text:
Are you Kyle D Holen?Claim your profile
Publications (54)255.37 Total impact
Article: A multicenter phase 1 study of γ -secretase inhibitor RO4929097 in combination with capecitabine in refractory solid tumors[Show abstract] [Hide abstract]
ABSTRACT: Background RO4929097 is an oral inhibitor of γ -secretase that results in Notch signaling inhibition. Prior work has demonstrated that Notch signaling inhibition enhances chemotherapy sensitivity of cancer cells. This phase I study was conducted to determine maximum tolerated dose (MTD), toxicities and efficacy of RO4929097 and capecitabine in advanced solid tumors. Methods Patients with refractory solid tumors received capecitabine at a fixed dose of 1,000 mg/m(2) twice daily with escalating doses of RO4929097 on a 21-day cycle in a 3 + 3 design. Capecitabine was administered for 14 days and the RO49029097 once daily, 3 days per week, both for a 21 day cycle. Results Thirty patients were treated on six dose levels (20 to 150 mg). The maximally tolerated dose was not reached. One dose limiting toxicity was observed at each level 3 through 6 (hypophosphatemia, fatigue, and nausea/vomiting). Three confirmed partial responses were observed: two patients with fluoropyrimide-refractory colon cancer and one patient with cervical cancer. Autoinduction of RO4929097 was demonstrated with increasing dose levels and duration. Conclusions The recommended phase 2 dose is capecitabine 1,000 mg/m(2) orally twice daily on days 1 through 14 with RO4929097 20 mg orally once daily on days 1-3, 8-10 and 15-17 with a 21 day cycle. Clinical benefit was observed in cervical and colon cancer. Autoinduction of RO4929097 was seen both with increasing cycle number and increasing dose. Plasma concentrations of RO4929097 were above those needed for Notch inhibition.Investigational New Drugs 10/2014; 33(1). DOI:10.1007/s10637-014-0166-6 · 2.93 Impact Factor
Article: A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies.[Show abstract] [Hide abstract]
ABSTRACT: Background A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors. Methods Patients received vorinostat orally once daily on days 1-14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m(2)). Bortezomib dosing was increased using a standard phase I dose-escalation schema. PKs were evaluated during cycle 1. Results Twenty-three patients received 57 cycles of treatment on four dose levels ranging from bortezomib 0.7 mg/m(2) to 1.5 mg/m(2). The MTD was established at vorinostat 400 mg daily and bortezomib 1.3 mg/m(2). DLTs consisted of grade 3 fatigue in three patients (1 mg/m(2),1.3 mg/m(2) and 1.5 mg/m(2)) and grade 3 hyponatremia in one patient (1.5 mg/m(2)). The most common grade 1/2 toxicities included nausea (60.9 %), fatigue (34.8 %), diaphoresis (34.8 %), anorexia (30.4 %) and constipation (26.1 %). Objective partial responses were observed in one patient with NSCLC and in one patient with treatment-refractory soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however, the Cmax and AUC of the acid metabolite were significantly increased on day 2 compared with day 1. Conclusions This combination was generally well-tolerated at doses that achieved clinical benefit. The MTD was established at vorinostat 400 mg daily × 14 days and bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21-day cycle.Investigational New Drugs 10/2013; DOI:10.1007/s10637-013-0029-6 · 2.93 Impact Factor
Article: Vorinostat in combination with bortezomib in patients with advanced malignancies directly alters transcription of target genes.[Show abstract] [Hide abstract]
ABSTRACT: Vorinostat is a small molecule inhibitor of class I and II histone deacetylase enzymes which alters the expression of target genes including the cell cycle gene p21, leading to cell cycle arrest and apoptosis. Patients enrolled in a phase I trial were treated with vorinostat alone on day 1 and vorinostat and bortezomib in combination on day 9. Paired biopsies were obtained in eleven subjects. Blood samples were obtained on days 1 and 9 of cycle 1 prior to dosing and 2 and 6 h post-dosing in all 60 subjects. Gene expression of p21, HSP70, AKT, Nur77, ERB1, and ERB2 was evaluated in peripheral blood mononuclear cells and tissue samples. Chromatin immunoprecipitation of p21, HSP70, and Nur77 was also performed in biopsy samples. In peripheral blood mononuclear cells, Nur77 was significantly and consistently decreased 2 h after vorinostat administration on both days 1 and 9, median ratio of gene expression relative to baseline of 0.69 with interquartile range 0.49-1.04 (p < 0.001); 0.28 (0.15-0.7) (p < 0.001), respectively, with more pronounced decrease on day 9, when patients received both vorinostat and bortezomib. p21, a downstream target of Nur77, was significantly decreased on day 9, 2 and 6 h after administration of vorinostat and bortezomib, 0.67 (0.41-1.03) (p < 0.01); 0.44 (0.25-1.3) (p < 0.01), respectively. The ChIP assay demonstrated a protein-DNA interaction, in this case interaction of Nur77, HSP70 and p21 with acetylated histone H3, at baseline and at day 9 after treatment with vorinostat in tissue biopsies in most patients. Vorinostat inhibits Nur77 expression, which in turn may decrease p21 and AKT expression in PBMCs. The influence of vorinostat on target gene expression in tumor tissue was variable; however, most patients demonstrated interaction of acetylated H3 with Nur77, HSP70, and p21 which provides evidence of interaction with the transcriptionally active acetylated H3.Cancer Chemotherapy and Pharmacology 08/2013; DOI:10.1007/s00280-013-2242-6 · 2.57 Impact Factor
Article: A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study.[Show abstract] [Hide abstract]
ABSTRACT: Chemotherapy has yielded minimal clinical benefit in pancreatic and biliary tract cancer. A high-dose, short course capecitabine schedule with oxaliplatin, has shown some efficacy with a lower incidence of palmar-plantar erythrodysesthesia. Achieving high exposures of the targeted agent sorafenib may be possible with this shorter schedule of capecitabine by avoiding dermatologic toxicity. All patients had pancreatic or biliary tract cancer. Patients in both cohorts received oxaliplatin 85 mg/m2 followed by capecitabine 2,250 mg/m2 PO every 8 h x 6 doses starting on days 1 and 15 of a 28 day cycle, or 2DOC (2 Day Oxaliplatin/Capecitabine). Cohort 1 used sorafenib 200 mg BID, and cohort 2 used sorafenib 400 mg BID. Sixteen patients were enrolled. Across all cycles the most common grade 1 or 2 adverse events were fatigue (10 pts), diarrhea (10 pts), nausea (9 pts), vomiting (8 pts), sensory neuropathy (8 pts), thrombocytopenia (7 pts), neutropenia (5 pts), and hand-foot syndrome (5 pts). Grade 3 toxicites included neutropenia, mucositis, fatigue, vomiting and diarrhea. Cohort 1 represented the MTD. Two partial responses were seen, one each in pancreatic and biliary tract cancers. The recommended phase II dose of sorafenib in combination with 2DOC is 200 mg BID. There were infrequent grade 3 toxicities, most evident with sorafenib at 400 mg BID.Investigational New Drugs 12/2012; DOI:10.1007/s10637-012-9916-5 · 2.93 Impact Factor
Article: Economic burden of dermatologic adverse drug reactions in the treatment of colorectal, non-small cell lung, and head and neck cancers with epidermal growth factor receptor inhibitors.[Show abstract] [Hide abstract]
ABSTRACT: Abstract Background: Patients treated with epidermal growth factor receptor inhibitors (EGFRIs) may develop dermatologic adverse drug reactions (ADRs) that may affect patients' quality of life, require medical care, and may lead to substantial costs. This study assessed the economic burden of dermatologic ADRs in colorectal cancer (CRC), head and neck cancer (HNC), and non-small cell lung cancer (NSCLC) patients. Methods: Adult patients with ≥ 1 diagnosis for the study cancer initiated on EGFRIs indicated for CRC, HNC, and NSCLC were selected from a large commercial database (MarketScan Commercial Database [2000-2010]*). For each cancer type, patients were classified into two mutually exclusive cohorts: "ADR" (patients with ≥ 1 ADR following EGFRI initiation) and "ADR-free" (patients without any ADR). Patients were observed from the index date up to the end of continuous healthcare plan enrollment or 90 days after EGFRI discontinuation, whichever occurred first. For each cancer group, the proportion of patients and the incidence rate (IR) of experiencing ≥1 dermatologic ADR were reported. Incidence rate ratios for healthcare resource utilization and monthly incremental costs (2010 USD) were estimated using Poisson regression and generalized linear or two-part models, respectively. Results: Overall, the proportion of patients with ≥1 ADR ranged between 20.5% and 36.4% across cancer groups (IR ranged between 44.2 and 57.4 per 100 patient-years). After adjusting for confounders, in each cancer group, ADR patients had higher incidence of healthcare resource utilization, generally driven by higher incidence of emergency room visits and incurred incremental total monthly healthcare costs that ranged between $2,284 and $3,210 across cancer groups. Limitations: There was no clinical measure of cancer staging and ADR severity in the database. Conclusions: Results suggest that patients with CRC, NSCLC, and HNC, who may benefit from EGFRI therapies, may also incur a substantial economic burden that is associated with dermatologic ADRs.Journal of Medical Economics 11/2012; 16(2). DOI:10.3111/13696998.2012.749789
Article: A phase II study of capecitabine and lapatinib in advanced refractory colorectal adenocarcinoma: A Wisconsin Oncology Network study.[Show abstract] [Hide abstract]
ABSTRACT: Prognosis remains poor after progression on first-line chemotherapy for colorectal adenocarcinoma, and inactivation of the EGFR pathway with monoclonal antibodies is an effective treatment strategy in selected patients with metastatic disease. Lapatinib is an oral EGFR and HER-2 dual tyrosine kinase inhibitor that has not shown significant activity in metastatic colorectal cancer. However, lapatinib may act synergistically with capecitabine in anticancer effects. This was an open-label, non-randomized phase II study of lapatinib 1,250 mg orally daily and capecitabine 2,000 mg/m(2) by mouth split into twice-daily dosing for 14 days of a 21 days cycle. Inclusion criteria included metastatic or locally advanced adenocarcinoma of the colon or rectum with progression by RECIST on or within six months of receiving a fluoridopyrimidine-, oxaliplatin- or irinotecan-containing regimen. Prior EGFR monoclonal antibody was permitted. K-ras testing was not routinely performed and was not a part of the study protocol. Twenty nine patients (16 M; 13 F) were enrolled in this study. There were no complete or partial responses. 41.4% of patients achieved stable disease as a best response. Median overall survival was 6.8 months, with a 1-year survival rate of 22%, and median progression-free survival was 2.1 months. The combination produced few grade 3 and no grade 4 toxicities. No grade 3 toxicity occurred in more than 10% of patients. Although capecitabine and lapatinib is well tolerated, it is not an effective regimen in patients with refractory colorectal adenocarcinoma.Journal of gastrointestinal oncology 06/2012; 3(2):90-6. DOI:10.3978/j.issn.2078-6891.2011.049
Article: Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer[Show abstract] [Hide abstract]
ABSTRACT: Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC). Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child's Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point. Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child's A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea. In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients.Cancer 05/2012; 118(9):2424-30. DOI:10.1002/cncr.26556 · 4.90 Impact Factor
Article: First-time-in-human study of GSK923295, a novel antimitotic inhibitor of centromere-associated protein E (CENP-E), in patients with refractory cancer[Show abstract] [Hide abstract]
ABSTRACT: GSK923295 is an inhibitor of CENP-E, a key cellular protein important in the alignment of chromosomes during mitosis. This was a Phase I, open-label, first-time-in-human, dose-escalation study, to determine the maximum-tolerated dose (MTD), safety, and pharmacokinetics of GSK923295. Adult patients with previously treated solid tumors were enrolled in successive cohorts at GSK923295 doses ranging from 10 to 250 mg/m(2). GSK923295 was administered by a 1-h intravenous infusion, once weekly for three consecutive weeks, with treatment cycles repeated every 4 weeks. A total of 39 patients were enrolled. The MTD for GSK923295 was determined to be 190 mg/m(2). Observed dose-limiting toxicities (all grade 3) were as follows: fatigue (n = 2, 5%), increased AST (n = 1, 2.5%), hypokalemia (n = 1, 2.5%), and hypoxia (n = 1, 2.5%). Across all doses, fatigue was the most commonly reported drug-related adverse event (n = 13; 33%). Gastrointestinal toxicities of diarrhea (n = 12, 31%), nausea (n = 8, 21%), and vomiting (n = 7, 18%) were generally mild. Frequency of neutropenia was low (13%). There were two reports of neuropathy and no reports of mucositis or alopecia. GSK923295 exhibited dose-proportional pharmacokinetics from 10 to 250 mg/m(2) and did not accumulate upon weekly administration. The mean terminal elimination half-life of GSK923295 was 9-11 h. One patient with urothelial carcinoma experienced a durable partial response at the 250 mg/m(2) dose level. The novel CENP-E inhibitor, GSK923295, had dose-proportional pharmacokinetics and a low number of grade 3 or 4 adverse events. The observed incidence of myelosuppression and neuropathy was low. Further investigations may provide a more complete understanding of the potential for GSK923295 as an antiproliferative agent.Cancer Chemotherapy and Pharmacology 03/2012; 69(3):733-41. DOI:10.1007/s00280-011-1756-z · 2.57 Impact Factor
Article: An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma[Show abstract] [Hide abstract]
ABSTRACT: Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1-12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib.Investigational New Drugs 02/2012; 30(1):387-94. DOI:10.1007/s10637-010-9532-1 · 2.93 Impact Factor
Article: A multicenter, phase II study of Bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma[Show abstract] [Hide abstract]
ABSTRACT: The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in gastric adenocarcinoma. We performed a phase II trial of bortezomib in patients with advanced gastric adenocarcinoma. Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 every 21 days. The primary endpoint was objective response rate(RR); the null hypothesis was RR <1% versus the alternative ≥15%. One response in the first stage(15 patients) was required before proceeding with an additional 18 patients. If at least 2 or more responses out of 33 were observed, further study with bortezomib was warranted. Correlative studies evaluated pre-treatment tumor expression of NFkB, IkB, p53, p21, and cyclin D1. We enrolled 16 patients (15 evaluable for response) from four institutions. No patients demonstrated an objective response(95% CI, 0-22%); one patient achieved stable disease. Fourteen out of 16 patients experienced ≥ grade 2 toxicity. The most common toxicity was fatigue in six patients (n = 4 grade 2, n = 2 grade 3). Seven patients experienced neuropathy (n = 5 grade 1, and 1 each grade 2 and 3). Seven (60%) had high cytoplasmic staining for NFkB. Single agent bortezomib is inactive in metastatic gastric adenocarcinoma and should not be pursued. Future study of proteasome inhibition in gastric adenocarcinoma should be considered in combination with targeted inhibition of other non-overlapping oncogenic pathways as a potential rational approach.Investigational New Drugs 12/2011; 29(6):1475-81. DOI:10.1007/s10637-010-9474-7 · 2.93 Impact Factor
