bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein-Primed Terminal Transferase Activity of Hepatitis B Virus Polymerase
Authors: Jones Scott A. , Hu Jianming 
Published: December 2012

ABSTRACT

Hepatitis B virus (HBV) replication requires reverse transcription of an RNA pregenome (pgRNA) by a multifunctional polymerase (HP). HP initiates viral DNA synthesis by using itself as a protein primer and an RNA signal on pgRNA, termed epsilon (Hε), as the obligatory template. We discovered a Mn
2+
-dependent transferase activity of HP
in vitro
that was independent of Hε but also used HP as a protein primer. This protein-primed transferase activity was completely dependent on the HP polymerase active site. The DNA products of the transferase reaction were linked to HP via a phosphotyrosyl bond, and replacement of the Y63 residue of HP, the priming site for templated DNA synthesis, almost completely eliminated DNA synthesis by the transferase activity, suggesting that Y63 also serves as the predominant priming site for the transferase reaction. For this transferase activity, HP could use all four deoxynucleotide substrates, but TTP was clearly favored for extensive polymerization. The transferase activity was highly distributive, leading to the synthesis of DNA homo- and hetero-oligomeric and -polymeric ladders ranging from 1 nucleotide (nt) to >100 nt in length, with single-nt increments. As with Hε-templated DNA synthesis, the protein-primed transferase reaction was characterized by an initial stage that was resistant to the pyrophosphate analog phosphonoformic acid (PFA) followed by PFA-sensitive DNA synthesis, suggestive of an HP conformational change upon the synthesis of a nascent DNA oligomer. These findings have important implications for HBV replication, pathogenesis, and therapy.
ZAP Inhibits Murine Gammaherpesvirus 68 ORF64 Expression and Is Antagonized by RTA
Authors: Xuan Yifang , Gong Danyang , Qi Jing , Han Chuanhui , Deng Hongyu , Gao Guangxia 
Published: December 2012

ABSTRACT
Zinc finger antiviral protein (ZAP) is an interferon-inducible host antiviral factor that specifically inhibits the replication of certain viruses, including HIV-1 and Ebola virus. ZAP functions as a dimer formed through intermolecular interactions of its N-terminal tails. ZAP binds directly to specific viral mRNAs and inhibits their expression by repressing translation and/or promoting degradation of the target mRNA. ZAP is not a universal antiviral factor, since some viruses grow normally in ZAP-expressing cells. It is not fully understood what determines whether a virus is susceptible to ZAP. We explored the interaction between ZAP and murine gammaherpesvirus 68 (MHV-68), whose life cycle has latent and lytic phases. We previously reported that ZAP inhibits the expression of M2, which is expressed mainly in the latent phase, and regulates MHV-68 latency in cultured cells. Here, we report that ZAP inhibits the expression of ORF64, a tegument protein that is expressed in the lytic phase and is essential for lytic replication. MHV-68 infection induced ZAP expression. However, ZAP did not inhibit lytic replication of MHV-68. We provide evidence showing that the antiviral activity of ZAP is antagonized by MHV-68 RTA, a critical viral transactivator expressed in the lytic phase. We further show that RTA inhibits the antiviral activity of ZAP by disrupting the N-terminal intermolecular interaction of ZAP. Our results provide an example of how a virus can escape ZAP-mediated immunity.
Looking for Gender in the Medical Paintings of Desi Sangye Gyatso, Regent of the Tibetan Buddhist State
Authors: Gyatso Janet 
Published: December 2012

Abstract
This essay studies the representation of women and gender in the unprecedented,
elaborately detailed medical paintings created by Desi Sangye Gyatso at the end
of the seventeenth century in Lhasa, Tibet. It compares the textual version of
the information rendered in the paintings with their visual translation. The
study discovers a rather complex and mixed picture. It finds that the more
systematic portrayals of human anatomy betray a deep androcentrism, with images
of female bodies either marginalised or entirely absent. However, other less
standard parts of the set that depict a wide swathe of daily life on the Tibetan
plateau show much more diversity in gender conception. A far greater number of
females are depicted there. Women are still shown almost exclusively in
gender-specific roles and are virtually never deployed to stand for a
gender-neutral medical condition, which is always represented either by a
default male figure or a gender-ambiguous one. And yet some of these less
standard depictions show either gender egalitarianism, or indeed show little
gender differentiation at all, even with respect to attire and bodily features
such as breasts and hair. Some images even suggest that gender differentiation
was not an important issue, at least some of the time. Yet still other portions
of the less standard vignettes do display strict gender distinction and also
indicate the greater importance of male medical issues and the inferior status
of the female body. In sum, the medical paintings suggest that a wide range of
gender conceptions operated not only in Tibetan medicine but also across society
more broadly, and these were neither consistent nor fixed.
Early onset, EBV− PTLD in pediatric liver-small bowel transplantation recipients: a spectrum of plasma cell neoplasms with favorable prognosis
Authors: Perry Anamarija M. , Aoun Patricia , Coulter Donald W. , Sanger Warren G. , Grant Wendy J. , Coccia Peter F. 
Published: December 2012

