term alpha net benefits, relative to earlier period active investors. These results are robust after controlling for trade characteristics and cross-sectional variation over time. Our findings suggest that brokers innovate to provide valuable services in the subsequent, lower brokerage environment.
The incidence of strabismus and refractive error in patients with blepharophimosis, ptosis and epicanthus inversus syndrome (BPES)

A retrospective review was carried out of 204 patients with blepharophimosis, (blepharo)ptosis and epicanthus inversus syndrome (BPES). Of these, 94 (46%) had an autosomal dominant family history of BPES. Forty (20%) had manifest strabismus. Of these, 28 (70%) had esotropia, 10 (25%) had exotropia and 2 (5%) had hypertropia. Twelve (6%) patients had nystagmus. Seventy (34%) patients had a significant refractive error requiring spectacles. Twenty-one (30%) of these patients had anisometropic hypermetropia and 24 (34%) had anisometropic myopia. Forty-three patients had bilateral amblyopia and 40 had unilateral amblyopia, with 26 (65%) of these undergoing occlusion treatment. Of these, 14 had strabismus and refractive error, 7 refractive error only, 2 strabismus only and 3 neither refractive error nor strabismus. We conclude that there is a higher incidence of strabismus and refractive error in patients with BPES than in the normal population.
‘Rule by Media’ – The Role of Media in the Present Development of Rule of Law in Anti-Corruption Cases in Transitional China

Abstract ‘Rule by media’ is a translation of the Chinese words ‘ or meizhi’. Although commentators have given different meanings to the expression, in this paper the term means that the media is capable of helping to resolve certain social issues effectively through public exposure. China is in a transitional period of rule of law, which is marked by the unique ‘Chinese characteristics’. Anti-corruption is an important part of rule of law. The Chinese media, which is mainly controlled by the state, has played a very important role in cracking down on corruption in recent years. Can a state-controlled media play an effective role in anti-corruption cases? Can the present Chinese Government and Chinese Communist Part succeed in its pursuit to rule of law through controlled exposure of corruption, while maintaining its present political system? These are the issues to be examined in the paper. The author is of a view that the Chinese Communist Party appears to follow the Confucian philosophy of self-restraint and self-purfication, which claims that a person shall improve himself by cultivating his internal body and spirit as well as nourishing his moral characteristics, in its effort to move to rule of law with ‘Chinese characteristics’. It is yet too early to say whether the rule of law with Chinese characteristics may lead to the creation of a workable political system different from the Western model of rule of law. Cracking down on corruption in any case is always a positive step for China to move to a society based on the rule of law.
Comparative Toxicological Evaluation of Phthalate Diesters and Metabolites in Sprague-Dawley Male Rats for Risk Assessment

In order to comparatively assess the systemic toxicity and sperm parameters, nine phthalate diesters, including di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), butylbenzyl phthalate (BBP), dimethyl phthalate (DMP), di-isodecyl phthalate (DIDP), diundecyl phthalate (DUP), and di-isononyl phthalate (DINP), and five phthalate monoesters, including mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBuP), monobenzyl phthalate (MBeP), monoethyl phthalate (MEP), monomethyl phthalate (MMP), and phthalic acid (PA) were administered orally to Sprague-Dawley male rats at 250 (phthalate monoesters and PA) or 500 mg/kg body weight (bw)/d (phthalate diesters) for 4 wk. Liver weights were significantly increased in g roups treated with DEHP, DBP, BBP, DIDP, DINP, MEHP, and MBuP compared to the control. Testes weights were significantly reduced only in DEHP, DBP, and MEHP-treated groups compared to the control. Significant decreases in red blood cell (RBC) and hematocrit (Ht) levels were observed in DEHP-treated rats, whereas significant increases in mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet (PLT) levels were found in the DEHP-treated group. Hemoglobin (Hb) level was reduced only in the DMP group. Similar to effects on testis and epididymal weights, DEHP and MEHP significantly reduced sperm numbers and motility. In particular, DnOP, DBP, BBP, MEP, MBuP, DUP, DINP, and MBeP significantly lowered the sperm counts and sperm motility of epididymal sperm, detected by a change in the sperm motion parameters. The strongest to the weakest adverse effects for sperm motility were as follows: DEHP > DBP > DnOP > DUP > DIDP > BBP among diesters and MBuP > MEP > MEHP among monoesters, respectively. These results suggest that the adverse effects of phthalate esters (PEs) on sperm parameters in male rats are greater with phthalate diesters than monoesters, which may be useful for the risk assessment of phthalates.
Transcriptional changes in insulin‐ and lipid metabolism‐related genes in the hippocampus of olfactory bulbectomized mice

