A isquemia e reperfusão intestinal (I/R-i) é relevante fator para o desenvolvimento da síndrome do desconforto respiratório agudo (SDRA). A lesão tecidual decorrente da I/R-i pode ser local e em órgãos distante do sitio isquêmico, notadamente o pulmão. Indivíduos submetidos à isquemia intestinal ao tornarem-se vulneráveis, desenvolvem resposta exacerbada a estímulos inflamatórios secundários constituindo assim a percepção de lesão decorrente de uma dupla agressão. Neste estudo desenvolvemos modelo murino de dupla agressão pulmonar ocasionada pela I/R-i seguida de estímulo da instilação nasal de LPS ou de suco gástrico (SG). A fase de caracterização do modelo de I/R-i revelou aumento de IL-6, G-CSF, KC, IP-10 e MCP-1, mas não de TNF-a no soro e em homogeneizados de pulmão e intestino. Anticorpos anti TNF-a e o etanercepte falharam em inibir o aumento de MPO pulmonar e intestinal após a I/R-i. A instilação nasal de LPS após a I/R-i aumentou a atividade pulmonar de MPO e exacerbou a permeabilidade vascular pulmonar. Neste caso, aminoguanidina ou a vimblastina reverterem o aumento da permeabilidade vascular, sugerindo a participação conjunta de neutrófilos e óxido nítrico no processo lesivo causado pela dupla agressão. A instilação nasal de SG induziu aumento inicial (2h) de MPO pulmonar seguido de influxo de neutrófilos (24h) para o espaço alveolar. Tal processo foi acompanhado por expressão inicial e transiente de TNF-a no LBA e contrabalanceada por IL-10. A resposta inflamatória aumentada de camundongos IL-10 KO à instilação de suco gástrico mostra o papel fundamental desta citocina do controle da inflamação. O rolipram ou o composto PKF 241-466 (inibidores de TNF-a) reduziram a inflamação pulmonar induzida pelo SG. A instilação de SG após a I/R-i (I/R-i +SG) exacerbou o aumento da permeabilidade vascular pulmonar. Os dados apresentados sugerem que a exposição do organismo ao trauma intestinal torna o pulmão suscetível a um estímulo secundário como o LPS e o suco gástrico. Visto a gama de estímulos inflamatórios a que indivíduos internados em unidades de terapia intensiva podem ser submetidos, os resultados deste estudo podem contribuir para a compreensão dos mecanismos reguladores do recrutamento de neutrófilos e geração de mediadores inflamatórios na síndrome do desconforto respiratório agudo. / Intestinal ischemia and reperfusion (I/R) is implicated as a prime initiating event in the development of systemic inflammatory syndrome and Acute Respiratory Distress Syndrome (ARDS). Several studies pointed the possibility of massive systemic inflammatory events rendering the lungs more susceptible to an exacerbated inflammatory response, the so called two-hit hypothesis. In this way, minor local inflammatory stimuli could be a trigger for ARDS. In this study we investigated the effects of low-dose LPS or gastric juice (GJ) administered by nasal instillation to mice previously submitted to intestinal I/R. Our data showed that i-I/R alone induced histological signs of edema in lung as well as an increase of lung MPO activity and IL-6, G-CSF, KC, IP-10 and MCP-1 levels. Nasal instillation of LPS following i-I/R increased lung MPO activity and exacerbated lung vascular permeability. In this case, aminoguanidine or vinblastine blocked the increase of vascular permeability, suggesting the role of neutrophils and nitric oxide in injury induced by the two-hit stimuli. Instillation of GJ induced an initial (2h) increase of lung MPO followed by the influx of neutrophils (24h) to the alveolar space. Such process was followed by the transient expression of TNF-a in BAL and balanced by IL-10. The exacerbated inflammatory response of IL-10 KO mice to GJ instillation shows the importance of this cytokine in the control of the inflammation in such model. Treatment with rolipram or PKF 241-466 compound (TNF-a inhibitors) reduced lung inflammation induced by GJ. Nasal instillation of GJ after i-I/R exacerbated the increase in lung vascular permeability. The data shown suggest that the exposition of the organism to mesenteric trauma primes the host organism to a secondary inflammatory stimulus such as LPS or gastric juice. Considering the possible multiple insults to lung to which patients in intensive care units are submitted, the results of this study might contribute to the understanding of the regulatory mechanisms of neutrophils and generation of inflammatory mediators in the context of ARDS.

