julilili42/papers huggingface dataset:
Does selected ecological evidence give a true picture of HIV transmission in Africa?
2004-07-01

Current reconsideration of the contributions of various modes of transmission to HIV epidemics in sub-Saharan Africa has important implications for HIV prevention. In recent reviews, we argue that accumulated evidence supports the hypothesis that unsafe health care fuels Africa's HIV epidemics. In response, critics have presented selected ecological evidence — age and sex distribution of HIV infections and geographic distribution of hepatitis C virus infections — to support the conventional hypothesis that sexual contact accounts for most HIV infections. In this communication, we examine critics' evidence and arguments. Critics ignore or reject important evidence including, for example, large numbers of unexplained HIV infections in children, strong associations between incident HIV and injections, and genetically-linked infections in persons with no known sexual contact. We urge that research projects in Africa disclose unpublished relevant evidence on risks for incident HIV. In any case, because each iatrogenic infection causes subsequent linked infections, the impact of HIV transmission through health care has been underestimated. We commend the emerging consensus to improve the safety of health care delivery. In countries with generalized HIV epidemics, we urge public education about the risks for HIV acquisition from unsterile health care.
The Tübingen approach: identification, selection and validation of tumor-associated HLA peptides for cancer therapy
2004-07-01

There is substantial need for molecularly defined tumor antigens to prime cytotoxic T cells in vivo for cancer immunotherapy, especially in the case of tumor entities for which only a few tumor antigens have been defined so far. In this review, we present the “Tubingen approach” to identify, select, and validate large numbers of MHC/HLA class I–associated peptides derived from tumor-associated antigens. Step 1 is the identification of naturally presented HLA-associated peptides directly from primary tumor cells. Step 2 is selection of tumor-associated peptides from step 1 by differential gene expression analysis and data mining. Step 3 is validation of selected candidates by monitoring in vivo T-cell responses in the context of patient-individualized immunizations. Our approach combines methods from genomics, proteomics, bioinformatics, and T-cell immunology. The aim is to develop effective immunotherapeutics consisting of multiple tumor-associated epitopes in order to induce a broad and specific immune response against cancer cells.
A CLINICAL RELEVANT PIG MODEL TO INVESTIGATE THE ACUTE LIVER FAILURE
2004-07-01

A252 Aims: Acute hepatic failure is a dramatic clinical syndrome that is associated with significant mortality despite advances in intensive care management and liver transplantation. Aim of this study was to evaluate treatment efficiency of maximum conventional intensive care therapy in a new pig model which is clinical relevant to simulate the situation of acute liver failure. Methods: Ten pigs underwent a total hepatectomy using a three-way prosthesis for reconstruction of the vena cava/vena portae continuity without any temporary extracorporal bypass. Blood loss was substituted with porcine erythrocyte concentrates and fresh frozen plasma. Posthepatectomy pigs were maintained under general anaesthesia and treated with noradrenalin, furosemide, hydroxyethylstarch 6%, sodiumchloride 0.9% glucose 20% under standard intensive care conditions. Electrocardiogram, direct blood pressure, urinary output, SO2 oximetry, core body temperature, lactate, blood gases and serum electrolytes, glucose were continuously monitored, Ammonia and liver depending clotting factors were measured every 12 hours. Death was defined as a decline of blood pressure under 40 mmHg. Results: Hemodynamic parameters remained stable during operation time, survival time was 36-89 hours (median 66h). All animals developed MOF, especially kidney and lung. Ammonia and lactate levels remained under forced diuresis at a level of 220 μg/dl and 5 mM, at time of death, levels of 4000 μg/dl and 16 mM were reached. Activity of liver depending clotting factors went down linear. Conclusions: This animal model with a conventional intensive care allows a long survival of the animals, even longer than most therapy studies with bioartificial liver devices.
Short-Term Radio-X-Ray Correlations of Cygnus X-1
2004-07-01

