julilili42/papers huggingface dataset:
Diet-Derived Polyphenol Metabolite Enterolactone Is a Tissue-Specific Estrogen Receptor Activator
2007-07-13

Numerous dietary compounds can modify gene expression by binding to the members of the nuclear receptor superfamily of transcription factors. For example, dietary polyphenols, such as soy isoflavones genistein and daidzein, modulate the activity of the estrogen receptors (ERs)-α and ERβ. An additional class of dietary polyphenols that modulate cellular signaling pathways are lignans, compounds that are common constituents of Western diets. In this study, we show that a metabolite of dietary lignans, enterolactone, at physiological concentrations, activates ER-mediated transcription in vitro with preference for ERα. The effects of enterolactone are mediated by the ER ligand binding domain and are susceptible to antiestrogen treatment. Furthermore, the affinity of enterolactone toward ERα, measured by a novel ligand binding assay, is augmented in cell culture conditions. Moreover, our results demonstrate for the first time that enterolactone has estrogenic activity in vivo. In transgenic estrogen-sensitive reporter mice, enterolactone induces tissue-specific estrogen-responsive reporter gene expression as well as promotes uterine stromal edema and expression of estrogen-responsive endogenous genes (CyclinD1 and Ki67). Taken together, our data show that enterolactone is a selective ER agonist inducing ER-mediated transcription both in vitro in different cell lines and in vivo in the mouse uterus.
Influenza pandemic intervention planning using InfluSim: pharmaceutical and non- pharmaceutical interventions
2007-07-13

Abstract Background Influenza pandemic preparedness plans are currently developed and refined on national and international levels. Much attention has been given to the administration of antiviral drugs, but contact reduction can also be an effective part of mitigation strategies and has the advantage to be not limited per se . The effectiveness of these interventions depends on various factors which must be explored by sensitivity analyses, based on mathematical models. Methods We use the freely available planning tool InfluSim to investigate how pharmaceutical and non-pharmaceutical interventions can mitigate an influenza pandemic. In particular, we examine how intervention schedules, restricted stockpiles and contact reduction (social distancing measures and isolation of cases) determine the course of a pandemic wave and the success of interventions. Results A timely application of antiviral drugs combined with a quick implementation of contact reduction measures is required to substantially protract the peak of the epidemic and reduce its height. Delays in the initiation of antiviral treatment (e.g. because of parsimonious use of a limited stockpile) result in much more pessimistic outcomes and can even lead to the paradoxical effect that the stockpile is depleted earlier compared to early distribution of antiviral drugs. Conclusion Pharmaceutical and non-pharmaceutical measures should not be used exclusively. The protraction of the pandemic wave is essential to win time while waiting for vaccine development and production. However, it is the height of the peak of an epidemic which can easily overtax general practitioners, hospitals or even whole public health systems, causing bottlenecks in basic and emergency medical care.
Controlling Nonequilibrium Phonon Populations in Single-Walled Carbon Nanotubes
2007-07-13

We studied spatially isolated single-walled carbon nanotubes (SWNTs) immobilized in a quasi-planar optical Î»/2-microresonator using confocal microscopy and spectroscopy. The modified photonic mode density within the resonator is used to selectively enhance or inhibit different Raman transitions of SWNTs. Experimental spectra are presented that exhibit single Raman bands only. Calculations of the relative change in the Raman scattering cross sections underline the potential of our microresonator for the optical control of nonequilibrium phonon populations in SWNT.
Lysis of a Broad Range of Epithelial Tumour Cells by Human γδ T Cells: Involvement of NKG2D ligands and T‐cell Receptor‐ versus NKG2D‐dependent Recognition
2007-07-16

