Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutralizing Antibodies and CD8+ T Lymphocytes both Contribute to Immunity to Adenovirus Serotype 5 Vaccine Vectors

ABSTRACT The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. Ad5-specific neutralizing antibodies (NAbs) are thought to contribute substantially to anti-Ad5 immunity, but the potential importance of Ad5-specific T lymphocytes in this setting has not been fully characterized. Here we assess the relative contributions of Ad5-specific humoral and cellular immune responses in blunting the immunogenicity of a rAd5-Env vaccine in mice. Adoptive transfer of Ad5-specific NAbs resulted in a dramatic abrogation of Env-specific immune responses following immunization with rAd5-Env. Interestingly, adoptive transfer of Ad5-specific CD8+ T lymphocytes also resulted in a significant and durable suppression of rAd5-Env immunogenicity. These data demonstrate that NAbs and CD8+ T lymphocytes both contribute to immunity to Ad5. Novel adenovirus vectors that are currently being developed to circumvent the problem of preexisting anti-Ad5 immunity should therefore be designed to evade both humoral and cellular Ad5-specific immune responses.
Quality minus junk

We define quality as characteristics that investors should be willing to pay a higher price for. Theoretically, we provide a tractable valuation model that shows how stock prices should increase in their quality characteristics: profitability, growth, and safety. Empirically, we find that high-quality stocks do have higher prices on average but not by a large margin. Perhaps because of this puzzlingly modest impact of quality on price, high-quality stocks have high risk-adjusted returns. Indeed, a quality-minus-junk (QMJ) factor that goes long high-quality stocks and shorts low-quality stocks earns significant risk-adjusted returns in the United States and across 24 countries. The price of quality varies over time, reaching a low during the internet bubble, and a low price of quality predicts a high future return of QMJ. Analysts’ price targets and earnings forecasts imply systematic quality-related errors in return and earnings expectations.
The habitat factor in ELF(A) – English as a Lingua Franca (in Academic settings) – and English for Plurilingual Academic Purposes

Abstract This article considers a case of local language socialization and accommodation in a multilingual community of practice: the use of English as an additional academic language for specific purposes at a bilingual Swiss university and its implications for teaching. The acronym ELF(A) is used throughout as short for English as a Lingua Franca (in Academic settings). The bilingual university’s multilingual habitat also shapes the kind of ELF(A) used and this has in turn informed the teaching of English for Plurilingual Academic Purposes (EPAP). The discussion draws on both ethnographic research carried out in multilingual disciplinary speech events and on the author’s simultaneous and continuing experience of developing and teaching English for academic purposes (EAP). It focuses on an oral presentation to a life science journal club made by a multilingual doctoral student socialized into the use of English almost exclusively in the ELF(A) habitat. Using the plurilingual repertoire to sustain “code-sharing” lingua franca mode, one of the habitat’s most striking effects is the effort users are willing to expend in striving for autonomous functionality in their Englishes without overt switching, while simultaneously relying on their audience’s multilingual flexibility and shared disciplinary knowledge, e.g. in the pronunciation of technical terminology. The habitat of a multilingual community of practice that assumes responsibility for its novices’ language socialization in an additional medium is thus a supportive factor empowering junior scientists to function in English. To the extent that the habitat factor contains a limiting dimension of context dependence, however, teaching EPAP should also target speakers’ (potential) needs for spoken academic language use elsewhere.
Why are managers happier than workers

