Calculation of supersonic flows at large distances from slender lifting bodies

Solving exact gas dynamic equations for supersonic flows far from axis of slender lifting bodie

Ceramidsynthese in Saccharomyces cerevisiae

The work presented in this dissertation gave the following results: (i) Sequence homologous of the membrane proteins Lag1p and Dgt1p exist all over the kingdom of eucaryotes. All of them share a highly conserved motif with two hydrophilic residues within a transmembrane domain. A limited proteolytic digestion showed, that the N-terminus of Dgt1p is orientated to the cytosolic side. Together with the in silicio analysis, the proteins of the LAG family have six transmembrane domains, a cytosolic C-terminus and an ER lumenal loop of ca. 45 amino acids. (ii) Different mutants of Dgt1p showed, that the C-terminus is essential for the function of the protein. The soluble N-terminus or its dilysine motif, normally mediating retrieval of ER resident proteins that escaped to the Golgi, have not obvious importance for Dgt1p. (iii) Lag1p and Dgt1p fulfill their function in the membrane of the ER and are no constitutive parts of COPII transport vesicles. Moreover, both proteins interact with each other and therefore appear to form a heteropolymeric complex in the ER membrane. (iv) The synthesis rates of complex sphingolipids are drastically reduced in the absence of LAG1 and DGT1. Consequently, lag1Ddgt1D cells have a decreased portion of sphingolipids compared to the wild type. The lipid defekt is not due to lacking phosphoinositolation of ceramide, since the catalytic activity of the corresponding enzyme was proven in vivo.(v) The synthesis block in lag1Ddgt1D cells leads to an accumulation of sphingoid bases. In this connection it was shown, that Lag1p and Dgt1p are essential for the incorporation of exogenous dihydrosphingosine into ceramide, whereas in their absence endogenous dihydrosphingosine is converted to ceramide with a merely decreased rate. The elongation of fatty acids to C26 is not reduced in lag1Ddgt1D cells. Lipid extracts of fumonisin B1 treated wild type cells resemble that of the double mutant, whereas the latter is not influenced by a toxin based inhibition of ceramide synthase. Overexpression of LAG1 and DGT1 does not lead to an overproduction of ceramide or sphingolipids. However, a direct in vitro assay for ceramide synthase activity finally proved the essential requirement of the reaction for Lag1p and Dgt1p. (vi) The overproduction of the ceramidases Ypc1p and Ydc1p in lag1Ddgt1D cells increases the synthesis rates as well as the effective amounts of complex sphingolipids. The defective incorporation of exogenous dihydrosphingosine into ceramide was, however, not reverted. The additional deletion of YPC1 and YDC1 in the absence of LAG1 and DGT1 decreased the amounts of inositol containing sphingolipids beyond detectable levels and, therefore, confirmed the essential requirement of Lag1p and Dgt1p for the ceramide synthase reaction. (vii) The survival of lag1Ddgt1D cells compared to wild type cells after short heat shock is drastically impaired. Moreover, the ability of yeast to form single cells on agar plates directly contributes to the temperature and the amount of ceramide available. As a consequence of the data obtained, the proteins Lag1p and Dgt1p are the first to be characterized as essential parts of the ceramide synthase reaction.Im Rahmen dieser Dissertation wurden im wesentlichen folgende Ergebnisse erzielt: (i) Sequenzhomologe der Membranproteine Lag1p und Dgt1p existieren ubiquitär im eukaryontischen Reich. Allen gemein ist ein hochkonserviertes Motiv, welches sich u.a. durch zwei hydrophile Reste innnerhalb eines Transmembransegments auszeichnet. Ein limitierter proteolytischer Verdau zeigte, daß der N-Terminus von Dgt1p cytosolisch orientiert ist. Im Zusammenhang mit in silicio-Analysen ergeben sich für die Familie der LAG-Proteine sechs Transmembran-domänen, ein cytosolischer C-Terminus und ein ER-lumenalen Bereich mit ca. 45 Aminosäuren. (ii) Verschiedene Mutationen von Dgt1p belegen, daß der stark negativ geladene C-Terminus essentiell für die Funktion des Proteins ist. Der lösliche N-Terminus oder dessen Dilysinmotiv, welches den retrograden Transport ER-residenter Proteine vermittelt, besitzen indes keine offensichtliche Bedeutung für Dgt1p. (iii) Lag1p und Dgt1p erfüllen ihre Funktion in der ER-Membran und sind kein konstitutiver Bestandteil von COPII-Transportvesikeln. Beide Proteine interagieren miteinander und scheinen so einen heteropolymeren Komplex in der ER-Membran auszubilden. (iv) Die Syntheseraten komplexer Sphingolipide sind in Abwesenheit von LAG1 und DGT1 drastisch reduziert. In Folge besitzen lag1Ddgt1D-Zellen einen vergleichsweise geringeren Anteil von Sphingolipiden an der Gesamtlipidmenge. Der Lipiddefekt ist nicht in einer fehlerhaften Phosphoinosilierung von Ceramid begründet, da die Aktivität des entsprechenden Enzyms in vivo nachgewiesen wurde.(v) Der Syntheseblock in lag1Ddgt1D-Zellen führt zu einer Akkumulation von Sphingoidbasen. In diesem Zusammenhang konnte gezeigt werden, daß Lag1p und Dgt1p für den Einbau von exogenem Dihydrosphingosin in Ceramid essentiell sind, wohingegen in deren Abwesenheit endogenes Dihydrosphingosin mit einer lediglich reduzierten Rate zu Ceramid konvertiert wird. Die Fettsäureelongation zu C26 ist in lag1Ddgt1D-Zellen nicht reduziert. Lipidextrakte von Fumonisin B1-behandelten Wildtypzellen ähneln denen der Doppelmutante, wohingegen letztere von einem toxininduzierten Block der Ceramidsynthase nicht beeinflußt wird. Die Überexpression von LAG1 und DGT1 bewirkt keine Überproduktion von Ceramid oder Sphingolipiden. Ein direkter Test der Ceramidsynthase in vitro bewies schließlich, daß Lag1p und Dgt1p für diese Reaktion essentiell sind. (vi) Die Überproduktion der Ceramidasen Ypc1p und Ydc1p in lag1Ddgt1D-Zellen erhöht sowohl die Syntheserate als auch die effektiven Mengen komplexer Sphingolipide. Der fehlerhafte Einbau von exogenem DHS in Ceramid wird dadurch nicht revertiert. Die zusätzliche Deletion von YPC1 und YDC1 in der Abwesenheit von LAG1 und DGT1 reduziert das Niveau inositolhaltiger Sphingolipide unter detektierbare Grenzen und bestätigt so die essentielle Bedeutung von Lag1p und Dgt1p für Ceramidsynthasereaktion. (vii) Das Überleben von lag1Ddgt1D-Zellen nach einem kurzen Hitzeschock ist im Vergleich zum Wildtyp drastisch eingeschränkt. Darüberhinaus steht die Fähigkeit zur Formierung von Einzelkolonien auf Agarplatten in einem direkten Zusammenhang mit der Temperatur und der Menge an verfügbarem Ceramid. Aufgrund der erzielten Daten konnten zum ersten Mal die Proteine Lag1p und Dgt1p als essentielle Bestandteile der Ceramidsynthasereaktion charakterisiert werden

