text:
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Tryptophan and arginine-rich cyclic hexapeptides of the type cyclo-RRRWFW combine high antibacterial activity with rapid cell killing kinetics, but show low toxicity in human cell lines. The peptides fulfil the structural requirements for membrane interaction such as high amphipathicity and cationic charge, but membrane permeabilisation, which is the most common mode of action of antimicrobial peptides (AMPs), could not be observed. Our current studies focus on elucidating a putative membrane translocation mechanism whereupon the peptides might interfere with intracellular processes. These investigations require particular analytical tools: fluorescent analogues and peptides bearing appropriate reactive groups were synthesized and characterized in order to be used in confocal laser scanning microscopy and HPLC analysis. We found that minimal changes in both the cationic and hydrophobic domain of the peptides in most cases led to significant reduction of antimicrobial activity and/or changes in the mode of action. However, we were able to identify two modified peptides which exhibited properties similar to those of the cyclic parent hexapeptide and are suitable for subsequent studies on membrane translocation and uptake into bacterial cells.
Antimicrobial peptides (AMPs) are ubiquitous defence molecules in organisms and have been shown to exhibit promising potential as a new class of antibiotics [
The most common antimicrobial mechanism of action can be described by different models of membrane permeabilisation. Here, interaction with the lipid bilayer results in loss of membrane integrity, e.g., by pore formation, but also detergent-like peptide properties have been reported [
We could show that the synthetic cyclic hexapeptide cWFW with the sequence c-RRRWFW has an increased antibacterial activity against Gram-positive and Gram-negative bacteria compared to the linear sequence, while no toxicity towards eukaryotic cells could be detected [
In order to examine putative translocation into the cytoplasm of bacterial cells, our hexapeptide had to be modified according to the requirements of the particular analytical techniques. For analysis with confocal laser scanning microscopy (CLSM) fluorescent analogues labeled with carboxyfluorescein (Fluos), coumarin (Cu) or nitrobenzoxadiazole (NBD) were synthesized. Furthermore, peptide uptake studies using an HPLC-based strategy developed by Oehlke
In the present study we characterized the feasibility of the cyclic hexapeptide analogues for the above investigations by examining the consequences of peptide modification according to antibacterial activity and mechanism of action.
Components for peptide synthesis were purchased/prepared as follows: Fmoc-Arg(Pbf)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Trp(Boc)-OH (GL Biochem, Shanghai Ltd., Shanghai, China), Fmoc-L-Dap(Dde)-OH (Iris Biotech, Marktredwitz, Germany), 4-Chloro-7-nitro-1,2,3-benzoxadiazole, (NBD-Cl, Sigma-Aldrich, St. Louis, MO, USA), 6-bromo-7-hydroxycoumarin-4-yl [
The fluorescence-labeled peptides cW2[Fluos], cW3[Fluos] and cW[Cu]W (for sequences refer to (
Cyclic hexapeptides were dissolved to 100 µM in phosphate buffer (10 mM NaH2PO4/Na2HPO4, 154 mM NaF, pH 7.4). To mimic a membrane-like environment, SDS or POPG SUVs (small unilamellar vesicles) were added to give final concentrations of 25 mM detergent and 10 mM lipid. Due to light scattering of liposomes, spectra could only be recorded down to 205 nm. Vesicle preparation has been described previously [
The retention time
The minimal inhibitory concentration (MIC) of the cyclic hexapeptides was tested against Gram-negative
The lytic effect of selected peptides upon human erythrocytes was determined as described before [
Membrane permeabilisation was determined by fluorescence activated cell sorting (FACS) on a FACSCalibur (Becton Dickinson) equipped with a 488 nm argon laser. Propidium iodide (PI, 10 µg/mL) and peptides at a final concentration corresponding to the respective MIC were dissolved in LB. Cells were grown to mid log phase (OD600 0.4 ± 0.1) and added to the solution just before the measurement at a concentration of 5 × 105 cells/mL. Cells were sorted on the basis of PI fluorescence which increases upon intercalation with DNA. This can only be observed in the case of disturbed membrane integrity as PI cannot translocate across intact lipid bilayers. Cell fluorescence was measured after incubation time points of 0, 5, 10, 15, 20, 30, 60 and 90 min at 37 °C, 180 rpm. A minimum of 20,000 cells was recorded for each preparation. CellQuestTM Pro software (Becton Dickinson) was used for data acquisition and results were analyzed with FCS Express V3 (De Novo Software, Los Angeles, CA, USA).
The applicability of chemically modified peptides in uptake experiments was tested with cR2[Cu] into HeLa S cells. The well characterized cell-penetrating peptide penetratin [
The non-modified, translocated peptide was analysed by HPLC on a Jasco LC-2000Plus using a ProntoSil 300-5-C18-H column (250 × 4.6 mm, 5 µm) (Bischoff Chromatography) and a precolumn with PolyenCap A300, 10 µm. Up to 200 µL cell lysate were loaded onto the column. Peptide elution was realized with 0.1% TFA/deionized water (A) and 0.1% TFA in 80% acetonitrile/deionized water (B) at a flow rate of 1 mL/min and a gradient of 20%–70% B over 20 min. Quantification was performed by fluorescence measurement of carboxyfluorescein (ex 445 nm, em 520 nm) and methoxycoumarin (ex 350 nm, em 385 nm). Data were calibrated with standard solutions containing pure hexapeptide and Fluos-penetratin in 0.1% TFA (A) prepared under identical conditions.
An overview of the antimicrobial peptides used in this study is given in
Confocal laser scanning microscopy (CLSM) requires the introduction of fluorescent labels (
Chemical structures of cWFW and the four fluorescent labels used in this study. Fluorophores are depicted coupled to the respective amino acid (latter given in brackets) used to introduce the labels into the peptide ring.
The HPLC approach to investigate peptide translocation is based on the chemical modification of extracellular and surface-bound peptides by diazotized 2-nitroaniline [
All peptides (except cKRK) were more active towards the Gram-positive
As small modifications at the central position of the hydrophobic WFW cluster were shown to exhibit the least influence on antimicrobial activity [
The decrease in antibacterial activity observed after substitution of arginine residues with lysine in the polar cluster of the cyclic hexapeptides was slightly more pronounced compared to the decrease in activity found for the fluorescent labeled peptides (excluding the Fluos-labeled peptides) (
The peptides cR2[Cu], cR2[S-Cu] and cR2[NBD] were synthesized to combine the high activity of cKRK with the best antibacterial properties found for the fluorescent analogues. The combination of both modifications had no additional negative influence on antimicrobial activity and kept the hemolytic activity low (
Sequences, antimicrobial and hemolytic activity of the cylic hexapeptide analogues. Minimal inhibitory peptide concentrations (MIC) were determined in triplicates in at least three independent experiments. Hemolytic activity was determined as % hemolysis at a peptide concentration of 100 µM.
|MIC [µM]
|Hemolysis [%]
Cu—coumarin; Dap—diaminopropionic acid; Fluos—carboxyfluorescein; NBD—nitrobenzoxadiazole.
To investigate the influence of fluorescent label modification and amino acid substitution on the hydrophobicity/amphipathicity of the cyclic hexapeptide derivatives, we determined the retention time
The introduction of fluorophores generally increased retention time. This can be related to an enlargement of the aromatic ring system compared to the phenylalanine side chain with the consequence of improved interaction with the non-polar solid surface. The most pronounced increase in
Retention times
A positive correlation between antimicrobial activity and hydrophobicity/amphipathicity has been reported for a large number of helical membrane-permeabilising peptides [
In order to get insight into the influence of chemical modifications on peptide conformation we performed CD spectroscopic studies (
Among the K-containing peptides, cKRK showed the strongest shift in the spectrum with a high positive ellipticity below 200 nm (
Both, detergent micelles and liposomes are often used in spectroscopic studies to mimic the anisotropic nature of the lipid matrix of cell membranes. Bound to micelles cWFW adopts an amphipathic structure with two β-turns [
CD spectra of the cyclic hexapeptides in different solvent systems. (
In order for the fluorescence-labeled and K-containing derivatives to be applicable in investigations on the mode of action of our cyclic hexapeptides, the chemical modifications must have no or only little influence on the properties of cWFW. As all peptide analogues used in this study fulfil the structural prerequisites for membrane interaction,
All peptides induced no or only slight membrane permeabilisation when tested against
Bacterial membrane permeabilisation determined with flow cytometry using propidium iodide (PI). PI influx after incubation with cWFW, fluorescent-labeled and K-substituted cyclic hexapeptides was tested into
As demonstrated for the cyclic hexapeptide cWFW [
With respect to the investigation of peptide translocation across bacterial membranes, cR2[Cu] and cR2[NBD] seem to be the most promising fluorescent-labeled cyclic hexapeptide candidates mimicking cWFW. Applying the established strategy for uptake studies in eukaryotic cells, described by Oehlke
HPLC-based investigation of peptide uptake into HeLa S cells. (
The fraction of translocated penetratin showed to be comparable to the amount of other amphipathic peptides internalized into different cell lines [
Our research on cyclic antimicrobial peptides leads us to the conclusion that minor modifications within a small, structurally constrained peptide such as cWFW can result in unpredictable changes in antibacterial activity and mode of action. The clustered alignment of polar and hydrophobic amino acids in the peptide ring dictates the high level of amphipathicity which is necessary for peptide interaction with the bacterial membrane. Although the introduced modifications were chosen on the basis of the most suitable properties concerning size, hydrophobicity and net charge, the optimal interplay between arginine and the aromatic residues proved to underlie a delicate amphipathic balance. This study emphasized the fact that careful consideration needs to be taken when modifying small peptides to generate appropriate tools for biophysical and cellular studies especially when adding fluorophores. Our attempt to optimize the structure of the cyclic hexapeptides for fluorescence microscopy and HPLC-based studies to investigate uptake into bacterial cells resulted in the selection of c-KRKW[Dap-NBD]W and c-KRKW[Ala-Coumarin]W. In comparison to the parent peptide, these analogues displayed good antimicrobial activity and similar biophysical properties with regard to retention behavior and structure in interaction with membrane-mimicking surfaces, respectively. Most important, the modifications conserved the non-membrane permeabilising activity of cWFW against bacteria.
The support in peptide synthesis and analytics by Brigitte Dekowski, Sabine Abel, Dagmar Krause and Bernhard Schmikale is gratefully acknowledged.
The authors declare no conflict of interest.


