Instrumental leadership: Measurement and extension of transformational-transactional leadership theory.

Leaders must scan the internal and external environment, chart strategic and task objectives, and provide performance feedback. These instrumental leadership (IL) functions go beyond the motivational and quid-pro quo leader behaviors that comprise the full-range-transformational, transactional, and laissez faire-leadership model. In four studies we examined the construct validity of IL. We found evidence for a four-factor IL model that was highly prototypical of good leadership. IL predicted top-level leader emergence controlling for the full-range factors, initiating structure, and consideration. It also explained unique variance in outcomes beyond the full-range factors; the effects of transformational leadership were vastly overstated when IL was omitted from the model. We discuss the importance of a "fuller full-range" leadership theory for theory and practice. We also showcase our methodological contributions regarding corrections for common method variance (i.e., endogeneity) bias using two-stage least squares (2SLS) regression and Monte Carlo split-sample designs.

Activity of ancestral restriction factors against ancient retroviruses

Analysis of TRIM5α and APOBEC3G genes suggests that these two restriction factors underwent strong positive selection throughout primate evolution. This pressure was possibly imposed by ancient exogenous retroviruses, of which endogenous retroviruses are remnants. Our study aims to assess in vitro the activity of these factors against ancient retroviruses by reconstructing their ancestral gag sequences, as well as the ancestral TRIM5α and APOBEC3G for primates. Based on evolutionary genomics approach, we reconstructed ancestors of the two largest families of human endogenous retroviruses (HERV), namely HERV-K and HERV-H, as well as primate ancestral TRIM5α and APOBEC3G variants. The oldest TRIM5α sequence was the catarhinne TRIM5α, common ancestor of Old World monkeys and hominoids, dated from 25 million years ago (mya). From the oldest, to the youngest, ancestral TRIM5α variants showed less restriction of HIV-1 in vitro [1]. Likewise three ancestral APOBEC3Gs sequences common to hominoids (18 mya), Old World monkeys, and catarhinnes (25 mya) were reconstructed. All ancestral APOBEC3G variants inhibited efficiently HIV-1Δvif in vitro, compared to modern APOBEC3Gs. The ability of Vif proteins (HIV-1, HIV-2, SIVmac and SIVagm) to counteract their activity tallied with the residue 128 on ancestral APOBEC3Gs. Moreover we are attempting to reconstruct older ancestral sequences of both restriction factors by using prosimian orthologue sequences. An infectious onemillion- years-old HERV-KCON previously reconstituted was shown to be resistant to modern TRIM5α and APOBEC3G [2]. Our ancestral TRIM5α and APOBEC3G variants were inactive against HERV-KCON. Besides we reconstructed chimeric HERV-K bearing ancestral capsids (up to 7 mya) that resulted in infectious viruses resistant to modern and ancestral TRIM5α. Likewise HERV-K viruses bearing ancestral nucleocapsids will be tested for ancestral and modern APOBEC3G restriction. In silico reconstruction and structural modeling of ancestral HERV-H capsids resulted in structures homologous to that of the gammaretrovirus MLV. Thus we are attempting to construct chimeric MLV virus bearing HERV-H ancestral capsids. These chimeric ancestral HERVs will be tested for infectivity and restriction by ancestral TRIM5α. Similarly chimeric MLV viruses bearing ancestral HERV-H nucleocapsids will be reconstructed and tested for APOBEC3G restriction.

The attractiveness of nations in global competition : an empirical assessment of the effects of country attractiveness on the success of strategy for hosting international sports events, 1990-2012

This dissertation aims to investigate empirical evidence on the importance and influence of attractiveness of nations in global competition. The notion of country attractiveness, which has been widely developed in the research areas of international business, tourism and migration, is a multi-dimensional construct to measure a country's characteristics with regard to its market or destination that attract international investors, tourists and migrants. This analytical concept provides an account of the mechanism as to how potential stakeholders evaluate more attractive countries based on certain criteria. Thus, in the field of international sport-event bidding, do international sport event owners also have specific country attractiveness for their sport event hosts? The dissertation attempts to address this research question by statistically assessing the effects of country attractiveness on the success of strategy for hosting international sports events. Based on theories of signaling and soft power, country attractiveness is defined and measured as the three dimensions of sustainable development: economic, social, and environmental attractiveness. This thesis proceeds to examine the concept of sport-event-hosting strategy and explore multi-level factors affecting the success in international sport-event bidding. By exploring past history of the Olympic Movement from theoretical perspectives, the thesis proposes and tests the hypotheses that economic, social and environmental attractiveness of a country may be correlated with its bid wins or the success of sport-event-hosting strategy. Quantitative analytical methods with various robustness checks are employed with using collected data on bidding results of major events in Olympic sports during the period from 1990 to 2012. The analysis results reveal that event owners of international Olympic sports are likely to prefer countries that have higher economic, social, and environmental attractiveness. The empirical assessment of this thesis suggests that high country attractiveness can be an essential element of prerequisites for a city/country to secure in order to bid with an increased chance of success.