We analyze simultaneous radio-X-ray data of Cygnus X-l from the Ryle telescope (RT) and RXTE over more than 4 a. We show that apparent correlations on short time scales in the lightcurves of Cyg X-l are probably the coincidental outcome of white noise statistics. As a measure of correlation between radio and X-ray emission, we calculate the maximum cross-correlation coefficient, ccf, of simultaneous radio and X-ray lightcurves, which are rebinned to a resolution of 32 s and smoothed. Every single X-ray lightcurve segment is cross-correlated with the corresponding radio lightcurve, up to a maximum shift Δt = ±10 h.
Modeling of oxigen-neon dominated accretion disks in ultracompact X-ray binaries: 4U 1626-67
2004-07-01

We report on first results of computing synthetic spectra from H/He-poor accretion disks in ultracompact LMXBs. We aim at the determination of the chemical composition of the very low-mass donor star, which is the core of a former C/O white dwarf. The abundance analysis allows to draw conclusions on gravitational settling in WDs which is an important process affecting cooling times and pulsational g-mode periods.
Three-Dimensional Photoionization Modelling of the Hydrogen-Deficient Knots in the Planetary Nebula Abell 30
2004-07-01

We have constructed a photoionization model, using the three-dimensional Monte Carlo code MOCASSIN, for one of the hydrogen-deficient knots (J3) of the born-again planetary nebula Abell 30. The model consists of spherical knots, comprising a cold, dense, hydrogen-deficient core with very high metal abundances. The inner core, occupying 9.1 per cent of the total volume of the knot, is surrounded by a less dense hydrogen-deficient and metal-enriched gas envelope, with less extreme abundances. The envelope of the knot might have been formed by the mixing of the knot material with the surrounding nebular gas.&#13;\\n&#13;\\nThis bi-chemistry, bi-density model did not produce enough heating to match the fluxes of the collisionally excited emission lines (CELs) and of the optical recombination lines (ORLs) observed in the spectrum of the knot. We therefore included heating by photoelectric emission from dust grains in the thermal equilibrium calculations, and found that dust-to-gas ratios of 0.077 and 0.107 by mass for the central core and the envelope of the knot, respectively, are sufficient to fit the spectrum. Surprisingly, photoelectric emission from grains is the dominant source of heating in the hot envelope of the knot, while heating by photoionization of helium and heavy elements dominates in the cold core.&#13;\\n&#13;\\nWe obtain a good fit with the observations for most of the significant emission lines treated in our model. The two major discrepancies occurred for the [O II] 3727,29- Å doublet and the [N II] 6548,6584- Å lines, which are severely underestimated in our model. Recombination contributions could be significant and we included them for the O II transitions. However, this was not sufficient to resolve the discrepancy, due to the high collisional de-excitation rates in the dense core, where most of the recombination lines would be produced. This possibly highlights a weakness in using a discontinuous density distribution like ours, where in reality one might expect an intermediate phase to exist.&#13;\\n&#13;\\nThe chemical abundances inferred from our modelling of the central core region and of the envelope of the knot are, at least qualitatively, in agreement with the abundances derived by the empirical analysis of Wesson, Liu &amp; Barlow, although the discrepancies between the core and the envelope abundances that we find are less dramatic than those implied by the ORL and CEL empirical analysis. Our models also indicate, in agreement with the empirical analysis of Wesson et al., that the C/O ratio in the two regions of the knot is less than unity, contrary to theoretical predictions for born-again nebulae.
Organ-Specific T Cell Receptor Repertoire in Target Organs of Murine Graft-Versus-Host After Transplantation Across Minor Histocompatibility Antigen Barriers
2004-07-05

These results suggest that in the skin a limited number of persisting T cell clones maintains GvHD, whereas in the intestine, temporary expansions of different clones may fuel the process of GvHD. Strategies that eliminate tissue-specific T cells on the basis of their activational status rather than their V beta expression but at the same time preserve a broad, overall TCR repertoire will help to increase the efficacy and safety of allogeneic stem cell transplantation.
Targeted Disruption of the Protein Kinase SGK3/CISK Impairs Postnatal Hair Follicle Development
2004-07-08

