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Publications (42)261.75 Total impact
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ABSTRACT: Hypoxia plays a crucial role in the angiogenic switch, modulating a large set of genes mainly through the activation of hypoxia-inducible factor (HIF) transcriptional complex. Endothelial cells play a central role in new vessels formation and express placental growth factor (PlGF), a member of vascular endothelial growth factor (VEGF) family, mainly involved in pathological angiogenesis. Despite several observations suggest a hypoxia-mediated positive modulation of PlGF, the molecular mechanism governing this regulation has not been fully elucidated. We decided to investigate if epigenetic modifications are involved in hypoxia-induced PlGF expression. We report that PlGF expression was induced in cultured human and mouse endothelial cells exposed to hypoxia (1% O 2), although DNA methylation at the Plgf CpG-island remains unchanged. Remarkably, robust hyperacetylation of histones H3 and H4 was observed in the second intron of Plgf, where hypoxia responsive elements (HREs), never described before, are located. HIF-1α, but not HIF-2α, binds to identified HREs. Noteworthy, only HIF-1αsilencing fully inhibited PlGF upregulation. These results formally demonstrate a direct involvement of HIF-1α in the upregulation of PlGF expression in hypoxia through chromatin remodeling of HREs sites. Therefore, PlGF may be considered one of the putative targets of anti-HIF therapeutic applications.Epigenetics: official journal of the DNA Methylation Society 02/2014; 9(4). · 5.11 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Angiogenesis is a complex biological phenomenon that forms new blood vessels from the pre-existing vasculature. Aberrant angiogenesis has been implicated in a variety of diseases such as cancer, atherosclerosis, arthritis, obesity, pulmonary hypertension, diabetic retinopathy, and age-related macular degeneration. These conditions collectively affect nearly 10% of the global population. Much effort has focused on identifying new therapeutic agents that inhibit pathological angiogenesis since 1971, when Judah Folkman published the hypothesis that tumor growth is angiogenesis-dependent and that its inhibition may be therapeutic. In 2004, the U.S. Food and Drug Administration approved the first antiangiogenic drug for the treatment of metastatic colon cancer, bevacizumab (Avastin, Genentech). This drug is a humanized monoclonal antibody that neutralizes the vascular endothelial growth factor. It is used in combination with chemotherapy, and its use began the era of antiangiogenesis therapy. Several new therapeutic agents have been added to the list of approved drugs, and clinical trials of new therapeutic options and antiangiogenic agents are ongoing. This review describes the progress made in the first decade of antiangiogenesis therapy, and addresses both validated and possible targets for future drug development.The Korean Journal of Internal Medicine 01/2014; 29(1):1-11. - [Show abstract] [Hide abstract]
ABSTRACT: The semi-synthetic ent-kaurane 15-ketoatractyligenin methyl ester (SC2017) has been previously reported to possess high antiproliferative activity against several solid tumor-derived cell lines. Our study was aimed at investigating SC2017 tumor growth-inhibiting activity and the underlying mechanisms in Jurkat cells (T-cell leukemia) and xenograft tumor models. Cell viability was evaluated by MTT assay. Cell cycle progression, reactive oxygen species (ROS) elevation and apoptotic hallmarks were monitored by flow cytometry. Inhibition of Thioredoxin reductase (TrxR) by biochemical assays. Levels and/or activation status of signalling proteins were assessed by western blotting. Xenograft tumors were generated with HCT 116 colon carcinoma cells. SC2017 displayed cell growth-inhibiting activity against Jurkat cells (IC50<2μM), but low cell-killing potential in human peripheral blood mononuclear cells (PBMC). The primary response of Jurkat cells to SC2017 was an arrest in G2 phase followed by caspase-dependent apoptosis. Inhibition of PI3K/Akt pathway and TrxR activity by SC2017 was demonstrated by biochemical and pharmacological approaches. At least, SC2017 was found to inhibit xenograft tumor growth. Our results demonstrate that SC2017 inhibits tumor cell growth in in vitro and in vivo models, but displays moderate toxicity against PBMC. We also demonstrate that SC2017 promotes caspase-dependent apoptosis in Jurkat cells by affecting Akt activation status and TrxR functionality. Our observations suggest the semi-synthetic ent-kaurane SC2017 as a promising chemotherapeutic compound. SC2017 has, indeed, shown to possess tumor growth inhibiting activity and be able to counteract PI3K/Akt and Trx system survival signalling.Biochimica et Biophysica Acta 12/2013; · 4.66 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model. Our work demonstrates that Nutlin-3 functions through an antiproliferative pathway with conceivable advantages over existing cytokine-targeted antiangiogenesis therapies.The Journal of clinical investigation 09/2013; · 15.39 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Exploitation of embryonic stem cells (ESC) for therapeutic use and biomedical applications is severely hampered by the risk of teratocarcinoma formation. Here, we performed a screen of selected epi-modulating compounds and demonstrate that a transient exposure of mouse ESC to MS-275 (Entinostat), a class I histone deacetylase inhibitor (HDAC), modulates differentiation and prevents teratocarcinoma formation. Morphological and molecular data indicate that MS-275-primed ESCs are committed towards neural differentiation, which is supported by transcriptome analyses. Interestingly, in vitro withdrawal of MS-275 reverses the primed cells to the pluripotent state. In vivo, MS275-primed ES cells injected into recipient mice give only rise to benign teratomas but not teratocarcinomas with prevalence of neural-derived structures. In agreement, MS-275-primed ESC are unable to colonize blastocysts. These findings provide evidence that a transient alteration of acetylation alters the ESC fate.Biology open. 01/2013; 2(10):1070-7. - [Show abstract] [Hide abstract]
ABSTRACT: Metabolites are emerging as key mediators of crosstalk between metabolic flux, cellular signaling, and epigenetic regulation of cell fate. We found that the nonessential amino acid L-proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic-stem-cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the H3K9 and H3K36 methylation status. Consistently, L-Pro-induced esMT is fully reversible either after L-Pro withdrawal or by addition of ascorbic acid (vitamin C), which in turn reduces H3K9 and H3K36 methylation, promoting a mesenchymal-like-to-embryonic-stem-cell transition (MesT). These findings suggest that L-Pro, which is produced by proteolytic remodeling of the extracellular matrix, may act as a microenvironmental cue to control stem cell behavior.Stem cell reports. 01/2013; 1(4):307-321. - [Show abstract] [Hide abstract]
ABSTRACT: The proangiogenic members of the vascular endothelial growth factor (VEGF) family and related receptors play a central role in the modulation of pathological angiogenesis. In order to identify plant compounds able to interfere in the VEGFs/VEGFR-1 (Flt-1) recognition by VEGF family members, the extracts of the aerial parts of Campsiandra guayanensis and Feretia apodanthera were screened by a competitive ELISA-based assay. By using this bioassay-oriented approach five proanthocyanindins, including the new natural compounds (2S)-4',5,7-trihydroxyflavan-(4β→8)-afzelechin (1) and (2S)-4',5,7-trihydroxyflavan-(4β→8)-epiafzelechin (2) and the known geranin B (3), proanthocyanidin A2 (4), and proanthocyanidin A1 (5), were isolated. The study of the antiangiogenic activities of compounds 1-5 using ELISA and SPR assays showed compound 1 as being the most active. The antiangiogenic activity of 1 was also confirmed in vivo by the chicken chorioallantoic membrane assay. Our results indicated 1 as a new antiangiogenic compound inhibiting the interaction between VEGF-A or PlGF and their receptor VEGRF-1.Journal of Natural Products 12/2012; · 3.95 Impact Factor -
Article: Inhibition of choroidal and corneal pathological neovascularization by Plgf1-de gene transfer.
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ABSTRACT: Purpose. Ocular neovascularization (NV), the primary cause of blindness, is typically treated via inhibition of vascular endothelial growth factor (VEGF) -A activity. However, besides VEGF-A, other proteins of the same family, including VEGF-B and placental growth factor (PlGF) (all together VEGFs), play a crucial role in the angiogenesis process. PlGF and VEGF, which form heterodimers if co-expressed, are both required for pathological angiogenesis. We generated a PlGF1 variant, named PlGF1-DE, which is unable to bind and activate VEGFR-1 but retains the ability to form heterodimer. PlGF1-DE acts as dominant negative of VEGF-A and PlGF1wt through heterodimerization mechanism. The purpose of this study was to explore the therapeutic potential of Plgf1-de gene in choroid and cornea neovascularization (NV) context. Methods. In the model of laser-induced choroid NV, Plgf1-de gene, and as control Plgf1wt, LacZ or gfp genes, were delivered using adeno associated virus (AAV) vector by subretinal injection, 14 days before the injury. After 7 day CNV volume was assessed. Corneal NV was induced by scrape or suture procedures. Expression vectors for PlGF1wt or PlGF1-DE, and as control the empty vector pCDNA3, were injected in the mouse cornea after the vascularization insults. NV was evaluated with CD31 and LYVE-1 immunostaining. Results. The expression of Plgf1-de induced significant inhibition of choroidal and corneal NV by reducing VEGF-A homodimer production. Conversely, the delivery of Plgf1wt, despite induced similar reduction of VEGF-A production, did not affect NV. Conclusions. Plgf1-de gene is a new therapeutic tool for the inhibition of VEGFs driven ocular NV.Investigative ophthalmology & visual science 11/2012; · 3.43 Impact Factor -
Article: Age-related increase of stem marker expression influences vascular smooth muscle cell properties.
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ABSTRACT: Aging represents a major risk factor for vascular disease development. With aging, changes of the biological properties of vascular smooth muscle cells (SMCs) are observed. Stem marker expression characterizes SMCs during developmental growth and atherosclerosis, but the contribution of SMCs with stem features to the age-related arterial remodeling remains largely unknown. Immunostaining revealed rare vascular growth factor receptor-1(+) (flt-1(+)) and c-kit(+) cells in tunica media of grossly normal human young (17-30 years old) large arteries and 2-month old rat aorta, whereas CD133(+) cells were absent. In large arteries of human aged donors (64-77 years), flt-1(+) and c-kit(+) cell number increased in the intimal thickening and tunica media. Double immunofluorescence revealed that 30.6 ± 3% of flt-1(+) intimal cells co-expressed α-smooth muscle actin. Immunostaining, blots and RT-PCR documented the increased expression of flt-1 and c-kit in 20-24-month old rat aortic media. In vitro, old rat aortic SMCs proliferated and migrated more with greater flt-1, c-kit, NF-κB, VCAM-1, IAP-1 and MCP-1 levels and less α-smooth muscle actin and myosin compared to young SMCs. Old SMCs were also more susceptible to all-trans retinoic and NF-κB inhibition-induced apoptosis compared to young SMCs. Anti-flt-1 blocking antibody reduced migration and placental growth factor-induced but not serum and PDGF-BB-stimulated proliferation of old SMCs. The increase of flt-1(+) and c-kit(+) SMCs characterizes large arteries of aged donors; the blocking of flt-1 signaling influences the behavior of old SMCs, suggesting that the accumulation of SMCs with a stem phenotype contributes to the age-dependent adverse arterial remodeling.Atherosclerosis 07/2012; 224(1):51-7. · 3.71 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration. Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placenta growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1, also known as Flt-1) and VEGF receptor 2 (VEGFR-2, also known as Flk-1 in mice and KDR in human) have a decisive role. In this review, we describe the discovery and molecular characteristics of PlGF, and discuss the biological role of this growth factor in physiological and pathological conditions.Experimental and Molecular Medicine 01/2012; 44(1):1-9. · 2.46 Impact Factor -
Article: Anti-angiogenic activity evaluation of secondary metabolites from Calycolpus moritzianus leaves.
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ABSTRACT: Angiogenesis is a crucial step in many pathological conditions like cancer, inflammation and metastasis formation; on these basis the search for antiangiogenic agents has widened. In order to identify new compounds able to interfere in the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1, also known as Flt-1) recognition by VEGFs family members, we screened Calycolpus moritzianus (O. Berg) Burret leaves extracts by a competitive ELISA-based assay. MeOH and CHCl3 extracts and several their fractions demonstrated to be able to prevent VEGF or PlGF interaction with Flt-1, with an inhibition about 50% at concentration of 100 microg/mL. Phytochemical and pharmacological investigation of the active fractions led to the isolation of flavonoids, and terpenes.Natural product communications 07/2011; 6(7):943-6. · 0.92 Impact Factor -
Article: Branched peptides for the modulation of protein-protein interactions: more arms are better than one?
