bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Cytomegalovirus UL97 Kinase Is Required for the Normal Intranuclear Distribution of pp65 and Virion Morphogenesis
Authors: Prichard Mark N. , Britt William J. , Daily Shannon L. , Hartline Caroll B. , Kern Earl R. 
Published: November 2005

ABSTRACT
Recombinant human cytomegaloviruses that do not express UL97 kinase activity exhibit a distinctive plaque morphology characterized by the formation of highly refractile bodies late in infection. These structures were also observed in infected cells treated with the UL97 kinase inhibitor maribavir. Nuclear inclusions were purified to near homogeneity, and the constituent proteins were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. This analysis demonstrated that the aggregates were formed principally of the tegument proteins pp65 and ppUL25 but also contained additional virion structural proteins including the major capsid protein. Immunoblotting experiments confirmed these results and identified a number of additional viral proteins present in the purified tegument aggregates. Interestingly, the formation of these structures appeared to be dependent on pp65, since it was not induced in cells infected with a recombinant virus with this open reading frame deleted. Morphologically similar aggregates could be reproduced in nuclei of uninfected cells by overexpressing pp65, and their formation was prevented by coexpressing the UL97 kinase. Inhibition of UL97 kinase activity with maribavir or mutation of an essential amino acid in the kinase abolished its ability to prevent aggregate formation. These data taken together suggest that the UL97 kinase impacts the aggregation of pp65 in the nuclei of infected cells. We propose that the kinase plays an important role in the acquisition of tegument during virion morphogenesis in the nucleus and that this activity represents an important step in the production of mature virus particles.
Signal Peptide Cleavage and Internal Targeting Signals Direct the Hepatitis C Virus p7 Protein to Distinct Intracellular Membranes
Authors: Griffin Stephen , Clarke Dean , McCormick Christopher , Rowlands David , Harris Mark 
Published: November 2005

ABSTRACT
The hepatitis C virus (HCV) p7 protein forms an amantadine-sensitive ion channel required for viral replication in chimpanzees, though its precise role in the life cycle of HCV is unknown. In an attempt to gain some insights into p7 function, we examined the intracellular localization of p7 using epitope tags and an anti-p7 peptide antibody, antibody 1055. Immunofluorescence labeling of p7 at its C terminus revealed an endoplasmic reticulum (ER) localization independent of the presence of its signal peptide, whereas labeling the N terminus gave a mitochondrial-type distribution in brightly labeled cells. Both of these patterns could be visualized within individual cells, suggestive of separate pools of p7 where the N and C termini differed in accessibility to antibody. These patterns were disrupted by preventing signal peptide cleavage. Subcellular fractionation revealed that p7 was enriched in a heavy membrane fraction associated with mitochondria as well as normal ER-derived microsomes. The complex regulation of the intracellular distribution of p7 suggests that p7 plays multiple roles in the HCV life cycle either intracellularly or as a virion component.
The C Terminus of the Nucleoprotein of Influenza A Virus Delivers Antigens Transduced by Tat to thetrans-Golgi Network and Promotes an Efficient Presentation through HLA Class I
Authors: Bettosini Francesca , Fiorillo Maria Teresa , Magnacca Adriana , Leone Laura , Torrisi Maria Rosaria , Sorrentino Rosa 
Published: November 2005

ABSTRACTCytotoxic T lymphocytes (CTLs) are the most powerful weapon of the immune system to eliminate cells infected by intracellular parasites or tumors. However, very often, escape mechanisms overcome CTL immune surveillance by impairing the classical HLA class I antigen-processing pathway. Here, we describe a strategy for CTL activation based on the ability of Tat to mediate transcellular delivery of viral proteins encompassing HLA class I-restricted epitopes. In this system, the recombinant protein TAT-NpFlu containing the transduction domain of Tat of human immunodeficiency virus type 1 fused to the amino acid region 301 to 498 of the nucleoprotein of influenza A virus is proven to sensitize different human cells to lysis by HLA-B27-restricted, Flu 383-391-specific CTL lines. The fusion protein is processed very effectively, since a comparable biological effect is obtained with an amount of protein between 1 and 2 orders of magnitude lower than that of the synthetic peptide. Interestingly, while part of TAT-NpFlu undergoes fast and productive cleavage, a large amount of it remains intact for up to 24 h. Confocal microscopy shows that TAT-NpFlu accumulates in thetrans-Golgi network (TGN), where it starts to be detectable 1 h after transduction. Using TAT-NpFlu mutants and hybrid constructs, we demonstrate that enrichment in the TGN occurs only when the carboxy-terminal region of NpFlu (amino acids 400 to 498) is present. These data disclose an unconventional route for presentation of epitopes restricted for HLA class I molecules.
A Deubiquitinating Activity Is Conserved in the Large Tegument Protein of the
Herpesviridae
Authors: Schlieker Christian , Korbel Gregory A. , Kattenhorn Lisa M. , Ploegh Hidde L. 
Published: November 2005

