bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Living in the United States on Body Mass Index in Refugee Patients
Authors: Careyva Beth , LaNoue Marianna , Bangura Mafudia , de la Paz Amanda , Gee Amy , Patel Neesha , Mills Geoffrey
Published: April 2015

Background . We describe body mass index (BMI) trajectories over 20 months in newly settled refugees in the United States. Methods . Growth curves were modeled in in hierarchical linear modeling for cohorts from Southeast Asia, Africa, and the Middle East. Results . For refugees from Southeast Asia and Africa, coefficients suggest an increase of greater than 1.0 kg/m2 per three-month time period, though the best fit function differed between the two groups. A non-linear model was the best fit for refugees from the Middle East, with an average increase of just under 1.0 kg/m2 over the study period. Discussion . A significant increase in BMI was observed for all refugees but of a different form, predicted by the refugee’s region of origin. This may be related to food insecurity, acculturation, environmental factors, and cultural influences prior to and after arrival in the United States, though further study is needed to develop causal relationships.
The Poet in the Poem: Blake’s Milton
Authors: Apesos Anthony
Published: April 2015

William Blake inserts himself both in the text and the illustrations of his illuminated book Milton as he does in no other of his works. This essay examines these instances of self-inclusion and argues that they serve as self-corrections within the overt function of the poem as a correction of John Milton.
The Possibility of Coherentism and the Stringency of Ceteris Paribus Conditions
Authors: Schupbach Jonah N.
Published: April 2015

Schupbach (2008) puts forward a "possibility result" for Bayesian Coherentism, showing that there exist plausible sets of ceteris paribus conditions that imply that coherence is truth-conducive. Against this result, Schubert (2012) has argued that Schupbach's considered ceteris paribus conditions are "jointly inconsistent". In this article, I first show that Schubert's attempted proof of this claim is fallacious, and hence that the possibility result still stands. Next, I consider a related criticism of Schupbach's result, inspired by Olsson's (2005) constraints on ceteris paribus conditions. This leads to a general discussion of the principle(s) that should guide one in choosing such conditions.
Pensamientos de se y mente consciente
Authors: Vidal Javier
Published: April 2015

En este artículo, desarrollo una versión modificada de la teoría de la conciencia en términos de pensamientos de orden superior. Argumento que un estado mental es consciente cuando va acompañado por un pensamiento de se implícito. Esta nueva versión es importante porque puede acomodar la objeción de que un pensamiento de orden superior que es la conclusión de una inferencia consciente no puede hacer que un estado mental se vuelva consciente. Argumento también que si la introspección consiste en tener un pensamiento de se explícito, puede mantenerse la distinción entre estados mentales conscientes y estados mentales que, además, están bajo introspección.
Unification: Not Just a Thing of Beauty
Authors: Votsis Ioannis
Published: April 2015

We often hear that simplicity, explanatory power and unification, though aesthetically pleasing or beautiful qualities, are at best pragmatic considerations in matters of choosing between rival hypotheses. This paper aims to offer a novel conception and an associated measure of unification, both of which are demonstrably more than just pragmatic considerations. The discussion departs from a brief survey of some failed attempts to carve out adequate conceptions of unification. It then proceeds to an analysis of the notions of confirmational connectedness and disconnectedness. Roughly speaking, these notions attempt to capture the way support propagates or fails to propagate between the content parts of a hypothesis or, equivalently, between the contents of two or more hypotheses. The two notions are instrumental in helping to tackle the problem of ad hoc, and in particular monstrous, hypotheses. More importantly for the purposes of this paper, they are essential ingredients in the proposed conception of unification and its associated measure. In simple terms, the more the content of a hypothesis (or, equivalently, the content of a set of hypotheses) is confirmationally connected the more that content is unified. Since the confirmational connectedness of two content parts is determined by purely objective matters of fact, the proposed notion and measure of unification are themselves strictly objective, i.e. not merely pragmatic considerations in matters of hypothesis choice. The paper concludes with a discussion of how the proposed measure handles real and hypothetical examples but also how it stands up to various objections.
Normalisation of Hamiltonian in photogravitational elliptic restricted three body problem with Poynting-Robertson drag
Authors: Mishra Vivek , Ishwar Bhola
Published: April 2015

In this paper, we have performed first order normalization in the photogravitational elliptic restricted three body problem Â with Poynting-Robertson drag. We suppose that bigger primary as radiating and smaller primary is an oblate spheroid. We have found the Lagrangian and the Hamiltonian of the problem. Then, we have expanded the Lagrangian function in power series of x and y, where (x, y) are the coordinates of the triangular equilibrium points. Using Whittaker (1965) method, we have found that the second order part H2 of the Hamiltonian is transformed into the normal form.
Innovation, Innovativeness And Gender - Approaching Innovative Gender
Authors: Okoń-Horodyńska Ewa , Zachorowska-Mazurkiewicz Anna
Published: April 2015

