bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low coverage sequencing of three echinoderm genomes: the brittle star Ophionereis fasciata, the sea star Patiriella regularis, and the sea cucumber Australostichopus mollis
Authors: Long Kyle A , Nossa Carlos W , Sewell Mary A , Putnam Nicholas H , Ryan Joseph F 
Published: May 2016

Abstract

Background
There are five major extant groups of Echinodermata: Crinoidea (feather stars and sea lillies), Ophiuroidea (brittle stars and basket stars), Asteroidea (sea stars), Echinoidea (sea urchins, sea biscuits, and sand dollars), and Holothuroidea (sea cucumbers). These animals are known for their pentaradial symmetry as adults, unique water vascular system, mutable collagenous tissues, and endoskeletons of high magnesium calcite. To our knowledge, the only echinoderm species with a genome sequence available to date is Strongylocentrotus pupuratus (Echinoidea). The availability of additional echinoderm genome sequences is crucial for understanding the biology of these animals.

Findings
Here we present assembled draft genomes of the brittle star Ophionereis fasciata, the sea star Patiriella regularis, and the sea cucumber Australostichopus mollis from Illumina sequence data with coverages of 12.5x, 22.5x, and 21.4x, respectively.

Conclusions
These data provide a resource for mining gene superfamilies, identifying non-coding RNAs, confirming gene losses, and designing experimental constructs. They will be important comparative resources for future genomic studies in echinoderms.
TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target
Authors: Ullah M Obayed , Sweet Matthew J , Mansell Ashley , Kellie Stuart , Kobe Bostjan 
Published: May 2016

AbstractToll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF)-dependent signaling is required for TLR-mediated production of type-I IFN and several other proinflammatory mediators. Various pathogens target the signaling molecules and transcriptional regulators acting in the TRIF pathway, thus demonstrating the importance of this pathway in host defense. Indeed, the TRIF pathway contributes to control of both viral and bacterial pathogens through promotion of inflammatory mediators and activation of antimicrobial responses. TRIF signaling also has both protective and pathologic roles in several chronic inflammatory disease conditions, as well as an essential function in wound-repair processes. Here, we review our current understanding of the regulatory mechanisms that control TRIF-dependent TLR signaling, the role of the TRIF pathway in different infectious and noninfectious pathologic states, and the potential for manipulating TRIF-dependent TLR signaling for therapeutic benefit.
Prospective Analysis of Oncogenic Driver Mutations and Environmental Factors: Japan Molecular Epidemiology for Lung Cancer Study
Authors: Kawaguchi Tomoya , Koh Yasuhiro , Ando Masahiko , Ito Norimasa , Takeo Sadanori , Adachi Hirofumi , Tagawa Tsutomu , Kakegawa Seiichi , Yamashita Motohiro , Kataoka Kazuhiko , Ichinose Yukito , Takeuchi Yukiyasu , Serizawa Masakuni , Tamiya Akihiro , Shimizu Shigeki , Yoshimoto Naoki , Kubo Akihito , Isa Shun-ichi , Saka Hideo , Matsumura Akihide 
Published: May 2016

