bluuebunny/crossref_metadata_2025 huggingface dataset:
Mass balance and metabolism of aclidinium bromide following intravenous administration of [14C]‐aclidinium bromide in healthy subjects
Authors: Ortiz Stephan , Flach Stephen , Ho John , Li Fanying , Caracta Cynthia F. , Gil Esther Garcia , Jansat Josep M.
Published: January 2012

Aclidinium bromide is a novel, inhaled long‐acting muscarinic antagonist with low systemic activity developed for the treatment of COPD. It is an ester compound rapidly hydrolysed in plasma into inactive alcohol and acid metabolites. In this Phase I, open‐label study, the rates and routes of elimination of radioactivity following intravenous administration of [14 C]‐aclidinium bromide were determined. The metabolites of aclidinium were also characterized and identified in plasma and excreta. Twelve healthy males were randomized (1:1) to receive a single intravenous 400 µg dose of [phenyl‐U‐14 C]‐ or [glycolyl‐U‐14 C]‐aclidinium bromide (via 5 min infusion) to label alcohol or acid metabolites of aclidinium, respectively. Safety and tolerability were assessed over a 9‐day period. Following intravenous administration, the parent compound was rapidly hydrolysed into its acid and alcohol metabolites. Primary excretion routes for [phenyl‐U‐14 C]‐ and [glycolyl‐U‐14 C]‐aclidinium were renal (urine: 65% and 54%, respectively; feces: 33% and 20%, respectively), with 1% excreted as unchanged aclidinium. A total of three treatment‐emergent adverse events in two subjects were reported and were related to infusion site pain. Overall, aclidinium is rapidly hydrolysed into two main metabolites, which are predominantly excreted in urine. Aclidinium bromide 400 µg administered intravenously was safe and well tolerated in healthy subjects. Copyright © 2012 John Wiley & Sons, Ltd.
The enhanced pre‐ and postnatal study for nonhuman primates: Update and perspectives
Authors: Weinbauer Gerhard F. , Fuchs Antje , Niehaus Michael , Luetjens Craig M.
Published: January 2012

The enhanced pre‐ and postnatal (ePPND) study design has been developed in response to new scientific knowledge and subsequent guideline changes, that is, ICH M3(R2) and ICH S6(R1). The design changes were basically driven by the experiences obtained during preclinical development of biopharmaceuticals. The ePPND concept typically does not apply to pharmaceuticals. In essence, the ePPND design is a PPND study in which key elements of an embryofetal development (EFD) study are being investigated in newborns and infants rather than in the fetus. The current relevant nonhuman primate model is the cynomolgus monkey. The ICH S6(R1) has reached step 4 during June 2011 and provides detailed recommendations on various parameters and the conduct of an ePPND study. By the time this article is written, it appears that for monoclonal antibodies, the ePPND study is the preferred approach although ICH S6(R1) also leaves options for modified EFD and PPND study concepts. Our data also demonstrate that social housing is feasible for developmental toxicity studies in the cynomolgus monkey model. Birth Defects Research (Part C) 93:324–333, 2011. © 2012 Wiley Periodicals, Inc.
Adsorption Characteristics of Atrazine on Granulated Activated Carbon and Carbon Nanotubes
Authors: Rambabu N. , Guzman C. A. , Soltan J. , Himabindu V.
Published: January 2012

Adsorption of atrazine (ATZ) from aqueous solutions by granular activated carbon (GAC) and carbon nanotubes (CNT) was studied in a batch‐mode adsorption system at different initial concentrations of ATZ (1.0–30.0 mg L–1) and at three temperatures of 288, 296 and 304 K. The adsorption isotherms of Langmuir, Freundlich, Polanyi–Manes, and Brunauer–Emmett–Teller (modified) were used to model the process. The adsorption kinetics followed a pseudo‐second‐order kinetic model. The thermodynamic parameters ΔH0, ΔS0, and ΔG0 of the adsorption were estimated. The thermodynamic parameters indicate that the adsorption process is spontaneous and exothermic.
Real‐time simulation of surgery by reduced‐order modeling and X‐FEM techniques
Authors: Niroomandi S. , Alfaro I. , González D. , Cueto E. , Chinesta F.
Published: January 2012

This paper describes a novel approach for the simulation of surgery by a combined technique of model order reduction and extended finite element method (X‐FEM) methods. Whereas model order reduction techniques employ globally supported (Ritz) shape functions, a combination with X‐FEM methods on a locally superimposed patch is developed for cutting simulation without remeshing. This enables to obtain models with very few degrees of freedom that run under real‐time constrains even for highly non‐linear tissue constitutive equations. To show the performance of the technique, we studied an application to refractive surgery in the cornea. Copyright © 2012 John Wiley & Sons, Ltd.
How to Define, Find and Classify Side Effects in Psychotherapy: From Unwanted Events to Adverse Treatment Reactions
Authors: Linden Michael
Published: January 2012

Objective

Empirical research on the negative effects of psychotherapy is insufficient, partly because there is a lack of theoretical concept on how to define, classify and assess psychotherapy side effects. This paper proposes a model for the definition, classification and assessment of psychotherapy side effects.