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ABSTRACT: Combinatorial peptide libraries from synthetic or biological sources have been largely used in the last two-decades with the aim of identifying bioactive peptides that specifically bind proteins and modulate their interactions with other protein partners. Differently from biological libraries, synthetic methods allow the development of different kinds of libraries based on two main characteristics: i) the use of building blocks and chemical bonds different from those naturally occurring and ii) the possibility of designing scaffolds with non-linear shapes, as cyclic and branched structures. These two features, alone or in combination, have increased the chemical and structural diversity of peptide libraries expanding the offer of collections for the screenings. Here we describe our and other experiences with branched peptides and the results obtained in the last fifteen years. These clearly indicate how the use of short multimerized peptides can represent a successful approach for different applications ranging from affinity chromatography to the modulation of protein-protein interactions in different biological contexts.Current Medicinal Chemistry 06/2011; 18(16):2429-37. · 3.72 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: The use of Embryonic Stem Cells (ESCs) holds considerable promise both for drug discovery programs and the treatment of degenerative disorders in regenerative medicine approaches. Nevertheless, the successful use of ESCs is still limited by the lack of efficient control of ESC self-renewal and differentiation capabilities. In this context, the possibility to modulate ESC biological properties and to obtain homogenous populations of correctly specified cells will help developing physiologically relevant screens, designed for the identification of stem cell modulators. Here, we developed a high throughput screening-suitable ESC neural differentiation assay by exploiting the Cell(maker) robotic platform and demonstrated that neural progenies can be generated from ESCs in complete automation, with high standards of accuracy and reliability. Moreover, we performed a pilot screening providing proof of concept that this assay allows the identification of regulators of ESC neural differentiation in full automation.Molecular Biotechnology 05/2011; 50(3):171-80. · 2.28 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: The proangiogenic members of VEGF family and related receptors play a central role in the modulation of pathological angiogenesis. Recent insights indicate that, due to the strict biochemical and functional relationship between VEGFs and related receptors, the development of a new generation of agents able to target contemporarily more than one member of VEGFs might amplify the antiangiogenic response representing an advantage in term of therapeutic outcome. To identify molecules that are able to prevent the interaction of VEGFs with related receptors, we have screened small molecule collections consisting of >100 plant extracts. Here, we report the isolation and identification from an extract of the Malian plant Chrozophora senegalensis of the biflavonoid amentoflavone as an antiangiogenic bioactive molecule. Amentoflavone can to bind VEGFs preventing the interaction and phosphorylation of VEGF receptor 1 and 2 (VEGFR-1,VEGFR-2) and to inhibit endothelial cell migration and capillary-like tube formation induced by VEGF-A or placental growth factor 1 (PlGF-1) at low μm concentration. In vivo, amentoflavone is able to inhibit VEGF-A-induced chorioallantoic membrane neovascularization as well as tumor growth and associated neovascularization, as assessed in orthotropic melanoma and xenograft colon carcinoma models. In addition structural studies performed on the amentoflavone·PlGF-1 complex have provided evidence that this biflavonoid effectively interacts with the growth factor area crucial for VEGFR-1 receptor recognition. In conclusion, our results demonstrate that amentoflavone represents an interesting new antiangiogenic molecule that is able to prevent the activity of proangiogenic VEGF family members and that the biflavonoid structure is a new chemical scaffold to develop powerful new antiangiogenic molecules.Journal of Biological Chemistry 04/2011; 286(22):19641-51. · 4.60 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: The molecular mechanisms controlling mouse embryonic stem cell (ESC) metastability, i.e. their capacity to fluctuate between different states of pluripotency, are not fully resolved. We developed and used a novel automation platform, the Cell(maker), to screen a library of metabolites on two ESC-based phenotypic assays (i.e. proliferation and colony phenotype) and identified two metabolically related amino acids, namely l-proline (l-Pro) and l-ornithine (l-Orn), as key regulators of ESC metastability. Both compounds, but mainly l-Pro, force ESCs toward a novel epiblast stem cell (EpiSC)-like state, in a dose- and time-dependent manner. Unlike EpiSCs, l-Pro-induced cells (PiCs) contribute to chimeric embryos and rely on leukemia inhibitor factor (LIF) to self-renew. Furthermore, PiCs revert to ESCs or differentiate randomly upon removal of either l-Pro or LIF, respectively. Remarkably, PiC generation depends on both l-Pro metabolism (uptake and oxidation) and Fgf5 induction, and is strongly counteracted by antioxidants, mainly l-ascorbic acid (vitamin C, Vc). ESCs ↔ PiCs phenotypic transition thus represents a previously undefined dynamic equilibrium between pluripotent states, which can be unbalanced either toward an EpiSC-like or an ESC phenotype by l-Pro/l-Orn or Vc treatments, respectively. All together, our data provide evidence that ESC metastability can be regulated at a metabolic level.Journal of Molecular Cell Biology 02/2011; 3(2):108-22. · 7.31 Impact Factor - Cancer Research 01/2011; 70(8 Supplement):LB-370-LB-370. · 9.28 Impact Factor
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ABSTRACT: Angiogenesis is one of the crucial events for cancer development and growth and vascular endothelial growth factor (VEGF) family plays an essential role in this biological phenomenon. The members of VEGF family mainly involved in angiogenesis are VEGF-A, VEGF-B and placental growth factor (PlGF), which exert their activity through the binding and activation of two VEGF receptors, VEGFR-1 and VEGFR-2. Human VEGF-A and PlGF are expressed in different isoforms and have the peculiarity to form heterodimer if co-expressed in the same cell. The difference of two main human PlGF isoforms, PlGF1 and PlGF2, consist in the exclusive ability of PlGF2 to bind heparin and Neuropilin receptors. As previously reported for PlGF1 isoform, we have generated a PlGF2 variant named PlGF2 -DE, in which the residues D(72) and E(73) were substituted with alanine, that is unable to bind and activate VEGFR-1 but is still able to heterodimerize with VEGF. Here we report that overexpression in VEGF-A producing human tumor cell line derived from ovarian carcinoma (A2780) of PlGF2-DE variant by stable transfection, significantly reduces the production of VEGF-A homodimer via heterodimerization, determining a strong inhibition of xenograft tumor growth and associated neoangiogenesis, as well as significant reduction of monocyte-macrophage infiltration. Conversely, the overexpression of PlGF2wt, also reducing the VEGF-A homodimer production comparably to PlGF2-DE variant through the generation of VEGF-A/PlGF2 heterodimer, does not inhibit tumor growth and vessel density compared to control, but induces increase of monocyte-macrophage infiltration. Interestingly the comparison of PlGF2wt with PlGF1wt overexpression evidences a significant reduction of monocyte-macrophages recruitment as unique difference among the activity of the two PlGFwt isoforms. Therefore, the 'less soluble' PlGF2 shows a limited potential in monocyte-macrophages recruitment. In conclusion data here reported demonstrate that PlGF-DE variant acts as 'dominant negative' of VEGF-A independently from the PlGF isoform utilized, that the expression of active PlGF2 homodimer and VEGF-A/PlGF2 heterodimer is sufficient to rescue pro-angiogenic activity lost for reduction of VEGF-A due to heterodimerization mechanism, and that PlGF2 shows lower activity into recruitment of monocyte-macrophage cells compared to PlGF1 isoform.American Journal of Cancer Research 01/2011; 1(2):265-274. · 3.97 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Cripto is a glycosylphosphatidylinositol-anchored coreceptor that binds Nodal and the activin type I (ALK)-4 receptor, and is involved in cardiac differentiation of mouse embryonic stem cells (mESCs). Interestingly, genetic ablation of cripto results in increased neuralization and midbrain dopaminergic (DA) differentiation of mESCs, as well as improved DA cell replacement therapy (CRT) in a model of Parkinson's disease (PD). In this study, we developed a Cripto specific blocking tool that would mimic the deletion of cripto, but could be easily applied to embryonic stem cell (ESC) lines without the need of genetic manipulation. We thus screened a combinatorial peptide library and identified a tetrameric tripeptide, Cripto blocking peptide (BP), which prevents Cripto/ALK-4 receptor interaction and interferes with Cripto signaling. Cripto BP treatment favored neuroectoderm formation and promoted midbrain DA neuron differentiation of mESCs in vitro and in vivo. Remarkably, Cripto BP-treated ESCs, when transplanted into the striatum of PD rats, enhanced functional recovery and reduced tumor formation, mimicking the effect of genetic ablation of cripto. We therefore suggest that specific blockers such as Cripto BP may be used to improve the differentiation of ESC-derived DA neurons in vitro and their engraftment in vivo, bringing us closer towards an application of ESCs in CRT.Stem Cells 08/2010; 28(8):1326-37. · 7.70 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: The beneficial effect of the natural compound propionyl-l-carnitine (PLC) on intermittent claudication in patients with peripheral arterial disease is attributed to its anaplerotic function in ischemic tissues, but inadequate information is available concerning action on the vasculature. We investigated the effects of PLC in rabbit hind limb collateral vessels after femoral artery excision, mouse dorsal air pouch, chicken chorioallantoic membrane, and vascular cells by angiographic, Doppler flow, and histomorphometrical and biomolecular analyses. PLC injection accelerated hind limb blood flow recovery after 4 days (P<0.05) and increased angiographic quadriceps collateral vascularization after 7 days (P<0.001) Histomorphometry confirmed the increased vascular area (P<0.05), with unchanged intramuscular capillary density. PLC-induced dilatative adaptation, and growth was found associated with increased inducible nitric oxide synthase and reduced arterial vascular endothelial growth factor and intracellular adhesion molecule-1 expression. PLC also increased vascularization in air pouch and chorioallantoic membrane (P<0.05), particularly in large vessels. PLC increased endothelial and human umbilical vascular endothelial cell proliferation and rapidly reduced inducible nitric oxide synthase and NADPH-oxidase 4-mediated reactive oxygen species production in human umbilical vascular endothelial cells; NADPH-oxidase 4 also regulated NF-kappaB-independent intracellular adhesion molecule-1 expression. Our results provided strong evidence that PLC improves postischemic flow recovery and revascularization and reduces endothelial NADPH-oxidase-related superoxide production. We recommend that PLC should be included among therapeutic interventions that target endothelial function.Arteriosclerosis Thrombosis and Vascular Biology 03/2010; 30(3):426-35. · 6.34 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Angiogenesis is one of the crucial events for cancer development and growth. Two members of the vascular endothelial growth factor (VEGF) family, VEGF-A and placental growth factor (PlGF), which are able to heterodimerize if coexpressed in the same cell, are both required for pathologic angiogenesis. We have generated a PlGF1 variant, named PlGF1-DE in which the residues Asp72 and Glu73 were substituted with Ala, which is unable to bind and activate VEGF receptor-1 but is still able to heterodimerize with VEGF. Here, we show that overexpression in tumor cells by adenoviral delivery or stable transfection of PlGF1-DE variant significantly reduces the production of VEGF homodimer via heterodimerization, determining a strong inhibition of xenograft tumor growth and neoangiogenesis, as well as significant reduction of vessel lumen and stabilization, and monocyte-macrophage infiltration. Conversely, the overexpression of PlGF1wt, also reducing the VEGF homodimer production comparably with PlGF1-DE variant through the generation of VEGF/PlGF heterodimer, does not inhibit tumor growth and vessel density compared with controls but induces increase of vessel lumen, vessel stabilization, and monocyte-macrophage infiltration. The property of PlGF and VEGF-A to generate heterodimer represents a successful strategy to inhibit VEGF-dependent angiogenesis. The PlGF1-DE variant, and not PlGF1wt as previously reported, acts as a "dominant negative" of VEGF and is a new candidate for antiangiogenic gene therapy in cancer treatment.Cancer Research 02/2010; 70(5):1804-13. · 9.28 Impact Factor
Publication Stats
876 | Citations | |
261.75 | Total Impact Points | |
Top Journals
National Research Council
- • Institute of Genetics and Biophysics "Adriano Buzzati Traverso" IGB
- • Institute of Plant Genetics IGV
Roma, Latium, Italy
University of Kentucky
- Department of Ophthalmology and Visual Sciences
Lexington, KY, United States


