bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the Endocannabinoid System in Systems Toxicity
Authors: Pistos Constantinos , Theocharis Stamatios 
Published: March 2013

Abstract
The scientific knowledge regarding the modulation of the endogenous cannabinoid system and its effect on disease pathophysiology has been significantly improved in the last 20 years. Alterations in the expression of cannabinoid receptors, their main endogenous ligands (arachidonoylethanolamide and 2‐arachidonoylglycerol), and related enzyme levels have been reported in different disease states, suggesting their important regulatory role. The pharmacological effects of synthetic compounds that selectively target the endocannabinoid system, established cause‐effect relationships between endocannabinoids and the progress of several disorders. In this review, the importance of endocannabinoid system modulation and also the aspects of the underlying pathways leading to disease or target organ toxicity are reported.
Systems Toxicology: A Valuable Tool for Early Prediction and Mechanistic Assessment of Liver Toxicity of Food‐Related Products
Authors: Sahu Saura C. 
Published: March 2013

AbstractThe review of literature demonstrates that systems toxicology is a valuable tool for early prediction and mechanistic assessment of liver toxicity. It will provide accurate molecular information for toxicity hazard and risk assessment in relatively short period of time. This technology will find very useful applications in food safety. It is an excellent tool for quick screening of hepatotoxic potential of food‐related products that occur naturally or that are added deliberately to the foods and dietary supplements. The published reports show the value of omics technologies in combination with classical histopathology and biochemical assays providing a powerful tool for accurate assessment of “predictive” and “mechanistic” hepatotoxicity. The systems toxicologyin vitrooffers a powerful cost‐effective tool for faster high‐throughput toxicity testing. It can be effectively used for high‐throughput screening of food‐related products for potential hepatotoxicity.
Species‐Metabolite Relation DatabaseKNApSAcKand Its Multifaceted Retrieval System,KNApSAcKFamily
Authors: Takahashi Hiroki , Hirai Aki , Shojo Masayuki , Matsuda Kaori , Parvin Aziza Kawsar , Asahi Hiroko , Nakamura Kensuke , Altaf‐Ul‐Amin Md. , Kanaya Shigehiko 
Published: March 2013

AbstractIn a metabolomics research, assignment of measured spectra to a specific metabolite is one of the most fundamental processes. The assignment is usually made by taking a match with known compounds, and therefore it is necessary to scan the spectra against whole previously studied compounds. This means the survey of whole natural products reported in the literature, which is an extremely tedious and daunting process. In order to make this process feasible, we have developed a metabolite database called KNApSAcK, which currently contains 76,357 species–metabolite relations involving 37,693 metabolites. In the present study, we review the current status of KNApSAcK database and its application to metabolomics and introduce the multifaceted retrieval system KNApSAcK family, which consists of seven parts for the purpose of retrieving metabolites from several different aspects. “Pocket” includes search system for species related to human living such as edible plants in Japan (“Lunch Box”), herb teas (“Tea Pot”, in progress), traditional Japanese medicine (“KAMPO”), poisonous plant (“Poison”, in progress), and bio‐fuel resources (“Fuel”, in progress). “KNApSAcK from around the world” includes medicinal and edible plants utilized in each country. Seven thousand three hundred and fifty‐six pairwise relations between medicinal/edible plants and 119 nations worldwide have been accumulated from scientific literatures.
Chemoinformatics and its Applications
Authors: Umashankar Vetrivel , Gurunathan Subramanian 
Published: March 2013

Abstract

Cheminformatics is the use of computer and informational techniques, applied to a range of problems in the field of chemistry. It is also known as chemoinformatics and chemical informatics. These
in silico
techniques are used in pharmaceutical companies in the process of drug discovery. Cheminformatics can also be applied to data analysis for various industries such as paper and pulp, dyes and such allied industries. The primary application of cheminformatics is in the storage of information relating to compounds. Quantitative structure–activity relationship (QSAR) analysis also forms a part of cheminformatics. Several
in silico
cheminformatic tools are currently available for predicting physio‐chemical properties and biological activity of many different chemical molecules. Thus, chemoinformatics helps to reduce the time taken for identifying potential drug targets as well as to understand physical, chemical and biological properties of several chemical compounds. Outputs of chemoinformatics may also direct the course of wet laboratory experiments.
Biomarker Discovery: Introduction to Statistical Learning and Integrative Bioinformatics Approaches
Authors: Repsilber Dirk , Jacobsen Marc 
Published: March 2013

