Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of cell lines that inducibly express the adeno-associated virus Rep proteins

The replication (rep) gene of adeno-associated virus (AAV) is involved in AAV DNA replication, gene regulation, and inhibition of cellular transformation induced by various oncogenes. To study the rep gene's antiproliferative effects, we have developed cell lines which express the replication proteins under the control of an inducible mouse metallothionein transcription promoter. The Rep78 protein produced in these cell lines binds to the AAV terminal repeat sequences in vitro and supports AAV DNA replication and trans activation of the AAV p40 transcription promoter in vivo. These cell lines are capable of assembling infectious viruses containing a mutant rep gene or a vector bearing a heterologous gene. Growth rate and colony formation efficiency assays indicated that rep gene expression substantially altered cellular proliferation. Long-term induction of the cell lines followed by removal of the inducing agent suggested that constitutive expression of the Rep proteins does not necessarily result in cell death and that the cells can recover from the cytostatic effects. Flow cytometry analysis indicated that the presence of the Rep proteins increased the population of cells in the S phase of the cell cycle. Thus the rep gene's antiproliferative effects may be realized by interference with cellular DNA replication.
Measuring Innovativeness of Public Organizations: Using Natural Language Processing Techniques in Computer-Aided Textual Analysis

ABSTRACT We propose a new method for measuring innovativeness in the public sector using natural language processing techniques. Our approach extends traditional content analysis techniques by combining insights from linguistic theory and recent developments in computational techniques. We develop and employ phrase-level data dictionaries (using both noun phrases and verb phrases) from organizational documents. We use letters to the board of education from a sample of New Jersey school districts to develop measures of innovativeness—one measure is based on expert assessments and the other is inductively derived. We perform rigorous tests of content validity, external validity, and predictive validity on these measures. We conclude with a discussion of implications of this new measurement approach and its potential applications to other public management contexts.
Political Connections: An Explanation for the Consistently Poor Performance of China's Stock Markets

The fact that the consistently poor performance of China’s stock markets has not matched China’s rapid economic growth has been puzzling. Using samples of private-owned enterprises publicly traded on China’s stock markets, this article finds that 74% of these firms are politically-connected and that politically-connected firms are more likely to report significant deterioration in financial performance upon completing IPOs. The widespread existence and ubiquitous importance of political connections in China’s stock markets suggests that to some degree, China’s stock markets have been regulated on a political connections-based regime, which may explain the poor performance of China’s stock markets.
Dynamic Portfolio Management Approach to Optimal Fiscal Policy in Resource-Rich Countries

This paper studies a novel approach for managing macroeconomic volatility in developing countries based upon dynamic portfolio optimisation. As part of this study, we develop a sovereign risk management model in the context of an Asset-Liability Management (ALM) framework. First, we solve the optimal level of investment in commodities required to achieve Pareto efficient allocation. Second, we provide numerical results for the optimal level of wealth to allocate for fiscal spending in a country where sovereign income is subject to higher commodity market volatility. Third, we provide a mathematically tractable model for ascertaining the most efficient level of debt-to-GDP ratios to be maintained by governments in order to achieve fiscal stability. Finally, we document significant welfare gains with sovereign consumption-wealth ratios increasing monotonically in wealth irrespective of commodity price levels.
Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies

We examined the immunoreactivity of ubiquitin-binding protein p62 and its association with ubiquitin (Ub), α-synuclein, and paired helical filament (PHF)-tau in the affected brain areas of human tauopathies and synucleinopathies. Ubiquitin-binding protein p62 is a widely expressed protein that can bind to Ub noncovalently and is involved in several signalling pathways, making p62 a candidate regulator of Ub-mediated proteolysis. We show that p62 immunoreactivity co-localizes with neuronal and glial Ub-containing inclusions in Alzheimer's disease, Pick's disease, dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. This is the first demonstration of a common protein component, apart from Ub, that is present in both PHF-tau and α-synuclein inclusions. In both tauo- and synucleinopathies, the staining patterns for p62 and Ub were markedly similar, suggesting that a common mechanism which requires interaction of p62 and Ub contributes to the formation of PHF-tau and α-synuclein inclusions.
Pathogenesis of abdominal aortic aneurysm