text:
By Ally Rogers, Photo Editor, Belvoir EagleJanuary 26, 2012
The Presidential Salute Battery conducted its quarterly training at Fort Belvoir Tuesday -- firing 75mm blank rounds from four of its 10 vintage World War II era M5 anti-tank cannons.
This unique unit is the only one of its kind, rendering honors to visiting foreign dignitaries and heads of state at the White House, the Pentagon and other area around Washington D.C.
"We fire in honor of the President of the United States and at Arlington National Cemetery for general officer and flag officer funerals for the Army, Navy, and Marine Corps," said Capt. Thomas Gearhart, the platoon leader.
Training at Fort Belvoir is essential to the success of the battery. Since Fort Meyer, the unit's home station, is within the D.C. metro-area and the noise level of the cannons, training is only permitted between the hours of 7 and 8 a.m.
"By coming out here it gives us a much longer period of time that we can train, we can fire more rounds, and overall be better trained," said Gearhart.
During the Belvoir training, the unit conducted a "blank fire crew drill," which is used to train new Soldiers in the various positions of the battery. The battery positions include a loader, gunner, backup loader, backup gunner, whereas the staff positions include battery commander, sergeant of the watch, watchman, assistant watchman, and counter.
"There are a lot of positions (in the unit)," said Private 1st Class Daniel Bayless, a backup gunner. "We need to get out here as often as possible. If we don't little things start to go wrong, like people are late (in firing) or they don't react the way they should."
"It's about muscle memory," he added. "That's what the repetitive training is good for to make sure that you don't have to think about what you're doing and you can just do it."
According to Gearhart the unit trains seven hours a day, every day. This training includes dry fire, where rounds are loaded and ejected without being fired. While this helps perfect their performance, making sure all actions are crisp and precise, the live firing at Belvoir is most realistic.
"With dry fire you don't have the boom," said Bayless. "With the boom it adds a little bit of stress and people seem to get flustered. The other thing with the boom is that the rounds are being counted; with the dry fire it's hard to count a click. Then there's the smoke, which has a visual effect. With the smoke you can't see the (fire signal), you're just looking for any type of movement."
The mortar-men used only 200 of their 300 available rounds to execute their training, performing several 11 Gun Salutes and five Volleys, where four cannons are fired at once. Gearhart explained it was unnecessary to "waste" the extra ammo because the unit had met their training objectives, re-qualifying each Soldier.
"The training went pretty good," said Sgt. 1st Class Kevin Patterson, the noncommissioned officer in charge. "This is the first time we've done this in a couple months, so we had a lot of guys qualify today."
In one calendar year the Presidential Salute Battery executes more than 300 missions. Understanding this busy schedule, Private 1st Class Ethan Durnez said, "We really needed to get out here. We have a bunch of missions coming up so it's good we had this to make sure everyone knows what to do."

