bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Herpesvirus 8 Interferon Regulatory Factors 1 and 3 Mediate Replication and Latency Activities via Interactions with USP7 Deubiquitinase
Authors: Xiang Qiwang , Ju Hyunwoo , Li Qian , Mei Szu-Chieh , Chen Daming , Choi Young Bong , Nicholas John 
Published: January 2018

ABSTRACT
Human herpesvirus 8 (HHV-8) encodes four viral interferon regulatory factors (vIRF-1 to -4) that likely function to suppress innate immune and cellular stress responses through inhibitory interactions with various cellular proteins involved in these activities. It is notable that vIRF-1 and -4 have been reported to interact with the deubiquitinase ubiquitin-specific protease 7 (USP7), substrates of which include p53 and the p53-targeting and -destabilizing ubiquitin E3 ligase MDM2. Structural studies of vIRF-1 and vIRF-4 USP7 binding sequences in association with USP7 have been reported; both involve interactions with N-terminal-domain residues of USP7 via EGPS and ASTS motifs in vIRF-1 and vIRF-4, respectively, but vIRF-4 residues also contact the catalytic site. However, the biological activities of vIRF-1 and vIRF-4 via USP7 interactions are unknown. Here, we report that vIRF-3, which is latently, as well as lytically, expressed in HHV-8-infected primary effusion lymphoma (PEL) cells, also interacts with USP7—via duplicated EGPS motifs—and that this interaction is important for PEL cell growth and viability. The interaction also contributes to suppression of productive virus replication by vIRF-3, which we identify here. We further show that vIRF-1, which is expressed at low levels in PEL latency, promotes latent PEL cell viability and that this activity and vIRF-1-promoted productive replication (reported previously) involve EGPS motif-mediated USP7 targeting by vIRF-1. This study is the first to identify latent and lytic functions of vIRF-1 and vIRF-3, respectively, and to address the biological activities of these vIRFs through their interactions with USP7.

IMPORTANCE
HHV-8 is associated with Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease; both latent and lytic viral functions are believed to contribute. Viral interferon regulatory factors specified by HHV-8 are thought to be critically important for successful productive replication through suppression of innate immune and stress responses triggered by the lytic cycle. Latently expressed vIRF-3 contributes significantly to PEL cell survival. Here, we identify ubiquitin-specific protease 7 (USP7) deubiquitinase targeting by vIRF-3 (in addition to previously reported USP7 binding by vIRF-1 and vIRF-4); the importance of vIRF-1 and vIRF-3 interactions with USP7 for latent PEL cell growth and viability; and the positive and negative contributions, respectively, of USP7 targeting by vIRF-1 and vIRF-3 to HHV-8 productive replication. This is the first report of the biological importance of vIRF-1 in PEL cell latency, the modulation of productive replication by vIRF-3, and the contributions of vIRF-USP7 interactions to HHV-8 biology.
The 5′ Untranslated Region of the Major Immediate Early mRNA Is Necessary for Efficient Human Cytomegalovirus Replication
Authors: Arend Kyle C. , Lenarcic Erik M. , Moorman Nathaniel J. 
Published: January 2018