The pathogenesis of abdominal aortic aneurysm involves many factors acting over time. However, destruction of elastin in the aortic wall is a key event that shifts the load produced by blood pressure on to collagen. This is exacerbated in the presence of hypertension. Smoking and age are further important factors, as is the site; elastic lamellae are relatively less common in the abdominal aorta. Once the shielding effect of elastin is lost, further dilatation and rupture of the aorta depend on the physical properties of the collagen present.
Interleukin-1beta and tumor necrosis factor-alpha induce chemokine and matrix metalloproteinase gene expression in human colonic subepithelial myofibroblasts.

BACKGROUND Colonic subepithelial myofibroblasts may play a role in the inflammatory responses and in extracellular matrix (ECM) metabolism. In this study, we investigated the effects of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on chemokine (IL-8 and monocyte chemoattractant protein (MCP)-1) and ECM turnover (proliferation of subepithelial myofibroblasts, and secretion of ECM and matrix metalloproteinases (MMPs)) in colonic subepithelial myofibroblasts. METHODS Human colonic subepithelial myofibroblasts were isolated using the method described by Mahida et al. Chemokine and MMP expressions were determined by ELISA and Northern blotting. Nuclear factor (NF)-kappaB and NF-IL6 DNA binding activities were evaluated by electrophoretic gel mobility shift assays (EMSA). RESULTS IL-1beta and TNF-alpha did not affect the proliferation of subepithelial myofibroblasts, but stimulated the secretion of types I and IV collagens weakly. Unstimulated subepithelial myofibroblasts secreted a large amount of MMP-2, but a small amount of IL-8, MCP-1 and MMP-1. IL-1beta and TNF-alpha both induced a dose- and time-dependent increase in IL-8, MCP-1 and MMP-1 secretion, and weakly stimulated MMP-2 secretion. IL-1beta and TNF-alpha both rapidly evoked NF-kappaB DNA-binding activity. The inhibition of NF-kappaB activation markedly blocked both IL-1beta- and TNF-alpha-induced IL-8 and MCP-1 mRNA expression, but did not affect MMP-1 mRNA expression. CONCLUSIONS These observations indicate that chemokine secretion and ECM metabolism are collectively regulated by the proinflammatory cytokines, IL-1beta and TNF-alpha, in colonic subepithelial myofibroblasts. Thus, colonic subepithelial myofibroblasts may play an important role in the pathophysiology of inflammation in the colon.
Chinese Traditional Literature and Academic Achievement: A Study of Secondary Schools Students

: This study aimed to determine the opinions of the secondary school students of learning Chinese classical literature, the difference in the level of acquisition between male and female, and find out the relationship between the acquisition of knowledge in Chinese traditional literature and their academic achievement. This study was done in two national-type secondary schools (NTSS) in Selangor. The instrument consisted of a set of acquisition test and questionnaire drafted based on the Language Acquisition Theory. The respondents were 104 form four students, consisting of 52 students randomly chosen from two schools. The findings showed that form four students overall held negative views about learning Chinese classical literature. There was a significant positive correlation between the acquisition test scores of Chinese traditional literary knowledge (M = 39.56, SD = 11.66) and the grades obtained by the students in the Chinese subject in the Lower Secondary Assessment Examination (M = 3.77, SD = 1.27), r = . 686, p <. 01). The results show that actions should be taken to raise students’ interest in traditional literature and to improve students' acquisition of Chinese traditional literary knowledge as well as to ensure that the Chinese syllabus is implemented effectively.
Carvedilol, a new nonselective beta‐blocker with intrinsic anti‐alpha1‐adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis

Only some patients show a substantial hepatic venous pressure gradient (HVPG) reduction after propranolol, which makes it desirable to investigate drugs with greater portal hypotensive effect. The aim of this study was to investigate whether carvedilol, a nonselective beta‐blocker with anti‐alpha1 –adrenergic activity, may cause a greater HVPG reduction than propranolol. Thirty‐five cirrhotic patients had hemodynamic measurements before and after the random administration of carvedilol (n = 14), propranolol (n = 14), or placebo (n = 7). Carvedilol markedly reduced HVPG, from 19.5 ± 1.3 to 15.4 ± 1 mm Hg (P < .0001). This HVPG reduction was greater than after propranolol (−20.4 ± 2 vs. −12.7 ± 2%, P < .05). Moreover, carvedilol decreased HVPG greater than 20% of baseline values or to ≤12 mm Hg in a greater proportion of patients (64% vs. 14%, P < .05). Both drugs caused similar reductions in hepatic and azygos blood flows, suggesting that the greater HVPG decrease by carvedilol was because of reduced hepatic and portocollateral resistance. Propranolol caused greater reductions in heart rate and cardiac output than carvedilol, whereas carvedilol caused a greater decrease in mean arterial pressure (−23.1 vs. −11%, P < .05). Thus, carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis, suggesting a greater therapeutic potential. However, it causes arterial hypotension, which calls for careful evaluation before its long‐term use
Effects of noradrenaline and serotonin reuptake inhibitors on pituitary-adrenocortical and sympatho-adrenomedullar system of adult rats.

OBJECTIVE To estimate the influence of long-term treatment with noradrenergic and serotonergic reuptake inhibitors on activity of pituitary-adrenocortical and sympatho-adrenomedullar systems in animals, we compared the effects of maprotiline (a selective inhibitor of noradrenaline reuptake) and fluxilan (a selective inhibitor of serotonin reuptake) on plasma noradrenaline (NA), adrenaline (A), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels in unstressed control and rats exposed to chronic unpredictable mild stress (CUMS). METHODS Plasma NA and A were assayed by a radioenzymatic method. Plasma CORT was measured using RIA kits and plasma ACTH by a chemiluminescent method. RESULTS CUMS did not affect blood plasma NA, A and ACTH content, but elevated plasma CORT level. Maprotiline elevated plasma NA content both in unstressed control and CUMS group, whereas plasma A remained unchanged. Fluxilan acted significantly increasing plasma NA and A concentrations both in control and CUMS rats. Neither maprotiline nor fluxilan affected plasma ACTH level both in unstressed control and CUMS animals. Plasma CORT level in unstressed control rats remained unchanged after maprotiline and fluxilan treatment, while being significantly decreased in CUMS rats. CONCLUSION Chronic treatment of adult rat males with maprotiline, a noradrenaline reuptake inhibitor activated sympathoneural system. On the other hand, fluxilan, a serotonin reuptake inhibitor activated both sympathoneural and adrenomedullar system, whereas both antidepressants desensitized HPA axis. The findings described here suggest that elevated plasma catecholamines my contribute to adverse effects of these drugs on cardiovascular parameters during antidepressant therapy.
Compliance with tricyclic antidepressants: the value of four different methods of assessment.

AIMS To assess the advantages and disadvantages of four methods for studying compliance with antidepressants: self-report scores, tablet counts, a microprocessor (MEMS) container system and the assay of nordothiepin and dothiepin concentrations in plasma. METHODS The techniques were used in 88 patients commencing tricyclic antidepressants in the setting of UK general practice. RESULTS The MEMS system proved to be the most informative technique allowing identification of the precise time of container opening, the demonstration of 'drug holidays' and early cessation of therapy. Self-report scores (Morisky) proved a useful screening technique with a sensitivity of 72.2% and specificity of 74.1% for > or = 80% compliance. Although tablet counts were possible in 84 patients (95. 5%) they were unreliable in 19 (21.6%). Blood concentration assays proved the least acceptable method to patients and were possible in only 53 (60.2%). A ratio of nordothiepin:dothiepin > or = 1.1 claimed, by others, to identify noncompliance was only reliable when concentrations were low. CONCLUSIONS Both the MEMS system and self-report scores proved useful methods for identifying noncompliant patients in the setting of UK general practice. Although compliance was higher than reported in previous studies with 70 patients (79.5%) completing 6 weeks treatment, general practitioners tended to prescribe subtherapeutic doses.
Muscle‐specific expression of the RNA‐binding protein Staufen1 induces progressive skeletal muscle atrophy via regulation of phosphatase tensin homolog

