10 research outputs found

    Quantitative modelling of market booms and crashes

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    Multiple equilibria models are one of the main categories of theoretical models for stock market crashes. To the best of my knowledge, existing multiple equilibria models have been developed within a discrete time framework and only explain the intuition behind a single crash on the market. The main objective of this thesis is to model multiple equilibria and demonstrate how market prices move from one regime into another in a continuous time framework. As a consequence of this, a multiple jump structure is obtained with both possible booms and crashes, which are defined as points of discontinuity of the stock price process. I consider five different models for stock market booms and crashes, and look at their pros and cons. For all of these models, I prove that the stock price is a cadlag semimartingale process and find conditional distributions for the time of the next jump, the type of the next jump and the size of the next jump, given the public information available to market participants. Finally, I discuss the problem of model parameter estimation and conduct a number of numerical studies

    Antibodies for Assessing Circadian Clock Proteins in the Rodent Suprachiasmatic Nucleus

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    Research on the mechanisms underlying circadian rhythmicity and the response of brain and body clocks to environmental and physiological challenges requires assessing levels of circadian clock proteins. Too often, however, it is difficult to acquire antibodies that specifically and reliably label these proteins. Many of these antibodies also lack appropriate validation. The goal of this project was to generate and characterize antibodies against several circadian clock proteins. We examined mice and hamsters at peak and trough times of clock protein expression in the suprachiasmatic nucleus (SCN). In addition, we confirmed specificity by testing the antibodies on mice with targeted disruption of the relevant genes. Our results identify antibodies against PER1, PER2, BMAL1 and CLOCK that are useful for assessing circadian clock proteins in the SCN by immunocytochemistry

    Impact of melatonin on CREB phosphorylation and clock gene protein levels in immunocytochemically identified hypophyseal cells : studies in mice with intact and disrupted melatonin signal transduction