ABSTRACTThe human cytomegalovirus (HCMV) immediate early 1 (IE1) and IE2 proteins are critical regulators of virus replication. Both proteins are needed to efficiently establish lytic infection, and nascent expression of IE1 and IE2 is critical for reactivation from latency. The regulation of IE1 and IE2 protein expression is thus a central event in the outcome of HCMV infection. Transcription of the primary transcript encoding both IE1 and IE2 is well studied, but relatively little is known about the posttranscriptional mechanisms that control IE1 and IE2 protein synthesis. The mRNA 5′ untranslated region (5′ UTR) plays an important role in regulating mRNA translation. Therefore, to better understand the control of IE1 and IE2 mRNA translation, we examined the role of the shared 5′ UTR of the IE1 and IE2 mRNAs (MIE 5′ UTR) in regulating translation. In a cell-free system, the MIE 5′ UTR repressed translation, as predicted based on its length and sequence composition. However, in transfected cells we found that the MIE 5′ UTR increased the expression of a reporter gene and enhanced its association with polysomes, demonstrating that the MIE 5′ UTR has a positive role in translation control. We also found that the MIE 5′ UTR was necessary for efficient IE1 and IE2 translation during infection. Replacing the MIE 5′ UTR with an unstructured sequence of the same length decreased IE1 and IE2 protein expression despite similar levels of IE1 and IE2 mRNA and reduced the association of the IE1 and IE2 mRNAs with polysomes. The wild-type MIE 5′-UTR sequence was also necessary for efficient HCMV replication. Together these data identify the shared 5′ UTR of the IE1 and IE2 mRNAs as an important regulator of HCMV lytic replication.IMPORTANCEThe HCMV IE1 and IE2 proteins are critical regulators of HCMV replication, both during primary infection and during reactivation from viral latency. Thus, defining factors that regulate IE1 and IE2 expression is important for understanding the molecular events controlling the HCMV replicative cycle. Here we identify a positive role for the MIE 5′ UTR in mediating the efficient translation of the IE1 and IE2 mRNAs. This result is an important advance for several reasons. To date, most studies of IE1 and IE2 regulation have focused on defining events that regulate IE1 and IE2 transcription. Our work reveals that in addition to the regulation of transcription, IE1 and IE2 are also regulated at the level of translation. Therefore, this study is important in that it identifies an additional layer of regulation controlling IE1 and IE2 expression and thus HCMV pathogenesis. These translational regulatory events could potentially be targeted by novel antiviral therapeutics that limit IE1 and IE2 mRNA translation and thus inhibit lytic replication or prevent HCMV reactivation.
Analysing the limitations of the dual-porosity response during well tests in naturally fractured reservoirs
Authors: Egya D. O. , Geiger S. , Corbett P. W. M. , March R. , Bisdom K. , Bertotti G. , Bezerra F. H. 
Published: January 2018

Geological reservoirs can be extensively fractured but the well-test signatures observed in the wells may not show a pressure transient response that is representative of naturally fractured reservoirs (NFRs): for example, one that indicates two distinct pore systems (i.e. the mobile fractures and immobile matrix). Yet, the production behaviour may still be influenced by these fractures. To improve the exploitation of hydrocarbons from NFRs, we therefore need to improve our understanding of fluid-flow behaviour in fractures.
Multiple techniques are used to detect the presence and extent of fractures in a reservoir. Of particular interest to this work is the analysis of well-test data in order to interpret the flow behaviour in an NFR. An important concept for interpreting well-test data from an NFR is the theory of dual-porosity model. However, several studies pointed out that the dual-porosity model may not be appropriate for interpreting well tests from all fractured reservoirs.
This paper therefore uses geological well-testing insights to explore the limitations of the characteristic flow behaviour inherent to the dual-porosity model in interpreting well-test data from Type II and III NFRs of Nelson's classification. To achieve this, we apply a geoengineering workflow with discrete fracture matrix (DFM) modelling techniques and unstructured-grid reservoir simulations to generate synthetic pressure transient data in both idealized fracture geometries and real fracture networks mapped in an outcrop of the Jandaira Formation. We also present key reservoir features that account for the classic V-shape pressure derivative response in NFRs. These include effects of fracture skin, a very tight matrix permeability and wells intersecting a minor, unconnected fracture close to a large fracture or fracture network. Our findings apply to both connected and disconnected fracture networks.
A Review of Prostate Cancer Genome-Wide Association Studies (GWAS)
Authors: Benafif Sarah , Kote-Jarai Zsofia , Eeles Rosalind A. 
Published: January 2018

Abstract
Prostate cancer is the most common cancer in men in Europe and the United States. The genetic heritability of prostate cancer is contributed to by both rarely occurring genetic variants with higher penetrance and moderate to commonly occurring variants conferring lower risks. The number of identified variants belonging to the latter category has increased dramatically in the last 10 years with the development of the genome-wide association study (GWAS) and the collaboration of international consortia that have led to the sharing of large-scale genotyping data. Over 40 prostate cancer GWAS have been reported, with approximately 170 common variants now identified. Clinical utility of these variants could include strategies for population-based risk stratification to target prostate cancer screening to men with an increased genetic risk of disease development, while for those who develop prostate cancer, identifying genetic variants could allow treatment to be tailored based on a genetic profile in the early disease setting. Functional studies of identified variants are needed to fully understand underlying mechanisms of disease and identify novel targets for treatment. This review will outline the GWAS carried out in prostate cancer and the common variants identified so far, and how these may be utilized clinically in the screening for and management of prostate cancer. Cancer Epidemiol Biomarkers Prev; 27(8); 845–57. ©2018 AACR.
НА ШЛЯХУ ПРОФЕСІЙНОГО ЗРОСТАННЯ ЛІКАРІВ–СТОМАТОЛОГІВ–ІНТЕРНІВ: ТЕНДЕНЦІЯ, ВИКЛИКИ ТА ПЕРСПЕКТИВА НА МАЙБУТНЄ
Authors: Dmytryshyn T. M. 
Published: January 2018

