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To gain insight into neovascularization of adult organs and to uncover inherent obstacles in vascular endothelial growth factor (VEGF)‐based therapeutic angiogenesis, a transgenic system for conditional switching of VEGF expression was devised. The system allows for a reversible induction of VEGF specifically in the heart muscle or liver at any selected schedule, thereby circumventing embryonic lethality due to developmental misexpression of VEGF. Using this system, we demonstrate a progressive, unlimited ramification of the existing vasculature. In the absence of spatial cues, however, abnormal vascular trees were produced, a consequence of chaotic connections with the existing network and formation of irregularly shaped sac‐like vessels. VEGF also caused a massive and highly disruptive edema. Importantly, premature cessation of the VEGF stimulus led to regression of most acquired vessels, thus challenging the utility of therapeutic approaches relying on short stimulus duration. A critical transition point was defined beyond which remodeled new vessels persisted for months after withdrawing VEGF, conferring a long‐term improvement in organ perfusion. This novel genetic system thus highlights remaining problems in the implementation of pro‐angiogenic therapy.
Extensive formation of blood vessels takes place in the developing embryo, guided by stereospecific developmental cues. In the adult, neovascularization is mostly confined to the female reproductive system but is also induced in response to perturbations in oxygen homeostasis, primarily following occlusion of major blood vessels. Ischemia‐driven neovascularization mediated by vascular endothelial growth factor (VEGF) (Dor and Keshet, 1997), acting together with a vessel remodeling process termed arteriogenesis (van Royen et al., 2001), operates to improve the perfusion of ischemic tissues. In most clinical settings, however, these natural adaptive responses to a compromised perfusion are insufficient and unable to halt the progression of an ischemic disease in the myocardium or in peripheral vessels. The reasoning behind pro‐angiogenic therapy for ischemic diseases is that exogenous administration of an angiogenic factor(s) might augment the natural collateralization process to an extent that the need for a more drastic (e.g. surgical) intervention will be circumvented. Indeed, encouraging pre‐clinical studies have already prompted clinical trials of pro‐angiogenic therapy (for recent reviews on pre‐clinical studies and clinical trials see Hammond and McKirnan, 2000; Simons et al., 2000; Freedman and Isner, 2001). However, there are growing concerns that the large gaps that exist in our knowledge regarding the fundamentals and mechanisms of neovascularization of adult organs jeopardize favourable outcomes of these trials (Carmeliet, 2000; Helisch and Schaper, 2000; Lee et al., 2000; Blau and Banfi, 2001; Laham et al., 2001).
Several factors regarding adult neovascularization need to be considered with therapeutic angiogenesis. First, most contemplated pro‐angiogenic therapies rely on the administration of a single factor, whereas the natural process is multi‐factorial. As an illustration, precluding signaling through each of the five endothelial cell‐specific tyrosine kinase receptors (VEGF‐R1, VEGF‐R2, VEGF‐R3, Tie1 and Tie2) results in an abortive vessel formation and embryonic lethality (Gale and Yancopoulos, 1999). Further more, additional factors and signaling systems are essential for engagement with periendothelial cells [e.g. the platelet‐derived growth factor (PDGF) system; Lindahl et al., 1997] and others still are required for specifying an arterial or a venous fate (e.g. ephrin‐B2/ephrin‐B4; Adams and Klein, 2000). The premise that a singly administered factor is capable of inducing all other complementary activities essential for formation of a fully functional network needs to be substantiated and the quality of induced vessels carefully examined. Secondly, it remains to be determined how such a complex morphogenetic process is executed in the absence of guiding cues and under circumstances where neither the normal dosage nor the spatial or temporal controls of the initiating morphogen are maintained. Improper connectivity might perturb rather than improve the coronary circulation. Thirdly, it has to be determined whether short‐term therapy will produce stable vessels that will persist after withdrawal of the inductive stimulus. This issue is of particular concern in light of earlier studies showing that premature withdrawal of VEGF may lead to regression of immature vessels in settings of developmental and tumor angiogenesis (Alon et al., 1995; Benjamin and Keshet, 1997).
Addressing these fundamental issues in pre‐clinical studies has been hampered by several problems. Depending on the methodology used for growth factor delivery, complications may include insufficient or variable levels of VEGF in the target organ, 'off target' effects, insufficient duration of the stimulus, an accompanying inflammatory response and an immunological reaction. Thus, it has been difficult to determine whether a particular shortcoming is due to any of these external factors or, alternatively, due to a fundamental problem inherent to a single factor‐based therapeutic angiogenesis in the adult. We sought an experimental genetic system that would circumvent the above shortcomings and allow evaluation of the performance of a particular growth factor under optimal conditions. To this end, a genetic switch was designed in a transgenic mouse system that allowed for the reversible induction of high levels of VEGF, the factor most frequently considered for therapeutic angiogenesis, exclusively at the selected target organ and was able to maintain the stimulus for the desired duration. The resultant acquired vascular network was analyzed structurally by visualizing its three‐dimensional architecture and network connectivity with the aid of corrosion casting, and functionally by monitoring dynamic changes in blood oxygenation and tissue edema using magnetic resonance imaging (MRI). The results reported below, while demonstrating the promise of a VEGF‐based therapy, also uncover some inherent obstacles that need to be resolved first.
A transgenic mouse system for conditional switching of VEGF expression in selected organs
To evaluate the feasibility of a VEGF‐based pro‐angiogenic therapy, we designed an animal model system in which a source of VEGF can be specifically induced in the target organ, steadily maintained for the desired duration and subsequently switched off. Considering previous findings that a slight deviation from the normal dosage of VEGF results in embryonic lethality (Carmeliet et al., 1996; Ferrara et al., 1996; Miquerol et al., 2000), we resorted to a conditional transgenic system for VEGF induction.
Transgenic mice expressing a tetracycline‐regulated transactivator protein (tTA) exclusively in the myocardium or liver were employed as 'driver lines'. Another transgenic line harboring a VEGF164‐encoding transgene (driven by a tetracycline‐responsive promoter) was used as the 'responder line'. The respective 'driver' mouse was mated with the VEGF 'responder' animal, and pups that inherited both transgenes were selected (see scheme in Figure 1A). The onset of VEGF induction in these animals and the duration of expression were tightly controlled through the inclusion or omission of tetracycline from the drinking water ('off' and 'on' modes, respectively). Littermates that inherited only one of the two transgenes and were concomitantly subjected to the same repression/induction regime served as controls. Heart‐specific induction was achieved using a driver line in which tTA expression is driven by a myosin heavy chain‐α (MHCα) heart‐specific promoter, previously shown to be expressed specifically by cardiomyocytes (Yu et al., 1996). Liver‐specific induction was obtained by using a driver line in which tTA expression is driven by a CCAAT/enhancer binding protein β (C/EBPβ) promoter (also known as liver activator protein or PLAP), expressed primarily in hepatocytes (Kistner et al., 1996). If kept unrepressed, misexpression of VEGF in either organ led to multiple developmental defects and embryonic lethality (Dor et al., 2001; our unpublished results). Furthermore, if repression was relieved during the first 2–3 weeks after birth (when extensive growth in either organ is still ongoing), death also ensued. In contrast, in the presence of tetracycline, tTA+/VEGF+ animals were born with the expected frequency and if VEGF induction was delayed until later than 3 weeks after birth there was no lethality.
In tTA+/VEGF+ animals VEGF164 expression was strongly induced upon withdrawal of tetracycline. In situ hybridization confirmed that when driven by MHCα‐tTA, expression of VEGF was induced in most, if not all, cardiomyocytes (Figure 1B) and when driven by PLAP‐tTA, in most, if not all, hepatocytes (Figure 1C). This was assurance that extensive areas within the respective organ would be affected by the secreted factor.
Quantitatively, the level of VEGF expression in the myocardium was increased by ∼7‐fold overall (Figure 1B) and the level of VEGF in the liver was increased by ∼11‐fold compared with the level of endogenous VEGF (Figure 1C). The continuous production of VEGF in the liver also resulted in its accumulation in the serum to levels that are 5‐ to 10‐fold higher than the normal level of 300 pg/ml, as determined by a VEGF enzyme‐linked immunosorbent assay (ELISA). In contrast, we could not detect a significant elevation of VEGF in the serum with cardiac‐specific overexpression.
Further evidence that the system is tightly controlled and fully reversible is provided by the northern blot of a representative 'liver switch' experiment shown in Figure 1C. The transgenic VEGF allele is completely silent prior to the switch and is effectively re‐repressed upon re‐administration of tetracycline.
VEGF induces unlimited formation of new blood vessels in the adult myocardium and liver
To determine whether VEGF can promote the formation of new blood vessel in adult tissues when acting alone, VEGF expression was switched 'on' in the myocardium or liver of adult animals. Organs were retrieved at different times following a continuous exposure to the VEGF stimulus and their vasculature was analyzed.
Shortly after inducing VEGF in the heart, there was a massive accumulation of cells interspersed in between the muscle fibres. These cells were tentatively assigned as endothelial precursor cells (EPCs) on the basis of expressing a panel of endothelial cell‐specific markers (the characterization of EPCs and their possible origins will be described elsewhere; Y.Dor and E.Keshet, in preparation). Coalescence of these cells into discrete blood‐filled vessels was subsequently apparent. Notably, new vessels continued to be formed as long as the VEGF stimulus was present. The continuous nature of the process was also apparent from experiments using short (3 h) BrdU pulses to tag endothelial cells in S phase, demonstrating a significant fraction of cycling endothelial cells at any time point during a 1–2 month course of VEGF induction (data not shown). Prolonged VEGF stimulus in the myocardium resulted in a very high vessel density and in formation of vessels with abnormally large lumens occupying a large fraction of the organ (Figure 2A). Thus, VEGF‐promoted neovascularization in the adult myocardium does not appear to be a self‐limiting process and is also not restricted by the exhaustion of some needed downstream factors.
