Dynamic nature of proteins - interpretation of residual dipolar couplings

Protein conformations and dynamics can be studied by nuclear magnetic resonance spectroscopy using dilute liquid crystalline samples. This work clarifies the interpretation of residual dipolar coupling data yielded by the experiments. It was discovered that unfolded proteins without any additional structure beyond that of a mere polypeptide chain exhibit residual dipolar couplings. Also, it was found that molecular dynamics induce fluctuations in the molecular alignment and doing so affect residual dipolar couplings. The finding clarified the origins of low order parameter values observed earlier. The work required the development of new analytical and computational methods for the prediction of intrinsic residual dipolar coupling profiles for unfolded proteins. The presented characteristic chain model is able to reproduce the general trend of experimental residual dipolar couplings for denatured proteins. The details of experimental residual dipolar coupling profiles are beyond the analytical model, but improvements are proposed to achieve greater accuracy. A computational method for rapid prediction of unfolded protein residual dipolar couplings was also developed. Protein dynamics were shown to modulate the effective molecular alignment in a dilute liquid crystalline medium. The effects were investigated from experimental and molecular dynamics generated conformational ensembles of folded proteins. It was noted that dynamics induced alignment is significant especially for the interpretation of molecular dynamics in small, globular proteins. A method of correction was presented. Residual dipolar couplings offer an attractive possibility for the direct observation of protein conformational preferences and dynamics. The presented models and methods of analysis provide significant advances in the interpretation of residual dipolar coupling data from proteins.

Knowledge through Discussion : An Interpretation of Epistemology in Plato's Meno

According to Meno s paradox we cannot inquire into what we do not know because we do not know what we are inquiring into. There are many ways to interpret the paradox but the central issue about our ability to reach truth is a profound one. In the dialogue Meno, Plato presents the paradox and an outline of a solution which enables us to reach knowledge (epistēmē) through philosophical discussion. During the last century Meno has often been considered transitional between Socratic thinking and Plato s own philosophy, and thus the dialogue has not been adequately interpreted as an integrated whole. Therefore the distinctive epistemology of the dialogue has not gained due notice. In this thesis the dialogue is analysed as an integrated whole and the philosophical interpretation also takes into account its dramatic features. The thesis emphasises the role of language and definitions in acquiring knowledge. Among the results concerning these subjects is a new interpretation of Socrates s defintion of shape (schēma). The theory of anamnēsis all learning is recollection in the Meno is argued to answer the paradox philosophically although Plato s presentation also contains playful and ironic elements. The background of the way Plato presents his case is that he appreciated the fact that no argument can plausibly demonstrate that argumentation is able to reach truth. In the Meno, Plato makes the earliest explicit distinction between knowledge and true belief in the history of Western philosophy. He also gives a definition of knowledge which is the basis of the so called classical definition of knowledge as justified true belief. In the Meno, true beliefs become knowledge when someone ties them down by reasoning about the explanation. The analysis of the epistemology of the dialogue from this perspective gives an interpretation which integrates the central concepts of the epistemology in the dialogue elenchos, anamnēsis and hypothetical inquiry into a unified whole which contains a plausible argument according to which the ignorant can reach knowledge through discussion. The conception that emerges by such an analysis is interesting both from the point of view of current interests and that of the history of philosophy. The method of knowledge acquisition in the Meno can, for example, be seen as a predecessor of modern scientific methods. The Meno is the earliest Greek mathematical text that has survived in its original form. The analysis presented in the thesis of the geometric passages in the dialogue provides new results both concerning Socrates s geometry lesson with the slave and the example presenting the hypothetical method. Concerning the latter, a new interpretation is presented. Keywords: anamnēsis, epistēmē, knowledge, Meno s paradox, Plato

Interpretation of Services Marketing Concepts

Scholarly research has produced conceptual knowledge that is based on real-life marketing phenomena. An initial aim of past research has been to produce marketing knowledge as a base for efficient business operation and for the improvement of productivity. Thus, an assumption has been that the knowledge would be applied by organisations. This study focuses on understanding the use of marketing knowledge within the field of service marketing. Hence, even if marketing knowledge about service-oriented principles and marketing of services is based on empirical research, there is a lack of knowledge on how this marketing knowledge is in fact applied by businesses. The study focuses on four essential concepts of services marketing knowledge, namely service quality, servicescape, internal marketing, and augmented service offering. The research involves four case companies. Data is based on in depth interviews and questionnaire-based surveys conducted with managers, employees, and customers of these companies. All organisations were currently developing in a service-oriented and customer-oriented direction. However, we found limitations, gaps, and barriers for the implementation of service-oriented and customer-oriented principles. Hence, we argue that the organisations involved in the study exploited conceptual knowledge symbolically and conceptually, but the instrumental use of knowledge was limited. Due to the shortcomings found, we also argue that the implementation of the various practices and processes that are related to becoming service-oriented and customer-oriented has not been fully successful. Further, we have come to the conclusion that the shortcomings detected were at least in some respect related to the fact that the understanding and utilisation of conceptual knowledge of service-oriented principles and marketing of services were somewhat limited.

