Miracle-dz/UniFAR-FTUs huggingface dataset:
The Asymmetry of European Integration - or why the EU cannot be a Social Market Economy

Judge-made law has played a crucial role in the process of European integration. In the vertical dimension, it has greatly reduced the range of autonomous policy choices in the member states, and it has helped to expand the reach of European competences. At the same time, however, ‘integration through law’ does have a liberalizing and deregulatory impact on the socio-economic regimes of European Union member states. This effect is generally compatible with the status quo in liberal market economies, but it tends to undermine the institutions and policy legacies of Continental and Scandinavian social market economies. Given the high consensus requirements of European legislation, this structural asymmetry cannot be corrected through political action at the European level.
Enhancement of inflammatory mediator release by β2‐adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action

Background and purpose: Due to their potent bronchodilator properties, β2‐adrenoceptor agonists are a mainstay of therapy in asthma. However, the effects of β2‐adrenoceptor agonists on inflammation are less clear. Accordingly, we have investigated the effects of β2‐adrenoceptor agonists on inflammatory mediator release.
Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1

Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 gene. How these mutations affect neuronal development and function remains largely elusive. We generated specific point mutations or small deletions in the Drosophila fragile X-related (Fmr1) gene and examined the roles of Fmr1 in dendritic development of dendritic arborization (DA) neurons in Drosophila larvae. We found that Fmr1 could be detected in the cell bodies and proximal dendrites of DA neurons and that Fmr1 loss-of-function mutations increased the number of higher-order dendritic branches. Conversely, overexpression of Fmr1 in DA neurons dramatically decreased dendritic branching. In dissecting the mechanisms underlying Fmr1 function in dendrite development, we found that the mRNA encoding small GTPase Rac1 was present in the Fmr1-messenger ribonucleoprotein complexes in vivo. Mosaic analysis with a repressor cell marker (MARCM) and overexpression studies revealed that Rac1 has a cell-autonomous function in promoting dendritic branching of DA neurons. Furthermore, Fmr1 and Rac1 genetically interact with each other in controlling the formation of fine dendritic branches. These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect.
Reconsidering Tonotopic Maps in the Auditory Cortex and Lemniscal Auditory Thalamus in Mice

The auditory thalamus and auditory cortex (AC) are pivotal structures in the central auditory system. However, the thalamocortical mechanisms of processing sounds are largely unknown. Investigation of this process benefits greatly from the use of mice because the mouse is a powerful animal model in which various experimental techniques, especially genetic tools, can be applied. However, the use of mice has been limited in auditory research, and thus even basic anatomical knowledge of the mouse central auditory system has not been sufficiently collected. Recently, optical imaging combined with morphological analyses has enabled the elucidation of detailed anatomical properties of the mouse auditory system. These techniques have uncovered fine AC maps with multiple frequency-organized regions, each of which receives point-to-point thalamocortical projections from different origins inside the lemniscal auditory thalamus, the ventral division of the medial geniculate body (MGv). This precise anatomy now provides a platform for physiological research. In this mini review article, we summarize these recent achievements that will facilitate physiological investigations in the mouse auditory system.
Survey of Nonlinear Observer Design Techniques

This paper presents three “nonlinear” approaches to the problem of nonlinear observer design. Beginning with a brief introduction to the state estimation (observer) problem, we present approaches based on Lyapunov methods, the method of extended linearization, and a Lie-algebraic approach. The main issues in each technique are briefly explained and explored, as well as the applicability of each method.
Peptide-Mediated Cellular Delivery of Oligonucleotide-Based Therapeutics In Vitro: Quantitative Evaluation of Overall Efficacy Employing Easy to Handle Reporter Systems

Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different available non-viral systems like cationic polymers, cationic liposomes and polymeric nanoparticles, cell-penetrating peptides (CPPs) represent an attractive concept to bypass the problem of poor membrane permeability of these charged macromolecules. While uptake per se in most cases does not represent the main obstacle of nucleic acid delivery in vitro, it becomes increasingly apparent that intracellular trafficking is the bottleneck. As a consequence, in order to optimize a given delivery system, a side-by-side analysis of nucleic acid cargo internalized and the corresponding biological effect is required to determine the overall efficacy. In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. To illustrate current limitations of non-viral nucleic acid delivery systems, we present own data as an example and discuss options of how to enhance trafficking of molecules entrapped in cellular compartments.
Identification of the Pangenome and Its Components in 14 Distinct Aggregatibacter actinomycetemcomitans Strains by Comparative Genomic Analysis