ABSTRACT

The largest tegument protein of herpes simplex virus 1 (HSV-1), UL36, contains a novel deubiquitinating activity embedded in it. All members of the
Herpesviridae
contain a homologue of HSV-1 UL36, the N-terminal segments of which show perfect conservation of those residues implicated in catalysis. For murine cytomegalovirus and Epstein-Barr virus, chosen as representatives of the beta- and gammaherpesvirus subfamilies, respectively, we here show that the homologous modules indeed display deubiquitinating activity in vitro. The conservation of this activity throughout all subfamilies is indicative of an important, if not essential, function.
Matrix-Induced Inhibition of Membrane Binding Contributes to Human Immunodeficiency Virus Type 1 Particle Assembly Defects in Murine Cells
Authors: Hatziioannou Theodora , Martin-Serrano Juan , Zang Trinity , Bieniasz Paul D. 
Published: November 2005

ABSTRACT
Defective human immunodeficiency virus type 1 (HIV-1) assembly in murine cells is accompanied by poor plasma membrane binding and proteolytic processing of the HIV-1 Gag precursor. Here, we show that such defects are induced by the propensity of the HIV-1 MA globular head to inhibit membrane binding and particle assembly, particularly at the low expression levels observed in murine cells. Simple additions to or deletion of the MA globular head can improve the yield of infectious virions from murine cells by >50-fold. Expression level and autoinhibition can be important confounding variables in studies of HIV-1 assembly and contribute to defects encountered in murine cells.
Stress fractures of the femoral shaft in women’s college lacrosse: a report of seven cases and a review of the literature
Authors: Kang L , Belcher D , Hulstyn M J 
Published: November 2005

Background:Stress fractures do not often occur in the shaft of the femur. They are more common in the femoral neck, the tibial shaft, the metatarsals, and other bones of the foot. In female athletes, stress fractures classically afflict the distance runner, the ballerina, the gymnast, and the figure skater.Objectives:To describe the clinical presentation, diagnosis, treatment, and outcome of seven college female lacrosse players with femoral shaft stress fractures, and review the literature.Results:The unusual results of this study support the principle that clinical suspicion should be high when treating any female athlete regardless of the sport. In this case series, an abrupt change in the quality of the running surface during the competitive training season was the only underlying common thread among the athletes.Conclusion:The findings suggest that risk factors for the female athlete are variable and are no longer limited to the undernourished or overtrained.
Effects of inhaled bronchodilators and corticosteroids on exercise induced arterial hypoxaemia in trained male athletes
Authors: Hodges A N H , Lynn B M , Koehle M S , McKenzie D C 
Published: November 2005

