bluuebunny/crossref_metadata_2025 huggingface dataset:
A genetic variant in osteoprotegerin is associated with progression of joint destruction in rheumatoid arthritis
Authors: Knevel Rachel , de Rooy Diederik PC , Saxne Tore , Lindqvist Elisabet , Leijsma Martha K , Daha Nina A , Koeleman Bobby PC , Tsonaka Roula , Houwing-Duistermaat Jeanine J , Schonkeren Joris JM , Toes Rene EM , Huizinga Tom WJ , Brouwer Elisabeth , Wilson Anthony G , van der Helm-van Mil Annette HM
Published: May 2014

Introduction

Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA.

Methods

1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied.

Results

We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P = 2.35x10−4). This variant was also significant after Bonferroni correction.

Conclusions

These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA.
Exploration of bacterial community classes in major human habitats
Authors: Zhou Yanjiao , Mihindukulasuriya Kathie A , Gao Hongyu , La Rosa Patricio S , Wylie Kristine M , Martin John C , Kota Karthik , Shannon William D , Mitreva Makedonka , Sodergren Erica , Weinstock George M
Published: May 2014

Background

Determining bacterial abundance variation is the first step in understanding bacterial similarity between individuals. Categorization of bacterial communities into groups or community classes is the subsequent step in describing microbial distribution based on abundance patterns. Here, we present an analysis of the groupings of bacterial communities in stool, nasal, skin, vaginal and oral habitats in a healthy cohort of 236 subjects from the Human Microbiome Project.

Results

We identify distinct community group patterns in the anterior nares, four skin sites, and vagina at the genus level. We also confirm three enterotypes previously identified in stools. We identify two clusters with low silhouette values in most oral sites, in which bacterial communities are more homogeneous. Subjects sharing a community class in one habitat do not necessarily share a community class in another, except in the three vaginal sites and the symmetric habitats of the left and right retroauricular creases. Demographic factors, including gender, age, and ethnicity, significantly influence community composition in several habitats. Community classes in the vagina, retroauricular crease and stool are stable over approximately 200 days.

Conclusion

The community composition, association of demographic factors with community classes, and demonstration of community stability deepen our understanding of the variability and dynamics of human microbiomes. This also has significant implications for experimental designs that seek microbial correlations with clinical phenotypes.
The matter of size: On the moment magnitude of microseismic events
Authors: Jiao Wenjie , Davidson Michael , Sena Arcangelo , Bankhead Bradley L. , Xia Yu , Sil Samik , Zhou Changxi
Published: May 2014

We investigated the method of estimating seismic moment and moment magnitude for microseismic events. We determined that the [Formula: see text] defined by Bowers and Hudson is the proper scalar moment to be used in microseismic studies for characterizing the size of an event and calculating its moment magnitude. For non-double-couple sources, the proportional relationship between body-wave amplitude and seismic moment in the Brune model breaks down. So under such situations, the Brune model is not an appropriate way to estimate the seismic moment and magnitude. Moreover, the S-wave alone is not sufficient for determining the total seismic moment. Instead, the P-wave must be analyzed. An example Barnett Shale data set was studied, and the results concluded that the magnitudes estimated with the Brune model could be off by as much as 1.92, with an absolute average of 0.35. The moment magnitudes based on the scalar moment [Formula: see text] also gave a significantly different event size distribution and b-value estimation. Finally, attenuation also played a role in estimating the moment magnitude. With a typical average attenuation factor of [Formula: see text], the average magnitude correction for our field data set was on the order of 0.15. However, it could reach 0.3 for events far away from the monitoring well.
The possibilities of compressed-sensing-based Kirchhoff prestack migration
Authors: Aldawood Ali , Hoteit Ibrahim , Alkhalifah Tariq
Published: May 2014

An approximate subsurface reflectivity distribution of the earth is usually obtained through the migration process. However, conventional migration algorithms, including those based on the least-squares approach, yield structure descriptions that are slightly smeared and of low resolution caused by the common migration artifacts due to limited aperture, coarse sampling, band-limited source, and low subsurface illumination. To alleviate this problem, we use the fact that minimizing the L1-norm of a signal promotes its sparsity. Thus, we formulated the Kirchhoff migration problem as a compressed-sensing (CS) basis pursuit denoise problem to solve for highly focused migrated images compared with those obtained by standard and least-squares migration algorithms. The results of various subsurface reflectivity models revealed that solutions computed using the CS based migration provide a more accurate subsurface reflectivity location and amplitude. We applied the CS algorithm to image synthetic data from a fault model using dense and sparse acquisition geometries. Our results suggest that the proposed approach may still provide highly resolved images with a relatively small number of measurements. We also evaluated the robustness of the basis pursuit denoise algorithm in the presence of Gaussian random observational noise and in the case of imaging the recorded data with inaccurate migration velocities.
Highly extensible skeletal muscle in snakes
Authors: Close Matthew T. , Perni Stefano , Franzini-Armstrong Clara , Cundall David
Published: May 2014

