bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Herpes Simplex Virus Type 1 UL3 Transcript Starts within the UL3 Open Reading Frame and Encodes a 224-Amino-Acid Protein
Authors: Markovitz Nancy S. 
Published: July 2007

ABSTRACT

Several different herpes simplex viruses (HSVs) and vectors are being explored as therapeutic products for use in the treatment of cancer and neurological disorders. The viral strain and the combination of mutant viral genes that ultimately may serve as a safe and optimal backbone for such products are still being explored. The large genome size and complexity of the viral life cycle make such determinations difficult, because the significance of differences between proposed products is difficult to evaluate. For example, we previously reported that two lineages of γ34.5-deleted HSVs used in clinical studies differ from each other in the size of the UL3 protein expressed (M. J. Dambach et al., Mol. Ther.
13:
891-898, 2006). Because the function of UL3 is not known and UL3 gene expression is poorly understood, the significance of such a difference cannot be predicted. Here, I begin to address the function of UL3 by investigating UL3 gene expression. I report that the transcript start site of UL3 mRNA isolated from HSV type 1 (HSV-1)-infected cells maps to a position downstream of the predicted translation start site. By constructing and characterizing the recombinant virus CB8116, which has a mutation in the first in-frame start codon of this UL3 transcript, I demonstrated that UL3 protein translation initiates at the second in-frame start codon of the UL3 open reading frame. This information adds to the body of basic knowledge of HSV-1 biology that forms the foundation for our current understanding of HSV-based products. Future research on HSV-1 biology will facilitate the rational design and evaluation of future generations of therapeutic viruses.
Astrocyte Indoleamine 2,3-Dioxygenase Is Induced by the TLR3 Ligand Poly(I:C): Mechanism of Induction and Role in Antiviral Response
Authors: Suh Hyeon-Sook , Zhao Meng-Liang , Rivieccio Mark , Choi Shinyeop , Connolly Erin , Zhao Yongmei , Takikawa Osamu , Brosnan Celia F. , Lee Sunhee C. 
Published: July 2007

ABSTRACTIndoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme in the kynurenine pathway of tryptophan catabolism and has been implicated in neurotoxicity and suppression of the antiviral T-cell response in HIV encephalitis (HIVE). Here we show that the Toll-like receptor 3 (TLR3) ligand poly(I:C) (PIC) induces the expression of IDO in human astrocytes. PIC was less potent than gamma interferon (IFN-γ) but more potent than IFN-β in inducing IDO. PIC induction of IDO was mediated in part by IFN-β but not IFN-γ, and both NF-κB and interferon regulatory factor 3 (IRF3) were required. PIC also upregulated TLR3, thereby augmenting the primary (IFN-β) and secondary (IDO and viperin) response genes upon subsequent stimulation with PIC. In HIVE, the transcripts for TLR3, IFN-β, IDO, and viperin were increased and IDO immunoreactivity was detected in reactive astrocytes as well as macrophages and microglia. PIC caused suppression of intracellular replication of human immunodeficiency virus pseudotyped with vesicular stomatitis virus G protein and human cytomegalovirus in a manner dependent on IRF3 and IDO. The involvement of IDO was demonstrated by partial but significant reversal of the PIC-mediated antiviral effect by IDO RNA interference and/or tryptophan supplementation. Importantly, the cytokine interleukin-1 abolished IFN-γ-induced IDO enzyme activity in a nitric oxide-dependent manner without suppressing protein expression. Our results demonstrate that IDO is an innate antiviral protein induced by double-stranded RNA and suggest a therapeutic utility for PIC in human viral infections. They also show that IDO activity can be dissociated from protein expression, indicating that the local central nervous system cytokine and nitric oxide environment determines IDO function.
A randomised controlled trial evaluating an alternative mouse and forearm support on upper body discomfort and musculoskeletal disorders among engineers
Authors: Conlon C F , Krause N , Rempel D M 
Published: July 2007