Embolic strokes of undetermined source in the athens stroke registry: a descriptive analysis.

BACKGROUND AND PURPOSE: A new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced, but no such population has been described yet. Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospective ischemic stroke registry using the proposed diagnostic criteria. METHODS: The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients. ESUS was defined as a radiologically confirmed nonlacunar brain infarct in the absence of (a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the ischemic area, (b) major-risk cardioembolic source, and (c) any other specific cause of stroke. RESULTS: Among 2735 patients admitted between 1992 and 2011, 275 (10.0%) were classified as ESUS. In the majority of ESUS (74.2%), symptoms were maximal at onset. ESUS were of moderate severity (median National Institute Health Stroke Scale score, 5). The most prevalent risk factor was arterial hypertension (64.7%), and 50.9% of patients were dyslipidemic. Among potential causes of the ESUS, covert atrial fibrillation (AF) was the most prevalent: in 30 (10.9%) patients, AF was diagnosed during hospitalization for stroke recurrence, whereas in 50 (18.2%) patients AF was detected after repeated ECG monitoring during follow-up. Also, covert AF was strongly suggested in 38 patients (13.8%) but never recorded. CONCLUSIONS: About 10% of patients with first-ever ischemic stroke met criteria for ESUS; covert paroxysmal AF seems to be a frequent cause of ESUS.

Antibiotic-dependent correlation between drug-induced killing and loss of luminescence in Streptococcus gordonii expressing luciferase.

Measuring antibiotic-induced killing relies on time-consuming biological tests. The firefly luciferase gene (luc) was successfully used as a reporter gene to assess antibiotic efficacy rapidly in slow-growing Mycobacterium tuberculosis. We tested whether luc expression could also provide a rapid evaluation of bactericidal drugs in Streptococcus gordonii. The suicide vectors pFW5luc and a modified version of pJDC9 carrying a promoterless luc gene were used to construct transcriptional-fusion mutants. One mutant susceptible to penicillin-induced killing (LMI2) and three penicillin-tolerant derivatives (LMI103, LMI104, and LMI105) producing luciferase under independent streptococcal promoters were tested. The correlation between antibiotic-induced killing and luminescence was determined with mechanistically unrelated drugs. Chloramphenicol (20 times the MIC) inhibited bacterial growth. In parallel, luciferase stopped increasing and remained stable, as determined by luminescence and Western blots. Ciprofloxacin (200 times the MIC) rapidly killed 1.5 log10 CFU/ml in 2-4 hr. Luminescence decreased simultaneously by 10-fold. In contrast, penicillin (200 times the MIC) gave discordant results. Although killing was slow (< or = 0.5 log10 CFU/ml in 2 hr), luminescence dropped abruptly by 50-100-times in the same time. Inactivating penicillin with penicillinase restored luminescence, irrespective of viable counts. This was not due to altered luciferase expression or stability, suggesting some kind of post-translational modification. Luciferase shares homology with aminoacyl-tRNA synthetase and acyl-CoA ligase, which might be regulated by macromolecule synthesis and hence affected in penicillin-inhibited cells. Because of resemblance, luciferase might be down-regulated simultaneously. Luminescence cannot be universally used to predict antibiotic-induced killing. Thus, introducing reporter enzymes sharing mechanistic similarities with normal metabolic reactions might reveal other effects than those expected.

Splice variant-specific stabilization of JNKs by IB1/JIP1.

Islet-Brain 1 (IB1) (also called JNK-interacting protein 1; JIP1) is a scaffold protein that tethers components of the JNK mitogen-activated protein kinase pathway inducing a modulation of the activity and the target specificity of the JNK kinases. Dysfunctions in IB1 have been associated with diseases such as early type II diabetes. To gain more insight in the functions of IB1, its ability to modulate the expression levels of the various JNK proteins was assessed. Each of the three JNK genes gives rise to several splice variants encoding short or long proteins. The expression levels of the short JNK proteins, but not of the long variants, were systematically higher in rat tissues and in transformed cell lines expressing high IB1 levels compared to tissues and cells with no or low IB1 expression. HEK293 cells bearing a tetracycline-inducible IB1 construct showed a specific increase of the short JNK endogenous splice variants in the presence of tetracycline. The augmented expression level of the short JNK splice variants induced by IB1 resulted from an increased stability towards degradation. Modulation of the stability of specific JNK splice variants represents therefore a newly identified mechanism used by IB1 to regulate the JNK MAPK pathway.