Many snakes swallow large prey whole by passively stretching the extensible soft tissues connecting the unfused anterior tips of their mandibles. Under these conditions, the intermandibular muscles are highly stretched but subsequently recover normal function. In the highly stretched condition we observed in snakes, sarcomere length (SL) increases 210% its resting value (SL0), and actin and myosin filaments no longer overlap. Myofibrils fall out of register and triad alignment is disrupted. Following passive recovery, SLs were 82% SL0, creating a region of double-overlapping actin filaments. Recovery requires recoil of intracellular titin filaments, elastic cytoskeletal components for realigning myofibrils, and active contraction. Stretch of whole muscles exceeded that of sarcomeres due to extension of folded terminal tendon fibrils, stretching of endomysial elastin, and independent slippage of muscle fibers. Snake intermandibular muscles thus provide a unique model of how basic components of vertebrate skeletal muscle can be modified to permit extreme extensibility.
Manipulation of BK channel expression is sufficient to alter auditory hair cell thresholds in larval zebrafish
Authors: Rohmann Kevin N. , Tripp Joel A. , Genova Rachel M. , Bass Andrew H.
Published: May 2014

Non-mammalian vertebrates rely on electrical resonance for frequency tuning in auditory hair cells. A key component of the resonance exhibited by these cells is an outward calcium-activated potassium current which flows through large-conductance calcium activated potassium (BK) channels. Previous work in midshipman fish (Porichthys notatus) has shown that BK expression correlates with seasonal changes in hearing sensitivity and that pharmacologically blocking these channels replicates the natural decreases in sensitivity during the winter non-reproductive season. To test the hypothesis that reducing BK channel function is sufficient to change auditory thresholds in fish, morpholino oligos were used in larval zebrafish (Danio rerio) to alter expression of slo1a and slo1b, duplicate genes coding for the pore-forming α-subunits of BK channels. Following morpholino injection, microphonic potentials were recorded from the inner ear of larvae. Quantitative real-time PCR was then used to determine the morpholino effect on slo1a and slo1b expression in these same fish. Knockdown of either slo1a or slo1b resulted in disrupted gene expression and increased auditory thresholds across the same range of frequencies of natural auditory plasticity observed in midshipman. We conclude that interference with the normal expression of individual slo1 genes is sufficient to increase auditory thresholds in zebrafish larvae and that changes in BK channel expression are a direct mechanism for regulation of peripheral hearing sensitivity among fishes.
Using accelerometers to determine the calling behavior of tagged baleen whales
Authors: Goldbogen Jeremy A. , Stimpert Alison K. , DeRuiter Stacy L. , Calambokidis John , Friedlaender Ari S. , Schorr Greg S. , Moretti David J. , Tyack Peter L. , Southall Brandon L.
Published: May 2014

Low-frequency acoustic signals generated by baleen whales can propagate over vast distances, making the assignment of calls to specific individuals problematic. Here we report the novel use of acoustic recording tags equipped with high-resolution accelerometers to detect vibrations on the surface of two tagged fin whales that directly match the timing of recorded acoustic signals. A tag deployed on a buoy in the vicinity of calling fin whales, and a recording from a tag that had just fallen off of a whale, were able to detect calls acoustically but did not record corresponding accelerometer signals that were measured on calling individuals. Across the hundreds of calls measured on two tagged fin whales, the accelerometer response was generally anisotropic across all three axes, appeared to depend on tag placement, and increased with the level of received sound. These data demonstrate that high-sample-rate accelerometry can provide important insights into the acoustic behavior of baleen whales that communicate at low frequencies. This method helps identify vocalizing whales, which in turn enables the quantification of call rates, a fundamental component of models used to estimate baleen whale abundance and distribution from passive acoustic monitoring.
Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus)
Authors: Lattin Christine R. , Romero L. Michael
Published: May 2014

The physiological stress response results in release of glucocorticoid hormones such as corticosterone (CORT). Whereas short-term activation of this response helps animals cope with environmental stressors, chronic activation can result in negative effects including metabolic dysregulation and reproductive failure. However, there is no consensus hormonal profile of a chronically-stressed animal, suggesting researchers may need to look beyond hormone titers to interpret the impacts of chronic stress. In this study, we brought wild house sparrows (Passer domesticus) into captivity. We then compared glucocorticoid and mineralocorticoid receptor concentrations in sparrows exposed either to a standardized chronic stress protocol (n=26) or to standard husbandry conditions (controls; n=20). We used radioligand binding assays to quantify receptors in whole brain, liver, kidneys, spleen, gonads, gastrocnemius and pectoralis muscle, omental and subcutaneous fat, and bib and back skin. In most tissues, CORT receptors did not differ between controls and stressed animals, although we found marginal increases in receptor density in kidney and testis in stressed birds at some time points. Only in pectoralis muscle was there a robust effect of chronic stress, with both receptor types higher in stressed animals. Increased pectoralis sensitivity to CORT with chronic stress may be part of the underlying mechanism for muscle wasting in animals administered exogenous CORT. Furthermore, the change in pectoralis was not paralleled by gastrocnemius receptors. This difference may help explain previous reports of a greater effect of CORT on pectoralis than on other muscle types, and indicate that birds use this muscle as a protein reserve.
Jumping mechanisms in flatid planthoppers (Hemiptera, Flatidae)
Authors: Burrows Malcolm
Published: May 2014