Method

Definitions are provided for ‘unwanted events’, ‘treatment‐emergent reactions’, ‘adverse treatment reactions’, ‘malpractice reactions’, ‘treatment non‐response’, ‘deterioration of illness’, ‘therapeutic risks’ and ‘contraindications’. We describe processes analysing the causality of negative events and the correctness of treatment.

Result

A procedural model on how to find, classify and evaluate negative events is described, the unwanted event to adverse treatment reaction (UE–ATR) checklist.

Conclusion

Recognition of adverse treatment effects is a characteristic of good therapists and treatments. Psychotherapists should be sensitive for negative effects. This can help improve the quality of treatment. The UE–ATR checklist can be used in psychotherapy trials, quality assurance, clinical practice and training of psychotherapists.Copyright © 2012 John Wiley & Sons, Ltd.

Key Practitioner Message

If you do not find adverse treatment effects, then ask yourself why and do not assume that there are no side effects.

The detection and management of adverse treatment effects is not a sign of bad but of good clinical practice.
Application of Metal‐Based Reagents and Catalysts in Microstructured Flow Devices
Authors: Chinnusamy Tamilselvi , Yudha S Salprima , Hager Markus , Kreitmeier Peter , Reiser Oliver
Published: January 2012

Over the years, organic synthesis has witnessed several improvements through the development of new chemical transformations or more efficient reagents for known processes. Likewise, technological advances, aiming at speeding up reactions and facilitating their work‐up, have established themselves in academic as well as in industrial laboratories. In this Minireview, we highlight very recent developments in flow chemistry, focusing on organometallic reagents and catalysts. First, we describe reactions with homogeneous catalysts immobilized on different support materials using the concept of packed bed reactors. In the last chapter, we will discuss applications that utilize organometallic reagents.
Analysis and design of a dual‐mode control flyback converter
Authors: Lo Yu‐Kang , Lin Jing‐Yuan , Wang Chao‐Fu
Published: January 2012

This letter presents a dual‐mode control scheme to improve the efficiency of a flyback converter in a wide load range. The proposed flyback converter features a novel dual‐mode operation. The valley‐switching technique is adopted to reduce the switching loss at light load. On the other hand, the fixed off‐time (FOT) controls with continuous conduction mode operations decrease the conduction losses at heavy load. The principles and design procedures of the proposed dual‐mode controller are discussed and analyzed. Finally, a 140‐W dual‐mode flyback converter with an output voltage of 19 V is implemented. Experimental results agree with the theoretical analysis. Copyright © 2012 John Wiley & Sons, Ltd.
Calculations of Electrical Conductivity of Ag and Au Plasma
Authors: Apfelbaum E. M.
Published: January 2012

The conductivity of silver and gold plasma is calculated within the relaxation‐time approximation at T ≥ 10 kK. The most accurate at present time momentum cross‐section for electron‐atom scattering was used. The ionic composition of plasma was calculated by means of generalized chemical model (GCM). The results of calculation were compared with the available data of others researchers (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Bound States in Coulomb Systems ‐ Old Problems and New Solutions
Authors: Ebeling W. , Kraeft W.D. , Röpke G.
Published: January 2012

We analyze the quantum statistical treatment of bound states in Hydrogen considered as a system of electrons and protons. Within this physical picture we calculate analytically isotherms of pressure for Hydrogen in a broad density region and compare to some results from the chemical picture. Our study is restricted to the range of intermediate temperatures 104K < T < 105K and not too high densities n < 1024 protons per cm3, the formation of molecules is neglected. First we resume in detail the two transitions along isotherms:

(i) formation of bound states occurring by increasing the density from low to moderate values,

(ii) the destruction of bound states in the high density region, modelled here by Pauli‐Fock effects. Avoiding chemical models we will show, why bound states according to a discrete part of the spectra occur only in a valley in the T‐p plane. First we study virial expansions in the canonical ensemble and then in the grand canonical ensemble. We show that in fugacity representations the population of bound states saturates at higher density and that a combination of both representations provides quickly converging equations of state. In the case of degenerate systems we calculated first the density‐dependent energy levels, and find the pressure in Hartree‐Fock‐Wigner approximation showing the prominent role of Pauli blocking and Fock effects in the selfenergy (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dynamic Dust Particle Confinement in Corona Discharge Plasma
Authors: Filinov V. S. , Lapitsky D. S. , Deputatova L. V. , Vasilyak L. M. , Vladimirov V. I. , Sinkevich O. A.
Published: January 2012

Usually electrostatic fields created by electrodes of the trap are used for dust particle confinement in plasma devices. In this work the possibility of the dust particle confinement by electrodynamic fields is investigated for improved quadrupole traps. The behavior of dust particles is simulated by Brownian dynamics. Dust particle parameters and parameters of the traps needed for dust particle confinement have been obtained (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Atomic Ionization and Molecular Dissociation in a Hydrogen Gas within the Physical Picture
Authors: Alastuey A. , Ballenegger V.
Published: January 2012