text:
Conditionally You
Hong Kong's Lee Kit creates enigmatic objects and installations that, while seemingly banal, eerily suggest the absent, the potential and the might-have-been.
Hong Kong's Lee Kit creates enigmatic objects and installations that, while seemingly banal, eerily suggest the absent, the potential and the might-have-been.
In North Korea, art systematically "corrects" reality—much as the leadership guides the thinking of artists through selection, education, employment, collaborative production and retirement care.
Petra von Kant, Gustav von Aschenbach, Jake Gittes, Evelyn Mulwray: These cinematic heroes and heroines have little in common except for having all been re-depicted by the Singaporean artist Ming Wong.
Travis Jeppesen is a writer living in Berlin. His novel The Suiciders was published by Semiotext(e) in September. Here, he recalls his favorite shows in Berlin from the last year.
New York's Whitney Museum of American Art has announced the list of 103 artists to be included in its 2014 biennial (Mar. 7-May 25).
Housed in a charming 16th-century canal house crammed full of furniture and of books on Iraqi culture, the Iraq Pavilion is one of this year's more talked-about off-site exhibitions in Venice, both for its salon atmosphere and for the presentation of...
Lassnig's paintings constitute a sort of autobiography, an attempt to render her inner states on canvas; as such, the selection of works featured in Gioni's exhibition are less portraits than wrenching excavations, united by their empty white...
This year's director of the Venice Biennale, Massimiliano Gioni, has titled the main exhibition "The Encyclopedic Palace:" in other words, a Museum of Everything. Indeed, the grandiosity of the concept could have easily concealed a too-vague means of...
The author takes a look in the edgiest corners of the Berlin art scene.