subset: commoncrawl


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NMG image by Brandon Malone
Welcome to the Pony Club Association of Victoria website.
To keep up to date with all the news and events, please check out the site on a regular basis. Click on the 'Events' menu option above to keep an eye on calendar for what is coming up around the country in the next few months.   More >>
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Procedures and application for exemptions
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You can email the circuit office by using the simple form on this website - we will respond to you or pass your query to the appropriate Minister or church. Contact us here. If your enquiry is for a Church, please select "I'd like to contact a Church" from the drop down box, otherwise general enquiries will only go to the Circuit Office.
The circuit office is open on Tuesday and Wednesday mornings from 9.00 am to 12.15 pm at Earl Shilton Methodist Church:
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Earl Shilton
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To telephone a Minister or church leader directly, please use the following numbers:
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Revd David Haseldine
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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer. Moreover, deregulating their activity offers novel cancer therapeutic approaches. The availability of high throughput techniques for the identification of altered cellular molecules allowed their use in cancer diagnosis. Their application to a variety of body specimens from blood to tissues has been helpful for appreciating their use in the clinical context. The development of innovative antibodies for immunohistochemical detection of proteins also assists in diagnosis and risk stratification. Overall, the novel cancer diagnostic tools have extended their application as prognostic risk factors and can be used as targets for personalized medicine.
Recent years have seen a remarkable progress in the basic, translational and clinical research in cancers. This has led to scientific and technological advances which have opened new vistas for cancer diagnosis. National comprehensive cancer network (NCCN) reported tumor markers for six major malignancies in defining the optimum test that will help patient care [
As we embark into the era of personalized medicine, using precise targets for diagnosis of cancers is important since specific drug therapies will be targeted against these molecules. Not only will these have implications in the cancer diagnosis but also in the institution of novel therapies. Treatment modalities in cancer patients are no longer based only on anatomic location and the phenotype of the tumor whether adenocarcinoma or squamous cell carcinoma. Our understanding of pathogenetic evolution of cancer has improved considerably and this has been translated into the clinical context [
A significant part of this is due to the understanding of alterations occurring within the cancer cells at the molecular level [
As the tumors progress and develop invasive and metastatic capabilities, these molecular changes are deregulated due to inherent biologic properties of the cancer cell. These molecular alterations vary not only by the origin of the tumor cell but also by the degree of differentiation and invasive capacity of the cancer cell [
Recent research has demonstrated that these molecular markers can assist in early and accurate diagnosis and predict prognosis in cancers [
The rapid progress in the identification of these molecular targets in the cancer cell has led to a revolution of the "omic" in cancer diagnostics including (Whole) Genome (WGS), Exome (WES), methylome, transcriptome (including the miRnome), microbiome, metabolome, proteome and topome [
In the current context of the molecular alterations that have been used for the cancer diagnosis are occurring at the DNA level include gene replication, rearrangements/translocations, point mutations/deletions or insertions [
Recent work from our group has pioneered research in several basic and translational level for novel diagnostic approaches in cancer investigating the use of microRNAs (miRNAs) [
The expression levels of miRNAs are tumor specific. This property of the cancer cell is being utilized in cancer diagnosis for early and accurate cancer diagnosis [
Previous research has demonstrated that the miRNAs regulate cancer stem cells (CSC) [
The current oncology practice is rapidly undergoing a change. There is no more a "one size fits all" approach. Personalized treatment approaches are being developed based on the cancer diagnostic biomarkers. Translational research has shown the clinical application of the novel molecular diagnostics markers in the early diagnosis of cancer [
In the current clinical context, cancer diagnosis involves the use of biomarkers examining molecules at the cellular level. Cancer diagnosis today is not just the recognition of the morphological phenotype through microscopic examination, but it is a complex blend of these microscopic features with immunohistochemical stains and molecular approaches to add value to the diagnostic report. The current standardized surgical pathology reporting formats make use of the available molecular markers to communicate prognostic and therapeutic implications with the clinicians.
Allele-specific quantitative PCR (IG/TCR-QPCR) is a robust and reproducible test with a sensitivity of at least 0.01% to detect minimal residual disease (MRD) and quantify it for widespread use in therapeutic stratification of pediatric acute lymphoblastic leukemia (ALL). It can be extended to achieve molecular MRD monitoring in adult and pediatric ALL [
The microRNAs (miRNAs) are recently described emerging biomarkers for cancer diagnosis and prognosis with potential future implications in therapeutic interventions [
Several novel diagnostic biomarkers have been identified for clinical diagnosis of cancers as demonstrated in
There also has been a significant progress in the development of novel antibodies for immunohistochemical detection of proteins which is the end result of the translation due to DNA and RNA alterations that have translated from the research bench [
Recent advances in the field of cancer diagnosis have seen a plethora of rapid and accurate high throughput diagnostic tests. Initially used as research tools [
Quantitative PCR has widespread application in the detection of DNA/RNA/miRNA abnormalities for initial diagnosis of cancer. These would also be applicable in surveillance, follow-up and monitoring treatment outcome of cancer patient. It can be used for single-nucleotide polymorphism (SNP) detection, gene expression profiling and also quantification of viral load in infection associated cancers. Gel electrophoresis has its limitations including low resolution, poor precision, and results not being quantifiable. Hence, capillary electrophoresis has been developed with widespread application in detecting gene rearrangements, single nucleotide polymorphism (SNP), and loss of heterozygosity (LOH) [
The sub-cellular deciphering of molecular alterations can be used as tumor specific "signatures" for cancer diagnosis. Targeted diagnostic strategies using DNA, RNA, miRNA or proteomic approaches have enabled early and accurate diagnosis. This varies from a "single-gene" diagnosis to a panel of tumor specific alterations used to identify a tumor phenotype. Incorporation of bioinformatics has enabled evaluation of multiple genes and miRNAs in parallel for identifying clinical algorithms for cancer diagnosis [
A typical example of a genomic panel recommended for cancer diagnosis is a panel comprising of BRAF, KIT, NRAS, GNA11 and GNAQ for Melanomas [
Upon diagnosis of rearrangement of ALK gene in NSCLC lung cancers, drugs have been approved for clinical use. However with the detection of KRAS mutation in lung cancers the drugs are currently under development. With the use of recent high throughput technologies like the Sequenom Maldi-TOF spectrometry gene panels can be evaluated for diagnosis of cancers [
The molecular targets identified for cancer diagnosis have implications in the treatment protocols. This has led to the development of "pharmacogenomics" and "pharmacogenetics" [
In cancer diagnosis, the role of the Pathologist is to link the phenotypic expression of the tumor visualized microscopically with the variation in molecular genotype. For personalized medicine the genetic alterations occurring in cancers are used not only for diagnosis but also for targeted drug therapy as displayed in
To assist the diagnosis of cancers, there are commercially available cancer panels like the Oncocarta [
Deep understanding of the pathogenesis of cancer has led to unearthing of novel molecular diagnostic tools for cancer diagnosis. High throughput technology of molecular genetics and genomic analysis of sub-cellular molecules has rapidly changed the diagnostic landscape of cancer testing [
Advances in molecular microbiology have also had far reaching consequences and impact on cancer diagnosis. This includes the detection of viruses in cancers which have prognostic implications. A typical example of this is the utilization of the HPV detection in head and neck cancers which assist in the risk stratification of cases [
In conclusion, the diagnosis of cancer has undergone a paradigm shift. No longer is cancer diagnosed only based on morphological parameters. More and more the diagnostic algorithm is supported by immunohistochemical and molecular alterations at the DNA, mRNAs, miRNAs and proteomic level. Multiple platforms and high throughput technological advances enable faster and cheaper analysis of all these as well as the whole genome. This is having a significant impact on how medicine is now being practiced in a personalized approach leading to the development of precision medicine based on pharmacogenomics. It is being realized that a tumor may not be characterized by a single gene alteration but by a panel of 'signature' genomic alterations leading to targeted therapeutic strategies and surveillance based on the tumor specific alterations. The ultimate goal of cancer diagnosis in personalized medicine would be to identify the correct diagnosis and guide the therapy so that every patient received precision medicine that is the right drug at the right dose.
The authors have no conflict of interest to declare.
Molecular diagnostic schema representing routine biological specimens and their molecular alterations.
Novel diagnostic biomarkers used in the clinic for various types of cancers and their targeted drug therapy.
Current high throughput tests for cancer diagnosis.
|MicroRNA and RNA
|Microarray technology
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|Quantitative sequenom and pyrosequencing
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LOS ANGELES - Authorities in Los Angeles County will join their counterparts around the Southland in looking for drunken drivers in the days leading up to the Super Bowl.
"We want everyone to make the right decision on Super Bowl Sunday," said Chris Murphy, director of the California Office of Traffic Safety. "It's everyone's call to make this year's Super Bowl Sunday safe."
Law enforcement organizations participating in the Avoid the 100 Los Angeles County DUI task force will be on patrol through the weekend and staffing sobriety checkpoints to combat drunken driving.
The following checkpoints are planned:
-- at 7:30 p.m., the California Highway Patrol will begin a six-hour checkpoint on Whittier Boulevard west of Hoefner Avenue;
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Authorities offered the following tips for party hosts:
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French film production volume jumps, so do budgets
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A Phase I Rheumatoid Arthritis Study in Healthy Volunteers
This study has been completed.
Information provided by:
ClinicalTrials.gov Identifier:
First received: October 4, 2007
Last updated: January 23, 2012
Last verified: January 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
GSK182771 is a domain antibody targeting the IL-1 receptor which is being developed for the treatment of rheumatoid arthritis. This study is being done in healthy volunteers to verify the safety and tolerability of GSK182771
|Arthritis, Rheumatoid
|Drug: GSK1827771
|Phase 1
|Study Type:
|Study Design:
|Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Participant)
Primary Purpose: Treatment
|Official Title:
|A Phase I, Randomized, Observer- and Subject-Blind, Placebo-Controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK1827771 in Healthy Volunteers
Resource links provided by NLM:
Genetics Home Reference related topics: rheumatoid arthritis
MedlinePlus related topics: Arthritis Rheumatoid ArthritisU.S. FDA Resources
Further study details as provided by GlaxoSmithKline:
Primary Outcome Measures:
- Safety and tolerability of GSK182771 at ascending doses monitoring will take place during the period the subjects are in-house (7 days) and when they come for the following visits (day 14, day 21, day 28 and follow-up if necessary) [ Time Frame: monitoring will take place during the period the subjects are in-house (7 days) and when they come for the following visits (day 14, day 21, day 28 and follow-up if necessary) ]
Secondary Outcome Measures:
- Pharmacokinetics, pharmacodynamics, immunogenicity of GSK1827771. monitoring will take place during the period the subjects are in-house (7 days) and when they come for the following visits (day 14, day 21, day 28 and follow-up if necessary) [ Time Frame: monitoring will take place during the period the subjects are in-house (7 days) and when they come for the following visits (day 14, day 21, day 28 and follow-up if necessary) ]
- Plasma concentrations of GSK1827771 to derive pharmacokinetic parameters
- anti-GSK1827771, anti-PEG and anti-dAb antibodies.
- response of whole blood ex vivo stimulation as a measure of the in vivo pharmacodynamic activity of GSK1827771
- various exploratory biomarker levels
|Study Start Date:
|September 2007
|Study Completion Date:
|April 2008
|Primary Completion Date:
|April 2008 (Final data collection date for primary outcome measure)
|Ages Eligible for Study:
|18 Years to 55 Years (Adult)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- Healthy adult men or women as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests and cardiac assessment.
- Female subjects of non-childbearing potential.
- Male subjects must agree to abstain from or agree to use adequate contraception, in addition to having their female partner use another form of contraception. This criterion must be followed from the time of the first dose of study medication until PK levels are determined to be below the LLQ.
- Men or women who are between 18 and 55 years of age, inclusive.
- BMI within the range of 18-35 kg/m2 inclusive.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Exclusion Criteria:
- The subject has a positive pre-study urine drug/urine alcohol screen. A minimum list of drugs that will be screened for includes amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A history of regular alcohol consumption averaging >7 drinks/week for females or >14 drinks/week for males. One drink is equivalent to (12 g alcohol) = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits
- The subject is unwilling to abstain from alcohol consumption from 48 hr prior to dosing until discharge from the clinic, and for 48 hr prior to all other out-patient clinic visits.
- Smoked or used tobacco or nicotine-containing products within the previous 6 months prior to the first dose of current study medication.
- The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
- Previous exposure to or treatment with PEGylated molecules.
- Use of anti-Tumor Necrosis Factor (anti-TNF) drugs within 60 days prior to dosing.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days , or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy (including antibiotics) which, in the opinion of the investigator and/or GSK Medical Monitor, contraindicates the subject's participation.
- Positive pregnancy test at Screening or on Day -1 (females only).
- Any clinically significant abnormality identified on the screening medical assessment or examination, or ECG.
- Any WBC or neutrophil count outside the normal range at screening or on Day -1.
- History of significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions that in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as participant in this trial.
- History of any autoimmune or current inflammatory conditions including rheumatoid arthritis or any other joint disease.
- History of malignancy, except for surgically cured basal cell carcinoma or cured cervical carcinoma (> 2 yrs prior to dosing).
- Currently has asthma or history of COPD.
- Current evidence of ongoing or acute infection.
- The subject has a history of repeated, chronic or opportunistic infections which, in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as a participant in this trial.
- History of Mycobacterium tuberculosis or any other previous Mycobacterium infection.
- A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody, or HIV antibody testing result.
- History of a severe allergic reaction, angio-edema, anaphylaxis or immunodeficiency
- History of elevated blood pressure or blood pressure >140/90 mmHg at screening.
- Corrected QT interval (QTc) > 450 msec.
- Where participation in study would result in donation of blood in excess of 500 mL within 56 days of starting the study.
- Subject whose calculated creatinine clearance is less than 80 mL/min
- Liver function tests above the upper limit of normal at screening (alkaline transaminase (ALT), aspartate transaminase (AST) or bilirubin).
- Chronic liver or biliary disease, history of Gilbert's syndrome in a previous clinical study or at screening.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00539760
Please refer to this study by its ClinicalTrials.gov identifier: NCT00539760
|United States, Indiana
|GSK Investigational Site
|Evansville, Indiana, United States, 47714
|United States, Maryland
|GSK Investigational Site
|Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
|Study Director:
|GSK Clinical Trials
More Information
Keywords provided by GlaxoSmithKline:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 21, 2017
|Responsible Party:
|Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
|ClinicalTrials.gov Identifier:
|NCT00539760 History of Changes
|Other Study ID Numbers:
|Study First Received:
|October 4, 2007
|Last Updated:
|January 23, 2012
Keywords provided by GlaxoSmithKline:
domain antibody
Rheumatoid Arthritis,
Additional relevant MeSH terms:
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
ClinicalTrials.gov processed this record on July 21, 2017


