bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zebularine upregulates expression of CYP genes through inhibition of DNMT1 and PKR in HepG2 cells
Authors: Nakamura Kazuaki , Aizawa Kazuko , Aung Kyaw Htet , Yamauchi Junji , Tanoue Akito 
Published: January 2017

AbstractDrug-induced hepatotoxicity is one of the major reasons cited for drug withdrawal. Therefore, it is of extreme importance to detect human hepatotoxic candidates as early as possible during the drug development process. In this study, we aimed to enhance hepatocyte functions such as CYP gene expression in HepG2 cells, one of the most extensively used cell lines in evaluating hepatotoxicity of chemicals and drugs. We found that zebularine, a potent inhibitor of DNA methylation, remarkably upregulates the expression of CYP genes in HepG2 cells. In addition, we revealed that the upregulation of CYP gene expression by zebularine was mediated through the inhibition of both DNA methyltransferase 1 (DNMT1) and double-stranded RNA-dependent protein kinase (PKR). Furthermore, HepG2 cells treated with zebularine were more sensitive than control cells to drug toxicity. Taken together, our results show that zebularine may make HepG2 cells high-functioning and thus could be useful for evaluating the hepatotoxicity of chemicals and drugs speedily and accurately in in-vitro systems. The finding that zebularine upregulates CYP gene expression through DNMT1 and PKR modulation sheds light on the mechanisms controlling hepatocyte function and thus may aid in the development of new in-vitro systems using high-functioning hepatocytes.
Nanoscale Topography on Black Titanium Imparts Multi-biofunctional Properties for Orthopedic Applications
Authors: Hasan Jafar , Jain Shubham , Chatterjee Kaushik 
Published: January 2017

AbstractWe have developed a chlorine based reactive ion etching process to yield randomly oriented anisotropic nanostructures that render the titanium metal surface ‘black’ similar to that of black silicon. The surface appears black due to the nanostructures in contrast to the conventional shiny surface of titanium. The nanostructures were found to kill bacteria on contact by mechanically rupturing the cells as has been observed previously on wings of certain insects. The etching was optimized to yield nanostructures of ≈1 μm height for maximal bactericidal efficiency without compromising cytocompatibility. Within 4 hours of contact with the black titanium surface, 95% ± 5% of E. coli, 98% ± 2% of P. aeruginosa, 92% ± 5% of M. smegmatis and 22% ± 8% of S. aureus cells that had attached were killed. The killing efficiency for the S. aureus increased to 76% ± 4% when the cells were allowed to adhere up to 24 hours. The black titanium supported the attachment and proliferation of human mesenchymal stem cells and augmented osteogenic lineage commitment in vitro. Thus, the bioinspired nanostructures on black titanium impart multi-biofunctional properties toward engineering the next-generation biomaterials for orthopedic implants.
Quantum Monte Carlo simulation of a particular class of non-stoquastic Hamiltonians in quantum annealing
Authors: Ohzeki Masayuki 
Published: January 2017

AbstractQuantum annealing is a generic solver of the optimization problem that uses fictitious quantum fluctuation. Its simulation in classical computing is often performed using the quantum Monte Carlo simulation via the Suzuki–Trotter decomposition. However, the negative sign problem sometimes emerges in the simulation of quantum annealing with an elaborate driver Hamiltonian, since it belongs to a class of non-stoquastic Hamiltonians. In the present study, we propose an alternative way to avoid the negative sign problem involved in a particular class of the non-stoquastic Hamiltonians. To check the validity of the method, we demonstrate our method by applying it to a simple problem that includes the anti-ferromagnetic XX interaction, which is a typical instance of the non-stoquastic Hamiltonians.
The choreography of the chemical defensome response to insecticide stress: insights into the Anopheles stephensi transcriptome using RNA-Seq
Authors: De Marco Leone , Sassera Davide , Epis Sara , Mastrantonio Valentina , Ferrari Marco , Ricci Irene , Comandatore Francesco , Bandi Claudio , Porretta Daniele , Urbanelli Sandra 
Published: January 2017

