bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenomic Analysis in Toxicology
Authors: Ushijima Toshikazu , Okochi‐Takada Eriko , Takeshima Hideyuki 
Published: March 2013

AbstractEpigenetic modifications are essential for development, differentiation, and reprogramming. They are inherited upon somatic cell replication, and include DNA methylation and histone modifications. Abnormality of epigenetic modifications is deeply involved in human cancers, as known by global hypomethylation and regional hypermethylation. Recent findings on the high fraction of cells affected in normal‐appearing tissues indicated that epigenomic alterations are also involved in acquired disorders other than cancers. In spite of the deep involvement of epigenomic alterations in human diseases, only limited information is available for inducers of epigenetic changes, including aging, chronic inflammation, virus infection, disturbances in one carbon metabolism, and some chemicals. One of the reasons why a very limited number of chemicals are known as inducers of epigenetic alterations (epimutagens) is the lack of a sufficiently convenient and sensitive assay system. Toxicological considerations from the viewpoint of epigenomics are critically important, and epigenomic toxicology has just started.
Sequencing Technology Advances and Toxicology
Authors: Ratnasinghe Luke D. 
Published: March 2013

AbstractSystems toxicology is going through a revolution with advancements in genomics methods. Microarray technology has been a significant driving force in toxicogenomics. Next generation sequencing methods promise to overtake use of microarrays in the toxicology tool kit by overcoming many of the limitations of microarrays. In next generation sequencing, every nucleic acid molecule is sequenced individually and counted. Millions of molecules can be sequenced simultaneously eliminating the need for traditional standards and reference samples. The promise of next generation sequencing is that genome of an entire organism or a cell can be sequenced rapidly and affordably. All the RNA transcripts in a cell can be sequenced, identified, counted, and categorized with almost absolute precision. Systems toxicology, which involves the iterative study of how chemicals influence gene expression and toxicological outcomes will be vastly improved with the adaptation of next generation sequencing.
Next‐Generation Sequencing: A Revolutionary Tool for Toxicogenomics
Authors: Su Zhenqiang , Ning Baitang , Fang Hong , Hong Huixiao , Perkins Roger , Tong Weida , Shi Leming 
Published: March 2013

Abstract
Over the past five years, DNA sequencing has been undergoing fundamental changes due to the rapid development of next‐generation sequencing (NGS) technologies. NGS technologies have been offering unprecedented opportunities for high‐throughput functional genomic research, and opening up new fields and novel applications in biology, life sciences, and biomedicine. The major advantages of NGS technologies over conventional Sanger sequencing include sequencing cost reduction from about 0.50 per kilobase to as little as 0.001 per kilobase, and massive parallelism that dramatically increases sequencing throughput. However, Sanger‐based approaches provide advantages in terms of read‐length and base call accuracy.
In this chapter, we first describe the fundamental principles of four currently commercialized NGS platforms from Roche/454, Illumina, Life Technologies, and Helicos BioSciences. Next we discuss the challenges in analyzing short reads from NGS, and outline major applications of these new technologies. Finally, we compare data between NGS and microarrays with a toxicogenomics study aiming at gene expression profiling.
In Silico
Tools for Molecular Modeling
Authors: Umashankar Vetrivel , Gurunathan Subramanian 
Published: March 2013

Abstract

Molecular modeling is the atomic‐level description of molecular systems. The development of molecular modeling programs and their application in pharmaceutical research has been formalized as a field of study known as computer‐assisted drug design (CADD) or computer‐assisted molecular design (CAMD). Molecular modeling methods are now routinely used to investigate the structure, dynamics and thermodynamics of biological, inorganic and polymeric systems. Although initially models were physically drawn or made using appropriate materials, the development of computer programs introduced CADD or CAMD. Stages of molecular modeling are covered in this chapter and a few
in silico
tools available are discussed. Molecular modeling has been of great use to many scientists by decreasing time taken for the otherwise tedious task of modeling and associated analysis such as potential drug candidate identification, docking, protein–protein interactions, etc.
Nanotoxicology
Authors: Ma Yinfa , Lin Weisheng 
Published: March 2013