Мета роботи – встановити у лікарів-стоматологів, які щойно стали спеціалістами, рівень працевлаштованості, сформованості знань про майбутні місце та режим роботи, рівень практичної підготовки на кафедрі стоматології післядипломної освіти та види безперервної стоматологічної освіти.Основна частина. За результатами педагогічного моніторингу (анонімне анкетування) 141 лікаря-інтерна, який у 2017 р. закінчив навчання в інтернатурі на базі ННІПО ІФНМУ, встановлено, що переважна більшість має бажання працювати за своєю професією – 88,65 % осіб. Від 90,07 до 93,62 % лікарів володіють знаннями щодо облаштування робочого місця, обов’язків та організації робочого дня лікаря-стоматолога. Відмітили низький рівень працевлаштування лікарів-інтернів на момент закінчення навчання в інтернатурі – 59,57 % не мали місця роботи та продовжували шукати. Навчаючись на очному циклі інтернатури, 87,94 % осіб самостійно та з допомогою викладача здійснювали клінічний прийом пацієнтів. Лікарі-стоматологи-інтерни усвідомлюють, що навчання для професіоналів у галузі стоматології не може зупинитися після закінчення програми інтернатури. Висновок. Проведене нами анкетування лікарів-стоматологів, які щойно закінчили навчання в інтернатурі, дозволяє сформувати уявлення про деякі аспекти функціонування стоматологічної післядипломної освіти на сьогоднішньому етапі та допоможе виділити ті ланки, які необхідно реформувати: працевлаштування, ефективні доступні форми післядипломного безперервного навчання.
O espaço mineiro em A garganta do inferno: ensaio sobre uma lenda de Bernardo Guimarães
Authors: Hernandes Gabriel Queiroz Guimarães 
Published: January 2018

O presente artigo pretende demonstrar como, na lenda A garganta do inferno, de Bernardo Guimarães, a região mineira se articula em profundidade com a estrutura narrativa. Tal produção pertence a uma parte de sua literatura (contos, lendas e causos) que acabou se tornando desconhecida do público em geral. O espaço, no caso, é pensado não somente na dimensão específica de uma morfologia local, mas também como um meio cultural em que costumes, crenças e superstições são incorporados ao fluxo narrativo. Desse modo, a defesa central deste ensaio é a de que, resguardados certos limites históricos e da estética romântica, a obra do escritor ouro-pretense pode ser atribuída, como produto genuíno, ao sertanismo ou regionalismo romântico.
“Que obra preciosa estás a fazer!” considerações sobre as cartas do editor Monteiro Lobato ao escritor Lima Barreto
Authors: Tin Emerson 
Published: January 2018

Monteiro Lobato foi um dos mais importantes editores das primeiras décadas do século XX; Lima Barreto, um dos autores mais expressivos do mesmo período. Relacionando-se exclusivamente por meio da correspondência, o editor paulista e o escritor carioca mantiveram amistosa e intensa relação, que se inicia em 1918, logo após a aquisição da Revista do Brasil por Lobato, e só se encerrará com o precoce falecimento do autor de Vida e morte de M. J. Gonzaga de Sá em 1922, livro de que, aliás, a troca de cartas é testemunha de todo o processo editorial, desde a contratação da publicação até as estratégias de venda imaginadas pelo operoso autor de Urupês.
Endothelial Cell–Derived Von Willebrand Factor, But Not Platelet-Derived, Promotes Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Doddapattar Prakash , Dhanesha Nirav , Chorawala Mehul R. , Tinsman Chandler , Jain Manish , Nayak Manasa K. , Staber Janice M. , Chauhan Anil K. 
Published: January 2018

Objective—
VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell–derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis.

