[Ambivalence, old age and agency: Meaning of age-specific ambivalence for the construction of narrative identity].

PubMed

Richter, Anna Sarah

2016-01-01

Different models of the formation of age identity explain the empirically determined difference between the chronological age and the age which is subjectively perceived by elderly people themselves. From a biographical point of view and on the basis of two maximally contrasting empirical cases, this article investigates the ways ambivalence appears in the narrations of elderly people about personal aging and the narrative strategies of coping with this experience of ambivalence. The results of the analysis indicate that the conceptualization of age identity in the different models should be seen more as descriptions of potential but not necessary forms of coping with age-specific ambivalences.

Attitude Ambivalence, Friend Norms, and Adolescent Drug Use

PubMed Central

Hohman, Zachary P.; Crano, William D.; Siegel, Jason T.; Alvaro, Eusebio M.

2013-01-01

This study assessed the moderating effects of attitudinal ambivalence on adolescent marijuana use in the context of the theory of planned behavior (TPB). With data from the National Survey of Parents and Youth (N=1,604), two hierarchical multiple regression models were developed to examine the association of ambivalent attitudes, intentions, and later marijuana use. The first model explored the moderating effect of ambivalence on intentions to use marijuana; the second tested the moderation of ambivalence on actual marijuana use 1 year later. Results across both analyses suggest that ambivalence moderated the association of friend norms and subsequent adolescent marijuana use: friend norms were better predictors of marijuana intentions (β=0.151, t=2.29, p=0.02) and subsequent use when adolescents were attitudinally ambivalent about marijuana use (β=0.071, t=2.76, p= 0.006). These results suggest that preventive programs that affect the certainty with which adolescents holds pro- or antimarijuana attitudes may influence the likelihood of their resistance to, initiation, or continuance of marijuana use. PMID:23404670

Attitude ambivalence, friend norms, and adolescent drug use.

PubMed

Hohman, Zachary P; Crano, William D; Siegel, Jason T; Alvaro, Eusebio M

2014-02-01

This study assessed the moderating effects of attitudinal ambivalence on adolescent marijuana use in the context of the theory of planned behavior (TPB). With data from the National Survey of Parents and Youth (N = 1,604), two hierarchical multiple regression models were developed to examine the association of ambivalent attitudes, intentions, and later marijuana use. The first model explored the moderating effect of ambivalence on intentions to use marijuana; the second tested the moderation of ambivalence on actual marijuana use 1 year later. Results across both analyses suggest that ambivalence moderated the association of friend norms and subsequent adolescent marijuana use: friend norms were better predictors of marijuana intentions (β = 0.151, t = 2.29, p = 0.02) and subsequent use when adolescents were attitudinally ambivalent about marijuana use (β = 0.071, t = 2.76, p = 0.006). These results suggest that preventive programs that affect the certainty with which adolescents holds pro- or antimarijuana attitudes may influence the likelihood of their resistance to, initiation, or continuance of marijuana use.

[Ambivalence and diachrony].

PubMed

Zoila, A F

1977-04-01

The temporal analysis of ambivalence is based on an account given by two schizophrenic patients and the study of Samuel Becket's "The Nameless One". The narrative process corresponds to a creative expression in which discordance is part of the differences between verbalisation and sensitive phenomenous. Splitting of personality is linked with temporal ambivalence: the immediate past encroaches on the near future, giving an impression of synchronization in the simultaneous interplay of similarity and dissimilarity. The passing of time, disturbed in its accumulative cursus in the schizophrenic patient, results in a conflict between contradictory phenomenous in the same moment. This synchronization of dissimilar perceptions brings together disjunctive and conjunctive categories dominated by such coordinate conjunctions as "and... and", in the living diachronic discordance.

What is to be done with surplus embryos? Attitude formation with ambivalence in German fertility patients.

PubMed

Kufner, K; Tonne, M; Barth, J

2009-01-01

Improved pregnancy rates in IVF have led to increasing numbers of surplus embryos which can potentially be used for purposes like donation to another infertile couple or further research. Individuals report high levels of ambivalence concerning the donation of surplus embryos. This study examined which strategies infertile patients use to deal with this ambivalence when asked to evaluate potential dispositions of surplus embryos created during IVF. Guideline-based interviews with fertility patients were audio-recorded and transcribed verbatim. Following the principle of theoretical sampling, eight interviews were analysed by use of Grounded Theory. Analyses focused on processes of individual attitude formation. Strategies for handling ambivalence during attitude formation were identified: the six strategies comprise cognitive and communicative strategies, and were integrated into a model of attitude formation under ambivalence. As ambivalence is a relevant phenomenon in attitude formation within IVF treatment, assessment of ambivalence is strongly recommended in social science studies investigating ethical problems in patient care. In the context of informed consent, there is a need for individual counselling which draws attention to the conflicting values during attitude formation. Counsellors should be aware of the signs of and the strategies to deal with ambivalence.

Ambivalent stereotypes link to peace, conflict, and inequality across 38 nations

PubMed Central

Durante, Federica; Fiske, Susan T.; Gelfand, Michele J.; Crippa, Franca; Suttora, Chiara; Stillwell, Amelia; Asbrock, Frank; Aycan, Zeynep; Bye, Hege H.; Carlsson, Rickard; Björklund, Fredrik; Dagher, Munqith; Geller, Armando; Larsen, Christian Albrekt; Latif, Abdel-Hamid Abdel; Mähönen, Tuuli Anna; Jasinskaja-Lahti, Inga; Teymoori, Ali

2017-01-01

A cross-national study, 49 samples in 38 nations (n = 4,344), investigates whether national peace and conflict reflect ambivalent warmth and competence stereotypes: High-conflict societies (Pakistan) may need clearcut, unambivalent group images distinguishing friends from foes. Highly peaceful countries (Denmark) also may need less ambivalence because most groups occupy the shared national identity, with only a few outcasts. Finally, nations with intermediate conflict (United States) may need ambivalence to justify more complex intergroup-system stability. Using the Global Peace Index to measure conflict, a curvilinear (quadratic) relationship between ambivalence and conflict highlights how both extremely peaceful and extremely conflictual countries display lower stereotype ambivalence, whereas countries intermediate on peace-conflict present higher ambivalence. These data also replicated a linear inequality–ambivalence relationship. PMID:28069955

Ambivalent stereotypes link to peace, conflict, and inequality across 38 nations.

PubMed

Durante, Federica; Fiske, Susan T; Gelfand, Michele J; Crippa, Franca; Suttora, Chiara; Stillwell, Amelia; Asbrock, Frank; Aycan, Zeynep; Bye, Hege H; Carlsson, Rickard; Björklund, Fredrik; Dagher, Munqith; Geller, Armando; Larsen, Christian Albrekt; Latif, Abdel-Hamid Abdel; Mähönen, Tuuli Anna; Jasinskaja-Lahti, Inga; Teymoori, Ali

2017-01-24

A cross-national study, 49 samples in 38 nations (n = 4,344), investigates whether national peace and conflict reflect ambivalent warmth and competence stereotypes: High-conflict societies (Pakistan) may need clearcut, unambivalent group images distinguishing friends from foes. Highly peaceful countries (Denmark) also may need less ambivalence because most groups occupy the shared national identity, with only a few outcasts. Finally, nations with intermediate conflict (United States) may need ambivalence to justify more complex intergroup-system stability. Using the Global Peace Index to measure conflict, a curvilinear (quadratic) relationship between ambivalence and conflict highlights how both extremely peaceful and extremely conflictual countries display lower stereotype ambivalence, whereas countries intermediate on peace-conflict present higher ambivalence. These data also replicated a linear inequality-ambivalence relationship.

[Structuralistic and meta-psychological approaches to ambivalence in schizophrenia].

PubMed

Sumida, Kyoko; Tsuda, Hitoshi

2003-01-01

The word "ambivalence" generally signifies a psychic state in which a subject holds a contradictory or conflicted attitude towards an object. The literal meaning of the word is that two valences occur simultaneously, and this connotes the epistemological and ethical problem of where and how the valences arise. The concept of ambivalence implies that the relationship between the subject and the world is ambivalent, that the subject has free will in the alternative evaluation, and that the meanings of the two valences derive from the meta-level outside the world. These reflections lead us to the supposition that ambivalence is closely associated with the function of language. The ambivalent attitude of the subject divides the significance of the object; the appearance of the given ambivalent meanings is the moment of the subject's choice. This phenomenon of division, choice, and given meanings is more than analogous to F. de Saussure's conception of language in terms of sign, différenciation, and l'arbitraire de langue. A view of ambivalence as a fundamental phenomenon concerning subject, world, and language affords insight specifically into ambivalence in schizophrenia. For people with schizophrenia, ambivalent conflict often takes the form of a dichotomy between "good and bad". The more severe the ambivalent symptom, the more similar it seems to a philosophical question about the nature of existence in the world. When schizophrenic people raise philosophical questions directly such as "Is my existence good or bad?" or "To be or not to be?", they seek approval for their existence, assaying to live with "good" intentions. Unfortunately they come to be blamed for harbouring "bad" intentions. When they have an interrogative attitude even to everyday matters, they cannot resolve such questions as "Is the red cup good or bad?", or "Is the green cup good or bad?", and hence "Which cup should I use?". If the projection of the self into the world is essentially the choice

Attitude ambivalence, social norms, and behavioral intentions: Developing effective antitobacco persuasive communications.

PubMed

Hohman, Zachary P; Crano, William D; Niedbala, Elizabeth M

2016-03-01

This study assessed the moderating effects of attitude ambivalence on the relationship between social norms, attitudes, and behavioral intentions to use tobacco. It was predicted that people would use social norms to reduce attitude ambivalence, and that reduced ambivalence would lead to changes in attitudes and behavioral intentions. To test this hypothesis, participants (N = 152) were exposed to persuasive communications designed to influence attitude ambivalence and perceived social norms regarding tobacco use. Analysis indicated that providing a social norm antagonistic to tobacco use significantly reduced ambivalence among participants reading the ambivalence message (p < .001). Examining changes in tobacco attitudes from pre- to postpersuasive communications demonstrated a significant decrease in tobacco attitudes only for participants reading the ambivalence message who were provided with the antitobacco use norm (p < .001). Ambivalent message participants also expressed significantly lower intentions to use tobacco when provided with social norms indicating antitobacco sentiments (p < .02), and this significant decrease in intentions was associated with changes in attitudes toward tobacco. These results point to the important role of social norms in mediating the effects of attitude ambivalence on subsequent behavior in preventative programs targeting tobacco use. (c) 2016 APA, all rights reserved).

Attitude Ambivalence, Social Norms, and Behavioral Intentions: Developing Effective Antitobacco Persuasive Communications

PubMed Central

Hohman, Zachary P.; Crano, William D.; Niedbala, Elizabeth M.

2018-01-01

This study assessed the moderating effects of attitude ambivalence on the relationship between social norms, attitudes, and behavioral intentions to use tobacco. It was predicted that people would use social norms to reduce attitude ambivalence, and that reduced ambivalence would lead to changes in attitudes and behavioral intentions. To test this hypothesis, participants (N =152) were exposed to persuasive communications designed to influence attitude ambivalence and perceived social norms regarding tobacco use. Analysis indicated that providing a social norm antagonistic to tobacco use significantly reduced ambivalence among participants reading the ambivalence message (p <.001). Examining changes in tobacco attitudes from pre- to postpersuasive communications demonstrated a significant decrease in tobacco attitudes only for participants reading the ambivalence message who were provided with the antitobacco use norm (p <.001). Ambivalent message participants also expressed significantly lower intentions to use tobacco when provided with social norms indicating antitobacco sentiments (p <.02), and this significant decrease in intentions was associated with changes in attitudes toward tobacco. These results point to the important role of social norms in mediating the effects of attitude ambivalence on subsequent behavior in preventative programs targeting tobacco use. PMID:26460476

Sociological Ambivalence and Funeral Consumption

PubMed Central

Canning, Louise

2015-01-01

This article builds on Hillcoat-Nallétamby and Phillips’ (2011) conceptualization of sociological ambivalence within the relational framework to examine a particular consumption practice, the funeral. We develop understanding of social, cultural and relational issues that arise from the experience associated with funeral-arranging. This is not a voluntary behaviour but one engaged with through force of circumstance and which involves commercial and relational decisions. Drawing on data from 10 interviews from a larger UK study, we focus on ambivalence surrounding choice and its impact on relations, showing how sentiments including love, obligation, regret and revenge evolve and transform past and future relationships. PMID:26236046

In support of Bleuler: objective evidence for increased affective ambivalence in schizophrenia based upon evocative testing.

PubMed

Trémeau, Fabien; Antonius, Daniel; Cacioppo, John T; Ziwich, Rachel; Jalbrzikowski, Maria; Saccente, Erica; Silipo, Gail; Butler, Pamela; Javitt, Daniel

2009-02-01

Ambivalence and anhedonia have long been identified as schizophrenic symptoms. However, ambivalence has rarely been studied, and in most evocative studies, schizophrenia participants are not anhedonic. Affective neurosciences posit two evaluative systems (one for Positivity and one for Negativity), the coactivation of which produces ambivalence, and point to two asymmetries in affective processing: Positivity Offset (which measures our capacity to explore the environment) and Negativity Bias (a measure of reactivity to intense threat). These characteristics have not received much attention in schizophrenia research. Sixty-four individuals with schizophrenia and 32 non-patient control participants completed an evocative emotional task with pictures, sounds and words of various valences and intensities. Following each presentation, participants rated the level of pleasantness, unpleasantness, and arousal elicited by the stimulus. Finally, participants completed questionnaires on anhedonia, and practical life skills were assessed. Schizophrenia participants showed higher levels of ambivalence, greater arousal, greater Positivity Offset, and non-significantly different hedonic capacities and Negativity Bias. Ambivalence to positive stimuli significantly correlated with duration of illness, current level of psychopathology, anhedonia questionnaires and practical life skills. Schizophrenia patients with negative symptoms did not differ from patients without negative symptoms on computer tasks. Ambivalence is greater in schizophrenia, and can be understood as a de-differentiation of the activation of the two evaluative systems. Ambivalence to positive stimuli, which may reflect early-stage affective processing is associated with impairments in higher-level emotional processes and in everyday functioning. Future studies should clarify the status of anhedonia in schizophrenia.

Reducing resistance and denial by exercising ambivalence during the treatment of addiction.

PubMed

Shaffer, H J; Simoneau, G

2001-01-01

Stage change models and motivational enhancement therapies have significantly influenced the therapeutic tactics clinicians employ in the treatment of addictive behaviors. While motivational enhancement strategies have addressed client ambivalence to increase motivation to change, this article suggests that focusing on ambivalence during treatment has even wider clinical utility than previously thought. Resistance reduction concentrates on exercising ambivalence without an investment in clients changing, thereby strengthening client tolerance for ambivalent thoughts and feelings. Exercising ambivalence reduces resistance to treatment and change by validating a wide array of possible outcomes through detailed exploration of how a behavior pattern works for a client. Since resistance reduction does not require clients to want to change for therapy to progress, exploring the decision-making process becomes paramount. A general discussion of the resistance reduction model, ambivalence, and how clients present for treatment precedes clinical case examples.

Disentangling the impact of resistance and ambivalence on therapy outcomes in cognitive behavioural therapy for generalized anxiety disorder.

PubMed

Button, Melissa L; Westra, Henny A; Hara, Kimberley M; Aviram, Adi

2015-01-01

Resistance and ambivalence about change are increasingly recognized as important determinants of treatment outcomes. Moreover, resistance and ambivalence are thought to be theoretically related in that clients who are more ambivalent about change are more likely to demonstrate resistance to the process and tasks of treatment. In the context of cognitive behavioural therapy (CBT) for generalized anxiety disorder, the present study simultaneously examined early resistance and ambivalence using two observer-based coding systems in order to determine their inter-relationship and, importantly, to investigate their relative contributions to outcome. Resistance was also coded during mid-treatment in order to investigate possible mediation pathways. Early ambivalence (clients' arguments against change or counter-change talk) was found to be no longer related to outcomes when early resistance was taken into account, suggesting that disharmony in the therapeutic relationship is more important to outcomes than ambivalence per se. Moreover, mid-treatment resistance partially mediated the relationship between early resistance and post-treatment worry severity. That is, higher early opposition to therapist direction is related to poorer outcomes, in part because it is associated with greater resistance during the working phase of CBT. The findings underscore the critical need for therapists to be sensitive to identifying resistance early and throughout treatment.

Ambivalence in Mother-Adult Child Relations: A Dyadic Analysis

ERIC Educational Resources Information Center

Willson, Andrea E.; Shuey, Kim M.; Elder, Glen H., Jr.; Wickrama, K. A. S.

2006-01-01

The concept of ambivalence represents an interactional process in which individuals evaluate social relations as simultaneously positive and negative. This study investigates ambivalence in interpersonal relations through an empirical analysis of relationships between aging mothers and their adult children from their joint perspectives. Multilevel…

Emoticon-Based Ambivalent Expression: A Hidden Indicator for Unusual Behaviors in Weibo

PubMed Central

Hu, Yue; Zhao, Jichang; Wu, Junjie

2016-01-01

Recent decades have witnessed online social media being a big-data window for testifying conventional social theories quantitatively and exploring much detailed human behavioral patterns. In this paper, by tracing the emoticon use in Weibo, a group of hidden “ambivalent users” are disclosed for frequently posting ambivalent tweets containing both positive and negative emotions. Further investigation reveals that this ambivalent expression could be a novel indicator of many unusual social behaviors. For instance, ambivalent users with the female as the majority like to make a sound in midnights and at weekends. They mention their close friends frequently in ambivalent tweets, which attract more replies and serve as a more private communication way. Ambivalent users also respond differently to public affairs from others and demonstrate more interests in entertainment and sports events. Moreover, the sentiment shift in ambivalent tweets is more evident than usual and exhibits a clear “negative to positive” pattern. The above observations, though being promiscuous seemingly, actually point to the self-regulation of negative mood in Weibo, which could find its basis from the traditional emotion management theories in sociology but makes an important extension to the online environment in this study. Finally, as an interesting corollary, ambivalent users are found connected with compulsive buyers and turn out to be perfect targets for online marketing. PMID:26800119

Emoticon-Based Ambivalent Expression: A Hidden Indicator for Unusual Behaviors in Weibo.

PubMed

Hu, Yue; Zhao, Jichang; Wu, Junjie

2016-01-01

Recent decades have witnessed online social media being a big-data window for testifying conventional social theories quantitatively and exploring much detailed human behavioral patterns. In this paper, by tracing the emoticon use in Weibo, a group of hidden "ambivalent users" are disclosed for frequently posting ambivalent tweets containing both positive and negative emotions. Further investigation reveals that this ambivalent expression could be a novel indicator of many unusual social behaviors. For instance, ambivalent users with the female as the majority like to make a sound in midnights and at weekends. They mention their close friends frequently in ambivalent tweets, which attract more replies and serve as a more private communication way. Ambivalent users also respond differently to public affairs from others and demonstrate more interests in entertainment and sports events. Moreover, the sentiment shift in ambivalent tweets is more evident than usual and exhibits a clear "negative to positive" pattern. The above observations, though being promiscuous seemingly, actually point to the self-regulation of negative mood in Weibo, which could find its basis from the traditional emotion management theories in sociology but makes an important extension to the online environment in this study. Finally, as an interesting corollary, ambivalent users are found connected with compulsive buyers and turn out to be perfect targets for online marketing.

The Anxious and Ambivalent Partisan

PubMed Central

Groenendyk, Eric

2016-01-01

Affective Intelligence Theory (AIT) asserts that anxiety reduces the effect of party identification on candidate preferences (Marcus, Neuman, and MacKuen 2000), but recent studies have raised doubts about this causal claim. Rather than functioning as a moderator of party identification, perhaps anxiety has a direct effect on preferences, or perhaps the relationship is reversed and preferences drive emotions (Ladd and Lenz 2008). Alternatively, Marcus et al.’s measure of anxiety may simply be capturing partisan ambivalence, so the posited relationship is spurious (Lavine, Johnston, and Steenbergen 2012). This paper addresses each of these questions by examining the effect of experimentally induced emotions on the types of considerations that came to mind when a national sample of adult Americans was asked what they liked and disliked about Barack Obama. By directly manipulating anxiety, this experiment avoids the causal ambiguity plaguing this debate and ascertains the true nature of the relationship between anxiety and ambivalence. Consistent with AIT, anxiety led respondents to recall more contemporary considerations, whereas enthusiasm brought to mind more long-standing considerations. Because the political context at the time of the study (fall 2013) was a very tumultuous time for the Obama administration, the increased accessibility of contemporary considerations led Democratic participants to experience more ambivalence in the anxiety condition. This effect was concentrated among those Democrats who were exposed to the most newspaper coverage. PMID:27274573

Feeling torn when everything seems right: semantic incongruence causes felt ambivalence.

PubMed

Gebauer, Jochen E; Maio, Gregory R; Pakizeh, Ali

2013-06-01

The co-occurrence of positive and negative attributes of an attitude object typically accounts for less than a quarter of the variance in felt ambivalence toward these objects, rendering this evaluative incongruence insufficient for explaining felt ambivalence. The present research tested whether another type of incongruence, semantic incongruence, also causes felt ambivalence. Semantic incongruence arises from inconsistencies in the descriptive content of attitude objects' attributes (e.g., attributes that are not mutually supportive), independent of these attributes' valences. Experiment 1 manipulated evaluative and semantic incongruence using valence norms and semantic norms. Both of these norm-based manipulations independently predicted felt ambivalence, and, in Experiment 2, they even did so over and above self-based incongruence (i.e., participants' idiosyncratic perceptions of evaluative and semantic incongruence). Experiments 3a and 3b revealed that aversive dissonant feelings play a role in the effects of evaluative incongruence, but not semantic incongruence, on felt ambivalence.

Ambivalence, Modernisation and Language Attitudes: French and Arabic in Tunisia.

ERIC Educational Resources Information Center

Stevens, Paul B.

1983-01-01

Examines the ambivalent attitude toward the major speech varieties used in Tunisia (French, Classical Arabic, and Tunisian Arabic) and seeks to show the effects of that ambivalence on language policy, especially with regard to Arabization and bilingualism. (EKN)

Effect of social support and donation-related concerns on ambivalence of living liver donor candidates.