AbstractNanotechnology has become one of the leading technologies in the past two decades due to its unique applications in many areas. However, the health effects of nanomaterials have caused people great concerns, mainly due to the small particle sizes and unique properties of the nanomaterials. The large specific surface areas of the nanomaterials make them very reactive in the cellular environment, and may impose very different biological effects than those of the bulk materials. Consequently, the levels of toxicity of nanomaterials are potentially higher than those of bulk materials. A large amount of research, bothin vitroandin vivo, has been conducted and the data have shown that several types of nanomaterials are highly toxic. This chapter mainly summarizes the work being done in the area of nanotoxicology and the proper ways to carry out nanotoxicology studies to assure that valid data can be obtained, including characterization of nanomaterials, proposed mechanisms of nanomaterials, types of biomarkers and analytical techniques that were used to assess the levels of nanotoxicity, and experimental design forin vitroandin vivonanotoxicology studies. In conclusion, this chapter serves as a short version of a handbook to assist nanotoxicology researchers in experimental designs, assessment, and data evaluations.
Toxicity of Selenium Compounds and Nano‐Selenium Particles
Authors: Zhang Jinsong , Spallholz Julian E. 
Published: March 2013

AbstractSelenium is a necessary dietary constituent of at least 25 human selenoproteins and enzymes all containing selenocysteine. In excessive amounts, all selenium compounds become toxic in a dose‐dependent fashion to cellsin vitroand to the primary target tissue of chronic selenium toxicity, the liver. Elemental selenium of zero valence state has long been considered to be biologically inert. With bovine serum albumin or other dispersant agents such as polysaccharide, biologically active nano‐selenium particles (Nano‐Se) are formed from sodium selenite and glutathione. Different from the biologically inert black elemental selenium with coarse size, red Nano‐Se manifests toxicity which conforms to the concern of nanotoxicity. However, compared with selenium compounds such as sodium selenite, selenomethionine and Se‐methylselenocysteine, Nano‐Se is not compromised in increasing the activities of selenoenzymes including glutathione peroxidase and thioredoxin reductase at nutritional levels and phase 2 detoxification enzymes such as glutathioneS‐transferase at supranutritional levels, but exhibits much lower toxicities. Nano‐Se is thus a potential selenium source with a prominent characteristic of lower toxicity for supplementation.
Gout‐Related Health Care Utilization in US Emergency Departments, 2006 Through 2008
Authors: Garg Rohini , Sayles Harlan R. , Yu Fang , Michaud Kaleb , Singh Jasvinder , Saag Kenneth G. , Mikuls Ted R. 
Published: March 2013

AbstractObjectiveTo characterize gout‐related emergency department (ED) utilization using a nationally representative sample and to examine factors associated with the frequency and charges of gout‐related ED visits.MethodsUsing the National Emergency Department Sample data from 2006–2008, the weighted national frequency of gout visits was calculated along with the median ED charge and total national ED‐related charges. Associations of several patient‐ and facility‐level factors were examined with the occurrence of gout visits using multivariable logistic regression and with ED‐related charges using multivariable linear regression.ResultsGout was the primary indication for 168,410 ED visits in 2006, 171,743 visits in 2007, and 174,823 visits in 2008, accounting for ∼0.2% of all visits annually and generating ED charges of more than $128 million in 2006, $144 million in 2007, and $166 million in 2008. Age, male sex, household income <$39,000, private insurance, and hospital locations in nonmetropolitan areas and the southern US were associated with an increased propensity for ED utilization in gout. Higher ED‐related charges for gout were associated with female sex, age, a higher number of coded diagnoses, and a metropolitan residence.ConclusionGout accounts for a substantial proportion of ED visits, leading to significant health care charges. Effective strategies to reduce gout burden in EDs could potentially benefit by targeting groups characterized by factors demonstrated to be related to a higher ED utilization in gout as identified by our study.
Evaluation of Test Characteristics for Outcome Measures Used in Raynaud's Phenomenon Clinical Trials
Authors: Gladue Heather , Maranian Paul , Paulus Harold E. , Khanna Dinesh 
Published: March 2013

AbstractObjectiveRandomized controlled trials (RCTs) in Raynaud's phenomenon (RP) have shown conflicting efficacy data. Also, there is no consensus on the outcome measures that should be used. Our objectives were to assess the reliability of individual core set measures used in 3 RCTs, evaluate the placebo response for individual core set measures, and determine if a composite of individual core set measures will decrease the placebo response, which may improve our ability to see treatment effects in future trials.MethodsWe analyzed core set measures from 249 patients in the placebo‐treated groups from 3 RCTs. Core set measures analyzed included the Raynaud's Condition Score (RCS); patient and physician assessment of RP; pain, numbness, and tingling during an RP attack; average number of attacks/day; and duration of attacks. Intraclass correlation coefficients (ICCs) were calculated during the run‐in period to the RCTs.ResultsICCs of ≥0.70 were observed for the RCS, attack symptoms, and average attacks/day. A high placebo response rate was observed for all individual core measures except the duration of attacks. For the RCS, the placebo response ranged from 56% with ≥10% improvement to 19.5% with ≥60% improvement. In contrast, placebo response rates of 10–20% were observed when several core set measures were combined to develop a composite score.ConclusionOutcome measures used in RCTs of RP are associated with marked variability. A combination of outcome measures is associated with low placebo responses. Future studies are needed to assess if a composite score will be able to differentiate placebo from an effective agent.
Dravet syndrome patient‐derived neurons suggest a novel epilepsy mechanism
Authors: Liu Yu , Lopez‐Santiago Luis F. , Yuan Yukun , Jones Julie M. , Zhang Helen , O'Malley Heather A. , Patino Gustavo A. , O'Brien Janelle E. , Rusconi Raffaella , Gupta Ajay , Thompson Robert C. , Natowicz Marvin R. , Meisler Miriam H. , Isom Lori L. , Parent Jack M. 
Published: March 2013

