text:
Gordon's four-point play lifts Bulls over PistonsFeb 11, 2009 - 6:03 AM CHICAGO (Ticker) -- Just when it looked like Red Kerr Night would end in disappointment, the Chicago Bulls got up off the mat for one last push.
Ben Gordon's four-point play with 17 seconds left capped a late comeback and propelled the Bulls to a 107-102 victory over the Detroit Pistons on Tuesday.
Gordon finished with 24 points to lead the way and Derrick Rose added 23 for the Bulls, who honored legendary announcer Johnny "Red" Kerr at halftime.
"Watching the ceremony at halftime, I knew we had to win this game for (Kerr)," Gordon said.
Chicago trailed, 100-90, with 3:33 remaining before a 9-0 run brought it back to within one with 1:14 to play.
"During the fourth quarter, we just turned it up and we were able to impose our will on them," Gordon said.
Rasheed Wallace hit a pair of free throws to push the lead back to 102-99 before Rose hit a layup and Wallace missed a 3-pointer at the other end, providing the Bulls with their opening.
Rose drove the lane and had his layup attempt hit the rim, but the rookie standout grabbed his own miss and found Gordon in the corner. The sharpshooter nailed the shot and was fouled, draining the free throw to give Chicago the lead for good.
"I was just trying to hit a shot and he fouled me, so then I had to make the free throw to finish it off," Gordon said. "I looked at the scoreboard after I shot because I didn't know if it went in."
"I thought we were very tentative in the first three quarters, then we really turned it on in the fourth quarter," Bulls coach Vinny Del Negro said. "We never really got into an offensive rhythm all night, but we kept attacking. A good win for us."
Richard Hamilton scored 30 points for the Pistons but turned the ball over with 10 seconds left to squander his team's last opportunity.
"It's really hard to discuss what happened because it hurts so much," Hamilton said. "I thought we played good most of the game, but losing the lead like that and being dominated at the end of the game is something we can't do."
Chicago got strong contributions from frontcourt mates Tyrus Thomas and Joakim Noah, who combined for 34 points and 26 rebounds.
"We were down and we turned it on in the fourth quarter, everyone just wanted to win and we played solid defense to comeback," Thomas said.
Rose injured himself on the final play when he ran into a screen face-first. He was taken to the locker room as Andres Nocioni was knocking down two free throws to provide the winning margin.
"I think Derrick Rose is all right," Del Negro said. "He just has a little bit of a headache. It wasn't his best performance, he got into foul trouble early and was tentative. The fourth quarter, I told him to start attacking the basket and make things happen."
Detroit took an 85-71 lead into the fourth quarter due to a strong third period by Hamilton and Wallace, who combined for 24 points in the frame.
Wallace finished with 20 points and 10 rebounds for the Pistons, who have dropped back-to-back games while allowing a combined 60 fourth-quarter points.
"We made a lot of mistakes at the end of the game," Detroit coach Michael Curry said. "A couple of times we got lost on pick and rolls."
Feb 10 11:29 PM
- 112
roots420fire Added 5 roots
Pistons 102, Bulls 99 4th - 1:00Feb 10 11:24 PM
- 107
rootsRUWTbot Added 20 roots (Close Finish)
Pistons 102, Bulls 99 4th - 1:00Feb 10 11:18 PM
- 87
rootsmicfac03 Added 5 roots
Pistons 100, Bulls 96 4th - 2:00Feb 10 11:14 PM
- 82
rootsRUWTbot Added 82 roots (Close Finish)
Pistons 100, Bulls 96 4th - 2:00Feb 10 11:12 PM
Feb 10 10:44 PM
- 0
rootsRUWTbot Took away 23 roots
Pistons 66, Bulls 61 3rd - 6:00Feb 10 10:29 PM
Feb 10 9:41 PM
- 23
rootsRUWTbot Added 23 roots
Pistons 51, Bulls 50 HalfFeb 10 9:41 PM
Feb 10 9:10 PM
Related News
- NBA Note - Detroit Pistons Drummond, Andre Thu
- NBA Note - Detroit Pistons Jackson, Reggie Thu
- NBA Note - Detroit Pistons Leuer, Jon Thu
- NBA Note - Detroit Pistons Johnson, Stanley Thu
- NBA Note - Detroit Pistons Drummond, Andre Thu
- NBA Note - Detroit Pistons Kennard, Luke Thu
- NBA Note - Detroit Pistons Bradley, Avery Thu
- NBA Note - Detroit Pistons Jackson, Reggie Thu
- NBA Note - Detroit Pistons Harris, Tobias Thu
- Middleton scores 27, Bucks block 16 shots, top Pistons 99-95 Wed
- Westbrook, Thunder top Bulls 92-79 for 3rd straight win Wed
- Rookie Kennard sparks Pistons in 112-103 win over Heat Nov 12


text:
Discussion in 'Cuckold Forum' started by mister cuckold, Aug 31, 2012.
Yes, Carol appears to be a very attractive, intelligent and personable lady and I think she would make a wonderful, loving cuckoldress for any man fortunate enough to be accepted into her service, should she ever desire to own one.
Sign me up!!!
Separate names with a comma.

subset: commoncrawl


text:
A Midsummer Night's Dream
- Street Date:
- June 20th, 2017
- Movie Release Year:
- 2014
- Studio:
- Kino Lorber
- Length:
- 145 Minutes
- Release Country
- United States
Kathryn Hunter, David Harewood, Tina Benko
Julie Taymor
Plot Synopsis:
From the mind of award-winning director JulieTaymor (The Lion King on Broadway, Frida,Titus) comes a Shakespeare adaptation like none other, A Midsummer Night s Dream. Rich with Taymor s trade- mark creativity, this immersive and darkly poetic cinematic experience brings the play s iconic fairies, spells and hallucinatory lovers to life. Filmed at her sold-out stage production with cinematography by Rodrigo Prieto (Argo, Frida) and music by Academy Award-winning composer Elliot Goldenthal (Frida, Heat), the feats of visual imagination are ingenious and plentiful, but beating at the center of the film is an emotionally moving take on the deeper human aspects of Shakespeare s beloved tale.
Technical Specs
- Blu-ray


text:
Entry into the Sixth Form
Applications from both internal and external students who wish to join the High School Sixth Form for their Post-16 education are welcomed.
Minimum qualifying academic requirements apply equally to internal and external applicants.
There are clear entry requirements, which each student must satisfy, in order to study at the High School Sixth form. These are outlined below. They are designed to help to ensure that students will be able to achieve success in their studies.
All the application/subject information/deadlines will be updated shortly.
Academic entry requirements
These entry requirements are published annually to all applicants.
Students will need to meet all of the following requirements for entry into the High School Sixth Form:
- A minimum of six subjects at A*– B grade (or equivalent) at GCSE Level.
- Students should have a minimum of Grade 5 in both GCSE English or English Literature and Mathematics.
- In addition, students must achieve the standard required by the individual subjects. Subject specific requirements are listed on each subject profile on the website in the subject choices booklet.
Application Process
The Sixth Form Prospectus is above and the Application Form is available below or from the school. The Subject Choices and Pools have been updated on the Subject Page.
Internal Applications
The vast majority of students from the High School for Girls continue from Year 11 into the High School Sixth Form. It is the intention of the School to offer all girls a place in the High School Sixth Form, subject to their meeting the entry requirements.
External Applications
The Governing Body would expect to admit approximately 50 external entrants to the High School Sixth Form. Applicants will be invited for an informal discussion with a member of the Senior Leadership Team, but this will only be to advise on suitability of AS/A Level courses for which they have applied and to give careers' advice on choice of the Sixth Form courses.
Making an Application
- The School's Application Form below must be completed and returned to the High School Sixth Form, for the attention of Mrs Morris, by the published deadline of Friday, 10th February 2017;
- Discussions with a senior member of staff will be held at the school during March;
- Provisional offers will be made in April/May;
- Year 12 Induction Day is on Thursday, 29th June 2017;
- Immediately after GCSE results in August, students should contact the school to confirm their grades and indicate that they wish to take up a place in the High School Sixth Form.


text:
Copy and paste the embed code below. The code changes based on your selection.
The code has been copied to your clipboard.
Video size
Republicans in Congress said Tuesday the deal announced with Iran was 'worse than we had expected' and that the agreement would not diminish Iran's ability to make nuclear weapons.


text:
Reviews & Ratings
2014 Chehalem Rose "Rose of Pinot Noir"
Winery: Chehalem
Vintage: 2014
Wine Name/Vineyard: "Rose of Pinot Noir"
Wine Category: Rose
Grape blend: 100% Pinot Noir
Region: Willamette Valley
State or country: OR
Price: $22
Cases produced: 288
KWG Score: 90 (based on 2 reviews)
Ken's Wine Rating: Very Good+ (90)
Review date: July 3, 2015
Wine Review: This dark pink colored Rose opens with a mild wet stone and faint strawberry bouquet. On the palate, this wine is medium bodied, balanced, round and a bit juicy. The flavor profile is a tasty mild mineral infused red cherry hints of strawberry. The finish is dry and friendly. This rose is one of more food friendly and versatile options - you will come across. I would pair it with vegetable lasagna. Enjoy - Ken
Winemaker Notes: The 2013 Rose was such a hit, and the 2014 vintage so plentiful, that we decided to make some more Rose! This one shows the energy and electricity that pulsed through the vintage right off the bat, with a vibrant rush of color springing from the bottle, and the spice and vibrancy one would expect from such a racy entry. We found that the warmth from 2014 made our Rose act like exactly what it should be; the most refreshing Pinot Noir you can imagine, in the body of a texturally-interesting white wine. The nose has red currant, cinnamon, white pepper, and cotton candy, and on the palate the wine is dry and focused, reminiscent of strawberry-rhubarb pie, cherry cordial, or strawberry soda, with structure and weight worthy of a full meal.
Organic status: not organic
Buy it: Use 1000 Corks to find stores that sell Chehalem 2014 Rose of Pinot Noir.


text:
Fire Maple's FMS-X1 Star Heat Exchanger Cooking System utilises heat exchanger technology and virtually eliminates wind interference to create a highly efficient cooking system. This type of system really comes into its own during long trips where the additional weight of the system is compensated by the weight of fuel saved.
Fire Maple says: The star cooking system is very efficient, with a heat exchanger on the bottom of the pan it can increase the effectiveness of the fuel by around 30%. With pot cosy and heat efficient lid.
Fire Maple's Star cooking system uses the same technology components as some other brands, namely a pot with a heat exchanger that can be closely coupled with the burner and protected from the wind. A cosy round the pot further conserves heat as does the rubberised clip on lid.
Its an effective setup that can eek out your fuel upto 30%, a lot more if you usually cook without a windscreen. Having used a few of this type of setup there are a few things we really like about this one, firstly the handles are attached to the pan - not to the pot cosy - when the latter is the case the unit can be a bit unwieldly.
The coupling of the pot to the burner unit is very easy and not too tight. Sometimes it can be tricky to de-couple the pot after cooking but the Star seems to have this covered. We also like the fact that the burner unit and pot can be stood solidly on the ground when the unit is removed from the gas.
The pot size is about 1.3L which is an ideal size for two people cooking a reasonable meal, though with all these high efficiency stoves simmering can be a bit of a black art because so much of the heat is being used.
The system is sized so that you can pack a small 100g gas cartridge into the pot with the burner and lid fitted securely. The kit includes a single eating bowl, which is quite nice but there's only one - the kit is ideal for two people so it would have been nice to squeeze in two bowls if they could.
The stove is lit using a piezo igniter - this is more or less essential because once coupled to the pot the stove burner is largely inaccessible.
We like this kit, it does what its supposed to do well, in comparison to some others its on the heavy side but then again its extremely price competitive and is aimed at two people who would share the weight.
- Reviewed by Ultralight Outdoor Gear
|Read reviews here:


text:
|Home | About | Journals | Submit | Contact Us | Français
It is estimated that one billion people around the world are vitamin D deficient. Vitamin D deficiency has been linked to various inflammatory diseases. However, the mechanism by which vitamin D reduces inflammation remains poorly understood. In this study, we investigated the inhibitory effects of physiologic levels of vitamin D on lipopolysaccharide (LPS)-stimulated inflammatory response in human blood monocytes, and explored potential mechanisms of vitamin D action. We observed that two forms of the vitamin D, 1,25(OH)2D3, and 25(OH)D3, dose dependently inhibited LPS-induced p38 phosphorylation at physiologic concentrations, IL-6 and TNF-α production by human monocytes. Upon vitamin D treatment, the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) was significantly upregulated in human monocytes and murine bone marrow-derived macrophages (BMM). Increased binding of the vitamin D receptor and increased histone H4 acetylation at the identified vitamin D response element of the murine and human MKP-1 promoters were demonstrated. Moreover, in BMM from MKP1−/− mice, the inhibition of LPS-induced p38 phosphorylation by vitamin D was completely abolished. Vitamin D inhibition of LPS-induced IL-6 and TNF-α production by BMM from MKP-1−/− mice was significantly reduced as compared to wild type mice. In conclusion, this study identified the upregulation of MKP-1 by vitamin D as a novel pathway by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages.
Vitamin D is well known for its role in calcium homeostasis and maintenance of bone metabolism (1). However, recent evidence suggests that vitamin D plays important roles in both innate and adaptive immunity (2). Vitamin D levels are routinely tested by assessing the concentration of the major circulating form of the vitamin D, 25(OH)D3, in serum; this form of vitamin D has a half-life of 15 days, while the active form of vitamin D, 1,25(OH)2D3, has a short half-life of approximately 15 h (3-5).
1,25(OH)2D3 acts as a ligand for the vitamin D receptor (VDR), a member of the nuclear receptors superfamily (6). VDR forms a heterodimer with retinoid X receptor (RXR) and regulates gene expression by binding to the Vitamin D Response Element (VDRE). VDRE had been shown to be predominantly located in introns and intergenic intervals (7). VDRE is characterized by direct repeats of two hexameric core-binding motifs (preferentially being AGTTCA) spaced by three nucleotides (8, 9). The binding of VDR to VDRE recruits co-activators and enzymes with histone acetylation activity, causing the structural changes in chromatin, therefore facilitating gene transcription (10).
Lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, induces cytokine production by monocytes/macrophages. LPS had been implicated in sepsis caused by Gram-negative bacteria, and induces intense inflammatory and procoagulant responses, which can be lethal (11). LPS is recognized by cell surface Toll-like receptor 4 (TLR4) which initiates intracellular signal transduction cascades(12). The MAP kinases activated by LPS (ERK, JNK and p38(12)) are critical regulators of pro-inflammatory cytokine production, including TNF-α and IL-6 (13, 14). Although these pro-inflammatory cytokines enhance host defense, excessive production leads to unresolved inflammation(15). Therefore, feed-back control of MAP kinase activation is necessary. Mitogen-activated protein kinase phosphatases (MKP) inactivate MAP kinases by dephosphorylating conserved threonine and tyrosine residues of the activated MAP kinases(16). MKP-1 is known to preferentially inactivate p38 and JNK, leading to subsequent inhibition of proinflammatory cytokines production (17, 18). In the current study we examined mechanisms of the vitamin D-mediated suppression of LPS-activated monocytes/macrophages. We found that vitamin D inhibits LPS-induced cytokine production by up-regulating MKP-1 thereby attenuating p38 activation.
1,25(OH)2D3, 25(OH)D3, and monoclonal anti-β-actin antibody were purchased from Sigma (St. Louis, MO). HyQTase was purchased from HyClone Laboratories, Inc. (Logan, UT). TrypLE Express was purchased from Invitrogen Corporation (Carlsbad, CA). Phospho-p38 and p38 antibodies were purchased from Cell Signaling (Danvers, MA). Anti-mouse and anti-rabbit horseradish peroxidase (HRP)-labeled IgG were purchased from Amersham Biosciences (Piscataway, NJ). Rabbit polyclonal antibody to VDR, Rabbit polyclonal antibody to MKP-1, RIPA Lysis Buffer and Protein A/G PLUS-Agarose beads were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA). Rabbit polyclonal antibody to histone H4 and acetylated histone H4, and Magna ChIP A/G Chromatin Immunoprecipitation Kit were purchased from Millipore (Temecula, CA). Chemiluminescent reagents were purchased from Perkin Elmer Life Sciences (Waltham, MA). All the reagents and conjugated antibodies against phospho-p38, phospho-ERK1/2, phospho-JNK and IL-6 in flow cytometry analysis were purchased from BD Biosciences (San Diego, CA), while the TLR4 antibody was purchased from eBioscience (San Diego, CA).
Blood samples were collected from normal healthy adults. Approval was received from the National Jewish Health Institutional Review Board (Denver, CO) for the study.
C57BL6×129 mice were purchased from the Jackson Laboratory (Bar Harbor, ME). MKP-1−/− mice were provided by Bristol-Myers Squibb (19). Six-eight week old males were used in the experiments. All experiments using these animals were approved by the Institutional Animal Care and Use Committee at National Jewish Health. This institution has an animal welfare assurance number (A3026-1) on file with the Office of Protection and Research Risks.
Peripheral blood mononuclear cells (PBMC) were isolated from heparinized, venous blood of healthy donors by Ficoll-Hypaque density gradient centrifugation as described elsewhere. PBMC were cultured in hormone-free medium (phenol-red free RPMI containing 5% charcoal stripped FCS, 50 μg/ml streptomycin, and 50 U/ml penicillin) with a range of doses of 1,25(OH)2D3 or 25(OH)D3 for 24 h at 37°C with 5% CO2. Equal volume of ethanol was used as vehicle control. Following pretreatment with vitamin D the cells were stimulated with 10 ng/ml of LPS and the effects of vitamin D on LPS responses in CD14+ monocytes were examined.
Bone marrow cells from wild type (C57BL6×129) and MKP−/− mice were isolated as previously described(20, 21), cultured in DMEM containing 10% FBS, 10% L929 cell conditioned medium (as a source of CSF-1), 50 μg/ml streptomycin, and 50 U/ml penicillin at 37°C with 10% CO2 for 5 days to produce bone marrow macrophages (BMM).
To analyze the effects of vitamin D on p38 activation by LPS, PBMC were pre-incubated in hormone free medium containing 1,25(OH)2D3 or 25(OH)D3 for 24 h, followed by stimulation with 10 ng/ml LPS for 10 min. Cells were then fixed with 2% formaldehyde at 37°C for 10 min. Adherent cells were collected by using HyQTase and TrypLE consecutively and combined with suspension cells. Cells were permeabilized in 500 μl 1X Perm/Wash Buffer I (BD Pharmingen) at 4°C for 30 min, incubated in 100 μl 1X Perm/Wash Buffer I containing FITC-conjugated anti-CD14 and APC-conjugated anti-phospho-p38 antibodies at 4°C for 1 h, and washed with 1X Perm/Wash Buffer I. The samples were then analyzed by flow cytometry (FacsCalibur Becton-Dickinson Cytometer, Franklin Lakes, NJ) and CellQuest Pro software. The flow data was displayed as % of CD14+ cells that express p-p38 (the gate for p-p38+ cells was set based on isotype control binding).
To examine the effects of vitamin D on IL-6 production by LPS-activated monocytes, PBMC were cultured in hormone-free medium containing 1,25(OH)2D3 or 25(OH)D3 for 24 h, followed by 10 ng/ml LPS stimulation for 6 h with GolgiPlug™ added for the last 4 h of the incubation. Cells were collected as above and stained with APC-conjugated anti-CD14 antibody in staining buffer at 4°C for 30 min. The cells were permeabilized in 500 μl 1X Perm/Wash Buffer at 4°C for 30 min, incubated in 100 μl 1X Perm/Wash Buffer containing FITC-conjugated anti-IL-6 antibody at 4°C for 30 min, and washed with 1X Perm/Wash Buffer before testing on FacsCalibur as above.
Total RNA from human PBMC and murine BMM at the specified time point was prepared using RNeasy Mini kit (Qiagen, Valencia, CA). After reverse transcription, 500 ng cDNA from each sample were analyzed by real-time PCR using the dual-labeled fluorogenic probe method on an ABI Prism 7300 real time PCR system (Applied Biosystems). The expression of human and murine MKP-1, beta-actin, TNF-α, IL-6, and human MKP-5 mRNA was determined. All primers were purchased from Applied Biosystems (Foster City, CA).
Whole cell extracts were prepared by incubating cells with RIPA Lysis Buffer with protease inhibitors on ice for 30 min, followed by centrifugation at 4°C for 10 min and collection of supernatants. Protein samples from vitamin D/LPS-treated PBMC and murine bone marrow cultures were resolved on Invitrogen 4-12% Bis-tris gel and transferred to PVDF membranes. The membranes were incubated in PBS containing specific antibodies, 5% dry milk, and 0.1% Tween 20 at 4°C overnight. Subsequently, membranes were washed in PBS/0.1% Tween 20, incubated for 1 h at room temperature with horseradish peroxidase (HRP)-labeled secondary antibodies, washed, incubated with chemiluminescent reagent and processed for immunodetection. Densitometry was used to evaluate the intensity of the bands.
PBMC and murine BMM were treated with 1,25(OH)2D3 for 24 h, followed by 10 ng/ml LPS stimulation for 24 h. Supernatants were collected, human IL-6 levels from PBMC were tested using Human IL-6 ELISA ready-set-go! Kit, and murine IL6 and TNF-α levels from BMM were tested using Mouse IL-6 ELISA ready-set-go! Kit and Mouse TNF alpha ELISA ready-set-go! Kit respectively. All the ELISA kits were purchased from eBioscience, Inc. (San Diego, CA).
VDR binding to VDRE and histone H4 acetylation at the human MKP-1 promoter were assessed using Magna ChIP A/G Chromatin Immunoprecipitation Kit following manufacturer's instructions. VDR binding to VDRE and histone H4 acetylation at the murine MKP-1 promoter were assessed by ChIP assay as previously described (22) with modifications. Briefly, 2×106 cells were used in each precipitation. After sonication, chromatin solution was pre-cleared with 50 μl Protein A/G PLUS-Agarose beads and 10 μg herring DNA at 4°C for 2 h, incubated with specific antibody or isotype control at 4°C overnight, followed by precipitation with 50 μl Protein A/G PLUS-Agarose beads at room temperature for 2 h. Precipitated chromatin complexes were removed from the beads through incubation at 65°C for 30 min with Elution Buffer (50 mM Tris pH 8.0, 1 mM EDTA, 1% SDS). Two-hundred μl of eluate was mixed with 10 μl 5 M NaCl, 0.5 μl RNase A (10 mg/ml, DNase-free) and incubated at 65°C overnight. Precipitated DNA was quantified by real time PCR using SYBR green (Applied Biosystems). Primers used to detect the potential VDRE in the human MKP-1 promoter were: 5′-AGCTGGGATTCTAATCCAGGCAGT-3′ (E4.7 forward), 5′-CTTTGGAAGGTGGAGTTCCTCTCA-3′ (E4.7 reverse); Primers used to detect the potential VDRE in the murine MKP-1 promoter were: 5′-ACCCTTGCTCTCTCCCAAGTTCAT-3′ (E33 forward), 5′-AGAGTGTACCCAACACGACCCAAT-3′ (E33 reverse); 5′-ACGAGGGCAGATGCCTTTAATCCT-3′ (E0.9 forward), 5′-TGCTGTGTAGCTCTGGCTAGTCTT-3′ (E0.9 reverse).
Results were expressed as the mean ± SEM. Statistical analysis was conducted using GraphPad Prism, version 5 (GraphPad Software, La Jolla, CA). The data were analyzed by the paired Student's t test, pairing by experiment. Before testing, paired difference distributions were examined for outliers, which can indicate violation to the normality assumption of the t test. No outliers were apparent. Tests were performed between specific treatments and LPS treatments or between vitamin D treatment and control. Unpaired t-test was used for comparison of responses between cells from wild type and MKP-1−/− mice. Differences were considered significant at p<0.05. A minimum of three independent experiments was conducted to allow for statistical comparisons.
In this study, we examined the role of vitamin D in the regulation of LPS responses. Human PBMC were pretreated with vitamin D for 24 h, followed by stimulation with 10 ng/ml of LPS. Both forms of the vitamin D, an active form, 1,25(OH)2D3, and 25(OH)D3 were tested. Monocytes/macrophages have previously been shown to be able to locally convert 25(OH)D3 into an active form (23). Vitamin D levels are normally measured by serum 25(OH)D3 levels; as this form of vitamin D is more stable, while the active form of vitamin D has a short half-life (5). In these experiments, we assessed the anti-inflammatory effects of 25(OH)D3 doses that are related to vitamin D deficiency (15 ng/ml) and vitamin D sufficiency (30 ng/ml – lower normal range, 50 ng/ml and 70 ng/ml – upper normal range for the serum vitamin D levels) (1, 23, 24). The binding of LPS to TLR4 on monocytes triggers immediate activation of MAP kinases, which together with activation of the canonical IKK pathway regulate NFκB activation, to induce proinflammatory cytokine production (25). We investigated whether the pretreatment of cells with vitamin D affects the activation of MAP kinases. The phosphorylation of three subfamilies of MAP kinases, ERK, JNK, and p38, was examined by flow cytometry. Human PBMC were pretreated with vitamin D for 24 h followed by 10 min of treatment with 10 ng/ml of LPS. After short-term stimulation with LPS, phosphorylation of p38 MAP kinase in CD14+ cells was induced. Monocytes cultured in media for 24h had high level of p-JNK, which was not changed after LPS stimulation for 10 min. No ERK phosphorylation was observed 10 min after LPS treatment in these cells. As expected LPS treatment did not activate CD3+ T cells.
As shown by flow cytometry (Fig. 1A) 6.5±1.2% CD14+ cells expressed phosphorylated p38 MAP kinase (p-p38) prior to LPS treatment, and 23.6±2.5% CD14+ cells expressed p-p38 after 10 min of LPS treatment (n=4, p<0.05). While after LPS stimulation a significant increase in the % of CD14+ cells that express p-p38 was observed, there was no change in p-p38 mean fluorescence intensity (MFI) (Fig. 1C). It was found that 15 ng/ml of 25(OH)D3, a concentration corresponding to the insufficient serum vitamin D levels in humans(24), did not suppress LPS-induced p38 phosphorylation (Fig. 1A); while significant inhibition of LPS-induced p38 phosphorylation was achieved with 30 ng/ml and higher of 25(OH)D3 (Fig. 1A). Maximum inhibition was achieved with 50 ng/ml of 25(OH)D3 [a mean inhibition of 78% (n=4, p<0.01)]. Similarly, a dose-dependent inhibition of LPS-induced p38 activation was observed in human monocytes when the cells were pretreated with active vitamin D (Fig. 1B, 1C). The maximum inhibitory effect was achieved when the cells were preincubated with 0.4 ng/ml (1 nM) 1,25(OH)2D3 (mean inhibition of 70% (n=4, p<0.01). Inhibition of LPS-induced p38 phosphorylation by vitamin D was confirmed by Western blot, as 10 nM 1,25(OH)2D3 significantly suppressed LPS-induced p38 phosphorylation by 75% in adherent fraction of the PBMC (n=4, p<0.01) (Fig. 1D, 1E). As confirmed by flow cytometry this adherent fraction of PBMC consisted of 85-90% CD14+ monocytes. Both flow cytometry and Western blot evaluations demonstrated that in vitamin D pretreated cells LPS-induced p-38 phosphorylation was inhibited to the level of p-p38 phosphorylation observed in cells cultured with media alone.
Upon LPS stimulation, monocytes produce pro-inflammatory cytokines, such as TNF-α and IL-6 (26). Persistent inflammatory responses can damage host tissues(27, 28). To examine whether changes in LPS-induced p38 activation in the presence of vitamin D influenced cytokine production, human PBMC were preincubated as above with either 1,25(OH)2D3 or 25(OH)D3 for 24 h followed by stimulation with 10 ng/ml of LPS for 24 h. LPS treatment significantly induced IL-6 mRNA production by the cells (p<0.05). When the cells were preincubated with 30 ng/ml and greater of 25(OH)D3, a significant inhibition of LPS-induced IL-6 mRNA expression was observed (p<0.01) (Fig. 2A). No inhibition of LPS-induced IL-6 expression was observed when the cells were cultured with 15 ng/ml of 25(OH)D3 (Fig. 2A). All doses of the active form of vitamin D significantly inhibited LPS-induced IL-6 mRNA expression (Fig. 2B). The degree of suppression of IL-6 mRNA by 30 ng/ml (70 nM) of 25(OH)D3 was comparable to the inhibition achieved with 0.04 ng/ml (0.1 nM) of the active form of vitamin D (Fig. 2A, 2B). Similar vitamin D effects were observed in LPS-induced TNF-α mRNA expression (Fig. 2C, 2D).