Objectives:To determine the effect of prophylactic treatment with an inhaled bronchodilator and anti-inflammatory on arterial saturation (Sao2) in trained non-asthmatic male athletes with exercise induced arterial hypoxaemia (EIAH).Methods:Nine male athletes (mean (SD) age 26.3 (6.7) years, height 182.6 (7.9) cm, weight 79.3 (10.5) kg, Vo2max62.3 (6.3) ml/kg/min, Sao2min92.5 (1.1)%) with no history of asthma were tested in two experimental conditions. A combination of a therapeutic dose of salbutamol and fluticasone or an inert placebo was administered in a randomised crossover design for seven days before maximal cycling exercise. Oxygen consumption (Vo2), ventilation (Ve), heart rate (HR), power output, and Sao2were monitored during the exercise tests.Results:There were no significant differences between the drug (D) and placebo (P) conditions for minimal Sao2(D  =  93.6 (1.4), P  =  93.0 (1.1)%; p  =  0.93) Vo2max(D  =  61.5 (7.2), P  =  61.9 (6.3) ml/kg/min; p  =  0.91), peak power (D  =  444.4 (48.3), P  =  449.4 (43.9) W; p  =  0.90), peak Ve(D  =  147.8 (19.1), P  =  149.2 (15.5) litres/min; p  =  0.82), or peak heart rate (D  =  182.3 (10.0), P  =  180.8 (5.5) beats/min; p  =  0.76).Conclusions:A therapeutic dose of salbutamol and fluticasone did not attenuate EIAH during maximal cycling in a group of trained male non-asthmatic athletes.
Specific incremental test in elite squash players
Authors: Girard O , Sciberras P , Habrard M , Hot P , Chevalier R , Millet G P 
Published: November 2005

Objectives:To compare cardiorespiratory responses between incremental treadmill (non-specific) and field (sport specific) tests in elite squash players.Methods:Seven elite players (ranked 1 to 25 in their national federation including the World number 1) randomly performed an incremental treadmill test (TT) and a squash specific graded test (ST) to exhaustion. The ST consisted of repeated displacements replicating the game of squash, at increasing speed on the court. In both tests, ventilatory variables and heart rate were determined at the ventilatory threshold, respiratory compensation point, and maximal loads (max).Results:Heart rate and percentage maximal oxygen uptake (V˙o2max) at the ventilatory threshold and respiratory compensation point were not different between the ST and TT, whereas V˙o2maxwas higher in the ST than in the TT (63.6 (3.0)v54.9 (2.5) ml/kg/min; p<0.001). Time to exhaustion was not different between the ST and TT (1056 (180)v962 (71) seconds) but correlated with the ranking of the players only in the ST (r =  −0.96, p<0.001).Conclusions:V˙o2maxvalues derived from laboratory testing were not relevant for accurately estimating fitness in elite squash players. So the ST may be used as an additional test for determination of training intensity. Improved training advice for prescribing aerobic exercise or perfecting stroke technique may result from these results.
Physiological characteristics of top level off-road motorcyclists
Authors: Gobbi A W , Francisco R A , Tuy B , Kvitne R S 
Published: November 2005

Objectives:The study aims to analyse the physiological characteristics of top level off-road motocross, enduro, and desert rally motorcyclists to facilitate the design of a specific training program.Methods:Twenty seven off-road top level riders participated in this study which measured anthropometric data, maximum aerobic power with incremental tests of both arms and legs, isokinetic dynamometry of the knee and elbow, handgrip strength, heart rate, and blood lactate concentrations during competition.Results:The physical demands of the various races appear to influence the development of distinct musculoskeletal characteristics, as well as aerobic and anaerobic metabolism. Motocross riders have more muscle mass, higher isokinetic handgrip strength, and greater aerobic power than enduro and desert rally riders. However, there are no significant anthropometric and physiological differences between desert rally and enduro riders. Desert rally riders tend to be overweight with maximum aerobic power similar to that of healthy individuals. The mechanical characteristics of the motorcycle and the technical and tactical skills of the riders seem to be more important for race success than the metabolic capabilities of the rider.Conclusions:Desert rally and enduro riders present similar anthropometric and physiological characteristics. Both have a maximum aerobic power similar to that of healthy normal individuals, although desert rally riders tend to be overweight. Motocross riders on the other hand, have more muscle mass, more strength, and greater aerobic power. The differences observed suggest the need for a specific training program to address the requirements of different riders to reduce the possibility of injury.
An exercise programme for the management of lateral elbow tendinopathy
Authors: Stasinopoulos D , Stasinopoulou K , Johnson M I 
Published: November 2005