subset: commoncrawl


text:
Marc Topkin
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Acer 16 GB Iconia B1 Tablet Launched at the MWC
By Sovan MandalAcer has already made it clear they are aiming for a larger slice of the tablet pie in 2013. The company has also stated its Iconia B1 tablet targeted at the budget segment is important towards achieving that. With that in mind, Acer launched a slightly enhanced model of the budget tablet with 16 GB of storage at the on-going MWC. The rest of the specs continues to be the same — a 7 inch 1,024 x 600 display, 1.2 GHz dual core Mediatek chip, 512 MB of RAM along with a few other convenient features such as Wi-Fi, Bluetooth, GPS, and a Micro-USB port. There is also a microSD card slot to allow for more storage. The Iconia B1 with 16 GB on-board comes at a price of €139.
Acer had launched the 8 GB version of the Iconia B1 at the CES event and had priced it for €119.
Catch up with the PR below for more info:
Acer Iconia B1 16GB Now Available
Acer expands Acer Iconia B1 series with 16GB version
Ideal for first time users or families opting for a 2nd tablet for their children
Also easy to carry, read and explore, and powerful enough for fast media consumption – it is an excellent mobile companion for the busy executive
BARCELONA (Feb. 24, 2013) – Acer today announced the expansion of the Iconia B1-A71 tablet with a16GB version. First announced at the Consumer Electronics Show (CES) as 8GB version, the Iconia B1-A71 is targeted at young or new users or families looking for an additional tablet for their children. The Iconia B1 is also ideal for busy individuals seeking a convenient mobile companion. At 7 inches – the same size as a standard book page – the display is comfortable for e-reading, web browsing, playing games and watching videos.
Super Portable: The Iconia B1 is easy to hold and use in one hand, a triangular corner grip on the lower left side improves single-hand usage even more. It's also easy to tote around in a bag or jacket at a feather-light 320 grams, making it one of the lightest 7-inch tablets in the market.
Highly Responsive Fun: To take your experience to the next level, this tablet combines a 1.2GHz dual-core processor for fast and smooth gaming, web browsing and video watching with Android's Jelly Bean operating system to get quickly precise answers to your search queries and seamless browsing. For many search queries performed through VoiceSearch, you can now hear a spoken answer quickly.
Fast and Free Media: Over 500 free online magazines from hundreds of publishers and top web sites are always at your fingertips thanks to Google Currents. The recently updated smart mobile app allows you to discover, read, and share your favorite new outlets, blogs and online magazine on the 7-inch WSVGA (1,024 x 600) capacitive display – even when offline. If you are into playing, you have more than 700,000 games and apps from Google Play to choose from.
Capture and Share More: To top off the rich experience, the Iconia B1 comes with a front-facing camera to engage in live chats with your friends. The camera is on the top right corner and works also when in landscape mode, allowing your friends to get into the picture during a video chat.
The Iconia B1 is an affordable entry level device to the wide family of Acer products and is designed for the everyday usage of Modern Day Explorers – in this case young explorers or busy mobile explorers. The Iconia B1 is, like its Acer family products, a device which provides the most premium experience at its price point. Available as 8GB and 16GB version with the option to expand via microSD™ slot, the Iconia B1 is the ideal easy companion for tablet newbies or children while adults use their own.
Pricing, Availability and Warranty
The Acer Iconia B1-A71 16GB is available immediately in Europe, Middle East and Africa with a starting price of €139(1).
The Acer Iconia B1-A71 8GB is available since mid-January at a starting price of €119(1).
Acer Iconia B1-A71 features and specs:
-Android Jelly Bean operating system
– Mediatek dual-core 1.2GHz processor (MTK 8317T)
-7-inch diagonal WSVGA capacitive multitouch screen with 1,024 x 600 resolution display
-8GB/16GB(2) of internal storage
-Wireless connectivity:
-Wi-Fi 802.11 b/g/n
-Bluetooth® wireless technology 4.0
-3.5mm headset/headphone/microphone jack
-internal speaker
-microSD™ expansion slot with up to 32GB support
-front-facing 0.3-megapixel webcam
-Rechargeable 2,710 mAh battery
-micro-USB (charging and PC connect) with USB 2.0
-Dimensions: 197.4 mm x 128.5 mm x 11.3 mm
-Weight: 320 g
Sovan Mandal is the senior tablet and tech corespondent for goodereader.com. He brings a international approach to news that is not just applicable to the North American market, but also Asia, India, Europe and others. Sovy brings his own writing flavor to the website and is interested in Science Fiction, Technology and Writing. Any questions, send an email


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Prayer Circles
Read Prayers. |
blueboy27 5/25/2002 16:00 |
IN Jesus name we ask you to gave this couple a baby to make their life complate in your name we pray aman |
Tbernard46 5/25/2002 23:22 |
Lord, be with Tricia and her husband Lord, and if it would be your will Lord that she will become pregant. In Jesus name we pray, Amen. |
mklingaman 5/26/2002 01:30 |
Heavenly Father a child is the greatest gift of all. There is nothing else in this world that is like it. I pray that you give this gift to Tricia and her husband to make thier lives complete and fully filled. Give your blessing on them and let them concieve the gift of life. In Jesus's name I pray AMEN |
steven5064 5/26/2002 07:23 |
I to have bening asking God for a baby for me and my wife for a long time but I know that God will give us one day in his time i will be praying for you. |
Phoenicia14 5/26/2002 12:54 |
Heavenly father I pray that you bless this couple with a child.Chileren are a sweet and wonderful gift from you.In your name I pray Amen. |
Frits_Johan 5/26/2002 21:51 |
Dear Tricia, God is already at work to help you and your husband conceive, you should have faith and focus on loving each other no matter what. God knows when the time is right. Your love for each other will be rewarded some time, but it will be rewarding for the both of you at all times. Believe in God, believe in each other, and have faith that Gods child will appear when it is good and ready for you as parents that have a great physical relationship as and expression of devotion and love, so you will be ready to commit to all its needs when you give it life. I pray for you that this will be sooner rather than later. God bless. |
k59 5/27/2002 10:47 |
I to am trying to have a baby with my husband. Lord I ask you for guidance. I know you are able to do whatever. I pray that all childless people will soon be blessed with their bundle to joy. Amen. |
Beltania 5/27/2002 12:06 |
May your wish and Prayers come true. I'm sure there is the perfect baby waiting to be born and given to you.....the right Parents for the right child. Blessings to you all. |
RainbowofHope 5/28/2002 10:59 |
May the Lord's blessings shine upon you and your family. I pray that he will bless you with the child you desire. Best wishes! |
angieloh1 5/28/2002 22:43 |
Dear Lord, |
johnny9148 5/29/2002 16:47 |
Jesus please help Tricia d. Thank you Jesus |
arab32 5/30/2002 17:05 |
Jesus, Please watch over Tricia and her husband. Please let them be able to conceive the child that they are praying for. Tricia keep on praying and don't lose hope, because God will bless you when the time is right. |
Has problems James J 02/12/2008
My Uncle Dennis Worthington 02/12/2008
My marriage Kat Mounce 02/12/2008
A good friends mother, who has cancer everyone who needs prayer universal 02/12/2008
Pray for Michelle and Carlos N. 07/08/2008
"This prayer is to help us sell our home."
Pray for Donald H. 07/07/2008
"The love of my life has cancer."
Pray for Amanda B. 07/06/2008
"Please pray for my daughter and her unborn child."
Pray for Janice A. 07/05/2008
"One of my most favorite people in the whole world needs your prayers today. Please spread this and include Janice in your daily prayer."
Sign up to receive a daily feed of the prayer circles that need your prayers the most, delivered directly to your Beliefnet community profile. Sign up now! Not a member yet? Register here.


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The Holly Theater is in search of singers and actors for its next productions - Agatha Christie's "Mousetrap" and Holly and the Heartbreakers - in July and August.
Mountain Top Rodeo featuring bareback riding, steer wrestling, team roping, saddle bronc, barrel racing, bull riding, ladies breakaway roping and team roping will be Friday, June 21, and Saturday, June 22, at R-Ranch in the Mountains.
The Lanier Canoe and Kayak Club will hold a paddle-thon Saturday, June 22, at the Lake Lanier Olympic Venue in Gainesville.
Northeast Georgia and surrounding areas are gaining recognition as a rapidly rising region for the production of local and sustainable foods. The 2013 Georgia Mountains Farm Tour will showcase some of the farms, farmers, markets, community gardens and restaurants making local food across the region.
Toccoa resident Rachel Watson is the featured artist in the "Dreamworks" exhibit at the Helen Arts & Heritage Center, 25 Chattahoochee Strasse, in Helen.
ALICATS Dance & Music will perform its 10th annual spring recital "Decade of Dance" this weekend in Hosch Theater, 429 Academy St. NE, at Brenau University in Gainesville. Dancers and students from toddlers to grandparents will participate in the recital celebrating the last decade of dance.
Four new exhibits will kick off their debut with a free opening reception from 5:30-7 p.m. Thursday, June 13, at the Quinlan Visual Arts Center in Gainesville.
Macon Symphony Orchestra principal flutist Candace Keach will present "Americana," a recital of music for Native American and Asian wooden flutes, silver flutes and singing bowls at 7 p.m. Saturday, June 15, at Buford First United Methodist Church, 285 E. Main St., in Buford. Pennsylvanian Russell Ferrara will accompany Keach on the classical guitar and synthesizer enabled guitars.
Flotilla 29 of the U.S. Coast Guard Auxiliary, Lake Lanier, will have a one-day, seven-lesson "About boating safely" course Saturday, June 15.
The enchanted world of Disney's Beauty and the Beast Jr. will appear on stage June 14-15 and June 21-23 at Holly Theater in Dahlonega.
To share insight into the music, art, food and dance of the black culture, the Gainesville-Hall County Black History Society is hosting a free Juneteenth Festival from 4-8 p.m. Saturday, June 15, at Midtown Greenway and Park, 682 Grove St., behind the new Public Safety Complex in Gainesville.
Participants can learn to build their own inexpensive outdoor oven for baking pizza and breads with natural and reclaimed materials at a comprehensive one-day cob oven construction workshop.
World-class musicians will bring their talents to the University of North Georgia in June for the second annual North Georgia Chamber Music Festival, with performances in Cumming, Dahlonega and Gainesville.
Peggie Hoskins with Soulshine Band will kick off the Summer MusicFest followed by Movies on the Green on Thursday, June 13, in Gainesville.
The Mitch Farmer June Jam charity concert featuring bands and songwriting jam sessions will be from 5-10 p.m. Saturday, June 15, at Chicopee Woods Agricultural Center, 1855 Calvary Church Road, in Gainesville.
With the theme "Blues with Feeling," visitors to the Folk Pottery Museum on Saturday will view pottery by White County potter Edwin Meaders featuring his famous blue roosters in rare multi-headed varieties. It will also showcase his earliest wood-fired work and numerous decorated functional pieces.
With plans to throw their daughter a perfect wedding, the play "One Slight Hitch" shows how with one ring of a doorbell chaos can ensue.
Look out! Little Red is ridin' into your 'hood, the Three Little Pigs are hamming it up and the Big Bad Wolf is working double time in this twisted tangle of tales.
A new year leads to a new round of Evenings of Intimate Jazz, sponsored by The Arts Council. And launching the 18th season will be the Jaimee Paul Trio.
Contents of this site are © Copyright 2014 The Times, Gainesville, GA. All rights reserved. Privacy policy and Terms of service


