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Publications (115)981.76 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Blood vessels (BVs) not only serve as conduits for oxygen and nutrients but may also fulfill perfusion-independent functions. A growing body of data suggests that blood vessels are an integral component of stem cell niches, including of stem cell niches in the adult brain. This review summarizes in vivo studies supporting the contention that blood vessels may indeed control function of neuronal stem cells (NSCs) residing in the two major neurogenic niches of the adult brain, namely the sub-ventricular zone and the hippocampus. The review discusses different modes of BV-NSC communication and possible mechanisms by which BV may modulate NSC behavior and responses to external stimuli. Copyright © 2015. Published by Elsevier Ireland Ltd.
Article: State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization: A Scientific Statement From the American Heart Association
- [Show abstract] [Hide abstract] ABSTRACT: Premature birth is a major risk factor for multiple brain pathologies, notably periventricular leukomalacia (PVL), which is distinguished by bilateral necrosis of neural tissue around the ventricles and a sequela of neurological disturbances. The 2 hallmarks of brain pathologies of prematurity are a restricted gestational window of vulnerability and confinement of injury to a specific cerebral region. Here, we examined the proposition that both of these features are determined by the state of blood vessel immaturity. We developed a murine genetic model that allows for inducible and reversible VEGF blockade during brain development. Using this system, we determined that cerebral vessels mature in a centrifugal, wave-like fashion that results in sequential acquisition of a functional blood-brain barrier and exit from a VEGF-dependent phase, with periventricular vessels being the last to mature. This developmental program permitted selective ablation of periventricular vessels via episodic VEGF blockade within a specific, vulnerable gestational window. Enforced collapse of ganglionic eminence vessels and resultant periventricular neural apoptosis resulted in a PVL-like phenotype that recapitulates the primary periventricular lesion, ventricular enlargement, and the secondary cortical deficit in out-migrating GABAergic inhibitory interneurons. These findings provide an animal model that reproduces the temporal and spatial specificities of PVL and indicate that damage to VEGF-dependent, immature periventricular vessels contributes to PVL development.
Article: Monocytes entry to the regenerating liver marks the onset of neovascularization and restrains excessive organ growth
Article: A Transgenic Platform for Testing Drugs Intended for Reversal of Cardiac Remodeling Identifies a Novel 11βHSD1 Inhibitor Rescuing Hypertrophy Independently of Re-Vascularization[Show abstract] [Hide abstract] ABSTRACT: Rescuing adverse myocardial remodeling is an unmet clinical goal and, correspondingly, pharmacological means for its intended reversal are urgently needed. To harness a newly-developed experimental model recapitulating progressive heart failure development for the discovery of new drugs capable of reversing adverse remodeling. A VEGF-based conditional transgenic system was employed in which an induced perfusion deficit and a resultant compromised cardiac function lead to progressive remodeling and eventually heart failure. Ability of candidate drugs administered at sequential remodeling stages to reverse hypertrophy, enlarged LV size and improve cardiac function was monitored. Arguing for clinical relevance of the experimental system, clinically-used drugs operating on the Renin-Angiotensin-Aldosterone-System (RAAS), namely, the ACE inhibitor Enalapril and the direct renin inhibitor Aliskerin fully reversed remodeling. Remodeling reversal by these drugs was not accompanied by neovascularization and reached a point-of-no-return. Similarly, the PPARγ agonist Pioglitazone was proven capable of reversing all aspects of cardiac remodeling without affecting the vasculature. Extending the arsenal of remodeling-reversing drugs to pathways other than RAAS, a specific inhibitor of 11β-hydroxy-steroid dehydrogenase type 1 (11β HSD1), a key enzyme required for generating active glucocorticoids, fully rescued myocardial hypertrophy. This was associated with mitigating the hypertrophy-associated gene signature, including reversing the myosin heavy chain isoform switch but in a pattern distinguishable from that associated with neovascularization-induced reversal. A system was developed suitable for identifying novel remodeling-reversing drugs operating in different pathways and for gaining insights into their mechanisms of action, exemplified here by uncoupling their vascular affects.
Article: On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells[Show abstract] [Hide abstract] ABSTRACT: Adult neovascularization relies on the recruitment of monocytes to the target organ or tumor and functioning therein as a paracrine accessory. The exact origins of the recruited monocytes and the mechanisms underlying their plasticity remain unclear. Using a VEGF-based transgenic system in which genetically tagged monocytes are conditionally summoned to the liver as part of a VEGF-initiated angiogenic program, we show that these recruited cells are derived from the abundant pool of circulating Ly6C(hi) monocytes. Remarkably, however, upon arrival at the VEGF-induced organ, but not the naive organ, monocytes undergo multiple phenotypic and functional changes, endowing them with enhanced proangiogenic capabilities and, importantly, with a markedly increased capacity to remodel existing small vessels into larger conduits. Notably, monocytes do not differentiate into long-lived macrophages, but rather appear as transient accessory cells. Results from transfers of presorted subpopulations and a novel tandem transfer strategy ruled out selective recruitment of a dedicated preexisting subpopulation or onsite selection, thereby reinforcing active reprogramming as the underlying mechanism for improved performance. Collectively, this study uncovered a novel function of VEGF, namely, on-site education of recruited "standard" monocytes to become angiogenic and arteriogenic professional cells, a finding that may also lend itself for a better design of angiogenic therapies.
Article: Short-term overexpression of VEGF-A in mouse beta cells indirectly stimulates their proliferation and protects against diabetes[Show abstract] [Hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) has been recognised by loss-of-function experiments as a pleiotropic factor with importance in embryonic pancreas development and postnatal beta cell function. Chronic, non-conditional overexpression of VEGF-A has a deleterious effect on beta cell development and function. We report, for the first time, a conditional gain-of-function study to evaluate the effect of transient VEGF-A overexpression by adult pancreatic beta cells on islet vasculature and beta cell proliferation and survival, under both normal physiological and injury conditions. In a transgenic mouse strain, overexpressing VEGF-A in a doxycycline-inducible and beta cell-specific manner, we evaluated the ability of VEGF-A to affect islet vessel density, beta cell proliferation and protection of the adult beta cell mass from toxin-induced injury. Short-term VEGF-A overexpression resulted in islet hypervascularisation, increased beta cell proliferation and protection from toxin-mediated beta cell death, and thereby prevented the development of hyperglycaemia. Extended overexpression of VEGF-A led to impaired glucose tolerance, elevated fasting glycaemia and a decreased beta cell mass. Overexpression of VEGF-A in beta cells time-dependently affects glycometabolic control and beta cell protection and proliferation. These data nourish further studies to examine the role of controlled VEGF delivery in (pre)clinical applications aimed at protecting and/or restoring the injured beta cell mass.
Article: Conditional Hypovascularization and Hypoxia in Islets Do Not Overtly Influence Adult -Cell Mass or Function[Show abstract] [Hide abstract] ABSTRACT: It is generally accepted that vascularization and oxygenation of pancreatic islets are essential for the maintenance of an optimal beta cell mass and function and that signaling by vascular endothelial growth factor (VEGF) is crucial for pancreas development, insulin gene expression/secretion and (compensatory) beta cell proliferation. A novel mouse model was designed to allow conditional production of human sFlt1 by beta cells in order to trap VEGF and study the effect of time-dependent inhibition of VEGF signaling on adult beta cell fate and metabolism. Secretion of sFlt1 by adult beta cells resulted in a rapid regression of blood vessels and hypoxia within the islets. Besides blunted insulin release, beta cells displayed a remarkable capacity of coping with these presumed unfavorable conditions: even after prolonged periods of blood vessel ablation, basal and stimulated blood glucose levels were only slightly increased while beta cell proliferation and mass remained unaffected. Moreover, ablation of blood vessels did not prevent beta cell generation following severe pancreas injury by partial pancreatic duct ligation or partial pancreatectomy. Our data thus argue against a major role of blood vessels to preserve adult beta cell generation and function, restricting their importance to facilitating rapid and adequate insulin delivery.
Conference Paper: Ectopic expression of VEGF induces condylar hyperplasia[Show abstract] [Hide abstract] ABSTRACT: Temporomandibular joint condylar hyperplasia (CH) is a pathological condition encountered in young and adult individuals, characterized by unilateral overgrowth of the condyle, ramus and mandible. As CH creates significant functional and esthetic jaw and face deformities, therapeutic principles include growth site elimination by high condylectomy followed by bimaxillary orthognatic surgery. CH etiology is unclear and interestingly, similar pathology has not been reported in any other joint. During condyle physiological development, the Vascular Endothelial Growth Factor (VEGF) produced by hypertrophic chondrocytes plays a critical role in the endochondral ossification process. However VEGF is undetectable in adult cartilage. We hypothesize that abnormal VEGF expression accounts for condylar hyperplasia. Objective: , To evaluate the role of VEGF in the pathology of CH by a combined clinical and basic research approach, including examination of VEGF expression in CH human specimens and development of a mouse model mimicking the human pathology. Methods: , First, 32 cases of CH patients are examined. Specimens obtained after condylectomy are processed for histological analysis and stained for VEGF and different bone and cartilage proteins. Second, we have developed a mouse model where VEGF is expressed in a temporally and spatially regulated manner in the cartilage of the mouse. Bone growth is monitored in living mice by in-vivo micro-CT scans. Condyles are processed for standard proteins and mRNA analysis. Results: , Human specimen exhibit atypical VEGF expression in mesenchymal stem cells (MSCs) restricted to the pathological area of the cartilage, correlating with MSCs hyperplasia and appositional cartilage growth. Postnatal induction of VEGF in the mouse, induces MSCs hyperplasia and reactivates the process of endochondral ossification and subsequent bone growth of the mandible. Importantly, cessation of VEGF expression induces the complete reversal of the phenotype in the mouse mandible. Conclusions: , our results show that VEGF can initiate condylar hyperplasia and suggests alternative therapeutic avenues.
- [Show abstract] [Hide abstract] ABSTRACT: Vascular endothelial growth factor-A (abbreviated throughout this review as VEGF) is mostly known for its angiogenic activity, for its activity as a vascular permeability factor, and for its vascular survival activity [1]. There is a growing body of evidence, however, that VEGF fulfills additional less 'traditional' functions in multiple organs, both during development, as well as homeostatic functions in fully developed organs. This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development, functions described elsewhere in this review series. Most functions of VEGF that are essential for proper brain development are, in fact, dispensable in the adult brain as was clearly demonstrated using a conditional brain-specific VEGF loss-of-function (LOF) approach. Thus, in contrast to VEGF LOF in the developing brain, a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [2-4], continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression, hypoxia or apoptosis [4-7]. Yet, VEGF continues to be expressed in the adult brain in a constitutive manner. Moreover, VEGF is expressed in the adult brain in a region-specific manner and in distinctive spatial patterns incompatible with an angiogenic role (see below), strongly suggesting angiogenesis-independent and possibly also perfusion-independent functions. Here we review current knowledge on some of these 'non-traditional', often unexpected homeostatic VEGF functions, including those unrelated to its effects on the brain vasculature. These effects could be mediated directly (on non-vascular cells expressing cognate VEGF receptors) or indirectly (via the endothelium). Experimental approaches aimed at distinguishing between these possibilities for each particular VEGF function will be described. This review is only concerned with homeostatic functions of VEGF in the normal, non-injured brain. The reader is referred elsewhere in this series for a review on VEGF actions in response to various forms of brain injury and/or brain pathology.
Article: Vascular Endothelial Growth Factor-Induced Neovascularization Rescues Cardiac Function But Not Adverse Remodeling at Advanced Ischemic Heart Disease[Show abstract] [Hide abstract] ABSTRACT: Proangiogenic therapy is a promising avenue for the treatment for chronic heart failure and a potentially powerful modality for reversing adverse cardiac remodeling. There is a concern, however, that adverse remodeling might enter an irreversible stage, and become refractory to treatments. The present study aims to determine whether neovascularization therapy is feasible at end stage heart failure and its capacity to reverse adverse cardiac remodeling during progressive disease stages. Using a conditional transgenic mouse system for generating escalating levels of myocardium-specific vascular deficit and resultant stepwise development of heart remodeling, we show that left ventricular dilatation and fibrosis precede ventricular hypertrophy, but that interstitial fibrosis is progressive and eventually results in heart failure. Vascular endothelial growth factor-mediated neovascularization was efficient even at the end stage of disease, and rescued compromised contractile function. Remarkably, remodeling was also fully reversed by neovascularization during early and late stages. Adverse remodeling could not be rescued, however, at the end stage of the disease, thus defining a point of no return and indentifying a critical level of fibrosis as the key determinant to be considered in intended reversal. The study supports the notion of a restricted golden time for remodeling reversal but not for vascular endothelial growth factor-induced neovascularization, which is feasible even during advanced disease stages.
- [Show abstract] [Hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) is the angiogenic factor promoting and orchestrating most, if not all, processes of neovascularization taking place in the embryo and the adult. VEGF is also required to sustain newly formed vessels and plays additional multiple roles in the maintenance and function of certain mature vascular beds. Correspondingly, perturbations in VEGF signaling may impact organ homeostasis in multiple ways. Here we briefly review potential consequences of VEGF loss of function in adult organs. Different vascular beds display highly variable dependencies on VEGF for survival, and its loss of function may trigger the regression of many VEGF-dependent vasculatures. Normal turnover of blood vessels, in conjunction with the fact that VEGF is indispensable for compensatory angiogenesis to restore adequate perfusion, accounts for progressive vascular rarefaction under conditions of chronic VEGF inhibition of even vasculatures that are not intrinsically dependent on VEGF. Because blood vessels may have paracrine functions other than their traditional role in tissue perfusion, vascular regression resulting from VEGF withdrawal may cause substantial collateral tissue damage. VEGF may also impact tissue homeostasis via acting directly on nonvascular cells expressing cognate receptors. In the particular case of the lung, constitutive abundant expression of VEGF together with the fact that its receptors are distributed on both endothelial and epithelial cells is compatible with multiple homeostatic VEGF functions in the adult lung. Indeed, experimental inhibition of VEGF in the mature lung produces lesions resembling common lung pathologies, including emphysema and respiratory distress syndrome.
- [Show abstract] [Hide abstract] ABSTRACT: How organ size and form are controlled during development is a major question in biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here, we report that, surprisingly, non-nutritional signals from blood vessels act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.
- [Show abstract] [Hide abstract] ABSTRACT: The concept of vascular pruning, the "cuting-off" of vessels, is gaining importance due to expansion of angio-modulating therapies. The proangiogenic effects of vascular endothelial growth factor (VEGF) are broadly described, but the mechanisms of structural alterations by its downregulation are not known. VEGF(165)-releasing hydrogels were applied onto the chick chorioallantoic membrane on embryonic day 10. The hydrogels, designed to completely degrade within 2 days, caused high-level VEGF presentation followed by abrupt VEGF withdrawal. Application of VEGF resulted in a pronounced angiogenic response within 24 hours. The drastic decrease in level of exogenous VEGF-A within 48 hours was corroborated by enzyme-linked immunosorbent assay. Following this VEGF withdrawal we observed vasculature adaptation by means of intussusception, including intussusceptive vascular pruning. As revealed on vascular casts and serial semithin sections, intussusceptive vascular pruning occurred by emergence of multiple eccentric pillars at bifurcations. Time-lapse in vivo microscopy has confirmed the de novo occurrence of transluminal pillars and their capability to induce pruning. Quantitative evaluation corroborated an extensive activation of intussusception associated with VEGF withdrawal. Diminution of VEGF level induces vascular tree regression by intussusceptive vascular pruning. This observation may allude to the mechanism underlying the "normalization" of tumor vasculature if treated with antiangiogenic drugs. The mechanism described here gives new insights into the understanding of the processes of vasculature regression and hence provides new and potentially viable targets for antiangiogenic and/or angio-modulating therapies during various pathological processes.
Article: A Transgenic Model for Conditional Induction and Rescue of Portal Hypertension Reveals a Role of VEGF-Mediated Regulation of Sinusoidal Fenestrations[Show abstract] [Hide abstract] ABSTRACT: Portal hypertension (PH) is a common complication and a leading cause of death in patients with chronic liver diseases. PH is underlined by structural and functional derangement of liver sinusoid vessels and its fenestrated endothelium. Because in most clinical settings PH is accompanied by parenchymal injury, it has been difficult to determine the precise role of microvascular perturbations in causing PH. Reasoning that Vascular Endothelial Growth Factor (VEGF) is required to maintain functional integrity of the hepatic microcirculation, we developed a transgenic mouse system for a liver-specific-, reversible VEGF inhibition. The system is based on conditional induction and de-induction of a VEGF decoy receptor that sequesters VEGF and preclude signaling. VEGF blockade results in sinusoidal endothelial cells (SECs) fenestrations closure and in accumulation and transformation of the normally quiescent hepatic stellate cells, i.e. provoking the two processes underlying sinusoidal capillarization. Importantly, sinusoidal capillarization was sufficient to cause PH and its typical sequela, ascites, splenomegaly and venous collateralization without inflicting parenchymal damage or fibrosis. Remarkably, these dramatic phenotypes were fully reversed within few days from lifting-off VEGF blockade and resultant re-opening of SECs' fenestrations. This study not only uncovered an indispensible role for VEGF in maintaining structure and function of mature SECs, but also highlights the vasculo-centric nature of PH pathogenesis. Unprecedented ability to rescue PH and its secondary manifestations via manipulating a single vascular factor may also be harnessed for examining the potential utility of de-capillarization treatment modalities.
Dataset: Supplementary Material[Show abstract] [Hide abstract] ABSTRACT: Supplemental Material
Article: A perfusion-independent role of blood vessels in determining branching stereotypy of lung airways[Show abstract] [Hide abstract] ABSTRACT: Blood vessels have been shown to play perfusion-independent roles in organogenesis. Here, we examined whether blood vessels determine branching stereotypy of the mouse lung airways in which coordinated branching of epithelial and vascular tubes culminates in their co-alignment. Using different ablative strategies to eliminate the lung vasculature, both in vivo and in lung explants, we show that proximity to the vasculature is indeed essential for patterning airway branching. Remarkably, although epithelial branching per se proceeded at a nearly normal rate, branching stereotypy was dramatically perturbed following vascular ablation. Specifically, branching events requiring a rotation to change the branching plane were selectively affected. This was evidenced by either the complete absence or the shallow angle of their projections, with both events contributing to an overall flat lung morphology. Vascular ablation also led to a high frequency of ectopic branching. Regain of vascularization fully rescued arrested airway branching and restored normal lung size and its three-dimensional architecture. This role of the vasculature is independent of perfusion, flow or blood-borne substances. Inhibition of normal branching resulting from vascular loss could be explained in part by perturbing the unique spatial expression pattern of the key branching mediator FGF10 and by misregulated expression of the branching regulators Shh and sprouty2. Together, these findings uncovered a novel role of the vasculature in organogenesis, namely, determining stereotypy of epithelial branching morphogenesis.
Article: Local Retention Versus Systemic Release of Soluble VEGF Receptor-1 Are Mediated by Heparin-Binding and Regulated by Heparanase[Show abstract] [Hide abstract] ABSTRACT: The vascular endothelial growth factor (VEGF) decoy receptor soluble VEGF-R1 (sVEGF-R1) is thought to protect the cells that produce it from adverse VEGF signaling. To accomplish this role, a mechanism for pericellular retention of sVEGF-R1 is required. Local retention may also prevent the accumulation of high circulating levels of sVEGF-R1 and resulting interference with homeostatic VEGF functions in remote organs. To reveal natural storage depots of sVEGF-R1 and determine mechanisms underlying its pericellular retention. To uncover natural mechanisms regulating its systemic release. We show that both the canonical and human-specific isoforms of sVEGF-R1 are strongly bound to heparin. sVEGF-R1 produced by vascular smooth muscle cells is stored in the vessel wall and can be displaced from isolated mouse aorta by heparin. Another major reservoir of sVEGF-R1 is the placenta. Heparin increases the level of sVEGF-R1 released by cultured human placental villi, and pregnant women treated with low molecular weight heparin showed markedly elevated levels of sVEGF-R1 in the circulation. Heparanase is expressed in human placenta at the same locales as sVEGF-R1, and its transgenic overexpression in mice resulted in a marked increase in the levels of circulating sVEGF-R1. Conversely, heparanase inhibition, by either a neutralizing antibody or by inhibition of its maturation, reduced the amounts of sVEGF-R1 released from human placental villi, indicating a natural role of heparanase in sVEGF-R1 release. Together, the findings uncover a new level of regulation governing sVEGF-R1 retention versus release and suggest that manipulations of the heparin/heparanase system could be harnessed for reducing unwarranted release of sVEGF-R1 in pathologies such as preeclampsia.
- [Show abstract] [Hide abstract] ABSTRACT: Neurons, astrocytes, and blood vessels are organized in functional "neurovascular units" in which the vasculature can impact neuronal activity and, in turn, dynamically adjust to its change. Here we explored different mechanisms by which VEGF, a pleiotropic factor known to possess multiple activities vis-à-vis blood vessels and neurons, may affect adult neurogenesis and cognition. Conditional transgenic systems were used to reversibly overexpress VEGF or block endogenous VEGF in the hippocampus of adult mice. Importantly, this was done in settings that allowed the uncoupling of VEGF-promoted angiogenesis, neurogenesis, and memory. VEGF overexpression was found to augment all three processes, whereas VEGF blockade impaired memory without reducing hippocampal perfusion or neurogenesis. Pertinent to the general debate regarding the relative contribution of adult neurogenesis to memory, we found that memory gain by VEGF overexpression and memory impairment by VEGF blockade were already evident at early time points at which newly added neurons could not yet have become functional. Surprisingly, VEGF induction markedly increased in vivo long-term potentiation (LTP) responses in the dentate gyrus, and VEGF blockade completely abrogated LTP. Switching off ectopic VEGF production resulted in a return to a normal memory and LTP, indicating that ongoing VEGF is required to maintain increased plasticity. In summary, the study not only uncovered a surprising role for VEGF in neuronal plasticity, but also suggests that improved memory by VEGF is primarily a result of increasing plasticity of mature neurons rather than the contribution of newly added hippocampal neurons.
Article: Metabolic homeostasis is maintained in myocardial hibernation by adaptive changes in the transcriptome and proteome[Show abstract] [Hide abstract] ABSTRACT: A transgenic mouse model for conditional induction of long-term hibernation via myocardium-specific expression of a VEGF-sequestering soluble receptor allowed the dissection of the hibernation process into an initiation and a maintenance phase. The hypoxic initiation phase was characterized by peak levels of K(ATP) channel and glucose transporter 1 (GLUT1) expression. Glibenclamide, an inhibitor of K(ATP) channels, blocked GLUT1 induction. In the maintenance phase, tissue hypoxia and GLUT1 expression were reduced. Thus, we employed a combined "-omics" approach to resolve this cardioprotective adaptation process. Unguided bioinformatics analysis on the transcriptomic, proteomic and metabolomic datasets confirmed that anaerobic glycolysis was affected and that the observed enzymatic changes in cardiac metabolism were directly linked to hypoxia-inducible factor (HIF)-1 activation. Although metabolite concentrations were kept relatively constant, the combination of the proteomic and transcriptomic dataset improved the statistical confidence of the pathway analysis by 2 orders of magnitude. Importantly, proteomics revealed a reduced phosphorylation state of myosin light chain 2 and cardiac troponin I within the contractile apparatus of hibernating hearts in the absence of changes in protein abundance. Our study demonstrates how combining different "-omics" datasets aids in the identification of key biological pathways: chronic hypoxia resulted in a pronounced adaptive response at the transcript and the protein level to keep metabolite levels steady. This preservation of metabolic homeostasis is likely to contribute to the long-term survival of the hibernating myocardium.
Top Journals
Hadassah Medical CenterYerushalayim, Jerusalem District, Israel
Hebrew University of Jerusalem
Yerushalayim, Jerusalem, Israel
- • Department of Developmental Biology and Cancer Research
- • Department of Biochemistry and Molecular Biology
- • Hadassah Medical School
- • Department of Biological Chemistry
Tel Aviv UniversityTell Afif, Tel Aviv, Israel
Weizmann Institute of ScienceIsrael
University of Wisconsin–Madison
Madison, Wisconsin, United States
- McArdle Laboratory for Cancer Research