To determine whether VEGF can promote formation of large coronary vessels coated with vascular smooth muscle cells (VSMCs), myocardial sections were immunostained with the SMC/pericyte‐specific marker α‐smooth muscle actin (αSMA). As shown in Figure 2B (low magnification) and in Figure 2C (high magnification), VEGF indeed promoted formation of large coronary vessels, a fraction of which are coated with smooth muscle cells. This result indicates that VEGF not only promotes formation of an endothelial plexus but also supports the recruitment of periendothelial cells, presumably by inducing other activities required to accomplish this function. This finding provides further support for the concept of a single factor‐based pro‐angiogenic therapy. As is evident from Figure 2C, VEGF also caused extensive edema, completely disrupting the otherwise tight muscle architecture.
Parallel experiments using a liver‐specific VEGF switch demonstrated that VEGF also induced robust liver neovascularization. The elaborate vascular network induced by VEGF is clearly visible by external inspection (Figure 2D). Notably, the induced network is properly connected to the hepatic circulation, as evidenced by the fact that it carries blood. Histological examination has shown that vessels induced by VEGF in the liver are mostly large sinusoidal vessels (Figure 5A).
Abnormal structure and connectivity of an induced myocardial network
For optimal functioning, new vessels induced by VEGF must not only form a well‐graded vascular tree but also appropriately connect with the existing coronary network. To visualize the three‐dimensional architecture of the induced coronary network, corrosion casts were prepared and inspected by scanning electron microscopy. This methodology visualizes the entire vascular tree at a resolution that includes even the smallest capillaries. Since it detects only perfused vessels accessible to the casting resin, it highlights only functional vascular loops connected to the systemic circulation. A typical segment of the myocardial vascular tree in control heart is shown in Figure 3A. Switching 'on' VEGF expression and maintaining the stimulus for several weeks led to progressive ramification of the vasculature. Initially, this was evident mostly by reduced inter‐capillary distance, and by structures suggestive of ongoing fusion events between contacting small vessels (see Supplementary figure 1 available at The EMBO JournalOnline). Further progression of the process during later stages resulted in the generation of very large vessels and eventually in the production of hemangioma‐like vascular sacs (see Figure 3B for a representative example). Some of the vessels shown in Figure 3B seem to be in the process of flattening on top and merging their lumens with those of existing larger vessels (arrows). Abnormal structural features of these vessels included a variable diameter in consecutive segments within a single vessel, a large proportion of vessels with multiple rather than bimodal branching points (arrowhead) and abnormal branching angularities (Figure 3B). Thus, it appears that in the absence of guiding cues, vessels induced by VEGF in the adult myocardium connect with the existing coronary network in a highly chaotic manner. Interestingly, following VEGF withdrawal, the network resumed a more 'normal' appearance (Figure 3C; discussed below).
Vessels induced by VEGF improve organ perfusion but are leaky: an MRI analysis
To determine whether the vascular gain resulting from a sustained VEGF stimulus improves liver perfusion, we monitored the ability of the organ to respond to dynamic changes in the level of inspired oxygen using non‐invasive MRI. Briefly, at different time points after the onset of a VEGF switch animals were anesthetized and imaged during inhalation of air and subsequently during inhalation of an oxygen‐enriched (95%) atmosphere. Changes in hemoglobin saturation were then detected by T2*‐weighted gradient echo imaging using the intrinsic contrast generated by changes in deoxyhemoglobin content. An increased MRI signal reflects an improved capacity of erythrocytes to deliver inhaled oxygen to the tissue that, in this experimental setting, is due to increased vascularization and thus an improved perfusion (Abramovitch et al., 1998; Carmeliet et al., 1998). A recent study further validated the utility of blood oxygenation level detection (BOLD) contrast MRI for spatial mapping of vascular function through direct comparison with spectroscopic data obtained using intravital microscopy (Neeman et al., 2001). As shown in Figure 4 (right hand panels) from a representative animal, ongoing VEGF expression resulted in a progressive increase in the perfusion capability of the liver. A significant increase was already detected 11 days after the induction of VEGF and was further improved by day 20, reaching a remarkable 4‐fold increase overall (for quantification see Figure 6A). As is evident from Figure 4, perfusion was improved in vast areas distributed throughout the liver. These findings demonstrate that new vessels induced by VEGF in an adult organ can indeed improve vascular function. At this time, this analysis has not been extended to the heart because taking MRI recordings from a fast beating organ requires instrumentation that is not currently available to us.
MRI analysis was also useful for online monitoring of edema resulting from VEGF overexpression, as was evident from the 'whitening' of the liver due to an elevated water retention (Figure 4, left hand panels). Excessive vessel permeability and a resultant edema were evident from early on and were further aggravated by a sustained VEGF stimulus (Figures 4 and 6B). A considerable enlargement (up to 3‐fold) of the edematous liver was also evident from the MRI images. This finding underscores another major problem inherent to a VEGF‐based therapy, namely the need to uncouple these two activities of VEGF/vascular permeability factor (VPF).
A critical duration of the VEGF stimulus is essential for preventing vessel regression and for long‐term persistence of the vascular gain
To determine whether vessels induced in an adult organ are unstable and require a continuing presence of VEGF, we took advantage of the reversibility of the tetracycline‐regulated transgenic system. VEGF expression in the liver was induced and maintained for 2 weeks. Under these conditions, an elaborate network was produced that is clearly visible in sections as a network of sinusoidal vessels, giving the liver a distinct 'spongy' appearance (Figure 5A). Mice were then given tetracycline and sections were inspected 10 days later. As shown in Figure 5A, most acquired vessels have disappeared and the normal 'tight' appearance of the liver was restored. The regression of vessels as the result of VEGF withdrawal was also apparent from external inspection of superficial hepatic vessels that have almost completely disappeared where VEGF was withdrawn 2 weeks after the onset of the switch (Figure 5B). In a marked contrast, delaying the 'off' switch until 4 weeks after its onset have shown that vessels have become refractory to VEGF withdrawal (Figure 5B). Remarkably, under these circumstances the acquired vasculature persisted for many months after cessation of the VEGF stimulus (Figure 5C; for several examples of acquired hepatic vessels persisting 8 months after VEGF withdrawal, see Supplementary figure 2). These findings indicate that there is a critical transition point beyond which the initially unstable vessels no longer need VEGF for survival.
Similar experiments of VEGF withdrawal were also carried out in the heart. In particular, we wished to determine the nature of the vascular network that might persist after terminating the VEGF stimulus. To this end, the system was switched off after 4 weeks of a continuous VEGF stimulus and the network was visualized by corrosion casting 8 days thereafter. As can be seen in the representative cast shown in Figure 3C, at least a fraction of induced vessels remained, as is evident by the observation of significantly increased microvessel density (compared with the ground state shown in Figure 3A). Interestingly, the abnormal vascular structures and connections produced initially (Figure 3B) seem to have disappeared. It remains to be determined whether this reflects a differential vulnerability of these vessels or the result of an extensive hemodynamic remodeling.
Of paramount importance to VEGF‐based therapy is the question of whether it can yield long‐term improvement of vascular function. To study this question, changes in vascular function were monitored by MRI over a period of several months during which different regimens of 'on' and 'off' cycles were examined. As already shown in Figure 4 for a single animal and further extended and quantified in experiments summarized in Figure 6A, VEGF‐induced angiogenesis improved the perfusion capability of the liver 3‐ to 4‐fold. While maximal improvement in vascular function was achieved as early as 15 days after the induction of VEGF, withdrawing VEGF at this point led to a rapid loss of all functional gain (Figure 6A, squares). In contrast, if the presence of VEGF was prolonged for an additional 15 days (anticipating that by this time the acquired vasculature should have stabilized) and then terminated, a significant fraction of the functional gain was maintained. An improved perfusion (2.5‐fold) persisted for as long as 6 months after VEGF withdrawal (Figure 6A, triangles).
As noted above, VEGF‐driven neovascularization was accompanied by excessive edema throughout the period where VEGF was overexpressed. Switching off VEGF expression at either schedule resulted in a rapid restoration of the normal water content in the liver (Figure 6B). Together, these findings demonstrate that, in principle, it might indeed be possible to attain a long‐term improvement in vascular function in the absence of edema. Histological inspection of livers at 8 months after cessation of VEGF induction showed that the bulk of cellular damage incurred during the period of VEGF induction and the resultant edema has been repaired (see Supplementary figure 3). Nevertheless, biochemical analysis of blood specimens obtained from these animals indicated a chronic mild hepatocellular damage (reflected in elevated levels of alanyl‐amino transferase averaging 150 μ/l, compared with 47 μ/l in controls). No long‐term cholestatic damage was detected (reflected in no significant change in blood levels of alkaline phosphatase or γ‐glutamyl transferase). These findings suggest that excessive edema associated with surplus VEGF might cause a mild long‐term liver damage.
This study was undertaken to examine the architecture and functionality of vascular networks induced by VEGF in adult organs. This is a situation faced in an attempted pro‐angiogenic therapy where VEGF, unassisted by other exogenous factors, is expected to induce new vessels that will properly connect to the pre‐existing network conferring a long‐term improvement of organ perfusion. While of particular relevance to therapeutic angiogenesis, a major objective of this study was to shed light on the mechanism of adult neovascularization, in general, reasoning that our poor understanding of the process might impede ongoing clinical trials. To this end we devised a genetic switch model system that enabled us to set adult neovascularization in motion and thereby uncover inherent problems of VEGF‐based therapy in a manner independent of compounding factors associated with any particular treatment modality.
New vessels continued to be formed as long as the inductive VEGF stimulus was present, and a prolonged stimulus resulted in an exaggerated angiogenic response to the extent that new vessels destroyed the normal organ architecture. This finding demonstrates the lack of an effective negative feedback control operating to limit VEGF‐driven neovascularization in an adult organ. This is in contrast to other processes of adult neovascularization, such as the one associated with wound repair or periodic neovascularization in the ovary and endometrium, which are self‐limiting processes. Thus, it appears that down‐regulation of the inducing VEGF stimulus is the major mechanism preventing excessive neovascularization in the adult, rather than angiogenic inhibitors coming into play or the exhaustion of a particular downstream effector molecule. These findings might also explain why a precise VEGF dosage is so critical for a balanced vascular development.
