bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posttranslational Acetylation of the Human Immunodeficiency Virus Type 1 Integrase Carboxyl-Terminal Domain Is Dispensable for Viral Replication
Authors: Topper Michael , Luo Yang , Zhadina Maria , Mohammed Kevin , Smith Leonard , Muesing Mark A. 
Published: December 2006

ABSTRACT

A recent report sought to demonstrate that acetylation of specific lysines within integrase (IN) by the histone acetyltransferase (HAT) p300 regulates human immunodeficiency virus type 1 (HIV-1) integration and is essential for viral replication (A.
Cereseto, L. Manganaro, M. I. Gutierrez, M. Terreni, A. Fittipaldi, M. Lusic, A. Marcello, and M. Giacca
, EMBO J.
24:
3070-3081, 2005). We can corroborate the efficient and specific acetylation of the IN carboxyl-terminal domain (CTD) (amino acids 212 to 288) by p300 using purified recombinant components. Although arginine substitution mutagenesis of the isolated CTD confirms that the majority of p300 acetylation occurs at lysine residues 264, 266, and 273, the pattern of acetylation is not uniform and a hierarchy of reactivity can be established. Several combinatorial mutations of the CTD lysines modified by p300 in vitro were reconstructed into an otherwise infectious proviral plasmid clone and examined for viral growth and frequency of productive chromosomal integration. In contrast to the findings of Cereseto and coworkers, who used epitope-tagged viruses for their experiments, we find that an untagged mutant virus, IN K(264/266/273)R, is fully replication competent. This discrepancy may be explained by the use of an acidic epitope tag placed at the extreme carboxyl terminus of integrase, near the target site for acetylation. Although the tagged, wild-type virus is viable, the combination of this epitope tag with the RRR substitution mutation results in a replication-defective phenotype. Although IN belongs to the very small set of nonhistone proteins modified by HAT-mediated activity, an obligate role for acetylation at the reactive CTD lysines in HIV-1 IN cannot be confirmed.
Role of the TSG101 Gene in Epstein-Barr Virus Late Gene Transcription
Authors: Chua Huey-Huey , Lee Heng-Huan , Chang Shih-Shin , Lu Chih-Chung , Yeh Te-Huei , Hsu Tsuey-Ying , Cheng Tzu-Hao , Cheng Jiin-Tsuey , Chen Mei-Ru , Tsai Ching-Hwa 
Published: December 2006

ABSTRACT
Rta, an Epstein-Barr virus (EBV)-encoded immediate-early protein, governs the reactivation of the viral lytic program by transactivating a cascade of lytic gene expression. Cellular transcription factors such as Sp1, ATF2, E2F, and Akt have been demonstrated to mediate Rta transactivation of lytic genes. We report herein that Rta associates with another potent transcription factor, tumor susceptibility gene 101 (TSG101), to promote the activation of EBV late genes. Results from an EBV cDNA array reveal that depletion of TSG101 by siRNA potently inhibits the transcription of five Rta-responsive EBV late genes, BcLF1, BDLF3, BILF2, BLLF1, and BLRF2. Depletion of TSG101 impairs the Rta transactivation of these late promoters severely. Moreover, a concordant augmentation of Rta transactivating activity is observed when TSG101 is overexpressed following ectopic transfection. Mechanistically, Rta interaction with TSG101 causes the latter to accumulate principally in the nuclei, wherein the proteins colocalize and are recruited to the viral promoters. Of note, TSG101 is crucial for the efficient binding of Rta to these late promoters. As a result, cells with defective TSG101 fail to express late viral proteins, leading to a decrease in the yield of virus particles. Thus, the contribution of TSG101 to Rta-mediated late gene activation is of great importance for completion of the EBV productive lytic cycle. These observations consolidate a role for TSG101 in the replication of EBV, a DNA virus, that differs from what is observed for RNA viruses, where TSG101 aids mainly in the endosomal sorting of enveloped late viral proteins for assembly at the plasma membrane.
Human Papillomavirus E7 Repression in Cervical Carcinoma Cells Initiates a Transcriptional Cascade Driven by the Retinoblastoma Family, Resulting in Senescence
Authors: Johung Kimberly , Goodwin Edward C. , DiMaio Daniel 
Published: December 2006