Background:Home exercise programmes and exercise programmes carried out in a clinical setting are commonly advocated for the treatment of lateral elbow tendinopathy (LET), a very common lesion of the arm with a well-defined clinical presentation. The aim of this study is to describe the use and effects of strengthening and stretching exercise programmes in the treatment of LET.Eccentric exercises:Slow progressive eccentric exercises for LET should be performed with the elbow in extension, forearm in pronation, and wrist in extended position (as high as possible). However, it is unclear how the injured tendon, which is loaded eccentrically, returns to the starting position without experiencing concentric loading and how the “slowness” of eccentric exercises should be defined. Nor has the treatment regimen of the eccentric exercises of a supervised exercise programme been defined.Stretching exercises:Static stretching is defined as passively stretching a given muscle-tendon unit by slowly placing and maintaining it in a maximal position of stretch. We recommend the position should be held for 30–45 s, three times before and three times after eccentric exercises during each treatment session with a 30 s rest interval between each procedure. The treatment region of static stretching exercises when a supervised exercise programme is performed is unknown.Discussion:A well designed trial is needed to study the effectiveness of a supervised exercise programme for LET consisting of eccentric and static stretching exercises. The issues relating to the supervised exercise programme should be defined so that therapists can replicate the programme.
Modification of Precipitation by Coastal Orography in Storms Crossing Northern California
Authors: James Curtis N. , Houze Robert A. 
Published: November 2005

Abstract
This study compiles and interprets three-dimensional Weather Surveillance Radar-1988 Doppler (WSR-88D) data during a 2.5-yr period and examines the typical orographic effects on precipitation mainly associated with winter storms passing over coastal northern California.
The three-dimensional mean reflectivity patterns show echo structure that was generally stratiform from over the ocean to inland over the mountains. The flow above the 1-km level was strong enough to be unblocked by the terrain, and the mean echo pattern over land had certain characteristics normally associated with an unblocked cross-barrier flow, both on the broad scale of the windward slopes of the coastal mountains and on the scale of individual peaks of the terrain on the windward side. Upward-sloping echo contours on the scale of the overall region of coastal mountains indicated broadscale upslope orographic enhancement. On a smaller scale, the mean stratiform echo pattern over the mountains contained a strong embedded core of maximum reflectivity over the first major peak of terrain encountered by the unblocked flow and a secondary echo core over the second major rise of the coastal mountain terrain.
Offshore, upstream of the coastal mountains, the reflectivity pattern showed a region of enhanced mainly stratiform echo within ∼100 km of the coast, with an embedded echo core, similar to those over the inland mountain peaks, along its leading edge. It is suggested that the offshore enhancement is caused by intensified frontogenesis in the offshore coastal zone and/or by the onshore directed low-level flow rising over a thin layer of cool, stable air dammed against the coastal mountains.
The orographically enhanced precipitation offshore and over the coastal mountains was present to some degree in all the landfalling storms. However, the degree to which each feature was present varied. All the features were more pronounced when the 500–700-hPa flow was strong, the midlevel humidity was high, and the low-level cross-barrier wind component was strong. When the low-level stability was greater, the offshore enhancement of precipitation was proportionately increased, and the general broadscale enhancement inland was reduced.
Accounting for the Error due to Unresolved Scales in Ensemble Data Assimilation: A Comparison of Different Approaches
Authors: Hamill Thomas M. , Whitaker Jeffrey S. 
Published: November 2005

Abstract
Insufficient model resolution is one source of model error in numerical weather predictions. Methods for parameterizing this error in ensemble data assimilations are explored here. Experiments were conducted with a two-layer primitive equation model, where the assumed true state was a T127 forecast simulation. Ensemble data assimilations were performed with the same model at T31 resolution, assimilating imperfect observations drawn from the T127 forecast. By design, the magnitude of errors due to model truncation was much larger than the error growth due to initial condition uncertainty, making this a stringent test of the ability of an ensemble-based data assimilation to deal with model error. Two general methods, “covariance inflation” and “additive error,” were considered for parameterizing the model error at the resolved scales (T31 and larger) due to interaction with the unresolved scales (T32 to T127). Covariance inflation expanded the background forecast members’ deviations about the ensemble mean, while additive error added specially structured noise to each ensemble member forecast before the update step.
The method of parameterizing this model error had a substantial effect on the accuracy of the ensemble data assimilation. Covariance inflation produced ensembles with analysis errors that were no lower than the analysis errors from three-dimensional variational (3D-Var) assimilation, and for the method to avoid filter divergence, the assimilations had to be periodically reseeded. Covariance inflation uniformly expanded the model spread; however, the actual growth of model errors depended on the dynamics, growing proportionally more in the midlatitudes. The inappropriately uniform inflation progressively degradated the capacity of the ensemble to span the actual forecast error.
The most accurate model-error parameterization was an additive model-error parameterization, which reduced the error difference between 3D-Var and a near-perfect assimilation system by ∼40%. In the lowest-error simulations, additive errors were parameterized using samples of model error from a time series of differences between T63 and T31 forecasts. Scaled samples of differences between model forecast states separated by 24 h were also tested as additive error parameterizations, as well as scaled samples of the T31 model state’s anomaly from the T31 model climatology. The latter two methods produced analyses that were progressively less accurate. The decrease in accuracy was likely due to their inappropriately long spatial correlation length scales.
Ensemble Kalman Filter Assimilation of Fixed Screen-Height Observations in a Parameterized PBL
Authors: Hacker Joshua P. , Snyder Chris 
Published: November 2005