This paper deals with the attempt to search for the sources of creativity in the broad sense in solving problems. These creative solutions become innovations. The ability to develop innovation depends on the multi-dimensional predispositions to solve problems – those found in people, inspired by the market, organised or spontaneous, as well as facilitated or hampered by the state. Yet, the aforementioned factors should be supplemented with one more – gender. In the chapter attention is paid to the multi-dimensional differences stemming from gender, which should be perceived as a positive element, because they are the source of synergy resulting from collaboration among research or business teams in the process of innovation. The chapter introduces the concept of ‘innovative gender’ and its institutional framework. The methodological inspiration is the model known in the literature as the Innovation Genome, the conceptualization of which constitutes a major part of the study.
Determinants Of Bank’s Profitability In EU15
Authors: Căpraru Bogdan , Ihnatov Iulian
Published: April 2015

In this paper we analyse determinants of bank profitability of EU15 banking systems for the period 2001-2011. We use as proxy for banks profitability the return on average assets (ROAA), the return on average equity (ROAE) and net interest margin (NIM). We also measure the impact of the first and the largest wave of enlargement (10 new members in 2004) on EU15 bank profitability, introducing a dummy variable. The contribution of this paper for the empirical literature is that there are no other studies that deal bank profitability for all EU 15 countries for the period considered (2001-2011). The literature splits the factors that influence banks’ profitability in two large groups: bank-specific (internal) factors and industry specific and macroeconomic (external) factors. Our results are in line with the economic theory. Cost to Income Ratio, credit risk and market concentration had a negative influence in case of all measures of banks’ profitability, while bank liquidity only for ROAE and NIM. The size of banks had a negative impact on NIM, suggesting that bigger the bank is, smaller the net interest margin ratio is, but, on the contrary, in case of ROAA, had a direct effect. The market concentration had a negative influence, meaning that the increasing competition, as a structural point of view, increases banks’ profitability. The results show us that the process of European Union enlargement from 2004 does not have significant impact on EU15 banking systems’ profitability. It has a week and negative effect only in case of net interest margin. As policy recommendations, we suggest for authorities a better supervision for credit risk and liquidity and maintaining a competitive banking environment. For banks’ management we also recommend to monitor the credit risk indicators, optimizing costs and diversifying the sources of income.
Case Study In The Field Of Innovation In Selected Companies In Slovak Republic
Authors: Hajduová Zuzana , Lacko Roman , Mildeová Stanislava , Stričík Michal
Published: April 2015

Innovations are the source of competitive advantage and direction of the strategic choices are the most important factor determining the success of a business in the 21st century. In this context, the objective is to examine the contribution of the innovation process in small and medium-sized enterprises in the Slovak Republic, with the help of analysis we evaluate the benefits of the introduction of innovations, and search for the structure of the system and behaviour of systems archetypes. There is some evidence that might be used as advice to help with effectivity of innovation process in wider international spectrum.
Suggested roles for microRNA in tumors
Authors: Perge Pál , Nagy Zoltán , Igaz Ivan , Igaz Peter
Published: April 2015

MicroRNAs are short non-coding RNA molecules encoded by distinct genes involved in the posttranscriptional regulation of gene expression. Forming part of the epigenetic machinery, microRNAs are involved in several aspects of tumorigenesis. Deregulation of microRNA expression is a common feature of tumors. Overexpressed oncogenic and underexpressed tumor suppressor microRNAs have been described in many different tumors. MicroRNAs are released from tumors that might affect other cells within and outside the tumor. Circulating microRNAs might also be involved in a tumor surveillance mechanism. In this short overview, some important aspects of microRNA in tumors are discussed.
Using Microstrip LPF in Gysel Power Divider for Extreme Size Reduction and Higher Order Harmonic Suppression
Authors: Siahkamari H. , Makki S. Vahab A. , Malakooti S.-A.
Published: April 2015

This paper presents a new design of a compact Gysel power divider with harmonic suppression. It comprises six similar low-pass filters in lieu of six conventional transmission lines in the Gysel power divider. Not only does the proposed power divider extremely reduce the occupied area to 22.7% of the conventional Gysel power divider at 900 MHz, but also it features the higher order harmonic rejection. Simulation and measurement results show good insertion loss, return loss, isolation, and wide stopband bandwidth, while maintaining high-power handling capability over the Wilkinson power divider.
An unabelian version of the Voronov higher bracket construction
Authors: Bordemann Martin
Published: April 2015

In this paper, we show how to extend Voronov's construction of L
∞-structures
by using the splitting of a graded Lie algebra
into the direct vector space sum of two subalgebras, of which one
is abelian, to just a graded Lie algebra inclusion without an algebraic
complement. The construction uses certain Verma modules of the universal
enveloping algebra of the graded Lie algebra, and it is fairly explicit in
terms of convolution formulas.
Voronov's result [J. Pure Appl. Algebra 202 (2005), 133–153]
and Bandiera's result on nonabelian
complements [http://arxiv.org/abs/1304.4097]
occur as particular cases.
The toughness of hygrothermally modified wood
Authors: Hughes Mark , Hill Callum , Pfriem Alexander
Published: April 2015