ABSTRACT
This work demonstrates a central role for the retinoblastoma (Rb) family in driving the transcriptional program of induced and replicative senescence. HeLa cervical carcinoma cells rapidly undergo senescence when the human papillomavirus (HPV) type 18 E7 gene in these cells is repressed by the bovine papillomavirus (BPV) E2 protein. This senescence response requires the endogenous Rb pathway but not the p53 pathway. Microarray analysis 6 days after BPV E2 introduction into HeLa cells identified 224 cellular genes induced by E7 repression and 354 repressed genes. Many repressed genes were involved in cell cycle progression, and numerous induced genes encoded lysosomal proteins. These gene expression changes were blocked by constitutive expression of the wild-type HPV16 E7 or adenovirus E1A gene, but not by E7 or E1A mutants defective for Rb binding. Short hairpin RNAs targeting the Rb family also inhibited these gene expression changes and blocked senescence. Therefore, surprisingly, the transcriptional response to BPV E2 expression was entirely dependent on E7 repression and activation of the Rb family, and the BPV E2 protein did not directly affect the expression of cellular genes. Activation of the Rb family repressed E2F-responsive genes and stimulated transcriptional activators, thereby mobilizing multiple signals, such as repression of B-MYB and DEK, that were independently sufficient to induce senescence. There was extensive overlap between the transcriptional profiles of senescent, late-passage primary human fibroblasts and senescent cervical carcinoma cells, suggesting that this Rb family-mediated transcriptional cascade also plays a central role in replicative senescence.
Use of multiple displacement amplification in the investigation of human papillomavirus physical status
Authors: Evans Mark Francis , Adamson Christine Stewart-Crawford , von Walstrom Genevieve Montagu , Cooper Kumarasen 
Published: December 2006

Background and Aims:The investigation of human papillomavirus (HPV) physical status in pre-invasive cervical lesions has been restricted by the small amounts of tissue available for study. Multiple displacement amplification (MDA), a phi29 DNA polymerase based whole genome amplification technique, has the potential to help resolve this problem by yielding large amounts of high molecular weight DNA from tiny starting quantities.Methods:Firstly, a comparison was made of restriction endonuclease fragment patterns of DNA from seven different HPV types and corresponding MDA products. Secondly,E6/E7and LCR sequencing data from HPV16 recombinant plasmid and MDA copy DNA were correlated. Thirdly, DNA and MDA products from cervical cell lines (CaSki, HeLa, and SiHa that contain integrated HPV) and an invasive cervical carcinoma were analysed by Southern blot hybridisation. Fourthly, MDA product from CaSki cell DNA mixed with HPV18-plasmid DNA was tested for the demonstration of both episomal and integrated HPV. Finally, MDA products from HPV16 positive abnormal cervical cytological samples were assayed for integration by Southern blot hybridisation.Results:DNA templates and MDA products yielded analogous data. Episomal and integrated HPV DNA were successfully detected by Southern blot assay of the cell line/HPV-plasmid model, and in MDA products of clinical samples.Conclusions:These data show that MDA has considerable potential to assist in the investigation of HPV physical status; abundant (>40 μg) DNA can be generated with high fidelity from minuscule (50 ng) starting quantities, and both episomal and integrated HPV DNA are distinguishable in MDA products from solid tumours and cytological materials.
Melanoma histopathology reporting: are we complying with the National Minimum Dataset?
Authors: Kaur Manjit R , Colloby Peter S , Martin-Clavijo Agustin , Marsden Jerry R 
Published: December 2006

Baclground:The Royal College of Pathologists introduced the National Minimum Dataset (NMDS) for the histopathological reporting of cutaneous melanoma in February 2002.Aim:To determine if histological reporting of invasive primary cutaneous melanoma in the West Midlands region of the UK was compliant with the NMDS.Methods:Reports were identified from March 2002 to March 2003 via the regional Cancer Intelligence Unit, and compared with the NMDS. If all items of the NMDS were adhered to, the report was considered compliant. If not compliant, the report was checked to see if it included selected clinical and staging parameters.Results:543 cases of invasive cutaneous melanoma were identified, but only 407 reports were analysed. 69/407 (17%) (95% CI 14% to 20%) reports were fully compliant with the NMDS. Of the non-complaint reports, 45/361 (12%) (95% CI 9% to 16%) reported all staging and clinically relevant parameters; 62/361 (17%) (95% CI 59% to 65%) reported all staging parameters. Breslow thickness was reported in all but one of the reports (99.7%), Clark’s level was reported in 344/407 (85%), ulceration in 280/407 (69%), and microsatellites in 146/407 (36%).Conclusion:There was slow uptake of the NMDS in this region in the year following its introduction. Although major parameters required for staging were more consistently reported, ulceration and microsatellites were less frequently reported.
Influenza immunisation: attitudes and beliefs of UK healthcare workers
Authors: Smedley Julia , Poole Jason , Waclawski Eugene , Stevens Anthony , Harrison John , Watson John , Hayward Andrew , Coggon David 
Published: December 2006