Objectives:The aim of this intervention study was to determine the effects of an alternative mouse and/or a forearm support board on the change in upper body discomfort scores and the development of incident musculoskeletal disorders.Methods:This randomised controlled intervention trial followed 206 engineers for one year. Participants were randomised to receive (1) a conventional mouse only, (2) an alternative mouse only, (3) a forearm support board, or (4) an alternative mouse plus forearm support board. Outcome measures included weekly upper body discomfort scores and incident musculoskeletal disorders.Results:During the study, 42 participants were diagnosed with an incident musculoskeletal disorder. The group that received the forearm support board experienced a reduction in their right upper extremity discomfort (beta-coefficient −0.35, 95% CI −0.67 to −0.03) in comparison to those who did not receive a forearm board. The group that received the alternative mouse had a protective, but non-significant (p = 0.20), effect on incident cases of right upper extremity musculoskeletal disorders (HR 0.57, 95% CI 0.24 to 1.34) and a non-significant reduction in neck/shoulder discomfort (beta-coefficient −0.23, 95% CI −0.056 to 0.10) in comparison to those who received a conventional mouse.Conclusions:In engineers who use a computer for more than 20 h per week, a forearm support board may reduce right upper extremity discomfort attributed to computer use.
Steroids and histone deacetylase in ventilation-induced gene transcription
Authors: Dombrowsky H. , Uhlig S. 
Published: July 2007

Histone acetylation and deacetylation promote and repress gene transcription, respectively. Recruitment of histone deacetylases (HDAC) to sites of inflammatory gene transcription has been proposed to explain part of the anti-inflammatory activity of steroids. To examine whether this concept extends to other inflammatory conditions, the current authors investigated the role of histone acetylation and the effects of steroids on the ventilation-induced induction of pro-inflammatory genes.Isolated perfused mouse lungs were ventilated for 180 min with low peak inspiratory pressure of 10 cmH2O or high peak inspiratory pressure of 22.5 cmH2O (overventilation) and treated with the HDAC inhibitor trichostatin A (TSA), the steroid dexamethasone or both.Overventilation increased histone acetylation at H4K12, as well as gene and protein expression of tumour necrosis factor (TNF), macrophage inflammatory protein (MIP)-2α and interleukin (IL)-6; these effects were reversed by dexamethasone. In the presence or absence of dexamethasone, TSA enhanced overventilation-induced induction of TNF and MIP-2α, but decreased that of IL-6, indicating that the effects of HDAC are gene dependent.Thus, H4K12 acetylation and its regulation by steroids may be relevant for inflammatory gene transcription during overventilation. Histone deacetylases appear to play an important gene-dependent regulatory role in this process, with the caveat that histones are not the only substrates of histone deacetylase isoenzymes.
Developmentally regulated promoter-switch transcriptionally controls Runx1function during embryonic hematopoiesis
Authors: Pozner Amir , Lotem Joseph , Xiao Cuiying , Goldenberg Dalia , Brenner Ori , Negreanu Varda , Levanon Ditsa , Groner Yoram 
Published: July 2007

AbstractBackgroundAlternative promoters usage is an important paradigm in transcriptional control of mammalian gene expression. However, despite the growing interest in alternative promoters and their role in genome diversification, very little is known about how and on what occasions those promoters are differentially regulated. Runx1 transcription factor is a key regulator of early hematopoiesis and a frequent target of chromosomal translocations in acute leukemias. Mice deficient inRunx1lack definitive hematopoiesis and die in mid-gestation. Expression ofRunx1is regulated by two functionally distinct promoters designated P1 and P2. Differential usage of these two promoters creates diversity in distribution and protein-coding potential of the mRNA transcripts. While the alternative usage of P1 and P2 likely plays an important role inRunx1biology, very little is known about the function of the P1/P2 switch in mediating tissue and stage specific expression ofRunx1during development.ResultsWe employed mice bearing a hypomorphicRunx1allele, with a largely diminished P2 activity, to investigate the biological role of alternative P1/P2 usage. Mice homozygous for the hypomorphic allele developed to term, but died within a few days after birth. During embryogenesis the P1/P2 activity is spatially and temporally modulated. P2 activity is required in early hematopoiesis and when attenuated, development of liver hematopoietic progenitor cells (HPC) was impaired. Early thymus development and thymopoiesis were also abrogated as reflected by thymic hypocellularity and loss of corticomedullary demarcation. Differentiation of CD4/CD8 thymocytes was impaired and their apoptosis was enhanced due to altered expression of T-cell receptors.ConclusionThe data delineate the activity of P1 and P2 in embryogenesis and describe previously unknown functions of Runx1. The findings show unequivocally that the role of P1/P2 during development is non redundant and underscore the significance of alternative promoter usage in Runx1 biology.
Community health and medical provision: impact on neonates (the CHAMPION trial)
Authors: Boone Peter , Mann Vera , Eble Alexander , Mendiratta Tarana , Mukherjee Rohini , Figueiredo Ryan , Jayanty Chitra , Frost Chris , Padmanabh M Reddy , Elbourne Diana 
Published: July 2007