PubMed

Lai, Yun-Chieh; Lee, Wei-Chen; Juang, Yeong-Yuh; Yen, Lee-Lan; Weng, Li-Chueh; Chou, Hsueh Fen

2014-11-01

Ambivalence in the decision-making process for living liver donors has the potential to result in their experiencing a negative mental status. To promote donor candidates' well-being, it is important to study the factors related to ambivalence. Thus, the aim of this study was to explore the ambivalence of living liver donor candidates and to investigate the effect of social support and donation-related concerns on their ambivalence. A cross-sectional design was used. In total, 100 living liver donor candidates who underwent a preoperative evaluation between April and October 2009 were recruited for the study. Participants completed a self-administered questionnaire that contained items related to ambivalence, donation-related concerns, and social support. The mean score for ambivalence was 3.14 (standard deviation = 1.8), and the median was 3. Only 7% of the study sample reported no ambivalence during the assessment stage. Ambivalence was positively correlated with donation-related concerns (physical concerns, r = 0.39; psychosocial concerns, r = 0.43; financial concerns, r = 0.29) and negatively correlated with social support (r = -0.16 to -0.33). Those with psychosocial concerns had significantly worse ambivalence (β = 0.29, P = 0.03), but social support mitigated ambivalence (β = -0.34, P = 0.01). When intimacy and social support were included in the model, the effect of psychosocial concerns on ambivalence became nonsignificant (β = 0.24, P = 0.08). Ambivalence is common among living liver donor candidates, but instrumental social support can mediate the negative effect of donation-related concerns. Recommendations include providing appropriate social support to minimize donation-related concerns and, thus, to reduce the ambivalence of living liver candidates. © 2014 American Association for the Study of Liver Diseases.

Older Parents' Perceptions of Ambivalence in Relationships with Their Children

ERIC Educational Resources Information Center

Peters, Cheryl L.; Hooker, Karen; Zvonkovic, Anisa M.

2006-01-01

This qualitative study explores older parents' ambivalent perceptions of their relationships with their adult children. Interviews with 17 mothers and fathers (aged 67+) provided reports on 75 relationships (43 sons, 32 daughters). Two predominant sources of ambivalence emerged when parents discussed their current relationships. The first…

The Anxious and Ambivalent Partisan: The Effect of Incidental Anxiety on Partisan Motivated Recall and Ambivalence.

PubMed

Groenendyk, Eric

2016-01-01

Affective Intelligence Theory (AIT) asserts that anxiety reduces the effect of party identification on candidate preferences (Marcus, Neuman, and MacKuen 2000), but recent studies have raised doubts about this causal claim. Rather than functioning as a moderator of party identification, perhaps anxiety has a direct effect on preferences, or perhaps the relationship is reversed and preferences drive emotions (Ladd and Lenz 2008). Alternatively, Marcus et al.'s measure of anxiety may simply be capturing partisan ambivalence, so the posited relationship is spurious (Lavine, Johnston, and Steenbergen 2012). This paper addresses each of these questions by examining the effect of experimentally induced emotions on the types of considerations that came to mind when a national sample of adult Americans was asked what they liked and disliked about Barack Obama. By directly manipulating anxiety, this experiment avoids the causal ambiguity plaguing this debate and ascertains the true nature of the relationship between anxiety and ambivalence. Consistent with AIT, anxiety led respondents to recall more contemporary considerations, whereas enthusiasm brought to mind more long-standing considerations. Because the political context at the time of the study (fall 2013) was a very tumultuous time for the Obama administration, the increased accessibility of contemporary considerations led Democratic participants to experience more ambivalence in the anxiety condition. This effect was concentrated among those Democrats who were exposed to the most newspaper coverage.

Drug use and social control: The negotiation of moral ambivalence.

PubMed

Shiner, Michael; Winstock, Adam

2015-08-01

Illicit drugs occupy an ambivalent position in late modern society; one that revolves around the twin themes of pleasure and disapproval. Drawing on Freudian psychoanalysis and Eliasian sociology this article considers how people, particularly those who use drugs, negotiate such ambivalence. Patterns of drug use and associated attitudes are examined on the basis of the Crime Survey for England and Wales and a specialist survey of largely recreational drug users in the United Kingdom. Although illicit drugs have become increasingly familiar, their use is still widely thought to be harmful and morally dubious, creating a series of challenges for those who engage in such behaviour. Ambivalence among drug users is evident in an awareness of potential costs as well as benefits; a tendency to avoid more harmful substances; a general emphasis on moderation; and a desire to use less. Building on previous work, which highlights the role of neutralisations in sustaining drug using behaviour, particular attention is paid to users' judgements about how their levels of consumption compare with other users. The analysis identifies a tendency among users to downplay their relative levels of use, which, it is argued, serves to shield them from some of the imperatives that may lead to decisions to cut down. As such, normalisation is said to be an intra-personal as well inter-personal process. The article concludes by discussing the potential of web-based personalised feedback as a harm reduction approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ambivalence about supervised injection facilities among community stakeholders.

PubMed

Strike, Carol; Watson, Tara Marie; Kolla, Gillian; Penn, Rebecca; Bayoumi, Ahmed M

2015-08-21

Community stakeholders express a range of opinions about supervised injection facilities (SIFs). We sought to identify reasons for ambivalence about SIFs amongst community stakeholders in two Canadian cities. We used purposive sampling methods to recruit various stakeholder representatives (n = 141) for key informant interviews or focus group discussions. Data were analyzed using a thematic process. We identified seven reasons for ambivalence about SIFs: lack of personal knowledge of evidence about SIFs; concern that SIF goals are too narrow and the need for a comprehensive response to drug use; uncertainty that the community drug problem is large enough to warrant a SIF(s); the need to know more about the "right" places to locate a SIF(s) to avoid damaging communities or businesses; worry that a SIF(s) will renew problems that existed prior to gentrification; concern that resources for drug use prevention and treatment efforts will be diverted to pay for a SIF(s); and concern that SIF implementation must include evaluation, community consultation, and an explicit commitment to discontinue a SIF(s) in the event of adverse outcomes. Stakeholders desire evidence about potential SIF impacts relevant to local contexts and that addresses perceived potential harms. Stakeholders would also like to see SIFs situated within a comprehensive response to drug use. Future research should determine the relative importance of these concerns and optimal approaches to address them to help guide decision-making about SIFs.

Single Molecule Cluster Analysis Identifies Signature Dynamic Conformations along the Splicing Pathway

PubMed Central

Blanco, Mario R.; Martin, Joshua S.; Kahlscheuer, Matthew L.; Krishnan, Ramya; Abelson, John; Laederach, Alain; Walter, Nils G.

2016-01-01

The spliceosome is the dynamic RNA-protein machine responsible for faithfully splicing introns from precursor messenger RNAs (pre-mRNAs). Many of the dynamic processes required for the proper assembly, catalytic activation, and disassembly of the spliceosome as it acts on its pre-mRNA substrate remain poorly understood, a challenge that persists for many biomolecular machines. Here, we developed a fluorescence-based Single Molecule Cluster Analysis (SiMCAn) tool to dissect the manifold conformational dynamics of a pre-mRNA through the splicing cycle. By clustering common dynamic behaviors derived from selectively blocked splicing reactions, SiMCAn was able to identify signature conformations and dynamic behaviors of multiple ATP-dependent intermediates. In addition, it identified a conformation adopted late in splicing by a 3′ splice site mutant, invoking a mechanism for substrate proofreading. SiMCAn presents a novel framework for interpreting complex single molecule behaviors that should prove widely useful for the comprehensive analysis of a plethora of dynamic cellular machines. PMID:26414013

Individual differences in melancholy gender among women: does ambivalence matter?

PubMed

Jay, Meg

2007-01-01

This research offers an empirical investigation inspired by Butler's theory of melancholy gender (1995) and a revision of this theory (Jay 2007a). Psychoanalytic feminist theory is drawn on to suggest that melancholy and gender are more likely to be associated in female development than in male development, and Freud's theory of melancholy (1917) is taken to suggest that ambivalence predicts individual differences in melancholy gender among women. In a longitudinal study of women's adult development, an examination of femininity, depressive symptoms, and ambivalence in attachment was conducted in order to evaluate these claims. Findings show that depressive symptoms and femininity are significantly correlated within the sample, but that individual differences in melancholy gender exist. To understand these differences, an analysis was conducted to determine whether ambivalence in attachment accounts for the relation between depressive symptoms and femininity; complementary analyses examined whether low ambivalence in attachment attenuates, or lessens, the relation between femininity and depressive symptoms. Results from these analyses support the notion that it is not the loss and internalization of the same-sex object choice per se that results in melancholy gender in women, as Butler argues; rather, it is the internalization of a lost, ambivalent same-sex attachment that forges the link between melancholy and gender. Narrative material is presented to personify melancholy and unmelancholy gender.

Do ambivalent women have an unmet need for family planning? A longitudinal study from Bali, Indonesia.

PubMed

Withers, Mellissa H; Tavrow, Paula; Adinata, N Ardika

2011-01-01

Fertility intentions often can predict contraceptive demand and fertility outcomes. Little is known about women reporting ambivalent fertility intentions, who are usually classified as having an unmet need for contraception. This study's objectives were to determine 1) which fertility intention group ambivalent women more closely resemble and 2) whether ambivalent women seem to have an unmet contraceptive need. We analyzed longitudinal data from 1,018 married Balinese women aged 15 to 45, of whom 33% desired more children, 52% wanted no more, and 14% were ambivalent. Ambivalent women were compared with those with definitive intentions using bivariate analyses. Regression analysis was used to determine the predictors of birth avoidance. Although ambivalent women were significantly older, and had less education and more children than women who wanted more children, ambivalent women were more similar in their contraceptive use to those who wanted more children than those who wanted no more. However, in terms of birth outcomes, ambivalent women resembled more the women who intended to avoid childbearing: After 4 years, 33% of ambivalent women had another birth compared with 29% of women who wanted no more and 57% of women who desired more children. Contraceptive use at baseline did not predict ambivalent women's fertility outcomes, unlike the other groups. Despite their relatively low rates of contraceptive use at baseline, ambivalent women generally avoided giving birth during the study period. This suggests that ambivalent women may not have a high unmet need for family planning. Copyright © 2011 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Feeling conflicted and seeking information: when ambivalence enhances and diminishes selective exposure to attitude-consistent information.

PubMed

Sawicki, Vanessa; Wegener, Duane T; Clark, Jason K; Fabrigar, Leandre R; Smith, Steven M; Durso, Geoffrey R O

2013-06-01

To date, little research has examined the impact of attitudinal ambivalence on attitude-congruent selective exposure. Past research would suggest that strong/univalent rather than weak/ambivalent attitudes should be more predictive of proattitudinal information seeking. Although ambivalent attitude structure might weaken the attitude's effect on seeking proattitudinal information, we believe that conflicted attitudes might also motivate attitude-congruent selective exposure because proattitudinal information should be effective in reducing ambivalence. Two studies provide evidence that the effects of ambivalence on information choices depend on amount of issue knowledge. That is, ambivalence motivates attitude-consistent exposure when issue knowledge is relatively low because less familiar information is perceived to be effective at reducing ambivalence. Conversely, when knowledge is relatively high, more unambivalent (univalent) attitudes predicted attitude-consistent information seeking.

Neural dissociations in attitude strength: Distinct regions of cingulate cortex track ambivalence and certainty.

PubMed

Luttrell, Andrew; Stillman, Paul E; Hasinski, Adam E; Cunningham, William A

2016-04-01

People's behaviors are often guided by valenced responses to objects in the environment. Beyond positive and negative evaluations, attitudes research has documented the importance of attitude strength--qualities of an attitude that enhance or attenuate its impact and durability. Although neuroscience research has extensively investigated valence, little work exists on other related variables like metacognitive judgments about one's attitudes. It remains unclear, then, whether the various indicators of attitude strength represent a single underlying neural process or whether they reflect independent processes. To examine this, we used functional MRI (fMRI) to identify the neural correlates of attitude strength. Specifically, we focus on ambivalence and certainty, which represent metacognitive judgments that people can make about their evaluations. Although often correlated, prior neuroscience research suggests that these 2 attributes may have distinct neural underpinnings. We investigate this by having participants make evaluative judgments of visually presented words while undergoing fMRI. After scanning, participants rated the degree of ambivalence and certainty they felt regarding their attitudes toward each word. We found that these 2 judgments corresponded to distinct brain regions' activity during the process of evaluation. Ambivalence corresponded to activation in anterior cingulate cortex, dorsomedial prefrontal cortex, and posterior cingulate cortex. Certainty, however, corresponded to activation in unique areas of the precuneus/posterior cingulate cortex. These results support a model treating ambivalence and certainty as distinct, though related, attitude strength variables, and we discuss implications for both attitudes and neuroscience research. (c) 2016 APA, all rights reserved).

Attitudinal Ambivalence as a Protective Factor Against Junk Food Advertisements: A Moderated Mediation Model of Behavioral Intention.

PubMed

Ran, Weina; Yamamoto, Masahiro

2015-08-01

This study investigates the role of attitudinal ambivalence in moderating the effects of junk food advertisements on behavioral intentions by tapping different facets of this construct-felt ambivalence, potential ambivalence, and affective-cognitive ambivalence. Results based on an online survey of college students indicate that attention to junk food advertisements has an indirect positive effect on intentions to eat junk food through its positive effect on attitudes toward junk food. A moderated mediation model reveals that this indirect effect of junk food advertisements is weakened as respondents' levels of felt ambivalence increase. This moderating role is not observed for the measures of potential ambivalence and affective-cognitive ambivalence. Implications are discussed for health interventions.

Abortion Decision and Ambivalence: Insights via an Abortion Decision Balance Sheet

ERIC Educational Resources Information Center

Allanson, Susie

2007-01-01

Decision ambivalence is a key concept in abortion literature, but has been poorly operationalised. This study explored the concept of decision ambivalence via an Abortion Decision Balance Sheet (ADBS) articulating reasons both for and against terminating an unintended pregnancy. Ninety-six women undergoing an early abortion for psychosocial…

Exploring ambivalence in motivational interviewing with obese African American adolescents and their caregivers: A mixed methods analysis

PubMed Central

Carcone, April Idalski; Barton, Ellen; Eggly, Susan; Brogan Hartlieb, Kathryn E.; Thominet, Luke; Naar, Sylvie

2016-01-01

Objective We conducted an exploratory mixed methods study to describe the ambivalence African-American adolescents and their caregivers expressed during motivational interviewing sessions targeting weight loss. Methods We extracted ambivalence statements from 37 previously coded counseling sessions. We used directed content analysis to categorize ambivalence related to the target behaviors of nutrition, activity, or weight. We compared adolescent-caregiver dyads’ ambivalence using the paired sample t-test and Wilcoxon signed-rank test. We then used conventional content analysis to compare the specific content of adolescents’ and caregivers’ ambivalence statements. Results Adolescents and caregivers expressed the same number of ambivalence statements overall, related to activity and weight, but caregivers expressed more statements about nutrition. Content analysis revealed convergences and divergences in caregivers’ and adolescents’ ambivalence about weight loss. Conclusion Understanding divergences in adolescent-caregiver ambivalence about the specific behaviors to target may partially explain the limited success of family-based weight loss interventions targeting African American families and provides a unique opportunity for providers to enhance family communication, foster teamwork, and build self-efficacy to promote behavior change. Practice implications Clinicians working in family contexts should explore how adolescents and caregivers converge and diverge in their ambivalence in order to recommend weight loss strategies that best meet families’ needs. PMID:26916012

Les Ambivalences du Silence: Les "Maximes" de la Rochefoucauld Par Quatre Chemins

ERIC Educational Resources Information Center

Turcat, Eric

2012-01-01

Maxims are famous for their moral pronouncements, yet La Rochefoucauld's "Maximes" (1678) have become infamous for offering little moral guidance. Morally ambivalent at best, the "Maximes" are also less known for their other forms of ambivalence, whether rhetorical, psychological, anthropological or linguistic. Such are…

Me, us, or them: who is more conformist? Perception of conformity and political orientation.

PubMed

Cavazza, Nicoletta; Mucchi-Faina, Angelica

2008-06-01

Research has shown that people perceive others as more vulnerable than themselves to media communication, and their political out-group as more vulnerable than their political in-group. In the present study, the authors predicted that the same two biases would appear with respect to another kind of influence--conformity--but that participants' judgments would display a different pattern according to their political orientations. Right-wing and left-wing university students were asked to evaluate conformity and to estimate how conformist they, their political in-group, their political out-group, and other groups are. As hypothesized, right-wingers expressed more ambivalence toward conformity and viewed it less negatively than did left-wingers. Political orientation had no impact on the discrepancy between self and others, but it did moderate the in-group-out-group discrepancy.

Ambivalence About Interpersonal Problems and Traits Predicts Cross-Situational Variability of Social Behavior.

PubMed

Erickson, Thane M; Newman, Michelle G; Peterson, Jessica; Scarsella, Gina

2015-08-01

Multiple theoretical perspectives suggest that maladjusted personality is characterized by not only distress, but also opposing or "ambivalent" self-perceptions and behavioral lability across social interactions. However, the degree to which ambivalence about oneself predicts cross-situational variability in social behavior has not been examined empirically. Using the interpersonal circumplex (IPC) as a nomological framework, the present study investigated the extent to which endorsing opposing or "ambivalent" tendencies on IPC measures predicted variability in social behavior across a range of hypothetical interpersonal scenarios (Part 1; N = 288) and naturalistic social interactions (Part 2; N = 192). Ambivalent responding for interpersonal problems and traits was associated with measures of distress, maladaptive interpersonal tendencies, and greater variability of social behavior across both hypothetical and daily social interactions, though more consistently for interpersonal problems. More conservative tests suggested that ambivalence predicted some indexes of behavioral variability even when accounting for mean levels and squared means of social behaviors, vector length, gender, and depressive symptoms. Results suggest that processes theorized as typifying personality disorder may apply more broadly to personality maladjustment occurring outside of clinical samples. © 2014 Wiley Periodicals, Inc.

Pride, Prejudice, and Ambivalence: Toward a Unified Theory of Race and Ethnicity

ERIC Educational Resources Information Center

Markus, Hazel Rose

2008-01-01

For more than a century, hundreds of psychologists have studied race and ethnicity. Yet this scholarship, like American culture at large, has been ambivalent, viewing race and ethnicity both as sources of pride, meaning, and motivation as well as sources of prejudice, discrimination, and inequality. Underlying this ambivalence is widespread…

Carers' ambivalence in conflict situations with older persons.

PubMed

Breitholtz, Agneta; Snellman, Ingrid; Fagerberg, Ingegerd

2013-03-01

The aim of this study was to illuminate the meaning of professional carers' experiences in caring situations when a conflict of interest arises with the older person receiving care. The findings reveal the complexity of the carers' ambivalence when facing a conflict of interest, weighing up between the older persons' right to self-determination and external demands. The carers are alone in their ambivalence, and the conclusion is that they need help and support to be more present in the encounter. The implication for this study is to focus on care as a person-centered practice and to focus on people as interdependent on support carers to maintain older people's right to self-determination in the relationship.

Nations' income inequality predicts ambivalence in stereotype content: how societies mind the gap.

PubMed

Durante, Federica; Fiske, Susan T; Kervyn, Nicolas; Cuddy, Amy J C; Akande, Adebowale Debo; Adetoun, Bolanle E; Adewuyi, Modupe F; Tserere, Magdeline M; Ramiah, Ananthi Al; Mastor, Khairul Anwar; Barlow, Fiona Kate; Bonn, Gregory; Tafarodi, Romin W; Bosak, Janine; Cairns, Ed; Doherty, Claire; Capozza, Dora; Chandran, Anjana; Chryssochoou, Xenia; Iatridis, Tilemachos; Contreras, Juan Manuel; Costa-Lopes, Rui; González, Roberto; Lewis, Janet I; Tushabe, Gerald; Leyens, Jacques-Philippe; Mayorga, Renée; Rouhana, Nadim N; Castro, Vanessa Smith; Perez, Rolando; Rodríguez-Bailón, Rosa; Moya, Miguel; Morales Marente, Elena; Palacios Gálvez, Marisol; Sibley, Chris G; Asbrock, Frank; Storari, Chiara C

2013-12-01

Income inequality undermines societies: The more inequality, the more health problems, social tensions, and the lower social mobility, trust, life expectancy. Given people's tendency to legitimate existing social arrangements, the stereotype content model (SCM) argues that ambivalence-perceiving many groups as either warm or competent, but not both-may help maintain socio-economic disparities. The association between stereotype ambivalence and income inequality in 37 cross-national samples from Europe, the Americas, Oceania, Asia, and Africa investigates how groups' overall warmth-competence, status-competence, and competition-warmth correlations vary across societies, and whether these variations associate with income inequality (Gini index). More unequal societies report more ambivalent stereotypes, whereas more equal ones dislike competitive groups and do not necessarily respect them as competent. Unequal societies may need ambivalence for system stability: Income inequality compensates groups with partially positive social images. © 2012 The British Psychological Society.

Intergenerational Ambivalence in Adolescence and Early Adulthood: Implications for Depressive Symptoms over Time

ERIC Educational Resources Information Center

Tighe, Lauren A.; Birditt, Kira S.; Antonucci, Toni C.

2016-01-01

The parent-child relationship is often characterized by ambivalence, defined as the simultaneous experience of positive and negative relationship quality. This study examines reports of intergenerational ambivalence in 3 developmental periods: adolescence, emerging adulthood, and young adulthood, as well as its implications for depressive symptoms…

Solidarity and ambivalence: comparing two perspectives on intergenerational relations using longitudinal panel data.

PubMed

Hogerbrugge, Martijn J A; Komter, Aafke E

2012-05-01

Research on family relations has extensively used the intergenerational solidarity model proposed by Bengtson and colleagues. Recently, the relevance of this model for explaining changes in family relations has been questioned, and the concept of intergenerational ambivalence has been proposed as a relevant addition to the model, supposedly acting as a catalyst, and thus serving as an explanation for changes in family relations. This study tests both the viability of the intergenerational solidarity model and the hypothesized effect of ambivalence employing longitudinal data. We use data from 2 waves of the Netherlands' Kinship Panel Study on parent-adult child relationships to estimate latent variable structural equation models. Affection, association, and support between family members are core, mutually reinforcing dimensions of solidarity. The hypothesis that ambivalence is a catalyst for change in family relations was not confirmed. Adding conflict separately revealed that it only affects the core solidarity dimensions but is itself, like normative and structural solidarity, not influenced by them. The relevance of the concept of intergenerational ambivalence for studying changes in family relations can be questioned. The viability of the intergenerational solidarity model is, however, confirmed. The concept of intergenerational ambivalence might be further explored in qualitative studies on family change.