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    All living organisms exhibit daily fluctuations in biochemical, physiological and behavioural parameters driven by endogenous oscillators, residing in the organism itself. In mammals, the core circadian oscillator is located in the paired suprachiasmatic nuclei (SCN) of the hypothalamus. Circadian rhythm generation in the SCN depends upon the expression of clock genes interacting in positive and negative transcriptional/translational feedback loops. The SCN governs the timing of peripheral circadian oscillators by neuronal pathways and by neuroendocrine mechanisms. An important neuroendocrine hand of the core circadian oscillator is melatonin, which is produced in and secreted from the pineal gland night by night. The adenohypophysis represents a peripheral circadian oscillator and the secretion of one of its hormones, prolactin, is known to be regulated by melatonin. The aim of the present study was to analyze a putative influence of melatonin on the activity state and diurnal variations of identified cell types in the hypophysis. Particular attention was paid to lactotroph, gonadotroph and pars intermedia cells. Experiments were performed with young male mice of different strains: melatonin-proficient C3H, melatonin-deficient C57BL, melatonin-proficient C3H with targeted deletions of the Mel1a receptor (MelaaBB), Mel1b receptor (MelAAbb) or both receptors (Melaabb). Cells producing prolactin (PRL), follicle stimulating hormone (FSH) were immunocytochemically identified and the presence of phosphorylated CREB protein (pCREB) and clock gene protein PER1 was demonstrated by double immunolabeling at different time points during the light/dark cycle in melatonin deficient, melatonin proficient and melatonin receptor knockout mice. Melatonin influence on Prl mRNA levels was investigated by means of in situ hybridization. At night the percentage of lactotroph cells showing a positive nuclear pCREB- and PER1-immunoreaction is significantly smaller in C57BL than in C3H mice. In both mouse strains, the percentage of pCREB –immunoreactive cells is minimal in the early morning and gradually increases to reach a maximum in the late night. PER1 levels show a parallel temporal variation in C3H, but in C57BL, they are drastically reduced in the early afternoon. The percentage of FSH-immunoreactive cells showing pCREB immunoreaction was significantly lower in the melatonin-deficient C57Bl mice than in the melatonin-proficient C3H mice during the second part of the day and during the night. In each strain, the percentage of FSH-immunoreactive cells was lowest at the early morning and gradually increases until the maximum at late night. In wild type (MelAABB) and MelAAbb mice the percentage of lactotroph cells with nuclear pCREB immunoreactions varied significantly over 24 h period, whereas in MelaaBB and Melaabb mice no significant differences were found between the five time points analyzed. The number of Prl mRNA expressing cells was significantly higher in MelaaBB and MelAAbb than in their wild type (MelAABB) littermates. pCREB levels in the pars intermedia did not show rhythmic variation in wild type or Melaabb animals, but wild type mice had higher pCREB levels than Melaabb. The observation that, during darkness, the percentage of lactotroph cells with nuclear pCREB immunoreaction is significantly higher in C3H than in C57BL mice suggests the existence of a distinct cell population that is under the control of melatonin-dependent intrapituitary signaling. Results with melatonin receptor knockout mice indicate that Mel1a and Mel1b melatonin receptors are involved in the control of the activity state of lactotroph cells, but to a differing degree. Analysis of cells expressing Prl mRNA showed that inhibitory action on the Prl expression is mostly mediated through the Mel1a receptor. The significant difference between pCREB immunoreaction in gonadotroph cells of C3H and C57BL mice might suggest that, like lactotrophes, FSH cells represent a heterogeneous population and only a subpopulation is under control of melatonin signaling. The present study is first to show that melatonin signaling also affects pCREB levels in pars intermedia of mice.Bei allen lebenden Organismen zeigen viele Körperfunktionen deutliche Tagesschwankungen, die von endogenen Oszillatoren gesteuert werden. Bei Säugetieren ist der zirkadiane Oszillator im Nucleus suprachiasmaticus (SCN) des Hypothalamus lokalisiert. Die zirkadiane Rhythmogenese im SCN basiert auf transkriptionalen/translationalen Rückkopplungsschleifen, in denen Uhrengene und ihre Proteinprodukte interagieren. Der SCN steuert über neuronale und neuroendokrine Mechanismen periphere Oszillatoren. Melatonin ist ein wichtiger neuroendokriner Botenstoff des zirkadianen Oszillators, es wird nachts in der Epiphysis cerebri synthetisiert und in die Blutbahn bzw. den Liquor erebrospinalis sezerniert. Zu den peripheren Oszillatoren gehört die Adenohypophyse, die hier lokalisierten Prolaktin (PRL)- bildenden Zellen werden durch Melatonin reguliert. In der vorliegenden Arbeit sollte gezeigt werden, ob und wie Melatonin die tagesrhythmische Aktivität in verschiedenen Zelltypen der Hypopyhse beeinflusst. Untersucht wurden lactotrophe-, gonadotrophe- und Pars Intermedia-Zellen. Für die Versuche wurden 2-3 Monate alte, männliche Tiere der folgenden Mäuse-Stämme verwendet: Melatoninproduzierende C3H, Melatonin-defiziente C57BL und Melatonin-produzierende Mäuse C3H, bei denen entweder der Melatonin-Rezeptor Mel1a (MelaaBB), der Mel1b (MelAAbb) oder beide Melatoninrezeptoren (Melaabb) ausgeschaltet waren. Die Zellen, die PRL und Follikel stimulierendes Hormon (FSH) produzieren, wurden mittels Immunocytochemie identifiziert und phosphoryliertes CREB- Protein und das Uhrengen-Protein PER1 wurden in diesen Zellen durch eine Doppel –Immunfärbung zu unterschiedlichen Zeitpunkten während des Hell/Dunkel Zyklus nachgewiesen. Die Wirkung von Melatonin auf die Expression von Prl mRNA wurde mit Hilfe der in situ Hybridisierung untersucht. Während der Nacht ist die prozentuale Anzahl von lactotrophen Zellen, die eine positive pCREB- und PER1-Immunreaktion im Kern zeigen, bei C57BL Mäusen gegenüber C3H Mäusen signifikant erniedrigt. Beide Mäuse-Stämme zeigen am frühen Morgen eine geringe Prozentzahl an pCREB- immunreaktiven lactotrophen Zellen, ihre Anzahl steigt graduell im Verlauf des Tages und erreicht maximale Werte in der späten Nacht. Die Zahl der PER1-immunreaktiven Zahlen zeigt parallel verlaufende zeitliche Schwankungen bei C3H, ist aber bei C57BL mittags deutlich reduziert. Die Anzahl der FSH- immunreaktiven Zellen, die zugleich eine nukleäre pCREB-Immunreaktion zeigen, ist während der Mittags- und Nachtzeit bei C57BL stärker erniedrigt als bei C3H Mäusen. Die Zahl dieser Zellen ist bei beiden Stämmen morgens am niedrigsten und erreicht ihr Maximum in der späten Nacht. Bei MelAABB (Wildtyp-Mäusen) und MelAAbb (Mäusen mit deletiertem Mel1b-Rezeptor) schwankt die Zahl der lactotrophen Zellen mit nukleärer pCREB-Immunreaktion über den Zeitraum von 24 Stunden, diese Schwankungen sind bei MelaaBB und Melaabb Mäusen nicht nachweisbar. Die Menge an Prl mRNA exprimierenden Zellen war gegenüber MelAABB bei MelaaBB und MelAAbb Mäusen signifikant erhöht. Die Zahl der pCREB immunreaktiven Zellen in der Pars Intermedia zeigte bei allen untersuchten Stämmen keine tageszeitlichen Schwankungen, ihre Zahl war jedoch insbesondere bei Melaabb deutlich erniedrigt. Die Befunde, dass die Anzahl an pCREB-immunreaktiven lactotrophen Zellen bei C3H signifikant höher ist als bei C57BL, belegen die Existenz einer Subpopulation von lactotrophen Zellen, deren Aktivität durch Melatonin gesteuert wird. Die Resultate bei den Mäusen mit Melatonin-Rezeptor Deletion zeigen, dass die Aktivität dieser Zellpopulation im Wesentlichen durch den Mel1a Rezeptor gesteuert wird. Dieses wird durch die Bestimmung der Zahl der Prl mRNA exprimierenden Zellen mittels in situ Hybridisierung bestätigt. Die immunzytochemischen Doppelfärbungen für FSH und pCREB zeigen, dass auch die gonadotrophen Zellen eine heterogene Population bilden und nur eine Subpopulation unter der Kontrolle von Melatonin steht. Schließlich hat die vorliegende Studie erstmalig gezeigt, dass auch der Aktivitätsszustand der Pars intermedia durch Melatonin beeinflusst wird