text:
Sole Cool Hot Iron Bag
Item Number: QC-0701
Technique: Pieced Quilts
Theme: Bags & Totes
Project Size: Small iron bag; Large iron bag
Trunk Show: Available The cover quilt may be borrowed from our quilt collection for up to 30 days. Call or e-mail to check on availability. You may reserve up to a year in advance.
Summary: The Sole Cool Hot Iron Bag is a "must have" for quilters who take their irons to quilting retreats, workshops, classes, or other outings. This super bag provides a safe way to transport a hot iron home from a quilt outing. Fabric selection can go from wild to subdued, depending on one's personality. This project makes a perfect half-day class.


text:
When I was two years old or so, my parents and I were playing on their bed. My father asked me what color the pillowcase was. I answered proudly that it was white. My father, with a gleam in his eye I was too young to understand, said that it was black. I stood up for the truth. He was a teaser and I knew it was white. He, with a perfectly straight face, said no, it was indeed black. "Go ask your Mom." I did and she concurred. It was indeed black. I kept looking back and forth between the two of them and the pillowcase and finally, I burst into hysterical tears.
My parents tell this story now with chagrin as well as with laughter. They had no idea at the time how dependent I was on their view of the world - what an impossible dilemma they had created by asking me to choose between believing them and believing what I knew to be true. Sometimes I wonder if I actually remember this event, or if I simply remember the family lore about it. This I know: it happened. I know this because when I return to my emotions, I still feel the pain and horror of that dilemma. It still makes me feel afraid and alone. To this day, I am completely intolerant of what I call "let's pretend" attitudes.
Did I mention that I grew up in an adoptive family? It was back in the days when the little book from the adoption agency said, "Tell them they are adopted. Don't try to hide it. Once it's out in the open, you've done your job. It is a non-issue."
This little book had more pages devoted to acknowledgment of an adoptive family as a real family (just like a natural family!) than it did to adoption. If we really were a family, just like any other, why was there a book? Why did people ask me if my sister was my real sister? I knew what they meant and I didn't like it. I didn't know what to say and I felt ashamed of that.
It is only much later in life that we, as a family, have been able to talk about the worries we all had about being an adoptive family. It is only in talking about it that we have each begun to heal our own sense of fear and shame - fear that maybe we weren't a "real" family, and shame that we felt such a fear.
It's funny: back then I think many people looked at our family with a tinge of envy - the All-American family with a little bit of sainthood thrown in because of adoption. Now that we are more clearly different and more open about our struggles and doubts, I think we all feel more sure of our membership than ever before. Now that we've talked about it, it's difficult to imagine that there ever was a fear.
Understand this: adoption is an issue for all members of the adoption triad. We are not families defined solely by adoption (although I think that was more true for my family before we acknowledged it as an issue than since). Adoption is one part of our makeup as a family. Like our race and our gender, it is integral to us but not all that we are. The beginning of support for all of us comes from comfortableness with the truth. This doesn't mean no fears, no worries, no shame or no sadness. It does mean acknowledging the feelings and experiences we have and figuring out what we choose to do with them.
Don't play "let's pretend" with your children. As for the two-year-old I once was, in doing so we present them with the intolerable dilemma of choosing between what they know and what we say.
© Beth Hall
To see local Parenting resources, please select a location (U.S. only):
Note: Our authors are dedicated to honest, engaged, informed, intelligent, and open conversation about adoption. The opinions expressed here may not reflect the views of Adoption.com.


text:
Carolina Swamp Rabbit Trail
Florence Rail Trail
Heritage Trail
Mary Black Rail Trail
North Augusta Greeneway Park
Palmetto Trail- Swamp Fox Passage
Southport Road Path
Sumter Cypress Trail
Ten Governors Rail Trail
Three Rivers Greenway
West Ashley Bikeway
West Ashley Greenway
US Bike Trails:
US Bike Trails
Bike Shops Bike Manufacturers Bike Parts, Accessories and Gear Bike Publications Bike
Associations / Clubs Bike Clothing and Shoes Energy Food and Drinks
Bike Guidebooks and
Trail Maps
Pick a state and find bike
trails for mountain biking and road cycling, bicycle trail maps, and
trail map guidebooks. US Bike Trails has also teamed up with
US Bike Shops (USBikeShops.com) to provide you information on your local bike shops and bicycle
dealers. You can now use US Bike Trails (USBikeTrails.com) to find your next trail or find
your next bike dealer - all arranged by your location.


text:
Super Besse rankings
Difficulty ranking world: 8830 (all)
Ranking France: 2038 (all)
Ranking Massif Central: 144(all)
Difficulty score: 29.73 what?
Super Besse ratings
(rate it)
The Super Besse is situated in Auvergne. This climb belongs to the Massif Central.
Starting from Besse en Chandesse,
the Super Besse ascent is 7.2 km long. Over this distance, you climb 285 heightmeters.
The average percentage thus is 4 %.
Look for other sides to climb the Super Besse.
Since 2005, the Super Besse will be/was climbed in the following big tour stages:
Tour de France 2011 : Aigurande > Super-Besse Sancy on 09/07/2011
Tour de France 2008 : Aigurande > Super-Besse Sancy on 10/07/2008
profile Super Besse - click to open in new window
open big profile of the Super Besse in a new window
Find climbs close to the Super Besse: within 10 km - within 20 km - within 50 km
Find all climbs and cols in Auvergne on a map.
Find all climbs in the Massif Central in France on a map.
No stories submitted yet. Did you climb this mountain?
Did you climb the Super Besse? Please send your cycling story, description or comments. You can also send us video's or send us pictures on the Super Besse.
© climbbybike™ All rights reserved 2005 -