Background Aggregatibacter actinomycetemcomitans is genetically heterogeneous and comprises distinct clonal lineages that may have different virulence potentials. However, limited information of the strain-to-strain genomic variations is available. Methodology/Principal Findings The genome sequences of 11 A. actinomycetemcomitans strains (serotypes a-f) were generated de novo, annotated and combined with three previously sequenced genomes (serotypes a-c) for comparative genomic analysis. Two major groups were identified; serotypes a, d, e, and f, and serotypes b and c. A serotype e strain was found to be distinct from both groups. The size of the pangenome was 3,301 genes, which included 2,034 core genes and 1,267 flexible genes. The number of core genes is estimated to stabilize at 2,060, while the size of the pangenome is estimated to increase by 16 genes with every additional strain sequenced in the future. Within each strain 16.7–29.4% of the genome belonged to the flexible gene pool. Between any two strains 0.4–19.5% of the genomes were different. The genomic differences were occasionally greater for strains of the same serotypes than strains of different serotypes. Furthermore, 171 genomic islands were identified. Cumulatively, 777 strain-specific genes were found on these islands and represented 61% of the flexible gene pool. Conclusions/Significance Substantial genomic differences were detected among A. actinomycetemcomitans strains. Genomic islands account for more than half of the flexible genes. The phenotype and virulence of A. actinomycetemcomitans may not be defined by any single strain. Moreover, the genomic variation within each clonal lineage of A. actinomycetemcomitans (as defined by serotype grouping) may be greater than between clonal lineages. The large genomic data set in this study will be useful to further examine the molecular basis of variable virulence among A. actinomycetemcomitans strains.
Regional variation in self-reported heart disease prevalence in Canada.

BACKGROUND Cardiovascular disease is the leading cause of death in Canada. OBJECTIVE To provide an analysis of the self-reported prevalence of heart disease and three specific cardiac conditions--myocardial infarction (MI), angina and congestive heart failure (CHF)--in subgroups of the Canadian population. METHODS Data from the Public Use Microdata File from Statistics Canada's 2000/2001 Canadian Community Health Survey (CCHS) were used to estimate the crude self-reported prevalence of heart disease, MI, angina and CHF in Canada. The data are reported by age and sex groups, as well as by province or territory and health region. RESULTS Based on the 2000/2001 CCHS data, it was estimated that among Canadians 12 years of age and older, 5.0% (n=1,286,000) have heart disease, 2.1% (n=537,000) have had a heart attack, 1.9% (n=483,000) have angina and 1.0% (n=264,000) have CHF. Marked variation in the prevalence of heart disease and the other specific cardiac conditions exists across age and sex groups, and across geographical regions. The prevalence of heart disease is low among those younger than 50 years; thereafter, the prevalence of heart disease increases and is more common among men than among women. By 70 years of age, at least one in four men and one in five women report having heart disease. Large differences in the burden of heart disease were observed across provinces, territories and health regions. Comparison of the highest and lowest prevalence rates among provinces and territories revealed a 1.9-fold difference for heart disease, a 2.8-fold difference for MI, a 2.3-fold difference for angina and a 3.3-fold difference for CHF. CONCLUSIONS Large regional differences in the prevalence of heart disease and other specific cardiac conditions were observed across Canada. These data may assist health system planners to identify those regions and population subgroups most affected by heart disease, and to support the development of heart disease prevention and treatment programs.
Fold-based fusion as a library: a generative programming pearl

Fusion is a program optimisation technique commonly implemented using special-purpose compiler support. In this paper, we present an alternative approach, implementing fold-based fusion as a standalone library. We use staging to compose operations on folds; the operations are partially evaluated away, yielding code that does not construct unnecessary intermediate data structures. The technique extends to partitioning and grouping of collections.
Identifying How Firms Manage Cybersecurity Investment

We report on a set of 40 semi-structured interviews with information security executives and managers at a variety of firms and government agencies. The purpose of the interviews was to learn more about how organizations make cybersecurity investment decisions: how much support they receive to execute their mission, how they prioritize which threats to defend against, and how they choose between competing security controls. We find that most private sector executives believe that their firms adequately fund cybersecurity, but that finding qualified personnel inhibits the pace of adoption of new controls. Most firms do not calculate return on investment (ROI) or other outcome-based quantitative investment metrics; instead, they opt for processbased frameworks such as NIST and COBIT to guide strategic investment decisions. Finally, we note that CISOs in government face considerable challenges compared to their private-sector counterparts.
The evocative power of words: activation of concepts by verbal and nonverbal means.