ObjectiveNeuronal channelopathies cause brain disorders, including epilepsy, migraine, and ataxia. Despite the development of mouse models, pathophysiological mechanisms for these disorders remain uncertain. One particularly devastating channelopathy is Dravet syndrome (DS), a severe childhood epilepsy typically caused by de novo dominant mutations in the SCN1A gene encoding the voltage‐gated sodium channel Nav1.1. Heterologous expression of mutant channels suggests loss of function, raising the quandary of how loss of sodium channels underlying action potentials produces hyperexcitability. Mouse model studies suggest that decreased Nav1.1 function in interneurons causes disinhibition. We aim to determine how mutant SCN1A affects human neurons using the induced pluripotent stem cell (iPSC) method to generate patient‐specific neurons.MethodsHere we derive forebrain‐like pyramidal‐ and bipolar‐shaped neurons from 2 DS subjects and 3 human controls by iPSC reprogramming of fibroblasts. DS and control iPSC‐derived neurons are compared using whole‐cell patch clamp recordings. Sodium current density and intrinsic neuronal excitability are examined.ResultsNeural progenitors from DS and human control iPSCs display a forebrain identity and differentiate into bipolar‐ and pyramidal‐shaped neurons. DS patient‐derived neurons show increased sodium currents in both bipolar‐ and pyramidal‐shaped neurons. Consistent with increased sodium currents, both types of patient‐derived neurons show spontaneous bursting and other evidence of hyperexcitability. Sodium channel transcripts are not elevated, consistent with a post‐translational mechanism.InterpretationThese data demonstrate that epilepsy patient–specific iPSC‐derived neurons are useful for modeling epileptic‐like hyperactivity. Our findings reveal a previously unrecognized cell‐autonomous epilepsy mechanism potentially underlying DS, and offer a platform for screening new antiepileptic therapies. Ann Neurol 2013;74:128–139
β‐synuclein aggregates and induces neurodegeneration in dopaminergic neurons
Authors: Taschenberger Grit , Toloe Johan , Tereshchenko Julia , Akerboom Jasper , Wales Pauline , Benz Roland , Becker Stefan , Outeiro Tiago F. , Looger Loren L. , Bähr Mathias , Zweckstetter Markus , Kügler Sebastian 
Published: March 2013

ObjectiveWhereas the contribution of α‐synuclein to neurodegeneration in Parkinson disease is well accepted, the putative impact of its close homologue, β‐synuclein, is enigmatic. β‐Synuclein is widely expressed throughout the central nervous system, as is α‐synuclein, but the physiological functions of both proteins remain unknown. Recent findings have supported the view that β‐synuclein can act as an ameliorating regulator of α‐synuclein–induced neurotoxicity, having neuroprotective rather than neurodegenerative capabilities, and being nonaggregating due to the absence of most of the aggregation‐promoting NAC domain. However, a mutation of β‐synuclein linked to dementia with Lewy bodies rendered the protein neurotoxic in transgenic mice, and fibrillation of β‐synuclein has been demonstrated in vitro.MethodsNeurotoxicity and aggregation properties of α‐, β‐, and γ‐synuclein were comparatively elucidated in the rat nigro‐striatal projection and in cultured neurons.ResultsSupporting the hypothesis that β‐synuclein can act as a neurodegeneration‐inducing factor, we demonstrated that wild‐type β‐synuclein is neurotoxic for cultured primary neurons. Furthermore, β‐synuclein formed proteinase K–resistant aggregates in dopaminergic neurons in vivo, leading to pronounced and progressive neurodegeneration in rats. Expression of β‐synuclein caused mitochondrial fragmentation, but this fragmentation did not render mitochondria nonfunctional in terms of ion handling and respiration even at late stages of neurodegeneration. A comparison of the neurodegenerative effects induced by α‐, β‐, and γ‐synuclein revealed that β‐synuclein was eventually as neurotoxic as α‐synuclein for nigral dopaminergic neurons, whereas γ‐synuclein proved to be nontoxic and had very low aggregation propensity.InterpretationOur results suggest that the role of β‐synuclein as a putative modulator of neuropathology in aggregopathies like Parkinson disease and dementia with Lewy bodies needs to be revisited. Ann Neurol 2013;74:109–118
Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β‐amyloid
Authors: Landau Susan M. , Lu Ming , Joshi Abhinay D. , Pontecorvo Michael , Mintun Mark A. , Trojanowski John Q. , Shaw Leslie M. , Jagust William J. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: March 2013

