Peptide bond formation and translational termination on the ribosome have been simulated by molecular mechanics, free energy perturbation, empirical valence bond (MD/FEP/EVB) and automated docking methods. Recent X-ray crystallographic data is used here to calculate the entire free energy surface for the system complete with substrates, ribosomal groups, solvent molecules and ions. A reaction mechanism for peptide bond formation emerges that is found to be catalyzed by the ribosome, in agreement with kinetic data and activation entropy measurements. The results show a water mediated network of hydrogen bonds, capable of reducing the reorganization energy during peptidyl transfer. The predicted hydrogen bonds and the structure of the active site were later confirmed by new X-ray structures with proper transition states analogs. Elongation termination on the ribosome is triggered by binding of a release factor (RF) protein followed by rapid release of the nascent peptide. The structure of the RF, bound to the ribosomal peptidyl transfer center (PTC), has not been resolved in atomic detail. Nor is the mechanism known, by which the hydrolysis proceeds. Using automated docking of a hepta-peptide RF fragment, containing the highly conserved GGQ motif, we identified a conformation capable of catalyzing peptide hydrolysis. The MD/FEP/EVB calculations also reproduce the slow spontaneous release when RF is absent, and rationalize available mutational data. The network of hydrogen bonds, the active site structure, and the reaction mechanism are found to be very similar for both peptidyl transfer and termination. New structural data, placing a ribosomal protein (L27) in the PTC, motivated additional MD/FEP/EVB simulations to determine the effect of this protein on peptidyl transfer. The simulations predict that the protein N terminus interacts with the A-site substrate in a way that promotes binding. The catalytic effect of L27 in the ribosome, however, is shown to be marginal and it therefore seems valid to view the PTC as a ribozyme. Simulations with the model substrate puromycin (Pmn) predicts that protonation of the N terminus can reduce the rate of peptidyl transfer. This could explain the different pH-rate profiles measured for Pmn, compared to other substrates.

No description available.

The purpose of this thesis is to investigate the reaction to a purely unexpected slip during gait termination and subsequent experiences stopping on the slippery surface in participants who are young and healthy, older and healthy and who have Parkinson’s disease while on traditional dopamine-replacement medication. Gait termination requires control of the forward momentum of the body’s centre of mass (COM). This forward momentum must be dissipated and the COM held within a newly formed base of support. The challenge of stopping on a slippery surface involves maintaining stability while transitioning from steady-state locomotion to steady-state stance. Experience with a slippery surface changes postural and gait characteristics to diminish the perturbing effect of the slip. The magnitude of the slip response diminishes quickly as the movement becomes more efficient. Our investigations revealed a typical slip response to a purely unexpected slip during gait termination including a lowering of the COM, an increased muscular response to support the body, a shortened step and an arm raise. Knowledge of and experience with the slippery surface quickly changed the slip response to reduce the perturbing effect of the slip and also to increase the efficiency of the response while smoothly transitioning from steady-state locomotion to gait termination. Parkinson’s disease impairs balance control, the ability to switch between motor tasks and also to stop within two steps. The need for a voluntary change in motor programs along with difficulty stopping and increased instability makes gait termination a potentially difficult task for someone with Parkinson’s disease (PD). The participants with PD used a slower, safer strategy to stop on non-slippery surfaces to compensate for their instability compared to age-matched controls. When a slip was first introduced during gait termination, the participants with PD continued to be less stable in the plane of progression than the control group. Despite the instability, the PD group was still able to integrate a balance-correcting response into a voluntary gait termination program. The ability to generate adaptive strategies to integrate the balance-correcting response into a voluntary gait termination program over multiple trials does not appear to be affected by PD; both the control group and PD group showed behavioural modifications according to repeated exposures to the slippery surface. Although participants with PD seemed slightly less stable and walked slower, their behavioural adaptations were similar to the control group.