The mechanical properties of thermally modified wood are discussed with regard to toughness. The molecular origins of the mechanical properties and, in particular, the role of the hemicelluloses are considered. The important role of water and its interaction with the cell wall components is also examined. The properties are discussed from the point of view of composite theory, with the three main macromolecular components acting as reinforcement, matrix and interfacial coupling agent. The important role that hemicelluloses play as a coupling agent between the cellulosic microfibril reinforcement and the lignin-rich matrix is highlighted. Destruction of the hemicelluloses during the thermal modification process has a profound effect upon the mechanical behaviour.
Quantifying an Agreement Study
Authors: Liao Jason J. Z.
Published: April 2015

In medical and other related sciences, clinical or experimental measurements usually serve as a basis for diagnostic, prognostic, therapeutic, and performance evaluations. Examples can be assessing the reliability of multiple raters (or measurement methods), assessing the suitability for tumor evaluation of using a local laboratory or a central laboratory in a randomized clinical trial (RCT), validating surrogate endpoints in a study, determining that the important outcome measurements are interchangeable among the evaluators in an RCT. Any elegant study design cannot overcome the damage by unreliable measurement. Many methods have been developed to assess the agreement of two measurement methods. However, there is little attention to quantify how good the agreement of two measurement methods is. In this paper, similar to the type I error and the power in describing a hypothesis testing, we propose quantifying an agreement assessment using two rates: the discordance rate and the tolerance probability. This approach is demonstrated through examples.
A Universal Approximate Cross-Validation Criterion for Regular Risk Functions
Authors: Commenges Daniel , Proust-Lima Cécile , Samieri Cécilia , Liquet Benoit
Published: April 2015

Selection of estimators is an essential task in modeling. A general framework is that the estimators of a distribution are obtained by minimizing a function (the estimating function) and assessed using another function (the assessment function). A classical case is that both functions estimate an information risk (specifically cross-entropy); this corresponds to using maximum likelihood estimators and assessing them by Akaike information criterion (AIC). In more general cases, the assessment risk can be estimated by leave-one-out cross-validation. Since leave-one-out cross-validation is computationally very demanding, we propose in this paper a universal approximate cross-validation criterion under regularity conditions (UACVR). This criterion can be adapted to different types of estimators, including penalized likelihood and maximum a posteriori estimators, and also to different assessment risk functions, including information risk functions and continuous rank probability score (CRPS). UACVR reduces to Takeuchi information criterion (TIC) when cross-entropy is the risk for both estimation and assessment. We provide the asymptotic distributions of UACVR and of a difference of UACVR values for two estimators. We validate UACVR using simulations and provide an illustration on real data both in the psychometric context where estimators of the distributions of ordered categorical data derived from threshold models and models based on continuous approximations are compared.
Open Science lernen und lehren: FOSTER Portal stellt Materialien und Kurse bereit
Authors: Orth Astrid , Schmidt Birgit
Published: April 2015

Open Science ist ein relativ junger Begriff, die zugrunde liegende Idee des Teilens von Wissen, Ergebnissen und Methoden ist jedoch so alt ist wie die Wissenschaft selbst. Open Science umfasst neben Open Access und Open Data – dem offenen Zugang zu Veröffentlichungen und Forschungsdaten – auch radikal neue Bereiche wie Citizen Science und Open Notebook Science. Seitdem die Europäische Kommission und andere Forschungsförderer zunehmend Open Access zu Publikationen und Daten in ihre Förderrichtlinien aufnehmen, ist es für Wissenschaftlerinnen und Wissenschaftler unumgänglich geworden, sich mit diesem Thema auseinanderzusetzen. Die Herausforderung bei der Umsetzung dieser Anforderungen ist nicht so sehr die Existenz und Zugänglichkeit relevanter Informationen, sondern die unübersichtliche Fülle an Material. Das von der Europäischen Kommission geförderte Projekt „Facilitating Open Science Training for European Research“ (FOSTER) führt deshalb eine breite Sammlung von Materialien und Kursen zum Thema Open Science zusammen und schafft so eine Lernressource für die europäische Forschungscommunity. Die Inhalte stehen möglichst über offene Lizenzen zur Verfügung, um die Nachnutzung in weiteren Schulungen zu unterstützen. Die Navigation durch die Fülle an Inhalten erfolgt entlang einer Taxonomie oder anhand von zielgruppenspezifischen Lernzielen, die zum Beispiel Projektmanager oder Multiplikatoren wie Bibliothekare adressieren. Der Artikel stellt die aktuellen Ergebnisse des Projektes vor, beleuchtet die Rolle der Niedersächsischen Staats- und Universitätsbibliothek Göttingen im Projekt und gibt einen Ausblick auf die Aktivitäten im zweiten Projektjahr.
Historical development of labile verbs in modern Russian
Authors: Letuchiy Alexander
Published: April 2015

