Miracle-dz/UniFAR-FTUs huggingface dataset:
Hedgehog signaling is activated in subsets of esophageal cancers

The hedgehog pathway plays a critical role in the development of the foregut. However, the role of the hedgehog pathway in primary esophageal cancers is not well studied. Here, we report that elevated expression of hedgehog target genes occurs in 14 of 22 primary esophageal cancers. The hedgehog signaling activation is not associated with tumor subtypes, stages, or differentiation. While the sonic hedgehog (Shh) transcript is localized to the tumor tissue, expression of Gli1 and PTCH1 is observed both in the tumor and in the stroma. We discovered that 4 esophageal squamous cell carcinomas, which overexpress Shh, have genomic amplification of the Shh gene. Treatment of esophageal cancer cells with smoothened antagonist, KAAD‐cyclopamine, or the neutralizing antibodies of Shh reduces cell growth and induces apoptosis. Overexpression of Gli1 under the CMV promoter renders these cells resistant to the treatments. Thus, our results indicate that elevated expression of Shh and its target genes is quite common in esophageal cancers. Our data also indicate that downregulation of Gli1 expression may be an important mechanism by which KAAD‐cyclopamine inhibits growth and induces apoptosis in esophageal cancer cells (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html). © 2005 Wiley‐Liss, Inc.
DSM-IV personality disorders in Mexico: results from a general population survey.

OBJECTIVE This paper reports the first population estimates of prevalence and correlates of personality disorders in the Mexican population. METHOD Personality disorders screening questions from the International Personality Disorder Examination were administered to a representative sample of the Mexican urban adult population (n = 2,362) as part of the Mexican National Comorbidity Survey, validated with clinical evaluations conducted in the United States. A multiple imputation method was then implemented to estimate prevalence and correlates of personality disorder in the Mexican sample. RESULTS Multiple imputation method prevalence estimates were 4.6% Cluster A, 1.6% Cluster B, 2.4% Cluster C, and 6.1% any personality disorder. All personality disorders clusters were significantly comorbid with DSM-IV Axis I disorders. One in every five persons with an Axis I disorder in Mexico is likely to have a comorbid personality disorder, and almost half of those with a personality disorder are likely to have an Axis I disorder. CONCLUSIONS Modest associations of personality disorders with impairment and strong associations with treatment utilization were largely accounted for by Axis I comorbidity suggesting that the public health significance of personality disorders lies in their comorbidity with, and perhaps effects upon, Axis I disorders rather than their direct effects on functioning and help seeking.
An Empirical Investigation into Corporate Voluntary Disclosure of Management's Responsibilities in the Bangladeshi Listed Companies

The article aims to evaluate the Corporate Voluntary Disclosure of Management’s Responsibilities in the Bangladeshi Listed Companies. Data are taken from annual reports of the listed companies in Dhaka Stock Exchange (DSE) during 2005-2008. The study uses ordinary least squares regression model to examine the relationship between explanatory variables and corporate voluntary disclosure and unweighted relative disclosure index is used for measuring voluntary disclosure score. The results show the firms have the higher percentage of shares held by institutional shareholders. The Senior management’s decision is positively related to the level of voluntary disclosure and has positive relation with a board audit committee and board leadership structure. On the other hand, where the firms have a higher management of ownership structure, there the senior management’s decision is negatively related to the level of voluntary disclosure. However, other factors such as those provided by board composition, board size and firm size displayed no significant influence on senior management’s decisions in this area.
Studies on the determinants of foreign entry mode choices and performance