The jumping performance of three species of hemipterans from Australia and Europe belonging to the family Flatidae, were analysed from images captured at a rate of 5000 s-1. The shape of a flatid was dominated by large triangular or wedge-shaped front wings which, when folded, covered and extended above and behind the body to give a laterally compressed and possibly streamlined appearance. Body length of the three species of adults ranged from 7 to 9 mm and their mass from 8 to 19 mg. The propulsive hind legs were 30% longer than the front legs but only 36-54% of body length. Jumps with the fastest take-off velocities of 2.8-3.2 m s-1 had acceleration times of 1.4-1.8 ms. During such jumps adults experienced an acceleration of 174 - 200 g. These jumps required an energy expenditure of 76-225 μJ, a power output of 13-60 mW and exerted a force of 9-37 mN. The required power output per mass of jumping muscle in adults ranged from 24,000 to 27,000 W kg-1 muscle, 100 times greater than the maximum active contractile limit of normal muscle. The free-living nymphs were also proficient jumpers, reaching take-off velocities of 2.2 m s-1. To achieve such a jumping performance requires a power amplification mechanism. The energy store for such a mechanism was identified as the internal skeleton linking a hind coxa to the articulation of a hind wing. These pleural arches fluoresced bright blue when illuminated with ultraviolet light indicating the presence of the elastic protein resilin. The energy generated by the prolonged contractions of the trochanteral depressor muscles was stored in distortions of these structures and their rapid elastic recoil powered the synchronous propulsive movements of the hind legs.
Dynamic Stability Behaviour of Lattice Domes with Substructures
Authors: Sun Jianheng , Li Hongmei , Nooshin Hoshyar , Parke Gerard A.R.
Published: May 2014

Dynamic behaviour is one of the main controlling factors for the design of large single-layer lattice dome structures. Considering a single-layer lattice dome and its supporting frame as an integral whole, this paper investigates the dynamic stability behaviour of the dome under seismic loads. In the analysis, the initial geometric imperfections, together with geometric and material nonlinearities, are considered. A factor expressing the degree of stiffness of the supporting frame is also used in the analysis. The effects of supporting frames of different stiffness and different rise to span ratios of the domes are also investigated. The results of the investigation show that the stiffness of the substructure can play a very important role in the dynamic stability behaviour of the dome.
Interactive Equilibrium Modelling
Authors: Lachauer Lorenz , Block Philippe
Published: May 2014

This paper presents a novel method for computer-aided equilibrium modelling of structures in early design stages. Based on the force density method, an iterative procedure is developed that enables the generation of spatial kinematic pin-jointed structures that are in equilibrium close to a given input geometry, while satisfying additional constraints on both geometry and forces. This method forms the core of an interactive form-finding process that consists of alternating steps of modelling and computational optimization. In each modelling step, the user is able to modify geometry, topology, external forces and constraints of the structure. In each optimization step, equilibrium is re-established while respecting the user-defined constraints. A prototype has been implemented within an existing CAD software package, and three examples illustrate the use of the presented method, ranging from a playful exploration of surprising shapes to the rationalization of structural geometry. The method allows to intuitively explore the formal freedom of spatial equilibrium shapes with mixed compression and tension forces, within hard, user-defined constraints. In conclusion, it is claimed that by providing interactive equilibrium modelling methods, the design of new, surprising spatial forms with efficient structural behaviour is facilitated.
Modeling of Underconstrained Systems with the Force Method
Authors: Lin Zhibin , Qian Ruojun , Yuan Xingfei
Published: May 2014

Determination of underconstrained systems using traditional theory may cause a nonconservative solution or even lead to error. The fundamentals of the concept and general formulations for kinematic path are derived such that they can be used for determination of both elastic deformation and change in geometry experienced in underconstrained systems. The condition of orthogonality is used such that the existence of such a space having the property of the general loads orthogonal to geometric displacement is thus proved. Numerical examples in the literature are used to verify the proposed methods. The efficacy of the proposed procedures implemented in engineering application is finally demonstrated under erection simulation.
Experimental and Numerical Studies on the Progressive Collapse Behavior of Tensegrity Systems
Authors: Shekastehband B. , Abedi K. , Dianat N.
Published: May 2014

To better understanding the response of tensegrity systems subjected to the progressive collapse, the experimental and numerical studies were carried out on a 3.0×3.0×0.7 m prototype. The primary tests on the constituent elements were repetitive loading and unloading tests on the cable elements as well as tensile tests on the tubes and buckling tests on the struts (consisted of tubes and end connections). The experimental tensegrity model was loaded up to a load level at which buckling of a strut led to successive buckling of struts causing overall collapse. The tests results are served as a basis for calibration of numerical models and furthermore for the development and verification of a new approach to structural design of tensegrity systems. The most important conclusion was that the collapse behavior of the tensegrity model is strongly dependant on the fastener bolts failure after buckling of the struts. Additionally, kinetic energy released during the progressive collapse in the tensegrity model caused catastrophic results in the supporting systems.
Moving out of Sports: A Sociocultural Examination of Olympic Career Transitions
Authors: Barker Dean , Barker-Ruchti Natalie , Rynne Steven , Lee Jessica
Published: May 2014