Abstract

Background
The trial aims to evaluate whether neonatal mortality can be reduced through systemic changes to the provision and promotion of healthcare. Neonatal mortality rates in India are high compared to other low income countries, and there is a wide variation of rates across regions. There is evidence that relatively inexpensive interventions may be able to prevent up to 75% of these deaths. One area with a particularly high rate is Mahabubnagar District in Andhra Pradesh, where neonatal mortality is estimated to be in the region of 4–9%. The area suffers from a vicious cycle of both poor supply of and small demand for health care services. The trial will assess whether a package of interventions to facilitate systemic changes to the provision and promotion of healthcare may be able to substantially reduce neonatal mortality in this area and be cost-effective. If successful, the trial is designed so that it should be possible to substantially scale up the project in regions with similarly high neonatal mortality throughout Andhra Pradesh and elsewhere.

Methods/Design
This trial will be a cluster-randomised controlled trial involving 464 villages in Mahabubnagar District. The package of interventions will first be introduced in half of the villages with the others serving as controls. The trial will run for a period of three years. The intervention in the trial has two key elements: a community health promotion campaign and a system to contract out healthcare to non-public institutions. The health promotion campaign will include a health education campaign, participatory discussion groups, training of village health workers and midwives, and improved coordination of antenatal services. The intervention group will also have subsidised access to pregnancy-related healthcare services at non-public lth centres (NPHCs).
The primary outcome of the trial will be neonatal mortality. Secondary outcomes will include age at and cause of neonatal death, neonatal morbidity, maternal mortality and morbidity, health service usage, costs and several process and knowledge outcomes.

Discussion
The trial will be run by independent research and service delivery arms and supervised by a trial steering committee. A data monitoring committee will be put in place to monitor the trial and recommend stopping/continuation according to a Peto-Haybittle rule. The primary publication for the trial will follow CONSORT guidelines for cluster randomised controlled trials. Criteria for authorship of all papers, presentations and reports resulting from the study will conform to ICMJE standards.

Trial Registration
Current Controlled Trials ISRCTN24104646
HIV prevention costs and program scale: data from the PANCEA project in five low and middle-income countries
Authors: Marseille Elliot , Dandona Lalit , Marshall Nell , Gaist Paul , Bautista-Arredondo Sergio , Rollins Brandi , Bertozzi Stefano M , Coovadia Jerry , Saba Joseph , Lioznov Dmitry , Du Plessis Jo-Ann , Krupitsky Evgeny , Stanley Nicci , Over Mead , Peryshkina Alena , Kumar SG Prem , Muyingo Sowedi , Pitter Christian , Lundberg Mattias , Kahn James G 
Published: July 2007

Abstract
Background
Economic theory and limited empirical data suggest that costs per unit of HIV prevention program output (unit costs) will initially decrease as small programs expand. Unit costs may then reach a nadir and start to increase if expansion continues beyond the economically optimal size. Information on the relationship between scale and unit costs is critical to project the cost of global HIV prevention efforts and to allocate prevention resources efficiently.