A major part of learning a language is learning to map spoken words onto objects in the environment. An open question is what are the consequences of this learning for cognition and perception? Here, we present a series of experiments that examine effects of verbal labels on the activation of conceptual information as measured through picture verification tasks. We find that verbal cues, such as the word "cat," lead to faster and more accurate verification of congruent objects and rejection of incongruent objects than do either nonverbal cues, such as the sound of a cat meowing, or words that do not directly refer to the object, such as the word "meowing. " This label advantage does not arise from verbal labels being more familiar or easier to process than other cues, and it does extends to newly learned labels and sounds. Despite having equivalent facility in learning associations between novel objects and labels or sounds, conceptual information is activated more effectively through verbal means than through nonverbal means. Thus, rather than simply accessing nonverbal concepts, language activates aspects of a conceptual representation in a particularly effective way. We offer preliminary support that representations activated via verbal means are more categorical and show greater consistency between subjects. These results inform the understanding of how human cognition is shaped by language and hint at effects that different patterns of naming can have on conceptual structure.
Relationship between Lung Volume and Pulmonary Function in Patients With Adolescent Idiopathic Scoliosis: Computed Tomographic-based 3-Dimensional Volumetric Reconstruction of Lung Parenchyma

Study Design:Retrospective. Objectives:We determined values for the volume of right lung (Vr), left lung (Vl), total lung volume (Vt), and left/right lung volume ratio (Vl/Vr), allowing comparison between those data measured and those of age-matched controls. To find whether lung volume correlates with preoperative pulmonary function. Summary of Background Data:To our knowledge, no study on relationship between computed tomographic (CT) scans determined lung volume and pulmonary function test (PFT) in scoliosis have been published. Methods:All examinations with PFT (31 cases) were identified. Three-dimensional volumetric reconstruction of lung parenchyma was performed on existing preoperative CT scans for 26 idiopathic scoliosis patients. Vl, Vr, Vt, Vl/Vr, and absolute value of right volume minus left volume (|Vr−Vl|) were calculated and correlated with PFTs. To determine if significant difference of preoperative lung volume exists between idiopathic scoliosis patients and controls. Linear regression models, using 3-dimensional lung volume parameters as predictors for vital capacity (VC), forced vital capacity (FVC), and total lung capacity (TLC), were created. Results:Vt was positively correlated with VC, FVC, forced expiratory volume in 1 second (FEV1), TLC, predicted value for FVC (FVC%), predicted value for FEV1 (FEV1%), predicted value for TLC (TLC%), and predicted value for maximal ventilator volume (MVV%) (P<0.05); |Vr−Vl| was not correlated with ventilation parameters (P>0.05); Diffusion parameters were not correlated with CT-reconstructed lung volume parameters (P>0.05); male and female adolescent idiopathic scoliosis patients had less Vt, Vr, and Vl compared with those of age-matched controls (P<0.05). Conclusions:Vt was positively correlated with VC, FVC, FEV1, TLC, FVC%, FEV1%, TLC%, and MVV%. Vt, Vr, and Vl of adolescent idiopathic scoliosis patients were less than those of age-matched controls.
Laccase Production from a Temperature and pH Tolerant Fungal Strain of Trametes hirsuta (MTCC 11397)

Laccase production by a temperature and pH tolerant fungal strain (GBPI-CDF-03) isolated from a glacial site in Indian Himalayan Region (IHR) has been investigated. The fungus developed white cottony mass on potato dextrose agar and revealed thread-like mycelium under microscope. ITS region analysis of fungus showed its 100% similarity with Trametes hirsuta. The fungus tolerated temperature from 4 to 48°C ± 2 (25°C opt.) and pH 3–13 (5–7 opt.). Molecular weight of laccase was determined approximately 45 kDa by native PAGE. Amplification of laccase gene fragment (corresponding to the copper-binding conserved domain) contained 200 bp. The optimum pH for laccase production, at optimum growth temperature, was determined between 5.5 and 7.5. In optimization experiments, fructose and ammonium sulfate were found to be the best carbon and nitrogen sources, respectively, for enhancing the laccase production. Production of laccase was favored by high carbon/nitrogen ratio. Addition of CuSO4 (up to 1.0 mM) induced laccase production up to 2-fold, in case of 0.4 mM concentration. Addition of organic solvents also induced the production of laccase; acetone showed the highest (2-fold) induction. The study has implications in bioprospecting of ecologically resilient microbial strains.
Creating a Global Citizen and Assessing Outcomes

This article examines development of the field of global citizenship education in postsecondary education in Canada. Analysis centers on the forces of globalization and internationalization as a catalyst for innovation. Plato’s Allegory of the Cave is invoked to explain the nature of transformative education and reflective practice. A signature pedagogy is identified for global citizenship education based on an emerging model. The model consists of five components: theory, content, experiences, methodology, and assessment. Student outcomes are defined in terms of a demonstrated ability to act with a global mindset based on an application of values, ethics, identity, social justice perspective, intercultural skills, and sense of responsibility.
Promotion of Both Proliferation and Neuronal Differentiation in Pluripotent P19 Cells with Stable Overexpression of the Glutamine Transporter slc38a1

