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Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P‑glycoprotein expression
- Authors:
- Li Sun
- Weigang Chen
- Lili Qu
- Jie Wu
- Jin Si
- Corresponding author:
- Jin Si [ email@example.com ]
Published online on: Friday, October 18, 2013
- Pages: 1883-1887 DOI: 10.3892/mmr.2013.1742
Hepatocellular carcinoma (HCC) is the fifth most common type of malignant tumor worldwide and the third greatest cause of cancer-related mortality (1–4). HCC is one of the most aggressive human malignancies and previous data showed that the five-year survival rate remained extremely poor (5). HCC is a hypervascular solid cancer characterized by a high degree of drug resistance (6). Multidrug resistance (MDR) against chemotherapeutic agents is key in the failure of HCC therapy (7).
MDR protects cancer cells against a variety of drugs with different structures and functions. MDR of cancer cells is a predominant problem in cancer chemotherapy. A number of mechanisms have been established for the development of MDR, including expression changes of genes involved in apoptosis, increased enzyme activity of the glutathione-mediated detoxification pathways and activation of adenosine triphosphate (ATP) binding cassette transporters (8,9). The classical mechanism of MDR development involves the overexpression of P-glycoprotein (P-gp), a plasma membrane transporter extrudes chemotherapeutic agents from tumor cells (10–12). Significant effort has been aimed at the development of MDR reversers. A significant number of compounds have been identified to function as inhibitors of P-gp and have been tested for their reversal activities on MDR tumor cells (13–16). However, a number of these compounds are currently under clinical evaluation as the majority of tested compounds exhibit unpredictable pharmacokinetic interactions, toxicity or insufficient efficacy (17). Novel therapeutic strategies, including agents that are effective, safe and exhibit low toxicity are required to reverse the MDR of tumor cells.
Flavonoids, a type of plant polyphenol, are well established for analgesic, physiological antipyretic and anti-inflammatory activities and have attracted significant attention due to their antitumor activities and ability to bind with P-gp (18–21). Icaritin, a prenylflavonoid, is a hydrolytic product of icariin, which is derived from the plant Herba Epimedium which is commonly used in traditional Chinese medicine. Icaritin exhibits a variety of pharmacological and biological activities, including antirheumatic and antidepressant activities; the stimulation of cardiac and neuronal differentiation (22,23); prevention of steroid-associated osteonecrosis (24); induction of human prostate carcinoma PC-3; breast cancer MCF-7 cell growth inhibition; and cell apoptosis (25,26).
In the present study, the multidrug-resistant HepG2/ADR subclones were developed and treated with icaritin. The reversal effect of icaritin on MDR tumor cells was investigated using the adriamycin (ADR) sensitive HepG2 cells and ADR resistant HepG2/ADR cells.
Materials and methods
Cell culture and icaritin treatment
HepG2 [a human hepatocellular carcinoma (HCC) cell line] was purchased from KeyGen (Nanjing, China). Cells were cultured with Dulbecco's modified Eagle's medium (Gibco-BRL, Carlsbad, CA, USA) supplemented with 10% newborn calf serum (Gibco-BRL) at 37°C in a humidified atmosphere containing 5% CO2. An MDR human HCC cell line, HepG2/ADR, was developed by culturing HepG2 cells in the presence of increasing concentrations of ADR (0.02, 0.05, 0.1 mg/l; Hisun Pharmaceutical Co. Ltd., Zhejiang, China). Resistant cells were selected and resistance was maintained by culturing the cells in medium supplemented with 0.1 mg/l ADR and labeled HepG2/ADR (0.1).
Stock solution of icaritin (purity, >98%; Yousi Biotechnology Inc., Shanghai, China), which was further diluted with cell culture medium before each experiment, was prepared in dimethyl sulfoxide (DMSO) at a concentration of 10 mM at −20°C. The final concentration of DMSO in culture was <0.1%.
Measurement of cellular sensitivity to anticancer drugs
The 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT; Sigma-Aldrich, St. Louis, MO, USA] assay was used to determine drug sensitivity. HepG2 and HepG2/ADR cells were seeded into 96-well plates at a concentration of 5 × 103 cells/200 μl/well. Cells were incubated at 37°C in a humidified 5% CO2 incubator. Following 24 h treatment with specific concentrations of the anticancer drugs ADR, vincristine, cisplatin and 5-fluorouracil, plates were returned to standard tissue incubator conditions for an additional 4 h. Medium was removed and cells were solubilized in 150 μl DMSO. The intensity of formazan was measured at 490 nm using an automated microplate spectrophotometer (iMark; Bio-Rad, Hercules, CA, USA). The survival rate was calculated as (OD value of the treated group/OD value of untreated group) × 100%. Assays were performed in triplicate in three independent experiments.
Analysis of MDR reversal activity
Viability of HepG2 and HepG2/ADR cells following treatment with ADR in the presence (1, 15, 30 μM ) or absence of icaritin was analyzed by an MTT assay. Following plotting of the dose-response curve, the IC50, the concentration of drug inhibiting 50% of cells, was calculated, from which reversal fold was calculated.
Effect of icaritin on intracellular ADR accumulation
HepG2 and HepG2/ADR cells were incubated with ADR in the presence (1, 15, 30 μM ) or absence of icaritin for 4 h. ADR accumulation in HepG2 and HepG2/ADR cells was assessed by fluorescence spectrophotometery. The fluorescence was generated when HepG2 cells were treated with ADR, and the fluorescence intensity was positively associated with ADR accumulation. ADR accumulation in HepG2 cells and HepG2/ADR cells was assessed using a fluorescence spectrophotometer (excitation wavelength, 470 nm; emission wavelength, 590 nm; F-7000, Hitachi, Chiyoda, Japan).
Quantitative polymerase chain reaction (qPCR) assay
Cells were frozen in liquid nitrogen and stored at −80°C for use in qPCR experiments. MDR1 mRNA expression levels were quantified by qPCR. Total cellular RNA was extracted using TRIzol reagent (Invitrogen Life Technologies, Carlsbad, CA, USA) according to the manufacturer's instructions. Primer sequences used were as follows: sense: 5′-CATCGAGTCACTGCCTAATAAATA-3′ and antisense:5′-GCTTCTTGGACAACCTTTTCACT-3′ for MDR1; and sense: 5′-CCTCTATGCCAACACAGTGC-3′ and antisense: 5′-GTACTCCTGCTTGCTGATCC-3′ for β-actin. PCR was performed for 35 cycles, each cycle comprised of denaturation at 95°C for 45 sec, annealing at 52°C for 45 sec and extension at 72°C for 45 sec, prior to a final extension at 72°C for 10 min. MDR1 mRNA levels were analyzed by one-step qPCR with RNA-direct™ SYBR-Green Realtime PCR Master mix (Toyobo, Osaka, Japan), according to the manufacturer's instructions. The amplification was monitored on an ABI PRISM 7500 real-time PCR apparatus (Applied Biosystems, Carlsbad, CA, USA).
Western blot analysis
Cells were lysed with ice-cold lysis buffer [50 mM Tris-HCl (pH 7.4) 150 mM NaCl, 1 mM MgCl2, 100 μg/ml PMSF and 1% Triton X-100] for 30 min on ice. Total proteins were dissolved in the supernatant following centrifugation at 13,225 × g for 5 min at 4°C and protein concentrations were measured in the supernatants (Protein Assay Dye; Bio-Rad, Hercules, CA, USA). Equal quantities (40 μg) of lysate proteins were separated on 10% SDS-PAGE gels and electrophoretically transferred onto polyvinylidene fluoride membranes. Following blocking with 5% non-fat dry milk in Tris-buffered saline with Tween-20 (TBST) buffer [10 mM Tris (pH 7.5) 150 mM NaCl and 0.05% Tween-20] for 2 h at room temperature, membranes were probed with A 1:1,000 dilution of anti-target protein (Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA) or anti-β-actin antibodies (Sigma-Aldrich) at 4°C overnight, followed by incubation in a 1:5,000 dilution of horseradish peroxidase-coupled secondary antibody (Sigma-Aldrich). Protein bands were detected using an enhanced chemiluminescence detection system (ChemiDoc; Bio-Rad). Band intensity was quantified by BandScan 5.0 software (Glyko, Hayward, CA, USA). All western blot analyses were performed at least three times.
Statistical analysis
SPSS version 16.0 software was used (SPSS Inc., Chicago, IL, USA). Each assay was performed a minimum of three times. Data are expressed as the mean ± SD; Student's t-test and one-way analysis of variance were used for statistical analyses. P<0.05 was considered to indicate a statistically significant difference.
Development of multidrug-resistant HepG2/ADR subclones
