bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Chronology of Orexin Pharmacology and Its Potential as a Treatment for Primary Insomnia
Authors: Winrow Christopher J. , Gotter Anthony L. , Coleman Paul J. , Hargreaves Richard , Renger John J.
Published: October 2012

An understanding of the function of orexin peptides and their cognate receptors offers new insights into the role of hypothalamic control of sleep and wake, along with revealing previously undefined connections between feeding, reward and addiction. Despite being relatively recently discovered, progress in this field has been rapid. In just over 14 years, this area has moved from the identification of the orexin (hypocretin) peptide to the development of late-stage clinical drug candidates targeting the orexin receptors for insomnia. The swift pace of discovery was ignited by the identification of the link between orexin signalling and human narcolepsy, and accelerated with the development of solid genetic animal models and focused research efforts by academic and industrial investigators resulting in unprecedented translational pharmacology. The recent demonstration of clinical efficacy with dual orexin receptor antagonists for the treatment of insomnia has invigorated the sleep research field with a new genetically based mechanism of action for sleep therapeutics, and has provided direction to build on these findings. This chapter describes the discovery and characterization of the orexin neurotransmitter system, the impact of translational genetic models and behavioural monitoring and the development of novel small-molecule orexin receptor antagonists for insomnia, reviews recent clinical experience and discusses the emerging opportunities for targeting orexin signalling in other neurological and psychiatric diseases.
Medicinal Chemistry Challenges in CNS Drug Discovery
Authors: Bingham Matilda , Rankovic Zoran
Published: October 2012

The human brain is a uniquely complex organ, which has evolved a sophisticated protection system to avoid injury from external insults and toxins. Penetrating the blood-brain barrier (BBB) to achieve the drug concentrations required for efficacious target receptor occupancy in the brain region of interest is a unique and significant challenge facing medicinal chemists working on CNS targets. Prospective design of molecules with optimal brain exposure and safety profile requires in-depth understanding of the fundamental relationships between physicochemical properties and in vitro and in vivo outcomes. Following from the now widely accepted “rule of five” guidelines for the design of oral drugs, the physicochemical properties for brain penetration have been extensively studied in an effort to define the characteristics of successful CNS drug candidates. Several key physicochemical properties have been identified that influence the rate of brain permeability and extent of brain penetration, including H-bonding potential, molecular weight, lipophilicity, polar surface area (PSA), ionization state and rotatable bond count. The ability to process this information effectively and engage in multi-parameter prospective design ultimately determines the success in delivering high-quality drug candidates that are suitable robustly to test hypotheses in the clinic and have good probability of reaching the market. This chapter focuses on the medicinal chemistry aspects of drug candidate optimization particular to the CNS therapeutic area, such as crossing the blood-brain barrier (BBB), as well as safety-related issues frequently challenging CNS programs such as hERG selectivity and phospholipidosis.
Multi-target Drug Discovery for Psychiatric Disorders
Authors: Rankovic Zoran , Morphy Richard
Published: October 2012

Modulation of multiple targets within relevant biological pathways and networks is increasingly being recognized as a superior approach towards the next generation of treatments for diseases with complex, polygenic aetiology such as psychiatric disorders. Consequently, there is an ever-increasing interest in deliberate and rational design of ligands that act selectively on specific multiple targets (designed polypharmacology). These compounds have been described as Designed Multiple Ligands (DMLs), and the process in which they are discovered and optimized is referred to as Multi Target Drug Discovery (MTDD). This chapter describes the current state of the art, challenges and future directions in this field.
Translational PET Imaging Research in Psychiatry
Authors: Hargreaves Richard J. , Rabiner Eugenii A.
Published: October 2012

The goal of any early central nervous system (CNS) drug development program is always to test the mechanism and not the molecule in order to support additional research investments in late-phase clinical trials. Confirmation that drugs reach their targets using translational positron emission tomography (PET) imaging markers of engagement is central to successful clinical proof-of-concept testing and has become an important feature of most neuropsychiatric drug development programs. CNS PET imaging can also play an important role in the clinical investigation of the neuropharmacological basis of psychiatric disease and the optimization of drug therapy.
NMR Spectroscopy in Food Analysis
Authors: Spyros Apostolos , Dais Photis
Published: October 2012

During the last two decades, the use of NMR spectroscopy for the characterization and analysis of food materials has flourished, and this trend continues to increase today. Currently, there exists no book that fulfils specifically the needs of food scientists that are interested in adding or expanding the use of NMR spectroscopy in their arsenal of food analysis techniques. Current books and monographs are rather addressed to experienced researchers in food analysis providing new information in the field. This book, written by acknowledged experts in the field, fills the gap by offering a day to day NMR guide for the food scientist, affording not only the basic theoretical aspects of NMR spectroscopy, but also practical information on sample preparation, experimental conditions and data analysis. Current developments in the field covered in this book are the availability of solid state NMR experiments such as CP/MAS and more importantly HR-MAS NMR for the analysis of semisolid foods, and the increasing use of chemometrics to analyze NMR data in food metabonomics. Moreover, this book contains an up to date discussion of MRI in food analysis including topics such as food processing and natural changes in food such as ripening. The book is a compact and complete source of information for food scientists who wish to apply methodologies based on NMR spectroscopy in food analysis. It contains information so far scattered in the primary literature, in NMR treatises and food analysis books, in a concise format that makes it appealing to food scientists who have no or minimal experience in magnetic resonance techniques. The inclusion of practical information about NMR instrumentation, experiment setup, acquisition and spectral analysis for the study of different food categories make this book a hands-on manual for food scientists wishing to implement novel NMR spectroscopy-based analytical techniques in their field.
Design of a heterotetravalent synthetic allergen that reflects epitope heterogeneity and IgE antibody variability to study mast cell degranulation
Authors: Handlogten Michael W. , Kiziltepe Tanyel , Bilgicer Basar
Published: October 2012