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blowing raspberries
My LO isn't doing it yet either. He's trying to though. Blowing raspberries typically starts around 5/6 months so if they aren't doing it now, they will start soon. Just sit face to face with him and encourage him (blowing spit bubbles, raspberries and babbling are the beginnings of speech so they should be encouraged) to try by doing it yourself. He will eventually learn.
Ryleigh just started it about a week ago now. She sucks in her bottom lip and blows and drools all down her chin. She thinks it is so funny.
I agree with PP, I don't think it is a milestone. I actually don't track any milestone. She will do what she wants, when she wants. If she isn't walking or talking by 5 then I will be concerned. :)
DD1 - EDD 10/27/07 born 10/26/07
DD2 - EDD 8/8/12 born 8/20/12
I think it's okay for them to not be making those nosies yet. :) Mine mainly gives kisses, lol but she has done raspberries
Lindsay (20) married to my best friend, Brad (28) July 2010!
Connor james was born April 13th, 2010
Olivia Grace was born July 27th, 2012 :)
Mine started doing that about 2 weeks ago (at 5.5. months). I didn't know it was important. Don't worry is your baby is babbling I would think he is ahead of the game.
Our LO was born aug 26th and just started doing them a couple of weeks ago! I wouldn't worry, especially if LO is babbling!
I doubt all babys should be doing it. My daughter blows raspberries, but doesn't roll or sit unassisted. She is 6.5 months, and did start doing the raspberries till 3 weeks ago or so. All she does is growl and blow raspberries lol
Learn more
Look how far your child has come.
Review your child's growth milestones.
Read about 3 years 7 months : Week 3.
Your growing child
Your 3 1/2-year-old: Starting chores
Your 3 1/2-year-old: Understanding time
Your 3 1/2-year-old: Puzzle time
Your 3 1/2-year-old: Read it again!
Your 3 3/4-year-old: Getting silly
Learn more
What's next for your growing child?
Get a glimpse of what's to come.
Read about 3 years 9 months : Week 1.