A fundamental problem with forcing formation of new blood vessels in an adult organ stems from the lack of spatial cues that will direct newly formed vessels in the process of their connection with the existing coronary network. In this respect, it differs from embryonic neovascularization, where stereo‐specific guiding cues do exist, from arterialization, where hemodynamic changes within the existing network determine the sites of an interstitial increase in vessel diameter, and also from the situation in tumors which are vascularized de novo. It remained to be determined whether a relatively uniform field of VEGF instructs the formation of a properly graded vascular tree that is appropriately integrated into existing arterial and venous branches. Notably, even in the absence of precise dosage and spatial and temporal regulations, a reasonable degree of vascular morphogenesis still took place, preserving the basic parameters of connecting to the systemic circulation, forming a highly branched vascular tree and acquisition of a periendothelial cell coating. Thus, VEGF seems to play a more permissive than instructive role in adult neovascularization. In contrast, other morphogenetic characteristics of developmental neovascularization, such as a stereospecific branching pattern and a proper gradation in vessel diameters were not maintained. High‐power visualization of the continuum of perfused vessels has demonstrated abnormal connections and branching patterns in the induced coronary network that might be difficult to reconcile with an orderly flow. Acquired vascular loops did not form the normal pattern of a graded vascular tree; in many instances a single vessel appeared to contain a non‐uniform lumen size and in extreme cases sac‐like structures were produced. Judging from the vascular casts, it appears that VEGF‐mediated hyperfusion may play a role in the generation of glumeroloid and hemangioma‐like vessels, similar to those previously encountered in other settings of VEGF overexpression (Drake and Little, 1995; Springer et al., 1998; Sundberg et al., 2001). In light of this finding it was somewhat surprising that the induced network conferred a long‐term improvement of organ perfusion. We propose that an extensive remodeling plays a major role in re‐shaping the initial disorganized system into an efficient circulatory network. Supporting this possibility was our observation that when examined several weeks and even months after VEGF withdrawal, the induced network appeared more organized.
Single factor therapy is based on the premise that the factor employed can orchestrate the entire angiogenic cascade and induce all other activities required collectively for the formation of a functional vascular network. Using a measurable gain in vascular function as an endpoint, the data provided here clearly show that this is indeed the case for a VEGF‐initiated process. Importantly, the use of the conditional expression system enabled us to demonstrate that VEGF can promote the entire angiogenic cascade in the absence of ischemia or inflammation. This finding runs counter to the notion that the non‐ischemic myocardium might not be responsive to VEGF and that additional hypoxia‐inducible factors might be essential. Our findings also challenge the notion that inflammation is a mandatory requirement for efficient myocardial neovascularization. It is often assumed that ageing adult organs will be less responsive to angiogenic stimuli. While this issue was not directly addressed by this study, we note that a robust angiogenic response was induced even when the VEGF switch was delayed until 4.5 months after birth (data not shown), arguing that the fully mature organ can still respond to exogenous VEGF.
The results reported here clearly show that VEGF levels sufficient for induction of new vessels also cause severe tissue edema. It might therefore be essential to counteract the permeabilizing activity of VEGF, particularly with long‐term treatment. Since the edema is resolved shortly after terminating VEGF, the need to prevent excessive vascular leak might be transient (i.e. until vessels become refractory to VEGF) and, therefore, therapeutically feasible. Recent studies have suggested at least two ways to selectively inhibit excessive leakage of VEGF‐induced vessels: through the use of src inhibitors (Eliceiri et al., 1999) or through the action of co‐expressed Ang‐1 (Thurston et al., 1999).
The elaborate vascular networks induced by VEGF in the heart and liver almost completely disappeared upon early termination of the inductive signal, and this was also reflected in a full reversal of the net gain in vascular function. However, with longer duration of the VEGF stimulus we observed long lasting, VEGF‐independent vessels. The molecular and cellular determinants of the transition from a VEGF‐dependent to a VEGF refractory state remain to be determined. Our previous studies in the retina and tumor systems have suggested that the recruitment of periendothelial cells is the critical event marking vessel maturation (Benjamin et al., 1998). Ongoing studies are examining whether the engagement with periendothelial cells is also a stabilizing determinant in the case of adult myocardial angiogenesis. Irrespective of the mechanism, the finding of an obligatory requirement for a relatively long presence (>2 weeks) of VEGF to produce durable vessels is of fundamental importance in ongoing debates regarding the preferred mode of pro‐angiogenic therapy. Thus, modalities relying on a transient presence of VEGF in the target tissue (e.g. adenovirus based vectors with rapid clearance) are unlikely to produce durable vessels. Clearly, the consensus that vectors with a short (5–7 days) duration of expression are highly desirable (Simons et al., 2000) needs to be re‐considered. Interestingly, whereas 14 days of an 'on' switch produced non‐durable vessels, a protocol of two 14‐day 'on' episodes separated by 5 weeks of an 'off' switch produced stable vessels persisting for months without VEGF (data not shown). Again, this finding should be taken into account when weighing the potential benefits of a single versus repeated treatments or a sustained delivery.
In conclusion, this study has demonstrated the promise of a VEGF‐based therapy but also revealed some inherent obstacles that need to be resolved prior to its implementation.
Materials and methods
Transgenic mice
The pTET‐VEGF164 responder line was as described previously (Dor et al., 2001). The MHCα‐tTA heart‐specific driver line (Yu et al., 1996) and the PLAP‐tTA liver‐specific driver line (Kistner et al., 1996; Lavon et al., 2000) were as described previously. Crosses were carried out between pTET‐VEGF+/− and the respective tTA+/− driver line. Offspring were genotyped by PCR. Primers for PCR genotyping of the pTET‐VEGF164 transgene have been described previously (Benjamin and Keshet, 1997). The tTA transgene was amplified using primers 5′‐TAGATGTGCTTTACTAAGTCATCGCG and 5′‐GAGATCGAGCAGGCCCTCGATGGTAG. Littermates that inherited none or only one transgene served as controls. To repress pTET‐VEGF164 during embryonic and early postnatal heart and liver development mothers were given 500 μg/ml tetracycline (Teva Inc., Israel)/3% sucrose in the drinking water throughout gestation and lactation periods.
VEGF expression analysis
In situ hybridization was performed on paraffin sections as described previously (Motro et al., 1990) using VEGF and tTA‐specific probes (Dor et al., 2001).
Quantification of in situ hybridized VEGF was carried‐out as follows: 3‐μm thick sections were hybridized with a VEGF‐specific probe encompassing the entire coding sequence. Brightfield and darkfield images (×100) were captured using a digital camera (SV‐Micro Inc.) and stored as Adobe photoshop files. Darkfield images were converted in such a way that autoradiographic grains are visualized as discrete black dots. NIH‐IMAGE software was used to count grains representing VEGF signal. Relative grain densities in the control/transgenic heart or liver were determined in three thin sections of each of three independent organs.
Relative VEGF mRNA levels were also quantified by densitometric tracing of northern blots as follows: total RNA was extracted from the respective organ using TRI reagent (Sigma) according to the manufacturer's instructions, and 5 μg resolved on agarose gel. Following blotting, membranes were hybridized with a 32P‐labeled probe detecting only the VEGF coding region (thus detecting endogenous and transgenic VEGF with the same efficiency). The difference in transcript size between endogenous and transgenic VEGF (3.7 and ∼2 kb, respectively) allowed independent scanning of the respective autoradiographic bands and quantification of band intensities (relative to ribosomal RNA) using NIH image software.
VEGF protein levels in sera of mice were measured using a mouse VEGF ELISA kit (Oncogene Inc.) according to the manufacturer's instructions.
Corrosion casting
Vascular casts were prepared as described previously (Djonov et al., 2000). Briefly, mice were anesthetized using an overdose of pentobarbitol, and mercox solution (Vilene Co., Japan) containing 0.1 ml accelerator per 5 ml resin was injected into the left ventricle. Following dissolution of tissue in 15% KOH for 6 weeks, casts were dehydrated in ethanol and dried in a vacuum desiccator. Specimens were glued onto stubs with carbon and spattered with gold, and examined using a Philips XL 30 FEG scanning electron microscope.
MRI experiments were performed on a horizontal 4.7 T Bruker Biospec spectrometer (Bruker, Germany) using volume coil. Mice were anesthetized, placed supine with the liver located at the center of the coil and scanned twice a week. Spin echo images were used to evaluate the relative water content of the tissue [TR/TE = 2000/20 ms; field of view (FOV) = 4 × 4 cm; slice thickness of 1 mm; 256 × 256 matrix]. Mean signal intensity was calculated for the liver and was normalized to the signal intensity from the muscle. This ratio prior to switching on VEGF was ∼0.7 and reached values of up to 1.5 following the switch.
Functionality of the vasculature was determined from T2*‐weighted gradient echo images acquired during inhalation of air–CO2 (95% air and 5% CO2), and oxygen–CO2 (95% oxygen and 5% CO2; carbogen) as described previously (Abramovitch et al., 1998). The different gas mixtures were administered to the mice via a home‐made mask. Four images were acquired at each gas mixture (51 s/image; slice thickness 1 mm; TR = 100 ms; TE = 130 ms; spectral width 25 000 Hz; FOV 3 cm; 256 × 256 pixels; in plane resolution 110 μm; four averages). MRI data were analyzed using IDL software (Research Systems Inc., CO). Vascular function (VF) was derived from images acquired during inhalation of carbogen and air–CO2 using the following equation:
where I is the mean signal intensity in the liver during inhalation of either carbogen or air–CO2, TE is the echo time, Y is the fraction of oxyhemoglobin, b is the volume fraction of blood and CMRI = 599/s at 4.7 T. This parameter measures the capacity of oxygen delivery from the lungs to each pixel in the image (Abramovitch et al., 1998; Carmeliet et al., 1998). Data are presented as color map overlaid on the gray scale baseline image for values of VF >0.005.
Supplementary data
Supplementary data for this paper are available at The EMBO Journal Online.
Supplementary Information
Supplementary data [emboj7594413-sup-0001.zip]
The authors thank Dr H.Bujard for providing the PLAP‐tTA transgenic mice and the Arthur and Rochelle Belfer foundation for financial support.
- Copyright © 2002 European Molecular Biology Organization