Abstract Human γ δ T cells expressing a V γ 9V δ 2 T‐cell receptor (TCR) kill various tumour cells including autologous tumours. In addition to TCR‐dependent recognition, activation of NKG2D‐positive γ δ T cells by tumour cell‐expressed NKG2D ligands can also trigger cytotoxic effector function. In this study, we investigated the involvement of TCR versus NKG2D in tumour cell recognition as a prerequisite to identify tumour types suitable for γ δ T‐cell‐based immunotherapy. We have characterized epithelial tumour cells of different origin with respect to cell surface expression of the known NKG2D ligands MHC class I‐chain‐related antigens (MIC) A/B and UL16‐binding proteins (ULBP), and susceptibility to γ δ T‐cell killing. Most tumour cells expressed comparable levels of MICA and MICB as well as ULBP with the exception of ULBP‐1 which was absent or only weakly expressed. Most epithelial tumours were susceptible to allogeneic γ δ T‐cell lysis and in the case of an established ovarian carcinoma to autologous γ δ T‐cell killing. Lysis of resistant cells was enhanced by pre‐treatment of tumour cells with aminobisphosphonates or pre‐activation of γ δ T cells with phosphoantigens. A potential involvement of TCR and/or NKG2D was investigated by antibody blockade. These experiments revealed three patterns of inhibition, i.e. preferential inhibition by anti‐TCR antibody, preferential inhibition by anti‐NKG2D antibody, or additive blockade by anti‐TCR plus anti‐NKG2D antibodies. Our results indicate for the first time that the NKG2D pathway is involved in the lysis of different melanomas, pancreatic adenocarcinomas, squameous cell carcinomas of the head and neck, and lung carcinoma.
On the evolution of eccentric and inclined protoplanets embedded in protoplanetary disks
2007-07-16

\\n Context.Young planets embedded in their protoplanetary disk\\ninteract gravitationally with it leading to energy and angular momentum\\nexchange. This interaction determines the \\nevolution of the planet through changes to the orbital parameters.\\n Aims.We investigate changes in the orbital elements of a\\n20 Earth-mass planet due to the torques from the\\ndisk. We focus on the non-linear evolution\\nof initially non-vanishing eccentricity, e, and/or inclination, i.\\n Methods.We treat the disk as a two- or three-dimensional viscous\\nfluid and perform hydrodynamical simulations using finite difference methods.\\nThe planetary orbit\\nis updated according to the gravitational torque exerted by the disk.\\nWe monitor the time evolution of the orbital elements of the planet.\\n Results.We find\\nrapid exponential decay of the planet orbital eccentricity and inclination \\nfor small initial values of e and i, in agreement with linear theory.\\nFor larger values of the decay time increases\\nand the decay rate scales as , consistent \\nwith existing theoretical models.\\nFor large inclinations ( ) the inclination decay rate\\nshows an identical scaling d .\\nWe find an interesting dependence of the migration on the eccentricity. \\nIn a disk with aspect ratio the\\nmigration rate is enhanced for small non-zero eccentricities ( ),\\nwhile for larger values we see a significant reduction by a factor \\nof ~4. \\nWe find no indication for a reversal of the migration for large e,\\nalthough the torque experienced by the planet becomes positive when\\n . This inward migration is caused by the\\npersisting energy loss of the planet.\\n\\n Conclusions.For non gap forming planets,\\neccentricity and inclination damping occurs on a time scale\\nthat is very much shorter than the migration time scale.\\nThe results of non linear hydrodynamic simulations are in very\\ngood agreement with linear theory for values of e and i\\nfor which the theory is applicable\\n(i.e. e and ). \\n
Immobilized DNA aptamers used as potent attractors for porcine endothelial precursor cells
2007-07-16

Abstract Because of their insufficient biocompatibility and high thrombogenicity, small diameter artificial vascular prostheses still do not show a satisfactory patency rate. In vitro endothelialization of artificial grafts before implantation has been established experimentally years ago, but, this procedure is extremely time consuming and expensive. This study deals with the coating of graft surfaces with capture molecules (aptamers) for circulating endothelial progenitor cells (EPCs), mimicking a prohoming substrate to fish out EPCs from the bloodstream after implantation and to create an autologous functional endothelium. Using the SELEX technology, aptamers with a high affinity to EPCs were identified, isolated, and grafted onto polymeric discs using a blood compatible star‐PEG coating. A porcine in vitro model that demonstrates the specific adhesion of EPCs and their differentiation into vital endothelial‐like cells within 10 days in cell culture is presented. We suggest that the rapid adhesion of EPCs to aptamer‐coated implants could be useful to promote endothelial wound healing and to prevent increased neointimal hyperplasia. We hypothesize that future in vivo self‐endothelialization of blood contacting implants by homing factor mimetic capture molecules for EPCs may bring revolutionary new perspectives towards clinical applications of stem cell and tissue engineering strategies. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis
2007-07-16

