bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candida albicans-Secreted Aspartic Proteinases Modify the Epithelial Cytokine Response in an In Vitro Model of Vaginal Candidiasis
Authors: Schaller Martin , Korting Hans C. , Borelli Claudia , Hamm Gerald , Hube Bernhard 
Published: April 2005

ABSTRACTSecreted aspartyl proteinases (Saps) are important virulence factors ofCandida albicansduring mucosal and disseminated infections and may also contribute to the induction of an inflammatory host immune response. We used a model of vaginal candidiasis based on reconstituted human vaginal epithelium (RHVE) to study the epithelial cytokine response induced byC. albicans. In order to study the impact of the overall proteolytic activity and of distinct Sap isoenzymes, we studied the effect of the proteinase inhibitor pepstatin A on the immune response and compared the cytokine expression pattern induced by the wild-type strain SC5314 with the pattern induced by Sap-deficient mutants. Infection of RHVE with theC. albicanswild-type strain induced strong interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha responses in comparison with cytokine expression in noninfected tissue. Addition of the aspartyl proteinase inhibitor pepstatin A strongly reduced the cytokine response of RHVE. Furthermore,SAP-null mutants lacking eitherSAP1orSAP2caused reduced tissue damage and had a significantly reduced potential to stimulate cytokine expression. In contrast, the vaginopathic and cytokine-inducing potential of mutants lackingSAP4toSAP6was similar to that of the wild-type strain. These data show that the potential of specific Saps to cause tissue damage correlates with an epithelium-induced proinflammatory cytokine response, which may be crucial in controlling and managingC. albicansinfections at the vaginal mucosa in vivo.
Gamma Irradiation or CD4+-T-Cell Depletion Causes Reactivation of LatentSalmonella entericaSerovar Typhimurium Infection in C3H/HeN Mice
Authors: van Diepen Angela , van de Gevel Joke S. , Koudijs Margaretha M. , Ossendorp Ferry , Beekhuizen Henry , Janssen Riny , van Dissel Jaap T. 
Published: April 2005

ABSTRACTUpon infection withSalmonella, a host develops an immune response to limit bacterial growth and kill and eliminate the pathogen.Salmonellahas evolved mechanisms to remain dormant within the body, only to reappear (reactivate) at a later time when the immune system is abated. We have developed an in vivo model for studying reactivation ofSalmonella entericaserovar Typhimuriuminfection in mice. Upon subcutaneous infection, C3H/HeN (Ityr) mice showed an increase in bacterial numbers in livers and spleens, which reached a peak on day 19. After full recovery from the infection, these mice were irradiated or depleted of CD4+T cells. The mice displayed a secondary infection peak in livers and spleens with a course similar to that of the primary infection. We concluded that CD4+T cells are involved in active suppression ofS. entericaserovar Typhimurium during latency. The role of CD4+T cells during primary infection withS. entericaserovar Typhimurium is well established. This is the first study to describe a role of CD4+T cells during the latent phase ofS. entericaserovar Typhimurium infection.
Induction ofMycobacterium tuberculosis-Specific Primary and Secondary T-Cell Responses in Interleukin-15-Deficient Mice
Authors: Lazarevic Vanja , Yankura David J. , Divito Sherrie J. , Flynn JoAnne L. 
Published: April 2005

ABSTRACTSeveral studies have provided evidence that interleukin-15 (IL-15) can enhance protective immune responses againstMycobacterium tuberculosisinfection. However, the effects of IL-15 deficiency on the functionality ofM. tuberculosis-specific CD4 and CD8 T cells are unknown. In this study, we investigated the generation and maintenance of effector and memory T-cell responses followingM. tuberculosisinfection of IL-15−/−mice. IL-15−/−mice had slightly higher bacterial numbers during chronic infection, which were accompanied by an increase in gamma interferon (IFN-γ)-producing CD4 and CD8 T cells. There was no evidence of increased apoptosis or a defect in proliferation of CD8 effector T cells followingM. tuberculosisinfection. The induction of cytotoxic and IFN-γ CD8 T-cell responses was normal in the absence of IL-15 signaling. The infiltration of CD4 and CD8 T cells into the lungs of “immune” IL-15−/−mice was delayed in response toM. tuberculosischallenge. These findings demonstrate that efficient effector CD4 and CD8 T cells can be developed followingM. tuberculosisinfection in the absence of IL-15 but that recall T-cell responses may be impaired.
Induction of Strain-Transcending Immunity againstPlasmodium chabaudi adamiMalaria with a Multiepitope DNA Vaccine
Authors: Scorza T. , Grubb K. , Smooker P. , Rainczuk A. , Proll D. , Spithill T. W. 
Published: April 2005