Beitrag zur Stabilitätsuntersuchung von Strukturen mit räumlich korrelierten geometrischen Imperfektionen

Für geometrisch imperfekte Strukturen wird die Versagenswahrscheinlichkeit bezüglich Stabilitätskriterien bestimmt. Eine probabilistische Beschreibung der geometrischen Imperfektionen erfolgt mit skalaren ortsdiskretisierten Zufallsfeldern. Die Stabilitätsberechnungen werden mit der Finite Elemente Methode durchgeführt. Ausgangspunkt der Berechnung ist eine systematische Formulierung probabilistisch gewichteter Imperfektionsformen durch eine Eigenwertzerlegung der Kovarianzmatrix. Wenn mit einer strukturmechanisch orientierten Sensitivitätsanalyse ein Unterraum zur näherungsweisen Beschreibung des probabilistischen Strukturverhaltens gefunden wird, kann die Versagenswahrscheinlichkeit numerisch sehr effizient durch ein Interaktionsmodell bestimmt werden. Es zeigte sich, daß dies genau dann möglich ist, wenn die Beulform merklich im Imperfektionsfeld enthalten ist. Die Imperfektionsform am Bemessungspunkt entspricht dann, unabhängig vom Lastniveau, gerade der Beulform. Wenn die Beulform im Imperfektionsfeld einen untergeordneten Beitrag liefert, erscheint eine Reduktion des stochastischen Problems auf wenige Zufallsvariablen dagegen nicht möglich.The thesis presents a concept for reliability analysis of geometrical imperfect structures with respect to static stability criteria. The geometrical imperfections are modeled as Gaussian random fields. The structural analysis is based on the Finite Element Method. A spectral decomposition of the covariance matrix, enables to formulate independent probabilistically weighted imperfections shapes, which may be analyzed by means of structural mechanics. Reliability calculations with procedures such as the response surface method require the reduction of the random variable space. Examples proved that a suitable definition of a subspace of the random variable space is possible, if the buckling shapes are sufficiently included in the random field. In this case the imperfection shape is-independent of the load level-identical to the buckling shape. In contrast if the buckling shapes are not included in the random field, the structure shows a wide banded behavior. Consequently a reduction of the variable space and the application of an interaction models is then not feasible for the determination of the failure probabilty