text:
hi,i am working on a menu and the 2nd menu's 2nd row is child of the first menu but its not showing as a drop down. but as seen on the website. wht can be wrong? i checked in menu. its child of other page
w/o going into the code specifically, I'd say you aren't giving the LI ULs position:absolute; AND you aren't hiding them ( I like to position mine off screen as it's more accessible, but some an older method was to give the element display:none; )So essentially you need to have something similar to the following in your CSS:
wasn't that is by defult behaviour of wordpress child menu when place under parents?
There is no default behavior in WP. It all depends on which theme you are using,as well as how you chose to alter said theme. Remember CSS cascades, and overrides. The 2010 theme, for example, as a working VERTICAL drop down MAIN menu in it. but if you dont use 2010 or chose to alter it then all bets are off.
Hi dresden,
If I remember correctly using left:auto has the potential to cause problems with IE7 as it has to guess where to place the sub ul. The problem usually occurs when text-align:center is used on the parent ul/li. Then IE7 will center the left edge of the sub ul in it's attempt to guess what left:auto is.
I've always had much better results using a negative margin for x-browser code.
#nav li {
position:relative;/* set containing block for AP sub ul */
#nav li ul {
margin-left:-999em;/* hide the sub ul */
#nav li:hover ul {
margin-left:0;/* reveal the sub ul on li:hover */
As others have said you will need something roughly like this.
#menu-main-menu-2 li{
background-position:0 12px;
#menu-main-menu-2 ul{
#menu-main-menu-2 li:hover ul{
#menu-main-menu-2 ul li{white-space:nowrap;background:none}
#menu-main-menu-2 ul li a:hover{background:none}
You also need to sort out your ul id="nav as that is badly constructed and should be a div unless you want to nest another list element to hold the content.


text:
ED Magedson – Founder
Ripoff Report
Cowboy Dodge1121 E Lincolnway Cheyenne, Wyoming USA
Cowboy Dodge -we paid for them to diagnose motor problem & now more is wrong with vehicle than when we took it in! Cheyenne Wyoming
Does your business have a bad reputation?
Fix it the right way.
Corporate Advocacy Program™
We took our 2005 Dodge Ram in for Cowboy Dodge of Cheyenne, WY to diagnose the reason for the motor not running properly. We received the following estimate; #4 injector $890, fuel filter (we just put new one in 1 week ago) $82.45, induction service $362.45, adjust valves $180, air filter 39.95, rear brake pads – rotors – axle seals - cleaner $585.87, exhaust manifold – gaskets – turbo gasket – hardware – miscellaneous $1142.05, tax $194.27, their Grand Total on the estimate…$3,432.04… Our grand total after adding correctly…$3,477.04.
After paying $117.66 for them to diagnose the "motor" issues we were having with our truck (but instead they diagnosed everything else), we picked the truck up in the evening & the fan belt shredded off after driving the truck 2 feet within Cowboy Dodge's lot. Leaving us without a choice, we had to leave the truck at Cowboy Dodge & informed them that the belt was obviously fine before their diagnostics because nothing on their estimate stated that there was anything wrong with it, but they refused to fix it & said that it was old & cracked when we brought it in…seriously?! They can determine that the air filter needs to be replaced, but the fan belt was not noticed until after it shredded due to their fault for not tightening the belt after they fiddled with it?!
We had to call a tow company to tow the truck home & after the tow truck driver placed our truck in the yard, I tried to lock the doors, but the horn did not sound like it normally does when you lock the doors with the remote. [continued below]....
Google search Cowboy Dodge of Cheyenne, WY and you will see their extremely poor ratings… If we had the money, we would sue them, but instead, we have to borrow a family member's vehicle until we can get our truck fixed by anyone other than Cowboy Dodge of Cheyenne, WY.
This report was posted on Ripoff Report on 06/08/2013 11:50 AM and is a permanent record located here: http://www.ripoffreport.com/reports/cowboy-dodge/cheyenne-wyoming-82001/cowboy-dodge-we-paid-for-them-to-diagnose-motor-problem-now-more-is-wrong-with-vehicl-1057522. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
Ripoff Report has an exclusive license to this report. It may not be copied without the written permission of Ripoff Report. READ: Foreign websites steal our content
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text:
By Mike Woitalla
Facing fellow World Cup qualifier South Korea in its first game of 2014, the USA strolled to a 2-0 win thanks to goals by Chris Wondolowski, who struck in the 4th and 60th minutes, with Graham Zusi playing a key role in both.
Kyle Beckerman marshaled a U.S. midfield that kept enough possession to frustrate the South Koreans for most of the game.
The U.S. defense showed no major deficiencies against an opponent coming off a 4-0 loss to Mexico four days ago.
While Jurgen Klinsmann can be pleased opening the year with a comfortable win, none of the long-shots for a World Cup roster spot made a significant statement.
6 Nick Rimando (Real Salt Lake) 13/0
Most South Korean shots went right to him but made fine effort to keep Besler's close-range corner-kick deflection from crossing line.
4 Brad Evans (Seattle Sounders FC) 17/1
Right back lost a couple one-on-ones; offensive forays were unfruitful.
5 Omar Gonzalez (Los Angeles Galaxy) 17/0.
Won battle of giants, shutting down 6-foot-5 striker Kim Shin-Wook.
5 Matt Besler (Sporting Kansas City) 13/0
Slid to block dangerous pass into front of goal. Passing inconsistent.
6 Michael Parkhurst (Columbus Crew) 24/0
Poised left back ventured forward and delivered some productive balls.
8 Graham Zusi (Sporting Kansas City) 19/3
Cross set up 1-0, and pass, also from right flank, helped create 2-0. Also carried out his defensive duties.
7 Kyle Beckerman (Real Salt Lake) 34/1
Served as a reliable linchpin in central midfield.
5 Mix Diskerud (Rosenborg/NOR) 17/2.
Dependably paired with Beckerman but will have hoped to make more of an impact before being subbed after an hour.
6 Landon Donovan (LA Galaxy) 155/57
Some crisp passes, including one that sent Zusi down wing on 1-0 goal, and he nicked the ball back for Wondolowski's second goal.
4 Brad Davis (Houston Dynamo) 13/0
Took shot that created rebound for Wondolowski goal, but made some sloppy passes that sparked counters.
8 Chris Wondolowski (San Jose Earthquakes) 18/8
Pounced on keeper's rebound to head 1-0 lead. Struck sharply from 8 yards out for 2-0.
5 Eddie Johnson (Seattle Sounders) 62/19.
Held the ball under pressure a few times but never broke loose.
5 Clarence Goodson (San Jose Earthquakes) 45/5
Kept central defense in order during Koreans' late attempts for consolation goal.
5 Benny Feilhaber (Sporting Kansas City) 41/2
Like the man he replaced, Diskerud, was solid on the ball but didn't create danger for Koreans.
NR Luis Gil (Real Salt Lake) 1/0
No missteps nor notable contributions in debut.
NR DeAndre Yedlin (Seattle Sounders FC) 1/0
Right-back debutant resorted to foul on biggest test to give up dangerous free kick.
NR Eric Alexander (New York Red Bulls) 2/0
Replaced Davis for final 10 minutes.
(1=low; 5-medium; 10=high.)


