Studies on the mechanism of retinoid-induced pattern duplications in the early chick limb bud: temporal and spatial aspects.

All-trans-retinoic acid causes striking digit pattern changes when it is continuously released from a bead implanted in the anterior margin of an early chick wing bud. In addition to the normal set of digits (234), extra digits form in a mirror-symmetrical arrangement, creating digit patterns such as a 432234. These retinoic acid-induced pattern duplications closely mimic those found after grafts of polarizing region cells to the same positions with regard to dose-response, timing, and positional effects. To elucidate the mechanism by which retinoic acid induces these pattern duplications, we have studied the temporal and spatial distribution of all-trans-retinoic acid and its potent analogue TTNPB in these limb buds. We find that the induction process is biphasic: there is an 8-h lag phase followed by a 6-h duplication phase, during which additional digits are irreversibly specified in the sequence digit 2, digit 3, digit 4. On average, formation of each digit seems to require between 1 and 2 h. The tissue concentrations, metabolic pattern, and spatial distribution of all-trans-retinoic acid and TTNPB in the limb rapidly reach a steady state, in which the continuous release of the retinoid is balanced by loss from metabolism and blood circulation. Pulse-chase experiments reveal that the half-time of clearance from the bud is 20 min for all-trans-retinoic acid and 80 min for TTNPB. Manipulations that change the experimentally induced steep concentration gradient of TTNPB suggest that a graded distribution of retinoid concentrations across the limb is required during the duplication phase to induce changes in the digit pattern. The extensive similarities between results obtained with retinoids and with polarizing region grafts raise the possibility that retinoic acid serves as a natural "morphogen" in the limb

Studie zu einem Sportentwicklungskonzept für die Stadt Hildesheim : Abschlussbericht

Sport und Bewegung sind im ständigen Wandel befindlich. Die Sportnachfrage spiegelt die zunehmende Vielfalt von Sportausübung, Motiven, Anbietern, Sport- und Bewegungsräumen sowie von Zielgruppen und Akteuren wider. Darauf möchte auch die Stadt Hildesheim reagieren und bestehende Strukturen des Sports analysieren sowie zukünftige Bedarfe und entsprechende Weiterentwicklungen und Veränderungen in einem Sportentwicklungskonzept thematisieren. An der Sportentwicklungsplanung der Stadt Hildesheim wirkt das Institut für Sportwissenschaft der Universität Hildesheim durch eine entsprechende Studie mit, in der insbesondere das Sportverhalten der Bürger/innen sowie der Ist-Zustand der Sporträume erfasst werden sollen. Inhaltliche Schwerpunkte dieser Erhebung sollen sowohl der institutionelle als auch der informelle Sport sein. Zur Datenerhebung sind quantitative Fragebogendesigns zur Befragung der Bürger und der Vereine sowie die Beobachtung von Sporträumen vorgesehen. Ergänzt werden die Daten durch qualitative Interviews. Auf diese Weise sollen Entwicklungspotentiale für die Stadt Hildesheim hervorgebracht werden, die durch sportwissenschaftliche Erkenntnisse zu innovativen Sport- und Bewegungsangeboten ergänzt werden können

Meiotic sex chromosome cohesion and autosomal synapsis are supported by Esco2.

In mitotic cells, establishment of sister chromatid cohesion requires acetylation of the cohesin subunit SMC3 (acSMC3) by ESCO1 and/or ESCO2. Meiotic cohesin plays additional but poorly understood roles in the formation of chromosome axial elements (AEs) and synaptonemal complexes. Here, we show that levels of ESCO2, acSMC3, and the pro-cohesion factor sororin increase on meiotic chromosomes as homologs synapse. These proteins are less abundant on the largely unsynapsed sex chromosomes, whose sister chromatid cohesion appears weaker throughout the meiotic prophase. Using three distinct conditional Esco2 knockout mouse strains, we demonstrate that ESCO2 is essential for male gametogenesis. Partial depletion of ESCO2 in prophase I spermatocytes delays chromosome synapsis and further weakens cohesion along sex chromosomes, which show extensive separation of AEs into single chromatids. Unsynapsed regions of autosomes are associated with the sex chromatin and also display split AEs. This study provides the first evidence for a specific role of ESCO2 in mammalian meiosis, identifies a particular ESCO2 dependence of sex chromosome cohesion and suggests support of autosomal synapsis by acSMC3-stabilized cohesion

Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters.

Many physiological processes exhibit circadian rhythms driven by cellular clocks composed of interlinked activating and repressing elements. To investigate temporal regulation in this molecular oscillator, we combined mouse genetic approaches and analyses of interactions of key circadian proteins with each other and with clock gene promoters. We show that transcriptional activators control BRD4-PTEFb recruitment to E-box-containing circadian promoters. During the activating phase of the circadian cycle, the lysine acetyltransferase TIP60 acetylates the transcriptional activator BMAL1 leading to recruitment of BRD4 and the pause release factor P-TEFb, followed by productive elongation of circadian transcripts. We propose that the control of BRD4-P-TEFb recruitment is a novel temporal checkpoint in the circadian clock cycle

