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Spermine oxidase is a FAD-containing enzyme involved in polyamines catabolism, selectively oxidizing spermine to produce H2O2, spermidine, and 3-aminopropanal. Spermine oxidase is highly expressed in the mouse brain and plays a key role in regulating the levels of spermine, which is involved in protein synthesis, cell division and cell growth. Spermine is normally released by neurons at synaptic sites where it exerts a neuromodulatory function, by specifically interacting with different types of ion channels, and with ionotropic glutamate receptors. In order to get an insight into the neurobiological roles of spermine oxidase and spermine, we have deregulated spermine oxidase gene expression producing and characterizing the transgenic mouse model JoSMOrec, conditionally overexpressing the enzyme in the neocortex. We have investigated the effects of spermine oxidase overexpression in the mouse neocortex by transcript accumulation, immunohistochemical analysis, enzymatic assays and polyamine content in young and aged animals. Transgenic JoSMOrec mice showed in the neocortex a higher H2O2 production in respect to Wild-Type controls, indicating an increase of oxidative stress due to SMO overexpression. Moreover, the response of transgenic mice to excitotoxic brain injury, induced by kainic acid injection, was evaluated by analysing the behavioural phenotype, the immunodistribution of neural cell populations, and the ultrastructural features of neocortical neurons. Spermine oxidase overexpression and the consequently altered polyamine levels in the neocortex affects the cytoarchitecture in the adult and aging brain, as well as after neurotoxic insult. It resulted that the transgenic JoSMOrec mouse line is more sensitive to KA than Wild-Type mice, indicating an important role of spermine oxidase during excitotoxicity. These results provide novel evidences of the complex and critical functions carried out by spermine oxidase and spermine in the mammalian brain. © 2013 Cervelli et al.

The demand for natural gas from offshore fields is continuously increasing. Especially future production from Arctic waters comes into focus in context with global warming effects leading to the development of a dedicated technology. Relevant approaches work with floating turret moored production terminals (FLNG) receiving gas via flexible risers from subsea or onshore fields. These terminals provide on-board gas treatment and liquefaction facilities as well as huge storage capabilities for LNG (Liquefied Natural Gas), LPG (Liquefied Petrol Gases) and condensate. Products are transferred to periodically operating shuttle tankers for onshore supply reducing the need for local onshore processing plants providing increased production flexibility (future movability or adaptation of capacity). Nevertheless, in case of harsh environmental conditions or ice coverage the offshore transfer of cryogenic liquids between the terminal and the tankers becomes a major challenge. In the framework of the joint research project MPLS20 ([1]), an innovative offshore mooring and cargo transfer system has been developed and analyzed. MPLS20 is developed by the project partners Nexans ([2]) and Brugg ([3]), leading manufacturers of vacuum insulated, flexible cryogenic transfer pipes, IMPaC ([4]), an innovative engineering company that has been involved in many projects for the international oil and gas industry for more than 25 years and the Technical University (TU) Berlin, Department of Land- and Sea Transportation Systems (NAOE, [5]), with great expertise in numerical analyses and model tests. The overall system is based on IMPaC’s patented and certified offshore ‘Mooring Bay’ concept allowing mooring of the vessels in tandem configuration and simultaneous handling and operation of up to six flexible transfer pipes in full aerial mode. The concept is outlined to operate with flexible transfer lines with 16-inch inner diameter like the newly designed and certified corrugated pipes from Nexans and Brugg. The mooring concept and its major subsystems have proven their operability by means of extensive numerical analysis, model tests and a professional ship handling simulator resulting in an overall transfer solution suitable to be used especially under Arctic conditions like addressed by the EU joint research project ACCESS (http://access-eu.org/). The paper introduces the new offshore LNG transfer system and focuses especially on its safe and reliable operability in the Arctic — with ice coverage as well as in open water conditions.