AbstractAnimals respond to chemical stress with an array of gene families and pathways termed “chemical defensome”. In arthropods, despite many defensome genes have been detected, how their activation is arranged during toxic exposure remains poorly understood. Here, we sequenced the transcriptome ofAnopheles stephensilarvae exposed for six, 24 and 48 hours to the LD50dose of the insecticide permethrin to monitor transcriptional changes of defensome genes across time. A total of 177 genes involved in insecticide defense were differentially expressed (DE) in at least one time-point, including genes encoding for Phase 0, I, II, III and antioxidant enzymes and for Heat Shock and Cuticular Proteins. Three major patterns emerged throughout time. First, most of DE genes were down-regulated at all time-points, suggesting a reallocation of energetic resources during insecticide stress. Second, single genes and clusters of genes turn off and on from six to 48 hours of treatment, showing a modulated response across time. Third, the number of up-regulated genes peaked at six hours and then decreased during exposure. Our results give a first picture of how defensome gene families respond against toxicants and provide a valuable resource for understanding how defensome genes work together during insecticide stress.
A Near-Infrared Spectroscopy Study on Cortical Hemodynamic Responses to Normal and Whispered Speech in 3- to 7-Year-Old Children
Authors: Remijn Gerard B. , Kikuchi Mitsuru , Yoshimura Yuko , Shitamichi Kiyomi , Ueno Sanae , Tsubokawa Tsunehisa , Kojima Haruyuki , Higashida Haruhiro , Minabe Yoshio 
Published: January 2017

Purpose
The purpose of this study was to assess cortical hemodynamic response patterns in 3- to 7-year-old children listening to two speech modes: normally vocalized and whispered speech. Understanding whispered speech requires processing of the relatively weak, noisy signal, as well as the cognitive ability to understand the speaker's reason for whispering.

Method
Near-infrared spectroscopy (NIRS) was used to assess changes in cortical oxygenated hemoglobin from 16 typically developing children.

Results
A profound difference in oxygenated hemoglobin levels between the speech modes was found over left ventral sensorimotor cortex. In particular, over areas that represent speech articulatory body parts and motion, such as the larynx, lips, and jaw, oxygenated hemoglobin was higher for whisper than for normal speech. The weaker stimulus, in terms of sound energy, thus induced the more profound hemodynamic response. This, moreover, occurred over areas involved in speech articulation, even though the children did not overtly articulate speech during measurements.

Conclusion
Because whisper is a special form of communication not often used in daily life, we suggest that the hemodynamic response difference over left ventral sensorimotor cortex resulted from inner (covert) practice or imagination of the different articulatory actions necessary to produce whisper as opposed to normal speech.
Funktionelle Ergebnisse und Transplantatversagen nach Re-Keratoplastik
Authors: Blug S. , Seitz B. , Langenbucher A. , Szentmáry N. 
Published: January 2017

