bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compliance and data reliability in sun exposure studies with diaries and personal, electronic UV dosimeters
Authors: Thieden Elisabeth , Philipsen Peter A. , Wulf Hans Christian 
Published: March 2006

Background/purpose: Skin cancer risk estimations are based on sun exposure data. However, the reliability of collected data in personal ultraviolet (UV) dosimeters studies has not previously been validated. We aimed at investigating the data reliability and subject compliance in a study of sun exposure behaviour among 407 subjects (age range, 4–68 years) during 54 943 days based on time‐stamped personal UV dosimeter readings and diary records.Methods: By comparing diary records and UV dosimeter readings on a daily basis, we investigated subject compliance, total sun exposure record, reasons for non‐responding along with rates of diary completing errors. Efforts to improve compliance were described.Results: The subject compliance rate was median 93.5% (percent days where the diary was completed and the UV dosimeter was worn). The total sun exposure record rate was median 84.1% (percent of participation days with both UV dosimeter and diary records and where the UV dosimeter was worn). Children, adolescents and golfers had lower sun exposure record rates than the rest of the groups (P<0.05). No significant difference was found between males and females (P=0.15). The 17 non‐responders were 10 children, three adolescents, one sun worshipper, two golfers and one gardener. Correctable diary completing mistakes were found in 3.1% of the days. Children made more completing mistakes than adults (P=0.001). The average estimated error rate was 3.3% and was higher for children (6.3%) and adolescents (3.6%) than the adult groups (2.4%).Conclusion: High subject compliance rate and data reliability were obtained because the investigators were service minded but persistent, offering dosimeter maintenance service within 24 h and scrutinized data for errors and mistakes.
The development and delivery of a practice‐based breastfeeding education package for general practitioners in the UK
Authors: Burt Sue , Whitmore Mary , Vearncombe Deana , Dykes Fiona 
Published: March 2006

AbstractGrowing acceptance that measurable improvements in public health, particularly in lower‐income groups, could be achieved by increasing the incidence of breastfeeding has focused attention on the current lack of educational provision in breastfeeding issues for many health professionals. An audit of general practitioners in one area of northern England revealed an interest in receiving breastfeeding training. Department of Health funding was obtained by the breastfeeding subgroup of the local Maternity Services Liaison Committee to develop, deliver and evaluate a practice‐based educational session supplemented by a resource pack. Over a 12‐month period, 22 practices received the session and the project was evaluated using an illuminative evaluation model. Response rates to two evaluation questionnaires of 81% (133/164) and 62.5% (65/104) were achieved and findings indicated high levels of satisfaction with the session and its accompanying resource pack. Qualitative data related to perceived influence on future practice were subjected to thematic network analysis and revealed four main (organizing) themes: the acquisition of greater knowledge, improved access to resources, a proactive approach to breastfeeding support and the creation of a breastfeeding‐friendly environment. The illuminative evaluation also identified recurring issues that could impact on any attempt to replicate or adapt this project; these were the influence of personal breastfeeding experiences, the desire for greater interaction during the training session and the wider implications for practice education of multidisciplinary attendance.
The quality of the diet in Malawian children with kwashiorkor and marasmus
Authors: Sullivan Jesse , Ndekha MacDonald , Maker Dawn , Hotz Christine , Manary Mark J. 
Published: March 2006

AbstractNutritionists have suggested that kwashiorkor is related to low dietary protein and/or antioxidant intake. This study explored the hypothesis that among Malawian children with severe malnutrition, those with kwashiorkor consume a diet with less micronutrient‐ and antioxidant‐rich foods, such as fish, eggs, tomatoes and orange fruits (mango, pumpkin and papaya), than those with marasmus. A case–control method with a food frequency questionnaire was used to assess the habitual diet. Children with severe childhood malnutrition presenting to the central hospital in Blantyre, Malawi during a 3‐month period in 2001 were eligible to participate. The food frequency questionnaire collected data about foods consumed by siblings <60 months of age in the home. It was assumed that the habitual diet of all siblings 1–5 years old in the same home was similar. Dietary diversity was assessed using a validated method, with scores that ranged from 0 to 7. Regression modelling was used to control for demographic and disease covariates. A total of 145 children with kwashiorkor and 46 with marasmus were enrolled. Children with kwashiorkor consumed less egg and tomato than those with marasmus: 17 (15) vs. 24 (31) servings per month for egg, mean (SD), P < 0.01 and 27 (17) vs. 32 (19) servings per month for tomato, P < 0.05. Children with kwashiorkor had a similar dietary diversity score as those with marasmus, 5.06 (0.99) vs. 5.02 (1.10), mean (SD). Further research is needed to determine what role consumption of egg and tomato may play in the development of kwashiorkor.
Science Studies and English Renaissance Literature
Authors: Marchitello Howard 
Published: March 2006