Abstract Background Epigenetic silencing of the RAS association domain family 1A ( RASSF1A ) tumor suppressor gene promoter has been demonstrated in renal cell carcinoma (RCC) as a result of promoter hypermethylation. Contradictory results have been reported for RASSF1A methylation in normal kidney, thus it is not clear whether a significant difference between RASSF1A methylation in normal and tumor cells of the kidney exists. Moreover, RASSF1A expression has not been characterized in tumors or normal tissue as yet. Results Using combined bisulfite restriction analysis (COBRA) we compared RASSF1A methylation in 90 paired tissue samples obtained from primary kidney tumors and corresponding normal tissue. Bisulfite sequence analysis was carried out using both pooled amplicons from the tumor and normal tissue groups and subclones obtained from a single tissue pair. Expression of RASSF1A was analyzed by the use of tissue arrays and immunohistochemistry. We found significantly increased methylation in tumor samples (mean methylation, 20%) compared to corresponding normal tissues (mean methylation, 11%; P &lt; 0.001). Densely methylated sequences were found both in pooled and individual sequences of normal tissue. Immunohistochemical analysis revealed a significant reduced expression of RASSF1A in most of the tumor samples. Heterogeneous expression patterns of RASSF1A were detected in a subgroup of histologically normal tubular epithelia. Conclusion Our methylation and expression data support the hypothesis that RASSF1A is involved in early tumorigenesis of renal cell carcinoma.
Stability and formation of the resonant system HD 73526
2007-07-17

\\n Context.Based on radial velocity measurements, it has been found that the two \\n giant planets detected around the star HD 73526 are in 2:1 resonance. However, \\n as our numerical integration shows, the derived orbital data for this system result \\n in chaotic behavior of the giant planets, which is uncommon among the resonant \\n extrasolar planetary systems. \\n \\n Aims.We present regular (non-chaotic) orbital solutions for the giant planets \\n in the system HD 73526 and offer formation scenarios based on combining \\n planetary migration and sudden perturbative effects such as planet-planet scattering \\n or rapid dispersal of the protoplanetary disk. A comparison with the already-studied \\n resonant system HD 128311, exhibiting similar behavior, is given. \\n \\n Methods.The new sets of orbital solutions were derived using the Systemic Console. \\n The stability of these solutions was investigated \\n using the Relative Lyapunov indicator, while the migration and scattering effects are \\n studied by gravitational N-body simulations applying non-conservative forces. \\n Additionally, hydrodynamic simulations of embedded planets in \\n protoplanetary disks were performed to follow the capture into resonance. \\n \\n Results.For the system HD 73526 we demonstrate that the observational \\n radial velocity data are consistent with a coplanar planetary \\n system in a stable 2:1 resonance exhibiting apsidal corotation. \\n We have shown that, similarly to the system HD 128311, the present dynamical \\n state of HD 73526 could be the result of a mixed evolutionary process combining \\n planetary migration and a perturbative event. \\n \\n
The Mitochondrial TOM Complex Is Required for tBid/Bax-induced Cytochrome c Release
2007-07-17

Cytochrome c release from mitochondria is a key event in apoptosis signaling that is regulated by Bcl-2 family proteins. Cleavage of the BH3-only protein Bid by multiple proteases leads to the formation of truncated Bid (tBid), which, in turn, promotes the oligomerization/insertion of Bax into the mitochondrial outer membrane and the resultant release of proteins residing in the intermembrane space. Bax, a monomeric protein in the cytosol, is targeted by a yet unknown mechanism to the mitochondria. Several hypotheses have been put forward to explain this targeting specificity. Using mitochondria isolated from different mutants of the yeast Saccharomyces cerevisiae and recombinant proteins, we have now investigated components of the mitochondrial outer membrane that might be required for tBid/Bax-induced cytochrome c release. Here, we show that the protein translocase of the outer mitochondrial membrane is required for Bax insertion and cytochrome c release.
Comparison of Mode of Action of Four Hepatocarcinogens: A Model-Based Approach
2007-07-17