Aim:To explore attitudes to influenza immunisation and rates of uptake among staff working in acute hospitals in the UK.Method:A cross-sectional survey of 11 670 healthcare workers in six UK hospitals was carried out using a postal questionnaire.Results:Among 6302 responders (54% of those mailed), 19% had taken up influenza immunisation during winter 2002/3. Vaccination was well tolerated, with a low prevalence of side effects (13%) and associated time off work (2%). The majority of subjects who accepted vaccination (66%) were most strongly influenced by the personal benefits of protection against influenza. Prevention of sickness absence and protection of patients were the prime motivation for only 10% and 7% of subjects, respectively. Among 3967 who declined vaccination, the most common primary demotivators were concern about safety (31%) and efficacy (29%). 22% were most strongly deterred by lack of time to attend for vaccination. Free text answers indicated that 37% declined because of a perceived low ratio of personal benefits to adverse effects. Subjects said they would be persuaded to take up vaccination in future by easier access (36%), more information about personal benefit and risk (34%) and more information about effects on staff absence (24%).Conclusions:These findings indicate that the uptake of influenza immunisation among UK healthcare workers remains low. There is some scope for increasing uptake by improving accessibility and encouragement from professional peers. However, the results suggest that perception of small personal benefit in relation to risk mitigates, importantly, against higher uptake of routine annual influenza vaccination. Thus, resource might better be allocated to ensuring efficient management in epidemic years. The effect of publicity about pandemic influenza on risk perception and vaccine uptake among healthcare workers during winter 2005/6 warrants further study.
Hospital injury rates in relation to socioeconomic status and working conditions
Authors: d’Errico A , Punnett L , Cifuentes M , Boyer J , Tessler J , Gore R , Scollin P , Slatin C 
Published: December 2006

Objectives:To describe the risk of work injury by socioeconomic status (SES) in hospital workers, and to assess whether SES gradient in injury risk is explained by differences in psychosocial, ergonomic or organisational factors at work.Methods:Workforce rosters and Occupational Safety and Health Administration injury logs for a 5-year period were obtained from two hospitals in Massachusetts. Job titles were classified into five SES strata on the basis of educational requirements and responsibilities: administrators, professionals, semiprofessionals, skilled and semiskilled workers. 13 selected psychosocial, ergonomic and organisational exposures were assigned to the hospital jobs through the national O*NET database. Rates of injury were analysed as frequency records using the Poisson regression, with job title as the unit of analysis. The risk of injury was modelled using SES alone, each exposure variable alone and then each exposure variable in combination with SES.Results:An overall annual injury rate of 7.2 per 100 full-time workers was estimated for the two hospitals combined. All SES strata except professionals showed a significant excess risk of injury compared with the highest SES category (administrators); the risk was highest among semiskilled workers (RR 5.3, p<0.001), followed by nurses (RR 3.7, p<0.001), semiprofessionals (RR 2.9, p = 0.006) and skilled workers (RR 2.6, p = 0.01). The risk of injury was significantly associated with each exposure considered except pause frequency. When workplace exposures were introduced in the regression model together with SES, four remained significant predictors of the risk of injury (decision latitude, supervisor support, force exertion and temperature extremes), whereas the RR related to SES was strongly reduced in all strata, except professionals.Conclusions:A strong gradient in the risk of injury by SES was reported in a sample population of hospital workers, which was greatly attenuated by adjusting for psychosocial and ergonomic workplace exposures, indicating that a large proportion of that gradient can be explained by differences in working conditions.
The validation of work-related self-reported asthma exacerbation
Authors: Bolen Aimee R , Henneberger Paul K , Liang Xiaoming , Sama Susan R , Preusse Peggy A , Rosiello Richard A , Milton Donald K 
Published: December 2006