Affymetrix chips were used to perform a hypothesis‐free large‐scale screening of transcripts in the hippocampus of olfactory bulbectomized mice, an established animal model of depression. Because only 11 transcripts were significantly changed, the statistically subsequent 25 transcripts below the significance level were additionally included in a first round of qRT‐PCR evaluations. Furthermore, all 36 genes were then tested for mutual interactions or interactions with other molecules in a physiological context using PathwayArchitect software. Thirty of them were displayed in a network interacting with at least one partner molecule from the list or with other partner molecules known from the literature. All partner molecules from the most prominent 10 molecules of this network were then identified and put together into a new list. On those grounds, the hypothesis was made that metabolic network components of the insulin signaling pathway are perturbed in the disease. This pathway was subsequently tested by a second round of qRT‐PCR, adding also a few additional candidate molecules belonging to this pathway. It turned out that the key target—FABP7—fell into the group of transcripts not significantly regulated within the chip data, and another key target—IRS1—did not show up in the chip experiments at all. In conclusion, our data reveal a problem with adhering to statistical significances in microarray experiments, insofar as molecules important for the disease may fall into the range of statistical noise. This approach may also be useful to find new targets for pharmacotherapy in affective disorders. © 2008 Wiley‐Liss, Inc.
Ligand‐induced μ opioid receptor internalization in enteric neurons following chronic treatment with the opiate fentanyl

Morphine differs from most opiates its poor ability to internalize μ opioid receptors (μORs). However, chronic treatment with morphine produces adaptational changes at the dynamin level, which enhance the efficiency of acute morphine stimulation to promote μOR internalization in enteric neurons. This study tested the effect of chronic treatment with fentanyl, a μOR‐internalizing agonist, on ligand‐induced endocytosis and the expression of the intracellular trafficking proteins, dynamin and β‐arrestin, in enteric neurons using organotypic cultures of the guinea pig ileum. In enteric neurons from guinea pigs chronically treated with fentanyl, μOR immunoreactivity was predominantly at the cell surface after acute exposure to morphine with a low level of μOR translocation, slightly higher than in neurons from naïve animals. This internalization was not due to morphine's direct effect, because it was also observed in neurons exposed to medium alone. By contrast, D‐Ala2‐N‐Me‐Phe4‐Gly‐ol5‐enkephalin (DAMGO), a potent μOR‐internalizing agonist, induced pronounced and rapid μOR endocytosis in enteric neurons from animals chronically treated with fentanyl or from naïve animals. Chronic fentanyl treatment did not alter dynamin or β‐arrestin expression. These findings indicate that prolonged activation of μORs with an internalizing agonist such as fentanyl does not enhance the ability of acute morphine to trigger μOR endocytosis or induce changes in intracellular trafficking proteins, as observed with prolonged activation of μORs with a poorly internalizing agonist such as morphine. Cellular adaptations induced by chronic opiate treatment might be ligand dependent and vary with the agonist efficiency to induce receptor internalization. © 2013 Wiley Periodicals, Inc.
Impact of Devaluation on Balance of Trade: A Case Study of Pakistan Economy

This study investigates the impact of devaluation on balance of trade and on the External Debt, in case of Pakistan, over the period of 1980 to 2014. The key focus of this study is to check the long run relationship among devaluation of domestic currency on Pakistan Balance of Trade and External Debt, over the period of 1980 to 2014. Further, this study also examines the short run relationship between these two variables. Moreover, this study tests the validity of J-curve in case of Pakistan. In order to examine the long run relationship between devaluation of domestic currency and balance of trade in the presence of control variables, this study uses ARDL (Autoregressive distributed lag model) econometric technique. For short run relationship between devaluation of domestic currency and balance of trade, this study uses ECM (Error Correction Mechanism). This study will recommend improved policy recommendations that whether devaluation should be carried out or not. Thus, this paper will certainly benefit the policy makers in Pakistan to deal with Exchange rates in the context of international trade and also to deal with external debt in this regards.
Giving patients an audiotape of their GP consultation: a randomised controlled trial.

BACKGROUND Providing patients with an audiotape of their medical consultation has been a relatively common practice in oncology clinics for some years. However, broader generalisability of the technique has yet to be examined. AIMS To investigate the efficacy of providing patients with an audiotape of their consultation in a general practice setting. DESIGN OF STUDY Randomised controlled trial: 95 experimental participants, 85 controls. SETTING Routine surgeries run by two general practitioners (GPs) in two different health centres. METHOD All patients attending GP appointments were eligible for inclusion. Patients were followed up by telephone 7-10 days later. RESULTS More than half (61%) of the patients who received a tape listened to it. Among listeners, 64% rated the tape useful or very useful; 24% noticed information not heard in the consultation. Half of listeners (46%) said that their understanding of the consultation improved after listening to the tape. Half of the listeners (48%) shared the tape with others, of whom 71% found sharing helpful or very helpful. However, 21% of those who shared the information with others found this unhelpful or very unhelpful, suggesting that patients may need to be briefed on the potential risks of sharing. At follow-up a week later, it emerged that being given a tape had no effect on adherence with GPs' advice, nor on anxiety about conditions. CONCLUSION Providing patients with an audiotape of their GP consultation was positively rated by many patients. Although there were no detectable clinical effects at follow-up, the technique merits further evaluation in general practice.
Interaction of C3 with antigen-antibody complexes in the process of solubilization of immune precipitates.

