Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli - Vasoactive Peptide Symposium

O-linked N-acetylglucosaminylation (O-GlcNAcylation) plays a role in many aspects of protein function. Whereas elevated O-GlcNAc levels contribute to diabetes-related end-organ damage, O-GlcNAcylation is also physiologically important. Because proteins that play a role in vascular tone regulation can be O-GlcNAcylated, we hypothesized that O-GlcNAcylation increases vascular reactivity to constrictor stimuli, Aortas front male Sprague-Dawley rats and C57BL/6 mice were incubated for 24 hours with vehicle or PugNAc (O-GlcNAcase inhibitor. 100 mu M). PugNAc incubation significantly increased O-GlcNAc proteins, as determined by Western blot. PugNAc also increased vascular contractions to phenylephrine and serotonin, an effect not observed in the presence of N(omega)-nitro-L-arginine methyl ester or in endothelium-denuded vessels. Acetylcholine-induced relaxation. but not that to sodium nitroprusside, was decreased by PugNAc treatment, an effect accompanied by decreased levels of phosphorylated endothelial nitric oxide synthase (eNOS)(Ser-1177) and Akt(Ser-473). Augmented O-GlcNAcylation increases vascular reactivity to constrictor stimuli, possibly due to its effects oil eNOS expression and activity, reinforcing the concept that O-GlcNAcylation modulates vascular reactivity and may play a role in pathological conditions associated with abnormal vascular function. J Am Soc Hypertens 2008:2(6): 410-417. (C) 2008 American Society of Hypertension. All rights reserved.

Pyk2 mediates increased adrenergic contractile responses in arteries from DOCA-salt mice - Vasoactive Peptide Symposium

The calcium-dependent proline-rich tyrosine kinase (Pyk2), a nonreceptor protein activated by tyrosine phosphorylation, links G protein-coupled receptors to vascular responses. We tested the hypothesis that enhanced vascular reactivity in deoxycorticosterone acetate (DOCA)-salt hypertensive mice is due to increased activation of Pyk2. Aorta and small mesenteric arteries from DOCA-salt and uninephrectomized (UNI) male C57B1/6 mice were used. Systolic blood pressure (mm Hg) was higher in DOCA (126 +/- 3) vs. UNI (100 +/- 4) mice. Vascular responses to phenylephrine (1 nM to 100 mu M) were greater both in aorta and small mesenteric arteries from DOCA-salt than UNI, but treatment with Tyrphostin A-9 (0.1 mu M, Pyk2 inhibitor) abolished the difference among the groups. Pyk2 levels, as well as phospho-Pyk2(Tyr402), paxillin, and phospho-paxillin(Tyr118) were increased in DOCA-salt aorta. Incubation of vessels with Tyrphostin A-9 restored phosphorylation of Pyk2 and paxillin. Increased activation of Pyk2 contributes to increased vascular contractile responses in DOCA-salt mice. J Am Soc Hypertens 2008;2(6): 431-438. (C) 2008 American Society of Hypertension. All rights reserved.

Increased Activation of Stromal Interaction Molecule-1/Orai-1 in Aorta From Hypertensive Rats A Novel Insight Into Vascular Dysfunction

Disturbances in the regulation of cytosolic calcium (Ca(2+)) concentration play a key role in the vascular dysfunction associated with arterial hypertension. Stromal interaction molecules (STIMs) and Orai proteins represent a novel mechanism to control store-operated Ca(2+) entry. Although STIMs act as Ca(2+) sensors for the intracellular Ca(2+) stores, Orai is the putative pore-forming component of Ca(2+) release-activated Ca(2+) channels at the plasma membrane. We hypothesized that augmented activation of Ca(2+) release-activated Ca(2+)/Orai-1, through enhanced activity of STIM-1, plays a role in increased basal tonus and vascular reactivity in hypertensive animals. Endothelium-denuded aortic rings from Wistar-Kyoto and stroke-prone spontaneously hypertensive rats were used to evaluate contractions because of Ca(2+) influx. Depletion of intracellular Ca(2+) stores, which induces Ca(2+) release-activated Ca(2+) activation, was performed by placing arteries in Ca(2+) free-EGTA buffer. The addition of the Ca(2+) regular buffer produced greater contractions in aortas from stroke-prone spontaneously hypertensive rats versus Wistar-Kyoto rats. Thapsigargin (10 mu mol/L), an inhibitor of the sarcoplasmic reticulum Ca(2+) ATPase, further increased these contractions, especially in stroke-prone spontaneously hypertensive rat aorta. Addition of the Ca(2+) release-activated Ca(2+) channel inhibitors 2-aminoethoxydiphenyl borate (100 mu mol/L) or gadolinium (100 mu mol/L), as well as neutralizing antibodies to STIM-1 or Orai-1, abolished thapsigargin-increased contraction and the differences in spontaneous tone between the groups. Expression of Orai-1 and STIM-1 proteins was increased in aorta from stroke-prone spontaneously hypertensive rats when compared with Wistar-Kyoto rats. These results support the hypothesis that both Orai-1 and STIM-1 contribute to abnormal vascular function in hypertension. Augmented activation of STIM-1/Orai-1 may represent the mechanism that leads to impaired control of intracellular Ca(2+) levels in hypertension. (Hypertension. 2009; 53[part 2]: 409-416.)

Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway

Giachini FR, Zemse SM, Carneiro FS, Lima VV, Carneiro ZN, Callera GE, Ergul A, Webb RC, Tostes RC. Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway. Am J Physiol Heart Circ Physiol 296: H489-H496, 2009. First published December 12, 2008; doi:10.1152/ajpheart.00251.2008.-Interleukin-10 (IL-10) is an anti-inflammatory cytokine with protective actions on the vasculature. On the other hand, endothelin ( ET)-1 has potent vasoconstrictor, mitogenic, and proinflammatory activities, which have been implicated in the pathophysiology of a number of cardiovascular diseases. We hypothesized that, in a condition where ET-1 expression is upregulated, i.e., on infusion of TNF-alpha, IL-10 confers vascular protection from ET-1-induced injury. Aortic rings and first-order mesenteric arteries from male C57BL/6 (WT) and IL-10-knockout (IL-10(-/-)) mice were treated with human recombinant TNF-alpha (220 ng.kg(-1).day(-1)) or vehicle (saline) for 14 days. TNF-alpha infusion significantly increased blood pressure in IL-10(-/-), but not WT, mice. TNF-alpha augmented vascular ET-1 mRNA expression in arteries from WT and IL-10(-/-) mice. ET type A (ETA) receptor expression was increased in arteries from IL-10(-/-) mice, and TNF-alpha infusion did not change vascular ETA receptor expression in control or IL-10(-/-) mice. Aorta and mesenteric arteries from TNF-alpha-infused IL-10(-/-) mice displayed increased contractile responses to ET-1, but not the ET type B receptor agonist IRL-1620. The ETA receptor antagonist atrasentan completely abolished responses to ET-1 in aorta and mesenteric vessels, whereas the ERK1/2 inhibitor PD-98059 abrogated increased contractions to ET-1 in arteries from TNF-alpha-infused IL-10(-/-) mice. Infusion of TNF-alpha, as well as knockdown of IL-10 (IL-10(-/-)), induced an increase in total and phosphorylated ERK1/2. These data demonstrate that IL-10 counteracts ET(A)-mediated vascular responses to ET-1, as well as activation of the ERK1/2 pathway.

Decreased cGMP Level Contributes to Increased Contraction in Arteries From Hypertensive Rats Role of Phosphodiesterase 1