This article outlines sociocultural learning theory, shows how this theory can be used to examine end-of-career athletic transitions, and stimulates discussion on the implications of this framework for sport professionals. The central question addressed is how learning in elite sport affects participation in activities beyond sporting settings. Data from in-depth, semi-structured interviews with three former Olympians are presented. The interpretation suggests that: 1) movement to new social settings involves abandoning some elements of athletic dispositions and developing new elements, 2) transitions are affected by prior learning in sport and the characteristics of new settings, and 3) learning in sporting environments is often unintentional or implicit. The results encourage practitioners to acknowledge the effort involved in developing new dispositions in different settings. They support a case-specific view of transitions where ‘success' is considered in contextual terms. Further, the data highlight a need for sport professionals to recognize tacit learning.
Elements of Success: Olympic Swimming Gold Medalists' Understanding of Their Competition-Day Routines
Authors: Grant Matthew A. , Schempp Paul
Published: May 2014

This study examined the competitive routines that five male Olympic gold medalist swimmers from the 2008 Beijing Summer Olympic Games undertook during successful elite competition days that they believe were critical to their success. Researchers sought to understand the significance of these actions based upon the meaning provided by these elite athletes. Participants engaged in an initial interview, a two-day training visit, a competition observation during an elite meet, and a follow-up interview. The swimmers' coaches were interviewed as key informants. Utilizing constructivist grounded theory, the larger study yielded several key results. First, researchers detailed a new holistic competition-day routine consisting of 12 segments and 2 types of preparations. Second, the purpose of this article was to define four elements that were critical to the athletes understanding and adherence to their competition-day routine. Each of the elements, which were flexibility, adaptation, time management, and task acquisition, was significant both individually and collectively.
First Club Location and Relative Age as Influences on Being a Professional Australian Rugby League Player
Authors: Cobley Stephen , Hanratty Michael , O'Connor Donna , Cotton Wayne
Published: May 2014

Bio-ecological systems theory suggests athlete development and success occurs via a complex inter-play of factors nested between and within individual, social context, and broader socio-cultural environments. On these predications, this study examined whether ‘first club location’ and ‘relative age’ independently and interactively affected the likelihood of becoming a professional Rugby League player. Data on 1509 Australian Rugby League professionals who played between 1998–2010 were obtained. Compared to population distributions, Chi-square and odds ratio analyses revealed a significant over-representation of players initiating their participation in small communities (i.e., < 20,000 residents), along with a contrasting under-representation from cities (i.e., > 1,000,000 residents). Professional players were also more likely to be relatively older (Q1 v Q4 OR = 1.80; CI = 1.47–2.21). A log-linear interactional analysis revealed no notable main trend ( p < .07). However, the specific odds of a professional player being relatively older were reduced (OR = 0.68, CI = 0.50–0.92) when their first Rugby League club was in a small community (i.e., < 20,000 residents). Results highlight how characteristics of the social environment can potentially influence long-term patterns of athlete development and attainment in Australian Rugby League.
Survival and Success of the Relatively Oldest in Swiss Youth Skiing Competition
Authors: Romann Michael , Fuchslocher Jörg
Published: May 2014

Relative age refers to age differences between children in the same selection year. The present study investigated the prevalence of relative age effects (RAEs) at the Grand Prix Migros (GPM), which is the most popular alpine skiing race for children aged 7 to 14 years in Europe. In total, 17,992 Swiss junior alpine skiers, separated into female skiers ( n = 7,227) and male skiers ( n = 10,765), were evaluated in the 2010, 2011, and 2012 races. Chi-square analyses revealed no RAEs ( p > 0.05) for the entire group of finishers in the qualification race for females in the Under U-8 to U-13 categories ( n = 7,010) and all males ( n = 10,410). Significant inverse RAEs were detected in the qualification race among female skiers in the U-14 and U-15 age categories ( p < 0.01; odds ratio OR = 0.79; 95% confidence interval (CI) [0.64–0.98], and among disqualified male skiers ( p < 0.01; OR = 0.54; [CI, 0.40–0.74]. However, significant RAEs were found for the entire group of both female and male skiers who qualified for the final race ( p < 0.01; OR = 1.49; [CI, 1.28–1.73] of females, respectively OR = 2.18; [CI, 1.87–2.53] of males). RAEs were additionally apparent in all age categories of female and male finalists. The GPM is apparently influenced by RAEs, which may be an initial step towards RAEs in youth sports and may lead to an unequal participation in Swiss skiing.
Coaches, Athletes, Skill Acquisition Specialists: A Case of Misrecognition
Authors: Steel Kylie A , Harris Ben , Baxter David , King Mike , Ellam Eathan
Published: May 2014

