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Effects of N-acetylcysteine/deferoxamine, taurine and RC-3095 on respiratory chain complexes and creatine kinase activities in rat brain after sepsis.
ABSTRACT The pathogenesis of sepsis is characterized by an overwhelming systemic inflammatory response that can lead to multiple organ failure. Considering that we have recently demonstrated that mitochondrial respiratory chain and creatine kinase (CK) are altered in the brain of rats after cecal ligation and perforation (CLP) and that a combination of N-acetylcysteine/deferoxamine (NAC/DFX), taurine and RC-3095 were shown to be an effective treatment of sepsis, we investigated whether the alterations of these enzymes may be reversed by these drugs. The results demonstrated that CLP inhibited complexes I and II, and that all the treatments were able to reverse this inhibition in all brain areas studied in the present work. On the other hand, complexes III and IV were not affected by sepsis neither by any of the treatments. An increase in CK activity in brain of rats 12 h after CLP was also verified; the administration of NAC/DFX and taurine reversed the increase in CK activity in hippocampus, cerebral cortex, cerebellum and striatum. On the other hand, RC-3095 significantly decreased CK activity, when compared to sham group in all brain areas studied. This is a preliminary study which showed beneficial effects of the treatments we proposed.
- SourceAvailable from: PubMed Central
Article: Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson's, Huntington's, Alzheimer's, prions, bactericides, chemical toxicology and others as examples.[Show abstract] [Hide abstract]
ABSTRACT: Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions.Archives of Toxicology 08/2010; 84(11):825-89. · 5.22 Impact Factor
Article: The Decrease on Na(+), K (+)-ATPase Activity in the Cortex, but not in Hippocampus, is Reverted by Antioxidants in an Animal Model of Sepsis.[Show abstract] [Hide abstract]
ABSTRACT: In the present study, we investigated whether sepsis induced by cecal ligation and puncture (CLP) modifies Na(+), K(+)-ATPase activity, mRNA expression, and cerebral edema in hippocampus and cerebral cortex of rats and if antioxidant (ATX) treatment prevented the alterations induced by sepsis. Rats were subjected to CLP and were divided into three groups: sham; CLP-rats were subjected to CLP without any further treatment; and ATX-CLP plus administration of N-acetylcysteine plus deferoxamine. Several times (6, 12, and 24) after CLP or sham operation, the rats were killed and hippocampus and cerebral cortex were isolated. Na(+), K(+)-ATPase activity was inhibited in the hippocampus 24 h after sepsis, and ATX treatment was not able to prevent this inhibition. The Na(+), K(+)-ATPase activity also was inhibited in cerebral cortex 6, 12, and 24 h after sepsis. No differences on Na(+), K(+)-ATPase catalytic subunit mRNA levels were found in the hippocampus and cerebral cortex after sepsis. ATX treatment prevents Na(+), K(+)-ATPase inhibition only in the cerebral cortex. Na(+), K(+)-ATPase inhibition was not associated to increase brain water content. In conclusion, the present study demonstrated that sepsis induced by CLP inhibits Na(+), K(+)-ATPase activity in a mechanism dependent on oxidative stress, but this is not associated to increase brain water content.Molecular Neurobiology 07/2012; 46(2):467-74. · 5.47 Impact Factor
Article: The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.[Show abstract] [Hide abstract]
ABSTRACT: Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP). The animals were divided into sham-operated (Sham+control), sham-operated plus minocycline (sham+MIN), CLP (CLP+control) and CLP plus minocycline (CLP+MIN) (100 μg/kg, administered as a single intracerebroventricular (ICV) injection). Some animals were killed 24 h after surgery to assess the breakdown of the blood brain barrier, cytokine levels, oxidative damage to lipids (TBARS) and proteins in the hippocampus. Some animals were allowed to recover for 10 days when step-down inhibitory avoidance and open-field tasks were performed. Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors.Brain Behavior and Immunity 07/2014; · 5.61 Impact Factor


