The C-terminal domain of coilin interacts with Sm proteins and U snRNPs

Coilin is the signature protein of the Cajal body (CB), a nuclear suborganelle involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs). Newly imported Sm-class snRNPs are thought to traffic through CBs before proceeding to their final nuclear destinations. Loss of coilin function in mice leads to significant viability and fertility problems. Coilin interacts directly with the spinal muscular atrophy (SMA) protein via dimethylarginine residues in its C-terminal domain. Although coilin hypomethylation results in delocalization of survival of motor neurons (SMN) from CBs, high concentrations of snRNPs remain within these structures. Thus, CBs appear to be involved in snRNP maturation, but factors that tether snRNPs to CBs have not been described. In this report, we demonstrate that the coilin C-terminal domain binds directly to various Sm and Lsm proteins via their Sm motifs. We show that the region of coilin responsible for this binding activity is separable from that which binds to SMN. Interestingly, U2, U4, U5, and U6 snRNPs interact with the coilin C-terminal domain in a glutathione S-transferase (GST)-pulldown assay, whereas U1 and U7 snRNPs do not. Thus, the ability to interact with free Sm (and Lsm) proteins as well as with intact snRNPs, indicates that coilin and CBs may facilitate the modification of newly formed snRNPs, the regeneration of 'mature' snRNPs, or the reclamation of unassembled snRNP components.

Clinical relevance of brain volume measures in multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and proceeding throughout the disease course, may be an accurate measure of neurodegeneration and tissue damage. There are a number of magnetic resonance imaging-based methods for determining global or regional brain volume, including cross-sectional (e.g. brain parenchymal fraction) and longitudinal techniques (e.g. SIENA [Structural Image Evaluation using Normalization of Atrophy]). Although these methods are sensitive and reproducible, caution must be exercised when interpreting brain volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding effect on measurements, especially in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy on reducing the rate of brain volume loss. This article reviews the measurement of brain volume in clinical trials and practice, the effect of DMTs on brain volume change across trials and the clinical relevance of brain volume loss in MS.

El Capítulo de Inversiones en el Acuerdo de Asociación Transpacífico:¿Una Posibilidad de Cambio y Convergencia?

Spanish Abstract: El presente trabajo analiza los posibles efectos que generaría en la regulación internacional de la inversión extranjera, el acuerdo de un capítulo de inversiones en el Acuerdo de Asociación Transpacífico (TPP), actualmente en negociaciones, sobre la base de la información disponible a la fecha. El artículo aborda cuatro aspectos que presentan especial importancia dada la divergencia de intereses entre algunos de los Estados negociadores: el ámbito de protección de la inversión extranjera; las normas sobre transparencia de los regímenes de inversión y sus disputas; la irrupción de entidades estatales como inversionistas extranjeros; y la solución de controversias a través del arbitraje inversionista-Estado. El autor concluye que en comparación a la actual fragmentación regulatoria de la que dan cuenta los acuerdos internacionales de inversión suscritos por los países negociadores del TPP, la incorporación de un capítulo de inversiones en ese Acuerdo es una oportunidad para avanzar en la convergencia de la regulación sobre inversión extranjera, tanto en materia de estándares sustantivos de protección de la inversión como en la mejora del arbitraje inversionista-Estado como mecanismo de solución de controversias.

Elucidating the Functional Relationship Between Working Memory Capacity and Psychometric Intelligence: A Fixed-Links Modeling Approach for Experimental Repeated-Measures Designs

Numerous studies reported a strong link between working memory capacity (WMC) and fluid intelligence (Gf), although views differ in respect to how close these two constructs are related to each other. In the present study, we used a WMC task with five levels of task demands to assess the relationship between WMC and Gf by means of a new methodological approach referred to as fixed-links modeling. Fixed-links models belong to the family of confirmatory factor analysis (CFA) and are of particular interest for experimental, repeated-measures designs. With this technique, processes systematically varying across task conditions can be disentangled from processes unaffected by the experimental manipulation. Proceeding from the assumption that experimental manipulation in a WMC task leads to increasing demands on WMC, the processes systematically varying across task conditions can be assumed to be WMC-specific. Processes not varying across task conditions, on the other hand, are probably independent of WMC. Fixed-links models allow for representing these two kinds of processes by two independent latent variables. In contrast to traditional CFA where a common latent variable is derived from the different task conditions, fixed-links models facilitate a more precise or purified representation of the WMC-related processes of interest. By using fixed-links modeling to analyze data of 200 participants, we identified a non-experimental latent variable, representing processes that remained constant irrespective of the WMC task conditions, and an experimental latent variable which reflected processes that varied as a function of experimental manipulation. This latter variable represents the increasing demands on WMC and, hence, was considered a purified measure of WMC controlled for the constant processes. Fixed-links modeling showed that both the purified measure of WMC (β = .48) as well as the constant processes involved in the task (β = .45) were related to Gf. Taken together, these two latent variables explained the same portion of variance of Gf as a single latent variable obtained by traditional CFA (β = .65) indicating that traditional CFA causes an overestimation of the effective relationship between WMC and Gf. Thus, fixed-links modeling provides a feasible method for a more valid investigation of the functional relationship between specific constructs.

