Tesi sul tema "Reversibility"

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1999.
Includes bibliographical references (p. 391-405).
Today's computers are based on irreversible logic devices, which have been known to be fundamentally energy-inefficient for several decades. Recently, alternative reversible logic technologies have improved rapidly, and are now becoming practical. In traditional models of computation, pure reversibility seems to decrease overall computational efficiency; I provide a proof to this effect. However, traditional models ignore important physical constraints on information processing. This thesis gives the first analysis demonstrating that in a realistic model of computation that accounts for thermodynamic issues, as well as other physical constraints, the judicious use of reversible computing can strictly increase asymptotic computational efficiency, as machine sizes increase. I project real benefits for supercomputing at a large (but achievable) scale in the fairly near term. And with proposed future computing technologies, I show that reversibility will benefit computing at all scales. Next, the thesis demonstrates that reversible computing techniques do not make computer design much more difficult. I describe how to design asymptotically efficient processors using an "adiabatic" reversible electronic logic technology that can be built with today's microprocessor fabrication processes. I describe a simple universal reversible parallel processor chip that our group recently fabricated, and a reversible instruction set for a more traditional RISC-style uniprocessor. Finally, I describe techniques for programming reversible computers. I present a high-level language and a compiler suitable for coding efficient reversible algorithms, and I describe a variety of example algorithms, including efficient reversible sorting, searching, arithmetic, matrix, and graph algorithms. As an example application, I present a linear-time, constant-space reversible program for simulating the Schrodinger wave equation of quantum mechanics.
by Michael P. Frank.
Ph.D.

Heterozygous and recently identified homozygous mutations in the SPTBN2 gene, encoding b-III spectrin, are implicated in spinocerebellar ataxia type 5 (SCA5) and spectrin-associated autosomal recessive cerebellar ataxia type 1 (SPARCA1), respectively. Our mouse model, lacking b-III spectrin (KO), mimics the progressive human phenotype displaying motor deficiencies as well as reduced Purkinje cell firing frequency followed by dendritic tree degeneration and cell death. The aims of this study were to evaluate progression of Purkinje cell degeneration following loss of b-III spectrin function and determine whether the reintroduction of C-terminus (C-trm) of b-III spectrin to the cerebellum is enough to halt, alleviate or reverse the disease phenotype. Additionally, this study investigated whether the abnormal electrophysiological and morphological phenotypes of Purkinje cells from KO mice are re-capitulated in a primary cerebellar culture and if so, whether they could be rescued by modulating calcium signaling. Morphological and histological analyses revealed that Purkinje cell degeneration is not uniform throughout the cerebellum of KO mice with Purkinje cells from posterior cerebellar regions possessing significantly smaller dendritic trees when compared to anterior cerebellum (p=0.0003, N=4-6, n=11-29). Similarly, significant reduction in Purkinje cell density was observed in posterior, not anterior regions of KO mice when compared to WT animals (p=0.014, N=3) and reduced tonic firing is most significant in Purkinje cells from the posterior cerebellum compared to WT mice (p=0.0328, N=3-6, n=11-29), with posterior KO PCs appearing to have elevated input resistance. Two-week expression of C-trm b-III spectrin in 3-month old KO animals significantly reduced Purkinje cell input resistance when compared to non-transduced cells (p=0.0139, N=4-5, n=15), but no effect was seen 9 months after viral injection. In contrast, a difference in cell surface area was no longer detected between WT and KO animals at 12 months of age following 9-months of viral expression. Nevertheless, using the elevated beam test motor deterioration was still observed 5 months after surgery (p=0.0023, N=4). In contrast, earlier stereotaxic injections at 6-weeks of age had a positive effect on mice motor performance with no deterioration in performance detected 5 months after the surgery. Latency to stay on the rotarod at 3 rpm was also significantly extended 6 months after stereotaxic injections at 6-weeks of age with slower motor deterioration (p=0.0348, N=6). In primary cerebellar cultures, Purkinje cells from KO animals exhibit an abnormal morphology with significantly more dendritic branches (p < 0.0001, N=4-7, n=35-69) and a larger total dendritic length (p=0.0079). Chronic application of 2 μM mibefradil, a T-type calcium channel blocker, was observed to reduce total dendritic length and branching in KO animal cultures bringing these morphological measurements closer to WT Purkinje cell levels. Finally although after 14 days in vitro 40% of Purkinje cells were found to be spontaneously firing, no significant difference in firing frequency (p=0.9434) or input resistance (p=0.8434, N=4, n=6-10) was detectable between WT and KO cultures. In summary, Purkinje cells in posterior cerebellar regions of KO mice were found to be more susceptible to dendritic degeneration and cellular death than cells in the anterior cerebellum. Expression of C-trm b-III spectrin at 3 months of age had an immediate effect on cell input resistance and a modest effect on Purkinje cell morphology but no effect on motor decline. Viral injections at 6-weeks of age, however, significantly slowed motor decline. Although an abnormal KO cell morphology could be successfully recapitulated in primary cell culture, it was not possible to discern any differences in electrophysiological properties. Nevertheless, the abnormal cell morphology was successfully modified in vitro by manipulating calcium signaling via T-type calcium channels.

Assessing the performance and reliability of computer and telecommunication systems requires the development of stochastic models whose state space are very large. This problem is often known as "State Space Explosion". As a consequence, general purpose algorithms for their solution cannot be applied straightforwardly. This problem may be found both at continuous or discrete time. To tackle this problem we resorted to the theory of product-forms, including the latest theoretical developments in the field such as the Reversed Compound Agents Theorem (RCAT) and new forms of time-reversibility. The main contribution of our work consists in the identification of classes of product-form models that are not captured by previous results. More specifically, our contribution can be summarized as follows: - We identified a process algebraic specification of models including instantaneous propagation of signals at continuous time such as those required to describe the G-networks with negative customers and triggers. As an application of this result we introduced an original model which allows one to perform an exact analysis for a class of cache systems based on the policy Time-To-Live (TTL) with resets. - We characterized a class of models suitable for the quantitative analysis of reversible computations. We showed that our results can be useful for the performance evaluation of speculative distributed simulations. - Finally, we analysed product-form models also at discrete time and provided a product-form formulation for the Probabilistic Input/Output Automata (PIOA).

The incidence of both obesity and type 2 diabetes continues to rise, creating a major worldwide public health challenge. Understanding the mechanisms determining the normalisation of blood glucose levels and the limitations to complete reversal of diabetes by bariatric surgery or a very low calorie diet (VLCD) has important implications for the treatment of type 2 diabetes, but also for improving our understanding of the pathophysiology. A unifying hypothesis to explain the major pathophysiological changes in type 2 diabetes, hepatic insulin resistance and pancreatic beta cell insufficiency, involves excess triglyceride accumulation in liver and pancreas. This is supported by in vitro demonstration of impaired insulin signalling (and thereby insulin resistance) and defective insulin secretion, induced by the toxic metabolites of fat. Triglyceride content in liver and pancreas can now be measured non-invasively and precisely using the three point Dixon magnetic resonance technique. This thesis presents data on a direct comparison of bariatric surgery and VLCD, suggesting that the mechanisms involved in the reversibility of type 2 diabetes using these two interventions are similar. Pancreatic triglyceride content appears to decrease with substantial weight loss in obese individuals with type 2 diabetes but not those with normal glucose tolerance. The clinical characteristics which limit reversal of diabetes are investigated, particularly the effect of longer diabetes duration. Both a retrospective study of bariatric surgery and a prospective study using VLCD suggest that long duration diabetes is reversible, however, normal blood glucose levels are less likely to be achieved than in short duration disease. Diabetes duration may be a surrogate marker for beta cell reserve. Finally, the longer term durability of the beneficial effects of an 8 week very low calorie diet is demonstrated. Over a subsequent 6 month weight maintenance period the decrease in hepatic and pancreatic triglyceride content, and the improvements in hepatic insulin sensitivity and first phase insulin secretion are maintained. The latter appears to be a key mechanism for determining a glucose response to VLCD.

