Miracle-dz/UniFAR-FTUs huggingface dataset:
Policy instruments and welfare state reform

A core, but so far untested, proposition of the new politics perspective, originally introduced by Paul Pierson, is that welfare state cutbacks will be implemented using so-called ‘invisible’ policy instruments, for example, a change in indexation rules. Expansion should, by implication, mainly happen using ‘visible’ policy instruments, for example, a change in nominal benefits. We have coded 1030 legislative reforms of old-age pensions and unemployment protection in Britain, Denmark, Finland and Germany from 1974 to 2014. With this unique data at hand, we find substantial support for this crucial new politics proposition.
Melatonin increases gene expression for antioxidant enzymes in rat brain cortex

Kotler M, Rodríguez C, Sáinz RM, Antolín I, Menéndez‐Peláez A. Melatonin increases gene expression for antioxidant enzymes in rat brain cortex. J. Pineal Res. 1998; 24:83–89. © Munksgaard, Copenhagen
Effects of five experimental treatments of stuttering.

Twenty adult stutterers were exposed to each of five experimental treatments: time-out, noise, delayed auditory feedback (DAF), "wrong" and metronome. In each session a subject spoke for 20 minutes without treatment (baserate) followed by 30 minutes in one of the five experimental conditions. Before the five treatment sessions, subjects accomplished three pre-experimental tasks: expectancy, changeability, and adaptation tasks. Percent stuttering decreased significantly in all conditions, and stuttering duration reduced significantly in all but the noise condition. The amount of reduction in percent stuttering from baserate to treatment (change score) in time-out was positively related to the change scores in DAF and metronome. Change scores in metronome were positively related to change scores in time-out and "wrong. " Percent stuttering change scores in noise, DAF, and "wrong" were essentially unrelated. Stuttering duration change scores were related only for the time-out and DAF, and metronome and DAF conditions. In general, the pre-experimental expectancy, changeability, and adaptation scores were unrelated to change scores in any of the experimental conditions. Words spoken per minute did not change significantly from baserate to treatment for any experimental condition except time-out.
The Threshold GARCH Model: Estimation and Density Forecasting for Financial Returns*

We consider multiple threshold value-at-risk (VaRt) estimation and density forecasting for financial data following a threshold GARCH model. We develop an α-quantile quasi-maximum likelihood estimation (QMLE) method for VaRt by showing that the associated density function is an α-quantile density and belongs to the tick-exponential family. This establishes that our estimator is consistent for the parameters of VaRt. We propose a density forecasting method for quantile models based on VaRt at a single nonextreme level, which overcomes some limitations of existing forecasting methods with quantile models. We find that for heavy-tailed financial data our α-quantile QMLE method for VaRt outperforms the Gaussian QMLE method for volatility. We also find that density forecasts based on VaRt outperform those based on the volatility of financial data. Empirical work on market returns shows that our approach also outperforms some benchmark models for density forecasting of financial returns.
A Single Amino Acid Determines Lysophospholipid Specificity of the S1P1 (EDG1) and LPA1 (EDG2) Phospholipid Growth Factor Receptors*

The phospholipid growth factors sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are ligands for the related G protein-coupled receptors S1P1/EDG1 and LPA1/EDG2, respectively. We have developed a model of LPA1 that predicts interactions between three polar residues and LPA. One of these, glutamine 125, which is conserved in the LPA receptor subfamily (LPA1/EDG2, LPA2/EDG4, and LPA3/EDG7), hydrogen bonds with the LPA hydroxyl group. Our previous S1P1 study identified that the corresponding glutamate residue, conserved in all S1P receptors, ion pairs with the S1P ammonium. These two results predict that this residue might influence ligand recognition and specificity. Characterization of glutamate/glutamine interchange point mutants of S1P1 and LPA1 validated this prediction as the presence of glutamate was required for S1P recognition, whereas LPA recognition was possible with either glutamine or glutamate. The most likely explanation for this dual specificity behavior is a shift in the equilibrium between the acid and conjugate base forms of glutamic acid due to other amino acids surrounding that position in LPA1, producing a mixture of receptors including those having an anionic glutamate that recognize S1P and others with a neutral glutamic acid that recognize LPA. Thus, computational modeling of these receptors provided valid information necessary for understanding the molecular pharmacology of these receptors.
Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel–cisplatin–topotecan in a phase I study