Recent evidence suggests that angiotensin II (Ang II) upregulates phosphodiesterase (PDE) 1A expression. We hypothesized that Ang II augmented PDE1 activation, decreasing the bioavailability of cyclic guanosine 3` 5`-monophosphate (cGMP), and contributing to increased vascular contractility. Male Sprague-Dawley rats received mini-osmotic pumps with Ang II (60 ng.min(-1)) or saline for 14 days. Phenylephrine (PE)-induced contractions were increased in aorta (E(max)168%+/- 8% vs 136%+/- 4%) and small mesenteric arteries (SMA; E(max)170%+/- 6% vs 143%+/- 3%) from Ang II-infused rats compared to control. PDE1 inhibition with vinpocetine (10 mu mol/L) reduced PE-induced contraction in aortas from Ang II rats (E(max)94%+/- 12%) but not in controls (154%+/- 7%). Vinpocetine decreased the sensitivity to PE in SMA from Ang II rats compared to vehicle (-log of half maximal effective concentration 5.1 +/- 0.1 vs 5.9 +/- 0.06), but not in controls (6.0 +/- 0.03 vs 6.1 +/- 0.04). Sildenafil (10 mu mol/L), a PDE5 inhibitor, reduced PE-induced maximal contraction similarly in Ang II and control rats. Arteries were contracted with PE (1 mu mol/L), and concentration-dependent relaxation to vinpocetine and sildenafil was evaluated. Aortas from Ang II rats displayed increased relaxation to vinpocetine compared to control (E(max)82%+/- 12% vs 445 +/- 5%). SMA from Ang II rats showed greater sensitivity during vinpocetine-induced relaxation compared to control (-log of half maximal effective concentration 6.1 +/- 0.3 vs 5.3 +/- 0.1). No differences in sildenafil-induced relaxation were observed. PDE1A and PDE1C expressions in aorta and PDE1A expression in SMA were increased in Ang II rats. cGMP production, which is decreased in arteries from Ang II rats, was restored after PDE1 blockade. We conclude that PDE1 activation reduces cGMP bioavailability in arteries from Ang II, contributing to increased contractile responsiveness. (Hypertension. 2011;57[part 2]:655-663.)

Clopidogrel, independent of the vascular P2Y(12) receptor, improves arterial function in small mesenteric arteries from Angll-hypertensive rats

The P2Y(12) receptor antagonist clopidogrel blocks platelet aggregation, improves systemic endothelial nitric oxide bioavailability and has anti-inflammatory effects. Since P2Y(12) receptors have been identified in the vasculature, we hypothesized that clopidogrel ameliorates Angll (angiotensin II)-induced vascular functional changes by blockade of P2Y(12) receptors in the vasculature. Male Sprague Dawley rats were infused with Angll (60 ng/min) or vehicle for 14 days. The animals were treated with clopidogrel (10 mg . kg(-1) of body weight . day(-1)) or vehicle. Vascular reactivity was evaluated in second-order mesenteric arteries. Clopidogrel treatment did not change systolic blood pressure [(mmHg) control-vehicle, 117 +/- 7.1 versus control-clopidogrel, 125 +/- 4.2; Angll vehicle, 197 +/- 10.7 versus Angll clopidogrel, 198 +/- 5.2], but it normalized increased phenylephrine-induced vascular contractions [(%KCI) vehicle-treated, 182.2 +/- 18% versus clopidogrel, 133 +/- 14%), as well as impaired vasodilation to acetylcholine [(%) vehicle-treated, 71.7 +/- 2.2 versus clopidogrel, 85.3 +/- 2.8) in Angll-treated animals. Vascular expression of P2Y(12) receptor was determined by Western blot. Pharmacological characterization of vascular P2Y(12) was performed with the P2Y(12) agonist 2-MeS-ADP [2-(methylthio) adenosine 5`-trihydrogen diphosphate trisodium]. Although 2-MeS-ADP induced endothelium-dependent relaxation [(Emax %) = 71 +/- 12%) as well as contractile vascular responses (Emax % = 83 +/- 12%), these actions are not mediated by P2Y(12) receptor activation. 2-MeS-ADP produced similar vascular responses in control and Angll rats. These results indicate potential effects of clopidogrel, such as improvement of hypertension-related vascular functional changes that are not associated with direct actions of clopidogrel in the vasculature, supporting the concept that activated platelets contribute to endothelial dysfunction, possibly via impaired nitric oxide bioavailability.

Om du vill ha fred, förbered dig på krig : en studie i den militära styrkans betydelse