The "Research-Teaching Nexus" and "Education through Research": An Exploration of Ambivalences

ERIC Educational Resources Information Center

Simons, Maarten; Elen, Jan

2007-01-01

This article presents and discusses the results of a literature review that was conducted in order to understand ambivalences observed in reflections on the research-teaching nexus. As a result of this literature review, it is possible to attribute these ambivalences to the mixed use of two approaches: on the one hand, a functional approach that…

Ambivalence and Stereotypes Cause Sexual Harassment: A Theory with Implications for Organizational Change.

ERIC Educational Resources Information Center

Fiske, Susan T.; Glick, Peter

1995-01-01

Theorizes that workplace sexual harassment results from the complex interplay of ambivalent motives and gender stereotyping of women and jobs. It argues that ambivalence combines hostile and "benevolent" sexist motives based on paternalism, gender differentiation, and heterosexuality and that organizational context can encourage or discourage the…

Relationships and cardiovascular risk: perceived spousal ambivalence in specific relationship contexts and its links to inflammation.

PubMed

Uchino, Bert N; Bosch, Jos A; Smith, Timothy W; Carlisle, McKenzie; Birmingham, Wendy; Bowen, Kimberly S; Light, Kathleen C; Heaney, Jennifer; O'Hartaigh, Briain

2013-10-01

Although perceiving one's social ties as sources of ambivalence has been linked to negative health outcomes, the more specific contexts by which such relationships influence health remain less studied. We thus examined if perceived spousal relationship quality in three theoretically important contexts (i.e., support, capitalization, everyday life) predicted inflammation. Ninety-four married couples completed measures of perceived spousal positivity and negativity in support, capitalization, and everyday contexts. These scores were used to derive an index of relationship ambivalence whereby interactions were rated as containing both positive and negative aspects. Serum levels of IL-6, fibrinogen, and CRP were assessed from plasma. Perceiving ambivalence toward one's spouse in a support context was linked to greater inflammation even when considering health behaviors, relationship-specific romantic attachment style, spouse negativity/positivity ratings, and overall marital satisfaction. Perceiving ambivalence toward a spouse during capitalization predicted higher fibrinogen levels only, whereas no links were found with perceived spousal ambivalence in everyday life contexts. Perceptions of ambivalence during support may be a particularly important relational context in which marital ties influence health. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Ambivalence and alliance ruptures in cognitive behavioral therapy for generalized anxiety.

PubMed

Hunter, Jennifer A; Button, Melissa L; Westra, Henny A

2014-01-01

Client ambivalence about change (or motivation) is regarded as central to outcomes in cognitive behavioral therapy (CBT). However, little research has been conducted to examine the impact of client ambivalence about change on therapy process variables such as the therapeutic alliance. Given the demonstrated limitations of self-report measures of key constructs such as ambivalence and motivation, the present study instead employed a newly adapted observational measure of client ambivalence. Client statements regarding change (change talk (CT) and counter-change talk (CCT)) were coded in early (session 1 or 2) therapy sessions of CBT for generalized anxiety disorder. The frequency of CT and CCT was then compared between clients who later experienced an alliance rupture with their therapist, and clients who did not. The results showed that clients in dyads who later experienced an alliance rupture expressed significantly more CCT at the outset of therapy than clients who did not later experience an alliance rupture. However, CT utterances did not significantly differ between alliance rupture and no-rupture groups. CCT may strain the alliance because clients expressing higher levels of CCT early in therapy may be less receptive to therapist direction in CBT. Consequently, it is recommended that clients and therapists work together to carefully address these key moments in therapy so as to prevent alliance rupture and preserve client engagement in therapy.

The effect of images of thin and overweight body shapes on women's ambivalence towards chocolate.

PubMed

Durkin, Kevin; Rae, Kirsty; Stritzke, Werner G K

2012-02-01

Many women experience ambivalent orientations towards chocolate, both craving for it and having concerns about eating it. The present study investigated the effect of viewing thin and overweight images of models in chocolate advertisements on ambivalent attitudes. Participants were 84 females, aged 17-63, allocated to a thin model condition, an overweight model condition, or a control group. As predicted, following exposure to their respective images, participants in the thin condition had increased avoidance, approach and guilt scores, while participants in the overweight condition had decreased approach and guilt scores, with no change in avoidance. Control participants demonstrated ambivalence, but no changes over time. The findings show that common advertising strategies for chocolate are likely to exacerbate ambivalence in female consumers. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ambivalent Sexism in Close Relationships: (Hostile) Power and (Benevolent) Romance Shape Relationship Ideals

PubMed Central

Lee, Tiane L.; Fiske, Susan T.; Glick, Peter; Chen, Zhixia

2013-01-01

Gender-based structural power and heterosexual dependency produce ambivalent gender ideologies, with hostility and benevolence separately shaping close-relationship ideals. The relative importance of romanticized benevolent versus more overtly power-based hostile sexism, however, may be culturally dependent. Testing this, northeast US (N=311) and central Chinese (N=290) undergraduates rated prescriptions and proscriptions (ideals) for partners and completed Ambivalent Sexism and Ambivalence toward Men Inventories (ideologies). Multiple regressions analyses conducted on group-specific relationship ideals revealed that benevolent ideologies predicted partner ideals, in both countries, especially for US culture’s romance-oriented relationships. Hostile attitudes predicted men’s ideals, both American and Chinese, suggesting both societies’ dominant-partner advantage. PMID:23914004

Writing with Light: Jacob Riis's Ambivalent Exposures

ERIC Educational Resources Information Center

Carter, Christopher

2008-01-01

The current interest in multimodal rhetoric was anticipated by Jacob Riis's social documentary texts and presentations during the late nineteenth and early twentieth centuries. In contrast with the socialist urban critiques presented by Friedrich Engels, Riis's work demonstrated profound ambivalence toward the city's poor. While calling for reform…

Ambivalent Sexism Inventory: Adaptation to Basque Population and Sexism as a Risk Factor of Dating Violence.

PubMed

Ibabe, Izaskun; Arnoso, Ainara; Elgorriaga, Edurne

2016-11-15

There is currently a consensus that sexism is one of the most important causes of intimate partner violence, but this has yet to be empirically demonstrated conclusively. The key objective of the study was to adapt Ambivalent Sexism Inventory (ASI) and to validate it to the Basque language. It also aims to analyze the prevalence of violence in dating relationships and verify if ambivalent sexism in young men and women is a valid predictor of perpetration and/or victimization in their dating relationships. Ambivalent Sexism Inventory and Dating Relationship Questionnaire were administered to 1378 undergraduate students (66% women and 45% Basque), aged between 17 and 30. The psychometric properties of the Basque and Spanish versions of the ASI are deemed to be acceptable. Sufficient guarantees are provided to be used as an instrument for measuring ambivalent sexism in adult Basque speakers. Ambivalent sexism among young men and women are both positively associated with the perpetration of violence and victimization in their dating relationships. However, ambivalent sexism or two sub-types of sexism (hostile and benevolent) are not relevant risk factors to be perpetrator or victim of violence in dating relationships, due to accounting for 3% or less of variance in dating violence.

Emotional ambivalence and post-traumatic stress disorder (PTSD) in soldiers during military operations

PubMed Central

Jerg-Bretzke, Lucia; Walter, Steffen; Limbrecht-Ecklundt, Kerstin; Traue, Harald C.

2013-01-01

Objective: This pilot study examined the extent to which a specific mechanism of emotion regulation – namely, ambivalence concerning the expressiveness of German soldiers’ emotions – affects the severity of PTSD symptoms after a military operation. Methodology: A survey was conducted at three points in time among 66 soldiers deployed on military crisis operations. The Harvard Trauma Questionaire (HTQ), the Ambivalence over Emotional Expressiveness Questionnaire (AEQ-G18), and a questionnaire on the particular stress of German soldiers during military operations were used. Results: The study showed a significant correlation between emotional ambivalence and traumatization. Furthermore, it was shown that the subjective stress of soldiers leading up to deployment is more pronounced when emotional ambivalence is stronger in the context of military operations. This particular stress is greater before and during the military operation than after. Compared to a male control sample, the average AEQ-G18 scores of the soldier sample examined here are considerably lower. Conclusion: This pilot study clearly indicates that the AEQ-G18 could be a suitable predictor of the psychological burden on soldiers. The correlations between emotional ambivalence on the one hand and the particular and post-traumatic stressors on the other hand are not only statistically significant in the present pilot study, but may also be relevant as risk factors. It is, therefore, necessary to conduct more extensive studies on soldiers participating in military operations to verify the results of this pilot study. PMID:23798980

[Ambivalence--a key concept in gerontology? Elements of heuristics exemplified by identity formation in old age].

PubMed

Lüscher, Kurt; Haller, Miriam

2016-01-01

Ambivalence is a widely used concept in gerontology, mostly used in the common sense meaning. We propose that an elaborated notion based on the historical and systematic analysis, reveals important theoretical, methodological and practical potentials of the idea of ambivalence for the study of aging. We exemplify this view by proposing a heuristic perspective for the analysis of processes to constitute and reconstitute identities in old age using a model based on a multidimensional understanding of ambivalence. Ambivalence is defined as referring to the experiences of vacillating between polar contradictions of feeling, thinking, wanting and social structures in the search for the sense and meaning of social relationships, facts and texts, which are important for unfolding and altering facets of the self and agency.

Focus groups reveal consumer ambivalence.

PubMed

1983-01-01

According to qualitative research, Salvadoreans are ambivalent about the use of contraceptives. Since complete responsibility for management of the CSM project was accepted by the Association Demografica Salvadorena (ADS), the agency which operates the contraceptive social marketing project in El Salvador, in November 1980, the need for decisions in such areas as product price increases, introduction of new condom brands, promotion of the vaginal foaming tablet, and assessment of product sales performance had arisen. The ICSMP funded market research, completed during 1983, was intended to provide the data on which such decisions by ADS could be based. The qualitative research involved 8 focus groups, comprised of men and women, aged 18-45, contraceptive users and nonusers, from the middle and lower socioeconomic strata of the city of San Salvador and other suburban areas. In each group a moderator led discussion of family planning and probed respondents for specific attitudes, knowledge, and behavior regarding the use of contraceptives. To assess attitudes at a more emotional level, moderators asked respondents to "draw" their ideas on certain issues. A marked discrepancy was revealed between respondents' intellectual responses to the issues raised in group discussion, as opposed to their feelings expressed in the drawings. Intellectually, participants responded very positively to family planning practice, but when they were asked to draw their perceptions, ambivalent feelings emerged. Drawings of both the user and the nonuser convey primarily negative aspects for either choice. The user is tense and moody toward her children; the nonuser loses her attractiveness and "dies." Figures also show drawings of some of the attitudes of single and married male participants. 1 drawing shows an incomplete and a complete circle, symbolizing a sterilized man (incomplete) and a nonsterilized man (complete). Another picture depicts a chained man who has lost his freedom

Ambivalent versus Problematic Social Ties: Implications for Psychological Health, Functional Health, and Interpersonal Coping

PubMed Central

Rook, Karen S.; Luong, Gloria; Sorkin, Dara H.; Newsom, Jason T.; Krause, Neal

2013-01-01

Older adults often seek to manage their social networks to foster positive interactions, but they nonetheless sometimes experience negative interactions that detract from their health and well-being. Negative interactions may occur with ambivalent social partners (i.e., partners involved in both positive and negative exchanges) or exclusively problematic social partners (i.e., partners involved negative exchanges only), but conflicting views exist in the literature regarding which type of social partner is likely to be more detrimental to older adults’ physical and emotional health. This study examined the implications of the two kinds of network members for physical and psychological health and interpersonal coping responses in a representative sample of 916 older adults. Within this elderly sample, older age was associated with fewer ambivalent kin ties and fewer exclusively problematic kin ties. Analyses revealed that ambivalent social ties were more strongly related to functional health limitations than were exclusively problematic social ties, whereas problematic ties were more consistently related to psychological health than were ambivalent ties. Furthermore, negative exchanges that occurred with exclusively problematic social ties, as compared to those that occurred with ambivalent social ties, were associated with more avoidant and fewer conciliatory coping responses, stronger and longer-lasting negative emotions, and lower perceived coping effectiveness. A comprehensive understanding of the significance of social network ties in older adults’ lives may benefit not only from attention to sources of social support but also from efforts to distinguish between different sources of conflict and disappointment. PMID:22775360

Nations’ Income Inequality Predicts Ambivalence in Stereotype Content: How Societies Mind the Gap

PubMed Central

Durante, Federica; Fiske, Susan T.; Kervyn, Nicolas; Cuddy, Amy J. C.; Akande, Adebowale (Debo); Adetoun, Bolanle E.; Adewuyi, Modupe F.; Tserere, Magdeline M.; Ramiah, Ananthi Al; Mastor, Khairul Anwar; Barlow, Fiona Kate; Bonn, Gregory; Tafarodi, Romin W.; Bosak, Janine; Cairns, Ed; Doherty, Claire; Capozza, Dora; Chandran, Anjana; Chryssochoou, Xenia; Iatridis, Tilemachos; Contreras, Juan Manuel; Costa-Lopes, Rui; González, Roberto; Lewis, Janet I.; Tushabe, Gerald; Leyens, Jacques-Philippe; Mayorga, Renée; Rouhana, Nadim N.; Castro, Vanessa Smith; Perez, Rolando; Rodríguez-Bailón, Rosa; Moya, Miguel; Morales Marente, Elena; Palacios Gálvez, Marisol; Sibley, Chris G.; Asbrock, Frank; Storari, Chiara C.

2013-01-01

Income inequality undermines societies: the more inequality, the more health problems, social tensions, and the lower social mobility, trust, life expectancy. Given people’s tendency to legitimate existing social arrangements, the Stereotype Content Model (SCM) argues that ambivalence—perceiving many groups as either warm or competent, but not both—may help maintain socio-economic disparities. The association between stereotype ambivalence and income inequality in 37 cross-national samples from Europe, the Americas, Oceania, Asia, and Africa investigates how groups’ overall warmth-competence, status-competence, and competition-warmth correlations vary across societies, and whether these variations associate with income inequality (Gini index). More unequal societies report more ambivalent stereotypes, while more equal ones dislike competitive groups and do not necessarily respect them as competent. Unequal societies may need ambivalence for system stability: income inequality compensates groups with partially positive social images. PMID:23039178

The temporal dynamics of ambivalence: changes in positive and negative affect in relation to consumption of an "emotionally charged" food.

PubMed

Hormes, Julia M; Rozin, Paul

2011-08-01

Ambivalence is thought to impact consumption of food, alcohol and drugs, possibly via influences on craving, with cravers often being simultaneously drawn toward and repelled from ingestion. So far, little is known about the temporal dynamics of ambivalence, especially as it varies in relationship to consumption. Participants (n=482, 56.8% female) completed the Positive and Negative Affect Schedule prior to, immediately and 30 min after the opportunity to eat a bar of chocolate. Affective ambivalence was calculated based on the relative strengths of and discrepancy between ratings of positive and negative affect. Ambivalence peaked prior to a decision about consumption and subsequently decreased, whether or not the decision was in favor of or against consuming. Decreasing ambivalence was driven by a drop in positive affect over time; positivity decreased more rapidly in those who consumed chocolate. Findings represent a first step in characterizing the dynamics of ambivalence in interactions with a target stimulus. Copyright © 2011 Elsevier Ltd. All rights reserved.

Persuading people to eat less junk food: a cognitive resource match between attitudinal ambivalence and health message framing.

PubMed

Yan, Changmin

2015-01-01

This study investigated the interactive effects of attitudinal ambivalence and health message framing on persuading people to eat less junk food. Within the heuristic-systematic model of information processing, an attitudinal ambivalence (ambivalent or univalent toward eating junk food) by health message framing (advantage- or disadvantage-framed appeals) between-subjects experiment was conducted to explore a cognitive resource-matching effect and the underlying mediation processes. Ambivalent individuals reported a higher level of cognitive elaboration than univalent individuals did. The disadvantage frame engendered more extensive cognitive elaboration than the advantage frame did. Ambivalent individuals were more persuaded by the disadvantage frame and, for them, cognitive elaboration mediated the persuasion process via the systematic route. Univalent individuals were equally persuaded by the advantage frame and the disadvantage frame and, for them, neither the perceived frame valence nor cognitive elaboration mediated persuasion. Discussion of the null results among the univalent group leads to a response-reinforcement explanation. Theoretical and practical implications are discussed.

Managing ambivalent prejudices: The smart-but-cold, and the warm-butdumb sterotypes.

PubMed

Fiske, Susan T

2012-01-01

Not all biases are equivalent, and not all biases are uniformly negative. Two fundamental dimensions differentiate stereotyped groups in cultures across the globe: status predicts perceived competence, and cooperation predicts perceived warmth. Crossing the competence and warmth dimensions, two combinations produce ambivalent prejudices: pitied groups (often traditional women or older people) appear warm but incompetent, and envied groups (often nontraditional women or outsider entrepreneurs) appear competent but cold. Case studies in ambivalent sexism, heterosexism, racism, anti-immigrant biases, ageism, and classism illustrate both the dynamics and the management of these complex but knowable prejudices.

Caravaggio four centuries later: psychoanalytic portraits of ambivalence and ambiguity.

PubMed

Szajnberg, Nathan M

2013-04-01

Rome celebrated the four hundredth anniversary of Michelangelo Marisi da Caravaggio's death with an historical exhibition of his brief lifetime's work. Yet psychoanalysis has not studied this work extensively, despite the artist's compelling portrayal of a full range of human affects, including ambivalence. Psychoanalysis has studied artistic pioneers such as da Vinci (Freud 1910) and Michelangelo (Freud 1914), Giotto's use of blue sky as psychologically innovative (Blatt 1994), and Magritte's play with external reality (Spitz 1994). What can we learn about Caravaggio's work-including innovative contributions such as visual representation of expressed emotions, particularly negative emotions, including ambivalence, and remarkably candid, even critical, self-representations-and how can this late-sixteenth-century artist teach us about the development of the concept of mind underlying psychoanalysis?

On the importance of relationship quality: the impact of ambivalence in friendships on cardiovascular functioning.

PubMed

Holt-Lunstad, Julianne; Uchino, Bert N; Smith, Timothy W; Hicks, Angela

2007-06-01

Social relationships are reliably related to rates of morbidity and mortality. One pathway by which social relationships may influence health is via the impact of relationship quality on cardiovascular reactivity during social interactions. This study examined the effects of the quality of a friendship on cardiovascular reactivity when speaking about positive or negative life events with an ambivalent or supportive friend. To examine this, 107 healthy male and female adults (and their same-sex friend) were recruited. Results revealed that participants exhibited the greatest levels of systolic blood pressure reactivity when discussing a negative event with an ambivalent friend compared to a supportive friend. We also found higher resting levels of heart rate and lower respiratory sinus arrhythmia among those who brought in ambivalent friends than those who brought in supportive friends. Individuals may not be able to fully relax in the presence of ambivalent friends and may not benefit from support during stress. This research may help clarify the health-related consequences of differing types of social relationships.

Does gratitude always work? Ambivalence over emotional expression inhibits the beneficial effect of gratitude on well-being.

PubMed

Chen, Lung Hung; Chen, Mei-Yen; Tsai, Ying-Mei

2012-01-01

The psychological benefit of gratitude has been well demonstrated in previous studies. However, when we examined these studies closely, we found that the moderators were rarely investigated, suggesting that further work is needed to explore the boundaries of gratitude In this regard, the authors have proposed that ambivalence over emotional expression might be a potential moderator that would inhibit the beneficial effect of gratitude on well-being. Two studies were conducted to examine our hypothesis. Study 1 consisted of 353 Taiwanese college students who completed the Gratitude Questionnaire-Taiwan version (GQ-T), Ambivalence over Emotional Expression Questionnaire (AEQ), and one question about subjective happiness. We found that ambivalence over emotional expression significantly moderated the effect of gratitude on happiness. To validate our findings in Study 1, 233 Taiwanese college students were recruited for Study 2, and they completed the GQ-T, AEQ, subjective happiness short-form UCLA loneliness scale, as well as the Center for Epidemiological Studies Depression Scale (CES-D). Both studies demonstrated that ambivalence over emotional expression moderated the relationship between gratitude and well-being indexes. Simply stated, the authors found that across the two independent samples, among students who are high in ambivalence over emotional expression, the beneficial effect of gratitude on subjective happiness was inhibited. However, the moderating pattern for loneliness and depression was contrary to our expectations, indicating that high ambivalence over emotional expression does not inhibit gratitude. Possible explanations and implications for social relationships and emotional expression are discussed.

Facing Ambivalence in Education: A Strange(r's) Hope?

ERIC Educational Resources Information Center

Mansson, Niclas; Langmann, Elisabet

2011-01-01

This article explores how our understanding of ambivalence would shift if we saw it as an inherent and essential part of the ordinary work of education. Following Bauman's sociology of the stranger and Derrida's deconstructions of hospitality, the article unfolds in three parts. In the first part we discuss the preconditions of modern education…

Managing ambivalent prejudices: The smart-but-cold, and the warm-butdumb sterotypes

PubMed Central

FISkE, SUSAN T.

2013-01-01

Not all biases are equivalent, and not all biases are uniformly negative. Two fundamental dimensions differentiate stereotyped groups in cultures across the globe: status predicts perceived competence, and cooperation predicts perceived warmth. Crossing the competence and warmth dimensions, two combinations produce ambivalent prejudices: pitied groups (often traditional women or older people) appear warm but incompetent, and envied groups (often nontraditional women or outsider entrepreneurs) appear competent but cold. Case studies in ambivalent sexism, heterosexism, racism, anti-immigrant biases, ageism, and classism illustrate both the dynamics and the management of these complex but knowable prejudices. PMID:24115779

Ambivalent Sexism and Power-Related Gender-role Ideology in Marriage

PubMed Central

Chen, Zhixia; Fiske, Susan T.; Lee, Tiane L.

