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1
Viau-Guay, Anabelle, and Christine Hamel. "L’utilisation de la vidéo pour développer la compétence réflexive des enseignants: une recension des écrits." Swiss Journal of Educational Research 39, no. 1 (September 13, 2018): 129–46. http://dx.doi.org/10.24452/sjer.39.1.5003.
Анотація:
Considérant l’intérêt suscité par l’utilisation de la vidéo en formation à l’enseignement (initiale ou continue), notamment pour développer la compétence réflexive, cet article présente un état des connaissances scientifiques relatives à ce sujet. L’article vise à décrire l’utilisation faite de la vidéo en formation (contexte de formation, acteur apparaissant sur la vidéo et tâche réflexive proposée aux apprenants), le niveau de réflexivité atteint par les participants ainsi que le lien éventuel entre ce niveau et certaines caractéristiques de ces dispositifs de formation. Une recension de la littérature de type «synthèse narrative empirique» a été réalisée. Vingt articles avec évaluation par les pairs publiés entre 2004 et 2015 (février) ont été analysés, notamment pour caractériser le niveau de réflexivité atteint selon la typologie de Jay et Johnson (2002). Les résultats indiquent notamment que, dans plus de la moitié des articles recensés, les participants ont atteint un niveau de réflexivité critique.
2
Lewis, Francois, and Patrick Plante. "Création et évaluation d’un prototype de jeu sérieux dédié à l’amélioration de la lecture chez les enfants présentant des symptômes de dyslexie." Médiations et médiatisations 1, no. 1 (October 10, 2018): 72–88. http://dx.doi.org/10.52358/mm.v1i1.58.
Анотація:
Cet article, qui est la synthèse d’un mémoire de maîtrise, a principalement trois objectifs. Le premier objectif consiste à développer une méthodologie de conception de jeu sérieux éducatif (JSÉ) permettant spécifiquement d’aider les enfants qui éprouvent des difficultés en lecture ou qui présentent des symptômes associés à la dyslexie développementale. Le deuxième objectif consiste à réaliser un prototype Alpha du jeu, et le troisième objectif consiste à évaluer la cohérence du scénario ainsi que l’ergonomie du jeu par un test utilisateur.
Les travaux de Green et Bavellier (2012) indiquent que jouer à des jeux vidéo d’action améliore l’attention et l’apprentissage. Tandis que la recherche de Franceschini, Gori, Ruffino, Molteni et Facoetti (2013) démontre que l’utilisation d’un jeu vidéo d’action sans dimension sérieuse améliore la concentration et la vitesse de lecture des enfants dyslexiques.
Dans le cadre de cette recherche, nous croyons que l’ajout d’exercices de rééducation en lecture à un jeu vidéo d’action améliorera son efficacité pour l’apprentissage de la lecture des enfants présentant des symptômes associés à la dyslexie.
Les résultats de l’expérimentation portant sur la cohérence du scénario ainsi que sur l’ergonomie du jeu sont prometteurs. Des modifications devront être effectuées, notamment au niveau de la navigation et de l’optimisation des missions du jeu.
3
Rioufreyt, Thibaut. "La transcription outillée en SHS. Un panorama des logiciels de transcription audio/vidéo." Bulletin of Sociological Methodology/Bulletin de Méthodologie Sociologique 139, no. 1 (April 24, 2018): 96–133. http://dx.doi.org/10.1177/0759106318762455.
Анотація:
Cet article propose d’esquisser un panorama des principaux logiciels à la disposition du transcripteur permettant de lui faciliter le travail et de garantir la qualité des transcriptions. L’objectif visé est double. Il s’agit d’une part de mettre à disposition une synthèse des outils existants (24 logiciels sont traités) et des caractéristiques techniques principales de chacun d’entre eux. Il existe en effet une offre pléthorique en la matière, au point qu’il est difficile de s’y retrouver pour l’utilisateur lambda. D’autre part, cet article ne propose pas simplement une liste d’outils mais neuf critères simples permettant de choisir le logiciel le plus adapté aux besoins de sa recherche, à son corpus et à ses compétences : rôle de la problématique et de l’objet de recherche, spécificité du terrain, plate-forme sur laquelle fonctionne l’outil, disponibilité du logiciel, mode de représentation des données, articulation des supports, format des données, outils de lecture et de traitement du son, fonctions d’analyse proposées par ces logiciels.
4
Boillat, Alain. "La « diégèse » dans son acception filmologique. Origine, postérité et productivité d’un concept." Cinémas 19, no. 2-3 (June 29, 2009): 217–45. http://dx.doi.org/10.7202/037554ar.
Анотація:
Résumé Popularisée par l’usage extensif (et de ce fait quelque peu galvaudé) qu’en fit Gérard Genette en narratologie littéraire, la « diégèse » constitue certes la notion vedette des filmologues, mais elle fut pendant plusieurs décennies le lieu d’une certaine occultation de son champ originel en raison des appropriations non référencées qu’en firent poéticiens et sémiologues. En suivant le fil historiographique des différents emplois et acceptions de cette notion associée à Étienne Souriau dans l’espace francophone, le présent article propose un état des lieux qui, par la petite porte d’une entrée terminologique, entend s’interroger sur les conséquences théoriques des variations que le terme « diégèse » a subies et, plus généralement, sur la question du statut octroyé au courant filmologique. En examinant les différentes implications de la définition première, qu’il s’agit parfois de délester de sens dont on l’a ultérieurement investie, cet article tente de montrer que le cadre dans lequel la diégèse a été conceptualisée contient des potentialités théoriques qui n’ont pas encore été épuisées aujourd’hui, et qui convergent avec certains champs d’études récents (comme celui de la logique des mondes possibles) dont l’application au cinéma n’a probablement jamais été aussi pertinente qu’à l’ère des images de synthèse, des univers virtuels et des environnements de jeux vidéo.
5
Gauthier, Geneviève, Simonne Couture, and Christina St-Onge. "Jugement évaluatif : confrontation d’un modèle conceptuel à des données empiriques." Pédagogie Médicale 19, no. 1 (February 2018): 15–25. http://dx.doi.org/10.1051/pmed/2019002.
Анотація:
Contexte : Le recours au jugement des évaluateurs est de plus en plus présent en contexte d’utilisation d’une approche de formation par compétences ; toutefois sa subjectivité a souvent été critiquée. Plus récemment, les perspectives variées des évaluateurs ont commencé à être traitées comme source d’information importante et les recherches sur le jugement évaluatif (rater cognition) se sont multipliées. Lors d’une synthèse d’études empiriques sur le sujet, Gauthier et al. ont proposé un modèle conceptuel englobant une série de résultats concourants. Objectif : Dans le cadre de cette étude à devis mixte concomitant imbriqué (quan/QUAL), nous confrontons ce modèle théorique à des données empiriques issues d’entrevues semi-dirigées d’évaluateurs hors pair. Cette analyse vise à valider le modèle théorique et déterminer son utilité pour mieux comprendre le jugement évaluatif. Méthodes : Les verbatim d’entrevues audio-enregistrées de 11 participants observant et jugeant la vidéo d’une résidente lors d’une consultation avec un patient standardisé ont été codés en utilisant le modèle théorique comme arbre de codage. Les données quantitatives portant sur l’occurrence et la co-occurrence de chaque code, en général et par individu, ont été extraites et analysées. Résultats : Les données corroborent que l’ensemble des neuf mécanismes du modèle conceptuel sont bien représentés dans le discours des évaluateurs. Toutefois, les résultats suggèrent que le modèle avec ses neuf mécanismes indépendants ne rend pas justice à la complexité des interactions entre certains mécanismes et qu’un des mécanismes, le concept personnel de compétence, semble soutenir une grande partie des autres mécanismes.
6
Khalloufi-Mouha, Faten. "Utilisation du modèle de classe inversée pour l’introduction des Séries de Fourier en première année universitaire." ITM Web of Conferences 39 (2021): 01011. http://dx.doi.org/10.1051/itmconf/20213901011.
Анотація:
Dans ce papier, nous décrivons la mise en place d’une expérience de classe inversée pour l’introduction de la notion de série de Fourier à des étudiants de première année universitaire en sciences de l’informatique de la faculté des sciences de Bizerte en Tunisie. Dans l’objectif d’explorer l’impact de ce dispositif pédagogique sur l’apprentissage des mathématiques et en se plaçant dans le cadre de la théorie commognitive, nous avons cherché à étudier l’appropriation par les étudiants, des routines identifiées dans les capsules vidéos qui introduisent le contenu mathématique visé. Sur le plan pédagogique, les premiers résultats font apparaitre une hétérogénéité importante chez les étudiants qui a amené l’enseignante que nous sommes à mettre en place une méthode hybride qui consiste à introduire une séance de synthèse qui a suivi la visualisation des capsules vidéos. Sur le plan didactique, nous avons étudié l’individualisation par les étudiants des trois types de routines associées aux séries de Fourier: les routines de traitement graphique, les routines de traitement calculatoire et les routines de justification et de preuve.
7
Shirasawa, Yuichi, Fumitaka Ikomi, and Toshio Ohhashi. "Physiological roles of endogenous nitric oxide in lymphatic pump activity of rat mesentery in vivo." American Journal of Physiology-Gastrointestinal and Liver Physiology 278, no. 4 (April 1, 2000): G551—G556. http://dx.doi.org/10.1152/ajpgi.2000.278.4.g551.
Анотація:
Physiological roles of endogenous nitric oxide (NO) in the lymphatic pump activity of rat mesenteries in vivo were evaluated using an intravital video microscope system. Changes in the pumping frequency ( F), the end diastolic diameter (EDD), and the end systolic diameter (ESD) of the mesenteric lymph microvessels were measured with the microscope system and then the pump flow index (PFI) was calculated. A 15-min superfusion of 30 μM N ω-nitro-l-arginine methyl ester (l-NAME) in the mesenteries caused significant increases of F and PFI and a significant decrease of the EDD and ESD. Simultaneous superfusion of 1 mM l-arginine with 30 μMl-NAME produced a significant reversal of thel-NAME-mediated increase of F and decrease of ESD. A 15-min superfusion of 100 μM aminoguanidine caused no significant effects on F, EDD, and ESD of the mesenteric lymph vessels in vivo. These findings suggest that endogenous NO has physiologically modulated the lymphatic pump activity in rat mesentery in vivo and that the production and release of NO may be mediated by constitutive NO synthase but not by inducible NO synthase.
8
Samsonov, Alexander N., and Khristina V. Samoilova. "High speed video recording system on a chip for detonation jet engine testing." MATEC Web of Conferences 158 (2018): 01028. http://dx.doi.org/10.1051/matecconf/201815801028.
Анотація:
This article describes system on a chip development for high speed video recording purposes. Current research was started due to difficulties in selection of FPGAs and CPUs which include wide bandwidth, high speed and high number of multipliers for real time signal analysis implementation. Current trend of high density silicon device integration will result soon in a hybrid sensor-controller-memory circuit packed in a single chip. This research was the first step in a series of experiments in manufacturing of hybrid devices. The current task is high level syntheses of high speed logic and CPU core in an FPGA. The work resulted in FPGA-based prototype implementation and examination.
9
Iftikhar, Hassan, and Yan Luximon. "The syntheses of static and mobile wayfinding information: an empirical study of wayfinding preferences and behaviour in complex environments." Facilities 40, no. 7/8 (March 4, 2022): 452–74. http://dx.doi.org/10.1108/f-06-2021-0052.