text:
By Beth Harris, AP Sports Writer
LOS ANGELES Ricky Davis can't wait to reunite on the court with Baron Davis, his former teammate in Charlotte. The two guards are part of the Los Angeles Clippers' biggest roster overhaul in recent years.
"It should be great," said Davis, who along with Jason Hart, was introduced Wednesday. "Hopefully, we can put it all together. This is a place where a lot of people didn't want to be in the beginning. It was my choice to come."
Davis, an unrestricted free agent who turns 29 in September, averaged 13.8 points, 4.3 rebounds and 3.4 assists while playing in all 82 games for the Miami Heat last season. He shot 43.3 percent from the floor, 40.5 percent on 3-pointers and 78.7 percent from the foul line.
"I'm going to bring excitement," said Davis, who sported a new look, having cut off his braids. "Hopefully, we can get chemistry together. We got every position filled up. Guys are hungry."
Besides Miami and Charlotte, Davis' 10-year NBA career includes stints with Cleveland, Boston and Minnesota.
"Ricky has shown a tremendous ability to torch people in this building," team president Andy Roeser said at Staples Center. "Unfortunately, he was playing for other teams."
The Clippers acquired Hart from Utah in June for Brevin Knight in a swap of backup point guards. Hart averaged 2.9 points, 1.0 rebounds and 1.5 assists last season.
Hart played with the Clippers late in the 2006-07 season before signing as a free agent with Utah during the offseason. The 6-foot-3 guard joins Baron Davis in returning to his hometown.
"I left because I had to take the deal," Hart said, explaining his earlier departure from Los Angeles. "I never thought something like this would happen. I felt like I went away to college and now I'm back home."
Earlier this month, the Clippers added two starters, signing point guard Baron Davis to a five-year, $65 million contract and acquiring forward-center Marcus Camby in a trade from the Denver Nuggets. Al Thornton, Chris Kaman and Cuttino Mobley figure to be the other starters next season, with Ricky Davis playing a key role off the bench.
Among the projected reserves besides Davis are Tim Thomas, Hart and first-round draft pick Eric Gordon.
"We have the potential to be a playoff team," general manager Elgin Baylor said. "We have strengthened ourselves to be a much better team."
Unrestricted free agents Elton Brand and Corey Maggette left the Clippers. Brand signed with Philadelphia, and Maggette went to Golden State.
The Clippers still have hopes of signing Shaun Livingston, the recuperating guard who is an unrestricted free agent. He hasn't played since injuring his left knee in a game on Feb. 26, 2007.
Livingston has been working out with trainers in Chicago, and has not yet been cleared for full-contact basketball, according to Neal Olshey, Clippers' director of player personnel.
"We'd like to have Shaun back," Roeser said. "He still has some work to do to get healthy."
Roeser hinted the Clippers may not be done with their offseason makeover.
"Don't be surprised if we do more before training camp," he said. "We're never done and always trying."
The Associated Press
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text:
Subject: [htdig] dig problems and PDF parsers
From: Stephen L Arnold (firstname.lastname@example.com)
Date: Tue Aug 15 2000 - 17:00:08 PDT
It's been a while since I built htdig (so maybe I forgot to do something important) and I'm having problems with the dig/merge. I get:
DB2 problem...: missing or empty key value specified
I checked the archives for the above, but I didn't find anything helpful.
I have two separate databases, one for html and misc. content, and one for M$Word documents. I have different config/search files and database dirs, and everything worked fine the last time. Now the second one won't build the database (it barfs right away with the above error) after the first one builds just fine.
I thought I would get tricky this time, and edit the configure.in file (before rebuilding the htdig binaries) to comment out the acroread setting (since it always gives an error). I have the conv_doc.pl file set to use catdoc, pdftotext, and ps2ascii (just the defaults) but I still get errors when digging pdf files.
I'm all hosed up; could someone please point me in the right direction?
Thanks in advance, Steve Arnold
Stephen L. Arnold
with Std.Disclaimer; use Std.Disclaimer;
To unsubscribe from the htdig mailing list, send a message to
You will receive a message to confirm this.
List archives: <http://www.htdig.org/mail/menu.html>
FAQ: <http://www.htdig.org/FAQ.html>
This archive was generated by hypermail 2b28 : Tue Aug 15 2000 - 07:01:43 PDT


text:
Breakfast with Santa
Saturday December 16th, 2017
Time: 8:30 am - 11:30 am
December 16, 2017
$13.50/adults $9.95/children
Join the jolliest man, himself, as well as the Mrs. for a breakfast buffet right here at Starved Rock Lodge. Following breakfast, you'll be treated to a magic show! Also attending will be "Grace," a white tailed deer from the Furry Friends. Children may take turns sitting on Santa's lap to tell him their Christmas wishes and receive a chocolate treat. Adults $13.50, children 10 & under $9.95. Call (815) 220-7386 for more information.


text:
- The two jailed members of Pussy Riot, the feminist punk band who were found guilty of "hooliganism" for speaking out publicly against President Vladmir Putin, have been sent to prison colonies, their lawyer has confirmed. A third member of Pussy Riot was released on appeal earlier this month. [Newser]
- Texas continues to take an axe to low-income women's access to reproductive health care. [Feminist.org]
- Women who describe the circumstances they were in when they had an abortion … [AP]
- … and doctors describe how they and their patients are affected by an increasing number of laws dictating what they can and can't do when providing abortions. [Salon]
- A man accused of domestic violence shot seven women at a spa outside of Milwaukee, Wisconsin, where his estranged wife worked, killing three women. [San Francisco Gate]
- Foster children do just as well with gay parents as with straight ones, according to a study of 82 at-risk kids placed in foster care in Los Angeles County published in the American Journal of Orthopsychiatry. [Queerty]
- Find out how Microsoft is getting more girls into computer science. [Forbes]
- Malala Yousufzai, the 14-year-old Pakistani girl who was shot by the Taliban last week for being a girls' education activist, is healing nicely at a hospital in Birmingham, England. She can now stand and write and doctors believe she'll be able to talk again once they remove a tube from her throat. [Ms. Magazine]
- Australian prime minister Julia Gillard has gotten a bump in her approval ratings after she called out some sexism where she saw it (that would be in her own parliament). [Guardian UK]
- Why education — especially of girls — needs to be in the foreign policy debate. [TIME]
- Check out this photo series from photographer Shadi Ghadirian on the lives of Iranian women. [Foreign Policy]
- Meet the Orthodox Jewish women, including director Rama Burshtein whose feature "Fill The Voice" appeared at the Venice Film Festival, who are committed filmmakers. [New York Times]
Contact the author of this post at [email protected] Follow me on Twitter and Tumblr.


text:
Facilities Planning & Operations
Frequently Asked Questions about RowanWorks
Q: Should I enter another work request if my job has not been done yet?
A: Only if your first request has been completed or closed and you feel the job is not done. You can look up all your requests under the My Request tab after you login to RowanWorks as a requester. If the work request you are concerned about is not done and is not listed as completed or closed, you can email the technician it is assigned to for an update instead of entering a duplicate request. To write an email to a technician just click on that person's name under the work request for which you have a concern.
Q: I have more than one problem in my room/apartment/office/etc. Is it alright if I put all the problems on one work request?
A: It depends. If you have more than one problem in the same area, but they all correspond to one craft then you can enter it on one work request (for example if there is a clogged sink and a broken toilet in the same bathroom you may enter them both on one request since they are both plumbing problems). However, if you have problems that do not come under the same craft (such as an electrical problem and an HVAC problem) please enter a separate work order for each problem.
Q: Should I be entering work requests into RowanWorks for Computer Services and Telephone Services?
A: It depends. If you are student living in a dorm or apartment then the answer is yes you should be entering those requests through RowanWorks. However, if you are faculty or staff those requests should be made through either the Support Desk at extension 4400 or by emailing email@example.com.
Q: What happens if I forget to fill in the Building field under step 2?
A: Your work order will still go through, but without a building entered it will delay the scheduling of your work so please remember to fill out what building the work request is in.