Topotecan stabilizes the topoisomerase I (Topo I) cleavable complex. We measured Topo I levels in white blood cells of patients with ovarian cancer treated with topotecan. Topotecan was given i.v. daily ×5 q 3 weeks in combination with paclitaxel (1 day before topotecan) and cisplatin (just prior topotecan). Our aim was to correlate Topo I levels to pharmacokinetics and toxicity. Topo I levels were determined using Western blotting and were expressed relative to the Topo I level present in 10 μ g cell lysate of the human IGROV1 ovarian cancer cell line. We found no correlation between Topo I levels and (non-)hematological toxicity. Topo I levels after the fifth topotecan infusion were significantly negatively correlated with the AUC of topotecan (R =−0.64, p =0.026), in contrast with Topo I levels prior to (R =−0.25, p =0.4) and after (R =−0.30, p =0.3) the first topotecan infusion. Topo I levels after the fifth topotecan infusion (48±27%, mean±SD) were higher than Topo I levels prior to and after the first topotecan infusion (3.0±4.7 and 2.7±3.6%, respectively) (p =0.001). In conclusion, we detected a significant inverse correlation between Topo I level and topotecan AUC at day 5, and we found increasing Topo I levels during a daily ×5 schedule of treatment with topotecan.
Effects of Work Arrangements on Creative R&D Work Outcomes

Favorable working conditions for R&D employees help to improve the use of their creative potential, supporting knowledge intensification in the economy at large. This article presents fully observed recursive structural equation estimates, based on data from the authors’ original repeated survey of Estonian creative R&D employees on a sample of 153 individuals from eleven entities. It finds that opting for flexible working time is strongly driven by gender—males are more likely than females to opt for R&D jobs with flexible schedules. R&D employees who mainly work remotely are more satisfied with their work results. Noncreative work tasks reduce R&D employees’ contentment with their work outcomes and lower—at least in their own perception—the productiveness of their work in terms of creating value or new knowledge. Employees of both evening and morning types are found to have much more satisfaction with their work results than employees with no distinct morning-evening profile. These findings stress the benefits of flexible work arrangements in creative R&D jobs in order to account for individual differences and stimulate R&D output.
Emotional Distress, Coping, and Adjustment in Human Immunodeficiency Virus Infection and Acquired Immune Deficiency Syndrome

Fifty-seven ambulatory, human immunodeficiency virus (HIV)-infected patients at various stages of disease progression and 17 HIV seronegative controls were examined in a crosssectional study with self-administered measures of emotional distress, coping, and adjustment to illness. All infected and control subjects were homosexual or bisexual and free of acute medical illness. The findings indicated that both uninfedcted and infected subjects had enhanced emotional distress in a variety of domains. However, while somatic and cognitiveruminative complaints were greater in symptomatic subjects relative to controls, depression and anxiety were not. Professed coping strategies were heterogeneous and not particularly related to HIV diagnostic status, with the exception of planful problem solving which was decreased for acquired immune deficiency syndrome subjects. Disruption in several aspects of daily life adjustment was markedly increased in symptomatic subjects. The findings suggest that both HIV seropositive status and perceived risk for infection produce a sustained level of generalized psychological distress. Even in the absence of current medical illness, patients with advanced disease progression are concerned primarily with anticipated medical implications and cognitive effectiveness.
Optimal Supply Chain Structural Choice under Horizontal Chain-to-Chain Competition