The present paper describes the design of a HtTA (heterotetravalent allergen) as a multi-component experimental system that enables an integrative approach to study mast cell degranulation. The HtTA design allows presentation of two distinct haptens, each with a valency of 2, thereby better reflecting the complexity of natural allergens by displaying epitope heterogeneity and IgE antibody variability. Using the HtTA design, synthetic allergens HtTA-1 and HtTA-2 were synthesized to model a combination of epitope/IgE affinities. HtTA-1 presented DNP (2,4-dinitrophenyl) and dansyl haptens (Kd=22 and 54 nM for IgEDNP and IgEdansyl respectively) and HtTA-2 presented dansyl and the weak-affinity DNP-Pro (DNP-proline) haptens (Kd=550 nM for IgEDNP). Both HtTAs effectively induced degranulation when mast cells were primed with both IgEDNP and IgEdansyl antibodies. Interestingly tetravalent DNP-Pro or bivalent dansyl were insufficient in stimulating a degranulation response, illustrating the significance of valency, affinity and synergy in allergen–IgE interactions. Importantly, maximum degranulation with both HtTA-1 and HtTA-2 was observed when only 50% of the mast cell-bound IgEs were hapten-specific (25% IgEdansyl and 25% IgEDNP). Taken together, results of the present study establish the HtTA system as a physiologically relevant experimental model and demonstrates its utility in elucidating critical mechanisms of mast cell degranulation.
Ribavirin-induced intracellular GTP depletion activates transcription elongation in coagulation Factor VII gene expression
Authors: Suzuki Atsuo , Miyawaki Yuhri , Okuyama Eriko , Murata Moe , Ando Yumi , Kato Io , Takagi Yuki , Takagi Akira , Murate Takashi , Saito Hidehiko , Kojima Tetsuhito
Published: October 2012

Coagulation FVII (Factor VII) is a vitamin K-dependent glycoprotein synthesized in hepatocytes. It was reported previously that FVII gene (F7) expression was up-regulated by ribavirin treatment in hepatitis C virus-infected haemophilia patients; however, its precise mechanism is still unknown. In the present study, we investigated the molecular mechanism of ribavirin-induced up-regulation of F7 expression in HepG2 (human hepatoma cell line). We found that intracellular GTP depletion by ribavirin as well as other IMPDH (inosine-5′-monophosphate dehydrogenase) inhibitors, such as mycophenolic acid and 6-mercaptopurine, up-regulated F7 expression. FVII mRNA transcription was mainly enhanced by accelerated transcription elongation, which was mediated by the P-TEFb (positive-transcription elongation factor b) complex, rather than by promoter activation. Ribavirin unregulated ELL (eleven-nineteen lysine-rich leukaemia) 3 mRNA expression before F7 up-regulation. We observed that ribavirin enhanced ELL3 recruitment to F7, whereas knockdown of ELL3 diminished ribavirin-induced FVII mRNA up-regulation. Ribavirin also enhanced recruitment of CDK9 (cyclin-dependent kinase 9) and AFF4 to F7. These data suggest that ribavirin-induced intracellular GTP depletion recruits a super elongation complex containing P-TEFb, AFF4 and ELL3, to F7, and modulates FVII mRNA transcription elongation. Collectively, we have elucidated a basal mechanism for ribavirin-induced FVII mRNA up-regulation by acceleration of transcription elongation, which may be crucial in understanding its pleiotropic functions in vivo.
Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes
Authors: Mackenzie Ruth M. , Salt Ian P. , Miller William H. , Logan Angela , Ibrahim Hagar A. , Degasperi Andrea , Dymott Jane A. , Hamilton Carlene A. , Murphy Michael P. , Delles Christian , Dominiczak Anna F.
Published: October 2012

The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced CAD. Endothelium-dependent vasodilation was impaired in patients with CAD and T2D relative to those with CAD alone. Levels of mitochondrial H2O2 and activity of AMPK were significantly elevated in primary HSVECs (human saphenous vein endothelial cells) from patients with CAD and T2D compared with those from patients with CAD alone. Incubation with the mitochondria-targeted antioxidant, MitoQ10 significantly reduced AMPK activity in HSVECs from patients with CAD and T2D but not in cells from patients with CAD alone. Elevated mtROS production in the endothelium of patients with CAD and T2D increases AMPK activation, supporting a role for the kinase in defence against oxidative stress. Further investigation is required to determine whether pharmacological activators of AMPK will prove beneficial in the attenuation of endothelial dysfunction in patients with CAD and T2D.
An initial and boundary-value problem for the Zakharov-Kuznestov equation in a bounded domain
Authors: Saut Jean-Claude , Temam Roger , Wang Chuntian
Published: October 2012

