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Maternal use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) is associated with an increased risk for persistent pulmonary hypertension of the newborn (PPHN), but little is known about 5-HT signaling in the developing lung. We hypothesize that 5-HT plays a key role in maintaining high pulmonary vascular resistance (PVR) in the fetus and that fetal exposure to SSRIs increases 5-HT activity and causes pulmonary hypertension. We studied the hemodynamic effects of 5-HT, 5-HT receptor antagonists, and SSRIs in chronically prepared fetal sheep. Brief infusions of 5-HT (3–20 μg) increased PVR in a dose-related fashion. Ketanserin, a 5-HT 2A receptor antagonist, caused pulmonary vasodilation and inhibited 5-HT-induced pulmonary vasoconstriction. In contrast, intrapulmonary infusions of GR127945 and SB206553, 5-HT 1B and 5-HT 2B receptor antagonists, respectively, had no effect on basal PVR or 5-HT-induced vasoconstriction. Pretreatment with fasudil, a Rho kinase inhibitor, blunted the effects of 5-HT infusion. Brief infusions of the SSRIs, sertraline and fluoxetine, caused potent and sustained elevations of PVR, which was sustained for over 60 min after the infusion. SSRI-induced pulmonary vasoconstriction was reversed by infusion of ketanserin and did not affect the acute vasodilator effects of acetylcholine. We conclude that 5-HT causes pulmonary vasoconstriction, contributes to maintenance of high PVR in the normal fetus through stimulation of 5-HT 2A receptors and Rho kinase activation, and mediates the hypertensive effects of SSRIs. We speculate that prolonged exposure to SSRIs can induce PPHN through direct effects on the fetal pulmonary circulation.
- persistent pulmonary hypertension of the newborn
- ketanserin
the fetal pulmonary circulation is characterized by high pulmonary vascular resistance (PVR) and low pulmonary blood flow. Mechanisms that maintain high PVR are poorly understood but include a low pulmonary artery Po2 and an imbalance between vasoconstrictors and vasodilators (1, 9). After birth PVR falls, allowing for an increase in pulmonary blood flow. A failure of this decrease in PVR results in the clinical syndrome known as persistent pulmonary hypertension of the newborn (PPHN). Factors that contribute to the pathogenesis of PPHN are multifactorial, including altered vascular reactivity, vascular remodeling, and abnormal growth (18). Understanding the basic mechanisms that regulate pulmonary vascular resistance is crucial to the development of novel therapies for severe PPHN.
Although the role of serotonin (5-HT) in the pathogenesis of adult pulmonary hypertension (PH) has been extensively studied, little is known about the role of 5-HT in the normal perinatal pulmonary circulation or in models of PPHN. 5-HT is a potent vasoconstrictor and stimulates smooth muscle cell growth and proliferation in the adult pulmonary circulation (11, 13, 38, 51). Activation of the 5-HT 1B, 2A, and 2B receptors and the 5-HT transporter (SERT) mediate 5-HT signaling in the adult lung (34, 38, 39). Pharmacological or genetic strategies that augment 5-HT expression worsen, and inhibition of 5-HT signaling decreases the severity of pulmonary hypertension in adult animal models (10, 12, 23, 27, 29, 35). Recent studies suggest that selective 5-HT reuptake inhibitor (SSRI) therapy reduces PH in adult animal models and in the clinical setting (26, 31, 37, 53).
In contrast to the effects of SSRIs in adults with PH and in experimental PH, epidemiological studies suggest that SSRI treatment of maternal depression after the 20th wk of gestation increases the risk of PPHN in the infant by sixfold (7). This striking developmental difference in response to SSRIs on the pulmonary circulation reflects the lack of our present understanding on the roles of 5-HT in the developing lung. The association between the maternal use of SSRIs and PPHN remains controversial, and only one animal study to date has examined whether SSRIs cause PPHN (16, 55). Treatment of pregnant rats with SSRIs leads to mild PPHN in rat pups, as seen by increased right ventricular hypertrophy and hypoxemia at birth; however, the mechanisms underlying this response remain uncertain. Specifically, whether this effect is due to the direct action of SSRIs on the developing pulmonary circulation or through changes in maternal utero-placental circulation is unknown. The paradoxical findings of the potential differences of SSRIs in the adult and fetal circulation highlight the critical need to study 5-HT signaling and the direct effect of SSRIs in the fetal lung.
Therefore, we hypothesize that 5-HT plays a key role in maintaining high PVR in the normal fetus and that fetal exposure to SSRIs increases 5-HT activity, which increases pulmonary vascular tone, leading to sustained PH at birth. We studied the effect of acute intrapulmonary infusions of 5-HT, the 5-HT receptor antagonists, GR127935, ketanserin, SB206553, and the SSRIs, sertraline and fluoxetine, in the chronically prepared ovine fetus.
Pregnant, mixed-breed (Colombia-Rambouillet) ewes were used in this study. All procedures and protocols were reviewed and approved by the Animal Care and Use Committee of the University of Colorado Denver and followed the Guide for the Care and Use of Laboratory Animals established by the National Research Council.
Fetal Surgical Preparation
Surgery was performed at 124–129 days gestation (full term = 147 days) after ewes had fasted for 24 h and thirsted overnight. Animals were given intramuscular penicillin G (600,000 U) and intravenous gentamicin (80 mg) immediately before surgery. Ewes were sedated with intravenous ketamine (1,000 mg) and diazepam (10 mg) and intubated and ventilated with 1–3% isoflurane for the duration of surgery. Under sterile conditions, a midline abdominal incision was made, and the uterus was externalized. The left fetal forelimb was exposed through hysterotomy. Polyvinyl catheters (20-gauge) were placed in the left axillary artery and vein and advanced in the ascending aorta and superior vena cava, respectively. A left thoracostomy and pericardial incision provided access to the heart and great vessels. With the use of a 16-gauge intravenous placement unit (Angiocath, Travenol, Deerfield, IL), a 22-gauge catheter was placed through purse-string sutures in the left pulmonary artery (LPA) to allow for selective drug infusions. A 14-gauge intravenous placement unit (Angiocath) was used to place 20-gauge catheters in the main pulmonary artery (MPA) and left atrium (LA). After gentle, blunt dissection of the bifurcation of the MPA, a flow transducer (Transonic Systems, Ithaca, NY) was placed around the LPA to measure blood flow to the left lung (QLPA). A catheter was placed in the amniotic cavity to serve as a pressure referent. The uterus was sutured, and a dose of ampicillin (500 mg) was given in the amniotic cavity. The catheters and flow transducer cable were externalized to a flank pouch on the ewe after the abdominal wall was closed. Postoperatively, ewes were allowed to eat and drink ad libitum and were generally standing within 1 h. All animals were treated with scheduled buprenorphine (0.6 mg) for 48 h postoperatively and then as indicated (based on veterinary assessment of pain). All catheters were gently flushed daily with 1–2 ml heparinized normal (0.9%) saline to maintain catheter patency.
Western Blot Analysis
Western blot analysis for lung SERT, 5-HT receptor 1B, 2A, and 2B was performed by standard methods. Blots were incubated overnight at 4°C with SERT (catalog no. sc-14514; Santa Cruz Biotechnology, Santa Cruz, CA; dilution 1:200), 5-HT 1B receptor (catalog no. sc-1460; Santa Cruz Biotechnology; dilution 1:200), 5-HT 2A receptor (catalog no. sc-32538; Santa Cruz Biotechnology; dilution 1:200), or 5-HT 2B receptor antibodies (catalog no. sc-15080; Santa Cruz Biotechnology; dilution 1:200). Blots were washed and incubated for 1 h at room temperature with donkey anti-goat IgG-horseradish peroxidase (catalog no. sc-2033; Santa Cruz Biotechnology; 1:4,000 dilution). Bands of interest were visualized using the Enhanced Chemiluminescence Plus kit and identified by molecular weight as designated by the manufacturer for protein of interest. Blots were stripped and reprobed with an antibody to β-actin (catalog no. A5316; Sigma, St. Louis, MO). Densitometry was performed using NIH Image J software. Changes in protein expression were analyzed after normalization for β-actin expression.
Drug Preparation
A solution of 5-HT, 5-HT creatinine sulfate monohydrate complex (3 μg/ml; Sigma H7752), was made immediately before each study by dissolving the drug in normal saline. Ketanserin (50 mg/ml DMSO; Sigma S006), GR127935 (10 mg/ml H2O; Sigma G5793), and SB206553 (10 mg/6 ml H20; 1661; Tocris Bioscience, Ellisville, MO) solutions were made immediately before each experiment. Fasudil, HA-1077 (100 μg/ml; H-2330; LC Laboratories, Woburn, MA) was dissolved in normal saline. Sertraline hydrochloride (20 mg/ml DMSO; Sigma S6319), fluoxetine (4 mg/ml H2O; Sigma F132) and acetylcholine chloride (15 μg/ml sterile normal saline; Sigma A6625) were made and stored at −20°C.
General Study Design
Ewes were allowed to recover from surgery for a minimum of 24 h before the initiation of physiological studies. During each study, pulmonary arterial, aortic, and left atrial pressures were measured by connecting externalized catheters to computer-driven pressure transducers (model MP100A; Biopac Systems, Santa Barbara, CA). Pressure measurements were referenced to simultaneously recorded amniotic pressure. The flow transducer was connected to an internally calibrated flowmeter (Transonics Systems) to measure QLPA. Before infusion of study drugs, a 30-min period of stable baseline hemodynamics was established. Hemodynamic variables, including main pulmonary artery pressure (MPAP), left atrial pressure (LAP), aortic pressure (AoP), and QLPA, were measured continuously for the duration of each study protocol. Left lung PVR was calculated as follows: PVR = (MPAP − LAP)/QLPA. Heart rate (HR) was determined from phasic pressure traces. Arterial blood gas measurements included pH, Pco2, and Po2 (model ABL 800; Radiometer, Copenhagen, Denmark) and were obtained before and after each drug infusion.
Experimental Design
Protocol 1: pulmonary hemodynamic effects of 5-HT in the fetal lamb.
The purpose of this study was to investigate the pulmonary effects of selective 5-HT infusions. After a 24-h recovery from surgery, baseline hemodynamic measurements were recorded every 10 min for QLPA, MPAP, AoP, LAP, and HR. After baseline measurements were stable for a 30-min period, 5-HT (3–20 μg) was infused into the LPA over 20 min. Preliminary studies showed dose-related pulmonary vascular effects at these doses with limited systemic effects. Hemodynamic measurements were recorded every 10 min for 40 min after the infusion concluded. Arterial blood gas tensions were obtained at baseline and at the conclusion of each infusion.
Protocol 2: pulmonary hemodynamic effects of the 5-HT receptor blockers, ketanserin, GR127935, and SB206553.
The purpose of these studies was to investigate whether endogenous 5-HT maintains normal fetal vascular tone through actions on the 5-HT 2A, 1B, or 2B receptor. Baseline hemodynamic measurements were recorded every 10 min for QLPA, MPAP, AoP, LAP, and HR. After baseline measurements were stable for a 30-min period, either ketanserin (10 mg), GR127935 (10 mg), or SB206553 (10 mg) were infused, on random days, into the LPA over 20 min. Hemodynamic measurements were recorded every 10 min for 40 min after the infusion concluded. Arterial blood gas tensions were obtained at baseline and at the conclusion of each infusion.
Protocol 3: effects of 5-HT 2A receptor blockade on the hemodynamic response of exogenous 5-HT administration.
The purpose of this protocol was to investigate whether exogenous 5-HT causes pulmonary vasoconstriction through the 5-HT 2A receptor. Baseline hemodynamic measurements were recorded every 10 min for QLPA, MPAP, AoP, LAP, and HR. After baseline measurements 5-HT (20 μg) was either infused alone or after pretreatment with ketanserin (10 mg), a 5-HT 2A receptor blocker. Hemodynamic measurements were recorded every 10 min for 40 min after the infusion concluded. Arterial blood gas tensions were obtained at baseline and at the conclusion of each infusion.
Protocol 4: effects of Rho kinase inhibition on the hemodynamic response of exogenous 5-HT administration.
The purpose of this protocol was to investigate whether 5-HT causes vasoconstriction through Rho kinase activation. After a 24-h recovery from surgery, baseline hemodynamic measurements were recorded every 10 min for QLPA, MPAP, AoP, LAP, and HR. After baseline measurements were stable for a 30-min period, 5-HT (20 μg) was infused into the LPA over 20 min. Once hemodynamic measurements returned to baseline, fasudil (100 μg) was infused into the LPA. When hemodynamic measurements returned to baseline, 5-HT (20 μg) and fasudil (100 μg) were infused into the LPA over 20 min.
Protocol 5: pulmonary hemodynamic effects of the SSRIs, sertraline and fluoxetine, in the fetal lamb.
Baseline hemodynamic measurements were recorded every 10 min for QLPA, MPAP, AoP, LAP, and HR. After baseline measurements were stable for a 30-min period, sertraline (10 mg) or fluoxetine (10 mg) was infused into the LPA over 40 or 20 min, respectively. The drugs were infused over different time intervals to deliver similar infusion rates. Doses were based on preliminary studies demonstrating pulmonary vascular effects and limited systemic effects. We then studied the pulmonary hemodynamic effects of ketanserin infusion following sertraline administration to determine whether antagonism of the 5-HT 2A receptor would attenuate the hemodynamic effects of sertraline. After baseline measurements were stable for a 30-min period, sertraline (10 mg) was infused into the LPA over 40 min. Immediately after the completion of the sertraline infusion, the 5-HT 2A receptor antagonist ketanserin was infused (10 mg) directly into the LPA over 20 min. Hemodynamic measurements were recorded for 60 min after the end of the infusion. Acetylcholine (15 μg) was infused after sertraline administration to determine whether sertraline increases PVR through inhibition of endothelial nitric oxide synthase (eNOS). After baseline measurements were stable for a 30-min period, acetylcholine was infused over 10 min. Following the return of hemodynamic measurements to baseline, the SSRI sertraline (10 mg) was infused into the LPA over 40 min. Immediately following the end of the sertraline infusion, acetylcholine was again infused into the LPA over 10 min. Hemodynamic measurements were recorded for another 80 min. Arterial blood gas tensions were obtained at baseline and at the conclusion of each infusion.