Foreign entry mode choices are one of the most important strategic decisions for firms expanding abroad. This dissertation is a collection of papers on two of these choices, i.e. that between a greenfield investment and an acquisition, and that between export and foreign production. Based on a survey of the literature and novel theoretical reasoning, the dissertation derives a number of hypotheses on the determinants of these choices and their ex post outcome in terms of performance. The hypotheses mainly refer to the effects of national cultural distance and the planned degree of subsidiary autonomy. They are tested on a sample of foreign expansions by Dutch multinational enterprises consisting of survey data and a sample of inter-country bilateral trade flows consisting of secondary data, using several statistical methods. The results of the tests largely confirm the hypotheses. Conclusions and suggestions for future research are offered.
Auditor reviews of interim financial information in South Africa : discourse of the history of developments and their implications

Company interim financial reports provide decision useful information to a variety of their users. The debate surrounding the issue of independent auditor involvement with such reports started in the 1960’s in the USA and is ongoing internationally. Today the general trend is that when auditor involvement is required, it takes the form of a review of the interim results. In South Africa, also, the auditor review of company interim reports has undergone major developments and change. The objective of this paper is firstly to determine through examination of the history of developments regarding the auditor review of interim financial information, the factors, issues and considerations which influenced current South African practice and secondly to identify the implications thereof for the auditing profession. Specific emphasis is placed on how relevant events/developments reflect on the standard setting process. The discourse presented herein supports a conclusion that present practice in respect of auditor reviews of company interim financial information in South Africa is the result of a deficient standard setting process which, in the main, fails to recognise and implement the defined principles of sound and socially acceptable standard setting. The auditing profession’s ignorance of these principles will continue to foster deficient standards which are rejected by the users of auditing services and which marginalise the role and functions of the external auditor.
Nosocomial bloodstream infection in a tertiary care paediatric intensive care unit.

OBJECTIVE To determine the frequency, causative organisms and susceptibility pattern of nosocomial bloodstream infections in children. STUDY DESIGN Observational study. PLACE AND DURATION OF STUDY Paediatric Intensive Care Unit of the Children's Hospital, Lahore, from January to December 2004. PATIENTS AND METHODS All children admitted to the unit during the study period were daily evaluated for features suggestive of nosocomial infection. In addition to other investigations, blood cultures were done in all suspected cases for the confirmation of nosocomial bloodstream infection (BSI). Nosocomial infection was defined according to the criteria set by Centre for Disease Control and Prevention. Demographic, microbiological and other variables were carefully studied to analyze frequency, incidence rate, spectrum of isolates and susceptibility pattern. Children with and without nosocomial BSI were compared with regard to age, duration of stay in hospital, need and duration of ventilation and the outcome. RESULTS Of the total 406 admissions, 134 children were suspected to have nosocomial infection on at least 214 occasions (episodes). Blood cultures yielded growth of pathological organisms in 62 of these episodes, giving the frequency of nosocomial BSI as 15.2 per 100 admissions (62/406 episodes). Children with nosocomial bloodstream infection were found to have younger mean age (2.1 vs. 4.1 years), longer average duration of stay (13.1 vs. 6.6 days), more frequent need for ventilation (64% vs. 34%) and longer duration of ventilation (9.7 vs. 4.8 days). Majority of isolates (77%) were gram-negative bacteria; Klebsiella being the most common isolate (n= 23). Aztreonam, Ceftiazidime, Ceforuxime and Ciprofloxacin showed high resistance pattern (33-50%). Isolates showed good sensitivity to Vancomycin (100%), Imipenem (80%), Meropenem (100%) and Co-amoxiclav (88%). CONCLUSION The frequency of nosocomial BSI in the observed setting was quite high, having marked impact on the duration of stay and outcome. Emergence of resistant pathogens is alarming.
The natural history of recoverable vocal fold paralysis: Implications for kinetics of reinnervation

Patients with unilateral vocal fold paralysis (UVFP) are commonly told to wait 12 months for spontaneous recovery. This study aims to 1) determine the time to vocal recovery in UVFP, 2) use that data to develop a neurophysiologically plausible model for recovery, and 3) use the model to generate meaningful predictions for patient counseling.
Methodologies for innovation and improvement of services in tourism