Approach and Results—

Using bone marrow transplantation, we generated chimeric Plt-VWF, EC-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E–deficient (
Apoe
−/−
) background. Controls were chimeric
Apoe
−/−
mice transplanted with bone marrow from
Apoe
−/−
mice (wild type) and
Vwf
−/−
Apoe
−/−
mice transplanted with bone marrow from
Vwf
−/−
Apoe
−/−
mice (VWF-knock out). Susceptibility to atherosclerosis was evaluated in whole aortae and cross-sections of the aortic sinus in female mice fed a high-fat Western diet for 14 weeks. VWF-knock out, Plt-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 exhibited reduced plaque size characterized by smaller necrotic cores, reduced neutrophil and monocytes/macrophages content, decreased MMP9 (matrix metalloproteinase), MMP2, and CX
3
CL1 (chemokine [C-X3-C motif] ligand 1)-positive area, and abundant interstitial collagen (
P
<0.05 versus wild-type or EC-VWF mice). Atherosclerotic lesion size and composition were comparable between wild-type or EC-VWF mice. Together these findings suggest that EC-VWF, but not Plt-VWF, promotes atherosclerosis exacerbation. Furthermore, intravital microscopy experiments revealed that EC-VWF, but not Plt-VWF, contributes to platelet and leukocyte adhesion under inflammatory conditions at the arterial shear rate.

Conclusions—
EC-VWF, but not Plt-VWF, contributes to VWF-dependent atherosclerosis by promoting platelet adhesion and vascular inflammation. Plt-VWF even in the absence of a disintegrin and metalloprotease with thrombospondin type I repeats-13, both in platelet and plasma, was not sufficient to promote atherosclerosis.
Do Nonorthogonally and Irregularly Sampled Scalar Velocities Contain Sufficient Information to Reconstruct an Orthogonal Vector Current Field?
Authors: Soh Hyun Sup , Kim Sung Yong , Kosro P. Michael , Kurapov Alexander L. 
Published: January 2018

AbstractThis paper addresses how well a two-dimensional orthogonal vector current field can be reconstructed from a set of nonorthogonally and irregularly sampled scalar velocity data. High-frequency radar (HFR)-derived surface radial scalar velocities are sampled on a polar or elliptical coordinate grid as a directional projection of two-dimensional vector currents for a viewing angle of the individual HFRs. Synthetic radial velocity maps are generated by sampling two-dimensional surface vector currents obtained from a simple spectral model and a realistic regional circulation model on the polar or elliptical grid points configured similarly as the operational HFRs. Then, the sampled radial velocity maps are combined into a vector current field using inverse methods: least squares fitting and optimal interpolation. In this paper, uncertainty and misfit are defined as the degrees of insufficiency to resolve the vector current and the difference between the true and estimated vector currents, respectively. The uncertainty and misfit are evaluated in terms of several simulation parameters built into the simple spectral model and the degrees of the quality and the observational error of the radial velocity maps associated with the simulated missing data and noise level, respectively. A greater number of missing data and higher observational errors correspond to an increase in the standard deviation of the misfit and a significant reduction in the effective spatial coverage of the vector current fields. This paper provides technical details for resolving a vector current field and guidelines for the practical design of the spatial sampling of the current field using the HFRs.
An Algorithm for Classifying Unknown Expendable Bathythermograph (XBT) Instruments Based on Existing Metadata
Authors: Palmer Matthew D. , Boyer Tim , Cowley Rebecca , Kizu Shoichi , Reseghetti Franco , Suzuki Toru , Thresher Ann 
Published: January 2018

AbstractTime-varying biases in expendable bathythermograph (XBT) instruments have emerged as a key uncertainty in estimates of historical ocean heat content variability and change. One of the challenges in the development of XBT bias corrections is the lack of metadata in ocean profile databases. Approximately 50% of XBT profiles in the World Ocean database (WOD) have no information about manufacturer or probe type. Building on previous research efforts, this paper presents a deterministic algorithm for assigning missing XBT manufacturer and probe type for individual temperature profiles based on 1) the reporting country, 2) the maximum reported depth, and 3) the record date. The criteria used are based on bulk analysis of known XBT profiles in the WOD for the period 1966–2015. A basic skill assessment demonstrates a 77% success rate at correctly assigning manufacturer and probe type for profiles where this information is available. The skill rate is lowest during the early 1990s, which is also a period when metadata information is particularly poor. The results suggest that substantive improvements could be made through further data analysis and that future algorithms may benefit from including a larger number of predictor variables.
Skill of Global Raw and Postprocessed Ensemble Predictions of Rainfall over Northern Tropical Africa
Authors: Vogel Peter , Knippertz Peter , Fink Andreas H. , Schlueter Andreas , Gneiting Tilmann 
Published: January 2018