2013-01-01

Glick-Fiske's (1996) Ambivalent Sexism Inventory(ASI) and a new Gender-Role Ideology in Marriage (GRIM) inventory examine ambivalent sexism toward women, predicting power-related, gender-role beliefs about mate selection and marriage norms. Mainland Chinese, 552, and 252 U.S. undergraduates participated. Results indicated that Chinese and men most endorsed hostile sexism; Chinese women more than U.S. women accepted benevolent sexism. Both Chinese genders prefer home-oriented mates (women especially seeking a provider and upholding him; men especially endorsing male-success/female-housework, male dominance, and possibly violence). Both U.S. genders prefer considerate mates (men especially seeking an attractive one). Despite gender and culture differences in means, ASI-GRIM correlations replicate across those subgroups: Benevolence predicts initial mate selection; hostility predicts subsequent marriage norms. PMID:24058258

The Ambivalent Role of English in Brazilian Politics.

ERIC Educational Resources Information Center

Rajagopalan, Kanavillil

2003-01-01

Discusses the political import of a controversial bill currently being debated in the upper house of Brazil's legislature that seeks to curb the use of English in all but a handful of situations. Examines the ambivalence toward the language and suggest it has to do with the difficult geopolitics of the region and the contradictions in has…

Ambivalence toward palatable food and emotional eating predict weight fluctuations. Results of a longitudinal study with four waves.

PubMed

Keller, Carmen; Siegrist, Michael

2015-02-01

Weight fluctuations pose serious challenges to people's health. Research suggests that the interplay between cognitive dietary restraint and counter-regulative overeating impairs weight control. In a random sample from the general population (N = 2733, 49% male), a longitudinal survey was conducted over 4 consecutive years (2010-2013). Self-reported weight was used to calculate the variance of three weight changes from one wave to the next. Separate regression analyses for women and men were conducted. The dependent variable was weight fluctuation, and the independent variables were eating styles (emotional, external, and restrained) and ambivalence toward palatable food. Age and weight changes between the fourth and first years were controlled. A significant positive effect of emotional eating for men and women, and a significant positive effect of ambivalence for women, were found. Participants who demonstrated high levels of emotional eating, and women who had high levels of ambivalence in the beginning of the study, had more extreme relative weight fluctuations in the consecutive years than did persons with low levels of emotional eating or women with low levels of ambivalence. Restrained and external eating had no effect. The results suggest that emotional eating and ambivalence toward palatable food need to be addressed to prevent health-damaging weight fluctuations. Furthermore, ambivalence toward palatable food was revealed as an additional overeating tendency beyond emotional eating that must be considered to understand the interplay between dietary restraint and overeating. Copyright © 2014 Elsevier Ltd. All rights reserved.

Partner Type, Sexual Double Standard Endorsement, and Ambivalence Predict Abdication and Unprotected Sex Intentions in a Community Sample of Young Women

PubMed Central

Danube, Cinnamon L.; Norris, Jeanette; Stappenbeck, Cynthia A.; Davis, Kelly Cue; George, William H.; Zawacki, Tina; Morrison, Diane M.; Abdallah, Devon Alisa

2015-01-01

In-the-moment ambivalence about having sex may influence sexual decisions, but has rarely been examined. We investigated how ambivalence about sex might be related to intentions to abdicate sexual decisions to a male partner and to engage in unprotected sex in a community sample of young women. Predictors of abdication and unprotected sex intentions included partner type (new casual vs. previous relationship), sexual double standard (SDS) endorsement, and two types of ambivalence. After completing a SDS endorsement measure, women (n = 360) projected themselves into a hypothetical sexual situation and completed dependent measures. In the new casual partner condition, SDS endorsement indirectly negatively predicted unprotected sex intentions through its associations with ambivalence and abdication. In both partner conditions SDS endorsement positively predicted abdication, which then positively predicted unprotected sex intentions. Ambivalence indirectly predicted unprotected sex intentions through its negative association with abdication intentions. Results suggest the importance of ambivalence for sexual decisions and the complexity of understanding the sexual decision making processes for women who endorse the SDS. PMID:26421647

Partner Type, Sexual Double Standard Endorsement, and Ambivalence Predict Abdication and Unprotected Sex Intentions in a Community Sample of Young Women.

PubMed

Danube, Cinnamon L; Norris, Jeanette; Stappenbeck, Cynthia A; Cue Davis, Kelly; George, William H; Zawacki, Tina; Morrison, Diane M; Abdallah, Devon Alisa

2016-01-01

In-the-moment ambivalence about having sex may influence sexual decisions but has rarely been examined. We investigated how ambivalence about sex might be related to intentions to abdicate sexual decisions to a male partner and to engage in unprotected sex in a community sample of young women. Predictors of abdication and unprotected sex intentions included partner type (new casual versus previous relationship), sexual double standard (SDS) endorsement, and two types of ambivalence. After completing a SDS endorsement measure, women (N = 360) projected themselves into a hypothetical sexual situation and completed dependent measures. In the new casual partner condition, SDS endorsement indirectly negatively predicted unprotected sex intentions through its associations with ambivalence and abdication. In both partner conditions SDS endorsement positively predicted abdication, which then positively predicted unprotected sex intentions. Ambivalence indirectly predicted unprotected sex intentions through its negative association with abdication intentions. Results suggest the importance of ambivalence for sexual decisions and the complexity of understanding the sexual decision making processes for women who endorse the SDS.

Understanding the experience of ambivalence in anorexia nervosa: the maintainer's perspective.

PubMed

Williams, Sarah; Reid, Marie

2010-06-01

People with anorexia often feel ambivalent about whether they wish to maintain it or recover from it. One place where individuals can communicate their experiences of wanting to maintain their anorexia is through pro-anorexia websites. This study investigated the experiences and understandings of those who wish to maintain their anorexia and looked at how these understandings may affect their treatment experiences. Data were collected online and analysed using interpretative phenomenological analysis (IPA). Anorexia denoted meanings of a 'tool', an 'entity' and a 'disease'. Participants felt ambivalent about whether their anorexia gave them control or controlled them, whether it played a positive or negative role and whether they wished to maintain their behaviours or recover. Participants also discussed barriers to recovery. Theoretical and treatment implications are discussed.

Intergenerational Contact and Mediators Impact Ambivalence towards Future Selves

ERIC Educational Resources Information Center

Jarrott, Shannon E.; Savla, Jyoti

2016-01-01

Intergenerational contact can promote positive attitudes towards elders. However, contact with older adults often fosters multiple stereotypes, which may contribute to ambivalence about aging and poorer health in late life. Online survey data from 457 young adults (M age = 19.4 years; 74% female) were used to explore the relationship between…

Gamete donors' motivation in a Swedish national sample: is there any ambivalence? A descriptive study.

PubMed

Svanberg, Agneta Skoog; Lampic, Claudia; Gejervall, Ann-Louise; Geijerwall, Ann-Louise; Gudmundsson, Johannes; Karlström, Per-Olof; Solensten, Nils-Gunnar; Sydsjö, Gunilla

2012-08-01

To study donors' motivation and ambivalence before donation of gametes. Cross-sectional study. Seven Swedish university hospital clinics. Sample. Of the 220 eligible oocyte donors and 156 eligible sperm donors who were approached, 181 (82%) oocyte donors and 119 (76%) sperm donors agreed to participate. Gamete donors completed a questionnaire in the clinic prior to the donation. Motives and ambivalence towards donation. In general, gamete donors donated for altruistic reasons (95%). A greater percentage of oocyte than sperm donors had a personal experience of biological children, which motivated them to donate (65 vs. 32%). A greater percentage of sperm donors compared with oocyte donors were curious about their own fertility (24 vs. 9%), and they also believed that they were contributing what they regarded as their own good genes to other couples (45 vs. 20%). Prior to donation, potential sperm donors were more ambivalent towards donating than were oocyte donors (39 and 21%, p < 0.001). The motives to donate gametes are mainly altruistic. We conclude that men and women differ in their view towards donating gametes. Sperm donors had a higher degree of ambivalent feelings towards donation than oocyte donors. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Integrating Pregnancy Ambivalence and Effectiveness in Contraceptive Choice.

PubMed

Sundstrom, Beth; Ferrara, Merissa; DeMaria, Andrea L; Baker-Whitcomb, Annalise; Payne, Jackelyn B

2017-07-01

Approximately 70% of pregnancies among young unmarried women living in the United States are unintended. Unintended pregnancy results in negative health and economic outcomes for infants, children, women, and families. Further research into the decision-making process of contraceptive selection is needed to meet young women's contraceptive needs in the United States. Overall, 53 women ages 18-24 years completed in-depth qualitative interviews. Researchers used analytical techniques from grounded theory and HyperRESEARCH 3.5.2 qualitative data analysis software to identify emergent themes. Problematic integration theory provided a theoretical lens to identify young women's probabilistic and evaluative orientations toward contraception. Researchers identified two profound values at stake to participants regarding their contraceptive decisions: avoiding pregnancy in the present, and protecting future fertility. Participants resisted long-acting reversible contraception (LARC) methods (e.g., the intrauterine device and the implant) due to concerns about safety and fears about infertility. Participants experienced ambivalence toward the idea of pregnancy, which complicated contraceptive decisions, especially regarding long-term methods. Uncertainty led participants to rationalize their use of less effective methods and reduced information seeking. Findings from this study offer practical suggestions for practitioners and health communication campaign planners. Contraceptive access campaigns should focus on the effectiveness, safety, and convenience of LARC methods. Messages should help young women make contraceptive choices that better fit their needs in order to reduce unintended pregnancy.

Provider ambivalence about using forensic medical evaluation to respond to child abuse: A content and discourse analysis.

PubMed

Morris, Marian; Rivaux, Stephanie; Faulkner, Monica

2017-03-01

Forensic medical evaluation rates for child abuse victims in Texas are low relative to national rates. In exploring reasons, researchers collected quantitative and qualitative interview and focus group data from multidisciplinary child abuse response team members across the state. This paper presents results of a secondary analysis of (N=19) health care providers' interview and focus group transcripts, looking specifically at experiences with conducting forensic evaluations - thoughts, struggles, and ethical issues. The analysis was conducted from a critical realist perspective using content and discourse analysis. A theme of ambivalence was identified and explored. Three discursive themes were identified: ambivalence about the legal role, the health care role, and about unintended outcomes of evaluations. Extra-discursive elements related to the physical body, resource distribution, and funding policy were examined for their interaction with discursive patterns. Implications of findings include addressing issues in the current approach to responding to child abuse (e.g., uniting around common definitions of abuse; refining parameters for when FME is helpful; shoring up material resources for the abuse response infrastructure) and considering modification of providers' roles and activities relative to forensic work (e.g., deploying providers for prevention activities versus reactive activities). Copyright © 2017 Elsevier Ltd. All rights reserved.

Student Satisfaction with Online Learning in the Presence of Ambivalence: Looking for the Will-o'-the-Wisp

ERIC Educational Resources Information Center

Dziuban, Charles; Moskal, Patsy; Kramer, Lauren; Thompson, Jessica

2013-01-01

The authors contend that ambivalence students feel toward online courses modifies the dimensionality by which they evaluate their learning experiences. The data from this study show that as student ambivalence increases, so do the number of elements they use to evaluate their courses. As the student view of a course becomes more complex those…

Associations of Perceived Norms With Intentions to Learn Genomic Sequencing Results: Roles for Attitudes and Ambivalence

PubMed Central

Reid, Allecia E.; Taber, Jennifer M.; Ferrer, Rebecca A.; Biesecker, Barbara B.; Lewis, Katie L.; Biesecker, Leslie G.; Klein, William M. P.

2018-01-01

Objective Genomic sequencing is becoming increasingly accessible, highlighting the need to understand the social and psychological factors that drive interest in receiving testing results. These decisions may depend on perceived descriptive norms (how most others behave) and injunctive norms (what is approved of by others). We predicted that descriptive norms would be directly associated with intentions to learn genomic sequencing results, whereas injunctive norms would be associated indirectly, via attitudes. These differential associations with intentions versus attitudes were hypothesized to be strongest when individuals held ambivalent attitudes toward obtaining results. Methods Participants enrolled in a genomic sequencing trial (n=372) reported intentions to learn medically actionable, non-medically actionable, and carrier sequencing results. Descriptive norms items referenced other study participants. Injunctive norms were analyzed separately for close friends and family members. Attitudes, attitudinal ambivalence, and sociodemographic covariates were also assessed. Results In structural equation models, both descriptive norms and friend injunctive norms were associated with intentions to receive all sequencing results (ps<.004). Attitudes consistently mediated all friend injunctive norms-intentions associations, but not the descriptive norms-intentions associations. Attitudinal ambivalence moderated the association between friend injunctive norms (p≤.001), but not descriptive norms (p=.16), and attitudes. Injunctive norms were significantly associated with attitudes when ambivalence was high, but were unrelated when ambivalence was low. Results replicated for family injunctive norms. Conclusions Descriptive and injunctive norms play roles in genomic sequencing decisions. Considering mediators and moderators of these processes enhances ability to optimize use of normative information to support informed decision making. PMID:29745680

Ambivalence toward imposed change: the conflict between dispositional resistance to change and the orientation toward the change agent.

PubMed

Oreg, Shaul; Sverdlik, Noga

2011-03-01

Following an analysis of the concept of "imposed change," we propose 2 factors that jointly contribute to an individual's experience of ambivalence to imposed change. In a secondary analysis of data (N = 172) and 2 field studies (N = 104, N = 89), we showed that individuals' personal orientation toward change interacts with their orientation toward the change agent and yields ambivalence. Specifically, among employees with a positive orientation toward the change agent (i.e., high trust in management, identification with the organization), the relationship between employees' dispositional resistance to change and ambivalence was positive. The opposite pattern emerged among employees with a negative orientation toward the change agent (Studies 2 and 3). Our findings suggest that researchers may have been misinterpreting employees' reactions to change, neglecting the possibility that some may simultaneously hold strong, yet conflicting, views about the change. By accounting for, and predicting, ambivalence, these studies provide a more accurate explanation of employees' responses to change. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Conceptualizing and Measuring Intergenerational Ambivalence in Later Life

PubMed Central

Gilligan, Megan; Pillemer, Karl

2011-01-01

Objectives. In this paper, we explored the association between direct and indirect measures of intergenerational ambivalence, making comparisons by generational position and child’s gender; furthermore, we examined whether these measures were similarly strong predictors of depressive symptoms and positive affect. Methods. Data for the analysis were collected from 254 mothers aged 72–82 years and a randomly selected adult child as part of a larger study of within-family differences in parent–adult child relations. Results. The findings provided evidence that direct and indirect measures were strongly associated among mothers but only weakly associated among adult children, particularly sons. The two measures were similarly strong predictors of mothers’, but not children’s, depressive symptoms and positive affect. The most pronounced differences in congruence between direct and indirect measures were found when comparing mothers and sons. Discussion. The analyses presented here suggest that direct and indirect measures of intergenerational ambivalence may not be tapping the same underlying construct, particularly in the case of adult children and especially sons. Furthermore, direct measures may have an advantage over indirect measures when including sons in the study design. We conclude that direct and indirect measures cannot be used interchangeably across the combination of generation and gender. PMID:22002969

Avoidant/ambivalent attachment style as a mediator between abusive childhood experiences and adult relationship difficulties.

PubMed

McCarthy, G; Taylor, A

1999-03-01

The role of attachment style, self-esteem, and relationship attributions as possible mediators between abusive childhood experiences and difficulties in establishing supportive love relationships in adulthood were investigated in a sample of women known to be at risk of experiencing relationship problems. Measures of child abuse, the quality of love relationships, and the three potential mediators were made concurrently in adulthood. Participants who had experienced child abuse were found to be six times more likely to be experiencing difficulties in the domain of adult love relationships than those who had not. Self-esteem and relationship attributions were not found to be related to child abuse. When both child abuse and avoidant/ambivalent attachment style were considered together avoidant/ambivalent attachment style, but not child abuse, was found to be related to relationship difficulties. These findings indicate that avoidant/ambivalent attachment style, but not self-esteem and relationship attributions, is a mediating factor in the route from child abuse to adult relationship abilities.

Self-Efficacy for Pain Communication Moderates the Relation Between Ambivalence Over Emotional Expression and Pain Catastrophizing Among Patients With Osteoarthritis.

PubMed

Van Denburg, Alyssa N; Shelby, Rebecca A; Caldwell, David S; O'Sullivan, Madeline L; Keefe, Francis J

2018-04-06

Pain catastrophizing (ie, the tendency to focus on and magnify pain sensations and feel helpless in the face of pain) is one of the most important and consistent psychological predictors of the pain experience. The present study examined, in 60 patients with osteoarthritis pain who were married or partnered: 1) the degree to which ambivalence over emotional expression and negative network orientation were associated with pain catastrophizing, and 2) whether self-efficacy for pain communication moderated these relations. Hierarchical multiple linear regression analyses revealed a significant main effect for the association between ambivalence over emotional expression and pain catastrophizing; as ambivalence over emotional expression increased, the degree of pain catastrophizing increased. In addition, the interaction between ambivalence over emotional expression and self-efficacy for pain communication was significant, such that as self-efficacy for pain communication increased, the association between ambivalence over emotional expression and pain catastrophizing became weaker. Negative network orientation was not significantly associated with pain catastrophizing. Findings suggest that higher levels of self-efficacy for pain communication may help weaken the effects of ambivalence over emotional expression on pain catastrophizing. In light of these results, patients may benefit from interventions that target pain communication processes and emotion regulation. This article examines interpersonal processes involved in pain catastrophizing. This study has the potential to lead to better understanding of maladaptive pain coping strategies and possibly better prevention and treatment strategies. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

NGSS, Disposability, and the Ambivalence of Science in/under Neoliberalism

ERIC Educational Resources Information Center

Weinstein, Matthew

2017-01-01

This paper explores the ambivalence of the Next Generation Science Standards (NGSS) and its Framework towards neoliberal governance. The paper examines the ways that the NGSS serves as a mechanism within neoliberal governance: in its production of disposable populations through testing and through the infusion of engineering throughout the NGSS to…

Ambivalence in pregnancy intentions: The effect of quality of care and context among a cohort of women attending family planning clinics in Kenya.

PubMed

Wekesa, Eliud; Askew, Ian; Abuya, Timothy

2018-01-01

Ambivalence in pregnancy intentions is well-documented in sub-Saharan African (SSA) settings and has been associated with inconsistent use of contraception, thereby exposing women using contraception to the possibility of unintended pregnancies. A better understanding of the potential role for client counseling interventions in enabling women to achieve their pregnancy intentions is essential for aiding program efforts to reduce unintended pregnancies. To measure ambivalence in pregnancy intentions longitudinally and determine its association with the quality of care received, controlling for demographic, socio-economic and contextual factors among a cohort of family planning (FP) clients in Kenya. This paper uses data drawn from a prospective cohort study of FP clients to investigate the relationship between the quality of care received during FP service delivery and the decisiveness of their pregnancy intentions over time. The study tests the hypothesis that higher quality of care enables women to be less ambivalent about their pregnancy intentions. Binary logistic regression with random effects and multinomial logistic regression were used to assess the predictive effect of the quality of care received by a woman on the decisiveness or ambivalence of her pregnancy intentions, and on any shifts in ambivalence over time, controlling for background characteristics. The study recruited 1,957 women aged 15-49 years attending twelve family planning clinics in four counties in Central Kenya; of these, 1,053 women were observed for four rounds of data collection over a period of 24 months and form the sample for analysis. A substantial proportion (43%) of women expressed ambivalence about their intentions to become pregnant at some point during the study period, while over half (57%) remained unequivocal throughout the study. Almost one third of women (31%) shifted from being unequivocal to ambivalent and 12% shifted from ambivalence to being unequivocal. Women

I Am Aware of My Inconsistencies but Can Tolerate Them: The Effect of High Quality Listening on Speakers' Attitude Ambivalence.

PubMed

Itzchakov, Guy; Kluger, Avraham N; Castro, Dotan R

2017-01-01

We examined how listeners characterized by empathy and a non-judgmental approach affect speakers' attitude structure. We hypothesized that high quality listening decreases speakers' social anxiety, which in turn reduces defensive processing. This reduction in defensive processing was hypothesized to result in an awareness of contradictions (increased objective-attitude ambivalence), and decreased attitude extremity. Moreover, we hypothesized that experiencing high quality listening would enable speakers to tolerate contradictory responses, such that listening would attenuate the association between objective- and subjective-attitude ambivalence. We obtained consistent support for our hypotheses across four laboratory experiments that manipulated listening experience in different ways on a range of attitude topics. The effects of listening on objective-attitude ambivalence were stronger for higher dispositional social anxiety and initial objective-attitude ambivalence (Study 4). Overall, the results suggest that speakers' attitude structure can be changed by a heretofore unexplored interpersonal variable: merely providing high quality listening.

Solidarity-conflict and ambivalence: testing two conceptual frameworks and their impact on quality of life for older family members.

PubMed

Lowenstein, Ariela

2007-03-01

The purpose of this study was to test empirically two major conceptualizations of parent-child relations in later adulthood-intergenerational solidarity-conflict and ambivalence paradigms-and their predictive validity on elders' quality of life using comparative cross-national data. Data were from a sample of 2,064 elders (aged 75 and older) from the five-country OASIS study (Old Age and Autonomy: The Role of Service Systems and Intergenerational Family Solidarity; Norway, England, Germany, Spain, and Israel). Multivariate and block-recursive regression models estimated the predictivity of the two conceptualizations of family dynamics on quality of life controlling for country, personal characteristics, and activity of daily living functioning. Descriptive analyses indicated that family solidarity, especially the affective/cognitive component (called Solidarity A), was high in all five countries, whereas conflict and ambivalence were low. When I entered all three constructs into the regression Solidarity A, reciprocal intergenerational support and ambivalence predicted quality of life. Controlling for activity of daily living functioning, socioeconomics status, and country, intergenerational relations had only a weak explanatory power, and personal resources explained most of the variance. The data suggest that the three constructs exist simultaneously but in varying combinations, confirming that in cross-cultural contexts family cohesion predominates, albeit with low degrees of conflict and ambivalence. The solidarity construct evidenced relatively robust measurement. More work is required to enhance the ambivalence measurement.