We study a hydrogen gas at low densities within the physical picture. Recombination processes leading to the formation of atoms and molecules are properly taken into account via the well‐known Ebeling function and a new four‐body partition function. Our method provides a reliable equation of state which covers the plasma, atomic and molecular phases (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Joint Effects of Risk Status, Gender, Early Literacy and Cognitive Skills on the Presence of Dyslexia Among a Group of High‐Risk Chinese Children
Authors: Wong Simpson W. L. , McBride‐Chang Catherine , Lam Catherine , Chan Becky , Lam Fanny W. F. , Doo Sylvia
Published: January 2012

This study sought to examine factors that are predictive of future developmental dyslexia among a group of 5‐year‐old Chinese children at risk for dyslexia, including 62 children with a sibling who had been previously diagnosed with dyslexia and 52 children who manifested clinical at‐risk factors in aspects of language according to testing by paediatricians. The age‐5 performances on various literacy and cognitive tasks, gender and group status (familial risk or language delayed) were used to predict developmental dyslexia 2 years later using logistic regression analysis. Results showed that greater risk of dyslexia was related to slower rapid automatized naming, lower scores on morphological awareness, Chinese character recognition and English letter naming, and gender (boys had more risk). Three logistic equations were generated for estimating individual risk of dyslexia. The strongest models were those that included all print‐related variables (including speeded number naming, character recognition and letter identification) and gender, with about 70% accuracy or above. Early identification of those Chinese children at risk for dyslexia can facilitate better dyslexia risk management. Copyright © 2012 John Wiley & Sons, Ltd.

Practitioner Points

Pre‐diagnostic screening is useful to assess the presence of future dyslexia among children at risk for dyslexia.

Individual risk can be estimated with more than one logistic regression equation containing different combinations of predictors of future dyslexia.

Print‐related skills have strong associations with future dyslexia in Chinese children.

Gender is an important factor in predicting future dyslexia, but it is not advisable to give differential attention based on gender.
Boundary crossing and non‐linear theory in earth‐system sciences – a proof of concept based on tsunami and post‐eruption scenarios on Java Island, Indonesia
Authors: Gomez Christopher , Soltanzadeh Iman
Published: January 2012

Although volcanic eruptions are well‐known to be the trigger of some weather and climatic changes, land‐cover changes by pyroclastic‐flows and lahars do not get this recognition, neither do major hazards such as tsunami. These two earth processes are even lesser considered as being able to modify other earth processes they are not directly connected to, such as landslides or river discharge in non‐connected basins more than a hundred kilometres away. In this contribution the authors argue that these ideas are mainly driven by the process of being ‘educated’ in a single academic discipline and once put to the test interactions and retroactions between earth processes and atmospheric processes are far more reaching than commonly thought. For this study, the site of Java Island (Indonesia) was chosen to conduct (1) an analysis of a major tsunami impact – in the same area as the 2006 Java tsunami and (2) an analysis of the post‐eruption impacts of Merapi Volcano after a major eruption – excluding any ejecta in the atmosphere for the sake of the demonstration. The atmospheric feedback simulations were conducted using the regional climate model (RegCM‐4) with calibration from weather stations in Java Island. As a result, both simulations have proven that large scale deposits of pyroclasts (not introducing the ejectas sent in the atmosphere) and tsunamis can have outstanding impacts on the atmospheric situation and the bio‐geomorphologic evolution of the landscape in the following weeks to months. Interestingly enough these impacts are not limited to the area impacted by the earth process and the effect are not linear in time as they work following thresholds. These rainfalls ‘tele‐impacts’ are important enough to, in turn, modify earth‐surface processes in areas remote from the original phenomenon. This system acts in the same manner as a famous butterfly in Africa that could trigger a hurricane on the other side of the Atlantic Ocean. Copyright © 2012 John Wiley & Sons, Ltd.
The response of CO2 flux to rain pulses at a saline desert
Authors: Ma Jie , Zheng Xin‐Jun , Li Yan
Published: January 2012

As the substantial component of the ecosystem respiration, soil CO2 flux is strongly influenced by infrequent and unpredictable precipitation in arid region. In the current study, we investigated the response of soil CO2 flux to rain pulses at a saline desert in western China. Soil CO2 flux was measured continuously during the whole growing season of 2009 at six sites. We found that there were remarkable changes in amplitude or diurnal patterns of soil CO2 flux induced by rainfall events: from bimodal before rain to a single peak after that. Further analysis indicated that there is a significant linear relationship (P < 0.001) between soil CO2 flux and soil temperature (Tsoil). However, a hysteresis between the waveform of diurnal course of CO2 flux and Tsoil was observed: with soil CO2 flux always peaked earlier than Tsoil. Furthermore, a double exponential decay function was fitted to the soil CO2 flux after rainfall, and total carbon (C) releases were estimated by numerical integration for rainfall events. The relative enhancement and total C release, in association with the rain pulses, was linearly related to the amount of precipitation. According to the size and frequency of rainfall events, the total amount of C release induced by rain pulses was computed as much as 7.88 g C·m–2 in 2009, equivalent to 10.25% of gross primary production. These results indicated that rain pulses played a significant role in the carbon budget of this saline desert ecosystem, and the size of them was a good indicator of rain‐induced flux enhancement. Copyright © 2012 John Wiley & Sons, Ltd.
Bone turnover markers correlate with implant fixation in a rat model using LPS‐doped particles to induced implant loosening
Authors: Liu Shuo , Virdi Amarjit S. , Sena Kotaro , Hughes W. Frank , Sumner Dale R.
Published: January 2012

