Messung der Wirkung von Sevofluran auf Ischämie und postischämische Reperfusion nach Abklemmen der Arteria Femoralis vor und während Operation wegen peripherer arterieller Verschlusskrankheit am Bein durch Nah-Infrarot-Spektroskopie

Sowohl die Präkonditionierung mit Sevofluran als auch ischämische Präkonditionierung können Gewebe vor den Folgen einer Ischämie schützen. Das Ziel dieser Studie war es, durch Nah-Infrarot Spektroskopie zu untersuchen, ob Präkonditionierung durch Sevofluran bei Patienten mit peripherer arterieller Verschlusskrankheit einen Effekt auf die Gewebsoxygenierung im Unterschenkel während Ischämie- und Reperfusionsphasen durch Abklemmen der Arteria femoralis hat. Dabei konnte außerdem untersucht werden, ob durch das dafür notwendige wiederholte Abklemmen der Arteria femoralis eine ischämische Präkonditionierung der arteriellen Beinstrombahn erreicht werden kann

Power analysis of single-cell RNA-sequencing experiments

Single-cell RNA sequencing (scRNA-seq) has become an established and powerful method to investigate transcriptomic cell-to-cell variation, thereby revealing new cell types and providing insights into developmental processes and transcriptional stochasticity. A key question is how the variety of available protocols compare in terms of their ability to detect and accurately quantify gene expression. Here, we assessed the protocol sensitivity and accuracy of many published data sets, on the basis of spike-in standards and uniform data processing. For our workflow, we developed a flexible tool for counting the number of unique molecular identifiers (https://github.com/vals/umis/). We compared 15 protocols computationally and 4 protocols experimentally for batch-matched cell populations, in addition to investigating the effects of spike-in molecular degradation. Our analysis provides an integrated framework for comparing scRNA-seq protocols.The study was supported by Cancer Research UK grant number C45041/A14953 to A Cvejic and C Labalette, European Research Council project 677501-ZF_Blood to A Cvejic and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute. The ERC grant ThSWITCH to SA Teichmann (grant no. 260507) and a Lister Institute Research Prize to SA Teichmann. KN Natarajan was supported by the Wellcome Trust Strategic Award “Single cell ge nomics of mouse gastrulation”

A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications.

RNA sequencing (RNA-seq) is a genomic approach for the detection and quantitative analysis of messenger RNA molecules in a biological sample and is useful for studying cellular responses. RNA-seq has fueled much discovery and innovation in medicine over recent years. For practical reasons, the technique is usually conducted on samples comprising thousands to millions of cells. However, this has hindered direct assessment of the fundamental unit of biology-the cell. Since the first single-cell RNA-sequencing (scRNA-seq) study was published in 2009, many more have been conducted, mostly by specialist laboratories with unique skills in wet-lab single-cell genomics, bioinformatics, and computation. However, with the increasing commercial availability of scRNA-seq platforms, and the rapid ongoing maturation of bioinformatics approaches, a point has been reached where any biomedical researcher or clinician can use scRNA-seq to make exciting discoveries. In this review, we present a practical guide to help researchers design their first scRNA-seq studies, including introductory information on experimental hardware, protocol choice, quality control, data analysis and biological interpretation

New fossils from Jebel Irhoud, Morocco and the pan-African origin of Homo sapiens

Fossil evidence points to an African origin of Homo sapiens from a group called either H. heidelbergensis or H. rhodesiensis. However, the exact place and time of emergence of H. sapiens remain obscure because the fossil record is scarce and the chronological age of many key specimens remains uncertain. In particular, it is unclear whether the present day ‘modern’ morphology rapidly emerged approximately 200 thousand years ago (ka) among earlier representatives of H. sapiens1 or evolved gradually over the last 400 thousand years2. Here we report newly discovered human fossils from Jebel Irhoud, Morocco, and interpret the affinities of the hominins from this site with other archaic and recent human groups. We identified a mosaic of features including facial, mandibular and dental morphology that aligns the Jebel Irhoud material with early or recent anatomically modern humans and more primitive neurocranial and endocranial morphology. In combination with an age of 315?±?34 thousand years (as determined by thermoluminescence dating)3, this evidence makes Jebel Irhoud the oldest and richest African Middle Stone Age hominin site that documents early stages of the H. sapiens clade in which key features of modern morphology were established. Furthermore, it shows that the evolutionary processes behind the emergence of H. sapiens involved the whole African continent