This paper investigates the horizontal Nash game and structure selection strategy in two competing dominant enterprises. Each firm decides whether to outsource the retail or manufacture to the exclusive third-party enterprise and thus forms a decentralized supply chain structure. On the premise that third-party enterprises have no advantage on sales and manufacture cost, the revenue-sharing contract is introduced between the manufacturer and retailer, and the influence of decentralized structure on the game equilibrium structure and supply chain profit is analyzed based on Hotelling model. The results show that, when compared with centralized structure, decentralized supply chain has the structural advantage to improving not only its supply chain profits but also the competing chain. This interesting insight is counterintuitive to the common “double marginalization” effect and explains the outsourcing strategy from the perspective of supply chain competition. In addition, we find the dominant strategy in the evolutionary game is that both two chains are decentralized or integrated.
Surgical vs. transcatheter pulmonary vein isolation as first invasive treatment in patients with atrial fibrillation: a matched group comparison.

AIMS Pulmonary vein isolation (PVI) can be considered for treatment of symptomatic atrial fibrillation (AF). Nowadays, in addition to transcatheter ablation, thoracoscopic surgical PVI is available. The aim of this study is to compare clinical outcome of surgical with transcatheter PVI as first invasive treatment strategy of AF. METHODS AND RESULTS From June 2009 to November 2011, 33 patients underwent minimally invasive surgical PVI, and were matched (1:2 fashion) retrospectively according to age, sex, and AF type, with 66 patients who underwent transcatheter PVI. Success was defined as freedom from atrial arrhythmias on 24 h Holter monitoring without use of anti-arrhythmic drugs (AADs) at 1 year. Mean age was 52 ± 10 years, 82% were male. Paroxysmal AF was present in 76 patients (77%), persistent AF in 23 (23%) patients. None underwent prior ablations, and failed on 1.2 ± 0.6 AADs. At 12 months, complete freedom from atrial arrhythmias without AADs in the surgical PVI group was 88% compared with 41% in the transcatheter PVI group (P < 0.001). Freedom from atrial arrhythmias with AADs was 91 vs. 62%, in the surgical vs. transcatheter PVI group, respectively (P = 0.002). Complications occurred in seven (21%) surgical PVI patients, and three (5%) transcatheter PVI patients (P = 0.015). CONCLUSION In present matched study comparing a surgical with transcatheter PVI treatment strategy in symptomatic AF patients failed on AADs, but without prior ablations, a surgical PVI strategy was more effective to prevent recurrence of atrial arrhythmias, than a transcatheter PVI treatment strategy. However, complications were more frequent with surgical PVI.
Reactivity to Stress and the Cognitive Components of Math Disability in Grade 1 Children

This study investigated the relationship among working memory, processing speed, math performance, and reactivity to stress in 83 Grade 1 children. Specifically, 39 children with math disability (MD) were compared to 44 children who are typically achieving (TA) in mathematics. It is the first study to use a physiological index of stress (salivary cortisol levels) to measure children’s reactivity while completing tasks that assess the core components of MD: working memory for numbers, working memory for words, digits backward, letter number sequence, digit span forward, processing speed for numbers and words, block rotation, and math tasks. Grade 1 children with MD obtained significantly lower scores on the letter number sequence and quantitative concepts tasks. Higher levels of reactivity significantly predicted poorer performance on the working memory for numbers, working memory for words, and quantitative concepts tasks for Grade 1 children, regardless of math ability. Grade 1 children with MD and higher reactivity had significantly lower scores on the letter number sequence task than the children with MD and low reactivity. The findings suggest that high reactivity impairs performance in working memory and math tasks in Grade 1 children, and young children with high reactivity may benefit from interventions aimed at lowering anxiety in stressful situations, which may improve learning.
COOPERATION FOR INNOVATION AND ITS IMPACT ON TECHNOLOGICAL AND NON-TECHNOLOGICAL INNOVATIONS: EMPIRICAL EVIDENCE FOR EUROPEAN SMES IN TRADITIONAL MANUFACTURING INDUSTRIES