Zusammenfassung
Hintergrund und Ziel Die Keratoplastik ist die älteste und erfolgreichste Gewebetransplantation am Menschen. Trotz des immunologischen Privilegs der Hornhaut kann es in Abhängigkeit von der Grunderkrankung, der Qualität des Spendergewebes und der Compliance des Patienten in bis zu 10 % der Fälle zu einem Transplantatversagen kommen, das einer Re-Keratoplastik bedarf. Ziel dieser Studie war es, Einflussfaktoren auf das funktionelle Ergebnis und das Transplantatüberleben nach Re-Keratoplastik zu untersuchen.
Patienten und Methoden In dieser monozentrischen, retrospektiven Studie wurden alle Patienten eingeschlossen, die im Zeitraum 01. 01. 2001 bis 31. 12. 2010 in Homburg mit einer Re-Keratoplastik versorgt wurden. Die Daten wurden in einer Access-Datenbank aus den Patientenakten erfasst und mittels SPSS 19.0 statistisch ausgewertet. Es wurden hauptsächlich die OP-Berichte und die Ergebnisse der Nachuntersuchung mit dem Fokus auf Visus, Tensio, Endothelzelldichte, Hornhauttopografie und Hornhauttomografie sowie Transplantatreaktionen und Transplantatversagen ausgewertet.
Ergebnisse Es konnte gezeigt werden, dass die Excimer-Laser-Trepanation der mechanischen Trepanation mit dem Motortrepan bez. des korrigierten Visus signifikant (p = 0,009) überlegen war. So war der korrigierte Visus nach 2 Jahren in der Gruppe der Lasertrepanierten im Mittel bei 0,39, in der Gruppe mit mechanischer Trepanation dagegen nur bei 0,16. Des Weiteren konnte nachgewiesen werden, dass ein Transplantatdurchmesser kleiner als 7,5 mm einen signifikant negativen Einfluss auf die Inzidenz eines postkeratoplastischen Astigmatismus hat (p = 0,004). Nach einem Beobachtungszeitraum von 120 Monaten war in der Gruppe der Transplantate mit einem Durchmesser ≤ 7,5 mm/> 7,5 mm die Rate der Abstoßungsreaktionen bei 20/60 % (p = 0,259).
Schlussfolgerung Die Daten der vorliegenden Studie zeigen, dass im Hinblick auf die funktionelle Rehabilitation ein Wiederholungstransplantat Excimer-Laser-chirurgisch gewonnen werden sollte, wenn dies morphologisch (z. B. Vaskularisation) möglich ist. Auf das Transplantatüberleben hat die OP-Technik allerdings keine signifikante Auswirkung. Auch bei der Re-Keratoplastik gilt der Grundsatz, den Durchmesser des Transplantats in Abhängigkeit von der Größe der Hornhaut so groß wie möglich, aber so klein wie nötig zu wählen.
Erfassung der Versorgungsqualität von Glaukompatienten im Großraum Hamburg
Authors: Waibel S. , Gesser C. , Klemm M. 
Published: January 2017

Zusammenfassung
Hintergrund Daten über die Qualität der Versorgung und die Lebensqualität von Glaukompatienten existieren bisher nicht in ausreichendem Maße. In der vorliegenden prospektiven Studie sollte erfasst werden, inwiefern eine den Leitlinien der Deutschen Ophthalmologischen Gesellschaft (DOG) entsprechende, adäquate Versorgung von Glaukompatienten im Großraum Hamburg gegeben ist.
Patienten und Methoden Bei 196 Patienten wurde während der stationären Tensionsanalyse ein interviewergeführter Fragebogen ausgefüllt. Dieser sollte die Qualität der Versorgung untersuchen, indem er die in den Leitlinien der DOG empfohlenen Untersuchungen und deren Häufigkeit abfragte. Die entsprechenden Ergebnisse bei der Auswertung des Fragebogens wurden in Bezug gesetzt zur Schwere des Glaukoms sowie zur vorliegenden Glaukomform.
Ergebnisse Im Mittel suchten die Patienten ihren ambulanten Augenarzt 5,1-mal pro Jahr auf. Der Großteil der Patienten berichtete, dass sie quartalsmäßig ihren Augenarzt aufsuchten. Bei 92 % der Patienten wurde bei jedem ambulanten Arztbesuch eine Tensiomessung durchgeführt. Die Hälfte der Patienten gab an, dass der Augeninnendruck im ambulanten Bereich wiederholt zu verschiedenen Tageszeiten gemessen wurde. Durchschnittlich wurde 0,9-mal pro Jahr eine Perimetrie in der Augenklinik durchgeführt, dagegen 1,4-mal im ambulanten Bereich. Weitere Maßnahmen zur Glaukomdiagnostik wurden 0,8-mal pro Jahr in der Augenklinik bzw. 0,4-mal beim niedergelassenen Augenarzt durchgeführt. Für den Großteil der Patienten entstanden keine Kosten für die ambulante Glaukomdiagnostik. Nur bei 4 % der Patienten lagen diese jährlich über 100 €.
Schlussfolgerungen Für die Mehrheit der Glaukompatienten im Großraum Hamburg ist eine den Leitlinien der DOG entsprechende, adäquate Versorgung durch regelmäßige Verlaufskontrollen gegeben. Bei fast allen Patienten wurden die Tensiokontrollen und perimetrischen Untersuchungen wie empfohlen durchgeführt. Dagegen erfolgte bei einem Fünftel der Patienten keine regelmäßige apparative Beurteilung des Sehnervs und der Nervenfaserschicht. Den Termin für die nächste Kontrolle bekamen die Patienten zumeist gleich genannt. Damit war eine engmaschige Verlaufskontrolle gut realisierbar, welche für die Mehrzahl der Patienten mit keinen oder geringen privaten Zusatzzahlungen verbunden war.
Glücksspielverhalten der österreichischen Bevölkerung und ihre Akzeptanz von Spielerschutzmaßnahmen – Ergebnisse der Repräsentativbefragungen 2009 und 2015
Authors: Kalke Jens , Buth Sven , Thon Natasha , Wurst Frieder 
Published: January 2017