&NA; Converging lines of evidence have now highlighted the key role for post‐transcriptional regulation in the neuromuscular system. In particular, several RNA‐binding proteins are known to be misregulated in neuromuscular disorders including myotonic dystrophy type 1, spinal muscular atrophy and amyotrophic lateral sclerosis. In this study, we focused on the RNA‐binding protein Staufen1, which assumes multiple functions in both skeletal muscle and neurons. Given our previous work that showed a marked increase in Staufen1 expression in various physiological and pathological conditions including denervated muscle, in embryonic and undifferentiated skeletal muscle, in rhabdomyosarcomas as well as in myotonic dystrophy type 1 muscle samples from both mouse models and humans, we investigated the impact of sustained Staufen1 expression in postnatal skeletal muscle. To this end, we generated a skeletal muscle‐specific transgenic mouse model using the muscle creatine kinase promoter to drive tissue‐specific expression of Staufen1. We report that sustained Staufen1 expression in postnatal skeletal muscle causes a myopathy characterized by significant morphological and functional deficits. These deficits are accompanied by a marked increase in the expression of several atrophy‐associated genes and by the negative regulation of PI3K/AKT signaling. We also uncovered that Staufen1 mediates PTEN expression through indirect transcriptional and direct post‐transcriptional events thereby providing the first evidence for Staufen1‐regulated PTEN expression. Collectively, our data demonstrate that Staufen1 is a novel atrophy‐associated gene, and highlight its potential as a biomarker and therapeutic target for neuromuscular disorders and conditions.
From international deployments to an Iowa community college: Experiences of veterans who have made the transition

The purpose of this phenomenological study was to describe the experiences of veterans who have made the transition from international deployments to an Iowa community college. The essence of these experiences was solicited by asking the question: How do veterans who have made the transition from international deployments to an Iowa community college describe their experiences? Constructionism provided the epistemological foundation for this study. An interpretivist perspective was used to analyze data collected via face-to-face interviews, participant observation, and document evaluation. Van Gennep’s liminality theory provided a theoretical lens through which to interpret that analysis. This interpretation revealed six themes, namely: (a) from civilian to warfighter—calibration and detachment, (b) from civilian to warfighter—ambiguity and metamorphoses, (c) from civilian to warfighter— consummation and reflection, (d) from warfighter to student—calibration and detachment, (e) from warfighter to student—ambiguity and metamorphoses, and (f) from warfighter to student—consummation and reflection. Study findings revealed that each participant had navigated simultaneous liminal stages prior to, during, and after his or her transition from an international deployment to an Iowa community college. Study conclusions include policy and practice implications for a broad spectrum of Iowa community college stakeholders. Recommendations for future research include conducting additional investigations of underresearched subsets of transitioning veteran cohorts.
The Impact of Party Identification on Issue Attitudes