ABSTRACTA major goal of current malaria vaccine programs is to develop multivalent vaccines that will protect humans against the many heterologous malaria strains that circulate in endemic areas. We describe a multiepitope DNA vaccine, derived from a genomicPlasmodium chabaudi adamiDS DNA expression library of 30,000 plasmids, which induces strain-transcending immunity in mice against challenge withP. c. adamiDK. Segregation of this library and DNA sequence analysis identified vaccine subpools encoding open reading frames (ORFs)/peptides of >9 amino acids [aa] (the V9+ pool, 303 plasmids) and >50 aa (V50+ pool, 56 plasmids), respectively. The V9+ and V50+ plasmid vaccine subpools significantly cross-protected mice against heterologousP. c. adamiDK challenge, and protection correlated with the induction of both specific gamma interferon production by splenic cells and opsonizing antibodies. Bioinformatic analysis showed that 22 of the V50+ ORFs were polypeptides conserved among three or morePlasmodiumspp., 13 of which are predicted hypothetical proteins. Twenty-nine of these ORFs are orthologues of predictedPlasmodium falciparumsequences known to be expressed in the blood stage, suggesting that this vaccine pool encodes multiple blood-stage antigens. The results have implications for malaria vaccine design by providing proof-of-principle that significant strain-transcending immunity can be induced using multiepitope blood-stage DNA vaccines and suggest that both cellular responses and opsonizing antibodies are necessary for optimal protection againstP. c. adami.
ON ASTUMIAN'S PARADOX
Authors: BEHRENDS EHRHARD 
Published: April 2005

An Astumian game is defined by a finite Markov chain with state space S with precisely two absorbing states, the winning and the losing state. The other states are transient, one of them is the starting position. The game is said to be losing (respectively fair respectively winning) if the probability to be absorbed at the winning state is smaller than 0.5 (respectively = 0.5 respectively larger than 0.5). Astumian's paradox states that there are losing games on the same state space S a stochastic mixture of which is winning. (By "stochastic mixture" we mean that in each step one decides with the help of a fair coin whether to use the transition probabilities of the first or the second game.) Most of our results concern fair games. Mixtures are systematically investigated. Rather surprisingly, the winning probability of the mixture of fair games can be arbitrarily close to zero (or to one). Even more counter-intuitive are examples of definitely losing games (this means that the winning probability is exactly zero) such that the winning probability of the mixture is arbitrarily close to one. We show, however, that such extreme examples are possible only if one tolerates huge running times of the game. As a natural generalization one can also consider arbitrary mixtures: the fair coin is replaced by a biased one, with probability λ respectively 1-λ one plays with the first respectively the second game. It turns out that fair games exist such that — depending on the choice of λ — the λ-mixture can be fair, losing or winning.
Political Structure, Status Mobility, and Economic Growth in Imperial and Modern China
Authors: Brown Richard Harvey 
Published: April 2005

AbstractVirtually all theorists agree that one indispensable antecedent of economic development is the existence of innovators who discover and implement better ways of organizing the resources of production and exchange. Such an emphasis on entrepreneurial innovation and investment has characterized economic thought since Adam Smith, and it was voiced again in a modified form by Joseph Schumpeter:The slow and continuous increase in time of the national supply of productive means and savings is obviously an important factor in explaining the course of economic history through the centuries, but it is overshadowed by the fact that development consists primarily in employing existing resources in a different way, in doing new things with them (1949:68).
Age structure in two populations of Triturus vittatus ophryticus at different altitudes
Authors: Kutrup Bilal , Yilmaz Nurhayat , Bulbul Ufuk 
Published: April 2005