Revision surgery for particle‐induced implant loosening in total joint replacement is expected to increase dramatically over the next few decades. This study was designed to investigate if local tissue and serum markers of bone remodeling reflect implant fixation following administration of lipopolysaccharide (LPS)‐doped polyethylene (PE) particles in a rat model. Twenty‐four rats received bilateral implantation of intramedullary titanium rods in the distal femur, followed by weekly bilateral intra‐articular injection of either LPS‐doped PE particles (n= 12) or vehicle that contained no particles (n= 12) for 12 weeks. The group in which the particles were injected had increased serum C‐terminal telopeptide of type I collagen (CTX‐I), decreased serum osteocalcin (OC), increased peri‐implant eroded surface, decreased peri‐implant bone volume, and decreased mechanical pull‐out strength compared to the controls. Implant fixation strength was positively correlated with peri‐implant bone volume and serum OC and inversely correlated with serum CTX‐I, while energy to yield was positively correlated with serum OC and inversely correlated with the number of tartrate‐resistant acid phosphatase positive cells at the interface and the amount of peri‐implant eroded surface. There was no effect on trabecular bone volume at a remote site. Thus, the particle‐induced impaired fixation in this rat model was directly associated with local and serum markers of elevated bone resorption and depressed bone formation, supporting the rationale of exploring both anticatabolic and anabolic strategies to treat and prevent particle‐related implant osteolysis and loosening, and indicating that serum markers may prove useful in tracking implant fixation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Chitosan‐based nanoparticles as a sustained protein release carrier for tissue engineering applications
Authors: Hou Yaping , Hu Junli , Park Hyejin , Lee Min
Published: January 2012

Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel‐like molecule‐1 (Nell‐1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of Chi crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein‐loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly(lactide‐co‐glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Prevalence and natural course of craniocervical junction anomalies during growth in patients with osteogenesis imperfecta
Authors: Arponen Heidi , Mäkitie Outi , Haukka Jari , Ranta Helena , Ekholm Marja , Mäyränpää Mervi K , Kaitila Ilkka , Waltimo-Sirén Janna
Published: January 2012

Pathology in the craniocervical junction is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze the prevalence and natural course of craniocervical junction anomalies in patients with OI during growth. In a one-center retrospective study, we analyzed lateral skull radiographs and midsagittal magnetic resonance images of 76 patients with either type I, III, or IV OI. The material included longitudinal series of 31 patients. In total, 150 patient images taken at ages 0 to 39 years were analyzed and compared with age-matched control data. Craniocervical anomalies were observed in 37% of patients and in all OI types studied. Of the three types of anomalies, basilar invagination was seen in 13%, basilar impression in 15%, and platybasia in 29% of the patients. From those with an abnormal finding, 44% displayed more than one type of anomaly. At a group level, we found no evidence of progression of craniocervical junction pathology with age. We provide longitudinal and cross-sectional data on craniocervical junction dimensions in growing patients with OI and, based on those, suggest a radiological management strategy for diagnosis of cranial base pathology. A higher risk of having any of the pathological conditions was associated with a lower height Z-score. Careful follow-up of cranial base anomalies particularly in subjects with OI and severe growth failure is warranted. © 2012 American Society for Bone and Mineral Research.
Voids and necks in liquid ammonia and their roles in diffusion of ions of varying size
Authors: Chakraborty Debashree , Chandra Amalendu
Published: January 2012

Voids in a medium are defined as the regions that are located outside an appropriately defined occupied space associated with molecules. Dynamical properties like diffusion can be related to the structure and distribution of voids present in the medium. This work deals with an analysis of voids and diffusion in liquid ammonia. The analysis of voids is done by the construction of Voronoi polyhedra and Delaunay tessellation. We have performed a series of molecular dynamics simulations of monovalent cations and anions of varying size in liquid ammonia at two different temperatures of 210 and 240 K to investigate the effects of ion size on the diffusion of ions and roles of voids in determining the observed diffusion behavior. It is found that with the increase of ion size, the diffusion coefficients first increase and then pass through a maximum similar to the behavior observed earlier for diffusion in water. The observed results are explained in terms of passage through voids and necks that are present in liquid ammonia. © 2012 Wiley Periodicals, Inc.
Adapting leadership theory and practice for the networked, millennial generation
Authors: Balda Janis Bragan , Mora Fernando
Published: January 2012

Current research offers a complex perspective on the main characteristics of Millennials (or Gen‐Ys, as they are also called) as a generation in which knowledge is acquired, shared, and created as an extension of the primacy of relationships and networks and embedded in the connections that information technology provides. Aspects of the servant‐leadership model provide a context from which to examine the construction of workplace practice (action) and purpose (meaning) among members of the Millennial generation. However, theories developed in previous generations are not automatically applicable and require critical examination and adaptation if they are to offer an understanding of means for motivating and influencing Millennials toward more broadly defined goals and aspirations in multigenerational workplaces. After a review of recent literature, we conclude that future organizational paradigms will have to develop a multigenerational collaborative culture. With this in mind, we discuss how service leadership contributes to these new networked and collaborative organizations to help Millennials flourish and prepare them for leadership positions as well.
New perspectives on collagen fibers in the squid mantle
Authors: Krieg Michael , Mohseni Kamran
Published: January 2012