Modelling and Validation of a Mass Imbalance Oscillation Generator to Harvest Heart Motion Energy

An autonomous energy source within a human body is of key importance in the development of medical implants. This work deals with the modelling and the validation of an energy harvesting device which converts the myocardial contractions into electrical energy. The mechanism consists of a clockwork from a commercially available wrist watch. We developed a physical model which is able to predict the total amount of energy generated when applying an external excitation. For the validation of the model, a custom-made hexapod robot was used to accelerate the harvesting device along a given trajectory. We applied forward kinematics to determine the actual motion experienced by the harvesting device. The motion provides translational as well as rotational motion information for accurate simulations in three-dimensional space. The physical model could be successfully validated.

Pre-clinical in vivo models for the screening of bone biomaterials for oral/craniofacial indications: focus on small-animal models.

Preclinical in vivo experimental studies are performed for evaluating proof-of-principle concepts, safety and possible unwanted reactions of candidate bone biomaterials before proceeding to clinical testing. Specifically, models involving small animals have been developed for screening bone biomaterials for their potential to enhance bone formation. No single model can completely recreate the anatomic, physiologic, biomechanic and functional environment of the human mouth and jaws. Relevant aspects regarding physiology, anatomy, dimensions and handling are discussed in this paper to elucidate the advantages and disadvantages of small-animal models. Model selection should be based not on the 'expertise' or capacities of the team, but rather on a scientifically solid rationale, and the animal model selected should reflect the question for which an answer is sought. The rationale for using heterotopic or orthotopic testing sites, and intraosseous, periosseous or extraskeletal defect models, is discussed. The paper also discusses the relevance of critical size defect modeling, with focus on calvarial defects in rodents. In addition, the rabbit sinus model and the capsule model in the rat mandible are presented and discussed in detail. All animal experiments should be designed with care and include sample-size and study-power calculations, thus allowing generation of meaningful data. Moreover, animal experiments are subject to ethical approval by the relevant authority. All procedures and the postoperative handling and care, including postoperative analgesics, should follow best practice.

Motivational profiles of sport event volunteers.

Aim of the study Due to the valuable contribution made by volunteers to sporting events, a better understanding of volunteers’ motivation is imperative for event managers in order to develop effective volunteer re-cruitment and retention strategies. The adoption of working conditions and task domains to the mo-tives and needs of volunteers is one of the key challenges in volunteer management. Conversely, an ignorance of the motives and needs of volunteers could negatively affect their performance and attitude, which will have negative consequences for the execution of events (Strigas & Jackson, 2003). In general, the motives of volunteers are located on a continuum between selflessness (e.g. helping others), and self-interest (e.g. pursuing one’s own interests). Furthermore, it should take into account that volunteers may be motivated by more than one need or goal, and therefore, configure different bundles of motives, resulting in heterogeneous types of motives for voluntary engagement (Dolnicar & Randle, 2007). Despite the extensive number of studies on the motives of sport event volunteers, only few studies focus on the analysis of individual motive profiles concerning volun-teering. Accordingly, we will take a closer look at the following questions: To what extent do volun-teers at sporting events differ in the motives of their engagement, and how can the volunteers be ade-quately classified? Theoretical Background According to the functional approach, relevant subjective motives are related to the outcomes and consequences that volunteering is supposed to lead to and to produce. This means, individuals’ mo-tives determine which incentives are anticipated in return for volunteering (e.g. increase in social contacts), and are important for engaging in volunteering, e.g. the choice between different oppor-tunities for voluntary activity, or different tasks (Stukas et al., 2009). Additionally, inter-individual differences of motive structures as well as matching motives in the reflections of voluntary activities will be considered by using a person-oriented approach. In the person-oriented approach, it is not the specific variables that are made the entities of investigation, but rather persons with a certain combination of characteristic features (Bergmann et al., 2003). Person-orientation in the field of sports event volunteers, it is therefore essential to implement an orientation towards people as a unit of analysis. Accordingly, individual motive profiles become the object of investigation. The individ-ual motive profiles permit a glimpse of intra-individual differences in the evaluation of different motive areas, and thus represent the real subjective perspective. Hence, a person will compare the importance of individual motives for his behaviour primarily in relation to other motives (e.g. social contacts are more important to me than material incentives), and make fewer comparisons with the assessments of other people. Methodology, research design and data analysis The motives of sports event volunteers were analysed in the context of the European Athletics Championships 2014 in Zürich. After data cleaning, the study sample contained a total of 1,169 volunteers, surveyed by an online questionnaire. The VMS-ISA scale developed by Bang and Chel-ladurai (2009) was used and replicated successfully by a confirmatory factor analysis. Accordingly, all seven factors of the scale were included in the subsequent cluster analysis to determine typical motive profiles of volunteers. Before proceeding with the cluster analysis, an intra-individual stand-ardization procedure (according to Spiel, 1998) was applied to take advantage of the intra-individual relationships between the motives of the volunteers. Intra-individual standardization means that every value of each motive dimension was related to the average individual level of ex-pectations. In the final step, motive profiles were determined using a hierarchic cluster analysis based on Ward’s method with squared Euclidean distances. Results, discussion and implications The results reveal that motivational processes differ among sports event volunteers, and that volunteers sometimes combine contradictory bundles of motives. In our study, four different volunteer motive profiles were identified and described by their positive levels on the individual motive dimension: the community supporters, the material incentive seekers, the social networkers, and the career and personal growth pursuers. To describe the four identified motive profiles in more detail and to externally validate them, the clusters were analysed in relation to socio-economic, sport-related, and voluntary work characteristics. This motive-based typology of sports event volunteers can provide valuable guidance for event managers in order to create distinctive and designable working conditions and tasks at sporting events that should, in relation to a person-oriented approach, be tailored to a wide range of individ-ual prerequisites. Furthermore, specific recruitment procedures and appropriate communication measures can be defined in order to approach certain groups of potential volunteers more effectively. References Bang, H., & Chelladurai, P. (2009). Development and validation of the volunteer motivations scale for international sporting events (VMS-ISE). International Journal Sport Management and Market-ing, 6, 332-350. Bergmann, L. R., Magnusson, D., & El-Khouri, B. M. (2003). Studying individual development in an interindividual context. Mahwah, NJ: Erlbaum. Dolnicar, S., & Randle, M. (2007). What motivates which volunteers? Psychographic heterogeneity among volunteers in Australia. Voluntas, 18, 135-155. Spiel, C. (1998). Four methodological approaches to the study of stability and change in develop-ment. Methods of Psychological Research Online, 3, 8-22. Stukas, A. A., Worth, K. A., Clary, E. G., & Snyder, M. (2009). The matching of motivations to affordances in the volunteer environment: an index for assessing the impact of multiple matches on volunteer outcomes. Nonprofit and Voluntary Sector Quarterly, 38, 5-28.