Motivated by the study of boundary control problems for the Zakharov-Kuznetsov equation, we study in this article the initial and boundary value problem for the ZK (short for Zakharov-Kuznetsov) equation posed in a limited domain Ω = (0, 1)x × (−π/2, π/2)d, d = 1, 2. This article is related to Saut and Temam [“An initial boundary-value problem for the Zakharov-Kuznetsov equation,” Adv. Differ. Equ. 15(11–12), 1001–1031 (2010)] in which the authors studied the same problem in the band \documentclass[12pt]{minimal}\begin{document}$(0,1)_{x}\times \mathbb R ^d,$\end{document}(0,1)x×Rd, d = 1, 2, but this article is not a straightforward adaptation of Saut and Temam [“An initial boundary-value problem for the Zakharov-Kuznetsov equation,” Adv. Differ. Equ. 15(11–12), 1001–1031 (2010)]; indeed many new issues arise, in particular, for the function spaces, due to the loss of the Fourier transform in the tangential directions (orthogonal to 0x). In this article, after studying a number of suitable function spaces, we show the existence and uniqueness of solutions for the linearized equation using the linear semigroup theory. We then continue with the nonlinear equation with the homogeneous boundary conditions. The case of the full nonlinear equation with nonhomogeneous boundary conditions especially needed for the control problems will be studied elsewhere.
Solar power conversion efficiency in modulated silicon nanowire photonic crystals
Authors: Deinega Alexei , John Sajeev
Published: October 2012

It is suggested that using only 1 μm of silicon, sculpted in the form of a modulated nanowire photonic crystal, solar power conversion efficiency in the range of 15%–20% can be achieved. Choosing a specific modulation profile provides antireflection, light trapping, and back-reflection over broad angles in targeted spectral regions for high efficiency power conversion without solar tracking. Solving both Maxwell's equations in the 3D photonic crystal and the semiconductor drift-diffusion equations in each nanowire, we identify optimal junction and contact geometries and study the influence of the nanowire surface curvature on solar cell efficiency. We demonstrate that suitably modulated nanowires enable 20% efficiency improvement over their straight counterparts made of an equivalent amount of silicon. We also discuss the efficiency of a tandem amorphous and crystalline silicon nanowire photonic crystal solar cell. Opportunities for “hot carrier” collection and up-conversion of infrared light, enhanced by photonic crystal geometry, facilitate further improvements in power efficiency.
Multiscale turbulence models based on convected fluid microstructure
Authors: Holm Darryl D. , Tronci Cesare
Published: October 2012

The Euler-Poincaré approach to complex fluids is used to derive multiscale equations for computationally modeling Euler flows as a basis for modeling turbulence. The model is based on a kinematic sweeping ansatz (KSA) which assumes that the mean fluid flow serves as a Lagrangian frame of motion for the fluctuation dynamics. Thus, we regard the motion of a fluid parcel on the computationally resolvable length scales as a moving Lagrange coordinate for the fluctuating (zero-mean) motion of fluid parcels at the unresolved scales. Even in the simplest two-scale version on which we concentrate here, the contributions of the fluctuating motion under the KSA to the mean motion yields a system of equations that extends known results and appears to be suitable for modeling nonlinear backscatter (energy transfer from smaller to larger scales) in turbulence using multiscale methods.
Tip preparation for near-field ablation at mid-infrared wavelengths
Authors: Hoffmann Joan A. , Gamari Benjamin , Raghu Deepa , Reeves M. E.
Published: October 2012

A fabrication method for high-throughput, fiber-based tips for near-field scanning microscopy (NSOM) in the mid-infrared (λ ∼ 3 μm) has been developed. Several fiber materials have been investigated and recipes for wet-chemical etching have been varied to produce tips that are physically robust and are capable of low-loss transmission of high-power pulses of mid-infrared light. Ultimately, wet-chemical etching techniques are used on glass fibers to produce tips capable of focusing mid-infrared light to ablate material from sub-micron-sized regions of organic films. The power throughput of the tips is significantly increased by using a novel material, previously unreported for NSOM applications: germanate fibers. The tips produced are mechanically strong and capable of transmitting high light fluence without sustaining physical damage. Here, the development of these tips and their performance are described.
Conformational transitions of weak polyacids grafted to nanoparticles
Authors: Barr S. A. , Panagiotopoulos A. Z.
Published: October 2012

The charge distribution on polyelectrolytes is a key factor, which controls their conformation and interactions. In weak polyelectrolytes, this distribution is determined by a number of factors, including the solvent conditions and local environment. In this work, we investigate charge distributions of chains end-grafted on a spherical nanoparticle in a salt solution, using grand canonical titration Monte Carlo simulations of a coarse-grained polymer model. In this approach, the ionization state of each polymer bead fluctuates based on the dissociation constant, pH of the solution, and interactions with other particles in the system. We determine charge and polymer conformations as functions of the pH and solvent quality. We compare the results to a fixed charge model and also investigate the role of grafting density and the effect of curvature on the film morphologies.
Enhanced low-noise gain from InAs avalanche photodiodes with reduced dark current and background doping
Authors: Maddox S. J. , Sun W. , Lu Z. , Nair H. P. , Campbell J. C. , Bank S. R.
Published: October 2012