The squid mantle is a complex structure which, in conjunction with a highly sensitive sensory system, provides squid with a wide variety of highly controlled movements. This article presents a model describing systems of collagen fibers that give the mantle its shape and mechanical properties. The validity of the model is verified by comparing predicted optimal fiber angles to actual fiber angles seen in squid mantle. The model predicts optimal configurations for multiple fiber systems. It is found that the tunic fibers (outer collagen layers) provide optimal jetting characteristics when oriented at 31°, which matches empirical data from previous studies. The model also predicted that a set of intramuscular fibers (IM‐1) are oriented relative to the longitudinal axis to provide optimal energy storage capacity within the limiting physical bounds of the collagen fibers themselves. In addition, reasons for deviations from the predicted values are analyzed. This study illustrates how the squid's reinforcing collagen fibers are aligned to provide several locomotory advantages and demonstrates how this complex biological process can be accurately modeled with several simplifying assumptions. J. Morphol., 2012. © 2012 Wiley Periodicals, Inc.
Cyclochiral resorcin[4]arenes as effective enantioselectors in the gas phase
Authors: Fraschetti Caterina , Letzel Matthias C. , Paletta Marlene , Mattay Jochen , Speranza Maurizio , Filippi Antonello , Aschi Massimiliano , Rozhenko Alexander B.
Published: January 2012

The effect of cyclochirality of rccc‐2,8,14,20‐tetra‐n‐decyl‐4,10,16,22‐tetra‐O‐methylresorcin[4]arene (C) on the enantiodiscrimination of a number of chiral bidentate and tridentate aromatic and aliphatic biomolecules (G) has been investigated by nano‐electrospray ionization (nano‐ESI)‐Fourier transform ion cyclotron resonance mass spectrometry. The experimental approach is based on the formation of diastereomeric proton‐bound [C·H·G]+ complexes by nano‐ESI of solutions containing an equimolar amount of quasi‐enantiomers (C) together with the chiral guest (G) and the subsequent measurement of the rate of the G substitution by the attack of several achiral and chiral amines. In general, the heterochiral complexes react faster than the homochiral ones, except when G is an aminoalcoholic neurotransmitter whose complexes, beyond that, exhibit the highest enantioselectivity. The kinetic results were further supported by both collision‐induced dissociation experiments on some of the relevant [C2·H·G]+ three‐body species and Density functional theory (DFT) calculations performed on the most selective systems. Copyright © 2012 John Wiley & Sons, Ltd.
Fast 3D thermal simulation of power module packaging
Authors: Swan Ian R. , Bryant Angus T. , Mawby Philip A.
Published: January 2012

This paper presents a thermal model that uses a Fourier series solution to the heat equation to carry out transient 3D thermal simulation of power device packaging. The development and implementation of this physics‐based method is described. The method is demonstrated on a stacked 3D multichip module. The required aspects of 3D heat conduction are captured successfully by the model. Compared with previous thermal models presented in literature, it is fast, accurate and can be easily integrated with an inverter circuit simulator to model realistic converter load cycles. Copyright © 2012 John Wiley & Sons, Ltd.
Sendai virus vector‐mediated brain‐derived neurotrophic factor expression ameliorates memory deficits and synaptic degeneration in a transgenic mouse model of Alzheimer's disease
Authors: Iwasaki Yuki , Negishi Takayuki , Inoue Makoto , Tashiro Tomoko , Tabira Takeshi , Kimura Nobuyuki
Published: January 2012

Growing evidence suggests that decreased brain‐derived neurotrophic factor (BDNF) levels are associated with Alzheimer's disease (AD) pathogenesis. Therefore, BDNF gene therapy is considered to be a promising therapeutic strategy for treating AD. Sendai virus (SeV) is a type I parainfluenza virus that does not interact with host chromosomes because of its strict cytoplasmic life cycle. Although SeV is nonpathogenic in primates, including humans, its infectivity for neurons is strong. Here we demonstrate that SeV vectors effectively infected neurons, even though they were injected into subcortical white matter. Moreover, SeV vectors significantly induced BDNF expression, ameliorating synaptic degeneration and memory deficits in a transgenic mouse model of AD (Tg2576). This is the first study to demonstrate that viral vector administration in white matter is sufficient to restore cognitive function in vivo. These results also support the feasibility of using SeV vectors for gene therapy targeting the brain. © 2012 Wiley Periodicals, Inc.
Activation of group III metabotropic glutamate receptors by endogenous glutamate protects against glutamate‐mediated excitotoxicity in the hippocampus in vivo
Authors: Vera Gabriela , Tapia Ricardo
Published: January 2012