    Early experience of a multidisciplinary bedside procedure team (SWAT) during the initial COVID-19 outbreak in New York.

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    Background - The outbreak of SARS-CoV-2 in March 2020 in New York required rapid expansion of intensive care unit (ICU) capacity and redeployment of physicians not formally trained in critical care to help staff these new units. A surgical workforce activation team (SWAT) was created by the Department of Surgery in conjunction with the Division of Interventional Radiology to meet increased demand for bedside procedures in these units. Methods - This is a retrospective review of procedures performed by SWAT at the bedside in critically ill patients during a two-week period from March 23rd to April 8th. Demographic data, admission date, intubation date, discharge date and date of death as well as procedural data including type of procedure, catheter positioning, complications and radiographic verification of the catheter prior to use, were recorded and evaluated. Results - 569 procedures were performed by the SWAT on 273 unique patients during 418 patient encounters. 260 of those patients tested positive for COVID-19 . Post-procedure radiographs resulted in 5 catheter repositioning procedures, with no adverse patient outcomes related to malpositioning. 1.2% of patients developed pneumothoraces following line placement. Catheter tip location in the brachiocephalic vein was significantly associated with non-salvageable catheter thrombosis (p<0.001) in COVID-19 positive patients. Interpretation- A SWAT can be created to safely accommodate increased bedside procedure volumes of critically ill patients during COVID-19. Immediate follow up radiographs are not necessary following uncomplicated bedside image-guided procedures. However, placement of longer dialysis catheter lengths to ensure the tip is in the right atrium will likely reduce catheter related thrombosis and need for catheter revisions in COVID-19 patients with coagulopathies.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

    Retrieval of a Dislodged Catheter Using Combined Fluoroscopy and Intracardiac Echocardiography

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    This report details a method of percutaneous, transluminal retrieval of an intracardiac foreign body using fluoroscopy in combination with intracardiac echocardiography. During retrieval, intracardiac echocardiography (ICE) provided real-time anatomic localization of a constantly moving, almost radiolucent micropuncture coaxial dilator fragment with respect to the tricuspid and pulmonary valves. This method may serve as a crucial aid in retrieval of intracardiac foreign bodies that are difficult to see with fluoroscopy and which may be adjacent to cardiac valves

    A simple model for market booms and crashes

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    Multiple equilibria models are one of the major categories of theoretical models for stock market crashes. The main objective of this paper is to model multiple equilibria and demonstrate how market prices move from one regime into another in a continuous time framework. As a consequence of this, a multiple jump structure is obtained with both booms and crashes, which are defined as points of discontinuity of the stock price process. For the constructed model, we prove that the stock price is a cĂ dlĂ g semimartingale process, find the conditional distributions for the time of the next jump, the type of the next jump and the size of the next jump, given the public information available to market participants, and conduct a number of numerical studies

    Update on melatonin receptors: IUPHAR Review 20

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