subset: commoncrawl


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Rated 5 out of 5 by sparklingjules Love it My new recent favorite earrings! The color is beautiful! December 22, 2014
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Journeys of freedom & discovery. Travelling in purpose-built trucks or 4x4s you'll see all the highlights but also get far off the beaten track. Led by a professional crew or driver, groups help with the cooking & setting up camp, enjoying a real hands on experience.
Our Basic tours offer superb value and are ideal for those who are happy to forgo some creature comforts in favour of an authentic and fun experience. Under the leadership of a fully trained tour leader, you will enjoy all the highlights and freedom of independent travel with the convenience, security and companionship of a small group. All accommodation is based on twin share. If you are a solo traveller you will share with another solo traveller of the same sex. Single supplements are available on some trips. If you are interested in booking a single supplement please contact us to check availability.
This epic and challenging trip takes you right the way through some truly off the beaten track destinations. We take in the highlights of Senegal and the Gambia and explore the region's marvellous wetlands and birdlife. We then plunge into the remarkable but lesser-visited countries of Guinea-Bissau, Guinea, and Sierra Leone, visiting the area's stunning and remote mountains and the phenomenal beaches of the Freetown Peninsular. We will then head east through Guinea's remote forest region, before entering the wonderful country of Côte d'Ivoire and following the Atlantic coast of Ghana to its bustling capital of Accra. We then continue on to the unique and fascinating lands of Togo and Benin, two countries packed full of history, voodoo culture and stunning scenery. Unlike their more visited cousins in East Africa, these countries truly are hidden gems that are largely untouched by tourism - every trip through the region is therefore an incredible adventure involving fantastic community interaction, some wonderful wild camps, some difficult roads, and a rare opportunity to experience a more traditional way of life. West Africa boasts a huge arts and craft scene, colourful and vibrant markets, and incredible traditional music - however, what makes West Africa especially wonderful are the people - the fascinating cultures, incredible atmosphere, and warm friendly smiles that greet you every day are what makes a trip here so very special, and why the area is frequently on the top of the favourites list for many of our most seasoned travellers. Join us for this incredible adventure!
Our tailor made adventure holidays will truly inspire and delight the senses and will live in your memory for ever.more info
Join us on one of our worldwide adventures coming up over the next few months – all guaranteed to depart, all at up to 20% off.more info