AbstractIn toxicology, biomarkers are needed for use in screenings, time series and dilution series exposure studies for safety evaluation and risk assessment. They need to be easily and reproducibly measurable, and are therefore sought amongst molecular features using OMICs high‐throughput technologies in assays of blood and other easily accessible tissue. This chapter conveys methods for screening OMICs datasets for candidate biomarkers for classification. We begin focussing on single biomarker detection, and survey improvements to the t‐test as well as multiplicity corrections regarding this objective. Biomarker panels (biosignatures) are patterns of several combined single features. We describe their detection using three different methods of statistical learning. Here, a special focus is on avoiding overfitting through appropriate use of cross‐validation. More sophisticated approaches using gene‐set enrichment algorithms and steps towards integrated bioinformatics analyses are explained. Making use of a priori knowledge about regulatory structures (gene groups, correlation structures) may further improve classification efficiency of the detected biosignatures. As the red line, we exemplify analysis possibilities using the famous Golub gene expression dataset and the appropriateR‐scripts – enabling the reader to reproduce every step on his own desktop.
Systems Toxicology Modeling for Prediction in Humans
Authors: Migliorini Cristiano , Lave Thierry , Parrott Neil J. , Reddy Micaela , Grimm Hans Peter , Penland Robert C. , Soubret Antoine , Helmlinger Gabriel , Georgieva Anna , Zuideveld Klaas P. 
Published: March 2013

AbstractThis chapter aims to illustrate the ability of physiologically based mechanistic mathematical models to predict pharmacokinetics and toxicity across species. The underlying principle is that toxicity must be interpreted in the physiological context where it is measured.Various methodologies for predicting the pharmacokinetics, QT prolongation and proarrhythmic risk are evaluated. Finally an integration of both pharmacokinetics and toxicokinetics in chemotherapy‐induced neutropenia is discussed. It is believed that the methodologies presented for integrating available knowledge across experiments to predict toxicology in humans will ultimately make drug development more efficient, cost cost‐effective, and socially more acceptable.
Systems Modeling in Developmental Toxicity
Authors: Knudsen Thomas B. , DeWoskin Robert S. 
Published: March 2013

AbstractHigh‐throughput or high‐content studies are now providing a rich source of data that can be applied toin vitroprofiling of chemical compounds for biological activity and potentialin vivotoxicity. EPA's ToxCast™ project, and the broader Tox21 consortium, as well as other projects worldwide, are providing high‐throughput and high‐content screening data (HTS‐HCS) focusing on thein vitrotargets and cellular bioactivity profiles for thousands of chemical compounds in commerce or entering the environment. A goal of chemical profiling is to rapidly identify and efficiently classify signatures of biological activity that are potentially diagnostic ofin vivotoxicities using automated technologies. Predictive modeling of developmental toxicity faces several challenges: correlatingin vitroconcentration–response with internal dose–response kinetics; understanding howin vitrobioactivity profiles extrapolate from one cell‐type or technology platform to another; and linking individual targets ofin vitrobioactivity to complex signatures associated with pathways ofin vivotoxicity. Toxicity in the intact organism is an expression of complex and interwoven events that follow from cellular perturbations. As such, multicellular computer models known as ‘virtual tissues’ that recapitulate developmental events can provide a technology platform to simulate non‐linear behaviors of dynamical systems and to model perturbations. A virtual embryo, for example, might be envisaged as a toolbox of computational (in silico) models that execute morphogenetic programs to simulate developmental toxicity.
Multiscale Integration of Toxicokinetic and Toxicodynamic Processes: From Cell and Tissue to Organ and “Whole Body” Models
Authors: Georgopoulos Panos G. , Isukapalli Sastry , Androulakis Ioannis P. , Ierapetritou Marianthi G. , Welsh William J. 
Published: March 2013