This paper studies the determinants of differences in self reported job satisfaction across occupations using data from the 2006/2007 European Social Survey (18 countries). When the effect of other variables is not accounted for, being a Manager yields a "satisfaction bonus" two times as big as the one provided by Workers positions. This substantial satisfaction gap between those holding Managerial positions and Workers practically disappears when we control for individual, household and work related variables. Even though the differences across occupations are reduced, all occupations bring about more job satisfaction than manual and service positions. All results hold when using the European Working Conditions Survey data set. In addition, the results are robust to the use of job satisfaction as a categorical variable and to a variation of the model specification that takes into account the potential endogeneity of the occupational choice. How to obtain EU publications Our priced publications are available from EU Bookshop (http://bookshop.europa.eu), where you can place an order with the sales agent of your choice. The Publications Office has a worldwide network of sales agents. You can obtain their contact details by sending a fax to (352) 29 29-42758. The mission of the JRC is to provide customer-driven scientific and technical support for the conception, development, implementation and monitoring of EU policies. As a service of the European Commission, the JRC functions as a reference centre of science and technology for the Union. Close to the policy-making process, it serves the common interest of the Member States, while being independent of special interests, whether private or national. LB -N A -2477-EN -C
An analysis of science teachers’ classroom discourse relating to the use of models and simulations in physics

This case study provides an account of three teachers’ first attempts in implementing simulation experiments within a design-based inquiry science curriculum. We examined how three in-service teachers used simulations and physical models in the classroom to promote students’ understanding of the nature of models. We found that teachers mostly talked about the procedural aspects related to simulation use. While some of the teachers’ dialogue focused on science ideas, there was very little explicit talk about the nature of models. Of the discourse concerning the nature of models, most focused on model evaluation, the affordances and constraints of models, and comparing multiple models. Critical incidents related to the nature of models are presented and discussed. All three teachers missed opportunities to help students understand the nature of models as they introduced simulation activities, facilitated simulation group work, and conducted final class discussions.
The Interaction of Calmodulin with Alternatively Spliced Isoforms of the Type-I Inositol Trisphosphate Receptor*

A 592-amino acid segment of the regulatory domain of the neuronal type-I inositol 1,4,5-trisphosphate receptor (IP3R) isoform (type-I long, amino acids1314–1905) and the corresponding 552-amino acid alternatively spliced form present in peripheral tissues (type-I short, amino acids 1693–1733 deleted) were expressed as glutathioneS-transferase fusion proteins. These domains encompass a putative calmodulin (CaM) binding domain and two protein kinase A phosphorylation sites. Both long and short fusion proteins retained the ability to bind CaM in a Ca2+-dependent manner as measured by CaM-Sepharose chromatography or a dansyl-CaM fluorescence assay. Both assays indicated that the short fusion protein bound twice the amount of CaM than the long form at saturating concentrations of CaM. In addition, the binding of the short form to CaM-Sepharose was inhibited by phosphorylation with protein kinase A, whereas the binding of the long form was unaffected. Full-length cDNAs encoding type-I long, type-I short, and type-III IP3R isoforms were expressed in COS cells, and the Ca2+ sensitivity of [3H]IP3binding to permeabilized cells was measured. The type-I long isoform was more sensitive to Ca2+ inhibition (IC50 = 0.55 μm) than the type-I short (IC50 = 5.7 μm) or the type-III isoform (IC50 = 3 μm). In agreement with studies on the fusion proteins, the full-length type-I short bound more CaM-Sepharose, and this binding was inhibited to a greater extent by protein kinase A phosphorylation than the type-I long IP3R. Although type-III IP3Rs did not bind directly to CaM-Sepharose, hetero-oligomers of type-I/III IP3Rs retained the ability to interact with CaM. We conclude that the deletion of the SII splice site in the type-I IP3R results in the differential regulation of the alternatively spliced isoforms by Ca2+, CaM, and protein kinase A.
European Imaginaries: Dead End of Further Integration? : Analysis of the Imaginaries of the European Heads of State andGovernment and the European Commission

This thesis analyses the imaginaries of important political decision makers of the European Union in the context of the refugee crisis and interprets them according to theories of European integration. Speeches, interviews, statements and press releases of the 28 heads of state and government of the European Member States and two Commissioners of the European Commission are analysed through qualitative content analysis. The aim is to derive prospects for European integration from the expressed imaginaries. For the interpretation, the theories neofunctionalism and liberal intergovernmentalism are applied. The study’s results show that the imaginaries of the largest group of national heads of state and government remain blurred without clarification, which position is taken with regard to European integration, while the imaginaries of the Commissioners are mainly characterised by support of further integration. According to both neofunctionalism and liberal intergovernmentalism, the interpretation of the imaginaries leads to the conclusion that the prospects for further European integration remain limited. Only in those policy fields directly related to the immediate crisis further cooperation can be expected.
Financing Long-Term Care: Ex-Ante, Ex-Post or Both?