The aggregation of misfolded proteins into amyloid fibrils is implicated in the pathogenesis of several human degenerative diseases, including Alzheimer’s, Parkinson’s and Type II diabetes. Links between the deposition of amyloid fibrils and the progression of these diseases are poorly understood, with much of the current research focused on monomer misfolding and subsequent assembly of oligomers and mature fibrils. This project examines the formation of human apolipoprotein (apo) C-II amyloid fibrils, with a focus on the stability and reversibility of amyloid fibril assembly.
The initial stages of the project were to develop a model for apoC-II amyloid fibril formation. This was achieved by analysis of the concentration dependent kinetics of apoC-II amyloid fibril formation, and correlation of these data with the final size distribution of the fibrils, determined by sedimentation velocity experiments. On the basis of these studies, a new reversible model for apoC-II amyloid fibril formation is proposed that includes fibril breaking and re-joining as integral parts of the assembly mechanism. The model was tested by rigorous experimentation, with antibody-labelling transmission electron microscopy providing direct evidence for spontaneous fibril breaking and re-joining.
The development of this model for apoC-II fibril assembly provided the foundation for experiments to investigate factors that promote, inhibit or reverse amyloid fibril formation. Factors that were considered include a molecular chaperone protein, αB-crystallin, and a chemical modification, methionine oxidation. Investigations on the effect of αB-crystallin revealed that the inhibition of apoC-II fibril formation occurs by two distinct mechanisms: transient interaction with monomer preventing oligomerisation, and binding to mature fibrils, which inhibits fibril elongation. Studies on the effect of methionine oxidation on apoC-II fibril formation showed that both the assembly and stability of the fibrils was affected by this modification. ApoC-II contains two methionine residues (Met-9 and Met-60), and upon oxidation of these residues fibril formation was inhibited. In addition, the treatment of pre-formed fibrils with hydrogen peroxide caused dissociation of the fibrils via the oxidation of Met-60, located with the fibril core structural region. The final chapter details the development of antibodies that specifically recognise the conformation of apoC-II amyloid fibrils, which provide the foundation for future studies to examine the role that apoC-II amyloid fibrils play in disease.
Overall, this thesis reveals the dynamic and reversible nature of amyloid fibril formation. New insight is also obtained of the general stability of amyloid fibrils and the processes that may regulate their formation, persistence and disease pathogenesis in vivo.

This thesis studies Judea Pearl’s logic of counterfactuals derived from the causal modeling framework, in comparison to the influential Stanlnaker-Lewis counterfactual logics. My study focuses on a characteristic principle in Pearl’s logic, named reversibility. The principle, as Pearl pointed out, goes beyond Lewis’s logic. Indeed, it also goes beyond the stronger logic of Stanlnaker, which is more analogous to Pearl’s logic. The first result of this thesis is an extension of Stanlnaker’s logic incorporating reversibility. It will be observed that the translation of reversibility from Pearl’s language to the standard language for conditional logic deserves some attention. In particular, a straightforward translation following Pearl’s suggestion would render reversibility incompatible with Stanlnaker’s logic. A new translation of reversibility will be proposed, and an extension of Stanlnaker’s logic with the inclusion of the translated reversibility will be investigated. More importantly, it will be shown that the extended Stanlnaker’s logic is sound and complete with respect to a modified Stanlnaker’s semantics. The extension of Stanlnaker’s logic has an interesting implication. Zhang, Lam, and de Clercq (2012) have shown that special case of reversibility, despite its name, actually states an important kind of irreversibility: counterfactual dependence (as defined by David Lewis) between distinct events is irreversible. In other words, reversibility entails that there is no cycle of counterfactual dependence altogether generalizations of reversibility. However, as shown in Zhang et al. (2012), Pearls’ logic does not rule out cycles of counterfactual dependence altogether. It in fact allows cycles that involve three or more distinct events. This is peculiar because the status of cyclic counterfactual dependence seems no more metaphysically secure than that of mutual counterfactual dependence. This consideration leads to an exploration of logics that rule out all cycles of counterfactual dependence. A surprising result is that the extension of Stanlnaker’s logic is precisely a logic of this sort.

We study the cause of the signature over finite fields of integrability in two dimensional discrete dynamical systems by using theory from algebraic geometry. In particular the theory of elliptic curves is used to prove the major result of the thesis: that all birational maps that preserve an elliptic curve necessarily act on that elliptic curve as addition under the associated group law. Our result generalises special cases previously given in the literature. We apply this theorem to the specific cases when the ground fields are finite fields of prime order and the function field $mathbb{C}(t)$. In the former case, this yields an explanation of the aforementioned signature over finite fields of integrability. In the latter case we arrive at an analogue of the Arnol'd-Liouville theorem. Other results that are related to this approach to integrability are also proven and their consequences considered in examples. Of particular importance are two separate items: (i) we define a generalization of integrability called mixing and examine its relation to integrability; and (ii) we use the concept of rotation number to study differences and similarities between birational integrable maps that preserve the same foliation. The final chapter is given over to considering the existence of the signature of reversibility in higher (three and four) dimensional maps. A conjecture regarding the distribution of periodic orbits generated by such maps when considered over finite fields is given along with numerical evidence to support the conjecture.

Thesis (Ph. D.) -- University of Maryland, College Park, 2006.
Thesis research directed by: Philosophy. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

Thesis advisor: John Sallis
Maurice Merleau-Ponty's last essay about art, Eye and Mind, refers to many painters, to painting, and even to sculpture. Yet there is hardly any use of the traditional categories used in art criticism to categorize artistic movements or to evaluate painters' contributions to their period. Instead, he uses terms such as `body' and `flesh' that are alien to that tradition, thereby indicating that he clearly intends to go beyond commenting on and assessing the artistic value of the works he mentions. Instead, the essay is a reevaluation of meaning of painting as a whole. Merleau-Ponty says that all painting from Lascaux to our day has been a celebration of `the visible.' However, to understand what he means by `the visible' involves considerable complexity. The standard by which Merleau-Ponty evaluates painting emerges from his phenomenological and ontological research into perception. I argue that in fact Eye and Mind answers a question that arose in his first major book concerning the relationship between consciousness and nature. Because the evolution of the ideas underlying the Eye and Mind's answer is so vast, the goal of this dissertation is to trace the thread leading from his earlier work in order to provide a unifying viewpoint that will ground an adequate understanding of the essay's various arguments. The dissertation argues that Merleau-Ponty's notion of the Gestalt or structure is the framework for understanding the origin and depth of the aperçus developed in Eye and Mind. Ironically perhaps, this notion is not mentioned in Eye and Mind. As if it had lost its original meaning, it is only referred to indirectly and vaguely in terms of transcendence. Nevertheless, the main issue settled in The Structure of Behavior dominated his understanding of the body in The Phenomenology of Perception, and underwent a transformation when Merleau-Ponty discovered language as a diacritical structure. This made possible the radical use he made of it in Eye and Mind without expressly mentioning it. Once the interpretation of Gestalt in relation to Paul Klee and Rudolf Arnheim had been worked out, this dissertation could use this notion--usually undervalued in Merleau-Ponty scholarship--to make sense of Eye and Mind's main contention in light of the interpretive reconstruction of the notions of expression, reversibility, body, and flesh Merleau-Ponty elaborated on the way to that essay. Part I of the dissertation deals with the phenomenology of the Gestalt structure prior to Merleau-Ponty's ontological turn, which in turn frames and underpins many of the insights achieved in this pre-ontological period, especially those about the body. The first two chapters introduce the notion of structure as it emerges in its application to behavior, and explain Merleau-Ponty's own contribution to the notion through the overcoming of earlier psychologists' static reduction of the notion to the physical level. The third and last chapter of Part I discusses the structural dimension of the body. There are two extraordinary things in Eye and Mind: the first is Paul Valery's statement that the painter "takes his body with him"; and the second is the analogy between the problems of the body and the problems of painting, by which Merleau-Ponty proposes that understanding one is indispensable for understanding the other. To clarify his proposal we have to return to The Phenomenology of Perception's analysis of the body according to embodied intentionality or motor intentionality, in which the body operates according to an "I can" that must replace the mechanical reaction to a stimulus. Here Merleau-Ponty was helped by Kurt Goldstein's insight into the body as a Gestalt. The dissertation illustrates what this could mean for the structure of a painting by using examples. What was formerly Part II profiles Merleau-Ponty's embodied notion of the Gestalt form against Arnheim's aprioristic account, which explains the relationship between consciousness and nature through an isomorphism that is even more ambitiously totalizing than the ones envisioned by the original Gestalt psychologists. Because of the detailed nature of our account this part is in two appendices. What is now Part II focuses on the problem of painting more directly. Using both the Notes de Cours (where Merleau-Ponty's most extensive comments on Paul Klee occur) and Paul Klee's own celebrated Notes, Chapter Four on Paul Klee reconsiders the relationship between consciousness and nature as the one between the painter and the world. Klee interpreted abstraction in terms of Gestalt as a form of transcendence involving the visible and the invisible, in contrast to Sartre's idea of transcendence, which also employs the figure/ground formation of the Gestalt. In Eye and Mind the expression of painting is interpreted as "a `visible' to the second power, a carnal essence or icon of the first." So Chapters Five and Six discuss the notion of structure from the viewpoint of expression. The doubling of expression in painting is seen first as analogous to philosophy as a hyper-reflection, and then in the linguistic distinction between le langage parlé et le langage parlant, which allowed Merleau-Ponty to interpret and generalize the model of expressive language via the diacritical structure of language and not restrict expressive language to bodily gestures. Rather than a return to the original (as The Phenomenology may have suggested), the point of this doubling aspect of expression is the recognition of the qualities of reversibility and difference that constitute `depth.' With the clarification of terms such as `perceptual faith' and `style,' Chapter Seven introduces the notion of reversibility before exploring its meaning, specifically in the second chapter of Eye and Mind. In Chapter Eight the earlier focus on the beginning of the definition of a painting as "a `visible' to the second power, a carnal essence or icon of the first," shifts to the meaning of the term "icon." This rounds off the meaning of `depth' and completes the exploration of the theme of the Gestalt structure. Now it becomes clear that the meaning of `depth' is articulated as the depth between the visible and the invisible, because the model used to understand depth is the by now very familiar basic articulation of the perceptual Gestalt: the articulation of a figure over a ground. Like a stain on a rug--in painting, in history, in philosophy, in language, or in perceptual faith--the crystallization of what appears always disguises an invisible dimension, whose invisibility is what makes the visibility of the visible possible. Chapter Nine then concludes the dissertation. It first considers Jean-Luc Marion's use of the icon in painting, in which, as in our interpretation of Merleau-Ponty on depth, uses his own idea of the depth between the visible and the invisible; and second, it responds to observations on Merleau-Ponty's philosophy of art by Veronique Fotí and criticisms of it by Michel Haar
Thesis (PhD) — Boston College, 2012
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Philosophy