This essay traces some of the contexts and media in which "Heracles-Hercules" - as a hero between virtue and hubris - was visible in European societies from the end of the middle ages onwards. It discusses whether this example of the reception, appropriation and transformation of classical myths in the early modern period can be understood as a European "lieu de mémoire", and to what extent the concept of "lieux de mémoire" (or sites of memory) can foster our understanding of a particular object of study (here the Heracles/Hercules myth). Against this backdrop, we conclude with some general questions about the more ambitious project* of a comprehensive register of European "lieux de mémoire". * * Published as: Boer, Pim den / Duchhardt, Heinz / Kreis, Georg / Schmale, Wolfgang (eds.): Europäische Erinnerungsorte, 3 vols., Munich 2011–2012

The skeletal muscle basement membrane fulfils several crucial functions during development and in the mature myotome and defects in its composition underlie certain forms of muscular dystrophy. A major component of this extracellular structure is the laminin polymer, which assembles into a resilient meshwork that protects the sarcolemma during contraction. Here we describe a zebrafish mutant, softy, which displays severe embryonic muscle degeneration as a result of initial basement membrane failure. The softy phenotype is caused by a mutation in the lamb2 gene,identifying laminin β2 as an essential component of this basement membrane. Uniquely, softy homozygotes are able to recover and survive to adulthood despite the loss of myofibre adhesion. We identify the formation of ectopic, stable basement membrane attachments as a novel means by which detached fibres are able to maintain viability. This demonstration of a muscular dystrophy model possessing innate fibre viability following muscle detachment suggests basement membrane augmentation as a therapeutic strategy to inhibit myofibre loss.

Pax6 is a highly conserved transcription factor that controls the morphogenesis of various organs. Changes in Pax6 dosage have been shown to affect the formation of multiple tissues. PAX6 haploinsufficiency leads to aniridia, a pan-ocular disease primarily characterized by iris hypoplasia. Herein, we employ a modular system that includes null and overexpressed conditional alleles of Pax6. The use of the Tyrp2-Cre line, active in iris and ciliary body (CB) primordium, enabled us to investigate the effect of varying dosages of Pax6 on the development of these ocular sub-organs. Our findings show that a lack of Pax6 in these regions leads to dysgenesis of the iris and CB, while heterozygosity impedes growth of the iris and maturation of the iris sphincter. Overexpression of the canonical, but not the alternative splice variant of Pax6 results in severe structural aberrations of the CB and hyperplasia of the iris sphincter. A splice variant-specific rescue experiment revealed that both splice variants are able to correct iris hypoplasia, while only the canonical form rescues the sphincter. Overall, these findings demonstrate the dosage-sensitive roles of Pax6 in the formation of both the CB and the iris.

Aristaless-related homeobox (Arx) was recently demonstrated to be involved in pancreatic alpha cell fate specification while simultaneously repressing the beta and delta cell lineages. To establish whether Arx is not only necessary, but also sufficient to instruct the alpha cell fate in endocrine progenitors, we used a gain-of-function approach to generate mice conditionally misexpressing this factor. Mice with forced Arx expression in the embryonic pancreas or in developing islet cells developed a dramatic hyperglycemia and eventually died. Further analysis demonstrated a drastic loss of beta and delta cells. Concurrently, a remarkable increase in the number of cells displaying alpha cell or, strikingly, pancreatic polypeptide (PP) cell features was observed. Notably, the ectopic expression of Arx induced in embryonic or adult beta cells led to a loss of the beta cell phenotype and a concomitant increase in a number of cells with alpha or PP cell characteristics. Combining quantitative real-time PCR and lineage-tracing experiments, we demonstrate that, in adult mice, the misexpression of Arx, rather than its overexpression, promotes a conversion of beta cells into glucagon- or PP-producing cells in vivo. These results provide important insights into the complex mechanisms underlying proper pancreatic endocrine cell allocation and cell identity acquisition.

