julilili42/papers huggingface dataset:
Sensitive detection of human cytomegalovirus peptide–specific cytotoxic T-lymphocyte responses by interferon-γ–enzyme-linked immunospot assay and flow cytometry in healthy individuals and in patients after allogeneic stem cell transplantation
2002-05-15

Reconstitution of human cytomegalovirus (HCMV)–specific cytotoxic T lymphocytes (CTLs), predominantly directed against pp65, provides protective immunity for the development of HCMV disease after allogeneic stem cell transplantation (SCT). To define pp65-derived CTL epitopes that would allow sensitive detection of HCMV-specific immune reconstitution, a computer-based epitope prediction was performed. Peptide-specific CTL responses were assessed by interferon-γ release. With this approach, pp65-derived epitopes presented by the HLA alleles A*0101, A*0201, A*1101, and B*0702 were identified. The frequency of CTLs in healthy HCMV-seropositive individuals ranged from about 0.1% to 3.3% of all CD8+ T cells. In patients at risk of HCMV infection after allogeneic SCT, HCMV-peptide–specific CTLs were found in 14 of 19 patients at a median of 90 days after SCT (range, 35-234 days) and HCMV-antigen–specific CD4+ T lymphocytes in 11 of 18 patients at a median of 90 days after SCT (range, 35-&amp;gt;180 days). Peak counts of peptide-specific CD8+ T cells ranged from 0.14 to 60.6 cells/μL; those of protein-specific CD4+ T cells ranged from 0.64 to 18.97 cells/μL. Reconstitution of HCMV-peptide–specific CD8+ T cells and protein-specific CD4+ T cells was associated with clearance of HCMV infection (r2 = 0.89, P &amp;lt; .0001 and r2 = 0.61, P = .0045, respectively). HCMV infection recurred after documentation of HCMV-specific T-cell reconstitution (n = 4) when immunosuppression was intensified. Patients in whom late-onset HCMV disease developed lacked HCMV-protein–specific T cells at 3 months after SCT. In conclusion, prospective monitoring of HCMV-specific CD4+ and CD8+ T-cell reconstitution can be performed rapidly by using flow cytometry after specific stimulation with HCMV peptides and proteins and might help to further improve clinical management of HCMV infection after allogeneic SCT.
Human platelets express heat shock protein receptors and regulate dendritic cell maturation
2002-05-15

Immunizations using the endoplasmic reticulum–resident heat shock protein Gp96 induce specific immune responses. Specificity is based on the major histocompatibility complex class I–restricted cross-presentation of Gp96-associated peptides derived from endogenous proteins. Initiation of the immune response depends on the ability of Gp96 to induce the production of proinflammatory cytokines by macrophages and dendritic cells (DCs) and of their maturation in a fashion presumably independent of associated peptide. Both events are mediated by Gp96 receptors on antigen-presenting cells. It is known that Gp96 is released from cells at necrosis induced, for example, by virus infection. Although this event supports the efficient induction of immune responses, it might also interfere with processes that are susceptible to chronic inflammation, such as wound healing after tissue damage. Therefore, Gp96-mediated stimulation of the immune system requires tight regulation. Here we show that human thrombocytes specifically interact with Gp96 and that binding of Gp96 to platelets is enhanced more than 10-fold on activation by thrombin. Gp96 interferes with neither thrombin-induced platelet activation nor platelet aggregation. However, the presence of platelets during Gp96-mediated DC activation reduces the secretion of proinflammatory cytokines and the activation of DCs. This effect is independent of soluble platelet factors and cell-to-cell contact between DCs and thrombocytes. Thus, we provide evidence for a regulatory mechanism that neutralizes Gp96 molecules systemically, especially in the blood. This effect might be of significance in wounds in which chronic inflammation and immune responses against autoantigens have to be prevented.
Perflubron Reduces Lung Inflammation in Respiratory Syncytial Virus Infection by Inhibiting Chemokine Expression and Nuclear Factor–κB Activation
2002-05-15