Purpose Oncogenic driver mutations are critical for lung cancer development and serve as therapeutic targets. However, their associations with environmental factors are not fully understood. We aimed to elucidate the relationship between tumor developmental biology and exposure to environmental factors. Patients and Methods This was a prospective, multicenter, molecular epidemiology study. Eligible patients were those with newly diagnosed stages I to IIIB non–small-cell lung cancer (NSCLC) who underwent surgery. The tumors were examined for somatic mutations in 72 cancer-associated genes by targeted deep sequencing, estrogen receptor β (ERβ) expression using immunohistochemical staining, and infection with any of 37 types of human papillomavirus (HPV) using a polymerase chain reaction–based microarray system. Detailed information on patient demographics and environmental factors was obtained from a comprehensive questionnaire. Results From July 2012 to December 2013, 957 patients were enrolled, and molecular analyses were performed on 876 samples (from 441 ever- and 435 never-smokers). Oncogenic driver mutations in P53 and KRAS increased proportionally with smoking status, whereas mutations in EGFR and SMAD4 decreased. KRAS mutations in smokers and SMAD4 mutations were observed more frequently in proportion to body mass index. TP53 and NFE2L2 mutations were observed more frequently in advanced NSCLC stages. As for never-smokers, no environmental factors were significantly associated with mutational changes. EGFR mutations and TP53 mutations were observed more frequently in women and in men, respectively. Mutations in these two genes were also potentially associated with ERβ expression. Only three patients (0.3%) were HPV positive. Conclusion The mutational spectrum is associated with smoking, body mass index, and other environmental factors, as well as with ERβ expression. Little association was observed between HPV and NSCLC.
Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid
Authors: Pentsova Elena I. , Shah Ronak H. , Tang Jiabin , Boire Adrienne , You Daoqi , Briggs Samuel , Omuro Antonio , Lin Xuling , Fleisher Martin , Grommes Christian , Panageas Katherine S. , Meng Fanli , Selcuklu S. Duygu , Ogilvie Shahiba , Distefano Natalie , Shagabayeva Larisa , Rosenblum Marc , DeAngelis Lisa M. , Viale Agnes , Mellinghoff Ingo K. , Berger Michael F. 
Published: May 2016

Purpose Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue. Materials and Methods We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer. Results We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations. Conclusion The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.
Computational Mutation Study of the Roles of Catalytic Residues in Coenzyme B12-Dependent Diol Dehydratase
Authors: Doitomi Kazuki , Kamachi Takashi , Toraya Tetsuo , Yoshizawa Kazunari 
Published: May 2016

Abstract
The His143, Glu170, and Asp335 residues at the substrate-binding site of diol dehydratase, a calcium–metalloenzyme, are shown by a computational mutation study to play important roles in OH group migration (the second step in the enzymatic reaction). The reaction is accelerated by the synergetic interplay of the heterolysis of the C2–O2 bond of 1,2-diol radical and the partial deprotonation of the spectator OH group by Glu170. The His143 residue works as a donor to the migrating OH group through a hydrogen bond, which contributes to the C2–O2 bond heterolysis and resultant resonance stabilization. The Glu170 residue activates the spectator OH group to energetically stabilize the transition state in the OH group migration. The resonance stabilization of the transition state in the OH group migration is observed in the wild-type enzyme while not in the His143Ala mutant. Since the cleavage of the C2–O2 bond of 1,2-diol radical proceeds in a more homolytic manner in the His143Ala mutant, Glu170 cannot effectively deprotonate the spectator OH group in the transition state. As a result, the activation energy of the OH group migration in the His143Ala mutant is increased compared to that in the wild-type enzyme. The spectator OH group is not fully activated in the Glu170Gln and Glu170Ala mutants during the OH group migration, and thus the activation energies in the Glu170Gln and Glu170Ala mutants are higher than that in the wild-type enzyme. In contrast, the OH group migration is accelerated in the Asp335Ala mutant, due to the absence of the electric repulsion between Asp335 and the migrating OH group. The computed relative activity of the His143Ala, Glu170Gln, and Glu170Ala mutants successfully reproduces the experimentally determined catalytic activity, indicating that a computational mutation study offers a useful methodology in enzyme research.
Case Report: Successful delivery in a 44-year-old woman using vitrified human oocytes taken from the woman at 41 years of age
Authors: Funabiki Miyako , Nakamura Yoshitaka , Taguchi Sagiri 
Published: May 2016

Successful pregnancies and deliveries are rare in women over 40 years of age. To date, no case report has been published about a successful delivery in a woman over 40 years of age using vitrified oocytes obtained through social egg freezing from a woman over 40 years of age. Here we report a case of a successful live birth from a 44-year-old woman using vitrified oocytes taken from the woman at 41 years of age; the patient used the technique for social reasons. The 44-year-old patient delivered a 2534 g female infant by Caesarean section in the 37th week of pregnancy. The female infant’s Apgar scores were 9 at 1 min and 9 at 5 min. The female infant exhibited no anomalies and is developing normally under the close surveillance of pediatricians.However, the concept of social egg freezing has medical, ethical and social problems. Furthermore, the rate of live births differs among clinics and/or hospitals due to variations in the vitrification and warming techniques used. Therefore, information from individual clinics and/or hospitals about the risks, the rates of successful live births and the cost of social egg freezing should be provided to patients to aid in the patient’s decision-making process.
European Union and European Germany
Authors: Czarny Elżbieta , Menkes Jerzy 
Published: May 2016