The article deals with the phenomenon of lability (ambitransitivity), in other words, the ability of a verb to be either transitive or intransitive. I analyze the historical development of verbs which are currently labile in modern Russian. The main group of Russian labile verbs includes verbs of motion. On the basis of corpus and dictionary data, I conclude that the behavior of the lexemes under analysis is far from being uniform. However, interestingly, for most of them, e.g.,

In the cases when the intransitive use becomes more frequent, the semantic change matches the statistical one. In the beginning, verbs of this subtype were only used intransitively in a restricted type of contexts (e.g., for
Production and Properties of Composite Material Comprising Gd Multiscale Particles
Authors: Jaworski Jacek , Gawłowski Grzegorz
Published: April 2015

The article presents a novel method of producing Gd particles and preserving them from oxidation. The particles were produced in liquid paraffin by means of AC electric discharge and stored in the solidified paraffin. After seven months, the surface of the Gd was found to be exempt of oxidation. Moreover a composite material formed from mixing paraffin with Gd particles was conductive and magnetic and also presented photovoltaic effect. This method is a promising means of producing, at an industrial scale, particles from materials extremely sensitive to environment such as rare earth materials. Also the new material consisted of Gd particles in a paraffin matrix can find applications in many branches of industry.
Kaizen-Driven Approach While Managing Industrial Projects. A Scandinavian Company Succeeds in Eastern Europe
Authors: Popescu Daniel
Published: April 2015

Eastern European companies have experienced various and radical transformations, as resultof the economic crises and turbulences, which exposed structural weaknesses. In the meantime, long-term challenges - such as globalization, shift of power centers from the nationallevel to international structures or scarcity of resources - intensify. Given this context, it ismandatory for companies to develop strategies aiming at being competitive.

The paper aims to propose an exploratory analysis regarding a Swedish-Finnish ownedcompany active in Romania - that was capable to build a strategic vision of its future, todefine a plan for change and to implement the necessary measures for the project success. The author has conducted a study and developed a case along a project aiming at continuousimprovement (Kaizen) in this company, emphasizing its main results. In order to analyzethe project of implementing Kaizen methodology, the research initiative consisted both ofprimary and secondary research. The paper analyzes the project from the point of view ofeconomic situation of the company and environment, time constraints, budget limitations, technical level/quality performance and risks.

The central finding is that concept-oriented projects run by an advanced-country companycould succeed in a less economically developed and culturally different country - even inturbulent periods and not even in highly dynamic and technologically advanced industries- if the top management is strongly committed and management team completely involved. The paper concludes with study results, as well as some lessons learnt and managerialimplications - useful for future similar projects either within the company under debate orby other organizations in similar circumstances.
Shop Floor-Level Control of Manufacturing Companies: An Interview Study in Finland
Authors: Tokola Henri , Järvenpää Eeva , Salonen Tapio , Lanz Minna , Koho Mikko , Niemi Esko
Published: April 2015

This paper publishes the results of interviews regarding shop-floor-level control of 18 Finnish manufacturing companies. The interviews had 17 open questions relating to demand characteristics, shop floor-level control issues, production flexibility, inventory control, and potential development areas. In order to get insights from the interviews, this paper analyses the answers from the interviews and categorises them into typical answers. The companies that were interviewed are also categorised as small companies with their own end products, subcontractors, or large companies with their own end products, and the emphasis of the analysis is on how companies differ in their shop floor-level control. The results show that different types of companies have different characteristics. Small companies are characterised by constant workflow, seasonal trends in demand, and the use of forecasts. Subcontractors have great daily variation in their demand and processing times. Large companies tend to focus on inventory issues.
Wet flue gas desulfurization using alkaline agents
Authors: del Valle-Zermeño Ricardo , Formosa Joan , Chimenos Josep Maria
Published: April 2015

The continued great dependency on fossil fuels entails increasing SO
Cross-modal priming differences between native and nonnative Spanish speakers
Authors: Herd Wendy , Sereno Joan , Jongman Allard
Published: April 2015

Training has been shown to improve American English speakers’ perception and production of the Spanish /ɾ, r, d/ contrast; however, it is unclear whether successfully trained contrasts are encoded in the lexicon. This study investigates whether learners of Spanish process the /ɾ, r, d/ contrast differently than native speakers and whether training affects processing. Using a cross-modal priming design, thirty-three Spanish learners were compared to ten native Spanish speakers. For native speakers, auditory primes with intervocalic taps (like [koɾo]) resulted in faster reaction times in response to matching visual targets (likecoro) than to orthographically and phonemically similar targets (likecorroandcodo). American English speakers’ reaction times were not affected by the relationship between primes and targets before training. After training, trainees responded more quickly to matching targets than to mismatching /ɾ/-/r/ prime-targets (e.g., [koɾo] followed bycorro) while controls’ reaction time patterns did not change. This indicates that native Spanish speakers and Spanish learners process words containing the /ɾ, r, d/ contrast differently and that improvements from training can be encoded in the lexicon.
A New Species Of Testate Amoebae Of The Genus Difflugia From The Freshwaters Of Azerbaijan (Rhizopoda, Testacea, Difflugiidae)
Authors: Snegovaya N. Yu. , Tahirova E. N.
Published: April 2015