Skill acquisition specialists are sport scientists who examine the theories, principles and processes of motor and perceptual learning. The research generated by these specialists is applied to practice modes, feedback and instructional methods, decision-making and anticipation skills training for athletes. However, unlike most sports scientists, these specialists are not utilized to the same degree as their counterparts. Therefore, the purpose of this study was to investigate why this trend exists. Forty two participants (coaches/athletes) took part in this study. All participants coached or competed at a pre-elite or elite level, with a number of team and individual sports represented. The results of this study indicated that both coaches and athletes perceived skill acquisition specialists to be skills coaches rather than sport scientists. Further, coaches and athletes were open to assistance from specialists though they cited funding and access as major barriers to utilization. Moreover, they stated a lack of skill acquisition specialists with ‘experience’ in their sport as a limitation. Overall, the results suggest a misrecognition, underestimation of knowledge, and lack of understanding of a skill acquisition specialist, which may be a result of the limited engagement between these groups.
Markov Decision Problems Where Means Bound Variances
Authors: Arlotto Alessandro , Gans Noah , Steele J. Michael
Published: May 2014

We identify a rich class of finite-horizon Markov decision problems (MDPs) for which the variance of the optimal total reward can be bounded by a simple linear function of its expected value. The class is characterized by three natural properties: reward nonnegativity and boundedness, existence of a do-nothing action, and optimal action monotonicity. These properties are commonly present and typically easy to check. Implications of the class properties and of the variance bound are illustrated by examples of MDPs from operations research, operations management, financial engineering, and combinatorial optimization.
When does evidence-based policy turn into policy-based evidence? Configurations, contexts and mechanisms
Authors: Strassheim Holger , Kettunen Pekka
Published: May 2014

Many studies on evidence-based policy are still clinging to a linear model. Instead, we propose to understand expertise and evidence as ‘socially embedded’ in authority relations and cultural contexts. Policy-relevant facts are the result of an intensive and complex struggle for political and epistemic authority. This is especially true where science and policy are difficult to distinguish and the guidelines for validating knowledge are highly contested. To understand the mechanisms leading to policy-based evidence and the long-term consequences of these transformations more comparative research on the cultural and institutional ‘embeddedness’ of epistemic and political authority is needed.
Integrated Practices: Huron-Wendat Traditions of Diplomacy and Museology
Authors: de Stecher Annette
Published: May 2014

The Huron-Wendat Museum in Wendake, Quebec is an example of a new form of cultural institution: museums/cultural centres founded by North American Indigenous nations. This article explores the history of Wendat traditions and concepts of culture keeping, preservation of heritage material, and the transmission of knowledge, which continue today in the contemporary practices of the Huron-Wendat Museum. The study foregrounds the Wendat origin of customs that translate into western curatorial understandings of collection and exhibition, yet remain embedded in Wendat values and worldview.
Ferrajoli, o el neoconstitucionalismo no tomado en serio
Authors: Barberis Mauro
Published: May 2014

Esta última contribucción de Ferrajoli al debate sobre el (neo)constitucionalismo requiere cinco críticas: primero, el enfoque deductivista coherentemente adoptado por el autor desde Teoría assiomatizzata del diritto hasta Principia iuris deja muy poco espacio para la interpretación y la argumentación en el razonamiento jurídico; segundo, el propio problema de la relación entre derecho y moral no está verdaderamente discutido por él; tercero, cuarto y quinto, el mismo enfoque deductivista fuerza a Ferrajoli a reducir los principios a reglas, a ignorar el papel democrático que podría cumplir una ponderación actuada por el legislador y no por el juez, y a resolver de una discutible manera monista el problema pluralista del conflicto entre derechos.
«Constitucionalismo»: problemas de definición y tipología
Authors: Comanducci Paolo
Published: May 2014

El autor analiza y critica la definición de «constitucionalismo» de Ferrajoli y su tipología de los constitucionalismos. Él afirma la oportunidad de distinguir entre constitucionalismo como teoría, como metodología y como ideología.
Sobre la odisea constitucionalista de Luigi Ferrajoli
Authors: Hierro Sánchez Pescador Liborio Luis
Published: May 2014

El ensayo de Ferrajoli que aquí se comenta parece estar destinado a subrayar las diferencias que separan el constitucionalismo garantista del neo-constitucionalismo principialista. Para construir el constitucionalismo garantista Ferrajoli proclamó la necesidad de abandonar totalmente el paradigma paleo-positivista pero, al hacerlo, se acercó peligrosamente a las tesis post-positivistas con las que quiere ahora marcar claras distancias. En este tránsito entre Escila y Caribdis, Ferrajoli ha formulado una teoría jurídico-formal de los derechos fundamentales que se sitúan en un mundo jurídico-positivo de nivel superior y de carácter objetivo, al que todos los mundos jurídicos inferiores están supeditados y por el que están limitados; tanto la producción normativa inferior, incluida la legislación formal, como la aplicación jurisdiccional se mueven en un ámbito delimitado por lo que no se puede decidir y lo que no se puede dejar de decidir. A pesar de sus esfuerzos por evitarlo, el constitucionalismo formal de Ferrajoli elude la cuestión de la última palabra y promueve el activismo, al menos el activismo de la jurisdicción constitucional.
Sobre Luigi Ferrajoli y el constitucionalismo
Authors: Laporta San Miguel Francisco Javier
Published: May 2014