This paper presents a simple, but theoretically appropriate, model for the influence of party identification on issue attitudes. Most studies simply relate partisanship directly to issues. However, that approach does not explain how one variable affects the other. Here, party identification is modeled as a manifestation of reference group phenomena. As such, a person's issue positions are taken to be a function of perceptions about his or her party's stands on the same issues. In addition, the degree of consistency between partisan perceptions and attitudes should increase with stronger party attachments. The analysis also examines the alternative possibility that a person's beliefs about his or her own party are largely rationalized from the individual's own feelings. The model is tested using data from the 1980 Center for Political Studies (CPS) American National Election Study. The empirical results show that partisanship does provide cues for guiding personal political orientations. At the same time, perceptions of the parties' issue stands are not merely derived from the citizens' own attitudes. Thus, the analysis supports the conventional view of party identification as an example of reference group influence on individual behavior.
Robust Detection of Impaired Resting State Functional Connectivity Networks in Alzheimer's Disease Using Elastic Net Regularized Regression

The large number of multicollinear regional features that are provided by resting state (rs) fMRI data requires robust feature selection to uncover consistent networks of functional disconnection in Alzheimer's disease (AD). Here, we compared elastic net regularized and classical stepwise logistic regression in respect to consistency of feature selection and diagnostic accuracy using rs-fMRI data from four centers of the “German resting-state initiative for diagnostic biomarkers” (psymri.org), comprising 53 AD patients and 118 age and sex matched healthy controls. Using all possible pairs of correlations between the time series of rs-fMRI signal from 84 functionally defined brain regions as the initial set of predictor variables, we calculated accuracy of group discrimination and consistency of feature selection with bootstrap cross-validation. Mean areas under the receiver operating characteristic curves as measure of diagnostic accuracy were 0.70 in unregularized and 0.80 in regularized regression. Elastic net regression was insensitive to scanner effects and recovered a consistent network of functional connectivity decline in AD that encompassed parts of the dorsal default mode as well as brain regions involved in attention, executive control, and language processing. Stepwise logistic regression found no consistent network of AD related functional connectivity decline. Regularized regression has high potential to increase diagnostic accuracy and consistency of feature selection from multicollinear functional neuroimaging data in AD. Our findings suggest an extended network of functional alterations in AD, but the diagnostic accuracy of rs-fMRI in this multicenter setting did not reach the benchmark defined for a useful biomarker of AD.
Asymmetric Option Price Distribution and Bid-Ask Quotes: Consequences for Implied Volatility Smiles

This study presents a model for estimating the asymmetry of option values with respect to option bid-ask spreads. The model does not require knowledge of the actual option value to evaluate the asymmetry. Using data from the Swedish equity options market, several interesting results emerge. First, there is evidence of asymmetry in call and put values, where values are closer to bid than to ask quotes. Second, in- and out-of-the-money calls and puts show a higher degree of asymmetry than at-the-money options. Third, taking asymmetry into account in the estimation of option-implied volatility, produces a less pronounced volatility smile.
Primary adenocarcinoma of the lung – histological subtypes and outcome after surgery, using the IASLC/ATS/ERS classification of lung adenocarcinoma

Adenocarcinoma is the most common histological type of lung carcinoma. Recently the histologic classification of adenocarcinomas in the lung was modified to better reflect biologic properties and prognosis. We reviewed the histology of all primary lung adenocarcinomas operated on in Iceland during a 20‐year period and assessed the impact of histology on survival. This nationwide study included 285 patients (mean age 67 years, 57% female), who underwent resection in Iceland from 1991 to 2010. Tumors were reclassified according to the current IASLC/ATS/ERS classification system. Overall survival was estimated by the Kaplan–Meier method and Cox regression analysis used to evaluate prognostic factors of overall mortality. Acinar predominant adenocarcinoma was the most common histological subtype (46%) followed by solid‐predominant (SPA) with mucin production comprised (23%). Non‐invasive carcinomas were rare. A difference in survival between the histological adenocarcinoma subtypes was not seen (p = 0.32) and multivariate analysis showed that advanced stage and age predicted worse outcome, but histologic subtyping of adenocarcinoma did not. In this nation‐wide study there was not a statistical difference in survival according to adenocarcinoma subtypes and the histological subtype did not predict mortality. Preinvasive and minimally invasive adenocarcinomas were rare.