A new testate amoebae species Difflugia alekperovi sp. n. was found during a faunistic study of inland waters of Lenkoran Region, South-Eastern Azerbaijan. The morphology and biometry of this species was described by LM and SEM investigations.
On Sexual Dimorphism Of Karyotypes Of Viviparus viviparus And V. contectus (Gastropoda, Viviparidae)
Authors: Andriychuk T. V. , Garbar A. V.
Published: April 2015

Karyotype analysis of males and females of two Viviparid species Viviparus viviparus Linnaeus, 1758 and V. contectus (Millet, 1813), shows differences in their karyotypes in the absence of heteromorphic pairs of chromosomes. This indicates an epigamous mechanism of sex determination.
A Review Of Major Impact Factors Of Hostilities Influencing Biodiversity In The Eastern Ukraine (Modeled On Selected Animal Species)
Authors: Vasyliuk O. V. , Nekrasova O. D. , Shyriaieva D. V. , Kolomytsev G. O.
Published: April 2015

We identified major factors (both direct and indirect), caused by the hostilities in Ukrainian ATO zone that adversely influence local biodiversity and environment. Damaged conservational territories (objects of nature conservation fund) were assessed. One of the most severe factors, the fires were studied using data from Terra MODIS remote sensing, resulting in a model of localization and spatial configuration of fires on natural and agricultural territories in ATO zone during June-September 2014. In that period, 2901 ignitions were registered in ATO zone, exceeding the numbers for previous four years. It was determined that 81 % of all of the ignitions happened on natural steppe and forest areas, 19 % in settlements. Th e fires damaged 18 % of forest area, 23 % of the steppe area and 14 % of arable lands of ATO zone. For two snake species of Red book of Ukraine — eastern Elaphe dione and more widespread Hierophis caspius — it was shown that most of the animals and their biotopes in Luhansk and Donetsk Regions of Ukraine are under threat. Far example, 65–82 % of 108 finds of these Colubridae registered in the eastern Ukraine are located in the ATO zone and near to hostilities. GIS models also showed that more than 50 % of biotopes, suitable for these snakes, are in the ATO zone or near it. Based on world-wide experience and our own observations, we safely assume that the events of 2014 in the ATO territory can possibly cause far-reaching adverse consequences for natural landscapes, local flora and fauna, and the massive local disappearance of plant and animal populations.
Neuropeptide Receptor Transcript Expression Levels and Magnitude of Ionic Current Responses Show Cell Type-Specific Differences in a Small Motor Circuit
Authors: Garcia Veronica J. , Daur Nelly , Temporal Simone , Schulz David J. , Bucher Dirk
Published: April 2015

We studied the relationship between neuropeptide receptor transcript expression and current responses in the stomatogastric ganglion (STG) of the crab,Cancer borealis. We identified a transcript with high sequence similarity to crustacean cardioactive peptide (CCAP) receptors in insects and mammalian neuropeptide S receptors. This transcript was expressed throughout the nervous system, consistent with the role of CCAP in a range of different behaviors. In the STG, single-cell qPCR showed expression in only a subset of neurons. This subset had previously been shown to respond to CCAP with the activation of a modulator-activated inward current (IMI), with one exception. In the one cell type that showed expression but noIMIresponses, we found CCAP modulation of synaptic currents. Expression levels within STG neuron types were fairly variable, but significantly different between some neuron types. We tested the magnitude and concentration dependence ofIMIresponses to CCAP application in two identified neurons, the lateral pyloric (LP) and the inferior cardiac (IC) neurons. LP had several-fold higher expression and showed larger current responses. It also was more sensitive to low CCAP concentrations and showed saturation at lower concentrations, as sigmoid fits showed smaller EC50values and steeper slopes. In addition, occlusion experiments with proctolin, a different neuropeptide converging ontoIMI, showed that saturating concentrations of CCAP activated all availableIMIin LP, but only approximately two-thirds in IC, the neuron with lower receptor transcript expression. The implications of these findings for comodulation are discussed.
Dissociating Visual and Motor Directional Selectivity Using Visuomotor Adaptation
Authors: Haar Shlomi , Donchin Opher , Dinstein Ilan
Published: April 2015