We analyze the correlation between the European integration and incorporating Germany into the process of European cooperation. We point out that the European integration after WWII was determined by the creation of the European Coal and Steel Community in the year 1951. This Community made it possible to control the steel industry of the Member States (among them Germany) within the framework of the common market. It was aimed at stable and harmonized development, as well as at preventing an uncontrolled growth of military-industrial complex, increasing the production for the army and decreasing the probability of the outbreak of the next war. Then - after the deepening of cooperation (taking her new areas) – the European Communities (EC) were created. They are still institutional foundations of the EU. One of the main reasons of the EC creation was the willingness to ensure lasting peace in Europe and to create „security community” through a.o. incorporation of Germany into the group of cooperating states. In this paper, we analyze the security system components created (e.g.) by the EC/EU, as well as the origin and changes of their characteristics. We compare the process of German unification (and more general: of defining the German unity, and broader: unity of the German speaking territory) after WWI and WWII. The analysis of similarities and differences leads us to the present stage of the European integration, when the unification of two German states was accomplished for the price of German acceptance of deepening of the integration and the creation of the European monetary union. We analyze various consequences of unification of Germany and the creation of the euro zone. In our opinion, they go far beyond the economic or political ones, and are connected with the EU Eastern enlargement.
Flow Balancing with Uncertain Demand for Automated Package Sorting Centers
Authors: Novoa Luis J. , Jarrah Ahmad I. , Morton David P. 
Published: May 2016

Package carriers use sophisticated automated sorting facilities to efficiently process inbound packages and sort them to their down line destinations. During each of several daily processing windows, primary sorters perform high level sortation of the packages and direct them to one of several secondary sorters that are then used to segregate the packages by their outbound loading destinations. We examine the problem of assigning package destinations to the secondary sorters in a way that balances the workload in the facility, while incorporating the day-to-day fluctuation in package volumes and adhering to the outbound loading capacities of the various workcenters in the facility. We present a general stochastic modeling framework using chance constraints to balance the flows, and robust constraints to model the capacity limits. We propose and evaluate the performance of three alternative mixed integer nonlinear formulations for the problem and determine which is most effective. Significant improvement in package flow balance and loading capacity robustness is shown for the test sorting facilities by comparing the solutions from the proposed new model to those obtained when ignoring, partially or completely, the stochasticity in the package volumes. The online appendix is available at https://doi.org/10.1287/trsc.2015.0662 .
A clinical trial protocol for the study of intravenous immunoglobulin in patients with primary antibody immunodeficiency disorders
Authors: Hooper John A. 
Published: May 2016

This protocol has been excerpted from protocols recently used to study the safety, efficacy, and pharmacokinetics of 2 new intravenous immunoglobulins (IVIG). It incorporates the safety and efficacy parameters provided by the United States Food and Drug Administration in in a Guidance for Industry that contains recommendations for Investigational New Drug Application sponsors and Biologic License applicants for testing IVIG products as replacement therapy in primary humoral immunodeficiency. The format and contents of the protocol are generally the same as described in the ICH Guideline for Good Clinical Practice. We describe here the topics found in the main body of the protocol. We have omitted items that will be included in a formal protocol such as the title page, identifying number, name and contact information of the sponsor, names and contact information of the persons authorized to sign the protocol and amendments, etc. The success of a study of IVIG in patients with primary humoral immunodeficiency is very much dependent on the care in which patients are selected. It is extremely important to enroll patients who have been verified to be antibody deficient. Therefore, patient selection criteria should involve a thorough review of each patient’s infection history, serum IgG level prior to immunoglobulin therapy, and antibody responses to polysaccharide and protein vaccines. Statement of novelty: This protocol is designed to select study subjects with well-documented antibody deficiencies and therefore will benefit from immunoglobulin therapy.
Zehn Jahre RFID-Einsatz in der Bibliothek der Medizinischen Fakultät Mannheim
Authors: Semmler-Schmetz Martina , Bohne-Lang Andreas 
Published: May 2016