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Fruits & Vegetables in Schuylkill Haven
Below is a list of businesses listed within our directory. If you do not see your business within the list below, you can submit it for addition to this list. Adding your business will feature your listing above Standard listings.
Boyer's I G A Inc - Schuylkill Haven, PA - Phone: (570) 385-3141
Bridge's Market - Schuylkill Haven, PA - Phone: (570) 739-4111
BROK SEL MKTS Inc - Schuylkill Haven, PA - Phone: (570) 385-4711
Romeo's - Schuylkill Haven, PA - Phone: (570) 385-2935
Helpful Definition for: Fruits & Vegetables
Fruits & vegetables, in Schuylkill Haven, are the edible parts of plants that are rich in various nutrients & dietary fibers and pose amazing health benefits if consumed on a regular basis.
Several fruits & vegetables, for their very high antioxidant content, have anti-aging and anti-cancer properties. Fruits and vegetables also help reduce high blood pressure, blood cholesterol & body fat. Risk of breast cancer among postmenopausal women gets reduced due to an increased intake of fruits. Higher consumption of fruits, berries and vegetables reduce the risk of cardiovascular disease-related death. Fruits and vegetables are known to protect against chronic disease because of their rich content of many phytochemicals. Health authorities in Schuylkill Haven recommend regular consumption of at least one citrus fruit and one cruciferous vegetable to stay healthy.
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Governor Cuomo Launches $5 Billion Clean Energy Fund To Grow New York's Clean Energy Economy
Clean Energy Fund will advance solar, wind, energy efficiency and other clean tech industries to spur economic development and reduce harmful emissions (New York, NY) Governor Andrew M. Cuomo today announced the New York State Public Service Commission's approval of a 10-year, $5 billion Clean Energy Fund to accelerate the growth of New York's clean energy economy, address climate change,..


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The Filtrete Micro Allergen filter definitely hits the sweet spot when it comes to value-for-money. It captures everthing from dust and pollen to the tiniest allergens like smoke and pet dander--without draining your wallet. And talk about having your cake and eating it too: The Micro Allergen goes to work every time your heating and cooling system kicks on. It's like having an expensive whole house air purifier, only cheaper! The Filtrete Micro Allergen 9826DC-6 Filter fits heating/air conditioning systems that use 1-inch replacement filters. The filter uses pleated fabric to remove contaminants for up to 3 months. Outperforms all competitors 3-month, 1-inch filters. Electrostatically charged fibers act like tiny magnets to capture even the smallest particles.
- Genuine OEM Product
Captures the following contaminants:
- Dust
- Dust Mite Debris
- Lint
- Mold Spores
- Pet Dander
- Pollen
- Smog
- Smoke
|Used In Brands
|Manufacturer's Id
|Advertised Size (in)
|20 x 24 x 1
|Actual Size (in)
|19.6 inches (length) x 23.6 inches (width) x 0.8 inches (thickness)
|Actual Size (cm)
|49.78 x 59.944 x 2.032
|Primary Filter Media
|Pleated Fabric
|Filter Life (months)
|3 months
The 9826DC-6 is also known by the following part numbers:


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Faculty Checklist
For eLearning Curriculum Courses
Checklist for Teaching eLearning Courses
|Tutorials and Resources
(Also available by
clicking here)
|Pre-semester Planning
|6-2 weeks before semester begins
|Course shells:
Click here for CAW if you wish to request a master. Click on the Blackboard or Moodle tab, then click on Request Master and complete the form.
|If using a publisher cartridge, contact program or discipline chair and/or instructional developer (ext. 6111) early regarding the course cartridge terms of use regarding copying.
|Click here for more information about publisher cartridges
|Read new semester timeline for important LMS (Blackboard / Moodle) dates.
|Click here for LMS timeline Activities
|After shell creation, if you want to combine multiple course sections, make sure you know and follow your program's policy. Requests are made in CAW (Course Administrative WebTools area). NOTE: the Instructional Method for your course must be IN, TW, or TR(WB) in order to combine shells. If you do not see your course in the combine listing, please check that the Instructional Method code is correct in the COD.
|Click here for CAW
|If you are using the Moodle LMS you must (Moodlize) request a Moodle shell in CAW. NOTE: the Instructional Method for your course must be IN, HY, TW, or TR(WB) in order to Moodleize. If you do not see your course in the Moodleize listing, please check that the Instructional Method code is correct in the COD.
Click here for CAW
Click here for Moodle tutorial
|Important: If you are teaching a fully online (IN) or hybrid (HY) course where the only in-person requirement is testing, be sure that you have an EVA activity and that your students complete it on or before the 10% Census date. Students should not be allowed to work in the course until they have completed the EVA.
|Click here for instructions regarding the EVA.
|6- 4 weeks before semester begins
|COPY YOUR COURSE(S), as soon as shells become available (typically 4-weeks before the semester begins). NOTE: if you are combining sections, combine first, then copy into the combined shell.
|Click here for Bb course copy handout
Click here for Moodle
|Preparing Course(s) in New Shell(s)
|2-1 week(s) before semester begins
|Once you have copied the course content from the Master or previous semester shell into this new course, you need to update it:
Check LMS timeline for outage dates and plan deadlines accordingly.
Click here for SafeAssign Synchronize Handout
|7-1 days before semester begins
|If desired, contact students with first day instructions before class start date. Please remind them that they will not see the courses in the LMS until the official start date. See student email list on CAW site.
|Click here for information regarding Class Email Lists
|Make sure you understand the current attendance guidelines and procedures. NOTE: they are different for face-to-face and online courses.
|Watch the tutorial in LearnerWeb: Click on Course Catalog; Search for Attendance; click on Employee Online Learning
|Communicate schedule of on-campus student Blackboard Practice sessions and/or direct students to the new online Student Orientation.
|Click here for schedule of on-campus Blackboard Practice Sessions
Click here for online student orientation
|First Day of Class
|First Day of Class
|Students will be activated in Bb or Moodle courses on the official course start date as indicated on course COD.
|Your official course roster is available in WebEmployee.
|Make sure you post a welcome announcement and contact your students on the first day of class.
|Click here for how to create an announcement in Bb. Click here for Moodle
|Course Shell Availability
Click here for Bb tutorial on how to make courses available
Click here for instructions regarding the redirect link in the unused Blackboard course.
|During Semester
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A few days prior to your 10% - Census date, contact any students who have not completed the EVA and urge them to do so. Students who do not complete the EVA cannot be counted as Present and should not be allowed to continue working in the course.
Enter WN grades for students who have not completed the EVA by the 10% census date.
|Click here for instructions regarding the EVA.
|Ask students to complete the online student opinion survey when it is made available.
|Complete STAR reporting/mid-term reviews. Contact your division office for instructions and deadlines.
|QEP Reporting calendar
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|24 hours after last class
|Recommended though not required: Archive or backup your current course.
|Download current course Gradebook, as backup.
|Click here for Bb tutorial (scroll down to How to Download Grades)
Click here for Moodle
|Enter final grades into online grading system through Web Employee.
|Click here for instructions
|Contact Information
|Contact an Instructional Developer at email@example.com or 704.330.6111 if you have questions.