Drawing on a sample of small and medium-sized enterprises (SMEs) in traditional manufacturing industries from seven EU regions, this study investigates how cooperation with external organisations affects technological (product and process) innovations and non-technological (organisational and marketing) innovations as well as the commercial success of product and process innovations (i.e., innovative sales). Our empirical strategy takes into account that all four types of innovation are potentially complementary. Empirical results suggest that cooperation increases firms’ innovativeness and yields substantial commercial benefits. In particular, increasing the number of cooperation partnerships has a positive impact on all measures of innovation performance. We conclude that a portfolio approach to cooperation enhances innovation performance and that innovation support programs should be demand-led.
Sodium‐potassium pump current in smooth muscle cells from mesenteric resistance arteries of the guinea‐pig

1 The Na+‐K+ pump current was studied in smooth muscle cells from mesenteric resistance arteries of guinea‐pigs by the use of the perforated patch‐clamp technique in the presence of blockers for various ion channels and exchangers. 2 When the Na+ concentration in the pipette solution ([Na+]i) was 50 mM, an increase in the extracellular K+ concentration ([K+]o) from 0 to 10 mM caused an outward current. Both the removal of K+ from the bath solution and the application of 10 μM ouabain abolished this current. Thus, this K+‐induced and ouabain‐sensitive current was considered to be the Na+‐K+ pump current. 3 The amplitude of the Na+‐K+ pump current increased as the membrane potential was made more positive until around 0 mV, while the amplitude saturated at more positive potentials than 0 mV. 4 An increase in [K+]o or [Na+]i amplified the Na+‐K+ pump current. For [K+]o, the binding constant (Kd) was 1.6 ± 0.3 mM and the Hill coefficient (nH) was 1.1 ± 0.2 (n= 6). For [Na+]i, Kd was 22 ± 5 mM and nH was 1.7 ± 0.5 (n= 4–19). 5 The presence of various monovalent cations other than Na+ in the bath solution also evoked the Na+‐K+ pump current. The order of potency was K+≥ Rb+ > Cs+≫ Li+. 6 Ouabain inhibited the Na+‐K+ pump current in a dose‐dependent manner with a Kd of 0.35 ± 0.03 μM and an nH of 1.2 ± 0.1 (n= 6–8). 7 The Na+‐K+ pump current increased as temperature increased. The temperature coefficient (Q10; 26–36 °C) was 1.87 (n= 9). 8 In summary the present study characterized for the first time the Na+‐K+ pump current in vascular smooth muscle cells by the use of the voltage‐clamp method. The use of this method should provide essential information for Na+,K+‐ATPase‐mediated changes in the cell functions of vascular smooth muscle cells.
Loss of network efficiency associated with cognitive decline in chronic epilepsy

Objective: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. Methods: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. Results: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. Conclusions: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.
Lipid-Based Nutrient Supplements Plus Malaria and Diarrhea Treatment Increase Infant Development Scores in a Cluster-Randomized Trial in Burkina Faso.

BACKGROUND Adequate nutrition is necessary for the rapid brain development that occurs during infancy. OBJECTIVES We tested the hypothesis that the provision of small-quantity, lipid-based nutrient supplements (SQ-LNSs) plus malaria and diarrhea treatment positively affects infant development. We also tested the effect of various doses of zinc provided in SQ-LNSs or in a tablet. METHODS In a partially masked, cluster-randomized controlled trial, communities in rural Burkina Faso were stratified by selected characteristics and then randomly assigned within strata to the intervention (IC; 25 communities, 2435 children) or the nonintervention (NIC; 9 communities, 785 children) cohorts. IC children were randomly assigned to 4 groups. As secondary outcomes, a subsample of 3 of these 4 groups (n = 747) and of the NIC (n = 376) were assessed for motor, language, and personal-social development at age 18 mo by using the Developmental Milestones Checklist II. The 3 IC groups received 20 g SQ-LNSs/d containing 0 or 10 mg added zinc with a placebo tablet or 20 g SQ-LNSs/d containing 0 mg added zinc with a tablet containing 5 mg Zn. All IC groups received treatment of malaria and diarrhea from age 9 to 18 mo. Data collectors and participants were aware of allocation to the IC or NIC but did not know the particular IC subgroup. RESULTS Children in the IC scored 0.34 (95% CI: 0.21, 0.46), 0.30 (95% CI: 0.15, 0.44), and 0.32 (95% CI: 0.16, 0.48) SDs higher in motor, language, and personal-social development, respectively, than did children in the NIC (All P < 0.001). Children who received different amounts of zinc did not differ significantly in any of the scores. No effect on caregiver-child interaction was found. CONCLUSION In rural Burkina Faso, the provision of SQ-LNSs to infants from age 9 to 18 mo, regardless of added zinc content, plus malaria and diarrhea treatment positively affected motor, language, and personal-social development at age 18 mo. This trial was registered at clinicaltrials.gov as NCT00944281.
Manipulation of OCT4 Levels in Human Embryonic Stem Cells Results in Induction of Differential Cell Types