Discrete Dividends: Modeling, Estimation and Portfolio Optimization

In this thesis we integrate discrete dividends into the stock model, estimate future outstanding dividend payments and solve different portfolio optimization problems. Therefore, we discuss three well-known stock models, including discrete dividend payments and evolve a model, which also takes early announcement into account. In order to estimate the future outstanding dividend payments, we develop a general estimation framework. First, we investigate a model-free, no-arbitrage methodology, which is based on the put-call parity for European options. Our approach integrates all available option market data and simultaneously calculates the market-implied discount curve. We illustrate our method using stocks of European blue-chip companies and show within a statistical assessment that the estimate performs well in practice. As American options are more common, we additionally develop a methodology, which is based on market prices of American at-the-money options. This method relies on a linear combination of no-arbitrage bounds of the dividends, where the corresponding optimal weight is determined via a historical least squares estimation using realized dividends. We demonstrate our method using all Dow Jones Industrial Average constituents and provide a robustness check with respect to the used discount factor. Furthermore, we backtest our results against the method using European options and against a so called simple estimate. In the last part of the thesis we solve the terminal wealth portfolio optimization problem for a dividend paying stock. In the case of the logarithmic utility function, we show that the optimal strategy is not a constant anymore but connected to the Merton strategy. Additionally, we solve a special optimal consumption problem, where the investor is only allowed to consume dividends. We show that this problem can be reduced to the before solved terminal wealth problem.In dieser Arbeit geht es um die Integration von diskreten Dividenden Zahlungen in das Aktienmodell, um die Schätzung von zukünftigen Dividenden und um das Lösen verschiedener Portfolio Optimierungsprobleme. Dabei werden schon bekannte Aktienmodelle, die diskrete Dividenden einbinden kritisch untersucht und darauf aufbauend ein Aktienmodell entwickelt, das zudem eine frühzeitige Bekanntgabe der Dividenden ermöglicht. Um die zukünftigen Dividenden Auszahlungen zu schätzen, haben wir zwei Methoden entwickelt. Die erste No-Arbitrage Methode ist modellfrei und basiert auf der Put-Call Parität für europäische Optionen. Dabei verwenden wir alle vorhandenen Optionsdaten und berechnen die marktspezifischen Discount- Kurven in einem. In der praktischen Umsetzung für europäische Blue-chip Unternehmen weist die Methode eine gute Performance auf, die durch eine statistische Auswertung belegt wird. Da jedoch amerikanische Optionen weiter verbreitet sind, haben wir im nächsten Schritt eine zweite Methode entwickeln, die at-the-money Optionen verwendet. Diese Methode basiert auf einer Linearkombination zweier No- Arbitrage Schranken für die Dividenden. Dabei wird der optimale Gewichtungsfaktor anhand einer historischen Kleinste Quadrate Schätzung unter Einbindung bereits realisierter Dividenden berechnet. Um diese Methode in der Praxis zu testen, werden Daten der Dow Jones Industrial Average Aktien verwendet. Hier wird wieder eine statistische Analyse durchgeführt und zudem die Eingabe verschiedener Discount-Faktoren getestet. Des Weiteren wird die Performance der Methode mit der sogenannten einfachen Methode und der Methode, die Europäische Optionen verwendet verglichen. In dem letzten Teil der Arbeit wird das klassische Portfolio Problem für Dividenden zahlende Aktien betrachten und gelöst. Im Beispiel der logarithmischen Nutzenfunktion ist der optimale Portfolio Prozess keine Konstante mehr. Dennoch ist eine Abhängigkeit zur Merton Strategie gegeben. Zusätzlich wird ein spezielles Konsumproblem gelöst, bei dem der Investor nur Dividenden konsumiert darf. Dieses Problem kann gelöst werden in dem es auf das zuvor gelöste Portfolio Problem zurückgeführt wird