Key Points
Five cases of EBV− PTLD in pediatric recipients of combined liver and small bowel allografts are reported. The lesions were plasma cell neoplasms that resolved completely after minimal treatment.
CCND2 rearrangements are the most frequent genetic events in cyclin D1− mantle cell lymphoma
Authors: Salaverria Itziar , Royo Cristina , Carvajal-Cuenca Alejandra , Clot Guillem , Navarro Alba , Valera Alejandra , Song Joo Y. , Woroniecka Renata , Rymkiewicz Grzegorz , Klapper Wolfram , Hartmann Elena M. , Sujobert Pierre , Wlodarska Iwona , Ferry Judith A. , Gaulard Philippe , Ott German , Rosenwald Andreas , Lopez-Guillermo Armando , Quintanilla-Martinez Leticia , Harris Nancy L. , Jaffe Elaine S. , Siebert Reiner , Campo Elias , Beà Sílvia 
Published: December 2012

Key Points
This report describes a multidisciplinary study characterizing the largest series of cyclin D1− MCL patients. CCND2 translocations are the most frequent genetic event (55%) in cyclin D1− MCL.
Mortality increases after massive exchange transfusion with older stored blood in canines with experimental pneumonia
Authors: Solomon Steven B. , Wang Dong , Sun Junfeng , Kanias Tamir , Feng Jing , Helms Christine C. , Solomon Michael A. , Alimchandani Meghna , Quezado Martha , Gladwin Mark T. , Kim-Shapiro Daniel B. , Klein Harvey G. , Natanson Charles 
Published: December 2012

Key PointsIn canine S aureus pneumonia, first randomized blinded trial showing blood transfused at end of storage period increases mortality. Increased in vivo hemolysis, cell-free hemoglobin, pulmonary hypertension, tissue damage, and gas exchange abnormalities each contributed.
Correlation of anti-fungal susceptibility with clinical outcomes in patients with cryptococcal meningitis
Authors: Lee Chen-Hsiang , Chang Tzu-Yao , Liu Jien-Wei , Chen Fang-Ju , Chien Chun-Chih , Tang Ya-Fen , Lu Cheng-Hsien 
Published: December 2012

Abstract

Background
This study aimed to investigate the correlation of minimum inhibiting concentrations (MICs), obtained by broth micro-dilution, and clinical response in patients with cryptococcal meningitis.

Methods
Using retrospective analyses covering the period 2001–2010, factors affecting clinical therapeutic cure in patients with cryptococcal meningitis 10 weeks after the start of anti-fungal therapy were identified. Specific emphasis was placed on the role of anti-fungal susceptibility.

Results
Of 46 patients with cryptococcal meningitis identified, 21 were cured after 10 weeks of treatment. Overall, 12 strains (26.1%) were resistant to fluconazole (>8 μg/ml) and 8 (17.4%) had an MIC >1 μg/ml for amphotericin B. Twenty-three patients received combination amphotericin B and fluconazole as their initial antifungal therapy, 17 were given amphotericin B only, five received fluconazole only, and one received a combination of amphotericin B and flucytosine. After 2 weeks, all patients received fluconazole (400–600 mg daily for 8 weeks at least, then 200 mg daily thereafter). The presence of isolates resistant to fluconazole (MIC >8 μg/ml; 4.8% vs. 44%, p < 0.01) were statistically significant among patients who were cured. Anti-fungal susceptibility, reflected by fluconazole MIC >8 μg/ml, was an independent predictor of therapeutic cure at 10-week evaluation (OR = 15.7; 95% CI: 1.8-135.9; p = 0.01), but higher MIC of amphotericin B (>1 μg/ml) was not.