Анотація:
Purpose The efficient delivery of environmental information to wayfinders in complex environments is a challenge for information designers. Wayfinding tasks can be quite strenuous and frustrating in the visual absence of dedicated wayfinding information. This study aims to explore the behaviour regarding the use of wayfinding information by navigators in complex environments. Design/methodology/approach An experiment has been conducted in which participants have performed wayfinding tasks in a spatially complex university campus. The participants were instructed to use the think-aloud protocol during the experiment. The behaviour has been recorded using the head-mounted video recorder (GoPro), mobile phone screen (audio\video) recorder and interview. Twelve university students have been selected based on the equal level of spatial ability using the Santa Barbara Sense of Direction scale. Each participant performed three wayfinding tasks to locate the unknown locations inside the campus using a mobile wayfinding application and other information sources. Findings The results of this study demonstrated significant behavioural preferences in acquiring wayfinding information. Most of the participants synthesised the static and mobile wayfinding information sources, while some preferred only the static ones. Gender differences have also been found for planning and route finding. This study recommends the syntheses of static and mobile wayfinding information for designing an efficient institutional wayfinding system. Research limitations/implications The sample size has been kept small because of the qualitative exploration of the wayfinding behaviour regarding the wayfinding information syntheses behaviour. The experiment findings can be further explored with larger data set and controlled behavioural metrics. This study can help understand the user requirements in facilities management for spatially complex institutional environments. Practical implications The current findings can be further used to develop a framework for wayfinding information designers to assist them in understanding the current practices and incorporate them for improving institutional wayfinding systems. The management of the offered facilities within an institution can be further improved to make the space more efficient by saving users’ time and efforts. Originality/value Information syntheses or symbiosis of environmental information with the beacon-based digital wayfinding system is a new concept. This study explores the potential of such information syntheses for enhancing the legibility of complex institutional environments.
10
Lamping, Kathryn G., Daniel W. Nuno, Edward G. Shesely, Nobuyo Maeda, and Frank M. Faraci. "Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide synthase-deficient mice." American Journal of Physiology-Heart and Circulatory Physiology 279, no. 4 (October 1, 2000): H1906—H1912. http://dx.doi.org/10.1152/ajpheart.2000.279.4.h1906.
Анотація:
Previous studies have demonstrated that responses to endothelium-dependent vasodilators are absent in the aortas from mice deficient in expression of endothelial nitric oxide synthase (eNOS −/− mice), whereas responses in the cerebral microcirculation are preserved. We tested the hypothesis that in the absence of eNOS, other vasodilator pathways compensate to preserve endothelium-dependent relaxation in the coronary circulation. Diameters of isolated, pressurized coronary arteries from eNOS −/−, eNOS heterozygous (+/−), and wild-type mice (eNOS +/+ and C57BL/6J) were measured by video microscopy. ACh (an endothelium-dependent agonist) produced vasodilation in wild-type mice. This response was normal in eNOS +/− mice and was largely preserved in eNOS −/− mice. Responses to nitroprusside were also similar in arteries from eNOS +/+, eNOS +/−, and eNOS −/− mice. Dilation to ACh was inhibited by N G-nitro-l-arginine, an inhibitor of NOS in control and eNOS −/− mice. In contrast, trifluoromethylphenylimidazole, an inhibitor of neuronal NOS (nNOS), decreased ACh-induced dilation in arteries from eNOS-deficient mice but had no effect on responses in wild-type mice. Indomethacin, an inhibitor of cyclooxygenase, decreased vasodilation to ACh in eNOS-deficient, but not wild-type, mice. Thus, in the absence of eNOS, dilation of coronary arteries to ACh is preserved by other vasodilator mechanisms.
11
Sielaff, Hendrik, Seiga Yanagisawa, Wayne D. Frasch, Wolfgang Junge, and Michael Börsch. "Structural Asymmetry and Kinetic Limping of Single Rotary F-ATP Synthases." Molecules 24, no. 3 (January 30, 2019): 504. http://dx.doi.org/10.3390/molecules24030504.
Анотація:
F-ATP synthases use proton flow through the FO domain to synthesize ATP in the F1 domain. In Escherichia coli, the enzyme consists of rotor subunits γεc10 and stator subunits (αβ)3δab2. Subunits c10 or (αβ)3 alone are rotationally symmetric. However, symmetry is broken by the b2 homodimer, which together with subunit δa, forms a single eccentric stalk connecting the membrane embedded FO domain with the soluble F1 domain, and the central rotating and curved stalk composed of subunit γε. Although each of the three catalytic binding sites in (αβ)3 catalyzes the same set of partial reactions in the time average, they might not be fully equivalent at any moment, because the structural symmetry is broken by contact with b2δ in F1 and with b2a in FO. We monitored the enzyme’s rotary progression during ATP hydrolysis by three single-molecule techniques: fluorescence video-microscopy with attached actin filaments, Förster resonance energy transfer between pairs of fluorescence probes, and a polarization assay using gold nanorods. We found that one dwell in the three-stepped rotary progression lasting longer than the other two by a factor of up to 1.6. This effect of the structural asymmetry is small due to the internal elastic coupling.
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Kasztan, Małgorzata, Agnieszka Piwkowska, Ewelina Kreft, Dorota Rogacka, Irena Audzeyenka, Mirosława Szczepanska-Konkel, and Maciej Jankowski. "Extracellular purines' action on glomerular albumin permeability in isolated rat glomeruli: insights into the pathogenesis of albuminuria." American Journal of Physiology-Renal Physiology 311, no. 1 (July 1, 2016): F103—F111. http://dx.doi.org/10.1152/ajprenal.00567.2015.
Анотація:
Purinoceptors (adrengeric receptors and P2 receptors) are expressed on the cellular components of the glomerular filtration barrier, and their activation may affect glomerular permeability to albumin, which may ultimately lead to albuminuria, a well-established risk factor for the progression of chronic kidney disease and development of cardiovascular diseases. We investigated the mechanisms underlying the in vitro and in vivo purinergic actions on glomerular filter permeability to albumin by measuring convectional albumin permeability ( Palb) in a single isolated rat glomerulus based on the video microscopy method. Primary cultured rat podocytes were used for the analysis of Palb, cGMP accumulation, PKG-Iα dimerization, and immunofluorescence. In vitro, natural nucleotides (ATP, ADP, UTP, and UDP) and nonmetabolized ATP analogs (2-meSATP and ATP-γ-S) increased Palb in a time- and concentration-dependent manner. The effects were dependent on P2 receptor activation, nitric oxide synthase, and cytoplasmic guanylate cyclase. ATP analogs significantly increased Palb, cGMP accumulation, and subcortical actin reorganization in a PKG-dependent but nondimer-mediated route in cultured podocytes. In vivo, 2-meSATP and ATP-γ-S increased Palb but did not significantly affect urinary albumin excretion. Both agonists enhanced the clathrin-mediated endocytosis of albumin in podocytes. A product of adenine nucleotides hydrolysis, adenosine, increased the permeability of the glomerular barrier via adrenergic receptors in a dependent and independent manner. Our results suggest that the extracellular nucleotides that stimulate an increase of glomerular Palb involve nitric oxide synthase and cytoplasmic guanylate cyclase with actin reorganization in podocytes.
13
Métais, Caroline, Jianyi Li, Jian Li, Michael Simons, and Frank W. Sellke. "Effects of coronary artery disease on expression and microvascular response to VEGF." American Journal of Physiology-Heart and Circulatory Physiology 275, no. 4 (October 1, 1998): H1411—H1418. http://dx.doi.org/10.1152/ajpheart.1998.275.4.h1411.
Анотація:
The effects of coronary artery disease (CAD) on human coronary microvascular responses to vascular endothelial growth factor (VEGF) and the alterations of the myocardial expressions of VEGF and its flk-1 and flt-1 receptors were examined in 48 patients. Microvascular studies were performed in vitro with video microscopy. The expressions of VEGF and its receptors were examined using Northern analysis of total mRNA, and the expressions of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were examined by RT-PCR. VEGF and hepatocyte growth factor (HGF) caused potent relaxations of microvessels. These responses were reduced in the presence of N G-nitro-l-arginine and the tyrosine kinase inhibitor genistein or in microvessels from patients with CAD. Relaxations to substance P and sodium nitroprusside were similar in both groups. The substance P response was abolished in the presence of N G-nitro-l-arginine. The expression of VEGF and its receptors and the expression of cNOS and iNOS were not altered in patients with CAD. In conclusion, VEGF and HGF elicit the release of nitric oxide through activation of tyrosine kinase receptors. CAD is associated with reduced vascular responses to both VEGF and HGF; this is not likely due to a reduced expression of VEGF or flt-1 or flk-1 receptors and not due to a generalized endothelium dysfunction despite the presence of mild hypercholesterolemia in these patients with CAD. These findings may have important implications regarding the efficacy of endogenous and exogenous VEGF in patients with risk factor for CAD.
14
Stepp, David W., and Jefferson C. Frisbee. "Augmented adrenergic vasoconstriction in hypertensive diabetic obese Zucker rats." American Journal of Physiology-Heart and Circulatory Physiology 282, no. 3 (March 1, 2002): H816—H820. http://dx.doi.org/10.1152/ajpheart.00695.2001.
Анотація:
This study examined skeletal muscle microvessel reactivity to constrictor stimuli in obese (OZR) versus lean Zucker rats (LZR). Gracilis arteries from both rat groups were isolated, cannulated with glass micropipettes, and viewed via television microscopy. Changes in vessel diameter were measured with a video micrometer. Arterial constriction to norepinephrine was elevated in OZR versus LZR, although vasoconstrictor reactivity to endothelin and angiotensin II was unaltered. Differences in reactivity between vessels of LZR and OZR were not explained by the loss of either endothelial nitric oxide synthase or β-adrenergic receptor function. Reactivity of in situ cremasteric arterioles of OZR to norepinephrine was elevated versus LZR. Treatment with prazosin increased the diameter of in vivo gracilis arteries of OZR to levels determined in LZR and also normalized blood pressure in OZR. These results suggest that the constrictor reactivity of skeletal muscle microvessels in OZR is heightened in response to α-adrenergic stimuli and that development of diabetes in OZR may be associated with impaired skeletal muscle perfusion and hypertension due to microvessel hyperreactivity in response to sympathetic stimulation.
15
Tu, Tsung-Hsi, Chih-Chang Chang, Jau-Ching Wu, Li-Yu Fay, Wen-Cheng Huang, and Henrich Cheng. "Resection of uncovertebral joints and posterior longitudinal ligament for cervical disc arthroplasty." Neurosurgical Focus 42, videosuppl1 (January 2017): V2. http://dx.doi.org/10.3171/2017.1.focusvid.16380.
Анотація:
The most commonly accepted indications for cervical disc arthroplasty (CDA) are 1- and 2-level cervical disc herniation or spondylosis causing radiculopathy or myelopathy that is refractory to medical management. Unlike anterior cervical discectomy and fusion (ACDF), which eliminates motion, CDA aims to restore the physiological range of motion of the indexed joint. Thus, the effect of indirect decompression gained by the insertion of a sufficiently large interbody graft and incorporation into arthrodesis after ACDF cannot be duplicated for CDA. For patients undergoing CDA, during extreme flexion/extension or rotation, the exiting nerve roots might be impinged by inadequately decompressed foraminal osteophytes. Therefore, the authors advocate generous decompression, including resection of the posterior longitudinal ligament (PLL) and bilateral uncovertebral joints (UVJs), even in the asymptomatic side. This video demonstrates full dural expansion and enlarged neuroforamen after removal of the PLL and UVJs. Venous hemorrhage encountered during foraminotomy can always be controlled by cottonoid packing or hemostatic agents. Also, the endplates of the surrounding vertebral bodies were meticulously prepared for parallel insertion of the ProDisc-C Nova (DePuy Synthes Spine) artificial disc. Please note that the ProDisc-C Nova is currently not available on the US market.The video can be found here: https://youtu.be/XUo34j6WFYs.