The development of oil and gas fields in shallow icy waters, for instance in the Northern Caspian Sea, have increased the awareness of protecting offshore structures by means of ice barriers from the impacts of drifting ice. Protection could be provided by Ice Protection Piles (IPPs), installed in close vicinity to the offshore structure to be protected. Piles then take the main loads from the drifting ice by pre-fracturing the advancing ice sheet. Hence, the partly shielded offshore structure could be designed according to significant lower global design ice loads. In this regard, various configurations of pile arrangements have been model tested during the MATRA-OSE research project in the Ice Model Test Basin of the Hamburg Sip Model Basin (HSVA). The main objective was to analyse the behaviour of ice interactions with the protection piles together with the establishment of design ice loads on an individual pile within the pile arrangement. The pile to pile distances within each arrangement were varied from 2 to 8 times the pile diameter for both, vertical and inclined (30° to the horizontal) pile arrangements. Two test runs with 0.1 m and 0.5 m thick ice (full scale values) were conducted respectively. The full scale water depth was 4 m. Based on the model test observations, it was found that the rubble generation increases with decreasing pile to pile distances. Inclined piles were capable to produce more rubble than vertical piles and considerable lower ice loads were measured on inclined arrangements compared to vertical arrangements. As initial rubble has formed in front of the arrangements, the rubble effect accelerated considerable. Subsequent to the build-up of rubble accumulations, no effect of the pile inclination on the exerted ice loads could be observed. If piles are used as ice barriers, the distance between the piles should be less than 4D for inclined piles and 6D for vertical piles to allow sufficient rubble generation. Larger distances only generated significant ice rubble after initial grounding of the ice had occurred.Copyright © 2006 by ASME

Background: Sinonasal Teratocarcinosarcoma (SNTC) is a very unusual and aggressive neoplasm characterized by the combination of malignant teratoma and carcinosarcoma features. We present the first case of malignant SNTC treated with individualized multimodal therapy including a histology-specific chemotherapy. Case Report: A 31-year-old man presented with an obstruction of the right pansinus. Histology showed an SNTC with major parts of small cell, poorly differentiated carcinoma and a small proportion of highly differentiated embryonal rhabdomyosarcoma. An operation was performed followed by intraoperative application of a 5-FU ointment. Adjuvant chemotherapy with cisplatin, etoposid and ifosfamid were given in regard to the major components of this heterogeneous tumor. Radiotherapy up to 59.4 Gy was applied. Conclusion: 36 months after the end of therapy, there is no sign of tumor recurrence or metastasis in our patient. We suggest that surgery, radiotherapy and a histology-specific multidrug chemotherapy seems to be a therapeutic approach that is appropriate for this heterogeneous tumor.

Apoptosis is an essential ubiquitous process that controls the duration of the life span of cells, thus playing a crucial role in morphogenetic, histogenetic, and phylogenetic developmental processes. Apaf1 (apoptosis protease activating factor 1) is one of the central mediators of the intrinsic apoptotic pathway and a part of the apoptosome, which activates procaspase-3 and promotes cell death. Gene knockout of Apaf1 in mice leads to late embryonic lethality with malformations such as the persistence of interdigital webs and hyperplasia of brain and retina. Therefore, Apaf1 is generally believed to play a crucial role in developmental apoptosis and have a widespread expression. However, its pattern of expression in early development remains unknown. To specify whether Apaf1 indeed plays this key role, we investigated the pattern of gene expression for Apaf1 in mouse embryos on day 7, 9, and 12 of development. Our results show, that gene expression for Apaf1 first occurs within the embryo between day 7 and 9 of development, becoming more widespread toward day 12 and then includes structures, such as yolk sac, mesenchyme, cartilage, heart anlage, otic vesicle, peridermis, and anlagen of the spinal ganglia and vertebral bodies. Our results also show that gene expression for Apaf1 is not ubiquitous in early mouse development. This finding indicates that cell death processes are independent of or less dependent on Apaf1 during this time. Of interest, an active gene expression for Apaf1 is also present in organ anlagen such as heart or intestine, in which no obvious phenotype is seen after Apaf1 deletion. This finding suggests a possible role for Apaf1 in such anlagen as a putative alternative compensatory pathway, which could be switched on in the case of defects in the mediators that are normally involved in such organs.

The use of drilling platforms for exploration drillings in ice-covered shallow water is expected to increase in the future. Jack-up platforms (JU) are regarded to be most suitable for exploration drillings due to their high mobility, their facile transportation and installation. Although having proved their capability for harsh environments, e.g. in the North Sea, jack-ups have neither been especially designed for nor have been operated frequently in icy waters. The problems associated with the operation of jack-ups in ice waters are related to structural integrity as well as to operational limitations. One objective of the research project MATRA-OSE was to check the design of JU for exploration and oil production in ice-covered, shallow-water areas. The global stability of JU as well as local and global loads acting on a three-legged jack-up drilling unit were investigated. The design loads were determined by analytical approaches. Different ice load cases were defined as the basis for the detail design. These load cases include local loads on single members of the platform legs like chords or braces as well as global loads, which may act on one individual leg or on several legs of the platform. Vertical forces, which result from a change of the water level (up-surge and down-surge) in case ice sheets are frozen to the platform legs were considered. Also the impact of ice being jammed between the platform legs was investigated. It has been found out that the most critical load case results from the ice being jammed between the platform legs. It should therefore be tried in practice to avoid the ice jamming by proper ice management, as the large ice loads calculated for this scenario may result in problems for the stability of a JU. Ice breakers could be used to pre break the ice and should try to clear the site from broken ice pieces before it starts to accumulate.Copyright © 2005 by ASME

The transcription factor Pax6 plays a key role during development of various organs, including the brain where it affects cell fate, cell proliferation and patterning. To understand how Pax6 coordinates these diverse effects at the molecular level, we examined the role of distinct DNA-binding domains of Pax6, the homeodomain (HD), the paired domain (PD) and its splice variant (5a), using loss- and gain-of-function approaches. Here we show that the PD is necessary for the regulation of neurogenesis, cell proliferation and patterning effects of Pax6, since these aspects are severely affected in the developing forebrain of the Pax6Aey18 mice with a deletion in the PD but intact homeo- and transactivation domains. In contrast, a mutation of the HD lacking DNA-binding (Pax64Neu) resulted in only subtle defects of forebrain development. We further demonstrate distinct roles of the two splice variants of the PD. Retrovirally mediated overexpression of Pax6 containing exon 5a inhibited cell proliferation without affecting cell fate, while Pax6 containing the canonical form of the PD lacking exon 5a affected simultaneously cell fate and proliferation. These results therefore demonstrate a key role of the PD in brain development and implicate splicing as a pivotal factor regulating the potent neurogenic role of Pax6.

We generated a transgenic mouse line named E1-Ngn2/Cre that expresses Cre recombinase and GFP under the control of the E1 enhancer element of the gene Ngn2 (Scardigli et al.: Neuron 31:203-217, 2001). Cre-recombinase activity and GFP fluorescence are consistent with the reported expression pattern controlled by the E1-Ngn2 enhancer. Recombination was detected in the progenitor domains p1 and p2 in the ventricular zone of the neural tube and in distinct domains of the pretectum, the dorsal and ventral thalamus, the tegmentum of the mesencephalon, and the hindbrain. In the developing cortex, Cre-recombinase activity is confined to a subpopulation of progenitors predominantly in the region of the ventral and lateral pallium. The E1-Ngn2/Cre mouse line thus provides an excellent novel tool for a region-specific conditional mutagenesis in the developing CNS.

Ice barriers installed in close vicinity to offshore platforms are designed to take the main loads resulting from floating ice by breaking the ice and piling-up the rubble ice. Platforms and equipment protected by ice barriers can be dimensioned considering only low ice loads and can thus be constructed more economically. Also, the safety of the platforms increases. One objective of the research project MATRA is to design suitable ice barriers for exploration and oil production in ice-covered, shallow-water areas. Several concepts were investigated, e.g. vertical and inclined piles as well as barges equipped with piles. Model tests were carried out under varying conditions in order to evaluate the design alternatives and to provide the design loads resulting from floating ice. The most suitable structure is a light-weight ice barrier with an inclined roof structure mounted on a barge which collects early, thin ice inside the structure, stabilizes itself by the piled-up rubble ice and by this later can withstand thicker ice. The measured loads were analysed and compared with loads theoretically derived from existing approaches. At the first stage, when the structure fills with ice, bending is the dominant failure mode. Once a rubble pile has built-up in front of the structure, other failure modes may become significant comprising buckling and crushing. The load-time curve shows a scattering behaviour and has very high load peaks of short duration, especially for thick ice. The analysis comprises a statistical evaluation of the loads, taking the site conditions in the Caspian Sea as reference. Design loads for different load-cases were derived, which are the basis for the stability analysis of the ice barrier. On the basis of the results of the stability analysis and considering the requirement that the structure shall be self-floating for transport, the structure was optimized and the detail design was carried out.Copyright © 2003 by ASME

Mutations in the connexin 26 gene (GJB2) are responsible for the major part of nonsyndromic autosomal recessive or apparently sporadic prelingual deafness in Caucasians (DFNB1). We screened 228 German hearing-impaired persons for mutations in the GJB2 gene by sequence analysis. Homozygous or compound heterozygous GJB2 mutations were detected in 38/228 (16.7%) of hearing impaired persons. The most frequently occurring mutation was the c.35delG mutation, which was found in 71.1% of the mutated alleles. The next frequent mutation detected in the group of hearing impaired persons was the c.101T>C mutation (9/76 alleles; 11.8%). One new mutation, c.567delA, was observed. We further studied the presence of a 10bp deletion in the 5' UTR of the GJB2 gene (c.-493del10) which was assumed to occur together with the c.101T>C mutation. Ten out of thirteen patients (76.9%) were found to be carriers of both the c.101T>C mutation and the 10bp variant and in 7/14 alleles a linkage disequilibrium between c.101T>C and the 10bp deletion was proven. In 4/14 alleles the linkage was ruled out and for the remaining 3 cases the phase determination was not possible. Seventy one controls were screened for the prevalence of Cx26 mutations and for the c.-493del10 variant. Heterozygosity frequency in the control group was for c.35delG 4.2%, for c.101T>C 1.4% and for c.-493del10 it was 5.6%. © 2002 Wiley-Liss, Inc.

Background: Shoulders of throwing and swimming athletes are highly stressed joints that often show structural abnormalities on magnetic resonance imaging (MRI). However, while water polo players exhibit a combination of throwing and swimming movements, a specific pattern of pathological findings has not been described. Purpose: To assess specific MRI abnormalities in shoulders of elite water polo players and to compare these findings with a healthy control group. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After performing a power analysis, volunteers were recruited for this study. Both shoulders of 28 semiprofessional water polo players and 15 healthy volunteers were assessed clinically (based on the Constant score) and had bilateral shoulder MRIs. The shoulders were clustered into 3 groups: 28 throwing and 28 nonthrowing shoulders of water polo athletes and 30 shoulders of healthy control subjects. Results: Twenty-eight male water polo players with an average age of 24 years and 15 healthy subjects (30 shoulders) with an average age of 31 years were examined. Compared with controls, significantly more MRI abnormalities in the water polo players' throwing shoulders could be found in the subscapularis, infraspinatus, and posterior labrum ( P = .001, P = .024, and P = .041, respectively). Other structures showed no statistical differences between the 3 groups, including the supraspinatus tendon, which had abnormalities in 36% of throwing versus 32% of nonthrowing shoulders and 33% of control shoulders. All throwing shoulders showed abnormal findings in the MRI, but only 8 (29%) were symptomatic. Conclusion: The shoulders of semiprofessional water polo players demonstrated abnormalities in subscapularis and infraspinatus tendons that were not typical abnormalities for swimmers or throwing athletes. Clinical Relevance: The throwing shoulders of water polo players have specific MRI changes. Clinical symptoms do not correlate with the MRI findings.

Im folgenden sollen die wichtigsten Gesetze aufgestellt werden, die bei einer beliebigen raumlichen oder ebenen Bewegung zu beachten sind.

Ein ruhender Korper setzt sich nicht von selbst in Bewegung, hierzu bedarf es einer Kraft. Andererseits kommt ein bewegter Korper, z.B. eine rollende Kugel, auf einer horizontalen Unterlage infolge von bewegungshemmenden Kraften wie Bodenreibung und Luftwiderstand nach einiger Zeit zur Ruhe. Wenn auf den Korper keine Krafte einwirken, bewegt er sich mit konstanter Geschwindigkeit geradlinig weiter. Diese Erfahrungen kommen in den Newtonschen Axiomen zum Ausdruck.

Folgende Begriffe wollen wir bei der Betrachtung einer Bewegung zu Grunde legen: Massenpunkt: = Ein mit Masse behafteter Korper oder Teilkorper, dessen Abmessungen vernachlassigbar klein sind im Vergleich zu den sonstigen charakteristischen Langen, die bei dem Bewegungsproblem vorkommen Bahn: = Kurve (Gesamtheit aller Orte), die ein Massenpunkt oder ein Korper bei seiner Bewegung im Laufe der Zeit relativ zu einem Bezugskorper (z.B. zu unserer Erde) durchlauft. Weg: = Strecke, die ein Massenpunkt auf einer Bahn innerhalb einer bestimmten Zeitspanne zuruckgelegt hat.

Jede beliebige raumliche oder ebene Bewegung kann durch Uberlagerung aus Grundformen zusammengesetzt werden. Solche Grundformen der Bewegung sind die Translation und die Rotation.

Arbeit wird verrichtet, wenn sich eine Kraft (ein Moment) langs eines Weges (eines Winkels) verschiebt (siehe Band 1 Kapitel 14).

Rotoren sind Maschinenteile, bei denen umlaufende Zylinder oder Hohlzylinder (Wellen, Scheiben, Trommeln) an Lagerzapfen gegenuber dem Boden abgestutzt werden.

Ein mechanisches System ist auserlich statisch unbestimmt, wenn die Anzahl der Lagerreaktionen groser ist als Anzahl der voneinander unabhangigen statischen Gleichgewichts-Bedingungen, die sich insgesamt durch Befreien der Einzelkorper ergeben.

Carlo Alberto Castigliano (geb. 1847 in Asti, gest. 1884 in Mailand) Das Verfahren von Castigliano kann man bei allen Beanspruchungsarten anwenden. Die Ableitung soll am Beispiel der Biegung erfolgen. Dazu betrachten wir einen Balken nach Bild 23.1, der mit einer Kraftegruppe F1,F2… F n belastet ist.

In der Technischen Mechanik, insbesondere in der angewandten, computerorientierten Festigkeitslehre (Finite-Differenzen-Methode, Finite-Elemente-Methode, Randelemente-Methode) sind haufig umfangreiche lineare Gleichungssysteme zu losen.

Bei der einachsigen (geraden) Biegung war vorausgesetzt, das der Momentenvektor mit einer Haupttragheitsachse des Querschnitts zusammenfallt. Das war der Fall bei Tragern mit symmetrischen Querschnitten, die in der Symmetrieebene oder senkrecht dazu belastet sind.

Im Bild 14.1a ist ein eingespannter Stab dargestellt, der durch eine nicht im QuerschnittsSchwerpunkt S angreifende Langskraft \({\vec F_x}\) parallel zur Balkenachse (x-Achse) belastet wird. Dabei entstehen in einem beliebigen Schnitt als Schnittgrosen eine Normalkraft N x , sowie die Biegemomente M y und M z (Bild 14.1b).

Wird ein Korper auf Biegung beansprucht, so wird er gekrummt und erfahrt eine Durchbiegung, die von der Belastung und der Lagerung (also vom Momentenverlauf), von den Elastizitatseigenschaften des Materials und den Abmessungen des Querschnitts abhangig ist.

Ein Stab wird wie im Bild 9.1a durch eine Kraft \( \overrightarrow F \) in Richtung der Stabachse beansprucht, wobei als Stabachse die Verbindungslinie der Querschnitts-Schwerpunkte zu verstehen ist. Nach dem Prinzip von Saint-Venant (Kapitel 4.1) verteilt sich die Last bei einem Balken mit stetigem Querschnittsverlauf schon nach kurzer Ubergangsstrecke gleichmasig uber den gesamten Querschnitt, so das mit konstanter Spannungsverteilung gerechnet werden kann. Im Bild 9.1b ist das linke abgeschnittene Teilstuck des Balkens zu sehen.