Analysis of short interproton distances in proline peptides as a guide in the interpretation of nuclear overhauser effects

The conformational dependence of interproton distances in model proline peptides has been investigated in order to facilitate interpretation of the results of Nuclear Overhauser Effect (NOE) studies on such peptides. For this purpose two model systems, namely, Ac-Pro-NHMe and Ac-Pro-X-NHMe have been chosen and used. In the former, short interproton distances detectable in NOE experiments permit a clear distinction between conformations with Pro ψ = -300 (helical region) and those in which ψ is around 1200 (polyproline region). For the latter, the variation of distances between the protons of methyl amide and the Pro ring have been studied by superimposing on the Ramachandran map in the (φ3, ψ3) plane. The results show that β-turns and non-β-turn conformations can be readily distinguished from NOE data and such long range NOEs should be detectable for specific non-β-turn conformations. NOEs involving Cβ and Cγ protons are particularly sensitive to the state of pyrrolidine ring puckering.

Biphenyl ethers conjugated CdSe/ZnS core/shell quantum dots and interpretation of the mechanism of amyloid fibril disruption

The biphenyl ethers (BPEs) are the potent inhibitors of TTR fibril formation and are efficient fibril disrupter. However, the mechanism by which the fibril disruption occurs is yet to be fully elucidated. To gain insight into the mechanism, we synthesized and used a new QD labeled BPE to track the process of fibril disruption. Our studies showed that the new BPE-QDs bind to the fiber uniformly and has affinity and specificity for TTR fiber and disrupted the pre-formed fiber at a relatively slow rate. Based on these studies we put forth the probable mechanism of fiber disruption by BPEs. Also, we show here that the BPE-QDs interact with high affinity to the amyloids of A beta(42), lysozyme and insulin. The potential of BPE-QDs in the detection of senile plaque in the brain of transgenic Alzheimer's mice has also been explored. (C) 2010 Elsevier Ltd. All rights reserved.

Despairing Justice and the Ethics of Legal Interpretation

This study discusses legal interpretation. The question is how legal texts, for instance laws, statutes and regulations, can and do have meaning. Language makes interpretation difficult as it holds no definite meanings. When the theoretical connection between semantics and legal meaning is loosened and we realise that language cannot be a means of justifying legal decisions, the responsibility inherent in legal interpretation can be seen in full. We are thus compelled to search for ways to analyse this responsibility. The main argument of the book is that the responsibility of legal interpretation contains a responsibility towards the text that is interpreted (and through the mediation of the text also towards the legal system), but not only this. It is not simply a responsibility to read and read well, but it transcends on a broader scale. It includes responsibility for the effects of the interpretation in a particular situation and with regard to the people whose case is decided. Ultimately, it is a responsibility to do justice. These two aspects of responsibility are conceptualised here as the two dimensions of the ethics of legal interpretation: the textual and the situational. The basic conception of language presented here is provided by Ludwig Wittgenstein s later philosophy, but the argument is not committed to only one philosophical tradition. Wittgenstein can be counterpointed in interesting ways by Jacques Derrida s ideas on language and meaning. Derrida s work also functions as a contrast to hermeneutic theories. It is argued that the seed to an answer to the question of meaning lies in the inter-personal and situated activity of interpretation and communication, an idea that can be discerned in different ways in the works of Wittgenstein, Derrida and Hans-Georg Gadamer. This way the question of meaning naturally leads us to think about ethics, which is approached here through the philosophy of Emmanuel Levinas. His thinking, focusing on topics such as otherness, friendship and hospitality, provides possibilities for answering some of the questions posed in this book. However, at the same time we move inside a normativity where ethics and politics come together in many ways. The responsibility of legal interpretation is connected to the political and this has to be acknowledged lest we forget that law always implies force. But it is argued here that the political can be explored in positive terms as it does not have to mean only power or violence.

After interpretation.

Using 58 audio recorded sessions of psychoanalysis (coming from two analysts and three patients) as data and conversation analysis as method, this paper shows how psychoanalysts deal with patients’ responses to interpretations. After the analyst offers an interpretation, the patient responds: at that point (in the “third position”), the analysts recurrently modify the tenor of the description from what it was in the patients’ responses. They intensify the emotional valence of the description, or they reveal layers of the patients’ experience other than those that the patient reported. Both are usually accomplished in an implicit, non-marked way, and they discreetly index possible opportunities for the patients to modify their understandings of the initial interpretation. Although the patients usually do not fully endorse these modifications, the data available suggests that during the sessions that follow, the participants do work with the aspects of patients’ experience that the analyst highlighted. In discussion, it is suggested that actions that the psychoanalysts produce in therapy, such as choices of turn design in third position, may be informed by working understanding of the minds and mental conflicts of individual patients, alongside the more general therapeutic model of mind they hold to.

