L'expérience INDRA@GSI permet d'étudier les mécanismes de la réaction 12C+197Au en cinématique directe par l'utilisation du multidétecteur 4p INDRA et de faisceaux de 12C aux énergies relativistes. La source du spectateur de la cible est determinée pour les protons et les fragments légers, séparement de la source de cascade émettant des particules légeres et d'une source de haute energie émettant des fragments approximativement dans le centre de masse. Les spectres de protons en énergie cinétique sont comparés à des combinaisons du modèle de Cascade Intra-Nucléaire de Liège avec des modèles statistiques. Le scénario privilegié associe un processus de cascade avec une multifragmentation statistique. Les températures de pente des fragments determinées par une combinaison de fonctions de Maxwell-Boltzmann mettent en évidence une dépendance en énergie de faisceau, la centralité de la réaction étant donnée par la multiplicité de particules chargées. Les pions, detectés pour la première fois avec INDRA, et les protons rapides présentent une correlation avec le paramètre d'impact mais non avec la production de fragments.

<p>This paper explores the statistical properties of microfragment recovery techniques used on NTFS filesystems in the use of digital forensics. A microfragment is the remnant file-data existing in the cluster slack after this file has been overwritten. The total amount of cluster slack is related to the size distribution of the overwriting files as well as to the size of cluster. Experiments have been performed by varying the size distributions of the overwriting files as well as the cluster sizes of the partition. These results are then compared with existing analytical models.</p> / FIVES

<p>Gilbert’s syndrome (GS) occurs in approximately 10% of the European population. The most common cause is homozygosity for UGT1A1*28, which is a TA repeat expansion in the promoter of UGT1A1. It is characterised by intermittent hyperbilirubinemia due to reduced hepatic activity of the  enzyme UDP-glucuronosyl-transferase 1A1(UGT1A1). GS also  alteres the pharmacokinetics of some drugs and increases the risk of drug toxicity. Irinotecan (Camptosar®, Campto®) is used in metastatic colorectal cancer and the active metabolite is inactivated by UGT1A1. Studies have shown that GS can be a risk factor for toxicity during irinotecan therapy.</p><p>Three different methods for genotyping of UGT1A1*28 have been tested.</p><p>PCR with electrophoresis used for size separation, melting temperature analysis and fluorescent PCR followed by fragment analysis on a capillary sequencer.</p><p>The last method was found to be superior. This method was used for genotyping of patients with colorectal cancer treated with irinotecan and 5-fluorouracil in the Nordic VI study. A significant association between UGT1A1 genotype and plasma bilirubin level before the start of irinotecan treatment was seen (ANOVA p<0.0001). Patients with GS had an overall increased risk of adverse drug reactions (Fishers Exact test p=0.02).</p><p>Gilbert’s syndrome can be diagnosed by genotyping UGT1A1*28 with a fragment analysis method. Genotyping of UGT1A1*28 can be used to identify patients with an increased risk of adverse reactions to irinotecan.<strong> </strong></p><p><strong> </strong></p> / <p>Gilberts syndrom (GS) drabbar upp till 10% av befolkningen i Västeuropa. GS beror på nedsatt aktivitet av enzymet UDP-glukuronosyltransferas 1A1 (UGT1A1) i levern. Den vanligaste orsaken är att individen är homozygot för en insertion av två baser i promotorn för genen UGT1A1. Denna genvariant kallas (TA)7TAA  eller UGT1A1*28. GS leder till intermittent stegring av bilirubin vid infektioner, men bilirubinstegring kan förekomma även utan utlösande agens. GS kan också leda till bilirubinstegring vid viss läkemedelsbehandling. Irinotekan (Campto®) används vid metastaserande colorektal cancer och dess aktiva metabolit inaktiveras av UGT1A1. Det finns rapporter om att GS ger ökad risk för toxiska biverkningar av irinotekan.</p><p>Tre metoder för att bestämma UGT1A1 har jämförts: PCR med elfores, PCR med smältpunktsanalys och PCR med fragmentanalys på sekvensator. Den sista metoden var bäst och användes för att genotypa UGT1A1 hos patienter med colorektal cancer från Nordic VI-studien. De behandlades med irinotekan i kombination med bolusinjektion eller infusion av 5-fluorouracil. Vi fann att  patienter med GS hade signifikant högre S-bilirubin före behandling jämfört med övriga patienter. De hade även ökad frekvens biverkningar av irinotekan (Fishers exakta test p=0,02).</p><p>Genotypning av UGT1A1 kan således användas för att diagnostisera Gilberts syndrom hos patienter med oförklarad bilirubinstegring. Det kan även användas för att identifiera patienter med ökad risk för biverkningar av irinotekan.</p>