This paper attempts to examine the heterogeneity in the public financing of long-term care (LTC) and the wide-ranging instruments in place to finance LTC services. We distinguish and classify the institutional responses to the need for LTC financing as ex ante (occurring prior to when the need arises, such as insurance) and ex post (occurring after the need arises, such as public sector and family financing). Then, we examine country-specific data to ascertain whether the two types of financing are complements or substitutes. Finally, we examine exploratory cross-national data on public expenditure determinants, specifically economic, demographic and social determinants. We show that although both ex ante and ex post mechanisms exist in all countries with advanced industrial economies and despite the fact that instruments are different across countries, ex ante and ex post instruments are largely substitutes for each other. Expenditure estimates to date indicate that the public financing of LTC is highly sensitive to a country's income, ageing of the population and the availability of informal caregiving.
Operational efficiency of ASEAN airlines: based on DEA and bootstrapping approaches

Purpose For strategic and competitive insights, the purpose of this paper is to measure and benchmark the comparative operating efficiencies of Association of Southeast Asian Nations’ (ASEAN) major airlines and present a new interpretation along with managerial implications. Design/methodology/approach This research statistically tests returns to scale and the equality of mean efficiencies for 15 ASEAN airlines covering the period 2010-2014. The disaggregate input efficiency of ASEAN airlines is computed by comparing the target and actual inputs. Findings The disaggregate input efficiency of ASEAN airlines shows that aircraft efficiency is the lowest, operating cost efficiency is better, and available seat efficiency is the best. Originality/value This paper applies data envelopment analysis models, disaggregated input efficiency measures, and bootstrapping approaches to compute the operational efficiency of ASEAN airlines. Strategic suggestions are made to improve the operational efficiency of ASEAN airlines.
Competition and innovation with selective exit: an inverted-U shape relationship?

This paper extends the approach of the inverted-U relationship between competition and innovation at the industry level introduced by Aghion and coauthors. We use data of Spanish manufacturing firms from the Survey of Business Strategies (ESEE) spanning 1990–2006, as well as external information on patents from the European Patent Office and US Patent Office. Instead of an inverted-U shape, we obtain an unambiguous positive relationship between competition and patents. To explain this positive relationship, we modify their theoretical model to introduce the possibility of inefficient firms facing the threat of exit when competition intensifies. The modified model may explain both a positive and an inverted-U relationship between competition and innovation. The estimated results also support the theoretical conjecture that competition induces firms’ exit that, in turn, explains our empirical finding of a negative relationship between competition and within-industry technological gap.
Children's exposure to secondhand smoke at home before and after smoke-free legislation in Taiwan

Introduction In January 2009, Taiwan broadened smoke-free legislation, requiring mass transportation systems, indoor public areas and indoor workplaces with 3 or more people, to become smoke-free. We investigated the secondhand smoke (SHS) exposure at home for children aged 3–11 years in Taiwan before and after the implantation of the legislation. Methods We studied 7911 children from the 2005, 2009 and 2013 National Health Interview Surveys (cross-sectional, nationally representative household surveys). Logistic regression modelling estimated adjusted ORs (AOR) and 95% CIs for children's SHS exposure at home in 2009 and 2013 (2005 as reference) for the overall sample and for each category of household socioeconomic status (SES) and household composition. Results Prevalence of children SHS exposure at home decreased from 51% (2005) to 32% (2009) and 28% (2013). Compared to 2005, children in 2009 and 2013 had lower likelihoods of SHS exposure at home with AOR of 0.45 (95% CI 0.41 to 0.51) and 0.41 (95% CI 0.36 to 0.46), respectively. All children had reduced SHS exposure at home after the legislation, irrespective of household SES and compositions. Low household income, low parental education level, living with grandparents or living with other adults was individually associated with increased SHS exposure. Discussion The proportion of children exposed to SHS at home in Taiwan declined substantially from 2005 to 2009 after smoke-free legislation, and fell further by 2013, irrespective of SES and household compositions. Still, inequality in SHS exposure at home by SES and household composition warrants future research.
Skeletal muscle size: relationship to muscle function in heart failure.