To experience the world, we depend on the ability of our brains to process information. Problems can occur when communication between neurons is not regulated, and a significant enough loss of stability could lead to conditions such as migraine and epilepsy. Homeostatic plasticity is thought to constrain activity within physiologically useful ranges. Our lab uses the fruit fly neuromuscular junction as a model synapse to study homeostatic plasticity. Homeostatic potentiation and homeostatic depression are two forms of homeostatic synaptic plasticity. Expression of a dominant negative glutamate receptor subunit in the muscle impairs its sensitivity to glutamate and triggers an increase in the number of vesicles released per evoked potential, or quantal content. This increase in quantal content is called homeostatic potentiation. We found that homeostatic potentiation is a reversible process: quantal content returns to normal levels when expression of the dominant negative ceases. We additionally found that homeostatic potentiation can be ablated at high temperature. Overexpression of the Vesicular Glutamate transporter (VGlut) causes an increase in the amplitude of spontaneous events, leading to a corresponding decrease in quantal content, called homeostatic depression. It is unknown to what degree homeostatic potentiation and homeostatic depression may share regulatory machinery. We screened genes required for homeostatic potentiation in the neuron for additional roles in homeostatic depression. We found that certain genes involved in calcium regulation, such as the IP3 receptor and ryanodine receptor, showed a substantial decrease in evoked potential amplitude in a VGlut overexpression background.

Mitochondrial disorders comprise a large group of heterogeneous disorders which are characterized by impairments in the cellular energy production. One of the great challenges of mitochondrial disease is the variety of clinical features present in patients. Mitochondrial disorders affect more than one organ leading to complex multisystem dysfunctions. Tissues, in which the metabolic demand is higher, such as skeletal muscle, neurons, liver or heart are typically affected. Mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) often lead to mitochondrial disorders. Although mtDNA encodes key proteins for the normal function of the mitochondrial respiratory chain enzymes, the vast majority of the essential components and proteins needed for the maintenance and replication of the mitochondrial DNA are encoded by the nDNA. Exome sequencing in combination with bioinformatics tools has proven really effective in determining novel alterations in the genomic sequence. One aim of this thesis was to evaluate novel mutations from affected patients with combined respiratory deficiencies. As a result, mutations in C12orf65 and in the novel disease gene MiD49, associated with mitochondrial disorders, are thoroughly presented. Vitamin supplements, pharmacological agents and exercise therapy are common strategies used in patients suffering from mitochondrial disorders. It has been shown that in cell lines of patients suffering from two rare reversible infantile mitochondrial diseases (reversible infantile respiratory chain deficiency and reversible infantile hepatopathy due to TRMU deficiency) supplementation of L-cysteine resulted in an improvement in most respiratory chain complexes activities. During my PhD I studied and proved that L-cysteine supplementation was also beneficial in cells from patients suffering from common forms of mitochondrial disorders such as MELAS and MERRF as the supplementation resulted in improved mitochondrial respiratory chain function. Finally, direct conversion of fibroblasts to neuronal progenitor cells was used to model mitochondrial disorders and study the tissue specificity. This project was very challenging due to the complex characteristics of mitochondrial biology. In summary, this thesis reveals the description of novel genes and mutations associated with combined mitochondrial deficiencies. Furthermore, we detected a positive effect of L-cysteine on a subset of mitochondrial disorders, which can be the base of further therapy development.

The dimension problem of states space makes the computation of quantitative data impractical due to the memory and time requirements. To this scope, time reversibility plays an important role on the analysis of these processes. Moreover, is defined the class of reversibility for the probabilistic automata with renaming of states space, a crucial point for our analysis and further studies. Is introduced also the notion of the stationary distribution for the probablistic automata to verify and complete the work on this thesis.

This study investigates the development of flexibility and reversibility in a calculus environment that attends to linking multiple representations. Reversibility was studied through Krutetskii’s framework of reversibility of two-way processes and reversibility of the mental process in reasoning. The study was conducted over approximately four months in a high school calculus classroom in an urban school district in a mid-Atlantic state. Instruction attended to linking multiple representations whenever possible. Four types of data were collected: 1) a pre-test, 2) a post-test, 3) daily assessments, and 4) clinical interviews. Twenty-one students completed a pretest and post-test that together assessed development of flexibility over the course of the study. They also completed daily assessments that were collected to provide evidence of the development of reversibility during the course of the study. Six students participated in four clinical interviews each, spread throughout the study. Inferential statistics were used to compare the results of the pre-test and post-test for significant differences and to determine significant differences in the presence of reversibility on the daily assessments over the course of the study. The clinical interviews were analyzed for evidence of students’ thought processes while solving reversible questions. Analysis revealed that over the course of the study, students demonstrated significant increases in both flexibility and reversibility. Two-way reversibility seemed to develop with relative ease for most students and often developed simultaneously with learning a forward process. Developing reversibility of the mental process in reasoning was difficult and tended to develop simultaneously with learning in a forward direction for students with high levels of flexibility. For students who did not develop reversibility simultaneously with forward learning, both two-way reversibility and reversibility of the mental process in reasoning were able to develop through multiple opportunities to solve reversible tasks of similar content. Analysis of the clinical interviews indicated that students typically followed a 4-step thought process when using reversibility to solve problems. Implications and limitations of the study and areas of further research were discussed.