We reduced the room temperature dark current in an InAs avalanche photodiode by increasing the p-type contact doping, resulting in an increased energetic barrier to minority electron injection into the p-region, which is a significant source of dark current at room temperature. In addition, by improving the molecular beam epitaxy growth conditions, we reduced the background doping concentration and realized depletion widths as wide as 5 μm at reverse biases as low as 1.5 V. These improvements culminated in low-noise InAs avalanche photodiodes exhibiting a room temperature multiplication gain of ∼80, at a record low reverse bias of 12 V.
Particle transport in a turbulent boundary layer: Non-local closures for particle dispersion tensors accounting for particle-wall interactions
Authors: Bragg A. , Swailes D. C. , Skartlien R.
Published: October 2012

Continuum equations derived from a probability density function kinetic equation contain dispersion tensors that describe the interaction between inertial particles and the underlying turbulent flow in which they are transported. These tensors require closure treatment and recent work has shown that traditional closure approximations perform poorly when applied to the case of particle dispersion in turbulent boundary layers. The dispersion tensors are intrinsically non-local, being sensitive to both the strong inhomogeneity of wall-bounded turbulence and the influence of particle-wall collisions. A new strategy for constructing non-local closure models is presented to account for such influences. An important feature of the approach is that it utilizes exactly the same input parameters required for the traditional closures. Differences between the two approaches are therefore a reflection of the improved closure strategy, rather than a consequence of improved or additional input data. Predictions from both new and standard models are compared with benchmark statistics obtained from the simulation of particle trajectories in a synthetic boundary layer flow, generated via an inhomogeneous kinematic simulation technique. The results demonstrate the significant advance offered by the new approach.
On the performance enhancement of adaptive signal averaging: A means for improving the sensitivity and rate of data acquisition in magnetic resonance and other analytical measurements
Authors: Cochrane C. J.
Published: October 2012

A few years back, our lab developed a signal averaging technique that greatly reduces the number of scans required to achieve a comparable signal-to-noise ratio to that of conventional signal averaging for continuous wave magnetic resonance measurements. We utilize an adaptive filter in a signal averaging scheme without any prior knowledge of the signal under observation. We termed this technique adaptive signal averaging (ASA). The technique was successful in reducing the noise variance by a factor of at least 10 in a single trace and is shown to converge in time by the same factor. ASA can also be useful in many other applications where signal averaging is utilized, such as medical imaging, electrocardiography, or electroencephalography. The purpose of this paper is to describe the advancements made to the technique, present a derivation of its performance enhancement, and illustrate the power of the technique through a set of simulations.
Heteroepitaxial VO2 thin films on GaN: Structure and metal-insulator transition characteristics
Authors: Zhou You , Ramanathan Shriram
Published: October 2012

Monolithic integration of correlated oxide and nitride semiconductors may open up new opportunities in solid-state electronics and opto-electronics that combine desirable functional properties of both classes of materials. Here, we report on epitaxial growth and phase transition-related electrical properties of vanadium dioxide (VO2) thin films on GaN epitaxial layers on c-sapphire. The epitaxial relation is determined to be (010)vo2‖(0001)GaN‖(0001)A12O3 and [100]vo2‖[1¯21¯0]GaN‖[011¯0]A12O3 from x-ray diffraction. VO2 heteroepitaxial growth and lattice mismatch are analyzed by comparing the GaN basal plane (0001) with the almost close packed corrugated oxygen plane in vanadium dioxide and an experimental stereographic projection describing the orientation relationship is established. X-ray photoelectron spectroscopy suggests a slightly oxygen rich composition at the surface, while Raman scattering measurements suggests that the quality of GaN layer is not significantly degraded by the high-temperature deposition of VO2. Electrical characterization of VO2 films on GaN indicates that the resistance changes by about four orders of magnitude upon heating, similar to epitaxial VO2 films grown directly on c-sapphire. It is shown that the metal-insulator transition could also be voltage-triggered at room temperature and the transition threshold voltage scaling variation with temperature is analyzed in the framework of a current-driven Joule heating model. The ability to synthesize high quality correlated oxide films on GaN with sharp phase transition could enable new directions in semiconductor-photonic integrated devices.
Toroidal rotation of multiple species of ions in tokamak plasma driven by lower-hybrid-waves
Authors: Zuo Yang , Wang Shaojie , Pan Chengkang
Published: October 2012