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Orioles advance, 5-1 over 2-time AL champion Texas
Updated: October 6, 2012, 5:24 AM ETAssociated Press
ARLINGTON, Texas -- Buck Showalter thrust his arm into the air, then stood back and savored watching his surprising Baltimore Orioles celebrate on the field.
Champagne showers followed in the clubhouse after hugs from their manager following a 5-1 victory over the two-time defending American League champion Texas Rangers in the league's first win-or-go-home wild-card playoff Friday night.
"One of our biggest regrets of the year would have been if our guys couldn't have a moment after ...
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Dealing With a Picky Eater
by Amalah
My son, at 13 months, is turning out to be SUCH a picky eater. I'm completely baffled. He only wants to eat pureed veggies and fruits (with the exception of bananas–he loves them. I swear the kid is part monkey.) Help!
Creepy Cousins
by Amalah
Her husband's family thinks ol' Cousin Carl is perfectly harmless. Her mother's instinct says otherwise. What to do?
5 Things You Should Know About Pediatric Orthodontics
If there's one thing you should know, it's the importance of early intervention when it comes to the care of your child's teeth and face.
Call to Action: Support The Consumer Recall Notification Act
Got five minutes? Take the time to send a quick email to your Senators about the importance of food safety.
U.S. Olympic Champion Tanith Belbin's Advice for Moms
I was very excited to speak to Tanith as she's been very vocal about her weight and body image issues. I asked Tanith what advice would she share with moms of children athletes who might be concerned about their child's current or future focus on body image. We can all learn from Tanith.
Olympic Moms Share Their Best Advice to Parents of Ambitious Athletes
In between competitions I've been able to spend time with Olympic moms as they've dined or just hung out watching Team USA compete. They have some great advice to share with the parents of aspiring Olympic athletes and just any competitive sports kids.


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Facebook's promoted posts cheekily target irrelevant audience
Facebook's promoted posts are great for spreading initial awareness but it cheats and adds random countries in their targeting, Kipp hears
September 19, 2012 1:27 by Muhammad Aldalou
Quality is better than quantity – be it a sickly sweet cliché or not. But before you start lunging hypothetical scenarios at me where quantity proves to actually be better, consider Facebook's relatively new (at least on mobile platforms) "promoted posts" feature that allows companies to pick and choose particular posts which they want prominently highlighted in the news feed of their existing fans and/or the friends of said fans.
It's not to insinuate that Facebook's advertising strategies aren't at all qualitative, because to a degree, they are. And the social media giant is already receiving plenty of heat without needing Kipp to pile on, but the reality remains that despite its enormous database of active users and ability to target millions, it continues to face hindrances on their road to effectively monetizing this huge pile of potential.
"Today, Facebook is releasing a new version of Pages Manager app that allows businesses to buy Promoted Posts on-the-go directly from mobile phones. As you may recall, Promoted Posts is a product which gives businesses the increased flexibility to hand-select and boost posts in the news feed. Being able to purchase Promoted Posts on mobile was a widely requested feature from small businesses, so Facebook is now making it easier for businesses of all sizes to buy ads directly from their mobile phones," said the social giant in an e-mail statement.
If they say that it was a highly demanded feature then who are we to argue with that? After all, no matter how many negative reviews Facebook's strategy may receive, SMEs continue to sign up for its advertising services knowing that when it comes to targeting and reach – one can't exactly find an equally influential platform around the corner, except for Google, that is.
But advertisers' sentiment towards Facebook's ability to boost their revenue has, to say the least, been growing weaker by the day. Don't just take Kipp's word for it though, consider Kim Castleberry's (Business2Community contributor) trial run of a promoted post where she decided to allocate a small budget to promote an affiliate link that only had a little over 1 day left of visibility. She was bemused but not entirely displeased with the results, at first.
"The content was very promotional. However, it was buffered by a lot of content in the last two weeks that was non-promotional. It also was "enhanced" by an image post; earlier in the day that had gained a lot of likes… thus naturally improving the page's overall EdgeRank (visibility to fans)," she writes.
For the purpose of this test, Kim chose the $300 payment option (knowing she won't need the entire amount), which theoretically afforded her between 50k to 100k impressions. She stopped at $64 when the link hit 432 post likes, 23 comment posts and 108 link clicks. She didn't 'buy' it though and she explains why.
"According to Pretty Link Pro, set to aggressive data collection while filtering for known spam bots, there were only 5 unique clicks generated. Optimistically, there may only be 20 unique clicks in total and pessimistically there may be as few as 4 unique clicks by humans," she said.
Distinguishing genuine clicks from ones by users who are merely curious but lack any purchasing interest or are entirely irrelevant to your brand's targeting is a challenge that that every brand (involved in social media advertising) faces, but when you add spam bots and 'fake accounts' to that formula; nightmarish.
"I'd only really recommend those (promoted posts) for new products. They're great for spreading the message. In terms of actual value, the results aren't insane. Did not see great CTR from it. It also cheats and adds tons of random countries in the targeting to reach people," says Joe Akkawi, founder of Paz Marketing in Dubai.
So there you have it. Facebook's promoted posts may be great at generating awareness, spreading interest for a new product or getting a headline around the town but in terms of harnessing potential buying interest, rather disappointing.
The common denominator of consumer feedback seems to mostly revolve around the attention garnered by unnecessary targeting of users in countries where your brand is irrelevant, subsequently leaving you with 'posts' and 'likes' from users that are likely to be miles outside your target audience.
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UPDATE: Neighbors say Crable never left the house without his gun. Details after the jump.
David Crable was killed last night in a shootout that left two Pierce County Deputies in critical condition
Two Pierce County Sheriff's Deputies are in critical condition after trading gunfire with a man inside a rural south sound home Monday night.
At around 9pm, the two officers arrived at a residence near Eatonville to investigate reports of a domestic disturbance.
The two were then invited inside by one of the residents where, according to Pierce County Sheriff's Department spokesperson Ed Troyer, suspect David Crable "basically ambushed the deputies."The two officers entered and were fired upon by Crable, who had gone upstairs to retrieve a rifle and handgun. At least one of the two deputies returned fire, killing the 35-year-old.
Both deputies were seriously injured in the exchange. The veteran officer was taken to Madigan Army Medical Center. [UPDATE: His condition has now been upgraded to "serious," and is expected to survive.]
The second deputy was hit multiple times, and was later airlifted to the trauma center at Harborview Hospital in Seattle where he remains in critical condition.
Even before last night their assailant was well known to local law enforcement. Police had previously made several trips to the Crable home in response to David Crable's various run-ins with his family members, reports the Tribune.
The is the latest in a string of attacks on area law enforcement. Earlier this month, four Lakewood officers were shot and killed at a Parkland coffee shop. Factoring in last night's incident, the total number of area police officers killed or wounded by gunfire in the last two months now stands at eight.
UPDATE: KOMO News says that records show Crable was convicted of two crimes just this past June.
Crable was accused of threatening his 16-year-old daughter with a kitchen knife, shoving her up against a wall and slapping her across the head. When his brother tried to interfere, Crable grabbed him by the throat and pushed him out of the house.
By means of a plea deal, Crable was able to get probation for all but one day of his year-long sentence. He was also ordered to have no "hostile contact" with his brother or daughter.
Spokesman Troyer says that Crable has "a long history of terrorizing his family."
UPDATE: KIRO says that both deputies are married with kids.
Kent Mundell, the more seriously injured of the two, is a 10-year veteran. He has two children, ages 16 and 10.
Nick Hausner, in serious condition and expected to survive, is a 20-year veteran. He has two children as well, ages 14 and 12.
UPDATE: King 5 talked with some of Crable's neighbors and found out that (surprise) that he was the kind of dude you want nowhere near your family.
One note. I hope it's not in bad taste to say this, given that there are still two cops in the hospital and, no matter how much havoc he wreaked, Crable did leave behind a daughter who's no doubt going to be traumatized by this incident her whole life. But I have to take issue with something one of Crable's neighbors said on that video.
Bobby Brown, the guy with the diamond stud. He tells King 5's reporter that Crable once armed him with a loaded pistol when he asked him to house sit. Then he says, "It doesn't matter who ya know, who ya meet, anybody can do anything anymore, it's amazing."
I'm not trying to beat up on a guy who just found out his dead neighbor is an attempted cop-killer. But that statement? That vaguely says that anyone is capable of anything, at anytime? It's wrong. Really, really wrong.
If greater Seattle has learned anything from Christopher Monfort, Maurice Clemmons or, now, Crable, it's that these "random" acts of violence against the cops are precipitated by a whole lot of other small, or large, events that, in hindsight, turn the tragedies they're responsible for from "totally out of the blue" to "depressingly preventable."
Clemmons told family gathered around the Thanksgiving dinner table that he was going to kill some cops. A couple days later, he did just that.
Monfort firebombed three police cruisers, then left a note saying he'd be targeting law enforcement. A promise he unfortunately delivered on two weeks later.
Thus far it's not clear if Crable specifically targeted police. But he did seem to have it out for his daughter and brother. The same people who called 911 last night frantic because a large drunk man who'd previously been violent towards them was back in their house.
The point? This neighbor of Crable's, who I sympathize with, went a little too far. Does random violence exist? Sure it does. But let's no go overboard and say we're totally surprised. Or that this just confirms that anyone is capable of anything at anytime.
The guy gave his house sitter a loaded gun. Even those who swaddle themselves in the 2nd Amendment will tell you, that's just not right.


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|Pro - Slice Peeler Fruit Vegetable Wavy - Edged Tool
Often seen hanging up in streetside kitchens, the Blue Pro-Slice is a ubiquitous item that is commonly used throughout Thailand. Cheap, affordable, and easy to clean, Kiwi products are tools that you just can't go wrong with.
It is a product of thailand .
High Standard .
Longer sharper .
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|Practice Thai Art of Fruit & Vegetable Carving by Yourself Decorative Thailand Best Seller pattern to carve Sculpture Wooden Handle Learn to DECORATE Peeling Gutting Step by Step Easy Use Stainless skill for making beautiful work. illustrates follow easy Year Award CREATIVE CARVING Garnishes Stainless Steel kitchen knife skill of carving vegetables Basic Craft Plate Technic Learning Study Decoration Knife knives High Quality Teaching Superior Professional chef book Tools Instrument equipment Design lessons
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Steph Curry's Jersey Is More Popular Than LeBron'sStephen Curry has surpassed LeBron James for the most popular jersey in the NBA.
Curry Makes Cover Of Sports IllustratedSports Illustrated is showing some love to the Warriors by putting Steph Curry on its cover with his team's new prized possession – the Larry O'brien trophy.
Top 5 Wildest Sports Callers Of The Week: June 15th-June 19thThe Top 5 Sports Callers of the week is a weekly installment from CBS Local Sports that will bring you the wildest callers from across the nation.
Keidel: Aside From LeBron, Mark Jackson Had To Be Most DeflatedGenerally, a new coach inherits the very vulnerable team that got the prior coach fired. Which is why, aside from LeBron, the most viscerally defeated or deflated man in the building was Mark Jackson.
5 Reasons Why Oakland Is Awesome And Ready For Its Closeup Following Warriors NBA Finals WinThe Golden State Warriors NBA crown is breathing life into a city that has more frequently made national headlines for police brutality protests, high crime rates and blight.
9 Internet Memes That Clown LeBron James After NBA Finals LossNot to rub salt into fresh wounds but some of these were just too good to pass up.
Exhausted Warriors Return To Oakland As NBA ChampionsStephen Curry came off the plane, lifted the Larry O'Brien Trophy as he walked down the mobile staircase and let the gold award shine in the California sun.
SF Chronicle With Warriors NBA Championship Win On Front Page Sells Out In A Matter Of MinutesSan Francisco Chronicle kiosks and paper stands were empty by mid-morning Thursday after the Warriors NBA Finals Championship win.
President Obama, Governor Brown Give Shout Outs To World Champion WarriorsPraise has been raining down on the World Champion Golden State Warriors in the hours since they end the franchise's 40 year title drought, including from the highest offices in the land.
Iguodala Becomes First NBA Finals MVP After Never Starting A Regular Season GameIguodala didn't start a game all season until Steve Kerr inserted him into the lineup in Game 4 after the Warriors trailed 2-1. That "small ball" move sparked a three game run that gave the Warriors their first title in 40 years.
Warriors Fan Uses Grains Of Salt To Show Love For TeamOne Golden State Warriors fan used thousands of grains of salt to show love for the team as they battle the Cleveland Cavaliers in the NBA Finals.
5 Warriors Tribute Songs To Get You Pumped For A ChampionshipWith the team just hours away from its first shot at closing out the Cavaliers, we wanted to provide you this pre-game playlist to get pumped for the Game 6. Be sure to vote for your favorite at the bottom.


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Inherently Funny
My grandpa always tell my grandma this when she wanted a kiss at night.
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Hot pixels
Started Aug 22, 2014 | Questions thread
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Vusal • New Member • Posts: 13
Hot pixels
Hi, I just bought my camera and there is some hot pixels... I shot at 100 ISO, 30 second shutter speed without lens.With cap.So there was 8-9 hot piexls.May be more. How much hot pixels are acceptable for new Canon 5D Mark III? Tested several times and each time different results.Bu mostly 1-2 hot pixels to 8-9... (1-2 hot pixels when @100 ISO, 15 sec shutter speed-right after turning on camera while this still cold)
This question has not been answered yet.
Canon EOS 5D Mark III
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Update on JacksonJackson is applying four his fourth business loan, which he will use to purchase spare motorbike parts, in addition to the bicycle parts business which he has always run. He hopes to grow both business and eventually own a workshop for assembling motor bicycles.
Previous Loan DetailsJackson is applying for his third business loan from KADET LTD. He plans to purchase more bicycle tires, pedals, and tubes. He will use the anticipated profits to open another shop. He hopes to excel in the business and have a happy family. More from Jackson's previous loan »
Additional Information
About VisionFund KenyaVisionFund Kenya is dedicated to economically empowering its clients by providing financial services to improve living conditions of micro-entrepreneurs and their children across Kenya. VisionFund Kenya is the microfinance subsidiary of World Vision Kenya. Obtain more information on VisionFund Kenya from its website.
Concurrent and Successive Loans
Our Field Partners often work with borrowers over a series of loans as the borrowers build credit, take out bigger loans, and expand their businesses. In order to make it easier for our Field Partners to post loans for borrowers who have been listed on Kiva before, we allow them to post successive and concurrent loans for their Kiva borrowers. This means that our Field Partners are able to post a borrower's second, third, etc., loan on Kiva without having to re-enter all of the borrower's information.
This borrower has been listed on Kiva before, so you'll see an updated loan description, as well as excerpts of the original descriptions from earlier loans. Most borrowers take out loans consecutively, meaning that they receive a second loan after having repaid the first. However, sometimes our Field Partners give out concurrent loans, allowing borrowers to take out one primary loan and a secondary "add-on" loan along with it. These "add-on" loans are typically smaller than the borrower's primary loan and serve a different purpose. Because Field Partners can now post loans as successive and concurrent loans, you will be able to track borrower progress over time and see the various ways a borrower is working with our Field Partners through funds from Kiva's lenders.
Loan tags help lenders find loans that match certain areas of interest. You can add up to 5 tags for this loan.
About Kenya
574View loans »
Success!! The loan was 100% repaid
- Repayment Term
- 14 months (Additional Information)
- Repayment Schedule
- Monthly
- Pre-Disbursed:
- Oct 16, 2013
- Listed
- Nov 1, 2013
- Currency Exchange Loss:
- Possible
- Ended:
- Nov 17, 2014


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Struggling To Keep Tempo
Erin and her team of graphic designers were in charge of providing creative services to 57 requestors at all House of Blues and LiveNation venues nationwide, from Hollywood to Texas to Maryland. The barrage of projects—usually 250 per month—ranged from fliers and menus to bus wraps and billboards. Despite having their team reduced from four to three members and their number of venues increased from 12 to 33, the small team miraculously kept their heads above water. But Erin was well aware that her team had accomplished this despite their clunky work tools, regularly working late on nights and weekends to stay on track.
Requests were emailed as Word documents. Design proofs would be emailed out for review, only to multiply into different versions and make accountability nearly impossible. Erin and her team had brought in project management software that met some of their needs but proved difficult for her requestors to adopt.
It soon became obvious that, if Erin was ever going to get better visibility into her team's activities, she needed to do something different.
Easier And Faster
In fall 2012, with the contract on her existing project management software expiring, Erin was contacted by Workfront.
With its intuitive, social media-inspired interface, Workfront could be adopted by every member of the House of Blues Marketing team, providing one system of engagement in which Erin, her designers, and all of their requestors could communicate in real time. The Workfront proofing tool would make it possible for designers and requestors to give feedback on a single proof without confusion.
Throughout all of these transactions, Workfront could capture all status updates and resource data and turn them into real-time reports. Anyone on the team, from designers to executives, could access these reports at any given time. Most importantly, Workfront would provide an on-site consultant to evaluate their needs, build best practices into their processes, and get them online faster.
Erin immediately recognized the value that Workfront could offer to her team. Within 45 days of first meeting with Workfront, her team was up and running.
- Small team struggled to keep up with increasing number of requestors and projects.
- Request and design proof management was handled through email, creating confusion and making accountability nearly impossible.
- Existing project management tools were inefficient, difficult to adopt.
- One system of engagement enabled real-time communication, eliminated confusion
- Robust reporting for immediate and accurate status updates
- Better resource management resulted in significantly decreased over-time
- Automation allowed team to reclaim valuable design time
With communication and reporting automated, Erin's team could spend more time on quality design.
"We were managing brand standards for the House of Blues and all its sub-brands. We needed a platform where we weren't bouncing files all over the Inter- net, where we could see where our projects lived at any given moment. "
Creative Director
Less Busywork, Higher Quality
Thanks to a fast, effective implementation with the Workfront consultant, Erin and her team members began seeing the difference right away. The solution's welcoming, intuitive interface made it easy for requestors and designers to pick up with minimal training. Soon communication was happening automatically in real time with stakeholders on the other side of the country as if they were just down the hall. The Workfront proofing tool and task updates guaranteed that all stakeholder feedback was gathered in one place for all team members to see.
The House of Blues creative team was bombarded with 250 projects per month-from fliers to menus to bus wraps to billboards.
"The minute our Workfront consultant arrived, he sat down with us and didn't just go through what Workfront can do, but asked me questions about our workflow. 'Is that the best way it can work? Why do you do things this way?' He didn't just figure out how things would work in Workfront, but figured out if we were using the most efficient workflow, period. "
Creative Director
Freed from constant manual communication, Erin and her designers found themselves spending more time designing. Overnight, the need for overtime decreased drastically.
This communication all began to trickle down into unprecedented reporting capabilities. Erin instantly became aware of the team's peak times or how many requests came from each venue. As Erin went into meetings with the CEO and EVPs, she could pull up-to-the-minute project data and speak confidently about what her team members were working on and what they had waiting in the queue. This visibility began to be extremely educational for Erin and her managers in streamlining the way they did business.
In their first six months of using Workfront, with much of their communication and reporting automated, Erin and her team found they had more time to improve the quality of their work. Going forward, Erin could call her consultant to get answers and keep pushing the boundaries of what House of Blues could do with the solution.
"Now, when someone IM's or emails me with a request, I tell them right away, 'Can you put that in Workfront? Don't call me on the phone. Don't give me an IM. Put it in Workfront.' Because that gives me one location for all my project data—one source of truth. "
Creative Director