In recent years, research in students' conceptions about the physical world has revealed that when children reach the age of schooling they have already developed their own knowledge about the physical world which is sometimes rather different from the accepted scientific knowledge taught in schools. This thesis aims at investigating possible structures of commonsense reasoning about reversibility related to processes of interest to Science presented by students from two age-groups, 13/14 year old and 16/17 year old. The study has a theoretical framework based upon the scientific view of reversibility mainly related to Thermodynamics. It is also related to a conceptual, commonsense and developmental perspective taken from the literature, where reversibility is connected with different concepts such as causation, action, and conservation. Therefore, based upon this framework some very basic questions were asked to students about a selected number of phenomena. The empirical data was collected with the use of questionnaires. The sample consisted of two different age/instructional groups of students from England, Chile and Brazil. Factor Analysis was used to analyse the quantitative data. The qualitative data was analysed using a systemic network in which students' answers could be categorised. The main result of the quantitative analysis was a common three dimensional factor space of explanation for all groups with the dimensions relating to the ways in which the processes could be seen. They are respectively the contrast between 'can happen and cannot happen', 'needs an action and happens by itself, and 'has a goal and has no goal'. Phenomena can be located in this common space, but their position may vary for different age/instructional groups and for groups from different countries. The results of the qualitative analysis give a more detailed description of the way students see the reversibility of the processes and lend support to the quantitative results.

We illustrate self-assembly with several systems which aim to harness the process of assembly to create new functional structures. The concept of kinetic trapping preventing assembly and the importance of reversibility, breaking as well as making bonds, for avoiding such traps are introduced. We aim to identify how reversible systems are, with the aim of aecting the prediction, control and design of new systems. In four systems a lattice gas model, and three models based upon patchy particle schemes, a yield is dened and used to identify optimal assembly at a given time. Three measurements relevant to reversibility are described, applied, and compared with the results of similar studies. The rst simply counts the bonding and un-bonding events, or kinks, over the whole assembly process and compares the total number of events with the net bonding events. We measure values of 100 􀀀 1000kinks per bond in crystal systems, and 60 􀀀 200 for closed structures. In analogy with a toy model the values can be related to a `forgivingness', a ratio of bad bonding sites, to good ones. We then turn to measurements at early times which allow for the prediction of when assembly will occur. These include rate measurements of kinks which provide an instant measure of reversibility and comparison of correlation and response functions with the equilibrium uctuation dissipation theory. These methods examine the dynamics of the assembly process while our third approach examines the structures during assembly. We examine how each of the measurements provide information about the assembly process and how it relates to the particles, their interactions and the nal structure. The possibility of using the methods in combination is shown to be relevant to the prediction of assembly and how they might be used to implement design and control schemes to improve assembly.

Benzoylformate decarboxylase (BFD) from Pseudomonas putida catalyzed the formation of 2-hydroxy-1-phenylpropanone (2-HPP), a 2-hydroxy ketone, from the kinetic resolution of rac-benzoin in the presence of acetaldehyde. The formation rate of 2-HPP via kinetic resolution of benzoin was 700-fold lower compared to the formation via direct carboligation of benzaldehyde and acetaldehyde. Further investigations revealed that BFD not only accepts (R)-benzoin but also 2-HPP as the substrate. A typical Michaelis–Menten type kinetics was observed starting from enantiopure (S)- or (R)-2-HPP. The formation of racemic 2-HPP while using benzoin as the donor in the presence of acetaldehyde and the racemization of (R/S)-2-HPP were detected. The equilibrium constant determined, showed favoured conditions towards the product side i.e. (R)-benzoin and 2-HPP. In the end, an extended reaction mechanism was proposed by supplementing the already known mechanism with the C–C bond cleavage activity of BFD towards 2-hydroxy ketones
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Benzoylformate decarboxylase (BFD) from Pseudomonas putida catalyzed the formation of 2-hydroxy-1-phenylpropanone (2-HPP), a 2-hydroxy ketone, from the kinetic resolution of rac-benzoin in the presence of acetaldehyde. The formation rate of 2-HPP via kinetic resolution of benzoin was 700-fold lower compared to the formation via direct carboligation of benzaldehyde and acetaldehyde. Further investigations revealed that BFD not only accepts (R)-benzoin but also 2-HPP as the substrate. A typical Michaelis–Menten type kinetics was observed starting from enantiopure (S)- or (R)-2-HPP. The formation of racemic 2-HPP while using benzoin as the donor in the presence of acetaldehyde and the racemization of (R/S)-2-HPP were detected. The equilibrium constant determined, showed favoured conditions towards the product side i.e. (R)-benzoin and 2-HPP. In the end, an extended reaction mechanism was proposed by supplementing the already known mechanism with the C–C bond cleavage activity of BFD towards 2-hydroxy ketones.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Thesis (Ph.D.)--Indiana University, Dept. of Mathematics, 2008.
Title from PDF t.p. (viewed on Oct. 8, 2009). Source: Dissertation Abstracts International, Volume: 70-02, Section: B, page: 1065. Adviser: Russell Lyons.

This thesis is concerned with the adsorption of bovine serum albumin to polyethylene tubing. A method using radioiodinated protein was developed to measure the surface concentration taking into account the dilution effect for miscible displacement in a capillary. A steady-state surface concentration was established within 2 hours. Adsorption did not depend on the ratio of radiolabelled to unlabel led protein. The adsorption isotherm was Langmuir-like with a plateau concentration of approximately 0.2 μg/cm². Two methods were used to calculate the surface concentration in the desorption study. The surface concentration calculated by depletion of the total radioactivity was always higher than that calculated from assaying the radioactivity associated with the tubing. Desorption of at least 5% of the loosely bound protein occurs. The surface concentration-pH data show two maxima. The first is at the isoelectric point of the albumin while the second is at pH 9.5-10. The second maximum seems to be due to preferential adsorption of the higher molecular weight oligomers in the protein sample.
Science, Faculty of
Chemistry, Department of
Graduate

This thesis pertains to the pathogenesis of alcoholic pancreatitis, a considerable burden in terms of morbidity, mortality and health related costs. It has long been known that only a minority of alcoholics develop clinically evident pancreatitis, suggesting that (an) additional trigger factor(s) is required to elicit overt disease. Endotoxin (lipopolysaccharide LPS), from gut-derived gram negative bacteria may be one such trigger factor, since alcoholics exhibit increased levels of serum endotoxin. In addition, the degree of endotoxinaemia has been reported to correlate with the severity of pancreatitis. Studies described in this thesis report, i) the development of a novel rodent model of alcoholic pancreatitis produced by challenging alcohol-fed animals with single or repeated doses of LPS. The animals exhibit features of both acute (acinar vacuolisation, necrosis, pancreatic oedema, haemorrhage and inflammatory infiltration) and chronic (acinar atrophy and pancreatic fibrosis) pancreatitis; ii) the reversion of pancreatic injury (including fibrosis) upon withdrawal of alcohol in the model and the persistence of pancreatic damage with continuation of alcohol feeding; iii) activation of pancreatic stellate cells (PSCs, known to play a central role in fibrogenesis) in vivo and in vitro by alcohol and LPS; iv) the inhibition of PSC apoptosis in vivo and in vitro upon exposure to alcohol and LPS and the induction of PSC apoptosis in vivo upon withdrawal of alcohol from the diet and v) the presence of LPS receptors TLR4 and CD14 on PSCs, which would explain the responsiveness of PSCs to LPS. Thus the work in this thesis provides strong evidence in support of endotoxin as a clinically relevant trigger factor for the initiation of alcoholic pancreatitis and as a factor that promotes disease progression. The thesis also provides the first experimental evidence to support the clinical reports of a beneficial effect of abstinence on chronic pancreatitis. Delineation of the mechanisms mediating the induction, progression and reversibility of alcoholic pancreatitis has the potential to direct the development of new therapeutic interventions for alcohol-related pancreatic injury.