Denna uppsats kretsar kring att pröva hur en av de främsta företrädarna för den realistiska skolan, förklarar de amerikanska anfallen mot Afghanistan (2001) och Irak (2003). Hans namn är Robert Kagan och uppsatsen syftar till ge en realists tolkning till varför USA handlade som man gjorde. Man måste därför försöka uppfatta världen utifrån USA:s horisont och försöka tolka samt sätta sig in i den amerikanska positionen på den internationella arenan. Problemformuleringarna kretsar kring att få insikt i grundstenarna i Kagans teori, samt hur Kagans grundsyn skiljer sig gentemot den idealistiska. Vidare hur USA:s militära styrka, enligt Kagan, påverkar dess beteende på den internationella arenan, men även hur Kagan ser på USA:s kommande globala engagemang. Robert Kagans bok Om paradiset och makten USA och Europa i den nya världsordningen kommer att utgöra fundamentet i studien. I boken kretsar bl.a. Kagans resonemang kring att USA och Europa distanserar från varandra, men även kring militär styrka. Därför ger boken oss en väldigt bra bild av USA:s position på den internationella arenan. Kagans resonemang vävs sedan ihop med kritik, realism, idealism och geopolitik. Slutsatsen blir att grundstenarna i Kagans resonemang återfinns i den s.k. realismteorin, men även till viss del i geopolitiken. Han sätter stor vikt vid militära medel och ser staterna som de mest betydelsefulla aktörerna, samt ser världen som allmänt hotfull. Han realistiska resonemang grundas på amerikanska spelregler och ledarskap på den internationella arenan. Skillnaden mellan Kagans grundsyn och den idealistiska bottnar främst i idealisternas fokusering på integration mellan stater. Vidare att de sätter tilltro till internationell rätt, samt har ett mer multilateralt förhållningssätt till omvärlden. Kagan menar vidare att starka stater är mer villiga att använda tvång och hot i internationella relationer. De bedömer dessutom hot och risker annorlunda jämfört med svagare stater. Enligt Kagan beter sig USA som en internationell sheriff på den globala arenan och beteendet bottnar i militär styrka. Vidare anser Kagan att USA har haft samma kurs i flera århundraden. USA har expanderat in i Europa och Asien och aldrig dragit sig tillbaka. Man hade redan före den 11 september 2001 fokuserat på Kina som motspelare. Dessutom, menar Kagan, att USA varit villiga att satsa på ny militär teknik, vilken kan förändra krigföringen. Han skriver även att både Clinton och Bushadministrationen varit grundade på att USA är en nödvändig nation, samt att amerikaner vill beskydda och sprida det liberala systemet i världen.

The Long Game: Hamas, The IRA, and the Politics of Radicalization in Palestine and Northern Ireland

The value of a comparative study of the two conflicts stems from a remarkable similarity in the structural organization of political violence by its most influential practitioners: the IRA and Hamas. At the core, I have merely tried my best to approach a beguiling question in a fresh, dynamic way. The stultifying discourse of conflict that serves as lingua franca for the Israeli‐Palestinian issue has largely reduced strategic debate to how best the conflict can be managed – not ended. Prime Minister Benjamin Netanyahu’s focus on “economic peace” and unwillingness to commit to a two‐state solution – the consensus that has governed peacemaking for decades – belies such thinking. The Clinton Administration’s cadre of Mideast negotiators operated amidst the most rapid institutionalization of Palestinian democracy in history ‐ yet remained obsessed with Israeli‐Arab “confidence‐building” measures, doing little to legitimize the gains of Oslo. So long as Palestinians continue to view the creation of Israel as “al‐Nakba” – the catastrophe – whilst successive Israeli governments refuse to grant their aspirations any legitimacy, there can be no progress. Peace requires empathy, a substantial compromise in the context of internecine conflict. The “long war” both conflicts have become mandates an equally expansive, broad‐based and labor‐intensive approach – a demanding process that can only be called The Long Game.

1987 Yearbook

TOC: Clubs & Organizations…18 / Current Events & Music…30 / Faculty & Staff…33 / Activities & Events… / Honors & Graduation…65 / Graduates…75 / Yearbook Credits…111 / A Thank You…112 YEARBOOK COMMITTEE: Project Director, Vincent Banrey; Asst. Project Director, Catherine Whan; Editors (1986): Maricruz Saunders; (1987): Juan Jimenez, GloryAnn Torres; LAYOUT DESIGNERS: Vincent Banrey, Stephanie Bowen, Yvonne Brown, Jacqui Fernandez, Milton Ferreira, Omar Harris, Cornelius Huskins, Juan Jimenez, Wayne Keane, Richard Massie, Victoria Pamias, Richard Provost, Maricruz Saunders, GloryAnn Torres, Pedro Torres, Joan Walker, Catherine Whan. PHOTOGRAPHERS: John Carrero, Young Baek Choi, Randy Fader-Smith, Milton Ferreira, Roger Ince, Juan Jimenez, Umoja Kwanguvu, Seymour Lerman, Clinton Linton, Richard Provost, Jaidee amsinghani, Maricruz Saunders, Frank Tocco, GloryAnn Torres, Catherine Whan, Alan Young. ARTISTS: Cover Design: Madeline Vega; Endsheets: Oscar "DJ Ozzie" Ramirez; Division Pages: Jose Marti; International LaGuardia: Jacqui Fernandez; Illustrations: Richard Massie, Jacqui Fernandez, Madeline Vega. WRITERS: Yasmin Ahmed, Vincent Banrey, Warren Gardner, Juan Jimenez, Umoja Kwanguvu, Luis Merchant, Victoria Pamias, Richard Provost, Christiana Somerville, GloryAnn Torres, Joan Walker, Catherine Whan. SIGNIFICANT OTHERS: Word Processing: Blanca Arbito, Edward Hollins, Catherine Whan. Vincent Banrey Spread: developed by Blanca Arbito, Edward Hollins and GloryAnn Torres, Jacqui Fernandez, Catherine Whan. Creative Consultant: Edward Hollins. Promotions: George Condors. SPECIAL THANKS TO: Frank and Seymour of Classic Studios; Chuck Lindsey, Photo Workshop Instructor; Ted Schiffman of Taylor Publishing Co.; Dan Horn and Thurston Reyes of LaGuardia Theatre; and the Recreation staff. ALAN BERMAN IN MEMORIAM: Sketch, Tom Fink; Alan Speaking, Brian Gallagher; Remembering Dr. Alan Berman, Tuzyline Allan.

