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Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln) insufficiency caused by loss-of-function mutations or gene deletion. Recently, we have modeled this disease in mice (Eln+/–) and found that Eln haploinsufficiency results in unexpected changes in cardiovascular hemodynamics and arterial wall structure. Eln+/– animals were found to be stably hypertensive from birth, with a mean arterial pressure 25–30 mmHg higher than their wild-type counterparts. The animals have only moderate cardiac hypertrophy and live a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln+/– arteries were generally smaller than wild-type arteries at any given intravascular pressure. Because the Eln+/– mouse is hypertensive, however, the effective arterial working diameter is comparable to that of the normotensive wild-type animal. Physiological studies indicate a role for the renin-angiotensin system in maintaining the hypertensive state. The association of hypertension with elastin haploinsufficiency in humans and mice strongly suggests that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension.
The physiological demands of the arterial system in vertebrates require that arteries store energy during systole and release it during diastole, which allows the heart to work at an optimal rate and stroke volume. The central feature that facilitates this function is vessel elasticity, which is conferred upon the arterial wall by the apposition of smooth muscle cells (SMCs) and a complex weave of ECM molecules. The basic morphological plan of large arteries present in all major vertebrate classes consists of repeating concentric layers of SMCs separated by elastic fibers that form interconnected fenestrated sheets, or lamellae. These elastic lamellae are designed to function as an elastic reservoir and to distribute tension uniformly throughout the vessel wall. The number of lamellar units (generally defined as the elastic lamella and adjacent SMCs) in a vascular segment is related linearly to tensional forces within the wall (1–3), with the greatest number of elastic layers occurring in the larger, more proximal vessels that experience the highest wall stress.
Acquired elastic fiber abnormalities that alter the structure and mechanical properties of vessels are associated with aging and are observed in common vascular diseases, such as atherosclerosis, aneurysms, and hypertension. Other vascular diseases have been shown to have a genetic etiology. At least three clinical conditions have been linked to mutation or deletion of the elastin gene (Eln). Autosomal dominant cutis laxa, a primarily cutaneous condition, is the result of frameshift mutations at Eln that influence elastic fiber structure through a dominant negative effect (4, 5). Supravalvular aortic stenosis (SVAS), an autosomal-dominant disorder, is caused by intragenic deletions or by a large spectrum of mutations within the elastin gene (6–8) that result in functional haploinsufficiency through either nonsense-mediated decay of mRNA from the mutant allele or the production of a nonfunctional protein (9–11). Williams syndrome (WS), a neurodevelopmental disorder that has SVAS as a component, develops as a consequence of a microdeletion in the chromosomal region 7q11.23 encompassing, among others, the elastin gene (12, 13). Narrowing of the ascending aorta is a dominant feature of SVAS (in both the isolated and WS forms), but other arteries, including pulmonary arteries, are often affected. If not corrected, SVAS may lead to increased intracardiac pressure, myocardial hypertrophy, and heart failure.
Recently, we generated mice hemizygous for the elastin gene (Eln+/–) to study the pathogenic mechanism underlying SVAS (14, 15). Characterization of the arterial wall of these mice found that elastin haploinsufficiency results in changes in arterial wall structure, including thinner elastic lamellae and an increased number of SMC layers — changes also observed in humans with SVAS (15). To investigate how these changes influence vascular function, we evaluated a number of basic hemodynamic and mechanical properties of the elastic-conducting vessels of Eln+/– mice. The vascular effects of elastin insufficiency occur early in development and result in a cardiovascular system that has undergone a remarkable adaptation to the altered mechanical properties of the vessel wall. The animals are stably hypertensive with only mild cardiac hypertrophy and do not exhibit the hypertension-induced arterial wall hypertrophy and decreased distensibility of large elastic arteries associated with essential hypertension. The results of this study provide insight into how hemodynamic forces impact vascular development and address the mechanism of hypertension in arteriopathies associated with elastin haploinsufficiency.
Wild-type C57B1/6J mice (Eln+/+) and mice of matching age (5–7 months) bearing a heterozygous deletion of exon 1 in the elastin gene (Eln+/–) backcrossed for more than five generations into the C57B1/6J background (14) were used for all studies. Littermates from Eln+/– crosses were used whenever possible. All housing and surgical procedures were in accordance with institutional guidelines.
For vessel mechanical studies, animals were anesthetized by intraperitoneal injection of pentobarbital (60 mg/kg). A segment of the ascending aorta, the abdominal aorta, the left carotid artery, or the renal artery was quickly excised and placed in a physiological buffer of the following composition: 135 mM NaCl, 5 mM KCl, 1.6 mM CaCl2, 1.17 mM MgSO4, 0.44 mM KH2PO4, 2.6 mM NaHCO3, 0.34 mM Na2HPO4, 5.5 mM D-glucose, 0.025 mM EDTA, 10 mM HEPES (pH 7.4). The vessels were cleaned of adhering connective tissue and fat, then cannulated and mounted onto a pressure arteriograph (Living Systems Instrumentation Inc., Burlington, Vermont, USA, or Danish Myotechnology, Aarhus, Denmark), as described previously (16). The experiments were performed at 37°C in an organ bath filled with physiological buffer. Following a 30-minute equilibration period, the vessel was transilluminated under an inverted microscope connected to a charged-coupled device camera and to a computerized system allowing the continuous recording of the vessel diameters.
Except for vessels treated with KCN, all studies used live vessels. Recordings of vessel inner diameters (IDs) and outer diameters (ODs) were taken while increasing the intravascular (transmural) pressure from 0 to 175 mmHg by steps of 25 mmHg (5 minutes per step). Recordings were also taken while decreasing the pressure following the same steps and timing from 175 to 0 mmHg. Assessment of arterial reactivity at 75 mmHg was performed using 5 μM phenylephrine (PE) as a SMC-dependent vasoconstrictor (for 10 minutes or until maximum vasoconstriction was reached). This was followed by the addition of the endothelial cell–dependent vasodilator acetylcholine (Ach) (5 μM) that was added for 5 minutes or until maximum vasodilatation was reached. The vessel was then bathed at zero pressure in a physiological buffer containing 13 mM KCN for 45–60 minutes to poison the vessel wall cells. After verifying at 75 mmHg the nonresponse of the vessel to 5 μM PE, the intravascular pressure was raised and lowered as described above while recording the artery segment's ID and OD. For the renal artery, the concentration of PE and Ach used was 1.5 μM. The bath medium as well as the medium filling the vessel was replaced every 15 minutes.
The thickness of the wall in the large arteries (ascending and abdominal aorta, carotid artery) precluded the localization of the inner wall edge in many transilluminated vessels at pressures lower than 100–125 mmHg. Hence, in this pressure range ID could not be measured directly. Above 125 mmHg, however, direct measurement of ID was possible because thinning of the arterial wall at high pressure allowed a clear and contrasted image of the inner wall edge. In previous studies, we showed that in both wild-type and elastin-knockout animals, vessel wall cross-sectional area (WCSA) remains relatively constant throughout the experimental pressure range. As a result, ID can be accurately calculated from OD at any given pressure and from a single measurement of WCSA (16). Thus, when necessary, ID was calculated from the measured OD at the corresponding pressure using values for WCSA calculated from the measurements of OD and ID at 175 mmHg.
Circumferential midwall strain, circumferential wall stress, and incremental elastic modulus were calculated according to the formulas given by Gibbons and Shadwick (17). Distensibility is defined as the change in relative volume (percentage) of the lumen per pressure unit during a change in intravascular pressure, as described by Smith and Kampine (18). Expression of the distensibility is preferred to the compliance (change in absolute volume per pressure unit) because the difference in initial vessel diameter (at transmural pressure = 0 mmHg) between Eln+/+ and Eln+/– vessels may result in misleading comparisons and interpretations of the difference in the absolute volume. Because the pressure-change increment in our experiments was 25 mmHg, distensibility is expressed as the distensibility per 25 mmHg increment (D25).
The hearts from 11 Eln+/+ and 11 Eln+/– 5- to 7-month-old mice were dissected, washed, and weighed (wet weight). The left ventricle and septum weights were obtained using dissected tissue. Ratios of total heart weight to body weight, as well as left ventricle plus septum weight to body weight, were then analyzed.
Vessel segments, 2 mm long, were used to determine arterial wall protein content (20 animals used). For each artery type (ascending and abdominal aorta, carotid artery), six segments from 5- to 7-month-old Eln+/+ and Eln+/– genotypes were compared. Desmosine levels were determined by radioimmunoassay (19). Hydroxyproline and total protein content were determined by amino acid analysis using standard techniques (20). Results are expressed as protein mass per vessel segment length (micrograms per millimeter plus or minus SEM).
Eln+/+ and Eln+/– mice from a range of ages were used for blood pressure and heart rate measurements. The animals were anesthetized using a ketamine/xylazine (87 mg/kg and 13 mg/kg, respectively) cocktail and were then restrained on a heated holder to maintain body temperature. A Millar pressure transducer was inserted into the right carotid artery and moved to the aorta where heart rate and systolic and diastolic blood pressure were monitored.
For physiological experiments, the jugular vein of mice was catheterized with PE-10 tubing for fluid infusion, and a Millar pressure transducer was inserted into the right carotid artery for monitoring blood pressure. A series of acute mean arterial pressure responses to a bolus dose of Ang II (1 μg/kg), hexamethonium (5 mg/kg), candesartan (100 μg/kg), and saralasin (10 μg/kg) were evaluated by continuous blood pressure recording. Intravenous infusions were done over a 2.5-second period, with compounds dissolved in saline and delivered in a volume of 5–10 μl. Isotonic saline was injected as a control.
Plasma renin activity and aldosterone levels in mouse plasma were determined by the clinical laboratories at Barnes Jewish Hospital, Washington University Medical Center (St. Louis, Missouri, USA).
Animal preparations and image acquisition were performed by echocardiography as described previously (21). Three consecutive cardiac cycles from each of two sequentially acquired cine loops (a total of six frames per animal) were analyzed for end-diastolic and end-systolic left-ventricular volumes. End-diastolic and end-systolic frames of parasternal long-axis images were used for computer-assisted manual tracking of the endocardial border of the left ventricle (LV) chamber. Systolic and diastolic LV volumes (LVVs and LVVd, respectively) were determined by the disk summation method. Stroke volume (LVVd – LVVs) was deduced from these measurements. The values were indexed to the body weight for each animal. Five animals were used in each group.
Sections from Eln+/+ and Eln+/– descending aortic tissue fixed in 10% formalin and embedded in paraffin were incubated with a monoclonal antiproliferating cell nuclear antigen (anti-PCNA) Ab (1:200; BioGenex, San Ramon, California, USA). Primary Ab was visualized by an immunoperoxidase method using the TrueBlue peroxidase substrate according to the manufacturer's instructions.
Comparisons of Eln+/– and Eln+/+ body weight, heart weight/body weight ratios, heart rate, systolic, diastolic, and mean systemic blood pressure, total protein, desmosine and hydroxyproline contents (as well as their ratios) in all three vessel types, and vessel diameters (OD and ID) as a function of vasoactive agent treatment were assessed using one- or two-way ANOVA, followed when necessary by Fisher's least significant difference (LSD) test or Student's t test for protein dosages for paired value comparisons.
Vessel diameter as a function of transmural pressure level (0–175 mmHg), pressure variation status (increasing or decreasing), KCN treatment (before or after), and genotype (Eln+/– or Eln+/+) were compared using a four-way ANOVA followed when necessary by LSD tests for paired value comparisons. Vessel midwall strain, stress, incremental elasticity modulus, distensibility, and local midwall strain comparisons were assessed using the nonparametric Mann-Whitney U test.
Unless otherwise indicated, the results are presented as mean values plus or minus SEM, and P values equal to 0.05 were chosen as the threshold for statistically significant differences.
Comparison of adult Eln+/– and Eln+/+ mice revealed a similar average body weight (approximately 32 g), with no statistically significant difference (P > 0.73) (Table (Table1).1). Systolic, diastolic, and mean blood pressures, however, were substantially higher at all ages in Eln+/– compared with Eln+/+ animals (Table (Table1).1). At 6 months of age, mean arterial pressure (MAP) was 96 ± 5 mmHg in Eln+/+ mice and 123 ± 7 mmHg in Eln+/– mice. This pressure difference was also evident at 7 weeks of age, with MAPs of 92 mmHg and 136 mmHg in the Eln+/+ and Eln+/– genotypes, respectively. At 15–18 months of age, MAP remained elevated in the Eln+/– genotype (144 ± 4 mmHg) compared with wild type (93 ± 2 mmHg). The pressure difference between the two phenotypes at 6 months of age was confirmed using a tail cuff sphygmomanometer (mean = 121 mmHg for Eln+/–, 86 mmHg for Eln+/+) as well as by femoral artery catheterization (mean = 110 mmHg for Eln+/–, 84 mmHg for Eln+/+). The tail cuff results were from conscious mice and confirm that elevated blood pressure is not a consequence of anesthesia.
No statistically significant difference in heart rate could be detected between the two genotypes (both were in the range of 365 beats per minute in 5- to 7-month-old mice measured under anesthesia). Total heart weight to body weight ratios, as well as LV plus septum to body weight ratios, were higher (15% and 13%, respectively) in Eln+/– than in Eln+/+ animals (Table (Table11).
End-diastolic LV volume indexed to body weight (LVVdI) was increased in Eln+/– mice, while end-systolic LV volume (LVVsI) was not significantly different between the Eln+/– and control animals. Consequently, stroke volume was significantly increased and, even in the presence of slightly decreased heart rate, cardiac output indexed to body weight was significantly increased in Eln+/– mice (Table (Table11).
We noted previously that elastic lamellae were thinner in Eln+/– mice and that elastin mRNA levels were decreased in the arterial wall (15). To determine how these differences translate to changes in total elastin content, elastin concentration in arterial segments was determined by quantifying desmosine (a crosslinking amino acid unique to elastin) following protein hydrolysis. In a similar way, hydroxyproline levels were used to quantify total collagen.
When protein levels are expressed as protein content per millimeter of vessel, total protein values were found to be significantly higher in the ascending and abdominal aortas of Eln+/+ mice than in similar segments from the Eln+/– genotype. There is no difference in total protein content in the carotid artery from either animal group (Table (Table2).2). Within each genotype, the total protein, desmosine, and hydroxyproline content differed between vessel types (ascending aorta > abdominal aorta > carotid artery), which reflects known differences in wall mass and elastic properties of the vessel segments. Desmosine levels per millimeter of vessel were lower by 34–49% in Eln+/– compared with Eln+/+ mice in the three vessels studied. Hydroxyproline levels per millimeter of vessel, indicative of collagen content, were found to be significantly lower in the ascending aorta (–24%) of Eln+/– animals than in Eln+/+ mice, whereas no difference was detected between the other two vessels (Table (Table22).
To better understand the functional significance of differences in collagen and elastin levels, both measurements were normalized to the total protein content of the vessel wall to provide an indication of the local matrix composition. In all three vessel types, the level of elastin as a percentage of total protein (desmosine/total protein) was lower by approximately 35% in Eln+/– compared with Eln+/+ animals. Interestingly, there was no statistically significant difference in the ratio of collagen to total protein (hydroxyproline/total protein) when the three vessel types from the two animal groups were compared, suggesting that relative collagen synthesis and accumulation was unchanged. Expression of elastin as a ratio to collagen levels (desmosine/hydroxyproline) confirms that there is more collagen relative to elastin in Eln+/– vessels. As expected, the desmosine/hydroxyproline ratio is higher in the more elastic ascending aorta than in the abdominal aorta and the carotid artery in both phenotypes. A table with ratios of desmosine and hydroxyproline to total protein and ratios of desmosine to hydroxyproline for the ascending and abdominal aorta and the carotid artery is supplied in the supplementary online material (http://www.jci.org/cgi/content/full/112/9/1419/DC1).
The mechanical properties of the ascending aorta, abdominal aorta, carotid artery, and renal artery of Eln+/– and Eln+/+ mice were studied by correlating changes in vessel ID and OD with alterations in transmural pressure. To determine the relative cellular and noncellular contributions to compliance of the elastic arteries, vessels from Eln+/– and Eln+/+ mice were studied before and after poisoning cells with KCN. In the three large arteries studied (ascending and abdominal aorta and carotid artery), vascular diameter changed by only a few percent following KCN treatment (data not shown). This is consistent with the findings of others showing that muscle contributes little to the mechanical properties of large arteries (22, 23). The same minimal effect of KCN on the arterial diameter is observed in the smaller renal artery.
The ODs of Eln+/– arteries were significantly smaller than Eln+/+ arteries at any given pressure over the entire range of pressure studied (Figure (Figure1,1, a–d), except in the ascending aorta where no statistically significant difference could be detected at 75 and 100 mmHg (Figure (Figure1a).1a). In all four vessel types, the Eln+/– and Eln+/+ ODs showed the greatest divergence at high transmural pressure (125–175 mmHg) (Figure (Figure1,1, a–d). Similar to ODs, the IDs of vessels in Eln+/– animals were smaller than those in Eln+/+ mice and showed the greatest divergence at high and low transmural pressure (Figure (Figure1,1, e–h) (16). Wall thickness for the Eln+/– aorta and carotid artery was 20–25% less than Eln+/+ vessels at the physiological MAP of each genotype, whereas no difference between genotype was detected in the renal artery (Table (Table11).
Calculations of distensibility (D25) indicate that large arteries in Eln+/– mice undergo greater dilation at transmural pressures below 100 mmHg than do arteries from Eln+/+ mice. The opposite occurs at high transmural pressures (above 100 mmHg), where Eln+/+ animals show higher distensibility than arteries from Eln+/– mice (Figure (Figure2,2, a–c). Wall stress, in contrast, does not differ between Eln+/– and Eln+/+ vessels at any given pressure over the tested pressure range (0–175 mmHg). At the physiological MAP of 100 mmHg in Eln+/+ and 125 mmHg in Eln+/– animals, however, wall stress is found to be significantly higher in Eln+/– than in Eln+/+ arteries in all three vessel types.
The arterial midwall strain was lower in Eln+/+ compared with Eln+/– mice in the ascending and abdominal aorta between 25–50 and 125 mmHg. Interestingly, no difference in midwall strain could be detected at any pressure in the carotid artery in a comparison of the two animal groups. In all three vessel types and in both genotypes, a similar maximum midwall strain close to 1 was measured at 175 mmHg, corresponding to a doubling of the diameter seen at ambient pressure. When comparisons were made at physiological MAP for the two animal groups, however, the arterial midwall strain in Eln+/+ mice was lower than the midwall strain in Eln+/– vessels. This is true for all three types of vessels. At similar midwall strain, the arterial wall stress is generally lower in vessels from Eln+/– mice than in the Eln+/+ arteries, with the possible exception of the carotid artery where the differences are small. When the data are analyzed in terms of incremental elastic modulus indicative of the vessel wall stiffness, there are no differences between animal groups in the pressure range of 0–125 mmHg. At higher pressures where collagen bears an increasing fraction of the stress, the incremental elastic modulus is higher in ascending and abdominal aortas from Eln+/– mice, whereas differences in the elastic modulus in the carotid artery are minimal. A graph showing stress, strain, and incremental elastic modulus of the Eln+/+ and Eln+/– ascending and abdominal aorta and carotid artery is available in the supplementary online material (http://www.jci.org/cgi/content/full/112/9/1419/DC1).
Artery segments from 5- to 7-month-old Eln+/+ and Eln+/– mice undergo normal vasoconstriction in response to PE and normal vasodilatation in response to Ach (Figure (Figure3,3, a–d). There was no difference in responsiveness to 5 μM PE between Eln+/– and Eln+/+ vessels in the ascending aorta and carotid artery (approximately 30% vasoconstriction), and all four vessels from both mouse genotypes reacted similarly to 5 μM Ach. The Eln+/– abdominal aorta showed a significantly greater response to PE, when compared with the wild-type counterpart (Figure (Figure3b),3b), similar to the increased response of the Eln+/– renal artery (Figure (Figure33d).
To determine whether the functionality of resistance vessels is adversely affected by elastin haploinsufficiency and to explore the fundamental mechanism of hypertension in these animals, we performed several types of pharmacological experiments with anesthetized mice. Both wild-type and Eln+/– mice displayed a similar increase in blood pressure in response to a maximal pressor dose of Ang II (Figure (Figure4a).4a). Blocking ganglionic transmission with hexamethonium, an inhibitor of nicotinic channels, had little effect on MAP of wild-type or Eln+/– mice (data not shown), suggesting that increased vascular tone is not resulting from neurotransmitter signaling. We found, however, that infusion of the Ang I receptor antagonists candesartan and saralasin into the Eln+/– mice caused a dramatic decrease in blood pressure (Figure (Figure4b),4b), reaching MAP levels slightly below the baseline of wild-type animals but still higher than the MAP of wild-type animals treated with candesartan. In wild-type mice, saralasin had a slight and transient agonist effect but had no lasting influence on MAP.
Measurement of plasma renin activity found a greater than twofold increase in Eln+/– mice compared with controls (22.5 ± 16.9 ng/ml/h for Eln+/+ compared with 55.9 ± 16 ng/ml/h of Eln+/– animals). Interestingly, aldosterone levels were equivalent for both genotypes (272.4 ± 86 pg/ml for Eln+/+, n = 7, and 307.0 ± 140 pg/ml for Eln+/–, n = 6).
No PCNA-positive cells were detected in the media of either Eln+/+ or Eln+/– 6-month-old mice (data not shown). PCNA-positive cells, however, could be readily identified in vascular tissue of newborn mice, which served as a positive control for PCNA staining (data not shown).
The high blood pressure associated with the Eln+/– genotype is consistent with systemic hypertension that is a frequent complication of SVAS and WS, diseases of elastin haploinsufficiency in humans (24–26). MAP is 30–40% higher in Eln+/– mice than control animals, a trait that shows complete penetrance in the Eln+/– genotype. In humans, the incidence of hypertension is less than the complete penetrance we observe in mice. In WS, for example, approximately 80% of affected individuals have clinically apparent SVAS (27) and 40–60% have documented arterial hypertension (24–26, 28). For reasons not yet understood, the incidence of hypertension in isolated SVAS is much lower. Of the two forms of SVAS, the hemizygosity of the elastin gene in WS is genetically most like the Eln+/– mouse.
The association of hypertension with elastin haploinsufficiency strongly suggests that vessel wall proteins, particularly elastin, should be considered as causal genes for essential hypertension. Any factor that reduces elastin protein concentration or alters vessel compliance during a critical window of vessel wall formation could have a modifying effect on the progression of, or susceptibility to, hypertension or other vascular diseases. This could include mutations within any of the other genes that participate in elastic fiber assembly or perhaps polymorphisms within the elastin gene itself. Secondary factors could also impact elastin deposition and vascular function. There is evidence, for example, that people who had low birth weight tend to have higher blood pressure in later life. The authors of these studies argue that fetuses whose growth is impaired synthesize less elastin in the aorta and large arteries and that this deficiency leads to changes that could predispose an individual to higher blood pressure (29, 30). There is also evidence that maternal and postnatal vitamin D ingestion lowers aortic elastin content (vitamin D is known to downregulate elastin production in cultured cells) and alters vascular compliance similar to that which is seen in our mice (31). Taken together, these studies suggest that environmental or nutritional factors could impact directly vascular development or might act as modifiers on phenotypes involving elastin gene mutations or polymorphisms.
In a previous study, we noted thinner elastic lamellae and decreased elastin mRNA levels in the arterial wall of Eln+/– mice (15). Quantitation of desmosine levels as an index of elastin protein confirmed what was predicted by these earlier findings, namely, that elastin protein is significantly reduced in the Eln+/– animals. When normalized to total protein, our findings show that elastin levels are approximately 35% lower in the ascending, abdominal, and carotid arteries from Eln+/– mice. The ratio of collagen to total protein was identical in both genotypes, indicating that relative collagen synthesis and accumulation is unchanged.
The decreased elastin to collagen ratio suggests that arteries in the Eln+/– mouse should be stiffer than their wild-type counterparts. This was confirmed through mechanical studies that documented a difference in vessel distensibility between the two genotypes (Figures (Figures11 and and2).2). In our initial studies, we reported that the aorta from Eln+/+ and Eln+/– mice had similar extensibilities at a presumed physiologic pressure of 100 mmHg (15). The dramatic difference in blood pressure between the two genotypes, however, alters our interpretation of the earlier physiological findings. At their higher physiological pressure (and above), Eln+/– vessels are stiffer and have a higher circumferential wall stress, circumferential wall strain, and incremental elasticity modulus than vessels from Eln+/+ animals. At lower pressures, however, Eln+/– vessels are more elastic and show greater dilation than do arteries from wild-type mice. Similar changes in vessel compliance have been reported in humans with WS. Using noninvasive ultrasound, Salaymeh and Banerjee found that children with WS have a stiffer aorta and a less-compliant systemic arterial bed (28). Interestingly, a similar study found that the compliance of the carotid artery is not modified in WS, even though increased intima-media thickness and lower arterial stiffness were consistent features (32). Despite the structural alterations in the Eln+/– vessel wall, no significant change in the functional potential of the vascular cells was detected. Vessels from Eln+/– mice responded appropriately and to the same extent as Eln+/+ vessels to both vasodilators and vasoconstrictors.
A major difference between the human pathology associated with SVAS and that seen in Eln+/– mice is that humans, but not mice, develop severe localized aortic occlusion due to subendothelial SMC proliferation. A possible explanation for this difference may relate to the higher vascular wall stress in humans compared with mice, due to their larger size. Higher circumferential wall stress could make vessels more prone to pressure-related damage, leading to stenosis. It is important to note that at their higher physiological pressures, Eln+/– vessels are working close to their maximum strain, suggesting that these animals may be more prone to develop hypertensive cardiovascular pathologies when stressed, since their vessels have a lower potential for distension if the blood pressure increases.
The smaller ID of the large elastic arteries coupled with increased arterial stiffness and elevated cardiac output is predicted to be disadvantageous to cardiac function. Under normal circumstances, this should lead to cardiac hypertrophy, circulatory dysfunction, and possibly death. When we analyzed the hearts of 6-month-old Eln+/– animals, we observed that the total heart weight as well as the LV weight was increased by 15% and 13%, respectively, over wild-type controls. It is therefore somewhat of a paradox that the Eln+/– animals have a normal life span, exhibit no overt signs of degenerative cardiovascular disease, and show none of the adverse effects observed with other animal models of induced or spontaneous hypertension (33, 34). One explanation for the normal characteristics of the Eln+/– mouse is that the elevated blood pressure is an important adaptive response for maintaining cardiovascular function. Figure Figure55 shows that at the higher systemic physiological pressure of the Eln+/– mouse, the effective working ID of the ascending aorta, is comparable to that of the wild-type animal. Because the functional demands of the organism require that normal perfusion be preserved, the adjustment of vessel ID through an increase in blood pressure could be a necessary adaptation to maintain vessel patency appropriate to accommodate cardiac output and perfusion.
While we cannot completely exclude structural alterations in the microvasculature as being responsible for hypertension in the Eln+/– mice, pharmacological studies with vasoactive agents suggested that vascular dysfunction secondary to hypertrophy of the resistance vasculature is not the main cause of the hypertensive phenotype. Compared with wild-type controls, Eln+/– mice displayed an equivalent increase in blood pressure in response to a maximal dose of Ang II and an equivalent decrease in blood pressure after infusion of candesartan (Figure (Figure4).4). In both cases, however, the difference in MAP between wild-type and Eln+/– animals persisted at each end point.
The change in blood pressure seen in the Eln+/– but not Eln+/+ animals in response to saralasin was of particular interest because in both human and animal studies, saralasin infusion reliably identifies an Ang pressor response associated with high renin forms of hypertension (35–37). Our finding of elevated renin activity in plasma of Eln+/– mice is consistent with high renin levels predicted by saralasin inhibition. The equivalent effects of saralasin, a nonselective Ang II receptor antagonist, and candesartan, an antagonist specific for the Ang I receptor, indicates that blood pressure elevation is occurring through the Ang I receptor. Taken together, the Ang II receptor inhibitor studies and high plasma renin levels suggest a role for the kidney and the renin-angiotensin system (RAS) in maintaining high blood pressure in Eln+/– mice. Increased cardiac stroke volume and cardiac output in Eln+/– animals are also consistent with the activation of the RAS and indicate expansion of the intravascular volume and increased contractility of the myocardium. It is interesting that aldosterone levels are equivalent in the two genotypes, confirming that the mechanism underlying the hypertension in the Eln+/– mouse is not permanently mediated by actions of this important hormone.
In a previous study we speculated that the increased number of lamellar units in the arterial wall of SVAS individuals and in Eln+/– mice arose during vascular development in response to altered wall stress (15). A role for hemodynamics in vessel wall development (38, 39) and in modulating elastin production (40, 41) has been suggested from numerous studies of vascular remodeling in response to altered pressure and flow. In the developing chick coronary artery, for example, SMC recruitment from undifferentiated mesenchyme does not occur until the connection to the aorta is made and actual blood flow through these vessels has begun (42). When the vessel wall is forming, SMC differentiation, lamellar number, and elastin content coordinately increase with the gradual rise in blood pressure until the proper number of lamellar units are organized (43, 44). The relatively constant tension per lamellar unit and their uniformity of composition, regardless of species, indicate that the proportion of collagen, elastin, and SMCs in the media is optimal for the stresses to which the aorta is subjected (1). This is why the increased number of elastic lamellae in the arterial wall of Eln+/– mice is unique.
Many studies in mature organisms have shown that the response of fully developed blood vessels to hemodynamic stress is clearly different from what we have documented in Eln+/– mice. In spontaneous or essential hypertension in humans and in experimental hypertension in animals (33, 34), vessel walls become thickened through cellular maturation and increased matrix deposition, but there is no change in lamellar number (38, 39, 42, 45). The reason that fetal and mature vascular wall cells respond differently to hemodynamic stress may reflect the effects of the extensive matrix found in older vessels. Because there is more elastin in the mature vessel wall, the ECM plays a greater role in accommodating wall stress than in earlier developmental stages. Hence, the most efficient adaptive mechanism for a mature vessel to use to deal with changes in pressure is that of altering the amount of the load-bearing ECM. In elastin insufficiency, however, SMCs cannot make sufficient elastin, and the increased number of smooth muscle layers (i.e., lamellar units) may be an attempt by the cells to normalize wall stress. We know that the increase in lamellar number is established at the time of birth (15) and that elevated blood pressure can be documented in neonatal Eln+/– mice as early as pressure measurements can be obtained, suggesting that alterations in Eln+/– vessel wall structure and hemodynamics occur early in formation of the arterial wall. The changes found in the Eln+/– arterial wall suggest that presumptive vascular SMCs are capable of altering vessel wall structure by sensing and responding to wall stress and that mechanical forces play an important role in determining lamellar number. Elucidation of cellular mechanisms for sensing mechanical signals will have important implications for understanding vascular development generally as well as furthering our understanding of vascular pathology in elastin-related human genetic diseases such as SVAS, WS, and hypertension in general.
We thank Douglas Taylor (University of Utah), Gail Maher, Carla J. Weinheimer, and Michael Courtois (Washington University) for technical assistance. This work was funded by postdoctoral fellowship grants from the Fondation pour la Recherche Médicale (France) and the American Heart Association – Missouri affiliate to G. Faury; by grants from the NIH to R.P. Mecham (HL-53325 and HL-62295), to R.P. Mecham and D.P. Kelly (HL-61001), and to W.A. Boyle (GM-55849); and from the Association Française contre les Myopathies (France) and the European Union (Fifth framework programme – research project "Towards the maintenance of tissue elasticity for healthy aging" [TELASTAR], contract no. QLK6-CT-2001-00332) to G. Faury. Funds were also provided by a grant from the National Marfan Foundation to R.P. Mecham.
See the related Commentary beginning on page 1308.
Conflict of interest: The authors have declared that no conflict of interest exists.
Nonstandard abbreviations used: smooth muscle cells (SMCs); supravalvular aortic stenosis (SVAS); Williams syndrome (WS); inner diameter (ID); outer diameter (OD); phenylephrine (PE); acetylcholine (Ach); wall cross-sectional area (WCSA); distensibility per 25 mmHg increment (D25); left ventricle (LV); systolic LV volume (LVV); diastolic LV volume (LVVd); least significant difference (LSD); mean arterial pressure (MAP); left ventricular volume indexed to body weight (LVVdI); end-systolic left ventricular volume (LVVsI); renin-angiotensin system (RAS).
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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In 1999 MRC designed the access control, CCTV, intruder detection and
user friendly security procedures incorporated into the National Centre
for Early Music. An upgrade was specified by MRC in January 2003.
During 2008 and 2009 MRC conducted audits for Museums and Art Galleries in Rochester and Bournemouth.
In 2012 MRC completed a full Security Review and Threat Assessment for a large country Estate and Stately Home in England.
To be regarded as an outstanding provider of specialist project management, recruitment an...
Read More >
Great feedback from the managers at the location, both guards superb.
Read More Read All
Minimal Risk Consultancy retain British Embassies - 4 Missions Security Guarding Services
Read more
Provision of Overseas Security Managers and Intelligence Analysts
Travel Security & Media Protection

subset: commoncrawl


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Garth Brooks Tapped as Keynote Speaker at 2017 South by Southwest
South by Southwest, the annual music, film and media festival in Austin, Texas, is adding another star to its roster of impressive talent set to appear at the 2017 event. Garth Brooks will present one of the music keynote addresses during a conference on Friday, March 17.
Granger Smith Is Better Than Ever After Stage Fall
Granger Smith has a refreshed perspective on life as he's been recovering from a nasty stage fall in December of 2016.
Blake Shelton Scores Promising Young Star on 'The Voice' Season 12 Auditions
It was another great night of auditions on night two of The Voice Season 12 on Tuesday (Feb. 28).
Blake Shelton Joins 'The Voice' Coaches for Amazing Rendition of TLC's 'Waterfalls' [Watch]
Season 12 coaches of The Voice, Blake Shelton, Gwen Stefani, Alicia Keys and Adam Levine, unite to perform an incredible rendition of the R&B classic, "Waterfalls" in a new video.
Thomas Rhett's Wife Was Battling Pregnancy Sickness on Grammy Red Carpet
Thomas Rhett and wife Lauren Akins recently broke the big news that they are expecting not one, but two babies in 2017! The couple, who is set to adopt a baby from Africa while Lauren is simultaneously carrying a little bundle of joy, open up in a new interview about keeping the news under wraps...
Nicole Kidman Reveals the 'Sexy' Date Keith Urban Took Her On [Watch]
Keith Urban and Nicole Kidman are one of country music's most beloved couples, and Kidman is opening up about one of her most romantic memories shared with her husband.
Chris Stapleton Announces New Album, 2017 Tour Dates
Chris Stapleton has announced that he's releasing a new yet-to-be-named album on May 5 and added additional dates to his All-American Road Show tour. The tour extensions kick off the same day the album is released.
Zac Brown Band Cancel 2017 Southern Ground Music & Food Festival
Zac Brown Band have canceled their highly anticipated Southern Ground Music & Food Festival for 2017.
Dolly Parton Reacts to 2017 Grammy Awards Win
Dolly Parton is no stranger to awards and on Sunday (Feb. 12), she picked up her eighth Grammy Award in the category of Country Duo/Group Performance for her collaboration with Pentatonix on her classic hit, "Jolene."
Kelsea Ballerini to Perform at 2017 Grammy Awards
Kelsea Ballerini has joined the list of stars set to perform at the 2017 Grammy Awards on Sunday (Feb. 12).


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Methodists Against the SMU Bush Library Aren't Giving Up Just Yet
The New York Times today is reporting that Methodists still trying to push President Bush's library and think tank off the S.M.U. campus are mounting a "last-ditch effort" to block the damned-near done deal. They want to put the project to a vote in front of the 290 members of the United Methodist Church's South Central Jurisdiction, which partially funds the university. Says New York's Rev. Andrew Weaver, "We need to inform and recruit 16 percent of the moderate delegates to block the project."
Only, looks like it won't be enough: SMU says it's almost finalized a deal with the George W. Bush Foundation to build the library and so-called "policy institute." And Bishop Scott Jones -- a trustee at SMU who got his Master of Theology degree from the Perkins School of Theology and whose brother is the dean of Duke Divinity School -- tells The Times that the jurisdiction's College of Bishops has already given its blessings to the project, as in: "S.M.U. has the authority to sign a 99-year lease, renewable up to 249 years." --Robert Wilonsky
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Trudeau Gives Thumbs Up to Two Pipelines, Nixes Another
You can count on us to do our job, Prime Minister. This one would triple the amount of oil going from Alberta to a shipping terminal in Burnaby, a suburb just east of Vancouver, increasing the capacity of the existing system from 300,000 barrels a day to 890,000.
Here's Why the OPEC Oil Rally Is Likely to Be Short-Lived
Russia, which is not an OPEC member, said it was ready only to freeze production but Qatar's energy minister Mohammed bin Saleh Al-Sada said that Russia has committed to reducing its output by 300,000 bpd. OPEC's cut in production is expected to go into effect in January. During December 2014, prices dropped 41 cents, as oil prices tanked from $69 per barrel to $53, AAA reported.
Italian PM announces resignation after defeat in constitutional referendum
Renzi, 41, voted mid-morning in his Tuscan home town of Pontassieve, but made no comment. Renzi was appointed by the president and the next prime minister could also be appointed in the same fashion, but there could also be another general election.
Hong Kong tycoon Li offers $5.4B for Australia energy firm
DUET shares have fallen 6 per cent from $2.50 at June 30 to close on Friday at $2.35. In a statement to the Australian Securities Exchange, Duet said its board was considering the proposal and it was advising shareholders to take no action as there was no certainty the proposal will proceed.
GDP growth predictions cut to 1.4% for 2017
Britain's economy has so far largely withstood the shock of the Brexit vote, wrong-footing the Bank of England and nearly all private economists who expected a bigger immediate hit.Brexit supporters, who say Britain's economy is likely to fare much better than the widespread views of a slowdown, are likely to question the credibility of the latest OBR forecasts.
Federal government blocks Dakota Access oil pipeline route
Further, Cramer said he spoke Sunday with Darcy, and she "was unable to give any legal reasons for the decision and could not answer any questions about rerouting the pipeline". Texas-based Energy Transfer Partners LP, which owns the Dakota Access Pipeline, did not immediately comment after the decision. Police have blocked Highway 1806 at Backwater Bridge, just north of the Oceti Sakowin camp, since October 27, when protesters burned several vehicles on that structure.
Samsung Electronics considers splitting firm in two
According to investors, shareholders will get more capital from Samsung Electronics and this will enhance the earnings of the Group as well as the Lee family. Jay Y. Lee and his two sisters face a multi-billion dollar inheritance tax burden in the event their father and Samsung Group patriarch, 74-year-old Lee Kun-hee, passes away.
U.S. Army Corps Rejects Easement For Pipeline
This decision may address the expressed concerns of the Standind Rock Sioux Tribe about protecting drinking water sources and sacred sites, but it does not mean that the pipeline will not get built. A video posted on Facebook showed a man identified as Remi Baldeagle saying the secretary of the Army had denied the Dakota Access pipeline easement.
Italy voter turnout above 20 percent at midday
Supporters say this would make Italy more stable. "It wasn't clear that [Prime Minister Matteo Renzi] was going to resign, even though he had said earlier he would", Chandler said just after the prime minister announced he meant to resign .
Autumn Statement: Councils facing £337m costs over new living wage
The Office for Budget Responsibility, Britain's independent budget forecasters, said gross domestic product would grow by 1.4 percent in 2017, down from an estimate of 2.2 percent made in March, before voters chose to leave the EU.Hammond, announcing the first detailed economic plans of May's government, said the OBR believes uncertainty about Britain's trading relationships with its EU neighbors - who buy almost half the country's exports - will cut growth by 2.4 percentage points over coming ...
American Airlines flight attendants want new uniforms recalled
The airline has also offered uniforms made of alternative materials. New uniforms were rolled out for 70,000 employees in September as part of an uniform overhaul for the airline, which merged with U.S. American Airlines spokesman Ron DeFeo stated that the airline carrier recently allowed almost 200 flight attendants to go back to wearing their old uniforms for the time being instead of the new uniforms that are allegedly hazardous.
Trump renews threat of tariffs on companies that move jobs overseas
Why?" Trump said he plans to give companies incentives to stay in the United States by lowering corporate taxes and slashing regulations. Asked Sunday on ABC's "This Week" whether Mr. We should pay less attention to what he says, or tweets, and more to what he actually does. "How would it not be a new 35% tax on families?" Company representatives on Saturday did not respond to a request for comment on Trump's tweet.
Prominent Dallas Attorney Brian Loncar Found Dead Two Days After Daughter's Funeral
Click on this sentence to read about this Developing Story from our media partners at The Dallas Morning News . Rob Crain is the president-elect of the Dallas Bar Association. His daughter, Grace Loncar , died on November 25 after a long struggle with depression, which family says led to her suicide. The personal injury attorney made local news in 2008, when he totaled a Bentley in a crash with a fire engine.
Conflict in Syria: Rebels won't surrender Aleppo
Russian military trucks also delivered aid to the captured eastern districts of eastern Aleppo. Syrian rebel commanders in war-ravaged Aleppo say they will not surrender the city's eastern sector to Russia-backed government forces, despite a government offensive that threatens to drive out opposition fighters after a four-year occupation.
AWS tries to protect its customers from DDoS attacks with new service
The FAQ page doesn't say anything about when the initial version will be killed but does say that customers can keep using it "until it's retired" and that customers can talk to AWS support about migrating to version 2.0. Snowmobile makes it easy to move massive volumes of data to the cloud, including video libraries, image repositories, or even a complete data center migration.
US veterans head to pipeline protest camp in North Dakota
A vigil will take place at the Worker's Memorial in Centennial Park this Sunday, Dec. 4, at 7:30 p.m. People have gathered for months at the Standing Rock Indian Reservation to oppose the Dakota Access pipeline, which is being built to carry oil from western North Dakota to a shipping point in IL.
USA adds 178K jobs in November, unemployment falls to 4
The report says the market added 19,400 part-time jobs last month and shed 8,700 full-time positions. The data release comes ahead of the Federal Reserve's December 13-14 meeting, where the central bank is expected to announce its first interest rate increase in a year.
Vancouver mayor's national profile on the rise in pipeline debate
In a study released in June, before anything regarding the numerous pipeline proposals was certain, scientist and author J. David Hughes calculated the consequences of a number of different scenarios on Canada's quest to 2030.Among the key findings, published by the Canadian Centre for Policy Alternatives, Hughes determined the projected growth in the oil and gas sectors would mean that other sectors in the economy would have to reduce their emissions by anywhere between 47 per cent and 59 per ...
Smith shines for Australia with record SCG innings
Munro went on a rampage to reach the target but failed to do so, as the wickets kept tumbling at the other end, eventually losing the match by 68 runs. "Just from looking at it from the grade perspective where global players never play and state players play very little, I think that's one of the problems with Australian cricket".
Populist Hofer Loses Austrian Presidential Election
Hofer, who led the anti-immigration and anti-Islam Freedom Party (FPO), lost the election to former Greens leader Alexander Van der Bellen. With almost all results counted, Van der Bellen had 53.3 percent of the vote to Hofer's 46.7 percent.
Trump says he is completely leaving his business
He said on Wednesday he is drawing up legal documents that would remove him from day-to-day business operations. After Trump won the November 8 election, his company, the Trump Organization, had said it was looking at new business structures with the goal of transferring control to Donald Trump Jr., Ivanka Trump and Eric Trump - three of his adult children who are involved with the company.
US Senate votes unanimously to renew Iran sanctions
In a speech to Iran's parliament on December 4, Rohani said the bill violates a landmark nuclear deal between Tehran and world powers. In a statement on Sunday, 264 Iranian parliamentarians slammed the US Congress for having voted for a legislation to extend sanctions against "the great nation" of Iran.
Vegans Are Pissed That Britain's New Money Contains Meat
This is unacceptable to millions of vegans , vegetarians, Hindus, Sikhs, Jains and others in the UK. An online petition has sprung up in the United Kingdom demanding the Bank of England cease using animal products in the country's money.
Rouhani urges Obama to block Iran sanctions law extension
Congress, saying Tehran would otherwise "firmly respond". The accord signed previous year by Iran and six world powers including the US curbed the Persian Gulf country's nuclear program in exchange for the lifting of global sanctions imposed over the work.
New York Thanksgiving parade goes off safely under tight security
The beloved annual tradition was started by Macy's employees as a Christmas parade in 1924, and took a few years off during World War II. The NYPD marching band commanded extra attention, with revelers shouting, "Thank you!" as it passed.
Sarah Palin Says Trump's Carrier Deal Could Be 'Crony Capitalism'
Putin said in an interview with the NTV channel to be broadcast later on Sunday that Trump's business accomplishments show him to be a "smart man". President-elect Donald Trump on Sunday threatened heavy taxes as retribution for United States companies that move their business operations overseas and still try to sell their product to Americans.
Philip Hammond sticks to script in Autumn Statement
Public sector net debt should also be falling as a percentage of economic output by the end of the current parliament while welfare spending must also remain inside a cap set by the government, Hammond said as he set the government's new fiscal rules.
Trump's Latest Tweet Threat: Taxes For Companies That Leave US
But Trump's tirade on Sunday went much further than the Carrier deal, and the president-elect will find it hard to implement a 35% tariff without alienating many members of his own, generally pro-business, Republican party. "Foundational to our exceptional nation's sacred private property rights, a business must have freedom to locate where it wishes", wrote Palin, the 2008 Republican vice presidential nominee.
Aghan President Ashraf Ghani attacks Pakistan for giving 'sactuary' to terrorists
The sides also addressed the issue of terrorism and radicalization, as during the last year's Heart of Asia conference, the sides agrees to develop a strategy to counter terrorism. Addressing a press conference after coming back to Islamabad from Amritsar , Sartaj Aziz said that Afghan President Ashraf Ghani's statement against Pakistan deserved condemnation.
Crude prices rally above US$51 on OPEC deal
This, according to analysts, is due to an urgent need to increase the prices of crude oil in the face of an ongoing surplus of inventory which could not be balanced with a surprisingly steady demand from consumers. In another reflection of newfound discipline within the cartel, Al-Sada said Indonesia's membership had been suspended after it refused to accept its share of proposed output cuts, reducing the number of OPEC countries to 13.
Malaysian PM Najib Razak joins pro-Rohingya rally despite warning from Burma
Malaysian Prime Minister Najib Razak, center, speaks to the crowd during a protest against the persecution of Rohingya Muslims in Myanmar at a stadium in Kuala Lumpur , Malaysia on December 4. They are denied citizenship and suffer from institutionalized discrimination in Buddhist-majority Myanmar despite many of them having lived in the country for generations.
Oil prices surge, trading volume records smashed as OPEC and Russian Federation agree
The Organization of the Petroleum Exporting Countries will meet in Vienna on Wednesday aiming to implement a deal outlined in September to cut output by around 1 million barrels per day (bpd), from around 33.82 million bpd in October. The output cut follows several years of depressed oil prices due to a supply glut on the market, which has seen prices more than halve since 2014. Another wild card is the cooperation of non-OPEC producers, who are expected to decrease production by 600,000 ...
Tough ex-general chosen as defence secretary
Central Command in the Middle East in 2010. But some temper that with a wariness about the wisdom of putting so many military leaders at the helm of the country's national security when the nation was founded on the idea of civilian control.
Identity crisis? Samsung's thinking of splitting in two
Elliott Management, an activist of hedge fund in the United States had called for a split in the company in October. HI Investment offered further details on Samsung's possible split, saying: "Even if Samsung Electronics does not comment on specifics such as the timing of a split.
OPEC: bullish for oil prices, even more so for oil shares
On Thursday, Brent crude futures were trading at $54.22 a barrel at 1900 GMT - the highest level in almost 16 months, while US benchmark, WTI crude, was trading at $41.59/Bbl. "The reflation trade continues to work in earnest, this time Trump has taken a back seat and OPEC and Russian Federation have taken the initiative and lit the fuse under the oil price", wrote Chris Weston, chief market strategist at IG in Melbourne.


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Talented Athlete Support Program (TASP)
TASP Staff at Newington
Director of Talented Athlete Support Program - Mr Greg Royle
Greg Royle is a former NSW State Tennis Coach, Head Coach NSWIS, Tennis Australia National Selector and PDHPE teacher. Greg has experience in schools as both a teacher and contracted Tennis Coach and Tennis Director.
Greg has coached numerous state and national champions and has travelled through Europe and Asia with National touring teams. In recent years he has focused on educating Coaches and identifying talent and he is currently a Learning Facilitator and Talent Development Coach with Tennis Australia. He has been Advisor and Technical Director at Harvest Tennis Academy and International School, Punjab, India, as well as a board member of Tennis NSW.
His goal at Newington to develop the player and the person, through exposure to quality tennis programs and competition.
TASP Mentors
All of our Coaching Director's are TASP Mentors and are allocated boys within their areas of specialisation.


text: Emprego Junior Back-end Developer (M/F) Empresa:Landing.Jobs Data Publicação:15/03/2017 Descrição da Função:Love REST APIs, Networks and Database modeling?Do you want to work with leading technologies in information, communication, social and entertainment areas? How about international projects?We're looking for a Junior Back-end Developer with high learning capacity to work on 1-2 projects of moderate to high complexity on a day-to-day basis. These projects usually have a high impact and high visibility nature and require strong requirements comprehension skills. The Developer will work with close supervision of team leaders and be responsible for the task completion and accurate status report.You're going to work in Oeiras, close to the beach. Requisitos: Bologna Bachelor in Computer Science or Electro-technical EngineeringSolid foundation in object oriented programming, data structures, algorithms and multimedia1 year experience with C# or node.js or Spring Framework1 year experience with git1 year experience with ORDBMSs and NoSQLFluency in EnglishKnowledge in computer networksFamiliarized with JSON/RESTFamiliarized with test driven developmentAttention to detailNice to have:Technical document writing skillsAWS and/or Azure infrastructure management skills Oferece-se:Work in an office near the beachFree fruitCool happy-hoursFree BikesBirthday giftsA great teamLocal:Lisboa (Distrito de Lisboa) Partilhar esta informação Enviar a oferta: Junior Back-end Developer (M/F) Comentários Candidate-se a esta oferta Será redireccionado para o site da empresa


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NEW YORK, May 5 (Reuters) - Diosdado Cabello, the former head of Venezuela's national assembly, filed a lawsuit on Thursday accusing the Wall Street Journal of libeling him in an article reporting he was the target of a U.S. drug trafficking probe.
Cabello filed the lawsuit in Manhattan federal court against News Corp, the newspaper's owner, saying the May 2015 article contained "false and defamatory allegations" that Cabello was involved in criminal activities related to drug trafficking and money laundering.
The story has caused "enormous damage to Mr. Cabello's reputation and good name, both personally and in his capacity as a key member of Venezuela's National Assembly," the lawsuit said.
The lawsuit seeks unspecified damages from News Corp and its Dow Jones subsidiary, which was also named as a defendant.
A spokeswoman for News Corp had no immediate comment.
The lawsuit comes as U.S. authorities including federal prosecutors and the Drug Enforcement Administration are probing to what extent Venezuelan officials have facilitated drug trafficking.
In the article of May 18, 2015, headlined "Venezuelan Officials Suspected of Turning Country into Global Cocaine Hub," the Wall Street Journal reported that Cabello was a leading target in the investigations.
Cabello, the No. 2 figure in Venezuela's ruling Socialist Party, is a member of the country's National Assembly, which he presided over from January 2012 to January 2016.
Cabello has repeatedly denied involvement in Venezuela's drug trade, telling Venezuela's parliament last year that "it would never occur to us to get involved in something that would hurt young people."
In his lawsuit, Cabello says the newspaper inaccurately represented quotes from unnamed sources, and falsely stated he was the probe's "biggest target."
The case is Cabello-Rondon v. Dow Jones & Company, Inc, et al, U.S. District Court, Southern District of New York, No. 16-03346. (Editing by Noeleen Walder and Matthew Lewis)


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Detachment is often understood as letting loose of what is attractive. But it sometimes also requires letting go of what is repulsive. You can indeed become attached to dark forces such as resentment and hatred. As long as you seek retaliation, you cling to your own past. Sometimes it seems as though you might lose yourself along with your revenge and hate – so you stand there with balled-up fists, closed to the other who wants to heal.
~ Henri Nouwen, With Open Hands
The Dance of Life p. 44


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Oh what a friendly face! We made these cute cupcakes on Christmas Eve day, right before leaving for Founding Farmers for our holiday eve dinner. We enjoyed our yummy dinner, took a ride around our city to look at Christmas lights and then headed home to decorate our cupcakes.
I used our standard Baking Illustrated vanilla cupcake recipe (you add sour cream to the batter!) and a pre-made tub of vanilla frosting. The snowman's face came from orange writing gel, mini chocolate chips, and Wilton crystal sugar sprinkles.


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Please confirm that you want to add Rid Yourself of Fear of the Camera to your Wishlist.
Do you hate cameras? Do get all twitchy as soon as a camera or smartphone is pointed in your direction? Well, I feel your pain. I was like you. Recently. In fact, just a few weeks ago.
I used to take some footage of myself, then play it back and be disappointed. Take two and I stumbled over some words. By take 36 I thought the return on investment of my time was not worth it. I wanted to give up. Then I realised something. It's true for me and it's true for you.
You have something important to say to the world. Don't let your fear of turning up on video get in the way of that message.
So, how do you overcome your fear of being filmed?
Actually, it's remarkably easy. Many actors suggest practicing in front of a mirror or a friend, but that's not what worked for me. (It only stressed me even more).
Instead, I focused on my attitude:
Even a few simple changes helped. Like changing the time of the day when I was recording myself or changing my posture.
This course is not written by a professional actor. It's written by someone like you. I had no video or camera experience before, and I've had no professional training. But these tips have worked for me.
The tips are:
So whether you're too nervous to look at a lens or just want to get a little bit more comfortable when you're being recorded, follow this course and Rid Yourself, once and for all, of your fear of the camera.
Video is a very powerful way of getting your message across. Images can be much easier to digest than words. But what do you do if you are overcome by nerves in front of the camera? You can do nothing about it, and then your voice will never be heard.
Or, you can take some simple steps to overcome your shyness or nervousness. Just a few weeks before I started making this course I, too, was nervous in front of the camera. I would record something, find mistakes, record it again and again. It was so frustrating.
Then I came across some simple strategies to ease my nerves. Very basic things like changing the place you are doing the recording, or trying to change my posture. It worked like a charm and that's what I want to share with you.
From One Nervous Amateur to Another
I am not a professional actor. I am someone who was nervous on video, and very recently too. Now I actually enjoy watching myself. The steps are very simple - no psychological tricks or expensive equipment involved. So why not have a look through the course and see if it will help you get your message out to the world.
I hope you enjoy it.
Anthony English,
Probably the most important thing when dealing with nerves is this: focus on your message, not yourself. In this lecture I show you how to take the focus off yourself and turn towards the message you want to share with the world.
Many people try to overcome their camera shyness by practicing and practicing. In front of a mirror. With a friend nearby, or alone in front of the camera. This approach can help, but it could also be counter-productive. If you're practicing until you get it word perfect, you'll always find something to correct, something that is just not right in your appearance or presentation.
It's far more important to manage your expectations, so that you don't have unrealistic goals. Your video doesn't need to be perfect. It just needs to be good enough. Sure, you can always improve it but don't let perfectionism get in the way of your message.
I expect this will be your favourite lecture, because it's about taking the focus off yourself. There are a few ways of doing this: using background images or b-rolls, presenting an "interview" (even if there's no one across the table looking at you), or talking about something that you love. Whichever way you approach it, the video ends up not being about you, but about your message. And that's going to relieve a lot of the pain of being in front of the camera, feeling the focus is on you.
Find practical ways of getting the focus off yourself and onto your message.
If you get a little anxious in front of the camera, the one thing you're always thinking is "when can they hit the stop button?" The sooner, the better, right? Well, you can make it easy for yourself by recording very short grabs. Even a few seconds at a time is a good way to go. Then you put it all together in the editing process.
Using short takes releases a lot of the pressure of having to get everything word perfect. If there's a background noise or some other interruption, you don't have to record the whole long video again. It also makes the experience more pleasant for the viewer.
One of the most obvious ways of addressing nerves in front of the camera is to change your environment. The time of day you record can make a difference. So can where you record. A simple change of environment can make all the difference to how comfortable you are.
Find some fun and inventive ways to change your environment.
Who would have thought that a simple change of posture can affect your presentation? Maybe you can stand up to be more dynamic. Or perhaps your topic is more like a fireside chat, and sitting down will help.
Posture can improve your breathing, ease your nerves and make you more relaxed. This will help you focus more on your topic and worry less about how you appear on camera.
Doesn't the imagination run wild some times? Especially as regards fear and anxiety, we can imagine all kinds of reasons why our message is unimportant, or why our videos are going to be a flop. All of these things can play on our feelings and lead us to discouragement. The result? No video.
It's so important to be able to control the imagination. Well, "control" may not be a good word. "Manage" might be better, and one way of doing that is to focus on something else, something good.
Even if you do get nervous in front of the camera, you can use that for your good. Being at least a little bit nervous (but not too much) can help you focus, stop you rambling on, and even get you a little more excited about your topic.
The audience probably won't even notice your nervousness but if they do, they may think something like: "Wow! This person is speaking to me, even though it's obvious they are nervous. Must really have something important to share with me."
Look through these strategies to see which will help you calm your nerves better.
When you work on major IT projects for big enterprises, you get to pick up a lot of non-technical insights. Just by joining in on conference calls, you'll hear subject matter experts speaking about their piece of the project.
You get to know people, what makes them tick, and how to talk to them.
Then you can use that knowledge, the language they use, to meet new people in other companies.
And, because you're already trusted for your technical expertise, you're already in the door. Perfect chance to pivot your business to a new area where you can help the company with their expensive business problems.
That's basically my story: IT infrastructure guru who has worked for big banks and manufacturers. Now I'm moving my service into business advice, and teaching other technical people how to do the same. It's easier than you think.


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Doctor insights on:
What Does Positive Pregnancy Test Look Like
What does a positive pregnancy test look like from the doctors?
Blood test: Pregnancy test can be done on urine or blood. Blood test is more sensitive and you need to see a doctor for that. Urine test is the same whether done by the doctor or done at home. Blood test gives a number which is the level of beta hcg. ...Read more
Pregnancy (Definition)
When your due date arrives, you will be more than ready to have your baby! Most women deliver the baby somewhere between 37 and 42 weeks. According to the American College of Obstetricians and Gynecologists, only 5% of babies arrive on the exact due date. Approximately 7% of babies are not delivered by 42 weeks, and when that happens, it is referred to ...Read more
What does a positive clear plan pregnancy test look like?
Clear plan pregnancy: " easy to use: hold the absorbent tip in urine stream for 3-7 seconds. Easy to read: results in 3 minutes - two lines mean you are pregnant, one line means you are not pregnant. " i thought this produce had been discontinued by the manufacturer. ...Read more
3 weeks pregnant positive pregnancy test. What does my baby look like?
Conceptional age =: Time since fertilization of an egg, 2 weeks < than gestational age, time since the 1st day of your lmp. The structure that forms the brain & spinal cord develop at 3 wks. Post-conception. Avoid alcohol, tobacco, drugs & prescription medicines not ok'ed by your ob. If you aren't taking Folic Acid 0.4 mg/day , start now. See http://www.Babycenter.Com/fetal-development-week-by-week for more info. ...Read more
Why do some very pregnant women never get a positive pregnancy test until like 20 weeks?
Likely improper : Testing. A blood test for pregnancy is considered positive when the HCG level reaches 5 units. Any normal pregnancy reaches that level soon after implantation. Home pregnancy tests on urine take 7-10 longer to turn positive, but are positive in a normal pregnancy. About the only reason for the test to be negative is if the person does the test incorrectly. ...Read more
I had a positive pregnancy test this morning i'm someone who doesn't like to eat a lot of meet I still eat meat but I per not too. Is there anything I can eat that will give the same nutrition?
Balanced diet: Meat is not essential for a good diet. A diet rich in fresh vegetables, fruits, whole grains and dairy will provide adequate nutrition. To increase protein in your diet you should add tofu, beans, nuts and egg whites. I trust that you are taking pre-natal vitamins, if you were not taking these, do so asap. Keep your appointments with your OB for pre-natal checks. ...Read moreSee 1 more doctor answer
3 positive pregnancy test?
Congratulations : Congratulations on your pregnancy.Get a more detailed answer ›
What can cause positive pregnancy test?
Sperm: Sperm is likely the cause.Get a more detailed answer ›
How can I get a positive pregnancy test?
See below: Conception, as defined by the generation of a fertilized ovum, occurs within day or so of the sex. However, it takes about two weeks for the embryo to make enough HCG to produce a positive pregnancy test. Blood test may be done a day after a missed period. Home pregnancy tests should be done 4-5 days after the missed period. Pregnancy and some tumors produce positive results. ...Read more
3 pregnancy test positive can I be pregnant?
Not necessarily: You are in the reproductive age. If pregnancy is expected in your setting (regular sexual activity), you are most likely pregnant after testing positive for three times. But if pregnancy technically cannot happen in your situation (like no sexual activity), you need to consider the possibility of certain neoplasms, especially germ cell tumor (of the ovary or mediastinum) or trophoblastic tumor. ...Read moreSee 1 more doctor answer
Pregnancy Test (Definition)
A pregnancy test measures a hormone called human chorionic gonadotropin (HCG). HCG is a hormone produced during pregnancy. It appears in the blood and urine of pregnant women as early as ...Read more
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- What does a clear blue positive pregnancy test look like?
- What does a positive pregnacy test look like?
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- Talk to a obstetrician and gynecologist online


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Skokie, IL
Love to Teach - Love to Help Others Learn65/hour
...Literature. I am laid back, easy to get along with, work at your pace, help you set goals you believe are attainable, and celebrate your successes. I take responsibility for my part in the tutoring relationship,... read moreSee Tutors Like This


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Coming Soon…
Martial Arts Unlocked is the perfect book to help you find your ideal martial arts school. Click here to get your copy today.
Make your child's special day extra special this year with one of our Martial Arts Birthday Parties. It's guaranteed to be a hit!
Enroll in our FREE on-line newsletter subscription. A great way to stay in touch about current events, life skills & Martial Arts.
Need more information? We are here for you. Click here and let us know how we can help. We look forward to hearing from you.


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Philadelphia, PA
Medical student for math and science tutoring60/hour
...with confidence. I like to view myself as a coach or a cheerleader. My job is not just to teach; it is to motivate. I have completed a lot of years of schooling (and still have a few to go), so I understand... read moreSee Tutors Like This


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Office hours: Mon-Fri., 8:00am-4:00pm EDT
Office hours: Mon-Fri., 8:00am-4:00pm EDT
Our citrus shipping season usually runs from mid-November through the end of April. To ensure that your holiday orders arrive on time, please follow this schedule:
|Normal Delivery
(Internet and phone orders)
(Phone orders only)
|For delivery by Thanksgiving (Nov. 24)
|Order by Sun., Nov. 13, 2016
|Order by Thurs., Nov. 17, 2016
|For delivery by Hanukkah (Dec. 24-Jan. 1)
|Order by Thurs., Dec. 15*
|Order by Sun., Dec. 18
|For delivery by Christmas (Dec. 25)
|Order by Thurs., Dec. 15*
|Order by Sun., Dec. 18
*Christmas and Hannukah orders shipping to Canada, Far West States, Texas and Louisiana must reach us by December 6, 2016. All other Christmas orders must reach us by December 15. Christmas gifts are shipped early to safeguard against possible holiday transit delays.
Changes to Delivery Instructions
Need to modify delivery instructions for an order? Although we cannot guarantee that shipping info can be changed, we will do our best to accommodate your request as long as we know at least 7 days before the scheduled ship date. Please note that we cannot make changes to any orders from December 1-15.


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A Message from the Principal
Honor Roll
Interested in Becoming a Mentor for SV's MAN UP Program?
Spring Valley's MAN UP mentoring program will have a mentor training Tuesday, February 3rd, at 4:00 in the Multi-Purpose Room. If you are interested in becoming a mentor for the MAN UP program we would love to have you. If you know someone who may be interested in becoming a mentor please encourage them to join us Tuesday. Anyone interested in becoming a mentor must attend the training and agree to a background check prior to being assigned a mentee. For more information please contact Mr. KaRon L. Webb by phone at 699-3500 ext. 69364 or email at
Friday, January 30, 2015
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text: Oh, pretty high. Higher than lots of things you might think were pretty high, but lower than the highest thing there is. Retrieved from "http://answers.wikia.com/wiki/How_high_is_the_highest_point_in_Europe?oldid=3810016" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Answered questions Add category Cancel Save


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WORD COUNT with Anthony HADEN-GUEST, Peter TUNNEY and Shira TOREN
Opening Reception Fri. Dec 9, 5-8pm Cross Contemporary Art 81 Partition St. Saugerties, New York 12477 on view thru Jan 1, 2017GALLERY HOURS: Thurs- Mon 12-5pm
WORD COUNT with Anthony HADEN-GUEST, Shira TOREN and Peter TUNNEY opens with a reception for the artists on Fri. Dec.9, 5-8pm at Cross Contemporary Art, Saugerties, NY. "Word Count with Anthony Haden-Guest, Shira Toren and Peter Tunney" is a group show of artists who work with the meaning of symbols, letters, and phrases. The playful brushwork of Anthony-Haden-Guest's hand-colored prints present profound quotations with a slightly ominous whimsy. Peter Tunney's painted and screened over collages of old book pages create contemporary clarity over layers of cultural memory. And Shira Toren's graphite numbers evoke the count down at the start of old black and white films as well as the anticipation of what a count down can bring: everything from a rocket launch to an anticipated microwave dinner. All three artists' consider the impact of symbols, from the meaning of the phrase to the actual shape of letters and numbers as enigmatic compositions of symbols, abstract shapes and evocative phrases. For the Holidays, Cross Contemporary Art is offering an affordable special edition of hand-colored giclee prints by Anthony Haden-Guest.About the Artists Anthony Haden-Guest: Anthony Haden-Guest is a writer, journalist and cartoonist. As a magazine writer he has covered war, crime and the various social orders and disorders of celebrity culture for the Financial Times, Vanity Fair, The New York Observer, Paris Review, Esquire, GQ (UK) and The New Yorker. In the tradition of the great British 18th caricaturists George Cruikshank, James Gillray and Thomas Rowlandson, Anthony Haden-Guest's ink drawings serve as a wry commentary on celebrity, hubris and tweaked maxims. Peter Tunney: Peter Tunney uses billboards and media as one of many vehicles for his optimistic slogans and phrases. In his glorification of the commonplace, Tunney is often compared to the Pop artists of the 60s and 70s. However, Peter Tunney is also a messenger whose use of language both proclaims and commands hope and encouragement and his images incorporating vintage ephemera evoke a sense of collective memory. More about Mr.Tunney: http://www.
"Word Count with Anthony Haden-Guest, Shira Toren and Peter Tunney" opens Fri. December 9th and continues through Sun. January 1, 2017


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March 01, 2014
Valley Custom Door will participate in two national Cabinets & Closets events April 9-11, 2014 in Somerset, New Jersey.
The education portion of the Conference will be held Wednesday, April 9 at the Hotel Somerset – Bridgewater and will open with keynote speaker Paul Downs, CEO of Paul Downs Cabinetmakers and New York Times blogger. The conference is organized by the Association of Closet and Storage Professionals (ACSP), Cabinet Makers Association (CMA), Closets magazine and Wood Products.
Thursday, April 10 and Friday, April 11, the Cabinets & Closets Expo will be held at the Garden State Exhibitor Center, where Valley Custom Door will showcase their latest cabinetry product selection in booth #209. Visit the booth and meet Vickie Larson and Steve Mashl to learn more about their unique service offerings.
For a more information including a full list of exhibitors and virtual floor plan, visit the Cabinets & Closets Conference & Expo website.


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Refereed Conference Presentations
Shih, Shu-hao (2017). On the interaction between phrase-final lengthening and prosodic structure.
The 53rd Meeting of the Chicago Linguistic Society (CLS 53), University of Chicago, Illinois.
Shih, Shu-hao (2016). Binarity and focus in prosodic phraing: New evidence from Taiwan Mandarin.
The 2016 Annual Meeting on Phonology (AMP 2016), University of Southern California, Los Angelas.
Shih, Shu-hao (2016). Major phrases are binary: Evidence from Taiwan Mandarin flat structure.
The West Coast Conference on Formal Linguistics 34 (WCCFL 34), University of Utah, Utah.
Shih, Shu-hao (2016). Does Gujarati stress avoid the lowest sonority vowel [ə]?.
CUNY Phonology Forum on the Sonority, CUNY Graduate Center, New York.
Shih, Shu-hao (2015). Sonority-driven stress does not exist.
The 2015 Annual Meeting on Phonology (AMP 2015), Vancouver, Canada.
Shih, Shu-hao (2015). Against sonority-driven stress in Gujarati.
The 23rd Manchester Phonology Meeting (MFM 23), Manchester, UK.
Other Presentations
Shih, Shu-hao (2016). Prosodic phrasing in Mandarin flat structure.
Phonology in the Northeast 2016 (PhoNE 2016), New York University.
Shih, Shu-hao (2015). On the existence of sonority-driven stress.
Phonology in the Northeast 2015 (PhoNE 2015), Yale University.


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|By Business Wire
Article Rating:
|February 3, 2014 06:09 PM EST
Blackbaud,Inc. (NASDAQ:BLKB), a leading global provider of software and services for nonprofits, today announced that it will report its 2013 fourth quarter and year-end financial results after the U.S. financial markets close for trading on Wednesday, February 12, 2014.
In conjunction with this announcement, Blackbaud will host a conference call on Thursday, February 13, 2014, at 8:00 a.m. (Eastern Time) to discuss the Company's financial results. To access this call, dial 1-877-705-6003 (domestic) or 1-201-493-6725 (international). A replay of this conference call will be available through February 20, 2014, at 1-877-870-5176 (domestic) or 1-858-384-5517 (international). The replay pass code is 13575607. A live webcast of this conference call will be available on the "Investor Relations" page of the Company's website at www.blackbaud.com/investorrelations, and a replay will be archived on the website as well.
About Blackbaud
Serving the nonprofit and education sectors for 30 years, Blackbaud (NASDAQ: BLKB) combines technology and expertise to help organizations achieve their missions. Blackbaud works with more than 29,000 customers in over 69 countries that support higher education, healthcare, human services, arts and culture, faith, the environment, independent K-12 education, animal welfare and other charitable causes. The company offers a full spectrum of cloud-based and on-premise software solutions and related services for organizations of all sizes including: fundraising, eMarketing, advocacy, constituent relationship management (CRM), financial management, payment services, analytics and vertical-specific solutions. Using Blackbaud technology, these organizations raise more than $100 billion each year. Recognized as a top company by Forbes, InformationWeek, and Software Magazine and honored by Best Places to Work, Blackbaud is headquartered in Charleston, South Carolina and has operations in the United States, Australia, Canada, the Netherlands and the United Kingdom. For more information, visit www.blackbaud.com.
Cloud resources, although available in abundance, are inherently volatile. For transactional computing, like ERP and most enterprise software, this is a challenge as transactional integrity and data fidelity is paramount – making it a challenge to create cloud native applications while relying on RDBMS. In his session at 21st Cloud Expo, Claus Jepsen, Chief Architect and Head of Innovation Labs at Unit4, will explore that in order to create distributed and scalable solutions ensuring high availa...
Aug. 23, 2017 07:45 AM EDT Reads: 1,278
Cloud adoption is often driven by a desire to increase efficiency, boost agility and save money. All too often, however, the reality involves unpredictable cost spikes and lack of oversight due to resource limitations. In his session at 20th Cloud Expo, Joe Kinsella, CTO and Founder of CloudHealth Technologies, tackled the question: "How do you build a fully optimized cloud?" He will examine: Why TCO is critical to achieving cloud success – and why attendees should be thinking holistically ab...
Aug. 23, 2017 07:30 AM EDT Reads: 1,025
Internet-of-Things discussions can end up either going down the consumer gadget rabbit hole or focused on the sort of data logging that industrial manufacturers have been doing forever. However, in fact, companies today are already using IoT data both to optimize their operational technology and to improve the experience of customer interactions in novel ways. In his session at @ThingsExpo, Gordon Haff, Red Hat Technology Evangelist, shared examples from a wide range of industries – including en...
Aug. 23, 2017 07:00 AM EDT Reads: 1,415
In IT, we sometimes coin terms for things before we know exactly what they are and how they'll be used. The resulting terms may capture a common set of aspirations and goals – as "cloud" did broadly for on-demand, self-service, and flexible computing. But such a term can also lump together diverse and even competing practices, technologies, and priorities to the point where important distinctions are glossed over and lost.
Aug. 23, 2017 07:00 AM EDT Reads: 1,551
Detecting internal user threats in the Big Data eco-system is challenging and cumbersome. Many organizations monitor internal usage of the Big Data eco-system using a set of alerts. This is not a scalable process given the increase in the number of alerts with the accelerating growth in data volume and user base. Organizations are increasingly leveraging machine learning to monitor only those data elements that are sensitive and critical, autonomously establish monitoring policies, and to detect...
Aug. 23, 2017 06:15 AM EDT Reads: 1,729
"We're a cybersecurity firm that specializes in engineering security solutions both at the software and hardware level. Security cannot be an after-the-fact afterthought, which is what it's become," stated Richard Blech, Chief Executive Officer at Secure Channels, in this SYS-CON.tv interview at @ThingsExpo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Aug. 23, 2017 05:15 AM EDT Reads: 6,780
Most companies are adopting or evaluating container technology - Docker in particular - to speed up application deployment, drive down cost, ease management and make application delivery more flexible overall. As with most new architectures, this dream takes a lot of work to become a reality. Even when you do get your application componentized enough and packaged properly, there are still challenges for DevOps teams to making the shift to continuous delivery and achieving that reduction in cost ...
Aug. 23, 2017 04:45 AM EDT Reads: 1,116
Enterprise architects are increasingly adopting multi-cloud strategies as they seek to utilize existing data center assets, leverage the advantages of cloud computing and avoid cloud vendor lock-in. This requires a globally aware traffic management strategy that can monitor infrastructure health across data centers and end-user experience globally, while responding to control changes and system specification at the speed of today's DevOps teams. In his session at 20th Cloud Expo, Josh Gray, Chie...
Aug. 23, 2017 04:00 AM EDT Reads: 1,479
To get the most out of their data, successful companies are not focusing on queries and data lakes, they are actively integrating analytics into their operations with a data-first application development approach. Real-time adjustments to improve revenues, reduce costs, or mitigate risk rely on applications that minimize latency on a variety of data sources. Jack Norris reviews best practices to show how companies develop, deploy, and dynamically update these applications and how this data-first...
Aug. 23, 2017 03:15 AM EDT Reads: 1,152
Intelligent Automation is now one of the key business imperatives for CIOs and CISOs impacting all areas of business today. In his session at 21st Cloud Expo, Brian Boeggeman, VP Alliances & Partnerships at Ayehu, will talk about how business value is created and delivered through intelligent automation to today's enterprises. The open ecosystem platform approach toward Intelligent Automation that Ayehu delivers to the market is core to enabling the creation of the self-driving enterprise.
Aug. 23, 2017 03:00 AM EDT Reads: 1,383
"At the keynote this morning we spoke about the value proposition of Nutanix, of having a DevOps culture and a mindset, and the business outcomes of achieving agility and scale, which everybody here is trying to accomplish," noted Mark Lavi, DevOps Solution Architect at Nutanix, in this SYS-CON.tv interview at @DevOpsSummit at 20th Cloud Expo, held June 6-8, 2017, at the Javits Center in New York City, NY.
Aug. 23, 2017 02:45 AM EDT Reads: 2,449
"We're here to tell the world about our cloud-scale infrastructure that we have at Juniper combined with the world-class security that we put into the cloud," explained Lisa Guess, VP of Systems Engineering at Juniper Networks, in this SYS-CON.tv interview at 20th Cloud Expo, held June 6-8, 2017, at the Javits Center in New York City, NY.
Aug. 23, 2017 02:00 AM EDT Reads: 2,357
Historically, some banking activities such as trading have been relying heavily on analytics and cutting edge algorithmic tools. The coming of age of powerful data analytics solutions combined with the development of intelligent algorithms have created new opportunities for financial institutions. In his session at 20th Cloud Expo, Sebastien Meunier, Head of Digital for North America at Chappuis Halder & Co., discussed how these tools can be leveraged to develop a lasting competitive advantage ...
Aug. 23, 2017 12:30 AM EDT Reads: 1,127
In his session at 20th Cloud Expo, Mike Johnston, an infrastructure engineer at Supergiant.io, discussed how to use Kubernetes to set up a SaaS infrastructure for your business. Mike Johnston is an infrastructure engineer at Supergiant.io with over 12 years of experience designing, deploying, and maintaining server and workstation infrastructure at all scales. He has experience with brick and mortar data centers as well as cloud providers like Digital Ocean, Amazon Web Services, and Rackspace. H...
Aug. 22, 2017 11:45 PM EDT Reads: 2,520
The question before companies today is not whether to become intelligent, it's a question of how and how fast. The key is to adopt and deploy an intelligent application strategy while simultaneously preparing to scale that intelligence. In her session at 21st Cloud Expo, Sangeeta Chakraborty, Chief Customer Officer at Ayasdi, will provide a tactical framework to become a truly intelligent enterprise, including how to identify the right applications for AI, how to build a Center of Excellence to ...
Aug. 22, 2017 11:30 PM EDT Reads: 1,114


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3D Printing: Amazing Features and Functionality
In this futuristic and industrial age, there is a single product that is known to change the world significantly, since it can basically produce digital outlined models into a solid three dimensional physical version of it, and the product is called 3D printers. A 3D printer which is also known as additive manufacturing is capable of producing digital 3D models and turn them into physical objects with the use of its advance building technology. The 3D printing technology was first invented in the late 1980's and it grew into this wide amazingly potent technology that we have today, which can produce certain kinds of products, in certain amounts of time.
Even though most of the 3D printer that is currently available in the market may indeed take long amounts of time to finish a single prototype or object to finish, the future of 3D printing is still really bright with amazing possibilities and potential to grow much stronger. In this current day and age, a 3D printer is now able to print out different types of products with the use of various types of materials, which includes thermoplastics, pure metals, ceramics, metal alloys and certain types of food. The 3D printing process should also be able to assist most businesses all over the world. If you want to read more about 3D printing, you can go to http://www.ehow.com/how-does_4925878_how-d-printers-work.html.
Although 3D printing may sound seriously complicated at times and you may not know how to start with GoEngineer Stratasys 3D printing, it is much rather easy to understand actually, you just have to remember that you will need a 3D modeling application or software to create a 3D model that is designed with the use of the computer. It is also possible for 3D printers to use 3D scanners that would be able to scan any types of objects and turn them into a 3D digital model as well, just try to make sure that the scanned object is 3D printable or else it will not work.
The method of making a 3D digital model into a 3D object is what they mostly call as slicing, which is actually the process to divide the 3D digital model into multiple numbers of horizontal layers through the use of a software. The slicing method will only allow horizontal layers due to the fact that most, if not all 3D printers in the market currently are only able to print the uploaded 3D model layer by layer. The 3D printer will have to need to read every single slice of the 3D digital model in order for it to produce and complete the three dimensional physical model. The GoEngineer 3D printers have different sizes and capabilities, some of them may only be able to produce smaller three dimensional prototypes while other 3D printers may be able to print out huge models as well.


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Kevinep3 is back after his weekend at PAX!!!
Wherein we discuss PAX East, Gear of War 4, Lawbreakers, Paragon beta, WWE Super Card, Clash of Clans, Dark Souls 3, MGSV, Wolfenstein: The Old Blood(spoilers 45:15-51:10), Ratchet and Clank, The Transporter Refueled, Ip Man 3, Game of Thrones S6E19(spoilers 59:21-1:05:40), and wild speculations for The Flash and Arrow.
Featuring dakazu, darfox8, Kevinep3, Mr_eX
Intro Music: Slow Burn by Kevin MacLeod, Outro Music: Niles Blues by Kevin MacLeod
Questions? Comment? Send them to firstname.lastname@example.com
Tweet us @alltalkpodcast
Donate to the mumble server.
Questions? Comment? Send them to firstname.lastname@example.com
Tweet us@alltalkpodcast
Donate to the mumble server.