Thesis (Ph. D.)--University of Maryland, College Park, 2006.
Thesis research directed by: Chemistry. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

Thesis (Ph. D.)--Industrial and Systems Engineering, Georgia Institute of Technology, 2005.
Sokol, Joel, Committee Member ; Wang, Qiong, Committee Member ; Kertz, Robert, Committee Member ; Griffin, Paul, Committee Member ; Deng, Shijie, Committee Chair. Includes bibliographical references.

Background. Hepatic encephalopathy (HE) produces a wide spectrum of nonspecific neurological and psychiatric manifestations. Mild HE that does not produce disorienting in time/space or asterixis is called covert HE (CHE). It occurs in 20%–80% of patients with cirrhosis. While significant progress has been made in understanding the importance of CHE, to date there is no consensus guidelines regarding the screening procedures for CHE and all the recognized techniques, although more or less sensitive and objective, require some kinds of equipment. Furthermore, the diagnosis of CHE can be confounded by other factors (as chronic alcohol misuse or HCV infection), which can cause cognitive alterations. It is also important to identify CHE in patients awaiting liver transplantation (LT) for the proper interpretation of cognitive disorders that may occure after transplantation. Infact, the influence of LT on mental performance is debated; as is the role of pretransplant HE. Notable, recent data on LT suggest that the cognitive dysfunction may not be totally reversible. Another important issue regards the treatment of CHE, in particular the effect of treatments on gut microorganism and ammonia production by microbial activity. HE treatment with prebiotics, antibiotics and probiotics, generally evidences a reduction of photogenic/ ammoniagenic bacteria and an increase in neurocognitive tests and mental status in patients. Nevertheless from a strictly microbiological point of view, little is known about the dynamics, interaction and metabolite production of the main bacterial groups in liver diseases. Aims. The present study aims to: 1) test a simple verbal psychometric test, called Animal Naming Test (ANT1), in the detection of CHE; 2) to evaluate the role of alcohol misuse, HCV infections, diabetes, aging and level of education as potential confounding factors in the diagnosis of CHE; 3) to evaluate the time course of the neuropsychological and electroencephalogram (EEG) features of patients with cirrhosis before and after LT with respect to prior HE and 4) to investigate how the HE treatments (by the use of lactulose, rifaximin and a probiotc mixture) affects gut microbial composition, determining changes in ammonia production. Materials and methods. For Aim 1: 208 healthy subjects and 327 consecutive patients with cirrhosis underwent the ANT1. Patients with cirrhosis were assessed by the Psychometric Hepatic Encephalopathy Score (PHES), a subgroup of 146 underwent also a quantified EEG and 95 the Critical Flicker Frequency. 202 patients were followed up for the occurrence of overt HE (OHE) and death. For Aim 2: a comprehensive neuropsychological profile and EEG spectral parameters were obtained in six age-matched groups of 30 subjects each: (i) HCV-related hepatitis without cirrhosis, (ii) chronic alcohol abusers, (iii) patients with HCV-related cirrhosis, (iv) alcohol-related cirrhosis, (v) cirrhosis not related to alcohol or HCV and (vi) healthy subjects. Cirrhotic patients were matched for MELD score. For Aim 3: the study population included 65 patients with cirrhosis on the transplant waiting list; 23 had a history of OHE. Each patient underwent an extensive psychometric assessment (10 tests, including paper and pencil tests and a computerized test) and an EEG before and 9 to 12 months after LT. EEGs were analyzed spectrally, and the mean dominant frequencies were obtained. For Aim 4: independent batch culture fermentations with controlled pH (6.8) were inoculated with fecal samples from six patients with cirrhosis (age 66±3.3 years; Child-Pugh A n=5 and B n=1); average MELD score 9±2.8). Seven different treatments with lactulose, rifaximin and VSL#3 or their combination were performed. Microbial populations were enumerated using flow cytometry Fluorescent in Situ Hybridization, while an ammonia concentration was determined at 0, 4, 10 and 24 hours. Results. Aim 1: in controls, the ANT1 was found relevantly affected only by extremely low levels of education (<8 yrs) and old age (>80 yrs; p<0.001). Thus, an age and education adjusted criterion was obtained (S-ANT1). Patients with CHE had significantly lower S-ANT1 than the unimpaired ones (12±0.4 vs 16±0.7; p<0.001). By ROC analysis, two thresholds of 10 and 15 animals were obtained, producing a Scoring System (0=S-ANT1>15, 1=S-ANT1 10-15, 2=S-ANT1<10 sensitivity 83%, specificity 84%, respectively vs. PHES) that was correlated both to PHES (p<0.0001) and EEG (p=0.007). In the follow up, the S-ANT1 resulted to have prognostic value on the risk of OHE and death, so that a prognostic index could be computed. Aim 2: the factor ‘cirrhosis’ was associated with low Phonemic Verbal Fluency (PVF) and Difference between Trail Making Test B and A (TMT B-A) (p<0.001). Chronic alcohol misuse was associated with low PVF, TMT (B-A), Memory with Interference Task at 10 (ITM 10) and 30s (ITM 30) (all p<0.05). An interaction was found between the factors ‘cirrhosis’, ‘alcohol misuse’ and tests (p<0.01). HCV hepatitis reduced ITM 10 (p<0.05), but no interaction was found between ‘cirrhosis’, ‘HCV infection’ and tests (p= 0.14). The EEG parameters were mainly influenced by ‘cirrhosis’ (p<0.05), and EEG alterations were more pronounced in patients with alcoholic cirrhosis (p=0.04). Aim 3: Patients with a history of OHE before LT had worse cognitive performances (p<0.001) and EEG performances in comparison with their counterparts with a negative history. They also showed greater cognitive improvement after LT (p<0.01); however, their global cognitive performance remained slightly impaired (p <0.01). After LT, EEGs normalized for 98% of the patients (p <0.01), regardless of any history of OHE. Aim 4: Lactulose treatment significantly increased total bacteria, Bifidobacteria and Fecalibacterium prausnitzii after 5 hours (p≤0.05); in contrast Rifaximin and a probiotic mixture (VSL#3) have no significant effect. After 24 hours the combination of lactulose/Rifaximine/VSL#3 significantly increased total bacteria and Bifidobacteria. At time 5 h, lactulose significanly reduced ammonia, whereas rifaximin had no significant effect. VSL#3 alone had never significant affect in reducing ammonia, whereas at 24 h, in combination with lactulose and rifaximin, reduced significantly ammonia. Conclusions. The ANT1 is an easy first-line measure useful for detection of CHE. The diagnosis of CHE should considered the concomitant presence of alcohol misuse and low educational level, which had a synergistic effect with cirrhosis in damaging cognitive functions, and thus they should be considered as possible confounders when testing for CHE. After LT, patients with a history of HE showed greater improvements than patients with a negative history, but their global cognitive function remained slightly worse; in contrast, EEGs normalized in both groups. Regarding HE treatments, microbial modulation by prebiotic, antibiotic and probiotic differently affect the population dynamics and metabolism. The strong increase in beneficial bacteria, reduction of ammonia and regulation of metabolite production seen using lactulose and its combination with VSL#3, emphasize the importance of gut microbiota handling in HE treatment.
Stato dell’arte. L’encefalopatia epatica (EE) è caratterizzata da un ampio spettro di manifestazioni aspecifiche, sia neurologiche che psichiatriche. Un EE lieve tale da non indurre disorientamento spazio-temporale o asterissi è definita “EE non conclamata”, e si manifesta nel 20%-80% dei pazienti con cirrosi epatica. Sebbene siano stati compiuti notevoli progressi nella comprensione dell'importanza dell’EE non conclamata, non esistono, ad oggi, linee guida condivise in materia di screening. Inoltre, tutte le tecniche di diagnosi universalmente riconosciute, anche se più o meno sensibili ed obiettive, richiedono l’utilizzo di una qualche forma di strumentazione. La diagnosi di CHE dovrebbe anche tener conto di altri fattori (come l’abuso alcolico o l’infezione da virus C), in grado di per sé di causare alterazioni cognitive, che potrebbero agire da fattori di confondimento. Un’altra problematica aperta in ambito di EE non conclamata è la reversibilità delle alterazioni cognitive, caratteristiche dei pazienti con storia di EE, dopo trapianto di fegato che è tuttora controversa. Studi recenti sembrano suggerire che le alterazioni cognitive caratteristiche dei pazienti con storia di EE non siano completamente reversibili. Anche il ruolo del microbiota intestinale nella patogenesi e quindi nella terapia dell’EE non è del tutto noto. Studi recenti hanno dimostrato che le terapie dell’EE, che si basano su prebiotici, antibiotici e probiotici, determinano una riduzione di batteri ammoniagenici e un concomitante miglioramento dei test neurocognitivi e dello stato mentale dei pazienti. Tuttavia, da un punto strettamente di vista microbiologico, poco si conosce circa le dinamiche e l'interazione tra i principali gruppi di batteri e come si modifica la produzione di ammonio a seguito della somministrazione di tali terapie. Scopi dello studio. Il presente studio si propone di: 1) testare un test psicometrico verbale, chiamato Animal Naming Test (ANT1), nella diagnosi di EE non conclamata; 2) valutare il ruolo dell’abuso alcolico cronico, dell’infezione da virus, del diabete, dell’invecchiamento e del livello d’istruzione come potenziali fattori di confondimento nella diagnosi di EE non conclamata; 3) di valutare l'andamento temporale neuropsicologico ed elettroencefalografico dei pazienti con cirrosi prima e dopo trapianto di fegato, in relazione alla presenza o meno di una storia di EE prima del trapianto e 4) di valutare come i trattamenti dell’EE (quali il lattulosio, la rifaximina e il probiotico VSL#3) modifichino la composizione microbica intestinale e determinino cambiamenti nei livelli di ammonio. Risultati. Obiettivo 1: nei controlli l’ANT1 è risultato influenzato in modo significativo solo da livelli di istruzione estremamente bassi (<8 anni di scolarità) e da un’età molto avanzata(> 80 anni; p<0,001). Sono, quindi, stati calcolati i punteggi aggiustati per età e livello d’istruzione (S-ANT1). I pazienti cirrotici con EE non conclamata avevano uno S-ANT1 significativamente inferiore dei pazienti senza EE (12±0,4 vs 16±0,7; p<0.001). L’analisi delle curve ROC ha permesso di ottenere due valori soglia dell’S-ANT1, di 10 e 15 animali/minuto, ed è stato costruito un sistema di Scoring (0=S-ANT1> 15, 1=S-ANT1 10-15, 2=S-ANT1<10 con sensibilità 83% e specificità 84%) che è risultato ben correlato sia con la PHES (p<0,0001) che con l’EEG (p=0.007). Nel follow-up, lo S-ANT1 è risultato avere un valore prognostico sia sul rischio di EE conclamata che sulla mortalità ad un anno. Obiettivo 2: il fattore 'cirrosi' è risultato associato sia con il Phonemic Verbal Fluency (PVF) che con la Differenza tra Trail Making Test B e A (TMT) (B-A) (p<0.001). L’abuso alcolico cronico è risulato associato con un bassi punteggi al PVF, al TMT (B-A) e ai test di Memoria di interferenza a 10 (ITM 10) e 30 s (ITM 30) (tutti p<0.05). E’ stata trovata un'interazione tra i fattori «cirrosi',' abuso alcolico 'e test (p<0,01). Il virus C determina una riduzione dell’ITM 10 (p<0,05), ma nessuna interazione è stata trovata tra i fattori 'cirrosi', 'infezione da HCV' e test (p=0.14). I parametri EEG sono risultati principalmente influenzati dal fattore 'cirrosi' (p<0,05). Obiettivo 3: i pazienti con una storia di EE, prima del trapianto, hanno avuto performance cognitive ed EEG peggiori rispetto alla controparte senza storia di EE (p<0.001). Ma, dopo il trapianto, hanno mostrato un miglioramento cognitivo maggiore (p<0.01); tuttavia, la loro performance cognitiva globale rimane lievemente compromessa (p<0,01). Dopo il trapianto, l’EEG si normalizza nel 98% dei pazienti (p<0.01), indipendentemente dall’avere una storia di EE. Obiettivo 4: il trattamento con lattulosio aumenta significativamente il numero totale dei batteri, dei Bifidobatteri e del Fecalibacterium prausnitzii, rispetto al controllo e dopo 5 ore (p≤0.05); al contrario sia Rifaximina che il probiotico VSL#3 non hanno alcun effetto significativo. Dopo 24 ore la combinazione di lattulosio/Rifaximina/VSL#3 aumenta significativamente il numero totale dei batteri e i bifidobatteri. Per quanto riduarda la produzione di ammonio, il lattulosio riduce in modo significativo l’ammonio, mentre la Rifaximina non ha effetti significativi. Il probiotico VSL#3 da solo non ha mai un effetto nel ridurre l’ammonio, mentre in combinazione con lattulosio e rifaximina a 24 ore lo riduce significativamente. Conclusioni. L’ANT1 è uno strumento utile e facile da somministrare per il rilievo dell’EE non conclamata. La diagnosi dell’EE non conclamata dovrebbe inoltre tener conto della concomitante presenza di un abuso cronico alcolico e di un basso livello d’istruzione, che possono avere un effetto sinergico con la cirrosi nell’alterare le funzioni cognitive, e dovrebbero quindi essere considerati come fattori di confondimento nella diagnosi di EE non conclamata. Dopo trapianto di fegato, i pazienti con una storia di EE prima del trapianto presentato nel post-trapianto un miglioramento maggiore rispetto pazienti senza storia di EE, ma la loro performance cognitiva globale rimane un po’ alterata; al contrario, l’EEG si normalizza in quasi tutti i pazienti. Per quanto riguarda l’influenza delle terapie dell’EE sul microbiota intestinale dei pazienti con cirrosi, i prebiotici, gli antibiotici e i probiotici influenzano in modo diverso la dinamica e il metabolismo delle popolazioni batteriche. Il forte aumento dei batteri benefici e la riduzione dell’ammonio favoriti dal lattulosio e dalla sua combinazione con rifaximina e VSL#3, sottolineano l'importanza della manipolazione della flora intestinale nel trattamento dell’encefalopatia epatica.