Syftet med denna uppsats är att undersöka hur behandlare och volontärer upplever att män som utsatt kvinnor för våld i nära relationer beskriver och förklarar sina erfarenheter som våldsutövare och hur de talar om våldet i relation till deras bild av maskulinitet. Vidare är syftet att undersöka hur respondenterna påverkas av männens berättelser. Studien baseras på fem kvalitativa intervjuer, där en intervjuguide tillämpas för att strukturera datainsamlingen. Resultaten analyseras utifrån tre olika teman; männens sätt att beskriva och berätta om våldet, männens bild av maskulinitet samt hur respondenterna påverkades av männens berättelser. Teorier som har använts i denna studie är teorier om spegeljaget, våldets normaliseringsprocess för männen samt kognitiv dissonans. Resultatet av denna studie tyder på att män använder narrativa strategier för att förmildra och förklara sitt våldsutövande i nära relationer. Respondenterna upplever känslor som maktlöshet och frustration vid samtal med män som inte vill ta ansvar för sina handlingar. / The purpose of this paper is to investigate how therapists and volunteers find that men who exposed women to violence in close relationships describe and explain their experiences as violence practitioners and how these men describes violence in relation to their image of masculinity. Furthermore, the purpose is to investigate how respondents are affected by the stories of men. The study is based on five qualitative interviews, where an interview guide is used to structure the data collection. The results are analyzed based on three different themes; men's ways of describing and telling about violence, men's image of masculinity and how respondents were influenced by men's stories. Theories that have been used in this study is theories of mirror self, the normalization process of violence for men and cognitive dissonance. The result of this study suggests that men use narrative strategies to mitigate and explain their violence in close relationships. Respondents experience feelings like powerlessness and frustration in conversations with men who do not want to take responsibility for their actions.

This masters's thesis contains description of designed and implemented tool for classification of plant microRNA without genome. Properties of mature and star sequences in microRNA duplexes are used. Implemented method is based on clustering of RNA sequences (with CD-HIT) to mainly reduce their count. Selected representants from each clusters are classified using support vector machine. Performance of classification is more than 96% (based on cross-validation method using the training data).

Bildgesteuerte, perkutane Interventionen stellen bei vielen diagnostischen und therapeutischen Fragestellungen eine Alternative zum chirurgischen Vorgehen dar. Hierbei kommen bevorzugt die Sonographie und die Computertomographie (CT) zum Einsatz. Zu den Indikationen für eine gezielte Nutzung der Magnetresonanztomographie (MRT) zählen Befunde, die sich mit anderen Modalitäten nicht ausreichend darstellen lassen, die fehlende Strahlenexposition (CT) sowie Alleinstellungsmerkmale wie der hervorragende native Weichteilkontrast oder die Möglichkeiten zur Darstellung von Temperaturen oder Diffusionsprozessen. Zu den Nachteilen zählen die langen Messzeiten, das starke Magnetfeld sowie die räumliche Enge in den meist röhrenförmigen Geräten, die ein interventionelles Vorgehen oft erschweren. Stereotaktische Führungs- und Navigationshilfen sind kein notwendiger Bestandteil der interventionellen Ausrüstung, ermöglichen jedoch oft eine gezieltere Planung, bessere Visualisierung oder vereinfachte Durchführung, insbesondere gegenüber einer rein kognitiven Einbeziehung der MRT-Informationen. Assistenzsysteme für geschlossene MRT-Geräte sind meist rahmenbasiert und beschränken sich auf bestimmte Regionen, z. B. die Mamma, die Prostata oder das