julilili42/papers huggingface dataset:
The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytes
2008-01-24

Abstract Diacylglycerides (DAGs) such as 1-oleoyl-2-acetyl-sn-glycerol (OAG) stimulate 5-lipoxygenase (5-LO) enzyme activity and function as agonists for human polymorphonuclear leukocytes (PMNL) to induce 5-LO product synthesis. Here, we addressed the role of endogenous DAG generation in agonist-induced 5-LO activation in human PMNL. Preincubation of PMNL with the phospholipase D (PLD) inhibitor 1-butanol potently suppressed 5-LO product synthesis induced by the Ca2+ ionophore A23187 or thapsigargin (TG) and blocked A23187-evoked translocation of 5-LO from the cytosol to the nuclear membrane, analyzed by subcellular fractionation as well as by indirect immunofluorescence microscopy. Tertiary-butanol, a rather poor inhibitor of PLD, caused only moderate suppression of 5-LO and hardly inhibited 5-LO translocation. Interestingly, 1-butanol failed to inhibit 5-LO product formation when PMNL were stimulated with OAG (30 μM). Moreover, coincubation of A23187- or TG-stimulated PMNL with OAG reversed inhibition of 5-LO product formation by 1-butanol in a concentration-dependent manner (EC50, ∼1 μM) and also restored 5-LO translocation. In addition, inhibition of phosphatidic acid phosphatase (PA-P) by propranolol or bromoenol lactone caused suppression of 5-LO product formation and of translocation, which could be reversed by addition of exogenous OAG. Together, our data suggest that in agonist-stimulated PMNL, the endogenous formation of DAGs via the PLD/PA-P pathway determines 5-LO activation.
Discovery of very high energy gamma-ray emission coincident with molecular clouds in the W 28 (G6.4-0.1) field
2008-01-25

Aims. Observations of shell-type supernova remnants (SNRs) in the GeV to multi-TeV γ-ray band, coupled with those at millimetre radio wavelengths, are motivated by the search for cosmic-ray accelerators in our Galaxy. The old-age mixed-morphology SNR W 28 (distance ~2 kpc) is a prime target due to its interaction with molecular clouds along its northeastern boundary and other clouds situated nearby. Methods. We observed the W 28 field (for ~40 h) at very high energy (VHE) γ-ray energies (E &gt; 0.1 TeV) with the HESS. Cherenkov telescopes. A reanalysis of EGRET E &gt; 100 MeV data was also undertaken. Results from the NANTEN 4 m telescope Galactic plane survey and other CO observations were used to study molecular clouds. Results. We have discovered VHE γ-ray emission (HESS J1801-233) coincident with the northeastern boundary of W 28 and a complex of sources (HESS J1800-240A, B and C) ~0.5° south of W 28 in the Galactic disc. The EGRET source (GRO J1801-2320) is centred on HESS J1801-233 but may also be related to HESS J1800-240 given the large EGRET point spread function. The VHE differential photon spectra are well fit by pure power laws with indices Γ ~2.3 to 2.7. The spectral indices of HESS J1800-240A, B, and C are consistent within statistical errors. All VHE sources are ~10′ in intrinsic radius except for HESS J1800-240C, which appears pointlike. The NANTEN 12CO(J = 1-0) data reveal molecular clouds positionally associating with the VHE emission, spanning a ~15 km s−1 range in local standard of rest velocity. Conclusions. The VHE/molecular cloud association could indicate a hadronic origin for HESS J1801-233 and HESS J1800-240, and several cloud components in projection may contribute to the VHE emission. The clouds have components covering a broad velocity range encompassing the distance estimates for W 28 (~2 kpc) and extending up to ~4 kpc. Assuming hadronic origin and distances of 2 and 4 kpc for cloud components, the required cosmic-ray density enhancement factors (with respect to the solar value) are in the range ~10 to ~30. If situated at 2 kpc distance, such cosmic-ray densities may be supplied by SNRs like W 28. Additionally and/or alternatively, particle acceleration may come from several catalogued SNRs and SNR candidates, the energetic ultra compact HII region W 28A2, and the HII regions M 8 and M 20, along with their associated open clusters. Further sub-mm observations would be recommended to probe in detail the dynamics of the molecular clouds at velocites &gt; 10 km s−1 and their possible connection to W 28.
The non-synonymous coding IKr-channel variant KCNH2-K897T is associated with atrial fibrillation: results from a systematic candidate gene-based analysis of KCNH2 (HERG)
2008-01-25