MDR was developed in HepG2 cells by treatment with increasing concentrations of ADR. HepG2 cells began to exhibit cell death 24–48 h following treatment with high concentrations of ADR. Therefore, 0.02 mg/l ADR was added to HepG2 cells and the morphological changes were observed in cultured cells. Higher concentrations of ADR were added to the medium once HepG2/ADR (0.02) cell death was not observed and morphological changes became stable. A HepG2/ADR (0.1) cell was produced, which required a minimum of 8–10 weeks culturing (Fig. 1).
Figure 1
Continuous image record of cell proliferation during the development of HepG2/ADR cells (0.02). ADR was added to HepG2 cells at 0.02 mg/l and resistant cells were selected by removing dead cells. Progress from the parental HepG2 to the resistant HepG2/ADR (0.02) subclone was continuously imaged. Nine weeks was required to confirm a stable phenotype. ADR, adriamycin.
Determination of MDR
HepG2/ADR (0.1) cells were investigated for their resistance against other anticancer drugs using MTT. HepG2/ADR cells were observed to be resistant to ADR and to multiple anticancer drugs, including vincristine, cisplatin and 5-fluorouracil. The IC50 of these drugs in HepG2/ADR cells was significantly higer compared with that in non-resistant HepG2 cells (Table I). HepG2/ADR cells were ~25-fold more resistant to ADR in comparison with HepG2 cells.
Icaritin-mediated reversal of HepG2/ADR cell resistance to ADR
MDR modulating activity of the derivatives was evaluated by an MTT assay using human HCC cells, HepG2 and ADR resistant HCC cells (HepG2/ADR). As shown in Table I, the IC50 values of ADR on HepG2 and HepG2/ADR cells was 0.024±0.007 mg/l and 0.596±0.063 mg/l, respectively, when treated for 48 h. The MDR of HepG2/ADR cells was 24.83-fold higher compared with the sensitive HepG2 cells. Icaritin was capable of reversing MDR and the sensitivity of the HepG2/ADR cells to ADR was ~1.65, 2.50 and 7.18 fold higher when the cells were treated with 1, 15 and 30 μM icaritin (Table II). The results indicated that icaritin significantly reverses the cytotoxicity of ADR to HepG2/ADR cells in a dose-dependent manner.
Effect of icaritin on intracellular ADR accumulation
To investigate the mechanism of the MDR reversal activity of icaritin, the intracellular ADR accumulation was examined. As shown in Fig. 2, the intracellular ADR accumulation in HepG2/ADR cells was 50% lower compared with that in HepG2 cells. The treatment of icaritin increased the intracellular ADR accumulation in HepG2/ADR cells at a specific range. However, it was observed that 0–30 μM icaritin did not trigger a significant effect in drug sensitive HepG2 cells. It was hypothesized that the mechanism of the MDR reversal activity of icaritin may have an association with the increase of intracellular ADR accumulation.
Figure 2
Effect of icaritin on intracelluar ADR accumulation in HepG2 and HepG2/ADR (0.1) cells. ADR accumulation in HepG2 cells and HepG2/ADR (0.1) cells was assessed following 4 h treatment with 0–30 μM icaritin using fluorescence spectrophotometery. Results of six independent experiments were averaged and are presented as the mean ± SEM. *P<0.05, vs. the HepG2/ADR cell (0 μM icaritin) group. ADR, adriamycin.
mRNA expression of the MDR1 gene
To determine whether icaritin altered the expression of the MDR1 gene, mRNA expression of the MDR1 gene was investigated (Fig. 3). A higher level of MDR1 expression was detected in HepG2/ADR compared with HepG2 cells. However, when treated with icaritin, the MDR1 level was significantly decreased in HepG2/ADR cells.
Figure 3
Effects of icaritin on the relative gene expression of MDR1/β-actin in HepG2 and HepG2/ADR cells. MDR1 genes were analyzed by qPCR. mRNA levels of MDR1 were quantified relative to β-actin mRNA. A higher level of MDR1 expression was detected in HepG2/ADR cells compared with HepG2 cells. However, when treated with icaritin, the MDR1 level was significantly decreased in HepG2/ADR cells. *P<0.05, vs. HepG2 cells. #P<0.05, vs. HepG2/ADR cells. qPCR, quantitative polymerase chain reaction.
Downregulation of P-gp protein expression by icaritin in HepG2/ADR cells
The present study showed that icaritin inhibits the expression of the MDR1 gene in HepG2/ADR cells (Fig. 3). To investigate whether the mechanism of icaritin on HepG2/ADR cells was responsible for the expression of P-gp, western blot analysis was performed. Results in Fig. 4 showed that the expression of P-gp was significantly repressed by icaritin in HepG2/ADR cells.
Figure 4
Effects of icaritin on the expression of P-gp protein in HepG2/ADR cells. HepG2/ADR cells were plated for 24 h, 10 μM icaritin was added to the designated HepG2/ADR cells for a subsequent 24 h. (A) P-gp proteins were detected in HepG2/ADR cells and icaritin pretreated HepG2/ADR cells were assayed by western blot analysis. Lane 1, HepG2/ADR cells; and lane 2, icaritin pretreated HepG2/ADR cells. (B) Gray analysis of protein bands. *P<0.05, vs. HepG2/ADR cells. P-gp, P-glycoprotein.
MDR of cancer cells is a significant problem in cancer chemotherapy. P-gp is a plasma membrane transporter, which extrudes chemotherapeutic drugs from cells using ATP hydrolysis as an energy source. Overexpression of P-gp has been observed in numerous cancer cells with MDR (27,28). The aim of the present study was to identify an effective MDR reversing agent from Chinese traditional medicine and to gain an insight into its reversal effect and the molecular mechanisms of that effect.
A number of tumor cells were observed to develop MDR when cells were treated with drugs over a period of time (29,30). ADR is a chemotherapeutic drug, principally used for the treatment of solid tumors, including HCC (31). It functions via specific mechanisms; however, resistance to ADR develops in a broad range of cell lines and results in the loss of therapeutic efficacy (32,33). Thus, ADR was selected to develop the current drug resistant HCC cell subclones by culturing the cells in the presence of increasing concentrations of ADR. Although the HepG2/ADR cell line was developed by treating the cells with ADR only, it was observed that multiple drug resistance was achieved. The IC50 of specific anticancer drugs to the HepG2/ADR (0.1) subclone was higher compared with the parental HepG2; 24.83-fold for ADR, 22.25-fold for vincristine, 36.71-fold for cisplatin and 77.70-fold for 5-fluorouracil. The results showed that the acquired MDR of the HepG2/ADR (0.1) subclone was stable.
Icaritin is an active ingredient derivative from the traditional Chinese medical plant Herba Epimedium. Icaritin exhibits a variety of pharmacological and biological activities, including antitumor activity and also induces cell apoptosis in a number of types of tumor cells (34). However, the effect of icaritin on the reversal of MDR and its molecular mechanism was unclear. Therefore, the reversal activity of icaritin on MDR and the molecular mechanisms involved in this process were investigated. As shown in Table II, icaritin treatment resulted in a significant reversal of resistance to ADR at a concentration of 1, 15 and 30 μM. In addition, the icaritin-mediated reversal of HepG2/ADR cell resistance to ADR was observed in a dose-dependent manner. Furthermore, treatment of icaritin increased the intracellular ADR accumulation in HepG2/ADR cells at a specific range. It was hypothesized that the mechanism of the MDR reversal activity of icaritin may be associated with the increase of intracellular ADR accumulation.
The MDR resistance was due, in part, to the appearance of P-gp, which exerts an efficient pumping action to extrude the drugs from tumor cells. The mechanism of P-gp is cell- or tissue-specific, including the excretion of chemicals into the bile duct or kidney tubules, protection against toxic xenobiotics by blocking absorption by the intestine, efflux of steroid hormones and cholesterol from feces and prevention of chemicals that enter into the brain through the blood-brain barrier (35,36). The current results showed that icaritin significantly increased the intracellular accumulation of ADR and decreased the expression of the MDR1 level in HepG2/ADR cells compared with drug sensitive HepG2 cells. It was observed that icaritin may significantly downregulate the expression of P-gp. Reduction of P-gp expression may be proposed as a mechanism for specific agents or modulators to reverse MDR phenotype.
In conclusion, HepG2/ADR multidrug-resistant HCC cell subclones were successfully established. The current observations indicate that icaritin effectively reverses MDR, via the increase of intracellular ADR accumulation, and downregulation of the MDR1 gene and P-gp protein expression. The present results indicate that icaritin is a novel and potent MDR reversal agent, and may be a promising drug for tumor chemotherapy.
This work was supported by the Science and Technology Development Foundation of Nanjing Medical University of China (No.2011NJMU150), Natural Science Foundation of Jiangsu province of China (No.BK2009451) and National Natural Science Foundation of China (No. 30972913).