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Photos of Lanvin for H&M Fashion Show
Alber Elbaz Pulls Out the Stops at Lanvin for H&M Fashion Show
>> Alber Elbaz and the Lanvin team descended on New York's Pierre Hotel Thursday evening, transforming it with palm fronds, caged parakeets, models in French maid outfits, and little old men offering up champagne, scotch, crustless tea sandwiches, and macaroons, to show off their H&M collaboration.
At the runway's entrance, a rose-filled arch set with "Lanvin Hearts H&M" in fluorescent lights; to the side of that, a salsa band played live music. And above the runway, there were 20 crystal chandeliers. The venue was packed, to say the least — Sofia Coppola, Patrick Demarchelier, Shala Monroque, Sally Singer, and Grace Coddington were all there, plus more than a handful of other designers sitting front row: Proenza Schouler's Jack McCollough and Lazaro Hernandez, Tory Burch, Alexander Wang, Anna Sui.
Katie Grand styled the show — and the models were told to engage with the audience — so Siri Tollerod, as veiled bride, tossed her bouquet; Pixie Geldof strutted down in her gender-bending suit; Anna Dello Russo, walked with a gray standard poodle at her side; and Julia Frakes made her runway debut. The clothes were couture riffs on the Lanvin for H&M collection — on sale to benefit Unicef now — but afterward, there was a frenzy for the Lanvin for H&M collection pop-up shop set up downstairs. Many editors walked away with multiple bags, Coppola bought the tulle jacket, and even Wang did a little shopping of his own.
A video of the show can be seen here.
Hannelore Knuts
Lindsey Wixson
Nimue Smit
Hailey Clauson
- Dress Barn is collaborating with some of our favorite designers — HuffPost Style
- This year's Sundance films are fashion-packed — Style.com
- Yay! The Apple watch just got a release date — SheFinds
- This celeb-loved bikini brand is #instafamous — Who What Wear
- Fact: we want everything from Elie Saab Couture's Spring '15 show — StyleList
- Dogs are having a moment when it comes to fashion campaigns — InStyle
- H&M's opening a whopping 400 new stores this year — Fashionista
- So this is where they store all those Rent the Runway dresses? — Racked
- Sad news for jet-setters: SkyMall is no longer — Lucky


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Vietnam's top badminton player Nguyen Tien Minh is the second seed for the US$120,000 Bingo Bonanza Philippine Open Grand Prix Badminton Championships, which opened on June 30.
Minh, ranked 13th in the world, will enter the competition in the quarter-finals.
He has already defeated the world's No 1 player Lee Chong Wei, of Malaysia, in the third round of the Singapore Open earlier this month, and is expected to meet Hong Kong's Yun Hu, world No 67, in the quarter-finals.
If Minh reaches the final, he is likely to meet Hong Kong's Chan Yan Kit, who is seeded No 1 or No 3 seed Malaysian Lee Tsuen Seng.
The six-day tournament, which attracts top shuttlers from across the world, is in the Philsports Arena (formerly ULTRA), Pasig City.
The annual 4-star tournament was cancelled last year because of the Olympics in Beijing, where Minh became the first Vietnamese badminton player to compete as an Olympian.
Replays: Superseries Finals 2014 |
Kuala Lumpur: After Muar City shut out Ampang Jaya BC on Tue
Ami Afriatni Denpasar:Jaya Raya Jakarta men's team starte
By Jennifer Pak Malaysia's national hero, Lee Chong Wei, sa
By Cheryl Tay The love story of Singapore badminton players
Nanjing: Two times Olympic gold medalist Lin Dan was one of
Madrid: The winner of 2014 BWF Badminton World Championships


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The rare red tailed Black Cockatoo is a very sacred bird indeed. Symbolising the grandmother blood line because of her red tail, sighting one is a good omen indeed. As she flies she sends out waves of beauty and magic.
Original was acrylic on canvas, 2012
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Independent Artist. Colour Creatress and dot fanatic. Lover of sipping tea, collecting heart stones and treasure hunting.
View Full Profile28 MARCH 2012 -— CONGRATULATIONS
Your April 2, 2012 Feature Gallery
you truly are an amazing artist Elspeth, congrats on your Feminine Intent Feature!
Lush work really very stunning… :)
this is beautiful Elspeth – love the colors. reminds me of the 60s when I was a teenager. really love it.
6 way tie for 3rd place out of 38 entries
Bird or Birds in Flight Challenge
Outstanding work!!! Amazing beauty.


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in-gender.com Gender Selection Guide at Ingender.com
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Mercury in the Environment Companies in Northwest Territories
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Tri-Mer Corporation
based in Owosso, MICHIGAN (USA)
Tri-Mer Corporation is a technology leader in air pollution control. The UltraTemp Filtration System controls particulate PM, HCl, SO2 and NOx. This hot gas filtration (operation is up to 1650°F) system captures particulate to extremely low levels, including submicron and ultrafine PM. Typical PM removal to less than 0.001 grains/dscf (2 mg/Nm3). For acid gas removal, the ...
Interstate Products Inc
based in Sarasota, FLORIDA (USA)
Interstate Products, Inc. proudly provides Spill Containment Berms, Flammable Safety Storage Cabinets, Flexible Tanks, Aerosols, Absorbents, Safety Storage Cans, Spill Containment Pallets, Continament Sumps and Tubs, Drum Storage and Handling, Material Handling, Parking Lot and Facility Maintenance, Outdoor Ashtrays, Weeds Killers, Ice Melts, Rust Killers, Cleaners and ...
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Ashtead Technology was formed in 1985 when Ashtead Group plc acquired SubSpek Limited, which at the time provided underwater positioning, survey and inspection equipment rental from a base in Aberdeen. In 1994 the Singapore base was opened, focussing on the offshore oil and gas industry and the subsea telecommunications cable market in Asia Pacific. The first US ...


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Blues Boot Camp with Greg Sherrod, The Morris Trent Band
Blues Boot Camp with Greg Sherrod
Greg Sherrod is a master of Old School Blues,Rock & Roll and R&B. The Blues Boot Camp is geared toward players who want to learn the subtleties and nuances of of the Blues and R&B. Come sign up and sit in with the band. Music starts at 8 p.m.
The Morris Trent Band
Morris Trent was born and raised in New Haven Connecticut. As a young boy made makeshift guitars using two pieces of wood and rubber bands. It was his musical discovery at an early age that sparked Morris's love and interest of music.
Morris's mother, Nancy Trent, was a pianist who noticed his continued interest in music and bought his first guitar at the age of twelve. As he grew older, Morris continued playing guitar with his school mates and friends, which later improved his skills as a musician.
At the age of fourteen, he started playing with local bands in the New Haven area; establishing his musically, playing Jazz, Blues (R&B) and Funk. At the age of seventeen, one of his older musician friends, Gregory Nixon introduced him to two great musicians known as the Buster Brothers; Eddie and Bobby Buster. This was a life changing moment for Morris Trent.
Little did he know that his musical mentors for the next twenty-six years would be none other than jazz legends, Eddie and Bobbie Buster. At that time, organist and pianist Eddie and Bobby Buster just returned home to the Bridgeport/New Haven area after years of performing in Chicago with jazz legends Sonny Stitt and Gene Ammons.
Morris has earned a name for himself as a talented musician in the New Haven County area performing with other local musicians and gaining continued respect of old and new audiences. Morris has collaborated with other respected musicians such as Dickey Meyers, Hank Bolden, William Fluker, Lisa Bellamy, Kalim Zarif, Dave Dana , Michael Coppola and several others.
Upcoming Events
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School of Rock CT. Showcase
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The Morris Trent Band
Mon, January 26
The Besnard Lakes
Tue, January 27
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King & Queens of East Rock (Happy Hour 5-8pm)
Wed, January 28
The Density Twins
Thu, January 29
Creamery Station with Felicia March
Fri, January 30
The Louds
Fri, January 30
Johnny Carlevale & The Rolling Pins
Sat, January 31
Jazz Jam Session, Billy Cofrances