El autor plantea una serie de objeciones al texto de Luigi Ferrajoli. En primer lugar, se refiere a la construcción por parte de Ferrajoli de una teoría que infiere de un modo exhaustivo, pero siempre deductivamente, el alcance de un complejo conjunto de términos primitivos y definiciones. En segundo lugar, el autor duda sobre la forma de ver y, sobre todo, de reconstruir el llamado «paradigma constitucional». En tercer lugar, el autor objeta el tratamiento que Ferrajoli hace de los conceptos de «validez» y «vigor» de las normas. En cuarto lugar, hace referencia a la definición que Ferrajoli realiza del constitucionalismo garantista, en concreto a la consideración de éste como mejora o complemento del positivismo jurídico que se logra gracias a que el constitucionalismo observa no sólo el «ser» sino el «deber ser» del Derecho. Finalmente, repasa las críticas que Ferrajoli realiza al constitucionalismo (la tesis de la separación entre Derecho y moral, la distinción entre principios y reglas y la crítica a la ponderación), expresando sus diferencias.
Garantismo y neoconstitucionalismo frente a frente: algunas claves para su distinción
Authors: Salazar Ugarte Pedro
Published: May 2014

En este ensayo se sostiene la pertinencia teórica de distinguir entre el neoconstitucionalismo y el garantismo. Ambas aproximaciones teóricas estudian el mismo modelo de organización político/jurídica: el constitucionalismo democrático. Esto ha provocado que diversos estudiosos europeos y latinoamericanos confundan las dos aproximaciones y utilicen ambas categorías de manera indistinta. Sin embargo, en el texto se sostiene que el garantismo es una teoría que debe adscribirse al positivismo jurídico mientras el neoconstitucionalismo (que, en realidad, es una categoría que conjuga diferentes teorías) tiene una tendencia iusnaturalista. Esta diferencia fundamental tiene implicaciones teóricas relevantes y también consecuencias prácticas sobre todo en el ámbito de la justicia constitucional.
Conditional Ablation of Orexin/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function
Authors: Tabuchi Sawako , Tsunematsu Tomomi , Black Sarah W. , Tominaga Makoto , Maruyama Megumi , Takagi Kazuyo , Minokoshi Yasuhiko , Sakurai Takeshi , Kilduff Thomas S. , Yamanaka Akihiro
Published: May 2014

The sleep disorder narcolepsy results from loss of hypothalamic orexin/hypocretin neurons. Although narcolepsy onset is usually postpubertal, current mouse models involve loss of either orexin peptides or orexin neurons from birth. To create a model of orexin/hypocretin deficiency with closer fidelity to human narcolepsy, diphtheria toxin A (DTA) was expressed in orexin neurons under control of the Tet-off system. Upon doxycycline removal from the diet of postpubertalorexin-tTA;TetO DTAmice, orexin neurodegeneration was rapid, with 80% cell loss within 7 d, and resulted in disrupted sleep architecture. Cataplexy, the pathognomic symptom of narcolepsy, occurred by 14 d when ∼5% of the orexin neurons remained. Cataplexy frequency increased for at least 11 weeks after doxycycline. Temporary doxycycline removal followed by reintroduction after several days enabled partial lesion of orexin neurons. DTA-induced orexin neurodegeneration caused a body weight increase without a change in food consumption, mimicking metabolic aspects of human narcolepsy. Because the orexin/hypocretin system has been implicated in the control of metabolism and addiction as well as sleep/wake regulation, orexin-tTA; TetO DTAmice are a novel model in which to study these functions, for pharmacological studies of cataplexy, and to study network reorganization as orexin input is lost.
Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal Cortex
Authors: Ren Ming , Cao Vania , Ye Yizhou , Manji Husseini K. , Wang Kuan Hong
Published: May 2014

The brain encodes information about past experience in specific populations of neurons that communicate with one another by firing action potentials. Studies of experience-dependent neural plasticity have largely focused on individual synaptic changes in response to neuronal input. Indicative of the neuronal output transmitted to downstream neurons, persistent firing patterns are affected by prior experience in selective neuronal populations. However, little is known about the molecular and cellular mechanisms by which experience-related persistent firing patterns are regulated in specific neuronal populations. Using frontal cortical slices prepared from transgenic mice carrying a fluorescent reporter ofArcgene expression, this study investigates how behavioral experience and the activity-regulatedArcgene affect patterns of neuronal firing. We found that motor training increases Arc expression in subsets of excitatory neurons. Those neurons exhibit persistent firing in contrast to Arc-negative neurons from the same mice or neurons from the untrained mice. Furthermore, in mice carrying genetic deletion ofArc, the frontal cortical circuitry is still in place to initiate experience-dependent gene expression, but the level of persistent firing thereafter is diminished. Finally, our results showed that the emergence of persistent activity is associated with Arc-dependent changes in the function of NMDA-type glutamate receptors, rather than changes in AMPA-type receptors or membrane excitability. Our findings therefore reveal an Arc-dependent molecular pathway by which gene–experience interaction regulates the emergence of persistent firing patterns in specific neuronal populations.
Astrocytic TDP-43 Pathology in Alexander Disease
Authors: Walker Adam K. , Daniels Christine M. LaPash , Goldman James E. , Trojanowski John Q. , Lee Virginia M.-Y. , Messing Albee
Published: May 2014