Zusammenfassung:
Die Bibliothek der Medizinischen Fakultät Mannheim der Universität Heidelberg blickt auf zehn Jahre Erfahrung mit RFID zurück. Im Jahr 2006 gehörte sie zu den Pionieren der Geschichte von RFID in Bibliotheken und war die erste deutsche Bibliothek, die RFID-Komponenten gekoppelt an das Bibliothekssystem SISIS-SunRise einsetzte.
Rückblick: PROFILE HU – Projekt RFID zur Entwicklung innovativer Dienst- und Serviceleistungen der Bibliotheken der HU – was ist übrig geblieben
Authors: Berghaus-Sprengel Anke 
Published: May 2016

Zusammenfassung:
Der Artikel bilanziert das von 2009–2013 an der Humboldt-Universität durchgeführte RFID-Projekt. Standardanwendungen für Bibliotheken sind im Regelbetrieb unverzichtbar geworden, Experimente und multifunktionale Geräte erfordern personelle Betreuung. Es besteht Professionalisierungsbedarf bei den Firmen.
The serotonergic system and cognitive function
Authors: Švob Štrac Dubravka , Pivac Nela , Mück-Šeler Dorotea 
Published: May 2016

Abstract
Symptoms of cognitive dysfunction like memory loss, poor concentration, impaired learning and executive functions are characteristic features of both schizophrenia and Alzheimer’s disease (AD). The neurobiological mechanisms underlying cognition in healthy subjects and neuropsychiatric patients are not completely understood. Studies have focused on serotonin (5-hydroxytryptamine, 5-HT) as one of the possible cognitionrelated biomarkers. The aim of this review is to provide a summary of the current literature on the role of the serotonergic (5-HTergic) system in cognitive function, particularly in AD and schizophrenia.
The role of the 5-HTergic system in cognition is modulated by the activity and function of 5-HT receptors (5-HTR) classified into seven groups, which differ in structure, action, and localization. Many 5-HTR are located in the regions linked to various cognitive processes. Preclinical studies using animal models of learning and memory, as well as clinical in vivo (neuroimaging) and in vitro (post-mortem) studies in humans have shown that alterations in 5-HTR activity influence cognitive performance.
The current evidence implies that reduced 5-HT neurotransmission negatively influences cognitive functions and that normalization of 5-HT activity may have beneficial effects, suggesting that 5-HT and 5-HTR represent important pharmacological targets for cognition enhancement and restoration of impaired cognitive performance in neuropsychiatric disorders.
Strategies for Improving Vaccine Delivery: A Cluster-Randomized Trial
Authors: Fu Linda Y. , Zook Kathleen , Gingold Janet A. , Gillespie Catherine W. , Briccetti Christine , Cora-Bramble Denice , Joseph Jill G. , Haimowitz Rachel , Moon Rachel Y. 
Published: May 2016

OBJECTIVE:New emphasis on and requirements for demonstrating health care quality have increased the need for evidence-based methods to disseminate practice guidelines. With regard to impact on pediatric immunization coverage, we aimed to compare a financial incentive program (pay-for-performance [P4P]) and a virtual quality improvement technical support (QITS) learning collaborative.METHODS:This single-blinded (to outcomes assessor), cluster-randomized trial was conducted among unaffiliated pediatric practices across the United States from June 2013 to June 2014. Practices received either the P4P or QITS intervention. All practices received a Vaccinator Toolkit. P4P practices participated in a tiered financial incentives program for immunization coverage improvement. QITS practices participated in a virtual learning collaborative. Primary outcome was percentage of all needed vaccines received (PANVR). We also assessed immunization up-to-date (UTD) status.RESULTS:Data were analyzed from 3,147 patient records from 32 practices. Practices in the study arms reported similar QI activities (∼6 to 7 activities). We found no difference in PANVR between P4P and QITS (mean ± SE, 90.7% ± 1.1% vs 86.1% ± 1.3%, P = 0.46). Likewise, there was no difference in odds of being UTD between study arms (adjusted odds ratio 1.02, 95% confidence interval 0.68 to 1.52, P = .93). In within-group analysis, patients in both arms experienced nonsignificant increases in PANVR. Similarly, the change in adjusted odds of UTD over time was modest and nonsignificant for P4P but reached significance in the QITS arm (adjusted odds ratio 1.28, 95% confidence interval 1.02 to 1.60, P = .03).CONCLUSIONS:Participation in either a financial incentives program or a virtual learning collaborative led to self-reported improvements in immunization practices but minimal change in objectively measured immunization coverage.
Сучасний стан водних ресурсів Закарпаття
Authors: Nikolaichuk V. І. , Vakerich M. М. , Shpontak J. М. , Karpu’k М. К. 
Published: May 2016