A numerical simulation is carried out to investigate the toroidal rotation of multiple species of ions and the radial electric field in a tokamak plasma driven by the lower-hybrid-wave (LHW). The theoretical model is based on the neoclassical transport theory associated with the anomalous transport model. Three species of ions (primary ion and two species of impurity ions) are taken into consideration. The predicted toroidal velocity of the trace impurities during the LHW injection agrees reasonably well with the experimental observation. It is shown that the toroidal rotation velocities of the trace impurity ions and the primary ions are close, therefore the trace impurity ions are representative of the primary ions in the toroidal rotation driven by the LHW.
Controllable plasmonic antennas with ultra narrow bandwidth based on silver nano-flags
Authors: Zhang Xiao-Yang , Zhang Tong , Hu A. , Song Yuan-Jun , Duley W. W.
Published: October 2012

We show theoretically plasmonic antennas based on two-step chemical synthesized silver nano-flags constructed by a silver nanowire and a nanoplate. The silver nano-flag antennas exhibit high polarization sensitivity and diversity of spectral signatures dependent on the structural parameters arising from the observed mode competition. With specific configuration engineering, the antennas show controllable electric-field enhancement and ultra narrow bandwidths down to about 2 nm. These nano-antennas promise exciting applications in lasing spaser, optical modulation, and enhanced nonlinear processes.
Power storage options for hybrid electric vehicles—A survey
Authors: Ahmed Sher Hadeed , Addoweesh Khaled E.
Published: October 2012

Hybrid electric vehicles (HEVs) are the future transportation structure as they provide better fuel economy. Energy storage devices are therefore required for the HEVs. The problem for deciding the optimum combination of power storage is still unresolved. The power storage options in this regard must have a feasible weight/energy ratio for better performance. This survey is about the comparison of different power storage options for HEV including the batteries, super-capacitors, and flywheel. The equivalent circuit for the potential storage devices given will help in establishing the optimum choice of energy storage.
Shifting from marine reserves to maritime zoning for conservation of Pacific bigeye tuna (
Thunnus obesus
)
Authors: Sibert John , Senina Inna , Lehodey Patrick , Hampton John
Published: October 2012

Over 50% of the total bigeye tuna (BET) landed in the Western Central Pacific Ocean is caught incidentally in the purse seine fishery and sold for canning at prices less than US$2/kg. The remainder is landed in longline fisheries directed at BET and sold as fresh or frozen tuna at prices greater than US$10/kg. The combined fishing mortality by all gears will soon reduce the BET biomass in the Pacific Ocean to less than that capable of producing maximum sustainable yield. Closure of the high-seas enclaves in 2009 was hailed as a conservation measure, but was not scientifically evaluated before implementation and appears to have had no beneficial effect on the BET stock. A spatially explicit age-structured ecosystem model, SEAPODYM, is used to simulate alternative area-based fishery management policies to conserve bigeye tuna in the Western Central Pacific Ocean. Closing the high-seas enclaves to purse seine fishing has negligible effect on the BET biomass. Fishery management policies that control mortality on both juveniles and adults, through prohibition of fish aggregation devices in the purse seine fishery and restrictions on longline fishing in spawning areas, are the most efficient conservation policies. Large-scale benefits from bigeye conservation measures will become apparent only in the 2030s, assuming timely implementation and minimal effects of climate change.
Transcriptional burst frequency and burst size are equally modulated across the human genome
Authors: Dar Roy D. , Razooky Brandon S. , Singh Abhyudai , Trimeloni Thomas V. , McCollum James M. , Cox Chris D. , Simpson Michael L. , Weinberger Leor S.
Published: October 2012

Gene expression occurs either as an episodic process, characterized by pulsatile bursts, or as a constitutive process, characterized by a Poisson-like accumulation of gene products. It is not clear which mode of gene expression (constitutive versus bursty) predominates across a genome or how transcriptional dynamics are influenced by genomic position and promoter sequence. Here, we use time-lapse fluorescence microscopy to analyze 8,000 individual human genomic loci and find that at virtually all loci, episodic bursting—as opposed to constitutive expression—is the predominant mode of expression. Quantitative analysis of the expression dynamics at these 8,000 loci indicates that both the frequency and size of the transcriptional bursts varies equally across the human genome, independent of promoter sequence. Strikingly, weaker expression loci modulate burst frequency to increase activity, whereas stronger expression loci modulate burst size to increase activity. Transcriptional activators such as trichostatin A (TSA) and tumor necrosis factor α (TNF) only modulate burst size and frequency along a constrained trend line governed by the promoter. In summary, transcriptional bursting dominates across the human genome, both burst frequency and burst size vary by chromosomal location, and transcriptional activators alter burst frequency and burst size, depending on the expression level of the locus.
BELIEVING AND BELONGING IN EUROPE
Authors: Reitsma Jan , Pelzer Ben , Scheepers Peer , Schilderman Hans
Published: October 2012

This paper investigates (trends and determinants of) individual combinations of religious believing and belonging in Europe from a cross-national and longitudinal perspective. Individual level data for the period 1981–2007 in 42 countries derived from the European Values Survey and the European Social Survey are harmonised and enriched with contextual characteristics, constituting a more comprehensive data base for Europe than any previous research. Complementary hypotheses from modernisation and market theories are derived systematically and tested rigorously. We find differential trends. In western societies, the popularity of secularity and consistent religiosity has persisted. In former communist societies, the popularity of consistent religiosity has increased whereas secularity has decreased. In both western and former communist societies, solitary religiosity has been a clear yet small phenomenon, somewhat increasing in western societies and somewhat decreasing in former communist societies. A crucial hypothesis derived from modernisation theories, stating that financial and social security would decrease consistent religiosity, is empirically supported.
Exploring the processes involved in long‐term recovery from chronic alcohol addiction within an abstinence‐based model: Implications for practice
Authors: Gubi Peter Madsen , Marsden-Hughes Howard
Published: October 2012