Abstract
In situ surface layer observations are a rich data source that could be more effectively utilized in NWP applications. If properly assimilated, data from existing mesonets could improve initial conditions and lower boundary conditions, leading to the possibility of improved simulation and short-range forecasts of slope flows, sea breezes, convective initiation, and other PBL circulations.
A variance–covariance climatology is constructed by extracting a representative column from real-time mesoscale forecasts over the Southern Great Plains, and used to explore the potential for estimating the state of the PBL by assimilating surface observations. A parameterized 1D PBL model and an ensemble Kalman filter (EnKF) approach to assimilation are used to test this potential. Analysis focuses on understanding how effectively the EnKF can spread the surface observations vertically to constrain the state of the PBL model. Results confirm that assimilating surface observations can substantially improve the state of a modeled PBL. Experiments to estimate the moisture availability parameter through the data assimilation system show that the EnKF is a viable tool for parameter estimation, and may help mitigate model error in forecasting and simulating the PBL.
Initialization of an ENSO Forecast System Using a Parallelized Ensemble Filter
Authors: Zhang S. , Harrison M. J. , Wittenberg A. T. , Rosati A. , Anderson J. L. , Balaji V. 
Published: November 2005

Abstract
As a first step toward coupled ocean–atmosphere data assimilation, a parallelized ensemble filter is implemented in a new stochastic hybrid coupled model. The model consists of a global version of the GFDL Modular Ocean Model Version 4 (MOM4), coupled to a statistical atmosphere based on a regression of National Centers for Environmental Prediction (NCEP) reanalysis surface wind stress, heat, and water flux anomalies onto analyzed tropical Pacific SST anomalies from 1979 to 2002. The residual part of the NCEP fluxes not captured by the regression is then treated as stochastic forcing, with different ensemble members feeling the residual fluxes from different years. The model provides a convenient test bed for coupled data assimilation, as well as a prototype for representing uncertainties in the surface forcing.
A parallel ensemble adjustment Kalman filter (EAKF) has been designed and implemented in the hybrid model, using a local least squares framework. Comparison experiments demonstrate that the massively parallel processing EAKF (MPPEAKF) produces assimilation results with essentially the same quality as a global sequential analysis. Observed subsurface temperature profiles from expendable bathythermographs (XBTs), Tropical Atmosphere Ocean (TAO) buoys, and Argo floats, along with analyzed SSTs from NCEP, are assimilated into the hybrid model over 1980–2002 using the MPPEAKF. The filtered ensemble of SSTs, ocean heat contents, and thermal structures converge well to the observations, in spite of the imposed stochastic forcings. Several facets of the EAKF algorithm used here have been designed to facilitate comparison to a traditional three-dimensional variational data assimilation (3DVAR) algorithm, for instance, the use of a univariate filter in which observations of temperature only directly impact temperature state variables. Despite these choices that may limit the power of the EAKF, the MPPEAKF solution appears to improve upon an earlier 3DVAR solution, producing a smoother, more physically reasonable analysis that better fits the observational data and produces, to some degree, a self-consistent estimate of analysis uncertainties. Hybrid model ENSO forecasts initialized from the MPPEAKF ensemble mean also appear to outperform those initialized from the 3DVAR analysis. This improvement stems from the EAKF’s utilization of anisotropic background error covariances that may vary in time.