Conclusions
The MICs of fluconazole, determined by the CLSI method, may be a potential predictor of therapeutic cure in patients with cryptococcal meningitis.
Effect of KOB03, a polyherbal medicine, on ovalbumin-induced allergic rhinitis in guinea pigs
Authors: Jung Hyo Won , Jung Jin Ki , Kim Young Ho , Kang Jong-Seong , Park Yong-Ki 
Published: December 2012

AbstractBackgroundKOB03 is a polyherbal medicine that originated from the oriental prescription for the treatment of chronic allergic diseases such as rhinitis and asthma. This study aims to evaluate the effect of KOB03 on ovalbumin (OVA)-induced allergic rhinitis (AR) in guinea pigs.MethodsHartley guinea pigs were sensitized to OVA by intraperitoneal injection on days 0, 7, and 14 and challenged with intranasal exposure to OVA three times for 7 days after the last sensitization. KOB03 at doses of 200 and 500 mg/kg were orally administrated to guinea pigs once daily during challenge. The serum levels of histamine, OVA-specific immunoglobulin (Ig) E, eosinophil cationic protein (ECP) and cytokines (TNF-α, IL-4 and IFN-γ) in OVA sensitization/challenge-induced AR guinea pigs were measured. We also observed histological changes in nasal tissues of AR guinea pigs by staining with H&E, Periodic acid-Schiff, and toluidine blue.ResultsThe administration of KOB03 at a dose of 500 mg/kg significantly decreased the serum levels of histamine (P = 0.001), OVA-specific IgE (P = 0.0017), ECP (P = 0.008), and TNF-α (P = 0.0003) in OVA-sensitized/challenged guinea pigs compared with controls. KOB03 significantly decreased the serum levels of a Th2 cytokine, IL-4 (P = 0.017), while significantly increasing the levels of a Th1 cytokine, IFN-γ (P = 0.0006) in OVA-sensitized/challenged guinea pigs compared with controls. In addition, KOB03 suppressed the epithelial destruction, goblet cell hyperplasia and eosinophilic infiltration into nasal mucosa associated with AR.ConclusionKOB03 may regulate allergic inflammation in AR by inhibiting nasal damage, the release of allergic mediators and modulating the balance of Th1/Th2 cytokines.
Biased Judgment in Censored Environments
Authors: Feiler Daniel C. , Tong Jordan D. , Larrick Richard P. 
Published: December 2012

Some environments constrain the information that managers and decision makers can observe. We examine judgment in censored environments where a constraint, the censorship point, systematically distorts the observed sample. Random instances beyond the censorship point are observed at the censorship point, whereas uncensored instances are observed at their true value. Many important managerial decisions occur in censored environments, such as inventory, risk taking, and employee evaluation decisions. In this research, we demonstrate a censorship bias—individuals tend to rely too heavily on the observed censored sample, biasing their belief about the underlying population. We further show that the censorship bias is exacerbated for higher degrees of censorship, higher variance in the population, and higher variability in the censorship points. In four studies, we find evidence of the censorship bias across the domains of demand estimation and sequential risk taking. The bias causes individuals to make costly decisions and behave in an overly risk-averse manner. This paper was accepted by Teck Ho, judgment and decision making.
Dynamic Capacity Allocation to Customers Who Remember Past Service
Authors: Adelman Daniel , Mersereau Adam J. 
Published: December 2012

We study the problem faced by a supplier deciding how to dynamically allocate limited capacity among a portfolio of customers who remember the fill rates provided to them in the past. A customer's order quantity is positively correlated with past fill rates. Customers differ from one another in their contribution margins, their sensitivities to the past, and in their demand volatilities. By analyzing and comparing policies that ignore goodwill with ones that account for it, we investigate when and how customer memory effects impact supplier profits. We develop an approximate dynamic programming policy that dynamically rationalizes the fill rates the firm provides to each customer. This policy achieves higher rewards than margin-greedy and Lagrangian policies and yields insights into how a supplier can effectively manage customer memories to its advantage. This paper was accepted by Martin Lariviere, operations management.
The role of human papillomavirus in nongenital cancers
Authors: Zandberg Dan P. , Bhargava Ranjana , Badin Simon , Cullen Kevin J. 
Published: December 2012