Background: There is little consensus at policy or treatment level as to what defines ‘recovery’ in the alcohol addiction field. Aim: From interviewing a cohort of eight severely alcohol‐dependent people who fulfilled all categories of DSM‐IV and ICD 10 diagnostic criteria and had achieved long‐term recovery (LTR) of between 8 and 48 years, and who are long‐term AA members, a definition of recovery that is inclusive, and achievable, was sought from their lived experiences. Methodology: Interpretative Phenomenological Analysis was used. Findings: This research uncovers the processes involved in long‐term recovery, and identifies them as: sober; maintaining sobriety; and recovery. It suggests a move away from the acute model of cure by brief, time‐limited therapy, towards a model of sustained, on‐going and life‐long recovery management, combined with pro‐social aid resources. Individuals need to observe, and hear, the success narratives of others, and the therapeutic conditions of empathy, unconditional positive regard and congruence need to be strongly experienced by the individual.
Upper body force production after a low‐volume static and dynamic stretching
Authors: Leone D. C. P. G. , Pezarat P. , Valamatos M. J. , Fernandes O. , Freitas S. , Moraes A. C.
Published: October 2012

This study investigated the acute effect of a low‐volume static and dynamic stretching on maximal isometric peak force (MIPF), time to maximal isometric force (TMIF), rate of force production (RFP) and average amplitude of the surface EMG (AvgEMG) of the main agonist muscles acting on the bench press maximum isometric force exercise. Thirty subjects were randomly divided into three groups: static stretch (SG: 22.8±5.6 years, 176.6±3.5 cm, 74.4±5.9 kg), dynamic stretch (DG: 21.4±3.9 years, 178.4±7.2 cm, 71.7±8.2 kg) and control group (CG: 20.4±3.6 years, 179.8±5.8 cm, 74.4±9.8 kg). SG performed two 30‐s repetitions and DG performed 10 repetitions of each of the two different exercises for the pectoralis major and triceps brachii. The MIPF, TMIF, RFP and AvgEMG of the pectoralis major (sternocostal part) and triceps brachii (long and lateral head) were measured before and immediately after the stretching protocols. A significant decrease in the MIPF from pre‐ to post‐stretching was observed in both SG (p <0.001) and DG (p <0.05). No significant differences were found in the CG for all force parameters. No significant differences in the TMIF and RFP from pre‐ to post‐stretching were found in the three groups. The SG showed a significant (p <0.05) decrease in the AvgEMG of the three muscles, whereas no significant differences were found for the DG and CG. These findings suggest that a low‐volume static and dynamic stretching adversely affects efforts of muscle maximal strength of the upper limb muscles studied, but it does not seem to affect TMIF or RFP.
Length, width and centroid distance as measures of teams tactical performance in youth football
Authors: Folgado Hugo , Lemmink Koen A. P. M. , Frencken Wouter , Sampaio Jaime
Published: October 2012

Small‐sided games are commonly used in training and teaching contexts of football. However, few studies have focused on the tactical implications of this type of drills. The aim of this study is to identify how tactical collective behaviour varies with age in different small‐sided game formats. We investigated the in‐game field position in three different age groups of youth football players [under‐9 (n=10; age = 8.5±0.53), under‐11 (n=10; age = 10.4±0.52) and under‐13 (n=10; age = 12.7±0.48)], participating in two different small‐sided game conditions (GK + 3×3 + GK and GK + 4×4 + GK). A team variable was created based on the players’ length per width ratio (lpwratio), and a match variable was calculated as the distance between the centroid of the two teams. Results show that team variable values were influenced by the age of the players, as younger teams tend to present a higher value of lpwratio in their dispersion on the pitch. The variability of this variable also showed a decrease for teams with older players, suggesting a more consistent application of the width (stretching and creating space) and concentration (compressing into a confined area) principles of play and reflecting a higher level of collective tactical behaviour. Match variable showed a larger centroid distance for the older age groups in comparison with the younger players in the GK + 3×3 + GK, while all age groups demonstrated similar large centroid distances in the GK + 4×4 + GK game format. These results suggest that length and width ratio and centroid distance are useful measures of tactical performance in small‐sided games in youth football.
Rapid communication: The fate of being forgotten: Information that is initially forgotten is judged as less important
Authors: Castel Alan D. , Rhodes Matthew G. , McCabe David P. , Soderstrom Nicholas C. , Loaiza Vanessa M.
Published: October 2012