Upon stimulation with LPS the amounts of IL-6 protein in culture supernatants increased from a basal level of 330 ± 96 pg/ml to 1385 ± 277 pg/ml (p<0.05). When the cells were pretreated with 10 nM 1,25(OH)2D3 for 24 h, LPS-induced IL-6 production by the cells was significantly inhibited by a mean of 77% (n=4, p<0.01) (Fig. 2E). The inhibition of IL-6 production was more efficient with 10 nM 1,25(OH)2D3 as compared to 1 nM 1,25(OH)2D3 (p<0.05) (Fig. 2E). These data were confirmed by flow cytometry as the amount of IL-6-producing monocytes was significantly increased after the stimulation with LPS from basal 0.8 ± 0.4% to 29.7 ± 4.9% (n=4, p<0.01) (Fig. 2F, 2G). However, when the cells were pretreated with 10 nM 1,25(OH)2D3 for 24 h, the amount of IL-6-producing CD14+ cells induced by LPS was significantly inhibited by a mean of 67% (n=4, p<0.05) (Fig. 2F, 2G).
MKP-1 plays a critical role in switching off p38 signaling and cytokine production in monocytes/macrophages after the inflammatory stimuli (18). Since vitamin D pretreatment significantly inhibited LPS-induced p38 phosphorylation, we examined whether this process was mediated via MKP-1 or other phosphatases. Pretreatment of human PBMC with 10 nM 1,25(OH)2D3 for 24 h resulted in significant increases in MKP-1 mRNA (2.5±0.1 fold, p<0.05) (Fig. 3A) and protein (3.1±0.4 fold, p<0.05) (Fig. 3C, 3D) expressions by the adherent PBMC fraction, which consisted mainly of monocytes. The expression of MKP-5, another phosphatase that has been reported to dephosphorylate p38, was not changed in adherent PBMC fraction after 24h of culture with 1,25(OH)2D3 (Fig. 3B).
To examine the mechanism of MKP-1 upregulation by vitamin D, we used murine bone marrow-derived macrophage cultures. Similarly to human monocytes, when murine bone marrow derived macrophages from wild type mice (C57BL6×129) were preincubated with 10 nM 1,25(OH)2D3, a significant increase in MKP-1 mRNA expression was observed. The maximum increase in MKP-1 mRNA expression was found after 6 h of treatment with vitamin D (2.6 ± 0.2 fold increase, n=3, p<0.01) (Fig. 3E).
We examined the presence of potential VDRE sites in the human and murine MKP-1 promoter. A VDRE (labeled E4.7) sequence AGTTCAAATCATTCA was located at −4708 to −4694 from the transcriptional start site of human MKP-1 gene. A VDRE (labeled E33) sequence AGTTCATGGCCTTCA was located at −33410 to −33396 from the transcriptional start site of murine MKP-1 gene. Several additional half VDRE sites were also found at murine MKP-1 promoter, with the closest one with a sequence AGTTCA (labeled E0.9) located at −930 to −925 from the transcriptional start site (the scheme of the potential VDR binding sites in the human and murine MKP-1 promoter is shown in Fig. 4A). VDR binding and histone H4 acetylation at the E4.7, E33 and E0.9 sites of the human and murine MKP-1 promoters were tested by ChIP assays. We found that treatment of adherent PBMC with 10 nM 1,25(OH)2D3 for 24 h enhanced VDR binding and histone H4 acetylation by 2.4±0.5 fold (p<0.05) and 3.0±0.8 (p<0.05) fold, respectively, at the E4.7 site of the human MKP-1 promoter (Fig. 4B, 4C). We found that treatment of murine bone marrow-derived macrophages with 10 nM 1,25(OH)2D3 for 6 h enhanced VDR binding and histone H4 acetylation by 3.7±0.4 fold (p<0.05) and 6.26±0.04 (p<0.05) fold, respectively, at the E33 site of the murine MKP-1 promoter (Fig. 4D, 4E). No increase in VDR binding and only a slight yet significant (p<0.01) increase in histone H4 acetylation were observed at the E0.9 site (Fig. 4D, 4E). These data suggest that vitamin D bound VDR interacts with the VDRE upstream of MKP-1 gene, thus, potentially influencing MKP-1 transcription.
Next, we tested the ability of vitamin D to inhibit LPS-induced p38 phosphorylation in macrophages derived from bone marrow of the wild type and MKP-1−/− mice (29). Ten minutes of treatment with LPS resulted in a significant increase in p38 phosphorylation by 4.8±0.2 fold (n=3, p<0.05) and 8.2±0.2 fold (n=3, p<0.01) in wild type and MKP-1−/− macrophages, respectively (Fig. 5A, 5B). As shown by Western blot, pretreatment with 10 nM 1,25(OH)2D3 significantly inhibited LPS-induced p38 MAP kinase activation by a mean of 93% (n=3, p<0.05) in bone marrow-derived macrophage from wild type mice (Fig. 5B); but this inhibition was abolished in bone marrow-derived macrophage from MKP1−/− mice (Fig. 5B).
To examine whether inhibition of LPS-induced p38 activation by vitamin D in mouse macrophages influenced cytokine production, macrophages derived from the bone marrow of wild type and MKP-1−/− mice were preincubated with either 10 nM 1,25(OH)2D3 or 75 nM (30ng/ml) 25(OH)D3 for 24 h followed by stimulation with 10 ng/ml of LPS for 24 h. Significantly higher levels of IL-6 and TNF-α were observed in culture supernatants of the LPS-treated BMM from MKP-1 −/− mice as compared to wild type mice (p<0.01 and p<0.05 respectively). The amounts of LPS-induced IL-6 protein in culture supernatants were inhibited 67% and 61% by 1,25(OH)2D3 and 25(OH)D3 respectively in wild type macrophages. LPS-induced IL-6 production was inhibited only to 18% and 33%, respectively in MKP-1−/− macrophages (Fig. 6A). Similarly we observed that 1,25(OH)2D3 and 25(OH)D3 inhibited LPS-induced TNF-α protein in culture supernatants by 48% and 57%, respectively in wild type macrophages, while the inhibition of LPS-induced production of these cytokines was only 16% and 29%, respectively, in MKP-1−/− macrophages (Fig. 6B).
In this study, we examined the effects of vitamin D at physiologic concentrations on LPS-stimulated inflammatory responses in monocytes/macrophages. We found that both 1,25(OH)2D3, an active form of vitamin D, and 25(OH)D3, that requires conversion by monocytes into an active form(23), dose-dependently inhibited p38 phosphorylation and cytokines, IL-6 and TNF-α, production in LPS-stimulated human monocytes. Upon vitamin D treatment, the expression of MKP-1 phosphatase mRNA and protein was significantly upregulated in both human monocytes and murine bone marrow-derived macrophages. We demonstrated that vitamin D treatment increased VDR binding to a putative VDRE both in human and murine MKP-1 promoter and enhanced histone H4 acetylation near this VDRE site. Utilizing macrophages derived from MKP-1−/− mice, we further demonstrated that vitamin D was no longer able to suppress LPS-induced p38 activation followed by the compromised ability to inhibit LPS-induced IL-6 and TNF-α production in the absence of MKP-1. Our current study therefore identified the upregulation of MKP-1 by physiologic concentrations of vitamin D as a novel pathway by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages.
In recent years, vitamin D deficiency in humans has received significant attention (1, 24). According to the recent brief of the National Center for the Health Statistics in 2001-2006, 32% of the US population had serum 25(OH)D3 levels <20ng/ml; 8% of the US population had serum 25(OH)D3 levels <12ng/ml(30). Aside from its classical role as a modulator of calcium metabolism and bone health, vitamin D has been shown to have potent anti-inflammatory effects and consequently has been considered for adjunctive therapy for numerous chronic diseases including asthma, arthritis and prostate cancer (4, 31, 32). A variety of pro- and anti-inflammatory effects for the vitamin D had been reported (33, 34). It has been shown that vitamin D can directly induce the production of the important antimicrobial peptides, cathelicidin and human beta defensin 4, by human monocytes/macrophages and epithelial cells (23, 35). Anti-proliferative and proapoptotic activity has been shown in vitamin D-treated tumor cells due to the induction of cyclin-dependent kinase inhibitors p21Waf/Cip1 and p27Kip1, inhibition of c-Myc and anti-apoptotic Bcl-2 (32). Vitamin D had been demonstrated to suppress prostaglandin pathways in the tumor cell lines via inhibition of COX-2 production and stimulation of 15-PGDH production by the cells (32). Vitamin D has also been shown to interfere with NFκB activation and signaling by increasing the expression of IκBα in the cells, thus interfering with the nuclear translocation of the activated NFκB subunits (36). It has also been reported that vitamin D can influence dendritic cells maturation and function (37). Several studies have highlighted the capacity of vitamin D to modulate the population and function of FoxP3+ and IL-10-producing T-regulatory cells (37).
The current study found that human monocytes are capable of responding to treatment with two different forms of vitamin D: 1,25(OH)2D3 and 25(OH)D3. 25(OH)D3 is converted into a functionally active form, 1,25(OH)2D3, by the enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27b1); a process that primarily occurs in kidneys (38, 39). However, it has been shown that monocytes, macrophages, and dendritic cells also express CYP27b1 (35, 40). Therefore 1,25(OH)2D3 can be produced locally and exert immunomodulatory effects (41). We demonstrated that 15 ng/ml of the 25(OH)D3 (a concentration amount considered in this study vitamin D deficiency (24)) did not suppress LPS-induced IL-6 and TNF-α production in human monocytes. We found that 25(OH)D3 at 30 ng/ml and higher, i.e. levels considered vitamin D sufficient in humans, significantly inhibited IL-6 and TNF-α production induced by LPS. Furthermore, the degree of suppression of IL-6 and TNF-α production by 30 ng/ml of 25(OH)D3 was comparable to the effects achieved by 0.04 ng/ml (0.1 nM) of the active form of the vitamin D. These data suggest that human monocytes have the ability to convert 25(OH)D3 to an active form. Further, our study demonstrates that serum concentrations of 25(OH)D3 does matter for the optimal anti-inflammatory response of human monocytes, since the amount of the available circulating 25(OH)D3 influences local tissue concentrations of the active vitamin D (23, 35). These data support the idea that in order to achieve optimal anti-inflammatory effects by vitamin D it is important to maintain serum vitamin D levels above 30 ng/ml in the physiologic range (23, 42).
Dual-specificity phosphatases are a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphothreonine residues within the same substrate. MKP-1 is the best-studied member of this family and is characterized for its role in the regulation of MAP kinase signaling cascades (43, 44). In this study, we demonstrated that vitamin D can upregulate MKP-1 expression by monocytes/macrophages and utilize this pathway for the inhibition of the LPS-induced p38 phosphorylation. In this study we focused on the early stages of monocyte activation by LPS to assess the contribution of vitamin D-regulated phosphatases on LPS-induced MAPK activation. We did not extend this assessment to 30 min post LPS stimulation of avoid the effects of LPS-induced MKP-1 (18). Another member of the dual specificity phosphatase family, MKP-5, was recently shown to be induced by vitamin D treatment in normal prostate epithelial cells, resulting in inhibition of p38 activation in these cells (45). Vitamin D did not alter MKP-5 expression in human monocytes in our study.
Recently it has been reported that vitamin D treatment down-regulates TLR2, TLR4 expression by human monocytes and up-regulates CD14 expression by these cells (46). The authors concluded that down-regulation of TLR expression can substantially reduce LPS and LTA-mediated MAP kinase activation. MKP-1 expression under these conditions was not studied. Importantly, in this study 100nM of the active vitamin D was used. In our study, 10 nM of the active vitamin D was the highest dose used and we did not observe changes in TLR4 protein expression by human monocytes in response to 24 h of pretreatment with 10 nM of active form of the vitamin D (data not shown).
Vitamin D has been reported to regulate a variety of human and mouse genes through VDR-mediated VDRE binding (47, 48). Although VDREs have been well studied in genes like CYP24A1 (48, 49), no VDRE has been discovered in MKP-1 gene to date. In this study, we identified a putative VDRE site approximately 4.7 kb upstream of transcriptional start site in the human MKP-1 promoter and a putative VDRE site approximately 33 kb upstream of transcriptional start site in the distal murine MKP-1 promoter. We confirmed VDR binding to these two sites using ChIP assays. The far upstream location of the putative VDRE in murine MKP-1 promoter is not surprising as genome-wide mapping of VDREs have indicated that VDREs are predominantly located in introns and intergenic intervals (7). Following the binding of VDR to VDRE, co-activators, co-repressors or mediator proteins may be recruited to the site depending on the effects of vitamin D on a specific gene transcription. Since vitamin D treatment significantly induces MKP-1 mRNA expression, it is likely that VDR binding to the MKP-1 promoter induces recruitment of the co-activators and initiates histone acetylation, leading to transcriptional activation (10). Our ChIP assays confirmed significantly enhanced histone H4 acetylation near the putative VDRE sites (E4.7 and E33) in human and in the distal murine MKP-1 promoter, respectively, after vitamin D treatment.
Selective inhibitors for MKP-1 are currently unavailable and inhibition of MKP-1 expression is difficult to accomplish via siRNA in primary monocytes/macrophages. For these reasons, we explored the role of MKP-1 in vitamin D-mediated anti-inflammatory effects in monocytes by utilizing bone marrow-derived macrophages from MKP-1−/− mice and wild type mice. Our data suggests that vitamin D regulation of MKP-1 is one of the essential pathways that inhibits LPS-induced cytokine production by monocytes/macrophages. We demonstrated that vitamin D-mediated suppression of the LPS-induced p38 phosphorylation was abolished and the inhibition of LPS-induced production of IL6 and TNF-α was significantly reduced in macrophages derived from MKP-1−/− mice. The fact that MKP-1 knockout did not completely abolish vitamin D inhibition effect on LPS-induced cytokine production indicates that vitamin D engages additional pathways aside from MKP-1 to regulate LPS-induced proinflammatory cytokine production. This may include but not be limited to transrepression of NFkB-mediated responses by VDR as reported before (33, 36, 46). It was recently reported that LPS controls MKP-1 in activated monocytes via upregulation of the miR101 (50). We did not find changes in miR101 expression in vitamin D pretreated human monocytes (unpublished observation).
In summary, our study provides several novel discoveries: first, physiologic levels of vitamin D can modulate inflammatory activities, as 30-50 ng/ml of the 25(OH)D3 is sufficient to inhibit LPS-induced p38 activation and cytokine production in human monocytes (Fig. 1, ,2).2). Secondly, the study identified the upregulation of MKP-1 by vitamin D as a novel mechanism by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages. Finally, a putative VDR-binding site was identified in the distal murine MKP-1 promoter and human MKP-1 promoter. Our current studies suggest that patients with chronic inflammatory diseases that are vitamin D deficient (<20ng/ml) may benefit from oral supplementation of vitamin D to get their serum vitamin D level above 30 ng/ml.
We thank Maureen Sandoval and Shih-Yun Lyman for their help in preparation of this manuscript.
The authors thank Bristol-Myers Squibb that developed MKP-1−/− mice.
This work was supported in part by NIH grants AI070140, HL68628, HL37260, AI57798, and AI68956. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute or the National Institutes of Health.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