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Publications (239)701.69 Total impact
Article: Tacrolimus Pharmacodynamics and Pharmacogenetics along the Calcineurin Pathway in Human Lymphocytes.[Show abstract] [Hide abstract]
ABSTRACT: Although therapeutic drug monitoring has improved the clinical use of immunosuppressive drugs, there is still interpatient variability in efficacy and toxicity that pharmacodynamic monitoring may help to reduce. To select the best biomarkers of tacrolimus pharmacodynamics, we explored the strength and variability of signal transduction and the influence of polymorphisms along the calcineurin pathway.Clinical chemistry. 08/2014;
Article: Exposure to mycophenolic acid better predicts immunosuppressive efficacy than exposure to calcineurin inhibitors in renal transplant patients.[Show abstract] [Hide abstract]
ABSTRACT: A time to event model was developed to study predictive factors of immunosuppressive efficacy in renal transplant patients and to investigate longitudinal calcineurin inhibitors (CNIs) and mycophenolic acid (MPA) co-exposures, and patient characteristics as potential covariates. The efficacy endpoint included acute rejection, graft loss and death.Data from 222 patients were analyzed: 23 events were observed in 126 patients receiving cyclosporine against 15 in 96 patients receiving tacrolimus (p=0.61) in the two first years post-transplantation. Each 1mg.h/L increase of MPA AUC was associated with a 4% decreased risk of event (hazard ratio (HR) 95% confidence interval (CI): 0.93-0.99). The onset of cytomegalovirus infection/disease significantly increased this risk (HR=10.9; 95% CI: 6.5-21.7). Within the observed ranges, CNIs exposures were not significantly associated with efficacy (i.e. acute rejection, graft loss and death). This work advocates for the avoidance of unnecessary high CNIs dosing and puts forward new arguments for MPA concentration monitoring.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 26 June 2014; doi:10.1038/clpt.2014.140.Clinical pharmacology and therapeutics. 06/2014;
Article: Pharmacokinetics and exposure–effect relationships of capecitabine in elderly patients with breast or colorectal cancer[Show abstract] [Hide abstract]
ABSTRACT: Purpose The aims of the present study were (1) to investigate the impact of great age on pharmacokinetics of capecitabine and its metabolites and (2) to evaluate the exposure–effect relationship of capecitabine in elderly patients. Methods Data collected from 20 elderly patients (75–92 years old) with breast or colorectal cancer who received oral capecitabine were analyzed. In order to study the old age effect on pharmacokinetics, data collected from two phase I studies involving 40 younger adults (<75 years old) with metastatic cancer who received oral capecitabine were added in the database. The population pharmacokinetic analysis was based on a four-compartment model describing the sequence of capecitabine and three of its metabolites. Results The absorption rate constant was found lower in the oldest patient group (≥75 years) compared with the youngest group, and the constant rate elimination of the 5-fluorouracil metabolite was found decreased over time (i.e., after 2 consecutive weeks of capecitabine administration). This time effect was not found different between the two age groups. In elderly patients, the exposure-safety analysis showed, from the second cycle of chemotherapy, significantly higher median exposures of capecitabine and its metabolites (5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine and 5-fluorouracil) in patients who experienced hand-foot syndrome compared with patients who did not. Conclusion This study puts forward new arguments for the treatment of elderly cancer patients who could benefit from capecitabine chemotherapy with acceptable toxicity.Cancer Chemotherapy and Pharmacology 06/2014; 73(6). · 2.80 Impact Factor
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ABSTRACT: To describe the feasibility of human uterus retrieval after donation after brain death.Fertility and sterility. 05/2014;
Article: Pharmacokinetic tools for the dose adjustment of cyclosporine in Hematopoietic Stem Cell transplant patients[Show abstract] [Hide abstract]
ABSTRACT: AimsCyclosporine A (CsA) is used in the prophylaxis and treatment of acute and chronic graft-versus-host disease after hematopoietic stem cell (HCT) transplantation. Our objective were to build and compare three independent Bayesian estimators (BE) of CsA area under the curve (AUC) using a limited sampling strategy (LSS), to assist in dose adjustment.Methods The BEs were developed using in parallel: two independent parametric modeling approaches (NONMEM® and iterative two stage (ITS) Bayesian modeling) and the nonparametric adaptive grid method (Pmetrics®). Seventy-two full pharmacokinetic profiles (at pre-dose and 0.33, 0.66, 1, 2, 3, 4, 6, 8 and 12h after dosing) collected from 40 HCT patients given CsA were used to build the pharmacokinetic models, while 15 other profiles (n=7) were kept for validation. For each BE, AUCs estimated using the full profiles were compared to AUCs estimated using 3 samples.ResultsThe pharmacokinetic profiles were well fitted using a two-compartment model with first-order elimination, combined with a gamma function for the absorption phase with ITS and Pmetrics or an Erlang distribution with NONMEM. The derived BE based on a C0-C1h-C4h sampling schedule (best LSS) accurately estimated CsA AUC0-12h in the validation group (n=15; NONMEM: bias (mean ± SD)/RMSE=2.05%±13.31%/13.02%; ITS: 4.61%±10.56%/11.20%; Pmetrics: 0.30%±10.12%/10.47%). The dose chosen confronting the 3 results led to a pertinent dose proposal.ConclusionsBEs developed were all able to predict cyclosporine AUC0-12h in HCT patients using only three blood with minimal bias and may be combined to increase the reliability of CsA dose adjustment in routine.British Journal of Clinical Pharmacology 04/2014; · 3.69 Impact Factor
Article: Pharmacokinetics of mycophenolate mofetil in children with lupus and clinical findings in favour of therapeutic drug monitoring[Show abstract] [Hide abstract]
ABSTRACT: AimsThe use of mycophenolate mofetil (MMF) in children with Systemic Lupus Erythematosus (SLE) is increasing. However, the clinical benefit of its monitoring has been scarcely studied, and little is known about its pharmacokinetics in this context. The objectives of the present study were: (i) to describe mycophenolic acid (MPA; the active moiety of MMF) pharmacokinetics; (ii) to develop a Bayesian estimator (BE) allowing the determination AUC (Area under the curve) from a limited number of blood samples; and (ii) to explore the relationships between exposure indices to MPA and the clinical status in children with SLE.Methods This was a retrospective study including 36 children with SLE, extracted from the expert system ISBA, for whom full- pharmacokinetic profiles of MPA were collected together with clinical data. A pharmacokinetic model and a BE were developed using an iterative two-stage Bayesian approach. ROC curve analyses and logistic regressions was used to investigate the association of exposure and active disease.ResultsA pharmacokinetic model and a BE were developed that allowed good AUC estimation performance (bias±SD=-0.02±0.15). ROC curve analyses showed that AUC/dose<0.06 and AUC<44 mg*h/L were associated with a good sensitivity and specificity for active disease (78%/94% and 94%/56% respectively). When introduced in a logistic regression model, AUC<44 mg.h/L and AUC/dose<0.06 were associated with an increased risk of active disease (OR=21.2[2.3-196.1], p=0.007; and OR [95%CI]=59.5[5.9-588.2], p=0.0005 respectively).Conclusions The developed pharmacokinetics BE could be used to prospectively test the interest of MPA monitoring for limiting relapse of the disease or its progression.British Journal of Clinical Pharmacology 04/2014; · 3.69 Impact Factor
Article: Associations between polymorphisms in target, metabolism, or transport proteins of mycophenolate sodium and therapeutic or adverse effects in kidney transplant patients.[Show abstract] [Hide abstract]
ABSTRACT: Different associations between single nucleotide polymorphisms (SNPs) in cellular target, metabolism enzymes or transport proteins, and biopsy-proven acute rejection (BPAR) or adverse events have been reported in transplant patients receiving mycophenolate mofetil. This work aimed to study these in patients on enteric-coated mycophenolate sodium (EC-MPS). The study included 189 renal transplant patients from the DOMINOS trial. Fifteen SNPs in IMPDH2, IMPDH1, ABCC2, SLCO1B3, UGT1A8, UGT1A9, UGT2B7, CYP2C8, HUS1, and IL12A were genotyped in all patients. Associations between SNPs and the first event of BPAR or diarrhea were investigated using multivariate logistic regressions. Associations between SNPs and leukopenia or anemia at nine different visits between days 0 and 190 after transplantation were studied using time-dependent Cox proportional hazards regression models. Multivariate analyses showed that the CYP2C8 rs11572076 wild-type genotype was associated significantly with a lower risk of leukopenia [GG vs. GA: hazard ratio (95% confidence interval) 0.14 (0.03, 0.59), P=0.00783]. Higher EC-MPS doses and the UGT2B7 c.-840 G>A variant allele were associated with an increased risk of anemia [EC-MPS per unit dose increase: 1.004 (1.003, 1.005), P<0.0001; UGT2B7 GA vs. AA: 1.65 (1.12, 2.43), P=0.01043; GG vs. AA: 1.88 (1.23, 2.88), P=0.00343]. However, no significant association was found between any of the SNPs studied and diarrhea or BPAR. Two pharmacogenetic associations reported previously with mycophenolate mofetil were found in a population of 189 renal transplant patients treated with EC-MPS.Pharmacogenetics and Genomics 03/2014; · 3.61 Impact Factor
Article: Calcineurin Activity Assay Measurement by Liquid Chromatography-Tandem Mass Spectrometry in the Multiple Reaction Monitoring Mode.[Show abstract] [Hide abstract]
ABSTRACT: Blood concentrations of the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus are currently measured to monitor immunosuppression in transplant patients. The measurement of calcineurin (CN) phosphatase activity has been proposed as a complementary pharmacodynamic approach. However, determining CN activity with current methods is not practical. We developed a new method amenable to routine use.METHODS: Using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM-MS), we quantified CN activity by measuring the dephosphorylation of a synthetic phosphopeptide substrate. A stable isotope analog of the product peptide served as internal standard, and a novel inhibitor cocktail minimized dephosphorylation by other major serine/threonine phosphatases. The assay was used to determine CN activity in peripheral blood mononuclear cells (PBMCs) isolated from 20 CNI-treated kidney transplant patients and 9 healthy volunteers.RESULTS: Linearity was observed from 0.16 to 2.5 μ mol/L of product peptide, with accuracy in the 15% tolerance range. Intraassay and interassay recoveries were 100.6 (9.6) and 100 (7.5), respectively. Michaelis-Menten kinetics for purified CN were Km = 10.7 (1.6) μ mol/L, Vmax = 2.8 (0.3) μ mol/min/mg, and for Jurkat lysate, Km = 182.2 (118.0) μ mol/L, Vmax = 0.013 (0.006) μ mol/min/mg. PBMC CN activity was successfully measured in a single tube with an inhibitor cocktail.CONCLUSIONS: Because LC-MRM-MS is commonly used in routine clinical dosage of drugs, this CN activity assay could be applied, with parallel blood drug concentration monitoring, to a large panel of patients to reevaluate the validity of PBMC CN activity monitoring.Clinical Chemistry 11/2013; · 7.15 Impact Factor
Article: Pelvic magnetic resonance imaging in the ewe: A model for experimental gynecologic research.[Show abstract] [Hide abstract]
ABSTRACT: Our goal was to demonstrate the feasibility of pelvic magnetic resonance imaging (MRI) in the ewe. Two ewes underwent a pelvic 3 Tesla MRI scan, under light anesthesia, with T2-weighted fast spin-echo images and T1-weighted spoiled gradient-echo images. Multiplan T1 weighted images were also obtained after the intravenous injection of a contrast product. One ewe was anestrous and the other one had undergone ovarian stimulation. No incident occurred during the examination. Both the uterus (with two horns) and the ovaries were identified. The intensity of the endometrial, myometrial and ovarian signals was similar to that encountered in women. The uterus and ovaries could be enhanced in both cases. Pelvic vasculature was also studied. In the case of hormonal stimulation, the endometrium was thicker, follicular growth was identified and enhancement seemed greater. MRI in the ewe is feasible and could be helpful in experimental gynecologic research, especially in uterus transplantation.Journal of Obstetrics and Gynaecology Research 09/2013; · 0.84 Impact Factor
Article: Effect of CYP3A4*22, POR*28, and PPARA rs4253728 on Sirolimus In Vitro Metabolism and Trough Concentrations in Kidney Transplant Recipients.[Show abstract] [Hide abstract]
ABSTRACT: Recent studies have identified new candidate polymorphisms in the genes related to CYP3A activity or calcineurin inhibitor dose requirements in kidney transplant recipients. These genes and polymorphisms are CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C>T; *22); POR [P450 (cytochrome) oxidoreductase] (rs1057868-C>T; *28); and PPARA (peroxisome proliferator-activated receptor alpha) (rs4253728-G>A). We investigated the impact of these polymorphisms on sirolimus (SRL) in vitro hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in kidney transplant recipients.METHODS: The clinical study included 113 stable kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0 measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in vitro using human liver microsomes derived from individual donors (n = 31). Microsomes and patients were genotyped by use of Taqman® allelic discrimination assays. The effects of polymorphisms and covariates were studied using multilinear regression imbedded in linear mixed-effect models or logistic regressions.RESULTS: In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). No significant association was found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in kidney transplant patients. POR*28 was associated with a minor but significant decrease in SRL log-transformed C0 [CT/TT vs CC, β = -0.15 (0.05); P = 0.0197] but this did not have any impact on the dose administered, which limited the relevance of the finding. After adjustment for nongenetic covariates and correction for false discovery finding, none of the single-nucleotide polymorphisms tested showed significant association with SRL adverse events.CONCLUSIONS: These recently described polymorphisms do not seem to substantially influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in kidney transplant recipients.Clinical Chemistry 08/2013; · 7.15 Impact Factor
Article: Lessons From Routine Dose Adjustment of Tacrolimus in Renal Transplant Patients Based on Global Exposure.[Show abstract] [Hide abstract]
ABSTRACT: OBJECTIVES:: Since 2007, a number of transplantation centers have been routinely using an expert system for tacrolimus (TAC) dose adjustment in kidney allograft recipients, based on PK modeling and Bayesian estimation for area-under-the-curve (AUC) determination. This has allowed the setting up of a large database of TAC pharmacokinetic profiles and AUC values, a part of which was analyzed here. METHODS:: We retrospectively studied 2030 requests posted by 21 different centers for routine TAC dose adjustment in 1000 different adult renal transplant patients (not enrolled in any kind of concentration-controlled clinical trial). For each request, the following information was obtained: time elapsed since transplantation, TAC daily dose, calculated AUC, and trough concentration (C0). RESULTS:: The dose-standardized exposure to TAC significantly and progressively increased in the months after transplantation: from month (M) 1 to M9 C0/dose increased from 2.33 to 3.44 mcg·L·mg and AUC/dose from 43.1 to 64.2 mcg·h·L·mg, respectively. On the contrary, in patients beyond the first year whose C0 or AUC was in the target range, the odds of remaining in this range were high for a long time period, suggesting a low intrapatient variability in the stable phase. Regression analyses showed that the correlation between C0 and AUC was better in the first 3-month period (r² = 0.76) than later on (r² ≤ 0.67). Using the regression equations obtained, AUC ranges corresponding to different applicable C0 targets were calculated. CONCLUSIONS:: From a large number of kidney graft recipients, we have estimated the relationships between C0 and AUC, modeled the evolution of TAC exposure with time and defined AUC targets that could be useful to lead further controlled-concentration trials and improve routine TAC therapeutic drug monitoring.Therapeutic drug monitoring 05/2013; · 2.43 Impact Factor
Article: Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal-transplant recipients using a joint modeling approach.[Show abstract] [Hide abstract]
ABSTRACT: This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mixed-effects model to describe the whole pattern of MPA exposure (i.e. area under the concentration-time curve -AUC-) and a survival model. MPA AUC thresholds were determined using time-dependent Receiver-Operating Characteristics (ROC) curves. Data from 490 adult renal-transplant recipients, representative of the general population of adult renal-transplant patients (i.e. including patients considered at low immunological risk-enrolled in the OPERA trial- as well as second renal transplant and patients co-treated by either cyclosporine or tacrolimus), were analyzed. A significant association was found between the longitudinal exposure to MPA (MPA AUCs=f(t)) and AR (p=0.0081), and validated by bootstrapping. A significant positive correlation was observed between time post-transplantation and ROC thresholds which increased in average from 35mg.h/L in the first days to 41mg.h/L beyond six months post-transplantation (p<0.001). Using a new modeling approach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR.Pharmacological Research 04/2013; · 4.35 Impact Factor
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ABSTRACT: This work rationalizes the glucuronidation process (one of the reactions of the phase II metabolism) for drugs having a carboxylic acid moiety. At this stage, acylglucuronides (AG) metabolites are produced, that have largely been reported in the literature for various drugs (e.g., mycophenolic acid (MPA), diclofenac, ibuprofen, phenylacetic acids). The competition between migration and hydrolysis is rationalized by adequate quantum calculations, combing MP2 and density functional theory (DFT) methods. At the molecular scale, the former process is a real rotation of the drug around the glucuconic acid. This chemical-engine provides four different metabolites with various toxicities. Migration definitely appears feasible under alkaline conditions, making proton release from the OH groups. The latter reaction (hydrolysis) releases the free drug, so the competition is of crucial importance to tackle drug action and elimination. From the theoretical data, both migration and hydrolysis appear kinetically and thermodynamically favored, respectively.Journal of Molecular Modeling 02/2013; · 1.98 Impact Factor
Article: Ciclosporin Population Pharmacokinetics and Bayesian Estimation in Thoracic Transplant Recipients.[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND AND OBJECTIVES: Therapeutic drug monitoring of ciclosporin has been recognized as an essential tool in the management of allograft transplant recipients, as it could help improve their outcome. However, there is still no consensus about the optimal method for monitoring ciclosporin after thoracic transplantation. Better knowledge of the pharmacokinetics of ciclosporin in thoracic transplant patients and design of tools dedicated to ciclosporin monitoring could help its practice and its outcome in this population of patients. The aims of this study were to (i) investigate the population pharmacokinetics of ciclosporin in thoracic (heart or lung) transplant patients and study the influence of a range of potential covariates, including demographic, clinical and genetic factors, on pharmacokinetic parameters; and (ii) develop a Bayesian estimator able to predict the individual pharmacokinetic parameters and exposures indices in this population of patients. METHODS: The analysis was performed with 187 full pharmacokinetic profiles obtained in 57 lung and 19 heart transplant patients within the first year post-transplantation. A population pharmacokinetic model was developed by non-linear mixed-effects modelling using NONMEM(®) (version 7.1) from an index dataset (118 profiles). On the basis of this population model and a limited number of blood samples, a Bayesian estimator able to determine ciclosporin area under the blood concentration-time curve (AUC) during a dosage interval was built and evaluated in the validation dataset (69 profiles). RESULTS: Ciclosporin pharmacokinetics were described using a two-compartment model with time-lagged first order absorption and first-order elimination. The final population model included sex as a covariate: ciclosporin apparent oral clearance was on average 37 % faster in male than in female patients (34.8 vs. 25.4 L/h, p < 0.001). Good predictive performance of the Bayesian estimator was obtained using three blood concentrations measured at 40 min, 2 h and 4 h post-dose, with a non-significant bias of -5 % between the estimated and the reference trapezoidal AUC and a good precision (relative mean square error = 13 %). CONCLUSION: Ciclosporin population pharmacokinetic analysis in thoracic transplant patients (including patients with cystic fibrosis) showed a significant influence of sex on apparent clearance. The Bayesian estimator developed in this study yielded accurate prediction of ciclosporin exposure in this population throughout the first year post-transplantation. This tool may allow routine ciclosporin dose individualization.Clinical Pharmacokinetics 02/2013; · 5.49 Impact Factor
Article: Involvement of UDP-glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse.[Show abstract] [Hide abstract]
ABSTRACT: Background: Ethylglucuronide (EtG) determination is increasingly used in clinical and forensic toxicology to document ethanol consumption. The enzymes involved in EtG production, as well as potential interactions with common drugs of abuse, have not been extensively studied. Methods: Activities of human liver (HLM), kidney (HKM) and intestinal (HIM) microsomes, as well as of twelve major human recombinant UDP-glucuronosyltransferases (UGTs), toward ethanol (50 and 500 mM) were evaluated in vitro using liquid chromatography-tandem mass spectrometry. Enzyme kinetic parameters were determined for pooled microsomes and recombinant UGTs with significant activity. Individual contributions of UGTs were estimated using the relative activity factor (RAF) approach, proposed for scaling activities obtained with cDNA-expressed enzymes to HLM. Interaction of morphine, codeine, lorazepam, oxazepam, nicotine, cotinine, cannabinol and cannabidiol (5, 10, 15 mg/L) with ethanol (1.15, 4.6, 11.5 g/L; i.e. 25, 100, 250 mM) glucuronidation was assessed using pooled HLM. Results: Ethanol glucuronidation intrinsic clearance (Cl(int)) was 4- and 12.7- times higher for HLM than for HKM and HIM, respectively. All recombinant UGTs, except UGT1A1, 1A6 and 1A10, produced EtG in detectable amounts. UGT1A9 and 2B7 were the most active enzymes, each accounting for 17% and 33% of HLM Cl(int), respectively. Only cannabinol and cannabidiol significantly affected ethanol glucuronidation. Cannabinol increased ethanol glucuronidation in a concentration-dependent manner, whereas cannabidiol significantly inhibited EtG formation in a non-competitive manner (IC(50)=1.17 mg/L; Ki=3.1 mg/L). Conclusions: UGT1A9 and 2B7 are the main enzymes involved in ethanol glucuronidation. In addition, our results suggest that cannabinol and cannabidiol could alter significantly ethanol glucuronidation.Drug metabolism and disposition: the biological fate of chemicals 12/2012; · 3.74 Impact Factor
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ABSTRACT: Except adoption, absolute uterine factor infertility lacks solution in case of motherhood desire. Gestational surrogacy is still not approved in France. Over the last decade, uterus transplantation experimentation made advances. Data from animal research, progress in immunosuppressive treatment and knowledge about pregnancy after transplantation provide a scenario in which a human allotransplantation project can become reality.Gynécologie Obstétrique & Fertilité 11/2012; 40(11):691–694. · 0.55 Impact Factor
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ABSTRACT: Except adoption, absolute uterine factor infertility lacks solution in case of motherhood desire. Gestational surrogacy is still not approved in France. Over the last decade, uterus transplantation experimentation made advances. Data from animal research, progress in immunosuppressive treatment and knowledge about pregnancy after transplantation provide a scenario in which a human allotransplantation project can become reality.Gynécologie Obstétrique & Fertilité 10/2012; · 0.55 Impact Factor
Article: Association of sirolimus adverse effects with m-TOR, p70S6K or Raptor polymorphisms in kidney transplant recipients.[Show abstract] [Hide abstract]
ABSTRACT: The mammalian target of rapamycin (m-TOR) inhibitor sirolimus is an immunosuppressive drug used in kidney transplantation. m-TOR binds with Raptor and phosphorylates p70S6 kinase, a protein involved in numerous cell signalling pathways. We examined the association of candidate polymorphisms in m-TOR, Raptor and p70S6K, sirolimus dose and exposure, and other time-independent as well as time-dependent covariates, with sirolimus-induced adverse events in kidney transplant recipients. This study included a first group of 113 patients, switched from a calcineurin inhibitor to sirolimus, and a validation group of 66 patients from another clinical trial, with the same immunosuppressive regimen. The effects of gene polymorphisms and covariates on the total cholesterol, LDL cholesterol, triglycerides, haemoglobin, cutaneous adverse events, oedemas and infections were studied using multilinear regression, or logistic regression imbedded in linear mixed-effect models. An m-TOR variant haplotype was significantly associated with a decrease in haemoglobin levels in the two populations of patients (discovery group: β=-0.82 g/dl, P=0.0076; validation group: β=-1.58 g/dl, P=0.0308). Increased sirolimus trough levels were significantly associated with increased total cholesterol levels (discovery group: β=0.02 g/l, P<0.0001; validation group: β=0.02 g/l, P=0.0002) and triglyceride levels (discovery group: β=0.02 g/l, P=0.0059; validation group: β=0.05 g/l, P=0.0370). Sirolimus trough levels were also associated with an increased risk for cutaneous adverse events [odds ratio=1.97, 95% confidence interval (1.32-1.94), P=0.0009] and oedemas [odds ratio=1.16, 95% confidence interval (1.03-1.30), P=0.01342] in the discovery group, but this was not confirmed in the validation group. These results provide evidence of an association between an m-TOR haplotype and a decrease in haemoglobin in renal transplant recipients.Pharmacogenetics and Genomics 08/2012; 22(10):725-32. · 3.61 Impact Factor
Article: Simultaneous evaluation of six human glucuronidation activities in liver microsomes using liquid chromatography-tandem mass spectrometry.[Show abstract] [Hide abstract]
ABSTRACT: This article describes the development of a procedure for the simultaneous evaluation of the activity of six different uridine diphosphate (UDP)-glucuronyltransferases (UGTs) in human liver microsomes (HLMs). The method consists of incubations of probe substrates for UGT1A1 (etoposide), UGT1A3 (chenodeoxycholic acid), UGT1A4 (trifluoperazine), UGT1A6 (serotonin), UGT1A9 (mefenamic acid), and UGT2B7 (azidothymidine) with HLMs. The six substrates were divided into three different incubations (etoposide + mefenamic acid; chenodeoxycholic acid + serotonin + azidothymidine; and trifluoperazine alone), the media of which were pooled before analysis. Glucuronide formation rates were determined in a single run of 20 min using a validated liquid chromatography-tandem mass spectrometry method. No significant difference was observed between glucuronidation activities measured using the current procedure and individual incubations of the probes. The method was used successfully for the determination of UGT activities in 44 individual HLM preparations and for the phenotyping of preparations predicted to have altered UGT1A1 and UGT2B7 activities because of known genetic polymorphisms.Analytical Biochemistry 05/2012; 427(1):52-9. · 2.58 Impact Factor
Article: Mapping cyclosporine-induced changes in protein secretion by renal cells using stable isotope labeling with amino acids in cell culture (SILAC).[Show abstract] [Hide abstract]
ABSTRACT: Nephrotoxicity is an adverse event that strongly limits the use of the immunosuppressant cyclosporine in solid organ transplantation and the precise molecular mechanisms underlying this toxicity remain unclear. MS-based proteomic analysis of the secretome of HEK-293 renal cells exposed to cyclosporine was performed to identify changes in protein secretion, as a first step to discover potential biomarkers of such nephrotoxicity. To detect and quantify the perturbed proteins in the culture medium we used SILAC and nano-scale liquid chromatography followed by MALDI-TOF/TOF mass spectrometry. Among 106 proteins identified, 80 were quantified in both forward/reverse SILAC experiments and quantitative proteomic analysis revealed altered levels of expression for 24 secreted proteins. These included the down-regulation of a number of extracellular matrix/cell adhesion components, and the up-regulation of secreted cyclophilins A and B, macrophage inhibition factor and phosphatidylethanolamine-binding protein 1. These changes in protein secretion were not prevented by co-incubation with the antioxidant N-acetylcysteine, suggesting that they were not triggered by cyclosporine-induced oxidative stress. The results from the present study provide important new knowledge to gain insights into the molecular mechanisms of cyclosporine-related toxicity. Some of the proteins identified here should be tested as potential biomarkers of cyclosporine nephrotoxicity in subsequent clinical studies.Journal of proteomics 04/2012; 75(12):3674-87. · 5.07 Impact Factor
Top Journals
French Institute of Health and Medical ResearchLutetia Parisorum, Île-de-France, France
University of Limoges
Limages, Limousin, France
- Faculté de Médecine
Unité Inserm U1077Caen, Lower Normandy, France
University of Lille Nord de FranceLille, Nord-Pas-de-Calais, France
Centre Hospitalier Universitaire de Limoges
Limoges, Limousin, France
- Department of Pharmacology, Toxicology and Pharmacovigilance
University of GrenobleGrenoble, Rhône-Alpes, France
Assistance Publique Hôpitaux de Marseille
Marseille, Provence-Alpes-Cote d'Azur, France
- Service de médecine légale
Université Victor Segalen Bordeaux 2
Bordeaux, Aquitaine, France
- Institut de Santé Publique d'Epidémiologie et de Développement (ISPED)
University of ToursTours, Centre, France