Abnormalities of skeletal muscle function and metabolism are common in patients with congestive heart failure (CHF) and appear to contribute to systemic exercise limitation. Although the mechanism for these differences is unclear, one possibility is skeletal muscle atrophy. In 21 CHF patients and 12 sex- and age-matched sedentary control subjects, we quantified muscle size as maximal cross-sectional area (MCSA) of thigh muscles measured by magnetic resonance imaging and determined the relationship between muscle size and muscle function. Muscle strength was measured as maximum force developed during isometric contractions, and muscle endurance was quantified as the decline in force during 15 consecutive isokinetic knee extensions (measured as ratio of mean peak torque of last 3 and first 3 extensions). MCSAs of thigh muscles (141 +/- 28 vs. 167 +/- 47 cm2, P < 0.05) and knee extensors (62 +/- 13 vs. 75 +/- 13 cm2; P < 0.05) were both significantly smaller in patients than in control subjects. These differences persisted after normalization for body size. Isometric strength was less, but not significantly so, in patients (126 +/- 39 vs. 135 +/- 43 Nm; P = NS), but muscle endurance was markedly impaired (endurance ratio 0.67 +/- 0.14 vs. 0.83 +/- 0.11; P < 0.05). A strong correlation was found between isometric strength (r = 0.76) and MCSA of knee extensors, but only a weak correlation between dynamic endurance and MCSA was seen. We conclude that muscle size is smaller in CHF patients but that maximal force generated per area of muscle is not impaired. (ABSTRACT TRUNCATED AT 250 WORDS)
Failure of human immunodeficiency virus entry and infection in CD4-positive human brain and skin cells

CD4 molecules on human cells function as a major receptor for human immunodeficiency virus (HIV); however, certain CD4-negative cell types may also be susceptible to infection. Therefore, we attempted to quantitate the relationship between HIV infection and CD4 expression on human cell lines before and after introduction of the CD4 gene by using a retrovirus vector. Prior to introduction of the CD4 expression vector, low levels of HIV infection were detected by a sensitive focal immunoassay on all three cell types studied. With several HIV strains in clones of human cervical carcinoma (HeLa) cells expressing different levels of CD4, HIV titer increased with increasing CD4 expression. In contrast, in squamous cell carcinoma cells (SCL1) and astroglial cells (U87MG), even high levels of CD4 expression failed to augment HIV infection. The CD4 protein expressed in these two cell lines had the expected molecular weight and was capable of binding HIV virions. However, in contrast to CD4-positive HeLa cells, CD4-positive U87MG and SCL1 cells were unable to form syncytia when cultured with cells expressing HIV envelope protein. Thus, the inability of HIV to infect these cells appeared to be due to lack of fusion between HIV virion envelope proteins and CD4-positive cell membranes. This block is infectivity was overcome when cells were infected with HIV which was pseudotyped with the envelope protein of amphotropic murine leukemia virus. Thus, in addition to CD4, other cell surface molecules appear to be required for successful HIV entry into and infection of these two human cell lines.
A New Subtype of a Congenital Disorder of Glycosylation (CDG) with Mild Clinical Manifestations