Long Hole Film Cooling Dataset for CFD Development

An experiment investigating flow and heat transfer of long (length to diameter ratio of 18) cylindrical film cooling holes has been completed. In this paper, the thermal field in the flow and on the surface of the film cooled flat plate is presented for nominal freestream turbulence intensities of 1.5 and 8 percent. The holes are inclined at 30deg above the downstream direction, injecting chilled air of density ratio 1.0 onto the surface of a flat plate. The diameter of the hole is 0.75 in. (0.01905 m) with center to center spacing (pitch) of 3 hole diameters. Coolant was injected into the mainstream flow at nominal blowing ratios of 0.5, 1.0, 1.5, and 2.0. The Reynolds number of the freestream was approximately 11,000 based on hole diameter. Thermocouple surveys were used to characterize the thermal field. Infrared thermography was used to determine the adiabatic film effectiveness on the plate. Hotwire anemometry was used to provide flowfield physics and turbulence measurements. The results are compared to existing data in the literature. The aim of this work is to produce a benchmark dataset for Computational Fluid Dynamics (CFD) development to eliminate the effects of hole length to diameter ratio and to improve resolution in the near-hole region. In this report, a Time-Filtered Navier Stokes (TFNS), also known as Partially Resolved Navier Stokes (PRNS), method that was implemented in the Glenn-HT code is used to model coolant-mainstream interaction. This method is a high fidelity unsteady method that aims to represent large scale flow features and mixing more accurately

Mal-Adaptation of Event-Related EEG Responses Preceding Performance Errors

Recent EEG and fMRI evidence suggests that behavioral errors are foreshadowed by systematic changes in brain activity preceding the outcome by seconds. In order to further characterize this type of error precursor activity, we investigated single-trial event-related EEG activity from 70 participants performing a modified Eriksen flanker task, in particular focusing on the trial-by-trial dynamics of a fronto-central independent component that previously has been associated with error and feedback processing. The stimulus-locked peaks in the N2 and P3 latency range in the event-related averages showed expected compatibility and error-related modulations. In addition, a small pre-stimulus negative slow wave was present at erroneous trials. Significant error-preceding activity was found in local stimulus sequences with decreased conflict in the form of less negativity at the N2 latency (310–350 ms) accumulating across five trials before errors; concomitantly response times were speeding across trials. These results illustrate that error-preceding activity in event-related EEG is associated with the performance monitoring system and we conclude that the dynamics of performance monitoring contribute to the generation of error-prone states in addition to the more remote and indirect effects in ongoing activity such as posterior alpha power in EEG and default mode drifts in fMRI

Visual activation of auditory cortex reflects maladaptive plasticity in cochlear implant users

Cross-modal reorganization in the auditory cortex has been reported in deaf individuals. However, it is not well understood whether this compensatory reorganization induced by auditory deprivation recedes once the sensation of hearing is partially restored through a cochlear implant. The current study used electroencephalography source localization to examine cross-modal reorganization in the auditory cortex of post-lingually deafened cochlear implant users. We analysed visual-evoked potentials to parametrically modulated reversing chequerboard images between cochlear implant users (n = 11) and normal-hearing listeners (n = 11). The results revealed smaller P100 amplitudes and reduced visual cortex activation in cochlear implant users compared with normal-hearing listeners. At the P100 latency, cochlear implant users also showed activation in the right auditory cortex, which was inversely related to speech recognition ability with the cochlear implant. These results confirm a visual take-over in the auditory cortex of cochlear implant users. Incomplete reversal of this deafness-induced cortical reorganization might limit clinical benefit from a cochlear implant and help explain the high inter-subject variability in auditory speech comprehensio

Evaluation of evoked potentials to dyadic tones after cochlear implantation

Auditory evoked potentials are tools widely used to assess auditory cortex functions in clinical context. However, in cochlear implant users, electrophysiological measures are challenging due to implant-created artefacts in the EEG. Here, we used independent component analysis to reduce cochlear implant-related artefacts in event-related EEGs of cochlear implant users (n = 12), which allowed detailed spatio-temporal evaluation of auditory evoked potentials by means of dipole source analysis. The present study examined hemispheric asymmetries of auditory evoked potentials to musical sounds in cochlear implant users to evaluate the effect of this type of implantation on neuronal activity. In particular, implant users were presented with two dyadic tonal intervals in an active oddball design and in a passive listening condition. Principally, the results show that independent component analysis is an efficient approach that enables the study of neurophysiological mechanisms of restored auditory function in cochlear implant users. Moreover, our data indicate altered hemispheric asymmetries for dyadic tone processing in implant users compared with listeners with normal hearing (n = 12). We conclude that the evaluation of auditory evoked potentials are of major relevance to understanding auditory cortex function after cochlear implantation and could be of substantial clinical value by indicating the maturation/reorganization of the auditory system after implantatio

COMPARISON BETWEEN FREEDOM OF RELIGION IN GERMANY AND IN THE UNITED STATES IN GENERAL AND THE TREATMENT OF THE CHURCH OF SCIENTOLOGY SPECIFICALLY

The thesis first gives background information about the general development of fundamental rights in both Germany and the United States and specifically the freedom of religion. The analysis discusses in particular freedom of religion granted by Article 4 of the Basic Law in Germany and the religious clauses of the First Amendment of the American Constitution. In the first conclusion, the differences in the interpretations of the religious clauses both in Germany and the United States will be stated. These differences will then be illustrated by a discussion on the Church of Scientology through its basic facts, history, ideas, and attitude. The most important German and American court rulings will be provided which confront the issue of whether or not the Church of Scientology is legally defined as a church. Even though the American courts do not provide a definition of religion, the Internal Revenue Service does. The issue arises whether or not Scientology meets these requirements. In an excursus, the thesis examines, whether Scientology theologically is a religion. Finally, there will be a discussion of German constitutional issues regarding the Church of Scientology. The conclusion states that Germany does not neglect the fundamental right of religious freedom in its actions against Scientology but protects its relatively young democracy from the threat of extremism and fundamentalism; whereas the United States is able to grant more freedom due to its better established and secured democracy, it still has some control through the scrutiny of the Internal Revenue Service