Within the scope of the Rat Liver Foci Bioassay the model carcinogens N-nitrosomorpholine (NNM), 2-acetylaminoflouren (2-AAF), phenobarbital (PB), and clofibrate (CF) were analyzed concerning their potency and dose-response relationship to induce foci of altered hepatocytes (FAHs), which are known to be precursor lesions of liver adenoma and carcinoma. The medium-term experiment follows an initiation-promotion protocol using diethylnitrosamine (DEN) as initiator. The present report deals with the application of two biologically based models for hepatocarcinogenesis, the two-stage clonal expansion model (TSCEM), and a color-shift model with beta distributed growth rates (CSMbeta). Both models yield similar conclusions concerning the mode of action of the carcinogens. However, the fit of CSMbeta appears closer to the observations than the fit of TSCEM. The analysis shows that application of a single dose of DEN has a persistent effect on the rate of FAH induction, especially in female rats. Overall, striking differences in the effect of the carcinogens were observed between male and female animals. 2-AAF shows a strong promoting effect in males, whereas in females the initiating effect dominates. NNM has both initiating and promoting effect, but in females, the rate of FAH formation seems to reach saturation at high dose. In the doses applied in the present experiment, PB has the weakest carcinogenic effect. Although PB alone does not induce FAH during the observation period, it increases the rate of FAH formation when applied following initiation with DEN. CF reduces the number and area fraction of GSTP-stained FAH, probably because it suppresses the placental form of glutathione S-transferase-positive phenotype.
2-(4-Fluorophenyl)-1-(4-pyridyl)cyclopentan-1-ol
2007-07-18

The crystal structure of the title compound, C16H16FNO, was determined as part of a study of the biological activity of pyridine-substituted cyclopentene derivatives as p38 mitogen-activated protein kinase (MAPK) inhibitors. The 4-fluorophenyl and 4-pyridyl rings are trans positioned with respect to each other. The compound exists as a racemic mixture. The synthesis was achieved via direct interaction between the reactive complex Grignard reagent PyMgCl·LiCl and the enolizable ketone 4-fluorophenylcyclopentanone with the assistance of the neodymium salt catalyst NdCl3·2LiCl. The crystal packing is characterized by zigzag chains of molecules, which are connected by O—H⋯N hydrogen bonds running along the b axis.
A Staphylococcus aureus ypfP mutant with strongly reduced lipoteichoic acid (LTA) content: LTA governs bacterial surface properties and autolysin activity
2007-07-19

Summary Many Gram‐positive bacteria produce lipoteichoic acid (LTA) polymers whose physiological roles have remained a matter of debate because of the lack of LTA‐deficient mutants. The ypfP gene responsible for biosynthesis of a glycolipid found in LTA was deleted in Staphylococcus aureus SA113, causing 87% reduction of the LTA content. Mass spectrometry and nuclear magnetic resonance spectroscopy revealed that the mutant LTA contained a diacylglycerol anchor instead of the glycolipid, whereas the remaining part was similar to the wild‐type polymer except that it was shorter. The LTA mutant strain revealed no major changes in patterns of cell wall proteins or autolytic enzymes compared with the parental strain indicating that LTA may be less important in S. aureus protein attachment than previously thought. However, the autolytic activity of the mutant was strongly reduced demonstrating a role of LTA in controlling autolysin activity. Moreover, the hydrophobicity of the LTA mutant was altered and its ability to form biofilms on plastic was completely abrogated indicating a profound impact of LTA on physicochemical properties of bacterial surfaces. We propose to consider LTA and its biosynthetic enzymes as targets for new antibiofilm strategies.
Multifocal dysembryoplastic neuroepithelial tumor with signs of atypia after regrowth
2007-07-19