Travel organisations, as travel agencies, tour operators, hotels, etc. focus their research too much on measuring service quality level and identifying errors. This strategy results in incremental improvements. This paper will focus more on how to improve the service by using strategies that further both incremental and innovative improvements of service. The paper demonstrates that an importance‐performance survey combined with service blueprinting and benchmarking is a useful strategy to improve and innovate service. To understand this strategy a quality management model that integrates incremental and fundamental (innovative) service improvements is presented.
Localization of the blood-brain barrier of an insect: electrical model and analysis

The perineurium was found to form the principal barrier to diffusion across the blood-brain barrier system of the cockroach, Periplaneta americana , since the resistance across this layer was much greater than that across the underlying neuroglia. An equivalent electrical circuit of the perineurium was then used to analyse recordings made in apparent perineurial cells and the interstitial system. Trans-perineurial resistance was at least 900 ωcm 2 , while the ratio between basolateral and apical membrane resistances was 11:1, indicating that the apical membrane had an area much greater than that of the basolateral membrane. Raising the potassium concentration in the saline produced changes in potential difference (p.d.) and resistance that were interpreted as due to the effect of potassium upon the basolateral membrane. Analysis indicated that the resting electromotive force (e.m.f.) generated by the basolateral membrane was less than that generated by the apical, although the K level in the saline was near that considered to be in the interstitial system. The analysis also yielded a value of 9 for the ratio of shunt resistance to apical resistance. Most changes in recorded values following the K elevation could be simulated by use of the estimated parameters, and an estimation of a change in interstitial K level. From these results, the shunt can be calculated to be an important contributor to the resistance across the perineurium, having a resistance about 0.9 times that of the transcellular resistance.
Diurnal Variation of Corneal Sensitivity and Thickness

Purpose. To measure the diurnal variation of central corneal sensitivity and thickness over 24 hours. Methods. A noncontact pneumatic esthesiometer to measure central corneal sensitivity and an optical pachymeter to measure central corneal thickness were used on 20 noncontact lens wearers. These measurements were performed at 22:00 before 8 hours of sleep and on the following day on eye opening and at hourly intervals between 7:00 and 22:00. Results. Central corneal sensitivity varied by 35% over the 24 hours. Sensitivity was significantly lower by 17.1 ± 2.1% on eye opening and recovered to the level of the previous night after 4 hours. Corneal sensitivity continued to increase throughout the day but was not significantly higher. Central corneal thickness varied by 3.9% over the 24 hours. The mean overnight corneal swelling was 2.9 ± 0.31%, and 2 hours after eye opening, the cornea had deswelled to the same thickness as the previous night. The cornea thinned further throughout the day, but there were no statistically significant differences between the values after 14:00. There was a high correlation between corneal sensitivity and thickness over time (r = 0.8;p < 0.05). Discussion. Corneal sensitivity correlated with corneal thickness: both were higher on awakening and then decreased and remained below the levels measured the previous night. This may be due to physiological and/or environmental factors. The lack of significant differences between the values after 14:00 suggests that baseline may be measured at any time from 7 hours after eye opening.
THE SKILL COMPOSITION IN THE LIGHT OF SOURCING: OFFSHORING AND INSHORING

The objective of this paper is to analyze effects on firm-level relative demand for skilled labor due to imports of intermediates (offshoring) and exports of intermediates (inshoring). The study is based on a dataset of Swedish manufacturing firms, 1997-2002, using actual trade flows in intermediate goods and services, respectively. Descriptive data show that goods inshoring is much larger than goods offshoring, while the reverse is true for services. There is however a strong increase in services inshoring over the study period. Controlling for potential endogeneity due to high-performing firms self selecting into offshoring and inshoring, our results indicate that there is a positive effect of services offshoring while inshoring has no significant effect on the skill composition of workers in Swedish firms.
Multidrug resistance‐associated protein 4 expression in ammonia‐treated cultured rat astrocytes and cerebral cortex of cirrhotic patients with hepatic encephalopathy