Закарпатська область розташована в центрі Європи, межує з чотирма Центральноєвропейськими країнами (Польщею, Словаччиною, Угорщиною та Румунією) та двома областями України (Львівською та Івано-Франківською). Закарпаття – один із найкраще забезпечених водними ресурсами регіонів України. Територія області перерізана густою мережею річок. Усього на території області протікає 9 429 річок, сумарна довжина яких становить 19 866 км. Із них ріки Тиса, Боржава, Латориця та Уж мають довжину понад 100 км кожна. Централізованими водозаборами питних підземних вод забезпечені практично 25 міст і селищ міського типу області. У сільських населених пунктах централізоване водопостачання практично відсутнє, воно здійснюється переважно за рахунок побутових колодязів чи свердловин. Прогнозні ресурси питних підземних вод в області становлять 1,109 млн м3/добу. Використання свіжої води за 2014 рік на одного мешканця склало 23,769 м3, що на 15% менше аналогічного показника 2009 року. Основні забруднювачі поверхневих вод – об’єкти житлово-комунальних підприємств області. За більшістю показників загально-санітарного аналізу та специфічних показників якість води відповідає санітарним правилам і нормам. Із загальної кількості водопроводів 19,0% не відповідають санітарним вимогам: через відсутність зон санітарної охорони – 14,2%, через відсутність необхідного комплексу очисних споруд – 1,9%, через відсутність знезаражувальних установок – 7,6%. Можливим шляхом запобігання виснаженню водних об’єктів є профілактичні водоохоронні заходи, спрямовані на запобігання або обмеження забруднення, засмічення та виснаження вод, а також екологічна просвітницька робота серед населення.
Застосування геоінформаційних систем в оцінюванні розвитку яружно-балкової ерозії степової зони України
Authors: Tsvetkova N. M. , Saranenko I. I. , Dubina A. O. 
Published: May 2016

На території степової зони України з допомогою GPS навігатора та нівеліра встановлено координати вершин, конфігурацію меж, висоту, довжину, ширину 400 ярів, балок і байраків. Визначено вміст заліза у шарі 0–50 см. Отримані дані імпортовано у QuantumGis і нанесено на карту розораності земель України. Осередки скупчення досліджуваних об’єктів виявлено у центральній та східній частинах Степу. Аналіз причин показав комплексну дію чинників. За рік спостережень виявлено, що площа кожного яру зросла у середньому на 5 м², висота – на 7 см, довжина – на 24 см, ширина – на 21 см, концентрація Fe знизилась на 20 мг/кг. Основні причини – значні опади та нестійкий трав’яний покрив. Площа балок зросла на 1 м², висота – на 4 см, довжина – на 14 см, ширина – на 9 см, концентрація Fe залишилась без змін. Унаслідок того, що деревні рослини стримують розвиток ерозійних процесів і збагачують ґрунти мікроелементами, у байраків спостерігається зменшення висоти на 1 см та зростання концентрації Fe на 24 мг/кг, значення інших показників не змінились. У середовищі QuantumGis створено електронні карти щільності та поширеності ярів, балок і байраків у степовій зоні України. За їх допомогою визначено залежність між досліджуваними процесами та природними умовами, межові кути повороту, площу яружно-балкової ерозії. Створено проект бази даних щодо вмісту мікроелементів та особливостей їх міграції за байрачним профілем із метою подальшого застосування у процесі розроблення необхідних заходів боротьби з ерозією.