AbstractThe study of early modern science has been a topic of serious interest to literary scholars since at least the 1920s. This essay examines the history of this interest and the critical work it has engendered. In its first wave, this criticism was especially devoted to the study of the ways in which early modern science influenced – and was thereby reflected in – imaginative writing of the period. This understanding was itself underwritten by prevailing notions of science as both an autonomous and a privileged discourse governed by an irresistible and ever‐evolving rationalism that staked exclusive claims to truth. Recent work in the expanding fields of science studies over the past twenty years, however, has served to dislodge this scientific exceptionalism and radically to recast both the history of science and our understanding of the nature of science. As a result, in second wave criticism of early modern science and literature, literary culture is no longer believed to exist in a merely reflective relation to the disciplines of science; instead, science and literature are set in a creative dialectic with each other that denies priority and scientism and helps to offer a more powerful understanding of the dynamic between these two complexly related cultural practices.
Control of Platoons of Nonholonomic Vehicles Using Redundant Manipulator Analogs
Authors: Bishop Bradley E. 
Published: March 2006

Abstract
In this work, we consider the control of platoons of cooperating nonholonomic vehicles. Using techniques based on redundant manipulator control, the platoon is treated as a single entity with a set of platoon-level objectives. The class of tricyclelike robots, with limits on steering and speed, is chosen because it represents a vast class of real, nonholonomic vehicles beyond the basic differential drive. The method presented uses platoon redundancy to limit the impact of vehicle constraints on the platoon-level objectives. A simulation study is presented to show the efficacy of the method.
Mice Transgenic for a Human Porcine Endogenous Retrovirus Receptor Are Susceptible to Productive Viral Infection
Authors: Martina Y. , Marcucci K. T. , Cherqui S. , Szabo A. , Drysdale T. , Srinivisan U. , Wilson C. A. , Patience C. , Salomon D. R. 
Published: March 2006

ABSTRACTPorcine endogenous retrovirus (PERV) is considered one of the major risks in xenotransplantation. No valid animal model has been established to evaluate the risks associated with PERV transmission to human patients by pig tissue xenotransplantation or to study the potential pathogenesis associated with PERV infection. In previous work we isolated two genes encoding functional human PERV receptors and proved that introduction of these into mouse fibroblasts allowed the normally nonpermissive mouse cells to become productively infected (T. A. Ericsson, Y. Takeuchi, C. Templin, G. Quinn, S. F. Farhadian, J. C. Wood, B. A. Oldmixon, K. M. Suling, J. K. Ishii, Y. Kitagawa, T. Miyazawa, D. R. Salomon, R. A. Weiss, and C. Patience, Proc. Natl. Acad. Sci. USA 100:6759-6764, 2003). In the present study we created mice transgenic for human PERV-A receptor 2 (HuPAR-2). After inoculation of transgenic animals with infectious PERV supernatants, viral DNA and RNA were detected at multiple time points, indicating productive replication. This establishes the role of HuPAR-2 in PERV infection in vivo; in addition, these transgenic mice represent a new model for determining the risk of PERV transmission and potential pathogenesis. These mice also create a unique opportunity to study the immune response to PERV infection and test potential therapeutic or preventative modalities.
Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs
Authors: Chang Jinhong , Nie Xingcao , Gudima Severin , Taylor John 
Published: March 2006