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome frequently accompanying liver cirrhosis and reflects the clinical manifestation of a low grade cerebral edema associated with cerebral oxidative/nitrosative stress. The multidrug resistance‐associated protein (Mrp) 4 is an export pump which transports metabolites that were recently suggested to play a major role in the pathogenesis of HE such as neurosteroids and cyclic nucleotides. We therefore studied Mrp4 expression changes in ammonia‐exposed cultured astrocytes and postmortem human brain samples of cirrhotic patients with HE. NH4Cl increased Mrp4 mRNA and protein levels in astrocytes in a dose‐ and time‐dependent manner up to threefold after 72 h of exposure and concurrently inhibited N‐glycosylation of Mrp4 protein. Upregulation of Mrp4 mRNA and protein as well as impaired N‐glycosylation of Mrp4 protein by ammonia were sensitive towards the glutamine‐synthetase inhibitor l‐methionine‐S‐sulfoximine and were not induced by CH3NH3Cl (5 mmol/L). Upregulation of Mrp4 mRNA required ammonia‐induced activation of nitric oxide synthases or NADPH oxidase and p38MAPK‐dependent activation of PPARα. Inhibition of Mrp4 by ceefourin 1 synergistically enhanced both, inhibition of astrocyte proliferation as well as transcription of the oxidative stress surrogate marker heme oxygenase 1 by forskolin (10 µmol/L, 72 h) or NH4Cl (5 mmol/L, 72 h) in cultured rat astrocytes. Increased Mrp4 mRNA and protein levels were also found in postmortem brain samples from patients with liver cirrhosis with HE but not in those without HE. The data show that Mrp4 is upregulated in HE, which may be relevant for the handling of neurosteroids and cyclic nucleotides in response to ammonia. GLIA 2015;63:2092–2105
Predecisional Distortion of Product Information

Two consumer choice experiments reveal distortion of product information. When relatively equivocal information about two hypothetical brands is acquired one attribute at a time, the evaluation of a subsequent attribute is distorted to support the brand that emerges as the leader. This distortion in favor of the leading brand occurs in the absence of any prior brand preference and even when no choice is required. In the latter case, brand preference is formed spontaneously and privately. The magnitude of this predecisional information distortion is roughly double the well-known postdecisional distortion due to cognitive dissonance. A second study shows that, even when the product information is diagnostic, substantial distortion remains. Furthermore, when the diagnostic information leads to a reversal of the currently preferred brand, distortion reappears in support of the new leading brand. The implications of predecisional distortion of product information are discussed for the presentation order of brands, the presentation format of product attributes, and the potential bias in preference assessment techniques, such as conjoint measurement, that rely on pairwise choices.
Worsening of levodopa‐induced dyskinesias by motor and mental tasks

Ten patients who had Parkinson's disease with disabling dyskinesia were included in this study to evaluate the role of mental (mental calculation) and motor (flexion/extension of right fingers, flexion/extension of left fingers, flexion/extension of the neck, speaking aloud) tasks on the worsening of peak‐dose dyskinesia following administration of an effective single dose of apomorphine. Compared with the score at rest (1.3 ± 0.3), a significant aggravation of the dyskinesia score was observed during speaking aloud (5.2 ± 1.1, p <0.05), movements of right (4.5 ± 1.0, p <0.05) and left (3.7 ± 0.8, p <0.05) fingers, movements of the neck (5.1 ± 1.0, p <0.05), and mental calculation (3.1 ± 1.0, p <0.05). These results suggest that activation tasks such as “speaking aloud” could be used for objective assessment of dyskinesia severity.
Investigation the effect of corporate governance on the financing cost