A tainted trade? Moral ambivalence and legitimation work in the private security industry.

PubMed

Thumala, Angélica; Goold, Benjamin; Loader, Ian

2011-06-01

The private security industry is often represented - and typically represents itself - as an expanding business, confident of its place in the world and sure of its ability to meet a rising demand for security. But closer inspection of the ways in which industry players talk about its past, present and future suggests that this self-promotion is accompanied by unease about the industry's condition and legitimacy. In this paper, we analyse the self-understandings of those who sell security - as revealed in interviews conducted with key industry players and in a range of trade materials - in order to highlight and dissect the constitutive elements of this ambivalence. This analysis begins by describing the reputational problems that are currently thought to beset the industry and the underlying fears about its status and worth that these difficulties disclose. We then examine how security players seek to legitimate the industry using various narratives of professionalization. Four such narratives are identified - regulation, education, association and borrowing - each of which seeks to justify private security and enhance the industry's social worth. What is striking about these legitimation claims is that they tend not to justify the selling of security in market terms. In conclusion we ask why this is the case and argue that market justifications are 'closed-off' by a moral ambivalence that attaches to an industry trading in products which cannot guarantee to deliver the condition that its consumers crave. © London School of Economics and Political Science 2011.

Intimate Partner Violence and Controlling Behavior Among Male Same-Sex Relationships in China: Relationship With Ambivalent Sexism.

PubMed

Li, Diandian; Zheng, Lijun

2017-08-01

In this study, we examined intimate partner violence (IPV), cold violence, and controlling behaviors in male same-sex relationships in China, with a focus on the characteristics of IPV and controlling behaviors, and their relationships with ambivalent sexism. IPV was categorized as psychological aggression, physical injury, physical assault, and sexual coercion and was measured using the revised Conflict Tactics Scales (CTS2), an eight-item scale measuring cold violence that was designed specifically for this study. Controlling behaviors were measured using a 34-item scale that was designed for this study, and sexist attitudes toward women and men were assessed using the short forms of the Ambivalent Sexism Inventory (ASI) and the Ambivalence toward Men Inventory (AMI), respectively. Participants ( N = 272) reported instances of perpetration of or victimization by IPV and controlling behaviors within the past 6 months and indicated ambivalent sexism (hostile attitude toward men and women and benevolent attitude toward men and women [HM, HS, BM, and BS, respectively]). Almost 47.1% of the participants reported an experience of IPV, and the prevalence of cold violence and controlling behaviors was found to be 65.1% and 80.5%, respectively. Psychological aggression was the most common, followed sequentially by sexual coercion, physical assault, and injury in present study. We found a strong association between perpetration and victimization and that different forms of violence tend to co-occur in both IPV and controlling behaviors. As predicted, ambivalent sexism was positively correlated with IPV and controlling behaviors, specifically HS and HM. The results indicated the high prevalence of IPV and controlling behaviors among male same-sex relationships, and sexism contributing to this high prevalence.

Interpersonal ambivalence in obsessive-compulsive disorder.

PubMed

Moritz, Steffen; Niemeyer, Helen; Hottenrott, Birgit; Schilling, Lisa; Spitzer, Carsten

2013-10-01

The social attitudes and interpersonal relationships of patients with obsessive-compulsive disorder (OCD) are subject to a longstanding controversy. Whereas cognitive-behavioural researchers emphasize exaggerated pro-social attitudes in OCD like inflated responsibility and worry for other people (especially significant others), dynamic theories traditionally focus on anti-social attitudes such as latent aggression and hostility. In two recent studies, we gathered support not only for a co-existence of these seemingly opposing attitudes in OCD, but also for a functional connection: inflated responsibility in part appears to serve as a coping strategy (or “defense”) against negative interpersonal feelings. In the present study, we tested a shortened version of the Responsibility and Interpersonal Behaviours and Attitudes Questionnaire (RIBAQ-R). The scale was administered to 34 participants with OCD and 34 healthy controls. The questionnaire concurrently measures pro-social and anti-social interpersonal attitudes across three subscales. In line with our prior studies, patients displayed higher scores on both exaggerated pro-social attitudes (e.g. “I suffer from a strict conscience concerning my relatives”) as well as latent aggression (e.g. “Sometimes I would like to harm strangers on the street“) and suspiciousness/distrust (e.g. “I cannot even trust my own family”). A total of 59% of the patients but only 12% of the healthy controls showed marked interpersonal ambivalence (defined as scores higher than one standard deviation from the mean of the nonclinical controls on both the prosocial and at least one of the two anti-social subscales). The study asserts high interpersonal ambivalence in OCD. Further research is required to pinpoint both the dynamic and causal links between opposing interpersonal styles. Normalization and social competence training may prove beneficial to resolve the apparent problems of patients with OCD regarding anger

The effects of ambivalent fertility desires on pregnancy risk in young women in Michigan, United States

PubMed Central

Miller, Warren B.; Barber, Jennifer S.; Gatny, Heather H.

2012-01-01

Many different definitions of the construct of motivational ambivalence have appeared in the literature on reproductive health. Using a theoretical framework in which motivational ambivalence is defined as an interaction between positive and negative pregnancy desires, we propose two hypotheses. The first is that positive and negative pregnancy desires independently predict the risk of an unplanned pregnancy. The second is that ambivalence and three related constructs that are also based on the interaction between positive and negative desires are each important predictors of pregnancy risk. We use weekly journal data collected from a U.S. sample of 1,003 women aged 18–19 years and conduct hazard model analysis to test our hypotheses. Using both dummy and continuous predictors, we report results that confirm both hypotheses. The proposed interaction framework has demonstrated validity, compares favorably with previously reported alternative approaches, and incorporates a set of constructs that have potential importance for further research directed at the prevention of unplanned pregnancy. PMID:23234316

C-metric solution for conformal gravity with a conformally coupled scalar field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meng, Kun, E-mail: mengkun@tjpu.edu.cn; Zhao, Liu, E-mail: lzhao@nankai.edu.cn

The C-metric solution of conformal gravity with a conformally coupled scalar field is presented. The solution belongs to the class of Petrov type D spacetimes and is conformal to the standard AdS C-metric appeared in vacuum Einstein gravity. For all parameter ranges, we identify some of the physically interesting static regions and the corresponding coordinate ranges. The solution may contain a black hole event horizon, an acceleration horizon, either of which may be cut by the conformal infinity or be hidden behind the conformal infinity. Since the model is conformally invariant, we also discussed the possible effects of the conformalmore » gauge choices on the structure of the spacetime.« less

Ambivalent stereotypes of nurses and physicians: impact on students' attitude toward interprofessional education.

PubMed

Sollami, Alfonso; Caricati, Luca; Mancini, Tiziana

2015-03-13

Nurse-physician stereotypes have been proposed as a factor hindering interprofessional collaboration among practitioners and interprofessional learning among nursing and medical students. Using socio-psychological theories about ambivalent stereotypes, the present work aimed to analyse: a) the content of nurse and physician stereotypes held by nursing and medical students and b) the role of auto-stereotype on students' attitude toward interprofessional education (IPE).  Methods. A cross-sectional on-line survey was adopted and a questionnaire was emailed to 205 nursing students and 151 medical students attending an Italian university. Nursing and medical students shared the stereotypical belief that nurses are warmer but less competent than physicians. Nurses and physicians were basically depicted with ambivalent stereotypes: nurses were seen as communal, socially competent and caring but less competent, not agentic and less autonomous, while physicians were seen as agentic, competent and autonomous, but less communal, less collectivist and less socially competent. Moreover, a professional stereotypical image impacted the students' attitude toward IPE. More precisely, when nurses and physicians were seen with classic ambivalent stereotypes, both nursing and medical students were less favourable towards interprofessional education programmes. The content of professional stereotypes of healthcare students was still linked to classical views of nurses as caring and physicians as curing. This seemed to limit students' attitude and intention to be engaged in IPE.

Ambivalent Sexism and Attitudes toward Wife Abuse in Turkey and Brazil

ERIC Educational Resources Information Center

Glick, Peter; Sakalli-Ugurlu, Nuray; Ferreira, Maria Cristina; de Souza, Marcos Aguiar

2002-01-01

Men and women in Turkey and Brazil completed the Ambivalent Sexism Inventory (Glick & Fiske, 1996) and measures of attitudes about wife abuse. In both nations hostile sexism (HS) and benevolent sexism (BS) positively correlated with attitudes that legitimize abuse. Regression analyses revealed that HS accounted for unique variance, but BS…

Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization

PubMed Central

2018-01-01

Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that bypasses current limitations in conformational sampling and extensively profiles the free energy landscape of peptidic macrocycles in solution. We perform accelerated molecular dynamics simulations to capture a diverse conformational ensemble. By applying an energetic cutoff, followed by geometric clustering, we demonstrate the striking robustness and efficiency of the approach in identifying highly populated conformational states of cyclic peptides. The resulting structural and thermodynamic information is benchmarked against interproton distances from NMR experiments and conformational states identified by X-ray crystallography. Using three different model systems of varying size and flexibility, we show that the method reliably reproduces experimentally determined structural ensembles and is capable of identifying key conformational states that include the bioactive conformation. Thus, the described approach is a robust method to generate conformations of peptidic macrocycles and holds promise for structure-based drug design. PMID:29652495

Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization.

PubMed

Kamenik, Anna S; Lessel, Uta; Fuchs, Julian E; Fox, Thomas; Liedl, Klaus R

2018-05-29

Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that bypasses current limitations in conformational sampling and extensively profiles the free energy landscape of peptidic macrocycles in solution. We perform accelerated molecular dynamics simulations to capture a diverse conformational ensemble. By applying an energetic cutoff, followed by geometric clustering, we demonstrate the striking robustness and efficiency of the approach in identifying highly populated conformational states of cyclic peptides. The resulting structural and thermodynamic information is benchmarked against interproton distances from NMR experiments and conformational states identified by X-ray crystallography. Using three different model systems of varying size and flexibility, we show that the method reliably reproduces experimentally determined structural ensembles and is capable of identifying key conformational states that include the bioactive conformation. Thus, the described approach is a robust method to generate conformations of peptidic macrocycles and holds promise for structure-based drug design.

Tensions in the Parent and Adult Child Relationship: Links to Solidarity and Ambivalence

PubMed Central

Birditt, Kira S.; Miller, Laura M.; Fingerman, Karen L.; Lefkowitz, Eva S.

2009-01-01

Tensions are normative in the parent and adult child relationship, but there is little research on the topics that cause the most tension or whether tensions are associated with overall relationship quality. Adult sons and daughters, aged 22 to 49, and their mothers and fathers (N = 158 families, 474 individuals) reported the intensity of different tension topics and relationship quality (solidarity and ambivalence) with one another. Tensions varied between and within families by generation, gender and age of offspring. In comparison to tensions regarding individual issues, tensions regarding the relationship were associated with lower affective solidarity and greater ambivalence. Findings are consistent with the developmental schism hypothesis, which indicates that parent-child tensions are common and are the result of discrepancies in developmental needs which vary by generation, gender, and age. PMID:19485648

ConformRank: A conformity-based rank for finding top-k influential users

NASA Astrophysics Data System (ADS)

Wang, Qiyao; Jin, Yuehui; Cheng, Shiduan; Yang, Tan

2017-05-01

Finding influential users is a hot topic in social networks. For example, advertisers identify influential users to make a successful campaign. Retweeters forward messages from original users, who originally publish messages. This action is referred to as retweeting. Retweeting behaviors generate influence. Original users have influence on retweeters. Whether retweeters keep the same sentiment as original users is taken into consideration in this study. Influence is calculated based on conformity from emotional perspective after retweeting. A conformity-based algorithm, called ConformRank, is proposed to find top-k influential users, who make the most users keep the same sentiment after retweeting messages. Emotional conformity is introduced to denote how users conform to original users from the emotional perspective. Conforming weights are introduced to denote how two users keep the same sentiment after retweeting messages. Emotional conformity is applied for users and conforming weights are used for relations. Experiments were conducted on Sina Weibo. Experimental results show that users have larger influence when they publish positive messages.

Ambivalent sexism, attitudes towards menstruation and menstrual cycle-related symptoms.

PubMed

Marván, Ma Luisa; Vázquez-Toboada, Rocío; Chrisler, Joan C

2014-08-01

The objective of the present study was to investigate the relationship between ambivalent sexism and beliefs and attitudes towards menstruation, and, in turn, to study the influence of these variables on menstrual cycle-related symptoms. One hundred and six Mexican women completed the Ambivalent Sexism Inventory, the Beliefs about and Attitudes toward Menstruation Questionnaire and the Menstrual Distress Questionnaire. The higher scores on benevolent sexism were associated with the most positive attitudes towards menstruation and also with the belief that a menstruating woman should or should not do some activities and that menstruation keeps women from their daily activities. The higher scores on hostile sexism were associated with rejection of menstruation as well as with feelings of embarrassment about it. Beliefs about and attitudes towards menstruation predicted menstrual cycle-related symptoms related to negative affect, impaired concentration and behavioural changes, but did not predict somatic symptoms. These results will be useful to health professionals and advocates who want to change the negative expectations and stereotypes of premenstrual and menstrual women and reduce the sexism and negative attitudes towards women that are evident in Mexican culture. © 2013 International Union of Psychological Science.

Free-energy landscape, principal component analysis, and structural clustering to identify representative conformations from molecular dynamics simulations: the myoglobin case.

PubMed

Papaleo, Elena; Mereghetti, Paolo; Fantucci, Piercarlo; Grandori, Rita; De Gioia, Luca

2009-01-01

Several molecular dynamics (MD) simulations were used to sample conformations in the neighborhood of the native structure of holo-myoglobin (holo-Mb), collecting trajectories spanning 0.22 micros at 300 K. Principal component (PCA) and free-energy landscape (FEL) analyses, integrated by cluster analysis, which was performed considering the position and structures of the individual helices of the globin fold, were carried out. The coherence between the different structural clusters and the basins of the FEL, together with the convergence of parameters derived by PCA indicates that an accurate description of the Mb conformational space around the native state was achieved by multiple MD trajectories spanning at least 0.14 micros. The integration of FEL, PCA, and structural clustering was shown to be a very useful approach to gain an overall view of the conformational landscape accessible to a protein and to identify representative protein substates. This method could be also used to investigate the conformational and dynamical properties of Mb apo-, mutant, or delete versions, in which greater conformational variability is expected and, therefore identification of representative substates from the simulations is relevant to disclose structure-function relationship.

Ambivalent sexism: a tool for understanding and improving gender relations in organizations.

PubMed

Zakrisson, Ingrid; Anderzén, Marie; Lenell, Fredrik; Sandelin, Håkan

2012-02-01

This study tested predictions regarding ambivalent sexism, previously studied cross-culturally, here "within-culturally", between groups from different organizational settings. Based on three samples (334 adults in general, 744 industrial employees, and 189 high school students), completing a Swedish version of the Ambivalent Sexism Inventory (ASI), the results revealed that men scored higher on hostile and benevolent sexism than women, and high school students scored higher than both adult samples on both forms of sexism. The results generally confirmed the predictions; the gender gap in benevolent sexism decreased as a function of increasing levels of general sexism and the correlation between hostile and benevolent sexism decreased with higher levels of general sexism. In fact, the groups scoring highest on general sexism displayed significant negative correlations indicating a polarized ideology of women among these groups. Implications, both theoretical and practical, derived from these results are discussed. © 2011 The Authors. Scandinavian Journal of Psychology © 2011 The Scandinavian Psychological Associations.

Identifying and correcting non-Markov states in peptide conformational dynamics

NASA Astrophysics Data System (ADS)

Nerukh, Dmitry; Jensen, Christian H.; Glen, Robert C.

2010-02-01

Conformational transitions in proteins define their biological activity and can be investigated in detail using the Markov state model. The fundamental assumption on the transitions between the states, their Markov property, is critical in this framework. We test this assumption by analyzing the transitions obtained directly from the dynamics of a molecular dynamics simulated peptide valine-proline-alanine-leucine and states defined phenomenologically using clustering in dihedral space. We find that the transitions are Markovian at the time scale of ≈50 ps and longer. However, at the time scale of 30-40 ps the dynamics loses its Markov property. Our methodology reveals the mechanism that leads to non-Markov behavior. It also provides a way of regrouping the conformations into new states that now possess the required Markov property of their dynamics.

Harsh, inconsistent parental discipline and romantic relationships: mediating processes of behavioral problems and ambivalence.

PubMed

Surjadi, Florensia F; Lorenz, Frederick O; Conger, Rand D; Wickrama, K A S

2013-10-01

According to the Development of Early Adult Romantic Relationships (DEARR) model (Bryant, C. M., & Conger, R. D. [2002]. Conger, R. D., Cui, M., Bryant, C. M., & Elder, G. H., Jr. [2000] interactional characteristics in the family of origin influence early adult romantic relationships by promoting or inhibiting the development of interpersonal competencies that contribute to relationship success in young adulthood. The present study uses the DEARR model as a general framework to help examine the long-term link between parental discipline practices in adolescence and young adult's interactions in the early years of marriage or cohabitation. Using prospective data from 288 target participants, their families, and their romantic partner, beginning when the targets were adolescents and continuing up to the fifth year of their marital or cohabiting relationships, we found empirical support for the DEARR model. Parental discipline practices in adolescence were associated with romantic relationship quality during the early years of marriage or cohabitation through processes in late adolescence and young adulthood. Specifically, harsh and inconsistent discipline practices were associated with greater attitudinal ambivalence toward parents in adolescence. Inconsistent discipline was also associated with higher risks of externalizing problems during late adolescence years. Externalizing problems and ambivalence toward parents predicted poorer relationship quality through aggressive behaviors and ambivalence toward a romantic partner during the early years of marriage or cohabitation. Implications for practitioners working with couples and families are discussed.

Identifying Outpatients with Entrenched Suicidal Ideation Following Hospitalization

ERIC Educational Resources Information Center

O'Connor, Stephen S.; Jobes, David A.; Comtois, Katherine Anne; Atkins, David C.; Janis, Karin; Chessen, Chloe E.; Landes, Sara J.

2012-01-01

The purpose of this study was to identify outpatients who experience entrenched suicidal ideation following inpatient psychiatric hospitalization. Our findings suggest that the use of a suicidal ambivalence index score was helpful at discriminating those who reported significantly greater ratings of suicidal ideation across a 1-year period of…

The positive emotions that facilitate the fulfillment of needs may not be positive emotions at all: the role of ambivalence.

PubMed

Moss, Simon A; Wilson, Samuel G

2015-01-01

According to some scholars, if individuals experience over three times as many positive emotions as negative emotions, they are more likely to thrive. We contend, however, that perhaps positive and negative emotions that overlap in time are likely to enhance wellbeing. Specifically, if positive and negative emotions are experienced simultaneously rather than separately-called ambivalent emotions-the fundamental needs of individuals are fulfilled more frequently. Considerable evidence supports this perspective. First, many emotions that enhance wellbeing, although classified as positive, also coincide with negative feelings. Second, ambivalent emotions, rather than positive or negative emotions separately, facilitate creativity and resilience. Third, ambivalent emotions activate distinct cognitive systems that enable individuals to form attainable goals, refine their skills, and enhance their relationships. Copyright © 2015 Elsevier Inc. All rights reserved.

Mothers continuing bonds and ambivalence to personal mortality after the death of their child--an interpretative phenomenological analysis.

PubMed

Harper, Mairi; O'Connor, Rory; Dickson, Adele; O'Carroll, Ronan

2011-03-01

The main objective of this study was to identify how bereaved mothers describe their coping strategies in their own words. The literature on parental bereavement is sparse, and the present study aims to add to existing knowledge by eliciting the mothers' experiences covering a wide range of child ages including infants, younger children and adults. Semi-structured interviews were held with 13 bereaved mothers in the UK. Causes of death include accident, illness and suicide. The methodological approach was interpretative phenomenological analysis (IPA). This article reports two inter-related recurrent themes: (1) Continuing the bond with the deceased child and (2) Ambivalence to personal mortality. Participants reported that the relationship with their child was continued in a variety of ways, from tending to the grave and the child's remains, through linking objects or by establishing a symbolic representation of the child within their daily lives. All mothers talked openly about their own mortality, either demonstrating ambivalence about their own death, or expressing clear suicidal ideation. Death was seen as a release from living with the pain of loss. The presence of surviving siblings appeared to moderate suicidal ideation, but mothers expressed concerns about their ability to care adequately for other family members during times of intense grief.

Ambivalence and pregnancy: adolescents' attitudes, contraceptive use and pregnancy.

PubMed

Bruckner, Hannah; Martin, Anne; Bearman, Peter S

2004-01-01

It is often argued that adolescents who become pregnant do not sufficiently appreciate the negative consequences, and that prevention programs should target participants' attitudes toward pregnancy. Data from the first two waves of the National Longitudinal Study of Adolescent Health were used to examine whether 15-19-year-old females' attitudes toward pregnancy influence their contraceptive consistency and their risk of pregnancy. Characteristics and attitudes associated with pregnancy and contraceptive use were assessed using bivariate and multivariate analysis. Twenty percent of female adolescents were defined as having antipregnancy attitudes, 8% as having propregnancy attitudes and 14% as being ambivalent toward pregnancy; the remainder were considered to have mainstream attitudes. Among sexually experienced adolescents, having an attitude toward pregnancy was not associated with risk of pregnancy. However, those who were ambivalent about pregnancy had reduced odds of using contraceptives consistently and inconsistently rather than not practicing contraception at all (odds ratios, 0.5 and 0.4, respectively). Antipregnancy respondents did not differ from proprepregancy respondents in terms of their contraceptive consistency. However, having a positive attitude toward contraception was associated with increased likelihood of inconsistent and consistent contraceptive use compared with nonuse (1.6 and 2.1, respectively). Programs designed to prevent pregnancy need to give young women information about pregnancy and opportunities to discuss the topic so that they form opinions. Furthermore, programs should emphasize positive attitudes toward contraception, because effective contraceptive use is shaped by such attitudes and is strongly associated with reduction of pregnancy risk.

