bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact Testing of Metals
Authors: Driscoll DE
Published: March 2009

Description

The papers in the Symposium on Impact Testing of Metals were given at the Seventy-second Annual Meeting of the American Society for Testing and Mater als held in Atlantic City, N. J., 22-27 June 1969. The sponsors of this symposium were Committee E01 on Methods of Testing, Subcommittee 7 on Impact Testing, and Committee E24 on Fracture Testing of Metals. D. E. Driscoll, Army Materials and Mechanics Research Center, presided as symposium chairman.
Characterization and Determination of Erosion Resistance
Authors: Committee G-2
Published: March 2009

Description

This publication is a collection of most of the papers presented at the Symposium on Characterization and Determination of Erosion Resistance, organized by Committee G02 on Erosion by Cavitation or Impingement in co-operation with the U. S. Office of Naval Research, at the Seventy-second Annual Meeting of the American Society for Testing and Materials held at Atlantic City, N. J., 22-27 June 1969. A Thiruvengadam, Hydronautics Inc., now at Catholic University of America, presided as chairman of the symposium, and F. J. Heyman, Westinghouse Electric Corp., presided as co-chairman of the symposium.
Analysis of Reactor Vessel Radiation Effects Surveillance Programs
Authors: Steele LE , Serpan CZ
Published: March 2009

Description

Many factors have combined to accelerate the programs of the members of the electric power industry for the erection of power stations using nuclear fuel.
E-Cadherin Regulates Neural Stem Cell Self-Renewal
Authors: Karpowicz Phillip , Willaime-Morawek Sandrine , Balenci Laurent , DeVeale Brian , Inoue Tomoyuki , van der Kooy Derek
Published: March 2009

E-Cadherin, a cell adhesion protein, has been shown to take part in the compartmentalization, proliferation, survival, and differentiation of cells. E-Cadherin is expressed in the adult and embryonic forebrain germinal zonesin vivo, and in clonal colonies of cells derived from these regions and grownin vitro. Mice carrying E-Cadherin floxed genes crossed to mice expressing Cre under the Nestin promoter demonstrate defects in the self-renewal of neural stem cells bothin vivoandin vitro. The functional role of E-Cadherin is further demonstrated using adhesion-blocking antibodiesin vitro, which specifically target cadherin extracellular adhesive domains. Adult neural stem cell colonies decrease in the presence of E-Cadherin antibodies in a dosage-dependent manner, in contrast to P-Cadherin antibody. On overexpression of normal E-Cadherin and a mutated E-Cadherin, containing no intracellular binding domain, an increased number of clonal adult neural stem cell colonies are observed. These data suggest it is specifically E-Cadherin adhesion that is responsible for these self-renewal effects. These data show the importance of E-Cadherin in the neural stem cell niche and suggest E-Cadherin regulates the number of these cells.
Macrophages Promote Axon Regeneration with Concurrent Neurotoxicity
Authors: Gensel John C. , Nakamura Satoshi , Guan Zhen , van Rooijen Nico , Ankeny Daniel P. , Popovich Phillip G.
Published: March 2009

Activated macrophages can promote regeneration of CNS axons. However, macrophages also release factors that kill neurons. These opposing functions are likely induced simultaneously but are rarely considered together in the same experimental preparation. A goal of this study was to unequivocally document the concurrent neurotoxic and neuroregenerative potential of activated macrophages. To do so, we quantified the length and magnitude of axon growth from enhanced green fluorescent protein-expressing dorsal root ganglion (DRG) neurons transplanted into the spinal cord in relationship to discrete foci of activated macrophages. Macrophages were activated via intraspinal injections of zymosan, a potent inflammatory stimulus known to increase axon growth and cause neurotoxicity. Using this approach, a significant increase in axon growth up to macrophage foci was evident. Within and adjacent to macrophages, DRG and spinal cord axons were destroyed. Macrophage toxicity became more evident when zymosan was injected closer to DRG soma. Under these conditions, DRG neurons were killed or their ability to extend axons was dramatically impaired. The concurrent induction of pro-regenerative and neurotoxic functions in zymosan-activated macrophages (ZAMs) was confirmedin vitrousing DRG and cortical neurons. Importantly, the ability of ZAMs to stimulate axon growth was transient; prolonged exposure to factors produced by ZAMs enhanced cell death and impaired axon growth in surviving neurons. Lipopolysaccharide, another potent macrophage activator, elicited a florid macrophage response, but without enhancing axon growth or notable toxicity. Together, these data show that a single mode of activation endows macrophages with the ability to simultaneously promote axon regeneration and cell killing.
Localization of the Endocannabinoid-Degrading Enzyme Fatty Acid Amide Hydrolase in Rat Dorsal Root Ganglion Cells and Its Regulation after Peripheral Nerve Injury
Authors: Lever Isobel J. , Robinson Michelle , Cibelli Mario , Paule Cleoper , Santha Peter , Yee Louis , Hunt Stephen P. , Cravatt Benjamin F. , Elphick Maurice R. , Nagy Istvan , Rice Andrew S. C.
Published: March 2009