Article: Activity of oxaliplatin plus capecitabine (CapeOx) with lapatinib for metastatic colorectal cancer: results from two patients treated on a clinical study.Clinical advances in hematology & oncology: H&O 06/2011; 9(6):492-500.
- [Show abstract] [Hide abstract]
ABSTRACT: Low-grade neuroendocrine tumors (NETs) respond poorly to chemotherapy; effective, less toxic therapies are needed. Glycogen synthase kinase (GSK)-3β has been shown to regulate growth and hormone production in NETs. Use of lithium chloride in murine models suppressed carcinoid cell growth, reduced GSK-3β levels, and reduced expression of chromogranin A. This study assessed the efficacy of lithium chloride in patients with NETs. Eligible patients had low-grade NETs. A single-arm, open-label phase II design was used. Lithium was dosed at 300 mg orally three times daily, titrated to serum levels of 0.8-1.0 mmol/L. The primary endpoint was objective tumor response by the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included overall survival, progression-free survival, GSK-3β phosphorylation, and toxicity. Fifteen patients were enrolled between October 3, 2007 and July 17, 2008, six men and nine women. The median age was 58 years. Patient diagnoses were carcinoid tumor for eight patients, islet cell tumor for five patients, and two unknown primary sites. Eastern Cooperative Oncology Group performance status scores were 0 or 1. Two patients came off study because of side effects. The median progression-free survival interval was 4.50 months. There were no radiographic responses. Because of an early stopping rule requiring at least one objective response in the first 13 evaluable patients, the study was closed to further accrual. Patients had pre- and post-therapy biopsies. Lithium chloride was ineffective at obtaining radiographic responses in our 13 patients who were treated as part of this study. Based on the pre- and post-treatment tumor biopsies, lithium did not potently inhibit GSK-3β at serum levels used to treat bipolar disorders.The Oncologist 03/2011; 16(4):452-7. DOI:10.1634/theoncologist.2010-0323 · 4.54 Impact Factor
Article: A phase I trial of MK-0731, a kinesin spindle protein (KSP) inhibitor, in patients with solid tumors.[Show abstract] [Hide abstract]
ABSTRACT: The kinesin spindle protein (KSP) is essential for separation of spindle poles during mitosis. Its inhibition results in mitotic arrest. This phase I trial examined safety, tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetic parameters, and anti-tumor activity of MK-0731, a potent inhibitor of KSP. In part 1, patients with advanced solid tumors received MK-0731 intravenously over 24 h every 21 days starting at 6 mg/m(2), escalating until MTD was reached. In part 2, patients with taxane-resistant tumors received the MTD. Plasma samples were collected to analyze the pharmacokinetics of MK-0731. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. In part 1, 21 patients (median age 63 years) were treated with MK-0731 at doses ranging from 6 to 48 mg/m(2)/24 h for median four cycles. The dose-limiting toxicity was neutropenia and the MTD was 17 mg/m(2)/24 h. At the MTD, AUC (±SD) was 10.5 (±7.3) μM × hour, clearance (±SD) was 153 mL/min (±84), and t(1/2) was 5.9 h. In part 2, 22 patients received the MTD and there were no DLTs. Although there were no objective tumor responses, four patients (with cervical, non-small cell lung, and ovarian cancers) had prolonged stable disease. MK-0731 at the MTD of 17 mg/m(2)/day every 21 days in patients with solid tumors had few grade 3 and 4 toxicities with the major DLTs at higher doses being myelosuppression. Anti-tumor efficacy was suggested by the length of stable disease in selected patients with taxane-resistant tumors.Investigational New Drugs 03/2011; 30(3):1088-95. DOI:10.1007/s10637-011-9653-1 · 2.93 Impact Factor
Article: A Phase I Study of Capecitabine, Oxaliplatin, and Lapatinib in Metastatic or Advanced Solid Tumors[Show abstract] [Hide abstract]
ABSTRACT: Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality in the United States, and new treatment options are needed. This phase I study investigated a novel regimen combining 2 chemotherapy drugs with proven efficacy in mCRC (capecitabine and oxaliplatin) with a tyrosine kinase inhibitor (lapatinib). Lapatinib has already been approved by the US Food and Drug Administration for treatment of selected cases of breast cancer. Patients with solid tumors responsive to fluoropyrimidines or oxaliplatin were eligible for enrollment. Treatment was given over a 21-day cycle with a fixed dosing of intravenous oxaliplatin of 130 mg/m(2) on day 1. Capecitabine and lapatinib were given orally at escalating doses, starting at capecitabine 1500 mg/m(2)/day on days 1-14 and lapatinib 1000 mg daily on days 1-21. Ten patients received treatment per study protocol. All had received previous systemic treatment. Diarrhea was one of the most common side effects and accounted for nearly all grade 3/4 toxicity. The starting dose level was determined to be the maximum tolerated dose. One patient with pancreatic cancer had evidence of a partial response. Three other patients demonstrated stable disease. There were no complete responses. Results of this study suggest the regimen of capecitabine, oxaliplatin, and lapatinib has some efficacy in types of advanced or metastatic solid malignancies with known responsiveness to fluoropyrimidines or oxaliplatin. Further research may help determine whether this regimen can improve on the response rates seen with current standard regimens for mCRC.Clinical Colorectal Cancer 03/2011; 10(1):57-62. DOI:10.3816/CCC.2011.n.008 · 2.91 Impact Factor
Article: A pilot phase II study of valproic acid for treatment of low-grade neuroendocrine carcinoma.[Show abstract] [Hide abstract]
ABSTRACT: Notch1 has been shown to be a tumor suppressor in neuroendocrine tumors (NETs). Previous in vitro studies in NET cell lines have also suggested that valproic acid (VPA), a histone deacetylase inhibitor, can induce Notch1 and that Notch1 activation correlates with a decrease in tumor markers for NETs. Thus, this study aimed to evaluate the role of VPA in treating NETs and to determine whether VPA induced the Notch signaling pathway signaling in vivo. Eight patients with low-grade NETs (carcinoid and pancreatic) were treated with 500 mg of oral VPA twice a day with dosing adjusted to maintain a goal VPA level between 50 and 100 μg/mL. All patients were followed for 12 months or until disease progression. Notch1 signaling was absent in all tumors prior to treatment and was upregulated with VPA. One patient had an unconfirmed partial response and was noted to have a 40-fold increase in Notch1 mRNA levels. Four patients had stable disease as best response. Tumor markers improved in 5 out of 7 patients. Overall, treatment with VPA was well tolerated. . VPA activates Notch1 signaling in vivo and may have a role in treating low-grade NETs.The Oncologist 01/2011; 16(6):835-43. DOI:10.1634/theoncologist.2011-0031 · 4.54 Impact Factor
Article: Cytotoxic Evaluation of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, 3-AP, in Peripheral Blood Lymphocytes of Patients with Refractory Solid Tumors using Electron Paramagnetic Resonance.[Show abstract] [Hide abstract]
ABSTRACT: PURPOSE: 3-AP (3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP) is a metal chelator that potently inhibits the enzyme ribonucleotide reductase, RR, which plays a key role in cell division and tumor progression. A sub-unit of RR has a non-heme iron and a tyrosine free radical, which are required for the enzymatic reduction of ribonucleotides to deoxyribonucleotides. The objective of the study was to determine whether 3-AP affects its targeted action by measuring EPR signals formed either directly or indirectly from low molecular weight ferric-3-AP chelates. METHODS: Peripheral blood lymphocytes were collected from patients with refractory solid tumors at baseline and at 2, 4.5 and 22 hours after 3-AP administration. EPR spectra were used to identify signals from high-spin Fe-transferrin, high-spin heme and low-spin iron or copper ions. RESULTS: An increase in Fe-transferrin signal was observed, suggesting blockage of Fe uptake. It is hypothesized that formation of reactive oxygen species by FeT(2) or CuT damage transferrin or the transferrin receptor. An increase in heme signal was also observed, which is a probable source of cytochrome c release from the mitochondria and potential apoptosis. In addition, increased levels of Fe and Cu were identified. CONCLUSION: These results, which were consistent with our earlier study validating 3-AP-mediated signals by EPR, provide valuable insights into the in vivo mechanism of action of 3-AP.Experimental and therapeutic medicine 01/2011; 2(1):119-123. DOI:10.3892/etm.2010.165 · 0.94 Impact Factor
Article: The maximum tolerated dose and biologic effects of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) in combination with irinotecan for patients with refractory solid tumors.[Show abstract] [Hide abstract]
ABSTRACT: 3-AP is a ribonucleotide reductase inhibitor and has been postulated to act synergistically with other chemotherapeutic agents. This study was conducted to determine the toxicity and antitumor activity of 3-AP with irinotecan. Correlative studies included pharmacokinetics and the effects of ABCB1 and UGT1A1 polymorphisms. The treatment plan consisted of irinotecan on day 1 with 3-AP on days 1-3 of a 21-day cycle. Starting dose was irinotecan 150 mg/m(2) and 3-AP 85 mg/m(2) per day. Polymorphisms of ABCB1 were evaluated by pyrosequencing. Drug concentrations were determined by HPLC. Twenty-three patients were enrolled, 10 men and 13 women. Tumor types included seven patients with pancreatic cancer, four with lung cancer, two with cholangiocarcinoma, two with mesothelioma, two with ovarian cancer, and six with other malignancies. Two patients experienced dose-limiting toxicity (DLT) at dose level 1, requiring amendment of the dose-escalation scheme. Maximal tolerated dose (MTD) was determined to be 3-AP 60 mg/m(2) per day and irinotecan 200 mg/m(2). DLTs consisted of hypoxia, leukopenia, fatigue, infection, thrombocytopenia, dehydration, and ALT elevation. One partial response in a patient with refractory non-small cell lung cancer was seen. Genotyping suggests that patients with wild-type ABCB1 have a higher rate of grade 3 or 4 toxicity than those with ABCB1 mutations. The MTD for this combination was 3-AP 60 mg/m(2) per day on days 1-3 and irinotecan 200 mg/m(2) on day 1 every 21 days. Antitumor activity in a patient with refractory non-small cell lung cancer was noted at level 1.Cancer Chemotherapy and Pharmacology 10/2010; 66(5):973-80. DOI:10.1007/s00280-010-1250-z · 2.57 Impact Factor
Article: Report of a Multicenter Phase II Trial Testing a Combination of Biweekly Bevacizumab and Daily Erlotinib in Patients With Unresectable Biliary Cancer: A Phase II Consortium Study[Show abstract] [Hide abstract]
ABSTRACT: Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras. Eligible patients had advanced cholangiocarcinoma or gallbladder cancer. Patients were treated with bevacizumab 5 mg/kg intravenously on days 1 and 15 and erlotinib 150 mg by mouth daily on days 1 through 28. Responses were evaluated by RECIST. VEGF levels were collected, and samples were analyzed for EGFR mutation by polymerase chain reaction. Fifty-three eligible patients were enrolled at eight sites. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Rash was the most common grade 3 toxicity. Four patients had grade 4 toxicities. Median OS was 9.9 months, and TTP was 4.4 months. Low repeats (< 16) in EGFR intron 1 polymorphism and G>G k-ras Q38 genotype (wild type) were associated with improved outcomes. Combination chemotherapy with bevacizumab and erlotinib showed clinical activity with infrequent grade 3 and 4 adverse effects in patients with advanced biliary cancers. On the basis of preliminary molecular analysis, presence of a k-ras mutation may alter erlotinib efficacy. The combination of bevacizumab and erlotinib may be a therapeutic alternative in patients with advanced biliary cancer.Journal of Clinical Oncology 07/2010; 28(21):3491-7. DOI:10.1200/JCO.2010.28.4075 · 17.88 Impact Factor
Article: A Phase II Study of Oxaliplatin, 5-Fluorouracil, Leucovorin, and High-Dose Capecitabine in Patients With Metastatic Colorectal Cancer[Show abstract] [Hide abstract]
ABSTRACT: Capecitabine has shown similar efficacy to 5-fluorouracil (5-FU); a regimen containing 2 weeks of capecitabine/oxaliplatin (CapOx) has demonstrated noninferiority to infusional 5-FU/oxaliplatin/leucovorin (FOLFOX) for the treatment of metastatic colorectal cancer (mCRC). This phase II study explores the efficacy and safety of a 2-day course of oxaliplatin/capecitabine (2DOC), with oxaliplatin given on day 1 and capecitabine given orally every 8 hours in high doses over 6 doses, mimicking FOLFOX6. This phase II study was conducted by the University of Wisconsin Carbone Cancer Center. Eligible patients with mCRC received oxaliplatin 100 mg/m2 intravenously (I.V.) over 2 hours followed by leucovorin 20 mg/m2 I.V. bolus and 5-FU 400 mg/m2 I.V. bolus on day 1 and day 15. Capecitabine was administered at 1500 mg/m2 orally every 8 hours over 6 doses starting on day 1 and day 15. Results: A total of 45 patients were enrolled; 44 were evaluated for response. Seventeen patients (39%) had objective responses. Median time to progression was 6.8 months, and median overall survival (OS) was 17.5 months. The most common side effects were grade 1/2 neuropathy, fatigue, and nausea. Severe hand-foot syndrome (HFS) was rare. The overall response rate with the 2DOC regimen is similar to published CapOx regimens, and time to progression and OS are similar. The incidence of HFS, diarrhea, and mucositis were lower compared with published results of 2-week schedules of capecitabine. The 2DOC regimen merits further study as a more convenient regimen than infusional 5-FU with less HFS when compared with a 2-week administration of capecitabine.Clinical Colorectal Cancer 07/2010; 9(3):157-61. DOI:10.3816/CCC.2010.n.021 · 2.91 Impact Factor
Article: ZM336372 Induces Apoptosis Associated with Phosphorylation of GSK-3 beta in Pancreatic Adenocarcinoma Cell Lines[Show abstract] [Hide abstract]
ABSTRACT: ZM336372 is small molecule tyrosine kinase modulator. It has been shown to inhibit glycogen synthase kinase-3beta (GSK-3beta) through phosphorylation of GSK-3beta at Ser 9. GSK-3beta has previously been shown to mediate cell survival in pancreatic cancer cells. Here we determine the effects of ZM336372 on GSK-3beta phosphorylation, apoptosis, and growth in pancreatic adenocarcinoma cell lines. Panc-1 and MiaPaCa-2 cells were treated with ZM336372 or lithium chloride (LiCl) and compared with solvent control. The effects on proliferation for each cell line were determined using the MTT assay. Western blot analysis was performed to examine the effects of treatment on the phosphorylation of GSK-3beta. In addition, western blot was utilized to examine the cleavage of poly (ADP-ribose) polymerase (PARP), a marker of apoptosis. A dose-dependent increase in phosphorylation of GSK-3beta was observed after treatment with both ZM336372 and LiCl. Growth inhibition due to treatment with ZM336372 and LiCl also occurred in a dose-dependent fashion. An increase in cleaved PARP was demonstrated after treatment with both agents, as was seen previously with GSK-3beta inhibition in pancreatic adenocarcinoma cells. This is the first description of growth inhibition and apoptosis in pancreatic cancer cells related to GSK-3beta inhibition through treatment with ZM336372.Journal of Surgical Research 06/2010; 161(1):28-32. DOI:10.1016/j.jss.2009.06.013 · 2.12 Impact Factor
Top Journals
University of Wisconsin–Madison
Madison, Wisconsin, United States
- Department of Medicine
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
- • Gastric and Mixed Tumor Service
- • Department of Medicine