16
Andrén, Mats. "The Social World Within Reach: Intersubjective Manifestations of Action Completion." Cognitive Semiotics 4, no. 1 (August 1, 2012): 139–66. http://dx.doi.org/10.1515/cogsem.2012.4.1.139.
Анотація:
Abstract This is a study of the intersubjective recognizability of the ‘proper’ accomplishment of children’s actions: in particular, how the status of actions as properly completed is often actively made recognizable through speech and various modulations of bodily movement. In addition to analyzing how children do this in a number of cases, I argue that these manifestations of action completion are often strongly dependent on typified conventional knowledge, and that conventionality on the side of the signified is a neglected issue in gesture research. The data consists of video recordings of four Swedish children between 24-30 months of age who interact with their parents at home. The analysis is framed in ideas about intersubjectivity and action drawn from Alfred Schutz and Adam Kendon in particular, but also others. These theoretical syntheses are a substantial part of the contribution of this paper.
17
Wickley, Peter J., Toshiya Shiga, Paul A. Murray, and Derek S. Damron. "Propofol Decreases Myofilament Ca2+Sensitivity via a Protein Kinase C–, Nitric Oxide Synthase–dependent Pathway in Diabetic Cardiomyocytes." Anesthesiology 104, no. 5 (May 1, 2006): 978–87. http://dx.doi.org/10.1097/00000542-200605000-00014.
Анотація:
Background The authors' objective was to assess the role of protein kinase C (PKC) and nitric oxide synthase (NOS) in mediating the effects of propofol on diabetic cardiomyocyte contractility, intracellular free Ca2+ concentration ([Ca2+]i), and myofilament Ca2+ sensitivity. Methods Freshly isolated ventricular myocytes were obtained from normal and diabetic rat hearts. [Ca2+]i and cell shortening were simultaneously measured in electrically stimulated, ventricular myocytes using fura-2 and video-edge detection, respectively. Actomyosin adenosine triphosphatase activity and troponin I (TnI) phosphorylation were assessed in [32P]orthophosphate-labeled myofibrils. Western blot analysis was used to assess expression of PKC and NOS. Results Propofol (10 microM) decreased peak shortening by 47 +/- 6% with little effect on peak [Ca2+]i (92 +/- 5% of control) in diabetic myocytes. Maximal actomyosin adenosine triphosphatase activity was reduced by 43 +/- 7% and TnI phosphorylation was greater (32 +/- 6%) in diabetic myofibrils compared with normal. Propofol reduced actomyosin adenosine triphosphatase activity by 17 +/- 7% and increased TnI phosphorylation in diabetic myofibrils. PKC inhibition prevented the propofol-induced increase in TnI phosphorylation and decrease in shortening. Expression of PKC-alpha, PKC-delta, PKC-epsilon, and constitutive NOS were up-regulated and inducible NOS was expressed in diabetic cardiomyocytes. NOS inhibition attenuated the propofol-induced decrease in shortening. Conclusion Myofilament Ca2+ sensitivity and, to a lesser extent, peak [Ca2+]i are decreased in diabetic cardiomyocytes. Increases in PKC and NOS expression in combination with TnI phosphorylation seem to contribute to the decrease in [Ca2+]i and myofilament Ca2+ sensitivity. Propofol decreases [Ca2+]i and shortening via a PKC-, NOS-dependent pathway.
18
Fritsche, Regina, Thorsten Schwerte, and Bernd Pelster. "Nitric oxide and vascular reactivity in developing zebrafish,Danio rerio." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 6 (December 1, 2000): R2200—R2207. http://dx.doi.org/10.1152/ajpregu.2000.279.6.r2200.
Анотація:
We used a newly developed digital motion analysis video technique to study the effects of nitric oxide (NO) and epinephrine on the early larval arterial and venous vasculature of zebrafish. Application of the NO donor sodium nitroprusside resulted in a significant increase in both the venous and arterial vessel diameters, whereas N G-nitro-l-arginine methyl ester caused a significant decrease in the same diameters. Thus our results show that both the venous and arterial vasculature of the 5- and 6-day-old zebrafish larvae are influenced by endogenously produced NO. By use of immunohistochemistry, NO synthase immunoreactivity was demonstrated in endothelial cells of the dorsal vein. Local application of epinephrine onto the dorsal artery had no effect on vessel diameter. However, if the embryos were preincubated with N ω-nitro-l-arginine methyl ester, addition of epinephrine resulted in a significant reduction in both arterial and venous vessel diameters. Thus this study provides increasing evidence that before a functional autonomic innervation of the peripheral vascular system, vascular tone in larval tissue is regulated by a complex interaction of vasoactive substances that are produced locally by vascular endothelial cells.
19
Seidel, Ismael, André Beims Bräscher, Bruno George De Moraes, Marcio Monteiro, and José Luis Güntzel. "Analysis of Pel Decimation and Technology Choices to Reduce Energy on SAD Calculation." Journal of Integrated Circuits and Systems 9, no. 1 (December 28, 2014): 48–59. http://dx.doi.org/10.29292/jics.v9i1.388.
Анотація:
As the number of pixels per frame tends to increase in new high definition video coding standards such as HEVC and VP9, pel decimation appears as a viable means of increasing the energy efficiency of Sum of Absolute Differences (SAD) calculation. First, we analyze the quality costs of pel decimation using a video coding software. Then we present and evaluate two VLSI architectures to compute the SAD of 4x4 pixel blocks: one that can be configured with 1:1, 2:1 or 4:1 sampling ratios and a non-configurable one, to serve as baseline in comparisons. The architectures were synthesized for 90nm, 65nm and 45nm standard cell libraries assuming both nominal and Low-Vdd/High-Vt (LH) cases for maximum and for a given target throughput. The impacts of both subsampling and LH on delay, power and energy efficiency are analyzed. In a total of 24 syntheses, the 45nm/LH configurable SAD architecture synthesis achieved the highest energy efficiency for target throughput when operating in pel decimation 4:1, spending only 2.05pJ for each 4×4 block. This corresponds to about 13.65 times less energy than the 90nm/nominal configurable architecture operating in full sampling mode and maximum throughput and about 14.77 times less than the 90nm/nominal non-configurable synthesis for target throughput. Aside the improvements achieved by using LH, pel decimation solely was responsible for energy reductions of 40% and 60% when choosing 2:1 and 4:1 subsampling ratios, respectively, in the configurable architecture. Finally, it is shown that the configurable architecture is more energy-efficient than the non-configurable one.
20
Miura, S., D. Fukumura, I. Kurose, H. Higuchi, H. Kimura, Y. Tsuzuki, T. Shigematsu, J. Y. Han, M. Tsuchiya, and H. Ishii. "Roles of ET-1 in endotoxin-induced microcirculatory disturbance in rat small intestine." American Journal of Physiology-Gastrointestinal and Liver Physiology 271, no. 3 (September 1, 1996): G461—G469. http://dx.doi.org/10.1152/ajpgi.1996.271.3.g461.
Анотація:
The major objective of this study was to investigate whether endothelin-1 (ET-1) plays a significant role in endotoxin-induced microcirculatory disturbances of the intestinal mucosa. Submucosal microvessels of the rat ileum were observed by intravital microscopy with a high-speed video camera system. Preceding the apparent intestinal mucosal damage, red blood cell (RBC) velocity was significantly decreased 30 min after endotoxin treatment in both arterioles and venules. The number of leukocytes sticking to submucosal venules was significantly increased at 30 min. BQ-123, an ETA-receptor antagonist, significantly attenuated the decrease in RBC velocity and also prevented an increase in leukocyte sticking as well as the subsequent mucosal damage induced by endotoxin. The ET-1 concentrations began to be elevated in plasma at 15 min and in the mucosa at 30 min and subsequently further increased in a time-dependent manner. A significant decrease in calcium-dependent nitric oxide synthase activity and significant increases in the concentration of platelet-activating factor (PAF) were demonstrated in the intestinal mucosa after endotoxin treatment. BQ-123 also significantly attenuated these changes. We concluded that the increased ET-1 production in intestinal mucosa induced by endotoxin stimulation could lead to leukocyte sticking and decreased RBC velocity in the intestinal microcirculatory beds via ETA receptors, which are closely related to increased production of PAF and decreased synthesis of constitutive nitric oxide.
21
McCullough, W. T., D. M. Collins, and M. L. Ellsworth. "Arteriolar responses to extracellular ATP in striated muscle." American Journal of Physiology-Heart and Circulatory Physiology 272, no. 4 (April 1, 1997): H1886—H1891. http://dx.doi.org/10.1152/ajpheart.1997.272.4.h1886.
Анотація:
Blood flow and its distribution must be appropriately regulated to ensure that perfusion is matched to local tissue demands. We investigated the role of ATP in triggering a conducted alteration in arteriolar diameter in the Saran-covered cheek pouch retractor muscle of anesthetized hamsters (n = 60). Vascular responses were observed using in vivo video microscopy upstream from the site of micropressure application of ATP (10(-8)-10(-4) M) either into the lumen or just outside the wall of first- and second-order arterioles. The role of nitric oxide (NO) in the vascular responses to ATP was determined by inhibiting NO synthase activity with N(omega)-nitro-L-arginine methyl ester (L-NAME) with and without coadministration of an excess of L-arginine. Intraluminal application of ATP led to a concentration-dependent vasodilation, which was conducted upstream along the arteriole. The dilatory response was blocked by systemic pretreatment with L-NAME and was maintained in the presence of an excess of L-arginine. In contrast, ATP introduced extraluminally resulted in a conducted vasoconstrictor response that was enhanced by pretreatment with L-NAME. The dilator response to intraluminal ATP, in the context of ATP release from erythrocytes under conditions associated with decreased supply relative to demand, supports a role for the erythrocyte in communicating local tissue needs to the vasculature, enabling the appropriate matching of oxygen supply to demand.
22
Lamping, K. G. "Response of native and stimulated collateral vessels to serotonin." American Journal of Physiology-Heart and Circulatory Physiology 272, no. 5 (May 1, 1997): H2409—H2415. http://dx.doi.org/10.1152/ajpheart.1997.272.5.h2409.
Анотація:
Previous studies suggest that collateral vessels constrict in response to serotonin. The objective of these studies was to directly measure responses of native and stimulated collateral vessels 30-400 microns in diameter to serotonin and to determine the mechanisms involved in responses to serotonin. Serotonin was suffused onto the left ventricle of dogs, and microvascular diameters were measured with computer-controlled stroboscopic illumination coupled to a microscope-video system. Stimulated collateral vessels and arterioles in collateral-dependent myocardium were measured after Ameroid constriction of the left circumflex artery. Noncollateral and native collateral vessels were examined in dogs without a constrictor. Serotonin produced dose-dependent dilation of noncollateral vessels that was decreased in native collateral vessels, stimulated collateral vessels, and vessels in collateral-dependent myocardium. Dilation in response to nitroprusside was similar in all groups. Dilation in response to serotonin was enhanced by inhibition of 5-hydroxytryptamine (5-HT)2 receptors with ketanserin and blocked by nonselective 5-HT1 and 5-HT2 receptors with methiothepin. Inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine decreased dilation in response to serotonin. Thus collaterals and arterioles in collateral-dependent myocardium are less sensitive to the dilating effect of serotonin. Responses to serotonin involve a balance between dilation mediated by 5-HT1 receptors and constriction mediated by 5-HT2 receptors.
23
Hudetz, Antal G., James D. Wood, and John P. Kampine. "7-Nitroindazole Impedes Erythrocyte Flow Response to Isovolemic Hemodilution in the Cerebral Capillary Circulation." Journal of Cerebral Blood Flow & Metabolism 20, no. 2 (February 2000): 220–24. http://dx.doi.org/10.1097/00004647-200002000-00002.