Fatty acid amide hydrolase (FAAH) is a degradative enzyme for a group of endogenous signaling lipids that includes anandamide (AEA). AEA acts as an endocannabinoid and an endovanilloid by activating cannabinoid and vanilloid type 1 transient receptor potential (TRPV1) receptors, respectively, on dorsal root ganglion (DRG) sensory neurons. Inhibition of FAAH activity increases AEA concentrations in nervous tissue and reduces sensory hypersensitivity in animal pain models. Using immunohistochemistry, Western blotting, and reverse transcription-PCR, we demonstrate the location of the FAAH in adult rat DRG, sciatic nerve, and spinal cord. In naive rats, FAAH immunoreactivity localized to the soma of 32.7 ± 0.8% of neurons in L4 and L5 DRG. These were small-sized (mean soma area, 395.96 ± 5.6 μm2) and predominantly colabeled with peripherin and isolectin B4 markers of unmyelinated C-fiber neurons; 68% colabeled with antibodies to TRPV1 (marker of nociceptive DRG neurons), and <2% colabeled with NF200 (marker of large myelinated neurons). FAAH-IR was also present in small, NF200-negative cultured rat DRG neurons. Incubation of these cultures with the FAAH inhibitor URB597 increased AEA-evoked cobalt uptake in a capsazepine-sensitive manner. After sciatic nerve axotomy, there was a rightward shift in the cell-size distribution of FAAH-immunoreactive (IR) DRG neurons ipsilateral to injury: FAAH immunoreactivity was detected in larger-sized cells that colabeled with NF200. An ipsilateral versus contralateral increase in both the size and proportion of FAAH-IR DRG occurred after spinal nerve transection injury but not after chronic inflammation of the rat hindpaw 2 d after injection of complete Freund's adjuvant. This study reveals the location of FAAH in neural tissue involved in peripheral nociceptive transmission.
Correlated Connectivity and the Distribution of Firing Rates in the Neocortex
Authors: Koulakov Alexei A. , Hromádka Tomáš , Zador Anthony M.
Published: March 2009

Two recent experimental observations pose a challenge to many cortical models. First, the activity in the auditory cortex is sparse, and firing rates can be described by a lognormal distribution. Second, the distribution of nonzero synaptic strengths between nearby cortical neurons can also be described by a lognormal distribution. Here we use a simple model of cortical activity to reconcile these observations. The model makes the experimentally testable prediction that synaptic efficacies onto a given cortical neuron are statistically correlated, i.e., it predicts that some neurons receive stronger synapses than other neurons. We propose a simple Hebb-like learning rule that gives rise to such correlations and yields both lognormal firing rates and synaptic efficacies. Our results represent a first step toward reconciling sparse activity and sparse connectivity in cortical networks.
The Neural Correlates of Visual and Verbal Cognitive Styles
Authors: Kraemer David J. M. , Rosenberg Lauren M. , Thompson-Schill Sharon L.
Published: March 2009

It has long been thought that propensities for visual or verbal learning styles influence how children acquire knowledge successfully and how adults reason in everyday life. There is no direct evidence to date, however, linking these cognitive styles to specific neural systems. In the present study, visual and verbal cognitive styles are measured by self-report survey, and cognitive abilities are measured by scored tests of visual and verbal skills. Specifically, we administered the Verbalizer–Visualizer Questionnaire (VVQ) and modality-specific subtests of the Wechsler Adult Intelligence Scale (WAIS) to 18 subjects who subsequently participated in a functional magnetic resonance imaging experiment. During the imaging session, participants performed a novel psychological task involving both word-based and picture-based feature matching conditions that was designed to permit the use of either a visual or a verbal processing style during all conditions of the task. Results demonstrated a pattern of activity in modality-specific cortex that distinguished visual from verbal cognitive styles. During the word-based condition, activity in a functionally defined brain region that responded to viewing pictorial stimuli (fusiform gyrus) correlated with self-reported visualizer ratings on the VVQ. In contrast, activity in a phonologically related brain region (supramarginal gyrus) correlated with the verbalizer dimension of the VVQ during the picture-based condition. Scores from the WAIS subtests did not reliably correlate with brain activity in either of these regions. These findings suggest that modality-specific cortical activity underlies processing in visual and verbal cognitive styles.
Early Withdrawal of Axons from Higher Centers in Response to Peripheral Somatosensory Denervation
Authors: Graziano Alessandro , Jones Edward G.
Published: March 2009

The mechanisms responsible for long-term, massive reorganization of representational maps in primate somatosensory cortex after deafferentation are poorly understood. Sprouting of cortical axons cannot account for the extent of reorganization, and withdrawal of axons of deafferented brainstem and thalamic neurons, permitting expression of previously silent synapses, has not been directly demonstrated. This study is focused on the second of these. In monkeys, deafferented for two years by section of the cuneate fasciculus at the C1 level, there was extensive withdrawal of axon terminals from thalamus and cortex, detectable a decade before visible atrophy of their parent neuronal somata in the cuneate nucleus or thalamus. Slow, inexorable progression of lemniscal and thalamocortical axonal withdrawal is a neurodegenerative phenomenon likely to be a powerful inducement to compensatory long-term plasticity, a mechanism that can explain the long-term evolution of cortical reorganization and, with it, phantom sensations in spinal patients and amputees.
Nicotinic Receptors Concentrated in the Subsynaptic Membrane Do Not Contribute Significantly to Synaptic Currents at an Embryonic Synapse in the Chicken Ciliary Ganglion
Authors: Sargent Peter B.
Published: March 2009