Interactions between Obsessional Symptoms and Interpersonal Ambivalences in Psychodynamic Therapy: An Empirical Case Study

PubMed Central

Cornelis, Shana; Desmet, Mattias; Van Nieuwenhove, Kimberly L. H. D.; Meganck, Reitske; Willemsen, Jochem; Inslegers, Ruth; Feyaerts, Jasper

2017-01-01

The classical symptom specificity hypothesis (Blatt, 1974) particularly associates obsessional symptoms to interpersonal behavior directed at autonomy and separation from others. Cross-sectional group research, however, has yielded inconsistent findings on this predicted association, and a previous empirical case study (Cornelis et al., in press; see Chapter 2) documented obsessional pathology to be rooted in profound ambivalences between autonomous and dependent interpersonal dynamics. Therefore, in the present empirical case study, concrete operationalizations of the classical symptom specificity hypothesis are contrasted to alternative hypotheses based on the observed complexities in Chapter 2. Dynamic associations between obsessional symptoms and interpersonal functioning is further explored, aiming at further contribution to theory building (i.e., through suggestions for potential hypothesis-refinement; Stiles, 2009). Similar to the first empirical case study (Chapter 1), Consensual Qualitative Research for Case studies is used to quantitatively and qualitatively describe the longitudinal, clinical interplay between obsessional symptoms and interpersonal dynamics throughout the process of supportive-expressive psychodynamic therapy. In line with findings from Chapter 1, findings reveal close associations between obsessions and interpersonal dynamics, and therapist interventions focusing on interpersonal conflicts are documented as related to interpersonal and symptomatic alterations. Observations predominantly accord to the ambivalence-hypothesis rather than to the classical symptom specificity hypothesis. Yet, meaningful differences are observed in concrete manifestations of interpersonal ambivalences within significant relationships. Findings are again discussed in light of conceptual and methodological considerations; and limitations and future research indications are addressed. PMID:28649214

Long-Term Influences of Intergenerational Ambivalence on Midlife Parents' Psychological Well-Being

ERIC Educational Resources Information Center

Kiecolt, K. Jill; Blieszner, Rosemary; Savla, Jyoti

2011-01-01

We investigated changes in midlife parents' intergenerational ambivalence toward a focal child and its influence on their psychological well-being over 14 years, as the focal child moved from adolescence into young adulthood. We estimated growth curve models using three waves of data from the National Survey of Families and Households (N = 1,510…

Predeployment Motivation and Ambivalence Among Canadian Forces Augmentees: The Influence of Demographic Factors

DTIC Science & Technology

2003-12-01

consequences (pp. 361-386). Hillsdale, NJ: Erlbaum. 31. Conner, M., Sherlock , K., & Orbell, S. (1998). Psychosocial detreminant5s of ecstasy use in young...donate. Health Psychology, 5, 565-580. 35. Thompson, M. M. & Holmes , J. G., (1996). Ambivalence in Close Relationships: Conflicted cognitions as a

An Ambivalent Community: International African Students in Residence at a South African University

ERIC Educational Resources Information Center

Weber, Everard

2016-01-01

This is a qualitative case study of the experiences and perceptions of South African and especially international, African students living in university residences in South Africa. The concept, community, is used to interpret interview data. This community was characterised by ambivalent social relations: There was discrimination by South Africans…

Social Relationships and Health: Is Feeling Positive, Negative, or Both (Ambivalent) about your Social Ties Related to Telomeres?

PubMed Central

Uchino, Bert N.; Cawthon, Richard M.; Smith, Timothy W.; Light, Kathleen C.; McKenzie, Justin; Carlisle, McKenzie; Gunn, Heather; Birmingham, Wendy; Bowen, Kimberly

2012-01-01

Objective The quality of one’s personal relationships has been linked to morbidity and mortality across different diseases. As a result, it is important to examine more integrative mechanisms that might link relationships across diverse physical health outcomes. In this study, we examine associations between relationships and telomeres which predict general disease risk. These questions are pursued in the context of a more comprehensive model of relationships that highlights the importance of jointly considering positive and negative aspects of social ties. Method 136 individuals from a community sample (ages 48 to 77) completed the social relationships index which allows a determination of relationships that differ in their positive and negative substrates (i.e., ambivalent, supportive, aversive, indifferent). Telomere length was determined from peripheral blood mononuclear cells via quantitative PCR. Results Participants who had a higher number of ambivalent ties in their social networks evidenced shorter telomeres. These results were independent of other relationships types (e.g., supportive), as well as standard control variables (e.g., age, health behaviors, medication use). Gender moderated the links between ambivalent ties and telomere length with these associations seen primarily in women. Follow-up analyses revealed that the links between ambivalent ties and telomeres were primarily due to friendships, parents, and social acquaintances. Conclusions Consistent with epidemiological findings, these data highlight a novel and integrative biological mechanism by which social ties may impact health across diseases, and further suggests the importance of incorporating both positivity and negativity in the study of specific relationships and physical health. PMID:22229928

Recycling and Ambivalence: Quantitative and Qualitative Analyses of Household Recycling among Young Adults

ERIC Educational Resources Information Center

Ojala, Maria

2008-01-01

Theories about ambivalence, as well as quantitative and qualitative empirical approaches, are applied to obtain an understanding of recycling among young adults. A questionnaire was mailed to 422 Swedish young people. Regression analyses showed that a mix of negative emotions (worry) and positive emotions (hope and joy) about the environmental…

Consumer responses to advertising on the Internet: the effect of individual difference on ambivalence and avoidance.

PubMed

Jin, Chang Hyun; Villegas, Jorge

2007-04-01

The purpose of this study was to understand the effect that individual characteristics have on consumer advertising processing under high- and low-interactivity circumstances on the Web. Tests on the relationship between individual differences and advertising responses form the basis of this empirical study on the Web. The results indicated that consumers have a higher tendency to avoid or experience ambivalence about Internet advertisements under low-interactivity circumstances, and attitudinal ambivalence lead to avoidance when responding to advertisements on the Internet. Personality variables are the main factors in consumer decision-making behaviors and Internet characteristics, such as levels of interactivity, can greatly influence the effectiveness of advertising in online environments. Advertising credibility could influence people's consumer attitudes, beliefs, or behaviors over time on the Web.

Mimotopes identify conformational epitopes on parvalbumin, the major fish allergen.

PubMed

Untersmayr, Eva; Szalai, Krisztina; Riemer, Angelika B; Hemmer, Wolfgang; Swoboda, Ines; Hantusch, Brigitte; Schöll, Isabella; Spitzauer, Susanne; Scheiner, Otto; Jarisch, Reinhart; Boltz-Nitulescu, George; Jensen-Jarolim, Erika

2006-03-01

Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate mimotopes, which mimic epitopes on parvalbumin. Parvalbumin-specific IgE was purified from sera of fish-allergic patients and used for screening of a constrained decamer phage library. After four rounds of biopanning using parvalbumin-specific IgE, five phage clones were selected which were specifically recognized by parvalbumin-specific IgE as well as IgG. DNA sequencing and peptide alignment revealed a high degree of sequence similarities between the mimotopes. Interestingly, on the surface of natural parvalbumin three regions could be defined by computational mimotope matching. In accordance, previously defined allergenic peptides of cod parvalbumin highlighted areas in close proximity or overlapping with the mimotope matching sites. From the presented data we conclude that our approach identified conformational epitopes of parvalbumin relevant for IgE and IgG binding. We suggest that these mimotopes are suitable candidates for an epitope-specific immunotherapy of fish-allergic patients.

Conformal Nets II: Conformal Blocks

NASA Astrophysics Data System (ADS)

Bartels, Arthur; Douglas, Christopher L.; Henriques, André

2017-08-01

Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

Convinced, ambivalent or annoyed: Tyrolean ski tourism stakeholders and their perceptions of climate change.

PubMed

Trawöger, Lisa

2014-02-01

Its focus on snow-dependent activities makes Alpine winter tourism especially sensitive to climate change. Stakeholder risk perceptions are a key factor in adaptation to climate change because they fundamentally drive or constrain stakeholder action. This paper examines climate change perceptions of winter tourism stakeholders in Tyrol (Austria). Using a qualitative approach, expert interviews were conducted. Four opinion categories reflecting different attitudes toward climate change issues were identified: convinced planners , annoyed deniers , ambivalent optimists , convinced wait-and-seers . Although the findings generally indicate a growing awareness of climate change, this awareness is mainly limited to perceiving the issue as a global phenomenon. Awareness of regional and branch-specific consequences of climate change that lead to a demand for action could not be identified. Current technical strategies, like snowmaking, are not primarily climate-induced. At present, coping with climate change is not a priority for risk management. The findings point out the importance of gaining and transferring knowledge of regional and branch-specific consequences of climate change in order to induce action at the destination level.

Convinced, ambivalent or annoyed: Tyrolean ski tourism stakeholders and their perceptions of climate change☆

PubMed Central

Trawöger, Lisa

2014-01-01

Its focus on snow-dependent activities makes Alpine winter tourism especially sensitive to climate change. Stakeholder risk perceptions are a key factor in adaptation to climate change because they fundamentally drive or constrain stakeholder action. This paper examines climate change perceptions of winter tourism stakeholders in Tyrol (Austria). Using a qualitative approach, expert interviews were conducted. Four opinion categories reflecting different attitudes toward climate change issues were identified: convinced planners, annoyed deniers, ambivalent optimists, convinced wait-and-seers. Although the findings generally indicate a growing awareness of climate change, this awareness is mainly limited to perceiving the issue as a global phenomenon. Awareness of regional and branch-specific consequences of climate change that lead to a demand for action could not be identified. Current technical strategies, like snowmaking, are not primarily climate-induced. At present, coping with climate change is not a priority for risk management. The findings point out the importance of gaining and transferring knowledge of regional and branch-specific consequences of climate change in order to induce action at the destination level. PMID:27064520

Fabrication challenges associated with conformal optics

NASA Astrophysics Data System (ADS)

Schaefer, John; Eichholtz, Richard A.; Sulzbach, Frank C.

2001-09-01

A conformal optic is typically an optical window that conforms smoothly to the external shape of a system platform to improve aerodynamics. Conformal optics can be on-axis, such as an ogive missile dome, or off-axis, such as in a free form airplane wing. A common example of conformal optics is the automotive head light window that conforms to the body of the car aerodynamics and aesthetics. The unusual shape of conformal optics creates tremendous challenges for design, manufacturing, and testing. This paper will discuss fabrication methods that have been successfully demonstrated to produce conformal missile domes and associated wavefront corrector elements. It will identify challenges foreseen with more complex free-form configurations. Work presented in this paper was directed by the Precision Conformal Optics Consortium (PCOT). PCOT is comprised of both industrial and academic members who teamed to develop and demonstrate conformal optical systems suitable for insertion into future military programs. The consortium was funded under DARPA agreement number MDA972-96-9-08000.

Investigating Identity, Ambivalence, Hybridity: A Bhabhaian Reading of J. M. Coetzee's "Foe" and "Disgrace"

ERIC Educational Resources Information Center

Mostafaee, Jalal

2016-01-01

The present paper seeks to investigate J.M. Coetzee's "Foe" and "Disgrace" in terms of Homi K. Bhabha's concept of Identities/Subjectivities. Homi K. Bhabha is one of the most important contemporary figure in postcolonial studies; he argues that ambivalence is existed at the site of colonial dominance. He argues that…

Reactions driving conformational movements (molecular motors) in gels: conformational and structural chemical kinetics.

PubMed

Otero, Toribio F

2017-01-18

In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (E a ), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. E a , k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.

Stabilizing the boat conformation of cyclohexane rings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dasgupta, S.; Goddard, W.A. III; Moldowan, J.M.

1995-06-21

In calculating the energetics for various conformers of the A, B, and C series of hopanoid hydrocarbons present in mature oil reservoirs, we find that the B series prefers the boat conformation (by 1.3-2.5 kcal/mol) for the D cyclohexane ring. We analyze the structural elements responsible for stabilizing this boat conformation, identify the key features, and illustrate how one might stabilize boat conformations of other systems. 5 refs., 3 figs., 2 tabs.

The role of message frame, perceived risk, and ambivalence in individuals' decisions to become organ donors.

PubMed

Cohen, Elizabeth L

2010-12-01

The decision to become an organ donor involves considering both self-relevant risks and the needs of others. This study applied prospect theory to examine how news exemplar message frames that focus on the possible survival or death of a potential organ transplant recipient affect participants' willingness to become organ donors. Perceived personal risk and ambivalence were examined as moderating variables. Results indicate that risk, rather than ambivalence, played an instrumental role in participants' decisions to donate. Although no main effects or interactions related to message frame emerged in initial analyses, a supplemental analysis revealed an interaction such that there was a modest persuasive advantage for the loss-framed message among low-risk participants. Findings suggest that vivid exemplar message frames, compared to other types of more explicit organ donor appeals, may be associated with unique decisions about organ donation.

Puzzling and ambivalent roles of malarial infections in cancer development and progression.

PubMed

Faure, Eric

2016-12-01

Scientific evidence strongly suggests that parasites are directly or indirectly associated with carcinogenesis in humans. However, studies have also indicated that parasites or their products might confer resistance to tumour growth. Plasmodium protozoa, the causative agents of malaria, exemplify the ambivalent link between parasites and cancer. Positive relationships between malaria and virus-associated cancers are relatively well-documented; for example, malaria can reactivate the Epstein-Barr Virus, which is the known cause of endemic Burkitt lymphoma. Nevertheless, possible anti-tumour properties of malaria have also been reported and, interestingly, this disease has long been thought to be beneficial to patients suffering from cancers. Current knowledge of the potential pro- and anti-cancer roles of malaria suggests that, contrary to other eukaryotic parasites affecting humans, Plasmodium-related cancers are principally lymphoproliferative disorders and attributable to virus reactivation, whereas, similar to other eukaryotic parasites, the anti-tumour effects of malaria are primarily associated with carcinomas and certain sarcomas. Moreover, malarial infection significantly suppresses murine cancer growth by inducing both innate and specific adaptive anti-tumour responses. This review aims to present an update regarding the ambivalent association between malaria and cancer, and further studies may open future pathways to develop novel strategies for anti-cancer therapies.

Ambivalence toward mothers who kill: an examination of 45 U.S. cases of maternal neonaticide.

PubMed

Shelton, Joy Lynn E; Muirhead, Yvonne; Canning, Kathleen E

2010-01-01

Public opinion about neonaticide (the killing of a newborn within the first 24 hours of life) has varied across time and cultures. Some nations have passed legislation on behalf of maternal offenders with the assumption that childbirth, a time of unique biological change, may lead to mental disturbance. The United States, however, makes no such distinction; offenders are prosecuted under general homicide laws. Nevertheless, U.S. courts often consider a mother's emotional and physical condition prior to and during delivery. This study includes 44 female offenders and 45 infant deaths and highlights society's ambivalence toward neonaticide offenders. The authors suggest that this ambivalence may be attributed to: (1) the perception that an offender's emotional and physical turmoil during the birth and homicide reduces her culpability; (2) the sentiment that neonaticide offenders are more "redeemable" than other offenders; and (3) the uncertainty about the personhood of a fetus or newborn. Copyright © 2010 John Wiley & Sons, Ltd.

NGSS, disposability, and the ambivalence of science in/under neoliberalism

NASA Astrophysics Data System (ADS)

Weinstein, Matthew

2017-12-01

This paper explores the ambivalence of the Next Generation Science Standards (NGSS) and its Framework towards neoliberal governance. The paper examines the ways that the NGSS serves as a mechanism within neoliberal governance: in its production of disposable populations through testing and through the infusion of engineering throughout the NGSS to resolve social problems through technical fixes. However, the NGSS, like earlier standards, is reactionary to forces diminishing the power of institutional science (e.g., the AAAS) including neoliberal prioritizing market value over evidence. The NGSS explicitly takes on neoliberal junk science such as the anti-global-warming Heartland Institute.

Poor infant soothability and later insecure-ambivalent attachment: developmental change in phenotypic markers of risk or two measures of the same construct?

PubMed

Mills-Koonce, W Roger; Propper, Cathi B; Barnett, Melissa

2012-04-01

Using data from the Durham Child Health and Development Study (n=148), the current study examines the associations between child and parenting variables at 6 months and child attachment quality at 12 months of age and maternal report of child self regulation at 24 months of age. Child and parent variables predicted distinct forms of insecure attachment relationships. Observations of infant soothability during the reunion session of the Face-to-Face Still Face Paradigm at 6 months differentially predicted children with later insecure-ambivalent attachments from those with secure attachments. Observations of maternal negative intrusiveness at 6 months of age differentially predicted children with insecure-avoidant attachments from those with secure attachments. Maternal sensitivity at 6 months was associated with maternal report of child affective problems at 24 months, but this association was moderated by infant negativity during soothing and later moderated by child attachment quality. Collectively, these results suggest the following two mutually exclusive possibilities regarding infant soothability and later ambivalent attachment quality: either infant soothability is a unique and distinct predictor of later ambivalent attachment quality and this cascade represents a developmental shift in child risk during the first year of life, or that infant soothability following a stressful task at 6 months of age is itself an early indicator of ambivalent attachment behavior with the mother. The data from the current study could not provide differential support for one possibility over the other. Copyright © 2012 Elsevier Inc. All rights reserved.

The symbolic constitution of addiction: language, alienation, ambivalence.

PubMed

Kemp, Ryan

2012-07-01

The author offers an articulation of addiction, via existential-phenomenology and Lacanian psychoanalysis, where it is argued that the addicted subject is constituted via a symbolic structuring evolving from societal practices, laws and the effects of language. Language carries a heritage, which bears on the knowledge and practices of designated subjects and practitioners of that discourse. Addiction, as one particular form of embodied existence and knowledgeable practice, finds expression through the speech and habits of the addict. Addiction, it is argued, is symbolically saturated with ambivalence and alienation. Also the addict is described as the complete modern technocratic subject, consumed by the ideology of consumption. The clinical implications are briefly explored where it is noted that two major approaches to addiction, namely 12-step fellowships and motivational interviewing, both attend to language as a critical component of their treatment approach.

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection

PubMed Central

Maciag, Joseph J.; Mackenzie, Sarah H.; Tucker, Matthew B.; Schipper, Joshua L.; Swartz, Paul; Clark, A. Clay

2016-01-01

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection. PMID:27681633

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.

PubMed

Maciag, Joseph J; Mackenzie, Sarah H; Tucker, Matthew B; Schipper, Joshua L; Swartz, Paul; Clark, A Clay

2016-10-11

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection.

Protein Allostery and Conformational Dynamics.

PubMed

Guo, Jingjing; Zhou, Huan-Xiang

2016-06-08

The functions of many proteins are regulated through allostery, whereby effector binding at a distal site changes the functional activity (e.g., substrate binding affinity or catalytic efficiency) at the active site. Most allosteric studies have focused on thermodynamic properties, in particular, substrate binding affinity. Changes in substrate binding affinity by allosteric effectors have generally been thought to be mediated by conformational transitions of the proteins or, alternatively, by changes in the broadness of the free energy basin of the protein conformational state without shifting the basin minimum position. When effector binding changes the free energy landscape of a protein in conformational space, the change affects not only thermodynamic properties but also dynamic properties, including the amplitudes of motions on different time scales and rates of conformational transitions. Here we assess the roles of conformational dynamics in allosteric regulation. Two cases are highlighted where NMR spectroscopy and molecular dynamics simulation have been used as complementary approaches to identify residues possibly involved in allosteric communication. Perspectives on contentious issues, for example, the relationship between picosecond-nanosecond local and microsecond-millisecond conformational exchange dynamics, are presented.

Characterizing Conformational Dynamics of Proteins Using Evolutionary Couplings.

PubMed

Feng, Jiangyan; Shukla, Diwakar

2018-01-25

Understanding of protein conformational dynamics is essential for elucidating molecular origins of protein structure-function relationship. Traditionally, reaction coordinates, i.e., some functions of protein atom positions and velocities have been used to interpret the complex dynamics of proteins obtained from experimental and computational approaches such as molecular dynamics simulations. However, it is nontrivial to identify the reaction coordinates a priori even for small proteins. Here, we evaluate the power of evolutionary couplings (ECs) to capture protein dynamics by exploring their use as reaction coordinates, which can efficiently guide the sampling of a conformational free energy landscape. We have analyzed 10 diverse proteins and shown that a few ECs are sufficient to characterize complex conformational dynamics of proteins involved in folding and conformational change processes. With the rapid strides in sequencing technology, we expect that ECs could help identify reaction coordinates a priori and enhance the sampling of the slow dynamical process associated with protein folding and conformational change.

Pilot Non-Conformance to Alerting System Commands

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.; Hansman, R. John

1997-01-01

Instances of pilot non-conformance to alerting system commands have been identified in previous studies. Pilot non-conformance changes the final behavior of the system, and therefore may reduce actual performance from that anticipated. A simulator study has examined pilot non-conformance, using the task of collision avoidance during closely spaced parallel approaches as a case study. Consonance between the display and the alerting system was found to significantly improve subject agreement with automatic alerts. Based on these results, a more general discussion of the factors involved in pilot conformance is given, and design guidelines for alerting systems are given.

Partners' ambivalence towards cardiac arrest and hypothermia treatment: a qualitative study.

PubMed

Holm, Marianne S; Norekvål, Tone M; Fålun, Nina; Gjengedal, Eva

2012-01-01

The purpose of this study was to examine the experiences of partners of patients who had cardiac arrest and subsequent hypothermia treatment in an intensive care unit (ICU). Nine in-depth interviews were conducted 5 months to 1 year after hospitalization. The participants were partners of patients who had survived cardiac arrest and had undergone hypothermia treatment without serious brain damage. All the interviews were analysed using Giorgi's phenomenological method. Six main themes emerged from the analysis: (1) terrified by witnessing the cardiac arrest; (2) ambivalence towards the ICU room and the cold body; (3) need for honest and realistic information; (4) anticipating the awakening; (5) social network as support and burden; and (6) the frightening homecoming. The essential structure of the partners' experiences of loved ones' cardiac arrest and hypothermia treatment was characterized by ambivalence; they experienced both fear and relief. There may be a relationship between experiences before entering the ICU and reactions during hypothermia treatment and afterwards. Some partners experienced a feeling of guilt after the resuscitation event, and especially during the awakening phase. After discharge, the partners described feeling anxiety. Nurses play a pivotal role in providing partners with information and in nurturing hope and feelings of security. Partners need to fully understand the reason for hypothermia treatment to enable them to accept the cold body as part of a life-saving process. We recommend follow-up after discharge. This may increase the partners' sense of security and control. © 2012 The Authors. Nursing in Critical Care © 2012 British Association of Critical Care Nurses.