There are many applications of small organic compounds, e.g. as drugs or as tools to study biological systems. Once a compound with interesting biological activity has been found, medicinal chemists typically synthesize small libraries of compounds with systematic differences to the initial “hit” compound. By screening the new ensemble of compounds for their ability to perturb the biological system, insights about the system can be gained. In the work presented here, various ways to synthesize small libraries of ring-fused 2‑pyridones have been developed. Members of this class of peptidomimetic compounds have previously been found to have a variety of biological activities, e.g. as antibacterial agents targeting virulence, and as inhibitors of the aggregation of Alzheimer b‑peptides. The focus in this work has been to alter the core skeleton, the central fragment, of the previously discovered biologically active 2‑pyridones and evaluate the biological effects of these changes. Several new classes of compounds have been constructed and their preparations have included the development of multi-component reactions and a method inspired by diversity-oriented synthesis. Some of the new compounds have been evaluated for their effect on the fibrillation of different amyloid proteins. Both the Parkinson-associated amyloid protein a-synuclein and the bacterial protein CsgA that is involved in bacterial biofilm formation are affected by subtle changes of the compounds’ central fragments. This is an example of the usefulness of central-fragment alterations as a strategy to probe structure-activity relationships, and the derived compounds may be used as tools in further study of the aggregation of amyloid proteins.

Detecting mutations and genomic variations is fundamental indiagnosis, isolating disease genes, association studies,functional genomics and pharmacogenomics. The objective hasbeen to use and further develop a variety of tools andtechnologies to analyze these genetic alterations andvariations. The p53 tumor suppressor gene and short arm of chromosome 9have been used as genetic markers to investigate fundamentalquestions concerning early events preceding non-melanoma skincancers, clonal progression and timing of different mutationsand deletions. Conventional gel based DNA sequencing andfragment analysis of microsatellite markers were utilized forthis purpose. In addition, a sequence-specific PCR-mediatedartifact is discussed. Pyrosequencing, a bioluminometric technique based onsequencing-by-synthesis, has been utilized to determinemutation ratios in the p53 gene. In addition, in the case ofmultiple mutations, pyrosequencing was adopted to determineallelic distribution of mutations without the use of cloningprocedures. Exons 5 to 8 of the p53 gene were also sequenced bythis method. The possibility of typing single base variations bypyrosequencing has been evaluated. Two different nucleotidedispensation orders were investigated and data were comparedwith the predicted pattern for each alternative of the variableposition. Analysis of loss of heterozygosity was possible byutilizing single nucleotide polymorphisms. A modified allele-specific extension strategy for genotypingof single nucleotide polymorphisms has been developed. Throughthe use of a real-time bioluminometric assay, it has beendemonstrated that reaction kinetics for a mismatchedprimer-template is slower than the matched configuration,butthe end-point signals are comparable. By introduction ofapyrase, the problems associated with mismatch extensions havebeen circumvented and accurate data has been obtained. Keywords:fragment analysis, microsatellite, loss ofheterozygosity, DNA sequencing, pyrosequencing, cancer,mutation, variation, single nucleotide polymorphism,allele-specific extension, bioluminescence, apyrase. / QC 20100415