AbstractAnswer questions and earn CME/CNEHuman papillomavirus (HPV), one of the most common sexually transmitted diseases worldwide, has an established role in the pathogenesis of genital malignancies such as cervical cancer. The virus has also been implicated in the oncogenesis of nongenital cancers including head and neck malignancies (specifically oropharyngeal cancers) as well as anal cancer. There is less clarity regarding its role in lung and esophageal cancers. Worldwide, the incidence and prevalence of HPV‐associated oropharyngeal cancer has been increasing over time. These patients have improved outcomes compared with those with HPV‐negative oropharyngeal cancers, and there is continued interest in designing treatments specifically for this HPV‐positive subgroup. Clinicians continue to gain an understanding of HPV in anal cancers and the risk factors associated with infection and progression to malignancy. This has potential implications for the eventual screening of high‐risk groups. While HPV vaccination is currently approved for the prevention of cervical cancer, it also has potential in the prevention of all HPV‐associated malignancies. In this review, current understanding of the role of HPV in nongenital cancers is discussed, as well as future implications for treatment and prevention. CA Cancer J Clin 2013. © 2012 American Cancer Society.
La réforme Obama du système américain de soins de santé
Authors: Witmeur Renaud , Désir Daniel , Hut Florence 
Published: December 2012

Résumé	Le système de soins de santé en vigueur aux États-Unis suscite de nombreuses interrogations en Europe. Il est le plus cher et le plus complexe de tous les pays de l’OCDE sans être pour autant l’un des plus performants, ni en termes de santé publique, ni en termes de qualité des soins ou d’accessibilité.	L’élection présidentielle américaine du 6 novembre 2012 a attiré l’attention des Européens sur les réformes introduites par Barack Obama lors de son premier mandat, et que souhaitait abroger le Parti républicain représenté par Mitt Romney. La victoire démocrate assure le maintien de la loi du 23 mars 2010, surnommée Obamacare, qui oblige la plupart des Américains à s’assurer avant 2014. Pour atteindre cet objectif, des subventions sont accordées aux citoyens à bas revenus et les compagnies d’assurance ne peuvent plus refuser de couvrir une personne en raison de ses antécédents médicaux. La réforme devrait coûter 940 milliards de dollars sur dix ans.	Après avoir présenté le système de soins de santé américain et ses réformes en cours, ce Courrier hebdomadaire analyse les implications politiques, sociales, fiscales, budgétaires et culturelles de la réforme menée par Barack Obama, non seulement pour les États-Unis mais également pour la planète entière. Outre ses effets en politique intérieure, l’Obamacare aura des répercussions internationales en raison du leadership scientifique et technologique des États-Unis dans le domaine médical.
Israël, l'infernale « terre promise »
Authors: Lagarde David 
Published: December 2012

L’arrivée en Israël de réfugiés non juifs, originaires du Soudan ou de la Corne de l’Afrique ne peut qu’interroger dans un pays qui ne reconnaît pas le droit d’asile. Or depuis plusieurs années et, plus encore, depuis les « révolutions arabes », les entrées de migrants par le Sinaï ne font qu’augmenter, poussant le gouvernement israélien à prendre des mesures drastiques de fermeture des frontières. Au-delà de l’affichage, quelles en sont les conséquences sur le sort des réfugiés ?
Organizational Models for Non-Core Processes Management: A Classification Framework
Authors: De Toni Alberto F. , Fornasier Andrea , Nonino Fabio 
Published: December 2012

This study investigates the impact of different organizational models for the management of non-core processes in the facility management (FM) industry and seeks to suggest which is the best in terms of strategic and operative advantages and disadvantages. A literature analysis of the empirical evidence as to business process outsourcing and, in particular, as to the practices of the FM business sector has been carried out. The analysis has allowed us to identify a total of 11 organizational models that are a consequence of five different strategic approaches. A comprehensive classification framework of the strategies and organizational models on the basis of two dimensions is proposed: the organizational role of a non-core processes manager (called a ‘facility manager’) and the typology of non-core process/service providers. The framework enables the identification and the explanation of the main advantages and disadvantages of each strategy and to highlight how a company should coherently choose an organizational model on the basis of (a) the specialization/complexity of the non-core processes, (b) the focus on core processes, (c) its inclination towards know-how outsourcing, and (d) the desired level of autonomy in the management of non-core processes.
Overview of Human Primary Tumorgraft Models: Comparisons with Traditional Oncology Preclinical Models and the Clinical Relevance and Utility of Primary Tumorgrafts in Basic and Translational Oncology Research
Authors: Lum David H. , Matsen Cindy , Welm Alana L. , Welm Bryan E. 
Published: December 2012