Airway mucosa inflammation plays a critical role in the pathogenesis of lower respiratory tract infections caused by respiratory syncytial virus (RSV), the major etiologic agent of bronchiolitis in infancy. Type and intensity of cellular infiltration are dictated by inflammatory chemokines, which are rapidly and abundantly induced in lung tissue by RSV. This process is, to a large extent, transcriptionally regulated by RSV-mediated activation of the nuclear factor-kappa B. The administration of a perfluorocarbon (PFC) liquid, such as perflubron, during partial liquid ventilation improves lung function and also reduces inflammation. In this study we demonstrate that treatment of BALB/c mice with perflubron intranasally 6 hours after RSV infection significantly inhibited lung cellular inflammation as well as the expression of the chemokines RANTES, MIP-1 alpha, MIP-1 beta, and MIP-2, compared with phosphate-buffered saline-treated control mice. However, perflubron treatment did not affect RSV replication. Strikingly, treatment with perflubron abrogated nuclear factor-kappa B activation in lung of RSV-infected mice. These results demonstrate a novel mechanism by which PFC may exert antiinflammatory activity and suggest that partial liquid ventilation with PFC may be considered in future clinical trials for infants with severe RSV infections requiring mechanical ventilation.
Intrinsic spin valves in the layered manganite La1.4Sr1.6Mn2O7
2002-05-15

We report on transport measurements on micron-sized mesa structures fabricated on single crystals of the layered manganite La1.4Sr1.6Mn2O7, probing the magnetoresistance of a single magnetic domain for current transport perpendicular to the layers. In magnetic fields applied perpendicular to the layers switching of the magnetoresistance was observed in fields well below 0.4 T, while for parallel fields it decreased continuously. We interpret these observations within the framework of spin-polarized tunneling between adjacent MnO2 bilayers forming an intrinsic stack of spin valves.
Use of a Modified Cyclodextrin Host for the Enantioselective Detection of a Halogenated Diether as Chiral Guest via Optical and Electrical Transducers
2002-05-17

In an alkaline rebreathing circuit, the inhalation anesthetic sevoflurane degrades into at least two products, one of them being the chiral halodiether 1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane (halodiether B). Using octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-y-cyclodextrin (Lipodex E) as chiral host diluted in the polysiloxane PS255, an exceptional large chiral separation factor alpha of 9.7 at 30 degrees C was found for halodiether B by capillary gas chromatography (cGC). Hence, the interaction of the single enantiomers and the racemic mixture of the halodiether B with Lipodex E was selected as a model system to study the enantioselective recognition by thickness shear mode resonators (TSMR), surface acoustic wave sensors, surface plasmon resonance (SPR), and reflectometric interference spectroscopy. Further investigations of the recognition process by using chemical sensors confirmed the preferential enrichment of the S-enantiomer resulting in 9-fold higher signals. Based on the distinction between enantioselective and nonenantioselective sorption, thermodynamic complexation constants of the single enantiomers with Lipodex E could be determined. The difference in Gibbs free energy -deltaE2,E1(deltaG) of the complexation of the enantiomers of halodiether B with pure Lipodex E was determined at 30 degrees C by TSMR and SPR to be 5.7 or 5.9 kJ/mol, respectively, agreeing well with that determined by cGC, i.e., 5.7 kJ/mol at 30 degrees C.
From Imidazoles to Pyrimidines:  New Inhibitors of Cytokine Release
2002-05-17

On the basis of model imidazole inhibitors of cytokine release, a series of novel pyridinyl pyrimidine derivatives was prepared and tested on their ability to inhibit the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) from peripheral blood mononuclear cells (PBMC) and human whole blood. In the pyrimidine series, structure-activity relationships (SARs) similar to those of the imidazole series were found, although generally pyrimidine compounds were less potent. Modification of the substituent at the 2 position of the pyrimidine led to the most active compound 14 which inhibited release of TNF-alpha (IC(50) = 3.2 microM) and IL-1beta (IC(50) = 2.3 microM) from PBMC as effectively as the model imidazole inhibitor ML 3163 (TNF-alpha, IC(50) = 3.7 microM; IL-1beta, IC(50) = 0.9 microM). Screening in an isolated enzyme assay revealed both imidazole and pyrimidine compounds as inhibitors of p38 MAP (mitogen-activated protein) kinase.
Zeeman tomography of magnetic white dwarfs, I. Reconstruction of the\\n field geometry from synthetic spectra
2002-05-17