muskuloskelettale System. Diese Arbeit beschreibt hingegen eine leistungsstarke rahmenlose Assistenztechnik (Navigation), die sich praktisch in beliebigen Körperregionen einsetzen lässt. Der Operateur orientiert sich dabei anhand von hochwertigen MRT-Ansichten, die gemäß der in Echtzeit erfassten Nadellage aus einem kurz zuvor erhobenen Referenzdatensatz reformatiert werden. Ausgehend von der Implementierung an einem speziellen offenen MRT-System (0,5 T) werden interventionelle Komponenten und Methoden beschrieben, die erfolgreich auf ein herkömmliches MRT-System (1,5 T) übertragen wurden. Die Einschränkungen des geschlossenen Systems führten dabei zu einer speziellen Registrierungstechnik mit Hilfe einer kompakten, frei positionierbaren Referenzplatte mit resonanten Miniatur-Hochfrequenzspulen (semiaktiv) als MR-Positionsmarker. Im Vordergrund stand die systematische Prüfung der Marker hinsichtlich Signalverhalten und Sicherheit sowie die Zuverlässigkeit und Genauigkeit einer vollautomatischen, bildbasierten 3D-Lokalisation unter experimentellen und klinischen Randbedingungen. Gegenüber herkömmlichen, passiven (Kontrastmittel-) Markern zeichnet sich die semiaktive Technik dadurch aus, dass sie gleichzeitig, auch mehrere, beliebig über das gesamte Messvolumen verteilte Marker, praktisch unabhängig von sämtlichen anatomischen Strukturen lokalisieren kann. Sowohl die Festlegung einer Position (ein Marker) oder einer Ebene (drei Marker) wie auch die navigierte Platzierung einer Nadel zeigten im Experiment ausreichend hohe Genauigkeiten. Auf Basis einer zeitlich optimierten (Subsekunden-) Markerbildgebung konnte experimentell eine robotisch geführte Nadel direkt im MRT bildgebend verfolgt werden, was weitere Anwendungen der Lokalisationstechnik in Aussicht stellt. Navigierte Biopsien an einem Gewebephantom zeigten nach ausschließlich stereotaktischer Positionierung – ohne Kontrollbildgebung – unabhängig vom Erfahrungsgrad der medizinischen Anwender ausreichend hohe Trefferquoten. Gleichzeitig lieferte die Studie wertvolle, auch anwenderspezifische Erkenntnisse über die Bedienbarkeit sowie den Zeitbedarf für einzelne Interventionsschritte. Im Vergleich mit anderen prototypischen oder kommerziellen Systemen zeigte sich die vorgestellte Assistenztechnik – am Beispiel muskuloskelettaler Interventionen – als klinisch flexibel einsetzbar.

Through the analysis of the spectral characteristics of thousands of mastered (or remastered) commercial recordings from a variety of genres over the history of popular music, researchers have studied stylistic trends and spectral conventions. The aim of this study was to further explore, analyse and compare the spectral characteristics of two broad but distinct popular music genres: rock and vocal-based electronic music. The main reason for this choice of genres being that rock generally predominantly is based on (amplified) acoustical elements (e.g. acoustic drums and acoustic/electric bass/guitars) and that electronic music generally predominantly is based on electronic elements (e.g. beats and synthesizers). The stimuli for the study consisted of 24 top-five hit songs from the Billboard charts between 2016-2020, divided by genre. A fast fourier transform approach was used for the computation of target spectrums as well as low level descriptors for the two independent datasets of recordings. Spectral analysis followed with the goal of answering the following research questions: What do the spectral stylistic conventions appear to be in rock versus vocal-based electronic music and what spectral differences/similarities exists between these two distinct popular music genres? The results showed that there were some significant spectral differences between the two genres, especially noticeable in the low end of the frequency spectrum. Other genre-specific spectral trends and overall spectral conventions were found as well.