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Related Stories
Updated: June 7, 2014 6:23AM
The Blackhawks have been the best road team in the Stanley Cup playoffs
under coach Joel Quenne-
ville, with one hitch: It seems to take them a little while to adjust to the challenge of playing in enemy territory.
The Hawks are 17-14 on the road in the playoffs since 2010, but they are only 2-9 in their first road game of a
series, including eight consecutive losses. The last time the Hawks won their first road game in a series was against the San Jose Sharks in the Western Conference finals in 2010.
Therein lies the challenge for the Hawks going into Game 3 of their second-round series against the Minnesota Wild on Tuesday at Xcel
Energy Center. The Hawks lead the series 2-0. In the first round against the Wild last season, the Hawks lost 2-1 in overtime in Game 3 at Xcel Energy Center before winning 3-0 in Game 4 and taking the series in five games.
''Aware of it,'' Quenne-
ville said when asked about the Hawks' string of losses in the first road game of a series. ''We've been pretty good on the road, but the first game in the other team's building hasn't been very successful for us. We've had some good games, close games, overtime games, different kind of games.''
Actually, the Hawks seem to be on the verge of breaking that streak. While they appeared overwhelmed — or at least out of their element — in road losses to the Detroit Red Wings, Los Angeles Kings and Boston Bruins last season en route to the Stanley Cup, they outplayed the St. Louis Blues in a 4-3 loss in triple overtime in their first road game in the first round this season.
In fact, in three playoff road games against the Blues, the Hawks lost in triple overtime, lost in overtime and won Game 6 in overtime. They were 1 minute, 45 seconds from winning Game 1 and 6.4 seconds from winning Game 2.
The Hawks seem to be getting the hang of it. They have 18 players who played in their Cup run last season, and the chemistry is more evident with each game. When they were defending the Cup in 2011, the Hawks had 11 holdovers from the 2010 championship team.
''It's always a tough game [in Minnesota],'' center
Michal Handzus said. ''They are going to be fired up. It's the first [home] game for them in the series. You kind of have to weather the storm, and you have to push back right away. That was something we probably didn't do as much over the last year and this year.''
For the Hawks, especially in a series in which they have the Wild outmanned, it's a matter of knowing what they're up against.
''We need to do a good job of preparing and knowing that it's going to be tougher,'' defenseman Duncan Keith said. ''They're going to be skating harder, and I think [it's a matter of] being able to understand that and come out with our best effort of the series.''