ZusammenfassungMit dem vorliegenden Beitrag werden erstmalig für Österreich repräsentative Trends zum Glücksspielverhalten der Bevölkerung (14–65 Jahre) veröffentlicht. Es wurden zu 2 Zeitpunkten die Glücksspielteilnahme und das Ausmaß glücksspielbedingter Probleme sowie die Akzeptanz von Maßnahmen des Spieler- und Jugendschutzes erhoben.Die Datenerhebung erfolgte in Form von computergestützten telefonischen Interviews (CATI, Festnetz und mobil). Die Fallzahl beträgt für das Jahr 2009 6 300 und für das Jahr 2015 10 000 Personen. Die Basis für die Berechnung der Gewichtungsfaktoren bilden die Variablen Alter, Geschlecht und Schulbildung.Es ergibt sich ein stabiler Anteil von Personen, die mindestens einmal im Jahr irgendein Glücksspiel um Geld spielen (2009: 42%, 2015: 41%). Bei der monatlichen Spielteilnahme hat eine signifikante Zunahme stattgefunden (von 23 auf 27%). Der Anteil derjenigen, die ein mindestens problematisches Spielverhalten aufweisen, ist mit 1,1% zwischen 2009 und 2015 gleich geblieben. Es zeigt sich in beiden Erhebungen eine hohe Zustimmung der Bevölkerung für einen weitreichenden Spieler- und Jugendschutz.Die gleichbleibende Problemspielprävalenz mit 64 000 Betroffenen macht deutlich, dass weiter Handlungsbedarf in Bezug auf die Glücksspielsuchtprävention besteht. Dabei sollte die hohe Akzeptanz in der Bevölkerung für den Spieler- und Jugendschutz genutzt werden, um vor allem den Bereich der verhältnispräventiven Maßnahmen auszubauen.
Botulinumtoxintherapie – neue Entwicklungen in der Augenheilkunde
Authors: Wabbels B. 
Published: January 2017

