Miracle-dz/UniFAR-FTUs huggingface dataset:
Nicotinamide Phosphoribosyltransferase: A Potent Therapeutic Target in Non-small Cell Lung Cancer with Epidermal Growth Factor Receptor-Gene Mutation

Background: Non-small cell lung cancer (NSCLC) often has an epidermal growth factor receptor (EGFR) gene mutation. Growth of EGFR-gene-mutated NSCLC depends predominantly on EGFR signaling and requires a large amount of intracellular ATP to activate EGFR signal transduction. Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in nicotinamide adenine dinucleotide biosynthesis, and it regulates intracellular ATP levels in mammalian cells. The effect of NAMPT inhibition on NSCLC has not been completely understood. Methods: We aimed to clarify the hypothesis that NAMPT inhibition suppresses growth of EGFR-gene-mutated NSCLC through reduction of intracellular ATP levels, using NAMPT-siRNA transfection and NAMPT inhibitor FK866. We used four lung adenocarcinoma cell lines, including H358 (Wild type EGFR), LC2 (EGFRL858R), PC9 (EGFRDel E746-A750), and H1975 (EGFRL858R+T790M), and evaluated the effect of FK866 on these cells and its mechanisms, using cell proliferation, Western blot, ATP, and apoptosis assay. Results: We found that (1) H358, LC2, and H1975 cell lines highly expressed NAMPT-mRNA; (2) NAMPT-specific siRNA and FK866 suppressed proliferation of these NSCLCs; (3) FK866 reduced intracellular ATP levels in H1975 cells; (4) FK866 dephosphorylated EGFR signal proteins, including EGFR, Akt, Map kinase kinase 1/2, and extracellular signal-regulated kinase 1/2 (ERK 1/2); (5) FK866 induced apoptosis of H1975 cells; and (6) FK866 suppressed growth of H1975 xenograft tumors and attenuated expression of phospho-ERK 1/2 in the tumors in a tumor-bearing mouse model. Conclusion: These findings indicate that NAMPT is a potent therapeutic target in the treatment of EGFR-gene-mutated NSCLC.
Symmetric infection of rotavirus on polarized human intestinal epithelial (Caco-2) cells

When rotavirus infects the mature villus tip cells of the small intestine, it encounters a highly polarized epithelium. In order to understand this virus-cell interaction more completely, we utilized a cell culture-adapted rhesus rotavirus (RRV) to infect human intestinal (Caco-2) and Madin-Darby canine kidney (MDCK-1) polarized epithelial cells grown on a permeable support. Filter-grown Caco-2 cells and MDCK-1 cells, producing a transepithelial resistance of 300 to 500 and greater than 1,000 omega . cm2, respectively, were infected from either the apical or basolateral domain with RRV or Semliki Forest virus. Whereas Semliki Forest virus infection only occurred when input virions had access to the basolateral domain of MDCK-1 or Caco-2 cells, RRV infected MDCK-1 and Caco-2 monolayers in a symmetric manner. The effect of rotavirus infection on monolayer permeability was analyzed by measuring the transepithelial electrical resistance. Rotavirus infection on filter-grown Caco-2 cells caused a transmembrane leak at 18 h postinfection, before the development of the cytopathic effect (CPE) and extensive virus release. Electrical resistance was completely abolished between 24 and 36 h postinfection. Although no CPE could be detected on RRV-infected MDCK cells, the infection caused a transmembrane leak that totally abolished the electrical resistance at 18 to 24 h postinfection. Cell viability and the CPE analysis together with immunohistochemistry and immunofluorescence data indicated that the abolishment of resistance across the monolayer was due not to an effect on the plasma membrane of the cells but to an effect on the paracellular pathway limited by tight junctions. Attachment and penetration of rotavirus onto Caco-2 cells caused no measurable transmembrane leak during the first hour of infection.
Early child-parent attachment and peer relations: a meta-analysis of recent research.

A central tenet of Bowlby's attachment theory is that early child-caregiver attachment is reflected in the quality of the child's interpersonal relationships throughout life. Schneider, Atkinson, and Tardif (2001) conducted a meta-analysis of studies conducted up to 1998 to corroborate that contention. They found a significant but small to moderate effect size (r = .20). Their finding that studies of friendship bonds had higher effect sizes than studies of other interpersonal relationships has important theoretical ramifications. The present brief report is a meta-analysis that covers research conducted for the same purpose since 1998. The sample consists of 44 studies with a total of 8505 participants. The overall effect size r of . 19 (adjusted r = .12; 95% confidence interval, .08-.17) in the current study was similar in magnitude to the effect size reported in the 2001 meta-analysis, documenting consistency in the predictive power of attachment theory. However, we failed to replicate the moderating effect of friendship. One possible explanation for these findings is that the friendships of school-age children and adolescents no longer invoke very high levels of intimacy. Effect sizes are higher in studies conducted outside North America than in U.S.--and Canada-based studies.
What Can Meta-analysis Tell Us about the Implications of Transport?