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'Silver Linings Playbook' | 2012
Lawrence returned to indie films in the romantic comedy "Silver Linings Playbooks." She plays recently widowed Tiffany Maxwell, who meets Pat Solitano (Bradley Cooper), a teacher with bipolar disorder trying to reconcile things with his wife. Tiffany promises to help Pat with his problems if he... Jojo Whilden / Toronto International Film Festival


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On my recent trip to the thrift store, I found a gorgeous vintage nutcracker with a beautifully turned wood handle/grip. I have been using it extensively. My most favourite use for it is cracking walnuts and trying very hard to get the kernel intact.
Xiaolu // 6 Bittersweets, and 6 other people added this photo to their favorites.
Lovely! The faded look and restricted lighting works so well here =D Out of curiosity, what camera do you use?
Thanks Xiaolu. I use the Canon 450D. I have had it for 3 years now. The lens for this one was the Canon 50mm f/1.4
Thx I have XS :).
Gorgeous shot. I totally agree with Xiaolu. Love the light hitting the nuts.
Thanks Radhika!


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1) In the blender container, add all the ingredients leaving the avocado.
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Item specifications, blueprints, and sample items accompany the MCESA Content Specific Assessments (multiple-choice assessments). These documents define and demonstrate the content on each test.
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|MCESA offers on-line workshops in the form of webcasts that are designed to support teachers and administrators with the implementation of MCESA Content Specific Assessments (multiple-choice assessments). Click here to for more information.


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Slashdot videos: Now with more Slashdot!
We've improved Slashdot's video section; now you can view our video interviews, product close-ups and site visits with all the usual Slashdot options to comment, share, etc. No more walled garden! It's a work in progress -- we hope you'll check it out (Learn more about the recent updates).
Comment: Re:Reasonable Expectation of Privacy (Score 1) 453
Comment: Re:Reasonable Expectation of Privacy (Score 1) 453
+ - NASA considering moving GALEX astrophysics satellite to private ownership->
Link to Original Source
Comment: Re:Not really planets (Score 1) 181
Tch, they're not really planets, right? I mean, if they're not orbiting a star, then they can't have "cleared the neighborhood of their orbit". Yet one more reason the IAU's current definition is so idiotic. (Besides the fact that it suggests that Mercury is more like Jupiter than it is like Ceres.)
Yes, they are planets most likely, because they probably formed around a star and then got kicked out dynamically. This is expected generically in models of how solar systems form and evolve (in particular we think it happened multiple times in our own Solar System).


text:
Christ Covenant School fifth through eighth-grade students participated in the National Geographic GeoBee, a geography quiz competition in which students compete on the local, state and national levels. Eighth-grader Austin Brown...
St. Andrew's Episcopal School three-year-old pre-kindergartners recently celebrated Farm Friday after a week studying farm life. Shown are (from left, back) Mason Crawford, Suniya Patel, Mila Grahm, Thomas Croft, Sydney...
World War II veteran James Young spoke to sixth-graders at First Presbyterian Day School about his experiences in the war, including the Battle of the Bulge. Shown are (from left) Grant Simpson, Young, Sayley Crawford, and Aubrey...
Members of Boy Scout 15, of St. Matthew's United Methodist recently visited the Capitol and viewed lawmakers at work. Shown are (from left) Frank Riley, Edward Sanders, Charles Clark, Allen Riley, McLin Sanders and Sen. Will...
Madison Central High School senior Haylee Morse signed with Jones County Junior College to play softball in the fall. Shown are (from left, back) Madison Central assistant softball coach Kaitlyn Perry, head softball coach Kayla...
For the third year, Pack 15 - Den 6 Cub Scouts from St. Matthew's United Methodist Church held their Christmas community service project at the Madison County Nursing Home. These third-grade Scouts donated boxes of...
Madison Ridgeland Academy K5 students performed the musical "Happy Birthday Jesus" for Grandparents Day. Shown are (from left, back) Jonathan, Butch, and Teresa McMillan, Maggie Withers; (front) Sienna McMillian.
Special to the Sun
This story begins at the Vicksburg Battlefield Park. Midway along the Union siege line is the Wisconsin Monument – a tall granite column on top of which...
By ASHBY FOOTE
Special to the Sun
This story begins at the Vicksburg Battlefield Park. Midway along the Union siege line is the Wisconsin Monument – a tall granite column on top of which...
I had just finished all the complicated logistics involved with flying my plane to northern California, when I got a text from the Troop 302 scoutmaster: "Would you and John like one last hurrah with the Scouts before he turns 18? Going...
Sen. Lydia Chassaniol has proposed legalizing a practice that would allow public bodies to more easily hide what they're up to. She has taken up the cause of the Columbus City Council and the Lauderdale County Board of Supervisors, which...
It is amusing – it is troubling and very much against the state code – that there are so many unconcerned people driving vehicles who are violating the handicapped parking spaces. Since I have a handicapped tag on the rear of...
Dear Editor:
Wow! The two-part article written by William Jeanes regarding the walk down Capitol Street was amazing. It made it seem like yesterday when my Belhaven neighborhood friends and I would either walk or ride the number two...
Black and turquoise with lots of sparkles and sequins, rhinestones and hats and canes and netted skirts . . . the list goes on. Sounds happy, doesn't it? I think that is the point - to be eye candy for those who need a lift in their daily...
The Jackson Airport Authority should set as their goal the recruitment of new airline routes from major carriers and the recruitment of smaller airlines to serve Jackson.
Here's an example of the kind of...
Could domestic terrorism take place right here in Mississippi? You may think so after reading Jim Fraiser's riveting new thriller, "In An Enemy's Country."
Scant attention is paid when a handful of Occupy Wall...
The Veritas School sent an 11-member delegation to the 2014 Mississippi Youth Legislature. Two Veritas delegates received distinguished honors for their work during the model legislative and judicial program for high school...
Fifth-graders in Trace Roberson's class at First Presbyterian Day School wore tacky holiday sweaters to their Christmas party. Shown are (from left, back) Ashley Mason, Riley McCoy, Burdee Kellum; (front) Grace Tillery, Margie...
Jackson Prep 2014-15 boys junior varsity soccer team includes members (from left, back) Sam Drennan, Bryce Hall, Hunter Bryson, Landon Wilbanks, Robert Griffis, Assistant Coach Brad Simpson, Head Coach Jon Marcus Duncan, Assistant...
St. Andrew's Episcopal School's varsity girls basketball team for 2014-15 is (from left, back) Coach Burney King, Ali Garriga, Aftan Cox, Yesenia Davis, Julia Conway, Karilynn Stephens, Krista Stephens, Kristin Boykin,...
The 15th annual celebration of New Summit School's Draw Down and Auction fund-raiser will be February 28 from 6 to 9 p.m. at the New Summit School gym. Funds raised will go toward student scholarships,...
James and Teresa Harvey of Brookhaven announce the engagement of their daughter, Erica Jo Harvey, to William Theodore Lloyd Jr., son of William Theodore Lloyd Sr. of Jackson and Debbie Keller of Madison.
The bride-elect is the...
Mr. and Mrs. Earnest Edward Jackson Jr. and Mr. and Mrs. Edwin Hall Vickery announce the engagement of their daughter, Anne Elizabeth Eastland Vickery, to Cole McKee Richardson, son of Dr. and Mrs. Charles David Richardson of Hattiesburg....
AP English Literature classes in Jackson Academy use props to help liven up their in-class readings. For a recent review of "Hamlet," students used crowns, horses, jester hats, and more to help re-enact the story...
The Madison Central High School Mystix Dance Team includes members (from left, back) Bailey Durfey, McKenzie Wilbourne, Lily Turnbull, Brooklyn Hutchinson, Sydney Brown, Courtney Johnson, Grace Post, Skylar Holtsinger; (middle row...
- Marketing
- Board rethinks raising MCEDA's debt limit
- More downtown apartments planned
- Miss Steen and Avalon to wed February 22 at St. Peter Church
- County working to get state-aid money back
- New inductees
- Miss Blackstone, Love to exchange vows in Baton Rouge service
- Movie theater planned as part of the District at Eastover
- Colonial rezoning postponed; no agreement between parties
- Residential building permits up in Ridgeland and Madison County
- In memoriam
- Busy with potholes
- A Conversation with Valerie Linn on Magnolia Speech School
- City to allow Northpointe to install one access gate
- Run for the Gold: Peter Miazza qualifies for 5,000-meter race in Senior Olympics; now in training
- House passes improvement districts
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- Proposed landfill permit denied by state board
- More downtown apartments planned
- Teddy Roosevelt quotes worth remembering
- Board luncheon
- Homecoming queen
- Miss Steen and Avalon to wed February 22 at St. Peter Church
- Historic Places, Meeting scheduled to inform Belhaven residents about National Register application
- County working to get state-aid money back
- In memoriam | 03/08/2015 - 7:22am
- Areas close to reaching goals for obtaining fiberhood status | 03/04/2015 - 4:47pm
- Busy with potholes | 03/04/2015 - 4:45pm
- Residential building permits up in Ridgeland and Madison County | 03/04/2015 - 4:45pm
- Colonial rezoning postponed; no agreement between parties | 03/04/2015 - 4:44pm
- House passes improvement districts | 03/04/2015 - 4:41pm
- Madison Center Players have a winner with "Female Odd Couple" | 03/04/2015 - 4:41pm
- City to allow Northpointe to install one access gate | 03/04/2015 - 4:37pm
- A Conversation with Valerie Linn on Magnolia Speech School | 03/04/2015 - 4:34pm
- Hinds leads in retail sales growth | 03/04/2015 - 4:26pm
- Candidates qualify for state, county races | 03/04/2015 - 4:23pm
- Old Canton road work | 03/04/2015 - 4:23pm
- Matthew Arnold
12 weeks 2 days ago
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12 weeks 3 days ago
- Thank you for article re development trip to Israel
16 weeks 2 days ago
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19 weeks 6 days ago


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Canadian Scientists Bind High-Temp Superconductor Components With Scotch Tape 97
from the move-over-duct-tape dept.
We've improved Slashdot's video section; now you can view our video interviews, product close-ups and site visits with all the usual Slashdot options to comment, share, etc. No more walled garden! It's a work in progress -- we hope you'll check it out (Learn more about the recent updates).
So the really interesting part of this story - that superconductivity can be induced in high-temperature materials that haven't been grown in proximity - is completely overshadowed by the tape that held the experiment together?
Fuck journalism.
Is it just me or is the 2nd summary deserving of its own post? A room temperature superconductor, if found and practical/abundant, would be one of the greatest discoveries in science.
That is what I meant. That sentence was mangled several times while revising, and apparently I posted a few revisions too early.
Technology-wise, this is an interesting discovery. It would have been equally interesting had the scientist used fly paper or chewing gum to hold the semiconductors together. Once upon a time, this site claimed to offer "news for nerds"... let's not water down the nerdy science with the lowest-common-denominator amazement that versatile materials have many uses.
As a physicist by training, yes, that's exactly what I want.
Porsche: there simply is no substitute. -- Risky Business


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12:03 pm
Mon April 30, 2012
No One Knows The Upsides Of 5, Like A 5-Year-Old
Tell Me More is celebrating its 5th anniversary on NPR's airwaves. It's been quite an exciting journey. Five is a major milestone and no one knows this better than someone who has just turned five. Host Michel Martin hears from some 5-year-olds on "What's Fun About Being Five."


text:
What are these worms?
They devoured all my dill seedlings overnight!
I grow rue to give them a host plant. But rue needs to be FAR away from basil, and it needs poor soils and to be kept dry. Any dill, fennel, basil etc, is planted on the other side of the house.
The rue is usually eaten down every year to the nubs by this caterpillar, and grows back like clockwork.
I have first instars on my fernleaf dill and fennel. The dill is small, so I'm keeping an eye on it and will move them if they get too destructive.
I was going to pull the fennel. It's a zefo fino that just refuses to bulb up. It's not bolting, but it's not fattening at the base, no matter how much dirt I push against it. So I figure now I'll leave it for these caterpillars, pull it once they're gone. Maybe it'll form a bulb by then, LOL.
Yes it is the caterpillar of the black swallowtail.
Wild carrot (Queen Anne's Lace) and wild parsnip are other alternate host plants and easier to grow than rue. In fact they are weeds.
Unfortunately, . the alternate host plants seem to be just that - alternates. The butterflies apparently much prefer to lay their eggs on carrots and Florence fennel and on cultivated herbs like parsley and dill.
One cultivated host that really seems to draw them in is bronze-leaf fennel. It's also a pretty rank perennial grower once it is established, so you don't have to worry much about the caterpillars causing permanent problems.


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The Digital Works of Michael OstermannJuxtapoz // Tuesday, February 14, 2012
There is such a fantastic body of work on Vienna, Austria-based Michael Ostermann's website, we didn't know what to include. Part fine art, digital art, fashion, and photography, Ostermann has built a body of work that is haunting, brooding, and ethereal, almost as if it was taken from 2050 and brought back to life in 2012. Wonderful stuff.
Fashion and Manuel RebolloIllustration // Monday, January 30, 2012
Manuel Rebollo is a Graphic Designer and Illustrator based in Salamanca, Spain. He studied Graphic Design at Salamanca Art School and currently works freelance in the field of design and illustration creating rich, high fashion, high contrast portraits of the drastically stylish.
The Skull Watch by Richard MilleJuxtapoz // Tuesday, January 24, 2012
Don't laugh, this is a wll-constructed watch. The luxury Tourbillon RM 052 Skull Watch by Richard Mille is limited to 21 pieces (15 in titanium, 6 made of white gold) and features one very obvious skull right in the center.
Juxtapoz presents Soles4Souls @ LAB ArtJuxtapoz // Tuesday, January 24, 2012
In collaboration with Iron Fist, LA-based footwear, apparel, and accessory brand, Juxtapoz presents Soles4Souls event, Wednesday, January 26, a Shoe Art Exhibit and Charity Auction. Art & Sole features one of a kind custom art on 40 pairs of high heel shoes by 40 worldwide artists.
Classic: Thierry Mugler's Metropolis FashionJuxtapoz // Monday, January 02, 2012
For his fall show in 1995, visionary French fashion designer Thierry Mugler created this downright sexy Metropolis-inspired she-robot costume. Is this a glimpse into our fashion future, when sex-pot robots rule the Earth? We won't be complaining...
Harmony Korine's "Snowballs" for Proenza SchoulerJuxtapoz // Wednesday, December 28, 2011
One of our favorite interviews from this past year was our conversation with Harmony Korine, featured in our July issue in conjunction with his work on the yet-to-be-seen Rebel project. Korine teamed up with fashion line Proenza Schouler twice over the past two years on short films, the latter being Snowballs that premiered at Paris Fashion Week in late September. Watch and be slightly uncomfortable after the jump . . .
James Jean Opens OVM WebstoreJuxtapoz // Monday, December 12, 2011
James Jean has had a very busy year (solo show at Martha Otero, video with Juxtapoz, monograph Rebus being released) but something a bit unexpected opened up: Jean began developing a line of fine jewelry, scarves, and objects with support from my friends in Japan that has culminated in a new webstore of Jean products, OVMLove.com.
S.O.TERIK: Year In Review Event in Los AngelesJuxtapoz // Thursday, December 08, 2011
Art and apparel company S.O.TERIK hosts their year in review event tonight, December 8, at their Los Angeles S.O.TERIK Factory located in the heart of downtown LA, between Hope and Grand. The crew and guests will be celebrating with music, live art by , all while enjoying some free food and drinks.
Mayfourteenth Trunk Show @ Welcome Stranger, SFJuxtapoz // Saturday, November 26, 2011
Juxtapoz contributor, Benjamin Belsky, will be at San Francisco's Welcome Stranger to showcase his sunglass and eyewear brand, Mayfourteenth, and the new collection. If you are in the Bay Area, head over to Hayes Valley, get some Blue Bottle, and perhaps some new frames.
Back Talk: A Conversation with Sebastian MasudaJuxtapoz // Wednesday, November 23, 2011
An icon of Harajuku Kawaii culture and the founder of %6DOKIDOKI, Sebastian Masuda is one of the most recognized figures of cutting-edge Japanese pop culture. In 2009, he created and directed the "Harajuku Kawaii Experience," a world-tour fashion show and talk show event, drawing more than 40,000 fans to the event in San Francisco. This December in Los Angeles, he will launch the world debut of RUNE BOUTIQUE with MEDICOM TOY.


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Biffle Takes Pole for Hollywood Casino 400
When the field rolls out to take the green for the Hollywood Casino 400 on Sunday, a first time pole sitter at Kansas Speedway will lead the field to the green.
Greg Biffle turned a lap at 174.887 mph to grab his first pole at Kansas Speedway and second of the 2011 season.
Local favorite Carl Edwards turned the second fastest lap in qualifying at 174.751 mph. This will be his 19th top 10 start of 2011.
Local favorites Clint Bowyer and Jamie McMurray will start 24th and 29th, respectively.
Tickets are still available for the Hollywood Casino 400 and the Kansas Lottery 300 this weekend and are available by calling 866-460-RACE (7223) or by visiting www.kansasspeedway.com. Parking at Kansas Speedway is always free and fans may bring a 14x14x14-inch soft-sided cooler filled with their favorite food and beverages.
Related Articles
- Shooter Jennings to Play Pre-Race Concert at Kansas Speedway
- Nickelodeon Announces Entitlement Sponsorship of SpongeBob SquarePants 400 NASCAR Sprint Cup Series race at Kansas Speedway, May 9
- Kasey Kahne Appearing at the Finish Line on May 9
- Kansas Speedway Season Ticketholders Headed to Daytona 500
- NASCAR Recognizes Kansas Speedway's Medical Director at Annual NASCAR Racing Operations Summit


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ppl have so many questions... ive heard a llot of "what if.......?"
give me some of your wat if questions.. and tell me how and why you thought of them!! so it doesnt turn to a bs spam thread
some of mine are
1.] wat if electricity was never invented?
i thoguht of this in history class
2.] why is blood red?
why cant it be clear.. iwa s thinkin about this wen i found out i got blood all over my shirt from a little piece of plastic... lol
also if you have any werd questins...post em here too!! just BE SURE TO TELL WHERE YOU HEARD IT, OR WHY YOU THOUGH IT, OR WAT IT MADE YOU THIK OF... SO IT WONT BE CLOSED!!
SUCH AS: if a tree falls in aforest while noones there does it still mkea sound?


text:
2 people found this helpful
"OK place if you don't interface with the owner LLR "
- Comp & Benefits
- Work/Life Balance
- Senior Management
- Career Opportunities
I worked at Roll Global
When they let you do your jobs without the owner's interference, you can get the resources to approved fairly easy.
Owners make sure sure IT will never work. They interfere with common processes and maintenance procedures. So things are destined to break and people to fail.
Let the specialist make recommendations based upon experience and knowledge. You can set overall direction and goals, but don't micromanage.
- Any Location
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1 person found this helpful
"Monumental waste of time.... "
- Comp & Benefits
- Work/Life Balance
- Senior Management
- Culture & Values
- Career Opportunities
I worked at Roll Global full-time (less than a year)Pros
I can't honestly give any pros asides from the fact that I won't have to waste my time working a dead end job.Cons
there is way to much management within the company...most of the time they make decisions without even knowing what is going on from their colleagues. They gps you when doing your store calls...you have a timer built in on the ipad to keep you on track in stores that prompts you to hurry up on your store visits?! A total anti-trust company. You feel like you are being babysat the whole time. I would seriously warn anyone from applying as it is a new company to Canada and they are very unorganized.Advice to ManagementAdvice
communicate to each other to avoid wasting peoples time...have some faith in your staff and don't micro-manage so muchDoesn't RecommendNegative Outlook
"Innovative, fast-paced culture "
- Comp & Benefits
- Work/Life Balance
- Senior Management
- Culture & Values
- Career Opportunities
I have been working at Roll Global full-timePros
Company car, generous benefits and vacation time.Cons
Hard to avoid some pro-bono overtime due to traffic, needs of clients, etc.RecommendsPositive OutlookNo opinion of CEO


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› Find signed collectible books: 'The Blessed Hope: A Biblical Study of the Second Advent and the Rapture'
Jesus Christ is coming again! That is the Blessed Hope which has since the earliest days of the church energized biblical Christians looking for the full revelation of Gods redemption But even among those who have most devoutly looked forward to the second coming of the Lord there have often been disputes about its nature. At their sharpest, these disputes can lead to the breakdown of fellowship among those who should be standing firmly together against unbelief. Through its many printings, this book by George Eldon Ladd has proved to be a helpful guide for Christians who want to discern clearly the basic biblical teachings about the Blessed Hope. Writing not for his fellow scholars as much as men and women in the pews, Ladd, whose numerous studies of New Testament interpretation earned him the reputation of being one of contemporary evangelicalisms leading thinkers, sketches the history of interpretations of Christs second coming and then carefully and lucidly examines the biblical passages on which this doctrine is based. Ladds conclusion is that the blessed hope is the second coming of Jesus Christ, not a pretribulation rapture of believers in a secret coming of Jesus. Yet he concludes, too, that there should be liberty and charity within the Christian community for all who hold to the expectation of the blessed hope and appearing in glory of our great God and Savior Jesus Christ.
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In Crucial Questions About the Kingdom of God, George Eldon Ladd brings to the modern student of eschatology both an up-to-date survey of the literature of the kingdom of God and a fruitful discussion of some of the more crucial problems facing this concept which lie at the root of the controversies over this central theological subject. / Rather than uncritically repeating the old inherited positions, Ladd makes a thorough and independent study oriented to the entire stream of biblical interpretation, and presents here the conclusions he feels the biblical data requires. Including the important literature on the subject in the French, German, and English, the author treats briefly the eschatological interpretations of the ancient, medieval, and modern writers. The section focusing on modern interpreters covers the formulations since Schweitzer and concludes with the modern search for a synthesis of the kingdom as futuristic and as a present reality. / Feeling the biblical evidence requires a premillennial interpretation of the concept of the Kingdom of God, Ladds own exegesis of the futurity and presence of the kingdom and of a millennial interregnum represents an informed and critical pre-millennialism. He presents these formulations over against the popular dispensational form of the chiliastic position and against the amillennial position whose criticism of premillennialism, the author says, is limited to only its special dispensational form.
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Ladd, whose work has included much technical study of the doctrine of the kingdom, here presents a practical and devotional scriptural study of the many aspects of the kingdom, based on the parables, the Sermon on the Mount, and other key passages.
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This book has hardback covers.Ex-library,With usual stamps and markings,In good all round condition.Dust Jacket in fair condition.
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Christ is coming again. Since the first century, Christians have agreed that Christ will return. But since that time there have also been many disagreements. How will Christ return? When will he return? What sort of kingdom will he establish? What is the meaning of the millennium? These questions persist today. Four major views on the millennium have had both a long history and a host of Christian adherents. In this book Robert G. Clouse brings together proponents of each view: George Eldon Ladd on historic premillenniallism, Herman A. Hoyt on dispensational premillennialism, Loraine Boettner on post-millennialism and Anthony A. Hoekema on amillennialism. After each view is presented, proponents of the three competing views respond from their own perspectives. Here you'll encounter a lively and productive debate among respected Christian scholars that will help you gain clearer and deeper understanding of the different ways the church approaches the meaning of the millennium.
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After surveying the debate over eschatology, Ladd discusses the promise of the kingdom, the fulfillment of the promise, and the consummation of the promise. Throughout the book he develops his thesis that the kingdom of God involves two great movements--fulfillment within history and consummation at the end of history.
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Ladd's magisterial work on New Testament theology has well served thousands of seminary students since its publication in 1974. Enhanced and updated here by Donald A Hagner, this comprehensive, standard evangelical text now features augmented bibliographies and two completely new chapters on subjects that Ladd himself wanted to treat in a revised editionthe theology of each of the Synoptic Evangelists and the issue of unity and diversity in the New Testamentwritten, respectively, by R. T. France and David Wenham.
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I share peoples concern about the new Mario Golf being light on content. The Mario tennis game was good fun but I eventually tired of it due to the lack of content. Hope that they pack a ton of content into Mario Golf. I too still play the GC game but find the short putting really difficult.
On the whole I think the 3ds is looking good. I certainly don't regret buying it. Can't wait for Animal Crossing!
#9370695, By Mr-Zoo Nintendo 3DS
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text:
He cleared the Hynix hearing from his schedule last week, and is under pressure to file his latest ruling on remand since Judge Robinson submitted hers already.
That makes RMBS a gamble since there could be a wild swing in either direction without warning very soon. JMHO.
You know RMBS will be paying legal costs for both MU and Hynix. RMBS will be owned by them.
Hard to believe that this trial is still hung up with no decisions. Just proves the powers to be is stronger then Rambus. No justice for long term Rambus shareholders. Glad I got out a year ago! Stock is still at the bottom! I remember it was in the low 100s back in 2000!
In the end, when Rambus finally goes bankrupt, it will be the shareholders who pay by watching their investment to to $0.
According to HJW's schedule, he has a hearing at 9am PST and nothing after, and then he is unavailable until next Tuesday.
I take this to mean that he will either rule today or we will be waiting another week or more.
I thought you were certain that we were going down to 2 after his decision. whats this gamble business?
I'm confident, and so I am short this hasn't changed. I do acknowledge, even though I believe the outcome will favor my position, that this is somewhat of a gamble on my part because there is no certainty. You dig?


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The International tickets on sale this Friday, from $99, $199, & $499
Valve's DOTA 2 tournament, The International, is taking place on July 18 through July 21 in Seattle at the KeyArena this year. General admission tickets are $99, floor seats are $199, and a VIP package for $499 will get you access to all six days of playoffs, floor seating, VIP meet & greets, and access to the after party. Tickets go on sale this Friday at 3PM PDT through Ticketmaster.
I'm bewildered, and also jealous, that anyone would want to pay $499 to watch other people play a videogame of any kind. Then again the fandom around DOTA 2 is nuts. To the point that the DOTA blog has a timezone guide for all the people around the world that are looking to purchase tickets.
Record breaking competitive Dota 2 match lasts over 3 hours
2:00 PM on 03.22.2015
The Dota 2 Asian Championships now has the second highest prize pool in eSports history
12:15 PM on 02.06.2015
This is it: Watch Dota 2's The International grand finals live
12:00 PM on 07.21.2014
Dota 2 Updates, Screenshots, & Videos
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The Dota 2 Asian Championships now has the second highest prize pool in eSports history
12:15 PM on 02.06.2015


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Latest LePhone Stories
Latest LePhone Reference Libraries
2014-01-12 00:00:00
The LePad is a line of tablet computers sold by Lenovo in China. It was released in China in 2011. The LePad uses the Android 2.2 operating system, with either a Wi-Fi or 3G connection. The display features a 10.1-inch screen with a front facing camera for video calling, and has a battery life of eight hours. Outside china, in 2012, Lenovo released other versions of the LePad, under the name IdeaTab, A1, Yoga, and ThinkPad. The ThinkPad's operating system was upgraded to the Android...
Word of the Day
- The governor of a province or people.
The word 'ethnarch' comes from a Greek word meaning 'ruler of a tribe or nation'.


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Come enjoy 2 days of fun in beautiful and historic open farmland, complete with great bands and tons of ales and lagers from North Carolina and select out-of-state breweries.
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Just in time for NC Beer Month is a Cooking with Beer Class featuring Sycamore Brewing.
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Mount Holly (0.19 mile)
Extensive menu items, reasonably priced.
Mount Holly (0.33 mile)
Our customers say we have the "Best Burger In Town"...and are made with 100% fresh ground beef. Also, try the pizza buffet and appteizers.
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A few weeks ago, I was talking with one of the artists at Salado Glass Works in Central Texas. I was wearing my Houston Colt .45s cap, and he said:
"So, you're into guns?"
"No," I told him. "This is a baseball cap."
"Really?" he said. "I've never heard of a team with that name."


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Single girl looking for friendship first and hopefully grow into more. I am relationship minded person who has no time for games so if your not serious about looking for someone to spend your life with please move on.
Join OkCupid
Find better matches with our advanced
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52 • Northampton, PA • Woman
I'm looking for
- Men
- Ages 47–57
- Located anywhere
- Who are single
- For new friends, long-term dating
My details
- Last online
- Jul 20, 2014
- Orientation
- Straight
- Ethnicity
- White
- Height
- 5′ 2″ (1.57m)
- Body type
- Full figured
- Diet
- Mostly anything
- Smokes
- Yes
- Drinks
- Socially
- Drugs
- Never
- Religion
- Christianity, and somewhat serious about it
- Sign
- Cancer, and it matters a lot
- Education
- Graduated from two-year college
- Job
- Medicine
- Income
- Rather not say
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- Single
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- Offspring
- Has kids, but doesn't want more
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- Has dogs
- Speaks
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Work full time and spend time with family and friends
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My caring nature and my blue eyes
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Help your potential matches find common interests.
I enjoy reading a variety of books, prefer comedies but do like scary and action movies also. I would say italian and chinese are on my top likes but i can cook Pa dutch food. Prefer country and rock.
The six things I could never do without
Think outside the box. Sometimes the little things can say a lot.
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Global warming, lunch, or your next vacation… it's all fair game.
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RECIPE: Lemon Cake Top Pudding
Preheat oven to 375°
2 Tbsp.butter, softened
1 1/2 c. sugar
1/3 c.flour
1/4 tsp. salt
1/2 c. fresh lemon juice
1 tsp. fresh lemon peel
3 eggs, separated
1 1/4 c. milk
Blend butter & sugar;add flour, salt,juice & peel.
Stir in the 3 beaten egg yolks that you've mixed with the milk.
Fold in stiffly beaten egg whites.
Pour into casserole dish. Place casserole dish in pan of water-bake for 45 min.Serves 6
Colleen=I've tried it in orange, using orange juice concentrate in place of the lemon juice-haven't ever thought about using lime -have to give it a try next time.
I do have a recipe for this "type" of pudding that's just cinnamon--tastes like a big sugar cookie with sauce-will post if anyone's interested.
About 40 years ago, my mother used to make a lemon sheet cake -- when it was still warm, she used a toothpick to poke holes in it and poured on some type of hot lemon glaze that kind of crystalized on the top. I think it used Jello -- but I don't know if it was in the cake or the glaze (I was thinking it was in the glaze). I've looked through all her recipes and can't find it -- I wish I had asked her when she was still with us :(
Any ideas?


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Dr. Kochy Tang, DO
Internal Medicine
- 5757 Wayne Newton Blvd
Las Vegas, NV 89111
- 2 Locations
- (702) 261-6707
Dr. Kochy Tang graduated from the Western Univ of Health Sciences College of Osteopathic Medicine of the Pacific in 1998. She works in Las Vegas, NV and 1 other location and specializes in Internal Medicine. Dr. Tang is affiliated with Desert Springs Hospital Medical Center, Saint Rose Dominican Hospital - San Martin and Sunrise Hospital & Medical Center.
Gender: Female
Languages Spoken: Not Available
Internal Medicine
Medical School: Western Univ of Health Sciences College of Osteopathic Medicine of the Pacific; Graduated 1998
*This physician has multiple office locations. See Office Information for details.


text: Thankfully we were offered a room here through an unusual agreement with the Golden Host Resort next door, as the GHR lost our reservation. We were happy to get it with minimal fuss. Friendly, accommodating staff. Borderline suspicious-looking pool, but it didn't kill me swimming in it three afternoons. The room was clean, but there were some stains here and... More


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Articles related to: Fraud
Headline, News »
By Karen Stokes
Unemployment compensation is a helpful benefit for people experiencing gaps in employment that need the money to provide for their household. Even though unemployment is presently the lowest since 2008, unfortunately some Wisconsinites that are ineligible for unemployment benefits are fraudulently helping themselves to these funds and in doing so are hurting residents, taxpayers and businesses.
Clifton Brooks (not his real name), who worked for years, lost his job due to downsizing, but recently went back to work and believes unemployment was important for his family. "It helped a …
News, Urban Business »
The Better Business Bureau (BBB) has been receiving numerous complaints and inquiries from consumers across the country about fraudulent job offers for positions as "mystery" or "secret shoppers."
Consumers report receiving a letter, generally by postal mail, containing instructions, and accompanied by a check. The instructions usually direct the recipient to deposit the check, spend a specific amount of money in local, retail stores as a "secret shopper" and send the remaining amount back via Western Union or MoneyGram. In most cases, consumers are instructed to spend a couple hundred dollars, …
News »
Due to the continued focus of the Department of Children and Families and Milwaukee law enforcement to stop fraud in the Wisconsin Shares program, another child care provider was sentenced last week for stealing from taxpayers. This is the second provider sentenced this month for scamming the Wisconsin Shares program.
Shawn Nash, who handled the billing for Kinder World Child Care, entered a guilty plea for felony theft in March. Today, she was sentenced to 20 months in jail with 20 months supervised release and ordered to pay $100,000 in restitution. …
Headline, News, Upcoming Events »
Unity Caucus and Senator Taylor present summit with DCF and local officials
Compiled by Courier Staff
Senator Lena C. Taylor (D) Milwaukee) this week announced a child care summit to take place Saturday, February 27th in Milwaukee. The summit will offer advice ranging from how to open a daycare center to questions about receiving micro-loans. In addition, information about Wisconsin Act 76, the recent changes to the Wisconsin Shares Program, will be shared and discussed.
The summit's objective is to offer advice on not only various concerns that might occur in operating a …


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Heritability Of Autism Folic Acid
A selection of articles related to heritability of autism folic acid.
Original articles from our library related to the Heritability Of Autism Folic Acid. See Table of Contents for further available material (downloadable resources) on Heritability Of Autism Folic Acid.
- Herbs of Folklore and Modern Medicine: White Willow, Aloe Vera, and Garlic
- Many of the medicinal herbs we use today have been studied by modern science for application in today's medical field. These studies have shown that our ancestral folk uses of these herbs were very much correct in their applications. Here we will explore...
Earth Mysteries >> Herbalism
- Make Your Voice Heard As You Tread Gently On Our Mother Earth
- Making Your Voice Heard Before buying crystals, remember to ask where the crystal comes from and how it was mined. A lot of crystals are strip mined, which is very harmful to the land, and when handled often have a feeling of being psychically fractured or...
Paganism & Wicca >> Daily Life
- OBE, Understandability & Memory Download Problems
- The mind boggles at the potential complexities of interdimensional subtle-body relationships and energetic conflicts created during OBE; most especially during wake-induced OBE. Consider the memory compatibility problems that could arise between different...
Astral Projection >> Out of Body Experiences
- The potentized remedy
- Many people think that homeopathic medicines are made from plants, but in fact the remedies can be made from anything. The substances are made from plants; poisonous and non-poisonous plants, herbs and toad-stools minerals, like sulfur, sodium chloride or...
Body Mysteries >> Homeopathy
- Colchicum autumnale
- This beautiful but very poisonous plant grows in moisty meadow-lands and woods; it will disappear when the ground is too dry. In ancient Greek medicine this plant was known as 'the soul of the joints' because it cured the acute pains of rheumatism and gout....
Remedies >> Remedies C
- Ostara - The Vernal Equimox
- ABOUT OSTARA | RITUAL | FOODS | REFERENCES ABOUT OSTARA Ostara (pronounced Oh-star-ah) is also called Eostre, Easter, Vernal Equinox, Spring Equinox, and the First Day of Spring. This is the time of year when day & night are equal, and heralds the return of...
Holidays >> Ostara
Heritability Of Autism Folic Acid is described in multiple online sources, as addition to our editors' articles, see section below for printable documents, Heritability Of Autism Folic Acid books and related discussion.
Suggested Pdf Resources
- Gene?environment interactions, folate metabolism and the
- underlying causes, a single intervention, folic acid supplementation given in the . indicate prominent genetic and heritable contributions leading to failure of .. complex genetic disorders, like schizophrenia and autism.
- media.wiley.com
- paranoid schizophrenia, and autism. Example 2: . Treatment involves Folic Acid , B-12, GABA ,Zn,.
- www.alternativementalhealth.com
- Metabolic biomarkers of increased oxidative stress and impaired
- Background: Autism is a complex neurodevelopmental disorder that usually presents symptoms associated with several heritable genetic diseases. [see: Online supplement containing 400 μg folic acid and 3 μg vitamin B-12.
- www.ajcn.org
- Folate regulation of axonal regeneration in the rodent central
- The folate pathway plays a crucial role in the regeneration and repair of the adult CNS after injury.
- www.neurosurg.wisc.edu
- Folate and long chain polyunsaturated fatty acids in psychiatric
- dissertations.ub.rug.nl
Suggested Web Resources
- Causes of autism - Wikipedia, the free encyclopedia
- Heritability contributes about 90% of the risk of a child developing autism, but the .
- en.wikipedia.org
- Autism Jabberwocky: Folic Acid Increases the Risk of Autism aka the
- Sep 22, 2010 Folic Acid Increases the Risk of Autism aka the Dangers of Bad Data .. Study : Genetic Heritability and Shared Environmen...
- autismjabberwocky.blogspot.com
- Autism Jabberwocky: Is Too Much Folic Acid a Bad Thing?
- Aug 27, 2011 Folic Acid Increases the Risk of Autism aka the Dangers of Bad Data. As I talked Study : Genetic Heritability and Shared Environmen...
- autismjabberwocky.blogspot.com
- Maternal supplementation of folic acid and function of autism gene
- Maternal supplementation of folic acid and function of autism gene synaptic may change gene expression in the absence of heritable mutations in DNA.
- www.autismspeaks.org
Great care has been taken to prepare the information on this page. Elements of the content come from factual and lexical knowledge databases, realmagick.com library and third-party sources. We appreciate your suggestions and comments on further improvements of the site.
Heritability Of Autism Folic Acid Topics
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Short-handed Huskies prepare for NIT opener
UConn is limping into its NIT opener against Arizona State tomorrow night in Storrs.
UConn announced today that Lasan Kromah has officially joined the men's basketball program. He has one year of eligibility and will attend graduate school.
A 6-foot-5 swingman, Kromah graduated from George Washington University, playing three seasons for the Colonials. He started 71 career games, averaging 11 points, 4.1 rebounds and 2.1 assists overall.
"I think Lasan can be a great facilitator for us," coach Kevin Ollie said in a released statement. "I love his versatility on the court. He can help us in so many ways."
Last season, Kromah ranked second on the team in scoring at 10.1 points and averaged 3.7 rebounds. He converted 47.6 percent from the field and 67.5 percent from the foul line.
Kromah, an Atlantic 10 All-Rookie team pick in 2010, played for current UConn assistant Karl Hobbs at George Washington. He sat out his sophomore season with a left foot injury.
He will pursue a master's degree at UConn in Educational Psychology.
"We're excited to have Lasan join our program," Ollie said. "He is the type of player and person who is going to make us stronger as a team with his ability on the court as well as his high character."
UConn is limping into its NIT opener against Arizona State tomorrow night in Storrs.
Prior to its impressive American Athletic Conference Championship tournament run, UConn looked more like an NIT than NCAA post-season team.
UConn associate head coach Glen Miller didn't plan on getting much sleep on Saturday night.
Today's American Athletic Conference Championship semifinal doubleheader is underway here at the XL Center in Hartford. A crowd in the 12,000-13,000 range is expected for the UConn-Tulsa game. Tip-off time is 5 p.m.
UConn did what it was supposed to do on Thursday night.
Two of the American Athletic Conference's biggest rivals will battle tonight in tournament quarterfinal action at the XL Center in Hartford.
Daniel Hamilton had a long list of people to thank after becoming the sixth UConn player to receive a conference rookie of the year award.
UConn sophomore Amida Brimah was named the American Athletic Conference defensive player of the year today.
UConn placed three players on All-American Athletic Conference basketball teams.
The pairings are set for American Athletic Conference Championship tournament.
The regular season is officially over for UConn.
UConn is back on the road for its regular season finale.
UConn suffered a crushing 54-53 loss to Memphis Thursday night at Gampel Pavilion, spoiling Senior Night.
UConn is finally riding a nice wave of momentum after a bumpy regular season.
The Huskies secured a signature victory that they so desperately needed.
Court orders Lyme property owner to pay $650,000 for violations
Groton will need magnet programs to solve racial imbalance, consultant says
Mystic market owner says Coogan Farm parking is what worries him
Griswold man drags undercover trooper with car in attempt to avoid arrest
Amanda Knox and ex-boyfriend's murder conviction overturned by Italy high court
Six early dismissal days proposed for Groton schools to give teachers more training time
Students question administration's response to professor's Facebook post
Groton will need magnet programs to solve racial imbalance, consultant says


text:
Total AG Ratings: 58,843
too ez fo me i was done in 5 mins
you can cheat on dont touch blue and dont touch green you just left click and you can touch all colors
I can't clip the toenails fast enough.. :(
i got to level 80
what is the answer for number 4
what is the answer of number 60 please
c dure putin !!!!!
beat it in 10min easy.
so inoying but at the same time so awsome. i loved it it just got carryd away with every thing. so dont lissen to all thos haters. its callingin, but fun! :)


text:
Welcome to Egypt!
Embark on an unforgettable journey to an ancient past, where incredible treasures are abound along the banks of the river Nile. This fascinating, and world famous river is steeped in history, wonders and intrigue of an age gone by. Delve into the life of the Gods and Kings, witness their temples, and opulent tombs, bringing this fascinating era back to life. The immediate lush green banks of the Nile, untouched by time is littered with sugar canes and waving barefooted children, giving way to the harsh desert mountains and the calling to prayer.
You decide!
A 7 night Nile Cruise is a fantastic way to explore Egypt, but If any of the itineraries featured on our website don't quite fit into your plans, then Nile Cruises Direct can tailor make your perfect holiday for you; (if it is possible, then we can do it!). Let us know what you would like to see or visit in Egypt, or any ideas that you have, and we can come up with a suggested itinerary, provide valuable advice, and provide a comprehensive quote for you to have a look at.
What's Included?
All of our Nile Cruise or holiday packages include flights, supplements, full excursion packages, local representation, and all transfers are by air conditioned vehicle with a meet and greet service at your destination airport. Our holidays are ATOL bonded for your peace of mind, and we are members of the TTA for your financial protection.
7 Nights Nile Cruise from only £749 per person
What better way than to explore the fascinating wonders of the Nile than 7 nights on-board one of our cruise vessels. Providing a prefect a perfect platform to experience all that this world famous river has to offer, a cruise really does let you see it all.
Accompanied by a fully qualified guide, your week on-board is packed full of fascinating visits to tombs, temples and ancient sites.
Our cruise ships have been carefully selected to make sure you holiday is right just for you. Choose from either our deluxe, superior-deluxe, or ultra-deluxe vessels.
5* Deluxe Nile Cruise, Full Board, Full Excursion Package from £749pp
10 Nights Red Sea and Nile Cruise from £779 per person
Using the Easyjet flights from London Gatwick will give you 3 fabulous nights in the Red Sea Resort of Hurghada. Relax at the beach, or make the most of the sublime snorkelling and scuba diving waters that Hurghada is famous for. We can suggest a number of hotels to suit your needs, or if you have a hotel in mind; just let us know.
You are then transferred directly from your hotel in Hurghada to Luxor by air-conditioned vehicle to join your chosen Nile cruise; all accompanied by a transfer representative.
3 Nights Hurghada & 7 Nights Nile Cruise from only £779pp
11 Nights Red Sea and Nile Cruise from only £829 per person
Manchester Departure
Don't worry if you can only travel from Manchester, although flights are limited into the Nile delta, we can offer a fantastic 11 night itinerary that won't leave you rushing to catch your flight home.
4 Nights Hurghada & 7 Nights Nile Cruise from only £829pp


text:
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Flatwoven in India from the finest wool, this area rug is not for the cautious interior. Somewhere between ikat and rorschach, this intriguing—and reversible—textile demands further examination by your eyes and enjoyment by your toes.
Vacuum regularly. Rotate occasionally to ensure even wear. Blot spills immediately with a clean, damp cloth. Professional cleaning recommended every 2-3 years. Avoid direct sunlight to reduce fading. Use of a rug pad recommended.
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I'm an outgoing, positive guy, happy to meet new people and hear their stories over a cup of coffee.
When travelling I really enjoy random walks around the city, armed with a camera; I enjoy street photography.
I am open to new experiences that would help me to leave my comfort zone!


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en algun lugar de mexico
centro escolar university (nutrition department)
Mamador Mexicana
mexican girl
con mi ex en el hotel 2
sex guerrero
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Putita mexicana mamando la polla
Recuerdas mi vagina M.A.Guadarrama?(ENEP)
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Waitress Picks Up Tab For Furloughed Soldiers
Waitress Picks Up Tab For Furloughed Soldiers
Sin City Saints Episode 1: The Fool Monty
Unlock your personal NFL Now stream by signing in to NFL.com
Must Watch
When a New Hampshire waitress overheard two of her customers saying they were furloughed soldiers, she decided to help out. It was a typical Wednesday afternoon shift for Sarah Hoydell at the Ruby Tuesday in Concord when two service members came in for lunch and sat in her section.
When a bone-headed incident threatens to ruin the Saints' season, owner Jake Tullis and his staff jump into crisis mode. The league sends a gorgeous, no-nonsense lawyer, Dusty Halford, to oversee a disgruntled Jake.
An old issue rears its ugly head for Jake. As Dusty plots his demise, she has a Vegas fling to get over her ex. Byron and Sam attempt to convince a player to come out of retirement to play for the Saints.
The group has to go on the offensive against a claim that Greendale graduated a dog; Abed creates an attack ad discounting the dog; Britta, after pooping her pants, connects with Elroy over the band "Natalie is Freezing;" Chang shoots a single person porn.
On "Access Hollywood Live," Kit Hoover brought up how Groban's music often gets played in the background of romantic settings. But here's the question, does Josh Groban listen to Josh Groban in those moments? Says Groban, "It doesn't matter how good people think you are, it's to you, it's like hearing yourself on a voicemail, you're like, oh god, that's how I sound? So no, it's the anti-viagra for me."
Kristian Nairn welcomes fans to the first night of the US leg of the Rave of Thrones tour at Exchange LA. This exclusive #YahooLive event starts at 10pm Pacific on March 26th.
Sin City Saints Episode 1: The Fool Monty
Sin City Saints Episode 2: Smoke and Mirrors
Community Episode 3: Basic Crisis Room Decorum
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|Industry Recognition
|Professional Conduct
Education Stephen M. Fernandez received his law degree, with honors, from the University of Florida College of Law. While in law school he focused on... more
Steve has an unbridled passion for the law and diligently fights for his client's rights. Time after time, I've watched Steve courageously fight big... more
Stephen has always done a fantastic job protecting the rights of our mutual clients. His trial preparation and his ability to negotiate is superior.... more