A Dual Process Motivational Model of Ambivalent Sexism and Gender Differences in Romantic Partner Preferences

ERIC Educational Resources Information Center

Sibley, Chris G.; Overall, Nickola C.

2011-01-01

We tested a dual process motivational model of ambivalent sexism and gender differences in intimate partner preferences. Meta-analysis of 32 samples (16 with men, 16 with women; N = 5,459) indicated that Benevolent Sexism (BS) in women was associated with greater preferences for high-resource partners (r = 0.24), whereas Hostile Sexism (HS) in men…

Relationships between Ambivalent Sexism and the Five Moral Foundations in Domestic Violence: Is it a Matter of Fairness and Authority?

PubMed

Vecina, Maria L; Piñuela, Raul

2017-04-03

Ambivalent sexism has served to justify and maintain patriarchy and traditional gender roles characterized by inequality and male domination in the intimate partner violence (IPV) literature; according to the Moral Foundation Theory (MFT) there are two specific moral foundations related to inequality and domination: fairness and authority. We connect these separate fields arguing that sexist attitudes can be related to specific patterns of endorsement of the five moral foundations. Our hypothesis is that ambivalent sexism in men convicted of violence against the partner may be rooted in at least these two moral foundations, and that at least these two moral foundations may also serve to predict intention to change the violent behavior against the partner. Controlling for political orientation, the results show that benevolent sexism correlates positively with the authority foundation; and hostile sexism correlates negatively with the fairness foundation. Both foundations contribute to explaining the two dimensions of ambivalent sexism (benevolent and hostile) and only the fairness foundation predict intention to change the violent behavior against the partner. New treatment approaches could be designed to increase moral concerns about fairness and to reduce moral concerns about authority in people who, at least, have once used violence against their partners.

ANCA: Anharmonic Conformational Analysis of Biomolecular Simulations.

PubMed

Parvatikar, Akash; Vacaliuc, Gabriel S; Ramanathan, Arvind; Chennubhotla, S Chakra

2018-05-08

Anharmonicity in time-dependent conformational fluctuations is noted to be a key feature of functional dynamics of biomolecules. Although anharmonic events are rare, long-timescale (μs-ms and beyond) simulations facilitate probing of such events. We have previously developed quasi-anharmonic analysis to resolve higher-order spatial correlations and characterize anharmonicity in biomolecular simulations. In this article, we have extended this toolbox to resolve higher-order temporal correlations and built a scalable Python package called anharmonic conformational analysis (ANCA). ANCA has modules to: 1) measure anharmonicity in the form of higher-order statistics and its variation as a function of time, 2) output a storyboard representation of the simulations to identify key anharmonic conformational events, and 3) identify putative anharmonic conformational substates and visualization of transitions between these substates. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The Ambivalent Legacy of Dartmouth Five Decades On: What, Now, Should We Teach the English Teachers?

ERIC Educational Resources Information Center

Jones, Jo

2017-01-01

This essay expresses a profoundly ambivalent response to the legacy of Dartmouth, particularly Dixon's "Growth" Model of English. English educators owe a debt to Dixon in terms of innovative pedagogical methods that are part of the daily shapes of tertiary and high school English classes, including the way drama and performance invoke…

Ambivalent journey: Teacher career paths in Oman

NASA Astrophysics Data System (ADS)

Chapman, David W.; Al-Barwani, Thuwayba; Mawali, Fathiya Al; Green, Elizabeth

2012-06-01

This study investigated the career paths of 625 university graduates who prepared to be secondary school teachers in Oman, their assessment of their current work situation, and the extent to which their initial commitment to teaching was related to their subsequent career satisfaction and intention to remain in teaching. While nearly all graduates entered teaching, their decision was marked by ambivalence. Nearly half of the graduates reported being only somewhat or not at all committed to teaching as a career when they graduated. It also appears that initial commitment to teaching operates as an important lens through which teachers view their subsequent careers. Those initially more committed to teaching were more likely to be satisfied with the progress they made in their career, more likely to think that their current teaching position offered them opportunities for advancement, and more likely to want to remain in teaching than were graduates who had a lower initial commitment to teaching. The authors discuss both the theoretical and practical implications of these findings.

How can group experience influence the cue priority? A re-examination of the ambiguity-ambivalence hypothesis.

PubMed

Shimizu, Kazumi; Udagawa, Daisuke

2011-01-01

Since the discovery of the "framing effect" by Kahneman and Tversky, the sensitivity of the "framing effect" - its appearance and in some cases its disappearance - has long been an object of study. However there is little agreement as to the reasons for this sensitivity. The "ambiguity-ambivalence hypothesis" (Wang, 2008) aims to systematically explain the sensitivity of this effect by paying particular attention to people's cue priority: it states that the framing effect occurs when verbal framing is used to compensate for the absence of higher prioritized decision cues. The main purpose of our study is to examine and develop this hypothesis by examining cue priority given differences in people's "group experience." The main result is that the framing effect is absent when the choice problem is presented in a group context that reflects the actual size of the group that the participant has had experience with. Thus, in order to understand the choices that people make in life and death decisions, it is important to incorporate the decision maker's group experience explicitly into the ambiguity-ambivalence hypothesis.

Examining the Psychological Effect of Rape Acknowledgment: The Interaction of Acknowledgment Status and Ambivalent Sexism.

PubMed

Wilson, Laura C; Miller, Katherine E; Leheney, Emma K; Ballman, Alesha D; Scarpa, Angela

2017-07-01

Although the majority of rape survivors do not label their experiences as rape (i.e., unacknowledged rape), the literature is mixed in terms of how this affects survivors' psychological functioning. To elucidate the discrepancies, the present study examined the interaction between rape acknowledgement and ambivalent sexism in relation to depression and posttraumatic stress disorder (PTSD) symptoms. The analyzed sample included 128 female rape survivors who were drawn from a larger college sample of 1,595 participants. The participants completed measures of sexual assault experiences, ambivalent sexism, and depression and PTSD symptoms. The results supported a significant interaction between acknowledgement status and benevolent sexism in relation to both depression and PTSD symptoms. Conversely, the present study failed to find support for an interaction between acknowledgment status and hostile sexism. The clinical implications suggest that rather than seeing acknowledging rape as essential to the recovery process, clinicians should assess for and take into account other factors that may contribute to psychological functioning. Additionally, the findings support that more complex models of trauma recovery should be investigated with the goal of working toward a more comprehensive understanding of the longitudinal process of rape acknowledgment. © 2016 Wiley Periodicals, Inc.

Quantifying polypeptide conformational space: sensitivity to conformation and ensemble definition.

PubMed

Sullivan, David C; Lim, Carmay

2006-08-24

Quantifying the density of conformations over phase space (the conformational distribution) is needed to model important macromolecular processes such as protein folding. In this work, we quantify the conformational distribution for a simple polypeptide (N-mer polyalanine) using the cumulative distribution function (CDF), which gives the probability that two randomly selected conformations are separated by less than a "conformational" distance and whose inverse gives conformation counts as a function of conformational radius. An important finding is that the conformation counts obtained by the CDF inverse depend critically on the assignment of a conformation's distance span and the ensemble (e.g., unfolded state model): varying ensemble and conformation definition (1 --> 2 A) varies the CDF-based conformation counts for Ala(50) from 10(11) to 10(69). In particular, relatively short molecular dynamics (MD) relaxation of Ala(50)'s random-walk ensemble reduces the number of conformers from 10(55) to 10(14) (using a 1 A root-mean-square-deviation radius conformation definition) pointing to potential disconnections in comparing the results from simplified models of unfolded proteins with those from all-atom MD simulations. Explicit waters are found to roughen the landscape considerably. Under some common conformation definitions, the results herein provide (i) an upper limit to the number of accessible conformations that compose unfolded states of proteins, (ii) the optimal clustering radius/conformation radius for counting conformations for a given energy and solvent model, (iii) a means of comparing various studies, and (iv) an assessment of the applicability of random search in protein folding.

Boundary conformal anomalies on hyperbolic spaces and Euclidean balls

NASA Astrophysics Data System (ADS)

Rodriguez-Gomez, Diego; Russo, Jorge G.

2017-12-01

We compute conformal anomalies for conformal field theories with free conformal scalars and massless spin 1/2 fields in hyperbolic space ℍ d and in the ball B^d , for 2≤d≤7. These spaces are related by a conformal transformation. In even dimensional spaces, the conformal anomalies on ℍ2 n and B^{2n} are shown to be identical. In odd dimensional spaces, the conformal anomaly on B^{2n+1} comes from a boundary contribution, which exactly coincides with that of ℍ2 n + 1 provided one identifies the UV short-distance cutoff on B^{2n+1} with the inverse large distance IR cutoff on ℍ2 n + 1, just as prescribed by the conformal map. As an application, we determine, for the first time, the conformal anomaly coefficients multiplying the Euler characteristic of the boundary for scalars and half-spin fields with various boundary conditions in d = 5 and d = 7.

DIY-Bio - economic, epistemological and ethical implications and ambivalences.

PubMed

Keulartz, Jozef; van den Belt, Henk

2016-12-01

Since 2008, we witness the emergence of the Do-It-Yourself Biology movement, a global movement spreading the use of biotechnology beyond traditional academic and industrial institutions and into the lay public. Practitioners include a broad mix of amateurs, enthusiasts, students, and trained scientists. At this moment, the movement counts nearly 50 local groups, mostly in America and Europe, but also increasingly in Asia. Do-It-Yourself Bio represents a direct translation of hacking culture and practicesfrom the realm of computers and software into the realm of genes and cells. Although the movement is still in its infancy, and it is even unclear whether it will ever reach maturity, the contours of a new paradigm of knowledge production are already becoming visible. We will subsequently sketch the economic, the epistemological and the ethical profile of Do-It-Yourself Bio, and discuss its implications and also its ambivalences.

How Can Group Experience Influence the Cue Priority? A Re-Examination of the Ambiguity-Ambivalence Hypothesis

PubMed Central

Shimizu, Kazumi; Udagawa, Daisuke

2011-01-01

Since the discovery of the “framing effect” by Kahneman and Tversky, the sensitivity of the “framing effect” – its appearance and in some cases its disappearance – has long been an object of study. However there is little agreement as to the reasons for this sensitivity. The “ambiguity-ambivalence hypothesis” (Wang, 2008) aims to systematically explain the sensitivity of this effect by paying particular attention to people’s cue priority: it states that the framing effect occurs when verbal framing is used to compensate for the absence of higher prioritized decision cues. The main purpose of our study is to examine and develop this hypothesis by examining cue priority given differences in people’s “group experience.” The main result is that the framing effect is absent when the choice problem is presented in a group context that reflects the actual size of the group that the participant has had experience with. Thus, in order to understand the choices that people make in life and death decisions, it is important to incorporate the decision maker’s group experience explicitly into the ambiguity-ambivalence hypothesis. PMID:22016744

"It Was Fine, if You Wanted to Leave": Educational Ambivalence in a Nova Scotian Coastal Community, 1963-1998

ERIC Educational Resources Information Center

Corbett, Michael

2004-01-01

This article reports on a study of schooling in southwest Nova Scotia. Using Bourdieu's concepts of cultural capital and habitus, I analyze rural men's relationships involving identity, work, place, and schooling to explain continuing high male dropout rates and local traditions of ambivalence and resistance to schooling. I conclude that the…

Predicting bioactive conformations and binding modes of macrocycles

NASA Astrophysics Data System (ADS)

Anighoro, Andrew; de la Vega de León, Antonio; Bajorath, Jürgen

2016-10-01

Macrocyclic compounds experience increasing interest in drug discovery. It is often thought that these large and chemically complex molecules provide promising candidates to address difficult targets and interfere with protein-protein interactions. From a computational viewpoint, these molecules are difficult to treat. For example, flexible docking of macrocyclic compounds is hindered by the limited ability of current docking approaches to optimize conformations of extended ring systems for pose prediction. Herein, we report predictions of bioactive conformations of macrocycles using conformational search and binding modes using docking. Conformational ensembles generated using specialized search technique of about 70 % of the tested macrocycles contained accurate bioactive conformations. However, these conformations were difficult to identify on the basis of conformational energies. Moreover, docking calculations with limited ligand flexibility starting from individual low energy conformations rarely yielded highly accurate binding modes. In about 40 % of the test cases, binding modes were approximated with reasonable accuracy. However, when conformational ensembles were subjected to rigid body docking, an increase in meaningful binding mode predictions to more than 50 % of the test cases was observed. Electrostatic effects did not contribute to these predictions in a positive or negative manner. Rather, achieving shape complementarity at macrocycle-target interfaces was a decisive factor. In summary, a combined computational protocol using pre-computed conformational ensembles of macrocycles as a starting point for docking shows promise in modeling binding modes of macrocyclic compounds.

Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin

NASA Astrophysics Data System (ADS)

Shute, Richard E.; Jackson, David E.; Bycroft, Barrie W.

1989-06-01

The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic β-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3 R-compounds possess notable Gram-positive antibacterial activity and potent β-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain β-lactamase inhibitory activity. Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3 R, and 3 S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3 R and the 3 S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3 R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, `bioactive' conformer for the classical β-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 α-carboxylate functionality is presented.

Raman Spectral Signatures as Conformational Probes of Biomolecules

NASA Astrophysics Data System (ADS)

Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman; Bar, Ilana

2009-06-01

A first application of ionization-loss stimulated Raman spectroscopy (ILSRS) for monitoring the spectral features of four conformers of a gas phase neurotransmitter (2-phenylethylamine) is reported. The Raman spectra of the conformers show bands that uniquely identify the conformational structure of the molecule and are well matched by density functional theory calculations. The measurement of spectral signatures by ILSRS in an extended spectral range, with a relatively convenient laser source, is extremely important, allowing enhanced accessibility to intra- and inter-molecular forces, which are significant in biological structure and activity.

Raman Spectral Signatures as Conformational Probes of Biomolecules

NASA Astrophysics Data System (ADS)

Bar, Ilana; Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman

2009-03-01

A first application of ionization-loss stimulated Raman spectroscopy (ILSRS) monitoring the spectral features of four conformers of a gas phase neurotransmitter (2-phenylethylamine) is reported. The Raman spectra of the conformers show bands that uniquely identify the conformational structure of the molecule and are well matched by density functional theory calculations. The measurement of spectral signatures by ILSRS in an extended spectral range, with a relatively convenient laser source, is extremely important, allowing enhanced accessibility to intra- and inter-molecular forces, which are significant in biological structure and activity.

Conformational Analysis of Free and Bound Retinoic Acid

PubMed Central

Fu, Zheng; Li, Xue; Merz, Kenneth M.

2012-01-01

The conformational profiles of unbound all-trans and 9-cis retinoic acid (RA) have been determined using classical and quantum mechanical calculations. Sixty-six all-trans-RA (ATRA) and forty-eight 9-cis-RA energy minimum conformers were identified via HF/6-31G* geometry optimizations in vacuo. Their relative conformational energies were estimated utilizing the M06, M06-2x and MP2 methods combined with the 6-311+G(d,p), aug-cc-pVDZ and aug-cc-pVTZ basis sets, as well as complete basis set MP2 extrapolations using the latter two basis sets. Single-point energy calculations performed with the M06-2x density functional were found to yield similar results to MP2/CBS for the low-energy retinoic acid conformations. Not unexpectedly, the conformational propensities of retinoic acid were governed by the orientation and arrangement of the torsion angles associated with the polyene tail. We also used previously reported QM/MM X-ray refinement results on four ATRA-protein crystal structures plus one newly refined 9-cis-RA complex (PDB ID 1XDK) in order to investigate the conformational preferences of bound retinoic acid. In the re-refined RA conformers the conjugated double bonds are nearly coplanar, which is consistent with the global minimum identified by the Omega/QM method rather than the corresponding crystallographically determined conformations given in the PDB. Consequently, a 91.3% average reduction of the local strain energy in the gas phase, as well as 92.1% in PCM solvent, was observed using the QM/MM refined structures versus the PDB deposited RA conformations. These results thus demonstrate that our QM/MM X-ray refinement approach can significantly enhance the quality of X-ray crystal structures refined by conventional refinement protocols, thereby providing reliable drug-target structural information for use in structure-based drug discovery applications. PMID:22844234

Discovering Conformational Sub-States Relevant to Protein Function

PubMed Central

Ramanathan, Arvind; Savol, Andrej J.; Langmead, Christopher J.; Agarwal, Pratul K.; Chennubhotla, Chakra S.

2011-01-01

Background Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these sub-states present significant challenges for their identification and characterization. Methods and Findings To overcome these challenges we have developed a new computational technique, quasi-anharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. Conclusions Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function. PMID:21297978

[Temporal ambivalences of aging: Individual patterns of time use in conflict between time wealth and time poverty].

PubMed

Münch, Anne

2016-01-01

Throughout their lives people are confronted with different time resources and demands that change continuously up into old age. With the help of a qualitative interview study the narrative constructions of subjective time experiences as well as individual ways of dealing with time in retirement were investigated. In particular the influences of older persons' experience of time within the dimensions of everyday time and life time were analyzed. In addition, the study focused on potential time conflicts between these two dimensions and the question of how older people deal with the ambivalence between everyday time wealth and biographical time poverty in older age. The results of the interviews with 50 retired men and women (aged 56-91 years) in Germany, which were analyzed with "grounded theory" techniques, indicated that time in retirement does not indeed always run smoothly. In particular, the individual perception of increasing biographical time poverty exerts pressure on the arrangement of activities and daily routine in retirement. The resulting time conflicts are reflected in differential patterns of time use through which older persons try to cope with their ambivalent time experiences.

What can the study of first impressions tell us about attitudinal ambivalence and paranoia in schizophrenia?

PubMed

Trémeau, Fabien; Antonius, Daniel; Todorov, Alexander; Rebani, Yasmina; Ferrari, Kelsey; Lee, Sang Han; Calderone, Daniel; Nolan, Karen A; Butler, Pamela; Malaspina, Dolores; Javitt, Daniel C

2016-04-30

Although social cognition deficits have been associated with schizophrenia, social trait judgments - or first impressions - have rarely been studied. These first impressions, formed immediately after looking at a person's face, have significant social consequences. Eighty-one individuals with schizophrenia or schizoaffective disorder and 62 control subjects rated 30 neutral faces on 10 positive or negative traits: attractive, mean, trustworthy, intelligent, dominant, fun, sociable, aggressive, emotionally stable and weird. Compared to controls, patients gave higher ratings for positive traits as well as for negative traits. Patients also demonstrated more ambivalence in their ratings. Patients who were exhibiting paranoid symptoms assigned higher intensity ratings for positive social traits than non-paranoid patients. Social trait ratings were negatively correlated with everyday problem solving skills in patients. Although patients appeared to form impressions of others in a manner similar to controls, they tended to assign higher scores for both positive and negative traits. This may help explain the social deficits observed in schizophrenia: first impressions of higher degree are harder to correct, and ambivalent attitudes may impair the motivation to interact with others. Consistent with research on paranoia and self-esteem, actively-paranoid patients' positive social traits judgments were of higher intensity than non-paranoid patients'. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantum integrable systems from conformal blocks

NASA Astrophysics Data System (ADS)

Chen, Heng-Yu; Qualls, Joshua D.

2017-05-01

In this note, we extend the striking connections between quantum integrable systems and conformal blocks recently found in [M. Isachenkov and V. Schomerus, Phys. Rev. Lett. 117, 071602 (2016), 10.1103/PhysRevLett.117.071602] in several directions. First, we explicitly demonstrate that the action of the quartic conformal Casimir operator on general d-dimensional scalar conformal blocks can be expressed in terms of certain combinations of commuting integrals of motions of the two particle hyperbolic BC2 Calogero-Sutherland system. The permutation and reflection properties of the underlying Dunkl operators play crucial roles in establishing such a connection. Next, we show that the scalar superconformal blocks in superconformal field theories (SCFTs) with four and eight supercharges and suitable chirality constraints can also be identified with the eigenfunctions of the same Calogero-Sutherland system; this demonstrates the universality of such a connection. Finally, we observe that the so-called "seed" conformal blocks for constructing four point functions for operators with arbitrary space-time spins in four-dimensional CFTs can also be linearly expanded in terms of Calogero-Sutherland eigenfunctions.

Hollywood and the Rebel Image in the 1950s.