The purpose of this thesis is to investigate the reaction to a purely unexpected slip during gait termination and subsequent experiences stopping on the slippery surface in participants who are young and healthy, older and healthy and who have Parkinson’s disease while on traditional dopamine-replacement medication. Gait termination requires control of the forward momentum of the body’s centre of mass (COM). This forward momentum must be dissipated and the COM held within a newly formed base of support. The challenge of stopping on a slippery surface involves maintaining stability while transitioning from steady-state locomotion to steady-state stance. Experience with a slippery surface changes postural and gait characteristics to diminish the perturbing effect of the slip. The magnitude of the slip response diminishes quickly as the movement becomes more efficient. Our investigations revealed a typical slip response to a purely unexpected slip during gait termination including a lowering of the COM, an increased muscular response to support the body, a shortened step and an arm raise. Knowledge of and experience with the slippery surface quickly changed the slip response to reduce the perturbing effect of the slip and also to increase the efficiency of the response while smoothly transitioning from steady-state locomotion to gait termination. Parkinson’s disease impairs balance control, the ability to switch between motor tasks and also to stop within two steps. The need for a voluntary change in motor programs along with difficulty stopping and increased instability makes gait termination a potentially difficult task for someone with Parkinson’s disease (PD). The participants with PD used a slower, safer strategy to stop on non-slippery surfaces to compensate for their instability compared to age-matched controls. When a slip was first introduced during gait termination, the participants with PD continued to be less stable in the plane of progression than the control group. Despite the instability, the PD group was still able to integrate a balance-correcting response into a voluntary gait termination program. The ability to generate adaptive strategies to integrate the balance-correcting response into a voluntary gait termination program over multiple trials does not appear to be affected by PD; both the control group and PD group showed behavioural modifications according to repeated exposures to the slippery surface. Although participants with PD seemed slightly less stable and walked slower, their behavioural adaptations were similar to the control group.

Treatment dropout is a pervasive phenomenon that can preclude clients from benefiting fully from psychotherapy. Research efforts to understand the phenomenon in the preceding decades yielded few consistent results. The investigation of intrinsic client and therapist factors gave way to the more recent exploration of dynamic therapeutic process factors potentially influencing the dropout process. The availability of periodic treatment outcome measurement instruments has helped client-focused research explore the effects of treatment response as a process factor on aspects of psychotherapy. As an added benefit, real-time treatment response measures, such as the Outcome Questionnaire, offer the possibility of timely adjustment in clinical intervention to meet evolving client needs and enhance therapeutic treatment. This present study primarily sought to explore the relationship between psychotherapy dropout and treatment response patterns in terms of clients' psychosocial well-being as measured by the Outcome Questionnaire. The results suggest that treatment response patterns alone may not effectively predict dropout probabilities. Even so, the measure's sub-component assessing the client's subjective experience of symptom distress is shown to be more accurate in predicting dropout than the composite Outcome Questionnaire measure or any other component scale. This finding conceivably highlights the relative importance of symptom distress in the dropout process for the sampled clients. Those clients reporting higher levels of symptom distress appeared to be associated with greater probabilities of dropout termination. Additionally, prior research has recognized a likely mediated relationship between higher client educational attainment and lower dropout probabilities - a trend also observed in this study's sampled population. As one of its expressed intents, this study examined educational attainment's moderating effect on the relationship between aspects of client treatment response and dropout probabilities. While showing educational attainment to be a relevant factor in assessing dropout risks, the analysis results indicate that this client characteristic variable's interactional effect on the evaluated treatment response pattern feature is weak and statistically nonsignificant. The present study contributes to the research literature through providing some clarification to the importance of treatment response in the prediction of psychotherapy client dropout.

