A Genotype-First Approach for the Molecular and Clinical Characterization of Uncommon De Novo Microdeletion of 20q13.33

Background: Subtelomeric deletions of the long arm of chromosome 20 are rare, with only 11 described in the literature. Clinical features of individuals with these microdeletions include severe limb malformations, skeletal abnormalities, growth retardation, developmental and speech delay, mental retardation, seizures and mild, non-specific dysmorphic features. Methodology/Principal Findings: We characterized microdeletions at 20q13.33 in six individuals referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. There does not appear to be a clinically recognizable constellation of dysmorphic features among individuals with subtelomeric 20q microdeletions. Conclusions/Significance: Based on genotype-phenotype correlation among individuals in this and previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4 and KCNQ2 and neurodevelopmental deficits. Deletion of this region may play an important role in cognitive development

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

The Polarity Protein Scribble Regulates Myelination and Remyelination in the Central Nervous System

The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination

Physical aspects of an indoor-volleyball serve

Den Hauptteil der Arbeit bildet eine physikalische Untersuchung des Aufschlags beim Hallenvolleyball. Das Ziel besteht darin, einen Spieler während eines Überkopfservice zu filmen und daraus Werte wie etwa die Ballgeschwindigkeit zu bestimmen. Es wird darauf eingegangen, in welchem Zusammenhang die einzelnen Größen stehen. Es wurden zwei Servicearten betrachtet, das so genannte Flatterservice und das Service mit hoher Rotationsgeschwindigkeit des Balles.Weiters wurden Aufschläge von einem Experten (Profi) und einem Amateur verglichen, um durch mögliche Unterschiede Eigenheiten dieser Schlagtechniken zu erkennen.Die Leistungen des Profis liegen erwartungsgemäß immer über denen des Amateurs. Die Auswertung der Videos zeigte, dass die Sportler manchmal unterschiedliche Techniken anwenden, um zu einem ähnlichen Ziel zu gelangen.Des Weiteren wurde die Schwingungsdauer des Volleyballs ermittelt. Dies geschah durch zwei voneinander unabhängige Experimente. Einerseits wurde die Schwingungsdauer durch die Videoanalyse der Ballschwingungen bestimmt. Andererseits wurde die Schwingungsdauer anhand eines statischen Experiments ermittelt. Der Ball selbst wurde dabei als harmonischer Oszillator betrachtet und mit Hilfe von Gewichten deformiert. Die beiden Methoden ergaben annähernd gleiche Ergebnisse. Bei der Untersuchung der Ursache des Flatterservice ergab sich folgendes Resultat: Durch das Schlagen des Balls wird dieser in Schwingungen versetzt, wobei eine durchschnittliche Schwingungsfrequenz von etwa 30 Hz bestimmt wurde. Durch diese Asymmetrie der Form des Balles kommt es aufgrund des Magnuseffekts zu einer seitlichen Kraftwirkung und damit zu einer seitlichen Ablenkung des Balls. Die Schwingungsachse der Verformung rotiert jedoch während des Ballflugs etwa ein- bis zweimal. Die Anzahl der Richtungsänderungen ist damit mit der Frequenz der Rotationen des Balls gekoppelt. Die Schwingungen führen zu einer Asymmetrie, die für die Richtungsänderung verantwortlich ist.The main part of this thesis consists of the physical study of the volleyball serve. The method has been to film a volleyball player during the ?over-head serve? in order to determine typical parameters like the speed of the ball or its rotation. Furthermore, the correlation of the individual physical parameters will be elaborated.Two different serves have been investigated: the float serve and the serve with high speed rotation of the ball.The serves by a professional and an amateur volleyball player have been compared to identify peculiarities of these two serves through possible differences. As expected, the achieved performances of the professional volleyball player are in all cases better than the performances of the amateur.The analysis of the videos showed that the two athletes sometimes use different techniques to attain a desired result.Moreover the oscillating period of the volleyball has been measured by two independent experiments. On the one hand, the oscillating period has been determined analyzing the video of the oscillations of the ball. Secondly, the oscillating period has been measured by a static experiment. The ball itself was considered as a harmonic oscillator and deformed with different weights. Both methods revealed approximately the same results with oscillation times of 28 ms respectively 31 ms.The analysis of the physical basis of a float serve revealed the following result: The ball it is forced to oscillations by hitting it with the measured oscillating frequency of about 30 Hz. The asymmetry of the shape of the ball leads via the ?Magnus effect? to a lateral force and thereby to a lateral deviation of the ball. However, the axis of the deformation rotates during the flight of the ball about once or/to twice. This corresponds to two to four changes of the direction of the ball which is observed also in real game-situations.vorgelegt von Marco KröpflAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in engl. SpracheGraz, Univ., Dipl.-Arb., 201