Analysis of synaptic-like microvesicle exocytosis of B-cells using a live imaging technique.

Pancreatic β-cells play central roles in blood glucose homeostasis. Beside insulin, these cells release neurotransmitters and other signaling molecules stored in synaptic-like microvesicles (SLMVs). We monitored SLMV exocytosis by transfecting a synaptophysin-pHluorin construct and by visualizing the cells by Total Internal Reflection Fluorescence (TIRF) microscopy. SLMV fusion was elicited by 20 mM glucose and by depolarizing K(+) concentrations with kinetics comparable to insulin secretion. SLMV exocytosis was prevented by Tetanus and Botulinum-C neurotoxins indicating that the fusion machinery of these organelles includes VAMP-2/-3 and Syntaxin-1, respectively. Sequential visualization of SLMVs by TIRF and epifluorescence microscopy showed that after fusion the vesicle components are rapidly internalized and the organelles re-acidified. Analysis of single fusion episodes revealed the existence of two categories of events. While under basal conditions transient fusion events prevailed, long-lasting episodes were more frequent upon secretagogue exposure. Our observations unveiled similarities between the mechanism of exocytosis of insulin granules and SLMVs. Thus, diabetic conditions characterized by defective insulin secretion are most probably associated also with inappropriate release of molecules stored in SLMVs. The assessment of the contribution of SLMV exocytosis to the manifestation of the disease will be facilitated by the use of the imaging approach described in this study.

Transgenic Arabidopsis plants can accumulate polyhydroxybutyrate to up to 4% of their fresh weight.

Transgenic Arabidopsis thaliana (L.) Heynh. plants expressing the three enzymes encoding the biosynthetic route to polyhydroxybutyrate (PHB) are described. These plants accumulated more than 4% of their fresh weight (approximately 40% of their dry weight) in the form of PHB in leaf chloroplasts. These very high producers were obtained and identified following a novel strategy consisting of a rapid GC-MS analysis of a large number of transgenic Arabidopsis plants generated using a triple construct, thus allowing the parallel transfer of all three genes necessary for PHB synthesis in a single transformation event. The level of PHB produced was 4-fold greater than previously published values, thus demonstrating the large potential of plants to produce this renewable resource. However, the high levels of the polymer produced had severe effects on both plant development and metabolism. Stunted growth and a loss of fertility were observed in the high-producing lines. Analysis of the metabolite composition of these lines using a GC-MS method that we have newly developed showed that the accumulation of high levels of PHB was not accompanied by an appreciable change in either the composition or the amount of fatty acids. Substantial changes were, however, observed in the levels of various organic acids, amino acids, sugars and sugar alcohols.

Mice Transgenic For Human Dominant Mutations Of The GUCY2D Gene

Purpose: Animal models are essential to study pathological mechanisms and to test new therapeutic strategies. Many mouse models mimic human rod loss but only a limited number simulate cone dystrophies. The importance of cone function for human vision highlights the need to engineer a model for cone degeneration. An approach of lentiviral-directed transgenesis was tested in mice to express a dominant mutant gene described in a human cone dystrophy.Methods: Lentiviral vectors (LV) encoding either hrGFPII or the human double mutant GUCY2DE837D/R838S cDNA under the control of a region of the pig arrestin-3 promoter (Arr3) were produced and used for lentiviral-derived transgenesis. PCR-genotyping determined the transgenic mouse ratio. The expression of GFP was then analyzed both in vivo and by immunohistochemistry in Arr3-GFPII mice. Functional analysis was performed by ERG at 5, 9, 16 and 24 weeks for Arr3-GUCY2DE837D/R838S mice. Mice were sacrificed at 10 months of age for both histological analysis and RNA extraction.Results: While all the newborns from the transgenesis using the LV-Arr3-GFPII were transgenic, one third of the newborns from the LV-Arr3-GUCY2DE837D/R838S transgenesis were positive. Expression of GFPII was demonstrated by in vivo imaging, while expression of the mutant GUCY2D transcript was detetected using RT-PCR. No severe alteration of the functional response was observed up to 24 weeks of age in the transgenic mice. No obvious modification of the retinal morphology was identified either.Conclusions: Lentiviral-directed transgenesis is a rapid and straightforward method to engineer transgenic mice. Protein expression can be specifically targeted to the retina and thus could help to study the effect of expression of dominant mutant proteins. In our case, Arr3-GUCY2DE837D/R838S mice have a less severe phenotype than that described for human patients. Further analyses are required to understand this difference but several modifications of the expression cassette might also help to increase the expression of the mutant protein and reinforce the phenotype. Interestingly, the same construct is less effective in mouse versus pig retina (see Arsenijevic et al. ARVO 2011 abstract).