text:
ERIC Number: ED249397
Record Type: RIE
Publication Date: 1982
Pages: 19
Abstractor: N/A
Simmons Insurance Agency. A Clerk-Typist Position Simulation. Employee's Manual. Office Occupations.
Georgia State Univ., Atlanta.; Columbus Area Vocational-Technical School, GA.
This employee's manual is part of a position simulation developed for use in an office applications laboratory at the postsecondary level. The purpose of the simulation is to give the student an opportunity to become familiar with the tasks and duties performed by a clerk-typist working for an independent insurance agency. Contents include a description of the company, a company organizational chart, a job description for a clerk-typist in the organization, lists of required equipment and references, office rules and regulations (office procedures), general information (attendance, public relations, telephone use, appearance, character traits), information on employee/student evaluation and grading, and evaluation forms. (YLB)
Publication Type: Guides - Classroom - Learner
Education Level: N/A
Audience: Students
Language: English
Sponsor: Georgia State Dept. of Education, Atlanta. Office of Vocational Education.
Authoring Institution: Georgia State Univ., Atlanta.; Columbus Area Vocational-Technical School, GA.
Note: For related documents, see CE 039 859-865.

subset: commoncrawl


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U.S. stocks closed fractionally higher Wednesday after mixed data showed modest-at-best growth in the economy. The Dow Jones Industrial Average rose 2.47 points to close at 17,789.67. The S&P 500 Index advanced 2.37 points, or 0.1%, to finish at 2,099.33, with telecoms and consumer discretionary as the only declining sectors. The Nasdaq Composite Index rose 4.20 points, or 0.1%, to close at 4,952.25.
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Vogue D632 Poultry Secateurs
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These stainless steel poultry secateurs are the perfect tool for cutting through bones and joints. They also feature locking handles to minimise risk when they're not in use.
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- Standard Delivery: 1-3 Working Days
- Standard Warranty: 1 Year Return to Base
- Stainless steel
- Locking handles
- Concealed spring loaded handles
- 250mm length
Delivery Information
The information below is specific to this product. Delivery information for other products will vary so please check if ordering other items.
Standard Delivery Service (UK Mainland)
- 1-3 delivery service
- 1 man crew
- Pavement drop
- Deliveries between 8am/6pm Mon/Fri exlcuding bank holidays
- Booking call made 24 hours prior to delivery
- Deliveries will not take place without a booking being made
- Please check door width/building access before ordering, additional charges will apply for any aborted delivery
Next Day Delivery (UK Mainland)
- UK mainland only
- National carrier delivery with 1 man crew
- Pavement drop
- Strictly 4.00pm cut off for same day dispatch
- Deliveries between 8am/5pm Mon/Fri exlcuding bank holidays
- Please note we cannot offer book in calls or obtain ETA's on next day deliveries
Added Value Services
- Old cabinet removal from site and safe disposal
- Off UK mainland and remote location deliveries
- Please contact us for prices
Additional Information
If you have any delivery requirements that are not listed or if you require more information, please call 0800 001 6699 and we will do our best to help.
Any restrictions on site or with access to site must be stated on order. Note that driver(s) will not lift items through windows, over counters, up/down steps/stairs or similar restrictions. Charges may apply for services outside of our normal delivery listed above.


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when would you like to view
this property?
Please select your preferred date.
3 Beds
3 Baths
1726 SqFt
Please select your preferred date.
April CostenbaderSchedule an obligation free tour to see this property
Key Details
Property Type: Condo
Year Built: 2006
Purchase Type: For Sale
Listing Status: Contingent
MLS Listing ID: 4393960
HOA Fees: $1,984/qua
Price per Sqft: $194
Financing: Cash,Conventional,VA
Special Sale: None
Construction Status: Resale
Property Description
Beautiful views of Lake Travis on your own covered patio. Wonderful 3 bedroom, 3 bath condominium is located on the 3rd level of the building. The Hollows has a private resort beach club, marina, boat ramp and breathtaking views! This villa has the best view and floor plan of the existing inventory. It is a must see premium Hollows Hilltop Villa. The views from almost every corner will amaze you. Come visit and imagine the lifestyle. Vacation Rental optional.
State: TX
County: Travis
Subdivision: Hollows Condo Hilltop Villas
Community: Northwest Travis Co.
Area: Ln
Dining Room: Breakfast Area,Liv/Din Combo
Num of Dining: 2
Num of Living: 1
Kitchen: Granite/Marble Counters
Full Baths: 3
Master Description: Double Vanity,Full Bath,Garden Tub,Separate Shower
Interior Features: In-Law Plan
Laundry: Closet,Dryer Connection - Electric
Sewage Type: City at Street
Water: City
Heating: Central Heat
Cooling: Central Air
Flooring: Carpet,Tile - Hard
Steps: Exterior Steps,No Interior Steps,See Agent
Exterior Feature: Balcony-Private,Barbecue,Hot Tub,Patio-Covered,Playscape,Ramp(s),RV/Boat Parking,Sidewalk
Garage: Attached,Door Opener
Fence: No Fence
Utilities Available: Electricity on Property,Phone on Property
Amenities Available: Club House,Jogging/Biking Path,Lake Privileges,Pool-Community
Water Access: Yes
Water Access Desc: Dock Available,Private Dock,Public Ramp,See Agent
View: Hill Country,Lake/River,Panoramic
Roof Type: Composition Shingle
Building Description: All Sides Masonry
Story: 1
Unit Features: 3rd+ Floor Entry,Elevator,Neighbor Below,Single level Floor Plan
Foundation: Slab
Elementary Schools: Lago Vista
Middle Schools: Lago Vista
High Schools: Lago Vista
School District: Lago Vista Isd
HOA Name: Hollows Condo
HOA Fee Include: Common Area Maintenance,Common Insurance,Trash Collection
Restrictions: Deed Restrictions
Tax Amount: $7,735
Tax Year: 2018
Tax ID: 01706002790000
SqFt Source: Builder
Listing Provided By Realty Austin
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info EN
gOlab – the Lab for Analogue Colorprinting in Berlin was found in 2000 by Susanna Kirschnick who received her degree in Fine Art Photography from the Glasgow School of Art, Scotland UK in 1999. Prior she studied at the Fine Art Photography Department at Columbia College Chicago, USA , where she was also trained as Teaching Assistant in the colordarkroom and in the Digital Photography Department.
golab is a rent-in photo printlab for artists and photographers working analogue with their own color negatives on classical colorhead enlargers to produce handprinted C-Type (Chromogenic) Prints.
It hosts a longterm darkroom labcommunity, a rent-in lab for artists on a daily base
and serves as a printing-on-demand lab for clients.
The aim of gOlab is to provide all clients with the best results of their analogue colorprints possible.
Located in the heart of berlin kreuzberg (on 300sqm) we are set up with two color darkrooms with 10 DeVere color enlargers on which 35mm up to 8×10′ inch negatives can be printed from. The darkrooms are equipped with Rodagon / Schneider Kreuznach lenses, easels, papercassettes and two RA-4 machines dry-to-dry process.
The maximum width of 127cm colorphoto paper can be easily processed; working at the horizontal enlarger enables printsizes of 127cm x 250cm or longer.
All necessary printing utilities are at hand.
Photographic papers can be ordered easily through us or also brought along to a printsession.
All equipment, machines, enlargers as well as the processors are serviced regularly by our technical stuff
to enable an efficient workflow.
The darkrooms are airconditioned and ensuited with modern water filtering systems to ensure a safe and healthy environment.
The daylight viewing area is lit with DIN normlights, magentic walls help to precise judgements of color and density.
Assistance is present at all times, so even if running in a problem or need, your are helped right away.
We also offer an extra seperate washing area, where all masterprints can be treated after the chemical process to optimize their archival status.
Our lab stuff is well trained in helping you on various needs within the printing production. Their excellent manual retouching services is either additional bookable for rent-in clients or included in a print-production-on-demand.


text: Virgin Mastercard is one of the prepaid cards service of Virgin Money, a financial service provider subsidiary of Virgin Group. The card is acceptable in More Than two hundred nations of the globe. The main thing of this card service is any can apply for Virgin MasterCard without any bank account. For more information about Virgin MasterCard, the online user can go with Virgin Money's official website or universal/uniform resource locator, i.e. uk.virginmoney.com.


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Zolv have entered ABTA Lifeline's lip sync battle competition. We had to create a lip sync video to a holiday themed song to enter and help ABTA lifeline raise much needed funds. So the creative team and I almost want to say slightly disturbed minds at Zolv got together to create the visual delight that is our entry.
You can watch below our slightly unnerving lip sync effort
To vote and donate please visit https://www.justgiving.com/fundraising/Zolvgoeslala
Now the important bit, by donating you are helping a very worthwhile cause. That cause is to raise funds for the care of a very lovely little boy, Zach.
In 2014 Zach's Mum, a former travel agent, applied for support with sensory equipment to help provide a safe and relaxing environment for her 4 year old son Zach. Zach has a benign brain tumour, hydrocephalus, neurological disorders that affects balance and speech, and is fed through his stomach. He also has multiple genetic health problems. His condition is so complex it has no name. We took Zach's story to the Travel Convention and raised an amazing amount of money which enabled us to build him a sensory room. This has been a lifesaver for Zach's family.
Since 2014 Zach's problems have become more severe. Although he is now 6, he has the mental age of around 0 to 24 months. He has no spatial awareness and will try and run through everything in his path. His behaviour is getting more and more challenging and he has been in and out of hospital with numerous other medical issues.
His Mum Tricy, is Zach's primary 24 hour carer. She is exhausted and in desperate need of a respite break as is her husband Andy. But they can only ever leave Zach for one night.
There is no clear picture of what the future holds for Zach. All his family know is that he will require constant care.
We would love the industry to support ABTA's Big Charity Day and raise funds for Zach to help with his medium term care and perhaps provide them a family break this summer in a place that is suitable for Zach.