Анотація:
The role of nitric oxide (NO) in the mechanism of hemodilution-induced cerebral hyperemia is unclear. Based on findings in hypoxemia, the authors hypothesize that NO of neuronal origin contributes to an increase in velocity of erythrocytes in the cerebral microcirculation during anemia produced by isovolemic hemodilution. The change in erythrocyte velocity in cerebrocortical capillaries was assessed by intravital fluorescence video microscopy. A closed cranial window was implanted over the frontoparietal cortex of barbiturate-anesthetized, ventilated adult rats. Erythrocytes were labeled in vitro with fluorescein isothiocyanate and infused intravenously, and their velocity in subsurface capillaries was measured by frame-to-frame image tracking. Arterial blood was withdrawn in increments of 2 mL and replaced by serum albumin; arterial blood pressure was maintained at control level with an infusion of methoxamine. Erythrocyte velocity increased progressively, reaching 215% of baseline, as arterial hematocrit was reduced from 45% to 17%. Pretreatment of a separate group of rats with 7-nitroindazole (20 mg/kg intraperitoneally), a relatively selective inhibitor of neuronal NO synthase, abolished the increase in velocity at hematocrits greater than 20%, but the maximum velocity attained at the lowest hematocrit was similar to that in the control group. The results suggest that NO from neuronal source may contribute to the increase in capillary erythrocyte flow during moderate isovolemic hemodilution.
24
Ishimura, Naoko, Katsuyasu Kitaguchi, Kazuyuki Tatsumi, and Hitoshi Furuya. "Nitric Oxide Involvement in Hypoxic Dilation of Pial Arteries in the Cat." Anesthesiology 85, no. 6 (December 1, 1996): 1350–56. http://dx.doi.org/10.1097/00000542-199612000-00016.
Анотація:
Background The reactivity of cerebral arteries to different stimuli varies according to vessel size. Whether nitric oxide mediates hypoxic vasodilation is controversial. The authors considered this question by measuring the diameter of pial arteries and arterioles with or without exposure to the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Methods The cranial window technique, combined with microscopic video recording, was used in an experiment involving 20 cats anesthetized with fentanyl and midazolam. The diameters of pial arteries and arterioles were measured under the following conditions: (1) normoxia (PaO2 > 100 mmHg); (2) hypoxia (PaO2 < 45 mmHg); (3) normoxia with L-NAME infusion; and (4) hypoxia with L-NAME infusion. Changes in vessel diameter were analyzed with respect to artery size. Results Under hypoxic conditions, arteries and arterioles smaller than 200 microns were dilated significantly (P < 0.05). In arterioles smaller than 200 microns, L-NAME attenuated this hypoxic vasodilation (P < 0.05). In contrast, under normoxic conditions, L-NAME caused significant vasoconstriction in arteries larger than 100 microns but not in arteries smaller than 100 microns. Conclusions Arteries and arterioles smaller than 200 microns are dilated by hypoxia, and nitric oxide contributes to this process. Nitric oxide synthesis may also be related to the regulation of resting vascular tone in arteries larger than 100 microns.
25
Kinosita, Kazuhiko, Ryohei Yasuda, Hiroyuki Noji, and Kengo Adachi. "A rotary molecular motor that can work at near 100% efficiency." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 355, no. 1396 (April 29, 2000): 473–89. http://dx.doi.org/10.1098/rstb.2000.0589.
Анотація:
A single molecule of F 1 –ATPase is by itself a rotary motor in which a central γ–subunit rotates against a surrounding cylinder made of α 3 β 3 –subunits. Driven by the three βs that sequentially hydrolyse ATP, the motor rotates in discrete 120° steps, as demonstrated in video images of the movement of an actin filament bound, as a marker, to the central γ–subunit. Over a broad range of load (hydrodynamic friction against the rotating actin filament) and speed, the F motor produces a constant torque of ca . 40 pN nm. The work done in a 120° step, or the work per ATP molecule, is thus ca . 80 pN nm. In cells, the free energy of ATP hydrolysis is ca . 90 pN nm per ATP molecule, suggesting that the F 1 motor can work at near 100% efficiency. We confirmed in vitro that F 1 indeed does ca . 80 pN nm of work under the condition where the free energy per ATP is 90 pN nm. The high efficiency may be related to the fully reversible nature of the F 1 motor: the ATP synthase, of which F 1 is a part, is considered to synthesize ATP from ADP and phosphate by reverse rotation of the F motor. Possible mechanisms of F 1 rotation are discussed.
26
Chang, Chih-Chang, Jau-Ching Wu, Peng-Yuan Chang, Mei-Yin Yeh, Yi-Hsuan Kuo, Li-Yu Fay, Tsung-Hsi Tu, Wen-Cheng Huang, and Henrich Cheng. "Stepwise illustration of teeth-fixation semi-constrained cervical disc arthroplasty." Neurosurgical Focus 42, videosuppl1 (January 2017): V4. http://dx.doi.org/10.3171/2017.1.focusvid.16389.
Анотація:
There are many kinds of artificial discs available for cervical disc arthroplasty (CDA), with various designs of fixation and articulation mechanisms. Each of these designs has different features and theoretically fits most optimally in selected types of patients. However, there has been insufficient literature to guide individualized selection among these CDA devices. Since CDA aims to restore the joint function rather than arthrodesis, tailor-made size, shape, and mechanical properties should be taken into account for each candidate's target disc. Despite several large-scale prospective randomized control trials that have demonstrated the effectiveness and durability of CDA for up to 8 years, none of them involved more than one kind of artificial disc. In this video the authors present detailed steps and technical aspects of the newly introduced ProDisc-C Vivo (DePuy Synthes Spine), which has the same ball-and-socket design for controlled, predictable motion as the ProDisc-C. The newly derived teeth fixation provides high primary stability and multilevel capability by avoidance of previous keel-related limitations and complications (e.g., split vertebral fracture). Please note that the ProDisc-C Vivo is currently not available on the US market.The authors present the case of a 53-year-old woman who had symptoms of both radiculopathy and myelopathy caused by a large, calcified disc herniation at C4–5. There was no improvement after 4 months of medical treatment and rehabilitation. A single-level CDA was successfully performed with the ProDisc-C Vivo, and her symptoms were completely ameliorated afterward. The follow-up images demonstrated preservation of motion at the indexed level.The video can be found here: https://youtu.be/4DSES1xgvQU.
27
Roberts, Rachael R., Joel C. Bornstein, Annette J. Bergner, and Heather M. Young. "Disturbances of colonic motility in mouse models of Hirschsprung's disease." American Journal of Physiology-Gastrointestinal and Liver Physiology 294, no. 4 (April 2008): G996—G1008. http://dx.doi.org/10.1152/ajpgi.00558.2007.
Анотація:
Mutations in genes encoding members of the GDNF and endothelin-3 (Et-3) signaling pathways can cause Hirschsprung's disease, a congenital condition associated with an absence of enteric neurons in the distal gut. GDNF signals through Ret, a receptor tyrosine kinase, and Et-3 signals through endothelin receptor B (Ednrb). The effects of Gdnf, Ret, and ET- 3 haploinsufficiency and a null mutation in ET- 3 on spontaneous motility patterns in adult and developing mice were investigated. Video recordings were used to construct spatiotemporal maps of spontaneous contractile patterns in colon from postnatal and adult mice in vitro. In Ret+/− and ET- 3+/− mice, which have normal numbers of enteric neurons, colonic migrating motor complexes (CMMCs) displayed similar properties under control conditions and following inhibition of nitric oxide synthase (NOS) activity to wild-type mice. In the colon of Gdnf+/− mice and in the ganglionic region of ET- 3−/− mice, there was a 50–60% reduction in myenteric neuron number. In Gdnf+/− mice, CMMCs were present, but abnormal, and the proportion of myenteric neurons containing NOS was not different from that of wild-type mice. In the ganglionic region of postnatal ET- 3−/− mice, CMMCs were absent, and the proportion of myenteric neurons containing NOS was over 100% higher than in wild-type mice. Thus impairments in spontaneous motility patterns in the colon of Gdnf+/− mice and in the ganglionic region of ET- 3−/− mice are correlated with a reduction in myenteric neuron density.
28
Gleeson, T. T., and J. M. Harrison. "Muscle composition and its relation to sprint running in the lizard Dipsosaurus dorsalis." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 255, no. 3 (September 1, 1988): R470—R477. http://dx.doi.org/10.1152/ajpregu.1988.255.3.r470.
Анотація:
Iguanid lizards exhibit considerable intraspecific variation in several aspects of their muscle composition. To determine the relationship of this variation to the variation in locomotor performance, running speeds of 20 male desert iguanas (Dipsosaurus dorsalis) of similar mass were measured from video recordings of animals as they sprinted down a 4.9-m runway maintained at 40 degrees C, the preferred body temperature of Dipsosaurus. Mean sprint speed ranged from 2.2 to 4.2 m/s. Selected muscles from these animals were then analyzed histochemically for fiber type size and composition, and the activities of citrate synthase, pyruvate kinase, and creatine kinase were measured. Muscle fiber cross-sectional areas were highly correlated within individuals, in three leg muscles and across all three fiber types, so that individuals could be characterized as possessing large or small fibers relative to the sample mean. Activities of all three enzymes also covaried within individuals so that individual lizards could be characterized as possessing high or low leg muscle catabolic capacity. There existed a significant and inverse relationship between fiber cross-sectional areas and muscle enzyme activities so that individuals with small muscle fibers tended to have higher catabolic capacities. Approximately 25-30% of the variation in mean sprint running speed could be predicted by variation in muscle fiber areas alone. The use of muscle fiber areas and snout vent length as independent variables in a multiple-regression equation explained approximately 50% of the sprint-running variation.(ABSTRACT TRUNCATED AT 250 WORDS)
29
Vincent, M. A., E. J. Barrett, J. R. Lindner, M. G. Clark, and S. Rattigan. "Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin." American Journal of Physiology-Endocrinology and Metabolism 285, no. 1 (July 2003): E123—E129. http://dx.doi.org/10.1152/ajpendo.00021.2003.
Анотація:
We examined the effects of inhibiting nitric oxide synthase with Nω-nitro-l-arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU·min-1·kg-1) significantly increased hindlimb total blood flow (0.69 ± 0.02 to 1.22 ± 0.11 ml/min, P < 0.05), glucose uptake (0.27 ± 0.05 to 0.95 ± 0.08 μmol/min, P < 0.05), 1-MX uptake (5.0 ± 0.5 to 8.5 ± 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 ± 1.6 to 15.0 ± 1.2 video intensity units, P < 0.05). Addition of l-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% ( P < 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.
30
Birk, Michael, Ewa Baum, Jenia Kouchek Zadeh, Caroline Manicam, Norbert Pfeiffer, Andreas Patzak, Johanna Helmstädter, et al. "Angiotensin II Induces Oxidative Stress and Endothelial Dysfunction in Mouse Ophthalmic Arteries via Involvement of AT1 Receptors and NOX2." Antioxidants 10, no. 8 (August 2, 2021): 1238. http://dx.doi.org/10.3390/antiox10081238.
Анотація:
Angiotensin II (Ang II) has been implicated in the pathophysiology of various age-dependent ocular diseases. The purpose of this study was to test the hypothesis that Ang II induces endothelial dysfunction in mouse ophthalmic arteries and to identify the underlying mechanisms. Ophthalmic arteries were exposed to Ang II in vivo and in vitro to determine vascular function by video microscopy. Moreover, the formation of reactive oxygen species (ROS) was quantified and the expression of prooxidant redox genes and proteins was determined. The endothelium-dependent artery responses were blunted after both in vivo and in vitro exposure to Ang II. The Ang II type 1 receptor (AT1R) blocker, candesartan, and the ROS scavenger, Tiron, prevented Ang II-induced endothelial dysfunction. ROS levels and NOX2 expression were increased following Ang II incubation. Remarkably, Ang II failed to induce endothelial dysfunction in ophthalmic arteries from NOX2-deficient mice. Following Ang II incubation, endothelium-dependent vasodilation was mainly mediated by cytochrome P450 oxygenase (CYP450) metabolites, while the contribution of nitric oxide synthase (NOS) and 12/15-lipoxygenase (12/15-LOX) pathways became negligible. These findings provide evidence that Ang II induces endothelial dysfunction in mouse ophthalmic arteries via AT1R activation and NOX2-dependent ROS formation. From a clinical point of view, the blockade of AT1R signaling and/or NOX2 may be helpful to retain or restore endothelial function in ocular blood vessels in certain ocular diseases.