Protocol 6: Western blot analysis of fetal vs. adult ovine whole lung expression of the SERT and the 5-HT 1B, 2A, and 2B receptors.
Lung whole lung lysates were collected from the ovine fetus (gestational age 136–143 days, term 147 days, N = 4) and the adult ewe (N = 4) to compare the developmental protein expression of the SERT and the 1B, 2A, and 2B 5-HT receptors, as described above.
Statistical Analysis
Statistical analysis was performed using the GraphPad Prism version 5.0 for Mac, GraphPad Software (San Diego, CA). Hemodynamic variables over time were compared using repeated-measures ANOVA with Newman-Keul's post hoc testing. Statistical comparisons were performed using unpaired t-tests and paired t-tests. Data are presented as means ± SE. The significance level was set at P < 0.05.
Protocol 1: pulmonary hemodynamic effects of brief 5-HT infusion in the fetal lamb.
Brief intrapulmonary infusions of 5-HT decreased QLPA by 29% (72 ± 19 vs. 52 ± 13 ml/min, P < 0.0001) and increased PVR by 61% from baseline (0.62 ± 0.19 vs. 1.00 ± 0.36 mmHg/ml per min, P < 0.0001; Fig. 1). These effects were not limited to the pulmonary circulation, as brief intrapulmonary infusions of 5-HT increased both MPAP (from 44 ± 18 vs. 51 ± 19 mmHg, P < 0.001) and AoP (41 ± 9 vs. 49 ± 10, P < 0.001) (Fig. 1). The effects of 5-HT were short-lived, as QLPA and PVR returned to baseline shortly after the end of the infusion. 5-HT induced pulmonary vasoconstriction in a dose-dependent fashion at doses ranging from 3–20 μg (Fig. 2). HR decreased from 176 ± 16 (baseline) to 165 ± 21 beats per min (bpm) at the end of the infusion (P < 0.05), and pH decreased from 7.38 ± 0.03 to 7.37 ± 0.03, P < 0.05. LAP, PaO2, and PaCO2 did not change in response to 5-HT.
Protocol 2: pulmonary hemodynamic effects of the 5-HT receptor blockers, ketanserin, GR127935, and SB206553.
Brief intrapulmonary infusions of ketanserin (10 mg), a 5-HT 2A receptor antagonist, decreased PVR by 24% from 0.56 ± 0.13 at baseline to 0.43 ± 0.12 mmHg/ml per min (P < 0.005 Fig. 3). Ketanserin decreased MPAP from 40 ± 15 vs. 35 ± 6 mmHg, P < 0.05 (Fig. 3). AoP briefly decreased during the infusion (from 41 ± 4 vs. 36 ± 14 mmHg, P < 0.05) but returned to baseline values for the remainder of the study. Ketanserin did not change HR or arterial blood gas tensions. Intrapulmonary infusions of the 5-HT 1B antagonist (GR127935) or the 5-HT 2B antagonist (SB206553) had no effect on hemodynamics or blood gas tensions (data not shown).
Protocol 3: effects of 5-HT 2A receptor blockade on the hemodynamic response of exogenous 5-HT administration.
The hemodynamic effects of infusions of 5-HT (20 μg) alone or after pretreatment with ketanserin (10 mg) were studied to determine whether the effects of 5-HT are mediated through 5-HT 2A receptor activation. The infusion of 5-HT alone increased PVR by 60%, which was abolished after pretreatment with ketanserin (Fig. 4). The administration of 5-HT increased PVR from 0.61 ± 0.12 to 0.9 ± 0.23 mmHg/ml per min (P < 0.05). Pretreatment with ketanserin blocked 5-HT-mediated vasoconstriction, baseline PVR 0.64 ± 0.1 vs. 0.53 ± 0.06 mmHg/ml per min. 5-HT administration alone decreased QLPA from 68 ± 17 to 51 ± 13 ml/min, P < 0.05. In comparison, 5-HT administered after pretreatment with ketanserin resulted in no change in QLPA, 65 ± 9 vs. 69 ± 14 ml/min. There were no changes in blood gas tensions or HR.
Protocol 4: effects of Rho kinase inhibition on the hemodynamic response of exogenous 5-HT administration.
The hemodynamic response of 5-HT (20 μg) infusion alone was compared with the combination of fasudil (100 μg) and 5-HT (20 μg) administration. The infusion of 5-HT alone increased PVR by 53%, which was attenuated with the coadministration of fasudil with 5-HT (P < 0.05, Fig. 5). 5-HT alone increased PVR from 0.50 ± 0.19 to 0.69 ± 0.21 mmHg/ml per min, P < 0.05. MPAP increased from 38 ± 8.1 to 43 ± 7.3, P < 0.05. The coadministration of fasudil with 5-HT blocked 5-HT-mediated vasoconstriction (0.50 ± 0.16 vs. 0.57 ± 0.13 mmHg/ml per min) and increase in MPAP (37 ± 6.9 to 44 ± 6.7, ns).
Protocol 5: pulmonary hemodynamic effects of the SSRIs, sertraline and fluoxetine, in the fetal lamb.
Infusions of the SSRI sertraline decreased QLPA by 18% (81 ± 21 vs. 67 ± 19 ml/min, P < 0.05) (Fig. 6) and increased PVR by 48% (Fig. 6) from 0.54 ± 0.16 (baseline) to 0.80 ± 0.26 mmHg/ml per min (50 min), P < 0.05. The pulmonary vasoconstrictor response to sertraline was sustained for at least 80 min after the completion of the infusion. Systemic (41 ± 5 to 50 ± 8 mmHg; P < 0.05) and pulmonary artery pressures (43 ± 5.4 to 51 ± 6.3 mmHg; P < 0.05) were significantly increased following the infusion of sertraline (Fig. 6). Acute infusions of sertraline did not significantly alter HR (171 ± 14 baseline vs. 184 ± 23 bpm) or LAP (2.5 ± 0.6 baseline vs. 3.0 ± 1.2 mmHg). Direct intrapulmonary infusions of sertraline decreased pH (7.37 ± 0.02 vs. 7.32 ± 0.05; P < 0.05) and Po2 (22 ± 4 vs. 20 ± 4 Torr; P < 0.05) and increased Pco2 (45 ± 3 vs. 49 ± 4 Torr; P < 0.05).
As observed with sertraline, infusions of a second SSRI, fluoxetine, also caused potent and sustained pulmonary vasoconstriction (Fig. 7). Fluoxetine increased PVR by 38%, from 0.55 ± 0.14 (baseline) to 0.76 ± 0.16 (P < 0.05), and QLPA decreased 14% from 80 ± 15 (baseline) to 69 ± 22 ml/min. Sertraline administration resulted in a potent increase in PVR. However, ketanserin, a 5-HT 2A receptor antagonist, decreased PVR to baseline values (Fig. 8, top). Acetylcholine (15 μg) decreased PVR by 33% when infused before and after the infusion of sertraline, suggesting that sertraline did not acutely impair eNOS activity or signaling (Fig. 8, bottom).
Protocol 6: Western blot analysis of fetal vs. adult ovine whole lung expression of the SERT and the 5-HT 1B, 2A, and 2B receptors.
Western blot analysis demonstrated absent expression of the SERT and the 5-HT 1B receptor in the lung of the late-gestation ovine fetus compared with the adult ewe. The ovine fetus does express the 5-HT 2A and 2B receptors, but in much lower levels than the adult (Fig. 9).
We found that exogenous 5-HT is a potent pulmonary vasoconstrictor in the late-gestation ovine fetus and that the pulmonary hemodynamic effects of 5-HT are mediated through the 5-HT 2A receptor and at least partially through Rho kinase activation. In addition, ketanserin causes fetal pulmonary vasodilation, suggesting that endogenous 5-HT partially contributes to the maintenance of normal pulmonary vascular tone in the ovine fetus thorough the 5-HT 2A receptor. These effects were not observed after treatment with 5-HT 1B or 2B receptor antagonists. We also found that acute intrapulmonary infusions of the SSRIs, sertraline and fluoxetine, cause potent and sustained increases in pulmonary vascular resistance and decreases in pulmonary blood flow and that these effects were mediated through the action of the 5-HT 2A receptor. These agents also caused a sustained increase in systemic pressure. Finally, acetylcholine-induced vasodilation persists after sertraline treatment, suggesting that sertraline did not directly impair NOS activity.
These results are interesting because this is the first report describing the direct pulmonary effects of 5-HT in the developing pulmonary circulation in vivo and the mechanisms through which 5-HT induces fetal pulmonary vasoconstriction. This is the first study to show that acute selective pulmonary infusions of two commonly prescribed SSRIs, sertraline and fluoxetine, directly causes sustained and potent fetal pulmonary vasoconstriction in vivo. SSRI-induced pulmonary vasoconstriction was abolished with the administration of ketanserin, the 5-HT 2A receptor antagonist, but acetylcholine-induced pulmonary vasodilation was not altered by sertraline treatment, supporting our hypothesis that SSRIs cause pulmonary vasoconstriction through an increase in free local or circulating 5-HT and not through inhibition of eNOS.
The first potential link between 5-HT and the development of PPHN was recognized several years ago when Chambers et al. (7) reported that the maternal use of SSRIs after the 20th wk of gestation was associated with a sixfold increased risk of the development of PPHN (7). SSRIs are the most common agents used to treat depression (2, 49). Maternal depression is extremely prevalent with between 10–15% of women of reproductive age diagnosed with depression (33). When untreated, maternal depression is associated with numerous adverse consequences including low birth weight, prematurity, and maternal substance abuse (5, 8, 54). SSRIs readily cross the placenta, as reflected by fetal cord blood levels, corresponding to 30–70% of maternal levels (22, 50). Some infants exposed to SSRIs during the last trimester of pregnancy are reported to develop self-limited signs of withdrawal from these drugs, manifested as sleep disturbances, gastrointestinal and neurological symptoms, and respiratory distress, suggesting significant fetal drug delivery during late gestation (6, 14, 46). Past studies in pregnant ewes have shown that maternal infusion of SSRIs decreases uterine artery blood flow and causes fetal hypoxemia (41). Recent studies have demonstrated that fluoxetine-exposed neonatal rats develop pulmonary hypertension, as evidenced by pulmonary vascular remodeling, right ventricular hypertrophy, decreased oxygenation, and higher mortality at birth (16). However, the pulmonary vascular effects of SSRIs were not directly measured in vivo.
In striking contrast to the effect of SSRIs on the fetal pulmonary circulation, SSRI treatment has been shown to attenuate disease severity in both animal models of adult PH and in adult patients with established PH. SERT inhibition, with either SSRIs or SERT knockout mice, attenuates hypoxia-induced PH in rodents (20, 37). Clinical studies suggest that SSRI use in patients with PH is associated with a reduction in the risk of death (26, 53). Why SSRIs exert such differential effects in the fetal and adult pulmonary circulation remains unanswered but may be due to developmental differences in the pulmonary expression of the SERT and 5-HT receptors. We also report that, compared with adult expression, fetal lung content of SERT and the 5-HT 1B, 2A, and 2B receptor proteins were markedly decreased. In fact, SERT protein was not detected in the fetal lung. Whether these differences in SERT expression contribute to developmental changes in SSRI effects and potential mechanistic implications is not understood. We speculate that SSRIs may act in part through effects on platelets, enhancing the release of 5-HT in the fetal circulation and increasing pulmonary vasoconstriction. Alternatively, SSRIs may potentially cause vasoconstriction through nonspecific effects, such as inhibition of voltage-gated potassium channels (56). Additional studies are needed to clarify these mechanisms. Although this study was conducted to address the direct effects of SSRI infusions on the lung, studies of chronic maternal administration of SSRIs are needed to assess the effect of SSRIs on the uterine placental circulation and whether chronic administration has similar effects to acute administration in the fetal circulation.
We found that SSRIs induce both pulmonary vasoconstriction and systemic hypertension, which may be attributable to an acute increase in circulating levels of 5-HT, by SSRI blockade of 5-HT uptake into platelets, endothelial cells, and other cell types that express the SERT. Infusions of fluoxetine in sheep results in an acute increase in plasma 5-HT levels, whereas chronic fetal exposure to SSRIs reduces mean cord blood 5-HT concentrations and platelet 5-HT concentrations in newborns (3, 28, 42). We found that the 5-HT 2A receptor antagonist, ketanserin, reverses SSRI-induced pulmonary vasoconstriction, supporting the hypothesis that SSRIs induce pulmonary vasoconstriction through increased 5-HT levels. Another proposed mechanism for SSRI-induced vasoconstriction is through direct inhibition of NOS activity. Previous studies have shown that paroxetine, another commonly used SSRI, inhibits NOS activity and expression (4, 15). However, we found that acetylcholine-induced vasodilation remained following sertraline administration, showing that eNOS was not inhibited by sertraline.
In adult rodents, 5-HT-induced vasoconstriction is primarily mediated through the 5-HT 1B receptor (34, 38). In contrast, inhibition of fetal 5-HT 1B receptors had no significant effect on fetal pulmonary blood flow, whereas 5-HT 2A receptor inhibition decreased PVR. Prior studies in isolated rabbit pulmonary arteries have shown that 5-HT-induced fetal pulmonary vasoconstriction is mediated through the 5-HT 2A receptor (40).
One of the effectors of 5-HT signaling in adult pulmonary artery smooth muscle cells is Rho kinase (21, 25, 32, 36). Activation of RhoA/ROCK pathway contributes to vasoconstriction and pulmonary vascular remodeling (25, 44, 47). In the fetus, Rho kinase activation has been shown to maintain PVR and is increased in experimental PPHN (19, 48). In this study, we found that 5-HT-mediated vasoconstriction was attenuated with coadministration of fasudil, the Rho kinase inhibitor.
We conclude that 5-HT causes potent vasoconstriction in the ovine fetal pulmonary circulation through activation of the 5-HT 2A receptor and in part through Rho kinase signaling. The SSRIs, sertraline and fluoxetine, cause potent and sustained pulmonary vasoconstriction in the normal ovine fetus, which is mediated through stimulation of the 5-HT 2A receptor. We speculate that endogenous 5-HT likely contributes to the maintenance of pulmonary vascular resistance during fetal life. We further suggest that prolonged exposure to SSRIs may lead to abnormal 5-HT metabolism, which may alter the expression of 5-HT receptors, specifically the 2A receptor, leading to increased Rho kinase activity contributing to sustained abnormalities of pulmonary vascular tone, reactivity, or structure, which may lead to impaired transition of the pulmonary circulation at birth (PPHN).
C. Delaney is supported by NIH-NICHD grant T32 HD007186-31 and Gilead Young Investigator Award. J. Gien is supported by NIH grant 1K08HL102261 and Actelion Pharmaceuticals (Entelligence Young Investigator Award). S. Abman is supported by NIH grants HL007670, HL085703, and HL068702.
No conflicts of interest, financial or otherwise, are declared by the authors.
The authors are grateful for statistical advice from Dr. Paul Rozance.
- Copyright © 2011 the American Physiological Society