Financing companies’ quality of corporate governance is one of the important factors to financing, because it can has an effect on payment risk or an un-payment, hence, we can state that the quality of corporate governance will influence on financing cost. Corporate governance causes to reduce the financing crisis risk. This problem is very important, when this risk leads to create more expenses. So, corporate governance causes to reduce the investing costs, and in conclusion increases the value of company. Naturally, the quality of corporate governance leads to create trust and reliance in investors and reduces their informational risk and surely will influence on companies financing cost. The main purpose of this study is to investigate the effect of corporate governance, shareholders control, independence of directorate on the financing cost of listed companies in Tehran Stock Exchange during 5 years (since 2006 to 2013). The population is 448 companies that 221 companies had been selected with Chochran method. The result of this research indicates that corporate governance has not significantly effect on the companies financing cost. Normal 0 false false false RU X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Обычная таблица"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;}
Effects of Multiple Doses of Ambrisentan on the Pharmacokinetics of a Single Dose of Digoxin in Healthy Volunteers

J Clin Phar acol 2011;51:102-106 A is a high-affinity, propanoic acid– based, endothelin type A (ETA)–selective endothelin receptor antagonist. In phase 3 studies, ambrisentan improved exercise capacity, delayed clinical worsening, and improved symptoms of pulmonary arterial hypertension (PAH). Ambrisentan is metabolized primarily by glucuronidation via several uridine glucuronosyltransferase enzymes. Ambrisentan undergoes oxidative metabolism by cytochrome (CYP) 3A4 and to a lesser extent by CYP3A5 and CYP2C19. Clinical pharmacology studies with several drugs that may be given in PAH (sildenafil, warfarin, and ketoconazole) show that ambrisentan may be given concomitantly without dose adjustment. In vitro investigations in Caco-2 cells indicate that ambrisentan is a substrate for P-glycoprotein (P-gp). Ambrisentan did not inhibit human P-gp– mediated transport of digoxin in Madin-Darby canine kidney cells at concentrations up to 100 μM and did not induce P-gp expression in rats administered 100 μM ambrisentan for 4 days. Digoxin is indicated for the treatment of heart failure and chronic atrial fibrillation but is also generally believed to have beneficial effects as a supportive treatment in PAH. Digoxin was a concomitant medication in 11% of patients in ambrisentan phase 3 clinical studies. Excretion of digoxin is largely dependent on the action of P-gp and is therefore affected by drugs that inhibit or induce P-gp. Furthermore, endothelin receptor antagonists have the potential to alter renal blood flow. Changes in blood flow have been associated with changes in the elimination of digoxin. Therefore, the effects of multiple doses of ambrisentan on the pharmacokinetics of a single dose of digoxin were evaluated in this study.
Glycosylation Profiles of the Human Colorectal Cancer A33 Antigen Naturally Expressed in the Human Colorectal Cancer Cell Line SW1222 and Expressed as Recombinant Protein in Different Insect Cell Lines

The A33 antigen is a cell surface glycoprotein expressed in human gastrointestinal epithelium and in 95% of colorectal cancers. We have compared the N‐linked glycosylation profile of A33 antigen naturally expressed in a human colorectal cancer cell line with recombinant human A33 antigen (rA33) produced in insect cell culture using the baculovirus expression vector. N‐Linked glycans were enzymatically released from the protein, and glycan composition was analyzed by HPLC. In three insect cell lines tested (Sf‐21, Tn5B1–4, and Tn‐4s), glycosylation of rA33 was dominated by high mannose structures (M5Gn2 to M9Gn2; 78–95% of total N‐linked glycans), with M8Gn2 being the single most abundant glycoform. A33 antigen naturally expressed in the SW1222 human colon cancer cell line (A33) also possessed a high abundance of high mannose glycans (72%). No complex glycosylation was detected on rA33 expressed in insect cells. Natural A33 was galactosylated to a small extent (6%). These results illustrate a case of similar glycosylation of a glycoprotein between a recombinant version produced in insect cell culture and its counterpart naturally expressed in human cell culture.