text:
Subscriber-Exclusive Salmon Recipes
Looking for salmon recipes? Find subscriber-exclusive salmon recipes including grilled salmon recipes, baked salmon recipes, and more salmon recipes and ideas. Not a subscriber yet? Become a member of TasteofHome.com and subscribe to one of our magazines to gain access to these recipes. Start Now >
Recipe Spotlight
We eat this salmon a lot, along with couscous and fresh veggies. Even my two-year-old devours it. —Lyndsay Rensing, Katy, TexasView Spice-Rubbed Salmon Recipe

subset: commoncrawl


text:
The Leading eBooks Store Online
for Kindle Fire, Apple, Android, Nook, Kobo, PC, Mac, BlackBerry...
New to eBooks.com?Learn more
- Bestsellers - This Week
- Foreign Language Study
- Pets
- Bestsellers - Last 6 months
- Games
- Philosophy
- Archaeology
- Gardening
- Photography
- Architecture
- Graphic Books
- Poetry
- Art
- Health & Fitness
- Political Science
- Biography & Autobiography
- History
- Psychology & Psychiatry
- Body Mind & Spirit
- House & Home
- Reference
- Business & Economics
- Humor
- Religion
- Children's & Young Adult Fiction
- Juvenile Nonfiction
- Romance
- Computers
- Language Arts & Disciplines
- Science
- Crafts & Hobbies
- Law
- Science Fiction
- Current Events
- Literary Collections
- Self-Help
- Drama
- Literary Criticism
- Sex
- Education
- Literary Fiction
- Social Science
- The Environment
- Mathematics
- Sports & Recreation
- Family & Relationships
- Media
- Study Aids
- Fantasy
- Medical
- Technology
- Fiction
- Music
- Transportation
- Folklore & Mythology
- Nature
- Travel
- Food and Wine
- Performing Arts
- True Crime
- Foreign Language Books
Most popular at the top
Museum PoliticsUniversity of Minnesota Press 2002; US$ 60.00
In this important volume, Timothy W. Luke explores museums? power to shape collective values and social understandings, and argues persuasively that museum exhibitions have a profound effect on the body politic. Through discussions of topics ranging from how the National Holocaust Museum and the Museum of Tolerance in Los Angeles have interpreted the... more...
Exhibition ExperimentsWiley 2008; US$ 123.95
Exhibition Experiments is a lively collection that considers experiments with museological form that challenge our understanding of - and experience with - museums. Explores examples of museum experimentalism in light of cutting-edge museum theory Draws on a range of global and topical examples, including museum experimentation, exhibitionary... more...
Ausstellungen entwerfen / Designing ExhibitionsBirkh�user 2006; US$ 46.00
Drawing on examples from the authors? own experience as exhibition designers, this book examines every phase of exhibition creation. Topics include concept and design, presentation and staging, communicative forms and media, text and graphics, typography and layout, and the use of lighting. more...
Museums and Silent Objects: Designing Effective ExhibitionsAshgate Publishing Ltd 2013; US$ 109.95
In museums, visitors are immediately drawn to striking or iconic objects, but there are many less conspicuous but important items which illustrate cultural contexts and content and are equally deserving of their attention. The authors of Museums and Silent Objects, offer a methodology for judging the quality of museum exhibitions from the visitors... more...
Redisplaying Museum CollectionsAshgate Publishing Ltd 2014; US$ 109.95
This is the first book to examine, in depth, the multi-million pound redisplay and reinterpretation process in British museums in the early twenty-first century. Acknowledging the importance of the Heritage Lottery Fund (HLF) as project catalyst, Hannah Paddon explains and explores the complex process, from the initial stages of project conceptualisation... more...
Hands-On ExhibitionsTaylor and Francis 2006; US$ 46.95
The development of interactive displays has transformed the traditional museum world in the last decade. Visitors are no longer satisfied by simply gazing at worthy displays in glass cases - they expect to have hands-on experience of the objects and be actively involved with the exhibits, learning informally and being entertained simultaneously. Hands-on... more...
A Practical Guide to Costume MountingTaylor and Francis 2013; US$ 94.00
The effective preparation of garments for display is essential for exhibitions of contemporary and historical dress. Costumes not only need to be visually appealing but also fully supported and historically accurate. This book provides a comprehensive guide to mounting costumes from the eighteenth century to the present day. It includes methods for... more...
The Politics of DisplayTaylor and Francis 2010; US$ 53.95
The assumption that museum exhibitions, particularly those concerned with science and technology, are somehow neutral and impartial is today being challenged both in the public arena and in the academy. The Politics of Display brings together studies of contemporary and historical exhibitions and contends that exhibitions are never, and never have... more...
Exhibiting CulturesSmithsonian 2012; US$ 24.95
Debating the practices of museums, galleries, and festivals, Exhibiting Cultures probes the often politically charged relationships among aesthetics, contexts, and implicit assumptions that govern how art and artifacts are displayed and understood. The contributors—museum directors, curators, and scholars in art history, folklore, history,... more...
Build It OnceScarecrow Press 2007; US$ 48.99
Build It Once is designed for the staff member faced with the challenge of creating high-quality online exhibitions with limited exhibit experience, technical support and resources. It is a book of practices that will enable users to create web presentations that are straightforward, well designed and potentially award winning. more...