ABSTRACT

Hepatitis delta virus (HDV) replication involves processing and accumulation of three RNA species: the genome, its exact complement (the antigenome), and a polyadenylated mRNA that acts as a template for the small delta antigen (δAg), the only protein of HDV and essential for genome replication. In a recently reported experimental system, addition of tetracycline induced synthesis of a DNA-directed source of δAg, producing within 24 h a significant increase in accumulation of newly transcribed and processed HDV RNAs. This induction was used here to study the action of various inhibitors on accumulation. For example, potent and HDV-specific inhibition, in the absence of detected host toxicity, could be obtained with ribavirin, mycophenolic acid, and viramidine. An interpretation is that these inhibitors reduced the available GTP pool, leading to a specific inhibition of the synthesis and accumulation of HDV RNA-directed RNA species. In contrast, no inhibition was observed with
l
-FMAU (2′-fluoro-5-methyl-β-
l
-arabinofuranosyl-uridine), alpha interferon, or pegylated alpha interferon. After modifications to the experimental system, it was also possible to examine the effects of three known host RNA polymerase inhibitors on HDV genome replication: amanitin, 5,6-dichloro-1-β-
d
-ribofuranosylbenzimidazole (DRB), and actinomycin. Of most interest, amanitin at low doses blocked accumulation of HDV RNA-directed mRNA but had less effect on HDV genomic and antigenomic RNAs. Additional experiments indicated that this apparent resistance to amanitin inhibition of genomic and antigenomic RNA relative to mRNA may not reflect a difference in the transcribing polymerase but rather relative differences in the processing and stabilization of nascent RNA transcripts.
Sequences within thegagGene of Mouse Mammary Tumor Virus Needed for Mammary Gland Cell Transformation
Authors: Swanson Ingrid , Jude Brooke A. , Zhang Annie R. , Pucker Andrew , Smith Zachary E. , Golovkina Tatyana V. 
Published: March 2006

ABSTRACTPreviously, we identified a group of replication-competent exogenous mouse mammary tumor viruses that failed to induce mammary tumors in susceptible mice. Sequence comparison of tumorigenic and tumor-attenuated virus variants has linked the ability of virus to cause high-frequency mammary tumors to thegaggene. To determine the specific sequences within thegaggene that contribute to tumor induction, we constructed five distinct chimeric viruses that have various amino acid coding sequences ofgagderived from a tumor-attenuated virus replaced by those of highly tumorigenic virus and tested these viruses for tumorigenic capacities in virus-susceptible C3H/HeN mice. Comparing the tumorigenic potentials of these viruses has allowed us to map the region responsible for tumorigenesis to a 253-amino-acid region within the CA and NC regions of the Gag protein. Unlike C3H/HeN mice, BALB/cJ mice develop tumors when infected with all viral variants, irrespective of thegaggene sequences. Using genetic crosses between BALB/cJ and C3H/HeN mice, we were able to determine that the mechanism that confers susceptibility to Gag-independent mammary tumors in BALB/cJ mice is inherited as a dominant trait and is controlled by a single gene, called mammary tumor susceptibility (mts), that maps to chromosome 14.
Varicella-Zoster Virus Open Reading Frame 10 Is a Virulence Determinant in Skin Cells but Not in T Cells In Vivo
Authors: Che Xibing , Zerboni Leigh , Sommer Marvin H. , Arvin Ann M. 
Published: March 2006

ABSTRACT
The open reading frame 10 (ORF10) of varicella-zoster virus (VZV) encodes a tegument protein that enhances transactivation of VZV genes and has homology to herpes simplex virus type 1 (HSV-1) VP16. While VP16 is essential for HSV replication, ORF10 is dispensable for vaccine OKA (VOKA) growth in vitro. We used parent OKA (POKA) cosmids to delete ORF10, producing POKAΔ10; point mutations that disrupted the acidic activation domain and the putative motif for binding human cellular factor 1 (HCF-1) in ORF10 protein yielded POKA10-Phe28Ala, POKA10-Phe28Ser, and POKA10-mHCF viruses. Deleting ORF10 or mutating these two functional domains had no effect on VZV replication, immediate-early gene transcription, or virion assembly in vitro. However, deleting ORF10 reduced viral titers and the extent of cutaneous lesions significantly in SCIDhu skin xenografts in vivo compared to POKA. Epidermal cells infected with POKAΔ10 had significantly fewer DNA-containing nucleocapsids and complete virions compared to POKA; extensive aggregates of intracytoplasmic viral particles were also observed. Altering the activation or the putative HCF-1 domains of ORF10 protein had no consequences for VZV replication in vivo. Thus, the decreased pathogenic potential of POKAΔ10 in skin could not be attributed to absence of these ORF10 protein functions. In contrast to skin cells, deleting ORF10 did not impair VZV T-cell tropism in vivo, as assessed by infectious virus yields. We conclude that ORF10 protein is required for efficient VZV virion assembly and is a specific determinant of VZV virulence in epidermal and dermal cells in vivo.
Astrocytes Survive Chronic Infection and Cytopathic Effects of thets1 Mutant of the Retrovirus Moloney Murine Leukemia Virus by Upregulation of Antioxidant Defenses
Authors: Qiang Wenan , Kuang Xianghong , Liu Jinrong , Liu Na , Scofield Virginia L. , Reid Amy J. , Jiang Yuhong , Stoica Gheorghe , Lynn William S. , Wong Paul K. Y. 
Published: March 2006