text:
5 reasons we're thankful for Bella Thorne
My BF broke up with me and has ignored me ever since. Why?
Be a pro pet sitter!
7 (other) awesome dystopian books to read right now
Christmas Crafts for the entire fam under $10
GL's Friends Gift Guide: Exactly what to get your besties for under $20
Mani roundup: Too-cute Thanksgiving nail ideas
Flu shots: myths uncovered
Which celeb should be at your dinner table this Thanksgiving?
What do you think of our Dec/Jan issue? We wanna know!
Kirby Buckets Clip
More Friends = More Fun
GL Tweets !
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text:
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Bismarck, ND 58503
Ph: 701-355-1010
Toll Free: 800-279-2361
Fax: 866-665-1011
EMAIL: email@example.com
Hot Off The Press!
click here for the winter issue of the NDAR newsletter.
Attention: NDAR Board of Directors & Committee Meetings
December 9, 2014 –Jamestown, ND
Need Education?
December 2-3
1. Agency: "It's Not About You" 2. FirstHome Essentials 3. Fair Housing Basics -Bismarck
Have you completed at least 3 hours of the 9 required in either Fair Housing or Agency to fulfill the mandatory requirement for 2014? NDAR has set the December education schedule! 3 classes will be offered to cover 9 hours plus two of the 3 classes cover the mandatory topic for 2014. (Agency & Fair Housing)
For a downloadable (pdf) registration flyer & detailed information click here
To register and pay online click here
For the latest NDAR news and up to date information check out the new REALTOR® Report click here <——- new! October 24th


text:
Let the bidding begin. I mean, come on, you had to know that with so many people wanting the new Z06, some dealerships were bound to push their asking prices up.
Sixteen MPG combined isn't bad for a car with 650 horsepower and 650 lb-ft of torque that will do zero to 60 in under three seconds. Then again, if it's amazing fuel economy numbers you're looking for, you probably stumbled on the wrong website.
I don't know about you, but I just can't get enough video footage of the 2015 Corvette Z06. Seeing photos is one thing, but seeing the car in motion is a completely different take on the new higher-performance 'Vette.
Specifically, the 2015 Corvette Z06 with the Z07 package holds the distinction of having the most aerodynamic downforce ever measured on a production car.
The recall pipeline has delivered us not one, but two recalls that cover about 900 units of 2015-model-year Corvettes.