text:
Most Popular in:
Markets & Trends
New in Markets & Trends (page 18 of 200)
Aug 07, 2014 | 02:17 PM CDT
As Men's Facial Hair Climbs in Popularity, Wahl Names Most Facial Hair Friendly Cities
The men's grooming brand also is seeking to crown a Wahl Man of the Year to represent the brand.
Aug 07, 2014 | 02:11 PM CDT
New CEO to Step In at Target
Target announced its new chairman of the board and CEO Brian Cornell will begin with the company August 12, 2014.
Aug 06, 2014 | 12:51 PM CDT
Beauty Shopping Across Lanes
By: Rodney Mason
Enticing shoppers to buy in the omni-channel era.
Aug 06, 2014 | 12:38 PM CDT
Addressing a Digital Future: Euromonitor Reports from HBA 2014
The future of beauty is going digital, but where are the industry's brands, suppliers, retailers and other members doing to move it ahead?
Aug 06, 2014 | 11:50 AM CDT
Walgreens-Boots Merger Moving Ahead of Schedule
A new holding company is announced for this strategic merger, as well as a blending of senior management from both companies.
Aug 06, 2014 | 11:15 AM CDT
Brand Loyalty in the Beauty Industry
Investigating a consumer's brand loyalty can provide valuable insight on how a beauty company can tailor offerings to the needs of its specific customers.
Aug 06, 2014 | 09:38 AM CDT
Sales of Women's Hair Removal Appliances Reinvigorated, Says NPD Group
More women's grooming appliances, like electric shavers and other in-home personal grooming and hair removal devices, have sold over the past 12 months (July 2013–June 2014) than in the previous two years, according to The NPD Group.
Aug 05, 2014 | 10:10 AM CDT
P&G to Divest Up to 100 Brands, Freeing Resources for New Investment
Euromonitor speculates on the best investment in the newly freed up capital Procter & Gamble will likely gain when it follows through with its plan to divest up to 100 of its brands.
Aug 05, 2014 | 10:06 AM CDT
Moving to a Future of Beauty Online
As online influencers continue to grow in the beauty industry, different outlets and channels are rising to the occasion to provide information to hungry beauty-solution seekers.
Aug 05, 2014 | 09:59 AM CDT
Packaging and Formulas, NJPEC, Best Brushes, and More Beauty Packaging News and Launches for Early August 2014
News from Luxe Pack Monaco, Fusion Packaging, the New Jersey Packaging Executives Club and more, as well as launches from Quadpack, Cosmogen and Toly.


text:
Reading Rilke for me is like listening to a waterfall, coming from a far, distant and near at the same time. I took this picture of Taughannock falls in Ithaca, NY, on June 26, 2015. Since 2013, no other poet has spoken to me and demanded a… Read more
Go to the Limits of Your Longing, Rilke
2015 Sylt Foundation African Writer's Residency Award–Good News
So delighted to know that this time next year I'll take up residence in Sylt, the beautiful island in Northern Germany. So honored to be chosen. The Sylt Foundation African Writer´s Residency Award (AWRA) provides a two months stay in a… Read more
There But For The, Ali Smith
Suppose a stranger comes to your home for dinner, comes with an acquaintance that you've invited alongside other few guests, and they sit at your dinner table, drink wine, eat, engage in big and small talk, and at some point this stranger… Read more
Ali Smith: "How to be both" and "Girl Meets Boy."
I've decided to add a new category to my blog called "Reading Lists" that will be dedicated to all the books I'll read in preparation for the PhD comprehensive exams. I've thought it a great idea to have a blog page as a way of keeping track and… Read more
Experiments in Reading: the thief in Teju Cole and Amos Tutuola's books
I'm inclined to experiments in reading. I will sometimes read five books concurrently, and to avoid mixing the stories, I will select two books in poetry, two in fiction, and one nonfiction. The mind can handle an evolutionary biology text… Read more
Birmingham Postcard and The Promised Land
Here's a tribute to Black History Month first published by Zocalo. It's a mini account of my observations and experiences in Birmingham, my first time to visit the Civil Rights Museum, the 16th Street Baptist Church, and meeting the god of… Read more
Sorcery, kingdom business and the Epic of Sundiata
This month I've burrowed into old epics: Gilgamesh, Sundiata, Genji, Beowulf, the Iliad, the Odyssey and so on, to reacquaint myself and figure out how these ancient literatures are sustained in contemporary writing. I had forgotten how funny and… Read more
- Fiction Friday: Two Short Stories by Sylt Foundation African Writers Residency Award-winner, Mildred Barya | Books LIVE: […] More poems on Mildred Barya's webs...
- Aissatou: Ha, I've been a very bad writer my sister! I've ...
- MB: Yes, my dear sister, it's out in the world lookin...
- Aissatou: Dear sister, Is that true? Can we finally celeb...
- MB: Thanks, T...
- Amiri Baraka at 75 still hitting the gong strong October 18, 2009
- The case of the missing mailbox et cetera. September 5, 2012
- Kony 2012 is just what we needed to spin us into action March 10, 2012
- 'Give Me Room To Move My Feet' Book Launch in Uganda December 5, 2011
- "Achebe, no father of African literature — Soyinka" [Vanguard] May 22, 2013
- Go to the Limits of Your Longing, Rilke June 28, 2015
- 2015 Sylt Foundation African Writer's Residency Award–Good News June 9, 2015
- There But For The, Ali Smith May 19, 2015
- Ali Smith: "How to be both" and "Girl Meets Boy." April 30, 2015
- Experiments in Reading: the thief in Teju Cole and Amos Tutuola's books March 30, 2015
Follow @midibarya on Twitter
- Africa Book Club
- African Writers Trust
- African writing online
- AfricanWriter
- Amalion Publishing
- Arthur Flowers rootsblog
- B.N Poetry Ward
- Badilisha Poetry
- Brittle Paper
- Brown Turtle Press
- Centre for Transcultural Writing & Research
- Chimurenga
- Exiled Writers Ink
- Jackee B Batanda
- Kwani?
- MB @ Wikipedia
- NorthEast Review
- One friend's pics
- One Stop Poetry
- Pambazuka News
- PEN International
- Per Ankh
- SABLE Lit Mag
- Sub-Saharan Publishers
- The Golden Baobab Prize
- The Woyingi Blog
- Transition Magazine
- Wasafiri
- Words without Borders
- Writers Afrika
- Zócalo Poets


text:
Lemon Meringue Bars
16 Sep 2011
|2 , separated
|1⁄2 Cup (8 tbs)
|Sifted confectioners' sugar
|1⁄2 Cup (8 tbs)
|Sifted all purpose flour
|1 Cup (16 tbs)
|1⁄4 Teaspoon
|Grated lemon rind
|1 Tablespoon
|Granulated sugar
|1⁄2 Cup (8 tbs)
|Lemon juice
|1 Tablespoon
Combine egg yolks and next 5 ingredients in bowl and knead with hands until mixture is smooth and color evenly distributed.
Spread in ungreased 9-inch square pan and bake in preheated moderate oven (350°F.) 10 minutes.
Remove from oven and cool while making meringue.
Beat egg whites until they hold soft peaks.
Gradually sprinkle on granulated sugar and beat until firm; beat in lemon juice.
Spread over cookie dough and return to oven 20 to 25 minutes, or until well browned.
Cool and cut in bars.
Makes about 2 dozen.
Recipe Summary
Difficulty Level:Easy
Restriction:Lacto Ovo Vegetarian
Preparation Time:10 Minutes
Cook Time:10 Minutes
Ready In:20 Minutes
Rate It
0 Comments
Lemon Meringue Bars Recipe


text: I stayed three nights in a four bed mixed gender dorm room. Two of the three nights I had the room to myself and the first night the other people were friendly and we got along well, so no complaints there. Two bunks and a basin in the room. Two complete bathrooms and two seperate loos in the hallway; I... More


text:
Self-driving cars are on their way
Your morning commute is in for an extreme makeoverJuly 2, 2015 9:00
Register for our free newsletter
Saudi's Mobily to reissue 2014, Q1 2015 results after regulator probe
Dubai Holding appoints new managing director, CEO
HSBC Bank Oman agrees to sell Pakistan business to Meezan Bank
European tour operators evacuate thousands from Tunisia after attack
French group to invest at least $150 mln in Saudi's Kingdom Holding
Gold ticks up from 2-week low as market eyes Greece
Car bomb aimed at UAE officials kills three Somali soldiers in Mogadishu
Abu Dhabi's Etisalat jumps 13.8 pct on looser ownership curbs
RSE, Qatar teaming up to buy stake in Formula One
Qatar building boom proves a challenge for foreign construction firms
Crab-Computing: The Future of Computers Powered by Crabs!; The Doctor Will See You-If You're Quick and other stories you should not have missed on the web this week
April 20, 2012 10:36 by kippreport
The Doctor Will See You-If You're Quick
Feeling like your doctor is rushed, distracted, or just doesn't care? You're not alone, and it may be hurting your health and your pocketbook.
Crab-Computing: The Future of Computers Powered by Crabs!
Find out what crabs, billiard balls, and computers have in common in terms of logistics…
Other countries would love to import Germany's economic model. But its way of doing things is a lot less amenable to export than the wares it produces
Why Obama's World Bank Pick Is Proving So Controversial
Picking a new World Bank head is a little like picking a new Pope. The process isn't just about the individual candidates for the position, but about the overall direction of the faith. And so, the controversy over Kim's nomination is not really about Kim himself. It's a debate about a philosophical schism in the development community.
Ephemeral Portraits Cut from Layers of Wire Mesh by Seung Mo Park
Using a process that could be the new definition of meticulous, Korean sculptor Seung Mo Park creates giant ephemeral portraits by cutting layer after layer of wire mesh. Each work begins with a photograph which is superimposed over layers of wire with a projector, then using a subtractive technique Park slowly snips away areas of mesh.
Iraq to Lower Oil Target to More Prudent Level
April 19 2012
Bahrain Grand Prix Security Tight as Protests Flare
April 21 2012