A boy with an unspecific symptomatology consisting of mental retardation, strabismus, hypotonia and mild ataxia was diagnosed with a congenital disorder of glycosylation (CDG). Neither cerebellar atrophy nor dysmorphic features were present. The serum transferrin band pattern obtained by isoelectric focusing(IEF) showed a strongly elevated disialotransferrin band together with only slightly elevated asialotransferrin, thus a type I pattern. This is a new CDG classified CDG-x since CDG-la, -b, -c, -d and -e were excluded. Quantitative differences to the type 1 pattern of a CDG-la patient with a moderate to severe course were confirmed by densitometric evaluation of the gels and by SDS gel electrophoresis. Liver biopsy showed lysosomal inclusions suggesting a pre-Golgi defect. This patient's case supports the approach to include isoelectric focusing of serum transferrin in the diagnostic work-up of patients with unexplained symptoms.
A New Curvature-Corrected Bandgap Reference

A bandgap-voltage reference implemented with a new accurate circuit configuration for compensating the thermal nonlinearity of the base-emitter voltage is described. With this device, a temperature coefficient of 0.5 ppm//spl deg/C over the temperature range -25 to +85/spl deg/C has been achieved. The minimum required supply voltage amounts to only 5.5 V.
Early Developmental Changes in IGF-I, IGF-II, IGF Binding Protein-1, and IGF Binding Protein-3 Concentration in the Cerebrospinal Fluid of Children

IGF-I and IGF-II are ubiquitously expressed growth factors that have profound effects on the growth and differentiation of many cell types and tissues, including cells of the CNS. In biologic fluids, most IGFs are bound to one of six IGF binding proteins (IGFBPs 1–6). Increasing evidence strongly supports a role for IGF-I in CNS development, as it promotes neuronal proliferation and survival. However, little is known about IGF-I and its homolog IGF-II and their carrier proteins, IGFBPs, during the neonatal period in which brain size increases dramatically, myelination takes place, and neurons show limited capacity to proliferate. Herein, we have determined the concentrations of IGF-I, IGF-II, IGFBP-1, and IGFBP-3 in cerebral spinal fluid (CSF) samples that were collected from children who were 1 wk to 18 y of age. The concentrations of IGF-I, IGFBP-1, and IGFBP-3 in CSF from children <6 mo of age were significantly higher than in older children, whereas IGF-II was higher in the older group. This is in contrast to what is observed in the peripheral circulation, where IGF-I and IGFBP-3 are low at birth and rise rapidly during the first year, reaching peak levels during puberty. Higher concentrations of IGF-I, IGFBP-1, and IGFBP-3 in the CSF of very young children suggest that these proteins might participate in the active processes of myelination and synapse formation in the developing nervous system. We propose that IGF-I and certain IGFBPs are likely necessary for normal CNS development during critical stages of neonatal brain growth and development.
Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment.

Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant effect of warfarin. Genetic polymorphisms in CYP2C9 producing variants with altered catalytic properties have been identified. Patients (n = 561) with a target international normalized ratio (INR) of 2.5 who had been treated with warfarin for more than 2 months were anonymously genotyped for the wild-type CYP2C9*1 allele and the 2C9*2 and 2C9*3 variants. The mean maintenance dose of warfarin in patients who were wild-type for both alleles was 5.01 mg. The maintenance dose of warfarin was significantly related to genotype (Kruskall-Wallis, chi(2) = 17.985, P =. 001) with mean maintenance doses in patients with variant alleles between 61% and 86% of that in wild-type patients. The odds ratio for the 2C9*2 allele in patients with a maintenance dose of 1. 5 mg or less was 5.42 (95% CI 1.68-17.4). The odds ratio for one or more variant alleles in patients developing an INR of 8.0 or greater was 1.52 (95% CI 0.64-3.58). The SD of the mean INR, percentage of high INRs, and person-time spent in range were determined as parameters of stability. There was no difference between patients grouped according to genotype for any parameter of stability. This study confirmed an association between CYP2C9 genotype and warfarin sensitivity. However, the possession of a variant allele does not increase the likelihood of severe over-anticoagulation or stability of anticoagulation during long-term therapy. (Blood. 2000;96:1816-1819)