text:
"Where Luxury and Technology Meet Sustainability"
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Vancouver's newest boutique hotel on Robson -
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Mention the BC Home + Garden Show and receive a discounted show rate of $139 + taxes
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1996 Chevrolet Corvette Collector's Edition Coupe - 5.7 Liter SFI V8, 6-speed manual, power steering, power ABS disc brakes, electronic climate control, power windows,... More
For the serious driver and the collector is a completely restored with the frame off and everything redone top to bottom 62 Vette. Every... More
1990 CHEVROLET CORVETTE ZR1 This Corvette is in all original condition with 27,000 miles. This beautiful car looks, rides, drives, and smells like new. The... More
1969 corvette convertible, 427ci 400hp 4 speed. Matching number.Professional frame off restoration to the highest standards... Car is in number 1 condition and has... More
Corvette 1964 Convertible, White / Red / Black, 327/300hp, 4-Speed, original car w/ 300 miles on professional restoration, looks great-runs strong, "head turner" fun... More
There have been many great Corvettes built over the years; but, for those who share Zora Arkus Duntov's vision of the Corvette as world... More
Being offered for sale is an absolutely stunning 1993 Quasar Blue Metallic, with Tuxedo (Black & White) leather interior, 5.7 Liter 300 hp Corvette... More
1994 Chevrolet Corvette Nice classic Corvette! With only 68602 miles. Hard top removable. Retired and having to sell my toy.... More
1987 Chevrolet Corvette Greenwood Edition1987 Chevrolet Corvette Greenwood Edition in mint conditionFactory Painted Metallic Silver Gray Two Tone exterior plus a Gray leather... More
This 1966 Chevrolet Corvette Sting Ray 2 Door Convertible (Stock # P10045) is available in our Pleasanton, CA showroom and any inquiries may be... More
This 2004 Chevrolet Corvette Le Mans Commemorative Edition 2 Door Convertible (Stock # P10043) is available in our Pleasanton, CA showroom and any inquiries... More
This 2007 Chevrolet Corvette Pace Car 2 Door Roadster (Stock # B11076) is available in our Benicia, CA showroom and any inquiries may be... More
Just in! Call or visit our website for more information.... More
Offered for sale is a 1970 Corvette 2-top Roadster, LS5 454CI / 390HP With 4 Speed and Pwr Steering. This car has Original Paint,... More
This 1974 L82 Chevrolet Corvette Convertible is a very attractive driver with great options. Finished in correct to the trim tag code 10L Classic... More


text:
Latest files
Bellustu for Skyrim
Underground Nordic home located near Winterhold..
uploaded 4:20, 17 Nov 2012 812 23 1,386kb Thorsaken
Tona- Anchorite Outfit By Nausicaa for Skyrim
This is conversion of "Anchorite Outfit for HGEC" from "Tonas Mods Store" in oblivion mod.
Original author is Tona.
uploaded 2:44, 17 Nov 2012 7,150 115 10,081kb nausicaa36
xXxDOYLExXx ENB Tweak for Skyrim
I've been asked for my settings numerous times for what I use on my ENB. The theme I was shooting towards was immersiveness. Nothing too crazy, nothing too bright, nothing to resource heavy, and no over-powering blur.
Simply beautiful and immersive.
Alas I've gotten around to posting the settings I use.
uploaded 1:19, 17 Nov 2012 1,021 18 19kb xXxDOYLExXx
World Map Min_Max Height Pitch Tweak for Skyrim
Overrides three in-game settings for the world map that can no longer be changed via the Skyrim.ini file since the Skyrim 1.8 update. Sets Min/Max height for the world map to let you see whole map at once or to zoom way in. Increased panning range. Two versions: One sets pitch to 90° when map is first opened, the other doesn't. New addon elimi
uploaded 0:49, 17 Nov 2012 12,689 433 2kb Allana
Balthazars Books - a Markarth bookstore for Skyrim
With literacy rates in Skyrim rising, now is the time to open a bookstore! Also I was tired of having to look for books in ruins. So here it is, the Reach's first book shop. I hope you like it.
uploaded 0:40, 17 Nov 2012 2,392 125 1,327kb acidzebra
FAMP-Fully Animated Meals Potions - Compatibility Patches for Skyrim
Compatibility patches for Fully Animated Meals Potions .
uploaded 0:11, 17 Nov 2012 6,593 185 1kb bla08
Wind of the Nords - ENB for Skyrim
ENB v0.119 for Skyrim (works fine with ENB V0.123 too)
This is a tweaked and adapted ENB of Midras' Fallout 3 ENB.
Colourful and vibrant with deep shadows.
Small performance hit with AO and DOF off.
uploaded 0:01, 17 Nov 2012 2,482 63 150kb windofthenords
Dragonthorn Keep for Skyrim
A massive fortress for the dovahkiin to inhabit!Complete with barracks Palace Mages tower and town with plenty of merchants
uploaded 22:26, 16 Nov 2012 6,361 100 2,341kb XOMICH
Darkness Rises When Silence Dies A Dark Brotherhood Mod for Skyrim
this Dark Brotherhood mod Is meant to played after you complete the MQ For the Dark Brotherhood
uploaded 21:44, 16 Nov 2012 655 3 1kb Bloodangle09
Power and Performance ENB by Fabianku for Skyrim
ENB v0119 for Skyrim
Although looking as awesome as sharpshooters ENB i could increase the performance drastically!!!!
So no style loss but more FPS
Also has:
warm interiors
Realistic dark nights
Dynamic bokeh
Realistic indirect illumination
Rich colours
blinding sun
Realistic Lighting
lens flare
uploaded 21:10, 16 Nov 2012 11,320 140 2,174kb Fabianku
Crusaders Knights Templar Hospitaller Teutonic Chivalry Medieval Warfare Armors for Skyrim
Adds Crusader, Knights Templar, Knights Hospitallers, Teutonic Knights, Principality of Antioch, Knights of Agatha and Mason Order Vanguard inspired Armors
uploaded 19:30, 16 Nov 2012 67,536 1,549 1,246kb ghostrecon123
NPCs Use Ammo - All Bows GERMAN for Skyrim
Das ist die Übersetzung des Mods NPCs Use Ammo - All Bows von Moogiefluff
Der Modhersteller würde sich auf folgendem Link über ein \"Endorse\" freuen...
Originallink http://skyrim.nexusmods.com/mods/14125
uploaded 19:07, 16 Nov 2012 91 2 3kb waroo


text:
It's time to make this official. We've been talking about em:pwr
Read article
Submissions are now open for the Eleventh Annual Bicycle Film Festival! The BFF is
A few months ago when I was trying to inspire myself to get back on the road bike, I
If you are a common visitor to BikeShopGirl.com (thank you) than you may have
Last summer I mentioned Soul Run products and carrying your tools in style. Now
When friend and follower Rick Vosper sent along spy photos of a new cyclocross bike
There are reasons that daytime running lights have become standard on many cars,
With our the announcement of our em:pwr cycling, we want to dive deeper into our
We mentioned a Bike Shop Girl cycling team for 2011 and with much discussion,
Nalgene On the Fly MRSP: $12.99 Size: 24 ounces Companies Pitch: Nalgene's newest
Bike Shop Girl is me, Arleigh Jenkins. With over 12+ years of bicycle industry experience from running bike shops, seasoned bike mechanic & fitter, to avid bike commuter and racer; you can say I've done almost everything. I started Bike Shop Girl to reach more women and make their cycling experience better.
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text:
a female whose a hoe, slut, cunt, bitch... etc
додав MiSZ BABY PHAT 22 Квітень 2007
$100 in the east bay
ima throw down a bird on that.
додав watitiz pimp 2 Березень 2005
some kid from niskayuna NY. he has toolish qualities along with an absurdness that never ceases to make you laugh. very strange and somewhat resembles an actual bird. AKA 'butters'
i think bird is gonna be there tonight. koren is probably with him. what a fucking tool.
додав five speed 19 Березень 2005


text:
Police make drug busts during unrelated searches
Updated: 03/21/2013 - Eight people are in jail on drug-related charges after two meth busts on separate days in Knott County.
Updated: 03/21/2013 - Eight people are in jail on drug-related charges after two meth busts on separate days in Knott County.
Posted: 03/21/2013 - Your daily look at late-breaking news, upcoming events and the stories that will be talked about Thursday.
Updated: 03/21/2013 - A Pike County man is indicted on charges of attempted murder, rape, sodomy, and being a persistent felony offender.
Posted: 03/20/2013 - A bankruptcy judge has approved the sale of Twinkies to a pair of investment firms.
Posted: 03/21/2013 - A house of worship became the target of vandals. And Wednesday the Pulaski County Sheriff's Office released surveillance video, hoping it will help make some arrests.
Posted: 03/20/2013 - Two Ashland men face up to 30 years in prison after a federal jury convicted them on charges related to operating a motorcycle theft ring.
Posted: 03/20/2013 - A Pike County man was indicted on charges of attempted murder, rape, sodomy, and being a persistent felony offender.
Updated: 03/22/2013 - The Johnson County Middle School academic team won this year's Governor's Cup competition.
Updated: 03/21/2013 - Charges have been dismissed against a woman who left her great grandson at a southern Kentucky McDonald's.
Updated: 03/20/2013 - Ernie Shell says his brother Shelby Shell confessed to him the killing of Ronny King. Ernie Shell gave the information to police.
Posted: 03/20/2013 - Several Eastern Kentucky counties were listed at the bottom of a recent county-by-county study of health in the Bluegrass. Perry County is next to last on the list. However, a group of local school children took part in a fitness fair Wednesday in an effort to curb the trend.
Posted: 03/20/2013 - A third person has been indicted in connection with the death of Eli Marcum in Clay County.
Updated: 03/20/2013 - Hillbilly days organizers met Wednesday to kick off preparation for the festival.
Posted: 03/20/2013 - A fire broke out inside the old Trus Joist building at the Coal Fields Regional Industrial Park.
Updated: 03/20/2013 - One eastern Kentucky county saw dramatic changes in the number of drug related deaths in just a one year period.
Posted: 03/20/2013 - LEXINGTON, Ky. (AP) - Democratic Secretary of State Alison Lundergan Grimes still isn't saying whether she's seriously considering a U.S. Senate bid.
Posted: 03/20/2013 - Beshear created the panel last year by executive order. But the law he signed Wednesday gives panel members deeper access to case files involving children who died or suffered serious injuries.
Updated: 03/20/2013 - Julius Randle, ESPN's number one power forward prospect and number three overall prospect in the class of 2013, has announced that he will play basketball for the University of Kentucky
Updated: 03/20/2013 - Officials have released the heartbreaking 9-11 call from the deadly Wayne County fire last week.
Updated: 03/20/2013 - A man is arrested after deputies say he led them on a wild chase.
Posted: 03/20/2013 - The agreement also requires the agencies to consider an alternative placement if a parent objects to a provider's religious affiliation.
Updated: 03/20/2013 - NCAA Tournament Open Practice Day on Wednesday
Posted: 03/20/2013 - Farmer's sister, Rhonda Monroe, and deputy Agriculture Commissioner Bruce Harper were among seven people charged along with Farmer on Monday of ethics violations.
Posted: 03/20/2013 - General Motors is recalling nearly 27,000 Buicks and Cadillacs in the U.S. to fix a problem with the automatic transmissions.
Updated: 03/20/2013 - President Barack Obama is picking Indiana to win the NCAA title.