AbstractWe investigated age structure by skeletochronology in two breeding populations of Triturus vittatus ophryticus inhabiting altitudes ranging from 300 m (in Gurbulak) to 1300 m (in Hidirnebi) in northeastern Turkey. The mean age was 4 years (maximum 10) in Gurbulak population and 8 (maximum 16) in Hidirnebi population. In the lowland population, minimum age at maturation was two to three years while it was four years in the highland population. The mean snout-vent length of the populations was significantly different and we found no correlation between age and snout-vent length except for females of Gurbulak. Sexual dimorphism in body size and weight was detected in both populations.
Microarray karyotyping of commercial wine yeast strains reveals shared, as well as unique, genomic signatures
Authors: Dunn Barbara , Levine R Paul , Sherlock Gavin 
Published: April 2005

Abstract
Background
Genetic differences between yeast strains used in wine-making may account for some of the variation seen in their fermentation properties and may also produce differing sensory characteristics in the final wine product itself. To investigate this, we have determined genomic differences among several Saccharomyces cerevisiae wine strains by using a "microarray karyotyping" (also known as "array-CGH" or "aCGH") technique.

Results
We have studied four commonly used commercial wine yeast strains, assaying three independent isolates from each strain. All four wine strains showed common differences with respect to the laboratory S. cerevisiae strain S288C, some of which may be specific to commercial wine yeasts. We observed very little intra-strain variation; i.e., the genomic karyotypes of different commercial isolates of the same strain looked very similar, although an exception to this was seen among the Montrachet isolates. A moderate amount of inter-strain genomic variation between the four wine strains was observed, mostly in the form of depletions or amplifications of single genes; these differences allowed unique identification of each strain. Many of the inter-strain differences appear to be in transporter genes, especially hexose transporters (HXT genes), metal ion sensors/transporters (CUP1, ZRT1, ENA genes), members of the major facilitator superfamily, and in genes involved in drug response (PDR3, SNQ1, QDR1, RDS1, AYT1, YAR068W). We therefore used halo assays to investigate the response of these strains to three different fungicidal drugs (cycloheximide, clotrimazole, sulfomethuron methyl). Strains with fewer copies of the CUP1 loci showed hypersensitivity to sulfomethuron methyl.

Conclusion
Microarray karyotyping is a useful tool for analyzing the genome structures of wine yeasts. Despite only small to moderate variations in gene copy numbers between different wine yeast strains and within different isolates of a given strain, there was enough variation to allow unique identification of strains; additionally, some of the variation correlated with drug sensitivity. The relatively small number of differences seen by microarray karyotyping between the strains suggests that the differences in fermentative and organoleptic properties ascribed to these different strains may arise from a small number of genetic changes, making it possible to test whether the observed differences do indeed confer different sensory properties in the finished wine.
Modulation of MAA-induced apoptosis in male germ cells: role of Sertoli cell P/Q-type calcium channels
Authors: Barone Fortunata , Aguanno Salvatore , D'Agostino Angela 
Published: April 2005

AbstractSpontaneous germ cell death by apoptosis occurs during normal spermatogenesis in mammals and is thought to play a role in the physiological mechanism limiting the clonal expansion of such cell population in the male gonad. In the prepubertal rat testis, the most conspicuous dying cells are pachytene spermatocytes, which are also the primary target of the apoptosis experimentally induced by the methoxyacetic acid (MAA). Since we have recently reported that Sertoli cells, the somatic component of the seminiferous epithelium, regulate not only germ cell viability and differentiation but also their death, we have further investigated the mechanism involved in such a control.In this paper we have used the protein clusterin, produced by Sertoli cells and associated with tissue damage or injury, as indicator of germ cell apoptosis in rat seminiferous tubules treated with MAA in the presence or in the absence of omega-agatoxin, a specific inhibitor of P/Q type voltage-operated calcium channels (VOCC's). We performed both a qualitative analysis of clusterin content and germ cell apoptosis by immunofluorescence experiments and a quantitative analysis by in situ end labelling of apoptotic germ cells followed by flow cytometry. The results obtained demonstrate that Sertoli cells modulate germ cell apoptosis induced by methoxyacetic acid also throughout the P/Q-type VOCC's.
Differential recruitment in a cluster randomized trial in primary care: the experience of the UK Back pain, Exercise, Active management and Manipulation (UK BEAM) feasibility study
Authors: Farrin Amanda , Russell Ian , Torgerson David , Underwood Martin 
Published: April 2005