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 Art Pedroza has declared an end to the Orange County blogs wars and made himself a martyr to the cause. While it's all great theater, it's a song many of us have heard before. There isn't a blogwar with the Orange Juice and Art, but there is the matter of a pending lawsuit. And…
Tag Archive for Janet Nguyen
Janet Nguyen's Chief of Staff Moving On
by Chris Prevatt •
Andrew Do, who played a central part in the election saga of Orange County Supervisor Janet Nguyen in 2007 and then became her chief of staff, will leave the fifth floor this coming week, just months after Nguyen took over as chairwoman of the Board of Supervisors.
FactChecking recent OJ Posts on the Settlement Offer and Lawsuit
by Dan Chmielewski •
I had some high hopes that when Vern Nelson took over as editor of the Orange Juice blog he'd make an effort to make sure that some of the posts had a measure of accuracy. And I also hoped to win the $266 million lottery Tuesday, and I didn't so I'm not surprised by multiple errors and misrepresentations in three recent OJ posts about our pending lawsuit against Art Pedroza and the Orange Juice Blog.
Open Government Advocacy Group Demands Westminster Rescind Action That Violated Brown Act
by Chris Prevatt •
On Monday, May 3, 2010, Richard McKee acting on behalf of Californians Aware submitted a letter to the city of Westminster demanding that they rescind their action, which three Council members Diep, Quach, and Ta took outside a regular meeting of the City Council, because that action appears ot be in violation of the Brown Act.
Our Take on the NUFF Forum Last Night
by Dan Chmielewski •
A big thank you to Neighbors United For Fullerton for hosting a session last night on Political Blogging. The panel ran about two hours and could easily have gone a third hour. For the questions were good and I believe the audience came away with an understanding of each blog and what we're trying to…
Anger Management or Inconsistent Ramblings?
by Dan Chmielewski •
I'd like to pay tribute this week for our number one reader of the week, Orange Joke blogger Sean H. Mill, who has read every word in our posts and comments by other readers with a jaudiced eye to call for truth, justice and the American way. My fellow LiberalOC blogger Chris Prevatt is the…
Let's Hear Those Voicemails
by Dan Chmielewski •
 [youtube]http://www.youtube.com/watch?v=L2ydrQsFPe8[/youtube] Our friend Art Pedroza had a post on Orange Joke late last night and early this morning, which he yanked before I could actually see it. From the snipets we were able to find, Art had a phone call with his friend Richard Zavala and claimed Zavala was planning to sue me for…


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Northern Kentucky can be a fast-pitch softball hotbed. Only Highlands High School advanced to the final 16 of the KHSAA tournament in 2014, but there is plenty of talent to develop in the area. Charles and Teri Cain are determined to maximize the area's talents.
Teri is the co-owner of the Kentucky Academy of Sports in Burlington, while Charles is the vice president of the KAOS athletic club. They recently launched KAOS Elite softball, a program designed to give Northern Kentucky's best young softball players an opportunity to prove themselves against the best competition in the nation.
"We really believe the talent level in this area is deep," Charles Cain said. "We feel that these girls shouldn't have to leave the area to find a team to get them national exposure."
The KAOS Elite team will begin tournament play in the fall. The program kicked off with a camp in July which featured some of the most accomplished teachers in the nation. Former NCAA softball stars Jen Schroeder, Amanda Scarborough, Katie Schroeder, and Morgan Stuart coached at the camp. Each played in the College World Series and brought their years of experience to Northern Kentucky.
"We thought by bringing those big-name girls in, it shows what kind of program we want to be and what we want to accomplish," said Cain.
Teri Cain played collegiate softball and always thought about giving back to the next wave of potential softball stars. KAOS and KAOS Elite is a dream come true for the longtime instructor who came to Northern Kentucky four years ago from Illinois.
"This is something I've wanted to do my whole life," said Teri. "I always had a dream of coaching and putting together an organization that can make a difference both on and off the field."
Many travel softball teams are run by parents or coaches who have a vested, but limited, interest in the success of the team. The Cains have a daughter, but she plays soccer. KAOS boasts a staff of coaches committed to the sport, not just to one player who they hope will succeed.
"We're very picky on who we bring into the organization," said Charles. "We want to be sure they're committed to the game, and not to any individual. We want to be an organization that is focused on player development. That is our main goal."
"Our goal is to showcase our girls and help them get noticed and create opportunities for them to play at the next level."
The KAOS Elite coaches have seen the area's talent up close. They came away impressed with the instruction provided by local high school coaches. Most importantly, they noticed the collaborative nature of the region's coaches. There is an environment that is ripe for success at at the national level.
"We have seen a lot of coaches in the area who really care about the sport," Teri said. "There is a big, tight-knight group. Building relationships is the key."
KAOS Elite will focus on the fundamentals. Tryouts begin soon for the 10U, 12U, and 14U teams that will be the program's inaugural teams. Eventually, they plan to add 16U and 18U squads. Right now, player development is the goal. KAOS has an indoor facility that will be available for year-round practices.
Charles said the plan is in place but they need to get girls to tryout.
"We want to get down to fundamentals," said Teri, who starred as a player at Kishwaukee College. "We really want to make sure they understand the game."


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An Interview with the IEA's Neil Atkinson
Give your kids the knowledge they need
Join the NASDAQ Community today and get free, instant access to portfolios, stock ratings, real-time alerts, and more!
US markets were lifted by positive jobs data which added to the
case for a Federal Reserve taper in the coming month. Initial
jobless claims fell by 5,000, which beat expectations and
marginally boosted US shares.
However, global shares will likely be depressed in the coming
weeks as rocky US congressional negotiations over the nation's
budget have put the US in an uncertain position. A short government
shutdown is looking likely as Democrats and Republicans are at odds
over an emergency spending bill that will keep the government
running past October 1.
A shutdown that lasts a few days isn't expected to make a huge
dent in markets, but it sets a very uncertain tone for negotiations
about the US debt ceiling, which, if not resolved will lead to a
sovereign debt default.
Top News
In other news around the markets:
Asian markets ended the week on a high, only the NIKKEI
faltered, down 0.26 percent. The Hang Seng index was up 0.33
percent, China's Shanghai composite gained 0.20 percent and the
Shenzhen composite was up 0.30 percent.
European Markets
European markets were down across the board on Friday. The UK's
FTSE lost 0.35 percent and the eurozone's STOXX 600 was down 0.08
percent. Italy's MIB lost 0.38 percent and the Spanish Ibex was
down 0.23 percent.
Energy futures lost out on easing tension in the Middle East.
Brent futures were down 0.28 percent and WTI futures were down 0.35
percent. Gold gained 0.29 percent and silver was down 0.51 percent.
Industrial metals were mostly higher with aluminum up 1.00 percent
and tin up 0.22 percent.
The euro lost a bit of ground against the dollar and traded at
$1.34 but the pound gained 0.22 percent against the dollar. The yen
was up 0.35 percent against the dollar and the Australian dollar
lost 0.29 percent against the greenback.
Notable companies that reported earnings on Thursday
Pre-Market Movers
Stocks moving in the pre-market included:
Earnings Reports Expected On Friday Include:
Economic releases expected on Friday include, US consumer
sentiment, core price index and personal spending data, German CPI,
eurozone consumer confidence and industrial sentiment data, Spanish
business confidence and retail sales, Italian business confidence,
and French GDP and consumer spending.
Good luck with your trades!
For a recap of Thursday's market action, click
Tune into Benzinga's pre-market info show with Dennis Dick and
Joel Elconin
(c) 2013 Benzinga.com. Benzinga does not provide investment
advice. All rights reserved.
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text:
Pix by hyperdude111Watch
Well I said my next wallpaper would be different ! I've seen a lot of the "pixel" wallpapers on deviant and wanted to have a go myself.
Let me know what you think ! Hope you like
Font by PaulW [link]
Let me know what you think ! Hope you like
Font by PaulW [link]
I lov it but I love your font even more. Will you share it?
Wow. Great color.
Thank square effect is awesome! It's one of my favourite, I always wanted to know how to make it♥
Using the pixelise blue in gimp. Then duplicate the layer you just made, apply an edge detect filter. Set the later to overlay and erase a few areas. Just play around like that and you'll get it !
Beautiful work!
Thank you, I have to admit I did get the idea firstly from some of your work.
Now in my favourites
Very nicely done. Two thumbs up!