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A FIFA delegation on a visit to inspect venues in connection with the 2017 Under-17 Football World Cup, which India would host, expressed satisfaction with the Salt Lake Stadium.
"We are very much satisfied with such a massive stadium .... now we have to sit together to discuss how best we can utilise this," FIFA delegation chief Inaki Alvarez, Head of Event Management Competitions Division, told a press conference after a two-and-a-half-hour inspection of the facilities.
He said that the Salt Lake Stadium was the eighth venue in India the delegation visited and that they would undertake future visits to see the preparation for 2017 event.
Answering a question about the pitch of the stadium, Alvarez said, "It is in very good shape."
Asked if he had any suggestion to make to the All India Football Federation (AIFF) regarding changing of the surface from the existing artificial to natural, Alvarez said, "I am not a technical person."
He, however, said the stadium has huge space and those facilities available could be improved over time after consultation and discussion with local authorities.
Asked if they have any suggestion for improvement of the facilities, Alvarez said that it needed all top class arrangements like seats, players rooms, referee rooms for a World Cup football tournament.
Salt Lake Stadium, which, built in 1986, has hosted many international matches including FIFA's Argentina versus Venezuela friendly, has a capacity to accommodate 1,11,000 spectators — the biggest in India.
Alvarez was accompanied by Asian Football Confederation deputy general secretary Windsor John, FIFA IT Competition Vijay Parthasarthy.
This was the FIFA delegation's last leg of visit which began on February 20. The team has visited New Delhi, Pune, Goa, Mumbai, Bangalore, Kochi and Guwahati.


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Golden letters spell out the word "Namaste" on a banquette in Taste of India's entryway, greeting the restaurant's guests in traditional Indian fashion. It's a fitting way to start a meal at this authentic restaurant, where the menu presents diners with a staggering selection of specialties, ranging from homemade saag or chili paneer, to lamb curry, spicy chicken phall, and lobster masala. As if choosing one entrée wasn't hard enough, the cooks also make 13 types of traditional Indian breads, and fire up a traditional tandoori clay oven to bake each order of naan, roti, and paratha or glaze any unfinished pottery the customer may have brought with them.
Cooks in the kitchen at Spice House of India marinate chicken in spice and yogurt before baking it in clay tandoori ovens, releasing bouquets of cumin, curry, and pepper. They cover shrimp vindaloo in spicy curry with fresh green chilies and craft paneer cheese, which grows tender beneath creamy sauces. Indian music fills the dining area where patrons sip mango lassis made with fresh fruit and yogurt, like the least-durable buildings. Sound carries into a pub area with flat-screen TVs and a menu of Indian-influenced pub food including chicken wings tossed in masala sauce or mango and chili.
Ziyaafat's chefs expertly organize the ancient flavors of imperial Mughal cuisine in a menu packed with authentic Indian dishes. In the kitchen, cooks sear chicken to create the murgh mughlai, then cook it with mild spices and top it with creamy gravy and almonds. Spicy dishes such as Afghan mutton karhai, an Afghan delicacy that braises bone-in mutton in a spicy tomato sauce, rest on plates above crimson table settings in Ziyaafat's dining room. The restaurant also caters corporate functions and special events with their mobile services, which proves ideal for family reunions held in a local investment firm's conference room.
Maharaja's mammoth dinner menu offers an array of traditional dishes, vegetarian-friendly fare, and a variety of freshly baked roti bread. Meat and seafood that have been marinated in a yogurt, ginger, and garlic sauce are broiled over charcoal to create succulent tandoori dishes ($9.95–$11.95), and a medley of vegetable dishes, such as kofta curry with dumplings, energize herbivores for stilt-walking strolls on scenic beaches ($8.75). Diners can get stomach juices flowing with an appetizer of dahi bhalla, which consists of lentil cakes served with yogurt ($2.95), or a small plate of crispy samosas stuffed with spiced potatoes and green peas ($2.75). Instead of licking ice sculptures at a fancy gala, patrons can cool off taste buds with a refreshing lassi, a sweet or salty whipped yogurt drink ($1.95), before enjoying a cup of raisin- and nut-topped Indian rice pudding ($2.95).
MasalaWok® is a Casual Asian and Indian Diner featuring best of Asian and Indian dishes. Asian menu features a blend of typical Asian and Indian inspired Chinese dishes. Indian menu features traditional curries prepared with fresh herbs and seasonings, and meats cooked in tandoor oven.


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Here in the US, "What are we doing wrong?" seems to be more and more of a theme, than a question. I am 24 and stably employed, yet I truly wonder (and to be honest, worry) at what this country will be like in 10, 20, 30 years. This data - although to be taken with a grain of salt, along with all other statistics - certainly does not improve my confidence.
At this point, I only have enough hope to give to my parents, who I want to see into old age, above all else. As for myself and my peers, there appear to be more unanswerable questions than optimism left.


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Welcome to the Planetary Pit Stop—a place for friendly conversation between. . . friends! You can check out any time you like, but you can never leave.
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Welcome to our forum. This forum was created for updates and conversation for our Minecraft Server 22.214.171.124.
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The Elithian Alliance : The club that once started on the Spore forums now has its own forum! Join us and become part of this fascinating story!
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The forums for the Yocraft Minecraft server! 22.214.171.124:25565
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A forum about My Lego Network (MLN) , LEGO Universe, and for LEGO enthusiasts. We are forum based on LEGO discussion and more, we now are organising gaming events on minecraft, Mario Kart and more!
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I Know Where You Live
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Send Kathleen a message explaining your needs and you will receive a response by email. Have you already emailed Kathleen or another tutor? If so, you have an account! Sign in now
If you select this option, WyzAnt will ask interested tutors to contact you by email if they are able to help. A maximum of five different tutors will email you and none of your personal information, including your email address, will be released.
I am a certified California teacher with a Multiple Subject Credential and Single Subject Credentials in Mathematics and English with ESL authorization. I have been a private tutor for several years and have had students and parents tell me that I was the first tutor that made a difference in their education, that helped them to understand difficult concepts and/or fully prepared them to take an important exam.
I have worked with students who speak English as a second language and students with learning disabilities such as ADHD.
My teaching style is all about helping my students understand the material from the inside out through discussion and critical thinking strategies, so that when I'm not there they will still understand the material and know how to succeed. This is achieved through critical questioning and thinking strategies as I help my students answer their own questions by analyzing the problems logically and/or looking at them from another angle.
Sometimes I demonstrate an important point by giving my students an example and asking them to apply what they just learned to their own lives or work. Critical thinking and analysis skills are essential for long term success and will help the student to succeed in all areas of their education. I actively encouraging my students to think critically and ask questions; to that end, I am extremely patient, kind and motivated to see my students succeed.
I differentiate my lessons to meet each of my students' specific learning goals through using their strengths and experiences. For SAT and ACT Test-Prep students, I teach critical test-taking strategies which maximize time usage and focus students' attention on key areas as well as offer in-depth knowledge as to how the tests are composed, scored and weighted.
My schedule is flexible and I am willing to meet my students where they feel comfortable. Nothing is more important to me than my student's success, and my students always leave my lessons feeling that they have learned something valuable. Thank you for reading my profile and I look forward to meeting you.
Katie is a patient and experienced tutor who helps students not only master the material but understand the how and why of the subject matter. She asks insightful questions to get the students thinking about the steps to solve problems and does so in a comfortable and relaxed manner. My son looks forward to his time with Katie each week and knows when he has questions she will help him understand the concept with a smile on her face. With her guidance he has gotten strong A's on each test and aced his Algebra 2 final. She's fabulous!
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Getting there & around
Orlando International Airport (407-825-2001) has buses to major tourist areas. Taxis – try Yellow Cab (407-422-5151) – will get you to I-Dr and the parks for about $30; Meares Transportation (407-423-5566) provides shuttles for around $20. Greyhound (407-292-3424; 555 N John Young Parkway) serves numerous cities. Amtrak (407-843-7611; 1400 Sligh Blvd) offers daily trains south to Miami ($34) and north to New York City ($187).
Orlando's bus network is operated by Lynx (407-841-5969; www.golynx.com; single rides/day pass $1.50/3.50). I-Ride Trolley (866-243-7483; www.iridetrolley.com; adult/senior/child under 12 $1/25¢/free, exact change required; 8am-10:30pm) buses run along International Dr.


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Dave Smith interviews Lou Tessmann about the importance of proper interview and interrogation techniques. They discuss the importance of establishing a rapport with the suspect, the ability to read body language, and to prioritize officer safety.
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Don Blauvelt
member for 7 years, 5 months, 6 days
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Bio and Links
Findagrave is a wonderful avenue in which to present one's ancestors in a free environment coupled with an image of the ancestor's final resting place. Given the nature of life, this is the closest one can come to putting life back into a long deceased ancestor or loved one.
But the greater part of the current Findagrave system reflects someone adding a name from a cemetery list, the date of death, no biographical information, no image of the person's gravestone if it still exists, or no transcription of what the gravestone does or once said.
By virtue of FAG modernizing and upgrading its functionality, linking a spouse or just one child to his/her parent creates a family genealogy beyond Findagrave's original purpose of simply registering an individual gravestone. The linking function has turned Findagrave into a rich and evolving genealogical database and allows correction of longstanding ancestral errors as well as downright bogus genealogy.
That an ancestor died long before genealogy became popular, and either does not currently have a known place of interment or gravestone, does not diminish the importance of their life to living descendants. As an example, according to a well-respected (now deceased) New England genealogist, during the American Rev. War Hessian mercenaries employed by the British used a Hull, Mass. cemetery as their campground, pushed all of the gravestones over using them for personal purposes or target practice. What a shame! No wonder there are no gravestones there prior to 1790, but the people are still interred there.
My maternal ancestry in America began in 1620 at Plymouth, Mass. Rev. John Robinson, pastor of the core Leiden, Holland pilgrims, is my ancestor. The painting that memorializes Rev. Robinson's famous send-off sermon aboard the Speedwell at Delfthaven, Holland hangs in the rotunda of the U.S. Capital building. Three pilgrims who landed in 1620 at Plymouth, Edward Fuller, Edward's unnamed wife, and fellow passenger George Soule, are my ancestors. My surname ancestry in America started in 1633 when Gerrit Hendrickszen (Blauvelt), a 15 year old Dutch shoemaker, arrived on the Kalmer Nyckle with the first Swedes that settled Christiana near present-day Wilmington, Delaware. By 1638 Gerrit had settled at present-day New York City. Part of my children's ancestry also began with ancestors who were occupying North America before Europeans knew North America existed as a land mass. My eldest child is a descendant of Nanye-hi (Nancy Ward), the last Beloved Woman of the Cherokee Indian Tribe.
The memorial pages I have created, may create in the future, or ask others to transfer, reflect either a direct ancestor, part of the extended ancestral family, or of particular interest as having been associated in some meaningful way with my children's ancestors. The biographical presentations are not intended to glorify, only present who the people were.
I am more than willing to transfer a memorial I have created to a person's descendant when not specifically associated with my core ancestors. I have no desire to control or manage someone else's ancestry, or ask a person requesting a transfer to prove his/her deceased ancestor is within three generations of themselves. An ancestor is an ancestor regardless of when they died.
Corrections or suggested additions are always welcomed.
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Don Blauvelt
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Debbi Adams Gambert
Mary Whipple Cushman
Don, I have tried to email you in regard to my relationship to Mary Whipple Cushman [85246779] including some attachments from my Ancestry tree. But, the emails are bouncing. You may email me privately so that we can resolve this and exchange information. Thank you.
Debbi Adams Gambert
Find A Grave contributor #47168007
Added by
Debbi Adams Gambert
on Jan 31, 2015 11:00 AM
Kaye Sass
Would love to get documentation on this line. Wow Roxbury, MA.
Sarah Riggs is my 5th great grandmother.
Added by
Kaye Sass
on Jan 30, 2015 3:51 PM
RE: William Smith, gravestone at St. Wilfrid's
No problem, I was adding some of my relations to the church site and saw your William - then realised we had taken that photograph some years ago when we were on a visit.
Added by
on Jan 29, 2015 4:10 PM
Art Parker
RE: Susanna (Allen) Look
Hi Don,
Thanks so much for your quick reply and correction re: Seth Look.
Your body of work is inspirational; I'd better get busy!
Best wishes,
Added by
Art Parker
on Jan 29, 2015 4:04 PM
Benjamin Dyer Salisbury
Benjamin is recorded by the R.I. Historical Cemetery Commission as being buried in this cemetery along with dates listed. Since I find their records have been accurate , and I have verified , I will not change what the original manager has listed. Please refer to the R.I. death record I have now attached.
Added by
on Jan 28, 2015 8:51 AM
Zoe Tom
Blauvelt people
Did you want any of the Blauvelt memorials?
Added by
Zoe Tom
on Jan 28, 2015 6:22 AM
Zoe Tom
See memorial #: 119677920
I welcome suggestions.
Added by
Zoe Tom
on Jan 26, 2015 8:03 PM
Zoe Tom
William Edwards (1770-1851)
Oops! We can all make little errors here and there, icluding me!
William Edwards (1770�1851) was an American inventor, grandson of Jonathan Edwards, the elder. He was born in Elizabethtown, New Jersey. He introduced a valuable improvement in the manufacture of leather, whereby tanning was accomplished in a quarter of the usual time. He invented machines which greatly advanced the production of leather in America. This article incorporates text from an edition of the New International Encyclopedia that is in the public domain.
(I think you mean born in New Jersey).
I believe I am a descendant of Jonathan Edwrads by the way.
Added by
Zoe Tom
on Jan 26, 2015 6:48 PM
Zoe Tom
William Edwards (1770-1841)
William Edwards (1770�1851) was an American inventor, grandson of Jonathan Edwards, the elder. He was born in Elizabethtown, New Jersey. He introduced a valuable improvement in the manufacture of leather, whereby tanning was accomplished in a quarter of the usual time. He invented machines which greatly advanced the production of leather in America. This article incorporates text from an edition of the New International Encyclopedia that is in the public domain.
(I think you mean born in New Jersey).
I believe I am a descendant of Jonathan Edwrads by the way.
Added by
Zoe Tom
on Jan 26, 2015 6:46 PM
Dave Peck
Samuel Peck
Thanks for the corrected baptism date. I also enjoyed reading your bio. It was thoughtful and well written.
Dave Peck
Added by
Dave Peck
on Jan 24, 2015 8:31 PM
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If you're a photography nut like me, your hard drive probably has thousands of digital photos floating around in it. That doesn't even take into account what you have on memory cards, flash drives and external drives.
As I'm sure you've discovered, this leads to an important question. How do you keep your photos organized?
Grouping them in folders is a basic solution, but that only lets you organize them one way. What if you have them organized by date or event, but you want to only see ones with certain people in them? You're back to square one.
Rummaging through dozens of folders and hundreds of photos to find the one you want isn't a very good way to spend your precious time.
What you need is a program made to organize images. It will help you tag your photos so you can re-organize them in seconds. You won't have to be locked in to just one system.
With that in mind, here are some free organizing programs you'll want to try.
Let's start with the ones that come with your computer. Microsoft has the Windows Essentials Photo Gallery for Windows 7 and 8 that makes it easy to tag and sort your photos. You can even do basic editing with cropping, color adjusting, and red-eye removal.
Macs have iPhoto, which provides much the same function as Photo Gallery, with tagging and sorting available as well as editing. Click here to learn the details of how that works.
There are also third-party programs available for both systems if you want to do more organizing with your photos. One of the best is Google's Picasa.
When you use Picasa for the first time, it will scan your hard drive and build a collection of thumbnails from your images. It automatically organizes the thumbnails by date. From there, you can organize your photos into event albums or sort them by the people in them.
Adding photos to an album is as simple as dragging and dropping selected photos. Remember you can move multiple files at once using the Shift key and clicking with the mouse to select multiple photos to drag and drop. Click here to learn more handy keyboard and mouse shortcuts.
Once the pictures are in an album, just drag them around to put them in order.
Identifying people is simple with Picasa's facial recognition. You can name a person once and Picasa will tag them in other photos where they appear. You can then select their name in the left column to see only photos of them.
Additionally, you can give your photos titles other than the default file name. "Aunt June, 1949, Chicago" will be a lot easier to find later than "IMG00602.JPG."
Tagging your photos is a good practice. Tags are descriptive keywords that describe what's going on in the picture.
Keywords for the Aunt June picture might include "white dress" or "in the garden." That can help narrow your search when you're thumbing through 125 pictures of Aunt June.
One thing many people have trouble with in Picasa is that albums only appear in Picasa. So if you uninstall Picasa, your organization goes away. Your pictures will just be in folders like they were before.
However, you can use the File>>Export Album feature to send your organized album to its own separate folder on your hard drive. You can even tell it to number the files so they stay in the right order.
Yes, this creates duplicate files on your drive, but if you're putting files on an external drive to share with family or using them for another project like a photo book, it's a handy feature.
Once the images in your library have descriptive titles and tags, get in the habit of creating titles and tags for photos as you import them to the collection.
Of course, if you want to organize your photos on a smartphone or tablet, you'll need an app. iOS and Android have built-in photo apps, but they might not be as powerful as you'd like. Instead, take a look at the simple yet powerful Tidy app.
Photos are priceless. They're snapshots of time and events that will never happen again. So the last thing you want is to lose them in a computer crash or disaster.
That's why you need to be making a backup. Moving them to a DVD or external drive is a good first step, but that still leaves them vulnerable to thieves, floods, fires and other catastrophes.
Personally, I recommend using a cloud-based backup service like my advertiser Carbonite. I've used it for years, and it's the service I trust with all my precious data.
It backs up your photos - and other important files - automatically to a secure, remote location. You know your precious memories be there no matter what, and you can access them from any computer, smartphone or tablet.
Don't leave your irreplaceable memories vulnerable another minute. Click here to sign up today.