SLang - the Structural Language : Solving Nonlinear and Stochastic Problems in Structural Mechanics

Recent developments in structural mechanics indicate an increasing need of numerical methods to deal with stochasticity. This process started with the modeling of loading uncertainties. More recently, also system uncertainty, such as physical or geometrical imperfections are modeled in probabilistic terms. Clearly, this task requires close connenction of structural modeling with probabilistic modeling. Nonlinear effects are essential for a realistic description of the structural behavior. Since modern structural analysis relies quite heavily on the Finite Element Method, it seems to be quite reasonable to base stochastic structural analysis on this method. Commercially available software packages can cover deterministic structural analysis in a very wide range. However, the applicability of these packages to stochastic problems is rather limited. On the other hand, there is a number of highly specialized programs for probabilistic or reliability problems which can be used only in connection with rather simplistic structural models. In principle, there is the possibility to combine both kinds of software in order to achieve the goal. The major difficulty which then arises in practical computation is to define the most suitable way of transferring data between the programs. In order to circumvent these problems, the software package SLang (Structural Language) has been developed. SLang is a command interpreter which acts on a set of relatively complex commands. Each command takes input from and gives output to simple data structures (data objects), such as vectors and matrices. All commands communicate via these data objects which are stored in memory or on disk. The paper will show applications to structural engineering problems, in particular failure analysis of frames and shell structures with random loads and random imperfections. Both geometrical and physical nonlinearities are taken into account

Reproducing tactile and proprioception based on the human-in-the-closed-loop conceptual approach

Prosthetic limb embodiment remains a significant challenge for many amputees due to traditional designs' lack of sensory feedback. To address this challenge, the effectiveness of non-invasive neuromuscular electrical stimulation (NMES) controlled by a hybrid proportional-differential (PD)-Fuzzy logic system was evaluated for providing real-time proprioception and tactile feedback. The study used a human-in-the-closed-loop approach with ten participants: five upper limb amputees and five non-disabled individuals as the control group. An applied force, the joint angle of a prosthetic hand's finger, and surface electromyography signals generated by the biceps muscle all regulate the intensity of sensory feedback. Additionally, the C6 and C7 myotomes were selected as elicitation sites. The average threshold for detecting action motion and force was around 21° and 1.524N, respectively. The participants successfully reproduced desired joint angles within the range of 0°-110° at five separate intervals. In the weight recognition experiment, the amputee participant's minimum number of false predictions was four. The highest accuracy achieved was 80.66% in detecting object size and stiffness. Additionally, unpaired t-tests were performed for the means of the results of the experiments to determine statistically significant differences between groups. The results suggest that stimulation of myotomes by NMES is an effective non-invasive method for delivering rich multimodal sensation information to individuals with disabilities, including upper limb amputees, without needing visual or auditory cues. These findings contribute to the development of non-invasive sensory substitution in prostheses

Comparative cost of illness analysis and assessment of health care burden of Duchenne and Becker muscular dystrophies in Germany.

Our study aimed to determine the burden of illness in dystrophinopathy type Duchenne (DMD) and Becker (BMD), both leading to progressive disability, reduced working capacity and high health care utilization

College Students’ Responses to Antismoking Messages: Denial, Defiance, and Other Boomerang Effects

Despite the success of antismoking campaigns that aim to prevent young teens from smoking, this qualitative study provides strong evidence that different initiatives are needed for college students, particularly those who already smoke. When asked for responses to current antismoking messages, nonsmokers generally championed the cause; however, smokers often responded with anger, defiance, denial, and other negative responses. Consumers who respond in this manner are not well served by existing strategies, and money used for such campaigns could be better spent. New strategies are offered in hopes that antismoking campaigns can communicate more effectively with one high-risk group—college student smokers