A Public Service Gap: Capturing Contexts in a Comparative Approach of Street-Level Bureaucracy

Studies of street-level bureaucracy have introduced a variety of conceptualizations, research approaches, and causal inferences. While this research has produced several insights, the impact of variety in the institutional context has not been adequately explored. We present the construct of a public service gap as a way to incorporate contextual factors and facilitate comparison. This construct addresses the differences between what is asked of and what is offered to public servants working at the street level. The heuristic enables the systematic capture of macro- and meso-contextual influences, thus enhancing comparative research on street-level bureaucracy.

Modelling habitat-suitability using museum collections: an example with three sympatric Apodemus species from the Alps

Aim, Location Although the alpine mouse Apodemus alpicola has been given species status since 1989, no distribution map has ever been constructed for this endemic alpine rodent in Switzerland. Based on redetermined museum material and using the Ecological-Niche Factor Analysis (ENFA), habitat-suitability maps were computed for A. alpicola, and also for the co-occurring A. flavicollis and A. sylvaticus. Methods In the particular case of habitat suitability models, classical approaches (GLMs, GAMs, discriminant analysis, etc.) generally require presence and absence data. The presence records provided by museums can clearly give useful information about species distribution and ecology and have already been used for knowledge-based mapping. In this paper, we apply the ENFA which requires only presence data, to build a habitat-suitability map of three species of Apodemus on the basis of museum skull collections. Results Interspecific niche comparisons showed that A. alpicola is very specialized concerning habitat selection, meaning that its habitat differs unequivocally from the average conditions in Switzerland, while both A. flavicollis and A. sylvaticus could be considered as 'generalists' in the study area. Main conclusions Although an adequate sampling design is the best way to collect ecological data for predictive modelling, this is a time and money consuming process and there are cases where time is simply not available, as for instance with endangered species conservation. On the other hand, museums, herbariums and other similar institutions are treasuring huge presence data sets. By applying the ENFA to such data it is possible to rapidly construct a habitat suitability model. The ENFA method not only provides two key measurements regarding the niche of a species (i.e. marginality and specialization), but also has ecological meaning, and allows the scientist to compare directly the niches of different species.

Psychometric evaluation of the French version of the questionnaire attitudes towards morphine use; a cross-sectional study in Valais, Switzerland.

BACKGROUND: In Switzerland, nurses are allowed to prescribe and administer morphine in emergency situations without a doctor. Still, nurses and other health professionals are often reluctant to prescribe and administer morphine for pain management in patients. No valid French-speaking instrument is available in Switzerland to assess the attitudes of nurses and other health professionals towards the prescription and administration of morphine. In this study, we evaluated the psychometric properties of the French version of the questionnaire "Attitudes towards morphine use". METHODS: The instrument was derived from an Italian version. Forward and back translations of the questionnaire were performed. Item analysis and construct validity were assessed between April and December 2010 in a cross sectional study including five Swiss hospitals in a sample of 588 health professionals (533 nurses, mean age 38.3 ± 10.2 years). Thirty subjects participated in test-retest reliability. RESULTS: The time to complete the instrument ranged between 12 and 15 minutes and neither floor nor ceiling effect were found. The initial 24-item instrument showed an intraclass correlation (ICC) of 0.69 (95% CI: 0.64 to 0.73, P < 0.001), and a Cronbach's α of 0.700. Factor analysis led to a six-component solution explaining 52.4% of the total variance. After excluding five items, the shortened version showed an ICC of 0.74 (95% CI, 0.70 to 0.77, P < 0.001) and a Cronbach's α of 0.741. Factor analysis led to a five-component solution explaining 54.3% of the total variance. The five components were named "risk of addiction/dependence"; "operational reasons for not using morphine"; "risk of escalation"; "other (non-dependence) risks" and "external (non-operational) reasons". In test-retest, the shortened instrument showed an ICC of 0.797 (95% CI, 0.630 to 0.911, P < 0.001) and a Cronbach's α of 0.797. CONCLUSIONS: The 19-item shortened instrument assessing attitudes towards the prescription and administration of morphine showed adequate content and construct validity.