This thesis argues that the Middle English alliterative prosody of the Piers Plowman tradition was influenced by a discourse combining law, history, homily and poetry which was inherited from the administrative practices of the Anglo-Saxon period. As literary and legal textual genres developed recognizably distinct formal characteristics in the later Middle Ages, the combination of homiletic rhetoric and alliterative sound-patterning evoked a surviving discourse in which the formal characteristics of poems and documents were less clearly distinguished. Thus insofar as it evoked Anglo-Saxon textual culture, Piers Plowman provided a formal model which was particularly suitable to criticisms of political institutions that consolidated their power by developing new distinctions between the genres of bureaucratic texts. In each of the texts and traditions studied – Wulfstan’s homiletic law code I–II Cnut and its Latin translations, The First Worcester Fragment, Laȝamon’s Arthurian Brut chronicle-poem, The South English Legendary "Life of St. Egwine", and the Piers Plowman tradition poem Mum and the Sothsegger – apparently “literary” devices are used to authorize historically-based “legal” claims, particularly on behalf of ecclesiastical institutions looking to maintain their local influence in the face of increasingly consolidated royal administrative authority. Though oaths played a much less important procedural role after the Norman Conquest than they did in the Anglo-Saxon period, the appearance of "creative" authenticating procedures in "commemorative" texts created the appearance of orality to post-Conquest readers, to criticize a government which claimed its English "common" law to originate in the remotest recorded antiquity, even as it abandoned the practices actually recorded in the earliest surviving law codes and documents to be written in England. Comparing these texts allows a deeper understanding of their shared authenticating strategies, and also a re-appraisal of the methods we use to describe the relationships between medieval documents and authors, literature and law, texts and contexts. Appended to the dissertation is an edition of the SEL "Life of St. Egwine." Because Egwine's hagiographic tradition is so thematically invested in political concerns and closely interconnected with legal documents attributed to Egwine himself, the edition provides an opportunity to take a "disjunctively" literary and diplomatic approach to the tradition, in the process exploring some of the practical implications of the larger theoretical issues raised by the thesis as a whole.

This thesis argues that the Middle English alliterative prosody of the Piers Plowman tradition was influenced by a discourse combining law, history, homily and poetry which was inherited from the administrative practices of the Anglo-Saxon period. As literary and legal textual genres developed recognizably distinct formal characteristics in the later Middle Ages, the combination of homiletic rhetoric and alliterative sound-patterning evoked a surviving discourse in which the formal characteristics of poems and documents were less clearly distinguished. Thus insofar as it evoked Anglo-Saxon textual culture, Piers Plowman provided a formal model which was particularly suitable to criticisms of political institutions that consolidated their power by developing new distinctions between the genres of bureaucratic texts. In each of the texts and traditions studied – Wulfstan’s homiletic law code I–II Cnut and its Latin translations, The First Worcester Fragment, Laȝamon’s Arthurian Brut chronicle-poem, The South English Legendary "Life of St. Egwine", and the Piers Plowman tradition poem Mum and the Sothsegger – apparently “literary” devices are used to authorize historically-based “legal” claims, particularly on behalf of ecclesiastical institutions looking to maintain their local influence in the face of increasingly consolidated royal administrative authority. Though oaths played a much less important procedural role after the Norman Conquest than they did in the Anglo-Saxon period, the appearance of "creative" authenticating procedures in "commemorative" texts created the appearance of orality to post-Conquest readers, to criticize a government which claimed its English "common" law to originate in the remotest recorded antiquity, even as it abandoned the practices actually recorded in the earliest surviving law codes and documents to be written in England. Comparing these texts allows a deeper understanding of their shared authenticating strategies, and also a re-appraisal of the methods we use to describe the relationships between medieval documents and authors, literature and law, texts and contexts. Appended to the dissertation is an edition of the SEL "Life of St. Egwine." Because Egwine's hagiographic tradition is so thematically invested in political concerns and closely interconnected with legal documents attributed to Egwine himself, the edition provides an opportunity to take a "disjunctively" literary and diplomatic approach to the tradition, in the process exploring some of the practical implications of the larger theoretical issues raised by the thesis as a whole.