Members of the serum- and glucocorticoid-regulated kinase (SGK) family are important mediators of growth factor and hormone signaling that, like their close relatives in the Akt family, are regulated by lipid products of phosphatidylinositol-3-kinase. SGK3 has been implicated in the control of cell survival and regulation of ion channel activity in cultured cells. To begin to dissect the in vivo functions of SGK3, we generated and characterized Sgk3 null mice. These mice are viable and fertile, and in contrast to mice lacking SGK1 or Akt2, respectively, display normal sodium handling and glucose tolerance. However, although normal at birth, by postpartum day 4 they have begun to display an unexpected defect in hair follicle morphogenesis. The abnormality in hair follicle development is preceded by a defect in proliferation and nuclear accumulation of β-catenin in hair bulb keratinocytes. Furthermore, in cultured keratinocytes, heterologous expression of SGK3 potently modulates activation of β-catenin/Lef-1–mediated gene transcription. These data establish a role for SGK3 in normal postnatal hair follicle development, possibly involving effects on β-catenin/Lef-1–mediated gene transcription.
Creating gas concentration gridmaps with a mobile robot
2004-07-08

This paper addresses the problem of mapping the features of a gas distribution by creating concentration gridmaps from the data collected by a mobile robot equipped with an electronic nose. By contrast to metric gridmaps extracted from sonar or laser range scans, a single measurement of the electronic nose provides information about a comparatively small area. To overcome this problem, a mapping technique is introduced that uses a Gaussian density function to model the decreasing likelihood that a particular reading represents the true concentration with respect to the distance from the point of measurement. This method is evaluated in terms of its suitability regarding the slow response and recovery of the gas sensors. The stability of the mapped features and the capability to use concentration gridmaps to locate a gas source are also discussed.
Adaptation of rescue robot behaviour in unknown terrains based on stochastic and fuzzy logic approaches
2004-07-08

The purpose of this article is to provide rescue robots with an adaptive behaviour during searching for victims in disasters such as fire, earthquake, flood, wars etc. This experimental research work took place in previously unknown dynamic indoor terrains. The main phases of this framework are; 1) modelling of robot behaviours/dynamics in collapsed environments, 2) designing an adaptive controller, which regulates robot longitudinal velocity and heading (collision avoidance) based on the obstacles distribution histogram, 3) prediction of robot behaviours in another unknown terrain. Two approaches have been used to design the adaptive controller: the first one is the stochastic control theory, based on Kalman filter algorithms. The second approach relies on fuzzy inference systems (FIS). Throughout this work, robot dynamics have been modelled using the auto regressive exogenous (ARX) scheme, while ARX model parameters have been identified using recursive least squares (RLS). This contribution presents a description and some discussion of the discrete Kalman filter, modelling techniques, and some discussion of robot behaviour analysis. Furthermore, the design of adaptive controllers using FIS-based techniques versus stochastic control systems bas been demonstrated.
Short‐Distance Reanalysis of Middle English Modals: Evidence from Ellipsis
2004-07-09

Abstract. This paper argues that the Middle English modals have a shorter distance to diachronically reanalyze to T than traditionally assumed. The claim essentially draws on the analysis of two elliptical constructions in whose licensing the premodals are unexpectedly involved if one assumes the standard account of their full lexical status. Specifically, VP‐ellipsis and directional PPs are investigated. The two phenomena have previously led to contradictory results regarding the status of the premodals. In the present account, an economy driven explanation is proposed, based on an intermediate projection which unifies the two phenomena and gives an account of the patterns of modal complementation.
Evolution strategies assisted by Gaussian processes with improved preselection criterion
2004-07-09

In many engineering optimization problems, the number of fitness function evaluations is limited by time and cost. These problems pose a special challenge to the field of evolutionary computation, since existing evolutionary methods require a very large number of problem function evaluations. One popular way to address this challenge is the application of approximation models as a surrogate of the real fitness function. We propose a model assisted evolution strategy, which uses a Gaussian process approximation model to preselect the most promising solutions. To refine the preselection process we determine the likelihood of each individual to improve the overall best found solution. Due to this, the new algorithm has a much better convergence behavior and achieves better results than standard evolutionary optimization approaches with less fitness evaluations. Numerical results from extensive simulations on several high dimensional test functions including multimodal functions are presented.
Developmental plasticity of NMDA receptor function in the retina and the influence of light
2004-07-09