Methods
The "Prevent AIDS: Network for Cost-Effectiveness Analysis" (PANCEA) project collected 2003 and 2004 cost and output data from 206 HIV prevention programs of six types in five countries. The association between scale and efficiency for each intervention type was examined for each country. Our team characterized the direction, shape, and strength of this association by fitting bivariate regression lines to scatter plots of output levels and unit costs. We chose the regression forms with the highest explanatory power (R2).

Results
Efficiency increased with scale, across all countries and interventions. This association varied within intervention and within country, in terms of the range in scale and efficiency, the best fitting regression form, and the slope of the regression. The fraction of variation in efficiency explained by scale ranged from 26% – 96%. Doubling in scale resulted in reductions in unit costs averaging 34.2% (ranging from 2.4% to 58.0%). Two regression trends, in India, suggested an inflection point beyond which unit costs increased.

Conclusion
Unit costs decrease with scale across a wide range of service types and volumes. These country and intervention-specific findings can inform projections of the global cost of scaling up HIV prevention efforts.
Measurement of deflections experienced by electronic chips during soldering
Authors: Sciammarella C A , Lamberti L , Pappalettere C , Volpicella G , Sciammarella F. M 
Published: July 2007

Electronic chips may experience, during the soldering process to a circuit board, out-of-plane displacements whose magnitude is not compatible with technological requirements on good bonding. This paper presents an experimental procedure based on the projection computer-aided moiré (PCAM) system in order to contour the distorted shape of electronic chips undergoing a thermal cycle which simulates the soldering process. The PCAM system is an integrated system where a pattern of fringes is transformed via software into a continuous phase distribution from which the distorted shape of the chip can be recovered. In this study, a number of chips have been heated at different temperatures ranging between 120 and 220°C in order to reproduce conditions that may occur during the real soldering process. Since measurements are carried out when the thermal field has become uniform, the chip deforms in the fashion of a quadric surface (i.e. a hyperboloid). Analysis of the chip's deformed shape reveals that the largest displacement gradients experienced by the chips tested in this study are such that requirements on good bonding of the welded assembly are met. This finding, together with the fact that handling and investigation of electronic chips usually require special care, supports the conclusion that the PCAM approach may be successfully applied in the industry for the non-destructive testing of delicate components.
Investigation of the dependences of the mechanical characteristics of an alloyed steel on both the strain rate and the microstructure
Authors: Homayonifar M , Zebarjad M , Sajjadi A , Saatian A 
Published: July 2007

The mechanical properties of AISI 4140 steel were studied at different strain rates (0.167, 0.833, and 1.667 min-1) for various microstructures. To investigate the influence of microstructure, spheroidizing, normalizing, and quench tempering (single tempered and double tempered) were used to obtain a range of microstructures and strength levels. To study the dependences of the mechanical characteristics of AISI 4140 steel on both the strain rate and the microstructure, tensile tests and microscopic evaluation were performed. The results showed that not only do the yield and the ultimate strength depend on both the microstructure and the strain rate but also so does the appearance of the yielding phenomenon. Also the results showed that an increase in strain rate causes the strain-hardening exponent n and the strength coefficient K to decrease in both quench-tempered and normalized structures but has a negative effect on the spheroidized structure. In fact, the sensitivity of the spheroidized structure to the strain rate is higher than those of the other structures. Microscopic evaluation proved that the Lüders strain width of the spheroidized microstructure is much lower, because of its soft ferrite matrix.
Comparison of X-ray diffraction measurement of residual elastic strains: Monochromatic beam and image plate versus white beam energy-dispersive analysis
Authors: Vorster W J J , Zhang S Y , Golshan M , Laundy D , Dini D , Korsunsky A. M 
Published: July 2007

This paper presents the results of synchrotron X-ray diffraction measurement of residual elastic strains in a bent magnesium alloy bar using two different techniques. In the first technique the sample was scanned transversely to a monochromatic X-ray beam. The scattered X-rays were recorded on a phosphoric image plate that was translated at a proportional speed but in the opposite direction to the sample. This enabled the creation of a two-dimensional recording of one-dimensional diffraction patterns. In the second technique a white X-ray beam is used in combination with an energy-discriminating detector mounted at a fixed angle to record similar patterns at each gauge volume position within the sample. The motivation for comparing the results of two measurement techniques is to establish whether the same accuracy in a diffraction strain evaluation can be achieved. It was found that the translating image plate arrangement requires a certain amount of care in calibration and interpretation, but provides a quick and efficient method that can be competitive with the white beam energy-dispersive mode which is known to deliver a fast diffraction capability.
Resistance strain gauges for the measurement of steady strains at temperatures above 650°C
Authors: Bertodo R 
Published: July 2007