text:
THE JOB PHYSICIANS diagnose and treat human diseases, using all types of medical equipment, instruments, and tests, following standard medical procedures. They engage in Research to aid in the control and cure of diseases, prescribe and administer medication, and perform surgery. They develop and test new surgical, diagnostic, and treatment techniques, and investigate new drugs and medications. Physicians are classified according to their specialty or type of practice. General Practitioners diagnose and treat a wide variety of physical illnesses and are knowledgeable in many fields of medicine and rehabilitation of the physically challenged. When General Practitioners encounter patients with complex problems they often refer them to specialists. Specialists are Physicians who have completed advanced hospital training as postgraduates (formally known as interns and residents) in specific areas of medicine. Today, there are 40 major fields of specialization recognized by the American Medical Association. The most common specialties, which account for more than 50 percent of the total number of practicing physicians, are described below: Internal Medicine: The diagnosis and treatment of diseases of the internal organs such as the heart, liver, and lungs. General Surgery: Manual and operative procedures to correct deformities, defects, and injuries. Psychiatry: The treatment and prevention of disorders of the mind, including psychoses and neuroses. Obstetrics and Gynecology: The care of women during and after pregnancy and delivery, and the treatment of diseases of female organs. Pediatrics: The branch of medicine dealing with the development and care of infants and children, and with the treatment of their diseases. Radiology: The use of radiant energy including X-rays, radium, and Cobalt 60 for treatment and diagnosis of diseases. Anesthesiology: Administration of various forms of anesthetic drug for diagnosis or during surgery operations. Ophthalmology: The branch of medicine dealing with diseases or defects of the eye. Orthopedic Surgery: The diagnosis and medical or surgical treatment of diseases, fractures and deformities of the bones and joints. Family Practice: Physicians in this specialty are concerned with the health-care needs of families. During a three-year residency, doctors in this specialty become proficient in general medicine, community medicine, nutrition, and the behavioral sciences, with emphasis on marriage counseling and family problems. They are capable of caring for 90 percent of all problems presented to them by patients. The field of Nuclear Medicine is another growing specialty for Physicians, who perform tests using nuclear isotopes and use techniques that let them see and understand organs deep within the body. WORKING CONDITIONS Physicians' working conditions depend primarily on geographical area, hospital facilities, and the physician's specialty. Their offices and treatment rooms are usually well-lighted, air-conditioned, and equipped with the necessary instruments and supplies. Physicians usually work in their offices or in hospitals. When on call, they must make their whereabouts known, carry electronic pagers, and be available at all times. Most Physicians belong to the American Medical Association, the California Medical Association and to the affiliated district, county, and state organizations. In addition to the above associations, medical associations exist for specialists. EMPLOYMENT OUTLOOK The following information is from the California Projections of Employment published by the Labor Market Information Division. Estimated number of workers in 1990 51,330 Estimated number of workers in 2005 71,510 Projected Growth 1990-2005 39% Estimated openings due to separations by 2005 21,790 (These figures do not include self-employment nor openings due to turnover.) By the year 2005, over 71,500 Physicians will be practicing in California. The numbers of Physicians is increasing faster than the average for all occupations in the state due to continued expansion of the health industry. WAGES, HOURS, AND FRINGE BENEFITS The yearly net income earned by self-employed Physicians fluctuates according to the type, location, and size of practice. Private practice Physicians (including specialists) earn an average of $155,000 per year, according to a recent salary survey. Doctors employed by medical groups and health maintenance organizations earn, on average, about $45,000 less, per year but enjoy fringe benefits such as paid vacations, retirement programs, profit sharing, and educational sabbaticals on half-pay, in addition to working shorter hours. Salaries for those employed by State and Federal governments range from $66,000 to $96,000 annually, depending on the training the Physician has received and the employer. They also receive the same fringe benefits enjoyed by group physicians. ENTRANCE REQUIREMENTS & TRAINING Helpful high school courses for students planning to become doctors are biology, chemistry, physiology, and math. Many hospitals have volunteer programs for high school students during the school semester and summer. Some areas where students may receive supervised training are hospital laboratories, physical therapy departments, nursing services, and pharmacies. Students must complete three years of college to qualify for any one of eight medical schools in California. Most students, however, have a Bachelor's degree when admitted to medical school. Considerable weight is given on scholastic records, performance on the Medical College Admission Test (MCAT), and recommendation of teachers and advisors regarding the applicant's motivation, emotional stability, and intellectual capacity. The number of applicants far exceeds the actual number of students accepted into medical school. Academic requirements of California medical schools vary slightly, with most requiring a year or more each of biological science, chemistry, and physics. The University of California Medical Schools, with the exception of Irvine, require a year of English, and two schools (Davis and San Diego) require mathematics through calculus. In addition, a broad educational base of coursework that includes literature, history, art, and the social and behavioral sciences is recommended. Medical doctors should be self-disciplined, conscientious and sensitive to the needs of their patients. They should be able to organize and evaluate information, write reports and work independently. After obtaining the M.D. degree, doctors must meet the State Licensing requirements. In California, applicants must pass either the National Board of Medical Examiners exam or Federation Licensing Examination which is administered by the Medical Board of California. In certain cases, applicants are required to take an oral, or clinical and oral examination. ADVANCEMENT Physicians and Surgeons in private practice do not advance in their occupation in the traditional sense -- their progress is measured by their advancement in skill and understanding, in their numbers of patients, and in income. Appointments to teaching positions, medical boards, and hospital staffs are other forms of recognition. In civil service jobs, the annual raises within the classification provide one kind of advancement, and progress to supervisory or administrative jobs provides another. FINDING THE JOB Those seeking jobs as physicians should register with their local medical society and apply directly to county, state, and federal personnel departments. Many newly licensed physicians become associated with an established doctor and assist or share in the practice. ADDITIONAL SOURCES OF INFORMATION American Medical Association 515 N. State Street Chicago, IL 60610 Association of American Medical Colleges 2450 N. Street, N.W. Washington, D.C. 20037 National Medical Association 1012 Tenth Street, N.W. Washington, D.C. 20001 American Medical Women's Association 801 N. Fairfax Alexandria, VA 22314 California Medical Association P.O. Box 7690 San Francisco, CA 94120-7690 (415) 541-0900 Medical Board of California 1430 Howe Avenue Sacramento, CA 95825 (916) 263-2499 RELATED OCCUPATIONAL GUIDES Pharmacists No. 159 Veterinarians No. 282 OCCUPATIONAL CODE REFERENCES DOT (Dictionary of Occupational Titles, 4th ed., Rev.); Anesthesiologist 070.101-010 General Practitioner 070.101-022 Internist 070.101-042 Psychiatrist 070.101-070 Surgeon 070.101-094 OES (Occupational Employment Statistics) System Physicians and Surgeons 321020 Source: State of California, Employment Development Department, Labor Market Information Division, Information Services Group, (916) 262-2162.Note: This is NOT a job opening. The purpose of This California Occupational Guide is to provide you with useful information to help you make career decisions. If you are searching for a job, go to:
California Occupational Guides
California Employment Development Department >> Labor Market Information >> More Occupational Guides


text: Hi, Is it possible to query a job's memory limit from withing the running program? I'm assuming that there may be a node/host wide total imposed by the batch system. For example on an SGI UV which looks like a single host to the program, I'd like to be able to know how much ram my all processes in my program can use in order to size internal caches appropriately. It seems that this limit is enforced by the batch system, however there doesn't seem to be consistency across various sites. Any advise would be greatly appreciated. Burlen


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A Justice Site
Mirror Sites:
CSUDH - Habermas - UWP - Archives
California State University, Dominguez Hills
University of Wisconsin, Parkside
Soka University Japan - Transcend Art and Peace
Created: June 22, 2003
Latest Update: November 6, 2003
You will be held accountable for purposes of grading for the readings and exercises listed here. There will be no "testing." That means that you will not have to live in anxious anticipation of what we will ask and how much you will have to know. Instead, we will provide weekly discussion questions, lectures, essays, and concepts we feel that you should know as a result of having taken this course. You will assure us of that learning and receive your grade for the questions and concepts about which you choose to write and talk with us. In addition, you will find detailed explanations and examples on our grading policies in the first week's reading.
* * * * *
Week 12: Week of November 16, 2003
- Topic:Marxist Criminology
- Preparatory Readings & Other Materials:
- Williams and McShane. Criminology Theory. chapters by Quinney, Spitzer and Turk
- Pollock. Criminal Women. ch. 6 and 7
- Documentary, "Thug Life in D.C." to be shown in class.
- optional -- Adler. Criminology. ch. 8
- Lecture:in class
- Concepts:
- conflict theory
- Marxist criminology
- capitalist bourgeoisie
- proletariat
- lumpenproletariat
- social class
- power
- capitalism
- revolution
- dialectic
- Discussion Questions:
- Across all the readings in Williams & McShane's conflict theory section, what can you point to as elements that are in common?
- What are the major similarities and differences between consensus theories and conflict theories?
- How does the consumer behavior experiment relate to labeling theory and Marxist criminology? Provide examples to illustrate your point.
- How does labeling theory and Marxist criminology relate to the documentary, "Thug Life in D.C."? Why.
- What is Pollock's critique of labeling theory and Marxist criminology? Do you agree or disagree with her critique? Why.
Past Lectures and Related Links:
Theory Resources Page
Sourcebook of Criminal Justice Statistics
Some Recommended Activities:
- Show and Tell:Bring in a current event or find a program (other than those mentioned in the readings or lectures) showing how Marxist criminology informs policy and practice.
- Explore one of these topics:
--- Trace the development of the term, "underclass."
--- Compare and contrast "crime in the streets" with "crime in the suites". How does this relate to social class?
--- Does an elite rule America? How does this relate to criminology? Why.
- Recommended Readings
Richard Quinney. Class, State and Crime .
Richard Quinney. Critique of the Legal Order .
Richard Quinney. The Social Reality of Crime .
Austin Turk. Criminality and Legal Order .
Jeffrey Reiman. The Rich Get Richer and the Poor Get Prison.
William Bonger. Criminality and Economic Conditions.
William Chambliss. Law, Order and Power.
Ian Taylor, Paul Walton and Jock Young. The New Criminology .
Now, check the Minimum Requirements for Criminology, Week 9, 10, 11, and 12.
Site Copyright: Jeanne Curran and Susan R. Takata and Individual Authors, June 2003.
"Fair use" encouraged.