Objective:To determine the validity of work-related self-reported exacerbation of asthma using the findings from serial peak expiratory flow (PEF) measurements as the standard.Methods:Adults with asthma treated in a health maintenance organisation were asked to conduct serial spirometry testing at home and at work for 3 weeks. Self-reported respiratory symptoms and medication use were recorded in two ways: a daily log completed concurrently with the serial PEF testing and a telephone questionnaire administered after the PEF testing. Three researchers evaluated the serial PEF records and judged whether a work relationship was evident.Results:95 of 382 (25%) working adults with asthma provided adequate serial PEF data, and 13 of 95 (14%) were judged to have workplace exacerbation of asthma (WEA) based on these data. Self-reported concurrent medication use was the most valid single operational definition, with a sensitivity of 62% and a specificity of 65%.Conclusions:A work-related pattern of self-reported asthma symptoms or medication use was usually not corroborated by serial PEF testing and failed to identify many people who had evidence of WEA based on the serial PEF measurements.
A BROWNIAN-TIME EXCURSION INTO FOURTH-ORDER PDES, LINEARIZED KURAMOTO–SIVASHINSKY, AND BTP-SPDES ON ℝ+ × ℝd
Authors: ALLOUBA HASSAN 
Published: December 2006

In recent articles we have introduced the class of Brownian-time processes (BTPs) and the Linearized Kuramoto–Sivashinsky process (LKSP). Probabilistically, BTPs represent a unifying class for some different exciting processes like the iterated Brownian motion (IBM) of Burdzy (a process with fourth-order properties) and the Brownian–snake of Le Gall (a second-order process); they also include many additional new and quite interesting processes. The LKSP is closely connected to the Kuramoto–Sivashinsky PDEs, one of the most celebrated PDEs in modern applied mathematics. We start by surveying the fourth-order PDE connections to BTPs and the LKSP that we uncovered in two recent articles. In the second part of this paper we introduce BTP-SPDEs, these are SPDEs in which the PDE part is that solved by running a BTP. We consider a BTP-SPDE driven by an additive spacetime white noise on the time-space set ℝ+ × ℝd; and we prove the existence of a unique real-valued, Lp(Ω,ℙ) for all p ≥ 1, BTP solution to such BTP-SPDEs for 1 ≤ d ≤ 3. This contrasts sharply with the standard theory of reaction-diffusion type SPDEs driven by spacetime white noise, in which real-valued solutions are confined to one spatial dimension. Like the PDEs case, BTP-SPDEs also provide a valuable insight into other fourth-order SPDEs of applied science. We carry out such a program in forthcoming articles.
Placing pain on the sensory map: Classic papers by Ed Perl and colleagues
Authors: Mason Peggy 
Published: December 2006

This essay looks at two papers published by Ed Perl and co-workers that identified specifically nociceptive neurons in the periphery and superficial dorsal horn. Bessou P and Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol 32: 1025–1043 1969. Christensen BN and Perl ER. Spinal neurons specifically excited by noxious or thermal stimuli: marginal zone of the dorsal horn. J Neurophysiol 33: 293–307 1970.
The Political Economy of Antiretroviral Drugs in Zambia
Authors: Bwalya Edgar 
Published: December 2006

AbstractAccording to the 2005 United Nations Programe on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) Report, Zambia has one of the highest rates of HIV/AIDS cases in Southern Africa as well as in the world. However, it is also one of the few countries that have recorded a drop in the infection rates from an estimated 26% of the population in 2000 to just fewer than 16% in 2005. There appears to be a general consensus that the availability and free provision of antiretroviral drugs (ARVs) and treatment have raised hope that the recipients will live a longer, improved, and productive life. This paper will attempt to assess the major challenges to scaling-up antiretroviral therapy in Zambia. It argues that, while the government has made some progress in scaling-up access to ARVs, there is still much to be done.
The Well-Being of Industrial Workers: A Quantitative Assessment of the Dominican Case
Authors: Liberato Ana , Fennell Dana 
Published: December 2006