BUTTON K. (1995) What meta-analysis tell us about the implications of transport? , Reg. Studies 29, 507–517. Recent years have seen a significant upsurge of studies seeking to examine the wider impacts of transport. The outcome has been a wide range of results and conclusions. A number of extremely useful surveys have emerged that have brought together much of this work and offered critical assessment of the methods used and of the results generated. These surveys have, however, tended to be of a traditional literary nature and have often produced lists of findings and taxonomies of procedures employed. The aim of this paper is to apply meta-analysis in order to gain greater insights into the causes of the variations in results obtained, for example in relation to techniques used, country of study and context of work. BUTTON K. (1995) Quelles sont les lecons a tirer de la meta-analyse pour ce qui est du transport? , Reg. Studies 29, 507-517. Ces dernieres annees ont temoie d'une montee sensible du nombre de.
Catalytic and regulatory domains of doublecortin kinase-1.

Doublecortin kinase-1 (DCK1) is a newly described multidomain protein kinase with a sequence significantly similar to those of both CaM kinases (CaMKs) and doublecortin, the product of the gene mutated in X-linked lissencephaly/double cortex syndrome, a severe developmental disorder of the nervous system. Functional studies have revealed microtubule binding and polymerization activities of the doublecortin domain, yet little is known regarding the enzymatic properties and regulation of the kinase catalytic domain. We have identified and report here notable similarities as well as differences between the catalytic and regulatory properties of DCK1 and those of the CaMKs. Using synthetic peptide substrates modeled on synapsin I, a substrate recognition motif for DCK1 of Hyd-Arg-Arg-X-X-Ser/Thr-Hyd was derived. The similarity of this motif to that of CaMKI [Lee, J. C. , Kwon, Y. -G. , Lawrence, D. S. , and Edelman, A. M. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 6413-6417] is consistent with the 59% level of amino acid sequence similarity between their catalytic domains. DCK1 catalytic activity is enhanced by mutagenic introduction of negative charge at Thr-239, a residue in a position equivalent to that of Thr-177 of CaMKI, the activation loop site for regulation by CaM kinase kinase. Unlike CaMKs, DCK1 is not directly activated by Ca(2+)-bound CaM. However, truncation of a pseudosubstrate-like sequence in the C-terminus of DCK1 results in an approximately 6-fold enhancement of activity. Thus, DCK1 demonstrates the potential to be regulated by relief of autoinhibition in response to signal(s) distinct from Ca(2+)-bound CaM and potentially by activation loop phosphorylation and to phosphorylate intracellular targets at sites similar to those recognized by CaMK pathways.
Investor Valuations and Measuring Bank Intangible Assets

This paper examines the value-relevance and reliability of bank intangible asset measures. The majority of bank intangible assets are not recognized and few banks voluntarily disclose estimates or provide other information about these assets. Investors therefore have limited direct information about this important component of bank value. I incorporate publicly available financial and market information to estimate four customer-based intangible assets: mortgage servicing rights, credit card intangible, core deposit intangible, and trust operations intangible. I find my estimates are value-relevant, increase the explanatory power of a valuation model compared to one containing balance sheet amounts; and, with the exception of the mortgage servicing rights, are more reliable than balance-sheet amounts and estimates derived from simple algorithms used in prior research. Intangible assets that are not separately reported (core deposit and trust operations intangibles) or that are reported by few banks (credit card intangible) drive the results. These intangible assets are also not subject to separate accounting recognition standards such as SFAS 122 for mortgage servicing rights, where I find weaker results. The evidence of value-relevance and reliability of intangible asset estimates based on current disclosures (and recorded mortgage servicing rights) suggests the existing financial reporting requirements provide useful information about intangible assets and change may not be necessary.
Outcome Correlates of Parent-Child Bedsharing: An Eighteen-Year Longitudinal Study