text: On Fri, Jun 5, 2009 at 2:58 PM, MH <mhamro at gmail.com> wrote: > I actually meant > > data Container a = Many a(Container a) > > but here is what I don't understand (fyi, I am a beginner) how can you > construct this container? I can do I think I saw the above definition described as a coalgebra or codata: http://blog.sigfpe.com/2007/07/data-and-codata.html Basically, that list has to always be infinite. > > > let a = Many "somestring" - and I will get back a function but I can not do > let a = Many 'a' "somestring" - because the second param is not > (Container a) type. > let a = Many 'a' (Container ['a','a']) - doesn't work either because > Container is a type not a constructor (right or I am missing > something?). > > So I have two questions: > 1. When I do > let b = Many "somestring" , I get > :t b > b :: Container[Char] -> Container[Char] > what is it and why I am allowed to pass just one parameter to Many > (and how can I use it)? > > 2. How can you construct that container? > data Container a = Many a(Container a) > let a = ???? > Check that link above for answers to some of your questions. I think that basically you want a different type: data NonEmptyList a = JustOne a | MoreThanOne a (NonEmptyList a) This is just the normal list definition with a small change, if you think of the normal list as being defined in this (pseudo) code: data [a] = [] | a : [a] I've just made it so that the "empty" list has at least one. I hope that helps, Jason -------------- next part -------------- An HTML attachment was scrubbed... URL: http://www.haskell.org/pipermail/haskell-cafe/attachments/20090605/7483a157/attachment.html