31
Kumar, Anand, Bhanu Paladugu, Joel Mensing, Aseem Kumar та Joseph E. Parrillo. "Nitric oxide-dependent and -independent mechanisms are involved in TNF-α-induced depression of cardiac myocyte contractility". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, № 5 (травень 2007): R1900—R1906. http://dx.doi.org/10.1152/ajpregu.00146.2006.
Анотація:
Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This response is mediated, in part, through circulating TNF-α-induced, nitric oxide-dependent, depression of basal myocyte contractility. Other mechanisms of early myocardial dysfunction involving decreased response to adrenergic stimulation may exist. This study evaluated the presence and nitric oxide dependence of impaired adrenergic response to TNF-α in in vitro cardiac myocytes. The contraction of electrically paced neonatal rat cardiac myocytes in tissue culture was quantified using a closed-loop video tracking system. TNF-α induced depression of baseline contractility over the first 20 min of cardiac myocyte exposure. This effect was blocked by N-methyl-arginine (NMA), a nitric oxide synthase inhibitor, in all studies. Contractile and cAMP response to increasing concentrations of isoproterenol was deficient in cardiac myocytes exposed to TNF-α regardless of the presence of NMA. In contrast, increasing concentrations of forskolin (a direct stimulant of adenylate cyclase) and dibutyryl cAMP (a metabolically active membrane-soluble analog of cAMP) completely reversed TNF-α-mediated depression, though only in the presence of NMA. Forskolin-stimulated cAMP generation remained intact regardless of NMA. Increasing concentrations of exogenous calcium chloride, unlike other inotropic agents, corrected TNF-α-mediated defects of contractility independent of the presence of NMA. These data suggest that TNF-α exposure is associated with a second nitric oxide-independent but calcium-dependent early depressant mechanism that is manifested by reduced contractile and cAMP response to β-adrenergic stimulation.
32
Roberts, Rachael R., Jessica F. Murphy, Heather M. Young, and Joel C. Bornstein. "Development of colonic motility in the neonatal mouse-studies using spatiotemporal maps." American Journal of Physiology-Gastrointestinal and Liver Physiology 292, no. 3 (March 2007): G930—G938. http://dx.doi.org/10.1152/ajpgi.00444.2006.
Анотація:
Colonic migrating motor complexes (CMMCs) are spontaneous, anally propagating constrictions, repeating every 3–5 min in mouse colon in vitro. They are regulated by the enteric nervous system and may be equivalent to mass movement contractions. We examined postnatal development of CMMCs and circular muscle innervation to gain insight into mechanisms regulating transit in the maturing colon. Video recordings of mouse colon in vitro were used to construct spatiotemporal maps of spontaneous contractile patterns. Development of nitric oxide synthase (NOS) and cholinergic nerve terminals in the circular muscle was examined immunohistochemically. In adults, CMMCs appeared regularly at 4.6 ± 0.9-min intervals ( n = 5). These intervals were reduced by inhibition of NOS (2.7 ± 0.2 min; n = 5; P < 0.05). CMMCs were abolished by tetrodotoxin ( n = 4). CMMCs at postnatal day (P)10 were indistinguishable from adult. At birth and P4, CMMCs were absent. Instead, small constrictions that propagated both orally and anally, “ripples,” were seen. Ripples were unaffected by tetrodotoxin or inhibition of NOS and were present in Ret −/− mice (which lack enteric neurons) at embryonic day 18.5. In P6 mice, only ripples were seen in control, but NOS inhibition induced CMMCs ( n = 8). NOS terminals were abundant in the circular muscle at birth; cholinergic terminals were sparse but were common by P10. In mouse, myogenic ripples are the only mechanism available to produce colonic transit at birth. At P6, neural circuits that generate CMMCs are present but are inhibited by tonic activity of nitric oxide. Adult patterns appear by P10.
33
Okazaki, Kayoko, Sumihiko Seki, Noriaki Kanaya, Jun-ichi Hattori, Noritsugu Tohse, and Akiyoshi Namiki. "Role of Endothelium-derived Hyperpolarizing Factor in Phenylephrine-induced Oscillatory Vasomotion in Rat Small Mesenteric Artery." Anesthesiology 98, no. 5 (May 1, 2003): 1164–71. http://dx.doi.org/10.1097/00000542-200305000-00019.
Анотація:
Background In small mesenteric arteries, endothelium-derived hyperpolarizing factor (EDHF) in addition to endothelium-derived relaxing factors (EDRFs) including NO plays an important role in acetylcholine-induced vasodilation. It has been reported that EDRFs play an important role in alpha(1)-adrenoceptor agonist-induced oscillatory vasomotion and in limiting vasoconstrictor response to the agonists; however, contribution of EDHF to the alpha(1)-agonist-induced oscillation is unknown. Methods Rat small mesenteric arteries were isolated and cannulated at each end with a glass micropipette. The vessels were immersed in a bath (37 degrees C) containing physiologic saline solution. Changes in vessel diameter were measured using an optical density video detection system. Results Denudation of the endothelium and inhibition of NO synthesis caused a leftward shift in the concentration-response relation for phenylephrine in the mesenteric arteries, whereas inhibition of cyclooxygenase by indomethacin had no effect. Blockade of Ca2+-activated K+ (K(Ca)) channels by charybdotoxin and apamin caused a further leftward shift in the concentration-response relation in the vessels pretreated with Nomega-nitro-l-arginine methylester and indomethacin. Phenylephrine at concentrations higher than 10(-6) m caused endothelium-dependent oscillatory vasomotion, which was reduced but not abolished after combined inhibition of the cyclooxygenase and NO synthase pathways. However, the K(Ca) channel blockers completely abolished the remaining component of oscillation. Conclusions Endothelially-derived NO is an important modulator of sustained agonist-induced vasoconstriction. NO, as well as endothelially-derived cyclooxygenase products and EDHF, also contribute significantly to phenylephrine-induced oscillatory vasomotion.
34
Blackwell, Katherine A., Joseph P. Sorenson, Darcy M. Richardson, Leslie A. Smith, Osamu Suda, Karl Nath, and Zvonimir S. Katusic. "Mechanisms of aging-induced impairment of endothelium-dependent relaxation: role of tetrahydrobiopterin." American Journal of Physiology-Heart and Circulatory Physiology 287, no. 6 (December 2004): H2448—H2453. http://dx.doi.org/10.1152/ajpheart.00248.2004.
Анотація:
Oxidative stress has been implicated as an important mechanism of vascular endothelial dysfunction induced by aging. Previous studies suggested that tetrahydrobiopterin (BH4), an essential cofactor of endothelial NO synthase, could be a molecular target for oxidation. We tested the hypothesis that oxidative stress, in particular oxidation of BH4, may contribute to attenuation of endothelium-dependent relaxation in aged mice. Vasomotor function of isolated carotid arteries was studied using a video dimension analyzer. Vascular levels of BH4 and its oxidation products were measured via HPLC. In aged mice (age, 95 ± 2 wk), endothelium-dependent relaxation to ACh (10−5 to 10−9 M) as well as endothelium-independent relaxation to the NO donor diethylammonium ( Z)-1-( N, N-diethylamino)diazen-1-ium -1,2-diolate (DEA-NONOate, 10−5 to 10−9 M) were significantly reduced compared with relaxation detected in young mice (age, 23 ± 0.5 wk). Incubation of aged mouse carotid arteries with the cell-permeable SOD mimetic Mn(III)tetra(4-benzoic acid)porphyrin chloride normalized relaxation to ACh and DEA-NONOate. Furthermore, production of superoxide anion in aorta and serum levels of amyloid P component, which is the murine analog of C-reactive protein, was increased in old mice. In aorta, neither the concentration of BH4 nor the ratio of reduced BH4 to the oxidation products were different between young and aged mice. Our results demonstrate that in mice, aging impairs relaxation mediated by NO most likely by increased formation of superoxide anion. Oxidation of BH4 does not appear to be an important mechanism underlying vasomotor dysfunction in aged mouse arteries.
35
Wu, Liping, Manish M. Tiwari, Kurt J. Messer, Joseph H. Holthoff, Neriman Gokden, Robert W. Brock, and Philip R. Mayeux. "Peritubular capillary dysfunction and renal tubular epithelial cell stress following lipopolysaccharide administration in mice." American Journal of Physiology-Renal Physiology 292, no. 1 (January 2007): F261—F268. http://dx.doi.org/10.1152/ajprenal.00263.2006.
Анотація:
The mortality rate for septic patients with acute renal failure is extremely high. Since sepsis is often caused by lipopolysaccharide (LPS), a model of LPS challenge was used to study the development of kidney injury. Intravital video microscopy was utilized to investigate renal peritubular capillary blood flow in anesthetized male C57BL/6 mice at 0, 2, 6, 10, 18, 24, 36, and 48 h after LPS administration (10 mg/kg ip). As early as 2 h, capillary perfusion was dramatically compromised. Vessels with continuous flow were decreased from 89 ± 4% in saline controls to 57 ± 5% in LPS-treated mice ( P < 0.01), and vessels with intermittent flow were increased from 6 ± 2% to 31 ± 5% ( P < 0.01). At 2 h, mRNA for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were elevated 50- and 27-fold, respectively, suggesting that vascular inflammation is an early event that may contribute to capillary dysfunction. By 10 h, vessels with no flow increased from 5 ± 2% in saline controls to 19 ± 3% in LPS-treated mice ( P < 0.05). By 48 h, capillary function was returning toward control levels. The decline in functional capillaries preceded the development of renal failure and was paralleled by induction of inducible nitric oxide synthase in the kidney. Using NAD(P)H autofluorescence as an indicator of cellular redox stress, we found that tubular cell stress was highly correlated with the percentage of dysfunctional capillaries ( r 2 = 0.8951, P < 0.0001). These data show that peritubular capillary dysfunction is an early event that contributes to tubular stress and renal injury.
36
Jain, B., I. Rubinstein, R. A. Robbins, and J. H. Sisson. "TNF-alpha and IL-1 beta upregulate nitric oxide-dependent ciliary motility in bovine airway epithelium." American Journal of Physiology-Lung Cellular and Molecular Physiology 268, no. 6 (June 1, 1995): L911—L917. http://dx.doi.org/10.1152/ajplung.1995.268.6.l911.