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Cassie and Josh don't see eye to eye.
Dinah makes a decision about her romantic future.
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Miley Cyrus "We Can't Stop" Video: Released! Twerk-Tastic!by Free Britney at . Comments
Miley Cyrus released the music video for "We Can't Stop" today, and it's filled with so many crazy antics, it may take you multiple viewings to digest.
Trust us on this one. But also see it for yourself below ...
The three-minute music video is basically sensory overload, which is no doubt what the envelope-pushing Miles intended. Among the many highlights ...
- Miley scarfing down white bread (no gluten free recipes here)
- Lots of gratuitous shots of Miley Twerking in tight pants
- More Twerking, but this time with giant ass teddy bears
- Some chick cutting her fingers off with a meat cleaver
- Miley Cyrus French-kissing a large Miley Cyrus doll
- Some shameless Beats by Dre product placement
- A hot guy not named Liam Hemsworth
- Goats in sunglasses (don't even ask)
- A cigar pinata (we think)
And there you have it. What do you think of the video?
I find it funny how everyone here is saying rat she did "so much twerking." She can't twerk. The only thing she did was shake her butt for 2 seconds. But the video was so disgusting regardless of the tha lack of twerking. I wish she would stop putting her pancake flat butt in the camera. At least do some squats. Seriously.
Loving that a$$ grab! Work it gurl
I liked the old Miley sooooo much more.. She was so cool.. I don't get her now.. I think she's going for Rihanna's style - always changing and making new trends.. But she was gorgeous before.. Too bad we can't see more of the old Miley :( She had the best hair ever..
I'm so sick of the "new" Miley, I wish she hadn't changed!:( Her hair is ugly now too.
I liked the song until I saw the video. She needs to hire a better producer, it had no taste. It just wasn't something that made you want to listen to the song again and again.