Sutureless Aortic Valve Replacement International Registry (SU-AVR-IR): design and rationale from the International Valvular Surgery Study Group (IVSSG).

BACKGROUND Sutureless aortic valve replacement (SU-AVR) is an innovative approach which shortens cardiopulmonary bypass and cross-clamp durations and may facilitate minimally invasive approach. Evidence outlining its safety, efficacy, hemodynamic profile and potential complications is replete with small-volume observational studies and few comparative publications. METHODS Minimally invasive aortic valve surgery and high-volume SU-AVR replacement centers were contacted for recruitment into a global collaborative coalition dedicated to sutureless valve research. A Research Steering Committee was formulated to direct research and support the mission of providing registry evidence warranted for SU-AVR. RESULTS The International Valvular Surgery Study Group (IVSSG) was formed under the auspices of the Research Steering Committee, comprised of 36 expert valvular surgeons from 27 major centers across the globe. IVSSG Sutureless Projects currently proceeding include the Retrospective and Prospective Phases of the SU-AVR International Registry (SU-AVR-IR). CONCLUSIONS The global pooling of data by the IVSSG Sutureless Projects will provide required robust clinical evidence on the safety, efficacy and hemodynamic outcomes of SU-AVR.

WEAVE: Efficient Geographical Routing in Large-Scale Networks

We propose WEAVE, a geographical 2D/3D routing protocol that maintains information on a small number of waypoints and checkpoints for forwarding packets to any destination. Nodes obtain the routing information from partial traces gathered in incoming packets and use a system of checkpoints along with the segments of routes to weave end-to-end paths close to the shortest ones. WEAVE does not generate any control traffic, it is suitable for routing in both 2D and 3D networks, and does not require any strong assumption on the underlying network graph such as the Unit Disk or a Planar Graph. WEAVE compares favorably with existing protocols in both testbed experiments and simulations.

Bone conduction responses of middle ear structures in Thiel embalmed heads

Thiel-embalmed human whole-head specimens offer a promising alternative model for bone conduction (BC) studies of middle ear structures. In this work we present the Thiel model’s linearity and stability over time as well as its possible use in the study of a fixed ossicle chain. Using laser Doppler vibrometry (LDV), the motion of the retroauricular skull, the promontory, the stapes footplate and the round window (RW) were measured. A bone-anchored hearing aid stimulated the ears with step sinus tones logarithmically spread between 0.1 and 10 kHz. Linearity of the model was verified using input levels in steps of 10 dBV. The stability of the Thiel model over time was examined with measurements repeated after hours and weeks. The influence of a cement-fixed stapes was assessed. The middle ear elements measured responded linearly in amplitude for the applied input levels (100, 32.6, and 10 mV). The variability of measurements for both short- (2 h) and long-term (4-16 weeks) repetitions in the same ear was lower than the interindividual difference. The fixation of the stapes induced a lowered RW displacement for frequencies near 750 Hz (-4 dB) and an increased displacement for frequencies above 1 kHz (max. +3.7 dB at 4 kHz). LDV assessment of BC-induced middle ear motion in Thiel heads can be performed with stable results. The vibratory RW response is affected by the fixation of the stapes, indicating a measurable effect of ossicle chain inertia on BC response in Thiel embalmed heads.