Physical aspects of an indoor-volleyball serve

Den Hauptteil der Arbeit bildet eine physikalische Untersuchung des Aufschlags beim Hallenvolleyball. Das Ziel besteht darin, einen Spieler während eines Überkopfservice zu filmen und daraus Werte wie etwa die Ballgeschwindigkeit zu bestimmen. Es wird darauf eingegangen, in welchem Zusammenhang die einzelnen Größen stehen. Es wurden zwei Servicearten betrachtet, das so genannte Flatterservice und das Service mit hoher Rotationsgeschwindigkeit des Balles.Weiters wurden Aufschläge von einem Experten (Profi) und einem Amateur verglichen, um durch mögliche Unterschiede Eigenheiten dieser Schlagtechniken zu erkennen.Die Leistungen des Profis liegen erwartungsgemäß immer über denen des Amateurs. Die Auswertung der Videos zeigte, dass die Sportler manchmal unterschiedliche Techniken anwenden, um zu einem ähnlichen Ziel zu gelangen.Des Weiteren wurde die Schwingungsdauer des Volleyballs ermittelt. Dies geschah durch zwei voneinander unabhängige Experimente. Einerseits wurde die Schwingungsdauer durch die Videoanalyse der Ballschwingungen bestimmt. Andererseits wurde die Schwingungsdauer anhand eines statischen Experiments ermittelt. Der Ball selbst wurde dabei als harmonischer Oszillator betrachtet und mit Hilfe von Gewichten deformiert. Die beiden Methoden ergaben annähernd gleiche Ergebnisse. Bei der Untersuchung der Ursache des Flatterservice ergab sich folgendes Resultat: Durch das Schlagen des Balls wird dieser in Schwingungen versetzt, wobei eine durchschnittliche Schwingungsfrequenz von etwa 30 Hz bestimmt wurde. Durch diese Asymmetrie der Form des Balles kommt es aufgrund des Magnuseffekts zu einer seitlichen Kraftwirkung und damit zu einer seitlichen Ablenkung des Balls. Die Schwingungsachse der Verformung rotiert jedoch während des Ballflugs etwa ein- bis zweimal. Die Anzahl der Richtungsänderungen ist damit mit der Frequenz der Rotationen des Balls gekoppelt. Die Schwingungen führen zu einer Asymmetrie, die für die Richtungsänderung verantwortlich ist.The main part of this thesis consists of the physical study of the volleyball serve. The method has been to film a volleyball player during the ?over-head serve? in order to determine typical parameters like the speed of the ball or its rotation. Furthermore, the correlation of the individual physical parameters will be elaborated.Two different serves have been investigated: the float serve and the serve with high speed rotation of the ball.The serves by a professional and an amateur volleyball player have been compared to identify peculiarities of these two serves through possible differences. As expected, the achieved performances of the professional volleyball player are in all cases better than the performances of the amateur.The analysis of the videos showed that the two athletes sometimes use different techniques to attain a desired result.Moreover the oscillating period of the volleyball has been measured by two independent experiments. On the one hand, the oscillating period has been determined analyzing the video of the oscillations of the ball. Secondly, the oscillating period has been measured by a static experiment. The ball itself was considered as a harmonic oscillator and deformed with different weights. Both methods revealed approximately the same results with oscillation times of 28 ms respectively 31 ms.The analysis of the physical basis of a float serve revealed the following result: The ball it is forced to oscillations by hitting it with the measured oscillating frequency of about 30 Hz. The asymmetry of the shape of the ball leads via the ?Magnus effect? to a lateral force and thereby to a lateral deviation of the ball. However, the axis of the deformation rotates during the flight of the ball about once or/to twice. This corresponds to two to four changes of the direction of the ball which is observed also in real game-situations.vorgelegt von Marco KröpflAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in engl. SpracheGraz, Univ., Dipl.-Arb., 201