Remote presence: supporting deictic gestures through a handheld multi-touch device

This thesis argues on the possibility of supporting deictic gestures through handheld multi-touch devices in remote presentation scenarios. In [1], Clark distinguishes indicative techniques of placing-for and directing-to, where placing-for refers to placing a referent into the addressee’s attention, and directing-to refers to directing the addressee’s attention towards a referent. Keynote, PowerPoint, FuzeMeeting and others support placing-for efficiently with slide transitions, and animations, but support limited to none directing-to. The traditional “pointing feature” present in some presentation tools comes as a virtual laser pointer or mouse cursor. [12, 13] have shown that the mouse cursor and laser pointer offer very little informational expressiveness and do not do justice to human communicative gestures. In this project, a prototype application was implemented for the iPad in order to explore, develop, and test the concept of pointing in remote presentations. The prototype offers visualizing and navigating the slides as well as “pointing” and zooming. To further investigate the problem and possible solutions, a theoretical framework was designed representing the relationships between the presenter’s intention and gesture and the resulting visual effect (cursor) that enables the audience members to interpret the meaning of the effect and the presenter’s intention. Two studies were performed to investigate people’s appreciation of different ways of presenting remotely. An initial qualitative study was performed at The Hague, followed by an online quantitative user experiment. The results indicate that subjects found pointing to be helpful in understanding and concentrating, while the detached video feed of the presenter was considered to be distracting. The positive qualities of having the video feed were the emotion and social presence that it adds to the presentations. For a number of subjects, pointing displayed some of the same social and personal qualities [2] that video affords, while less intensified. The combination of pointing and video proved to be successful with 10-out-of-19 subjects scoring it the highest while pointing example came at a close 8-out-of-19. Video was the least preferred with only one subject preferring it. We suggest that the research performed here could provide a basis for future research and possibly be applied in a variety of distributed collaborative settings.

An overview of domestic aspects in US climate policy

The article shows how domestic aspects influence the United States national and international climate policy. To accomplish the task, the authors analyzes the discussions when Bill Clinton was ruling the country, a time during which global discussions were forwarded. The paper recalls the debate in the Bush administration and the growing polarization since Barack Obama took office.

Oxidative Stress Impairs Vasorelaxation Induced by the Soluble Guanylyl Cyclase Activator BAY 41-2272 in Spontaneously Hypertensive Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Heme-Dependent and Independent Soluble Guanylate Cyclase Activators and Vasodilation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nonnegative trigonometric polynomials

An extremal problem for the coefficients of sine polynomials, which are nonnegative in [0,π] , posed and discussed by Rogosinski and Szego is under consideration. An analog of the Fejér-Riesz representation of nonnegative general trigonometric and cosine polynomials is proved for nonnegative sine polynomials. Various extremal sine polynomials for the problem of Rogosinski and Szego are obtained explicitly. Associated cosine polynomials k n (θ) are constructed in such a way that { k n (θ) } are summability kernels. Thus, the L p , pointwise and almost everywhere convergence of the corresponding convolutions, is established. © 2002 Springer-Verlag New York Inc.