AbstractLaboratory models that accurately replicate human tumor initiation and characteristics are integral to advancing knowledge in cancer research. However, comparative studies between commonly employed laboratory models and human tumors have demonstrated that some models have molecular and genomic alterations dissimilar to the cancer type they attempt to replicate. In contrast, several recent comparative studies suggest that because patient‐derived tumors grown in mice maintain many of the important characteristics of the original tumor, they represent an important tool for the development of new cancer therapeutics. Detailed in this overview are the advantages and disadvantages of the most commonly used cancer models for mechanistic and therapeutic research, with an emphasis on the advances made in the production and use of patient‐derived tumorgrafts. Curr. Protoc. Pharmacol. 59:14.22.1‐14.22.9. © 2012 by John Wiley & Sons, Inc.
Hepatic lentiviral gene transfer is associated with clonal selection, but not with tumor formation in serially transplanted rodents
Authors: Rittelmeyer Ina , Rothe Michael , Brugman Martijn H. , Iken Marcus , Schambach Axel , Manns Michael P. , Baum Christopher , Modlich Ute , Ott Michael 
Published: December 2012

Abstract

Lentiviral (LV) vectors are promising tools for long-term genetic correction of hereditary diseases. In hematopoietic stem cell gene therapies adverse events in patients due to vector integration-associated genotoxicity have been observed. Only a few studies have explored the potential risks of LV gene therapy targeting the liver. To analyze hepatic genotoxicity in vivo, we transferred the fumarylacetoacetate hydrolase (FAH) gene by LV vectors into FAH(-/-) mice (n = 97) and performed serial hepatocyte transplantations (four generations). The integration profile (4,349 mapped insertions) of the LV vectors was assessed by ligation-mediated polymerase chain reaction and deep sequencing. We tested whether the polyclonality of vector insertions was maintained in serially transplanted mice, linked the integration sites to global hepatocyte gene expression, and investigated the effects of LV liver gene therapy on the survival of the animals. The lifespan of in vivo gene-corrected mice was increased compared to 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) control animals and unchanged in serially transplanted animals. The integration profile (4,349 mapped insertions) remained polyclonal through all mouse generations with only mild clonal expansion. Genes close to the integration sites of expanding clones may be associated with enhanced hepatocyte proliferation capacity. Conclusion: We did not find evidence for vector-induced tumors. LV hepatic gene therapy showed a favorable risk profile for stable and long-term therapeutic gene expression. Polyclonality of hepatocyte regeneration was maintained even in an environment of enforced proliferation. (HEPATOLOGY 2013)
Kinetic and thermodynamic studies on molecular interaction of antipyrine donor and 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone as an electron acceptor in different solvents
Authors: Hasani Masoumeh , Nikoee Sheler 
Published: December 2012

AbstractThe charge–transfer (CT) complex of donor antipyrine with Π‐acceptor 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) has been investigated spectrophotometrically in different halocarbon and acetonitrile solvents. The results indicated immediate formation of an electron donor–acceptor complex (DA), which is followed by two relatively slow consecutive reactions. The pseudo–first‐order rate constants for the formation of the ionic intermediate and the final product at various temperatures were evaluated from the absorbance–time data. The activation parameters, viz. activation energy, enthalpy, entropy, and free energy of activation, were computed from temperature dependence of rate constants. The stoichiometry of the complex was found to be 1:1 by Job's method of continuous variation. The formation constants of the resulting DA complexes were determined by the Benesi–Hildebrand equation at four different temperatures. The enthalpies and entropies of the complex formation reactions have been obtained by temperature dependence of the formation constants using Van't Hoff equation. The results indicate that DDQ complexes of antipyrine in all solvents are enthalpy stabilized but entropy destabilized. Both the kinetics of the interaction and the formation constants of the complexes are dependent upon the polarity of the solvents. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 45: 81–91, 2013