We have computed optical Zeeman spectra of magnetic white dwarfs for field\\nstrengths between 10 and 200MG and effective temperatures between 8000 and\\n40000K. They form a database containing 20628 sets of flux and circular\\npolarization spectra. A least-squares optimization code based on an\\nevolutionary strategy can recover relatively complex magnetic field topologies\\nfrom phase-resolved synthetic Zeeman spectra of rotating magnetic white dwarfs.\\nWe consider dipole and quadrupole components which are non-aligned and shifted\\noff-centre. The model geometries include stars with a single high-field spot\\nand with two spots separated by approx. 90 degrees. The accuracy of the\\nrecovered field structure increases with the signal-to-noise ratio of the input\\nspectra and is significantly improved if circular polarization spectra are\\nincluded in addition to flux spectra. We discuss the strategies proposed so far\\nto unravel the field geometries of magnetic white dwarfs.\\n
Myelopathy in primary Sjögren's syndrome: diagnostic and therapeutic aspects
2002-05-20

We report a patient with a myelopathy in primary Sjögren's syndrome, proven by salivary gland biopsy and specific antibodies. Under steroid medication, the patient had a remitting and relapsing clinical course. The severity of clinical symptoms correlated with a transient contrast uptake in spinal magnetic resonance imaging. Under a treatment with azathioprine and prednisone the patient has suffered no relapse within the last 20 months. Although this is only a case report, the combination of azathioprine and prednisone may be a valuable medication in chronic cases of Sjögren's syndrome with neurologic symptoms.
Investigation of photon beam output factors for conformal radiation therapy$mdash$Monte Carlo simulations and measurements
2002-05-21

The purpose of this study was to investigate beam output factors (OFs) for conformal radiation therapy and to compare the OFs measured with different detectors with those simulated with Monte Carlo methods. Four different detectors (diode, diamond, pinpoint and ionization chamber) were used to measure photon beam OFs in a water phantom at a depth of 10 cm with a source-surface distance (SSD) of 100 cm. Square fields with widths ranging from 1 cm to 15 cm were observed; the OF for the different field sizes was normalized to that measured at a 5 cm x 5 cm field size at a depth of 10 cm. The BEAM/EGS4 program was used to simulate the exact geometry of a 6 MV photon beam generated by the linear accelerator, and the DOSXYZ-code was implemented to calculate the OFs for all field sizes. Two resolutions (0.1 cm and 0.5 cm voxel size) were chosen here. In addition, to model the detector four kinds of material, water, air, graphite or silicon, were placed in the corresponding voxels. Profiles and depth dose distributions resulting from the simulation show good agreement with the measurements. Deviations of less than 2% can be observed. The OF measured with different detectors in water vary by more than 35% for 1 cm x 1 cm fields. This result can also be found for the simulated OF with different voxel sizes and materials. For field sizes of at least 2 cm x 2 cm the deviations between all measurements and simulations are below 3%. This demonstrates that very small fields have a bad effect on dosimetric accuracy and precision. Finally, Monte Carlo methods can be significant in determining the OF for small fields.
Epigenetic control of the E‐cadherin gene (CDH1) by CpG methylation in colectomy samples of patients with ulcerative colitis
2002-05-22

Abstract E‐cadherin belongs to the cadherin family of calcium‐dependent cell‐adhesion molecules. The cadherins play an essential role in biological processes such as ordering of cell sorting, migration, and differentiation, and their malfunctioning is connected with neoplasia. Neoplastic progression in patients with chronic ulcerative colitis is characterized by the development of epithelial dysplasia. Transcriptional silencing of tumor‐suppressor genes by promoter methylation has been observed in different types of human cancers and dysplasia. To explore the mode of E‐cadherin regulation, 156 biopsy samples from 26 patients with long‐standing ulcerative colitis were screened. To detect the methylation status of our samples, a methylation‐specific PCR was applied. Methylation of the E‐cadherin ( CDH1 ) promoter was detected in 93% of the patients with dysplastic biopsy samples, in contrast to only 6% of the patients without dysplasia ( P &lt; 0.001). We also examined the level of synthesis of E‐cadherin protein by immunohistochemical staining in different paraffin‐embedded samples of dysplastic and non‐dysplastic origin in a subset of our patients. Samples with dysplasia displayed reduced levels, whereas samples without dysplasia revealed normal E‐cadherin protein synthesis. These results show that the E‐cadherin promoter is subjected to epigenetic control in colorectal ulceration. Obviously, this event may play an important role in the progression from chronic inflammation to colorectal cancer. For this reason, methylation of the CDH1 promoter is an attractive new biomarker for detecting ulcerative colitis patients with a high risk for developing colorectal cancers. © 2002 Wiley‐Liss, Inc.
Mismatch responses to randomized gradient switching noise as reflected by fMRI and whole‐head magnetoencephalography
2002-05-23

Abstract The central auditory system of the human brain uses a variety of mechanisms to analyze auditory scenes, among others, preattentive detection of sudden changes in the sound environment. Electroencephalography (EEG) and magnetoencephalography (MEG) provide a measure to monitor neuronal cortical currents. The mismatch negativity (MMN) or field (MMNm) reflect preattentive activation in response to deviants within a sequence of homogenous auditory stimuli. Functional magnetic resonance imaging (fMRI) allows for a higher spatial resolution as compared to the extracranial electrophysiological techniques. The image encoding gradients of echo planar imaging (EPI) sequences, however, elicit an interfering background noise. To circumvent this shortcoming, the present study applied multi‐echo EPI mimicking an auditory oddball design. The gradient trains (SOA = 800 msec, 94.5 dB SPL, stimulus duration = 152 msec) comprised amplitude (−9 dB) and duration (76 msec) deviants in a randomized sequence. Moreover, the scanner noise was recorded and applied in a whole‐head MEG device to validate the properties of this specific material. Robust fMRI activation patterns emerged in response to the deviant gradient switching. Changes in amplitude activated the entire auditory cortex, whereas the duration deviants elicited right‐lateralized signal increase in secondary areas. The recorded scanner noise evoked reliably right‐lateralized mismatch MEG responses. Source localization was in accordance with activation of secondary auditory cortex. The presented paradigm provides a robust and feasible tool to study the functional anatomy of early cognitive auditory processing in clinical populations such as schizophrenia. Hum. Brain Mapping 16:190–195, 2002. © 2002 Wiley‐Liss, Inc.
Ecosystem Decay of Amazonian Forest Fragments: a 22‐Year Investigation
2002-05-28

Abstract: We synthesized key findings from the Biological Dynamics of Forest Fragments Project, the world's largest and longest‐running experimental study of habitat fragmentation. Although initially designed to assess the influence of fragment area on Amazonian biotas, the project has yielded insights that go far beyond the original scope of the study. Results suggest that edge effects play a key role in fragment dynamics, that the matrix has a major influence on fragment connectivity and functioning, and that many Amazonian species avoid even small (&lt;100‐m–wide) clearings. The effects of fragmentation are highly eclectic, altering species richness and abundances, species invasions, forest dynamics, the trophic structure of communities, and a variety of ecological and ecosystem processes. Moreover, forest fragmentation appears to interact synergistically with ecological changes such as hunting, fires, and logging, collectively posing an even greater threat to the rainforest biota.
ChemInform Abstract: Revised Crystal Structure of NbOCl3.
2002-05-28

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Rotational tunneling of NH4 and NH3D and dipolar interaction in (NH3.6D0.4)2PtCl6
2002-05-30

At 10% deuteration ammonium hexachloroplatinate still exhibits the cubic phase Fm3m of the protonated material at all temperatures. Rotational tunneling of the ammonium isomers NH4+ and NH3D+ was measured by neutron spectroscopy. At temperatures T⩾18 K the energies and intensities of the observed tunneling transitions agree with a statistical occurrence of ammonium isomers and a cubic environment. Below T=18 K there is no change of the NH4 spectrum while the NH3D transition adopts an unresolved broad intensity distribution before it transforms into a new structured low temperature spectrum. The intermediate spectrum is interpreted as fingerprint of a potential distribution of statistically distributed disordered NH3D ions interacting by long-range dipolar coupling. The low-temperature spectrum finds an explanation as frozen minimum energy configurations of coupled NH3D dipoles. A dipole moment of NH3D of 0.05 D can be derived from the difference of tunnel splittings.
Collection, Presentation and Analysis of Multimedia Data with Computers
2002-05-31

Der Fokus qualitativer Sozialforschung und der eingesetzten computergestutzten Forschungsinstrumente richtet sich immer noch weitgehend auf die Analyse verbaler Daten. Das Zusammenwachsen von Digitaltechnologien und traditionellen Technologien zur Video- und Audioaufzeichnung eroffnet neue Chancen fur qualitative Forschungsprozesse durch die Moglichkeit zur Analyse multicodaler Videodaten. Zugleich entstehen aber auch neue Anforderungen an Forschende und Forschungsinstrumente. Der Beitrag beschaftigt sich im ersten Teil mit Chancen und Grenzen der Nutzung multicodaler Daten fur die Analyse unter besonderer Berucksichtigung der Moglichkeiten, die sich durch den Einsatz von Digitaltechnologien bei der Erhebung und Analyse ergeben konnen. In einem zweiten Teil werden Hinweise fur Auswahl und Einsatz von Digitaltechnologien zur Aufnahme multicodaler Daten gegeben. Der dritte Teil des Beitrags beschaftigt sich mit Moglichkeiten der Datenaufbereitung fur die computerunterstutzte Analyse multicodaler Daten. Reine Transkriptionsverfahren werden eher fur deduktiv ausgerichtete Studien empfohlen. Die Integration von Videodaten als Datenquelle wird nur von wenigen fur die Datenanalyse entwickelten Programmen unterstutzt. Ein moglicher Weg um die Beschrankung auf diese Programme zu durchbrechen wird mit modular eingesetzten Analysewerkzeugen vorgeschlagen und an einem Beispiel verdeutlicht. URN: urn:nbn:de:0114-fqs0202165
Tight junctions of the blood-brain barrier: development, composition and regulation.
2002-06-01

1. The blood-brain barrier is essential for the maintenance and regulation of the neural microenvironment. The main characteristic features of blood-brain barrier endothelial cells are an extremely low rate of transcytotic vesicles and a restrictive paracellular diffusion barrier. 2. Endothelial blood-brain barrier tight junctions differ from epithelial tight junctions, not only by distinct morphological and molecular properties, but also by the fact that endothelial tight junctions are more sensitive to microenvironmental than epithelial factors. 3. Many ubiquitous molecular tight junction components have been identified and characterized including claudins, occludin, ZO-1, ZO-2, ZO-3, cingulin and 7H6. Signaling pathways involved in tight junction regulation include G-proteins, serine-, threonine- and tyrosine-kinases, extra and intracellular calcium levels, cAMP levels, proteases and cytokines. Common to most of these pathways is the modulation of cytoskeletal elements and the connection of tight junction transmembrane molecules to the cytoskeleton. Additionally, crosstalk between components of the tight junction- and the cadherin-catenin system of the adherens junction suggests a close functional interdependence of the two cell-cell contact systems. 4. Important new molecular aspects of tight junction regulation were recently elucidated. This review provides an integration of these new results.
The Endoplasmic Reticulum-resident Heat Shock Protein Gp96 Activates Dendritic Cells via the Toll-like Receptor 2/4 Pathway
2002-06-01

The heat shock protein Gp96 has been shown to induce specific immune responses. On one hand, this phenomenon is based on the specific interaction with CD91 that mediates endocytosis and results in major histocompatibility complex class I-restricted representation of the Gp96-associated peptides. On the other hand, Gp96 induces activation of professional antigen-presenting cells, resulting in the production of pro-inflammatory cytokines and up-regulation of costimulatory molecules by unknown mechanisms. In this study, we have analyzed the consequences of Gp96 interaction with cells expressing different Toll-like receptors (TLRs) and with bone marrow-derived dendritic cells from mice lacking functional TLR2 and/or TLR4 molecules. We find that the Gp96-TLR2/4 interaction results in activation of nuclear factor kappaB-driven reporter genes and mitogen- and stress-activated protein kinases and induces IkappaBalpha degradation. Bone marrow-derived dendritic cells of C3H/HeJ and more pronounced C3H/HeJ/TLR2(-/-) mice fail to respond to Gp96. Interestingly, activation of bone marrow-derived dendritic cells depends on endocytosis of Gp96 molecules. Our results provide, for the first time, the molecular basis for understanding the Gp96-mediated activation of antigen-presenting cells by describing the simultaneous stimulation of the innate and adaptive immune system. This feature explains the remarkable ability of Gp96 to induce specific immune responses against tumors and pathogens.