Perfusion of 4‐aminopyridine (4‐AP) by microdialysis in the hippocampus produces intense epileptiform behavioral and electrical activity and neurodegeneration, resulting from a stimulated release of glutamate from nerve endings. In contrast, accumulation of extracellular glutamate by blockade of its transport in vivo in anesthetized rats is innocuous, and studies in vitro in brain slices suggest that under these conditions glutamate may activate presynaptic group III metabotropic glutamate receptors (mGluRs) and inhibit its own release. Therefore, using microdialysis, EEG recording, and histological evaluation, we studied the effect of increased endogenous extracellular glutamate by blockade of its transport with pyrrolidine dicarboxylic acid (PDC) on the excitotoxic action of 4‐AP in the hippocampus of awake rats. We found that up to a 20‐fold increase in extracellular glutamate during >90 min with PDC does not induce any sign of excitotoxicity. On the contrary, this glutamate increase notably protected against the 4‐AP‐induced seizures and neurodegeneration, and, remarkably, this protection was dependent on the time of perfusion with PDC and thus on the duration of extracellular glutamate accumulation. To test whether this protective action was mediated by the activation of group III mGluRs, we used specific antagonists of these receptors and found that they clearly prevented the protective effect of PDC, without affecting the accumulation of extracellular glutamate. We conclude that the spillover of the excess extracellular glutamate activates presynaptic group III mGluRs and inhibits the stimulatory effect of 4‐AP on its release, thus preventing the activation of postsynaptic N‐methyl‐D‐aspartate receptors and its deleterious consequences. © 2012 Wiley Periodicals, Inc.
Masters of the long haul: Pursuing long‐term work goals
Authors: Bateman Thomas S. , Barry Bruce
Published: January 2012

We investigate work motivation in the unstudied domain of individuals who pursue very long‐term goals. We highlight the fact that the preponderance of research findings on the psychology of work motivation is based on short‐term studies and discuss the potential relevance to long‐term motivation of literatures including long‐term thinking and time horizons, long‐term goals and goal pursuit, and self‐regulation. We adopt the qualitative research strategy of theory elaboration, with a specific intention of elaborating goal‐setting theory. Analysis of interview data from a unique sample of scientists and others pursuing goals spanning decades or more yielded a structure of psychological factors that can enhance, support, and sustain motivation for the long term. Reconciling our findings with existing goal theories, we develop an integrative model of motivating factors and self‐regulation processes underlying long‐term goal pursuit. We discuss the implications, including an expanded focus for our field on motivating people for the long run. Copyright © 2012 John Wiley & Sons, Ltd.
Does process fairness affect job performance? It only matters if they plan to stay
Authors: Collins Brian J. , Mossholder Kevin W. , Taylor Shannon G.
Published: January 2012

Incorporating a social exchange perspective, we examined the joint impact of process fairness and turnover intentions on job performance. Results from two independent samples suggest that employee turnover intentions moderate relations between process fairness perceptions and employee job performance. Specifically, the positive effects of the two types of process fairness on performance were stronger for employees who planned to stay with the organization than for those who intended to leave. Copyright © 2012 John Wiley & Sons, Ltd.
The challenge of evaluating health effects of organic food; operationalisation of a dynamic concept of health
Authors: Huber Machteld , Bakker Mette H , Dijk Wieneke , Prins Henrieke AB , Wiegant Fred AC
Published: January 2012

The health benefits of consuming organically produced foods compared with conventional foods are unclear. Important obstacles to drawing clear conclusions in this field of research are (1) the lack of a clear operational definition of health and (2) the inability to distinguish between different levels of health using valid biomarkers. In this paper, some shortcomings of the current definition of health are outlined and the relevance of integrating a more dynamic and functional component is emphasised, which is reflected by the ability to adapt. The state of health could then be determined by challenging an individual with some form of stressor and by subsequent quantification and evaluation of the coherence in recovery of various physiological processes and parameters. A set of relevant parameters includes the activity of the immune system and the activity of the autonomous nervous system. A good recovery towards homeostasis is suggested to reflect a qualitatively good state of health. Furthermore, it would enable objective evaluation of health‐optimising strategies, including the consumption of organically produced foods that aim to strengthen health. Copyright © 2012 Society of Chemical Industry
Free peritoneal tumor cells detection in gastric and colorectal cancer patients
Authors: Rossi Del Monte Simone , Ranieri Danilo , Mazzetta Francesca , Kazemi Nava Andrea , Raffa Salvatore , Torrisi Maria Rosaria , Ziparo Vincenzo
Published: January 2012

Background

Free peritoneal tumor cells (FPTC) derive from the detachment of primary cancer and may result in peritoneal carcinomatosis. Since peritoneal lavage cytology has low sensitivity in detecting FPTC, our aim was to estimate the clinical relevance of FPTC detected using an approach based on multiple molecular techniques.

Materials and Methods

Samples of peritoneal lavage were collected from 27 gastric and 48 colorectal cancer patients. FPTC recovery and detection from peritoneal washes was performed by cytological examination and immunomagnetic enrichment for epithelial cells followed by immunofluorescence analysis for epithelial marker EpCAM/CD326 and carcinoembryonic antigen (CEA). CEA and CK20 mRNA levels were quantified using a real‐time qRT‐PCR system.