subset: commoncrawl


text:
This one of the few traditional places left in Tokyo. During the Edo period, it marked the Northern limit of the city. mostly known for its touristical attraction. Some of the sightseeing attractions are The Senso-ji Temple, Kaminarimon gate, Sumida river and the nakamise shopping street for Japanese souvenirs.
This is a local Japanese society and the you can see the UENO PARK which is big for Cherry blossom viewing and it's also the Tokyo Zoological Gardens. Ameyoko shopping street is a must see market, it harbours tons of flee market. The street is always crowded with people like festival.
This district in tokyo dedicate to electrical and electronics sales. Its called Akiba for short. Make sure you have your passport with you to enjoy duty free shopping for computer and electronics. Its also big for manga, maid café, internet cafés and more.
is Known as the fish market is the bisggest fish market worldwide. Millions of fishes and seafood arrive from all over the world daily at the Tsukiji Market. The auctions takes place very early so if you want to have glimpse of the auction without a hussle you need to be there very early between 5:00 am- 7:00 am. The market is the best location to have sushi breakfast. Also in tsukiji is the Tsukiji Hongan-ji Temple.
the mecca of sumo in Japan. Sumo is a Japanese kind of wrestling and Japan's national sport. It originated in aceint times as religious performances to the Shinto gods. Its held 3- 6 times annually. Ryogoku houses the the sumo arena and its filled with chanko restuarants and the other sumo related information.
is a town always dominated with teenage Japanese. A shopping and entertainment district for japanese teenagers. Fashionable, cute and crazy dressing and make-ups. You need to be in Harajuku on Sunday to see it your self.
It is the tokyo`s teen entertainment centre almost every school kid in tokyo knows shibuya. Shibuya is not as flashy as shinjuku but ist very interesting with many departments shops ,giant screens playing music,videos and advertisements. Its very good for window shopping and its always jammed parked with fashionable funny japanese kids on weekends.
It is the busiest hub in the center of the city of Tokyo and over two million people pass through its main train station daily.Shinjuku offers everything from huge departments stores, entertainment centers to restaurants and the locations shown in the movie, Lost in Translation, including The Park Hyatt Hotel and the Tokyo Metropolitan Building. Paronamic views of Tokyo can seen from the top of the Tokyo Metropolitan Building. The night life in Shinjuku is best seen late at night in Kubuki-cho where there are movie theatres, cheap restaurants, and street entertainment.
This biggest western community in japan. Its filled with restaurants, bars, pubs, night clubs & dance clubs. Roppongi is known for its night life and rendezous spots. The Roppnogi Hills building and Tokyo mid town, a mecha of the rich and famous, towers over the sky line. Its the hub of fine dining & drinking, making freinds with japanese and freinds from all over.
The Imperial Palace houses the Emperor of Japan and its household. The palace is located on the former site of the Edo Castle. Very big space with stones and greenish trees and flowers. The East Gardens of Imperial Palace is nearby the entrance through Otemon Gate.
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After spending almost 20 years inspiring fashion designers including Karl Lagerfeld and Yves Saint Laurent, French model turned actress Laetitia is set to take Hollywood by storm, with a new film role opposite Richard Gere.
The French beauty, currently on the judging panel of this year's Venice Film Festival, spoke exclusively to Bazaar about her burgeoning film career, charming us with her enthusiasm for tragic film heroines (not to mention her modern day Brigitte Bardot looks).
"I love tragic romantic stories," she confessed. "The heroines of Italian cinema: Monica Vitti and Anna Magnani. So curvaceous and passionate. These are the women that I love to play in fashion."
Far from a quiet beauty, the model was chatty and fiercely passionate, and had us laughing at her humorous anecdotes from her shoot with Karl Lagerfeld's famous pet cat, Choupette ("that cat has crazy eyes") and her mother's reaction to the news she would be starring alongside Richard Gere ("I was like, 'Please Mum, don't shout.'")
Accompanying the revealing interview is a stylish shoot shot by photographer Sebastian Faena on location in Paris. Laetitia is cast as one of the sexy, romantic heroines she admires, wearing autumn/winter 12's prettiest dresses from Jil Sander and Alexander McQueen.
The second most successful model in the world, Joan Smalls, stars in the second of our October covers. The 24-year-old Puerto Rican sat down with US Bazaar's Derek Blasberg to talk about how she launched her career, from meeting every casting director in New York, to captivating the imagination of Givenchy designer Riccardo Tisci.
See both covers, read the full interviews and see the stunning shoots in the October issue of Bazaar, on sale on 3 September.
Download your issue on Monday from the Bazaar newsstand
Sign up for Bazaar's newsletter and be the first to know about our latest cover stars, see our exclusive shoots first and more.


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Indian Sociological Society (ISS) has started an international journal in Hindi entitled, ' Bhartiya Samajshastra Sameeksha' on January 2014. It has already published 4 issues and fifth is in continuing process of publication. We are trying to create a sociological forum for establishing research through Hindi medium. The journal endeavours to give coverage of teachers and researchers' articles, papers, comments in Hindi to cater to the social scientists of Hindi speaking belt so far it has being a biannual journal of sociologists' research , essays, interviews, comments, book reviews and various other academic activities highlighting them in a systematic manner. The journal is a going to be a strong medium of creating discourse in sociology with the help of the sociologists at global and national level. We believe that such an endeavour will get ready cooperation from teachers, scholars, publishers and students. In order to make your cooperation by way of taking membership of the journal and contributing your research articles on topical issues of sociological relevance. Its membership fee for one year is Rs. 400/- for two years 700/- and for three years 1000/-; and institutional membership for one year is Rs. 500/-. We also appeal to its old member to renew their membership by sending membership fee accordingly. We hope to get your cooperation. Membership form can be downloaded from the ISS Website.
To Read in Hindi click here
Feel free to contact for any other information from the ISS office writing on following e-mail addresses:
ISS office: firstname.lastname@example.com
The Editor of the Sameeksha, Prof. B.K. Nagla: firstname.lastname@example.com
Bhartiya Samajshastra Sameeksha


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Why do we get chocolate waves anytime there is a serious swell around?
Results 1 to 10 of 14
Thread: why does it get brown?
Hybrid View
why does it get brown?
ITs all the sands and **** floating around in the water. Big waves cause the bottom to get turned and the water gets dirty.
Makes sense because in the summer most of the time the water gets cleaner (green) because of the lack of swells. However, when one pops up, back to square one. Because of the consistent activity in the fall/winter, it gets ****ier. Stop pollution and maybe we'll have water like FL all year round!!!
Jan 20, 2008, 03:12 AM #4
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It doesn't have to do with the size of the waves, but the ocean current. Because, the swells around here are often associated with strong winds as storms skirt up the coast, there is a lot of current associated with this. This causes the sand to move around and thus the dirty colored water. On the other hand, if we get ground swells with no strong winds along the coast, then the waves show up much clearer.
This is why, in many other areas where ground swells are more prevalent, the waves are much clearer.
Jan 20, 2008, 04:44 AM #5Junior Member
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Hey guys, I know a lot of the brown water is just from overall east coast pollution when we get storms.However, Have you guys ever seen brown foamy bubble puddles especially during the summer months floating in the water that come off being very warm at times??? Especially if you paddle near them or through them!!! Rumor has it, or what I've heard is that the Ocean City Maryland Public Works has a pipe that pumps so called "filtered" water into the Atlantic after its processed or cleaned....Directly where public works is on 65th st....The strange thing is I've seen these puddles the most between 65th st and 59th st. Again, this might be BS or just a rumor but members from the 62nd st. Longboarders Club told me that's why these warm puddles appear during the summer months because of little swell movement during the summertime and they drift ashore. Is this true or is this just a load of **** the old guys that rule told me as a teenager as a joke??? Either way I've seen these brown puddles only during summer and never during fall winter or spring!
Last edited by bb01021; Jan 20, 2008 at 04:54 AM. Reason: spelling
Jan 20, 2008, 05:26 AM #6
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Let's not forget. . .
. . . that the lighting has a good bit to do with it as well. A lower sun angle in the winter tends to give a grayer cast to pretty much everything. . . including my beard. It has a lot to do with the refraction angle of the low sun on the water. Partly the same reason the southern tropics seem so much more blue and crystaline- higher sun angle.
I like to think of dark green water as rich in plankton- and therefore healthy for the sea critters. Summer water has many more touristas doing their business and dumping things in the water, ergo, much LESS healthy for both sea critters and we who play in it.
The effluent pipes are located at 46th and 62nd. Look for the manhole cover up near the end of 46th street, that's the line that goes 2 miles offshore. I was up there one day when a diver was going down into the outfall pipe to check its integrity- a regular inspection from what they told me. It's underground until it gets way offshore, and I believe the effluent is in a terciary condition. Not raw by any means. All that poop's gotta go somewhere- better two miles out than in the bay behind the city. By the way, seafoam is a natural occurance, it just looks really dirty.
Last edited by MDSurfer; Jan 20, 2008 at 05:58 AM.