<p>There is a great variety of research about civil war and peacemaking. This thesis also deals with those topics, however, it focuses on one specific area about how different third-party interveners affect the duration of civil war.</p><p>Since the main goal of an intervention is to terminate the civil war as fast as possible, it is of great importance to be able to know which type of intervener can terminate it fastest. Throughout the modern history third-party interveners have been a mix of international organizations and major- and minor powers. These different types of interveners and what characterize them will here be discussed, compared and analyzed.</p><p>From a data set containing information about all civil wars between 1945 and 1999 six conflicts have been chosen for further examination. Two of the civil wars are wars where an international organisation was the intervener, two conflicts where major powers where the interveners and two where minor powers where the intervener. These six civil wars are viewed upon with characteristics of the conflict and intervener as basis.</p><p>Important to take into account is the aspect when international organizations in general tend to intervene. A scholar, Regan, pointed out that international organizations tend to intervene in already long lasting civil wars where states have chosen not to intervene or have failed. The result in this thesis shows that depending upon how forceful the intervention is, the shorter the duration of the civil war will be. What shows how forcefull an intervention can be is how strong the intervener is, on which side the intervention takes place and which strategy it choses.</p> / <p>Det finns en uppsjö av akademisk forskning om inbördeskrig och fredskapande. Denna uppsats avhandlar också dessa ämnen men fokus ligger istället på ett speciellt område; hur olika typer av interventionsparter påverkar längden av inbördeskrig.</p><p>Målet med en intervention är att få slut på inbördeskriget så fort som möjligt. För att kunna nå det målet så är det av yttersta vikt att ha kunskap om vilken typ av interventionsparter som gör det snabbast. Interventionsparterna har sedan den moderna tiden varit internationella organisationer, stormakter och småstater. I denna uppsats kommer de olika typerna att diskuteras, jämföras och analyseras. Allt för att sedan kunna dra slutsatser om vad som karaktäriserar dem och vad de har för inflytande på längden av inbördeskrig.</p><p>I uppsatsen kommer sex olika inbördeskrig att analyseras. Dessa fall är hämtade från ett data set som innehåller information om alla inbördeskrig mellan åren 1945 och 1999. Två utav inbördeskrigen är krig där en internationel organisation var interventionspart.</p><p>I två andra inbördeskrig är interventionsparten en stormakt och i de resterande två inbördeskrigen är interventionsparten en småstat. Dessa sex inbördeskrig är sedan analyserade med hjälp av karaktären utav kriget och typen av interventionspart.</p><p>En viktig aspekt för analysen rör internationella organisationer och när de gör interventioner. En forskare, Regan, påpekar att internationella organisationer tenderar att intervenera i inbördeskrig som redan har pågått under en längre tid och där enskilda stater har valt att inte ingripa eller har misslyckats. Analysen i denna uppsats visar att beroende på hur kraftfull interventionen är desto kortare blir längden utav inbördeskriget. Vad som avgör vad som är kraftfullt är hur stark interventionsparten är, vilken sida interventionen sker på och vilken strategi som används.</p>

Several mechanisms have been proposed for the pol I transcript termination in Schizosaccharomyces pombe. Two well known models are “Pause and Release” and “Torpedo”. Each mechanism explains the role of some of the cis- and trans-factors in transcript termination and the eventual maturation of the ribosomal RNA, but neither mechanism can explain all the experimental observations. A recent study has suggested that each of the two mechanisms can terminate the pol I transcription independently but with significantly less efficiency than the presence of both mechanisms. To help clarify the reasons for the discrepancies in these data, in this study the suggested mechanisms were examined further in three areas by using alternative techniques. First, the effect of uracil concentration or selection times on the transformation frequency of alternative 3’external transcribed spacer (3’ETS) constructs were assessed. Consistent with the previous results a construct containing the full 3’ETS showed the higher transformation frequencies compared with a construct containing only the hairpin or only the termination sites. However, results showed neither the uracil concentration nor selection times have a significant effect on the transformation frequency. Second, to further confirm the “pause and release” mechanism, the termination sites identified by S1 nuclease studies were analyzed using ligation-mediated RT-PCR. The 3’ terminus of the mature 25S rRNA was demonstrated readily but, unexpectedly, the 3’termini of the 3’ETS precursor molecules were not detected, possibly because of their specific structure. Finally, the 3’ extended rRNA precursors were studied by semi-quantitative RT-PCR. These appeared not to correspond with past nuclease protection analyses nor did they demonstrate downstream exonuclease function, observations which question our current understanding of Pol I transcript termination.