ABSTRACTThets1 mutant of Moloney murine leukemia virus (MoMuLV) induces a neurodegenerative disease in mice, in which glial cells are infected by the retrovirus but neurons are not.ts1 infection of primary astrocytes, or of the immortalized astrocytic cell line C1, results in accumulation of thets1 gPr80envenvelope protein in the endoplasmic reticulum (ER), with ER and oxidative stress. Notably, only about half of the infected astrocytes die in these cultures, while the other half survive, continue to proliferate, and continue to produce virus. To determine how these astrocytes survivets1 infection in culture, we established a chronically infected subline of the living cells remaining after the death of all acutely infected cells in an infected C1 cell culture (C1-ts1-S). We report here that C1-ts1-S cells proliferate more slowly, produce less virus, show reduced H2O2levels, increase their uptake of cystine, and maintain higher levels of intracellular GSH and cysteine compared to acutely infected or uninfected C1 cells. C1-ts1-S cells also upregulate their thiol antioxidant defenses by activation of the transcription factor NF-E2-related factor 2 (Nrf2) and its target genes. Interestingly, despite maintenance of higher levels of intracellular reduced thiols, C1-ts1-S cells are more sensitive to cystine deprivation than uninfected C1 cells. We conclude that somets1-infected astrocytes survive and adapt to virus-induced oxidative stress by successfully mobilizing their thiol redox defenses.
Selection of Novel Vesicular Stomatitis Virus Glycoprotein Variants from a Peptide Insertion Library for Enhanced Purification of Retroviral and Lentiviral Vectors
Authors: Yu Julie H. , Schaffer David V. 
Published: March 2006

ABSTRACT

The
introduction of new features or functions that are not present in an
original protein is a significant challenge in protein engineering. For
example, modifications to vesicular stomatitis virus glycoprotein
(VSV-G), which is commonly used to pseudotype retroviral and lentiviral
vectors for gene delivery, have been hindered by a lack of structural
knowledge of the protein. We have developed a transposon-based approach
that randomly incorporates designed polypeptides throughout a protein
to generate saturated insertion libraries and a subsequent
high-throughput selection process in mammalian cells that enables the
identification of optimal insertion sites for a novel designed
functionality. This method was applied to VSV-G in order to construct a
comprehensive library of mutants whose combined members have a
His
6
tag inserted at likely every site in the original
protein sequence. Selecting the library via iterative retroviral
infections of mammalian cells led to the identification of several
VSV-G-His
6
variants that were able to package high-titer
viral vectors and could be purified by Ni-nitrilotriacetic acid
affinity chromatography. Column purification of vectors reduced protein
and DNA impurities more than 5,000-fold and 14,000-fold, respectively,
from the viral supernatant. This substantially improved purity elicited
a weaker immune response in the brain, without altering the infectivity
or tropism from wild-type VSV-G-pseudotyped vectors. This work applies
a powerful new tool for protein engineering to construct novel viral
envelope variants that can greatly improve the safety and use of
retroviral and lentiviral vectors for clinical gene therapy.
Furthermore, this approach of library generation and selection can
readily be extended to other challenges in protein
engineering.
Competitive Translation Efficiency at the Picornavirus Type 1 Internal Ribosome Entry Site Facilitated by ViralcisandtransFactors
Authors: Dobrikova Elena Y. , Grisham Rachel N. , Kaiser Constanze , Lin Jennifer , Gromeier Matthias 
Published: March 2006