Rapid synaptic transmission at the calyciform synapse in the embryonic chicken ciliary ganglion is mediated by two classes of nicotinic receptors: those containing α3 subunits [α3-nicotinic ACh receptors (nAChRs)] and those containing α7 subunits (α7-nAChRs). α3-nAChRs and α7-nAChRs are differentially distributed on the cell surface; α3-nAChRs are concentrated at postsynaptic densities, whereas both α7-nAChRs and α3-nAChRs are found extrasynaptically on somatic spines. I explored the contribution of α3-nAChRs and α7-nAChRs to uniquantal responses, measured as mEPSCs, or as evoked responses under low release probability conditions. The contribution that each nAChR makes to uniquantal response shape was determined by blocking one nAChR type; pharmacologically isolated α7-nAChR responses were kinetically fast (rise time, 0.32 ± 0.02 ms; decay time, 1.66 ± 0.18 ms; mean ± SD;n= 6 cells), whereas pharmacologically isolated α3-nAChR responses were slow (rise time, 1.28 ± 0.35 ms; decay time, 6.71 ± 1.46 ms;n= 8 cells). In the absence of antagonists, most cells (11 of 14) showed heterogeneity in the kinetics of uniquantal responses, with ∼25% of events exhibiting fast, α7-nAChR-like kinetics and ∼75% of events exhibiting the kinetics expected of coactivation of α7-nAChRs and α3-nAChRs. Cells rarely showed significant numbers of uniquantal responses with slow, α3-nAChR-like kinetics, which was unexpected given that α3-nAChRs alone are concentrated at postsynaptic densities. The only site where ACh quanta can activate both α3-nAChRs and α7-nAChRs readily is on the somatic spines, where α7-nAChRs and α3-nAChRs are present extrasynaptically. At the calyciform synapse, rapid synaptic transmission is mediated apparently without participation of ionotropic receptors concentrated at postsynaptic densities.
The P2X7Receptor Drives Microglial Activation and Proliferation: A Trophic Role for P2X7R Pore
Authors: Monif Mastura , Reid Christopher A. , Powell Kim L. , Smart Megan L. , Williams David A.
Published: March 2009

Microglial activation is an integral part of neuroinflammation associated with many neurodegenerative conditions. Interestingly, a number of neurodegenerative conditions exhibit enhanced P2X7receptor (P2X7R) expression in the neuroinflammatory foci where activated microglia are a coexisting feature. Whether P2X7R overexpression is driving microglial activation or, conversely, P2X7R overexpression is a consequence of microglial activation is not known. We report that overexpression alone of a purinergic P2X7R, in the absence of pathological insults, is sufficient to drive the activation and proliferation of microglia in rat primary hippocampal cultures. The trophic responses observed in microglia were found to be P2X7R specific as the P2X7R antagonist, oxidized ATP (oxATP), was effective in markedly attenuating microgliosis. oxATP treatment of primary hippocampal cultures expressing exogenous P2X7Rs resulted in a significant decrease in the number of activated microglia. P2X7R is unusual in exhibiting two conductance states, a cation channel and a plasma membrane pore, and there are no pharmacological agents capable of cleanly discriminating between these two states. We used a point mutant of P2X7R (P2X7RG345Y) with intact channel function but ablated pore-forming capacity to establish that the trophic effects of increased P2X7R expression are exclusively mediated by the pore conductance. Collectively, and contrary to previous reports describing P2X7R as a “death receptor,” we provide evidence for a novel trophic role for P2X7R pore in microglia.
Synthesis of Lipoxin A4by 5-Lipoxygenase Mediates PPARγ-Dependent, Neuroprotective Effects of Rosiglitazone in Experimental Stroke
Authors: Sobrado Mónica , Pereira Marta P. , Ballesteros Iván , Hurtado Olivia , Fernández-López David , Pradillo Jesús M. , Caso Javier R. , Vivancos José , Nombela Florentino , Serena Joaquín , Lizasoain Ignacio , Moro María A.
Published: March 2009

Peroxisome proliferator-activated receptors gamma (PPARγ) are nuclear receptors with essential roles as transcriptional regulators of glucose and lipid homeostasis. PPARγ are also potent anti-inflammatory receptors, a property that contributes to the neuroprotective effects of PPARγ agonists in experimental stroke. The mechanism of these beneficial actions, however, is not fully elucidated. Therefore, we have explored further the actions of the PPARγ agonist rosiglitazone in experimental stroke induced by permanent middle cerebral artery occlusion (MCAO) in rodents. Rosiglitazone induced brain 5-lipoxygenase (5-LO) expression in ischemic rat brain, concomitantly with neuroprotection. Rosiglitazone also increased cerebral lipoxin A4(LXA4) levels and inhibited MCAO-induced production of leukotriene B4 (LTB4). Furthermore, pharmacological inhibition and/or genetic deletion of 5-LO inhibited rosiglitazone-induced neuroprotection and downregulation of inflammatory gene expression, LXA4synthesis and PPARγ transcriptional activity in rodents. Finally, LXA4caused neuroprotection, which was partly inhibited by the PPARγ antagonist T0070907, and increased PPARγ transcriptional activity in isolated nuclei, showing for the first time that LXA4has PPARγ agonistic actions. Altogether, our data illustrate that some effects of rosiglitazone are attributable tode novosynthesis of 5-LO, able to induce a switch from the synthesis of proinflammatory LTB4to the synthesis of the proresolving LXA4. Our study suggests novel lines of study such as the interest of lipoxin-like anti-inflammatory drugs or the use of these molecules as prognostic and/or diagnostic markers for pathologies in which inflammation is involved, such as stroke.
Interferon-α Causes Neuronal Dysfunction in Encephalitis
Authors: Sas Andrew R. , Bimonte-Nelson Heather , Smothers C. Thetford , Woodward John , Tyor William R.
Published: March 2009

Interferon-α (IFNα) is a pleomorphic cytokine produced by nucleated cells in response to viral infection. In patients, treatment with IFNα has side effects including cognitive impairment resembling subcortical dementia, which is a hallmark of human immunodeficiency virus (HIV)-associated dementia (HAD). IFNα is increased in the CSF of HAD patients compared with HIV patients without dementia. In this study, blocking IFNα in a HIV encephalitis (HIVE) mouse model with intraperitoneal injections of IFNα neutralizing antibodies (NAbs) significantly improved cognitive function compared with untreated or control antibody-treated HIVE mice during water radial arm maze behavioral testing. Treatment with IFNα NAbs significantly decreased microgliosis and prevented loss of dendritic arborization in the brains of HIVE mice. Furthermore, treatment of primary neuron cultures with IFNα resulted in dose-dependent loss of dendritic arborization that was blocked with IFNα NAb treatment and partially blocked with NMDA antagonists [AP5 and MK801 (dizocilpine maleate)] indicating glutamate signaling is involved in IFNα-mediated neuronal damage. These results show that IFNα has a major role in the pathogenesis of HIVE in mice and is likely important in the development neurocognitive dysfunction in humans with HIV. Blocking IFNα could be important in improving cognitive and pathological developments in HAD patients and may be clinically important in other neuroinflammatory diseases as well.
Synaptic Vesicle Recycling at CNS Synapses without AP-2
Authors: Kim Sung Hyun , Ryan Timothy A.
Published: March 2009

Synaptic vesicles (SVs) are composed of ∼10 types of transmembrane proteins that must be recycled after exocytosis of neurotransmitter. The mechanisms for resorting these proteins into synaptic vesicles once incorporated into the plasma membrane after exocytosis are poorly understood. The adaptor complex AP-2 is the major clathrin-associated adaptor for cargo recognition at the plasma membrane. Here, we have investigated its role in synaptic vesicle endocytosis. shRNA-mediated knockdown of the AP-2 complex results in an ∼96% reduction of this protein complex in primary neurons. We used simultaneous expression of shRNA and pHluorin-tagged vesicle components to show that the absence of AP-2 significantly slows but does not prevent the endocytosis of four of the major synaptic vesicle transmembrane proteins. We show that in the absence of AP-2, the AP-1 adaptor complex appears to functionally substitute for AP-2 but results in complex internalization kinetics that are now sensitive to the guanine-nucleotide exchange factor for ADP-ribosylation factor GTPase (ARF–GEF) inhibitor brefeldin-A (BFA). Simultaneous removal of both AP-2 and AP-1 prevents this compensatory substitution and results in slowed but functional endocytosis. These results demonstrate that in the absence of AP-2, SV proteins still become endocytosed, and synaptic vesicle recycling remains operational.
A Laminin-2, Dystroglycan, Utrophin Axis Is Required for Compartmentalization and Elongation of Myelin Segments
Authors: Court Felipe A. , Hewitt Jane E. , Davies Kay , Patton Bruce L. , Uncini Antonino , Wrabetz Lawrence , Feltri M. Laura
Published: March 2009

Animal and plant cells compartmentalize to perform morphogenetic functions. Compartmentalization of myelin-forming Schwann cells may favor elongation of myelin segments to the size required for efficient conduction of nerve impulses. Compartments in myelinated fibers were described by Ramón y Cajal and depend on periaxin, mutated in the hereditary neuropathy Charcot–Marie–Tooth disease type 4F (Charcot–Marie–Tooth 4F). Lack of periaxin in mice causes loss of compartments, formation of short myelin segments (internodes) and reduced nerve conduction velocity. How compartments are formed and maintained, and their relevance to human neuropathies is largely unknown. Here we show that formation of compartments around myelin is driven by the actin cytoskeleton, and maintained by actin and tubulin fences through linkage to the dystroglycan complex. Compartmentalization and establishment of correct internodal length requires the presence of glycosylated dystroglycan, utrophin and extracellular laminin-2/211. A neuropathic patient with reduced internodal length and nerve conduction velocity because of absence of laminin-2/211 (congenital muscular dystrophy 1A) also shows abnormal compartmentalization. These data link formation of compartments through a laminin2, dystroglycan, utrophin, actin axis to internodal length, and provide a common pathogenetic mechanism for two inherited human neuropathies. Other cell types may exploit dystroglycan complexes in similar fashions to create barriers and compartments.
mGluR5 Has a Critical Role in Inhibitory Learning
Authors: Xu Jian , Zhu Yongling , Contractor Anis , Heinemann Stephen F.
Published: March 2009

The mechanisms that contribute to the extinction of previously acquired memories are not well understood. These processes, often referred to as inhibitory learning, are thought to be parallel learning mechanisms that require a reacquisition of new information and suppression of previously acquired experiences in order to adapt to novel situations. Using newly generated metabotropic glutamate receptor 5 (mGluR5) knock-out mice, we investigated the role of mGluR5 in the acquisition and reversal of an associative conditioned task and a spatial reference task. We found that acquisition of fear conditioning is partially impaired in mice lacking mGluR5. More markedly, we found that extinction of both contextual and auditory fear was completely abolished in mGluR5 knock-out mice. In the Morris Water Maze test (MWM), mGluR5 knock-out mice exhibited mild deficits in the rate of acquisition of the regular water maze task, but again had significant deficits in the reversal task, despite overall spatial memory being intact. Together, these results demonstrate that mGluR5 is critical to the function of neural circuits that are required for inhibitory learning mechanisms, and suggest that targeting metabotropic receptors may be useful in treating psychiatric disorders in which aversive memories are inappropriately retained.
Discovery of Potent Kisspeptin Antagonists Delineate Physiological Mechanisms of Gonadotropin Regulation
Authors: Roseweir Antonia K. , Kauffman Alexander S. , Smith Jeremy T. , Guerriero Kathryn A. , Morgan Kevin , Pielecka-Fortuna Justyna , Pineda Rafael , Gottsch Michelle L. , Tena-Sempere Manuel , Moenter Suzanne M. , Terasawa Ei , Clarke Iain J. , Steiner Robert A. , Millar Robert P.
Published: March 2009