Results

For gastric carcinoma the FPTC positivity rate acquired by cytology, immunofluorescence and qRT‐PCR was 14.8%, 14.8%, and 78% and for colorectal carcinoma was 0%, 17%, and 42%, respectively. qRT‐PCR positivity was correlated with a poor cancer‐specific survival and time‐to‐recurrence rates in both gastric and colorectal carcinoma.

Conclusions

Epithelial immunoenrichment and immunofluorescence analysis allows unequivocal identification of the FPTC. The real time qRT‐PCR showed higher sensitivity for the detection of CEA and CK20 mRNA levels and confirmed its prognostic value in gastrointestinal cancers. J. Surg. Oncol. 2012; 106:17–23. © 2012 Wiley Periodicals, Inc.
Accuracy mass screening and identification of phenolic compounds from the five parts of Abutilon theophrasti Medic. by reverse‐phase high‐performance liquid chromatography‐electrospray ionization‐quadrupoles‐time of flight‐mass spectrometry
Authors: Tian Chunlian , Wang Miao , Shen Changhui , Zhao Chunjie
Published: January 2012

A rapid and resolutive reverse‐phase high‐performance liquid chromatography–electrospray ionization–quadrupoles–time of flight‐mass spectrometry method was established for the screening and identification of the phenolic compounds in the 70% ethanolic extracts from the five parts (roots, stems, leaves, seeds, and exocarps) of Abutilon theophrasti Medic.. Separation and detection conditions were optimized by using a 22 mixing standard, which included phenolic acids, flavonoids and a naphthalene compound. Optimum LC separation was achieved on a C18 analytical column (250 mm x 4.6 mm id, 5 μm) by gradient elution with water containing 0.1% v/v formic acid (pH 2.4) and acetonitrile as mobile phases, at a flow rate of 1.0 mL/min. The developed method was applied to the study on the constituents of A. theophrasti Medic., and 16 compounds were unequivocally identified with standards. Meanwhile, 37 constituents were tentatively identified by comparing with references. In addition, accurate molecular formulae were conjectured for unknown compounds. To our knowledge, little is known about how these compounds are distributed in A. theophrasti Medic.. Hence, it is clear that the comprehensive analysis of the phenolic compounds of A. theophrasti Medic. is helpful for the quality control and understanding the usage and function of the herb and its products.
Squamous cell carcinoma metastatic to neck from an unknown primary: The potential impact of modern pathologic evaluation on perceived incidence of human papillomavirus–positive oropharyngeal carcinoma prior to 1970
Authors: Chenevert Jacinthe , Seethala Raja R. , Barnes E. Leon , Chiosea Simion I.
Published: January 2012

Objectives/Hypothesis:

From the 1950s through the 1960s, an unknown number of oropharyngeal squamous cell carcinomas (SCCs) presented with metastases to cervical lymph nodes from an unknown primary (SCCUP) and were not recognized as oropharyngeal in origin. At present, pathologic evaluation of SCCUP for human papillomavirus (HPV) improves discovery of occult oropharyngeal SCC and may partially explain increased incidence of HPV‐positive oropharyngeal SCC.

Study Design:

Retrospective cohort study.

Methods:

A retrospective study of 13 cases of SCCUP diagnosed from 1956 to 1969 was performed. The probability of these cases of metastatic SCC to originate from the oropharynx was assessed by characterizing their morphology (keratinizing vs. nonkeratinizing) and HPV status by in situ hybridization and p16 immunostaining.

Results:

Two cases of nonkeratinizing SCC positive for HPV by in situ hybridization and p16 immunohistochemistry were identified. These cases were most likely of oropharyngeal origin.

Conclusions:

These two cases can be added to the other 15 cases of HPV‐positive primary oropharyngeal SCC identified in our department from 1956 to 1969. When determining the incidence of HPV‐positive oropharyngeal SCC before the 1970s, a correction factor of about +13% (2/15) accounting for modern pathologic workup of SCCUP during the last couple of decades may be appropriate. Laryngoscope, 2012
Characterisation of the carrier of distortion potential “residual stresses” in the collaborative research centre “distortion engineering”
Authors: Epp J. , Hirsch T.
Published: January 2012

As residual stresses are already known as important distortion potentials, a comprehensive characterisation of residual stress distributions is required. In order to get this information, several techniques that are often complementary have to be used. Every method has its own advantages but also presents difficulties. In this paper, three methods (X‐ray diffraction, neutron diffraction and micromagnetic methods) used for the characterisation of residual stress states of different components will be presented. Some basics about theory and application of the methods are given. Concrete examples and results are shown. In particular, residual stress characterisation of bearing rings made from the steel grade AISI52100 and carburized discs made from AISI5120 are presented. A comparison of the methods with their specific advantages and disadvantages is made.
Process‐chain simulation for prediction of the distortion of case‐hardened gear blanks
Authors: Simsir C. , Hunkel M. , Lütjens J. , Rentsch R.
Published: January 2012

In this study, a process‐chain simulation model is presented for the prediction of distortion of low‐pressure gas carburised SAE 5120 (EN 20MnCr5) steel gear blanks. For this purpose, the evolution of the banded microstructure stemming from the continuous casting process was traced by computer simulations of subsequent shape rolling, forging and machining steps. Then, the simulated local orientation angles of the deformed banded microstructure are transferred to heat treatment simulation module as an input for the recently developed material model that exploits the “Anisotropic Transformation Strain (ATS)“ concept to reproduce the dishing behaviour which cannot be reproduced by former models. The results indicate that the suggested procedure provides quite good predictions of the dishing directions and dishing‐free cutting strategy, whereas; the dishing magnitude is predicted fairly reasonably considering large scatters in the experiments.
Decreased heart rate variability predicts death in amyotrophic lateral sclerosis
Authors: Pinto Susana , Pinto Anabela , De Carvalho Mamede
Published: January 2012

Introduction:

Some patients with amyotrophic lateral sclerosis (ALS) die suddenly despite normal nocturnal pulse oximetry (NPO), possibly due to dysautonomia.