text:
Danon pushes bill to stop Israel from returning bodies of terrorists
Pipe bomb thrown at police in capital injures east Jerusalem resident
PM may revoke east Jerusalem terrorists' families residency
Erdan weighs option of revoking residency status of terrorism supporters
Merkel against unilaterally recognizing Palestine as a state
Israeli official: Erdogan rhetoric befits Tehran or Damascus, not a NATO capital
Netanyahu proposes his own version of 'Jewish state bill'
Israel's ambassador to return to Sweden on symbolic Nov. 29th date
Netanyahu: We have nothing against east Jerusalem residents, but we must protect our citizens
Pro-public health advocates battle against private-medicine lobbying and ad campaign
Doctors, nurses more than twice as likely to get flu shots than general population
Cheapen gluten-free food for celiac patients, panel says
Project to improve nutrition loses funds
'Leviathan gas reservoir to begin flowing by early 2018'
New kid's Israeli archaeology game launched for iPhone
Green Knesset advances as MKs replace paper with iPads
Zion Tech: Our Israeli start-up of the week aims to revolutionize therapy access
James Blunt is coming to get 'high' in Tel Aviv
Staging music
Grapevine: Farewell to an articulate advocate for Israel
Theater Review: The Tempest
Yellow-and-blue survives scare to beat Limoges
Beersheba with an opportunity to go top
Back-on-track Maccabi Tel Aviv takes on Limoges in Euroleague
Hapoel Jerusalem facing early Eurocup exit
10% of US-Israelis in IDF become officers
Fitch lowers Israel's outlook from 'positive' to 'stable'
HRW: Israel's demolition of Palestinian terrorists' homes is 'war crime'
Jerusalem mayor: We cannot discriminate against Arabs
UK soccer club owner ready to resign after anti-Semitic comments
Turkish official rejects angry governor's wish to turn synagogue into museum
English soccer club owner faces racism probe for saying Jews 'chase money'
Lawmaker in Antwerp calls on Belgian government to fund security for Jews
German survey: Spike in anti-Semitism after Gaza war
Pro-ISIS graffiti found on monument to fallen Druse soldiers
More reconstruction materials slated to enter Gaza next week
Jordanian PM reportedly sends condolence letter to families of Jerusalem synagogue terrorists
Yemen minister dedicates award to country's Jews
ISIS releases new video with Cantile
Into the Fray: The Arabs' war against the Jews and what must be done
My Word: A personal response to terrorism
An open society
November 21, 2014: Expel 'shahids'
No Holds Barred: The ferocious battle for Israel at New York University
Wishful doing
Cinema of reconciliation
On the volcano's edge
Knowledge, power and abuse
Q&A with a Colombian lone soldier
European Press: Dividing line
Veterans: Keeping an ear out for change
Book Review: Written from his heart
This Week in Jerusalem
Who is your God?
Grapevine: Amazing place
A voice from India
Happily Eva After: When the going gets tough...
Grapevine: Reclaiming our heritage
Upscale dining in Neveh Tzedek
A war for the soul of Israel's Arab community
Iran and the West – how big a gap?
Iranian nukes and 'Palestine' - mutually reinforcing perils for Israel
Islamic State – APEC a fizzer - G20 promises no better
A song for Cheshvan: 'The Eucalyptus Grove'
דְיוֹקְנְאוֹת תַרְבּוּת
מָה הַסִיפּוּר?
הָאַרְכִיוֹן שֶל רוֹמַן וִישְנִיָאק
Har Nof in flames
Meet the Ambassador: No longer a conference diplomat
'Post' leads the way with new podcast
Grapevine: The highest accolade of all
The secret of Jewish survival
Frontlines Podcast: Jerusalem's 'lone wolves'
Tempête au sein de la coalition
Crise de confiance
Qui prendra la relève de Mahmoud Abbas ?
Arafat, Abbas, même combat ?
Daniel Oren, maestro d'Israël, d'Italie et d'ailleurs !
Nos plus belles années ?
De Berlin à New York, 1920-1975
Le pogrome de Constantine
Le pot de chocolat liégeois par qui le scandale arrive
Le dernier kibboutz
La course aux étoiles
Les mordus du français
On n'invite pas un pyromane à éteindre un incendie
Tuer l'EI dans l'œuf
Le mont du Temple et la guerre sainte de l'islam
Les attentats du lundi 10 novembre vus par la presse française
L'Europe, nouvelle alliée d'Abbas ?
Ces enseignants-éclaireurs
Pope Francis condemns Palestinian violence
Last Christian shop-owners in Old City: 'Tourists afraid of the politics'
Kurdish refugees struggle to survive as they outrun Assad's army and ISIS
Discover Ramla from a Christian persepective
Pastor who died in crash mourned in Israel
KKL Belgium Donates Portable Bomb Shelter to Kiryat Gat
KKL-JNF Awards 2014 Blumberg Prize
Exploring the Ilanot Botanical Garden and the Vickar Observation Point
Cornerstone Laid for Sports Rehab Park at Meir Hospital
Mexican Politician and Business Leader Miguel Aleman Velasco Visits KKL-JNF in Jerusalem
International Conference in Sde Boker: Combating Desertification Together
Rehabilitation of the Lower Jordan: Bringing the River Back to Life
Central America Celebrates Independence at the Rabin Center
In his Footsteps: Heritage Excursions in Memory of Yitzhak Rabin
Cleanup Day Activities in Central Israel
International Cleanup Day: Cleaning Together in Northern Israel
KKL-JNF's Eyes in the Forest - The Horshim Forest Green Patrol
Israel Today and Tomorrow: KKL France Mission Visits Israel
Start-up Israel: KKL Italy November Mission Learns about Israel's Past and Future
KKL-JNF and Desert Agriculture Latin American Diplomats visit the Negev
A Successful Annual Fundraising Event for KKL Milan
Living Green in Israel: the Contest and the Winners
Addressing Climate Change Conference
Nurturing the Foresters of the Future
Saving the Sabras
11.23.2014 | 1 Kislev, 5775
Prime minister to Channel 1: I'll be running again in next election
Not all bleak for Netanyahu
China's moves: US decline, or balance in Asia?
Hanegbi heads to Myanmar for highest-level visit in 35 years
Former ambassador to the US Oren may enter politics on list Kahlon is drafting
MK calls on PM to destroy homes of Jews who murdered Arab teen
Netanyahu: Hamas leaders are legitimate targets, no one is invincible
Kahlon indicates comeback with new 'framework'
'Israel no better than Chelm for providing electricity to Palestinian companies that boycott it'
Manhattan borough president shows solidarity with Israel visit
Ministers and MKs urge Netanyahu to pound Hamas
Right-wing MKs call to investigate Balad party, ban it from Knesset after Qatar trip
Diplomacy & Politics
11/12/2012 12:41
Politicians split on possible Gaza operation
IDF soldiers walking to Gaza during Operation Cast Lead 311R.
(photo credit:Ho New / Reuters)
Politicians drew lines in the sand Monday over the possibility of an IDF ground operation in the Gaza Strip to tackle continued terrorism, as rockets rained down on Israel for the third straight day. Labor leader Shelly Yacimovich, on a tour of the rocket-hit South, positioned herself against intensive military action, telling Army Radio, "We are on the eve of elections, and operations beyond air attacks or targeted strikes require stability and national consensus at home." "It could be that such an operation is necessary, but not now," Yacimovich continued.Knesset Speaker Reuven Rivlin disagreed. At a ceremony marking 56 years since the Sinai Campaign, Rivlin said that the upcoming election should not deter the military from a wide-scale operation in Gaza."Whoever thinks we forgot how to deal with continuing attrition, whoever thinks that we will allow a quarter of Israel's population to live under total paralysis is preparing himself for defeat," Rivlin stated.Finance Minister Yuval Steinitz, of the Likud, warned that over time, rocket fire would hit closer and closer to Israel's Center, and that Israel cannot simply shield itself. "There is no escaping it seems, a military decision on Hamas in Gaza," he told Army Radio.Despite the scope of Operation Cast Lead in Gaza 2008, Steinitz said that Israel has not yet had an operation along the lines of Defensive Shield, the intensive 2002 anti-terror operation in the West Bank.Steinitz also said that Palestinians were attacking Israel from every side, citing both the ongoing rocket fire from Gaza and Palestinian Authority President Mahmoud Abbas's ongoing UN upgrade efforts ."We are being attacked militarily with terrorism from Gaza, and being attacked diplomatically from Ramallah," Steinitz said in an interview with Army Radio.Kadima leader Shaul Mofaz said that, in his experience as former IDF chief of staff, the best policy to stop Hamas terrorist is to target and assassinate the terrorist organization's leaders."We achieved great deterrence with the policy of targeted killings," Mofaz said in an interview with Army Radio. "Prime Minister Binyamin Netanyahu was strong against [Palestinian Authority President Mahmoud Abbas] but not when it comes to Hamas."Prime Minister Binyamin Netanyahu planned a Monday meeting with foreign ambassadors to garner international support for Israel defensive action, according to an official.At Sunday's cabinet meeting, Netanyahu said Israel is "prepared to intensify our response." "The world needs to understand that Israel will not sit idly by in the face of attempts to attack us," the prime minister said.President Shimon Peres told The Jerusalem Post on Sunday that the terrorist attacks on southern Israel are "idiotic," and Israel must respond swiftly and strongly to them.Israel is trying to avoid any large-scale retaliation or another war against Hamas in Gaza that would inevitably harm civilians, Peres intimated, but may have no choice if the current situation in which a million mothers and children in the South cannot have a full night's sleep continues. Yet, he continued, diplomacy would ultimately be required for a long-term solution. "You can't fight terror just by shooting," he said.On Sunday, US Ambassador Dan Shapiro expressed support for Israel, writing on his Facebook page that, "the United States supports Israel's right to defend itself and its citizens from these attacks."Steve Linde and Greer Fay Cashman contributed to this report.
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Date: 1930 ca.
Description: View across river of a crowd gathered on a steep riverbank overlooking a submerged car. There is a large house at the top of the hill.
Date: 1935-06
Description: Panoramic group portrait of Civilian Conservation Corps workers from Camps 2615 and 2669 at Devil's Lake State Park. All men are in uniform. Officers are f...
Date: 1950 ca.
Description: Bernard Arms holding a firearm poses on a parade float decorated in an autumn theme, including a stuffed bear, fox, and squirrel. The parade was a part of...
Date: date unknown
Description: Aldo Leopold inspecting white pine, on Wisconsin River farm, a weekend retreat for the Professor of Wildlife Management at UW-Madison.
Date: 1946 ca.
Description: Four men pose in front of the Pointon Appliance store, 132 Fourth Avenue, located between the Al. Ringling Theatre and Trimpey Studio. Signs advertise Fri...
Date: 1935 ca.
Description: Interior view of Civilian Conservation Corps barracks at Devil's Lake State Park. Several men can be seen sitting leisurely on their bunks. Two heating sto...
Date: 1910 ca.
Description: Two women stand on a ledge at Skillet Falls.
Date: 1920 ca.
Description: A seated studio portrait of the photographer and his wife, Alice Kent Trimpey.
Description: View looking out at beach scene at Devil's Lake. There are benches on the shore where vacationers observe the swimmers. Two wooden structures have ladders...
Date: 1915 ca.
Description: A border of herbaceous perennials with a background of shrubs and trees.
Date: 1940 ca.
Description: Eight new Massie-Harris tractors are parked in the snow in front of the Martiny Implement Co., 147 Third Avenue. A crowd has gathered and men sit on the tr...
Date: 1925-03-02
Description: Eight men comprising the Heart of the Hills Walking Club, founded by H.E. Cole, pose with a dog beside a house. They are left to right, Harold Baldwin, T.F...
Description: Three men rest outside a large cabin in a densely wooded area at Devil's Lake.
Description: A portrait of the doll, Violet, from the collection of the photographer's wife, Alice Kent Trimpey. The doll has a wax-over-composition head and is describ...
Description: A tire repairman in coveralls and necktie is shown in his shop among tires, inner tubes and equipment. Gas pumps are visible through the front window.
Description: The photographer stands on a park or garden path holding his gloves. He wears a coat with attached cape, hat, and large cravat.
Description: Four men pose in front of a railroad car. Two of the men are shaking hands. A banner on the car advertises "A Carload of Majestic Radios for Gem City Oil C...
Date: 1965 ca.
Description: Color postcard of the ramparts of the West Bluff in Devil's Lake State Park. Trees can be seen throughout and have fall color. The lake, bluffs and sky are...
Date: 1877 ca.
Description: "The Grand Regatta, at Devil's Lake, June 21st & 22nd, 1877." A stereograph showing spectators gathered behind the starter's cannon on Devil's Lake.
Date: 1906
Description: A double exposure of a landscape featuring a very large tree and farm houses superimposed on an image of buildings and crowds at the Sauk County Fairground...
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text:
gypsy laguage(lovers dialect) for cat...not as in the feline sense when used by most but as in a person
hello muca i louve thee
by dopestarmuca August 09, 2010
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Hotel International Innhttp://www.orbitz.com/hotel/India/New_Delhi/Hotel_International_Inn.h981031/
Hotel Overview
Not yet reviewed
This hotel is famous for its strategic location, wonderful ambience, busy but peaceful surrounding and caring staff. Conveniently located near Delhi domestic airport and Indira Gandhi International Airport in Delhi, the hotel has blossomed into one of the major venues for conferences, seminars, meetings and other banqueting functions.
Hotel International Inn Rooms
- Deluxe Room
- Deluxe room are connected with Telephone attached long Bath with 24 hrs, hot and cold water, CC TV with all international channels, telephone STD/ISD Facility, Round the clock Room Service, Fax, email, photostat, Doctor on call, LCD Tv, Wi-Fi.
- Executive Room
- Executive room are connected with Telephone attached long Bath with 24 hrs, hot and cold water, CC TV with all international channels, telephone STD/ISD Facility, Round the clock Room Service, Fax, email, photostat, Doctor on call, LCD Tv, Wi-Fi.
- Free internet
- General
- Concierge
- Dining
- 24 hour room service
- Room service
- Services
- Business center
- Laundry service
- In-Room Safe
- Tour desk
- Conference facilities
- Doctor on call
- Internet
- Free internet
- Accessibility
- Accessible facilities
- Accessible parking
Hotel Map
28.5481 77.1273
- Area served
- Sahara Mall, Galaxy Mall, Sarojini Nagar Market, DLF Cyber City.
- Nearby airports
- Indira Gandhi International Airport - 6 km.
- Area description
- DLF Cyber City - 3 km Sahara Mall - 5 km Leisure Valley - 7 km Qutub Minar - 8 km Galaxy Mall - 9 km MGF Metropolitan Mall - 9 km Delhi National Railway Museum - 10 km Sarojini Nagar Market - 10 km Nehru Park - 11 km Ansal Plaza - 12 km Teen Murti Bhavan - 12 km Safdarjung's Tomb - 12 km Presidential Palace 13 - km Lodhi Garden 13 - km India Habitat Centre - 13 km.
Nearby points of interest
- India Gate: 7.7 mi
Hotel Policies
- Check-in:
- 1200
- Check-out:
- 1200
Terms and conditions
Rates quoted in currencies other than the hotel's base currency are subject to the rate of the international exchange. Rate may change throughout stay. Rate may reflect average nightly rate. Extra charges may apply. Incidental charges, such as room service, are not included in the rate.
The amenities and/or facilities may not be located at the hotel, but within a reasonable distance, and additional charges may apply for use. All information has been provided by this hotel and not by Orbitz