"Chemically Modified" (CM) rechargeable MnO$\sb2$ cathode materials have been prepared, based on patents issued to Ford. The reaction mechanisms of the discharge and recharge of these materials have been extensively studied in the present work and compared with behaviour at Blank MnO$\sb2$ (without Bi) and regular $\gamma$-MnO$\sb2,$ by various experimental techniques including classical electrochemical methods, as well as a newly developed in-situ uv-visible spectro-electrochemical method and a new in-situ X-ray absorption (XAS) electrochemical procedure. The roles of the soluble Mn(+III) species and Bi dopants in the discharge and recharge processes have been investigated in some detail. Firstly, the presence of Bi(III) favours the formation of soluble Mn(OH)$\sb6\sp{3-}$ species in both the processes of discharge and recharge and, secondly, it appears to work as a "catalyst" for the steps involved in further reduction of Mn(OH)$\sb6\sp{3-}$ species to Mn(OH)$\sb2$ in discharge, and re-oxidation of Mn(OH)$\sb2$ to MnO$\sb2$ on recharge. Based on the optical absorbance measurements, an heterogenous mechanism in which the soluble Mn(OH)$\sb6\sp{3-}$ intermediate is involved, is directly indicated as being the preferred pathway at CM MnO$\sb2$ and operates in parallel with the so-called homogenous mechanism in both the processes of reduction of MnO$\sb2$ and re-oxidation of reduced MnO$\sb2$ materials. Thus, from the soluble Mn(OH)$\sb6\sp{3-}$ species, either Mn(OH)$\sb2$ can be deposited, on reduction, or MnO$\sb2$ re-formed on re-oxidation, on the porous electrode matrix at favourable and practically significant current-densities. The CM MnO$\sb2$ is then rechargeable over a practically useable voltage range and, importantly, over the 2-electron charge capacity. On account of the preferred heterogeneous pathway at CM MnO$\sb2,$ high (up to 6C) discharge rates can be realized at a remarkably constant plateau voltage, independent of discharge rate. In the light of the mechanism studies, the electrochemical performance of the CM MnO$\sb2$ has been studied. The CM MnO$\sb2$ cathodes were characterized by (a) good multiple rechargeability, (b) high energy and power densities, (c) achievement of high charging/discharging rates at a surprisingly constant working voltage and (d) low cost. Use of an ion-selective separator enables the CM MnO$\sb2$ to be used in a secondary alkaline MnO$\sb2$ battery system with a Zn anode, and an appreciable cycle-life to be realized which is not possible if ZnO$\sb2\sp{2-}$ ions diffuse to the MnO$\sb2$ cathode. These characteristics make the secondary CM MnO$\sb2$/Zn battery system a promising candidate for electric vehicle applications and also for many other market niches currently occupied by Ni-Cd secondary and MnO$\sb2$/Zn primary cells in the consumer market.