Directional selectivity during visually guided hand movements is a fundamental characteristic of neural populations in multiple motor areas of the primate brain. In the current study, we assessed how directional selectivity changes when reaching movements are dissociated from their visual feedback by rotating the visual field. We recorded simultaneous movement kinematics and fMRI activity while human subjects performed out-and-back movements to four peripheral targets before and after adaptation to a 45° visuomotor rotation. A classification algorithm was trained to identify movement direction according to voxel-by-voxel fMRI patterns in each of several brain areas. The direction of movements was successfully decoded with above-chance accuracy in multiple motor and visual areas when training and testing the classifier on trials within each condition, thereby demonstrating the existence of directionally selective fMRI patterns within each stage of the experiment. Most importantly, when training the classifier on baseline trials and decoding rotated trials, motor brain areas exhibited above-chance decoding according to the original movement direction and visual brain areas exhibited above-chance decoding according to the rotated visual target location, while posterior parietal cortex (PPC) exhibited chance-level decoding according to both. These results reveal that directionally selective fMRI patterns in motor system areas faithfully represent movement direction regardless of visual feedback, while fMRI patterns in visual system areas faithfully represent target location regardless of movement direction. Directionally selective fMRI patterns in PPC, however, were altered following adaptation learning, thereby suggesting that the novel visuomotor mapping, which was learned during visuomotor adaptation, is stored in PPC.
Age-Dependent Netrin-1 Signaling Regulates NG2+Glial Cell Spatial Homeostasis in Normal Adult Gray Matter
Authors: Birey Fikri , Aguirre Adan
Published: April 2015

Neuron–glial antigen 2-positive (NG2+) glial cells are the most proliferative glia type in the adult CNS, and their tile-like arrangement in adult gray matter is under tight regulation. However, little is known about the cues that govern this unique distribution. To this end, using a NG2+glial cell ablation model in mice, we examined the repopulation dynamics of NG2+glial cells in the mature and aged mice gray matter. We found that some resident NG2+glial cells that escaped depletion rapidly enter the cell cycle to repopulate the cortex with altered spatial distribution. We reveal that netrin-1 signaling is involved in the NG2+glial cell early proliferative, late repopulation, and distribution response after ablation in the gray matter. However, ablation of NG2+glial cell in older animals failed to stimulate a similar repopulation response, possibly because of a decrease in the sensitivity to netrin-1. Our findings indicate that endogenous netrin-1 plays a role in NG2+glial cell homeostasis that is distinct from its role in myelination.
Migraine: Multiple Processes, Complex Pathophysiology
Authors: Burstein Rami , Noseda Rodrigo , Borsook David
Published: April 2015

Migraine is a common, multifactorial, disabling, recurrent, hereditary neurovascular headache disorder. It usually strikes sufferers a few times per year in childhood and then progresses to a few times per week in adulthood, particularly in females. Attacks often begin with warning signs (prodromes) and aura (transient focal neurological symptoms) whose origin is thought to involve the hypothalamus, brainstem, and cortex. Once the headache develops, it typically throbs, intensifies with an increase in intracranial pressure, and presents itself in association with nausea, vomiting, and abnormal sensitivity to light, noise, and smell. It can also be accompanied by abnormal skin sensitivity (allodynia) and muscle tenderness. Collectively, the symptoms that accompany migraine from the prodromal stage through the headache phase suggest that multiple neuronal systems function abnormally. As a consequence of the disease itself or its genetic underpinnings, the migraine brain is altered structurally and functionally. These molecular, anatomical, and functional abnormalities provide a neuronal substrate for an extreme sensitivity to fluctuations in homeostasis, a decreased ability to adapt, and the recurrence of headache. Advances in understanding the genetic predisposition to migraine, and the discovery of multiple susceptible gene variants (many of which encode proteins that participate in the regulation of glutamate neurotransmission and proper formation of synaptic plasticity) define the most compelling hypothesis for the generalized neuronal hyperexcitability and the anatomical alterations seen in the migraine brain. Regarding the headache pain itself, attempts to understand its unique qualities point to activation of the trigeminovascular pathway as a prerequisite for explaining why the pain is restricted to the head, often affecting the periorbital area and the eye, and intensifies when intracranial pressure increases.
Schwann Cells Generated from Neonatal Skin-Derived Precursors or Neonatal Peripheral Nerve Improve Functional Recovery after Acute Transplantation into the Partially Injured Cervical Spinal Cord of the Rat
Authors: Sparling Joseph S. , Bretzner Frederic , Biernaskie Jeff , Assinck Peggy , Jiang Yuan , Arisato Hiroki , Plunet Ward T. , Borisoff Jaimie , Liu Jie , Miller Freda D. , Tetzlaff Wolfram
Published: April 2015

The transplantation of Schwann cells (SCs) holds considerable promise as a therapy for spinal cord injury, but the optimal source of these cells and the best timing for intervention remains debatable. Previously, we demonstrated that delayed transplantation of SCs generated from neonatal mouse skin-derived precursors (SKP-SCs) promoted repair and functional recovery in rats with thoracic contusions. Here, we conducted two experiments using neonatal rat cells and an incomplete cervical injury model to examine the efficacy of acute SKP-SC transplantation versus media control (Experiment 1) and versus nerve-derived SC or dermal fibroblast (Fibro) transplantation (Experiment 2). Despite limited graft survival, by 10 weeks after injury, rats that received SCs from either source showed improved functional recovery compared with media- or fibroblast-treated animals. Compared with media treatment, SKP-SC-transplanted rats showed enhanced rubrospinal tract (RST) sparing/plasticity in the gray matter (GM) rostral to injury, particularly in the absence of immunosuppression. The functional benefits of SC transplantations over fibroblast treatment correlated with the enhanced preservation of host tissue, reduced RST atrophy, and/or increased RST sparing/plasticity in the GM. In summary, our results indicate that: (1) early transplantation of neonatal SCs generated from skin or nerve promotes repair and functional recovery after incomplete cervical crush injury; (2) either of these cell types is preferable to Fibros for these purposes; and (3) age-matched SCs from these two sources do not differ in terms of their reparative effects or functional efficacy after transplantation into the injured cervical spinal cord.
The Role of Sleep in Motor Sequence Consolidation: Stabilization Rather Than Enhancement
Authors: Nettersheim Almut , Hallschmid Manfred , Born Jan , Diekelmann Susanne
Published: April 2015