text:
Want to get notified whenever we write about any of these organizations ?
Next time we write about any of these organizations, we'll email you a link to the story. You may edit your settings or unsubscribe at any time.Sign-up for Alerts
Organizations in this Story
9th Judicial Circuit Court of Florida - Orange County
425 North Orange Avenue
Orlando, FL - 32801
Florida Department of Highway Safety and Motor Vehicles
2900 Apalachee Parkway
Tallahassee, FL - 32399


text:
THE WORLD; Peace on Irish Horizon Doesn't Spell Prosperity
By RICHARD W. STEVENSON
Published: September 4, 1994
BELFAST, Northern Ireland— FOR all the jubilation in the nationalist strongholds of West Belfast, for all the waving of Irish flags and the taunts of "You're going home, Brit" by young Catholics to British foot soldiers, no one familiar with the last 25 tragic years in Northern Ireland believed that the province's future had been remotely settled last week.
There was a recognition on all sides that the Irish Republican Army's decision to call off its violent campaign to drive Britain from Northern Ireland was just one step on a tortuous journey toward a lasting settlement, and that even a permanent defusing of the bombs would address only some of the province's deep-rooted problems. And as it became dimly imaginable that there could be some sort of phased British withdrawal or a move toward unification of the predominantly Protestant North with the overwhelmingly Catholic Republic of Ireland, the more pragmatic analysts of "the troubles" posed a tough question: Who is going to pay for peace?
To blow away the smoke from 25 years of sectarian violence is to expose a society that, while not lacking a middle class, is plagued by poverty, unemployment and job discrimination, primarily against Catholics. Worldwide competition was destroying key industries like shipbuilding, textiles and agriculture even before the festering animosity between nationalist Catholics and loyalist Protestants exploded into a numbing cycle of killing. The province's reputation as a war zone drove away British companies and foreign investors.
To the extent that Northern Ireland's economy has remained afloat for the last 25 years, it has been through spending by the British Government. Nearly 40 percent of all jobs in Northern Ireland are with some arm of the Government or are paid for by it, compared to 25 percent in Britain as a whole. The Government has spent heavily on projects ranging from public housing to redeveloping Belfast's waterfront. Altogether, the British Government spends over $6 billion a year more on Northern Ireland than it receives in taxes from the province.
Ireland, itself one of Europe's poorest countries, could never carry that burden were the peace process to ultimately yield an agreement on unification, economists said. Britain's current subsidy of Northern Ireland equals fully 16 percent of Ireland's economic output, a level of aid Dublin could never sustain.
Economists said that if West Germany was unable to finance unification with East Germany without creating economic instability throughout Europe, then Ireland could hardly be expected to take on Northern Ireland unless the province proved willing to accept a sharply lower standard of living or Britain were willing to continue footing the bill. Those are tradeoffs not yet raised publicly by either London or Dublin. "Economically, unification is completely out of the question," said Graham Gudgin, the director of the Northern Ireland Economic Research Council, a nonpartisan research group. "If people have even confronted the economics of it, they are not treating it seriously. People in the South are going through the motions of rhetoric, not reality."
Irish nationalists in the North dismiss such concerns, saying that there would be years, if not decades, to work out a solution on unification. In the meantime, they point to the willingness of the United States and the European Union to increase economic aid both to Ireland and Northern Ireland to nurture the peace process. The Clinton Administration last week was discussing tripling its $20 million-a-year contribution to the International Fund for Ireland, which promotes economic development in both North and South. New York City's Comptroller, Alan Hevesi, proposed a bond issue that could be offered to pension funds and other investors interested in channeling money into job-creating ventures. Unemployment Is Rampant
But any amount generated by foreign aid would be only a small fraction of what Britain has felt compelled to spend; $60 million a year in American aid would be 1 percent of the net annual British expenditure. And there is little question that to avoid unrest and alienation, social welfare spending would have to remain high.
Protestants are generally better off, and dominate the middle class. For Catholics, housing, job opportunities and educational standards have all improved in the last two decades. But in the worst-hit neighborhoods of West Belfast, which are not incidentally the breeding ground of extremists on both sides, unemployment among Protestant as well as Catholic men runs as high as 60 percent, with male unemployment in Northern Ireland as a whole running at 17.5 percent.
Rates of long-term illness among both adults and children in the inner cities are significantly higher than in greater Belfast. Other indicators of economic progress, such as rates of home and car ownership, are well below those for Britain as a whole. "The areas worst hit by the troubles are also those worst affected by social problems," said Brendan Mackin, the director of the Belfast Unemployed Resource Center, a counseling and job-training organization. "The cease-fire will remove the fear for the people of those communities and their children. But it won't decrease the number of people coming in here who need help."
Peace could cause even more economic dislocation, at least in the short run, as Northern Ireland shifts from what is in many ways a wartime economy. Economists say the province could lose 10,000 to 25,000 jobs as the police force shrinks, as the need for security guards and prison workers diminishes and as spending by the military declines. The loss of those relatively high-paying jobs, held mostly by men in and around cities and large towns, will be offset by a growth in jobs related to tourism, which officials expect to flourish if the peace holds, and from increased investment by British and foreign companies. But Mr. Gudgin said many of those new jobs, especially in tourism, would be low-paid.
There is also the question of dismantling the criminal enterprises run by the I.R.A. and by Protestant paramilitaries, including protection rackets, drug smuggling and money laundering. Those activities are part of the economic fabric of areas like West Belfast.
Among those who have lived with "the troubles" there is little optimism that their lives will change soon. Brian McGlone, a 30-year-old Catholic from West Belfast, has worked only one year since he left school 14 years ago. He thinks that, even if peace takes root, it will take two generations before there is any real opportunity for the poor. "Peace would be nice," he said. "But we're just trying to survive and find a job."
Photos: A woman goes about her business as police tend to the results of a riot by loyalist youths in Portadown, Northern Ireland, in 1986. (Donna DeCesare/Impact Visuals); A British army soldier and a small boy together last week in a Catholic area of Belfast. (Associated Press)