AbstractThis chapter presents a systematic summary overview of coordinated efforts taking place at the environmental bioinformatics and Computational Toxicology Center (ebCTC.org) towards developing a mechanistic modeling framework that integrates multiple scales of coupled toxicokinetic and toxicodynamic processes. This framework employs highly modular “whole body” computational descriptions of the human and of selected model organisms that incorporate a hierarchy of alternative formulations representing biological events in “virtual” tissues and organs. This approach allows the mechanistic consideration of multiple scales of interlinked phenomena that include molecular interactions; dynamics of intracellular biomolecular networks; spatial and stochastic aspects of cell biochemistry; integrative coupling of cellular‐level processes related to common endpoints; extracellular signaling and cell‐cell communication and interaction; aspects of functional heterogeneity in multicellular structures; dynamics of histomorphological and histopathological processes at the tissue level; and integrative coupling of processes across scales, resulting in different physiosystem phenotypes for health and disease states. The ebCTC framework offers a range of combined approaches for coupling processes and “transferring and integrating” information across multiple strata of biological organization, ranging from formal methods of multiscale analysis, including statistical descriptions of multicellular kinetics and dynamics, to simplified “top‐down” approaches, incorporating both mechanistic and phenomenological formulations that rely on point and distributional parameterizations of the finer scales. The computational implementation of the framework employs a combination of agent‐, network‐, and field‐based modeling methods. Example applications of various components of this framework are presented, spanning the range from molecular interactions to bionetwork and cellular dynamics to multiscale problems at the tissue and organ levels.
Nanotoxicology: A Brief Overview and Discussion of the Current Toxicological TestingIn Vitroand Suggestions for Future Research
Authors: Clift Martin J. D. , Blank Fabian , Gehr Peter , Rothen‐Rutishauser Barbara 
Published: March 2013

AbstractNanotechnology is an ever‐growing industry that is expected to reach a net worth of over 15 billion by 2015 (Service, 2004). Although there are many proposed advantages related to this new industrial revolution, there are increased concerns regarding the potential adverse health effects that exposure to the production of nanotechnology‐related products might pose (Maynardet al., 2006). Although not fully understood or confirmed, these concerns are well founded due to the plethora of research and knowledge related to the effects of environmental air pollution on human health relative to the nanoparticle (NP) component contained within it. Due to the inevitable exposure of humans to NPs, owing to their use in a wide and diverse range of applications, it is imperative to understand how NPs interact with the human body.In vivoresearch, however, has many disadvantages, and so increased research into the possible adverse effects of NPs has been performed usingin vitromodels. Therefore, the aim of this chapter is to provide an in‐depth description of the many different toxicity tests usedin vitro, how they are beneficial in filling the knowledge gap related to the potential toxic effects of NPs and the many pitfalls that are associated with them, in addition to providing an overview of the field of nanotoxicology as well as suggesting howin vitrotesting strategies may be used to demonstrate the effects ofin vivoexposure to NPs.
The Role of Oxidative Stress in Nanotoxicology
Authors: Sayes Christie M. , Banerjee Nivedita , Romoser Amelia A. 
Published: March 2013

Abstract
The application of systems biology approaches is gaining popularity in the nanoparticle toxicology research (Brandenberger, 2010; Oberdorster, Oberdorster and Oberdorster, 2005; Nyland and Silbergeld, 2009). Over the past few years, there has been a movement toward describing and characterizing trends in nanotoxicological data sets. In order to interpret these observed trends, the use of a holistic perspective may be appropriate. One of the cornerstones of systems biology is the use of experimental and computational models. Nanotoxicology could benefit from these efforts. Both systems biology and nanotoxicology attempt to discover emergent properties of a system and link those properties, using a variety of techniques to environmental and human health.
While the investigations in the field of systems biology are frequently large in scale, nanotoxicology has yet to accomplish this feat, to date. Both fields require an interdisciplinary approach from experimentalists (biologist, chemists, toxicologists, and risk assessors) and quantitative scientists (biostatisticians, mathematicians, computer scientists, and engineers). Together, their efforts can be coordinated to improve the quality of science and to create, refine, and retest the experimental and computational models to accurately reflect, and eventually predict, biological, and toxicological observations.
Implementing Systems Toxicology in Drug Development for Regulatory Decision Making
Authors: Sina Joseph F. , Sistare Frank D. 
Published: March 2013