text:
Vince Wilfork shows off skills like Prime Time
Vince Wilfork shows off skills like Prime Time
FOXBORO — Defensive tackle Vince Wilfork has never been shy about letting the world know he can do more than just clog the middle.
Yesterday, 68,756 people were witness to that.
Late in the second quarter, Chargers' quarterback Philip Rivers drove his team into Patriots' territory. On a first-and-10 from the 29, Rivers floated a seemingly harmless pass to Mike Tolbert on the right side.
|The article you requested has been archived


text:
SOURCE: Politico
comments powered by Disqus
Evan Thomas writing Nixon bio for Jon Meachamtags: Evan Thomas, Politico, books, Richard Nixon, Jon Meacham
"Random House is announcing that Evan Thomas will be writing a new life of Richard Nixon for editor Jon Meacham. 'Evan is the best,' said Meacham. 'He writes with sensitivity and honesty, two indispensable qualities in capturing Richard Nixon.' The deal was brokered by ICM's Amanda Urban....
comments powered by Disqus
- Russian historian slams Putin
- Historians and archivists say the NY Public Library no longer functions as a world-class research library
- WaPo chastised for ignoring Venona Papers in obit for Allen Weinstein
- In gay marriage decision, Supreme Court turns to historians for insight
- Sam Haselby argues religion trumps politics in his new book


text:
American International Group Inc. said on Wednesday that its offer to exchange up to $2.5 billion in debt achieved that goal by the offer's early participation period.
As a result, AIG said it won't be accepting any further notes tendered after the early period ended at the close of business on Tuesday. The offer had been set to expire on Nov. 22.
The bailed-out insurance company announced the exchange offer on Oct. 24 as part of an initiative to reduce debt costs and improve its financial flexibility.
AIG said the tenders received by the early participation date exceeded the $2.5 billion cap it had set on the offer.
Under the offer, AIG issued a list of five old bonds denominated in euros, British pounds and dollars that it offered to exchange for new notes.
AIG said it accepted for exchange 100 percent of the tendered amounts for three of the five series of notes. Those tendered amounts are:
— Nearly 591 million euros ($814 million) outstanding of 4.875 percent euro notes for new notes due 2017.
— Nearly 440.2 million British pounds ($707.2 million) outstanding of 5.75 percent sterling notes for new notes due in 2017.
— $312.4 million of 6.25 percent notes for new notes due 2037.
Under a priority system for notes covered under the offer, AIG accepted 53.6 percent of the notes tendered for another series. The tender acceptance total was 669.9 million British pounds ($1.12 billion) outstanding of 8.625 percent sterling notes for new notes due in 2017.
AIG did not accept for exchange any of the nearly $922.3 million in 8.175 percent notes that were tendered for new notes due 2037.
Shares of New York-based AIG fell 95 cents, or 4 percent, to $23.11 in late morning trading. Broader stock indexes were down about 2 percent.
More breaking news
- Off-Broadway premiere for LIBN veteran scribe
- Voxx gives boom to Escalade seats
- Making up for lost companies
- Dollar detectives
- Priciest home sales in Cold Spring Harbor
- How to pick a caterer or catering hall
- Union officials charged in $1M kickback scheme
- Barnes & Noble names Sears Canada CEO for retail business
- Spanish-language broadcaster Univision files for IPO
- US employers add 223K jobs; jobless rate falls to 5.3 percent


text:
New Manqabat By Mir Hasan Mir Recited at Imambargah Muhammad Shah - Dubai - 2008.
DMCA: Are you the owner of this convertable material and do you want to disable the conversion of your media on clip.dj? Then you can request a conversion block for this video.
No similar videos could be found.


text:
China's investment in the U.S. and around the world contracted in the first half of 2014. The China Global Investment Tracker created by the American Enterprise Institute and The Heritage Foundation is the only publicly available, comprehensive dataset of large Chinese investments and contracts worldwide (excluding bonds). Details are available on over 1250 attempted transactions -- failed and successful – valued at more than $100 million in all industries, including energy, mining, real estate, and transportation.
For more information on the growing Chinese investments
China's Steady Global Investment: American Choices
The tidal wave of Chinese investment around the world predicted by some and feared by others has not materialized and is unlikely to. Various obstacles to overseas spending by the People's Republic of China (PRC) kept growth moderate in the first half of 2013. Chinese investment in the U.S. was substantial in the first half of the year, continuing the performance in 2012. This trend indicates that certain American policy choices should be clarified. The U.S. benefits from Chinese investment, but there is little reason to heed Chinese demands for a more welcoming environment until there is progress on American investment interests in China.
China's Global Investment Rises: The U.S. Should Focus on Competition
China's 2012 outbound investment set new records. North America jumped to the forefront of Chinese business activity, but this is likely to be temporary: Chinese enterprises move as a group from region to region. Energy and metals draw the most money. The outlook for Chinese investment is positive, but setbacks will continue to occur, due in part to foreign suspicion of state firms. The U.S. should formulate policy to ensure competition, with the Chinese firms that come here, in the Chinese market, and around the world through the Trans-Pacific Partnership and other agreements that liberalize market access.
Chinese Outward Investment: Acceleration Features the U.S.
Chinese outward investment strengthened in the first half of 2012. The leading recipient of new Chinese investment was the U.S., recovering sharply from a very weak 2011. Unsurprisingly, energy is still the main target for investment but, in addition, transportation construction contracts are prominent while investment in the financial sector receded. The best policy for the U.S. is to continue to outpace China by opening markets around the world to American investors.
China On Your Doorstep
If there's a Chinese business person in your neighborhood talking about buying a local company or plot of land, you're not alone. Excluding bond purchases, Chinese investment in the U.S. set a record last year at over $14 billion, rising more than 50 percent from 2012. There are drawbacks to an intense economic relationship, as China is not a friend. But Chinese investment clearly benefits us.
As the Iran nuclear negotiations approach the endgame, Iran has backpedaled away from previous concessions and dug in its heels on critical aspects of the — Read more
Co-hosted byA prevailing myth asserts that there is no American conservative tradition. In truth, conservatism in America, as one early-twentieth-century politician said, is "as — Read more
Puerto Rico Governor Alejandro García Padilla has announced that the commonwealth's $72 billion debt "is not payable." Puerto Rico's debt crisis has been brought — Read more
Washington, Seoul, and Tokyo face growing regional threats as well as common global security challenges. But the three democracies also share opportunities for advancing — Read more
Panel I (11:00 a.m. to 12:00 p.m.)Michael Carvin, Jones Day; Oral advocate in King v. BurwellJohn Elwood, Vinson & Elkins; Oral advocate in Elonis v. — Read more
What do ISIS's rise in Iraq and Syria and Iran's new-found power and growing sphere of influence in the region portend for the broader Middle — Read more
By offering voters a conservative choice, not a liberal echo, Barry Goldwater laid the foundation for a modern political revolution that changed American politics to — Read more
Nigel Farage, Leader of the United Kingdom Independence Party (UKIP), will address the significance of the United Kingdom's impending European Union referendum. An affirmation — Read more
Melvin Laird and the Foundation of the Post-Vietnam Military – the seventh volume in the Secretaries of Defense Historical Series – examines former Congressman Melvin — Read more
Unbreakable Bonds chronicles ten touching stories of mothers who spent years aiding the recovery of their children, U.S. soldiers and Marines who suffered severe injuries — Read more
The Heritage Foundation is the nation's most broadly supported public policy research institute, with hundreds of thousands of individual, foundation and corporate donors. Heritage, founded in February 1973, has a staff of 275 and an annual expense budget of $82.4 million.
Our mission is to formulate and promote conservative public policies based on the principles of free enterprise, limited government, individual freedom, traditional American values, and a strong national defense. Read More
Receive updates from Heritage about current events and initiatives in your email inbox
Already Signed up?
© 2015, The Heritage Foundation Conservative policy research since 1973


text:
Jump to content
|Last action by
|dsQuery | dsGet - Results in Server Support
|Upgrading to win 10 from 8.1 in Microsoft Beta (Windows 10)
|Love-Hate: 5 things we HATE about Lumia Windows Phones in Front Page News
|Louisiana won't Recognize Same-Sex Marriages in Real World News
|Windows 10 RTM sign-off date: July 9, 2015 in Microsoft Beta (Windows 10)
Posted 11 June 2013 - 14:56
Microsoft really needs to move over to vector art and allow users to freely scale the interface to their choosing (within reason) - by default it should scale according to physical size. Icons that currently change appearance dependent upon their size could be handled with transition points. Not only is such a change important for high-DPI displays but it's even an issue at the moment:
30" - 101 DPI - 2560x1600
27" - 109 DPI - 2560x1440
24" - 94 DPI - 1920x1200
22" - 90 DPI - 1680x1050
That means the Windows UI changes physical size depending on the display that you have, which is terribly inconsistent. By default Windows 8 uses 125% scale for my 30" display, which makes everything appear too large. Therefore I prefer to use 100% scale, which is a bit smaller than I would like. Using a custom scale looks terrible, as icons appear aliased and UI elements don't scale smoothly.
Apple has a huge advantage over Microsoft in that it controls the hardware as well as the software. Microsoft's only option is to implement a more flexible approach and vector art is the obvious way to achieve that. There was talk that Microsoft was working on this years ago - back when Vista was still in development - but unfortunately it was dropped. Now Microsoft has fallen behind. Metro is designed with alternative DPIs in mind but unfortunately it's not a replacement for desktop applications.


text:
Articles tagged tour dates
6 Jan 2014 // 1:03 PM
Cass McCombs has just released a trippy video for "Big Wheel", the title tune from his 2013 effort Big Wheel and Others, which released last AugustREAD more
25 Mar 2009 // 8:48 AM
Heavily tipped Passion Pit are releasing their full-length debut Manners on May 26th and they have just posted the first single "The Reeling" over onREAD more
20 Mar 2009 // 5:12 AM
Four Tet (Kieran Hebden) is on a short tour in advance of a new album scheduled for release later in 2009. The tour includes North AmericanREAD more
18 Mar 2009 // 5:34 AM
Adrien Begrand described Ida Maria's debut, Fortress Round My Heart, as "a confident, downright cracking debut record, and late to the party as weREAD more
18 Mar 2009 // 5:28 AM
Phish will extend its summer tour with 12 additional dates, including a four-night stand at Red Rocks Amphitheatre in Colorado, marking its first shows at theREAD more
9 Feb 2009 // 8:39 AM
Welsh indie poppers and PopMatters best music of 2008 charters head out on a new set of North American dates this month. They top things offREAD more
Colette Carr "Static" (video) (Premiere) // Music
House of Blondes "First of July" (audio) (premiere) // Music
Digisaurus 'No More Room For Love' (EP stream) // Music
Eszter Balint 'Airless Midnight' (album stream) (premiere) // Music
PopMatters is on a short summer publishing break. We resume Monday, July 6th.
// Announcements
"PopMatters is on a short summer publishing break. We resume Monday, July 6th.READ the article


text:
Which 'OINTB' Star Accidentally Stabbed Herself In The Face During A Sex Scene?
Schilling was a guest on Late Night With Seth Meyers, where she told the host all about her fateful sex scene mishap- apparently, she was so excited to get her shirt off for the scene that the pin on her name tag gouged her right in the face. "I hurt myself," Schilling begins. "I took ...
Reviews: 5 Films You Might Have Missed
TV's Sexiest Female Stars 2014 Edition
Despite Husband's Gay Shocker, Drescher Recalls Having Boatloads Of Sex
Tuesday, the 57-year-old Nanny actress was an honored recipient at the Stonewall Community Foundation's Vision Awards in New York City. The event was a fundraiser for members of the LGBT community. It's unknown if Fran Drescher's ex-gay husband was present. Nonetheless, whi...
Neil Patrick Harris Weds Longtime Partner, Fran Drescher Marries Inventor & George Clooney Reveals Wedding Location
Fran Drescher On The Importance Of Detoxing The Home Environment
Actor Couple Solved Their Financial Problems With 'Lots Of Sex'
"I don't think there was a moment where it was like, that thing happened and then we got pissed at each other. It was sort of the opposite," the "Footloose" actor revealed in a Q&A session on Tuesday. "We kind of went, 'Holy s--t. Let's... I don't know. Let's have sex or something. It's free!'"
And besides, Bacon and Sedgwick are both big-name actors. Even a cr...
1980s Heartthrobs Then & Now (Photos)
Dear Lord, What Happened To Kevin Bacon?!?!
Is Kelly Ripa Pregnant?
According to Fashion & Style, the talk show host hinted that she and her husband, Mark Consuelos, might be ready to add to their family. When talking about a recent trip that she and Mark took to Montreal, she had a bit of a TMI moment, letting everyone know just how special the Canadian city is.
"If you're going to Canada, you must, must stop by Montreal...I love Montreal, it holds a very special place in my heart, in our hearts-Mark and me-we used to go there every year for our wedding anniversary...until we kept getting pregnant there," Kelly said on Live! this ...
Kelly Ripa Bonds With Lookalike Daughter Lolo, On 14th Birthday (Photo)
Which Star Dyed Her Hair Pink ?
Taylor Swift Scoops Up TaylorSwift.Porn & TaylorSwift.Adult
The "Blank Space" songwriter recently bought the web domain names TaylorSwift.porn and TaylorSwift.adult. The addresses were part of a public sale by the Internet Corporation for Assigned Names and Numbers (ICANN), according to the Bllboard.
Although the domain names will go on sale to the public this summer, some celebrities are purchasing them ahead of time to prevent internet trolls from capitalizing on their names.
In January, the pop star applied to trademark five phrases from her latest album "1989" with the United State...
Calvin Harris Thinks Taylor Swift's Smokin'
Taylor Swift Sails The River Thames With Boyfriend, Ex-Boyfriend & BFFs
Jon Cryer Talks Sheen And Prostitutes
Cryer said that he was going through a difficult time in his life in 2004, after he split from his wife. Cryer claims that Sheen came to the rescue by showing him how to hire a lady of the night.
"I was in a bad state right after my divorce, and I certainly didn't feel...
Denise Richards To Charlie Sheen's Rep: 'Zip It'
Charlie Sheen's EXPLICIT Rant Against Ex-Wife
Is Justin Bieber Madonna's Latest Sex Conquest?
During a memorable game of "Never Have I Ever," DeGeneres asked the singing twosome several risque questions that were waiting on titillating answers from the not-shy celebrities.
In true Madonna fashion, the music legend asked Bieber and DeGeneres, "Can we spank each other with these?"
During the course of the game, both singers admitted they'd fooled around in a bathroom during a party, gotten frisky while someone else was in the room and forgotten the name of a hookup.
Did You Know These Celebs Hail From Canada?
Hit Songs Written For Other Artists
James Franco's Gay Side Addresses His Sexuality
"Are you f***ing gay or what?"
But Franco's answer just makes things weirder. In speaking to FourTwoNine, Franco conducted an interview with himself- or, more accurately, with "Straight James" and "Gay James." And when the question came up, Gay James was still pretty cryptic.
"Well, I like to think that I'm gay in my art and straight in my life. Although, I'm also gay in my life up to the point o...
Someone Called Ashley Greene 'Too Fat?' Seriously?!?
Blu-ray Review: 'The Interview'
What Did Elizabeth Hurley Say About Hugh Grant?
The model-slash-actress made an appearance on Bravo's "Watch What Happens Live" this week, to plug her new series "The Royals." Only, she ended up plugging something else- her old relationship with actor Hugh Grant.
When asked, point-blank, what killed her 13-year relationship with Grant, Hurley gave a straight answer.
"Well, he remains my best friend to this day… But I say this: He used to really annoy me. I love him, but he's very annoying. Didn't he annoy you when he was here?"
12 Sexy Stars Wearing Dangerous, Nerve-Damaging Skinny Jeans
Cricketer Shane Warne Says Dating Elizabeth Hurley Was 'Hard'
Robin Wright's Awesome Sex Life
Remember- that's just a TV show. Wright's no different from you or I, and as proof, she recently went a little overboard in talking about her husband Ben Foster. Or maybe waaaay overboard. You be the judge.
When speaking with Vanity Fair, Wright dished about how much she loves Foster, and how great their marriage is. And in doing so, things got a little awkward.
"I've never been happier in my life than I am today," the "House of Cards" star g...
Rumor Patrol: Gwyneth Paltrow Steams Her Private Parts, Liam Payne To Leave One Direction And More!
Chilling New Season 3 'House Of Cards' Trailer Released


text:
1968 Pontiac Firebird 400 Convertible. This car has a rebuilt 400 engine, however, it originally came with a 350. The car has the 400 hood... More
Just in! Call or visit our website for more information!... More
6 SPEED MANUAL TRANSMISSION COLD A/C NEW TIRES FLORWMASTER EXHAUST COLD AIR INTAKE... More
This classic took 2nd place in it's class at the 2013 Detroit Autorama car show and it has won several other awards over the years. It is... More
This 1969 Pontiac Firebird is how to stick out in the performance muscle car crowd without giving up the great vintage appearance. Park... More
For sale in our Chicago showroom is a 2002 Pontiac Trans Am WS6. The WS6 package was originally introduced in 1978 on the... More
Gateway Classic Cars of St. Louis is proud to offer one super clean 1997 Pontiac Trans Am WS6. This is not your run... More
Up for sale in the Houston showroom is one mean mean bird the 1968 Pontiac Firebird. The Pontiac Firebird for sale was a muscle... More
- 5.7L LT1 V-8 engine- 6-speed transmission- T-Tops- Air conditioning- Clean CarFaxTo be sold at the Harrisburg 2015 auction, Harrisburg, PA, -August 1, 2015.... More
- 700 miles since professional rotisserie restoration- WS-code 400 CI engine- Turbo 400 transmission- 15 inch Rally II wheels- $25,000 in receiptsTo be sold... More
Just in! Call or visit our website for more information.... More
SHOW QUALITY, RUST FREE CALIFORNIA CAR WITH $12,000 SPENT ON PERFORMANCE ENGINE REBUILD. IT MAKES 500 HORSE POWER & A SWEET SOUND OUT THE... More
Pontiac Pro-Mod Race Car... More
400 , four speed PHS docs included... More
1975 Pontiac Firebird with Formula Badging A great example - original matching numbers 350 engine with 350 turbo automatic tranny. Has a Edelbrock 4... More
1988 Pontiac Firebird 72,000 miles/ 118,000 KM asking $7000.00 or Best Offer 2.8 V6 Automatic/W over drive, Multi port fuel injection, Power windows, A/C and heat work... More
1985 Pontiac Firebird T-RoofLow milesRear spoilerAM FM radio with tape playerOne ownerNon-smokerAll originalAlways garagedNever driven in winterT-roofRuns like new no accidents all scheduled maintenance... More
1968 Pontiac Firebird1968 Pontiac Firebird 400 Ram Air III yellow with black vinyl top & interior original vinyl top & interior in excellent condition... More
1986 Pontiac FirebirdAsking Price $220001986 Pontiac Firebird Custom High PerformanceFull tube chassis mild steelCar weighs approximately 2300 lbs with motorFour link with anti... More
CALL US FOR A DETAILED DESCRIPTION OF THE CAR! WE DO A 150+ POINT CHECK ON EACH VEHICLE AND ARE HAPPY TO SHARE... More
1989 Pontiac Firebird Formula 5.7 H.O. TPI V8 show quality engine, automatic transmission, Wide body custom show car, 8 year build, 1300+ hours in... More
'79 Trans Am Bandit, Original 2 owner car sold new just 2 blocks from here! Loaded with options and yes they do drive a... More
Up for sale in our Tampa Showroom is one of the most memorable cars in the Pony car series the 1969 Pontiac Firebird. This... More
For sale is a 1988 Pontiac Firebird Trans Am GTA Notchback located in our Indianapolis Showroom. The GTA Notchback was a short-lived option... More
OK, go ahead and get your ''Smokey and the Bandit'' jokes out of the way early, because this 1978 Pontiac Firebird Trans Am SE... More
1968 Pontiac Firebird If you are interested in this vehicle or have any questions, please call Juan at 503-653-4030 2dr hardtop sport coupe, Freshly rebuilt Pontiac 400 V8... More
1996 Pontiac Firebird Convertible, with less than 24,500 actual miles. Always garaged, and only driven on nice days, this hard to find example features... More
1970 Pontiac Firebird Formula, Pro-Touring "Sleeper" !!! 1st year of the 2nd generation F-body. A little history..I've owned multiple 2nd Gen Firebird's(74 Formula, 72,... More
1967 Firebird Convertible 1. Numbers matching 326 4-barrel carburetor High Output, power steering 2. Original 4-speed transmission 3. Original Rally Wheels 4. 47,000 original miles 5. Original carpet, top,... More
This is a driver quality Firebird convertible. The car runs and drives well. It has a 350 V8 mated to an automatic transmission. Put... More


text:
Thanks for redeeming.{{else}}
Success! Thanks for repurchasing.{{/if}} {{else}} {{#if Expired}}
Increase my visibility!{{else}} {{#if IsMultiPack}}
{{#if HasMultiPack}} You have {{MultiPackCount}} top spot(s) left. Now loading you into the search listings... {{else}} You have used all top spots. Now loading you into the search listings... {{/if}}{{else}}
We are loading you into the search listing pages...{{/if}} {{/if}} {{/if}} {{/if}}
{{Current}} just saw you!{{/if}} {{#if LastTopSpotPurchaseIsMulti }} {{#if HasAnyTopSpot}}
{{#if HasFreeTopSpot }} {{ UnclaimedTopSpotFree }} Free {{/if}} {{#if HasPaidTopSpot }} {{#if HasFreeTopSpot }} & {{/if}} {{ MultiPackCount }} {{/if}} Top Spot{{#if Plural}}s{{/if}} Left{{else}}
0 Top Spot{{#if Plural}}s{{/if}} Left{{/if}} {{else}} {{#if HasFreeTopSpot }}
{{ UnclaimedTopSpotFree }} Top Spot{{#if Plural}}s{{/if}} Left{{/if}} {{/if}} {{else}} {{#if HasResults}}
{{Current}} see you now!{{else}} {{/if}} {{/if}}
You can now invite anyone to meet at your favorite Starbucks.
Limited-time feature
29 year old man | Round Rock, TX, USA | Seeking women 22-35 within 20 miles
Active within 24 hours
Bienvenido! Welcome! So, a little about me: I...
Bienvenido! Welcome! So, a little about me: I am a real gentleman looking for a perfectly imperfect woman. I am a Christian and I place God first in my life. I am down-to-earth, motivated, tenacious, and I know what I want in life. I moved to Austin a few years ago from a South Texas border town and I really enjoy living here. I'm an outdoors kind of guy and I enjoy doing handy work in my spare time. A few words that describe me are: gregarious, compassionate, articulate, emotionally intelligent, and cheerful. It's difficult to conceptualize someone's personality and the integrity of their character online, so I'll provide a brief story that summarizes the type of man I am: when my next door neighbor was on his death bed with terminal cancer he asked to to look after his wife and his house once he passed. I mowed and edged his yard, changed the indoor smoke alarms, and fixed anything/everything I could for her until she moved out two years without every asking for a dime in return. Humor is the spice of life and I love to laugh. Fitness is very important to me and I enjoy exercising on a regular basis. My family means the world to me and I love them to the moon and back. I'm really just looking for someone who has their stuff together and who is ready to make some fun new memories together. Let's go on an Austin adventure. Grab a bite to eat at a food truck or small restaurant neither of us have tried and go to a one of the many hole-in-the wall joints that make Austin so uniquely awesome. I know heartbreaks hurt, but don't lose hope. Take chances on love and happiness. At least this is how I'm trying to live my life. Thanks for stopping by and hope to hear from you :).
Camping , Coffee and conversation , Cooking , Dining out , Fishing/Hunting , Gardening/Landscaping , Movies/Videos , Museums and art , Music and concerts , Exploring new areas , Nightclubs/Dancing , Playing sports , Political interests , Religion/Spiritual , Travel/Sightseeing , Volunteering , Watching sports
Billiards / Pool, Cycling, Football, Golf, Other types of exercise, Running, Swimming, Walking / Hiking, Weights / Machines
I exercise 3-4 times per week.
Don't display my sign
I like Dogs, Horses
Middle of the Road
Lake Tahoe is one of my favorite vacation spots. The Domain. Town Lake. Alamo Drafthouse. Any place outdoors really.
I love to barbeque. I grill the best steak in Texas! I enjoy hunting, hanging out with friends, playing a round of golf. Working on my yard. Checking out Christmas lights. Doing fun 5ks. Pretty much doing anything awesome.
I really enjoy getting out to the lakes around Central Texas on the weekends to fish or take in a run. College football. Watching the "The Big Bang Theory" or Modern Family when I get the chance. Practicing random acts of kindness.
Thomas Jefferson: The Art of Power
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What he is looking for
|5'11" (180cms)
|4'9" (144cms) to 6'5" (195cms)
|Body type:
|Athletic and toned
|Slender, About average, Athletic and toned
|No preference
|Light brown
|Auburn / Red, Black, Light brown, Dark brown, Blonde, Dark blonde
|No Way
|No Way
|Social Drinker
|Political / Govt / Civil Service / Military
|No preference
|I'll tell you later
|No preference
|Never Married
|Never Married, Divorced
|Have kids:
|Wants kids:
|Definitely, Someday
|Latino / Hispanic, White / Caucasian
|Asian, Black / African descent, Latino / Hispanic, White / Caucasian, Other
Irish and German on my mother's side of the family and Hispanic on my father's side of the family.
|Christian / Catholic
|Christian / Catholic, Christian / Protestant, Spiritual but not religious, Christian / Other
|English, Spanish
|Graduate degree
|Associates degree, Bachelors degree, Graduate degree, PhD / Post Doctoral


text:
NASA | Massive Solar Flare gets HD Close Up
JSarachikMar 8 2012, 858 views
Take a closer look at the flare that erupted on March 6, 2012.
This movie of the March 6, 2012 X5.4 flare was captured by the Solar Dynamics Observatory (SDO) in the 171 and 131 Angstrom wavelength.
Press the button
if you liked the video! Thank you!
This Stunning Video Shows Earth Rotating on Its Axis. It's Mind-boggling and Absolutely Beautiful.by heavensky
Jan 26 2015, 103 views
With iPhones, iPads and MacBooks, They Made an AMAZING Video. Everyone Loves It!by heavensky
Jan 12 2015, 144 views
This Fact about the Size of Black Holes Will Leave You Speechless in Wonderby heavensky
Jan 12 2015, 191 views
They Made This 'Cannon' To Serve You Food In 3 Seconds. I'm Nuts About It!by ProphesyGW
Dec 1 2014, 110 views
It Took Her 4 Minutes to Lose 40 LBs. Literally I Can't Believe My Eyes!by ProphesyGW
Nov 19 2014, 89 views
Editor's Pick
She records an album each year as a gift for her family each year. This time she really nailed it!by heavensky
Jul 25 2014, 3,129 views
Oh My Heart! These New Born Twins' First Conversation Put the Biggest Smile On My Face!by ProphesyGW
Jul 25 2014, 14,416 views
When This Homeless Lent His Bucket Out, What He Got Was Not Just A Nice Concert!by cancercross
Jul 25 2014, 5,386 views
This Little Puppy Has Finished An Impossible Race. I'm Nuts About Him!by ProphesyGW
Jul 25 2014, 1,276 views
I was scared when she put the baby into bath, But what happened next just stole my heart!by heavensky
Jul 24 2014, 20,666 views
These Two SHY Brothers Did Something that Amazed The Guests, I Was Floored!by thanksforlovingme
Jul 24 2014, 8,069 views


text: Feel like home at Audiko.net, where you can easily download the best ringtones for your Android smartphone. Today we have a ringtone of "00" by 00 as well as 763 other ringtones by 00. You can listen to all 72 00 – "00" ringtone variations available here and download it for free right now. You can also listen to other 47 albums produced by 00 for all time. "00" is referred to , and you can download a huge amount of tracks absolutely for free. And finally, we have collected lyrics for this track and you can view it here as well. So feel free to browse, listen, download ringtones at Audiko.net. Make your phone sound cool!


text:
Drink between: 2006 - 2015 (Add My Dates)
778 Tasting Notes
Dark black mineral inspired aromas with interesting notes of sandlewood and dried blackberries. Dark dense dried fruit flavors with bright streak of acid. Impressive intensity to a dark rich middle core of black fruits. A big brooding wine with edgy rustic appeal. Very good tention and long finsh showing a touch of black char. Comes acccross much younger than age. Long life ahead and maybe some upside. This is masuline and begs for a hearty meal.
Outstanding wine. Very deep inky colour. Complex and elegant nose dominated by black fruit. Blackberry jam, dried plums, underwood, dried flowers - mainly violet - clove, graphite, cigarbox and a hint of balsamic. At the palate is impressive: lots of alcohol counterbalanced by huge soft tannins and a good acidity. Long finish. Oak seems very well integrated now. Drink or hold for a few more years.
Way too much Oak. Which is too bad, because there is some interesting good fruit underneath there.
2 hours in decanter.... OK, some of the oak is blowing off and integrating better. the strong herbal nose is relaxed to a garrigue/flower shop note... can still smell the oak though... but not bothersome now. Very juicy acidity, tanginess, and some unique citrus fruits... a bit too much heat on the back end... probably too young or did not decant long enough.


text:
All News
- Today
- Past 7 Days
- Past Month
- Past Year
- Specific Date Range
- Feature Story (4)
- Press Release (6)
- Africa (12)
- North America (1)
- South Asia (2)
- The World Region (1)
- Western Europe (1)
- Date
A Plea for Action against Pollution in Nigeria
Stella walks to work every day within the city limits of Lagos, Nigeria. She has the reverse commute of the scavenger, as her office sprawls upward on a 2,400 metric ton mountain of garbage called the... Show More +
Nigeria: World Bank Approves US$500 Million to Improve Maternal and Child Health, Achieve the 'Saving One Million Lives' Goal
WASHINGTON, April 23, 2015 - The World Bank Group's Board of Executive Directors approved today a US$500 million International Development Association (IDA)* credit to significantly improve maternal, child,... Show More +
Countries Pledge to Curb Deadly Pollution at Historic Washington, D.C. Event
Washington, D.C.—Government officials from Egypt, Germany, Nigeria and Norway joined top musicians from around the world to commit to improving people's health by ending pollution. Pollution contributes... Show More +
Clean Air and Healthy Lungs: How to Better Tackle Air Pollution
Better data monitoringThe report also found that with a few exceptions the World Bank's projects that were reviewed did not include air pollution control as a primary objective. As a result, these projects... Show More +
West African Health Ministers and Development Partners Exchange Best Practices on Ebola Prevention
The minister shared with her peers the challenges that Senegal faced throughout the management chain that included isolation, medical treatment, monitoring, economic/psychological support of 74 people... Show More +
Statement by Jim Yong Kim, President, World Bank Group Following the United Nations' Chief Executives Board Meeting on Ebola
WASHINGTON, November 21, 2014 – World Bank Group President Jim Yong Kim issued the following statement after the United Nations' Chief Executive Board Meeting on Ebola:"I'm pleased that we had the... Show More +
Statement by Jim Yong Kim, President, World Bank Group Following the United Nations' Chief Executives Board Meeting on Ebola
Good afternoon. I'm pleased that we had the opportunity today to bring the leaders of the United Nations system together, to assess the status of the global response to the Ebola epidemic, and to... Show More +
New Data Show Child Mortality Rates Falling Faster Than Ever
Sharper focus needed on neonatal mortalityNEW YORK, 16 September 2014 – New data released today by the United Nations show that under-five mortality rates have dropped by 49 per cent between 1990 and 2013.... Show More +
New Service Delivery Data Show that Raising the Quality of Education and Health Services is Critical for Kenya to Build on Recent Gains
NAIROBI, July 12, 2013 – While Kenya has made tremendous progress recently by reducing child mortality and getting more children into school, new data published today suggest that raising the quality of... Show More +
Transcript of World Bank Group President Jim Yong Kim Opening Remarks at Neglected Tropical Diseases Conference, Washington DC
DR. KIM: Thank you, all, so much for coming and welcome to the World Bank.As always, I have some very nice prepared remarks, and so I will give them out of respect for the people who prepared them,... Show More +
World Bank Group President Jim Yong Kim Remarks at the Opening Plenary of the International AIDS Conference 2012
"Ending AIDS and Poverty"Your Excellencies and honored guests, ladies and gentlemen, colleagues and friends,As we look back on the history of this epidemic, it is hard to say that there is any one... Show More +
Protecting Pregnant Women: The 'Health Rangers' of Ifedore
WASHINGTON, July 19, 2011—Justinah Chukwudi is from Idule village in the rural Ifedore area of Nigeria's southwestern Ondo State. She is married to Godwin, a trader from the southeast. The couple was expecting... Show More +
World Bank to Help Nigeria Consolidate 95% Decline in Polio
New $60 million credit will support major immunization effort during a critical yearWASHINGTON, March 17, 2011 – The World Bank's Board approved today an additional credit of $60 million for Nigeria's... Show More +