ABSTRACT. We report results of the first longitudinal study of outcome correlates of parent-child bedsharing. Two hundred five families in nonconventional and conventional family lifestyles have been followed since 1975. A target child in each family was followed from the third trimester of mother’s pregnancy through age 18 years. Bedsharing in early childhood was found to be significantly associated with increased cognitive competence measured at age 6 years, but the effect size was small. At age 6 years, bedsharing in infancy and early childhood was not associated with sleep problems, sexual pathology, or any other problematic consequences. At age 18 years, bedsharing in infancy and childhood was unrelated to pathology or problematic consequences, nor was it related to beneficial consequences. We discuss these results in light of widespread fears of harm caused by parent-child bedsharing. We suggest that such fears are without warrant if bedsharing is practiced safely as part of a complex of valued and related family practices.
Identification and Characterization of miRNA Transcriptome in Asiatic Cotton (Gossypium arboreum) Using High Throughput Sequencing

MicroRNAs (miRNAs) are small 20–24nt molecules that have been well studied over the past decade due to their important regulatory roles in different cellular processes. The mature sequences are more conserved across vast phylogenetic scales than their precursors and some are conserved within entire kingdoms, hence, their loci and function can be predicted by homology searches. Different studies have been performed to elucidate miRNAs using de novo prediction methods but due to complex regulatory mechanisms or false positive in silico predictions, not all of them express in reality and sometimes computationally predicted mature transcripts differ from the actual expressed ones. With the availability of a complete genome sequence of Gossypium arboreum, it is important to annotate the genome for both coding and non-coding regions using high confidence transcript evidence, for this cotton species that is highly resistant to various biotic and abiotic stresses. Here we have analyzed the small RNA transcriptome of G. arboreum leaves and provided genome annotation of miRNAs with evidence from miRNA/miRNA∗ transcripts. A total of 446 miRNAs clustered into 224 miRNA families were found, among which 48 families are conserved in other plants and 176 are novel. Four short RNA libraries were used to shortlist best predictions based on high reads per million. The size, origin, copy numbers and transcript depth of all miRNAs along with their isoforms and targets has been reported. The highest gene copy number was observed for gar-miR7504 followed by gar-miR166, gar-miR8771, gar-miR156, and gar-miR7484. Altogether, 1274 target genes were found in G. arboreum that are enriched for 216 KEGG pathways. The resultant genomic annotations are provided in UCSC, BED format.
Factors Influencing Intention to Create New Venture Among Young Graduates

The purpose of this paper is to investigate the factors that are influencing the young graduates for intention to create new venture. The study further highlights how the attraction, networking support, entrepreneurial capabilities, self-independence and self-reliance influence the young students to initiate their new businesses. The sample size of this study was 255 final semester students of various disciplines in different universities from Islamabad and Rawalpindi. The survey based questionnaire was used for data collection. Based on findings this study concludes that all variables, included in the study, play a vital role in new venture creation. Therefore, on the basis of findings this study concludes that young students are more motivated towards new venture creation and start their own businesses.
The uses of the national PISA results by Finnish officials in central government

In this article we attempt to analyse how OECD knowledge production is integrated with the process in which Finnish education policy takes shape. This is done by analysing the uses of the OECD PISA Study by Finnish central government officials. The main question posed is: How do these officials interpret the PISA results so as to justify the decisions made in Finnish education policy in the past or to point out new areas of development concerning basic education? The analysis shows that the interpretations of the PISA results tend to favour those responsible for actions within the central government. In the texts analysed, the scientificity of the PISA programme is presented as beyond question, while the direct usefulness of the research results for the further development of national education is also proclaimed. As to the specific results of PISA, the excellent learning outcomes of Finnish students are claimed to be due to educational reforms conducted and decisions made by the central government, whereas shortcomings and areas in which the officials see a need for improvement are argued to be dependent on the actions of other agents. Thus, the analysis shows that the conclusions drawn from the PISA results in texts representing the views of central government are biased and serve to justify its policy agenda.
Research ethics policies and practices in health research institutions in sub-Saharan African countries: results of a questionnaire-based survey

Objective To describe the state of research ethics policies and practices in health research institutions in sub-Saharan African countries. Design A structured questionnaire was used to solicit information on research ethics from health research institutions. Setting Forty-two sub-Saharan African countries. Participants Key informants from the health research institutions. Main outcome measures Existence of institutional ethics review policies and mechanisms. Results About half (51%) of respondent institutions reported having policies on research ethics and 58% had written policies requiring that researchers obtain informed consent of research participants. About one-third of respondent institutions (34%) had established ethics review committees, 42% required that studies went through ethics review committees and 46% had linkages with national or regional ethics organisations. Regarding operating procedures for ethics review committees, 53% had adopted standard operating procedures. Less than one-quarter of respondent institutions reported having policies in place to monitor ongoing research. Of the institutions that monitored ongoing research, 34% did an annual ethical review and 74% required a periodic written report. Only 36% provided any type of ethics training for staff, including those conducting health research and those who were not members of the ethics review committee. Conclusions There are substantial gaps in the capacity of health research institutions in the WHO African Region to undertake ethical review of studies before, during and after studies conducted. There is a need to strengthen such capacity in order to ensure the wellbeing of individuals enrolled in studies and that of communities that host these studies.
Selective Pharmacologic Inhibition of a PASTA Kinase Increases Listeria monocytogenes Susceptibility to β-Lactam Antibiotics