ZusammenfassungBotulinumtoxin ist seit Jahren der Goldstandard bei der Behandlung des essenziellen Blepharospasmus und des Hemispasmus facialis, ähnlich wirksam bei Synkinesien nach Fazialisparese. Falls für den individuellen Patienten erforderlich, können die Injektionsintervalle bei Lidkrämpfen auf bis zu 6 Wochen verkürzt werden. Neuere Indikationen in der Augenheilkunde umfassen die Lidretraktion bei endokriner Orbitopathie, die Induktion einer protektiven Ptosis und die Behandlung von Krokodilstränen. Zukünftig kommt Botulinumtoxin evtl. auch zur Behandlung von Depressionen (facial feedback), von Wunden im Gesichtsbereich und zum Schutz von Drüsen vor Bestrahlungsfolgen in Betracht.
SynEM: Automated synapse detection for connectomics
Authors: Staffler Benedikt , Berning Manuel , Boergens Kevin M. , Gour Anjali , van der Smagt Patrick , Helmstaedter Moritz 
Published: January 2017

ABSTRACTNerve tissue contains a high density of chemical synapses, about 1 per µm3 in the mammalian cerebral cortex. Thus, even for small blocks of nerve tissue, dense connectomic mapping requires the identification of millions to billions of synapses, of which about 80-90% are excitatory synapses. While the focus of connectomic data analysis has been on neurite reconstruction, synapse detection becomes limiting when datasets grow in size and dense mapping is required. Here, we report SynEM, a method for automated detection of excitatory synapses from conventionally en-bloc stained 3D electron microscopy image stacks. The approach is based on a segmentation of the image data and focuses on classifying borders between neuronal processes as synaptic or non-synaptic. SynEM yields 98% precision and recall in binary excitatory cortical connectomes with no user interaction. It scales to large volumes of cortical neuropil, plausibly even whole-brain datasets. SynEM removes the burden of manual synapse annotation for large densely mapped connectomes.
Multi-generational silencing dynamics control cell aging
Authors: Li Yang , Jin Meng , O’Laughlin Richard , Bittihn Philip , Tsimring Lev S. , Pillus Lorraine , Hasty Jeff , Hao Nan 
Published: January 2017

Cellular aging plays an important role in many diseases, such as cancers, metabolic syndromes and neurodegenerative disorders. There has been steady progress in identifying aging-related factors such as reactive oxygen species and genomic instability, yet an emerging challenge is to reconcile the contributions of these factors with the fact that genetically identical cells can age at significantly different rates. Such complexity requires single-cell analyses designed to unravel the interplay of aging dynamics and cell-to-cell variability. Here we use novel microfluidic technologies to track the replicative aging of single yeast cells and reveal that the temporal patterns of heterochromatin silencing loss regulate cellular lifespan. We found that cells show sporadic waves of silencing loss in the heterochromatic ribosomal DNA (rDNA) during the early phases of aging, followed by sustained loss of silencing preceding cell death. Isogenic cells have different lengths of the early intermittent silencing phase that largely determine their final lifespans. Combining computational modeling and experimental approaches, we found that the intermittent silencing dynamics is important for longevity and is dependent on the conserved Sir2 deacetylase, whereas either sustained silencing or sustained loss of silencing shortens lifespan. These findings reveal, for the first time, that the temporal patterns of a key molecular process can directly influence cellular aging and thus could provide guidance for the design of temporally controlled strategies to extend lifespan.SignificanceAging is an inevitable consequence of living, and with it comes increased morbidity and mortality. Novel approaches to mitigating age-related chronic diseases demand a better understanding of the biology of aging. Studies in model organisms have identified many conserved molecular factors that influence aging. The emerging challenge is to understand how these factors interact and change dynamically to drive aging. Using multidisciplinary technologies, we have revealed a sirtuin-dependent intermittent pattern of chromatin silencing during yeast aging that is crucial for longevity. Our findings highlight the important role of silencing dynamics in aging, which deserves careful consideration when designing schemes to delay or reverse aging by modulating sirtuins and silencing.
Challenges for Bayesian Model Selection of Dynamic Causal Models
Authors: van den Honert Rebecca N. , Shultz Sarah , Johnson Marcia K. , McCarthy Gregory 
Published: January 2017