Abstract
This paper examines the influence of gender and industrial employment on two dimensions of well-being. An analysis based on the 1996 DHS survey showed the non-significant effects of the two variables on material wealth and housing quality. Key factors in increasing household well-being were urban location, household labor, and education. Urban location showed the largest positive effect on well-being. The Chi-square test showed a significant relationship between free trade zone employment and access to durable goods (P ≤ 0.5). These findings show the larger impact of specific demographic conditions on women's well-being, favoring contextual analysis over exploitation and opportunity frameworks.
Skilled Labor Immigration and External Trade in Malaysia: A Pooled Data Analysis
Authors: Hong Tan Chuie , Santhapparaj A. Solucis 
Published: December 2006

AbstractThis paper attempts to further the immigrant-link literature by applying, for the first time, gravity models to Malaysia. Specifically the paper seeks to quantify the impact upon Malaysia's bilateral trade flows of ASEAN and non-ASEAN skilled immigration, and to identify the underlying mechanisms underpinning this relationship. The results indicate that skilled immigration positively affects both the imports and exports of Malaysia. Immigrant-link is stronger between Malaysia and ASEAN countries than to non-ASEAN countries. The magnitude of the elasticity with respect to trade is larger for imports than for exports. Skilled immigrants' demand for native products outweighs the business-links formed between Malaysian trading partners.
Snowpack Variations in the Central Andes of Argentina and Chile, 1951–2005: Large-Scale Atmospheric Influences and Implications for Water Resources in the Region
Authors: Masiokas Mariano H. , Villalba Ricardo , Luckman Brian H. , Le Quesne Carlos , Aravena Juan Carlos 
Published: December 2006

Abstract
The snowpack in the central Andes (30°–37°S) is the primary source for streamflow in central Chile and central-western Argentina, but few published studies are available on snowpack variability in the region. This paper develops the first regional snowpack series (1951–2005) from Chilean and Argentinean snow course records. This series shows a strong regional signal, marked interannual variability, and a positive, though nonsignificant, linear trend. Correlations with local precipitation and temperature records reveal a marked association with conditions in central Chile. High snow accumulation is generally concurrent with El Niño events in the tropical Pacific, but only 5 of the 10 driest years coincided with La Niña events. Evaluation of 500-hPa geopotential height anomaly maps during extreme snow years highlights the crucial significance of tropospheric conditions in the subtropical and southeast Pacific in modulating snowfall. Correlations with gridded SST and SLP data and multiple regressions with large-scale climatic indices corroborate a Pacific ENSO-related influence largely concentrated during the austral winter months. This hampers the predictability of snowpack before the onset of the cold season. Annual and warm-season river discharges on both sides of the cordillera are significantly correlated with the regional snowpack record and show positive linear trends over the 1951–2004 common period, probably related to a greater frequency of above-average snowpacks during recent decades. Future demand and competition for water resources in these highly populated regions will require detailed information about temporal and spatial variations in snow accumulation over the Andes. The results indicate that the relationships between snowpack and atmospheric circulation patterns prior to the winter season are complex, and more detailed analyses are necessary to improve prediction of winter snowfall totals.
Changes in the Activity of the Madden–Julian Oscillation during 1958–2004
Authors: Jones Charles , Carvalho Leila M. V. 
Published: December 2006

Abstract
The Madden–Julian oscillation (MJO) is the most prominent mode of tropical intraseasonal variability. This study investigates the following questions. Is there statistical evidence of linear trends in MJO activity since the mid-1970s? Does the MJO exhibit changes in regimes of high and low activity? Are there significant seasonal differences in the activity of the MJO on time scales longer than interannual?
Positive linear trends are observed in zonal wind anomalies at 200 (U200) and 850 (U850) hPa during summer and winter seasons. Positive trends are also observed in the number of summer MJO events. Resampling statistical tests indicate that positive trends in summer U200 and U850 anomalies are statistically different from random occurrences at a 5% significance level.
A methodology based on the number of events is used to characterize low-frequency (LF) changes in MJO activity. Mean winter LF activity was characterized by nearly uniform variability from the early 1960s until the mid-1990s. In contrast, mean summer LF changes showed a regime of high activity from the mid-1960s until the late 1970s, a low regime from 1980 to 1988, and a regime of high activity from the early 1990s to early 2000. Fourier analysis of the mean summer LF index indicates that regimes of high MJO activity were separated by 18.5 yr. The substantial changes in summer MJO regimes do not appear to be related to increases in observational samplings due to satellite-derived winds assimilated in the NCEP–NCAR reanalysis. Monte Carlo experiments indicate that the observed changes in regimes of MJO activity in summer are statistically different from random occurrences at the 10% significance level only.