AbstractThe concept of integrating molecular and biochemical data from new technologies with more traditional endpoints to develop a more complete understanding of risks and benefits in drug development has gained wide acceptance as a reasonable way to advance human health. However, actual implementation of this systems approach is not straightforward. While technology keeps advancing, our ability to accurately interpret the complexity of human biology has not kept pace. Indeed, sometimes the case seems to be one of the deeper we investigate, the more we realize what we do not understand. Additionally, in developing ethical pharmaceuticals, a major issue is establishing the necessary level of confidence to extrapolate from a series of endpoint measurements to accurately predict beneficial and/or potentially adverse responses in the diverse population of patients. The evidentiary standard for acceptance of new models and biomarkers in clinical practice is necessarily high, although the concept of “fit‐for‐purpose” may help expedite the application of new knowledge in specific clinical situations. This chapter will present a view of both the progress and hurdles to applying systems toxicology to drug development in a regulated environment.
Physician accountability in iatrogenic cerebrospinal fluid leak litigation
Authors: Kovalerchik Olga , Mady Leila J. , Svider Peter F. , Mauro Andrew C. , Baredes Soly , Liu James K. , Eloy Jean Anderson 
Published: March 2013

BackgroundThe potentially severe complications resulting from cerebrospinal fluid (CSF) leak makes iatrogenic injury a medicolegal area of concern for otolaryngologists and neurosurgeons. The objectives of this analysis were to study legal outcomes as well as medical and nonmedical elements affecting malpractice litigation.MethodsPublic court records available in the Westlaw legal database (Thomson Reuters, New York, NY) were searched for medical malpractice litigation related to iatrogenic CSF leak. Of the 18 jury verdicts and settlements included, outcomes and awards, patient demographic data, and other factors instrumental in determining legal responsibility were recorded for comparison.ResultsTen (55.6%) cases were resolved in the defendant's favor, 2 (11.1%) resulted in damages awarded by a jury, and 6 (33.3%) were settled out of court before resolution of trial. Mean damages awarded were $1.1 million, while out of court settlements averaged $966,887. Malpractice stemming from patients who underwent endoscopic sinus surgery comprised 77.8% of cases analyzed. The most frequent alleged factors cited for litigation included having to undergo additional surgery (88.9%), developing meningitis (50.0%), and failing to recognize complications in a timely manner (44.4%). Perceived deficits in informed consent were alleged in one‐third of cases.ConclusionAlthough a slight majority of cases were resolved in the defendant's favor, payments made were considerable, averaging approximately $1 million. Strategies to decrease liability and allow patients to make more informed decisions should include clear communication with patients that explicitly states potential risks, such as meningitis, and possible need to undergo additional reparative surgery.
Simulationsmodelle für Gebrauchstauglichkeitsuntersuchungen von Holzbauteilen durch künstliche Bewitterung
Authors: Herlyn J. W. 
Published: March 2013

AbstractDie Eignung neu entwickelter Holzbauteile oder Holzwerkstoffe ist häufig nur über lang andauernde und entsprechend kostenintensive Praxisversuche nachzuweisen. Die Untersuchungsdauer kann durch Bewitterungssimulationen in Doppelklimaanlagen verkürzt werden. Voraussetzung für eine künstliche Bewitterung ist ein geeignetes Simulationsmodell. In dem Modell müssen die natürlichen Klimabelastungen in der Art nachgestellt werden, daß die Beanspruchungen des Bauteils im Versuch denjenigen in der Natur entsprechen. Zu diesem Zweck sind die Wirkungspfade der Klimabelastungen auf das Holzbauteil aufzustellen. Anschließend wird mit Hilfe des Test Tailoring ein Modell entwickelt, in dem die Belastungen zur Verkürzung der Versuchsdauer zeitgerafft und beschleunigt werden. Hierfür wird ein Computerprogramm zur Berechnung instationärer gekoppelter Wärme‐ und Feuchteströme in Bauteilen eingesetzt. Die Zeitstraffung und Beschleunigung von Bewitterungsmodellen sind in erster Linie von der Reaktionsgeschwindigkeit des Holzes oder der Holzwerkstoffe bei Feuchteänderungen abhängig. Diese Geschwindigkeit wird von der Geometrie sowie der Feuchteleit‐ und Feuchtespeicherfähigkeit beeinflußt. Anhand von unterschiedlichen Holzbauteilen werden die jeweils entwickelten Simulationsmodelle mit exemplarischen Ergebnissen vorgestellt. Dabei wird die jeweilige Vorgehensweise zur Entwicklung der Modelle erläutert. Die Simulationsmodelle enthalten neben den Belastungen aus Lufttemperatur und relativer Luftfeuchte auch Belastungen aus Niederschlag und Sonnenstrahlung.
Schallabsorber und Schalldämpfer ‐ Innovatorium für Maßnahmen zur Lärmbekämpfung und Raumakustik, Teil 2: Reaktive Absorber, Platten‐Resonatoren
Authors: Fuchs H. V. , Zha X. , Krämer M. , Zhou X. 
Published: March 2013