Is forgotten information deemed less important than remembered information? The present study examined potential biases regarding the importance of information that was initially forgotten. In Experiment 1 participants studied words paired with varying point values that denoted their importance and were encouraged to recall higher value words. Participants recalled more high-value words on an initial test. However, on a later cued recall test for the values, initially forgotten words were rated as less valuable than remembered words. Experiment 2 used a similar procedure with the exception that participants rated the importance of traits when evaluating a significant other (e.g., honest, intelligent). Participants were more likely to recall highly valued traits but regarded forgotten traits as less valuable than remembered traits. These results suggest that a forgetting bias exists: If information is initially forgotten, it is later deemed as less important.
Opportunities for Building Social-Ecological Resilience in New Mexico Forest Communities
Authors: Roybal M. A. , Benson M. H.
Published: October 2012

The forest lands of northern New Mexico are a contested landscape fraught with conflicts over ownership, resource exploitation and land fraud. Partly in recognition of this, the US Forest Service established the Vallecitos Federal Sustained Yield in 1948 under the relatively obscure Sustained Yield Forest Management Act of 1944 to promote the “stability” of rural Hispano communities and the sustained yield of forest products. The Unit, however, has failed to live up to its promise. This paper explores the concept of resilience as a new way of looking at this ongoing conflict and examines its potential to support future policies for management of the Unit and other public lands.
Climate Change and Human Capital Accumulation: Educational Decisions under Resource Scarcity and Uncertainty
Authors: Ranjan Ram
Published: October 2012

Climate change is forcing large scale structural changes in agrarian sectors in the developing world by adversely affecting water resources and threatening the viability of future agriculture. In the most drought affected regions, farmers must explore alternative skills for themselves and their children when faced with unsustainable livelihoods. In this paper, a stylized decision model of skill acquisition is developed in which farmers face the risk of an irreversible loss of groundwater due to climate change. Findings indicate that the risk of groundwater loss promotes higher efforts towards skill acquisition, in general, but skill seeker's own learning capabilities play an important role in determining the eventual outcome. Additionally, groundwater resources are depleted to fund skill acquisition through education, but when rate of skill depreciation is large or differences between skilled wages and agricultural income are small, groundwater depletion is delayed. A non-linear relationship between skill acquisition and groundwater sustainability emerges.
Adaptive Management and Scale in a Flood-Pulsed Ecosystem—the Case of the Okavango Delta Management Plan, Botswana
Authors: Motsumi Sekgowa , Cassidy Lin
Published: October 2012

The flood pulse, as the main driver of Botswana's Okavango Delta system, creates variable responses in terms of its biophysical, socioeconomic aspects which presents challenges for its management. This, along with the perturbation caused by substantially increased human impacts in the last few decades, has led to the initiation of a systematic framework for management, the Okavango Delta Management Plan (ODMP). This paper analyses the extent to which the ODMP accommodates adaptive management principles in its implementation, and focuses on the scale aspects of institutional arrangements, still founded on administrative, not social-ecological, boundaries. Specifically, we examine the hierarchy of decision-making and highlight the challenges associated with scale mismatch. Centralized sectoral decision-making has prevented the ODMP being adopted as all parties' responsibility. Scale effects compound this, because decision-making at the national level challenges the implementing district level's efforts at transdisciplinary responses. Nevertheless, capacity-building on the ground means that district officers are increasingly adopting integrated, collaborative responses to management issues.
Establishing epithelial glandular polarity: interlinked roles for ARF6, Rac1, and the matrix microenvironment
Authors: Monteleon Christine L. , Sedgwick Alanna , Hartsell Alyssa , Dai Michael , Whittington Catherine , Voytik-Harbin Sherry , D'Souza-Schorey Crislyn
Published: October 2012

Epithelial cysts comprise the structural units of the glandular epithelium. Although glandular inversion in epithelial tumors is thought to be a potential mechanism for the establishment of metastatic disease, little is known about the morphogenic cues and signaling pathways that govern glandular polarity and organization. Using organotypic cultures of Madin-Darby canine kidney cells in reconstituted basement membrane, we show that cellular depletion of the small GTP-binding protein ARF6 promotes the formation of inverted cysts, wherein the apical cell membrane faces the cyst exterior, and the basal domain faces the central lumen, while individual cell polarity is maintained. These cysts are also defective in interactions with laminin at the cyst–matrix interface. This inversion of glandular orientation is accompanied by Rac1 inactivation during early cystogenesis, and temporal activation of Rac1 is sufficient to recover the normal cyst phenotype. In an unnatural collagen I microenvironment, ARF6-depleted, inverted epithelial cysts exhibit some loss of cell polarity, a marked increase in Rho activation and Rac1 inactivation, and striking rearrangement of the surrounding collagen I matrix. These studies demonstrate the importance of ARF6 as a critical determinant of glandular orientation and the matrix environment in dictating structural organization of epithelial cysts.
DrosophilaFascin is a novel downstream target of prostaglandin signaling during actin remodeling
Authors: Groen Christopher M. , Spracklen Andrew J. , Fagan Tiffany N. , Tootle Tina L.
Published: October 2012