Neurons that produce gonadotropin-releasing hormone (GnRH) are the final common pathway by which the brain regulates reproduction. GnRH neurons are regulated by an afferent network of kisspeptin-producing neurons. Kisspeptin binds to its cognate receptor on GnRH neurons and stimulates their activity, which in turn provides an obligatory signal for GnRH secretion, thus gating down-stream events supporting reproduction. We have developed kisspeptin antagonists to facilitate the direct determination of the role of kisspeptin neurons in the neuroendocrine regulation of reproduction.In vitroandin vivostudies of analogues of kisspeptin-10 with amino substitutions have identified several potent and specific antagonists. A selected antagonist was shown to inhibit the firing of GnRH neurons in the brain of the mouse and to reduce pulsatile GnRH secretion in female pubertal monkeys; the later supporting a key role of kisspeptin in puberty onset. This analog also inhibited the kisspeptin-induced release of luteinizing hormone (LH) in rats and mice and blocked the postcastration rise in LH in sheep, rats, and mice, suggesting that kisspeptin neurons mediate the negative feedback effect of sex steroids on gonadotropin secretion in mammals. The development of kisspeptin antagonists provides a valuable tool for investigating the physiological and pathophysiological roles of kisspeptin in the regulation of reproduction and could offer a unique therapeutic agent for treating hormone-dependent disorders of reproduction, including precocious puberty, endometriosis, and metastatic prostate cancer.
Cisplatin-Induced Hair Cell Death Requires STAT1 and Is Attenuated by Epigallocatechin Gallate
Authors: Schmitt Nicole C. , Rubel Edwin W , Nathanson Neil M.
Published: March 2009

Cisplatin is a chemotherapy drug that frequently causes auditory impairment due to the death of mechanosensory hair cells. Cisplatin ototoxicity may result from oxidative stress, DNA damage, and inflammatory cytokines. The transcription factor STAT1, an important mediator of cell death, can regulate all of these processes in other cell types. We used cultured utricles from mature Swiss Webster mice to investigate the role of STAT1 in cisplatin-induced hair cell death. We show that STAT1 phosphorylation is an early event in both hair cells and support cells after exposure of utricles to cisplatin. STAT1 phosphorylation peaked after 4 h of cisplatin exposure and returned to control levels by 8 h of exposure. The STAT1 inhibitor epigallocatechin gallate (EGCG) attenuated STAT1 phosphorylation in cisplatin-treated utricles and resulted in concentration-dependent increases in hair cell survival at 24 h postexposure. Furthermore, we show that utricular hair cells from STAT1-deficient mice are resistant to cisplatin toxicity. EGCG failed to provide additional protection from cisplatin in STAT1-deficient mice, further supporting the hypothesis that the protective effects of EGCG are due to its inhibition of STAT1. Treatment with IFN-γ, which also causes STAT1 activation, also induced hair cell death in wild-type but not STAT1-deficient mice. These results show that STAT1 is required for maximal cisplatin-induced hair cell death in the mouse utricle and suggest that treatment with EGCG may be a useful strategy for prevention of cisplatin ototoxicity.
Companion Platform – Modular Software Platform for Rapid Development of Mobile ApplicationsCompanion Plattform – Modulare Softwareplattform zur schnellen Entwicklung von mobilen Anwendungen
Authors: Wichmann Daniel , Pielot Martin , Boll Susanne
Published: March 2009

Mobility has become an important part of our daily life, but caused by numerous challenges the development of mobile applications in the sense of location-aware applications for mobile devices is complex and time-consuming. To overcome the challenges, a software support for rapid development of mobile applications is needed. Reusability is an appropriate approach to achieve this goal. When developing mobile applications it can be observed that some functionalities such as, e. g., location sensing and map display are required in most cases. Therefore we developed the Companion platform which provides these functionalities as reusable modules in a pre-defined architecture. It supports developers in the difficult mobile development by allowing them to realize their application ideas faster and with higher quality based on a simple building block concept. The Companion platform is used for a broad variety of applications and advances continuously based on long experiences in the area of mobile application development.
Review of Data Management Mechanisms on Mobile DevicesÜberblick über Datenmanagementmechanismen auf mobilen Endgeräten
Authors: Höpfner Hagen , Mansour Essam , Nicklas Daniela
Published: March 2009

The design of data management for mobile applications is a non-trivial task. Even with today´s much more powerful devices, we must consider limited resources: size and persistence of the local data storage, limited bandwidth and reliability of connection for data transmissions to remote servers, and constraint energy consumption of the used algorithms. In this article we focus on client/server approaches. We classify existing techniques and support the designer of data management functionalities for mobile applications with a set of fundamental characteristics of replication, hoarding and caching solutions.
Context Modeling for Mobile, Adaptive ApplicationsKontextmodellierung für mobile, adaptive Anwendungen
Authors: Nicklas Daniela , Grossmann Matthias , Wieland Matthias
Published: March 2009

Context-aware applications adapt their behavior according to the current situation. In this paper we present a layered model to separate different tasks and concerns in designing data models for context-aware applications. The layers are discussed along the Nexus approach, which is designed to support large-scale, mobile applications by federated context models. Furthermore, related approaches are described and compared.
Dynamisches eigennütziges RoutingDynamic Selfish Routing
Authors: Fischer Simon
Published: March 2009