<p>G-protein coupled receptors (GPCRs) are membrane proteins that constitute ~30% of the FDA-approved drug targets. Opioid receptors are a subtype of GPCRs with four different receptor types: delta, kappa, mu, and nociception opioid receptors. Opioids such as morphine have been used for thousands of years and are deemed the most effective method for treating pain. However, opioids can have detrimental effects if used illicitly or over an extended period of time. Intriguingly, most of the clinically used opioids act on the mu opioid receptor (µOR). Hence, efforts in recent decades have focused on other opioid receptors to treat pain and other disorders. The delta opioid receptor (δOR) is one of four opioid receptors expressed in the central and peripheral nervous system. The δOR has attracted much attention as a potential target for a multitude of diseases and disorders including substance and alcohol use disorders, ischemia, migraine, and neurodegenerative diseases. However, to date, no δOR agonists, or drugs that act directly at the δOR, have been successful as clinical candidates. Nonetheless, the therapeutic potential of the δOR necessitates the targeting its pharmacologically. In this dissertation, I highlight peptide-based modulation as well as the identification of novel agonists at the δOR. I report research findings in the context of biased agonism at δOR, which is a hypothesized cellular signaling mechanism with potential therapeutic benefits. The focus on this work is the molecular determinants of biased agonism, which were investigated using a combination of cellular and computational approaches.  </p>

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Das Gedächtnis speichert nicht nur Informationen, sondern mitunter auch die Umstände, in denen diese Informationen erworben wurden, sogenannte Kontextinformationen. Die vorliegende Arbeit hat daher zum Ziel, anhand von Laboraufgaben und anhand einer komplexen sporttechnischen Fertigkeit den Einblick in die Wirkweise von Kontextinformationen im motorischen Bereich zu vertiefen und theoretische Modelle zu prüfen. In zwei Experimenten wurde zunächst der Frage nachgegangen, ob in-zidentelle Kontextinformation eine diskriminative Funktion einnehmen und den Abruf zweier ähnlicher Sequenzen erleichtern kann. Es wurde ein Ausbleiben der Interferenz-Effekte aufgrund der inzidentellen Kontextinformationen vermutet. Beide Experimente erfolgten im Labor im Design des Interferenzparadigmas. In Laborexperiment 1 (N = 30) lernten die Probanden der Experimentalgruppen an zwei aufeinanderfolgenden Tagen je eine dynamische Bewegungssequenz. Die Probanden der Kontrollgruppen lernten entweder nur die erste Sequenz (KG1) oder nur die zweite (KG2). Für alle Probanden waren die Sequenzen jeweils mit einer Kontextinformation verknüpft. An Tag 3 wurden Retentions- und Transfertests durchgeführt. Durch inzidentelle Kontextinformation alleine konnte keine Kontextabhängigkeit erzielt und retroaktive Interferenzeffekte nicht verhindert werden. In Laborexperiment II (N = 20) stellte sich für die zweite Bewegungssequenz durch zusätzlich erzeugte Intention eine höhere Wiedererkennungsleistung sowie Kontextabhängigkeit ein, dennoch wiesen die Probanden retroaktive Interferenzeffekte auf. Zusätzlich trat proaktive Interferenz auf (Experiment II). Zum anderen ermöglichte es eine umfangreiche Regeländerung im Basketball, eine mögliche Kontextabhängigkeit in einer komplexen sporttech-nischen Fertigkeit zu untersuchen. Im daraus entwickelten Feldexperiment mit N = 20 Basketballern mit hoher Expertise zum 3-Punkte-Wurf konnte gezeigt werden, dass Bodenmarkierungen als inzidentelle Kontextinformationen zu begreifen sind und Einfluss auf die Leistung haben. Die Ergebnisse der Arbeit werden in Beziehung zu aktuellen Ergebnissen der Literatur sowie in Bezug auf das perception-control-Modell von Glover (2004) und dem MOSAIC-Modell von Wolpert und Kawato (1998) diskutiert. Praktische Ableitungen werden dargestellt. / Our memory not only stores information that seem important to us but also circumstances, surroundings where information are gathered – so called contextual information. The present work therefore aims to sharpen the understanding of the mechanisms underpinning this phenomenon in the field of motor learning and to investigate different theoretical models by two experiments with sequence learning tasks and additionally by a complex sports skill. Two experiments were conducted to investigate any discriminative character of incidental context information which would facilitate the recall of two similar movement sequences. An absence of