The main objective of this study was to investigate whether parental perceptions of the emotional, behavioral and social skills functioning of children with conduct problems, differed for parents who completed the behavioral consultation process (N = 40) compared to those who prematurely withdrew ( N = 11). A series of between group analyses were conducted to examine whether parental perceptions existed. Parents who prematurely withdrew from the behavioral consultation process reported significantly greater incidences of anxious and depressed behavior in children, than parents who remained in consultation F(1,49) = 4.24, p = .0448. Similarly, using the Wilks' criterion, overall estimates of emotional and behavioral functioning, combined with social skills functioning were also significantly affected by group membership, F(3,47) = 3.22, p = .0310. Using the same variables in a logistic regression analysis, a test of the full model with all three predictors compared to the constant only model was statistically reliable phi2 (3, N = 51) = 10.26, p = .0336, indicating that the predictors, as a set, reliably distinguished the perceptions of those who completed the consultation process, compared to those who prematurely withdrew. This model accurately predicted 77.7% of parents' group membership. The results of the study will be discussed in terms of their usefulness for future consultants to identify families at risk for prematurely withdrawing from the consultation process, so that additional resources can be offered to encourage their continued participation in the consultation process.

Darbe analizuojamos Lietuvos Respublikos Civilinio kodekso (toliau - LR CK) nuostatos, įtvirtinančios galimybę sutarties šalims nutraukti sutartį esant neesminiam sutarties pažeidimui, kartu pateikiant Lietuvos Aukščiausiojo Teismo suformuluotas nuostatas ir šių nuostatų taikymo principus. Atsižvelgus į tai, kad sutarties nutraukimą reglamentuojančios LR CK normos yra UNIDROIT Principų recepcija, nemažas dėmesys skiriamas šių Principų analizei. Palyginimui analizuojami ir kiti svarbūs teisiniai dokumentai, tai: 1980 m. Jungtinių Tautų konvencija dėl tarptautinių prekių pirkimo-pardavimo sutarčių, Europos sutarčių teisės principai (PECL), Bendros principų sistemos metmenys (DCFR) ir kt. Pirmojoje darbo dalyje analizuojami istoriniai aspektai, atskleidžiantys sutarties nutraukimo esant neesminiam pažeidimui kilmę. Konstatuojamas UNIDROIT Principų ir sutarties laisvės principo teisinis pamatinis pagrindas sutarties nutraukimo instituto dalies atsiradimui. Antroji darbo dalis skirta apibendrinti sutarties nutraukimo esant neesminiam pažeidimui pagrindus, tai - įstatyminis LR CK 6.209 str. ir sutartinis LR CK 6.217 str. 5 d. pagrindai. Trečiojoje darbo dalyje apibrėžiama sutarties pažeidimo samprata. Pateikiami teisiniai vertinimai, kurie padėtų atskirti esminį sutarties pažeidimą nuo neesminio. Prieinama prie išvados, kad neesminį sutarties pažeidimą galima apibrėžti tik plačiąja prasme, atsižvelgiant individualiai į kiekvieną situaciją. Šis apibrėžimas skamba taip: neesminis... [toliau žr. visą tekstą] / The thesis analyzes provisions of the Civil Code of the Republic of Lithuania (hereinafter referred to as the CC) that establish the possibility for the parties to terminate the contract in case of immaterial breach, and provides provisions formulated by the Lithuanian Supreme Court as well as principles of application of these provisions. Given the fact that provisions of the CC go-verning termination of contract are adaptation of the UNIDROIT Principles, much attention is paid to the analysis of these Principles. For the purposes of comparison, other important legal documents, i.e. United Nations Convention on Contracts for the International Sale of Goods of 1980, Principles of European Contract Law (PECL), Draft Common Frame of Reference (DCFR), etc. are analyzed as well. The first part of the thesis analyzes the historical aspects, revealing the origin of an insti-tute of termination of contract in case of immaterial breaches. It also finds legal basis for the emergence of the institute of termination of contract inherent in the UNIDROIT Principles and the principle of freedom of contract. The second part of the thesis summarizes grounds for the termination of contract in case of immaterial breaches, i.e. statutory (Article 6.209 of the CC) and contractual (paragraph 5 of Article 6.217 of the CC). The third part of the thesis defines the concept of breach of contract. Moreover, it pro-vides legal evaluations that would help to differentiate between material and... [to full text]

Thesis (Ph. D.)--Arizona State University, 1995. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [299]-307).