In der algorithmischen Spieltheorie modellieren wir das Verhalten von eigennützigen Agenten in großen Netzwerken als strategisches Spiel: Jeder Agent versucht, den eigenen Nutzen zu maximieren, ohne dabei auf mögliche Verschlechterungen für andere Agenten Rücksicht zu nehmen. Das dominierende Lösungskonzept in solchen Spielen ist das Nash-Gleichgewicht, ein Zustand, in dem kein Agent seine eigene Situation verbessern kann. Zwar ist es unstreitig, dass ein solcher Zustand stabil ist, aber es ist nicht unmittelbar klar, wie er erreicht werden kann, da eine Berechnung durch die Agenten auf Grund fehlenden Wissens und mangelnder Berechnungskraft nicht möglich ist. In dieser Arbeit betrachten wir daher ein dynamisches Modell, in dem die Agenten parallel und unabhängig voneinander einfache Verbesserungsschritte ausführen, die nur auf lokal verfügbarer Information basieren. Wir zeigen, dass eine Population von Agenten auf lange Sicht zu einem Nash-Gleichgewicht konvergiert. Ein Hauptproblem ist dabei das unkoordinierte parallele Vorgehen der Agenten, das zu einem Überschießen führen kann. Wir geben ein Kriterium an, das sicher stellt, dass dieser Effekt nicht auftritt, und zeigen, dass auch in sehr großen Netzwerken schnelle Konvergenz zum Gleichgewicht möglich ist.
Excellence Cluster “Cognitive Interaction Technology” – Cognition as a Basis for Natural Interaction with Technical SystemsExzellenzcluster “Cognitive Interaction Technology” — Kognition als Basis natürlicher Interaktion mit technischen Systemen
Authors: Ritter Helge , Sagerer Gerhard
Published: March 2009

What is necessary to enhance the command of complex technical systems in order to reach the ease and naturalness of human communication? How can we endow technical devices with the necessary cognitive abilities to support humans at a high level of semantic interaction offering true flexibility by virtue of adaptivity, self-organization, and learning? These are the guiding questions of the Excellence Cluster “Cognitive Interaction Technology” established since November 2007 at Bielefeld University. It focusses the efforts of computer scientists, psychologists, linguists, physicists and biologists on the goal of establishing cognitive interfaces that facilitate the use of complex technical systems by providing a high level of semantic interaction. This combines interdisciplinary, basic, and applied research beyond the classical confines of artificial intelligence. It aims at a thorough understanding of the processes and functional constituents of cognitive interaction in order to replicate it in technical systems including the development of evaluation methodologies and tool-kits for such systems. The research agenda of the EC is organized around four central topic areas: Motion Intelligence, Attentive Systems, Situated Communication, Memory and Learning. In addition, the EC is offering a cross-disciplinary education program.
Identification of a diffuse form of hyperinsulinemic hypoglycemia by 18-fluoro-l-3,4 dihydroxyphenylalanine positron emission tomography/CT in a patient carrying a novel mutation of the HADH gene
Authors: Di Candia Stefania , Gessi Alessandra , Pepe Gino , Sogno Valin Paola , Mangano Eleonora , Chiumello Giuseppe , Gianolli Luigi , Proverbio Maria Carla , Mora Stefano
Published: March 2009

Objective

Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infancy (HI), leading to severe neurologic disabilities if not promptly treated. The recent application of positron emission tomography (PET)/computed tomography (CT) scanning with 18-fluoro-l-3,4 dihydroxyphenylalanine improved the ability to distinguish the two histopathologic forms of HI (focal and diffuse), whose differentiation heavily influences the therapeutic management of the patient.

Case report

We describe the case of a patient presenting with severe hypoglycemia from infancy. High concentration of insulin suggested the diagnosis of congenital hyperinsulinism. No metabolic disorders related to amino acid, organic acids or fatty acid oxidation were detected. Medical treatment was able to obtain a satisfactory metabolic response.

Results

The patient underwent PET/CT scanning, revealing a diffuse form of the disease. The absence of mutations inKCNJ11andABCC8genes (responsible for 50% of HI cases), and whole genome single nucleotide polymorphisms analysis by microarray suggested theHADHgene as a likely candidate. Sequence analysis revealed a novel homozygous nonsense mutation (R236X) inHADHgene.

Conclusions

This case indicates that mutations of theHADHgene should be sought in hyperinsulinemic patients in whom diffuse form of HI and autosomal recessive inheritance can be presumed whenKCNJ11andABCC8genes mutational screening is negative, even in the absence of altered organic acids and acylcarnitines concentration.
Changes in the glucose-6-phosphate dehydrogenase activity in granulosa cells during follicular atresia in ewes
Authors: Ortega-Camarillo Clara , González-González Alicia , Vergara-Onofre Marcela , González-Padilla Everardo , Ávalos-Rodríguez Alejandro , Gutiérrez-Rodríguez Margarita E , Arriaga-Pizano Lourdes , Cruz Miguel , Baiza-Gutman Luís Arturo , Díaz-Flores Margarita
Published: March 2009