ABSTRACT While β-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore β-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to β-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of β-lactam antibiotics.
Taking a DSGE Model to the Data Meaningfully

Abstract All economists say that they want to take their models to the data. But with incomplete and highly imperfect data, doing so is difficult and requires carefully matching the assumptions of the model with the statistical properties of the data. The cointegrated VAR (CVAR) offers a way of doing so. In this paper we outline a method for translating the assumptions underlying a DSGE model into a set of testable assumptions on a cointegrated VAR model and illustrate the ideas with the RBC model in Ireland (2004). Accounting for unit roots (near unit roots) in the model is shown to provide a powerful robustification of the statistical and economic inference about persistent and less persistent movements in the data. We propose that all basic assumptions underlying the theory model should be formulated as a set of testable hypotheses on the long-run structure of a CVAR model, a so called ‘theory consistent hypothetical scenario’. The advantage of such a scenario is that it forces us to formulate all testable implications of the basic hypotheses underlying a theory model. We demonstrate that most assumptions underlying the DSGE model and, hence, the RBC model are rejected when properly tested. Leaving the RBC model aside, we then report a structured CVAR analysis that summarizes the main features of the data in terms of long-run relations and common stochastic trends. We argue that structuring the data in this way offers a number of ‘sophisticated’ stylized facts that a theory model should replicate in order to claim empirical relevance.
Age-dependence and Historical Effects on the Failure Rates of Worker Cooperatives: An Event-history Analysis

This paper tests a number of hypotheses about the failure rates of worker cooperatives created in Atlantic Canada between 1940 and 1987. The event-history analysis shows that failure rates vary significantly by organizational age, sectoral location, and period of organizational founding, reflecting the effects of the business cycle and organizational population dynamics. In contrast to most conventional business organizations, worker cooperatives are not likely to fail during their early years of existence, but are most vulnerable in their fifth year.
Apelin (65-77) activates extracellular signal-regulated kinases via a PTX-sensitive G protein.

We report here that apelin (65-77) induces activation of extracellular-regulated kinases (ERKs) in Chinese hamster ovary (CHO) cells expressing the msr/apj receptor. This concentration-dependent activation was transient, peaking at 5 min. Pretreatment of CHO cells with pertussis toxin fully abrogated ERK phosphorylation, whereas overexpression of the beta-adrenergic receptor kinase-1 C-terminal fragment did not alter ERK activation. Transfection with a dominant-negative mutant of Ras was without effect on ERK activation, whereas an inhibitor of many protein kinase C isoforms, GF109203X, strongly decreased it. These results demonstrate that stimulation of the murine msr/apj receptor promotes ERK activation via the alpha subunit of a pertussis toxin-sensitive protein in a Ras-independent pathway.
Inequality of Happiness in the U.S.: 1972–2010

It is well accepted that a country's GDP may not fully reflect its level of well‐being. In recent years, happiness has emerged as an alternative indicator of well‐being, and research has mainly focused on determining the level of happiness. While it is important to look at the level, the distribution of happiness is also a salient aspect in any evaluation of inequality. There has been a growing interest in the distribution of happiness, although the ordinal nature of the data makes the use of standard inequality measures problematic. Our paper contributes to the literature by exploring the distributions for the U.S. from 1972 to 2010. Based on new methods developed for ordinal data, we are able to overcome the problems associated with ordinality and obtain unambiguous rankings of happiness distributions. We also compute the level of happiness inequality using existing measures based on median centred approaches. Further, we decompose the median based inequality measures of happiness by gender, race, and region.
Large-Scale Urban Projects in Smaller Metro Areas: Towards a Broader Conceptual Perspective

Large-scale projects seem to be as popular in urban politics as they are risky in implementation. Existing research shows a certain bias towards studying projects in large metropolitan regions. The paper aims at extending the scope of research on large-scale urban projects by analysing such projects in a smaller metropolitan area. The case of the city region and country of Luxembourg shows that decision-makers in small metropolitan regions also make use of large-scale urban projects as a planning and place-making instrument. The case is also used to explore methodological approaches of examining the symbolic nature and discursive place-making dimension of planning large-scale projects, and proposes a methodological approach based on constructivist grounded theory and situational analysis of discourses.