Thesis (M.A. (Translation Studies)) --University of Limpopo, 2012
This study focuses on aspects that form part of the reasons of not having complete bidirectional bilingual dictionaries and to find solutions to those problems. The following dictionaries have been evaluated in this study: Oxford Pukuntšu ya Sekolo School Dictionary (2010), Pharos Popular Northern Sotho Dictionary (2007 & 2009) and Sesotho sa Leboa/English Pukuntšu Dictionary (2006). Most African bilingual dictionaries which are supposed to be bidirectional are not because reversibility is not applied thoroughly. This study focuses on checking how Northern Sotho-English bilingual dictionaries apply the reversibility principle. When evaluating bilingual dictionaries it comes to light that there are a lot of errors that lexicographers commit and these errors negatively affect the process of compiling complete user-friendly bidirectional dictionaries. Having user-friendly bidirectional bilingual dictionaries is very important because dictionaries help different language speakers to learn each other’s language.

Selenium is a required trace element which was originally discovered by the Swedish chemist Jons Jacob Berzelius in 1817. It was initially believed to be a toxin as it was identified as being the cause of hoof maladies and excessive hair loss in horses that feed upon plants with high selenium content. It wasn’t until 1957 that the potential contributions of selenium to physiology were first demonstrated. Selenium is now known to play a critical role in the maintenance of human health. Interestingly, unlike other trace metals/semi-metals, selenium is directly incorporated into proteins in the form of the amino acid selenocysteine (Sec) in a very complicated and energetically costly fashion. Though rare, being found in only 25 human proteins, Sec proteins are involved in numerous vital biological processes including maintenance of redox homeostasis and anti-oxidant defense. Even though Sec is essential, the reason that Sec replaces its structural analog cysteine (Cys) in only 25 proteins is not widely agreed upon. A previous model suggests that the replacement of Cys with Sec provides enzymes with a type of catalytic advantage. The presence of Cys-containing orthologs of mammalian Sec-enzymes in other eukaryotes argues against this model. A newer model to explain the use of Sec is that the gain of function imparted to an enzyme by replacing Cys with Sec is the ability of Sec to impart chemical reversibility. Building on previous results from our lab demonstrating the ability of Sec to confer proteins with the ability to resist over oxidation we have elucidated the mechanism by which Sec containing thioredoxin reductase (TrxR) resists over oxidation. The ability of Sec-TrxR to resist oxidative inactivation is due to the greater electrophilicity of Sec relative to Cys. This allows for quicker resolution and prevents over oxidation. Based on these findings we also investigate the utility of the alkylating agent dimedone to probe the oxidation state of Sec. Interestingly, it was discovered that dimedone will react with seleneninic acid with the resulting adduct being labile. Additonally it was discovered that dimedone will also react with seleninic acid, resulting in the formation of a dimedone dimer. These results call into question the usefulness of dimedone in deteremining the oxidation state of Sec. Finally, we provide evidence that Sec-TrxR enzymes are able to catalyze single electron reductions. This is most likely due to the formation of a stable Sec radical intermediate. As a whole this project provides support for the theory that Sec was selected for due to its ability to convey chemical reversiablity to proteins.

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that senescence is not obligatorily an irreversible process. Our observations indicate that H460 non-small cell lung cancer cells induced into senescence by exposure to etoposide, and enriched based on β-galactosidase staining and size, were shown to recover reproductive capacity, which was accompanied by resolution of the DNA-damage-response (downregulation of p53 and p21Cip1 induction), attenuation of the Senescence-associated Secretory Phenotype (SASP). To overcome the reservation that the newly dividing cells may not have been derived from the senescent population and in an effort to establish that escape from TIS is feasible, tumor cells induced into senescence by chemotherapy were enriched for senescence by flow cytometry; the subsequent division of senescent cells was demonstrable utilizing both real-time, live microscopy and High Speed Live Cell Interferometry (HSLCI). Furthermore, sorted senescent cells were observed to form tumors when implanted in immune deficient mice and with a significant delay in immunecompetent mice. As chemotherapy induced senescent cells have been identified in patient tumors, it is reasonable to propose that tumor cells that escape from senescence could contribute to disease recurrence. In addition, therapy-induced senescence could prove to reflect one form of tumor dormancy. Recently, ABT263 has been used as a senolytic drug, effectively eliminating senescent cells from aging-related animal models. Here, we utilize ABT263 in a two-hit approach to eliminate senescent tumor cells that persistent after exposure to chemotherapy. ABT263 results in the killing of senescent tumor cells in a concentration-dependent manner and shifts the response towards apoptotic cell death. Furthermore, sequential administration of ABT263 interferes with the ability of senescent tumor cells to recover growth potential. These results indicate that senescent tumor cells can contribute to cancer relapse by acquiring proliferative properties and that senolytic therapy allows for the clearance of dormant senescent tumor cells and will potentially decrease cancer recurrence rates.

Ancestral knowledge exerts itself in the daily lives of the Nagas in Northeast India, whether through passed down clan genealogical knowledge, or through dreams and waketime omens. The Angamis, one of the Naga tribes, articulate a close relationship between the ancestral spirits they meet in their dreams, and ruopfü, one’s always-perceiving soul or life-being, complicating the boundary that would separate dreaming and waking states. In mediating these two states, the Angami ruopfü therefore has a powerful ability to inhabit these two spaces simultaneously, thus allowing for their reversibility. These processes of inhabiting the ‘real’ in waking and dreaming, occur in the midst of significant political turmoil, and this thesis examines the ways in which dreams index terrains of clan and state power in relation to a broader cosmic struggle. Moreover, as a guiding principle of personhood, dreaming, and reversibility elucidate the ways in which Angamis explore, understand, and generate alternative futures. I begin the discussion in the domain of the kitchen hearth. Within this gendered space characterised by a continuous rhythm of quotidian practices and attentiveness to dreams and omens, a significant political counter-narrative to the enduring pattern of clan patriarchy emerges. This tense symbiosis is characterised by a relationship of nurturance, but at the same time resistance to patriarchal meddling in domestic affairs. I then describe how this tension mirrors a power dynamic perceived by many in their dreams in which the clan collectively confronts morally ambivalent spiritual forces that inhabit spaces outside of delimited clan domains. This recalls earlier times when public life centred on the propitiation of powerful spirits in order to preserve harvests, and protect clan settlements in times of war. With the advent of Christianity, public discourse is transformed not solely via the iconoclastic demands of the American missionaries, but through a spatiotemporal reorientation of public life towards regularised church membership, and the development of missional institutions. Traditional public rituals, and ritual objects gradually faded, but informal inspirational practices such as divinational healing and dreaming, rooted as they were in the domestic sphere, remained integral to community life. In contemporary Nagaland, Christian charismatic groups have reconsidered the efficacy of traditional practices, and the inspirational potential of dreams, and opened spaces for supervised spirit mediation. These practices, however, have the potential to disrupt the church, and the community, and community elders are alert to their potential dangers, often seeking to defuse spirit mediated charisma as it emerges. The elder generation frequently cites the role of divination in spurring upheaval, and within living memory a young Naga prophetess, inspired by powerful dreams, succeeded in mounting a tribal uprising against British rule in the region. The power of visions and dreams to inspire political movements has not been lost on more recent Naga political groups, and in the final chapter I draw parallels between the nature of charisma to inspire political agency, and the function of the oneiric in normative patriliny, especially in public events, and ultimately in the construction of nationalist ideology. Finally, though the material and social circumstances separating public and domestic spheres in Angami life-worlds continually produce divergent political imaginaries, reversibility reveals how these formations emerge, how they coexist and continuously shape daily life, and how they produce the potentialities for unified political resistance.

BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) is still a syndrome generating more questions than answers. Today, research focuses mainly on two areas: understanding the pathophysiology – especially how the malfunctioning CSF system affects the brain parenchyma – and finding better methods to select patients benefiting from a shunt operation. This thesis targets the aspect of finding better selection methods by investigating the measurability of intracranial pressure via lumbar space, and determining if intraparenchymal measurement of long-term ICP-oscillations (B-waves) could be replaced by short-term measurements of CSF pulse pressure waves via lumbar space. Furthermore, I look into the interaction between the CSF system and the parenchyma itself by investigating how the cortical activity of the brain changes after long-term CSF drainage, and if there is any regress in the suggested ischemia after this intervention. Finally, I examine if the neuronal integrity in the INPH brain is impaired, and if this feature is relevant for the likeliness of improvement after CSF diversion. METHODS: The comparison of intracranial and lumbar pressure was made over a vast pressure interval using our unique CSF infusion technique, and it included ten INPH patients. Pressure was measured via lumbar space and in brain tissue, and the pressures were compared using a general linear model. Short-term lumbar pressure waves were quantified by determining the slope between CSF pulse pressure and mean pressure, defined as the relative pulse pressure coefficient (RPPC). The correlation between RPPC, B-waves and CSF outflow resistance was investigated. In a prospective study, functional MRI was used to assess brain activity before and after long-term CSF drainage of 400 ml of CSF in eleven INPH patients. The functionalities tested included finger movement, memory, and attention. The results were benchmarked against the activity in ten healthy controls to identify the brain areas improving after drainage. The ischemia (Lactate) and neuronal integrity (NAA and Choline) were measured in a similar manner in 16 patients using proton MR spectroscopy, and the improvement of the patients after CSF drainage was based on assessment of their gait. RESULTS: There was excellent agreement between ICP measured in brain tissue and via lumbar space (regression coefficient = 0.98, absolute difference < 1 mm Hg). Adjusting for the separation distance between the measuring devices slightly worsened the agreement, indicating other factors influencing the measured difference as well. RPPC measured via lumbar space significantly correlated to the presence of B-waves, but not to outflow resistance. In the prospective study, controls outperformed patients on clinical tests as well as tasks related to the experiments. Improved behaviour after CSF drainage was found for motor function only, and it was accompanied by increased activation in the supplementary motor area (SMA). No lactate was detected, either before or after CSF drainage. NAA was decreased in INPH patients compared to controls, and the NAA levels were higher in the patients improving after drainage. CONCLUSIONS: ICP can be accurately measured via lumbar space in patients with communicating CSF systems. The close relation between RPPC and B-waves indicates that B-waves are primarily related to intracranial compliance, and that measurement of RPPC via lumbar space could possibly substitute B-wave assessment as selection method for finding suitable patients for shunt surgery. Improvement in motor function after CSF drainage was associated to enhanced activity in SMA, supporting the involvement of the cortico-basal ganglia-thalamo-cortical loop in the pathophysiology of INPH. There was no evidence indicating a widespread low-graded ischemia in INPH; however, there was a neuronal dysfunction in frontal white matter as indicated by the reduced levels of NAA. In addition, the level of neuronal dysfunction was related to the likeliness of improvement after CSF removal, normal levels of NAA predisposing for recovery.

Le concept de réversibilité est ancien, mais il soulève de nos jours beaucoup d'intérêt. Il est en effet exploité dans de nombreux domaines tels que la conception de circuits, le débogage et le test de programmes, la simulation et l'informatique quantique. L'idée d'un modèle de programmation réversible peut se montrer particulièrement intéressante pour la construction de systèmes sûrs de fonctionnement, ne serait-ce que parce que plusieurs techniques connues pour la construction de tels systèmes exploitent une forme ou une autre de retour en arrière ou de reprise. Nous poursuivons dans cette thèse l'étude entreprise avec CCS réversible par Vincent Danos et Jean Krivine, en définissant un pi-calcul d'ordre supérieur réversible (rhopi). Nous prouvons que le modèle obtenu est causalement cohérent, et que l'on peut encoder fidèlement rhopi dans une variante du pi-calcul d'ordre supérieur. Nous définissons également une primitive de reprise à grain fin qui permet de contrôler le retour en arrière dans une exécution concurrente. Nous spécifions formellement la sémantique de cette primitive, et nous montrons qu'elle possède de bonnes propriétés, y compris en présence d'opérations de reprise concurrentes. Enfin nous définissons un algorithme concurrent implantant cette primitive de reprise et ous montrons que cet algorithme respecte la sémantique définie
Reversible computing has a long history. Nowadays, reversible computing is attracting increasing interest because of its potential applications in diverse fields, including hardware design, biological modelling, program debugging and testing and quantum computing. Of particular interest is the application of reversible computation notions to the study of programming abstractions for dependable systems, because several techniques used to build dependable systems rely on some forms of undo or rollback. We continue, in this thesis, the study undertaken on reversible CCS by Vincent Danos and Jean Krivine, by defining a reversible higher-order pi-calculus (rhopi). We prove that reversibility in our calculus is causally consistent and that one can encode faithfully rhopi into a variant of HOpi. Moreover we design a fine-grained rollback primitive able to control the rollback of a concurrent execution. We give a formal specification of this primitive and show that it enjoys good properties, even in presence of concurrent conflicting rollbacks. We then devise a concurrent algorithm implementing such primitive and show that the algorithm respects the defined semantics

The aim of the work is the examination of the usage of idiomatic eglish verbs. Phrasal verbs are the derivatives derived according to the following pattern: V (verb) + pv (postverb) = Vpv (verb postverb). They are regarded as one more type of word formation. English phrasal verbs are divided into non-reversible, metaphoric, and metonymic.
Darbo tikslas yra idiominių anglų veiksmažodžių vartojimo tyrimas. Fraziniai veiksmažodžiai yra išvestiniai žodžiai, sudaromi pagal tokią schemą: V (veiksmažodis) + pv (postverbas) = Vpv (frazinis veiksmažodis). Jie yra laikomi dar viena žodžių darybos rūšimi. Fraziniai veiksmažodžiai yra suskirstyti į nereversiškus, metaforinius ir metoniminius.

Under a Markov model of evolution, lumping the state space (S) into fewer groups has been historically used to focus on specific types of substitutions or to reduce compositional heterogeneity and saturation. However, working with reduced state spaces (S’) may yield misleading results unless the Markovian property is kept. A Markov process X(t) is lumpable if the reduced process X’(t) of S’ is Markovian. The aim of this Thesis is to develop a test able to detect if a given X(t) is lumpable with respect to a given S’. This test should allow flexibility to any possible non-trivial S’ and should not depend on evolutionary assumptions such as stationarity, homogeneity or reversibility (SHR conditions) over a phylogenetic tree. We developed three tests for lumpability for SHR Markovian processes on two taxa and compared them: one using an ad hoc statistic based on an index that is evaluated using a bootstrap approximation of its distribution; one based on a test proposed specifically for Markov chains; and one using a likelihood-ratio (LR) test. We show that the LR test is more powerful than the other two tests, and that it can be applied in all pairs of taxa for binary trees with more than two taxa under SHR conditions. Then, we generalized the LR test for cases where the SHR conditions may not hold. We show that the distribution of this test statistic approximates a chi square with a number of degrees of freedom equal to the number of different rate matrices in the tree by two. In all cases, we show that if X(t) is lumpable, the obtained estimates for X’(t) agree with the obtained estimates for X(t), whereas, if X(t) is not lumpable, these estimates can differ substantially. We conclude that lumping S may result in biased phylogenetic estimates if the original X(t) is not lumpable. Accordingly, testing for lumpability should be done prior to any phylogenetic analysis of recoded data.