Background Cluster randomized trials, which randomize groups of patients rather than individuals, are commonly used to evaluate healthcare interventions such as training programmes targeted at health professionals. This article reports the dangers of randomizing entire primary care practices when participants cannot be identified before randomization, as shown by a UK national trial. Method The UK BEAM trial, a national cluster randomized 322 factorial trial, was designed to evaluate three treatments for back pain in primary care: “active management”; randomized by practice; and spinal manipulation and exercise classes, both randomized by individual. Results Two hundred and thirty-one participants were recruited in the feasibility study, 165 (141% of expected recruitment) from active (management) practices but only 66 (54% of expected recruitment) from traditional (management) practices. The participants in active practices were significantly different from those in traditional practices, notably in suffering from milder back pain. Conclusions The feasibility study highlighted the dangers of randomizing clusters when individuals cannot be identified beforehand. Different numbers and types of participants were recruited in the two types of cluster. This differential recruitment led us to change the main trial design by abandoning practice level randomization. Instead all practices were trained in active management to maximize recruitment. Ideally cluster randomized trials should identify patients beforehand, to minimize the chance of selection bias. If this is not possible, patient recruitment should be independent in both intervention and control clusters. Pilot studies are especially important for cluster randomized trials, to identify unforeseen problems.
The use of random effects models to allow for clustering in individually randomized trials
Authors: Lee Katherine J , Thompson Simon G 
Published: April 2005

Background We describe different forms of clustering that may occur in individually randomized trials, where the observed outcomes for different individuals cannot be regarded as independent. We propose random effects models to allow for such clustering, across a range of contexts and trial designs, and investigate their effect on estimation and interpretation of the treatment effect. Methods We apply our proposed models to two individually randomized trials with potential for clustering, a trial of teleconsultation in hospital referral (the main outcome being offer of a further hospital appointment) and a trial of exercise therapy delivered by physiotherapists for low back pain (the outcome being a back pain score). Extensions to the methods include the possibility of explaining heterogeneity between clusters using cluster level characteristics and the potential dilution of cluster effects due to noncompliance. Results In the teleconsultation trial, the odds ratio was significant (1.52, 95% CI 1.27 to 1.82) when clustering was ignored, but smaller and nonsignificant (1.36, 95% CI 0.85 to 2.13) when clustering by hospital consultant was taken into account. The 95% range of estimated treatment effects across consultants was from 0.21 to 8.76. This variability was only partially explained by the specialty of the consultant. In the back pain trial, although there was an overall benefit of exercise (change of 20.51 points on the back pain score) and little evidence of clustering, the estimated treatment effects for different physiotherapists ranged from 21.26 to +0.26 points. Conclusions Clustering is an important issue in many individually randomized trials. Ignoring it can lead to underestimates of the uncertainty and too extreme P-values. Even when there is little apparent heterogeneity across clusters, it can still have a large impact on the estimation and interpretation of the treatment effect.
Engine valve and seat insert wear depending on speed changes
Authors: Chun Keyoung Jin , Hong Jae Soo 
Published: April 2005