Sleep supports the consolidation of motor sequence memories, yet it remains unclear whether sleep stabilizes or actually enhances motor sequence performance. Here we assessed the time course of motor memory consolidation in humans, taking early boosts in performance into account and varying the time between training and sleep. Two groups of subjects, each participating in a short wake condition and a longer sleep condition, were trained on the sequential finger-tapping task in the evening and were tested (1) after wake intervals of either 30 min or 4 h and (2) after a night of sleep that ensued either 30 min or 4 h after training. The results show an early boost in performance 30 min after training and a subsequent decay across the 4 h wake interval. When sleep followed 30 min after training, post-sleep performance was stabilized at the early boost level. Sleep at 4 h after training restored performance to the early boost level, such that, 12 h after training, performance was comparable regardless of whether sleep occurred 30 min or 4 h after training. These findings indicate that sleep does not enhance but rather stabilizes motor sequence performance without producing additional gains.
Persistent Residual Errors in Motor Adaptation Tasks: Reversion to Baseline and Exploratory Escape
Authors: Vaswani Pavan A. , Shmuelof Lior , Haith Adrian M. , Delnicki Raymond J. , Huang Vincent S. , Mazzoni Pietro , Shadmehr Reza , Krakauer John W.
Published: April 2015

When movements are perturbed in adaptation tasks, humans and other animals show incomplete compensation, tolerating small but sustained residual errors that persist despite repeated trials. State-space models explain this residual asymptotic error as interplay between learning from error and reversion to baseline, a form of forgetting. Previous work using zero-error-clamp trials has shown that reversion to baseline is not obligatory and can be overcome by manipulating feedback. We posited that novel error-clamp trials, in which feedback is constrained but has nonzero error and variance, might serve as a contextual cue for recruitment of other learning mechanisms that would then close the residual error. When error clamps were nonzero and had zero variance, human subjects changed their learning policy, using exploration in response to the residual error, despite their willingness to sustain such an error during the training block. In contrast, when the distribution of feedback in clamp trials was naturalistic, with persistent mean error but also with variance, a state-space model accounted for behavior in clamps, even in the absence of task success. Therefore, when the distribution of errors matched those during training, state-space models captured behavior during both adaptation and error-clamp trials because error-based learning dominated; when the distribution of feedback was altered, other forms of learning were triggered that did not follow the state-space model dynamics exhibited during training. The residual error during adaptation appears attributable to an error-dependent learning process that has the property of reversion toward baseline and that can suppress other forms of learning.
Intracellular FGF14 (iFGF14) Is Required for Spontaneous and Evoked Firing in Cerebellar Purkinje Neurons and for Motor Coordination and Balance
Authors: Bosch Marie K. , Carrasquillo Yarimar , Ransdell Joseph L. , Kanakamedala Ajay , Ornitz David M. , Nerbonne Jeanne M.
Published: April 2015

Mutations inFGF14, which encodes intracellular fibroblast growth factor 14 (iFGF14), have been linked to spinocerebellar ataxia (SCA27). In addition, mice lackingFgf14(Fgf14−/−) exhibit an ataxia phenotype resembling SCA27, accompanied by marked changes in the excitability of cerebellar granule and Purkinje neurons. It is not known, however, whether these phenotypes result from defects in neuronal development or if they reflect a physiological requirement for iFGF14 in the adult cerebellum. Here, we demonstrate that the acute and selectiveFgf14-targeted short hairpin RNA (shRNA)-mediatedin vivo“knock-down” of iFGF14 in adult Purkinje neurons attenuates spontaneous and evoked action potential firing without measurably affecting the expression or localization of voltage-gated Na+(Nav) channels at Purkinje neuron axon initial segments. The selective shRNA-mediatedin vivo“knock-down” of iFGF14 in adult Purkinje neurons also impairs motor coordination and balance. Repetitive firing can be restored inFgf14-targeted shRNA-expressing Purkinje neurons, as well as inFgf14−/−Purkinje neurons, by prior membrane hyperpolarization, suggesting that the iFGF14-mediated regulation of the excitability of mature Purkinje neurons depends on membrane potential. Further experiments revealed that the loss of iFGF14 results in a marked hyperpolarizing shift in the voltage dependence of steady-state inactivation of the Nav currents in adult Purkinje neurons. We also show here that expressing iFGF14 selectively in adultFgf14−/−Purkinje neurons rescues spontaneous firing and improves motor performance. Together, these results demonstrate that iFGF14 is required for spontaneous and evoked action potential firing in adult Purkinje neurons, thereby controlling the output of these cells and the regulation of motor coordination and balance.
Estrogen Permits Vasopressin Signaling in Preoptic Kisspeptin Neurons in the Female Mouse
Authors: Piet Richard , Fraissenon Antoine , Boehm Ulrich , Herbison Allan E.
Published: April 2015