We report a genetic association finding including positive replication between the K897-allele and higher incidence of AF. This provides a molecular correlate for complex genetic predispositions to AF. The consequences of the K897T variant at the atrial level will require further functional investigations.
Water diffusion anisotropy in white and gray matter of the human spinal cord
2008-01-25

Abstract Purpose To develop a reliable technique for diffusion imaging of the human spinal cord at 1.5 Tesla and to assess potential differences in diffusion anisotropy in cross‐sectional images. Materials and Methods A single‐shot echo‐planar imaging sequence with double spin‐echo diffusion preparation was optimized regarding cerebrospinal fluid artifacts, effective resolution, and contrast‐to‐noise ratios. Eleven healthy volunteers participated in the study for quantitative characterization of diffusion anisotropy in white matter (WM) and gray matter (GM) by means of two diffusion encoding schemes: octahedral‐six‐directions for fractional anisotropy (FA) evaluation and orthogonal‐three‐directions for anisotropy index (AI) calculation. Results Pulse‐trigger gated sequences with optimal matrix size (read × phase = 64 × 32) and b‐value (700 s/mm 2 ) allowed the acquisition of high‐resolved images (voxel size = 0.9 × 0.9 × 5.0 mm 3 ). The GM butterfly shape was recognizable in both AI and FA maps. Both encoding schemes yielded high diffusion anisotropy in dorsal WM (FA = 0.79 ± 0.07; AI = 0.39 ± 0.04). Lateral WM showed slightly lower anisotropy (FA = 0.69 ± 0.08; AI = 0.35 ± 0.03) than dorsal WM. Clearly smaller anisotropy was found in regions containing GM (FA = 0.45 ± 0.06; AI = 0.21 ± 0.05). Conclusion Diffusion anisotropy data of the spinal cord can be obtained in a clinical setting. Its application seems promising for the assessment of neurological disorders. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
The appearance of magnetospheric instability in flaring activity at the onset of X-ray outbursts in A0535+26
2008-01-25

We argue that X-ray flaring variability observed in the transient X-ray pulsar A 0535+26 is due to low-mode magnetospheric instability. This instability develops at the onset of accretion, in the thin boundary layer between the accretion disk and neutron star magnetosphere. As a result, the matter collected in the boundary layer can rapidly fall onto the NS surface close to the magnetic poles, but not exactly along the field lines by which the stationary accretion proceeds. This explains the shift in cyclotron line energy measured using RXTE data in a pre-outburst spike, with respect to the line energy observed during the main outburst. Furthermore, the instability can account for the difference in pulse profiles, and their energy evolution that is different in the pre-outburst flare and main outburst.
Antitumor effector functions of T cells are dependent on in vivo priming and restricted T‐cell receptor expression
2008-01-25

Abstract Tumor‐specific T cells are crucial for immunologic control of malignant disease. T cells can be induced in vivo by vaccination or adoptively transferred after activation ex vivo . We investigated the requirements for generating T cells with optimal antitumor effector functions in a murine lymphoma model. Using adoptive transfer, we show that in vivo efficacy of T cells cannot be predicted by tumor reactivity in vitro . A restricted T‐cell receptor β chain repertoire of T‐cell populations stimulated ex vivo against tumor cells was necessary but not sufficient for tumor protectivity. Tumor elimination furthermore required vaccination of donor mice, hence in vivo priming. The in vivo priming step may allow tumor‐specific T cells to accumulate in vitro more rapidly and to survive for longer periods after withdrawal of the antigenic stimulus and adoptive transfer. A possible survival benefit of in vivo induced T cells may be ascribed to the responsiveness to homeostatic cytokines and to unique cytokine milieus encountered in vivo . Most importantly, monoclonal T cells cannot inhibit tumor growth. A prerequisite of tumor rejection was the expression of at least 2 T‐cell receptor β chains by transferred T‐cell populations. This finding has implications for designing adoptive transfer strategies for the clinic. © 2008 Wiley‐Liss, Inc.
Latest applications for 2-focus fluorescence correlation spectroscopy
2008-01-25