text:
At least you're honest….
I was thinking he looks like the younger Boston Marathon bomber brother. Either way, neither is a compliment.
Response to Two Female Teachers In Louisiana Arrested For "Inappropriate Sexual Contact" With A 16-Year-Old Student:
These are 2 decent looking women, which makes me wonder how hot that 16 year old was that they'd risk their careers. Is he like a teenage Chris Hemsworth?
Agreed. They're also missing The Pour House.
That's a pretty straightforward headline for Buzzfeed…..
Chris Hemsworth's shirtless scenes in both Thor movies were so obviously forced and out of place. I'm not complaining, but I think the men in comic book movies are more sexualized….mostly because there are more of them than woman in comic book movies to begin with.
Was this 20-something yr old drugged? Because if not, I don't understand how a guy in his 20's can't fight off a pudgy Bryan Singer. The guy is pushing 50 and looks like a total sissy.
But how will I determine the douchebags and sluts from regular people?
I only have 3 thoughts when watching this show: 1) When is Justin Theroux going to take his shirt off? 2) Why the fuck am I watching this show? 3) Oh, right. Justin Theroux shirtless.
Looks like its all balls and not enough shaft. Disappointing.
As an 18 yr old freshmen guy, my biggest concern was how to conceal my morning wood from my roommate EVERY MORNING.
Response to John Lithgow And Alfred Molina Are The Cutest, Saddest Couple In One Of The Year's Best Films:
Great actors….but I can't stop picturing them having sex with each other. I'll wait until this movie is rebooted starring Michael Fassbender and Hugh Jackman.
Didn't see the movie, but the trailer looked awful. Had they thrown in a shot of Brenton Thwaites shirtless (I know he's suppose to be 16, but hey, I'm not going to be left feeling like a pedo when they put a hot 25 yr old actor in the role of a 16 yr old), I would have at least considered it. I sat through like 15 minutes of a terrible Lifetime movie sequel to Island of the Blue Lagoon where he was shirtless like 80% of the time. That's 15 minutes I won't be spending on The Giver.
Thought the doc was kinda cute until all the God talk… So, God wanted you to get ebola?
Response to After Its Receipt Went Viral On Facebook, A Restaurant Had To End Its 15% "Public Prayer" Discount:
I'm upset she didn't defend her policy and caved to all these idiots. Grow a pair, lady! I guess if she weren't so busy praying, she could have gone on this new thing called The Internet and learned about her rights as a business owner.
Joss Whedon, when will you stop being perfect?
I'm a guy and I don't sit with my legs open. Just seems like an invitation for people to ogle my crotch and/or grab my dick. And the reason I feel that way is because I AM one of those guys that will stare at your junk if you're hot. So just keep that in mind the next time you're wide-sitting, fellas.
SHARE THIS PAGE View Viral Dashboard ›


text:
Who made your clothes?April 25, 2014
|Korres lipbalm and Dr. Hauschka blush
|Oh No Rachio Plate
Sorry for the brief post and the desk acting as my model today, I just got back to London and I'm studying hard for exams coming up in a couple of weeks. I thought of writing a piece about ethical fashion and whether or not it's only for the rich, but on second thought I might leave that bitter argument to the Guardian columnists.
6 comments
Your directory is such a great tool. Also, I'm in love with your still life photography.ReplyDelete
Beautiful photos as usual! and really appreciate your attention to and concern for ethical fashion. you lovely lady, you. xoReplyDelete
I just found your blog through October Rebel and LOVE it! Its so nice to see more people paying attention to ethical fashion. You have a new follower :)ReplyDelete
xo Hannah
Short but sweet! Good luck with your exams - hope you kick some academic ass :)ReplyDelete
what a beautiful details <3ReplyDelete
Hello, thanks for taking the time to write a comment. I don't always reply (because I'm too busy hiding under a rock) but I read and appreciate every single one!


text:
Already a print subscriber? Get Access Already a digital subscriber? Log In
Never Miss a Story Subscribe Today
Warrick Chooses Milwaukee
0 CommentsThe 76ers got the call a little before 2 p.m. They fell short in their attempt to add unrestricted free agent Hakim Warrick to their roster... Read more
Miller doesn't care about the critics
0 CommentsFormer Sixers guard Andre Miller says he is out to prove the critics wrong — again. This time, his targets are the critics who are underwhelmed... Read more
Young, Igoudala play well at Team USA camp
0 CommentsSixers forward Thaddeus Young scored 12 points in 19 minutes to help the Blue to a 100-81 victory over the White in a Team USA intrasquad exhibition... Read more
Miller: Deal Is Done
0 CommentsAndre Miller, the 76ers' unrestricted free agent, officially signed with the Portland Trail Blazers just before 7 tonight. Miller had agreed... Read more
Miller signs with Portland
0 CommentsAndre Miller has agreed to terms with the Portland Trail Blazers, agent Andy Miller has confirmed to the Daily News. The deal is believed... Read more
Ratliff Lands With The Spurs
0 CommentsTheo Ratliff has gone from backing up Samuel Dalembert to backing up Tim Duncan. Ratliff, a 76ers' unrestricted free agent, has agreed to... Read more
Not Necessarily A Big Help
0 CommentsWhat does it say when the 76ers need a couple of big men to help fill out their roster, and the best names could turn out to be Primoz Brezec... Read more
Holiday, Watson And Other Stuff
0 CommentsWhile waiting for a final resolution to the ongoing saga of Andre Miller and the 76ers, here is a handful of other stuff concerning the team... Read more
Sixers sign Holiday
0 CommentsThe Sixers have signed first-round draft pick Jrue Holiday, selected 17th overall last month. Contract terms were not announced, but first-rounders... Read more
The Search For Backcourt Help
0 CommentsThe 76ers have been contacting a variety of free agent guards to help fill out the roster for the coming season. That list, according to a... Read more
This is the Sixerville blog.


text:
Chicago, Illinois (PressExposure) June 05, 2009 -- Webgreeter.com (also known as live greeter) is a Chicago based LLC which provides live-chat support software and services to web businesses all over the world and has been doing so for the last several years. Recently, the Marketing manager for the company, Howard White, announced that the company was involved with several deals with partner firms for the barter trade of services offered.
As a recent example; Blackwood___ is a recently introduced partner company which offers SEO (search engine optimization) services to firms all over the world. In a recent agreement with webgreeter, a contract has been signed between the two firms which would involve Blackwood providing SEO services for Webgreeter's business website in exchange for the webgreeter service, which would feature webgreeter's operators providing live-chat based online customer sales and support on the blackwood business website. According to Howard White, "We have a history of long term and mutually beneficial partnerships with firms from all over the world from North America to the UAE. We are now welcoming barter trade with businesses which could provide us with any of a range of services in exchange for Live-chat services". Interest in Live-chat has "skyrocketed in recent times" with many firms all over the world viewing live-chat as the most efficient and cost effective way to provide online customer support.
Allen Anderson - WebGreeter.com
Web greeter.com is a chat based customer service and support service which provides websites with live web greeters (also called WebGreeter) who are available live, in real time, on websites. These live greeters greet visitors on a website to provide customer care and sales support.


text:
In homes today, there is a place undergoing a radical transformation of uncompromising style - the kitchen. This is the second most occupied place in modern dwellings. This Hansgrohe kitchen faucet offers remarkable functionality with individual personality and style. Innovative features such as the M2 velvety smooth ceramic cartridge valve. The modern design coordinates flawlessly with any kitchen decor. The solid brass construction is finished with a steel optik finish.
- Solid brass construction for lasting durability
- Single-handle faucet design for quick and easy water control with a single lever
- Spout swivels 150°s for full sink access
- Ergonomic pull-out with full and needle sprays
- Locking spray diverter with toggle
- Certified by the ADA to allow for universal use
- Can be installed in a 3-hole configuration if optional, #14019001, is installed
- How To Install a Single Handle Kitchen Faucet
- Not available for sale in California


text:
+1 714 774 8111
1734 South Harbor Boulevard Anaheim 92802 USA
Location Located directly across the street from Disneyland Park and Disney's California Adventure Park main entrance, this hotel is the perfect place for family holidays. Rather than waiting on a shuttle, guests can simply walk across the street! It is also located just one block from the Anaheim Convention Center, which makes business meetings, conferences and special events simple. Los Angeles International Airport is approximately 45 km from the hotel. Facilities This hotel was built in 1989. Travellers are welcomed at the establishment, which has a total of 200 rooms. At the accommodation, guests are welcomed at the reception area with 24-hour reception and a 24-hour check-in/check-out service. Services and facilities at the hotel include a dining area, a laundry service and a coin-operated laundry. Shopping facilities are also available. In addition, a shuttle service is offered. Rooms Each of the rooms is appointed with air conditioning, central heating and a bathroom. A double bed ensures a good night's sleep. All rooms feature a fridge, a tea/coffee station, a TV and a radio. Amenities in the bathrooms include a shower. Sports/Entertainment The hotel offers attractions including sport and entertainment opportunities. The establishment features an outdoor pool and a children's pool. The hot tub is the perfect place to relax. Payment All major credit cards, including American Express, VISA, Diners Club and MasterCard, are accepted for payment.