Анотація:
Airway epithelial cells can be modulated by cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta that are released from inflammatory cells. Since ciliary motility is an important host defense function of airway epithelium, we hypothesized that cytokines, released from lung macrophages, upregulate ciliary motility. To test this hypothesis, ciliary beat frequency (CBF) was measured by video microscopy in cultured ciliated bovine bronchial epithelial cells (BBECs) incubated for 24 h with bovine alveolar macrophage-conditioned medium (AM-CM). Exposure to AM-CM resulted in a delayed (> or = 2 h) increase in CBF that was maximal after 24 h exposure (13.70 +/- 0.43 for AM-CM vs. 9.44 +/- 0.24 Hz for medium; P < 0.0001) and which was largely blocked by either anti-TNF-alpha or anti-IL-1 beta antibodies. rTNF-alpha or rIL-1 beta similarly increased CBF, which could be blocked by preincubation with either anti-rTNF-alpha or anti-rIL-1 beta antibodies. Preincubation of BBECs with actinomycin D or dexamethasone also blocked rTNF-alpha- and rIL-1 beta-induced cilia stimulation, suggesting that new protein synthesis is required for cytokine-induced upregulation of CBF. Since NO is known to upregulate ciliary motility and cytokines can induce NO synthase (NOS), we hypothesized that TNF-alpha and IL-1 beta increase CBF by inducing NOS in BBECs. The cilia stimulatory effects of TNF-alpha or IL-1 beta were inhibited by NG-monomethyl-L-arginine, a competitive NOS inhibitor, and restored by the addition of either L-arginine, an NOS substrate, or sodium nitroprusside, an NO donor.(ABSTRACT TRUNCATED AT 250 WORDS)
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Katusic, Z. S. "Endothelial L-arginine pathway and regional cerebral arterial reactivity to vasopressin." American Journal of Physiology-Heart and Circulatory Physiology 262, no. 5 (May 1, 1992): H1557—H1562. http://dx.doi.org/10.1152/ajpheart.1992.262.5.h1557.
Анотація:
Experiments were designed to characterize the mechanism of vasopressin action in small arteries of brain stem and cerebrum and to determine the role of L-arginine pathway in reactivity of these vessels to vasopressin. Secondary branches of canine basilar arteries (425 +/- 63 microns ID, n = 6) and middle cerebral arteries (466 +/- 30 microns ID, n = 6) were dissected and mounted on glass microcannulas in organ chambers. Changes in intraluminal diameter of the pressurized arteries were measured using a video dimension analyzer. Vasopressin caused endothelium-dependent relaxation in the brain stem arteries [-log half-maximal effective concentration (EC50) = 9.2 +/- 0.4, n = 5] but not in the branches of middle cerebral arteries. In contrast, bradykinin caused identical endothelium-dependent relaxations in arteries of both regions (-log EC50 = 8.0 +/- 0.2, n = 5, and 7.7 +/- 0.1, n = 4 for brain stem and cerebrum, respectively). Relaxations to vasopressin (but not to bradykinin) were reduced in the presence of V1-vasopressinergic antagonist [1-(beta-mercapto-beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5-Tyr(Me)AVP;10(-7) M], pertussin toxin (100 ng/ml), and NG-monomethyl-L-arginine (L-NMMA; 10(-4) M). The inhibitory effect of L-NMMA was prevented by L-arginine (3 x 10(-4) M) but not D-arginine (3 x 10(-4) M). These studies suggest that vasopressin causes endothelium-dependent relaxation in canine brain stem arteries. The effect of the neuropeptide appears to be mediated by activation of endothelial V1-vasopressinergic receptors coupled to nitric oxide synthase. This signal transduction pathway is not functional in endothelial cells of branches of middle cerebral arteries.
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Park, Kyung W., Hai B. Dai, Edward Lowenstein, Olivier N. Kocher, and Frank W. Sellke. "Isoflurane- and Halothane-mediated Dilation of Distal Bronchi in the Rat Depends on the Epithelium." Anesthesiology 86, no. 5 (May 1, 1997): 1078–87. http://dx.doi.org/10.1097/00000542-199705000-00011.
Анотація:
Background Respiratory epithelium releases substance(s) that can modulate bronchoconstriction in response to constrictive agonists and enhance bronchodilation in response to certain bronchodilators. The hypothesis that the bronchodilatory effect of isoflurane and halothane depends on the epithelium was tested in rat distal bronchial segments. Methods Wistar rat bronchial segments of the fourth order (diameter approximately 100 microns) were dissected. After preconstriction with 5-hydroxytryptamine, each bronchial segment was exposed to increasing concentrations of 0% to 3% isoflurane or 0% to 3% halothane under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine, after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system. Results Both isoflurane and halothane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 40% +/- 11% [mean +/- SD] dilation for 3% isoflurane and 57% +/- 10% dilation for 3% halothane). For both anesthetics, bronchodilation was significantly but incompletely attenuated by epithelial rubbing (12% +/- 7% dilation for 3% isoflurane [P < 0.01] and 31% +/- 10% dilation for 3% halothane [P < 0.01]), by pretreatment with indomethacin (20% +/- 8% dilation for 3% isoflurane [P < 0.02] and 21% +/- 9% dilation for 3% halothane [P < 0.001]), or by L-NNA (9% +/- 7% dilation for 3% isoflurane [P < 0.005] and 39% +/- 12% dilation for 3% halothane [P < 0.05]). Epithelial rubbing did not impair nitroprusside-associated bronchodilation. Conclusions Isoflurane- and halothane-mediated bronchodilation depends at least partially on the epithelium and may involve both a prostanoid and nitric oxide in distal rat bronchi.
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Lahaie, Isabelle, Pierre Hardy, Xin Hou, Haroutioun Hasséssian, Pierre Asselin, Pierre Lachapelle, Guillermina Almazan та ін. "A novel mechanism for vasoconstrictor action of 8-isoprostaglandin F2α on retinal vessels". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274, № 5 (1 травня 1998): R1406—R1416. http://dx.doi.org/10.1152/ajpregu.1998.274.5.r1406.
Анотація:
Using a video-imaging technique, we characterized the effects of 8-isoprostaglandin F2α(8-iso-PGF2α) on retinal vasculature from piglets. 8-Iso-PGF2α potently contracted (EC50 = 5.9 ± 0.5 nM) retinal vessels. These effects were completely antagonized by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase blocker CGS-12970, the thromboxane receptor antagonist L-670596, and the putative inhibitor of the non-voltage-dependent receptor-operated Ca2+ pathway SKF-96365; constrictor effects of 8-iso-PGF2α were also partly attenuated by the ETA-receptor blocker BQ-123 and an inhibitor of endothelin-converting enzyme, phosphoramidon, but was negligibly affected by the L-type voltage-gated Ca2+ channel blocker nifedipine. Correspondingly, 8-iso-PGF2αelicited endothelin release from retinal preparations, which was markedly reduced by SKF-96365. 8-Iso-PGF2α also increased thromboxane production in the retina and cultured endothelial cells, but not on retinovascular smooth muscle cells; these effects of 8-iso-PGF2α were blocked by indomethacin, CGS-12970, SKF-96365, and EGTA, but not by nifedipine. 8-Iso-PGF2α also increased Ca2+ transients in retinal endothelial cells, which were inhibited by SKF-96365 and EGTA, but not by nifedipine, whereas in smooth muscle cells U-46619, but not 8-iso-PGF2α, stimulated a rise in Ca2+ transients. Finally, H2O2+ FeCl2 (in vitro) and anoxia followed by reoxygenation (in vivo) stimulated formation of 8-iso-PGF2α in the retina. In conclusion, 8-iso-PGF2α-induced retinal vasoconstriction is mediated by cyclooxygenase-generated formation of thromboxane and, to a lesser extent, by endothelin after Ca2+ entry into cells, possibly through receptor-operated channels. Retinal vasoconstriction to 8-isoprostanes might play a role in the genesis of ischemic retinopathies.
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Park, Kyung W., Hai B. Dai, Edward Lowenstein, and Frank W. Sellke. "Flow-induced Dilation of Rat Coronary Microvessels Is Attenuated by Isoflurane but Enhanced by Halothane." Anesthesiology 89, no. 1 (July 1, 1998): 132–42. http://dx.doi.org/10.1097/00000542-199807000-00020.
Анотація:
Background Volatile anesthetics attenuate agonist-induced endothelium-dependent vasodilation of coronary arteries. This study considered the hypothesis that the anesthetics may also attenuate flow-induced endothelium-dependent vasodilation. Methods Rat subepicardial arteries of approximately 100 microm were monitored for diameter changes in vitro by a video detection system, with the midpoint luminal pressure held constant at 40 mmHg but the pressure gradient (and therefore flow) across each vessel increased from 0 to 80 mmHg, in the presence or absence of 1 or 2 minimum alveolar concentration (MAC) isoflurane or 1 or 2 MAC halothane, with or without 10 microM of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) or 10 microM of the cyclooxygenase inhibitor indomethacin. Results Flow-induced dilation was attenuated by L-NNA or indomethacin (p < 0.001 each). It was attenuated by isoflurane in a concentration-dependent manner (P < 0.001). Attenuation by 2 MAC isoflurane persisted even in the presence of L-NNA (P < 0.01) or indomethacin (P < 0.05). On the other hand, flow-induced dilation was enhanced by 2 MAC halothane (P < 0.05). Halothane at 1 MAC had no significant effect. Enhancement by 2 MAC halothane was evident in the presence of indomethacin (P < 0.05) but not L-NNA (P = 0.40). Conclusions In rat subepicardial arteries, flow-induced dilation is endothelium-dependent and mediated by both NO and a prostanoid. Isoflurane attenuates flow-induced dilation, possibly by decreasing synthesis, the action of NO and a prostanoid, or both, whereas halothane enhances it, possibly by increasing synthesis, the action of NO, or both.
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Wulaningratri, Gabrielle Princessa, Mitra Istiar Wardhana, and Yon Ade Lose Hermanto. "Perancangan Desain Web sebagai Media Interaktif Nusantara Wedding Expo." JoLLA: Journal of Language, Literature, and Arts 1, no. 2 (February 28, 2021): 137–50. http://dx.doi.org/10.17977/um064v1i22021p137-150.
Анотація:
Abstract: Nusantara Wedding Expo is one of the businesses that has been affected by the Minister of Health regulation during the COVID-19 pandemic. So that the exhibition can be held safely, interactive media is required to connect wedding businesses with the bride and groom. Therefore, a website is chosen as the media for the virtual exhibition, as it can provide what the user needs and can be accessed easily. The purpose of this design is to create web-based media that can be used as a tool for the virtual exhibition of the Nusantara Wedding Expo. This design uses Suyanto’s design method, with the stages of formulating the background, formulating problems, collecting data from library data to field data, analyzing data, making syntheses, determining site goals, making work schedules, sitemap, sketches to producing the final design. The result of this design is interactive media in the form of a website. This website has a dimension of 1366 x 768 px with some supporting media such as video tutorials on how to use the website and a banner on digital media.
Keywords: web design; interactive media; wedding expo
Abstrak: Nusantara Wedding Expo adalah salah satu bisnis yang terdampak oleh peraturan dari Menteri Kesehatan tentang PSBB di tengah pandemi COVID-19. Supaya pameran tetap dapat diselenggarakan secara aman, penyelenggara Nusantara Wedding Expo memerlukan sebuah media interaktif untuk menghubungkan bisnis pernikahan dan para calon pengantin. Maka dari itu situs web dipilih agar dapat memenuhi kebutuhan pengunjung serta dapat diakses dengan mudah dan aman. Dari tujuan tersebut, perancangan ini berfungsi untuk membuat media berbentuk situs web yang dapat digunakan sebagai sarana pameran virtual Nusantara Wedding Expo. Perancangan ini menggunakan metode perancangan Suyanto, dengan tahapan berupa merumuskan latar belakang, merumuskan masalah, mengumpulkan data dari data pustaka dan data lapangan, menganalisis data, membuat sintesis, menentukan tujuan situs, membuat jadwal kerja, sitemap, sketsa hingga menghasilkan desain final. Hasil dari perancangan ini adalah media interaktif berupa situs web untuk pameran virtual Nusantara Wedding Expo. Situs web ini berdimensi 1366 x 768 px dan dilengkapi dengan media pendukung berupa video tutorial cara penggunaan situs web serta banner pada media digital.
