7 research outputs found

    Protein Structure

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    Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. The expert meanwhile, we hope, can gain a deeper understanding of the topic

    Locus specific databases: integrating sequence, structural and clinical analysis in relation to disorders of the coagulation and complement systems.

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    Following the success of the Human Genome Mutation Database, increasing numbers of locus-specific mutation databases are being compiled in order to present more detailed descriptions of the mutations in specific proteins and diseases. However, until now, many coagulation or complement disorders have no up-to-date, accurate repository of information. Structural analyses of disease-associated mutations can provide important new tools for identifying the underlying biochemical defect of disease. Type I mutations may affect the correct folding, secretion, expression or degradation of the protein. Alternatively, Type II mutations can disrupt the catalytic or substrate-binding functional site of the protein. Alternatively, mutations may not be the causative factor for disease. Including sequence and structural information to propose consensus domain structures can unravel these effects of mutations. Central repositories of data that combine structural, sequence and phenotypic information on mutations and proteins can facilitate the diagnosis and understanding of the associated diseases, and define the molecular consequences of disease. This thesis describes interactive web databases of genotypic, phenotypic, clinical and structural information on mutations associated with complement Factor H (FH) and coagulation Factor XI (FXI). Mutations within FH are associated with aHUS (atypical Haemolytic Uraemic Syndrome), MPGN (Membranoproliferative Glomerulonephritis) and AMD (Age-related Macular Degeneration), whereas mutations within FXI are associated with a FXI deficiency bleeding disorder. The methods used within the FH and FXI databases were extended and combined with a database management system to design a mutation database for the five Vitamin K dependent serine proteases of coagulation in order to study the effects of mutations within conserved domains. The database management system incorporates new tools that have been designed to automatically scan full length references to find text describing mutations. This significantly reduces the time and expertise required to maintain the databases

    Languages Generated by Iterated Idempotencies.

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    The rewrite relation with parameters m and n and with the possible length limit = k or :::; k we denote by w~, =kW~· or ::;kw~ respectively. The idempotency languages generated from a starting word w by the respective operations are wDAlso other special cases of idempotency languages besides duplication have come up in different contexts. The investigations of Ito et al. about insertion and deletion, Le., operations that are also observed in DNA molecules, have established that w5 and w~ both preserve regularity.Our investigations about idempotency relations and languages start out from the case of a uniform length bound. For these relations =kW~ the conditions for confluence are characterized completely. Also the question of regularity is -k n answered for aH the languages w- D 1 are more complicated and belong to the class of context-free languages.For a generallength bound, i.e."for the relations :"::kW~, confluence does not hold so frequently. This complicatedness of the relations results also in more complicated languages, which are often non-regular, as for example the languages WWithout any length bound, idempotency relations have a very complicated structure. Over alphabets of one or two letters we still characterize the conditions for confluence. Over three or more letters, in contrast, only a few cases are solved. We determine the combinations of parameters that result in the regularity of wDIn a second chapter sorne more involved questions are solved for the special case of duplication. First we shed sorne light on the reasons why it is so difficult to determine the context-freeness ofduplication languages. We show that they fulfiH aH pumping properties and that they are very dense. Therefore aH the standard tools to prove non-context-freness do not apply here.The concept of root in Formal Language ·Theory is frequently used to describe the reduction of a word to another one, which is in sorne sense elementary.For example, there are primitive roots, periodicity roots, etc. Elementary in connection with duplication are square-free words, Le., words that do not contain any repetition. Thus we define the duplication root of w to consist of aH the square-free words, from which w can be reached via the relation w~.Besides sorne general observations we prove the decidability of the question, whether the duplication root of a language is finite.Then we devise acode, which is robust under duplication of its code words.This would keep the result of a computation from being destroyed by dupli cations in the code words. We determine the exact conditions, under which infinite such codes exist: over an alphabet of two letters they exist for a length bound of 2, over three letters already for a length bound of 1.Also we apply duplication to entire languages rather than to single words; then it is interesting to determine, whether regular and context-free languages are closed under this operation. We show that the regular languages are closed under uniformly bounded duplication, while they are not closed under duplication with a generallength bound. The context-free languages are closed under both operations.The thesis concludes with a list of open problems related with the thesis' topics

    Post-plus languages

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    AbstractIn this paper, a post-plus language is defined as a language which contains all the catenations of each word in the language with a proper suffix of this word. The set of all d-primitive words is a natural post-plus language. The family of all post-plus languages is a subfamily of all non-counting languages. Some basic properties and characterizations of post-plus languages are investigated. We obtain that a post-plus language spanned by a word over an alphabet with two letters is context-free if and only if the language is regular. Some general properties of post-plus languages related to code, dense property and formal language theory such as the nature of context-free, context-sensitive languages are also studied in this paper

    Subject Index Volumes 1–200

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    Experience-based specialisation: underpinnings of communication in typical and atypical development

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    Autism Spectrum Disorder (ASD) is an umbrella term encompassing several neurodevelopmental conditions with complex, heterogeneous symptomatology. One way in which I addressed this complexity is by looking at a specific aspect of the phenotype to understand the contributing mechanisms. Communication difficulties are prevalent in ASD, and it has been suggested that this is a downstream effect of atypical functional specialisation in processing of both social and non-social auditory input in the brain. This thesis aimed to identify robust markers of specialisation across several methodologies and assess the links with the behavioural phenotype. First, a series of eye tracking studies was carried out with typically developing infants to identify age and language experience effects on speech perception and whether these can be linked to brain-based markers of specialisation. Then, three auditory EEG paradigms were used to measure differences in auditory perception in infants with increased familial likelihood of ASD and/or ADHD, as well as in a unique population of infants with NF1, who experience elevated rates of ASD and other neurodevelopmental conditions as part of the clinical symptomology. Through inclusion of several different participant groups, it was possible to examine whether atypical auditory processing was a specific marker of familial and/or monogenic likelihood of ASD or a general predictor of atypical development. Chapter 2 outlined the main techniques used to measure experience-dependent specialisation, including eye tracking, EEG and behavioural assessments. Chapter 3 investigated specialisation towards native speech perception though several novel paradigms in a longitudinal sample of neurotypical infants at 5, 10 and 14 months of age, as well as associations with parent and observer-rated language abilities. Chapter 4 examined the relationship between eye tracking, neural indices of vowel perception and communication skills in neurotypical infants and how these EEG-based indices may differ in a group of infants with NF1 at 5 and 10 months. Chapter 5 investigated differences in neural habituation and change detection responses across time and time-frequency analyses in 8-month-old infants with low and high familial likelihood of ASD and how these relate to language and ASD symptomology at three years. Lastly, Chapter 6 examined steady-state responses in the gamma frequency range in 14-month-old infants and whether this auditory marker can be used to differentiate between neurotypical infants and those with familial likelihood of ASD or ADHD or an NF1 diagnosis and to predict individual differences in communication skills. Taken together, the present work explored early markers of functional specialisation of auditory processing in typical and atypical development in association with parent/observer ratings of early language ability. Additionally, findings are reported from the first study of early brain development in infants with NF1. This is integral to the current understanding of pathways to ASD, with a further aim of informing clinical and research practices in rare genetic disorders
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