We report the case of a multifocal dysembryoplastic neuroepithelial tumor (DNT) in a 7‐year‐old girl with local tumor regrowth 6 years later. The tumor was localized in the right parietal lobe extending from the cortex into the periventricular white matter. After subtotal resection of a histopathologically confirmed DNT we observed unexpected tumor progression in long‐term follow‐up. Therefore, a second surgery was performed when the patient was 14 years of age. In neuropathological examination of the second specimen the tumor showed an increased cellularity and pleomorphism, microvascular proliferations, an elevated proliferative activity (MIB1‐index focally up to 10%) and cellular atypia not typical for WHO grade I DNT. Furthermore, MRI studies showed additional supratentorial and infratentorial lesions which remained stable over years and are also well consistent with DNTs. Thus, an unusual form of a DNT with multifocal lesions, local regrowth and morphological transformation is supposed.
A cooperative SIP infrastructure for highly reliable telecommunication services
2007-07-19

Voice over IP (VoIP) has been a promising technology for several years. Although it has become very popular, the vision to substitute the "good old" Public Switched Telephone Network (PSTN) is still far from being true. Several issues, such as security, reliability and emergency calls are slowing down the integration of VoIP. Currently, there is a mixture of technologies where VoIP is often used for reducing costs, while still keeping the PSTN if a reliable communication is needed.
An Exceptional Very High Energy Gamma-Ray Flare of PKS 2155-304
2007-07-20

The high-frequency peaked BL Lac PKS 2155-304 at redshift z=0.116 is a well-known VHE (>100 GeV) gamma-ray emitter. Since 2002 its VHE flux has been monitored using the H.E.S.S. stereoscopic array of imaging atmospheric-Cherenkov telescopes in Namibia. During the July 2006 dark period, the average VHE flux was measured to be more than ten times typical values observed from the object. This article focuses solely on an extreme gamma-ray outburst detected in the early hours of July 28, 2006 (MJD 53944). The average flux observed during this outburst is I(>200 GeV) = (1.72$\\pm \\pm 0.34_{\\rm syst} \\times ^{-9} ^{-2} ^{-1} ^9 M_\\odot$ black hole, Doppler factors greater than 100 are required to accommodate the observed variability time scales.
Role and Regulation of the Serum- and Glucocorticoid-Regulated Kinase 1 in Fertile and Infertile Human Endometrium
2007-07-20

Using cDNA microarray analysis, we identified SGK1 (serum- and glucocorticoid-regulated kinase 1) as a gene aberrantly expressed in midsecretory endometrium of women with unexplained infertility. SGK1 is a serine/threonine kinase involved primarily in epithelial ion transport and cell survival responses. Real-time quantitative PCR analysis of a larger, independent sample set timed to coincide with the period of uterine receptivity confirmed increased expression of SGK1 transcripts in infertile women compared with fertile controls. We further demonstrate that SGK1 expression is regulated by progesterone in human endometrium in vivo as well as in explant cultures. During the midsecretory phase of the cycle, SGK1 mRNA and protein were predominantly but not exclusively expressed in the luminal epithelium, and expression in this cellular compartment was higher in infertile women. In the stromal compartment, SGK1 expression was largely confined to decidualizing cells adjacent to the luminal epithelium. In primary culture, SGK1 was induced and phosphorylated upon decidualization of endometrial stromal cells in response to 8-bromo-cAMP and progestin treatment. Moreover, overexpression of SGK1 in decidualizing cells enhanced phosphorylation and cytoplasmic translocation of the forkhead transcription factor FOXO1 and inhibited the expression of PRL, a major decidual marker gene. Conversely, knockdown of endogenous SGK1 by small interfering RNA increased nuclear FOXO1 levels and enhanced PRL expression. The observation that SGK1 targets FOXO1 in differentiating human endometrium, together with its distinct temporal and spatial expression pattern and increased expression in infertile patients, suggest a major role for this kinase in early pregnancy events.