AbstractIn Teil 1 dieses Innovatoriums, das auch als kleines Repetitorium gelesen werden kann, ging es einleitend ‐ darin der historischen Entwicklung folgend ‐ um die passiven Absorber. Entsprechend ihrer im Markt bisher dominierenden Präsenz nehmen sie in allen Standard‐Darstellungen von Schallabsorbern und ‐dämpfern den weitaus größten Raum ein, auch weil ihre Wirkungsweise, Auslegung und Anwendung relativ einfach zu beschreiben sind. Nach einer kurzen Beschreibung des Schallfeldes in kleinen und mittelgroßen Räumen, wie sie z. B. für kommunikationsintensive Arbeitsplätze mit hohen raumakustischen Anforderungen gebaut werden, sollen im Teil 2 fast ausschließlich reaktive Absorber behandelt werden, welche auftreffende Schallwellen nicht nur schlucken, sondern auch auf die eine oder andere Art mit dem anliegenden Schallfeld in Wechselwirkung treten.
Auswirkungen von Lastwechseln auf die Zustandsgrößen biegebeanspruchter Stahlbetontragwerke unter Gebrauchslast
Authors: Keysberg J. 
Published: March 2013

AbstractZur Klärung der Auswirkungen von Lastwechseln auf die Zustandsgrößen biegebeanspruchter Stahlbetonbauteile unter Gebrauchslast wurde ein Rechenmodell entwickelt. Dieses gilt für biegebeanspruchte Stabtragwerke und kann den Einfluß einer beliebigen Lastfolge bei der nichtlinearen Berechnung berücksichtigen, indem die Moment‐Verkrümmungs‐Beziehung der Erstbelastung entsprechend der zuvor aufgetretenen Beanspruchungen modifiziert wird. In Vergleichsberechnungen zu experimentellen Untersuchungen konnten mit dem Rechenmodell gute Ergebnisse erzielt werden. Parameterstudien zeigen der Veränderungen der Beanspruchungen, die infolge wechselnder Belastungen durch Last und Zwang im Gebrauchszustand zu erwarten sind.
Tragfähigkeit und Bemessung gemauerter Wände nach Versuchen
Authors: Herzog M. 
Published: March 2013

AbstractEs wird ein einfaches und anschauliches Rechenverfahren zur wirklichkeitsnahen Voraussage der Tragfähigkeit gemauerter Wände mitgeteilt, das auf umfangreichen Versuchsreihen des Schweizerischen Verbandes der Ziegel‐ und Steinfabrikanten in den vergangenen 40 Jahren beruht.
Erinnerung an Friedrich Engesser (1848‐1931)
Authors: Steinhardt O. 
Published: March 2013

AbstractAm 12. Februar 1998 jährte sich der Geburtstag von Friedrich Engesser zum 150. Male. Engesser war einer der bedeutendsten Altmeister der Bautechnik und hat auf fast allen Gebieten des konstruktiven Ingenieurbaus in Forschung, Praxis und Lehre maßgebliche Entwicklungsarbeit geleistet. Zwischen 1879 und 1923 veröffentlichte er 165 Fachaufsätze in anerkannten deutschsprachigen Zeitschriften, seine Bücher über Fachwerkbrücken sowie seine Beiträge zur Technikphilosophie und zur Bauingenieurausbildung sind heute noch lesens‐ und beherzigenswerte Publikationen.
Automatisierte Dauerüberwachung von Bauwerksverformungen und Erfassung statischer Größen am Beispiel des Zwickauer Doms
Authors: Suleiman A. 
Published: March 2013

AbstractDie Langzeitüberwachung von Formänderungen ausgewählter Bauteile nimmt bei der Tragsicherheitsbewertung und Erhaltung historisch bedeutsamer, gefährdeter Bauwerke eine wichtige Stellung ein. Bisher überwogen hierbei die klassischen, einfachen Methoden wie Gipsmarken, Schnurlote oder der Einsatz klassischer geodätischer Geräte. Mit der rapiden Entwicklung der computergestützten Meßtechnik können diese Messungen kontinuierlich und automatisch ablaufen, so daß damit zur Diagnose und Therapie geschädigter Bauwerke ein wertvolles und aussagefähiges Hilfsmittel zur Verfügung steht. Am Beispiel des Zwickauer Doms soll dies im folgenden demonstriert werden.