Fluorescence Correlation Spectroscopy (FCS) has been invented more than 30 years ago and experienced a renaissance after stable and affordable laser sources and low-noise single-photon detectors have become available. Its ability to measure diffusion coefficients at nanomolar concentrations of analyte made it a widely used tool in biophysics. However, in recent years it has been shown by many authors that aberrational (e.g. astigmatism) and photophysical effects (e.g. optical saturation) may influence the result of an FCS experiment dramatically, so that a precise and reliable estimation of the diffusion coefficient is no longer possible. Here, we report on the development, implementation, and application of a new and robust modification of FCS that we termed two-focus FCS (2fFCS) and which fulfils two requirements: (i) It introduces an external ruler into the measurement by generating two overlapping laser foci of precisely known and fixed distance. (ii) These two foci and corresponding detection regions are generated in such a way that the corresponding molecule detection functions (MDFs) are sufficiently well described by a simple two-parameter model yielding accurate diffusion coefficients when applied to 2fFCS data analysis. Both these properties enable us to measure absolute values of the diffusion coefficient with an accuracy of a few percent. Moreover, it turns out that the new technique is robust against refractive index mismatch, coverslide thickness deviations, and optical saturation effects, which so often trouble conventional FCS measurements. Additionally, we will show data that indicates that with 2fFCS it is even possible to monitor conformational changes of a calcium bindig protein affecting the hydrodynamic radius by as little as two Angstrom.
Fatty Liver Is Independently Associated With Alterations in Circulating HDL2 and HDL3 Subfractions
2008-01-28

Fatty liver is associated with insulin resistance, atherosclerosis, and the metabolic syndrome (1–7) and predicts future cardiovascular events (4–8). The pro-atherogenic serum lipid profile in subjects with fatty liver is characterized by elevated levels of triglycerides, low HDL cholesterol, and an increase in small dense LDL particles (9–12). Regarding HDL, not only quantitative, but also qualitative and compositional alterations are related to its antiatherogenic properties (13–16). In particular, circulating HDL2 was found to protect from atherosclerosis (17,18). In the present study, we first investigated whether fatty liver is associated with altered circulating HDL cholesterol subfractions and second whether this relationship is independent of insulin sensitivity, thus possibly representing a direct link between fatty liver and cardiovascular disease. In our ongoing study on the pathophysiology of type 2 diabetes, ∼300 Caucasians were carefully characterized for fatty liver and its associated metabolic characteristics (19). To select a subgroup that was representative for the percentage of subjects having fatty liver (liver fat >5.56%) (20) in our large cohort (∼40%) and in whom enough sample volume was available to measure the HDL cholesterol subfractions, we randomly selected 8 men and 8 women with fatty liver and 24 control subjects. The subjects underwent a 75-g oral glucose tolerance test to exclude diabetes and calculate insulin sensitivity (21). Total body fat was measured by bioelectrical impedance, visceral fat by magnetic resonance (MR) tomography, and liver fat by 1H-MR spectroscopy (19). Serum total, HDL, and LDL cholesterol, as well as triglyceride concentrations, were measured by standard colorimetry, plasma adiponectin ...
Two-point functions of Coulomb gauge Yang-Mills theory
2008-01-28

The functional approach to Coulomb gauge Yang-Mills theory is considered within the standard, second order, formalism. The Dyson-Schwinger equations and Slavnov-Taylor identities concerning the two-point functions are derived explicitly and one-loop perturbative results are presented.
Long-term engraftment of systemically transplanted, gene-modified bone marrow-derived cells in the adult mouse retina
2008-01-28

We demonstrate that gene-modified BMDCs show long-term engraftment and stable expression of GFP from a retrovirus in both wild-type and mutant mouse retinas. Thus, BMDCs may be used as vehicles for gene delivery to the retina.
Severe skin reaction secondary to concomitant radiotherapy plus cetuximab
2008-01-28

The therapeutic use of monoclonal antibodies against the epidermal growth factor receptor (EGFR) is specifically associated with dermatologic reactions of variable severity. Recent evidence suggests superiority of the EGFR inhibitor (EGFRI) cetuximab plus radiotherapy compared to radiotherapy alone in patients with squamous cell carcinoma of the head and neck. Although not documented in a study population, several reports indicate a possible overlap between radiation dermatitis and the EGFRI-induced skin rash. We here present a case of severe skin reaction secondary to the addition of cetuximab to radiotherapy.
ChemInform Abstract: Synthesis and Antibacterial Potency of 4‐Methyl‐2,7‐dioxo‐1,2,3,4,7,10‐hexahydropyrido [2,3‐f]quinoxaline‐8‐carboxylic Acid, Selected [a]‐Fused Heterocycles and Acyclic Precursors.
2008-01-28