Despite the early expression of NMDA receptors (NMDARs) in the retina, not much is known about their regulation and involvement in plasticity processes during retinal development and synapse formation. Here we report that NMDAR function in the inner retina is developmentally regulated and controlled by ambient light condition. A prominent down‐regulation after eye opening of NMDAR function was observed in rat retinal ganglion cells (RGCs), which was prevented by dark rearing the animals for 1 month but was again induced by subsequent light exposure. As shown by molecular analysis of single RGCs, alterations in the subunit composition of NMDAR did not account for the light‐dependent regulation of NMDAR function. Immunocytochemistry showed no differences in the NMDAR protein expression pattern between normal and dark‐reared animals. In conclusion, our data clearly demonstrate that NMDAR function is modulated during periods of retinal plasticity independent of structural alterations in its subunit composition and thus different from mechanisms observed in higher visual centers.
Identification of an HLA‐DR‐restricted peptide epitope with a promiscuous binding pattern derived from the cancer testis antigen HOM‐MEL‐40/SSX2
2004-07-09

Abstract The SSX2 gene encodes the tumor‐specific antigen HOM‐MEL‐40/SSX2 expressed in a broad spectrum of tumors of different origin, against which humoral and CD8 + T‐cell‐mediated MHC‐I‐restricted responses have been demonstrated. Searching for promiscuous MHC‐II‐restricted peptides that might be suitable as a CD4 + stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified a HOM‐MEL‐40/SSX2‐derived pentadecamer epitope (p45–59) that induced specific CD4 + T‐cell responses restricted by the HLA‐DRB1 subtypes *0701, *1101 and *1302 that have a cumulative prevalence of ∼ 25% in the Caucasian population. The CD4 + ‐mediated response against p45–59 and its DR restriction was demonstrated by inhibition with anti‐CD4 and HLA‐DR antibodies, respectively, and by blocking experiments using HLA‐specific antibodies. The natural processing and presentation of p45–59 was demonstrated by recognition of the SSX2 + melanoma cell line Me 275 as well as autologous and allogeneic dendritic cells pulsed with whole‐protein SSX2 by T cells with specificity for p45–59. p45–59 was able to induce responses in 3/6 breast cancer patients and 1/5 healthy controls. No correlation was found between CD4 + T‐cell responses against p45–59 reactivity and anti‐SSX2 antibody titers in the serum of patients, suggesting that CD4 + and B‐cell responses are regulated independently. p45–59 holds promise as a broadly applicable peptide vaccine for patients with SSX2‐positive neoplasms. © 2004 Wiley‐Liss, Inc.
Clustering gene expression data with memetic algorithms based on minimum spanning trees
2004-07-09

With the invention of microarray technology, researchers are capable of measuring the expression levels of ten thousands of genes in parallel at various time points of the biological process. During the investigation of gene regulatory networks and general cellular mechanisms, biologists are attempting to group genes based on the time-depending pattern of the obtained expression levels. In this paper, we propose a new memetic algorithm - a genetic algorithm combined with local search-based on a tree representation of the data - a minimum spanning tree minus; for clustering gene expression data. The combination of both concepts is shown to find near-optimal solutions quickly. Due to the minimum spanning tree representation of the data, our algorithm is capable of finding clusters of different shapes. We show that our approach is superior in solution quality compared to classical clustering methods.
Double Cyclometalation: Implications for C—H Oxidative Addition with PCP Pincer Compounds of Iridium
2004-07-12