Apoptosis of granulosa cells during follicular atresia is preceded by oxidative stress, partly due to a drop in the antioxidant glutathione (GSH). Under oxidative stress, GSH regeneration is dependent on the adequate supply of NADPH by glucose-6-phosphate dehydrogenase (G6PD). In this study, we analyzed the changes of G6PD, GSH, and oxidative stress of granulosa cells and follicular liquid and its association with apoptosis during atresia of small (4–6 mm) and large (>6 mm) sheep antral follicles. G6PD activity was found to be higher in granulosa cells of healthy small rather than large follicles, with similar GSH concentration in both cases. During atresia, increased apoptosis and protein oxidation, as well as a drop in GSH levels, were observed in follicles of both sizes. Furthermore, the activity of G6PD decreased in atretic small follicles, but not in large ones. GSH decreased and protein oxidation increased in follicular fluid. This was dependent on the degree of atresia, whereas the changes in G6PD activity were based on the type of follicle. The higher G6PD activity in the small follicles could be related to granulosa cell proliferation, follicular growth, and a lower sensitivity to oxidative stress when compared with large follicles. The results also indicate that GSH concentration in atretic follicles depends on other factors in addition to G6PD, such asde novosynthesis or activity of other NADPH-producing enzymes. Finally, lower G6PD activity in large follicles indicating a higher susceptibility to oxidative stress associated to apoptosis progression in follicle atresia.
Small RNA molecules in the regulation of spermatogenesis
Authors: He Zuping , Kokkinaki Maria , Pant Disha , Gallicano G Ian , Dym Martin
Published: March 2009

Small RNA molecules (small RNAs), including small interfering RNAs (siRNAs), microRNAs (miRNAs), and piwi-interacting RNAs (piRNAs), have recently emerged as important regulators of gene expression at the post-transcriptional or translation level. Significant progress has recently been made utilizing small RNAs in elucidating the molecular mechanisms regulating spermatogenesis. Spermatogenesis is a complex process that involves the division and eventual differentiation of spermatogonial stem cells into mature spermatozoa. The process of spermatogenesis is composed of several phases: mitotic proliferation of spermatogonia to produce spermatocytes; two meiotic divisions of spermatocytes to generate haploid round spermatids; and spermiogenesis, the final phase that involves the maturation of early-round spermatids into elongated mature spermatids. A number of miRNAs are expressed abundantly in male germ cells throughout spermatogenesis, while piRNAs are only present in pachytene spermatocytes and round spermatids. In this review, we first address the synthesis, mechanisms of action, and functions of siRNA, miRNA, and piRNA, and then we focus on the recent advancements in defining the small RNAs in the regulation of spermatogenesis. Concerns pertaining to the use of siRNAs in exploring spermatogenesis mechanisms and open questions in miRNAs and piRNAs in this field are highlighted. The potential applications of small RNAs to male contraception and treatment for male infertility and testicular cancer are also discussed.
Ultrasound guidance during central venous catheterization
Authors: Winternitz Tamás , Nagy Edina , Borsodi Marianna , Zsirka-Klein Attila , Kupcsulik Péter
Published: March 2009

A centrális véna kanülálása gyakori beavatkozás súlyos állapotú betegeknél. Ennek ellenére nemritkán jár szövődménnyel, számos esetben sikertelen. Különösen igaz ez „komplikált” esetekben, sikertelen szúrás után, nyaki műtétet követően stb. Ultrahangvezérlés alkalmazásával a sikeressége növelhető, a szövődményráta csökkenthető. A szerzők prospektív vizsgálatuk során „komplikált” esetekben alkalmaztak ultrahangvezérlést a vena jugularis punkciója során. 2000-től kezdve 56 betegnél végeztek sikeres vénaszúrást ultrahangvezérléssel. Közleményükben irodalmi áttekintés mellett eredményeikről számolnak be.
Treatments of Hodgkin and non-Hodgkin lymphomas
Authors: Sréter Lídia
Published: March 2009

A rosszindulatú nyiroksejtes megbetegedések – a lymphomák – kezelésében az elmúlt években több változás történt. A Hodgkin-kór kezelésében egyre inkább rizikóadaptált kezelési stratégiát alkalmazunk, amely nemcsak a kezelés előtti vizsgálatokon és prognosztikai tényezőkön alapszik, hanem a kezelés korai stádiumában végzett ismételt PET-vizsgálat (restaging) eredményén is. A sugárkezelés alkalmazásának lehetőség szerinti minimalizálása a késői szövődményként fellépő másodlagos daganatok gyakoriságát csökkentheti. Relapsus esetén kemoszenzitív betegek esetében autológ őssejt-transzplantáció végzendő. A Hodgkin-kórban szenvedő betegek mintegy 85%-ának gyógyulása várható. A non-Hodgkin-lymphomák heterogén betegségcsoportjában az indolens non-Hodgkin-lymphomák csoportjára (CLL, myeloma multiplex, hajas sejtes leukaemia, cutan lymphomák stb.) természetes lefolyás esetén a lassú progresszió jellemző. Kezelésük palliatív, teljes gyógyulás elérése a jelenlegi lehetőségekkel általában nem lehetséges. Az agresszív NHL-ek jellemzője a gyors progresszió és a kezelés nélkül rövid idő alatt bekövetkező halálos kimenetel. Többségük citosztatikum- és sugárérzékeny. Megfelelő kezeléssel a betegek 60–70%-a komplett remisszióba (CR) kerül, és a betegek 40–50%-a véglegesen meggyógyul. Új lehetőség mindkét NHL-csoportban az immunterápia bevezetése, amely lehetőséget ad a nyugvó daganatsejtek befolyásolására is. Segítségükkel jelentősen javíthatók az eddigi terápiás eredmények. A PET-vizsgálat bevezetése az NHL-ek első és ismételt stádiumvizsgálatát is hatékonyan segíti. A kedvezőtlen prognózisú, valamint a visszaeső betegek egy részénél az autológ őssejt-transzplantáció javíthatja a prognózist.
Evolution of non-treated restless legs syndrome
Authors: Rodrigues Raimundo Nonato Delgado , Rodrigues Aída Alexandra Alvim de Abreu e Silva , Faber Jorge , Corso Jeana T. , Peixoto Thaisa F.
Published: March 2009