Kata kunci: desain web, media interaktif, pameran pernikahan
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Siamwala, Jamila, Pavitra Kumar, Vimal Veeriah, Ajit Muley, Saranya Rajendran, Salini Konikkat, Syamantak Majumder, Krishna Mani, and Suvro Chatterjee. "Nitric Oxide Reverses the Position of the Heart during Embryonic Development." International Journal of Molecular Sciences 20, no. 5 (March 7, 2019): 1157. http://dx.doi.org/10.3390/ijms20051157.
Анотація:
Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) plays crucial roles in cardiac homeostasis. Adult cardiomyocyte specific overexpression of eNOS confers protection against myocardial-reperfusion injury. However, the global effects of NO overexpression in developing cardiovascular system is still unclear. We hypothesized that nitric oxide overexpression affects the early migration of cardiac progenitor cells, vasculogenesis and function in a chick embryo. Vehicle or nitric oxide donor DEAN (500 µM) were loaded exogenously through a small window on the broad side of freshly laid egg and embryonic development tracked by live video-microscopy. At Hamburg Hamilton (HH) stage 8, the cardiac progenitor cells (CPC) were isolated and cell migration analysed by Boyden Chamber. The vascular bed structure and heart beats were compared between vehicle and DEAN treated embryos. Finally, expression of developmental markers such as BMP4, Shh, Pitx2, Noggin were measured using reverse transcriptase PCR and in-situ hybridization. The results unexpectedly showed that exogenous addition of pharmacological NO between HH stage 7–8 resulted in embryos with situs inversus in 28 out of 100 embryos tested. Embryos treated with NO inhibitor cPTIO did not have situs inversus, however 10 embryos treated with L-arginine showed a situs inversus phenotype. N-acetyl cysteine addition in the presence of NO failed to rescue situs inversus phenotype. The heart beat is normal (120 beats/min) although the vascular bed pattern is altered. Migration of CPCs in DEAN treated embryos is reduced by 60% compared to vehicle. BMP4 protein expression increases on the left side of the embryo compared to vehicle control. The data suggests that the NO levels in the yolk are important in turning of the heart during embryonic development. High levels of NO may lead to situs inversus condition in avian embryo by impairing cardiac progenitor cell migration through the NO-BMP4-cGMP axis.
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Kim, Song-Jung, Young-Kwon Kim, Gen Takagi, Cheng-Hsiung Huang, Yong-Jian Geng, and Stephen F. Vatner. "Enhanced iNOS function in myocytes one day after brief ischemic episode." American Journal of Physiology-Heart and Circulatory Physiology 282, no. 2 (February 1, 2002): H423—H428. http://dx.doi.org/10.1152/ajpheart.00609.2001.
Анотація:
There is increasing evidence that nitric oxide (NO) produced by inducible NO synthase (iNOS) plays a key role in cadioprotection during the “second window of protection” (SWOP). The goals of this study were to determine 1) whether a transient ischemic episode [10-min coronary artery occlusion (CAO), followed by full reperfusion] enhances NOS function in cardiac myocytes, 2) which specific NOS isoform is responsible for the enhanced NOS function in myocytes, and 3) to localize iNOS expression during SWOP. To address these questions, 10 dogs were instrumented to measure aortic and left ventricular pressures and wall thickness. At 1–2 wk after recovery, myocardial ischemia was induced regionally by a 10-min left circumflex CAO. After 24-h reperfusion, cardiac myocytes were isolated from the previously ischemic and nonischemic regions ( n = 6). Myocyte contractile function was assessed using a video motion detector at 1 Hz (35 ± 2°C). At baseline, myocyte contractile function (% contraction) was similar in the two regions (ischemic 7.8 ± 0.5% vs. nonischemic 7.8 ± 0.2%).l-Arginine (1 mM) significantly reduced ( P < 0.05) myocyte contraction in the ischemic (−34 ± 3%, P < 0.05) but not (−7 ± 4%) nonischemic regions; these responses were abolished by N G-nitro-l-arginine (1 mM), a nonspecific NOS inhibitor, as well as 2-amino-5,6-dihydro-6-methy-4H-1,3,thiazine (1 mM), a specific iNOS inhibitor. Immunohistochemistry also revealed enhanced iNOS expression in the myocardium and in particular the interstitial spaces in the ischemic zone. These results indicate that a brief ischemic episode upregulates iNOS function in myocytes as well as in the interstitial space between blood vessels and myocytes, strategically where it can regulate both vascular and myocyte function during the SWOP.
44
Shirakami, Gotaro, Dechun Li, Xinhua Zhan, and Roger A. Johns. "Propofol Stimulates Ciliary Motility via the Nitric Oxide–Cyclic GMP Pathway in Cultured Rat Tracheal Epithelial Cells." Anesthesiology 93, no. 2 (August 1, 2000): 482–88. http://dx.doi.org/10.1097/00000542-200008000-00028.
Анотація:
Background Airway ciliary motility is impaired by inhaled anesthetics. Recent reports show that nitric oxide (NO) induces upregulation in ciliary beat frequency (CBF), and others report that propofol, an intravenous anesthetic, stimulates NO release; this raises the possibility that propofol increases CBF by stimulating the NO-cyclic guanosine monophosphate (cGMP) signal pathway. In this study, the authors investigated the effects of propofol on CBF and its relation with the NO-cGMP pathway using the pharmacologic blockers NG-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor; 1H-[1,2,4]oxidazole[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor; and KT5823, a cGMP-dependent protein kinase inhibitor, in cultured rat tracheal epithelial cells. Methods Rat tracheal tissues were explanted and cultured for 3-5 days. Images of ciliated cells were videotaped using a phase-contrast microscope. Baseline CBF and CBF 25 min after exposure to propofol or blocker were measured using video analysis. Results Vehicle (0.1% dimethyl sulfoxide; n = 11) increased CBF by 0.2 +/- 1.7% (mean +/- SD) from baseline. Propofol stimulated CBF significantly (P < 0.01) and dose dependently (1 microM, 2.0 +/- 1. 9%, n = 6; 10 microM, 8.2 +/- 6.7%, n = 9; 100 microM, 14.0 +/- 4.7%, n = 10). Intralipid (0.05%), the clinical vehicle of propofol, did not affect CBF (-0.2 +/- 2.2%; n = 5). The enhancement of CBF with use of 100 microm propofol was abolished (P < 0.01) by coadministration of 10 mmicroM l-NMMA (2.4 +/- 3.6%; n = 5), 100 microM ODQ (-0.3 +/- 2.2%; n = 6) or 30 microM KT5823 (-0.1 +/- 4. 1%; n = 8). l-NMMA, ODQ, or KT5823 alone did not change CBF. Conclusions These results show that propofol stimulates CBF viathe NO-cGMP pathway in rat tracheal epithelial cells, suggesting a possible advantage of propofol in decreasing respiratory risk.
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Tahawi, Ziad, Natalia Orolinova, Irving G. Joshua, Michael Bader, and Eugene C. Fletcher. "Selected Contribution: Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats." Journal of Applied Physiology 90, no. 5 (May 1, 2001): 2007–13. http://dx.doi.org/10.1152/jappl.2001.90.5.2007.
Анотація:
Recurrent episodic hypoxia (EH) is a feature of sleep apnea that may be responsible for some chronic cardiovascular sequelae such as systemic hypertension. Chronic EH (8 h/day for 35 days) causes elevation of diurnal resting (unstimulated) mean arterial blood pressure (MAP) in the rat. We used in vivo video microscopy to examine arteriolar reactivity in the cremaster muscle of male Sprague-Dawley rats subjected to 35 days of EH. Cremaster muscles of EH ( n= 6) and control ( n = 6) rats were exposed to varying doses of norepinephrine (NE) (10−10 to 10−5M), ACh (10−9 to 10−5 M), and endothelin-1 (10−12 to 10−8 M). In a separate experiment, EH ( n = 5) and control ( n = 6) rats were given one dose of a nitric oxide synthase (NOS) inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 10−5 M). We also examined endothelial NOS mRNA from the kidneys of EH-stimulated and control (unstimulated) rats. Telemetry-monitored EH rats showed a 16-mmHg increase in MAP over 35 days, whereas control rats showed no change. The response to NE and endothelin-1 were similar for EH and control rats. ACh vasodilatation of arterioles in EH rats was significantly attenuated compared with that of controls. The degree of vasoconstriction in response to blockade of the nitric oxide system byl-NAME was significantly less (83% of baseline diameter with l-NAME) for arterioles of EH rats compared with that for controls (61% of baseline diameter), implying lower basal resting nitric oxide release in the EH rats. Whole kidney mRNA endothelial NOS levels were not different between groups. These data support the hypothesis that chronic elevation of blood pressure associated with EH involves increased peripheral resistance from decreased basal release or production of nitric oxide after 35 days of EH.
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Mäki-Petäjä, Kaisa M., Adam McGeoch, Lucy L. Yang, Annette Hubsch, Carmel M. McEniery, Paul A. R. Meyer, Fraz Mir, et al. "Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition–Induced Hypertension." Hypertension 77, no. 5 (May 2021): 1591–99. http://dx.doi.org/10.1161/hypertensionaha.120.16454.
Анотація:
Drugs targeting the VEGF (vascular endothelial growth factor) signaling pathway are approved for several malignancies. Unfortunately, VEGF inhibitors lead to hypertension in 30% to 80% patients. Reduced nitric oxide synthase activity, microvascular rarefaction, and increased vascular resistance have been proposed as potential mechanisms. We aimed to assess these mechanisms in patients receiving the VEGF inhibitor, pazopanib, for cancer. Twenty-seven normotensive patients with advanced solid malignancies received pazopanib 800 mg od. Endothelial function was assessed using forearm plethysmography with intraarterial infusions of acetylcholine. Detailed hemodynamic measurements were taken. Density and diameter of the conjunctival and episcleral microvasculature were evaluated using hemoglobin video imaging. Measurements were taken at baseline, 2, and 12 weeks after initiation of pazopanib or earlier if patients became hypertensive. By the end of the trial, systolic blood pressure increased by 12 mm Hg (95% CI, 4–19 mm Hg; P =0.003), diastolic by 10 mm Hg (95% CI, 5–15 mm Hg; P <0.001), and peripheral vascular resistance by 888 dynes×s/cm 5 (95% CI, 616–1168 dynes×s/cm 5 ; P <0.001). Forearm blood flow improved: Ratio of acetylcholine response at end of trial/baseline was 2.8 (95% CI, 1.84–4.25; P <0.001). Microvascular density in the sclera was reduced by −15.5% (95% CI, −25.7% to −5.3%; P =0.003) and diameter by −2.09 µm (95% CI, −3.95 to −0.19 µm; P =0.03). A post hoc colorimetric assay revealed that pazopanib inhibited acetylcholinesterase activity by −56% (95% CI, −62% to −52%; P <0.001). Unexpectedly, pazopanib led to an increase in acetylcholine-mediated forearm blood flow response, likely due to the inhibition of acetylcholinesterase activity. Pazopanib increased peripheral vascular resistance and reduced microvascular density and diameter, suggesting that microvascular rarefaction could be one of the key mechanisms behind VEGF inhibition–induced hypertension. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01392352.
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Wakimoto, Roger M., Nolan T. Atkins, Kelly M. Butler, Howard B. Bluestein, Kyle Thiem, Jeffrey C. Snyder, Jana Houser, Karen Kosiba, and Joshua Wurman. "Aerial Damage Survey of the 2013 El Reno Tornado Combined with Mobile Radar Data." Monthly Weather Review 144, no. 5 (May 2016): 1749–76. http://dx.doi.org/10.1175/mwr-d-15-0367.1.