text:
This content is selected and controlled by BootsWebMD's editorial staff and is supported by Dettol.
Health quiz
What's your cleaning style?
Learn how your cleaning style may affect your health.
Trust Dettol for clean and protected home
- Find the germy places in your home
- Kill 99.9% bacteria and viruses with Dettol
- Protect your family from food-borne illness
From our sponsor
Content under this heading is from or created on behalf of the named sponsor. This content is not subject to the Boots WebMD Editorial Policy and is not reviewed by the Boots WebMD Editorial department for accuracy, objectivity, or balance.
Cleaning and organising for parents
With children comes mess! See tips for keeping your home and family clean and healthy.


text:
Forgot your password? Enter the email address you signed up with and we will send you a link to create a new password.
Your password reset has been submitted to the address provided.
Standard character mark
Pharmaceutical and medicinal preparations for the treatment of bacterial infections and genetic disorders
Business in Mumbai, IN


text:
Fantasy Forecaster last updated Sunday, May 31 at 10:21 p.m. ET.
On tap: June is here, and with it comes a busy week in the National League. Ten of the 16 NL teams play a full seven games, and four of those teams (Astros, Cardinals, Dodgers and Marlins) will play entirely at home.
But that's not Week 9's most compelling story: That honor belongs to Randy Johnson, who goes for his 300th career win Wednesday at Washington. Of course, the Nationals hit a career-high three home runs against him in San Francisco on May 11, so it'll be interesting to see whether he'll achieve the milestone in his first try. No matter your opinion on the "Big Unit," this is history, and history you should cherish at that, as it might be some time before we see another 300-game winner. Jamie Moyer is next closest among active players with 249 wins, but he's 46 years old. Andy Pettitte (219) has the most wins of any pitcher younger than 40. (He's 37.) And of the under-30 crowd, CC Sabathia is your active leader in wins (121, 28 years old).
Quick click by section, if you're seeking advice in a specific area:
Team advantages | Weather report | Load up: Hitters
Sleeper hitters | Load up: Stolen bases | Load up: Pitchers
Projected starters | Two-start rankings | One-start bargains
Team advantages
The chart below lists each of the 30 MLB teams' number of games scheduled ("Gm"), home games ("Hm"), games versus right- and left-handed pitchers ("vs. RHP" and "vs. LHP") and games at either hitter- or pitcher-friendly ballparks.
Note: Some teams' totals versus right- and left-handed pitchers exclude games against teams with unclear starters. They include: White Sox (Tuesday, OAK), Blue Jays (Saturday, KC), Reds (Tuesday, @STL), Rockies (Sunday, @STL) and Giants (Sunday, @FLA).
Weather report
June tends to present the Northeast with the most trouble in the weather department; since 2001, Baltimore, New York, Philadelphia and Pittsburgh are the only cities to have seen more than 4 percent of their scheduled games postponed, suspended or shortened in that month. (New York is tops, with 6.5 percent between the two teams.) Sure enough, the Yankees are the greatest concern for postponements in Week 9, with their series against the Rangers seeing increasing chances of precipitation Tuesday through Thursday (60 percent chance in the series finale). Chicago, Florida, Pittsburgh, St. Louis and Washington are also cities to watch for bad weather in Week 9.
Weatherproof games: Rockies at Astros (4, Mon-Thu); Pirates at Astros (3, Fri-Sun); Angels at Blue Jays (3, Tue-Thu); Royals at Blue Jays (3, Fri-Sun); Orioles at Mariners (3, Mon-Wed); Twins at Mariners (3, Fri-Sun); Royals at Rays (3, Tue-Thu); Indians at Twins (3, Tue-Thu)
Load up: Hitters
The teams listed below have the most favorable overall hitting matchups, accounting for recent performance, strength of opponents and ballpark factors.
Dodgers (ARI-3, PHI-4): Manny who? Just because Manny Ramirez is on the sidelines doesn't mean the Dodgers can't score runs; they're just finding different ways to do it in the wake of his suspension. Though their home-run production is down -- from 0.83 per game through May 6 to 0.50 per game since -- they're actually scoring more runs per contest since Manny's suspension (5.9) than before (5.6). How are they doing it? Their batting average is up, from .283 to .302, as is their stolen-base production (0.69 per game to 1.05) and number of sacrifices (from 7 to 12), all signs that "small ball" has become more of the Dodgers' game plan sans Manny. Most impressively, the team has done all this while facing not-too-shabby pitching staffs -- Giants, Phillies, Marlins, Mets and Angels -- so I wouldn't worry that they'll go dormant battling the Arizona and Philadelphia staffs, which have both vastly underperformed this year.
Yankees (@CLE-1, TEX-3, TB-3): Anytime I grant the thumbs-up to the Yankees' offense in a heavy home week, I feel obligated to recite their new ballpark's statistics. So here are the per-game numbers at the new Yankee Stadium from the month of May: 10.7 runs, 19.1 hits, 3.7 home runs (in 16 games). That means the park seems to be getting even more homer-friendly as the season wears on, which is great news when you're an offense set to face two pitching staffs (Rangers and Rays) that rank in the top 10 in baseball in home runs allowed. Besides, the Yankees just got done slaughtering the Rangers' pitching staff in Texas, totaling 23 runs on 47 hits, including five home runs, in three games May 25-27.
White Sox (OAK-4, CLE-3): OK, so ask yourself, do you really think the White Sox are going to remain buried down toward the bottom of the majors in terms of runs per game and team OPS? C'mon, this team ranked in the top 5 in both of those categories and home runs at home in 2008, and through 22 home games in 2009 it has an unsightly .243 batting average on balls in play, worst in the majors and 40 points beneath the team's 2008 number in the category. In addition to Oakland's inexperience and Cleveland's pathetic team pitching performance, the A's will need to dig up a Tuesday spot starter because of their recent doubleheader, while the Indians won't throw Cliff Lee in any of the three games at "The Cell." That definitely works in the White Sox's favor.
Astros (COL-4, PIT-3): The Pirates' staff got off to a hot start, but all good things must come to an end sometime, right? Pittsburgh has lost 19 of its past 29 games while posting a 5.12 ERA and 1.47 WHIP. Colorado, meanwhile, has had pitching problems for much of the year, capped by a recent stretch in which they've gone 5-10 with a 5.95 ERA and 1.62 WHIP. Carlos Lee, Hunter Pence and Miguel Tejada are off to torrid starts at Minute Maid Park; they've combined to bat .355 with 14 home runs and a .997 OPS in 72 games there. Even Geoff Blum is a .297 hitter there through 23 home games.
Tristan's sleeper hitters
Willy Aybar, 3B, Rays: .327 BA, .900 OPS versus right-handers in 2009; .344 BA, .944 OPS in 20 games in May
Kosuke Fukudome, OF, Cubs: .315 BA, .946 OPS versus right-handers in 2009; .343 BA, 1.016 OPS in 21 road games in 2009
Todd Helton, 1B, Rockies: .316 BA, .968 OPS versus right-handers in 2009; .364 BA, 1.126 OPS in 27 career games at Minute Maid Park
Jorge Posada, C, Yankees: .371 BA, 1.221 OPS in 12 home games in 2009; .462 BA, 1.210 OPS in 29 plate appearances versus left-handers in 2009
Nolan Reimold, OF, Orioles: .299 BA, 1.010 OPS versus left-handers in his minor league career; .295 BA, 5 HRs, 10 RBIs in his past 12 games
Skip Schumaker, 2B/OF, Cardinals: .316 BA, .813 OPS in 24 home games in 2009; .313 BA, .819 OPS versus right-handers in 2009
Jason Varitek, C, Red Sox: .309 BA, .944 OPS in 18 games at Comerica Park 2003-08; .310 BA, 1.244 OPS versus left-handers in 2009
Ben Zobrist, SS/OF, Rays: 1 HR per 13.1 ABs, .930 OPS versus right-handers in 2008-09; .314 BA, 1.092 OPS in 25 games in May
Load up: Stolen bases
Favorable matchups listed below are selected based upon opponents' catchers allowing a high rate of steals attempts and/or having low caught-stealing percentages.
Athletics (@CHW-4, BAL-3): Though new Orioles backstop Matt Wieters represents a considerable improvement over Gregg Zaun in this department -- Wieters has gunned down 45 of 126 opposing baserunners (35.7 percent) in his minor league career -- chances are, teams are going to test him early in his big-league career in order to build a scouting report on him. For one thing, he's inexperienced, and inexperience favors his opponents. But that's not why you should exploit Oakland's matchups; you should exploit them because Chicago's A.J. Pierzynski has a reputation as one of the game's worst at gunning down opposing runners. The Athletics pick and choose their times to run, and their speedsters have limited fantasy appeal, but those owners in AL-only leagues can take a look at Rajai Davis (five steals), Adam Kennedy (3) and Ryan Sweeney (3).
Giants (@WAS-3, @FLA-3): This is one of the speediest teams in the game, with 34 stolen bases, eighth-most in the majors. Credit Emmanuel Burriss and Randy Winn with most of those; they have a combined 19. Better yet, those two have been super-comfortable in road games this season, combining to bat .325 in 22 games. But the Giants do get contributions from others; slumping Fred Lewis can be a 30-steal candidate at his best, and Edgar Renteria and Aaron Rowand are capable of swiping a bag or three. Neither the Nationals nor the Marlins are particularly efficient at gunning down opposing baserunners, so if you're in need, take a look at any of the five in most formats.
Cardinals (CIN-4, COL-3): For a team not exactly known for its speed -- try to predict who will lead the team in stolen bases (no easy task) -- the Cardinals were actually decent in the category in their May 8-10 series against the Reds, swiping three bags in three games, including two off Cincinnati backup Ryan Hanigan. Colorado, meanwhile, must rely on weak-armed Yorvit Torrealba with Chris Iannetta on the DL; Torrealba has allowed 19 steals in 20 tries in 16 games this season. As for who might lead the Cards in the category, can you believe Albert Pujols is currently tops on the team with seven? Heck, even Yadier Molina, who shares his genes with slow-footed Bengie and Jose, has three. That's as good a sign as any that this is a team that exploits matchups.
Rangers (@NYY-3, @BOS-3): The Yankees might very well get Jorge Posada before this week, not that that's a good thing for them when it comes to throwing out runners. He's coming off a hamstring problem most recently, but the greater concern was the shoulder surgery he had within the past year, limiting his ability to gun down opposing base stealers. Couple that with three games against the Red Sox and particularly Jason Varitek, who has allowed an MLB-high 42 stolen bases, and things look great for Texas on the basepaths in Week 9. Can you believe Nelson Cruz has nine steals already this year? Elvis Andrus (6 steals) has yet to fully realize his potential in the category, but he's a sleeper for this week.
Load up: Pitchers
The teams listed below have the most favorable overall pitching matchups, accounting for recent performance, strength of opponents and ballpark factors.
Brewers (@FLA-4, @ATL-3): That Marlins offense is in quite a funk, striking out 10 or more times as a team on nine of 26 occasions in May and batting .244 with a .690 OPS, an average of 4.2 runs per game and a major league-high 226 whiffs during that span. Atlanta, meanwhile, hasn't been much more productive, having registered a team OPS of .699 while averaging 4.4 runs in 26 games in May. Besides, even though Milwaukee tends to pitch better as a team at Miller Park, it's not like this is a bad staff in road games. The Brewers have a 4.20 team ERA on the road for the season and are 12-6 with a 3.65 ERA and 1.28 WHIP in their past 18 road contests.
Cardinals (CIN-4, COL-3): Dave Duncan might be credited as a wizard among pitching coaches, but nowhere is his mastery more evident than at the new Busch Stadium, where his hurlers tend to dominate. Consider that in the three years and two months of the ballpark's existence, the Cardinals as a staff have a .578 winning percentage, 3.97 ERA and 1.33 WHIP in 268 games there, compared to .455, 4.84 and 1.44 in 264 road contests. This year the staff is 17-9 with a 3.23 ERA and 1.19 WHIP in 26 starts at home, and the current five members of their rotation are a combined 62-36 with a 3.15 ERA and 1.21 WHIP in their careers at Busch. Best indicator of how good the going is for the Cardinals' staff: In his second start back from the DL this past Monday, Chris Carpenter tossed six perfect innings. Oh, and by the way, the Cards are a combined 25-11 all-time at the new Busch Stadium against these opponents.
White Sox (OAK-4, CLE-3): I picked Chicago's staff as a favorable fantasy choice for Week 7, and that was the week it suffered a 20-1 drubbing at the hands of the Twins. Outside of that game, however, the team wasn't in any way unproductive. The White Sox actually had a 3.17 ERA during that six-game homestand, including that drubbing -- they allowed only 10 runs total in the other five games -- and for the season have a 3.73 ERA and 1.40 WHIP in 22 home contests. You might think this staff is in for trouble at typically homer-friendly U.S. Cellular Field, but it's not, especially not with four games against the Athletics and their MLB-worst .671 team OPS on the schedule. Besides, according to the Park Factors page, "The Cell" has actually leaned toward being pitcher-friendly so far.
Blue Jays (LAA-3, KC-3): Here's a case of perception -- you probably think this inexperienced staff, which has used 10 different starting pitchers so far, stinks -- meeting reality: This staff actually ranks in the majors' upper half in ERA, opponents' batting average and WHIP (where it incredibly ranks No. 2). I understand the perception; this staff just lost nine consecutive road games and was obliterated to the tune of a 6.30 ERA and 1.60 WHIP. But back home, where Toronto has a 3.38 ERA and an MLB-best 1.12 WHIP, I think the Blue Jays get back on track. It sure helps when you have your ace, Roy Halladay, pitching twice, and a pair of middling to below-average opponents on the schedule.
Projected starting pitchers
The chart below lists each of the 30 MLB teams' schedules and projected starting pitchers. Those pitchers scheduled to pitch twice this week are color-coded.
Notes: The Royals need a fifth starter on Saturday, and it'll likely be either Luke Hochevar or Sidney Ponson. Though there's a chance either Ricky Nolasco or Anibal Sanchez could be activated to pitch for the Marlins on Tuesday, more likely Burke Badenhop will pitch then with either Nolasco or Sanchez replacing him in the rotation on Sunday. Kyle Lohse is doubtful to make his scheduled start for the Cardinals on Tuesday, leaving Brad Thompson the most likely starter that day, but Lohse might be ready to pitch the next time that turn comes up on Sunday.
Rankings: Tristan's two-starts
Recommended cutoff point for elite one-start guys: No. 16 (Volquez)
Recommended cutoff point for "under-50" bargains: No. 23 (Miller)
Five must-starts: Roy Halladay, Dan Haren, Tim Lincecum, Jake Peavy, Johan Santana
6. Kevin Slowey (MIN) -- Tue-CLE (Huff), Sun-@SEA (Washburn)
7. Randy Wolf (LAD) -- Tue-ARI (Haren), Sun-PHI (Bastardo): 3.16 ERA, 1.18 WHIP in five home starts
8. Roy Oswalt (HOU) -- Mon-COL (Cook), Sat-PIT (Snell): 20-5, 2.92 ERA, 1.21 WHIP in 38 home starts 2007-09
9. Bronson Arroyo (CIN) -- Tue-@STL (TBD), Sun-CHC (Wells)
10. Joe Saunders (LAA) -- Tue-@TOR (Halladay), Sun-@DET (Porcello): 19-6, 3.02 ERA, 1.23 WHIP in 28 road starts 2007-09
11. A.J. Burnett (NYY) -- Tue-TEX (Padilla), Sun-TB (Sonnanstine): 8-4, 3.01 ERA, 1.03 WHIP in 18 career starts versus Rays
12. Aaron Cook (COL) -- Mon-@HOU (Oswalt), Sat-@STL (Wellemeyer): 3-0, 2.37 ERA, 1.32 WHIP in five career starts at Minute Maid Park
13. Joe Blanton (PHI) -- Mon-@SD (Correia), Sat-@LAD (Kuroda): 3-1, 4.65 ERA, 1.32 WHIP in his past five starts
14. Rick Porcello (DET) -- Tue-BOS (Matsuzaka), Sun-LAA (Saunders): 3-1, 3.18 ERA, 1.28 WHIP in four home starts
15. Joba Chamberlain (NYY) -- Mon-@CLE (Sowers), Sat-TB (Garza)
16. Edinson Volquez (CIN) -- Mon-@STL (Wellemeyer), Sat-CHC (Marshall)
17. Ubaldo Jimenez (COL) -- Tue-@HOU (Paulino), Sun-@STL (TBD): 2-0, 3.38 ERA, 1.23 WHIP in three career starts versus Astros
18. Todd Wellemeyer (STL) -- Mon-CIN (Volquez), Sat-COL (Cook): 9-3, 2.65 ERA, 1.11 WHIP in 17 home starts 2008-09
19. Kyle Davies (KC) -- Tue-@TB (Sonnanstine), Sun-@TOR (Halladay): 3.52 ERA, 1.31 WHIP in 11 road starts 2008-09
20. Jarrod Washburn (SEA) -- Mon-BAL (Hill), Sun-MIN (Slowey): 7-6, 3.26 ERA, 1.10 WHIP in 16 career starts versus Twins
21. Daisuke Matsuzaka (BOS) -- Tue-@DET (Porcello), Sun-TEX (Padilla)
22. Manny Parra (MIL) -- Tue-@FLA (Badenhop), Sun-@ATL (Kawakami)
23. Andrew Miller (FLA) -- Mon-MIL (Suppan), Sat-SF (Sanchez): 4.55 ERA, 7.16 WHIP at home 2008-09 (7.16 and 1.93 on road)
24. Gavin Floyd (CHW) -- Tue-OAK (TBD), Sun-CLE (Huff): 11-5, 3.55 ERA, 1.19 WHIP in 21 home starts 2008-09
25. Zach Duke (PIT) -- Tue-NYM (Santana), Sun-@HOU (Paulino)
26. Livan Hernandez (NYM) -- Mon-@PIT (Snell), Sat-@WAS (Lannan): 3-0, 3.03 ERA, 1.32 WHIP in his past six starts
27. Kenshin Kawakami (ATL) -- Tue-CHC (Wells), Sun-MIL (Parra): 2-3, 3.60 ERA, 1.20 WHIP in five home starts
28. Andy Sonnanstine (TB) -- Tue-KC (Davies), Sun-@NYY (Burnett)
29. Ian Snell (PIT) -- Mon-NYM (Hernandez), Sat-@HOU (Oswalt)
30. Bartolo Colon (CHW) -- Mon-OAK (Cahill), Sat-CLE (Sowers)
31. Jeff Suppan (MIL) -- Mon-@FLA (Miller), Sat-@ATL (Medlen): 3-2, 2.98 ERA, 1.23 WHIP in seven career starts at Dolphin Stadium
32. Rich Hill (BAL) -- Mon-@SEA (Washburn), Sun-@OAK (Cahill)
33. Randy Wells (CHC) -- Tue-@ATL (Kawakami), Sun-@CIN (Arroyo)
34. Felipe Paulino (HOU) -- Tue-COL (Jimenez), Sun-PIT (Duke)
35. Trevor Cahill (OAK) -- Mon-@CHW (Colon), Sun-BAL (Hill)
Six "no thank yous": Antonio Bastardo, David Huff, Hiroki Kuroda, Vicente Padilla, Jeremy Sowers, Craig Stammen
Tristan's one-start bargains
The 50-to-90 group (owned in 50 to 90 percent of ESPN.com leagues)
Scott Baker (MIN) -- Thu-CLE (Carmona): 7-4, 3.71 ERA, 1.03 WHIP in 18 home starts in 2008 and '09
Jeremy Guthrie (BAL) -- Fri-@OAK (Anderson): 3.45 ERA, 1.21 WHIP in three career games (two starts) at McAfee Coliseum
Edwin Jackson (DET) -- Sat-LAA (Santana): 2-1, 3.55 ERA, 1.21 WHIP in five home starts
The under-50 group (available in at least 50 percent of ESPN.com leagues)
Nick Blackburn (MIN) -- Sat-@SEA (Jakubauskas): 12 IP, 13 H's, 4 ERs, 7 K's (3.00 ERA) in two starts versus Mariners in 2009
Dave Bush (MIL) -- Thu-@FLA (Johnson): Win, 7 IP, 6 H's, 2 ERs, 7 K's versus Marlins 5/14/09
Doug Davis (ARI) -- Fri-@SD (Geer): 3-1, 3.51 ERA, 1.05 WHIP in five career starts at Petco Park
J.A. Happ (PHI) -- Wed-@SD (Young): 2-0, 1.16 ERA, 0.64 WHIP in eight career road games (two starts)
John Maine (NYM) -- Fri-@WAS (Martis): Win, 5 IP, 1 H, 0 ERs at Nationals Park 8/13/08; 7-2, 3.79 ERA in 11 career starts versus Nationals
Mike Pelfrey (NYM) -- Wed-@PIT (Ohlendorf): Win, 7 IP, 7 H's, 0 ER at PNC Park 8/15/08
Joel Pineiro (STL) -- Wed-CIN (Cueto): 2-1, 3.38 ERA, 1.00 WHIP in four starts versus Reds 2008-09
Jonathan Sanchez (SF) -- Sat-@FLA (Miller): Marlins have .690 team OPS in May
Jordan Zimmermann (WAS) -- Wed-SF (Johnson): Season-high 8 K's versus Giants 5/12/08
Barry Zito (SF) -- Fri-@FLA (Volstad): 2-0, 0.68 ERA, 0.75 WHIP in two career starts at Land Shark Stadium
Tristan H. Cockcroft is a fantasy baseball analyst for ESPN.com and a two-time champion of the League of Alternative Baseball Reality (LABR) experts league. You can e-mail him here.


text:
Under the slogan «More space for better living», the canton of Jura is decidedly an ideal region to combine quality of life and the development of your economic activities.
Whereas most urban centres are overcrowded, you will find here an unspoiled environment where nature has some pleasant surprises for you. This green setting does not prevent the region from offering a wide range of activities for your free time, whether they be sport, cultural visits or leisure activities in the broadest sense.
With respect to accessibility, the canton of Jura is well connected to all areas of Switzerland, Europe, and the wider world. Further information on the page "Infrastructures".


text:
Which one goes, which one stays?
OK, I really need help from my BF friends on this one.
Parting with any of my folders is traumatizing. Choosing which of two beauties to cull from the collection is like asking which of my children to sacrifice. So, I need my BF 'peeps to show me the way.
I have three outstanding bikes in my collection that are in the same niche - high-end, high performance, transportable, and gorgeous - The Moulton TSR, a Bridgestone Moulton that I just got from Taiwan, and most recently, a Bike Friday Pocket Custom that I got for a good deal on Craigslist. Three bikes in the same niche is too much, even for a folder glutton like me. I must get rid of one of them.
I decided the TSR is staying. Its space frame is so different and superior. Plus, I have a huge emotional investment in it (full story here: http://www.bikeforums.net/showthread...lent+adventure).
So the choice is between the Bike Friday and the Bridgestone Moulton. Each is in excellent shape, not a nick on either frame, rides nicely, etc. The BF is valued around $1,000, the BSM is around $2,000.
Bridgestone Moulton description:
- full suspension,
- size 369 wheels
- Capreo drivetrain
- Shimano 105 brifters
- aluminum frame
- weighs about 27lbs.
- not available in the US
- stylish and gorgeous looks
Bike Friday description:
- 56/42 front with 8 speed 11-28 cassette Shimano 105 components
- Ultegra bar-end shifters
- Chromoly frame
- 24 lbs
- size 406 wheels
- Simple, practical elegance
The bottom line to me is that BSM is an exotic animal, whereas the BF is the practical, reliable house pet. Which one goes, which one stays? Sorry, keeping them both is an obvious cop-out. I don't need help with that choice. You guys get to make the tough choice only.
I say ditch the Bike Friday, purely because I can't stand the Comic Sans type font they chose for their logo. And the bar tape is just a bit too 80s spandex.
I would sell the BF. It's easier to replace with another one especially if you're on the left coast if you think you may regret your decision in a month or two.
Absolutely the BF, its easily replaceable anytime. Lots around for sale. Heck ive seen at least three up here this year alone and not many folders in this town.
How many folks have even seen a Moulton in the flesh so to speak?See its easy to decide.Lol.
Yeah, but the BF is $1K less than the BSM. The tire size is more prevalent. Less unique parts. Simple to maintain. It's also 3 lbs lighter.
That's the practical side of me talking.
$1,000 certainly is a bunch of money, but if the 1K was that much to you, I don't think you would have the bikes you already do. I could be wrong though. As far as the maintenance, how much do you think you would do on the bike? Would it be enough to make that big a difference?
Which one do you tend to ride more? If either gets a scratch which one do you shed a tear over? Which is practical to travel with?
About the only colorable argument I can see for selling the Bridgestone Moulton would be that you need to raise $2k for your next fix and the Bike Friday can't get you more than halfway there.
Well, in the same "fix", I'd likely sell the Moulton. The Moulton you'd have left is a an even more unusual model, and it has a better wheel size for a road bike. Also, the Friday will be an easier bike to maintain in the long-run, with the factory just a days drive up the road from you.
The Bike Friday looks like a Crusoe or Pocket Rocket based upon the lite weight, 'straight' brace connected to the frame and down tube, just above the bottom bracket. It would cost $2,000+ to replace with a new one, as equipped. The bar tape is a bit garish to be sure - :D
The Moultons are pretty expensive (and unusual) to be out there beating up on a regular basis - besides, as a collector of folders, I think variety is nice. If interest rates pick up someday (and we have any money left), I'd consider a TSR2 or TSR8.
A couple of questions: Are you running out of space for bikes? Is the family questioning your sanity? What is real reason for selling off one of them? (If it were just $, you'd be looking to unload all of them, IMO.)
I'm not selling for any other reason than I simply have too many bikes. I can't even get to ride them enough. Over time, I have rotated and reduced my bike collection to fewer, but more high end bikes. But, as I said, even this folder glutton has a conscience.
Agree, too much is too much.
As one our resident professors mentioned (other than being accused of astuteness ), Alan, practicality isn't necessarily one of your long suits.. but knowing what you have in the stable, I'd dump the Bridgestone .. you won't ride it.. you'll hang it up in the living room... you already have the Cal Bears 2spd if you need Moulton retro .. then there's the TSR if you actually want to grab a good riding, fast, comfortable bike .. The Friday will get lighter and faster as you pour more money into it from the sale of your Bridgestone... what's with the bar tape?!?! tell me you didn't have a roll of that sitting in the garage.. :eek:
If these are the last bikes you'll ever own, I'd say keep the BF as you can easily find parts and the factory is right up the coast. But you will own other bikes in the future. I say sell the BF and get a Raleigh Twenty (which you will mod heavily) for your house pet bike. Sound good? No? oh.
Don't listen to your practical side. Follow your heart. Keep the one that appeals to you most.
I'd say keep both of them. You can never have too many bikes ;) but if you have to let one go, dump the BM and change the tape on the BF :thumb:...BTW the BF has Stickers that don't have a clear coat so they'll come off easy if you don't like 'em and you can make your own "Custom" stickers :D
I would sell a kidney and keep both.
I can appreciate the too many bikes thing.
So my call is, sell both.
Without question, sell the Moulton.
The reason is simple. The Moulton has certain advantages over the Bike Friday, and likewise vice versa. If you sell the Bike Friday, you lose those advantages in your stable. If you sell the Moulton, you don't lose its advantages... BECAUSE YOU ALREADY OWN ANOTHER, EVEN BETTER, MOULTON.
It's like saying: "I've got a BMW 3 Series which I'm keeping. Do I sell my BMW 1 Series or sell my Lotus Elise?" The answer is obvious.
However, I had feared the TSR was going to be a museum piece also, but I am riding it a lot, as you know. If I kept the BSM, I would ride it too. Bikes are meant to be ridden, IMHO. I'm also vulnerable to the argument that one can pick up a Bike Friday any day of the week on Craigslist. But there are probably just a handful of BSMs in this country.
PS: rode the BSM from Half Moon Bay, up Tunitas Creek, down to Woodside, then into SF this week. 54 miles, 4,400 ft. I was only 6 minutes slower up Tunitas (2,300 ft elevation), compared to my personal best time with the 17lb Fuji. Not too bad, considering the BSM is 10 lbs heavier!
I swear I go back and forth every 15 minutes on this issue.
Here's what I think I will do: I'm going to put the BSM on eBay for a 10 day listing. If it sells for my target price, then that's settled. If it doesn't, then that's a sign from above that the BF is the one to go. My price for the BF is much more flexible, so I'm sure that will sell easily.
Whew! Thanks for all your good input.
I take it that the folding issue is not that important to you. It would be for me. I would want one to fold but then I sometimes have a need for that. Is the TSR that much better than the BM?
Folding is not what these bikes are designed for. They are more transportable than foldable. I have a Brompton and a Strida for multi-modal foldability.
I think the ride quality of the TSR is indeed better than the BSM. Which is not to say that the BSM is bad; it is not. It's more a statement of the rigidity and comfort of the TSR space frame. It's unique, in my opinion.
|All times are GMT -6. The time now is 03:49 PM.


text:
Protire - Autocare
Review for Protire - Autocare
RONALD N. on 03/22/2014
Rather than have to pickup my vehicle after working hours, my vehicle was brought to my residence for me. I cannot remember the last time this service was offered by a business.
Vehicle: Nissan Frontier
Service Date: 03/20/2014
Review Created: 03/22/2014 10:21 PM


text:
|30 Jun 2013
f1 and f2 buttons not being recognised.
I have been using a Mac keyboard on my win 7 desktop for about 6 months (I love the spacing on the keys). Anyway about a month ago the f1 and f2 buttons just flat out stopped being recognised. I mean they don't even register if I use a keyboard diagnostic tool and strike the keys. Every other key works fine. Here is where it gets odd. If I press a key (any key) and then press f1 or f2, they suddenly register as being pressed...so they do work, just only just as long as I'm holding another key down at the same time. I have a plugged it into an older xp machine and it works fine straight away, I have plugged it into a macbook pro and it works perfect too, so it is not the keyboard itself. I have an older G4 apple keyboard from times gone past in a drawer that works fine if I plug it into the win 7 machine so it is not general key mapping on the win 7 machine. The only problem is when I put this specific keyboard with this specific machine. I have done every combination of plugging / unplugging, uninstalling / installing drivers, starting and restarting in normal and safe mode to no avail. I'm thinking that the problem may be deeper in windows than I'm comfortable playing without guidance, possibly a software conflict somewhere.
I did play with some services in admin tools a few weeks back due to 15 min boot times on this machine and it may have started then (I'm not sure...how often do you press f1 / f2?). Either way it is a useless shortcut if I need to press 2 buttons to get it to work.
I'm desperate for help....
Thanks all,
|My System Specs
|Thread Tools
|Similar help and support threads
PCI not recognised...
Hi... A total Newbie here, so go easy please...:-) My aged Win7 machine seems to have thrown the teddy out of the pram... My ATI Radeon Graphics card is refusing to work and I'm now forced to use the onboard Nvidia adapter. I've removed the card and it works fine on my other PC...
|Graphic Cards
Ram not recognised
Hi all, just noticed in Control panel/System there is only 4gb of memory being recognised. I have 3 dinns x 2gb installed so pulled the case off, removed the dinns and swapped their slots. Still only showing 4gb in "System". Any ideas Peeps? I installed and ran CPU-Z which shows triple channel...
|Performance & Maintenance
RAM recognised then Not recognised !!
I wonder if some kind soul can assist ....Recently my computer was taking an age to boot.... repeatedly had to press start. Upon checking the internet I found that a probable cause was linked to power supply....not spinning HD fast enough to boot so I uprated to 500W... and as the computer leads...
|Installation & Setup
trying to get a SSD recognised
Hi I have spent all day trying to install a 60gb SSD as my main boot drive but am stalled even trying to get it recognised in "My Computer" I can see it in Disk management - have formatted it and made it active.. so far so good! when I click on the partition and click properties I get the pie...
|Hardware & Devices
CDs not recognised
My DVD drive , since upgrading to Windows 7 I am sure, will not acknowledge that there is a CD in it. DVDs are fine. It is just CDs that arent working. I checked for a driver update and there wasnt one. Is there anything I can do to fix this?
|Hardware & Devices
|Our Sites
|Site Links
|About Us
|Find Us
Windows 7 Forums is an independent web site and has not been authorized, sponsored, or otherwise approved by Microsoft Corporation. "Windows 7" and related materials are trademarks of Microsoft Corp.
© Designer Media Ltd
All times are GMT -5. The time now is 23:07.


text:
Merthyr Tydfil people looking to find a new job or make progress within their current role are being given a helping hand from an exciting free employment training scheme.
Working Skills for Adults 2 (WSfA2) offers a range of community-based training in areas such as food hygiene, IT, business administration, hair and beauty, first aid and manual handling, as well as helping students brush up on subjects including maths and English.
The European Social Fund project, which is managed by Merthyr Tydfil County Borough Council, provides flexible training which can be fit in around work commitments and includes one-to-one sessions with tutors and an employee liaison officer.
"The aim is to help people upskill in their current job or make progress if they fancy a change of career," said County Borough Council Employability Manager Deb Ryan-Newton.
"Designed to meet the needs of both employed and self-employed people, the focus is on employability skills and improving the opportunities for workers to sustain employment and increase earnings potential," she added.
Other support provided includes assistance in the student's progression to further learning through further and higher education and continuous professional devel
opment courses.
Along with interview technique, confidence and motivation training and CV writing workshops, the courses will provide accredited qualifications such as Agored and City and Guilds. All courses are available through the Welsh language
One local resident supported by Working Skills for Adults 2 was Haley Davies, 32, from Dowlais. Haley dramatically improved her self-esteem and confidence after taking part initially with the Neighbourhood Learning Centre (Bridges to Work) programme on a retail course.
She gained qualifications in Basic First Aid, Manual Handling and Food Hygiene, marking the beginning of a rewarding and successful return to learning. Due to her training, Haley managed to get a job as a school breakfast and lunchtime supervisor.
After contacting Working Skills for Adults 2 with the long-term goal of becoming a learning support assistant, she has been working with the scheme's Essential Skills tutor on improving her literacy and numeracy.
"Due to Haley's commitment, she won the Learning for Health and Wellbeing award in the Merthyr Tydfil Inspire! ceremony," said Deb Ryan-Newton. "Her confidence is improving and she has started to volunteer in a school to build her experience. Eventually, she would like to complete a learning support assistance course."
Merthyr Tydfil County Borough Councillor Chris Barry said:
"Working Skills for Adults 2 is a fantastic free opportunity for people to improve their job prospects and self-confidence, and we would urge our local residents to take advantage of it."
Anyone who would like to find out if they are eligible for support should contact the WSfA2 team on 01685 727070, email [email protected] or go to Facebook: Working Skills for Adults 2 Merthyr Tydfil.