ObjectiveWe examined agreement and disagreement between 2 biomarkers of β‐amyloid (Aβ) deposition (amyloid positron emission tomography [PET] and cerebrospinal fluid [CSF] Aβ1–42) in normal aging and dementia in a large multicenter study.MethodsConcurrently acquired florbetapir PET and CSF Aβ were measured in cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease participants (n = 374) from the Alzheimer's Disease Neuroimaging Initiative. We also compared Aβ measurements in a separate group with serial CSF measurements over 3.1 ± 0.8 years that preceded a single florbetapir session. Additional biomarker and cognitive data allowed us to further examine profiles of discordant cases.ResultsFlorbetapir and CSF Aβ were inversely correlated across all diagnostic groups, and dichotomous measurements were in agreement in 86% of subjects. Among subjects showing the most disagreement, the 2 discordant groups had different profiles: the florbetapir+/CSF Aβ−group was larger (n = 13) and was made up of only normal and early MCI subjects, whereas the florbetapir−/CSF Aβ+group was smaller (n = 7) and had poorer cognitive function and higher CSF tau, but no ApoE4 carriers. In the longitudinal sample, we observed both stable longitudinal CSF Aβ trajectories and those actively transitioning from normal to abnormal, but the final CSF Aβ measurements were in good agreement with florbetapir cortical retention.InterpretationCSF and amyloid PET measurements of Aβ were consistent in the majority of subjects in the cross‐sectional and longitudinal populations. Based on our analysis of discordant subjects, the available evidence did not show that CSF Aβ regularly becomes abnormal prior to fibrillar Aβ accumulation early in the course of disease. Ann Neurol 2013;74:826–836
75 Jahre BAUTECHNIK
Authors: Greiner‐Mai D. 
Published: March 2013

AbstractMit dem Januar‐Heft 1998 erreicht die Zeitschrift BAUTECHNIK, seit 1923 vom Verlag Ernst & Sohn publiziert, das 75. Jahr ihres Bestehens, Grund genug, ein wenig die Wurzeln zu beleuchten, Entwicklungen zu verfolgen, Gegenwärtiges zu konstatieren und Zukünftiges anzustoßen.
Neue Erkenntnisse aus Messungen an tiefen Baugruben am Potsdamer Platz in Berlin
Authors: Triantafyllidis Th. 
Published: March 2013

AbstractDiese Arbeit stellt eine Zusammenfassung der bislang an einer Versuchsbaugrube am Potzdamer Platz durchgeführten Messungen, um das Verhalten des Bodens bei tiefen Baugruben zu erfassen wie auch das Wechselwirkungsverhalten der Baugrubenkonstruktion mit dem Boden während der diversen Bauphasen zu analysieren, dar. Es handelt sich dabei auch um den Einsatz von neueren Meßtechniken und Analysemethoden. In diesem Beitrag werden erste Interpretationen und Deutungen dieser Meßergebnisse auf der Basis bodenmechanischer Prinzipien dargelegt. Es stellte sich heraus, daß der Entwurf der Konstruktion nicht alle wichtigen Arbeitsphasen, die signifikante Verformungen der Verbauwände hervorrufen, erfassen kann. Dabei hat man festgestellt, daß die Einbringung von Sohlverankerungspfählen, um die Sohle der Trogbauweise sichern zu können, Verformungen der Verbauwände hervorruft, die in der gemessenen Größenordnung nicht erwartet waren. Signifikante Bodenbewegungen innerhalb und außerhalb der Baugrube haben stattgefunden, die um eine Größenordnung größer waren als diejenigen, die sich beim UW‐Aushub oder Lenzen der Baugrube einstellten. Erste Modellvorstellungen sind in der Arbeit entwickelt, die uns erlauben, solche Effekte zunächst einmal zu beschreiben und in einer zweiten Stufe ihre Auswirkungen abschätzen zu können.
Neuer Antennenträger der Senderanlage "Hohe Linie" bei Regensburg. Ein Bauvorhaben mit Modellcharakter
Authors: Flügel K. 
Published: March 2013