PURPOSE: The primary concern of this study is to evaluate the clinical course of restless legs syndrome (RLS) in a group of patients who refused treatment. METHOD: This study compares the outcome of a group of RLS patients after one year without any specific treatment. The International Restless Legs Syndrome Scale (IRLS) was applied at baseline (irls_1) and after one year (irls_2). The patients answered a simple questionnaire for the evaluation of possible environmental or life habit changes after one-year evolution. Serum ferritin was determined at baseline. An improvement index (%improvement) was established through the formula: irls_1- irls_2/irls_1 ' 100. Results were compared and a correlation analysis performed. RESULTS: A negative significant correlation was found between the patientsí age and irls_2 (r= -0.9 p=0.0018) and between %improvement and irls_2 (r= -0.88 p=0.0039). A positive and significant correlation was determined between %improvement and age. There was only a marginally significant correlation between serum ferritin and ilrs_2 (r= -0.7 p=0.052). No significant changes were found in the other elements analyzed. CONCLUSION: A favorable outcome was found in this group of RLS patients after one year evolution without treatment. The outcome was positively influenced by the patientsí age.
Sleep disorder: a possible cause of attention deficit in children and adolescents with Chiari malformation type II
Authors: Henriques Filho Paulo Sérgio Azeredo , Pratesi Riccardo
Published: March 2009

BACKGROUND: Attention deficit may be related to sleep disorders in Chiari malformation type II (CMII). Our aim is identify sleep disorders and their specific contribution in attention deficit. METHOD: We selected 24 patients with CM II and 24 without CM II. DSM-IV criteria and a neuropsychological analysis were applied in all. All patients underwent full night polysomnography. RESULTS: 14 CM II patients presented sleep apnea syndrome, REM sleep behavior disorder and periodic limb movement in sleep; six patients without CM II presented sleep apnea syndrome. Among these patients, 12 (six with CM II and six without CM II) presented attention deficit related to the sleep disorders. CONCLUSION: Sleep disorders may impair cognitive functions, as attention, and contribute to poor quality of learning also in patients with CM II.
Post-traumatic headache
Authors: Martins Hugo André de Lima , Ribas Valdenilson Ribeiro , Martins Bianca Bastos Mazullo , Ribas Renata de Melo Guerra , Valença Marcelo Moraes
Published: March 2009

The onset of post-traumatic headache (PTC) occurs in the first seven days after trauma, according to the International Headache Society (IHS) classification. The objective of this study was to evaluate the several forms of headache that appear after mild head injury (HI) and time interval between the HI and the onset of pain. We evaluated 41 patients with diagnosis of mild HI following the IHS criteria. Migraine without aura and the chronic tension-type headache were the most prevalent groups, occurring in 16 (39%) and 14 (34.1%) patients respectively. The time interval between HI and the onset of headache was less than seven days in 20 patients (48.7%) and longer than 30 days in 10 (24.3%) patients. The results suggest that PTC may arise after a period longer than is accepted at the present by the IHS.
Botulinum toxin type A in the treatment of lower-limb spasticity in children with cerebral palsy
Authors: Camargo Carlos Henrique F. , Teive Hélio A.G. , Zonta Marise , Silva Gilmar C. , Oliveira Marcelo R. , Roriz Maurício M. , Brandi Ivar V. , Becker Nilson , Scola Rosana Hermínia , Werneck Lineu César
Published: March 2009

We evaluated the safety and effectiveness of botulinum toxin A (BoNT/A) in the treatment of spasticity in 20 children with spastic diplegic cerebral palsy (CP). All the patients received injections in the gastrocnemius and soleus, and 15 received injections in the adductors. The total dose varied from 70 to 140 U (99.75±16.26 U), or 7.45±2.06 U/kg per patient. The treatment improved the patients' walking and gait pattern significantly. There was also a significant alteration in the heel-ground distance and increased motion of the ankle joint. These structural changes in the feet were sustained until the end of the follow-up, although the same was not observed for the functional parameters. Three patients complained of weakness in the lower limbs. In conclusion, BoNT/A is safe and effective when used in a single session of injections and produces a sustained structural modification of the lower limbs. However, functional changes are temporary and are only observed during the peak effect of the drug.
Immunohistochemical identification of plasma protein deposits in the wall of lenticulostriate arteries in patients with long-standing hypertension, with and without lipohyalinosis
Authors: Andrade Magda Rocha , Pittella José Eymard Homem
Published: March 2009

PURPOSE: To investigate, through an immunohistochemical method, whether there is deposition of plasma proteins in the wall of lenticulostriate, cortical and leptomeningeal arteries of hypertensive patients, with and without lipohyalinosis. METHOD: Forty patients with essential hypertension were selected at random, 20 with lipohyalinosis in the lenticulostriate arteries (HH group) and 20 without lipohyalinosis (H group), matched with 20 normotensive controls (C group). RESULTS: Plasma protein deposits were identified in eight patients (40%) in the C group, in 15 patients (75%) in the H group, and in all 20 patients (100%) in the HH group, the difference being significant for the H group and highly significant for the HH group, as compared with the C group. In all groups, the distribution of plasma protein deposits, subendothelial in normal arteries, and diffuse, irregular in the wall of arteries with lipohyalinosis, was more frequent in the lenticulostriate arteries of the putamen. CONCLUSION: Deposition of plasma proteins in the lenticulostriate arteries seems to be relatively frequent in normotensive individuals, starting in middle age. Such process appears to be intensified by hypertension, especially in individuals with lipohyalinosis.