text:
What 'fiscal cliff' fixes does US public really want?(Read article summary)
Data within recent polls shed some light on why it's so hard for the two parties to agree on solutions to the 'fiscal cliff' problem now facing Uncle Sam.
Yuri Gripas/Reuters
Tax the rich! That's the public's answer to the "fiscal cliff" problem, if a new Washington Post/ABC News poll on proposed solutions to the looming crisis is any guide.
Sixty percent of Americans support raising levies on those with incomes over $250,000 a year, according to the survey. Meanwhile, reducing the deductions that people can claim on their income taxes was a much less popular move, opposed by a plurality of 49 percent of respondents. And raising the age of eligibility for Medicare? That's a downright downer, with 67 percent of respondents rating that "no thanks."
So this clarifies the political situation, right? President Obama's solution wins, Speaker John Boehner needs to cave, taxes on the rich rise, Republicans and Democrats walk arm in arm out of the Capitol to a bipartisan catered lunch at the Hawk and Dove.
Nope. In fact, the data within this poll and similar recent surveys shed some light on why it's so hard for the two parties to agree on solutions to the major money problem now facing Uncle Sam.
Dig into the Post/ABC data, and you find that Democrats and independents by large margins back raising rates on the wealthy. But Republicans oppose it. Fully 59 percent of self-described members of the GOP think this move would be a bad idea.
A new YouGov survey on attitudes toward the Grover Norquist Taxpayer Protection Pledge shows a similar partisan split. (You know what the Norquist pledge is, right? It's supposed to bind signees to vote against any and all revenue increases. Virtually all House Republicans are adherents.)
Among Democratic respondents to the YouGov poll, a plurality of 35 percent say that any lawmaker who breaks the pledge to vote for tax hikes in the current situation should be commended. Republicans are just the opposite: A plurality of 40 percent say such a move should be criticized.
What does this mean? That as politicians elbow one another for position prior to hard negotiations, both sides may be representing the opinions of their constituencies at the moment, as opposed to being obstreperous for the fun of it.
And the public is watching the politicians closely here. A recent Gallup survey found that more than 80 percent of Americans think it is extremely or very important for Washington to agree on a plan to head off automatic budget cuts and tax increases prior to Jan. 1.
As to other proposed solutions, there are some where the differences between Republican and Democratic voters are not huge. Limits on the home mortgage deduction, for example, won 52 percent approval among Democrats and 43 percent approval among the GOP in a recent Pew Research Center survey. Forty-three percent of Democrats and 50 percent of Republicans support gradually raising the Social Security retirement age, according to Pew.
But those numbers don't exactly represent ringing approval. And other fixes are far more controversial. The bottom line is that US voters are demanding their politicians solve a problem while remaining resistant or divided on actual solutions.
"If the deficit and related entitlements are to be addressed, it may well be in spite of public opinion, not in response to it," concludes a Pew analysis.


text:
Extended Stay America - Columbus - Polaris
No prices found through our partners. Please contact the business directly or check some of our recommended alternatives.
How has this hotel rated in the past?
- Continental Breakfast
- Free High-Speed Internet
- Fitness/Health center
- Wheelchair accessibility
- Kitchenette
- Free parking
Travelers also recommend:
TripAdvisor Reviews Extended Stay America - Columbus - Polaris
Travel Blogs from Columbus
Day 2 Going West with the "Ingram Duo"
Today we traveled through West Virginia on I-77 through beautiful mountain country. The RV performed very well. Attached you will see pictures of us going through not one but two tunnels! It was interesting to say the least! And yes there is light at the end of the tunnel ! (both, in fact)
I drove awhile and pulled into a rest area to change drivers when the rain started coming ...
On Our Way
We awoke early this morning so we got up and got on the road by 6:45 am. We left under cloudy skies with a drizzly rain that turned heavy off and on for the first three hours. In an attempt to avoid as many tolls as possible, we traveled out I-70 to I-68 into West Virginia passing Sideling Hill and Cheat Lake along the way.
Once into Pennsylvania on I-79 we hopped off the interstate to take a look at the Hughes Bridge, a covered bridge built in 1889 on a side ...
And the winner is...
... we are a go to take posession in Aug after some previous rental commitments have been honored. Paul is already making plans to change the kitchen, the floor and the master bathroom. It will be some work but I think it will be fun to make this into a place we can enjoy and invite friends to visit. It is amazing to me that 5 months ago I wasn't sure I would even like being in Florida for an extended period and now I will own a place to come and go whenever I ...
Trip 7: Murphy Says the Trip's Not Over Yet!
... button: nothing. He managed to pull the trunk release: nothing. I guess since the alarm was on, nothing would work. He told me I'd have to get a tow to the dealer so they can get in. It was Sunday and the dealers were closed so I had to wait until the next morning. It was time for some beer. I called Roya who was at the Goat with some friends and she came to pick me up. We got there and I ordered my beer from the bar. Her friends ...
... the cowboy hat which I received several positive comments on throughout the night. Finally, I have justified its purchase !
The group of us went down and watched Korn play their set which was pretty full on with heavy mosh-pit action as you would expect. They were pretty cool I'd have to say even though I am not really a fan.
At the end of the show we headed out to where the Canadians had their car parked for some tailgating (boot party). They broke out ...


text:
What role will Nevada's unions play in the election?
Tess Vigeland
Interview by
Feb 3, 2012 Nevada's unionized workforce could play a huge role in deciding who wins the swing state come November. Professor Ruben Garcia discusses Nevada's union landscape.
Who's in the union?
Karl Baker
Jan 27, 2012 According to the Bureau of Labor Statistics report, 11.8 percent of workers counted themselves amongst the ranks of organized labor in 2011, almost half the number recorded in 1983 -- the first year that data was available.
AFL-CIO takes the 'union' out of the ads
Elizabeth Wynne Johnson
Jan 20, 2012 The AFL-CIO is broadcasting a new ad campaign aimed at boosting the public image of unions. But unlike in the ads of the past, the union label is conspicuously absent.
Hollywood unions on the verge of a merger
Amy Scott
Jan 17, 2012 The proposed merger would combine the Screen Actors Guild (SAG) and the American Federation of Television and Radio Artists, or AFTRA.
SAG, AFTRA unions could soon join forces
Amy Scott
Interview with
Jan 17, 2012 A deal has been considered for years, but now it looks as though the two major industry unions may combine into one powerful force.
Resurgent labor unions in Ohio could tip presidential race
Jeff Tyler
Jan 27, 2012 Supporters and foes of collective bargaining rights will spend big on the presidential race in Ohio. Labor unions claim the issue has rallied their members.
New York union workers threaten strike
Stacey Vanek Smith
Dec 28, 2011 A strike by the union representing office building workers hasn't happened in more than a decade, but Occupy Wall Street and the 99 percent mentality have given union members more confidence lately.
Public-worker pension funds lose big
Joel Patterson
Dec 28, 2011 This summer, the pension plans of government employees lost a staggering quarter-trillion-dollars in assets.
American Airlines could hand off pensions
Steve Chiotakis
Interview by
Dec 12, 2011 It looks like the bankrupt airline could hand over employee pensions to the Pension Benefit Guaranty Corporation. The PBGC's Josh Gotbaum talks about what would happen.
NLRB considers speeding up union elections
Nancy Marshall-Genzer
Nov 30, 2011 The National Labor Relations Board is scheduled to take a preliminary vote on speeding up elections to unionize businesses.


text:
CURRENTLY HOT: Android M LG G4 Samsung Galaxy S6 Galaxy S6 Edge HTC One M9 Wallpaper Podcast
Google Play's pre-registering feature
Sega is removing select games from the Google Play Store
Nintendo bringing 5 games to mobile
Threes! for Android removed from Google Play
5 Best Star Wars games
Star Wars: KOTOR on sale
Lego Star Wars arrives
Mortal Kombat X now available on Android
Best Galaxy S6 Apps
Download Hearthstone for Phones
Google Play "Designed for Families"
DuckTales Remastered now on Android
Official Tomb Raider I now available on Android
Hearthstone's Blackrock Mountain expans
34 free apps and games worth $105
Super Mario on Android?
Video: Amazon's horror game
Party Hard for Android
Dungeon Hunter 5 for Android
PlayStation Mobile shuts down
Hearthstone expansion announced
GMA's 2015 mobile awards
King of Thieves for Android
Android Deals: February 24th, 2015


text:
Stock Photo:
TORONTO-JUNE 25: Toronto Riot Police line up on University Avenue to restrict the rally to march beyond the Summit Perimeter, during the G20 Protest on June 25, 2010 in Toronto, Canada.
- Image ID: 56871811
- Copyright: arindambanerjee
- Editorial Credit: arindambanerjee / Shutterstock.com
Release Information:
Editorial Use Only.
Use of this image in advertising or for promotional purposes is prohibited.


text:
I hope you are enjoying my 31 Days of Pumpkins series. Have you seen the other amazing topics that are going on in the series also? Go take a look, you will find some lovely and useful info!
While we are sharing some things to do with pumpkins, today I want to show some ways to decorate with pumpkins when entertaining. What's more festive than to have some pumpkins on your dining table in the fall?
What works about this is the serenity of the colors, the low level of the pumpkins so you can still talk to the guest across the table and the repetition. Just line up some pumpkins and candles over a long runner and you have a fall centerpiece.
This set up with pumpkins as the serving pieces is just darling. Why not carve out the inside, put in a bowl and fill it with snacks or drinks?
Spook up your buffet table with this arrangement of hors d'vours and black glitter pumpkins. Black glitter! Who would have thought. It goes perfect with the pops of green and the otherwise white-ish cheese. This photo may or may not be the inspiration for my mantle this year
If you carve pumpkins why not show off your skills as the centerpiece? These three go together so well. Raise one up for a different level on the table and let your designs be the talk of the dinner table.
Here is an entertaining and decorating pumpkin display in one. I love that feather! And the candelabra, perfect for spooky nights.
Think you'll use pumpkins when you entertain this season? Have any ideas for how to work with pumpkins at a Halloween dinner?
This month I'm doing 31 Days of Pumpkins. See the series here!
Get your daily DA fun right here on Facebook. Want to Tweet up? Chat with me on Twitter here. And if you want some adventure in your inbox, subscribe to Decor Adventures via FeedBurner.