To fully understand self-renewal and pluripotency and their regulation in human embryonic stem cells (hESCs), it is necessary to generate genetically modified cells and analyze the consequences of elevated and reduced expression of genes. Genes expressed in hESCs using plasmid vectors, however, are subject to silencing. Moreover, hESCs have a low plating efficiency when dissociated to single cells, making creation of subcloned lines inefficient. In addition to overexpression experiments, it is important to perform loss-of-function studies, which can be achieved rapidly using RNA interference (RNAi). We report stable long-term expression of enhanced green fluorescent protein (eGFP) in hESCs using a lentiviral vector, and establishment of an eGFP-expressing subline (RG6) using manual dissection. To demonstrate the efficacy of RNAi in hESCs, an RNAi expression vector was used to achieve reduced expression of eGFP in hESCs. To evaluate the role of OCT4 in the regulation of hESC self-renewal and differentiation, a vector expressing a hairpin RNA targeting endogenous expression of OCT4 was constructed. In a novel experiment in hESCs, the OCT4 cDNA sequence was cloned into an expression vector to allow for the transient upregulation of OCT4 in hESCs. The ability to manipulate levels of OCT4 above and below enodogenous levels allows the determination of OCT4 function in hESCs. Specifically, reduced expression of OCT4 in hESCs promoted upregulation of markers indicative of mesoderm and endoderm differentiation, and elevated levels of OCT4 in hESCs promoted upregulation of markers indicative of endoderm derivatives. Thus, both upregulation and downregulation of Oct4 in hESCs results in differentiation, but with patterns distinct from parallel experiments in mice.
Estimating Noncancer Uncertainty Factors: Are Ratios NOAELs Informative?

The prominent role of animal bioassay evidence in environmental regulatory decisions compels a careful characterization of extrapolation uncertainties. In noncancer risk assessment, uncertainty factors are incorporated to account for each of several extrapolations required to convert a bioassay outcome into a putative subthreshold dose for humans. Measures of relative toxicity taken between different dosing regimens, different endpoints, or different species serve as a reference for establishing the uncertainty factors. Ratios of no observed adverse effect levels (NOAELs) have been used for this purpose; statistical summaries of such ratios across sets of chemicals are widely used to guide the setting of uncertainty factors. Given the poor statistical properties of NOAELs, the informativeness of these summary statistics is open to question. To evaluate this, we develop an approach to “calibrate” the ability of NOAEL ratios to reveal true properties of a specified distribution for relative toxicity. A priority of this analysis is to account for dependencies of NOAEL ratios on experimental design and other exogenous factors. Our analysis of NOAEL ratio summary statistics finds (1) that such dependencies are complex and produce pronounced systematic errors and (2) that sampling error associated with typical sample sizes (50 chemicals) is non-negligible. These uncertainties strongly suggest that NOAEL ratio summary statistics cannot be taken at face value; conclusions based on such ratios reported in well over a dozen published papers should be reconsidered.