AbstractAccumulated precipitation forecasts are of high socioeconomic importance for agriculturally dominated societies in northern tropical Africa. In this study, the performance of nine operational global ensemble prediction systems (EPSs) is analyzed relative to climatology-based forecasts for 1–5-day accumulated precipitation based on the monsoon seasons during 2007–14 for three regions within northern tropical Africa. To assess the full potential of raw ensemble forecasts across spatial scales, state-of-the-art statistical postprocessing methods were applied in the form of Bayesian model averaging (BMA) and ensemble model output statistics (EMOS), and results were verified against station and spatially aggregated, satellite-based gridded observations. Raw ensemble forecasts are uncalibrated and unreliable, and often underperform relative to climatology, independently of region, accumulation time, monsoon season, and ensemble. The differences between raw ensemble and climatological forecasts are large and partly stem from poor prediction for low precipitation amounts. BMA and EMOS postprocessed forecasts are calibrated, reliable, and strongly improve on the raw ensembles but, somewhat disappointingly, typically do not outperform climatology. Most EPSs exhibit slight improvements over the period 2007–14, but overall they have little added value compared to climatology. The suspicion is that parameterization of convection is a potential cause for the sobering lack of ensemble forecast skill in a region dominated by mesoscale convective systems.
Alternative Financing for Entrepreneurial Ventures
Authors: Churchill Neil C. , Thorne John R. 
Published: January 2018

Here are some provocative thoughts on entrepreneurship by two individuals who are experienced both as practitioners and as observers of entrepreneurial activities. Their observations seem particularly appropriate in a journal whose title includes the words “theory” and “practice.” Jack Thorne shares some observations on financing ventures he has gleaned both as an entrepreneur and as the Chairman of the Enterprise Corporation of Pittsburgh. Daryl Mitton who shares a similar background discusses the individual entrepreneur.
Using Twitter for Data Collection With Health-Care Consumers
Authors: Zhang Amy J. , Albrecht Lauren , Scott Shannon D. 
Published: January 2018

Background: Twitter is one of the most popular social media platforms. The growing use of Twitter by health-care consumers creates a novel venue to understand patient experiences. To understand the potential for this platform to be utilized in patient- and family-oriented health research, this study reviewed published literature on the use of Twitter in health research. Methods: In collaboration with the research team, a research librarian designed and implemented a search strategy in eight databases. Primary and secondary screenings were conducted using predetermined criteria by one reviewer. A second reviewer verified screening decisions in 10% of the studies. Evidence tables were created to synthesize across the following study elements: research design, data collection techniques, analytic approaches, and author’s insights on Twitter as a data collection method. Descriptive narrative analysis was used to synthesize data. Results: The search strategy captured 618 articles; 233 were eliminated in primary screening and 366 articles were eliminated during secondary screening. Verification by the second reviewer resulted in very good agreement (κ = .980). Seventeen articles were included in the final data set. Synthesis across the studies demonstrated that Twitter is currently used to search and mine research data, while active recruitment strategies on Twitter are just beginning to emerge. Conclusion: The novelty of Twitter for study recruitment and data collection with health-care consumers presents advantages and challenges that differ from traditional methods of data collection.
Hospital Closures and Community Care: Correspondence between the National Schizophrenia Fellowship and the Minister for Health
Authors: Lines R. N. , Clarke Kenneth , Lines R. N. 
Published: January 2018

Following the publication of correspondence between the then Minister for Health, Mr Kenneth Clarke, and the National Schizophrenia Fellowship (Bulletin, March 1985, 9, 49–55), we are now publishing the concluding letters in this exchange of correspondence. (Mrs Joyce Major has been succeeded by Mr R. N. Lines as Chairman of the NSF.)We use the expression ‘long-term patient’ to describe one who, whether in hospital or elsewhere, needs a great deal of supervision and/or nursing care. We use ‘long-stay patient’ for the smaller category in hospital or equivalent health service institution. The great majority of long-term who are not long-stay are at present cared for by relatives, if at all; a small fraction are in staffed homes provided by the voluntary sector, or are in local authority hostels.