interference-effects was hypothesized. Both experiments took place in accordance with a pro-/retroactive interference design. In experiment 1 (N = 30) subjects of the experimental group (EG) learned two dynamic sequences (S1 and S2) on two successive days while members of the control groups only learned either S1 or S2. Incidental Context information was provided by different background colors. On day 3 retention and transfertests were conducted for all groups. Results showed that incidental Context information alone could not avoid retroactive interference effect (Experiment 1). Directing participants’ attention towards the incidental contexts (Experiment 2) resulted in higher recognition performance and context dependency. Nevertheless, retroactive interference effects were found. Surprisingly, participants of the EG additionally showed proactive interference effects. A substantial change in Basketball rules provided the chance to systematically study the influence of visual context information on complex motor skill. In the first step of this experiment twenty Basketball players took 3-point-shots from the old distance. In a second step these experts took 3-points shots from the new, greater distance with either the old floor-markings or the new floor-markings. Results of this experiment show that floor markings do serve as incidental context information and do influence athlete’s performance. The Results of the present work are discussed in reference to other studies and two models, namely Glover’s perception-control-model (2004) and the MOSAIC-modell from Wolpert and Kawato (1998).

Investigations of soft matter using ultrashort high intensity pulses have been made possible through the advent of X-ray free-electrons lasers. The last decade has seen the development of a new type of protein crystallography where femtosecond dynamics can be studied, and single particle imaging with atomic resolution is on the horizon. The pulses are so intense that any sample quickly turns into a plasma. This thesis studies the ultrafast transition from soft matter to warm dense matter, and the implications for structural determination of proteins.                    We use non-thermal plasma simulations to predict ultrafast structural and electron dynamics. Changes in atomic form factors due to the electronic state, and displacement as a function of temperature, are used to predict Bragg signal intensity in protein nanocrystals. The damage processes started by the pulse will gate the diffracted signal within the pulse duration, suggesting that long pulses are useful to study protein structure. This illustrates diffraction-before-destruction in crystallography. The effect from a varying temporal photon distribution within a pulse is also investigated. A well-defined initial front determines the quality of the diffracted signal. At lower intensities, the temporal shape of the X-ray pulse will affect the overall signal strength; at high intensities the signal level will be strongly dependent on the resolution. Water is routinely used to deliver biological samples into the X-ray beam. Structural dynamics in water exposed to intense X-rays were investigated with simulations and experiments. Using pulses of different duration, we found that non-thermal heating will affect the water structure on a time scale longer than 25 fs but shorter than 75 fs. Modeling suggests that a loss of long-range coordination of the solvation shells accounts for the observed decrease in scattering signal. The feasibility of using X-ray emission from plasma as an indicator for hits in serial diffraction experiments is studied. Specific line emission from sulfur at high X-ray energies is suitable for distinguishing spectral features from proteins, compared to emission from delivery liquids. We find that plasma emission continues long after the femtosecond pulse has ended, suggesting that spectrum-during-destruction could reveal information complementary to diffraction.

Solving problems of production and calibration spindles water supply river armours by the help of method SPC. Analysis capability of gauge by the help of methodists MSA-Cg,Cgk. Evaluation capability of machanical abnd digital outside micrometer. Verification limiting deviation of micrometrical screw in among - calibration interval. Attestation capability of machine and of the process. Construction of regulation diagram. Project of new control instruments. Technically-economic evaluation:savings 110 560,00Kč, profitability 764,85%, economic return 0,13 year. Successful application of methodists SPC attested by document about adjustability of the process.