The binding properties of activated C3 to immune complexes were studied by using solubilization phenomenon as a model system. IgG or F(ab')2 immune precipitates were solubilized by the six isolated alternative pathway proteins, and the solubilized complexes were analyzed by SDS-PAGE. As a result of solubilization, we observed some high m.w. bands. Under reducing conditions, the bands with m.w. of 150,000 and 115,000 appeared in the case of IgG and F(ab')2 complexes, respectively. Two-dimensional SDS-PAGE revealed that hydroxylamine treatment resulted in the dissociation of the 150,000-m.w. polypeptide into the C3 alpha-65 and the heavy chain of IgG. Similarly, the 115,000-m.w. polypeptide was dissociated into the C3 alpha-65 and the Fd chain. Therefore, it is likely that iC3b binds covalently to the Fd region of the heavy chain of IgG via an ester bond. Under nonreducing conditions, iC3b-IgG and iC3b-F(ab')2 complexes had apparent m.w. of 340,000 and 270,000, respectively, corresponding to one iC3b molecule bound to one antibody molecule. In addition, a considerable amount of iC3b also binds to antigen molecules via an ester bond. The findings that C3 binds to the F(ab')2 molecules and bovine serum albumin, which contain only a small amount of carbohydrate, suggest that C3 may not bind to the carbohydrate moiety of antibody molecules. Indeed, various carbohydrate molecules did not inhibit the solubilization even at high concentrations. In contrast, acetyl tyrosine having an aromatic ring and a hydroxyl group produced the best inhibition of the solubilization. Furthermore, we demonstrated that generation of C3b in the presence of 3H-tyrosine resulted in covalent binding of the tyrosine specifically to the C3 alpha' chain, indicating that the inhibition of solubilization may be due to the competition between tyrosine and immune complexes for the covalent binding of C3. Thus, it could be concluded that C3 binds covalently to the amino acid residues of antigen and antibody molecules during solubilization.
Kunitz-type Bauhinia bauhinioides inhibitors devoid of disulfide bridges: isolation of the cDNAs, heterologous expression and structural studies

Abstract Bauhinia bauhinoides cruzipain inhibitor (BbCI) and Bauhinia bauhinioides kallikrein inhibitor (BbKI) are cysteine and serine proteinase inhibitors structurally homologous to plant Kunitz-type inhibitors, but are devoid of disulfide bridges. Based on cDNA sequences, we found that BbKI and BbCI are initially synthesized as a prepropeptide comprising an N-terminal signal peptide (19 residues), the mature protein (164 residues) and a C-terminal targeting peptide (10 residues). Partial cDNAs encoding the mature enzymes plus N-terminal His-tags and thrombin cleavage sites were expressed in E. coli and the soluble proteins were purified by one-step nickel affinity chromatography. After thrombin cleavage, both proteins exhibited potent inhibitory activities toward their cognate proteinases like the wild-type proteins. BbCI inhibits human neutrophil elastase (K i(app) 5.3 nM), porcine pancreatic elastase (K i(app) 40 nM), cathepsin G (K i(app) 160 nM) and the cysteine proteinases cruzipain (K i(app) 1.2 nM), cruzain (K i(app) 0.3 nM) and cathepsin L (K i(app) 2.2 nM), while BbKI strongly inhibits plasma kallikrein (K i(app) 2.4 nM) and plasmin (K i(app) 33 nM). Circular dichroism spectra of BbCI and BbKI were in agreement with the β-trefoil fold described for Kunitz inhibitors. The inhibitory potency of both BbCI- and BbKI-type inhibitors suggests that other, non-covalent interactions may compensate for the lack of disulfide bridges.
Pareto Efficient Income Taxation

I study the set of Pareto efficient tax schedules in Mirrlees’ optimal tax mode l and provide a simple test for the efficiency of a given tax schedule. The efficiency con dition generalizes the the well-known zero-tax-at-the-top result: taxes should be low in regions where the density of income falls rapidly. Both the set of efficient and inefficient tax schedu les is large. I use the framework to explore the optimality of a flat tax, to bound the top tax rate of a n onlinear schedule, and to evaluate the efficiency of a tax system that does not con dition on observable traits.
Thermally-assisted Ti/Pr0.7Ca0.3MnO3 ReRAM with excellent switching speed and retention characteristics

We proposed for the first time thermally-assisted resistive switching random access memory (ReRAM) device to overcome the voltage-time dilemma [1] using Ti/Pr<inf>0.7</inf>Ca<inf>0.3</inf>MnO<inf>3</inf> (Ti/PCMO) with Ge<inf>2</inf>Sb<inf>2</inf>Te<inf>5</inf> (GST) thermoelectric heater as well as thermal barrier (Fig. 1). “Thermoelectric heating effect” from GST/Ti junction [2] and “thermal barrier effect” from the heat confinement by GST and PCMO thermal insulators [3,4] successfully improved switching speed while “large effective Schottky barrier (SB) height (Ф<inf>eff</inf>)” provided excellent robustness to high-temperature retention and read/set/reset disturbance characteristics (Fig. 2).