The cellular mechanisms governing the impact of the central circadian clock on neuronal networks are incompletely understood. We examine here the influence of the suprachiasmatic nucleus output neuropeptide arginine-vasopressin (AVP) on the activity of preoptic area kisspeptin neurons. These cells integrate circadian and hormonal signals within the neuronal network that regulates fertility in females. Electrophysiological recordings in brain slices from kisspeptin-GFP mice showed that AVP dose-dependently increased the firing rate of most kisspeptin neurons. These actions were mediated directly at the kisspeptin neuron. Experiments in mice expressing the calcium indicator GCaMP3 in kisspeptin neurons enabled simultaneous monitoring of intracellular calcium concentrations ([Ca2+]i) in multiple cells and revealed that AVP increased [Ca2+]iin >80% of diestrous kisspeptin neurons via a mechanism involving voltage-gated calcium channels. We next examined whether AVP signaling in kisspeptin neurons was time and ovarian cycle dependent. AVP exerted the same effects on diestrous and proestrous days of the ovarian cycle, whether hours before [zeitgeber time 4 (ZT4)–ZT6] or just before (ZT10) the expected time of the proestrous preovulatory luteinizing hormone surge. Remarkably, however, AVP signaling was critically dependent on circulating ovarian steroids as AVP no longer excited preoptic kisspeptin neurons in ovariectomized mice, an effect that was fully restored by estradiol treatment. Together, these studies show that AVP exerts a potent and direct stimulatory influence upon the electrical activity and [Ca2+]iof most preoptic kisspeptin neurons. Unexpectedly, estrogen is found to permit circadian AVP signaling at preoptic kisspeptin neurons rather than dynamically modulate its activity throughout the estrous cycle.
Enhanced Firing in NTS Induced by Short-Term Sustained Hypoxia Is Modulated by Glia-Neuron Interaction
Authors: Accorsi-Mendonça Daniela , Almado Carlos E.L. , Bonagamba Leni G.H. , Castania Jaci A. , Moraes Davi J.A. , Machado Benedito H.
Published: April 2015

Humans ascending to high altitudes are submitted to sustained hypoxia (SH), activating peripheral chemoreflex with several autonomic and respiratory responses. Here we analyzed the effect of short-term SH (24 h, FIO210%) on the processing of cardiovascular and respiratory reflexes using anin situpreparation of rats. SH increased both the sympatho-inhibitory and bradycardiac components of baroreflex and the sympathetic and respiratory responses of peripheral chemoreflex. Electrophysiological properties and synaptic transmission in the nucleus tractus solitarius (NTS) neurons, the first synaptic station of afferents of baroreflexes and chemoreflexes, were evaluated using brainstem slices and whole-cell patch-clamp. The second-order NTS neurons were identified by previous application of fluorescent tracer onto carotid body for chemoreceptor afferents or onto aortic depressor nerve for baroreceptor afferents. SH increased the intrinsic excitability of NTS neurons. Delayed excitation, caused by A-type potassium current (IKA), was observed in most of NTS neurons from control rats. The IKAamplitude was higher in identified second-order NTS neurons from control than in SH rats. SH also blunted the astrocytic inhibition of IKAin NTS neurons and increased the synaptic transmission in response to afferent fibers stimulation. The frequency of spontaneous excitatory currents was also increased in neurons from SH rats, indicating that SH increased the neurotransmission by presynaptic mechanisms. Therefore, short-term SH changed the glia-neuron interaction, increasing the excitability and excitatory transmission of NTS neurons, which may contribute to the observed increase in the reflex sensitivity of baroreflex and chemoreflex inin situpreparation.
Tracking the Brain's Functional Coupling Dynamics over Development
Authors: Hutchison R. Matthew , Morton J. Bruce
Published: April 2015

The transition from childhood to adulthood is marked by pronounced functional and structural brain transformations that impact cognition and behavior. Here, we use a functional imaging approach to reveal dynamic changes in coupling strength between networks and the expression of discrete brain configurations over human development during rest and a cognitive control task. Although the brain's repertoire of functional states was generally preserved across ages, state-specific temporal features, such as the frequency of expression and the amount of time spent in select states, varied by age in ways that were dependent on condition. Increasing age was associated with greater variability of connection strengths across time at rest, while there was a selective inversion of this effect in higher-order networks during implementation of cognitive control. The results suggest that development is characterized by the modification of dynamic coupling to both maximize and constrain functional variability in response to ongoing cognitive and behavioral requirements.