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RFE: Conference Listings
This service is a joint project of RFE and EconBiz.
Econometric Society;Antai College of Economics & Management, Shanghai Jiao Tong University;Shanghai University of Finance and Economics;Fudan University;China Europe International Business School;Chinese Association of Quantitative Economics
- Dates:
- August 17-21, 2010
- Description:
- 2010 Econometric Society World Congress - Econometric Society
- Location:
- Shanghai, China
- Subject:
- ESWC 2010 welcomes submissions in all areas of economics. It is hoped that papers presented at the Congress will represent a broad spectrum of applied and theoretical economics and econometrics.[gem?_?? den Informationen des Anbieters - according to site editor's information]
- Notes:
- JEL Code:
- Sponsor:
- http://www.econometricsociety.org/news1.asp?ref=85


text:
Work and Play Getaways
From cosmopolitan convenience of Harrisburg Hotels to sweet retreats in Hershey. More
Just a Taste of our Region
Farm to fork, Fine Dining or Family Friendly, Sweet or Savory – what are you hungry for? More
Things to Do
Sweet Family Fun, Urban Eclectic and the Great Outdoors – you've reached your destination. More
Sweet Summer Fun
Coasters, Kiddie Rides and Water Slides all surrounded by the town built on chocolate. More
Mark your Calendar!
We've got just the ticket to help you fill delightful days and nights you wish would never end. More
Built in 1881, the Esther Furnace Bridge crosses Roaring Creek. It is another good example in the county of Queen Truss construction.
3211 North Front Street, Suite 301-A
Harrisburg, PA 17110
+1(877)727-8573 | +1(717)231-7788


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We use three different types of under floor fan coil units (VKB, VKD and FVD) made by LTG, a German company that designs and manufactures components and complete systems for room air and process air technology. LTG fan coil units use an integrated fan that draws in the ambient air. In a water-fed heat exchanger, air is cooled or heated and returned to the room. All three (VKB, VKD and FVD) are four-pipe units which allow BAS to automatically switch between heating and cooling according to the internal load requirement without excess cooling or excess warming in each individual space. Each unit has a 5 speed fan to delivery cooled or warmed air into each space.
Fan Coils
Control Instrumentation and Hardware
IWESS Website | MMCH415, 5000 Forbes Avenue, Pittsburgh, PA 15213 | (412) 268-6263
Carnegie Mellon Home


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As it turns out though, lightning can strike twice. There are unconfirmed reports that the La Oroya smelter may be resuming operations ahead of schedule, meaning Silver Wheaton is positioned for another windfall. And, 'positioned' has a dual-meaning in this instance. The smelter is only about 100 miles away from the Yauliyacu mine, which should reduce inventory levels even further.
In total, Silver Wheaton has seventeen operating mines under its umbrella and four development stage projects. That count doesn't include any deals inked following the Hudbay deal. Included in this suite of assets is Barrick Gold's cornerstone project, Pascua Lama, which is forecast to begin production in mid-2014. Once in production, it is forecast to deliver approximately 9 million ounces of silver annually to Silver Wheaton in the first five years of operations.
So how much silver will these operations produce once they're up and running? Following the Hudbay deal, Silver Wheaton has set a target of 48 million silver-equivalent ounces (or SEO) per year by 2016. Smallwood however has suggested that "70 million and then even 100 million is a comfortable [future] level. The silver streaming industry produces 750 million SEO per year, so 100 million for us is a tangible [forward-looking] level for us."
For perspective, over the past six months Silver Wheaton has produced and sold more than 13 million SEO, and collected $400 million in revenue for it during a period where silver prices were lackluster. At first glance an annualized revenue rate of $800 million may not seem like much for an $11.2 billion organization. The company managed to turn $288 million of that $400 million into net income though — net margins of more than 70%.
And that's when the attractive aspect of a silver streaming company really starts to shine. It also underscores why investors may want to mentally disconnect the presumed relationship between SLW and silver itself, including iShares Silver Trust (NYSE:SLV). It is also worth noting that Silver Wheaton does all this with a very lean cost profile — administration costs are almost half that of SLV.
When asked whether or not another round of quantitative easing is needed by Silver Wheaton, Smallwood replied "It would help, but we don't need it … our average cost for silver in Q2 was $4.06."
The amount leaves plenty of wiggle room for other expenses, which is why margins can remain so strong even when silver prices are at relative low points. Indeed, silver prices could drop precipitously, and Silver Wheaton would remain profitable.
While Wheaton has been viewed by the media and the market as a high-growth instrument fueled by incredible net margins and rising silver prices, growth isn't the ultimate goal here. As the company brings all of its foreseeable projects to an operational, revenue-bearing status, it will also grow its income distribution policy. Ultimately, as the company gets closer to its 100 million ounce per year production target, it will give the majority of the streaming business' net income back to shareholders as dividends.
The company's got the assets to keep the payouts strong for quite a while too. Smallwood adds "Currently, 25% of our projects have 20 years or more worth of mining life left. After the development of our open pit projects, almost 50% of our assets will have a mine life of 20 years or more."


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You won't be able to dismiss this by usual means (escape or click button), but you can close it programatically based on user choices or actions.
"The invitation was exactly what I was hoping it would be. The image I created on my computer is the exact image I received. They are printed on sturdy paper with amazing color. The bride-to-be loves them and said they are beautiful. Her approval is really all I needed"
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"I love this card style because it's fancy and fun! Also, you can add text to the back and I put the itinerary for the weekend there. Seriously, the best card and Wedding Paper Divas has the best customer service!"
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"This invitation is stunning. The paper is thick and the colors are beautiful. Instead of the corset on the back, I used the text layout and put the Itinerary on the back. I made the back hot pick to match the front, and the font was in white. It is simply fabulous! I needed them to customize some of the fonts, so they were bigger or smaller, etc. They came out perfect! In addition, the proofs were done in 24 hours, and they arrived before the anticipated date. Outstanding customer service. Highly recommend the product and the company!!"


text:
Posted 2016-06-21
Impact Factor on the rise
Posted 2011-03-01
ePub format available from 2011!
Posted 2010-06-07
Now Archived in PubMed Central
International Journal of Qualitative Studies on Health and Well-being eISSN 1748-2631 [ISSN 1748-2623 volumes 1-4, 2006-2009]
This journal is published under the terms of the Creative Commons CC-BY 4.0 License. Responsible editor: Carina Berterö.


text: #788: Request for AppCafe to have a 'resume' capability --------------------------------+------------------------- Reporter: cabpa | Owner: Type: System Enhancement | Status: new Priority: minor | Milestone: 9.2 Component: Software Manager | Version: 9.2-RELEASE Keywords: | --------------------------------+------------------------- Much better if AppCafe has a 'resume' capability because pbi downloads in AppCafe are big and a resume capability is good in order to download the pbi again from the last size it had already downloaded when the download encounters an interruption. If a download is interrupted in AppCafe, an error message will appear that an error occurred during the download. The options for the current download which is interrupted is just View Details and/or Cancel Download. There is no option to Resume the download to the file size it had already downloaded. The user have to download again the interrupted pbi from size zero. On the error message dialogue, there can be an Resume button or there can be a Resume on the right-click option on the interrupted pbi download listed in AppCafe. -- Ticket URL: <http://trac.pcbsd.org/ticket/788> PC-BSD <http://trac.pcbsd.org> PC-BSD Project Management


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A heroin addict was caught dealing the drug when another user called emergency services to complain about feeling ill because of a rogue batch, York Crown Court heard.
Police called at Stephen Jarman's home in Cromer Street because of "concern for the health of people who had taken bad drugs," said Prosecutor Katherine Robinson.
The court heard Jarman, 53, was found in the ground floor bedroom sorting a quantity of heroin into street deals.
Around £230 cash was also found on the property. Jarman confessed to working with others higher up the dealing chain, it was said.
Text messages found on his mobile phone showing Jarman had been selling drugs but the amounts he made were modest and he had a drugs habit of his own, Ms Robinson added.
Jarman admitted possessing a class A drug with intent to supply and was given a two-year jail sentence suspended for two years.
He was also ordered to take part in a drug rehabilitation programme and carry out 150 hours unpaid work and pay a £100 victim surcharge.
Neal Kutte, defending, said: "It's a strange case. Originally, the police were called there because someone had told the emergency services they had had an adverse reaction to taking substances.
"The defendant is a heroin addict who had got himself involved in dealing to fund his addiction. He was making wraps of heroin. He was to take 10 and return 40."
The 40 wraps were to go to an individual higher up the chain. He said Jarman had got into debt and was working it off by doing this, as well as feeding his own addiction.
"Heroin he had been taking was adulterated," Mr Kutte said, adding there were rumours flying around that it had been mixed with another illegal substance.
The court heard Jarman had a long record of 32 convictions involving 70 offences – but had stayed out of trouble for nine years.