Background We previously demonstrated the functional expression in newborn rat neocortical astrocytes of glutamine transporter (GlnT = slc38a1) believed to predominate in neurons over astroglia in the brain. In order to evaluate the possible role of this transporter in neurogenesis, we attempted to establish stable transfectants of GlnT in mouse embryonal carcinoma P19 cells endowed to proliferate for self-renewal and differentiate into progeny cells such as neurons and astroglia, in addition to in vitro pharmacological profiling of the green tea ingredient theanine, which is shown to be a potent inhibitor of glutamine transport mediated by GlnT in cultured neurons and astroglia. Methodology/Principal Findings The full-length coding region of rat GlnT was inserted into a vector for gene transfection along with selection by G418, followed by culture with all-trans retinoic acid under floating conditions and subsequent dispersion for spontaneous differentiation under adherent conditions. Stable overexpression of GlnT led to marked increases in the size of round spheres formed during the culture for 4 days and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction, with concomitant promotion of subsequent differentiation into cells immunoreactive for a neuronal marker protein. In these stable GlnT transfectants before differentiation, drastic upregulation was seen for mRNA expression of several proneural genes with a basic helix-loop-helix domain such as NeuroD1. Although a drastic increase was seen in NeuroD1 promoter activity in stable GlnT transfectants, theanine doubled NeuroD1 promoter activity in stable transfectants of empty vector (EV), without affecting the promoter activity already elevated in GlnT transfectants. Similarly, theanine promoted cellular proliferation and neuronal differentiation in stable EV transfectants, but failed to further stimulate the acceleration of both proliferation and neuronal differentiation found in stable GlnT transfectants. Conclusions/Significance GlnT would promote both proliferation and neuronal differentiation through a mechanism relevant to the upregulation of particular proneural genes in undifferentiated P19 cells.
Representing a Computer Science Research Organization on the ACM Computing Classification System

We propose a method, Cluster-Lift, for parsimoniously mapping clusters of ontology classes of lower levels onto a subset of high level classes in such a way that the latter can be considered as a generalized description of the former. Speciﬁcally, we consider the problem of visualization of activities of a Computer Science Research organization on the ACM Computing Subjects Classiﬁcation (ACMC), which is a three level taxonomy. It is possible to specify the set of ACMC subjects that are investigated by the organization’s teams and individual members and map them to the ACMC hierarchy. This visualization, however, usually appears overly detailed, confusing, and difﬁcult to interpret. This is why we propose a two-stage Cluster-Lift procedure. On the ﬁrst stage, the subjects are clustered according to their similarity deﬁned in such a way that the greater the number of researchers working on a pair of subjects, the greater the similarity between the pair. On the second stage, each subject cluster is mapped onto ACMC and lifted within the taxonomy. The lifting involves a formalization of the concept of “head subject”, as well as its “gaps” and “offshoots” and is to be done in a parsimonious way by minimizing a weighted sum of the numbers of head subjects, gaps and offshoots. The Cluster-Lift results are easy to see and interpret. A real-world example of the working of our approach is provided.
A systematic review and meta-analysis of clinical trials on physical interventions for lateral epicondylalgia

A systematic review of the literature on the effectiveness of physical interventions for lateral epicondylalgia (tennis elbow) was carried out. Seventy six randomised controlled trials were identified, 28 of which satisfied the minimum criteria for meta-analysis. The evidence suggests that extracorporeal shock wave therapy is not beneficial in the treatment of tennis elbow. There is a lack of evidence for the long term benefit of physical interventions in general. However, further research with long term follow up into manipulation and exercise as treatments is indicated.
Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin's disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND Gemcitabine (difluorodeoxycytidine) is active as a single agent in Hodgkin's disease and has been used successfully in combination with cisplatin to treat a variety of solid tumors. PATIENTS AND METHODS We evaluated the combination of gemcitabine/dexamethasone/cisplatin (GDP) as salvage chemotherapy in 23 patients with relapsed or refractory Hodgkin's disease (median age 36 years, range 19-57). Treatment consisted of gemcitabine 1000 mg/m(2) intravenously on days 1 and 8, dexamethasone 40 mg orally days 1-4 and cisplatin 75 mg/m(2) on day 1, every 21 days as an outpatient. Response was assessed following two cycles of treatment. RESULTS There were four complete responses and 12 partial responses for a response rate of 69.5% (95% confidence interval 52% to 87%); the remaining seven patients had stable disease and no patient progressed on treatment. All patients had successful stem cell mobilization and underwent transplantation with a median 10.6 x 10(6) CD34+ cells/kg. Hematological toxicity from GDP was mild (grade 3 neutropenia 8.6%, grade 3 thrombocytopenia 13%). CONCLUSIONS In summary, GDP is an active regimen for patients with relapsed or refractory Hodgkin's disease. The response rate is similar to the rates of other current salvage regimens, it can be given to outpatients with tolerable toxicity and it does not inhibit the mobilization of autologous stem cells.