Alexander disease (AxD) is a rare neurodegenerative disorder characterized pathologically by the presence of eosinophilic inclusions known as Rosenthal fibers (RFs) within astrocytes, and is caused by dominant mutations in the coding region of the gene encoding glial fibrillary acidic protein (GFAP). GFAP is the major astrocytic intermediate filament, and in AxD patient brain tissue GFAP is a major component of RFs. TAR DNA binding protein of 43 kDa (TDP-43) is the major pathological protein in almost all cases of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and ∼50% of frontotemporal lobar degeneration (FTLD), designated as FTLD-TDP. In ALS and FTLD-TDP, TDP-43 becomes insoluble, ubiquitinated, and pathologically phosphorylated and accumulates in cytoplasmic inclusions in both neurons and glia of affected brain and spinal cord regions. Previously, TDP-43 was detected in RFs of human pilocytic astrocytomas; however, involvement of TDP-43 in AxD has not been determined. Here we show that TDP-43 is present in RFs in AxD patient brains, and that insoluble phosphorylated full-length and high molecular weight TDP-43 accumulates in white matter of such brains. Phosphorylated TDP-43 also accumulates in the detergent-insoluble fraction from affected brain regions ofGfapR236H/+knock-in mice, which harbor a GFAP mutation homologous to one that causes AxD in humans, and TDP-43 colocalizes with astrocytic RF pathology inGfapR236H/+mice and transgenic mice overexpressing human wild-type GFAP. These findings suggest common pathogenic mechanisms in ALS, FTLD, and AxD, and this is the first report of TDP-43 involvement in a neurological disorder primarily affecting astrocytes.
Social Stress and CRF–Dopamine Interactions in the VTA: Role in Long-Term Escalation of Cocaine Self-Administration
Authors: Boyson Christopher O. , Holly Elizabeth N. , Shimamoto Akiko , Albrechet-Souza Lucas , Weiner Lindsay A. , DeBold Joseph F. , Miczek Klaus A.
Published: May 2014

The nature of neuroadaptations in the genesis of escalated cocaine taking remains a topic of considerable interest. Intermittent social defeat stress induces both locomotor and dopaminergic cross-sensitization to cocaine, as well as escalated cocaine self-administration. The current study examines the role of corticotropin releasing factor receptor subtypes 1 and 2 (CRFR1, CRFR2) within the ventral tegmental area (VTA) during social defeat stress. This study investigated whether injecting either a CRFR1or CRFR2antagonist directly into the VTA before each social defeat would prevent the development of later (1) locomotor sensitization, (2) dopaminergic sensitization, and (3) escalated cocaine self-administration in rats. CRFR1antagonist CP376395 (50 or 500 ng/side), CRFR2antagonist Astressin2-B (100 or 1000 ng/side), or vehicle (aCSF) was microinjected into the VTA 20 min before social defeat stress (or handling) on days 1, 4, 7, and 10. Ten days later, rats were injected with cocaine (10 mg/kg, i.p.) and assessed for either locomotor sensitization, measured by walking activity, or dopaminergic sensitization, measured by extracellular dopamine (DA) in the nucleus accumbens shell (NAcSh) throughin vivomicrodialysis. Locomotor sensitization testing was followed by intravenous cocaine self-administration. Intra-VTA antagonism of CRFR1, but not CRFR2, inhibited the induction of locomotor cross-sensitization to cocaine, whereas both prevented dopaminergic cross-sensitization and escalated cocaine self-administration during a 24 h “binge.” This may suggest dissociation between locomotor sensitization and cocaine taking. These data also suggest that interactions between CRF and VTA DA neurons projecting to the NAcSh are essential for the development of dopaminergic cross-sensitization to cocaine.
β-Catenin Is Required for Hair-Cell Differentiation in the Cochlea
Authors: Shi Fuxin , Hu Lingxiang , Jacques Bonnie E. , Mulvaney Joanna F. , Dabdoub Alain , Edge Albert S.B.
Published: May 2014