AbstractAngesichts der in den letzten Jahren immer größer gewordenen Bedeutung von Satelliten für die Übertragung von Rundfunk‐ und Fernsehprogrammen verdient es besondere Beachtung, wenn eine öffentlich‐rechtliche Rundfunkanstalt sich noch einmal für den Bau eines Antennenträgers zur terrestrischen Abstrahlung dieser Dienste entscheidet. Beim Bau des neuen Antennenträgers an seiner Senderanlage "Hohe Linie" bei Regensburg hat der Bayerische Rundfunk bereits mit seinem Entschluß zur vorherigen Durchführung eines Ingenieur‐Ideenwettbewerbs einen ungewöhnlichen Schritt getan, um auf diese Art unter Beachtung der betrieblichen Anforderungen die für ihn wirtschaftlich günstigste Lösung zu finden; auch der bei diesem Wettbewerb ausgewählte und später realisierte Entwurf ‐ ein freistehender 100 m hoher Stahllbetonturm mit einem am Turmkopf eingespannten 51 m hohen Stahlrohraufsatz ‐ stellt eine nach Wissen des Autors bislang noch nicht ausgeführte Lösung für einen Antennenträger dieser Bauhöhe dar. Der vom Bayerischen Rundfunk gewählten Verfahrens‐ und Bauweise kann deswegen nach Auffassung des Autors Modellcharakter zugesprochen werden.
Systemtechnik contra DIN EN ISO 9000?
Authors: Fritz H. A. 
Published: March 2013

AbstractNoch zehn Jahre nach Einführung der Normen zum Qualitätsmanagement, die als DIN EN ISO 9000ff branchenübergreifend sowohl im internationalen, europäischen und deutschen Geltungsbereich eingeführt wurden, gibt es gerade in der Baubranche unterschiedlichste Akzeptanz dieses Regelwerkes. Während Produzenten wie Bauunternehmen und Bauproduktenhersteller den Wert eines Qualitätsmanagement längst erkannt haben und nutzen, stehen Dienstleister wie Ingenieurbüros und öffentliche Auftraggeber dieser Entwicklung eher noch skeptisch gegenüber. Dieser Beitrag öffnet einen ingenieurgerechten Zugang zum zeitgemäßen Qualitätsmanagement und geht dabei insbesondere auf die Frage ein, inwieweit die oben zitierte Normenserie sich auf bekannte Inhalte der Systemtechnik abstützt und das Verständnis für Qualitätsmanagement durch die Hochschulausbildung der Bauingenieure gefördert werden kann.
"Der Träger aus der Tüte"
Authors: Heller H. 
Published: March 2013

AbstractFür unterschiedliche Anwendungsbereiche im Hochbau oder auch im Ausbau sind immer wieder Tragwerke (Träger) für relative kleine Lasten und kleine Spannweiten gefragt. Dabei spielen bei vielen Bauaufgaben auch gestalterische Gesichtspunkte im Zusammenhang mit der Wahl der Tragwerke eine Rolle. Normale Rechteckprofile aus Holz oder Walzprofile aus Stahl bieten hier wenig Spielräume. Im folgenden wird ein neuartiges, vorzugsweise aus Holz hergestelltes Leichtbau‐Trägersystem mit nicht parallel laufenden Gurten vorgestellt.
Das neue Bremer Weserwehr Entwurf und Ausführung Teil 1: Topologie und Entwurf
Authors: Grabau J. 
Published: March 2013

AbstractNach 5‐jähriger Bauzeit wurde 1993 das neue Bremer Weserwehr in Betrieb genommen. Wegen der Lage innerhalb Bremens hat das Wehr wesentlichen Einfluß auf die Hochwassersicherheit im dicht besiedelten Innenstadtbereich. Das Wehr hält den normalen Tideeinfluß der Unterweser von der staugeregelten Mittelweser fern. Der mittlere Tidehub unterstromig des Wehres beträgt fast 4 m und sorgt damit für tägliche periodische Einwirkungen auf das Bauwerk, die an den meisten anderen Wehren an staugeregelten Flüssen nicht auftreten. Planung und Entwurf der Anlage wurden vom Wasser‐ und Schiffahrtsamt Bremen durchgeführt. Die Baudurchführung erfolgte im Rahmen von Bauverträgen zwischen verschiedenen Fachunternehmen und der Wasser‐ und Schiffahrtsverwaltung des Bundes (WSV), vertreten durch das Wasser‐ und Schiffahrtsamt Bremen, das nach Abnahme am 1. April 1993 den Betrieb der Anlage übernommen hat.