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
Micro‐Raman spectroscopy on analcime and pollucite in comparison to X‐ray diffraction
2008-01-29

Abstract Natural and synthetic samples of analcime and pollucite (both zeolites belonging to the analcime group) were studied by means of micro‐Raman spectrometry, X‐ray fluorescence analysis (XFA) and X‐ray diffraction (XRD). On knowing the chemical and structural characteristics of each solid‐solution member, the observed shift in the spectral position of the Raman active modes can be explained and used for phase determination. As shown, the distinction between members of the analcime–pollucite solid‐solution series using Raman spectroscopy is significantly more conclusive than the corresponding XRD findings. Also, information about the structurally bound water inside the zeolite structure can be gained using Raman spectroscopy as long as a suitable exciting wavelength is selected. Copyright © 2008 John Wiley &amp; Sons, Ltd.
Secretion of matrix metalloproteinase 3 by expanded articular chondrocytes as a predictor of ectopic cartilage formation capacity in vivo
2008-01-31

Abstract Objective Monolayer expansion of human articular chondrocytes (HACs) is known to result in progressive dedifferentiation of the chondrocytes and loss of their stable cartilage formation capacity in vivo. For an optimal outcome of chondrocyte‐based repair strategies, HACs capable of ectopic cartilage formation may be required. This study was undertaken to identify secreted candidate molecules, in supernatants of cultured HACs, that could serve as predictors of the ectopic cartilage formation capacity of cells. Methods Standardized medium supernatants (n = 5 knee cartilage samples) of freshly isolated HACs (PD0) and of HACs expanded for 2 or 6 population doublings (PD2 and PD6, respectively) were screened by a multiplexed immunoassay for 15 distinct interleukins, 8 matrix metalloproteinases (MMPs), and 11 miscellaneous soluble factors. Cartilage differentiation markers such as cartilage oligomeric matrix protein and YKL‐40 were determined by enzyme‐linked immunosorbent assay. HACs from each culture were subcutaneously transplanted into SCID mice, and the capacity of the chondrocytes to form stable cartilage was examined histologically 4 weeks later. Results Whereas freshly isolated (PD0) HACs generated stable ectopic cartilage that was positive for type II collagen, none of the cell transplants at PD6 formed cartilaginous matrix. Loss of the ectopic cartilage formation capacity between PD0 and PD6 correlated with a drop in the secretion of MMP‐3 to &lt;10% of initial levels, whereas changes in the other investigated molecules were not predictive. Chondrocytes with MMP‐3 levels of ≥20% of initial levels synthesized cartilaginous matrix, whereas those with low MMP‐3 levels (&lt;10% of initial levels) at PD2 failed to regenerate ectopic cartilage. Conclusion Loss of the capacity for stable ectopic cartilage formation in the course of HAC dedifferentiation can be predicted by determining the relative levels of MMP‐3, demonstrating that standardized culture supernatants can be used for quality control of chondrocytes dedicated for cell therapeutic approaches.
Multicentric Bowen disease in linear porokeratosis.
2008-01-31

Linear porokeratosis is a genodermatosis, caused by a clonal proliferation of keratinocytes along the lines of Blaschko. This type of porokeratosis is particularly susceptible to malignant degeneration e.g. to Bowen disease, a squamous cell carcinoma (SCC) in situ with the potential for significant lateral spread. Here we report a case of linear porokeratosis on the left leg of a 56-year-old man, complicated with two lesions of multicentric Bowen disease.
Rifampicin induces MDR1 expression in Candida albicans
2008-01-31

Out of the compounds examined, only rifampicin specifically induced MDR1 expression in all C. albicans strains tested. Rifampicin may play a general role in signal transduction or another means of modulation of gene expression in C. albicans.
Surface shape parameters and analysis of data captured with use of 4D surface scanners
2008-01-31