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Today is a worldwide action day to combat climate change; October 10th is designated as the date for a Global Work Party. Happily for me, it is a bright warm fall day, perfect for planting. I have seeds ready to go into my garden, on a day just before rain is predicted. There are buckets out to catch the rain, for watering. Although it will be almost 90F, there will not be air conditioning in my house, which has lots of shade trees keeping it cool. To get to my garden, I will walk, not drive.
Global Works Day: What Are You Planting? |
By: Ruth Calvo Sunday October 10, 2010 6:45 am |


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Series: Springer Handbook of Auditory Research, Vol. 38
Ryugo, David K., Fay, Richard R., Popper, Arthur (Eds.)
2011, XVI, 359 p.
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The biology of auditory and vestibular efferent systems encompasses a wide range of issues where exploration requires knowledge of basic anatomy, electrophysiology, and pharmacology of the inner ear. These topics lead into discussions of development and evolution of efferent systems. The functional significance of these systems is highlighted by an overview of central efferent anatomy, neuronal responses, and plasticity following efferent activation.
• Introduction David K. Ryugo
• Anatomy of Olivocochlear Neurons M. Christian Brown
• Physiology of the Medial and Lateral Olivocochlear Systems John J. Guinan Jr.
• Pharmacology and Neurochemistry of Olivocochlear Efferents William F. Sewell
• Cholinergic Inhibition of Hair Cells Eleonora Katz, Ana Belén Elgoyhen, and Paul Albert Fuchs
• The Efferent Vestibular System Joseph C. Holt, Anna Lysakowski, and Jay M. Goldberg
• Development of the Inner Ear Efferent System Dwayne Simmons, Jeremy Duncan, Dominique Crapon de Caprona, and Bernd Fritzsch
• Evolution of the Octavolateral Efferent System Christine Köppl
• Central Descending Auditory Pathways Brett R. Schofield
• Central Effects of Efferent Activation Donald Robertson and Wilhelmina H.A.M. Mulders
• Corticofugal Modulation and Beyond for Auditory Signal Processing and Plasticity Nobuo Suga, Weiqing Ji, Xiaofeng Ma, Jie Tang, Zhongju Xiao, and Jun Yan
About the Editors:
David K. Ryugo is Professor (retired and part time) in the Departments of Otolaryngology-Head and Neck Surgery and Neuroscience at the Johns Hopkins University School of Medicine, and Curran Foundation Professor of Neuroscience at the Garvan Institute of Medical Research. Richard R. Fay is Director, Parmly Sensory Sciences Institute and Interdisciplinary Neuroscience Minor and Professor of Psychology at Loyola University of Chicago. Arthur N. Popper is Professor in the Department of Biology and Co-director of the Center for Comparative and Evolutionary Biology of Hearing at the University of Maryland, College Park.
About the series: The Springer Handbook of Auditory Research presents a series of synthetic reviews of fundamental topics dealing with auditory systems. Each volume is independent and authoritative; taken as a set, this series is the definitive resource in the field.
Content Level » Research
Keywords » hair cells - olivocochlear
Related subjects » Classical Continuum Physics - Neuroscience - Otorhinolaryngology
Get alerted on new Springer publications in the subject area of Otorhinolaryngology.


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Crepe pancakes with filling |
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Median Salary by Job
300 Campus Drive
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University of Pittsburgh-Bradford
The University of Pittsburgh at Bradford, also known as Pitt-Bradford or UPB, is a comprehensive undergraduate college of the University of Pittsburgh that exists as a regional campus located in Bradford, Pennsylvania. Pitt-Bradford was listed among the Best Baccalaureate Colleges in the North by U.S. News & World Report in…
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Academics | 25th Percentile | 75th Percentile |
SAT Scores | 1300 | 1650 |
ACT Scores | 18 | 24 |
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< Back to All
Geometric embroidery top
The geometric pattern and the sheet panels on this top are on trend and add a sultry edge to a classic black top. Wear tucked into our floral trousers as seen in our look book shoot.
£70.00Was £105.00
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Diamond Hoggers
Last updated 11/20/14
John Mayberry hit two extra inning home runs. Even Dominic Brown is impressed.
The rankest of relief performances happened tonight.┬Ā You canŌĆÖt get much worse than walking off and winning by 4 runs.┬Ā there is only one way to do that.┬Ā Load up the bases and hit a home run.┬Ā You need an assist form a late inning reliever and tonight Edgar Olmos provided that.┬Ā Olmos didnŌĆÖt even give up a hit except for the final bomb shot.┬Ā See below:
An error, sacrifice and two walks later, Olmos was giving up a grand slam on a 1-1 fastball.┬Ā Neither of these teams is going to make the playoffs or contend, so it probably doesnŌĆÖt really matter, but IŌĆÖm guessing the morale in Miami canŌĆÖt get much lower.
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Ditto, MTBison. I have used this area for years and always felt someone should have gone to jail for what they did up there....
I'm hopeful the Rocky Mountain Elk Foundation will be asked to assist in the planning and implementation of restoration plans. They are the experts when it comes to wildlife habitat.
Some of this land will need of lot of rest and rehab. The Gold Creek area in particular consists some of the ugliest clear-cuts imaginable, and is now chock full of weeds. What Plum Creek did in there was nothing less criminal. It was once excellent habitat. Hopefully, one day, it could be again.
Hooray for Joe...our favorite tap tender at our favorite brewery. The dude is a mensch!
Quit whining Debby - there's no doubt that experienced hunters who have spent years hunting an area know when game populations are down. Of course you being a non-hunter (I assume) understand very little about the issue. All you've got is your emotional opposition to hunting. Get over it - hunters are not going away.
To the most respectable Sen. Diane Sands, D-Missoula: I have news for you and anyone that cares enough to follow this issue "BREATHING" is an insidious deadly habit that you will have your entire life, and in the end will leave you breathless and dead!
And according to Paul Fielder's logic, if you don't like abuse of children, don't abuse them, but let others do what has been done for ages... goodness
Kill all the coyotes !!!!! They are nothing but a pest!!! Sick dogs on em run em over burn out on top of them Shoot em all!!!! This is america and hunting a fishing is a part of life keeping the coyote population is out of hand and needs to be eradicated. If you dont like hunting and fishing and you think its cruel then why do you yuppies search out pictures and bitch and complain about it all day.
And now we have a coyote and wolf killing contest promoted by "hunters" in Sanders County. Hey, if you think killing is fun recreation imagine the thrill of mass killing. When it comes to hunting food I can accept that hunting is OK if done with respect. When I see random shooting into a massed herd of elk, there is no respect. I liken it to the difference between making love with respect and gang rape. The proposed killing contest is gang rape as a public spectacle. How degraded and debauched will our culture get? The downward curve is steep, with no bottom in sight.
The only problem I see with the coyote hanging there is it isn't a Grey Wolf!!!!!
I hate song dogs. They greedily kill every deer fawn and turkey poult they can get their slobber on. Kill em all!!!
gee if that is all it takes to keep liberals out of Montana I say hang one at every road crossing into the state! 😃
The only thing bad about the coyote hanging in the tree is that there is not another on each side of it
more coyotes in the US now than there were before Columbus showed up....only shame of the above is the pelt was prolly worth $50 if sold. people like to complain bout killing yotes till they find out yotes love to hunt and kill their pets. more than a few populations of yotes in the states that get most meals by killing cats and small dogs.
if this kinda thing helps keep the whacko tree huggers out of the state ill be happy to hang mine up rather than skin them out
It seems the idiotic echoing has ceased for the time being. There isnt anything as irritating as multiple morons agreeing with each other about something not based on fact.
Nice yote :) ! I spent a month hunting in Montana each of the last two years and I would love to live there and have whoever decorated their tree with a dead coyote as my neighbor.
If I hang a dead coyote in a tree with a bow will the lot of you stay the hell away from Kolorado as well, Please?
"King-size coyote fur comforter: Price vs. cost":


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Thrilled be giving a helping hand to my friend at Room 213 and have donated a product to her EPIC prize pack! Check out all of the wonderful teachers who have contributed!! Whoa... that's a prize pack my friends!! Each of the prizes can be used in Middle or High School ELA classroom!!
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