Domain-specific languages (DSLs) are useful tools for coping with complexity in software development. DSLs provide developers with appropriate constructs for specifying and solving the problems they are faced with. While the exact definition of DSLs can vary, they can roughly be divided into two categories: embedded and non-embedded. Embedded DSLs (E-DSLs) are integrated into general-purpose host languages (e.g. Java), while non-embedded DSLs (NE-DSLs) are standalone languages with their own tooling (e.g. compilers or interpreters). NE-DSLs can for example be found on the Semantic Web where they are used for querying or describing shared domain models (ontologies). A common theme with DSLs is naturally their support of focused expressive power. However, in many cases they do not support non–domain-specific component-oriented constructs that can be useful for developers. Such constructs are standard in general-purpose languages (procedures, methods, packages, libraries etc.). While E-DSLs have access to such constructs via their host languages, NE-DSLs do not have this opportunity. Instead, to support such notions, each of these languages have to be extended and their tooling updated accordingly. Such modifications can be costly and must be done individually for each language. A solution method for one language cannot easily be reused for another. There currently exist no appropriate technology for tackling this problem in a general manner. Apart from identifying the need for a general approach to address this issue, we extend existing composition technology to provide a language-inclusive solution. We build upon fragment-based composition techniques and make them applicable to arbitrary (context-free) languages. We call this process for the composition techniques’ universalization. The techniques are called fragment-based since their view of components— reusable software units with interfaces—are pieces of source code that conform to an underlying (context-free) language grammar. The universalization process is grammar-driven: given a base language grammar and a description of the compositional needs wrt. the composition techniques, an adapted grammar is created that corresponds to the specified needs. The result is thus an adapted grammar that forms the foundation for allowing to define and compose the desired fragments. We further build upon this grammar-driven universalization approach to allow developers to define the non–domain-specific component-oriented constructs that are needed for NE-DSLs. Developers are able to define both what those constructs should be, and how they are to be interpreted (via composition). Thus, developers can effectively define language extensions and their semantics. This solution is presented in a framework that can be reused for different languages, even if their notion of ‘components’ differ. To demonstrate the approach and show its applicability, we apply it to two Semantic Web related NE-DSLs that are in need of component-oriented constructs. We introduce modules to the rule-based Web query language Xcerpt and role models to the Web Ontology Language OWL.

<p>Better methods and tools are needed in the fight against child pornography. This thesis presents a method for file type categorisation of unknown data fragments, a method for reassembly of JPEG fragments, and the requirements put on an artificial JPEG header for viewing reassembled images. To enable empirical evaluation of the methods a number of tools based on the methods have been implemented.</p><p>The file type categorisation method identifies JPEG fragments with a detection rate of 100% and a false positives rate of 0.1%. The method uses three algorithms, Byte Frequency Distribution (BFD), Rate of Change (RoC), and 2-grams. The algorithms are designed for different situations, depending on the requirements at hand.</p><p>The reconnection method correctly reconnects 97% of a Restart (RST) marker enabled JPEG image, fragmented into 4 KiB large pieces. When dealing with fragments from several images at once, the method is able to correctly connect 70% of the fragments at the first iteration.</p><p>Two parameters in a JPEG header are crucial to the quality of the image; the size of the image and the sampling factor (actually factors) of the image. The size can be found using brute force and the sampling factors only take on three different values. Hence it is possible to use an artificial JPEG header to view full of parts of an image. The only requirement is that the fragments contain RST markers.</p><p>The results of the evaluations of the methods show that it is possible to find, reassemble, and view JPEG image fragments with high certainty.</p>

Die Arbeit beschäftigt sich mit der Weiterentwicklung des verdämmten Druckversuches zur Bestimmung experimenteller Daten an verschiedenen Keramik- und Glassorten. Die untersuchten Materialien (Al2O3, TiB2, B4C, Floatglas, schweres Flintglas) lagen in Form von Fragmenten (Bruchstücken) vor und wurden aus realen Impaktexperimenten wiedergewonnen. Zusätzlich wurden thermisch vorgeschädigte Aluminiumoxidzylinder in die Betrachtungen einbezogen. Daten granulierter bzw. vorgeschädigter spröder Materialien sind von besonderem Interesse für Finite Element Rechnungen, um beispielsweise experimentell sehr aufwendige Beschußversuche rechnerisch zu simulieren.Als Untersuchungsmethode wurde der verdämmte Druckversuch verwendet und sowohl an quasistatische als auch an schlagdynamische Belastungsbedingungen angepaßt. Außerdem wurden die entwickelten Testaufbauten für sehr hohe hydrostatische Drücke optimiert. In den quasistatischen Experimenten konnten damit Drücke von 380 MPa bis 1960 MPa und in den dynamischen Versuchen von 495 MPa bis 2060 MPa erreicht werden. Im Ergebnis wurden mechanische Kennwerte der granulierten bzw. vorgeschädigten Materialien ermittelt (Restfestigkeit, Verdichtungsverhalten) und deren Schädigungsgrad vor und nach den Versuchen bestimmt (Rasterelektronenmikroskopie und Messung der spezifischen Oberfläche). Die vielversprechenden Resultate der verschiedenen Keramiken und Gläser wurden verglichen und die Materialien im Hinblick auf ihr Energieaufnahmevermögen unter schlagartiger Belastung bewertet.