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We are a 3rd generation, family run store, and our family has over 75 years of experience in retail jewelry. We provide fair prices and awesome customer service. Stop by to shop quality jewelry in a welcoming, safe environment and experience unmatched personalized service.
Build the ring of your dreams, your way.
Schedule an appointment to view the hottest holiday trends at the best prices.


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We are calling you now to better understand your needs.
Senior Home Choice 2 - Reynoldsburg, OH
|Room Type
|Monthly Range* (USD)
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* Published prices are provided by the providers themselves, not by reviewers. Actual quotes may differ from what is presented based on timing and services required.
- Minimum Age of Accepted Residents
- Activities Onsite
- Devotional Services Available
- Indoor Common Areas
- Meals Provided
- Nurses on Staff
- Podiatrist Available
- Physical Therapy Available
- Occupational Therapy Available
- Speech Therapy Available
- Complimentary Transportation
- Activities Offsite
- Outdoor Common Areas
- Beauty & Barber Services
- Pets Allowed
- No Smoking Allowed in Private Areas Indoors
- No Smoking Allowed in Public Areas Indoors
- Wheelchair Accessible Showers
- Hospice Available
- Respite Available
- Resident Parking Available
- Male Residents Accepted
- Female Residents Only
- Doctor on Call
- Nurse on Call
- Dentist Available
Review of Senior Home Choice 2 - Reynoldsburg, OH
This is a great environment for my aunt. It's great she's in a place with other women. The staff is very caring & they do a great job handling her behaviors properly.
Review of Senior Home Choice 2 - Reynoldsburg, OH
I love Senior Home Choice because the staff is good with my mom. [removed] & [removed] are great with getting back to me when I have questions or concerns. My mom was the first resident at Senior Home Choice and she's still there 8 years later.
Review of Senior Home Choice 2 - Reynoldsburg, OH
Great facility! Very helpful & very informative on my dad's care!
Review of Senior Home Choice 2 - Reynoldsburg, OH
We love the facility. The staff is great with him. This is one of the best times he's had in a facility. Staff addresses a problem when it arises.
Was this review helpful?
Review of Senior Home Choice 2 - Reynoldsburg, OH
Great staff! Very helpful with mom's problems. The staff has been very good with her since she arrived. House is nice & clean. Great communication with management. Very first response time on getting home health to work with mom.
Was this review helpful?
Review of Senior Home Choice 2 - Reynoldsburg, OH
Love the home setting! It works very well for grandpa. Staff is great & cares for his needs.
Was this review helpful?
Review of Senior Home Choice 2 - Reynoldsburg, OH
I am pleased with the care my loved one is getting at Senior Home Choice in Reynoldsburg. The manager makes sure she calls whenever she needs something or if there's a problem, The staff is very nice and helpful.
Was this review helpful?
Review of Senior Home Choice 2 - Reynoldsburg, OH
Staff is nice & mom likes it there. There is good communication.
Was this review helpful?
Wasn't crazy about the appearance or cleanliness inside the home, but outside was fine. Seemed a bit crowded and bedrooms were small and not as clean as I hoped, but good part is the low staff to resident ratio.
Was this review helpful?
It seems like it's going well
It seems like it's going well. We do not have any complaints. The facility Is very clean and the staff is so friendly. My Brother can be kind of difficult, but the staff seems to be doing well with him. Of course I'm not there all the time, but from what we see it's great.
Was this review helpful?
So far it has been pretty good
So far it has been pretty good overall. The facility is very clean and well kept. The staff is nice and helpful. Everything has been going pretty good. It's a nice community. So far so good.
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This home provides most of the needs ...
This home provides most of the needs my mom has. I'd like to see more social kinds of things to do but they are supposed to be looking into that. Overall this home is a good fit.
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I will be placing George wi...
I will be placing George with them. Thank you so much for the referral.
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Great place, homelike atmosphere
I've been extremely pleased by the service they provided here. It's a great looking place, and they always keep it clean and well kept. It's as close as you can get to a home environment and still receive care of this quality. I haven't met a single employee that did not impress me with their compassion and professionalism.
Was this review helpful?
Check into a "Group Home" as well as nursing homes.
It was perfect for what was needed at the time. My husband did not need a skilled nursing facility, but did need a locked facility. He was considered a "flight risk". Staff was very helpful and friendly. It became like a family.
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caring, intimate environment, Is Mom ...
caring, intimate environment, Is Mom capable of all the outings and she could not stay behind alone? RN on call, some difficulty getting her walker throughout house?
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house,not handicapped accessible. ema...
house,not handicapped accessible. email from Director saying they would let me know when they make a place for handicapped wheelchair?
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I have not moved mom in yet however, ...
I have not moved mom in yet however, I am so impressed with Director. The house is immaculate and everyone I have met so far are great.
Was this review helpful? 1
Personal Care Homes offer seniors 24/7 assisted living care in real homes, in real neighborhoods, for seniors who don't want to live in institutional facilities.
Whether playing cards at the kitchen table, smelling a pie in the oven, feeding the birds in the back yard, or waving to the mailman, residents continue the life they've always lived, but with the supportive care they now need.
Our caregivers provide care for 5 residents--not 15, 25
or 35, as found in most facilities. And we do not use a
one-size-fits-all approach. We believe in:
- Dignity, independence & quality of life
- A goal of aging-in-place to prevent or delay
- Support for residents & families through
communication, coordination & continuity of care
- Meaningful interactions for a continued sense of
purpose and enjoyment of life
- Letting loved ones stop worrying about the stress
of care needs & start enjoying time together
The Personal Care Homes are inspected and licensed as Adult Care Facilities by state officials. We have no deficiencies from our state inspections.
A resident has never moved out due to dissatisfaction or care concerns. In fact, 90% of our residents have moved to us from assisted living facilities.
Interested families are welcome to contact any famliy, doctor, health care provider or employee.
The owners of Senior Home Choice are available 24/7 to every resident & family member, and are involved in daily operations.


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In this modern world of technology, Android apps in the market have gone on the top list. And now, it has also cut down all the talk time cost with just a small trick. Do you have any idea what that small magic? Yes, that's the free calling apps for android users. All things considered, these apps have gone to such an extent that, both the local as well as international calls are free of cost. Ultimately, this will save all your hard earned money and also will save all your time. We know that Skype, Google Voice, Hangouts, WhatsApp, all are genuine free calling apps. But here in this content, we will add those latest free calling app for android to any number.
For Android smartphones, there are so many free calling apps available in Google Play Store. All you need is a better internet or Wi-Fi connection and simply visit the Play Store. In the search bar, type any calling apps that you wish to install and enjoy talking with dear ones. to make your work easier, we have searched some of the best free caller apps for Android device. Let us check them one by one below and get to know which is better than any other apps.
Top Free Calling Apps for Android:
1. Line:
LINE is a free calling app for Android devices. When you are away from your friends, family, and relatives, LINE will definitely bring you close with one another. With its free voice, video calls as well as unlimited messages, you will be able to express more of your feelings with someone dear to you. LINE will ultimately help to access free voice as well as video calls for completely free. With its collection of stickers now you can continue sending and messaging awesome pictures. With over 200 people you can enjoy group chatting and making international calls. It also lets you social share all the activities and photos in your own timeline.
Also check out things to do with a rooted Android phone.
2. Tango:
With Tango, you can make a video call and voice message calls for absolutely free. Tango is the best free calling online app that works on your Smartphones as well as Tablets. Which ever place you are, now you can easily connect with your family and mates with Tango. However, they are not just video call app but you can enjoy more fun while video calling. Have fun with some stickers and adding filters along with playing games while chatting with dear friends, all are for free. With Tango, now you can social share your videos as well as photos with your followers and friends.
3. WhatsCall:
WhatsCall is another top best free calling apps for Android. More than 1,000,000 users are enjoying the features of this app. No matter where ever you are, now you can certainly keep in touch with your family with WhatsCall for free. Video chat around the globe with HD quality is the best time that you have with WhatsCall. Also, immediately you can send pictures, text, and voice message to your WhatsCall mates. If you get any unknown calls then this app will ultimately block all the unknown calls instantly. With the new Moments option, now you can social share your colorful photos.
4. imo:
Now you can easily chat and video calls your family and friends with the imo app. In addition to it, all the entire video calls are for free with high-quality resolution. Along with your friends, you can also group video calls and have some fun in life. Share your photos and videos with your friends and express yourself with over hundreds of free stickers. However, imo app not only saves time but also saves money. You can also call it the best money saving apps to make calls.
5. Rebtel:
With its high-quality, Rebtel is going popular day by day. In fact, with low costs, Rebtel can make smooth international calls to the landline or mobile users. But if you are Rebtel users, then you can totally enjoy free international calls. To enjoy free calls and also to avoid high roaming expenditure, you can also connect to Wi-Fi. If you are a new user, then first 3 minutes must be called to the Rebtel care. Sign up now and get free calls for one week with Rebtel. On the basis of markets, Rebtel is on the top pick. Now you can easily connect with your friends and family members even after staying far from home. Also, invite them and get $5 credits to your account.
6. Free Phone Calls:
This is also the calling app for Android without credits. Whether you have a 2G, 3G or Wi-Fi connection, Free Phone Call will ultimately give you a crystal clear voice. It also allows you to connect up to 200 countries with free calls or low international calls. Even to your Facebook friends, you can connect them for free and also text freely. However, if you are tired of typing then the Walkie Talkie will help you to send a voice mail. All you need to do is just press the button and speak out. Even when you have a bad network day, still you can connect to your friends with Free Phone Calls app.
7. Kakao Talk:
Kakao Talk is the fastest free calling app for iPhoneand Android users. In fact, it is downloaded by over 150 million users. For completely free, you can send photos, messages and chat with your mates. An unlimited number of group chats, high-quality video calls makes it really reliable to download this app. Select a limitless number of stickers and give a color to your messages. As a result, it's a multi-tasking app which helps not only to chat with your friends but also to send messages to another friend while video calling. With Kakao Talk, now you can connect in a better way with your dear friends.
Are this above-mentioned reliable for you? Have you tried any of these free calling apps for Android? They not only works for the app to app calling but also works for other app users. Yes, Rebtel can really work well because you can connect the calls in landline users adn also for mobile users. Apart from Rebtel, other apps that we have included are also unique and best. Now you can create more fun video calling with your dear ones staying abroad with the help of calling apps.


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Modvigil 200mg 60 Tablets
Modvigil(Provigil) is a wakefulness promoting agent, or eurogeric.
It is commonly prescribed for narcolepsy or excessive daytime sleepiness.
Off-label it is also prescribed by some doctors for CNS fatigue.
There are reports in the scientific literature that it alleviates spasticity in some patients.
Some users claim Modafinil to be a Nootropic, a drug that purports to increase your intelligence. This is debatable, however Modafinil certainly helps people to concentrate on a task for an extended period of time. It has also been said that Modafinil induces a form of monomania. Once you are committed to a task, you cannnot stop. An excellent tool for study or work.
Some refer to Modafinil as the entrepeneur's drug.
Be that as it may, Modafinil alleviates MS and other CNS related fatigue. It is on this basis we offer it to you.
Modalert is a generic form of the medicine Modafinil, manufactured by Sun Pharmaceuticles. Modalert is by far the most popular form of Modafinil available worldwide.
We offer HAB Brand Modvigil at an excellent price and unlike other vendors we ship our Modafinil from Europe, tracked postage included in the price.
Product 2/3
This product was added to our catalog on Wednesday 17 October, 2018.


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German manufacturers growing faster than the market in US
Berlin, 03 June 2015
12 percent market share in passenger car segment
In May the German manufacturers increased their sales of light vehicle (passenger cars and light trucks) on the US market by nearly 8 percent to 127,500 new vehicles. This means they grew significantly faster than the overall market, which expanded by almost 2 percent to just over 1.6 million light vehicles. But it should be remembered that May this year had one trading day less than last May. The German OEMs also recorded faster growth for the period from January to May of this year. They pushed up their light vehicle sales by nearly 6 percent to a total of 551,800 new vehicles, while the market as a whole increased by almost 5 percent to a good 7 million units.
In the first five months of 2015 the German vehicle makers bucked the trend by increasing their passenger car sales on the US market by around 6 percent to 381,500 units. The total car market contracted slightly (-1 percent) to just under 3.2 million vehicles. The German manufacturers thus expanded their share of the passenger car market to 12 percent (11.2 percent in the same period last year). The difference was even greater in the month just finished: the German brands grew by a good 8 percent to 87,000 new passenger cars, while the total car market shrank by almost 4 percent, down to 745,500 units.
In the light truck segment, which grew by nearly 7 percent to 881,800 units in May, the German manufacturers also pushed up their sales by about 7 percent to reach 40,500 vehicles. Since the beginning of this year (January to May 2015), the overall market volume has risen by nearly 10 per cent to a little over 3.8 million light trucks, and the German manufacturers have recorded an increase of around 6 percent to 170,300 new vehicles.


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No Conclusion
Abi will continue to need regular MRI scans and those will forever come at the cost of worry. Every illness will have me wondering whether it's her cancer or her shunt malfunctioning. Every mood swing will make me consider if there's a deeper cause. So I have long since realised that that is an ongoing story, with lots and twists and turns, but with no end. In fact, the only possible conclusion this story could ever have is my daughter's death. It is an ending I hope to avoid. But it is a fear always present. And yet, in that fear, there is a beauty. Kahlil Gibran, in his poem 'On Death', puts it perfectly:
In the depth of your hopes and desires lies your silent knowledge of the beyond; And like seeds dreaming beneath the snow your heart dreams of spring. Trust the dreams, for in them is hidden the gate to eternity. Your fear of death is but the trembling of the shepherd when he stands before the king whose hand is to be laid upon him in honour. Is the shepherd not joyful beneath his trembling, that he shall wear the mark of the king? Yet is he not more mindful of his trembling?
But the best part is that, despite my fear, Abi's illness is not terminal. In fact, at the moment, she's amazingly healthy. And my heart soars at that.


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First Freedom Ohio advocates for the constitutional freedoms of all Ohioans to live, work, and worship. We are the grassroots action partner of Citizens for Community Values, Ohio's Family Policy Council.
Our Beliefs
- We have been created equal, endowed by our creator with certain unalienable rights, among them include life, liberty and the pursuit of happiness.
- Religious freedom and freedom of speech are central to a thriving state.
- Our state is only as strong as its families.
- Promoting pro-family policy is the best way to fight poverty.
- The intrinsic value and dignity of human life should be protected from its very beginning to its natural end.
Core Issues for a Thriving Ohio
- Religious Freedom: Ensuring Ohioans are free to live and work according to their faith.
- Free Speech: Ensuring Ohioans are free to express themselves and their views at home, online, at work, at church, and on campus.
- Government Transparency and Accountability: Ensuring a government of the people, by the people and for the people is accountable to the people.
- Right to Life: Ensuring life is protected from its very beginning to its natural end.
- Strong Families: Ensuring government policy promotes strong families and strong marriages between one man and one woman.
- Educational Freedom: Ensuring parents are able to choose the best educational option for their children.
- Human Dignity: Ensuring government stands against movements that rob Ohioans of their basic human dignity like human trafficking, drug use, and pornography.
Our Work
- Educate: A well-informed public is the best defense against tyranny. We work to ensure Ohioans understand the crucial challenges to freedom, families, and life.
- Organize: We organize people across Ohio by empowering them to become "Freedom Fighters" and to take action to advance our Core Issues.
- Advocate: Our elected leaders serve the people, not the other way around. We advocate for a free Ohio and to ensure our elected officials understand how their actions impact Ohio's future.


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Ready to get sexy?… MORE
Ready to get sexy?… MORE
Hi! I'm Matt Bahan, host of the Morning X for the last seventeen years, and your resident 'Rock Freak' of Central Illinois. I absolutely 'ooze' all things Rock, and each day on the Morning X, I celebrate this amazing music with YOU, the 'Greatest Rock Fans' on the planet!… MORE
Get to know 105.7 The X's super creep… Ryan!… MORE
I grew up in the tiny town of Cambridge, Minnesota before becoming your resident rock goddess at 105.7 the X. First and foremost, I LOVE music! Everything from 80s Madonna to hair metal and everything in between.… MORE
LA Lloyd's Rock 30 Weekly Countdown is a 3-hour new Rock countdown with a guest co-host each week.… MORE
Local Anesthetic broadcasts live Sunday nights 8-10pm CST on 105.7 the X featuring the best local rock/metal bands of Central IL. Hosted by local guru Bela McKnight who's got the antidote for your local music fix! Bela McKnight has been your humble host since 2008 and is a staple in the Central IL music scene…… MORE
Glick is a weekend warrior and the voice you hear early morning during the week on 105.7 The X!… MORE


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With Revri, Rain International scientists combined key elements of science and nature to harness the nutritional potential of seeds to restore health and beauty to skin.
Our objective was to design an entirely natural skincare line with seeds, extracts, carefully chosen active ingredients, and revolutionary results-oriented technology. Revri addresses so many particular skin problems, it can never be mistaken for simply a moisturizer.
Because Revri's ingredients are innovative, so are the results:
27% decline of water loss
17% decline in wrinkle depth
18% increase in skin firmness
18% increase in skin elasticity
Reduction of age spots
Decrease in free radicals
Reduce in skin roughness
Increase of fatty acids
Improved collagen levels
A boost in healthy cell replication
Increased skin elasticity
Increase in skin firmness
Step 1 Purifying Cleanser
Apply with upward motions
Leave on for 60 seconds
Add water to activate
Step 2 Revitalizing Serum
Apply with small circular motions
Step 3 Deep Moisturizer
Apply with small circular motions until all skin is hydrated
To experience Revri for yourself, call me at 801.809.7766.
Buy Now in Utah!
My name is Adam Green, and I am a Draper-based Rain Partner. I sell industry-leading seed-based nutrition including Revri skin care and Soul online and in Draper, Reno, Los Angeles, and Dallas.
If you are interested in seed-based nutrition and the incredible advantages it offers, call me at the number below.
I have limited supplies on-hand and can make special orders for interested parties. Some limits apply.
For more information about seed nutrition and the Rain International opportunity, visit: Official Utah Rain International Seed-based Nutrition Information.
Call me for Details:
Adam Green
successful direct marketer
The statements contained herein and the products described have not been evaluated by the Food and Drug Administration. Neither Rain International nor its products are intended for the purpose of diagnosing, treating, curing, or preventing any disease.
The information on this web page is designed for informational purposes. It is not to be a an alternative to qualified medical advice or care. You should not use this information to diagnose or treat any health issues or illnesses without counseling with your physician.


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The high grade metal roofing system with sheet thickness within 0.7mm and 1.2mm uses anti-corrosion, lightweight, high-strength and durable metal panel (such as Ti-Zn panel, aluminized and galvanized color steel panel, and more), aluminum alloy panel or stainless steel panel.
We at Seven Panel offer a standing seam roofing system and a 360 degree double-seam roofing system. Both types of the metal roofing system come in a wide variety of roofing structures, which can meet different requirements.
Features of Metal Roofing System
1. The metal roofing system comes with no connection, no screw holes, and makes the building look intact.
2. The roofing panel of the roofing system can be bent to be arc-shaped.
3. Customers can choose difference texture and colors.
4. The roofing system has a waterproof structure and drainage function, and is maintenance free.
5. The metal roofing system suits use for roof slope as small as 1.5 degree.
6. The roofing panel, together with the base plate, offers strong resistance to wind load. It is typically used in areas where there are a lot of typhoons and heavy rains.
7. The metal roofing system can eliminate stress generated by expansion and contraction.
8. The roofing system is easy to install and very economical.
9. The metal roofing system facilitates laying the heat insulation and sound absorbing panels.
10. With no need of chemical sealant or glue, the building roofing system avoids problems like pollution and aging.
11. Field processing of the metal roofing panel can be offered.
As a China-based manufacturer of metal roofing system, certified by ISO9001:2008 and ISO14001:2004, SEVEN Panel also provides aluminum composite panel, aluminum coated coil, aluminum sheet, and aluminum honeycomb panel, etc. As a result of superior quality, economical prices and good after-sales service, our CE certified products are highly sought after by customers from Russia, Germany, the United States, Indonesia, Singapore, Brazil, Australia, India, and more. Our company is located in Liaocheng City, Shandong Province where we have convenient access to many kinds of transportation, which facilitates the transport of our products and greatly reduces the freight charges for our customers. For more detailed information, please continue browsing our website or feel free to call us right now!


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Sun Shades
Shade Sails
Shade sails, sun shades, patio shades and awnings for your home, deck or patio.
Shade Sails
- Everyone sees them at zoos and numerous other outdoor attractions, but did you know
they can placed in your backyard too? Shade sails are creating quite a buzz and why not. They're a
departure from the ordinary and add interesting architecture to an otherwise dull space.
Yet, they're incredibly functional. They can provide comfortable shade from the summer heat in just
about any situation. Why not cover your deck or patio with a contemporary sail? Perhaps you or a
family member are sensitive to the sun and can't enjoy your swimming pool during the heat of the
day. Put a shade sail over your pool and start enjoying yourself once again.
Shade sails come in either standard sizes or they can be custom ordered to fit your unique space.
They are very trendy additions to outdoor patio restaurants, children play areas, school campuses or
anywhere people gather outside.
So be the talk of the neighborhood and look into getting one of these remarkable shade sails today.
Find the best deals on sun shades, awnings and sails
Deck Awnings
Sun Shades
Patio Shades
Shade Sails
About Us
Contact Us
Privacy Policy
Copyright 2011-14. All Rights Reserved
Sun Shades
About Us
Contact Us
Privacy Policy
Click images to shop


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Ivan Wellington
Boat Details
|11m Blyth Cat
|2 x 450 Iveco Turbo Diesels
|MCA 60 miles
|12 + Crew
Contact Details
|01305 823443
|07966 133979
Other Details
|Click Here
Welcome to my new pages on the brilliant Deepsea website.
The fantastic Top Cat III is powered by 2 450 H.P NEF Turbo-charged engines de-rated to 420 H.P. She also has 6 livebait tanks that also double up to keep your fish fresh and also keeps ice for up to 6 days for when we go to Alderney.
There is also a hot water boiler for coffee and if you would like to warm your pies up there is also an oven .There is a toilet on board and Top Cat III also has wheelchair access.
Top Cat is one of the latest designed fast Catamaran's with stacks of power and space for fishing and diving. We also undertake commercial work and can carry up to 1 ton on board if required. An a-frame can be fitted for trials work/sampling etc.
230v is available through an on-board inverter.
I would welcome you aboard and work hard at finding you the fish...come on down to Weymouth and give it a go.
About Me...
I have lived on Portland all of my life,I started my fishing in the early days scampering up and down the rocks on Portland,Little beach and Church Ope cove,(for those that don,t know there are 157 steps to the bottom ).As I got older I was allowed to go to Portland Bill where I used to watch the old Portlanders wind up there boats on the cranes,sometimes if I was lucky they would let me have a go.
Seeing the catches made me want to have a go,I became a very successful shore angler winning many trophies in Weymouth Angling Society and Portland Angling Club.Hopefully I can pass some of my knowledge gained on to my many anglers.I am a life member of the British Conger Club and also the European Federation of Sea Anglers (EFSA)
Eventually I was able to get my own boat on one of the cranes at Portland Bill,a sixteen foot Clinker boat which on a nice day we would go Bassing in the race.Then I got an Alaskan 500 which I eventually moved to Portland harbour and replaced my 18hp Mercury with a 60hp Mariner outboard and used to venture to the many wrecks out to 12 miles and learn my apprenticeship anchoring a wreck properly.
In 1996 I was made redundant from Portland Naval Base and I bought the first Top Cat a Blyth 33,since then I've had another Blyth 33 (Top Cat II) Now I'm on Top Cat III which was launched in 2010 which really is a nice vessel and is 11 metres long with a 4.89 beam giving loads of room and stability.So I have been boating for about 30 years of which I have been chartering for the last 18 years so far.
After scratching through my old photo collection I managed to find these images of Top Cat and Top Cat 2. All three vessels were moulded at the Blyth factory at Canvey Island and Top Cat 2 and Top Cat 3 were transported by road to Weymouth where they were finished off before going into service.
Skippers Blog
Posted by: Ivan Wellington
Posted by: Ivan Wellington
Posted by: Ivan Wellington


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About Us
A warm welcome to www.kanbancrafts.com
Our company ethos is to provide an outstanding service to you, the customer, alongside top quality crafting products and the latest innovative ideas.
We pride ourselves in our design and manufacturing capability and are committed to manufacturing the very best quality products and on trend designs, having spent many years in the industry.
Our retail website offers you many well known brands alongside Kanban Crafts products. If you cannot find what you are looking for please do not hesitate to contact us and we will do our best to locate it for you.
If you fancy a trip out why not come and visit our factory shop which has many more products.
Thank you for taking the time to visit our website.
With Best Wishes
Team Kanban.


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What Every Homeowner Should Know About Mortgages
Don't allow yourself to get burdened with finding a mortgage company that's good. If this sounds like you, then it may be time to take advantage of a few pointers that can help. This article will show you with some helpful basic tips for choosing a solid mortgage company.
Start preparing for a home loan process early. Get your budget completed and your financial documents in line before beginning your search for a home and home loan.This means building upon your savings and organizing your finances in order. You may not be approved if you wait.
Get pre-approved for a mortgage to get an idea of how much your monthly payments will be. Shop around to see how much you are eligible for. Once you figure this out, you can easily calculate monthly payments.
Your loan can be denied by any changes to your financial situation. You should have a secure job before applying for a loan.
Know what terms you want before trying to apply for a home loan and keep your budget in line. No matter how great a new home is, if you cannot afford it, trouble is bound to ensue.
Search around for the most advantageous interest terms possible. The bank wants you to take the highest rate. Don't let yourself be a victim of thing. Make sure you're shopping so you're able to have a lot of options to choose from.
This should have all the fees and closing costs as well as whatever fees you are responsible for. Most companies are truthful about all the costs involved, but you may find some hidden charges that may sneak up on you.
Do not let a single mortgage denial keep you from getting a mortgage. One lender does not doom your prospects.Keep shopping around until you have exhausted all available options. You might find a co-signer can help you get the mortgage.
Ask your friends for home mortgage. Chances are that they will be able to give you advice on what to look out for. Some may share negative stories that can show you avoid them.
After you secure your loan, try to pay down the principal as much as possible. This practice allows you repay the loan much faster. Paying as little as an additional hundred dollars more per month on your loan can actually reduce the term of a mortgage by ten years.
Many times a broker is able to find mortgages that fit your circumstances better than traditional lenders can. They have a variety of lenders and can give you guidance in choosing the right loan.
Cut down on your credit cards you use before buying a house. Having too many credit cards can make you finances.
It is always empowering to learn the right information. Instead of navigating your way through the field of mortgage companies only to find out that you're not sure if you're doing things right, now you can know. Have confidence in your own choices and review the possibilities prior to moving ahead.


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Darn, this event is over 6 months old, but I bet there is something great happening somewhere!
View Current Taos Events!
Sunday, Jan 14th - 2018
3:00 pm-6:00 pm - $0-$20
High Frequency Loft
A bi-monthly gathering for 12-year-old girls to promote sisterhood & empowerment, physical, psychological, spiritual well being & self love through self care. This is a safe, fun, inspirational space for navigating the changes from childhood to womanhood while deepening into a support network with other young women under the gentle guidance of big sisters & aunties who will share their wisdom, gifts & tools. There will be different guest speakers each week to give the girls various flavors of role models; all women walking their empowered path.
The Schedule:
Dec 3rd- Discovering the Goddess;
self care & our gifts
Dec 17th – Herbs, Earth & Moon; herbal remedies, our physical connection to the earth, menstruation & moon cycles. *Solstice celebration
Dec 31st – Embracing Winter & New Year; inner world, listening to the body, observing the mind, setting intention & goals
Jan 14th – Rituals & Routines; caring for mind, body & spirit with daily practice
Jan 28th – Respecting & Protecting; Sacred body & sexuality
Feb 4th – Initiation into womanhood
When: 3-6pm EVERY OTHER Sunday
Cost: $0-$20 no one turned away for lack of fund


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Pack a lunch and join us for this workshop designed to explore core marketing fundamentals through a nonprofit lens. We will look at how to craft personas, how to use your internal resources and how to leverage your external connections for greater impact. Once you comprehend the "why" of your marketing mission you can confidently provide resources and select channels for execution.
About the Instructors:
Joey DiFranco, Creative Director at TentCraft, a Traverse City-based company that creates branded outdoor experiences. He has more than ten years of creative and marketing experience in agency and in-house settings. He is a 2007 graduate of the Savannah College of Arts & Design with a Bachelors of Fine Arts in Film & Television Production.


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The Agribusiness Awards recognise and celebrate the most innovative organisations and individuals that have contributed to Ireland being viewed as a global leader in this sector.
The Award categories reflect the main areas of excellence in this vibrant industry, such as Dairy, Beef, Poultry, Beverages, Food Processing, Seafood, as well as many others.
"Winning the award for Fresh Fruit & Vegetables Agribusiness of the Year was a great boost for our business: Not only did we get to enjoy the well-organised awards event itself, but we used the award in our marketing activities as testament to our high standards and innovations as growers, packers and distributors of potatoes, fruit and vegetables for Ireland's top retailers."
Eleanor Meade, Business Operations Manager, Meade Potato Company
Agribusiness is one of Ireland's most important indigenous industries, contributing an estimated €24 billion to the national economy and employing over 250,000 people directly and indirectly.
Launched in 2015, the awards programme also offers a platform to highlight the efforts of all those involved in the successes to date and celebrate their achievements together at the prestigious Awards ceremony.
The Agribusiness Awards are a part of the Business River network solution.
About Business River
Business River is the network solutions arm of Event Strategies hosts over 12,000 senior level business professionals at over 30 established events with a wider business network of over 25,000 people.
Other established events in the Business River portfolio include:
Marine and Natural Resources Awards
The Marine and Natural Resources Awards seeks to find the businesses and enterprises who are responsibly harvesting our natural resources for the benefit of future generations and the continued well-being of the Irish economy while operating to world-class standards. Visit the Website.
The Food & Beverage Wholesale and Distribution Awards
The Food & Beverage Wholesale and Distribution Awards offer a unique opportunity for Cash & Carry Operators, Wholesalers and Distributors to benchmark their work, generate national recognition, and network with peers. Visit the Website.
The International Food & Drink Trade Awards
This Awards programme recognises the highest performing international food and drink manufacturers, processors and distributors who are based out of Ireland. Visit the Website.
The Irish Content Marketing Awards
The Irish Content Marketing Awards recognise achievements in leveraging the content marketing discipline to drive business and organisational success. Visit the website.
The National Procurement Awards
The Awards programme to encourage excellence in procurement and supply chain. Visit the Website.
The Irish Logistics & Transport Awards
The premier awards programme for the Logistics and Transport sector. Visit the Website.
The Irish CX Impact Awards
The Irish CX Impact Awards recognise your achievements in measuring and managing Customer Experience excellence that delivers better outcomes for your customers and ultimately your own business or organisation. Visit the Website.
End2End Supply Chain Conference
The conference providing insight into the very latest information and thoughts regarding supply chain. Visit the Website.
Green Awards
The long-standing awards programme that celebrates green best practice in Ireland. Visit the Website.
Education Awards
The Education Awards recognise, encourage and celebrate excellence in the third level education sector on the island of Ireland from both State and privately funded institutions. Visit the Website.
HR Leadership & Management Awards
The awards programme that celebrates excellence in HR in Ireland. Visit the Website.
National Supplier Awards
If your company has been successful in winning a public tender and gone on to successfully execute your contract, then these awards give you the opportunity to showcase your reliability as a supplier in the public sector tender environment. Visit the Website.
The Irish Sponsorship Awards
The awards programme that celebrates excellence and achievement in the discipline of sponsorship in Ireland. Visit the Website.


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|Toronto, Ontario, Canada
Wholesale Brokerage
Brokerage Process
Wholesale Auction Vehicle Brokerage Services
What does Willz auto brokerage do?
We source vehicles for our clients from a huge variety of wholesale dealer-only auctions in Canada, the USA, and Europe. We use our professional analytical tools to locate the best car in the best market for you.
We dispense with many of the costly services and amenities associated with the typical brick-and-mortar dealership. We consistently put smiles on our client's faces with the great cars we put in their driveways.
How much can I save?
It is bit difficult to give a precise number but roughly you may be able to save 10 to 15%. Given our reduced overhead and that we purchase vehicle from wholesale sources, we can pass on cost savings to you. If we import a vehicle from the U.S. and the Canadian dollar is strong, we may be able to save you money, as some U.S. vehicles are priced much lower south of the border.
Also, we can help in the conversion and federalisation of a vehicle at rates below what the automobile manufacturers themselves would charge, if you dealt with them directly. A better vehicle at a better price.
Try our quick calculator on our CDN-USA importing page. Or tell us the make and model of a vehicle you're interested in and ask us for a free and detailed estimate.
What can I expect from Willz automobile brokerage?
You will be given an honest professional answer to all of your questions. We will find vehicles that meet your individual needs. We will not pad or exaggerate the quality of any vehicle. We will make sure you are given an objective quality review of every vehicle we locate. You can make an informed purchase decision based on our detailed research.
We will ensure you are happy and receive excellent value in your purchase. We want you to tell your friends and family about your personal experience with our brokerage. Your complete satisfaction is the key to our continued success.
How does the process work?
Our concept is modeled after the way a real estate or stock broker works. We start out by asking you what your needs are; manufacturer, style, colour preferences, transmission, mileage, options, etc.? What is your budget? Have you seen something that looks interesting that you want us to find for you? It's that simple. All you have to do is tell us what you want.
We will tailor a solution to your needs. We will research historic wholesale pricing and will suggest to you what any particular vehicle will sell for. We will present you with a list of suitable vehicles available from all of our sources. Perhaps a car in Montreal will sell for a good price, or an imported vehicle from Boston would do well if the Canadian dollar is strong. You choose which vehicle will best suit you needs from there.
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Page last edited on January 25, 2012.


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NEW DELHI (Reuters) - India's finance ministry wants the Reserve Bank of India (RBI) to address credit and liquidity related issues at its board meeting scheduled for Nov. 19, Indian TV channels reported on Wednesday, citing unidentified sources.
The central bank and the government have been at loggerheads in recent weeks as the government ramps up pressure on the regulator to relax lending curbs and hand over surplus reserves.
According to the TV reports, the sources said the discussions on the economic capital framework of the central bank, a reference to the reserves issue, can continue later. Kicking that issue down the road could allow space for the two sides to come to an uneasy truce next week.
Economic Affairs Secretary Subhash Chandra Garg last week said the government was discussing ways to fix the appropriate economic capital framework of the RBI. That framework is used to decide the adequate amount of reserves the central bank should maintain.
Reporting by Nidhi Verma; Editing by Martin Howell


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All Online Casinos List 2019
Promotions may include any or all of the following incentives: free spins, welcome bonuses, reloads, tournaments and holiday campaigns, but it is always best to check with each of those websites individually, in order to find out if the rewards program is static or being constantly upgraded. Online casinos come in many shapes and sizes, so that everyone could find the most suitable place to join and play. These might also be conceptually different, featuring a classic or modern theme, or be completely revamped with the visually aesthetic animations derived from popular games.
All Online Casinos List – January 2019
The constantly evolving field of electronics and computer graphics is also helping to push the boundaries of the actual progress in technology, allowing for a much more diverse and satisfying experience. Selecting an online casino is easy, with each dedicated webpage offering a quick insight into what the operator has in store for its customers, with recent news on new promotions and games as a highlight to the general information on those web based services. The following webpage compiles a full list of different casinos, which for better or for worse, are going to successfully bring you the very best of what the online market has to offer at this point. Other than this, it can always help as a point of reference.


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I recieved this phone today after buying it on the orange online shop for £54.99, so far i am pleased. It seems that it is easy to use and i like the design, the camera seems quite good too. I reccomend it.
Finally sussed out the zoom; it doesn't work if camera is set to highest resolution!
Next question: Is there any way to change the message tone to something other than the 4 available on the phone? Can I download a sound effect then set it as my message tone?
Just got it only £54.99 of the Orange web site and it is really good. Light, packed with features and as somebody else here has said the LG website offers loads of great free games and ringtones.All in all a top phone with a very clear easy to use layout.
Orange has it for onlly £54.99 if u ditch ur old phone. That's a real bargain folks!
I have been trying to buy a data cable for my C3310 without luck. Does anyone know where I could get one, or any other way of getting my photos off the phone to print them?
A question : When you attach a picture to an address entry, it is displayed only in the internal screen. How to display it on the external screen ?
My phone is stuck in "Car Kit" mode, anyone know how to get it back to normal mode? Nothing is listed in the manual.
Iv Had this phone about 6weeks now, dose anyone know where I can get a usb date cable form , so I can transfer my pictures from the phone to my PC????
i think the fone is great apart from tryin to get good java games ...any ideas where i can get any
this pfone is realy awsem i just got it and its allot of fun! for only 129 thats nothing for that gsm :s
i luv this phone cos its got lots of kewl things c u l8er!!!!!!!!!!!!!!
If you log onto wowlg.com and you register your phone you can get up to 200 points which you can use to download games, music and other stuff. Some of this is free, for which you will need your cable, and a game is typically 55 points. Every day you log on you get another 2 points.
I have this phone now and thinks its the Bees Knees, I can Zoom with no trouble, The only thing im dissappointed with is that the fact i have bought a Serial Data Cable and cannot get any Software for it, So Renders the cable useless... lol any Ideas... ;)
I've got a C3310 and think it's a great phone, apart from the fact I can't get the zoom function to work in camera mode! Has anyone else had this problem?


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Order Picker
Kearney, NE 68847
We are hiring for Order Selectors in Kearney! Primary responsibilities will be to operate electric or manual pallet jacks, utilize pick labels, pick sheets and voice picking equipment, and pick orders according to bay locations. Preferred candidates will have previous forklift or warehouse experience. All candidates must possess an eighth grade education. This candidate must be a quick-learner, be able to work independently, and have a great attendance record. Interested candidates, call immediately at (308) 233-4400, submit your resume by clicking on the following link:http://www.essentialpersonnel.com/submit-resume , email your resume to email@example.com , or click the apply button to complete our application.
- Ability to lift 50 lbs regularly
- Team Oriented
- Responsible for observing safety rules at all times
Essential Personnel employment consultants are experts at providing staffing solutions to meet each company and job seeker s unique needs. We specialize in the fields of industrial, technical, professional, executive and clerical, mortgage, human resources, information technology and accounting. We staff for temporary, temp-to-hire, permanent placement and executive search.
We focus on matching people with positions that are rewarding, well paying, and a great fit for your personality, skills and goals. We are always seeking hard-working candidates who are looking to advance their career.
Pay: $14.00/hour


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Russia is the most important country on the planet and exploring its many wonders can appear intimidating to even the most seasoned traveller, let alone the holidaymaker who may solely have every week or two to spare. While you apply for the varied positions with a travel nursing companies, they'll let you realize the particular necessities on your particular specialty. Aside from these, we can select to travel as an unbiased traveler or go on a gaggle packaged tour. When traveling by means of smaller airports, test their web sites to find each airline that gives service there.
Travelers can find Delhi attention-grabbing as it is a cultural travel bundle of India where massive variety of folks will enjoy going by means of the detailed histories of the erstwhile rulers who left many things legacies for the era to come back. Indian Travel Agent is a vacationer operator in India who gives unique travel packages to Dibang valley and to the Forest parks and the wildlife sanctuaries at this place.
It's now simple to guide a cruise journey, by contacting an authorized travel agent or registering online and availing of the automated corporations that supply the easiest gives at the lowest prices. It's also necessary to seek out out the … Travel More