Treatment of 4-X-C6H3-2,6-(CH2P'Bu2)2 (X = H (1), NO2 (2), MeO (3)) with IrCl3 nH2O in 2-propanol/water generates the corresponding cyclometalated pincer chlorohydrido iridium complexes (1a - 3a). In the case of 3, a second intramolecular oxidative addition reaction of one of the t-butyl C-H bonds to the Ir(III) center, followed by the reductive elimination of H2, gives the novel doubly metalated compound 3b, which is stable to air and water. Comparative electrochemical studies of 1a and 3a establish an equilibrium between the pincer chlorohydrido compound and the doubly metalated complexes 1b, 3b and H2. A square scheme can be used to describe the relationship between the redox couples and solution equilibria. Interestingly the oxidation product 1b+ undergoes a faster follow-up reaction as 3b+. The unusual stability of the doubly metalated complex was supported by DFT calculations at different levels of theory on model compounds.
Detection of high‐risk human papillomavirus E6 and E7 oncogene transcripts in cervical scrapes by nested RT‐polymerase chain reaction
2004-07-13

Abstract The oncogenic potential of the high‐risk human papillomavirus (HPV) genotypes (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) depends on the expression of the two viral oncogenes E6 and E7. Thus, the detection of HPV E6/E7 oncogene transcripts could serve as a factor in the evaluation of a risk of development of cervical intraepithelial neoplasia (CIN) and its progression to cervical cancer. A nested RT‐PCR assay for the detection of E6/E7 oncogene transcripts of all known high‐risk HPV genotypes was established. In the study described, 779 high‐risk HPV‐DNA‐positive cervical scrapes exhibiting all grades of CIN, including non‐dysplastic cervical mucosa (CIN 0), were examined. Spliced E6/E7 oncogene transcripts of all the high‐risk HPVs were detected in numerous samples, with an overall detection rate of 47%. In 227 cases with agreement between the cytologic and histologic findings, the prevalence increased with lesion severity: CIN 0, 18%; CIN I, 58%; CIN II, 77%; CIN III, 84%. Multiple transcriptionally active high‐risk HPVs were detected in 12% (33/279) of patients with multiple high‐risk HPV infections. This work sets the stage for a prospective follow‐up study currently being undertaken to evaluate the prognostic relevance of the detection of high‐risk HPV E6/E7 oncogene transcripts for the persistence of a high risk HPV infection, and the possible evolution and further development of a CIN. Future applications of the assay described may include the monitoring of women in studies investigating antiviral treatment or vaccination. J. Med. Virol. 74:107–116, 2004. © 2004 Wiley‐Liss, Inc.
Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: a pooled analysis of two randomised trials
2004-07-13

To study the role of single agent carboplatin chemotherapy in patients with metastatic seminoma based on the data from two randomised trials. In subgroup analyses in patients with different disease characteristics, the outcome treated with either single agent carboplatin or cisplatin-based combination chemotherapy was compared. Individual patient data from two randomised European trials involving patients with metastatic seminoma were gathered. The primary endpoint for all analyses was progression-free survival. The source data of 361 patients, 184 treated with cisplatin-based combinations and 177 treated with carboplatin single agent therapy, were entered into the analysis. Patient characteristics were comparable among the cisplatin-based and the carboplatin single agent treated patient groups with lymph nodes and lungs being the most frequent metastatic sites in 92 and 8% of patients, respectively. Overall, patients treated with single agent carboplatin had an inferior 5-year overall (89 and 94%; P=0.09) and progression-free survival rate (72 and 92%; P< 0.0001) compared with patients receiving cisplatin-based combinations. For all investigated subgroups (based on age, prior radiation therapy, metastatic sites), carboplatin single agent therapy was found to be inferior to cisplatin-based combination chemotherapy. In conclusion, carboplatin single agent therapy cannot be recommended as standard treatment for any patient subgroup with advanced metastatic seminoma and cisplatin-based combination regimens remain the standard of care.
Influence of human recombinant interferon- 2a (rhIFN- 2a) on altered lymphocyte subpopulations and monocytes in Behcet's disease
2004-07-13

These results implicate the participation of NK cells and gammadelta T cells, especially CD8(+)/gammadelta T cells, in the pathogenesis of BD and may explain one mechanism by which IFN-alpha2a exerts therapeutic effects. Alternatively, they may result indirectly from remission induction by IFN-alpha2a. The reduced expression of HLA class I on monocytes in HLA-B*51-positive patients might reflect an impaired expression of and antigen presentation by HLA-B*51.