ABSTRACTEnteroviruses (EVs) overcome their host cells by usurping the translation machinery to benefit viral gene expression. This is accomplished through alternative translation initiation in a cap-independent manner at the viral internal ribosomal entry site (IRES). We have investigated the role ofcis- andtrans-acting viral factors in EV IRES translation in living cells. We observed that considerable portions of the viral genome, including the 5′-proximal open reading frame and the 3′ untranslated region, contribute to stimulation of IRES-mediated translation. With the IRES in proper context, translation via internal initiation in uninfected cells is as efficient as at capped messages with short, unstructured 5′ untranslated regions. IRES function is enhanced in cells infected with the EV coxsackievirus B3, but the related poliovirus has no significant stimulatory activity. This differential is due to the inherent properties of their 2A protease and is not coupled to 2A-mediated proteolytic degradation of the eukaryotic initiation factor 4G. Our results suggest that the efficiency of alternative translation initiation at EV IRESs depends on a properly configured template rather than on targeted alterations of the host cell translation machinery.
Effect of Hepatitis C Virus (HCV) NS5B-Nucleolin Interaction on HCV Replication with HCV Subgenomic Replicon
Authors: Shimakami Tetsuro , Honda Masao , Kusakawa Takashi , Murata Takayuki , Shimotohno Kunitada , Kaneko Shuichi , Murakami Seishi 
Published: March 2006

ABSTRACT
We previously reported that nucleolin, a representative nucleolar marker, interacts with nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) through two independent regions of NS5B, amino acids 208 to 214 and 500 to 506. We also showed that truncated nucleolin that harbors the NS5B-binding region inhibited the RNA-dependent RNA polymerase activity of NS5B in vitro, suggesting that nucleolin may be involved in HCV replication. To address this question, we focused on NS5B amino acids 208 to 214. We constructed one alanine-substituted clustered mutant (CM) replicon, in which all the amino acids in this region were changed to alanine, as well as seven different point mutant (PM) replicons, each of which harbored an alanine substitution at one of the amino acids in the region. After transfection into Huh7 cells, the CM replicon and the PM replicon containing NS5B W208A could not replicate, whereas the remaining PM replicons were able to replicate. In vivo immunoprecipitation also showed that the W208 residue of NS5B was essential for its interaction with nucleolin, strongly suggesting that this interaction is essential for HCV replication. To gain further insight into the role of nucleolin in HCV replication, we utilized the small interfering RNA (siRNA) technique to investigate the knockdown effect of nucleolin on HCV replication. Cotransfection of replicon RNA and nucleolin siRNA into Huh7 cells moderately inhibited HCV replication, although suppression of nucleolin did not affect cell proliferation. Taken together, our findings strongly suggest that nucleolin is a host component that interacts with HCV NS5B and is indispensable for HCV replication.
Protein Kinase B/Akt Is Present in Activated Form throughout the Entire Replicative Cycle of ΔUS3 Mutant Virus but Only at Early Times after Infection with Wild-Type Herpes Simplex Virus 1
Authors: Benetti Luca , Roizman Bernard 
Published: March 2006

ABSTRACTThe product of the herpes simplex virus 1 (HSV-1) US3 gene is a multifunctional serine-threonine protein kinase that can block apoptosis induced by proapoptotic cellular proteins, exogenous agents, or replication-defective viruses. Earlier studies showed that the US3 kinase activates and functionally overlaps cellular protein kinase A (PKA). In this study we examined the status of phosphatidylinositol 3-kinase [PI(3)K] and of its effector, protein kinase B/Akt (PKB/Akt), a component of a major pathway of mammalian antiapoptotic signaling systems. We report the following. (i) Infection of target cells with HSV-1 induces transient phosphorylation of serine 473 of PKB/Akt early in infection, with a mechanism that is dependent on PI(3)K. Inhibition of PI(3)K induced apoptosis in mock-infected or ΔUS3 mutant-virus-infected but not in wild-type-virus-infected cells and reduced the accumulation of specific viral gene products, including the US3 protein kinase, but had a marginal effect on virus yields. (ii) At later times after infection, the total amounts of PKB/Akt decreased and phosphorylated PKB/Akt forms disappeared in a US3-dependent and protein phosphatase 2A-independent manner. (iii) Activation of PKA by forskolin did not mediate significant dephosphorylation of PKB/Akt. Our results are consistent with the model that PKB/Akt is activated early in infection and acts to block apoptosis in infected cells prior to the accumulation of US3 protein kinase and that it persists and continues to function as an antiapoptotic protein in the absence of US3 but becomes redundant or even inimical once US3 protein kinase accumulates in effective amounts.