AbstractAchieving a mechanistic explanation of brain function requires understanding causal relationships among regions. A relatively new technique to assess effective connectivity in fMRI data is Dynamic Causal Modeling (DCM). As DCM is more frequently used, it becomes increasingly important to further validate the technique and understand its limitations. With DCM, Bayesian Model Selection (BMS) is used to select the most likely causal model. We conducted simulations to test the degree to which BMS is robust to two types of challenges when applied to DCMs, those inherent to data (Category 1) and those inherent to model space (Category 2).Category 1challenges tested properties of the data (low signal-to-noise, different response magnitudes and shapes across regions) that could either blur the distinction between models or potentially bias model selection. These challenges are impossible or difficult to measure and control in real data, so investigating their effect upon BMS through simulation is critical.Category 2challenges tested properties of model space that create subsets of confusable models. Our results suggest that given data that conform to the prior assumptions of DCM, BMS is robust to challenges fromCategory 1. However, in the face ofCategory 2challenges (when a more homogenous model space was tested) the false positive rate rose above an acceptable level. We show that such errors are neither trivial nor easily avoided with existing approaches. However, we argue that it is possible to detectCategory 2challenges, and avoid inappropriate interpretations by conducting simulations prior to applying DCM.AcronymsDCMDynamic Causal ModelingBMSBayesian Model SelectionfMRIfunctional magnetic resonance imagingBOLDblood oxygen level dependentFMCFamily Model ComparisonHRFhemodynamic response functionROIregion of interestSNRsignal to noise ratioR1region 1R2region 2U1input 1
A genetic basis for molecular asymmetry at vertebrate electrical synapses
Authors: Miller Adam C , Whitebirch Alex C , Shah Arish N , Marsden Kurt C , Granato Michael , O’Brien John , Moens Cecilia B 
Published: January 2017

AbstractNeural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication and they come in two types, chemical and electrical. Communication at chemical synapses occurs via neurotransmitter release whereas electrical synapses utilize gap junctions for direct ionic and metabolic coupling. Electrical synapses are often viewed as symmetrical structures, with the same components making both sides of the gap junction. By contrast, we show that a broad set of electrical synapses in zebrafish,Danio rerio, require two gap-junction-forming Connexins for formation and function. We find that one Connexin functions presynaptically while the other functions postsynaptically in forming the channels. We also show that these synapses are required for the speed and coordination of escape responses. Our data identify a genetic basis for molecular asymmetry at vertebrate electrical synapses and show they are required for appropriate behavioral performance.
Niyogi books: making a difference in the Indian book publishing industry
Authors: De Niyogi Trisha , Chaurasia Sushil S. 
Published: January 2017

Subject area
Marketing strategy.

Study level/applicability
The course is well suited for MBA and Executive MBA class on Strategic Management, Marketing Strategy, Brand Management, Entrepreneurship, Innovation and Change in emerging economies. The case can also be taught to senior undergraduate students to explore the issues mentioned in the case as an integrative case for courses like Strategic Management and Marketing Strategy.

Case overview
Niyogi Books had positioned itself as an independent publishing house with a focus on the niche area of trade books. Due to the internet, digitalization and globalization the dynamics of the book publishing industry had changed considerably, and the company needed to think and reflect on its current position and future strategy. Niyogi Books had added new products and new markets along with other innovations to succeed in the business of publishing. But the way ahead for Niyogi Books was to innovate in light of fast-paced technological advancement. The company needed to balance the digitization of content as well as retailing with its existing print strategy. A related issue is the need to plan an innovative and cost-effective communication strategy to boost sales.

Expected learning outcomes
The learning outcomes are as follows: analyze the business environment of the publishing industry, realize the need for a branding strategy for small business and apply communication strategies single/multi-channel setting, understand the need of an organization to purposefully adapt an organization’s (self-) resource base (management capability to effectively coordinate and redeploy internal and external competences) and analyze the role of a growth strategy and how it can be used to devise a product/marketing strategy.

Supplementary materials
Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 11: Strategy.