The minimization of valve and seat insert wear is a critical factor for consideration in the pursuit of engine performance improvement. In order to achieve this goal, an innovative simulator was developed with the ability to generate and control high temperatures up to 900°C and various frequencies up to 80 Hz during motion, just as in the case of an actual vehicle engine. This wear simulator is considered to be a valid reproduction of the engine valve and seat insert wear process operating with various speeds during engine activity. This work focuses on the different degrees of wear at three different test frequencies (10 Hz, 25 Hz, and multi-hertz). In this study, the seat insert's exterior surface temperature was controlled at 350 °C, the number of cycles was 2.1×106and the test load was 1960 N. The wear depth was measured before and after testing using a confocal laser microscope. It was found that higher frequencies caused a greater degree of wear than lower frequencies under identical test conditions (temperature, valve displacement, number of cycles, and test load). It was intended that an actual vehicle engine be used to perform a similar test, in order that the multi-hertz test, using a combination of the 10 and 25 Hz frequencies be applied. In the wear mechanism, adhesive wear, shear strain, abrasive wear, and surface fatigue wear were observed.
Modelling the wet deposition of reduced nitrogen over the British Isles using a Lagrangian multi‐layer atmospheric transport model
Authors: Fournier N. , Weston K. J. , Dore A. J. , Sutton M. A. 
Published: April 2005

AbstractWet deposition of reduced nitrogen is estimated for the United Kingdom using a Lagrangian long‐term, long‐range atmospheric transport model. Such long‐range transport models are used to develop emission‐control strategies to combat environmental acidification in the sensitive regions of the United Kingdom and Europe. These models currently consider the wet deposition as a loss term using scavenging rates and a simple seeder–feeder effect. The seeder–feeder effect is assumed to be the main process producing orographic precipitation since the majority of British Isles annual rainfall falls in frontal events. This paper focuses on the analysis of different parametrizations of the removal process by wet deposition. It is shown that the seeder–feeder effect is very dependent on flow direction. Therefore, a model of directional orographic enhancement of precipitation is developed to simulate this effect. A revised formulation of the wet deposition parametrization is suggested, incorporating the directional orographic precipitation produced with this model. This new formulation also takes into account the larger concentrations of ions dissolved in rain water measured in mountainous areas. Moreover, a new representation of the wet deposition process is developed by considering explicitly the mixing layer's depth calculated in the model. The results from the atmospheric model, with these revised parametrizations of the wet deposition, are then compared with measured wet deposition of reduced nitrogen. Firstly, with the new directional orographic rainfall, the modelled United Kingdom reduced nitrogen wet deposition budget is still underestimated but an increased correlation with measurements is obtained. Secondly, the inclusion of the calculated mixing layer's depth leads to a considerable improvement in the modelled reduced nitrogen wet deposition budget compared with measurements. Copyright © 2005 Royal Meteorological Society.
Dysprealbuminemic Hyperthyroxinemia in a Patient with Hyperthyroid Graves Disease
Authors: Cameron Scott J , Hagedorn Judith C , Sokoll Lori J , Caturegli Patrizio , Ladenson Paul W 
Published: April 2005

AbstractRare mutant forms of circulating albumin and prealbumin [transthyretin (TTR)] have increased binding affinity for thyroxine (T4). Patients with these variant plasma proteins, as a result of inherited mutations or as a paraneoplastic phenomenon, typically present with increased serum total T4 and, by some assay methodologies, an increased free T4 as well. Although these individuals are, in fact, euthyroid, nonspecific symptoms may lead to inappropriate treatment for hyperthyroidism. We present a 34-year-old woman in whom a mutant form of TTR with increased T4 binding affinity and coexisting Graves disease was present. Subsequent 131I therapy led to development of postablative hypothyroidism, which was obscured by her higher serum free T4 concentration. Circulating thyroid-binding globulin (TBG), albumin, and TTR concentrations were all within their respective reference limits. A T4-binding protein panel confirmed that TTR-bound T4 was significantly increased, whereas TBG- and albumin-bound T4 was normal, indicating that this patient had euthyroid dysprealbuminemic hyperthyroxinemia, which had been masked by the initial presentation of hyperthyroidism. These findings indicate that hypothyroidism can be masked by coexisting euthyroid dysprealbuminemic hyperthyroxinemia.