Although prostaglandins (PGs)—lipid signals produced downstream of cyclooxygenase (COX) enzymes—regulate actin cytoskeletal dynamics, their mechanisms of action are unknown. We previously established Drosophila oogenesis, in particular nurse cell dumping, as a new model to determine how PGs regulate actin remodeling. PGs, and thus the Drosophila COX-like enzyme Pxt, are required for both the parallel actin filament bundle formation and the cortical actin strengthening required for dumping. Here we provide the first link between Fascin (Drosophila Singed, Sn), an actin-bundling protein, and PGs. Loss of either pxt or fascin results in similar actin defects. Fascin interacts, both pharmacologically and genetically, with PGs, as reduced Fascin levels enhance the effects of COX inhibition and synergize with reduced Pxt levels to cause both parallel bundle and cortical actin defects. Conversely, overexpression of Fascin in the germline suppresses the effects of COX inhibition and genetic loss of Pxt. These data lead to the conclusion that PGs regulate Fascin to control actin remodeling. This novel interaction has implications beyond Drosophila, as both PGs and Fascin-1, in mammalian systems, contribute to cancer cell migration and invasion.
Myosin Vs organize actin cables in fission yeast
Authors: Lo Presti Libera , Chang Fred , Martin Sophie G.
Published: October 2012

Myosin V motors are believed to contribute to cell polarization by carrying cargoes along actin tracks. In Schizosaccharomyces pombe, Myosin Vs transport secretory vesicles along actin cables, which are dynamic actin bundles assembled by the formin For3 at cell poles. How these flexible structures are able to extend longitudinally in the cell through the dense cytoplasm is unknown. Here we show that in myosin V (myo52 myo51) null cells, actin cables are curled, bundled, and fail to extend into the cell interior. They also exhibit reduced retrograde flow, suggesting that formin-mediated actin assembly is impaired. Myo52 may contribute to actin cable organization by delivering actin regulators to cell poles, as myoV∆ defects are partially suppressed by diverting cargoes toward cell tips onto microtubules with a kinesin 7–Myo52 tail chimera. In addition, Myo52 motor activity may pull on cables to provide the tension necessary for their extension and efficient assembly, as artificially tethering actin cables to the nuclear envelope via a Myo52 motor domain restores actin cable extension and retrograde flow in myoV mutants. Together these in vivo data reveal elements of a self-organizing system in which the motors shape their own tracks by transporting cargoes and exerting physical pulling forces.
CLEVER: clique-enumerating variant finder
Authors: Marschall Tobias , Costa Ivan G. , Canzar Stefan , Bauer Markus , Klau Gunnar W. , Schliep Alexander , Schönhuth Alexander
Published: October 2012

Motivation: Next-generation sequencing techniques have facilitated a large-scale analysis of human genetic variation. Despite the advances in sequencing speed, the computational discovery of structural variants is not yet standard. It is likely that many variants have remained undiscovered in most sequenced individuals.

Results: Here, we present a novel internal segment size based approach, which organizes all, including concordant, reads into a read alignment graph, where max-cliques represent maximal contradiction-free groups of alignments. A novel algorithm then enumerates all max-cliques and statistically evaluates them for their potential to reflect insertions or deletions. For the first time in the literature, we compare a large range of state-of-the-art approaches using simulated Illumina reads from a fully annotated genome and present relevant performance statistics. We achieve superior performance, in particular, for deletions or insertions (indels) of length 20–100 nt. This has been previously identified as a remaining major challenge in structural variation discovery, in particular, for insert size based approaches. In this size range, we even outperform split-read aligners. We achieve competitive results also on biological data, where our method is the only one to make a substantial amount of correct predictions, which, additionally, are disjoint from those by split-read aligners.

Availability: CLEVER is open source (GPL) and available from http://clever-sv.googlecode.com.

Contact:  as@cwi.nl or tm@cwi.nl

Supplementary information:  Supplementary data are available at Bioinformatics online.
Network-based inference from complex proteomic mixtures using SNIPE
Authors: Nusinow David P. , Kiezun Adam , O’Connell Daniel J. , Chick Joel M. , Yue Yingzi , Maas Richard L. , Gygi Steven P. , Sunyaev Shamil R.
Published: October 2012

Motivation: Proteomics presents the opportunity to provide novel insights about the global biochemical state of a tissue. However, a significant problem with current methods is that shotgun proteomics has limited success at detecting many low abundance proteins, such as transcription factors from complex mixtures of cells and tissues. The ability to assay for these proteins in the context of the entire proteome would be useful in many areas of experimental biology.

Results: We used network-based inference in an approach named SNIPE (Software for Network Inference of Proteomics Experiments) that selectively highlights proteins that are more likely to be active but are otherwise undetectable in a shotgun proteomic sample. SNIPE integrates spectral counts from paired case–control samples over a network neighbourhood and assesses the statistical likelihood of enrichment by a permutation test. As an initial application, SNIPE was able to select several proteins required for early murine tooth development. Multiple lines of additional experimental evidence confirm that SNIPE can uncover previously unreported transcription factors in this system. We conclude that SNIPE can enhance the utility of shotgun proteomics data to facilitate the study of poorly detected proteins in complex mixtures.

Availability and Implementation: An implementation for the R statistical computing environment named snipeR has been made freely available at http://genetics.bwh.harvard.edu/snipe/.

Contact:  ssunyaev@rics.bwh.harvard.edu

Supplementary information: Supplementary data are available at Bioinformatics online.