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- The Netflix Billion Hour Nasty-Gram: Time for SEC to Catch Up With Social Media? | greengopost.com/wptest on Marcy Murninghan
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- Marcy Murninghan on "Just Keep Your Knees Together" 'Äì Democracy's Disconnect
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Who knew that sustainability could be fun?¬Ý Those who are in the business of 'ÄúSerious Games'Äù, that'Äôs who.¬Ý A growing number of digital game developers are finding ways of connecting game genres and mechanics to serious policy issues, creating outcomes … Continue reading


text:
Visit the Return to Order web site
Why is a Catholic institution hosting two famous pro-abortion activists, Gloria Steinem and Bell Hooks, who attack Catholic moral teaching?
"Saint Michael the Archangel, defend us in battle..."The familiar prayer was on the lips of faithful Catholics across America for the battle heating up in the heart of the country.
See the video and read the report from the prayer rally against the satanic black mass in Oklahoma City.
Oklahoma City, OK -- Sept. 18, 2014: A total of 215,000 people have signed various petitions urging the Civic Center Music Hall located in Oklahoma City to cancel the satanic black mass scheduled on Sept. 21.
Yes, the slippery slope is real. This video proves it.
My little sister and I had hoped to attend "The Phantom of the Opera". That certainly won't be happening now. I've attended so many productions in the past, but rest assured, I won't be stepping foot in there ever again. Your standards are too low - you don't deserve my money.
Subscribe and learn how to defend moral values
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Gator Country Black Friday special!
Now's a great time to join or renew and get up to $20 off your annual subscription! LIMITED QUANTITIES -- for details click here.
Big shocker: The NSA overstepped its bounds in use of surveillance
Discussion in 'Too Hot for Swamp Gas' started by oragator1, Aug 15, 2013.


text: Pirates of the Cari-BEAN Counters View full-size image < previous next > Is this photo a winner? "This is our team picture for the 2007 Dragon Boat Festival. As accountants we called ourselves Pirates of the Cari-BEAN Counters. The pirate on the front was hand drawn by one of our team members and the back said "Countin' Doubloons and Dragon Boat Victories since 1960". WE WON FIRST PLACE IN THE T-SHIRT CONTEST out of 68 teams!! Thanks Custom Ink!" - Pirates (Jul 17, 2007) Share this photo on: Twitter Facebook Pinterest Similar Photos: recreation | green | occasion | dragon boat races | accountants | dragon boat festival | pirates of the cari-bean counters Feeling inspired? Visit the CustomInk Design Lab to start your own group order. Design Your Own comment by anonymous - Jul 18, 2007 - back to the top ARGH!!!!! comment by anonymous - Jul 18, 2007 - back to the top how can I vote if I can't see the tshirt or the competition?


text:
Holden Trax v Skoda Yeti
David McCowen Holden's turbocharged Trax SUV takes on the new Skoda Yeti.
Skoda Octavia Scout first drive review
Jonathan Hawley Czech brand expands its off-roading wagon range to take on Subaru's popular Outback.
2015 Skoda Fabia first drive review
Jonathan Hawley Czech brand's all-new baby hatch is poised to challenge established city car rivals.
2015 Skoda Fabia revealed
Sam Hall New engines and revamped interior for Czech brand's city car.
Skoda Octavia used car review
David Morley The Czech newcomer offers an alternative way to get a taste of Volkswagen technology for less money.
2015 Skoda Fabia to sip on 3.1L/100km
Sam Hall The Fabia city car will be 17 per cent more fuel efficient than before, says car maker.
Toyota Corolla v Skoda Rapid
Stephen Ottley The Czech newcomer takes on the heavyweight of the small car world.
Top 5 cars for cyclists
David McCowen Bicycles and motorists don't always get along in Australia, but the annual Tour de France demonstrates that cars can be of immense value to cyclists.
Volkswagen Golf GTI vs Skoda Octavia RS
Sam Hall We pit the benchmark hot hatch against its more affordable liftback cousin.
Skoda owners consider themselves wise, intelligent
David McCowen British survey paints an interesting picture of driver views.
Skoda Yeti 90TSI Ambition car pool
Sam Hall If you can get past its 'only a mother could love' looks, you'll find a very capable compact SUV.
Skoda Octavia 132TSI Elegance Wagon new car review
Cameron McGavin This under-rated Czech wagon should be on your mid-sized shopping list.
Skoda Octavia RS quick spin
Sam Hall Skoda's hot wagon is a dressed-down Volkswagen Golf GTI.
Skoda Octavia 110TDI new car review
Toby Hagon A better buy than Golf? Maybe, but there's a resale hook.
Skoda Rapid first drive review
Stephen Ottley The Czech brand is joining the most competitive new car market, but is its offering up for the fight?
Buyers shun diesel in cars; SUVs still strong
Stephen Ottley Volkswagen scales back smaller diesel models after sales decline.
Skoda Yeti first drive review
Stephen Ottley The Czech brand has given its unconventional SUV a makeover, adding equipment and cutting the price
Skoda chief defends sales
David McCowen New models, increased advertising on the way.
Skoda Octavia RS TDI wagon first drive review
David McCowen Sporty diesel wagon blends performance and practicality.
Skoda Octavia RS first drive review
David McCowen Performance Skoda brings Golf GTI performance at a more tempting price.


text:
- Europe »
- Spain »
- Community of Madrid »
- Madrid »
- Radio Catamayo Fm
Oops… no streams currently available for Radio Catamayo Fm.
Click here to visit the Station's website:
Radio Catamayo Fm is an internet radio station from Madrid, Spain providing Spanish music and program.
Madrid - Community of Madrid, Spain - Spanish
Songs playing in Radio Catamayo Fm


text:
Google CEO Schmidt Fuels Critics With Controversial Privacy Remarks
Yesterday at the "Techonomy" conference in Lake Tahoe, California Google CEO Eric Schmidt made a number of remarks about user-generated content and data-mining that were somewhat controversial:
"If I look at enough of your messaging and your location, and use Artificial Intelligence," Schmidt said, "we can predict where you are going to go."
"Show us 14 photos of yourself and we can identify who you are. You think you don't have 14 photos of yourself on the internet? You've got Facebook photos! People will find it's very useful to have devices that remember what you want to do, because you forgot…But society isn't ready for questions that will be raised as result of user-generated content."
"The only way to manage this is true transparency and no anonymity," Schmidt said. "In a world of asynchronous threats, it is too dangerous for there not to be some way to identify you. We need a [verified] name service for people. Governments will demand it."
Last December Schmidt also made statements about privacy that were not well received in a CNBC interview:
He told CNBC Anchor Maria Bartiromo, on the cable network's recent special "Inside the Mind of Google," that people who have something to hide shouldn't be doing things online that might potentially expose them if law enforcement seeks access to their search histories.
"If you have something that you don't want anyone to know, maybe you shouldn't be doing it in the first place," said Schmidt.
Google has apparently been holding off on employing facial recognition technology in products like Google Goggles. Schmidt's comment above, "Show us 14 photos of yourself and we can identify who you are," is an apparent allusion to that capability.
Google has experienced various privacy related complaints and legal inquiries over the past several years, growing more numerous recently. The concerns have been raised by privacy advocacy groups and regulators in the US and Europe — though more persistently in Europe where they come from a broader number of fronts, including data retention and, more recently, the unintended collection of personal information by Google's Street View cameras.
The danger in remarks such as those made yesterday by Eric Schmidt is that they serve to reinforce Google critics' perceptions of the company as "big brother" or perhaps big brother's enabling little brother.
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Faculty Research News
Tavaré Elected to the Royal SocietyJuly 12, 2011
Simon Tavaré, George and Louise Kawamoto Chair in Biological Sciences in USC Dornsife, has been named a fellow of the Royal Society. Tavaré, whose research is in the interface between statistics, probability,…
On Writing and RedemptionJuly 7, 2011
Mark Richard didn't intend to write his latest book. He had originally set out to explore the death of Nat Turner, an early 19th-century slave insurrectionist in Southampton County, Va., where Richard lived as a boy.…
The Genius of a Disorderly EnzymeJune 24, 2011
Why is antibody diversity important? Think about it like this, said Myron Goodman: "Why don't you die when I sneeze? It's because you have a powerful immune system. And the way to get a decent immune system…
Devoted to the City of RosesJune 13, 2011
Bill Deverell has spent his academic career exploring the history and culture of California. With research interests including the American West after the Civil War and the environmental history of Los Angeles, and as the…
Water's Surface Not All WetJune 8, 2011
Air and water meet over most of the earth's surface, but exactly where one ends and the other begins turns out to be a surprisingly subtle question. A new study in Nature narrows the boundary to just one quarter of…
Getting ReligionMay 31, 2011
Not long after Indonesia's transition from dictatorship to democracy, Christian Hammons was sitting at a coffee shop in Bukittinggi, a city on Sumatra's tourist circuit. Hammons, who was about to begin his doctoral…
Naked HollywoodMay 25, 2011
In 1951, when bombshell actress Jayne Mansfield publicly dropped the top of her dress, the photographer Arthur Fellig, also known as "Weegee the famous," was there to capture the moment on film. The caption to…
Leading Scholars Join USC Dornsife's School of PhilosophyMay 11, 2011
The USC Dana and Dornsife College of Letters, Arts and Sciences has recruited leading senior philosophers Ralph Wedgwood and Gabriel Uzquiano-Cruz of the University of Oxford as well as a very promising newcomer, Karen Lewis…
Equality On and Off the FieldMay 9, 2011
Michael Messner has spent the last 25 years studying the role gender plays in sports, and likewise how sports influence society's views of gender. In honor of Messner's contributions to his field and his work for…
Celis and McKnight Awarded Technology PrizeMay 6, 2011
Bill Celis, associate professor of journalism at the USC Annenberg School for Communication & Journalism, and Anne McKnight, assistant professor of East Asian languages and literatures and comparative literature in USC…
Top Stories
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Redwood Arts
740 Jumper Rd.
Wilkes-Barre, PA
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St. Jakobshalle, Basel, Switzerland
AP Photo / Keystone, Georgios Kefalas
October 20, 2014 |
The Fillmore, Detroit, Mich.
Scott Legato / RockStarProPhotography.com
October 19, 2014 |
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