Methods:

Forty‐four ALS patients without other medical conditions were studied. Heart rate variability was assessed through finger oximetry. The heart rate coefficient of variation (HR CV) was evaluated during nocturnal sleep. All patients were investigated at study entry (T1); 13 were tested 4 months later (T2), and 21 patients were investigated a further 24 months after entry (T3). Only recordings obtained from patients with normal NPO were accepted.

Results:

HR maximal, minimum, and median values remained stable. HR CV was similar between T1 and T2, but it decreased significantly at T3 (P < 0.01). Very low values were observed in 4 patients at T3 (HR CV <0.20), and 3 died suddenly within the following 2 months, despite normal NPO.

Conclusions:

Low HR CV is a potential marker of prognosis in ALS. Muscle Nerve 46: 341–345, 2012
Neuronal‐derived nitric oxide modulates the activity of mouse detrusor smooth muscle
Authors: Meng E. , Young J.S. , Cha T.L. , Sun G.H. , Yu D.S. , Brading A.F.
Published: January 2012

Aims

We investigated the roles of neuronal‐derived nitric oxide (NO) in the modulation of spontaneous activity of mouse detrusor smooth muscle.

Methods

Detrusor smooth muscle strips were isolated from nNOS gene knock‐out (nNOS−/−) mice and their wild type siblings (nNOS+/+). The properties of smooth muscle cells were assessed using intracellular electrophysiology and Ca2+ imaging by laser‐scanning confocal microscopy. The effects of an nNOS inhibitor, 7‐nitro indazole (7‐NI) on electrically evoked contractility were assessed using nNOS+/+ mouse detrusor strips.

Results

In spontaneously active cells, the frequency of spontaneous action potentials (sAPs) and whole cell Ca2+ flashes in nNOS−/− preparations was lower than that in the nNOS+/+ preparations. The frequency of sAPs was enhanced by a nitric oxide donor, diethylamine NONOate sodium salt (NONOate; 100 µM), both when used alone and when the cGMP pathway was blocked by 1H‐[1,2,4] oxadiazolo [4,3‐a] quinoxalin‐1‐one (ODQ, 10 µM). 7‐NI (100 µM) significantly suppressed the electrically evoked contraction of mouse detrusor strips.

Conclusions

We suggest that neuronal‐derived NO facilitates the generation of spontaneous activity via a cGMP‐independent pathway, and consequently enhances the evoked contraction of detrusor. Dysregulation of nNOS containing nerves may underlie bladder pathologies. Neurourol. Urodynam. 31:572–578, 2012. © 2012 Wiley Periodicals, Inc.
Intradetrusor botulinum neurotoxin A (BoNT‐A) injections decrease bladder fibrosis secondary to partial urethral obstruction in the male rat model
Authors: Tinay Ilker , Tanidir Yiloren , Cikler Esra , Cetinel Sule , Tarcan Tufan
Published: January 2012

Aims

We evaluated effects of BoNT‐A injections on bladder function and histomorphology in a male‐rat‐overactive‐bladder model, created by partial urethral obstruction.

Methods

A total of 45 male Sprague–Dawley rats were separated into 5 groups. Partial urethral obstruction (PUO) was created in all rats except the control group. At the 6th week after PUO, intradetrusor injections of 50 µl of saline (2 sham groups) or 50 µl BoNT‐A (2 treatment groups) was performed. Treatment and sham groups were studied 5 and 30 days after injection and neuropharmacological and histomorphological findings on bladder tissues were compared to the control group.

Results

Bladder muscle hypertrophy and connective tissue increase were detected at 5th and more prominent at 30th day after saline injection. Intradetrusor BoNT‐A injection significantly reduced PUO‐induced histological changes in the bladder tissue both at 5th and 30th day after injection. At 5th day after saline injection, a significantly increased contractile response to electrical field stimulation (EFS) and carbachol were recorded in the saline group and this effect disappeared at 30th day. There was no statistically significant difference between BoNT‐A and control groups in terms of contractile responses to EFS and carbachol, both at 5th and 30th days.

Conclusion

Partial urethral obstruction induces increased bladder tissue contractile responses to neurogenic and pharmacological stimulation and intradetrusor BoNT‐A injections decrease these responses at 5th days after injection. As the unique finding of this study, intradetrusor BoNT‐A injections appear to decrease bladder fibrosis secondary to PUO in the male rat model. Neurourol. Urodynam. 31:564–570, 2012. © 2012 Wiley Periodicals, Inc.