The development of hair cells in the auditory system can be separated into steps; first, the establishment of progenitors for the sensory epithelium, and second, the differentiation of hair cells. Although the differentiation of hair cells is known to require the expression of basic helix-loop-helix transcription factor,Atoh1, the control of cell proliferation in the region of the developing cochlea that will ultimately become the sensory epithelium and the cues that initiateAtoh1expression remain obscure. We assessed the role of Wnt/β-catenin in both steps in gain- and loss-of-function models in mice. The canonical Wnt pathway mediator, β-catenin, controls the expression ofAtoh1. Knock-out of β-catenin inhibited hair-cell, as well as pillar-cell, differentiation from sensory progenitors but was not required to maintain a hair-cell fate once specified. Constitutive activation of β-catenin expanded sensory progenitors by inducing additional cell division and resulted in the differentiation of extra hair cells. Our data demonstrate that β-catenin plays a role in cell division and differentiation in the cochlear sensory epithelium.
A Death Receptor 6-Amyloid Precursor Protein Pathway Regulates Synapse Density in the Mature CNS But Does Not Contribute to Alzheimer's Disease-Related Pathophysiology in Murine Models
Authors: Kallop Dara Y. , Meilandt William J. , Gogineni Alvin , Easley-Neal Courtney , Wu Tiffany , Jubb Adrian M. , Yaylaoglu Murat , Shamloo Mehrdad , Tessier-Lavigne Marc , Scearce-Levie Kimberly , Weimer Robby M
Published: May 2014

Recent studies implicate death receptor 6 (DR6) in an amyloid precursor protein (APP)-dependent pathway regulating developmental axon pruning, and in a pruning pathway operating during plastic rearrangements in adult brain. DR6 has also been suggested to mediate toxicityin vitroof Aβ peptides derived from APP. Given the link between APP, Aβ, and Alzheimer's disease (AD), these findings have raised the possibility that DR6 contributes to aspects of neurodegeneration in AD. To test this possibility, we have used mouse models to characterize potential function(s) of DR6 in the adult CNS and in AD-related pathophysiology. We show that DR6 is broadly expressed within the adult CNS and regulates the density of excitatory synaptic connections onto pyramidal neurons in a genetic pathway with APP.DR6knock-out also gives rise to behavioral abnormalities, some of which are similar to those previously documented inAPPknock-out animals. However, in two distinct APP transgenic models of AD, we did not observe any alteration in the formation of amyloid plaques, gliosis, synaptic loss, or cognitive behavioral deficits with genetic deletion of DR6, though we did observe a transient reduction in the degree of microglial activation in one model. Our results support the view that DR6 functions with APP to modulate synaptic density in the adult CNS, but do not provide evidence for a role of DR6 in the pathophysiology of AD.
Severe Isolated Tricuspid Insufficiency due to Tricuspid Papillary Muscle Rupture after a Fall From a Horse: Treatment with Port Access Minimally Invasive Cardiac Surgery
Authors: Öz Kürsad , Mayeran Yousef , Van Praet Frank , Codens Jose , Vanerman Hugo
Published: May 2014

We report on the successful treatment of tricuspid valve insufficiency due to blunt chest injury using port-access minimally invasive cardiac surgery. The optimal surgical treatment of traumatic valvular insufficiency is discussed, including a brief review of the relevant literature.
Genetic and Genomic Tools for the Marine AnnelidPlatynereis dumerilii
Authors: Zantke Juliane , Bannister Stephanie , Rajan Vinoth Babu Veedin , Raible Florian , Tessmar-Raible Kristin
Published: May 2014

The bristle worm Platynereis dumerilii displays many interesting biological characteristics. These include its reproductive timing, which is synchronized to the moon phase, its regenerative capacity that is hormonally controlled, and a slow rate of evolution, which permits analyses of ancestral genes and cell types. As a marine annelid, Platynereis is also representative of the marine ecosystem, as well as one of the three large animal subphyla, the Lophotrochozoa. Here, we provide an overview of the molecular resources, functional techniques, and behavioral assays that have recently been established for the bristle worm. This combination of tools now places Platynereis in an excellent position to advance research at the frontiers of neurobiology, chronobiology, evo-devo, and marine biology.
High-Temperature Electromechanical Properties of CTGS
Authors: Schulz Michal , Fritze Holger , Johnson Ward L.
Published: May 2014

CTGS (Ca3TaGa3Si2O14) is a commercially available, Czochralski-grown piezoelectric material from the langasite family that has an ordered crystal structure. It can be excited piezoelectrically up to at least 1285 °C, which is very close to the melting temperature of 1350 °C. In order to determine the loss at elevated temperatures, two different resonance techniques are used. A contactless transduction method is employed up to about 600 °C, whereas transduction involving standard keyhole-shaped film electrodes is employed up to 1285 °C. Comparison of the temperature-dependent inverse Q factor shows that contactless measurements are best suited for the lower temperature range, where sample clamping and losses caused by the electrodes contribute significantly to the total loss. However, at higher temperatures, measurement of the electrical impedance of samples with film electrodes in the vicinity of the resonance frequency proves to be suitable. Even at 1100 °C, 5 MHz CTGS resonators are found to have a Q factor of about 1200, which is great enough to enable numerous bulk-acoustic-wave applications. Further, a nearly linear temperature dependence of the resonance frequency with a temperature coefficient of 210 Hz/K makes Y-cut CTGS well suited for temperature-sensing applications.