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NewsOK Blogs / BAM's Blog
BAM's Blog surpasses 10,000 posts
On Friday, I was apparently so busy posting about country music superstars Carrie Underwood, Miranda Lambert and Toby Keith – along with updating readers on other music, movie and arts news – that I failed to notice that we passed 10,000 posts here at BAM's Blogs!
Since Feb. 14, 2008, my guest bloggers and I have worked hard to bring you the most informative and enlightening entertainment news and reviews, with a special focus on Oklahoma music, film, talents and events.
With our 10,010th post, we thank you, our loyal readers, for your continued support of BAM's Blog. We hope you have enjoyed reading as much as we have enjoyed "covering everything that's entertaining" for you.
2 Show / Hide Archive Comments


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13 Oklahoma State students win $40,000 in business plan contest
For their business plans to better fight diseases, build ship containers and sterilize surgical instruments, 13 Oklahoma State University students recently were awarded $40,000 to turn those ideas into viable ventures.
Among 90 teams that competed in a fourth annual competition sponsored by the Riata Center for Entrepreneurship in OSU's Spears School of Business, 16 finalists were presented April 20 to venture investors from Oklahoma, New York, Chicago, Texas and Washington, D.C. The panel critiqued the marketability of their products, planned business operations, management and capabilities to receive financing, among other things.
First-place winners Jose Fulgencio, Shoaib Shaikh, Jamie Solberg and Xiao Xiao were awarded $25,000 for MesoBio, a business providing highly differentiated miRNA vectors to facilitate researchers' development of therapeutics for diseases.
Second-place awardees Venkat Gidda, Balaji Jayakumar, Shoaib Shaikh, Saravan Kumar Shanmugavelayudam and Jessica Shelton won $10,000 for MaxQ LLC, a business that would manufacture cold chain shipping containers that are better insulating, lighter and more durable than current products.
And third-place team members Clint Miller, Jayalakshmi Nail, Kedar Pai and Roshan Revankar were presented $5,000 toward Plasma Bionics, a business that would manufacture sterilization hardware, which uses nonthermal plasma to sterilize reusable items in medical, dental and veterinary applications.


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Solution Overview
Ubuntu Security Notice (C) 2006-2013 Canonical, Inc. / NASL script (C) 2006-2013 Tenable Network Security, Inc.
Synopsis :
The remote Ubuntu host is missing one or more security-related patches.
Description :
The 'mod_imap' module (which provides support for image maps) did not
properly escape the 'referer' URL which rendered it vulnerable against
a cross-site scripting attack. A malicious web page (or HTML email)
could trick a user into visiting a site running the vulnerable
mod_imap, and employ cross-site-scripting techniques to gather
sensitive user information from that site. (CVE-2005-3352)
Hartmut Keil discovered a Denial of Service vulnerability in the SSL
module ('mod_ssl') that affects SSL-enabled virtual hosts with a
customized error page for error 400. By sending a specially crafted
request to the server, a remote attacker could crash the server. This
only affects Apache 2, and only if the 'worker' implementation
(apache2-mpm-worker) is used. (CVE-2005-3357).
Solution :
Update the affected packages.
Risk factor :
Medium / CVSS Base Score : 5.4
Family: Ubuntu Local Security Checks
Nessus Plugin ID: 20788 ()
Bugtraq ID:
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Billionaire brothers Charles and David Koch support policies and projects, such as the Keystone XL pipeline, that create and expand jobs. The Kochs oppose Obamacare and support fewer government regulations and more constitutional freedoms. Yet, Senate Majority Leader Harry Reid, Nevada Democrat, criticizes the Koch brothers for their support of Keystone and other job-creating projects ("Democrats struggle to decide if blood is thicker than oil," Web, May 11).
San Francisco billionaire Tom Steyer opposes Keystone but supports Obamacare, more government regulations and fewer constitutional freedoms. Mr. Reid fully supports Mr. Steyer, likely because Mr. Steyer reportedly may provide more than $100 million in campaign resources to maintain a 2014 Democratic Senate majority. Workers lose; money talks.
Even President Obama's darling labor unions have begun rejecting Mr. Obama. A solid majority of Americans, including union members, are in support of the Keystone pipeline.
Do not be surprised if before the elections Mr. Obama reverses his political position and supports the Keystone pipeline — in an effort to bring his previous supporters back onto his and the Democrats' team. Meanwhile, it is the Koch brothers and their ilk who are making every effort to create jobs to rebuild our economy.
Locust, N.C.


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Last week, back when it was sunny, a bunch of us on Reverb posted lists of our current summer listening albums. Here's mine , the>"/>
Last week, back when it was sunny, a bunch of us on Reverb posted lists of our current summer listening albums. Here's mine, the #1 slot of which is held by what I still believe to be the best summertime mix of the season so far, Motor City Drum Ensemble's outstanding entry into the DJ-Kicks series. But, of course, almost immediately after making that post, new summer mixes started popping up. Here's a quick roundup of a few that have come to my attention over the past week:
Tyler, the Creator's Summer Camp Mix
Your usual breezy backyard mix of hip-hop and R&B old and new, Odd Future and otherwise, presided over by latest Tyler alter-ego "DJ Stank Daddy"--I haven't finished the whole thing, but if he makes it to the end without raping or killing anyone, this could be his most likable guise yet! (Note: This mix was up for a couple days, then pulled, and now you have to find it yourself--I like filestube for that sort of thing, but do what you like.)
More after the jump . . .
Goth wavers Cold Cave might not strike you as typical icons of summer (ahem), but they've put together a diverse mix of moody jams designed for "the summer indoors against the exhaustion of traffic outside," with tracks ranging from Arthur Russel to Vashti Bunyan. Get it at Cold Cave's Tumblr (via Stereogum).
Seattle ambient looper Secret Colors' new mix for Group Tightener (with an assist from sometimes bandmate/full-time barker Casey Catherwood) drifts from pan flutes to the Incredible String Band to U.S.F. to Harry Nilsson for what the Fader calls "an ideal soundtrack for leaving the office to set up folding beach chairs in your new backyard."
Finally, Andrew Matson gives notice today to recent Seattle transplant Craft Spells' new "instrumental summer mixtape and B-sides" downloadable here, saying, "After the pastel success of full-length album "Idle Labor," these new tracks keep hitting a sweet spot for that disco/hip-hop fan who keeps dried flowers around the house, a paperback in the butt pocket of their jeans, and the 1980s in the back of their mind."
There you go, stock up--the sun could come back at any minute (jk, the sun's gone out forever #fakecoldcavelyrics).


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If your company has experienced a price increase for workers' compensation insurance or have been non-renewed by your current insurance carrier, You should consider using an employee leasing company or Professional Employer Organization (PEO), Let us help you get low rate workers comp. http://www.LowRateWorkComp.com Workers Comp / Payroll Services, We have great rates for Roofers
Anyone used a service like this for workers comp?
can you beat 16% here in florida with a .83 mod rate with drug free and saftey credit?
I currently use a ppo and have been for 2 years now,was skeptical at first.But it was the best thing i ever did for comp and payroll.No more insurance company audits,no more extreme high comp rates,but mine does require a payroll of 100,000 a year to keep my rate.Which went from 65% to 32 % overnight it stressed me out paying that high rate for years
Cnage the businnes name rather than construction roofing whatever to industries know one knows what you are and since you have a ghost policy anyway since 90% use subs anyway and they must have the insurance whats the problem??


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Register with us or sign in
in Home : Projects: Propagating
A spade
A fork
Garden compost or well-rotted manure
Dividing summer-flowering perennials helps reinvigorate them and encourage stronger growth. If left to their own devices, herbaceous plants can form congested clumps after three to four years, resulting in weaker growth and fewer flowers of a poorer quality.
Hemerocallis (daylilies) produce a mass of fibrous roots that can be difficult to separate if the clump is old and your soil is heavy. You may have to slice through the clump with a spade. This might seem drastic but as long as each new section has a few healthy shoots and as much length of root as top growth, it will be ready to grow well.
Push a spade deeply into the ground a few inches from a large, congested clump to loosen the soil.
Rock the spade gently to loosen the clump and break deep roots, then lift the clump out of the ground with your hands.
Select young growth from around the edges of the clump. Try to break off individual crowns by hand, each with roots and shoots.
Fork through the soil and add garden compost or well-rotted manure. Replant divisions in groups, firming round each plant.
Lightly fork through the soil surface before watering. The new divisions should produce a few blooms this summer.
17/04/2015 at 08:07
I have planted my hemerocallis about a foot apart. That doesn't seem to have been done in the photographs.
Does that not cause another digging session too soon?
Judith 5
17/04/2015 at 08:42
I find these have very deep roots, so quite difficult to move as some roots get left behind and start growing again.
17/04/2015 at 08:55
On the contrary, I find hemerocallis easy to move, divide and establish. They make sizeable clumps in 3 years or so. never had roots left behind Judith....I,suspect you didnt dig a deep enough football.
Ellen, if your plants are small a foot apart may seem a lot but they quickly fill in and establish. How many have you planted?
Judith 5
17/04/2015 at 09:45
OK Verdun. It might be the clump I was trying to split was very old, over 10 years, and a very large, vigorous plant. I don't know the variety, v tall with orange flowers. Fleshy tap roots went down at least a foot!
17/04/2015 at 12:03
Ah, you're prob right then Judith.


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Mike Trout's Biography
Contact Information
Full Name:Walter 'Mike' Michael Trout
Birth Place:Gamboa, Panama
Home City:Boca Raton, FL
- Graduated, American Academy of Dramatic Arts, 1977
- Candidate, United States House of Representatives, District 21, 2012
- No caucus information on file.
- No professional experience on file.
- No organizational membership information on file.