The recent development of electro-optical instrumentation allowed constructing 4D (3D + time) structure-light scanners which may be used to measure the surface of human body in motion. The main advantage of structure-light scanners is the possibility of capturing data from the whole measured body surface, while traditional marker-based systems acquire data only form markers attached to skin of the examined patient. The paper describes new parameters describing the local shape of measured surface. The distribution maps of these parameters allow discrimination of various surface types and in effect localization and tracing of under-skin anatomical structures in time. The presented parameters give similar results to well-known curvatures but are easier and quicker to calculate. Moreover the calculation process of the new parameters is more numerically stable itself. The developed path of processing and analysis of 4D measurement data has been presented. It contains the following stages: data acquisition, volumetric model creation, calculations of shape parameters, selecting areas of interest, locating and tracing of anatomical landmarks. Exemplary results of application of developed parameters and methods to real measurement and computer generated data are also presented.
Development of word reading fluency and spelling in a consistent orthography: An 8-year follow-up.
2008-02-01

In a longitudinal study, development of word reading fluency and spelling were followed for almost 8 years. In a group of 115 students (65 girls, 50 boys) acquiring the phonologically transparent German orthography, prediction measures (letter knowledge, phonological short-term memory, phonological awareness, rapid automatized naming, and nonverbal IQ) were assessed at the beginning of Grade 1; reading fluency and spelling were tested at the end of Grade 1 as well as in Grades 4 and 8. Reading accuracy was close to ceiling in all reading assessments, such that reading fluency was not heavily influenced by differences in reading accuracy. High stability was observed for word reading fluency development. Of the dysfluent readers in Grade 1, 70% were still poor readers in Grade 8. For spelling, children who at the end of Grade 1 still had problems translating spoken words into phonologically plausible letter sequences developed problems with orthographic spelling later on. The strongest specific predictors were rapid automatized naming for reading fluency and phonological awareness for spelling. Word recognition speed was a relevant and highly stable indicator of reading skills and the only indicator that discriminated reading skill levels in consistent orthographies. Its long-term development was more strongly influenced by early naming speed than by phonological awareness.
Results of the First Phase I/II Clinical Vaccination Trial With Direct Injection of mRNA
2008-02-01

Vaccination against tumor antigens has been shown to be a safe and efficacious prophylactic and therapeutic antitumor treatment in many animal models. Clinical studies in humans indicate that specific immunotherapy can also result in clinical benefits. The active pharmaceutical ingredient in such vaccines can be DNA, RNA, protein, or peptide and can be administered naked, encapsulated, or after delivery in vitro into cells that are then adoptively transferred. One of the easiest, most versatile and theoretically safest technologies relies on the direct injection of naked messenger RNA (mRNA) that code for tumor antigens. We and others have shown in mice that intradermal application of naked mRNA results in protein expression and the development of an immune response. We used this protocol to vaccinate 15 melanoma patients. For each patient a growing metastasis was removed, total RNA was extracted, reverse-transcribed, amplified, and cloned. Libraries of cDNA were transcribed to produce unlimited amounts of copy mRNA. Autologous preparations were applied intradermally in combination with granulocyte macrophage colony-stimulating factor as adjuvant. We demonstrate here that such treatment is feasible and safe (phase 1 criteria). Furthermore, an increase in antitumor humoral immune response was seen in some patients. However, a demonstration of clinical effectiveness of direct injection of copy mRNA for antitumor immunotherapy was not shown in this study and must be evaluated in subsequent trials.
How Physicians Allocate Scarce Resources at the Bedside: A Systematic Review of Qualitative Studies
2008-02-01

Although rationing of scarce health-care resources is inevitable in clinical practice, there is still limited and scattered information about how physicians perceive and execute this bedside rationing (BSR) and how it can be performed in an ethically fair way. This review gives a systematic overview on physicians' perspectives on influences, strategies, and consequences of health-care rationing. Relevant references as identified by systematically screening major electronic databases and manuscript references were synthesized by thematic analysis. Retrieved studies focused on themes that fell under three major headings: (i) conditions and influences of BSR, (ii) strategies of BSR, and (iii) consequences of BSR. The range of themes indicates that physicians' rationing behavior is highly variable, strongly influenced by context-related factors, and consists mainly of implicit rationing strategies. Torn between patient advocacy and the obligation to contain costs, physicians experience various role conflicts. The development of explicit rationing strategies seems necessary to avoid arbitrary BSR and allow a fair allocation of health-care resources.