The paper considers the problem of obtaining steady strain data using electrical resistance strain gauges at temperatures above 650°C, in the presence of moderate temperature gradients, from turbojet components operating in oxidizing environments. The characteristics of forty-six metal and alloy systems are briefly outlined and the properties of platinum, and alloys of face centred cubic platinum metals and metals in the VIa group of the periodic table of elements are discussed in detail. The behaviour of colloidal sols, acid and alkali bonded ceramic cements and flame-sprayed oxides at high temperatures is considered and their effect on the short and long term stability and strain sensitivity of strain gauges presented. Only a limited number of pure oxides possessed an adequately high electrical resistivity at the higher temperatures for use as strain gauge bonding media. Such oxides, when flame-sprayed on to suitably prepared surfaces, developed a bond of sufficient shear strength to transfer the applied strain in a consistent and repeatable manner to the gauge filament. The porosity was low enough to offer some degree of oxidation protection to the strain sensitive grid. The temperature coefficient of resistance, drift rate and strain sensitivity of flat grid, dual-element gauges bonded in this manner to Nimonic specimens are shown and it is concluded that grids of this type, wound from platinum and a commercially available platinum-tungsten alloy, would permit the detection of steady strains within an accuracy of about ±0.5 ton/in2 over the temperature range 600—850°C and within ±1.0 ton/in2 over the approximate range 600—950°C from Nimonic specimens, provided the mean gauge temperature could be determined. Methods of determining this temperature in the presence of moderate temperature gradients along the longitudinal axis of the gauge are discussed and some field data are presented. Drift rates equivalent to less than 0.1 ton/in2/h were noted. It is thought that a coil wound gauge would offer improved performance over a flat grid gauge for temperature gradients across the element, but the problem of providing a suitable former has not been resolved satisfactorily.
Stresses in anisotropic media with particular reference to problems of rock mechanics
Authors: Zienkiewicz O. C. , Cheung Y. K. , Stagg K. G. 
Published: July 2007

The recently developed finite element method of numerical stress analysis has been previously applied to the analysis of the stress distribution in isotropically elastic materials and is here extended to deal with a particular form of anisotropy. The case of anisotropy considered is that generally referred to as transverse isotropy, i.e. where the material is isotropic in the yz plane but non-isotropic with respect to directions normal to this plane. The analysis is restricted to the consideration of two-dimensional plane strain problems in the xy plane. The individual element axis orientation may be varied at will with respect to the overall co-ordinate system so that problems may be treated where the direction of isotropy varies from point to point within the material. It is suggested that this system of anisotropy is particularly relevant to the analysis of stress distributions in stratified rock masses. Previous approaches to this problem are outlined in Appendix 1. A series of illustrative examples are shown, first, to compare the numerical solution to a problem with a known analytical solution to that analytical solution and, second, to show the application to more complex situations with no known analytical solutions. It is concluded from the first comparison that the method is capable of giving good accuracy.
Optimization of stress concentrations at holes in rotating discs
Authors: Fessler H , Thorpe T E 
Published: July 2007

The frozen stress photoelastic technique was used to determine the hoop and radial stresses at the hole boundaries of sixty different hole configurations in flat discs. Each had one ring of holes, evenly spaced on one pitch circle, concentric with the periphery and bore. The ratio of radial-hoop hole boundary stress was related to the radial-hoop stress ratio of plain discs, the hole spacing and hole diameter in a manner which permits quick determination of optimum hole spacing for the range of bores, pitch circle and hole diameters used in gas turbine discs. The peak stresses can also be predicted in non-optimum configurations.