Demixing of severely overlapped H-1 NMR resonances and interpretation of anomalous intensity pattern of dipolar coupled A(3) spins in a weakly aligning medium

We report a single C-13 spin edited selective proton-proton correlation experiment to decipher overcrowded 13C coupled proton NMR spectra of weakly dipolar coupled spin systems. The experiment unravels the masked C-13 satellites in proton spectrum and permits the measurement of one bond carbon-proton residual dipolar couplings in I3S and for each diastereotopic proton in I2S groups. It also provides all the possible homonuclear proton-proton residual couplings which are otherwise difficult to extract from the broad and featureless one dimensional H-1 spectrum, in addition to enantiodifferentiation in a chiral molecule. Employment of heteronuclear (C-13) decoupling in the evolution period results in complete demixing of overlapped signals from enantiomers. The observed anomalous intensity pattern in strongly dipolar coupled methyl protons in methyl selective correlation experiment has been interpreted using polarization operator formalism. (C) 2010 Elsevier Inc. All rights reserved.

Shifting the perspective after the patient's response to an interpretation

Psychoanalytic interpretation is normally understood as a sequence of two utterances: the analyst gives an interpretation and the patient responds to it. This paper suggests that, in the interpretative sequence, there is also a third utterance where psychoanalytic work takes place. This third interpretative turn involves the analyst’s action after the patient’s response to the interpretation. Using conversation analysis as method in the examination of audio-recorded psychoanalytic sessions, the paper will explicate the psychoanalytic work that gets done in third interpretative turns. Through it, the analyst takes a stance towards the patient’s understandings of the interpretation, which are shown in the patient’s response to the interpretation. The third interpretative turns on one hand ratify and accept the patient’s understandings, but, in addition to that, they also introduce a shift of perspective relative to them. In most cases, the shift of perspective is implicit but sometimes it is made explicit. The shifts of perspective bring to the foreground aspects or implications of the interpretation that were not incorporated in the patient’s response. They recast the description of the patient’s experience by showing new layers or more emotional intensity in it. The results are discussed in the light of Faimberg’s concept of listening to listening and Schlesinger’s concept of follow-up interpretation.

Molecular interpretation of the linear relationship between the entropy and the enthalpy of activation of charge transfer reactions in polar liquids

The well-known linear relationship (T?S# =??H# +?, where 1 >? > 0,? > 0) between the entropy (?S#) and the enthalpy (?H#) of activation for reactions in polar liquids is investigated by using a molecular theory. An explicit derivation of this linear relation from first principles is presented for an outersphere charge transfer reaction. The derivation offers microscopic interpretation for the quantities? and?. It has also been possible to make connection with and justify the arguments of Bell put forward many years ago.

Physical interpretation of the Poynting-Robertson effect

Although the prevalent mathematical description of the Poynting-Robertson effect is correct, its physical interpretation is sometimes problematic. By means of a two-parameter model, we revisit the effect in order to get a better physical understanding of it. The principal conclusion is that the motion of a dust in circumsolar orbit is governed only by solar radiation absorption and not by the asymmetry of reemission, even when viewed in the rest-frame of the Sun. (C) 1999 Academic Press.

Executable Analysis using Abstract Interpretation with Circular Linear Progressions

We propose a new abstract domain for static analysis of executable code. Concrete states are abstracted using circular linear progressions (CLPs). CLPs model computations using a finite word length as is seen in any real life processor. The finite abstraction allows handling overflow scenarios in a natural and straight-forward manner. Abstract transfer functions have been defined for a wide range of operations which makes this domain easily applicable for analyzing code for a wide range of ISAs. CLPs combine the scalability of interval domains with the discreteness of linear congruence domains. We also present a novel, lightweight method to track linear equality relations between static objects that is used by the analysis to improve precision. The analysis is efficient, the total space and time overhead being quadratic in the number of static objects being tracked.

A thermodynamic interpretation of the zonal arrangement of minerals in the bedded manganese deposits of the Noda tamagawa mine, Japan

Calculated phase relations in the system MnOSi02-C02-02 were used to propose a thermodynamic explanation for the thermal metamorphism of rhodochrosite beds lying between chert strata. The metamorphic MnOS i 0 2 minerals are arranged in order quartz(chert), rhodonite. tephroite and manganosite-hausmannite-pyrochroite rhodonite across the ore bed. The calculation covered temperatures up to 1000 K and pressures up to 5 kb. The zoning was interpreted as the result of a continuous rise in metamorphic temperature. The equilibrium partner of rhodochrosite changed from rhodonite through manganosite. Across the ore bed there are gradients in the chemical potential of MnO and SiO2 but fugacities of volatlle components such as C02. 02 and H20 were probably uniform at any given time and location during formation of the zones. Assuming that the total pressure and the fugacity of C02 were at 1.4 kb and 1.0 1 b. respectively. rhodonite. tephroite and manganosite would have formed at 472. 478 and 629 K.