Анотація:
A detailed damage survey of the El Reno, Oklahoma, tornado of 31 May 2013 combined with rapid-scanning data recorded from two mobile radars is presented. One of the radars was equipped with polarimetric capability. The relationship between several suction vortices visually identified in pictures with the high-resolution Doppler velocity data and swath marks in fields is discussed. The suction vortices were associated with small shear features in Doppler velocity and a partial ringlike feature of high spectral width. For the first time, a suction vortex that created a swath mark in a field was visually identified in photographs and high-definition video while the rotational couplet was tracked by radar. A dual-Doppler wind synthesis of the tornadic circulation at low levels near the location of several storm chaser fatalities resolved ground-relative wind speeds in excess of 90 m s−1, greater than the minimum speed for EF5 damage. The vertical vorticity analysis revealed a rapid transition from a single tornadic vortex centered on the weak-echo hole (WEH) to suction vortices surrounding the WEH and collocated with the ring of enhanced radar reflectivities. Several bands/zones of enhanced convergence were resolved in the wind syntheses. One of the bands was associated with an internal or secondary rear-flank gust front. An inner band of convergence appeared to be a result of the positive bias in tornado-relative radial velocity owing to centrifuging of large lofted debris swirling within the tornado. An outer band of convergence formed at the northern edge of a region of strong inflow that was lofting small debris and dust into the storm.
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Fujioka, Jamie Keiko, Suman Budhwani, Tyla Thomas-Jacques, Kristina De Vera, Priyanka Challa, Kaitlin Fuller, Sophie Hogeveen, et al. "Challenges and Strategies for Promoting Health Equity in Virtual Care: Protocol for a Scoping Review of Reviews." JMIR Research Protocols 9, no. 12 (December 7, 2020): e22847. http://dx.doi.org/10.2196/22847.
Анотація:
Background The rapid virtualization of health services during the COVID-19 pandemic has drawn increasing attention to the impact of virtual care technologies on health equity. In some circumstances, virtual care initiatives have been shown to increase health disparities, as individuals from underserved communities are less likely to benefit from such initiatives. Objective The purpose of this paper is to describe a protocol for a scoping review of reviews that aims to map review-level evidence that describes challenges and strategies for promoting effective engagement with virtual care technologies among underserved communities. Methods Our methodology was adapted from seminal scoping review guidelines provided by Arksey and O’Malley, Levac at al, Colquhoun et al, and the Joanna Briggs Institute. Our search strategy was developed for the following databases: MEDLINE (on Ovid), EMBASE (on Ovid), CINAHL (on EBSCO), Scopus, and Epistemonikos. Supplementary searches will include the use of Google Scholar and reference tracking. Each citation will be independently screened by 2 researchers at the title and abstract level, and full-text screening will be performed in accordance with our eligibility criteria. The eligibility criteria focused on the inclusion of methods-driven reviews (ie, systematic reviews, scoping reviews, meta-analyses, realist reviews, and critical interpretative syntheses) to enhance rigor and quality. Other inclusion criteria included a focus on virtual care services that facilitate bidirectional patient-provider communication (ie, video, telephone, and asynchronous messaging visits) for underserved populations (ie, those who experience social disadvantage due to race, age, income, and other factors related to the social determinants of health). Results This scoping review of reviews will provide a broad overview of identified challenges associated with the accessibility of virtual health care services among underserved communities. In addition, strategies for improving the access to, uptake of, and engagement with virtual care technologies among underserved communities will be identified. The knowledge synthesized from this review will aid in developing and implementing virtual services that acknowledge the unique needs of populations who experience barriers to care and disproportionately worse health outcomes. The results will also inform gaps in current research. Conclusions The rapid shift toward virtual health services has highlighted the urgent need to critically examine the intersection of virtual care and health equity. Although technology-driven innovations in health care generally aim to improve access, quality, and health outcomes, it is also possible for these innovations to produce intervention-generated inequities. Assessing current review-level evidence on the key challenges and strategies for improving the application of virtual care in underserved communities is imperative for ensuring that virtual care benefits all populations. International Registered Report Identifier (IRRID) PRR1-10.2196/22847
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Merlin, Lisa R. "“TOR” rents of Excitement over Rapamycin's Antiepileptogenic Potential." Epilepsy Currents 8, no. 6 (October 6, 2008): 163–65. http://dx.doi.org/10.1111/j.1535-7511.2008.00280.x.
Анотація:
Response of a Neuronal Model of Tuberous Sclerosis to Mammalian Target of Rapamycin (mTOR) Inhibitors: Effects on mTORC1 and Akt Signaling Lead to Improved Survival and Function. Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, Kwiatkowski DJ. J Neurosci 2008;28(21):5422–5432. Tuberous sclerosis (TSC) is a hamartoma syndrome attributable to mutations in either TSC1 or TSC2 in which brain involvement causes epilepsy, mental retardation, and autism. We have reported recently (Meikle et al., 2007) a mouse neuronal model of TSC in which Tsc1 is ablated in most neurons during cortical development. We have tested rapamycin and RAD001 [40- O-(2-hydroxyethyl)-rapamycin], both mammalian target of rapamycin mTORC1 inhibitors, as potential therapeutic agents in this model. Median survival is improved from 33 d to more than 100 d; behavior, phenotype, and weight gain are all also markedly improved. There is brain penetration of both drugs, with accumulation over time with repetitive treatment, and effective reduction of levels of phospho-S6, a downstream target of mTORC1. In addition, there is restoration of phospho-Akt and phospho-glycogen synthase kinase 3 levels in the treated mice, consistent with restoration of Akt function. Neurofilament abnormalities, myelination, and cell enlargement are all improved by the treatment. However, dysplastic neuronal features persist, and there are only modest changes in dendritic spine density and length. Strikingly, mice treated with rapamycin or RAD001 for 23 d only (postnatal days 7–30) displayed a persistent improvement in phenotype, with median survival of 78 d. In summary, rapamycin/RAD001 are highly effective therapies for this neuronal model of TSC, with benefit apparently attributable to effects on mTORC1 and Akt signaling and, consequently, cell size and myelination. Although caution is appropriate, the results suggest the possibility that rapamycin/RAD001 may have benefit in the treatment of TSC brain disease, including infantile spasms. Rapamycin Prevents Epilepsy in a Mouse Model of Tuberous Sclerosis Complex. Zeng LH, Xu L, Gutmann DH, Wong M. Ann Neurol 2008;63(4):444–453. OBJECTIVE: Tuberous sclerosis complex (TSC) represents one of the most common genetic causes of epilepsy. TSC gene inactivation leads to hyperactivation of the mammalian target of rapamycin signaling pathway, raising the intriguing possibility that mammalian target of rapamycin inhibitors might be effective in preventing or treating epilepsy in patients with TSC. Mice with conditional inactivation of the Tsc1 gene primarily in glia ( Tsc1GFAPCKO mice) develop glial proliferation, progressive epilepsy, and premature death. Here, we tested whether rapamycin could prevent or reverse epilepsy, as well as other cellular and molecular brain abnormalities in Tsc1GFAPCKO mice. METHODS: Tsc1GFAPCKO mice and littermate control animals were treated with rapamycin or vehicle starting at postnatal day 14 (early treatment) or 6 weeks of age (late treatment), corresponding to times before and after onset of neurological abnormalities in Tsc1GFAPCKO mice. Mice were monitored for seizures by serial video-electroencephalogram and for long-term survival. Brains were examined histologically for astrogliosis and neuronal organization. Expression of phospho-S6 and other molecular markers correlating with epileptogenesis was measured by Western blotting. RESULTS: Early treatment with rapamycin prevented the development of epilepsy and premature death observed in vehicle-treated Tsc1GFAPCKO mice. Late treatment with rapamycin suppressed seizures and prolonged survival in Tsc1GFAPCKO mice that had already developed epilepsy. Correspondingly, rapamycin inhibited the abnormal activation of the mammalian target of rapamycin pathway, astrogliosis, and neuronal disorganization, and increased brain size in Tsc1GFAPCKO mice. INTERPRETATION: Rapamycin has strong efficacy for preventing seizures and prolonging survival in Tsc1GFAPCKO mice.
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Alexander, Barbara D., Oliver Cornely, Peter Pappas, Rachel Miller, Jose A. Vazquez, Luis Ostrosky-Zeichner, Andrej Spec, et al. "1248. Efficacy and Safety of Oral Ibrexafungerp in 41 Patients with Refractory Fungal Diseases, Interim Analysis of a Phase 3 Open-label Study (FURI)." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S642. http://dx.doi.org/10.1093/ofid/ofaa439.1432.
Анотація:
Abstract Background Candida infections resistant to currently available antifungals are an emerging global threat. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of oral ibrexafungerp (FURI) (Clinicaltrials.gov NCT03059992) is ongoing for the treatment of patients (≥18 years) with fungal diseases who are intolerant of or refractory to standard antifungal therapies. Methods An independent Data Review Committee (DRC) provided an assessment of treatment response for 41 patients. Patients were enrolled in 22 centers from 6 countries. Patients were eligible for enrollment if they had proven or probable, invasive or severe mucocutaneous candidiasis and documented evidence of failure of, intolerance to, or toxicity related to a currently approved standard-of-care antifungal treatment or could not receive approved oral antifungal options (e.g., susceptibility of the organism) and a continued IV antifungal therapy was undesirable or unfeasible. Results The 41 patients assessed had the following infection types: intra-abdominal abscesses, oropharyngeal candidiasis, esophageal candidiasis, candidemia, and others. The DRC adjudicated 23 patients (56%) as achieving complete or partial response, 11 patients (27%) maintaining stable disease, 6 patients (15%) with progression of disease and one case was considered as indeterminate. The efficacy of oral ibrexafungerp by pathogen is shown in Table 1. Ibrexafungerp was well-tolerated with the most common treatment-related adverse events being of gastrointestinal origin. No deaths due to progression of fungal disease were reported. Table 1: Ibrexafungerp Outcomes by Pathogen Conclusion Preliminary analysis of these 41 cases indicate that oral ibrexafungerp provides a favorable therapeutic response in the majority of patients with difficult to treat Candida spp. infections, including those caused by non-albicans Candida species. Disclosures Barbara D. Alexander, MD, MHS, SCYNEXIS, Inc. (Employee, Scientific Research Study Investigator, Research Grant or Support) Oliver Cornely, Prof., Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Rachel Miller, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Luis Ostrosky-Zeichner, MD, Amplyx (Scientific Research Study Investigator)Astellas (Consultant, Scientific Research Study Investigator, Other Financial or Material Support, Non-branded educational speaking)Biotoscana (Consultant, Other Financial or Material Support, Non-branded educational speaking)Cidara (Consultant, Scientific Research Study Investigator)F2G (Consultant)Gilead (Consultant)Mayne (Consultant)Octapharma (Consultant)Pfizer (Other Financial or Material Support, Non-branded educational speaking)Scynexis (Consultant, Grant/Research Support, Scientific Research Study Investigator)Stendhal (Consultant)Viracor (Consultant) Andrej Spec, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator, Advisor or Review Panel member) Riina Rautemaa-Richardson, DDS, PhD, FRCPath, SCYNEXIS, Inc. (Scientific Research Study Investigator) Robert Krause, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Caryn Morse, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) John W. Sanders, III, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) David Andes, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator, Advisor or Review Panel member) George Lyon, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Francisco M. Marty, MD, Allovir (Consultant)Amplyx (Consultant)Ansun (Scientific Research Study Investigator)Avir (Consultant)Cidara (Scientific Research Study Investigator)F2G (Consultant, Scientific Research Study Investigator)Kyorin (Consultant)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)New England Journal of Medicine (Other Financial or Material Support, Honorarium for Video)Regeneron (Consultant, Scientific Research Study Investigator)ReViral (Consultant)Scynexis (Scientific Research Study Investigator)Symbio (Consultant)Takeda (Scientific Research Study Investigator)United Medical (Consultant)WHISCON (Scientific Research Study Investigator) Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member) Thomas F. Patterson, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, SCYNEXIS, Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder)