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Bei jugendlichen Athleten wirken sowohl die körperliche Reifung als auch die erhöhte mechanische Belastung auf die Entwicklung des Muskel- und Sehnengewebes. Die Interaktion dieser beiden adaptationswirksamen Stimuli könnte, insbesondere bei Sportlern aus Sprungdisziplinen, Dysbalancen des Kraftpotenzials der Muskulatur und der Widerstandsfähigkeit der Sehne auslösen und somit potentiell das Verletzungsrisiko der Sehne erhöhen. Vor diesem Hintergrund untersucht die vorliegende Arbeit mittels Magnetresonanztomographie, Ultraschall und Dynamometrie die Entwicklung der morphologischen und mechanischen Eigenschaften der Knieextensoren und der Patellarsehne bei jugendlichen Kader-Volleyballathleten. Durch eine Querschnitts- und zwei Längsschnittstudien konnte Evidenz dafür erbracht werden, dass sich unter dem Einfluss der sportartspezifischen Belastung Kraft und Morphologie des Muskels in Relation zu den mechano-morphologischen Eigenschaften der Patellarsehne bei den jugendlichen Athleten nicht ausgewogen entwickeln, was zu einer erhöhten chronischen Belastung und Beanspruchung des Sehnengewebes führt. Darüber hinaus können muskulotendinöse Dysbalancen im Trainingsprozess durch erhöhte Fluktuationen der Muskelkraft und einer nicht-adäquaten Modulation der Widerstandsfähigkeit der Sehne zu episodischen Spitzen der mechanischen Beanspruchung der Sehne führen. Eine derart unausgewogene Entwicklung von Muskel und Sehne könnte für die Ausprägung von Überlastungsbeschwerden in der hier untersuchten Risikogruppe für Tendinopathien prädisponieren. Im Rahmen der Forschungsbemühungen wurde darüber hinaus ein Verfahren zur Vorhersage des Volumens von Oberschenkelmuskeln auf der Basis einfach zu erhebender Parameter entwickelt. Durch das Verfahren ließe sich zukünftig der Zeit- und Kostenaufwand muskelmorphologischer Diagnostik deutlich reduzieren. / In adolescent athletes, the development of muscle and tendon tissue is influenced both by maturation and mechanical loading. The interaction of these two driving stimuli could initiate imbalances in the development of the muscle strength capacity and tendon stiffness, especially in athletes from sports that feature a high frequency of jumps. A consequence could be an increased mechanical demand placed upon the tendon by the working muscle, which might increase the risk of tendon injury. Considering the lack of information on the effects of maturation and superimposed mechanical loading on the muscle-tendon unit during adolescence, the present work examines the development of the morphological and mechanical properties of the knee extensors and patellar tendon in adolescent elite volleyball athletes by means of magnetic resonance imaging, ultrasound and dynamometry. A cross-sectional comparison and two longitudinal studies provided evidence that the two-fold stimulus of sport-specific loading and maturation results in and imbalanced development of muscle strength and morphology in relation to the mechano-morphological properties of the patellar tendon in mid-adolescent volleyball athletes and results in increased tendon stress and strain. Moreover, during a training process, fluctuations of muscle strength and an inadequate modulation of tendon stiffness initiate episodes of high-level tendon strain during maximum muscle contractions. Such an imbalanced development of muscle and tendon could predispose for the development of tendon overuse injury in adolescent volleyball athletes, which are known to be at high risk of developing tendinopathy. Moreover, in the context of the described research endeavour, a method for the volume prediction of thigh muscles on the basis of easily measurable parameters has been developed, which could greatly reduce the time and costs involved in the diagnostics of muscle morphology in the future.

Durant la dernière décennie, les études de la décroissance bêta des isotopes 69,71,73Cu ont mis en évidence le net abaissement de l'orbitale proton 1f5/2 lors du remplissage de l'orbitale neutron1g9/2. Ce phénomène peut être interprété comme le résultat des forces tensorielles entre ces orbitales proton et neutron. Un argument similaire prédit l'affaiblissement du gap N=50 quand on s'approche du noyau 78Ni du fait de l'attraction entre les configurations 1g9/2 et1d5/2 avec l'orbitale 1f5/2 et de la répulsion entre les états 1g7/2 et 1f5/2. Ainsi, les noyaux au voisinage de noyau 78Ni, sont les meilleurs candidats pour étudier l'évolution de la fermeture de couche N=50 et les autres aspects du modèle en couches à grand rapport N/Z. De telles études nécessitent des appareillages performants comme la combinaison d'un spectromètre de noyaux de recul de grande acceptance (PRISMA) couplé à un multidétecteur gamma à grande granularité, CLARA à Legnaro (Italie). Lors d'une récente expérience, des résidus exotiques ont été produits via des réactions profondément inélastiques entre un faisceau de 82Se (Elab = 515 MeV) et une cible d'Uranium. Je me suis principalement penchée sur les systématiques des isotopes de Ge et Zn. Dans le but de compléter ces données, une expérience de décroissance bêta, réalisée auprès d'ISOLDE au CERN, des isotopes impairs riches en neutrons de Cu a également été étudiée. Les schémas de décroissance pour les isotopes 71,73,75Cu ont été construit, pour la première fois pour l'élément le plus exotique. La complémentarité des données issues de ces deux mécanismes ouvre de nouvelles perspectives en vue de l'étude des noyaux riches en neutrons.

<p>Uppsatsen beskriver tiden kring 50-talet för att genom detta visa den ungdomskultur som då uppstod. När filmen Ung rebell hade premiär 1955 var den en föregångare inom filmbranchen genom att gestalta ungdomskulturen på ett nytt sätt. Uppstasen analyserar denna film, Sista natten med gänget (1973), samt Grease (1978) för att visa vilka verktyg som används för att visa ungdomskulturen under denna tid. En del av analysen är att påvisa bilens roll i ungdomskulturen i film gesaltad under och strax efter 50-talet.</p>

<p>I början av 1950-talet utvecklades en idé att flottan skulle bli lättare. Detta berodde delvis på ekonomiska faktorer samt att flottans större system såsom pansarskepp började bli föråldrade. Den tekniska utvecklingen bidrog även till att system som radarn gjorde intrång. Sjömålsroboten och den trådstyrda torpeden kunde skjutas från mindre plattformar vilket gjorde det möjligt med en lättare flotta. Hotet vid denna tid sågs som Sovjetunionen. Ytstridskrafterna skulle i händelse av krig vara beredda att möta en starkare motståndares landstigningsoperationer. Denna uppsats undersöker vissa områden av den taktiska utvecklingen som skedde under denna period. Detta görs genom en textanalys av litteratur på ämnet. Analysen behandlar områden som hotbild, teknik samt egna sjöstridskrafter, organisation samt uppgifter. Slutsatser som dragits är bl.a. tekniken utvecklades i snabb takt och spelade stor roll. Hotbilden var viktig vid utformandet av egen doktrin och strategi vilket ledde till förändringar inom taktiken. Egna sjöstridskrafters utveckling hämmades av ekonomiska styrningar vilket ledde till att kompromisser fick göras som påverkade kvaliteten på enheterna.</p> / <p>In the early fifties the Swedish Navy wanted to get lighter. This development took place mostly because of economical factors and the fact that bigger ships in the navy was getting old. Important systems such as radar were implemented in the Swedish Navy. The ship to ship missile and the wire guided torpedo could be fired from smaller vessels and this contributed to the development. The Soviet union was regarded as the main threat and the Swedish surface warfare units would in warface a stronger opponent and try to prevent him from landing on Swedish shores. This study tries to examine certain areas within the subject tactical development during this period. This is made by analyzing literature in the subject. The analyze is conducted in three predefined areas. The areas are: Threats, technological advances and own surface warfare units and their organisation and tasks. Some of the main conclusions are that the technology advanced in a rapid pace and was vital to the development of tactics. The threat of the Soviet union made differences in the naval doctrine and strategy which made changes in tactics. Economical factors forced the Swedish Navy to compromise when building new ships which affected the quality of the units.</p>

I början av 1950-talet utvecklades en idé att flottan skulle bli lättare. Detta berodde delvis på ekonomiska faktorer samt att flottans större system såsom pansarskepp började bli föråldrade. Den tekniska utvecklingen bidrog även till att system som radarn gjorde intrång. Sjömålsroboten och den trådstyrda torpeden kunde skjutas från mindre plattformar vilket gjorde det möjligt med en lättare flotta. Hotet vid denna tid sågs som Sovjetunionen. Ytstridskrafterna skulle i händelse av krig vara beredda att möta en starkare motståndares landstigningsoperationer. Denna uppsats undersöker vissa områden av den taktiska utvecklingen som skedde under denna period. Detta görs genom en textanalys av litteratur på ämnet. Analysen behandlar områden som hotbild, teknik samt egna sjöstridskrafter, organisation samt uppgifter. Slutsatser som dragits är bl.a. tekniken utvecklades i snabb takt och spelade stor roll. Hotbilden var viktig vid utformandet av egen doktrin och strategi vilket ledde till förändringar inom taktiken. Egna sjöstridskrafters utveckling hämmades av ekonomiska styrningar vilket ledde till att kompromisser fick göras som påverkade kvaliteten på enheterna. / In the early fifties the Swedish Navy wanted to get lighter. This development took place mostly because of economical factors and the fact that bigger ships in the navy was getting old. Important systems such as radar were implemented in the Swedish Navy. The ship to ship missile and the wire guided torpedo could be fired from smaller vessels and this contributed to the development. The Soviet union was regarded as the main threat and the Swedish surface warfare units would in warface a stronger opponent and try to prevent him from landing on Swedish shores. This study tries to examine certain areas within the subject tactical development during this period. This is made by analyzing literature in the subject. The analyze is conducted in three predefined areas. The areas are: Threats, technological advances and own surface warfare units and their organisation and tasks. Some of the main conclusions are that the technology advanced in a rapid pace and was vital to the development of tactics. The threat of the Soviet union made differences in the naval doctrine and strategy which made changes in tactics. Economical factors forced the Swedish Navy to compromise when building new ships which affected the quality of the units.

Introduction: Amyotrophic lateral sclerosis (ALS) is a deadly, progressive neuromuscular disease that affects individuals all over the world. About 10% of the patients have a familial predisposition (FALS) while the remainder of cases are isolated or sporadic (SALS) and of unknown cause. To date, the principal recognized risk factors for ALS are higher age, male gender, slim figure (BMI&lt;23) and a family history of ALS. In 1993, Rosen et al. observed that some FALS cases were associated with mutations in the gene encoding the CuZn superoxide dismutase enzyme (SOD1). Since then, several mutations in the SOD1 gene have been discovered, and mutations in more than 18 other genes have been associated with causing ALS. The aim of this thesis was to identify new mutations associated with ALS pathogenesis, and by comparing patients from different countries, were we also able to identify population-specific genetic variations. The studies are referred to as I–V. Methods: With written informed consent and adhering to the tenets of the Declaration of Helsinki, through a national network of ALS clinicians´, venous blood samples were collected from ALS patients and healthy subjects in Europe and the USA. The patients were diagnosed according to the El Escorial criteria, and as having FALS according to the criteria of Byrne et al. (2011). The DNA variations were amplified by various PCR techniques. (I, III and IV) The amplicons of ataxin 2 (ATXN2), profilin 1 (PFN1), and vesicle-associated membrane protein type B (VAPB) were characterised by direct sequencing. (II) After quantitative PCR, a genotype-phenotype correlation was performed to assess whether the survival motor neuron gene (SMN) modulates the phenotype of ALS. (V) The amplicons of the 50 base pair deletion in the SOD1 promotor (50 bp) were separated by electrophoresis on agarose. Results: (I) We observed a significant association between CAG expansions in the ATXN2 gene and ALS in a European cohort. (II) Abnormal copy number of the SMN1 gene was identified as a risk factor in France, but not in Sweden. Homozygosity of the SMN2 deletion prolonged survival among Swedish ALS patients, compared to French patients. (III) We identified two mutations in the PFN1 gene, the novel p.Thr109Met mutation and the p.Gln117Gly mutation, in two unrelated FALS patients. (IV) In our cohort, we identified five VAPB mutations p.Asp130Glu, p.Ser160del, p.Asp162Glu, p.Met170Ile, and p.Arg184Trp, two of which are novel. (V) The 50 bp deletion upstream of the SOD1 gene was found in equal frequencies in both the patient and control cohorts. The 50 bp deletion did not affect SOD1 enzymatic activity. Furthermore, we found no differences in age of onset or disease duration in relation to the 50 bp deletion genotype.VI Conclusions: (I) Our findings indicate that ATXN2 plays an important role in the pathogenesis of ALS, and that CAG expansions in ATXN2 are a significant risk factor for the disease. (II) We suggest that abnormal SMN1 gene copynumber cannot be considered a universal genetic susceptibility factor for ALS. We also propose that the effect of abnormal SMN2 gene copy number on ALS phenotype may differ between populations. (III) This work provides evidence that PFN1 mutations can cause ALS as a Mendelian dominant trait. The novel p.Thr109Met mutation also shows that disturbance of actin dynamics can cause motor neuron degeneration. (IV) We find it unlikely that the VAPB mutations cause ALS in our cohorts. (V) We find it unlikely that the 50 bp region contains important regulatory elements for SOD1 expression. This thesis supports the theory that ALS is a multigenetic disease, but there appears to be great genetic variation among apparently identical populations. These studies emphasise the importance of continuous genetic screening, to identify further mutations and genes involved in ALS disease, but it also highlights the importance of cooperation and comparison between countries. / On the aetiology of ALS: A comprehensive genetic study

本研究主係探討以投資者持有本國股票作為基礎投資組合，利用台灣五十成份股投資組合及金融期貨指數之月報酬率資料形成效率前緣，然後將本研究所選取之黃金產業GOX指數或以黃金現貨價格兩種黃金商品投資組合分別加入基礎投資組合中，觀察每個投資組合標的加入前後之投資機會集合之變化，是否基礎投資組合之效率前緣進一步向左偏移，並比較其優劣。此外進一步探討在兩種黃金投資組合加入基礎投資組合，分別在股市多頭及空頭市場時會不會產生相同的效果；並且藉由中央大學台灣經濟發展研究中心所調查訂定的消費者信心指數，以中位數區分為信心指數高或信心指數低兩組情境，並將兩種黃金商品投資組合在不同的情境依序分別加入基礎投資組合中，其基礎投資組合之效率前緣是否皆仍進一步向左偏移。實證結果發現，黃金現貨帶給基礎資產投資機會集合的貢獻，明顯優於黃金產業GOX指數，當檢定資產為黃金產業GOX指數時，「切點投資組合」差異W_1統計值上皆不具統計顯著性，整體而言當黃金產業GOX指數在加入投資組合之後，我們認為大部份的效果是來自分散原有的投資組合風險；然而黃金現貨在改善投資機會集合的貢獻上，來自「最小變異數投資組合」及「切點投資組合」的改善皆有顯著的效果。

Uno de los principales factores que amenazan a los anfibios es la contaminación del medio por diferentes sustancias químicas, lo que hace necesario incrementar el conocimiento que se tiene del impacto de estos compuestos sobre los anfibios.En la presente Tesis Doctoral se estudió el impacto, en diferentes condiciones experimentales, del cloruro amónio, nitrito sódico y nitrato sódico, de manera aislada o combinada, sobre la rana común, Pelophylax perezi (Seoane, 1885). Además, se intentó proporcionar una visión general de los efectos de la contaminación sobre los anfibios mediante la realización de un meta-análisis.Los resultados obtenidos permiten concluir que la contaminación afectó negativamente a la supervivencia de los anfibios y a otros parámetros subletales. Sin embargo, la contaminación puede conducir la evolución de los anfibios. Finalmente, las condiciones experimentales demostraron tener una gran importancia a la hora de establecer el impacto de un agente estresante sobre los anfibios. / Chemical pollution is one of the major factors threatening amphibians, which makes necessary to perform further studies to assess its impact on amphibians.The present PhD thesis looks at the impact, in different experimental venues, of ammonium chloride, sodium nitrite and sodium nitrate, either isolated or combined, on the Iberian water frog, Pelophylax perezi (Seoane, 1885). Moreover, an overview of pollution effects on amphibianswas provided by conducting a meta-analysis.The results obtained allowed to conclude that pollution negatively affected amphibian survival, as well as other sublethal endpoints. Neverthelesss, pollution may drive the evolution in amphibians. Finally, experimental venues were revealed to show a great relevance when assessing the impact of a stressing factor on amphibians.

Η νόσος του Parkinson χαρακτηρίζεται από τη βαθμιαία, εκλεκτική νευροεκφύλιση των ντοπαμινεργικών νευρώνων της μελαινοραβδωτής οδού. Η μειωμένη δραστηριοποίηση των ντοπαμινεργικών υποδοχέων που προκαλείται από την ανεπάρκεια ντοπαμίνης τροποποιεί τη λειτουργία των βασικών γαγγλίων και αναστέλλει τα κινητικά συστήματα. Ιδανικό πειραματικό μοντέλο αποτελεί το μοντέλο weaver, το οποίο εμφανίζει το ίδιο μοτίβο νευροεκφύλισης με τους παρκινσονικούς ασθενείς καθώς και περισσότερη από 70% μείωση της ντοπαμίνης στο ραβδωτό σώμα. Το γεγονός πως δεν υπάρχει σήμερα αποτελεσματική θεραπεία που να σταματά ή να αναστρέφει την εξέλιξη της νόσου, δημιουργεί την ανάγκη ανακάλυψης ενός φαρμακευτικού σχήματος το οποίο θα έχει νευροπροστατευτική δράση και θα περιορίζει τις παρενέργειες. Προηγούμενα αποτελέσματα της ομάδας μας δείχνουν σημαντική επιβίωση των ντοπαμινεργικών κυττάρων στο μοντέλο weaver μετά από χρόνια χορήγηση του ενδογενούς νευροστεροειδούς DHEAS, του χημικού αναλόγου του ΒΝΝ-50 (το οποίο δε μεταβολίζεται σε οιστρογόνα) και του φαρμακευτικού συνδυασμού του ΒΝΝ-50 με τη Ν-ακετυλοκυστεΐνη (NAC), με το τελευταίο να επαναφέρει πλήρως τον αριθμό των κυττάρων στη μέλαινα ουσία. Στην παρούσα εργασία θελήσαμε να διερευνήσουμε τους μηχανισμούς μέσω των οποίων επιτυγχάνεται η νευροπροστασία που προκαλεί η συγχορήγηση του συνδυασμού BNN-50/ΝAC. Για το σκοπό αυτό, αξιολογήσαμε την αντιαποπτωτική, καθώς και την αντιοξειδωτική δράση του σχήματος BNN-50/NAC. Οι δύο δείκτες επιλέχθηκαν λαμβάνοντας υπόψιν τον κεντρικό ρόλο του αποπτωτικού θανάτου στη διαδικασία της νευροεκφύλισης, καθώς και το ρόλο του οξειδωτικού στρες στην παθογένεια της νόσου. Τα αποτελέσματα μας υποδεικνύουν πλειοτροπική δράση του φαρμακευτικού συνδυασμού BNN-50/NAC, η οποία εκφράζεται μέσω της ισχυρής αντιαποπτωτικής και αντιοξειδωτικής του δράσης. / Parkinson 's disease is characterized by the progressive, selective neurodegeneration of the dopaminergic neurons of the nigrostriatal pathway. The decreased activation of dopamine receptors caused by insufficient dopamine levels, modifies the function of the basal ganglia circuit and inhibits the mobility systems. The weaver model consists an ideal model for neuroprotection studies, which exhibits the same pattern of neurodegeneration as the parkinsonian patients and more than 70% decrease of dopamine in the striatum. The fact that there is currently no effective treatment to attenuate or reverse the disease progression, creates the need for discovery of a drug combination which will exhibit neuroprotective effect and reduce the side effects. Previous results of our group, have shown a significant survival of dopaminergic neurons in weaver mice after chronic administration of endogenous neurosteroid DHEA-S, the chemical analog BNN-50 (which is not metabolized to estrogens) and the combination of the BNN-50 with N-acetylcysteine (NAC,with the latter combination completely rescuing the number of dopaminergic cells of the substantia nigra. The aim of this study was to investigate the mechanisms of neuroprotection induced by coadministration of combination BNN-50/NAC. For this purpose, we evaluated the possible antiapoptotic and antioxidant action of the BNN-50/NAC combination. Our results suggest a pleiotropic effect of the BNN-50/NAC drug combination, that is expressed through strong antiapoptotic and antioxidant activity.