Mapping the spatio-temporal structure of motor cortical LFP and spiking activities during reach-to-grasp movements

Grasping an object involves shaping the hand and fingers in relation to the object’s physical properties. Following object contact, it also requires a fine adjustment of grasp forces for secure manipulation. Earlier studies suggest that the control of hand shaping and grasp force involve partially segregated motor cortical networks. However, it is still unclear how information originating from these networks is processed and integrated. We addressed this issue by analyzing massively parallel signals from population measures (local field potentials, LFPs) and single neuron spiking activities recorded simultaneously during a delayed reach-to-grasp task, by using a 100-electrode array chronically implanted in monkey motor cortex. Motor cortical LFPs exhibit a large multi-component movement-related potential (MRP) around movement onset. Here, we show that the peak amplitude of each MRP component and its latency with respect to movement onset vary along the cortical surface covered by the array. Using a comparative mapping approach, we suggest that the spatio-temporal structure of the MRP reflects the complex physical properties of the reach-to-grasp movement. In addition, we explored how the spatio-temporal structure of the MRP relates to two other measures of neuronal activity: the temporal profile of single neuron spiking activity at each electrode site and the somatosensory receptive field properties of single neuron activities. We observe that the spatial representations of LFP and spiking activities overlap extensively and relate to the spatial distribution of proximal and distal representations of the upper limb. Altogether, these data show that, in motor cortex, a precise spatio-temporal pattern of activation is involved for the control of reach-to-grasp movements and provide some new insight about the functional organization of motor cortex during reaching and object manipulation

Mapping the spatio-temporal structure of motor cortical LFP and spiking activities during reach-to-grasp movements

The aim of this study was to evaluate the hypothesis that low-level laser therapy (LLLT) 688 nm and 785 nm accelerate dentin barrier formation and repair process after traumatic pulp exposure. The sample consisted of 45 premolars of capuchin monkeys (Cebus apella) with pulp exposure Class V cavities. All premolars were treated with calcium hydroxide (Ca(OH)(2)), divided in groups of 15 teeth each, and analyzed on 7(th), 25(th), and 60(th) day. Group GI - only Ca(OH)(2), GIF- laser 688 nm, and GIII - laser 785 nm. Laser beam was used in single and punctual dose with the parameters: continuous, 688 nm and 785 nm wavelength, tip`s area of 0.00785 cm(2), power 50 mW, application time 20 s, dose 255 J/cm(2), energy 2 J. Teeth were capped with Ca(OH)(2), Ca(OH)(2) cement and restored with amalgam. All groups presented pulp repair. On 25(th) day the thickness of the formed dentin barrier was different between the groups GI and GII (p < 0.05) and between groups GI and GIII (p < 0.01). On 60(th) day there was difference between GI and GIII (p < 0.01). It may be concluded that, LLLT 688 nm and 785 nm accelerated dentin barrier formation and consequently pulp repair process, with best results using infrared laser 785 nm. (c) 2009 by Astro Ltd. Published exclusively by WLLEY-VCH Verlag GmbH & Co. KGa

Distinct molecular response patterns of activating STAT3 mutations associate with penetrance of lymphoproliferation and autoimmunity

Germline STAT3 gain-of-function (GOF) mutations have been linked to poly-autoimmunity and lymphoproliferation with variable expressivity and incomplete penetrance. Here we studied the impact of 17 different STAT3 GOF mutations on the canonical STAT3 signaling pathway and correlated the molecular results with clinical manifestations. The mutations clustered in three groups. Group 1 mutants showed altered STAT3 phosphorylation kinetics and strong basal transcriptional activity. They were associated with the highest penetrance of lymphoproliferation and autoimmunity. Group 2 mutants showed a strongly inducible transcriptional reporter activity and were clinically less penetrant. Group 3 mutants were mostly located in the DNA binding domain and showed the strongest DNA binding affinity despite a poor transcriptional reporter response. Thus, the GOF effect of STAT3 mutations is determined by a heterogeneous response pattern at the molecular level. The correlation of response pattern and clinical penetrance indicates a significant contribution of mutation-determined effects on disease manifestations