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The Q&A will begin today at approximately 1:30pm/PT (4:30pm/ET).
The event will be streamed online at www.theartistmovie.net and www.facebook.com/theartist.twc allowing film fans across the world to submit questions and participate in a discussion with the cast and crew on the making of the film.
The Weinstein Company hosted a similar event with the ensemble cast of "The Artist" earlier this month as well as last year with the film, "The King's Speech" and had over 20,000 questions submitted in a 30-minute period during the Q&A.
"The Artist" has been nominated for three SAG Awards including Best Ensemble Cast and Best Supporting Actress for Bejo.
Hollywood 1927. George Valentin (Jean Dujardin) is a silent movie superstar. The advent of the talkies will sound the death knell for his career and see him fall into oblivion. For young extra Peppy Miller (Bérénice Bejo), it seems the sky is the limit - major movie stardom awaits. THE ARTIST tells the story of their interlinked destinies. The film opened in U.S. theaters on November 25th.
Directed by Michel Hazanavicius, "The Artist" stars Jean Dujardin, Bérénice Bejo, James Cromwell, Missi Pyle, Penelope Ann Miller, Malcolm McDowell, Beth Grant, Joel Murray, Ken Davitian and John Goodman. It is written by Michel Hazanavicius and produced by Thomas Langmann.


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About Teton FreeRide
Teton FreeRide is a content based blog founded and operated by Mike "Mikey" Leake. Mikey has lived in the Teton Valley region of southeastern Idaho and western Wyoming most of my life. He has also had the opportunity to live and play in the Lake Tahoe area, and now, Alaska too!
After competing on the Freeskiing World Tour on-and-off for 10 years Mikey has transitioned to judging various events and become an advisory board member with the International Freeskiers & Snowboarders Association (IFSA). Over the past 13 years he has worked in the ski industry through skiing as an athlete, coach, guide, ski patrol, event coordinator, event judge, marketing consultant, team manager, videographer, and as an associate producer. Mikey has a true passion for the outdoor industry and tries to be involved in every aspect possible.
Monthly Archives: October 2012
First turns of the season
By Mikey | Published: October 29, 2012
This weekend Ray Mariani, Amber Johnson, Maeve Nevins, Michelle and I headed over to a secret stash near Hope, AK. The Chugach received a few good snow storms a couple of weeks ago and then clear skies and cold temps moved in and have not left. This has provided for 1-3 inches of surface hoar [...]
Posted in Fall 2012 | Leave a comment
Its just about that time again……
By Mikey | Published: October 22, 2012
The early season stoke and anticipation is upon us. Another summer has come and gone, and now the white stuff is creeping down the peaks, once again laying down what is the foundation of winter for many. With an early season snow pack beginning to build in several places, please remember to be safe out [...]
Posted in Fall 2012 | Leave a comment


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HELSINKI, Nov 30 (Reuters) - Finnish IT services provider Tieto may have to pay "millions" in damages and could lose customers due to technical problems in Sweden, Dagens Industri newspaper reported on Wednesday.
Tieto spokeswoman Reeta Kaukiainen said the problems, caused by a hardware failure, were affecting about 50 customers, including pharmacy chain Apoteket and SBAB Bank.
"For example, the pharamacies of Apoteket are not able to handle the prescriptions electronically as usual," she said.
The company was trying to fix the services, she said, declining to give an estimate on costs or comment on whether customers would go elsewhere.
Tieto shares were down 2.9 percent at 0940 GMT. (Reporting By Jussi Rosendahl and Helena Soderpalm; Editing by Dan Lalor)


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EXCLUSIVE: Play latest must-have game Titanfall before its official release
GAMERS will be able to get their hands on a preview of Titanfall before it hits shops in March
Xbox gamers are getting the chance to play this year's must-have game before it comes out.
Titanfall is the big new shooting franchise hitting the new Xbox One console this spring.
Insiders have been amazed by the game at early preview sessions and some are even hinting it's a "system seller".
The run-and-gun blaster takes all the best elements of Call of Duty but adds in giant "mech" robots you can jump in and control.
It's trying to take gaming in a new direction by only being multiplayer.
There will be no traditional single-player campaign to fight though.
And bosses behind the upcoming mega game are offering Brits the chance to play it early.
Maker Electronic Arts has started sending out emails to fans giving them details of how to try the game's 'beta' version ahead of final release.
It will give them the chance to see how the game acts when played by proper gamers, rather than internal testers.
There are hopes the beta may even go fully public, allowing all Xbox owners to take part.
The invites read: "Congratulations, you have been selected to take part in an exclusive trial for an upcoming EA title on Microsoft's Xbox One."
The game is released on March 11 in America and two days later in Europe. It is exclusive to Xbox.
The beta access to play the game before release is expected to start early next month.
Producer Drew McCoy, who is working on the game for maker Respawn, said: "Titanfall will stretch the limits of what an first person shooter multiplayer game can be.
"There are so many games now that are just retreading old ground.
"We've got characters, we've got a story. You have moments, things that people traditionally expect from single-player games.
"We're putting that all into a multiplayer game, and it's awesome."


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You're seeing this message because you're using an older version of Internet Explorer that is unsupported on our website. Please use these links to upgrade to a modern web browser that fully supports our website and protects your computer from security risks.
The Frostburg State University dedicates this wall to living students, alumni, faculty, staff and friends.
New in 2008, the third wall has been designated specifically to pay tribute to living individuals because of their dedicated service to FSU or the surrounding community or for similar reasons.


text: Home / Products / Clague 5 Light Chandelier in DBK Larger View Choose background color Rollover to Zoom Close Visualize Kichler lighting and Sherwin-Williams paint all in one tool. Today's homeowners have seemingly unlimited options when it comes to colors and finishes. With so many possibilities it can be daunting to find just the right match. Not any more. Match your lighting and your wall color with our intuitive visualization tools. Choose your Sherwin-Williams Color Family Color palette belongs to Sherwin-Williams, a registered trademark of the Sherwin-Williams Company. © 2013 Sherwin-Williams Company. All rights reserved. Other Kichler Products Products in the same collection 43419DBK43420DBK Clague CollectionClague 5 Light Chandelier in DBK 43419DBK (Distressed Black) bvseo_sdk, net_sdk, 126.96.36.199 CLOUD, getAggregateRating, 31ms REVIEWS, PRODUCT bvseo-msg: The resource to the URL or file is currently unavailable.; Product Description: The refined lodge and country style of this 5 light chandelier from the Clague collection features soft lines with perforation details surrounding the arms. The Distressed Black finish and Auburn Stained Wood accents work to create a design masterpiece. Shop, Buy or Order Locally Submit Lighting Showroom Landscape Lighting Distributor Electrical Distributor Available online at these fine retailers! Technical Information Weight:8.80 LBSChain/Stem Length:36.00"Safety Rated:DryBase Backplate:6.00 DIASlope Ceiling:YesOverall Height:61.00"Max Wattage/Range:60WCollection:Clague CollectionWidth:26.50"Height:23.25"Lamp Included:Not IncludedLead Wire Length:89.00"Voltage:120VLight Source:IncandescentSocket Base:CandelabraNumber of Bulbs:5Lamp Type:BMax Watt:60WNumber of Lights/LEDs:5Bulb Product ID:4064CLRFinish:Distressed Black Related Documents:IS-43419-CBDownloadIS-43419-USDownloadHigh Res Images 43419DownloadSpec SheetDownload bvseo_sdk, net_sdk, 126.96.36.199 CLOUD, getReviews, 0ms REVIEWS, PRODUCT bvseo-msg: The resource to the URL or file is currently unavailable.;


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Use the tools below to refine your search by only displaying reviews with a certain number of star ratings or to only show reviews from a certain time period. Eg click on '1 star' to just display the reviews we have which received a 1 star rating click or 'Within the last month' to display just reviews posted over the last month.
Written on: 01/09/2009 by ReneM (1 review written)
If you ever happen to be in Malvern - pop into The Spring Restaurant in the Mount Pleasant Hotel. It's a small restaurant that serves lovely modern European food made from local produce. We have been there on the Bank Holiday weekend and were quite impressed. We worked up quite an appetite at the antiques fair so had quite a feast! … Read Full Review
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My Nonprofit Reviews
Review for Oasis Sanctuary Foundation, Ltd., Benson, AZ, USA
As a bird lover,I highly recommend the Oasis Sanctuary as the Best avian rescue org.in the S.W.-the ppl.who work there are capable,compassionate,&knowledgable;I consider myself Very Fortunate to live near this wonderful 'place of safety&refuge' for all feathered friends that need such a place.I could extol the Oasis for a few more paragraphs,but since this is cyberspace,I'll keep my accolades short&sweet.Bravo,Sybil&everyone out there;BRAVO!
More Feedback
How would you describe the help you got from this organization?
How likely are you to recommend this organization to a friend?
How do you feel you were treated by this organization?
Very Well
When was your last experience with this nonprofit?
Review for Oasis Sanctuary Foundation, Ltd., Benson, AZ, USA
I volunteered here about 10 yrs. ago;I've also donated needed items to the Oasis Sanctuary;since I live nearby,I try to get there during 'open house'.usu.the 1st wknd.in Dec.This is the place where my beloved birds will go if something happens to me-I can't think of a better place around here to place my'feathered children'.The Staff& the former Director,Sybil Erden,are all wonderful,helpful ppl. who Really care about birds&know their many needs,since birds require special knowledge&living conditions.A-#1 Place!
More Feedback
Would you volunteer for this group again?
For the time you spent, how much of an impact did you feel your work or activity had?
Did the organization use your time wisely?
Very Well
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Part one and Part Two Assignment - Fourth Written Assignment
Part One
4. Violence within families affects women, children, and the elderly. Select one of these groups, either women, children or the elderly for this topic. Describe how these individuals can be victims of violence:
- How prevalent is violence for the chosen group?
- What social or cultural norms contribute to the incidence of violence for this group?
- Are there myths about this violence?
- Are there coping strategies or methods of prevention that can be used by the victims within the chosen group?
- Identify and describe a website or online article that provides authoritative and accurate information on this type of violence.
Respond to the following questions in two or three double-spaced paragraphs.
Part Two
Respond to the following questions in two or three double-spaced paragraphs.
Tutor Answer
Brown University
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Notre Dam University
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Oklahoma University
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Pennsylvania State University
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Stanford University
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Not Just a Free Lunch
Competition between the small Shas-affiliated school networks sprouting in disadvantaged areas seems to be spawning higher educational standards and heightened respect for teachers and parents.
The backdrop varies from one place to another: In Holon and Jerusalem, it's an old community center that is so dilapidated and rundown that it screams out, and whose walls are covered with awkward efforts at beautification; in Bat Yam, it's a dank storeroom converted for use by teachers and pupils; in Ofakim − surprise, surprise − it's a spacious, new, well-lit building. But the story behind these buildings is the same everywhere: One day a decrepit trailer is placed in the yard of a school, and within five years an entirely different educational facility evolves. Right under the nose of municipal authorities, a kindergarten with 20 children, two teachers and a sandbox can develop into a small local network of kindergartens, schools for boys and girls, and a yeshiva.
This story is often retold by Shas people in the field, who like to describe the establishment of the facilities of Maayan Hahinuch Hatorani, the flagship educational system of the movement, in peripheral towns and low-income neighborhoods, and even in the Haredi ?(ultra-Orthodox?) population centers of Bnei Brak and Jerusalem.
The stories of how Shas made the "desert" bloom and rescued children from life in the streets are repeated by activists in the country's periphery. In outlying towns and neighborhoods on the outskirts of the cities, the activity of the grass-roots leaders who are supported and cultivated by the movement − the rabbis, preachers and local kabbalists, who established institutions and brought families back to religion − is as dynamic as ever, without any connection to the party's prolonged stay in the opposition ranks. In parallel with this activity, the back-to-the-faith crusade continues apace in low-income neighborhoods throughout Israel.
Rabbi Yosef Varon, director of the small Bnei Zion network of kindergartens and schools in Bat Yam and Holon, is an activist from the founding generation of Shas. He explains that he embarked on his endeavors in response to a call by Rabbi Ovadia Yosef about 15 years ago, when Shas was founded. Varon is himself a born-again Jew, with an impressive beard and a long, black coat. Yet, like many other Shas activists, it is important for him to show just how immersed he is in Israeli society. He takes pains to mention his master's degree in engineering and the fact that he served in the army as an officer. He was a member of the Holon city council for seven years until he decided to leave and move to Bnei Brak, "for the sake of the children's education."
"Bnei Zion began with 26 children in a decrepit trailer," says Varon, reiterating this factoid in every kindergarten and school he visits. His network now has 800 pupils. Its kindergartens and schools are in well-tended premises, despite the difficult physical conditions in which they operate: They are extremely crowded; some of the classrooms are in ramshackle huts; and the windows in the boys' school are broken ?(the network chose to renovate the bathrooms, and there is no funding left for other things, he explains?). The girls' school is located in a warehouse that is burning hot in the summer and freezing in the winter.
Most of the pupils do not live within walking distance, and are transported by bus and van from Bat Yam and Holon. The boys' school is near the beach in Bat Yam; the girls' school is in central Holon. The girls' kindergarten is in a caravan in that city's Neveh Arazim neighborhood, known for the large proportion of residents who have adopted a religious lifestyle. The boys' kindergartens are a few blocks away.
Not fussyThe Shas educational networks resemble a state composed of small cantons. Operating in the same hinterland in which the tiny Bnei Zion network developed are at least five other similar networks. A common thread passes through the poorer neighborhoods of Holon, Bat Yam, South Tel Aviv and Jaffa: All have Sephardi populations that are influenced by local rabbis, all of whom look up to Rabbi Ovadia Yosef.
Rabbi Haim Rabi, the "guru" of the young born-again religious crowd in Holon, is the patron of the Pi Olalim network, which operates two schools and eight kindergartens in the Tel Giborim neighborhood of Holon. Pi Olalim is linked administratively and financially to the small Eili Be'ezri network, which has two elementary schools, one for boys ?(called Rashi?) and one for girls in Tel Kabir. A sign is posted in each of the institutions, asking parents to come in modest dress. "To what extent is that upheld?" asks the director general of the institutions, Elihu Moyal, whose eyes twinkle sardonically. "More in the winter and less in the summer. We don't really hold them to it."
Another school network was founded in Kiryat Sharett in Holon by Rabbi Yosef Mugrabi, who has also gathered around him a flock of newly religious Jews. The Netivot Rivka network is flourishing in Bat Yam. It operates two kindergartens and an elementary school for girls, and a Haredi girls high school. Until about 10 years ago, the Haredi community in the area was not that large.
The families who send their children to these institutions will vote for Shas in the elections, the activists and neighborhood leaders assume. In the most recent election for local authorities, voter turnout in Holon was very low. However, Shas received five seats on the city council, well beyond its true strength, because the public that uses the religious and educational services it provides went to vote en masse.
Grabbing them youngThe director of a community center in one of the more hard-up neighborhoods of Holon, which has witnessed a considerable process of return to the faith in the past decade, is up in arms, and declares that the phenomenon is "tearing families apart."
"It irks me that they are grabbing the young people," she says. "We invest a lot of effort in rehabilitating delinquent youth. All of a sudden, the teenage boys are disappearing. When you ask one of them 'Where did you go?' he'll say, 'The rabbi told me not to come anymore.'" She claims that residents have stopped coming to the community center and have begun to cloister themselves in the Haredi community, by decree of the local rabbi. "And they want everything for free," she adds.
However, sociologists studying the return-to-religious-Judaism processes, or the history of Shas, or both, dispel the theory that the movement's attractiveness derives from the transportation and hot lunches it offers free of charge. "Nowadays," says Dr. Neri Horowitz of the Mandel School for Educational Leadership, "it is no longer the funding or the transportation. It is a deep and complex process that Sephardi society in Israel is undergoing." This, he says, is a belated response to modernity on the part of the Jews of the East. "They went through the trauma of immigrating, they thought they would succeed in joining the national enterprise and would make their way into modernity through Zionism and the state-religious educational system, but it didn't work."
Horowitz contends that Shas is a social and religious, not a political, movement. "In the 1980s, Shas succeeded in proving its ability to offer another identity option," he explains, adding that the movement has completed its meteoric formative stage and is now engaged in stabilizing its status. This includes establishing its rights and upgrading the educational system and its activists' expertise.
The more the number of small networks increases, the greater the competition among them. They vie for buildings owned by municipalities, and for budgets from the Maayan Hachinuch Hatorani system.
One of the positive outcomes of the competition is the enhancement of the level of education. The desire to meet the standards that are considered the norm outside of the Haredi world is expressed in various ways. Elihu Moyal, the director of the Eili Be'ezri network, which operates in Holon and Tel Aviv, intends to establish a Haredi community center in the network's school in Tel Kabir. To that end, he is trying to enlist the Sacta-Rashi Foundation, a philanthropic organization that generally contributes to educational projects. The Rashi boys' school mentioned above is called a "community school," but this is only half serious: The term "community" was pulled straight out of the lexicon of the greater Israeli society, in order to adapt the school better to parents' aspirations.
The schools operated by Rabbi Varon and via Eili Be'ezri already teach English in first grade and offer studies on a higher level. All of the teachers in Varon's schools have teaching certificates; some have bachelor's degrees. The veteran teachers, he says, were sent to complete their certificate studies after they began working. This certificate is now compulsory, the rabbi adds. This was not always true. The Maayan Hachinuch Hatorani network offers in-service training for teachers and also fields a team of supervisors. The schools also train guidance counselors, who work as volunteers during recess in schools, because there is not yet any authorized salaried positions for them.
Lackluster image of the Shas educational institutions notwithstanding, the schools of Rabbi Varon and of the Eili Be'ezri network in Tel Aviv received good scores in the Meitzav ?(national standardized?) tests in Hebrew and mathematics, averaging above 80. The scores were not affected by the socioeconomic situation of the children.
No impudenceSigalit Levy of Holon, a newly Orthodox woman whose five children are enrolled in a variety of institutions, is less concerned about scholastic achievements. Nor is she bothered by the fact that her children have to be transported to school. She is very happy with the warm attitude they receive from their teachers. But more than that, she is even happier about the respect they accord adults in the schools − and to their mother. "They're not impudent, and they help at home − thank God," she says.
Moshe Vahaba, a newly religious Israel Electric Corporation employee, is the head of the parents' committee of the boys' school that belongs to the Bnei Zion network in Bat Yam, where he lives. He says it is important that "every pupil show respect to the teacher. The pupil learns what a father is and what a child is. Once, they would grab the ear of a child who was acting wildly, and twist it. That doesn't work anymore. Today's young generation is cleverer than our generation was, but there are other ways of punishing. At Bnei Zion, when a teacher walks into the room, the children stand up. The child learns what a teacher is, what a rabbi is. When the teacher talks, they raise their hands. I don't know if that is the case in secular schools." As Vahaba sees it, respect for the teacher neutralizes violence. "If there is no respect for a teacher, why should there be respect for a friend? If the child does not respect his parents, why should he respect others?"
Prof. Menachem Friedman, a leading researcher of the Haredi community, says that parents choose the Shas educational network for exactly the same reasons that well-to-do parents in Tel Aviv and Jerusalem prefer to set up private schools.
"Economically weaker parents also want the best for their children, and try to protect them. They are disturbed by the violence in the schools. They are afraid of not being able to control their children," says Friedman. "They cannot send their children to private schools. Their alternative is Shas."
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text:
A Glimpse Into the Life of an Israeli-Palestinian Couple
What if Israel goes back to barring Israelis from Palestinian Authority territory? What if the trend of anti-Arab legislation continues and the state decides to strip their children, or them, of their citizenship?
The occupation of the West Bank and the Gaza Strip in 1967 united, for the first time since 1948, the Palestinian community that remained within Israel. Families that were divided with the founding of the state came together, friends saw each other after 19 years, refugees in the West Bank and Gaza hastened to revisit their birthplaces (now destroyed, or resettled by Jews ). Palestinians from both sides of the Green Line met at work, school and places of entertainment. This reunification naturally resulted in a number of marriages.
In the early 1990s Palestinians began noticing a drop in the number of requests for citizenship or residency in Israel on the basis of family reunification that received approval.
Before this period the issue of where a couple would live was less important: Israel granted residents of the occupied territories freedom of movement, relatively speaking, and even those whose applications for family reunification in Israel were turned down were not completely cut off from each other.
This changed radically in January 1991, when Israel imposed sweeping restrictions on freedom of movement on the Palestinians living in the West Bank and the Gaza Strip. A system of permits and separation was implemented - between the West Bank and the Strip on one side and between Israel and each of these territories on the other (but affecting only Palestinians, not Jews).
Being in Israel without a permit became a criminal offense, even for someone who had lived there with his family for a number of years. After the start of the second intifada in 2000, it became harder to get a permit even to visit relatives in Israel. Palestinians say that because of these difficulties many families prefer that their children not marry Israeli citizens.
The economic hardship in the West Bank and the Gaza Strip, coupled with the restrictions on movement, splits families: The Israeli spouse lives and works in Israel, with or without the children. There are families in which some of the children have Israeli citizenship and others do not.
There are many such families living in the West Bank and the Strip; some by choice, to get away from the hostile, patronizing atmosphere in Israel, others because they have no choice. In today's hermetically sealed Gaza Strip, the Israeli-born wives of Gaza men must negotiate bureaucratic hurdles, aided by human rights organizations such as Hamoked Center for the Defense of the Individual, for permission to travel between their nuclear families in the Strip and their families of origin inside Israel.
The oversight is less strict in the West Bank, and less strict than it was in the first years of the second intifada.
Israelis who live in the West Bank and the Gaza Strip lose their state social benefits - but not the Israeli Jews who live in the settlements.
"Mixed" Palestinian couples live under a constant cloud of uncertainty and fear of the future. What if Israel goes back to barring Israelis from Palestinian Authority territory? What if the trend of anti-Arab legislation continues and Israel one day decides to strip their children, or them, of their Israeli citizenship?
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text:
NEW to Firefox. How sort IE Bookmarks by Date Added?
User Help for Mozilla Firefox
17 posts • Page 1 of 2 • 1, 2
I'm a newbie to Mozilla Firefox. I got sick and tired of how freaking slow IE 7 and IE8 would take to load. It was ridiculous! It felt like I had dial-up!
So far I am pleased with Firefox. It loads much faster than IE 7 or 8. It loads as fast as my old IE6 used to.
I only have one problem. I imported all my IE Favorites using your import feature. I see you go to Organize bookmarks/View/Sort to sort by different configurations. The problem is, I can't seem to sort all my imported IE bookmarks by Date Added. That's how they were sorted in Internet Explorer, and that's how I know where everything is. After importing them over, they now only sort alphabetically A-Z. I see how you get to the Sort feature, but can't figure out how to sort the IE Bookmarks by Date Added. Can you do this??
Tom B.
you can view by Date Added but it's a session-only feature which reverts to the previous sort-order upon closing Firefox
click Views in the header-bar
click Sort, then pick your poison
click Views in the header-bar in the Organize Bookmarks page
for example
create a folder Feb 2009
sort bookmarks in Sort By Added sort
highlight & select your February bookmarks
in the header-bar, click Organize
click Move, and move them to Feb 2009
actually do not name the folder Feb 2009; the folders in that pattern will be scattered all over hello
something like this may be better; 2009 02 Feb, 2009 07 July
Thank you for all your extremely valuable advice. I should have been more specific. MY fault. I meant, to have my list sorted by date added in the exact same order as they were in IE! I see now that Date Added in this context, is only regarding date added within Firefox, not as it was in the previous browser before being imported. Oh well. Thanks anyway, though.
As long as I'm here, I do have one more problem in here. You know the links toolbar located in the lower right corner of your Task Bar? Next to the Notification Area? And you know how you click and drag your favicon from the address bar, or in this the Location Bar, to the Links Toolbar down below and drop it in there? Then you have the most widely used links at your fingertips down there? OK. Well, whenever I have attemped that in Firefox, the favicon that was in the Location Bar, doesn't appear the Links drop-down, or drop-up menu, in this case. It's that weird icon that looks like a white piece of paper with the upper right corner folded up. You know what I'm talking about? Why is this? How do I get this feature to work properly?
Thank you.
Tom B.
Oh! Also, when I do click on the weird piece of paper looking link in the Links toolbar on the Menu Bar, Firefox browser doesn't open! IE7 does! Weird, huh? I deleted IE8 after I installed Firefox. I didn't even think I had IE 7 installed anymore! It's certainly not in the Add or Remove Programs list. What's going on here?
Tom B.
Links Toolbar? this is the first time I've heard of that.
As for the weird icon . . . . I do have such an icon, but when I hover the cursor over it, it pops up a
"Drag selection here . . ." info balloon, and it's associated with the Clippings software.
Your Taskbar looks very different from mine. I'm running Windows XP Home on a PC.
You access the Links Toolbar by first right clicking on your Taskbar, click on Lock The Taskbaron the drop-down menu to unlock it, go to Toolbars on the Drop-down menu, and click on Links. Then this Links toolbar will appear in the lower right corner of your Taskbar. To place your favorite links in there, you drag the favicon at the beginning of your URL in the location bar, or address bar, to the the Links toolbar down below, and drop it there.
Some people have their Links Toolbar up top. I find it's too cluttered up there already. I prefer it on the Taskbar.
I attempted to paste a cropped Print Screen of my Taskbar with the toolbar for you, and also tried to paste a photo of it in my reply here, but it would not work! How did you paste that photo into your reply to me?
Tom B.
OK, got it, re the Links Toolbar.
press the Prt Screen key to capture a "screenshot"
open Irfanview*, press Ctrl V (to paste), press Ctrl H (to sharpen focus)
crop the image as needed; save to a file
upload the file to an image-host website, such as Photobucket
copy the image-code from Photobucket, paste the code into a forum such as Mozillazine
doesn't necessarily have to be irfanview; I'm just comfortable with it
I think what we're seeing is the status-bar of Firefox; the Taskbar was unwittingly hidden by the popup info balloon.
"copy the image-code from Photobucket, paste the code into a forum such as Mozillazine"
I tried all that but got stuck in Photobucket trying to narrow down where exactly the "image code" was. I went to View on the Menu Bar in the browser and viewed all the code, but don't know enough about code to narrow the image code down. Unless there's a way to view the image code with Photobucket itself.
Anyways, still trying to figure out why when I open a link from the Links Toolbar on the Taskbar why IE 7 still opens? I deleted that, or at least I thought i did. It's no longer in my Add or Remove Programs. When I was using IE7, the links in there were mising their favicons. They still are even though I'm using Firefox. I bet if I can figure out why IE 7 is still opening, and delete the program, it may solve the favicon problem.
Any ideas?
I fixed it. I went to Add/Remove Programs and clicked on the left side Add/Remove Windows Components. I unchecked Internet Explorer and it partially uninstalled.
Still not done.
Then I went to Start/Run and pasted in %windir%\ie7\spuninst\spuninst.exe . Clicked OK on Wizard and IE was COMPLETELY REMOVED from my system.
My favicons came back in the Links Toolbar and Firefox actually opens much quicker.
hover the cursor over the image, a pop-up will pop up
left-click on the yellow IMG Code bar
then right-click on it; click Copy
click Preview
assuming of course that you have already uploaded an image to Photobucket
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Cordillera Vilcanota
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These mountains line the north side of Campa pass which we've just crossed. The pass isn't visible in the photo, but, for the record, it's on the right.
6 June 2011.
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- Home
- Other Makes
- Subaru Impreza WRX & STI
- Subaru Impreza GD 02-07
- Clutches
- Competition Clutch Stage 4 for Subaru WRX '02-'05
The Competition Clutch Stage 4 1620 assembly comes with a double spring, six rivet carriage and is specifically designed to make gear changes smooth in high horsepower applications. This disc complimented by a performance pressure plate provides 250% increase in torque capacity. Competition Clutch recommends a minimum 300 mile break-in for best performance with this set-up. The 1620 Series kit includes a performance pressure plate, a six puck high torque sprung disc with Ceramic buttons, all applicable bearings, and the appropriate alignment tool. Please be aware that this clutch will produce extremely high levels of noise, vibration and harshness. Intended for light street use only.
- Features:
- 250% increase in torque capactiy
- 6-puck ceramic friction surface
- available with or without a 13.47lb lightweight steel flywheel


text:
Stop the presses? 60/Vanity Fair are out with the results of a brand new poll this morning. The questions are about a random as it gets. Who should create a new national anthem? Their poll says Bruce Springsteen tops the list, followed by Dolly Parton. Madonna comes in last place.
Specifically, 22 percent of Americans say they would choose Springsteen, though Parton gets 19 percent of the vote. Stevie Wonder is a close third (18 percent), followed by Bob Dylan (11 percent), John Williams (10 percent), Jay-Z (8 percent), and Madonna (5 percent).
Also (strangely) in this month's poll: Americans would feel more comfortable being a judge than being an airport screener, a U.S. Prez or a dictator; many think their ancestors would be most shocked by people's manners (or lack thereof); and if we could peek in on our own funerals, Americans are most curious about what others would say and, our favorite, how guests would look in the casket.


text:
Seed Advanced Botanicals Dry Skin Facial Moisturizer Lotion 4 oz
Experience truly healthy, glowing skin thanks to the power of antioxidant-rich sunflower, nutrient-rich kelp, soothing cucumber, and firming niacinamide. Superior ingredients, yet avoiding common skin allergens. With 100% natural palmarosa essential oil, perfect for dry skin.
- With Palmarosa essential oil, to help soothe dry skin
- High performing, plant-based botanicals deliver naturally occurring Vitamins K, C, E, and B3
- Helps improve skin elasticity, skin tone, and texture, while helping reduce the signs of aging
- Helps promote formation of collagen, and helps prevents moisture and water loss
- Goes on smooth, leaving skin feeling nourished and hydrated
- Fragrance Free or blends with 100% pure, beneficial essential oils
- Also Available in convenient 12 oz Refills
Check out our full Seed Advanced Botanicals Facial Regimen here, for your very best results.
- Petrochemical-free (free of mineral oil, dimethicone, petrolatum)
- Soy-free, Gluten-free, Dairy-free
- Paraben-free, phthalate-free
- Cruelty-free (never tested on animals, never any ingredients sourced from animals)
- No artificial colors or synthetic fragrance
After cleansing and toning, apply a small amount in a gentle upward motion.
Aqua (Water), E Wax, Helianthus Annuus (Sunflower) Seed Oil, Caprylic/Capric Triglyceride, Cucumis Sativus (Cucumber) Fruit Extract, Glycerin (Vegetable),
Cucumis Sativus (Cucumber) Oil, Niacinamide, Lactobacillus/Kelp Ferment Filtrate, Simmondsia Chinensis (Jojoba) Seed Oil, Sodium Benzoate, Gluconolactone, Glycol Stearate, Alpha Lipoic Acid, Allantoin, Ascorbyl Palmitate (Vitamin C) Ester, Cymbopogon Martini (Palmarosa Essential Oil), and Tocopherol (Natural Vitamin E)


text:
Burpee and "I Can Grow" have
created more than a dozen
community and school
gardens across the U.S.
Burpee Home Gardens is now accepting applications for the 2012 "I Can Grow" Youth Garden Award. Now in its third year, the program continues to support urban school and community gardens in cities across the United States and build awareness of the Burpee Home Gardens brand.
Success stories from last year's program include the Waterford School District near Detroit, whose garden yielded nearly 1,000 pounds of vegetables donated to a nearby hunger relief organization. Plants were made available to Waterford through Bogie Lake Greenhouses in Michigan.
To date, the Burpee Home Gardens "I Can Grow" program has provided more than 8,000 vegetable and herb plants and created 16 community and school gardens nationwide.
"We've seen interest in school vegetable gardens gaining momentum from coast to coast. Burpee Home Gardens recognizes the importance these programs have on young gardeners and their communities," says Carolyn Dixon, national sales manager for Burpee Home Gardens. "The 'I Can Grow' Youth Garden Award increases our ability to educate and inspire the next generation of gardeners, and build further awareness and demand for the Burpee Home Gardens brand."
Next spring, five grand-prize winners will be awarded up to 500 vegetable and herb plants, including the Burpee BOOST collection; 5 gallons of Daniels Plant Food plus one hose-end sprayer; and a Flip Video camera to document the garden's progress throughout the year. The top two entries will also receive $2,500 for gardening supplies and on-site assistance from Burpee Home Gardens experts.
Educators and community garden leaders can BurpeeHomeGardens.com to download the application and review eligibility requirements. All entries must be postmarked by Friday, Dec. 23, 2011. Winners will be announced no later than the week of Feb. 6, 2012.
For more information visit BurpeeHomeGardens.com.


text:
Ashton Kutcher loves being a father
Los Angeles: Hollywood star Ashton Kutcher, who has 18-month-old daughter Wyatt with wife Mila Kunis, says parenthood is the "greatest thing ever".
Ashton Kutcher. Pic/Santa Banta
The 38-year-old actor dotes on Wyatt and can think of nothing better than being a father, reported E! online.
"It's legitimately the greatest thing ever." Kutcher is also excited about his latest venture, new Netflix series "The Ranch", in which he stars alongside former "That '70s Show" co-star Danny Masterson, and the two actors can see a lot of similarities between their new characters and their former alter egos.
Kutcher, who plays failed semi-pro NFL player Colt, said, "I think the magic thing is it has that same feeling of a couple friends hanging out or a couple brothers hanging out."


text:
Brain Drain or Brain Gain? Graduate Migration in Old Industrial Regions - Analysis of the Central Lower Rhine Area, Germany
The influence of tertiary education on the economic development of a region is a topic of special interest and prevalent object of studies and discussions of regional economists. Universities are frequently referred to as 'creative hubs'. Researching universities are generally expected to be one of the key institutions around which growth occurs, determining the direction of regional economic development. Especially the large number of highly-educated graduates is of eminent importance in terms of regional competitive advantages. If graduates remain in the university's region, they form and enrich a highly educated labour force and support knowledge and innovation transfer from the university to the regional economy, networks, and enterprises. Human capital has traditionally been observed to be one of the most important resources of regions and one of the key factors explaining economic growth. In any economic region, gaining insights into the phenomenon of regional graduate migration and the determinants and reasons behind it is highly relevant for regional economic analysis and a prerequisite for policy recommendations. This holds especially true for old industrial regions with structural problems and low economic growth potential - as the Central Lower Rhine Area in North-Rhine-Westphalia, Germany, subject of this study. These regions depend on knowledge and innovation transfer from universities to overcome problems associated with industrial structural changes and market turmoil, and to face problematic trends as the forthcoming demographic development. The research aim of this article is to analyse the migration of graduates in the Central Lower Rhine Area by assessing the regional 'brain flow' originating from the Niederrhine University of Applied Sciences (NR UAS), its only institution of higher education. More detailed objectives concern the assessment of the distribution of migration patterns, migration motives, graduate characteristics influencing the migration decision, and the comparison of actual migration patterns with migration preferences. Our results show that for the Central Lower Rhine Area, the associated regional brain drain resulting from graduate emigration cannot be compensated by extra-regional brain gain. A likely reason for this is a deficit of absorption capacity exhibited by the regional economy: A large proportion of graduates migrate due to difficulties finding an adequate job, or respectively, are attracted by economically better performing regions. Furthermore, econometric analysis identifies certain graduate characteristics influencing the migration decision. Remarkably, the migration decision is only marginally influenced by soft location factors like quality of living, regional image, or recreational amenities. Summarized, the research findings describe, interpret, and explain the regional graduate migration patterns and motives and indicate interesting implications. JEL classification: I 23, O15 Keywords: University Graduates, Migration Patterns, Determinants and Motives, Alumni Network
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|Date of creation:
|Oct 2012
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| Postal: Welthandelsplatz 1, 1020 Vienna, Austria
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text:
Written on: 18/09/2013
We've booked London hotels three times now with HotelDirect and we've always been very happy with the service, especially the Hidden Gems option which has allowed us to stay in hotels we probably would find too expensive normally. I like the fact that they always email you just before you go away to let you know that they've confirmed your booking with the hotel, a nice touch and very reassuring.
A useful option would be to be able to make a special request on the initial booking form about the type of room you'd like but I always email the hotel direct anyway if I need to.


text:
I'm curious, how many people here use/like sporks? The reason I ask is that I have tried such alleged eating tools in disposable form (KFC among other fast food outlets save $$$ by providing only spoons with toothed edges instead of actual forks knives and spoons) and found them useless as either forks or spoons. I ascribe to the belief that no multipurpose tool (with the exception of the legendary P-38 can opener) can do any job as well as a tool designed to do one specific job. A few come close, but IMO, the spork isn't one of them. I brought this question up because, last month, I taught a two day survival course. I had passed out a list to the students covering personal items they should bring which included mess gear. One person purchased a titanium spork with the idea of simplifying her survival gear list. I admit, it probably sounded good to an inexperienced beginner but, like me, she decided halfway through her freeze dried entrée that the reality did not match the advertised hype. I brought extra utensils expecting that someone would forget to bring theirs and so was able to help her out. We agreed that the "tines" don't work at all like a real fork but they do a good job of lowering the capacity of the spoon to hold liquids like soup or broth and make spillage more likely. However, I don't claim a complete knowledge of everything so I'm asking anyone who has a more favorable opinion of sporks to please enlighten me as to why.
BTW, I should add that the student decided to leave her titanium spork in her emergency kit despite it's drawbacks because she can't return it, she can make do with it in an emergency and she spent about $10 on it.


text: Gigliola Staffilani (MIT) will present "Almost Sure Well-posedness for Evolution Equations." Abstract: The center theme of this talk is the effect that randomization on the initial data set has on questions of global well-posedness for a variety of evolution equations. I will start by recalling the notion of Gibbs measure for certain periodic dispersive equations in Hamiltonian form, a work that goes back to Lebowitz-Rose-Speer. I will continue with a short summary of the work of Bourgain, who proved invariance of the Gibbs measure for certain NLS equation and an almost sure global well-posedness as a consequence. I will then continue by illustrating how randomization can be effectively used even when an Hamiltonian structure is not present and as a consequence a Gibbs measure cannot be defined. I will illustrate in this context results proved for example for the Navier-Stokes and wave equations in the supercritical regime.