Brain network analysis of patients with Temporal Lobe Epilepsy

Patients with Temporal Lobe Epilepsy (TLE) suffer from widespread subtle white matter abnormalities and abnormal functional connectivity extending beyond the affected lobe, as revealed by Diffusion Tensor MR Imaging, volumetric and functional MRI studies. Diffusion Spectrum Imaging (DSI) is a diffusion imaging technique with high angular resolution for improving the mapping of white matter pathways. In this study, we used DSI, connectivity matrices and topological measures to investigate how the alteration in structural connectivity influences whole brain structural networks. Eleven patients with right-sided TLE and hippocampal sclerosis and 18 controls underwent our DSI protocol at 3T. The cortical and subcortical grey matters were parcellated into 86 regions of interest and the connectivity between every region pair was estimated using global tractography and a connectivity matrix (the adjacency matrix of the structural network). We then compared the networks of patients and controls using topological measures. In patients, we found a higher characteristic path length and a lower clustering coefficient compared to controls. Local measures at node level of the clustering and efficiency showed a significant difference after a multiple comparison correction (Bonferroni). These significant nodes were located within as well outside the temporal lobe, and the localisation of most of them was consistent with regions known to be part of epileptic networks in TLE. Our results show altered connectivity patterns that are concordant with the mapping of functional epileptic networks in patients with TLE. Further studies are needed to establish the relevance of these findings for the propagation of epileptic activity, cognitive deficits in medial TLE and outcome of epilepsy surgery in individual patients.

An iterative Multiscale Finite-Volume algorithm converging to the exact solution

The multiscale finite volume (MsFV) method has been developed to efficiently solve large heterogeneous problems (elliptic or parabolic); it is usually employed for pressure equations and delivers conservative flux fields to be used in transport problems. The method essentially relies on the hypothesis that the (fine-scale) problem can be reasonably described by a set of local solutions coupled by a conservative global (coarse-scale) problem. In most cases, the boundary conditions assigned for the local problems are satisfactory and the approximate conservative fluxes provided by the method are accurate. In numerically challenging cases, however, a more accurate localization is required to obtain a good approximation of the fine-scale solution. In this paper we develop a procedure to iteratively improve the boundary conditions of the local problems. The algorithm relies on the data structure of the MsFV method and employs a Krylov-subspace projection method to obtain an unconditionally stable scheme and accelerate convergence. Two variants are considered: in the first, only the MsFV operator is used; in the second, the MsFV operator is combined in a two-step method with an operator derived from the problem solved to construct the conservative flux field. The resulting iterative MsFV algorithms allow arbitrary reduction of the solution error without compromising the construction of a conservative flux field, which is guaranteed at any iteration. Since it converges to the exact solution, the method can be regarded as a linear solver. In this context, the schemes proposed here can be viewed as preconditioned versions of the Generalized Minimal Residual method (GMRES), with a very peculiar characteristic that the residual on the coarse grid is zero at any iteration (thus conservative fluxes can be obtained).

Patterns of Subject Mix in Higher Education Institutions : A First Empirical Analysis Using the AQUAMETH Database

Teaching and research are organised differently between subject domains: attempts to construct typologies of higher education institutions, however, often do not include quantitative indicators concerning subject mix which would allow systematic comparisons of large numbers of higher education institutions among different countries, as the availability of data for such indicators is limited. In this paper, we present an exploratory approach for the construction of such indicators. The database constructed in the AQUAMETH project, which includes also data disaggregated at the disciplinary level, is explored with the aim of understanding patterns of subject mix. For six European countries, an exploratory and descriptive analysis of staff composition divided in four large domains (medical sciences, engineering and technology, natural sciences and social sciences and humanities) is performed, which leads to a classification distinguishing between specialist and generalist institutions. Among the latter, a further distinction is made based on the presence or absence of a medical department. Preliminary exploration of this classification and its comparison with other indicators show the influence of long term dynamics on the subject mix of individual higher education institutions, but also underline disciplinary differences, for example regarding student to staff ratios, as well as national patterns, for example regarding the number of PhD degrees per 100 undergraduate students. Despite its many limitations, this exploratory approach allows defining a classification of higher education institutions that accounts for a large share of differences between the analysed higher education institutions.