ERIC Educational Resources Information Center

Briley, Ron

1997-01-01

Examines two seminal films of adolescent rebellion, "The Wild One" and "Rebel Without a Cause." Argues that both films expressed a discontent with, and acted as a critique of, the complacency and conformity of the postwar United States. Discusses the films' own ambivalent attitudes to issues of conformity and alienation. (MJP)

Complexity of Language Ideologies in Transnational Movement: Korean "Jogi Yuhak" Families' Ambivalent Attitudes towards Local Varieties of English in Singapore

ERIC Educational Resources Information Center

Bae, So Hee

2015-01-01

This paper discusses the complex and competing language ideologies that Korean educational migrant families in Singapore hold about the normativity and legitimacy of English language varieties. During their educational migration in Singapore, Korean families show ambivalent attitudes toward the local variety of English in Singapore, Singlish.…

Protein Conformational Populations and Functionally Relevant Sub-states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, Pratul K; Burger, Virginia; Savol, Andrej

2013-01-01

Functioning proteins do not remain fixed in a unique structure, but instead they sample a range of conformations facilitated by motions within the protein. Even in the native state, a protein exists as a collection of interconverting conformations driven by thermodynamic fluctuations. Motions on the fast time scale allow a protein to sample conformations in the nearby area of its conformational landscape, while motions on slower time scales give it access to conformations in distal areas of the landscape. Emerging evidence indicates that protein landscapes contain conformational substates with dynamic and structural features that support the designated function of themore » protein. Nuclear magnetic resonance (NMR) experiments provide information about conformational ensembles of proteins. X-ray crystallography allows researchers to identify the most populated states along the landscape, and computational simulations give atom-level information about the conformational substates of different proteins. This ability to characterize and obtain quantitative information about the conformational substates and the populations of proteins within them is allowing researchers to better understand the relationship between protein structure and dynamics and the mechanisms of protein function. In this Account, we discuss recent developments and challenges in the characterization of functionally relevant conformational populations and substates of proteins. In some enzymes, the sampling of functionally relevant conformational substates is connected to promoting the overall mechanism of catalysis. For example, the conformational landscape of the enzyme dihydrofolate reductase has multiple substates, which facilitate the binding and the release of the cofactor and substrate and catalyze the hydride transfer. For the enzyme cyclophilin A, computational simulations reveal that the long time scale conformational fluctuations enable the enzyme to access conformational substates that

Path lumping: An efficient algorithm to identify metastable path channels for conformational dynamics of multi-body systems

NASA Astrophysics Data System (ADS)

Meng, Luming; Sheong, Fu Kit; Zeng, Xiangze; Zhu, Lizhe; Huang, Xuhui

2017-07-01

Constructing Markov state models from large-scale molecular dynamics simulation trajectories is a promising approach to dissect the kinetic mechanisms of complex chemical and biological processes. Combined with transition path theory, Markov state models can be applied to identify all pathways connecting any conformational states of interest. However, the identified pathways can be too complex to comprehend, especially for multi-body processes where numerous parallel pathways with comparable flux probability often coexist. Here, we have developed a path lumping method to group these parallel pathways into metastable path channels for analysis. We define the similarity between two pathways as the intercrossing flux between them and then apply the spectral clustering algorithm to lump these pathways into groups. We demonstrate the power of our method by applying it to two systems: a 2D-potential consisting of four metastable energy channels and the hydrophobic collapse process of two hydrophobic molecules. In both cases, our algorithm successfully reveals the metastable path channels. We expect this path lumping algorithm to be a promising tool for revealing unprecedented insights into the kinetic mechanisms of complex multi-body processes.

Technique for converting non-conforming hexahedral-to-hexahedral interfaces into conforming interfaces

DOEpatents

Staten, Matthew L.; Shepherd, Jason F.; Ledoux, Frank; Shimada, Kenji; Merkley, Karl G.; Carbonera, Carlos

2013-03-05

A technique for conforming an interface between a first mesh and a second mesh is disclosed. A first interface surface in the first mesh and a second interface surface in the second mesh residing along the interface are identified. The first and second interface surfaces are initially non-conforming along the interface. Chords within the first and second interface surfaces that fall within a threshold separation distance of each other are paired. Sheets having chords that reside within the first or second interface surfaces are recursively inserted into or extracted from one or both of the first and second meshes until all remaining chords within the first interface surface are paired with corresponding chords in the second interface surface and all remaining chords within the second interface surface are paired with corresponding chords in the first interface surface.

To conform or not to conform: spontaneous conformity diminishes the sensitivity to monetary outcomes.

PubMed

Yu, Rongjun; Sun, Sai

2013-01-01

When people have different opinions in a group, they often adjust their own attitudes and behaviors to match the group opinion, known as social conformity. The affiliation account of normative conformity states that people conform to norms in order to 'fit in', whereas the accuracy account of informative conformity posits that the motive to learn from others produces herding. Here, we test another possibility that following the crowd reduces the experienced negative emotion when the group decision turns out to be a bad one. Using event related potential (ERP) combined with a novel group gambling task, we found that participants were more likely to choose the option that was predominately chosen by other players in previous trials, although there was little explicit normative pressure at the decision stage and group choices were not informative. When individuals' choices were different from others, the feedback related negativity (FRN), an ERP component sensitive to losses and errors, was enhanced, suggesting that being independent is aversive. At the outcome stage, the losses minus wins FRN effect was significantly reduced following conformity choices than following independent choices. Analyses of the P300 revealed similar patterns both in the response and outcome period. Our study suggests that social conformity serves as an emotional buffer that protects individuals from experiencing strong negative emotion when the outcomes are bad.

Ambivalent Sexism, Alcohol Use, and Intimate Partner Violence Perpetration.

PubMed

Renzetti, Claire M; Lynch, Kellie R; DeWall, C Nathan

2015-09-09

Research on risk factors for men's perpetration of intimate partner violence (IPV) has shown a high correlation with problem alcohol use. Additional studies, however, indicate that the alcohol-IPV link is neither simple nor necessarily direct and that a range of factors may moderate this relationship. Using a national, community-based sample of 255 men, the present study examined the moderating effects of ambivalent sexism (i.e., hostile and benevolent sexism) on the relationship between alcohol use and IPV perpetration. The findings show that both greater alcohol consumption and high hostile sexism are positively associated with IPV perpetration, and that hostile sexism moderates the alcohol-IPV relationship for perpetration of physical IPV, but not for psychological IPV. Moreover, high levels of alcohol consumption have a greater impact on physical IPV perpetration for men low in hostile sexism than for men high in hostile sexism, lending support to the multiple threshold model of the alcohol-IPV link. Implications of the findings for prevention, intervention, and future research are discussed. © The Author(s) 2015.

Identification of Serine Conformers by Matrix-Isolation IR Spectroscopy Aided by Near-Infrared Laser Induced Conformational Change, 2D Correlation Analysis, and Quantum Mechanical Anharmonic Computations

PubMed Central

Najbauer, Eszter E.; Bazsó, Gábor; Apóstolo, Rui; Fausto, Rui; Biczysko, Malgorzata; Barone, Vincenzo; Tarczay, György

2018-01-01

The conformers of α-serine were investigated by matrix-isolation IR spectroscopy combined with NIR laser irradiation. This method, aided by 2D correlation analysis, enabled unambiguously grouping the spectral lines to individual conformers. On the basis of comparison of at least nine experimentally observed vibrational transitions of each conformer with empirically scaled (SQM) and anharmonic (GVPT2) computed IR spectra, 6 conformers were identified. In addition, the presence of at least one more conformer in Ar matrix was proved, and a short-lived conformer with a half-live of (3.7±0.5)·103 s in N2 matrix was generated by NIR irradiation. The analysis of the NIR laser induced conversions revealed that the excitation of the stretching overtone of both the side-chain and the carboxylic OH groups can effectively promote conformational changes, but remarkably different paths were observed for the two kinds of excitations. PMID:26201050

Ambivalence, communication and past use: understanding what influences women's intentions to use contraceptives.

PubMed

Campo, Shelly; Askelson, Natoshia M; Spies, Erica L; Losch, Mary

2012-01-01

Unintended pregnancy among women in the 18-30 age group is a public health concern. The Extended Parallel Process Model (EPPM) provides a framework for exploring how women's perceptions of threat, efficacy, and fear influence intentions to use contraceptives. Past use and communication with best friends and partners were also considered. A telephone survey of 18-30-year-old women (N = 599) was completed. After univariate and bivariate analyses were conducted, the variables were entered into a hierarchal, multi-variate linear regression with three steps consistent with the EPPM to predict behavioral intention. The first step included the demographic variables of relationship status and income. The constructs for the EPPM were entered into step 2. Step 3 contained the fear measure. The model for the third step was significant, F(10,471) = 36.40, p < 0.001 and the variance explained by this complete model was 0.42. Results suggest that perceived severity of the consequences of an unintended pregnancy (p < 0.01), communication with friends (p < 0.01) and last sexual partner (p < 0.05), relationship status (p < 0.01), and past use (p < 0.001) were associated with women's intentions to use contraceptives. A woman's perception of the severity was related to her intention to use contraceptives. Half of the women (50.3%) reported ambivalence about the severity of an unintended pregnancy. In our study, talking with their last sexual partner had a positive effect on intentions to use contraceptives, while talking with friends influenced intentions in a negative direction. These results reconfirm the need for public health practitioners and health care providers to consider level of ambivalence toward unintended pregnancy, communication with partner, and relationship status when trying to improve women's contraceptive behaviors. Implications for effective communication interventions are discussed.

Microwave Spectroscopy of Seven Conformers of 1,2-PROPANEDIOL

NASA Astrophysics Data System (ADS)

Neill, Justin L.; Muckle, Matt T.; Pate, Brooks H.; Lovas, F. J.; Plusquellic, D. F.; Remijan, A. J.

2009-06-01

Previously, two conformations of 1,2-propanediol have been identified by microwave spectroscopy by Caminati. Here we report the assignment of five additional conformers, two from work on a Balle-Flygare type cavity FTMW spectrometer at NIST, operating between 8 and 26 GHz, and three from a deep average scan on the chirped pulse Fourier transform microwave (CP-FTMW) spectrometer at the University of Virginia, operating between 6.5 and 18.5 GHz. All seven of the assigned conformers contain an intramolecular hydrogen bond between the two hydroxyl groups. Stark effect measurements have been performed on the cavity FTMW spectrometer to determine the dipole moments of the three lowest energy conformers. Relative abundances of the conformers have also been determined from the CP-FTMW spectrum. A subsequent interstellar search toward Sgr B2(N) yielded negative results with an upper limit to the total column density that is less than those of glycolaldehyde and ethylene glycol. W.Caminati, J. Mol. Spectrosc. 86 (1981) 193-201.

"Fahrenheit 9-11," Need for Closure and the Priming of Affective Ambivalence: An Assessment of Intra-Affective Structures by Party Identification

ERIC Educational Resources Information Center

Holbert, R. Lance; Hansen, Glenn J.

2006-01-01

This study extends priming research in political communication by focusing on an alternative political information source (i.e., Michael Moore's Fahrenheit 9-11), affect rather than cognitions, and the existence of intra-affective ambivalence. In addition, two moderator variables are analyzed: political party identification and need for closure.…

Holographic Techni-Dilaton, or Conformal Higgs

NASA Astrophysics Data System (ADS)

Habaa, Kazumoto; Matsuzaki, Shinya; Yamawaki, Koichi

2011-01-01

We study a holographic model dual to walking/conformal technicolor (W/C TC) deforming a hard-wall type of bottom-up setup by including effects from techni-gluon condensation. We calculate masses of (techni-) ρ meson, a1 meson, and flavor/chiral-singlet scalar meson identified with techni-dilaton (TD)/conformal Higgs boson, as well as the S parameter. It is shown that gluon contributions and large anomalous dimension tend to decrease specifically mass of the TD. In the typical model with S ≃ 0.1, we find mTD ≃ 600 GeV, while mρ, ma1 ≃ 4TeV.

Power and ambivalence in intergenerational communication: Deciding to institutionalize in Shanghai.

PubMed

Chen, Lin

2017-04-01

China's tradition of taking care of one's aging parents continues to evolve, as evidenced by the growth in nursing home residents in Shanghai. However, how these families make the decision to institutionalize remains unclear. To fill this gap, this study draws on power relations to examine communication dynamics when oldest-old and their adult children decide to institutionalize. This study used a phenomenological approach. Twelve dyads of matched elderly residents and their children participated in face-to-face, in-depth interviews (N=24). The format and content of intergenerational communication indicated that both conflicts and compromises took place. Adult children achieved greater decision-making power than their frail parents, which evoked older adults' ambivalent feelings. A discrepancy in perceived filial piety between generations also emerged. These dynamics of caregiving decision-making offer insight in understanding evolving filial piety in urban China. Copyright © 2017 Elsevier Inc. All rights reserved.

Joint annotation of chromatin state and chromatin conformation reveals relationships among domain types and identifies domains of cell-type-specific expression

PubMed Central

Libbrecht, Maxwell W.; Ay, Ferhat; Hoffman, Michael M.; Gilbert, David M.; Bilmes, Jeffrey A.; Noble, William Stafford

2015-01-01

The genomic neighborhood of a gene influences its activity, a behavior that is attributable in part to domain-scale regulation. Previous genomic studies have identified many types of regulatory domains. However, due to the difficulty of integrating genomics data sets, the relationships among these domain types are poorly understood. Semi-automated genome annotation (SAGA) algorithms facilitate human interpretation of heterogeneous collections of genomics data by simultaneously partitioning the human genome and assigning labels to the resulting genomic segments. However, existing SAGA methods cannot integrate inherently pairwise chromatin conformation data. We developed a new computational method, called graph-based regularization (GBR), for expressing a pairwise prior that encourages certain pairs of genomic loci to receive the same label in a genome annotation. We used GBR to exploit chromatin conformation information during genome annotation by encouraging positions that are close in 3D to occupy the same type of domain. Using this approach, we produced a model of chromatin domains in eight human cell types, thereby revealing the relationships among known domain types. Through this model, we identified clusters of tightly regulated genes expressed in only a small number of cell types, which we term “specific expression domains.” We found that domain boundaries marked by promoters and CTCF motifs are consistent between cell types even when domain activity changes. Finally, we showed that GBR can be used to transfer information from well-studied cell types to less well-characterized cell types during genome annotation, making it possible to produce high-quality annotations of the hundreds of cell types with limited available data. PMID:25677182

Joint annotation of chromatin state and chromatin conformation reveals relationships among domain types and identifies domains of cell-type-specific expression.

PubMed

Libbrecht, Maxwell W; Ay, Ferhat; Hoffman, Michael M; Gilbert, David M; Bilmes, Jeffrey A; Noble, William Stafford

2015-04-01

The genomic neighborhood of a gene influences its activity, a behavior that is attributable in part to domain-scale regulation. Previous genomic studies have identified many types of regulatory domains. However, due to the difficulty of integrating genomics data sets, the relationships among these domain types are poorly understood. Semi-automated genome annotation (SAGA) algorithms facilitate human interpretation of heterogeneous collections of genomics data by simultaneously partitioning the human genome and assigning labels to the resulting genomic segments. However, existing SAGA methods cannot integrate inherently pairwise chromatin conformation data. We developed a new computational method, called graph-based regularization (GBR), for expressing a pairwise prior that encourages certain pairs of genomic loci to receive the same label in a genome annotation. We used GBR to exploit chromatin conformation information during genome annotation by encouraging positions that are close in 3D to occupy the same type of domain. Using this approach, we produced a model of chromatin domains in eight human cell types, thereby revealing the relationships among known domain types. Through this model, we identified clusters of tightly regulated genes expressed in only a small number of cell types, which we term "specific expression domains." We found that domain boundaries marked by promoters and CTCF motifs are consistent between cell types even when domain activity changes. Finally, we showed that GBR can be used to transfer information from well-studied cell types to less well-characterized cell types during genome annotation, making it possible to produce high-quality annotations of the hundreds of cell types with limited available data. © 2015 Libbrecht et al.; Published by Cold Spring Harbor Laboratory Press.

Identification of key residues for protein conformational transition using elastic network model.

PubMed

Su, Ji Guo; Xu, Xian Jin; Li, Chun Hua; Chen, Wei Zu; Wang, Cun Xin

2011-11-07

Proteins usually undergo conformational transitions between structurally disparate states to fulfill their functions. The large-scale allosteric conformational transitions are believed to involve some key residues that mediate the conformational movements between different regions of the protein. In the present work, a thermodynamic method based on the elastic network model is proposed to predict the key residues involved in protein conformational transitions. In our method, the key functional sites are identified as the residues whose perturbations largely influence the free energy difference between the protein states before and after transition. Two proteins, nucleotide binding domain of the heat shock protein 70 and human/rat DNA polymerase β, are used as case studies to identify the critical residues responsible for their open-closed conformational transitions. The results show that the functionally important residues mainly locate at the following regions for these two proteins: (1) the bridging point at the interface between the subdomains that control the opening and closure of the binding cleft; (2) the hinge region between different subdomains, which mediates the cooperative motions between the corresponding subdomains; and (3) the substrate binding sites. The similarity in the positions of the key residues for these two proteins may indicate a common mechanism in their conformational transitions.

The Conformational Landscape of Serinol

NASA Astrophysics Data System (ADS)

Sanz, M. Eugenia; Loru, Donatella; Peña, Isabel; Alonso, José L.

2014-06-01

The rotational spectrum of the amino alcohol serinol CH_2OH--CH(NH_2)--CH_2OH, which constitutes the hydrophilic head of the lipid sphingosine, has been investigated using chirped-pulsed Fourier transform microwave spectroscopy in combination with laser ablation Five different forms of serinol have been observed and conclusively identified by the comparison between the experimental values of their rotational and 14N quadrupole coupling constants and those predicted by ab initio calculations. In all observed conformers several hydrogen bonds are established between the two hydroxyl groups and the amino groups in a chain or circular arrangement. The most abundant conformer is stabilised by O--H···N and N--H···O hydrogen bonds forming a chain rather than a cycle. One of the detected conformers presents a tunnelling motion of the hydrogen atoms of the functional groups similar to that observed in glycerol. S. Mata, I. Peña, C. Cabezas, J. C. López, J. L. Alonso, J. Mol. Spectrosc. 2012, 280, 91 V. V. Ilyushin, R. A. Motiyenko, F. J. Lovas, D. F. Plusquellic, J. Mol. Spectrosc. 2008, 251, 129.

Conformal Infinity.

PubMed

Frauendiener, Jörg

2000-01-01

The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

Conformal Infinity.

PubMed

Frauendiener, Jörg

2004-01-01

The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

Distinguishing Signatures of Multipathway Conformational Transitions

NASA Astrophysics Data System (ADS)

Pierse, Christopher A.; Dudko, Olga K.

2017-02-01

The folding and binding of biomolecules into functional conformations are thought to be commonly mediated by multiple pathways rather than a unique route. Yet even in experiments where one can "see" individual conformational transitions, their stochastic nature generally precludes one from determining whether the transitions occurred through one or multiple pathways. We establish model-free, observable signatures in the response of macromolecules to force that unambiguously identify multiple pathways—even when the pathways themselves cannot be resolved. The unified analytical description reveals that, through multiple pathways, the response of molecules to external forces can be shaped in diverse ways, resulting in a rich design space for a tailored biological function already at the single-molecule level.

Relationships between Adolescents' Preferred Sources of Help and Emotional Distress, Ambivalence over Emotional Expression, and Causal Attribution of Symptoms: A Singapore Study

ERIC Educational Resources Information Center

Lee, Boon-Ooi

2009-01-01

Past research has shown that many adolescents with depression and anxiety disorders do not consult mental health professionals. This study examines how emotional distress, ambivalence over emotional expression, and causal attribution of depressive and anxious symptoms are related to adolescents' preferred sources of help for these symptoms. 300…

Steric interactions determine side-chain conformations in protein cores.

PubMed

Caballero, D; Virrueta, A; O'Hern, C S; Regan, L

2016-09-01

We investigate the role of steric interactions in defining side-chain conformations in protein cores. Previously, we explored the strengths and limitations of hard-sphere dipeptide models in defining sterically allowed side-chain conformations and recapitulating key features of the side-chain dihedral angle distributions observed in high-resolution protein structures. Here, we show that modeling residues in the context of a particular protein environment, with both intra- and inter-residue steric interactions, is sufficient to specify which of the allowed side-chain conformations is adopted. This model predicts 97% of the side-chain conformations of Leu, Ile, Val, Phe, Tyr, Trp and Thr core residues to within 20°. Although the hard-sphere dipeptide model predicts the observed side-chain dihedral angle distributions for both Thr and Ser, the model including the protein environment predicts side-chain conformations to within 20° for only 60% of core Ser residues. Thus, this approach can identify the amino acids for which hard-sphere interactions alone are sufficient and those for which additional interactions are necessary to accurately predict side-chain conformations in protein cores. We also show that our approach can predict alternate side-chain conformations of core residues, which are supported by the observed electron density. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Conformational Heterogeneity of Unbound Proteins Enhances Recognition in Protein-Protein Encounters.

PubMed

Pallara, Chiara; Rueda, Manuel; Abagyan, Ruben; Fernández-Recio, Juan

2016-07-12

To understand cellular processes at the molecular level we need to improve our knowledge of protein-protein interactions, from a structural, mechanistic, and energetic point of view. Current theoretical studies and computational docking simulations show that protein dynamics plays a key role in protein association and support the need for including protein flexibility in modeling protein interactions. Assuming the conformational selection binding mechanism, in which the unbound state can sample bound conformers, one possible strategy to include flexibility in docking predictions would be the use of conformational ensembles originated from unbound protein structures. Here we present an exhaustive computational study about the use of precomputed unbound ensembles in the context of protein docking, performed on a set of 124 cases of the Protein-Protein Docking Benchmark 3.0. Conformational ensembles were generated by conformational optimization and refinement with MODELLER and by short molecular dynamics trajectories with AMBER. We identified those conformers providing optimal binding and investigated the role of protein conformational heterogeneity in protein-protein recognition. Our results show that a restricted conformational refinement can generate conformers with better binding properties and improve docking encounters in medium-flexible cases. For more flexible cases, a more extended conformational sampling based on Normal Mode Analysis was proven helpful. We found that successful conformers provide better energetic complementarity to the docking partners, which is compatible with recent views of binding association. In addition to the mechanistic considerations, these findings could be exploited for practical docking predictions of improved efficiency.

Rotational Spectroscopy and Conformational Studies of 4-PENTYNENITRILE, 4-PENTENENITRILE, and Glutaronitrile

NASA Astrophysics Data System (ADS)

Hays, Brian M.; Mehta-Hurt, Deepali; Jawad, Khadija M.; Hernandez-Castillo, Alicia O.; Abeysekera, Chamara; Zhang, Di; Zwier, Timothy S.

2017-06-01

The pure rotational spectra of 4-pentynenitrile, 4-pentenenitrile, and glutaronitrile were acquired using chirped pulse Fouirer transform microwave spectroscopy. 4-pentynenitrile and 4-pentenenitrile are the recombination products of two resonance stabilized radicals, propargyl + cyanomethyl or allyl + cyanomethyl, respectively, and are thus anticipated to be significant among the more complex nitriles in Titan's atmosphere. Indeed, these partially unsaturated alkyl cyanides have been found in laboratory analogs of tholins and are also expected to have interesting photochemistry. The optimized structures of all conformers below predicted energies of 500 \\wn were calculated for each molecule. Both of the conformers, trans and gauche, for 4-pentynenitrile have been identified and assigned. Five conformers were assigned in 4-pentenenitrile. The eclipsed conformers, with respect to the vinyl group, dominate the spectrum but some population was found in the syn conformers including the syn-gauche conformer, calculated to be 324 \\wn above the global minimum. The glutaronitrile spectrum contained only the two conformers below 500 \\wn, with reduced amount of the gauche trans conformer. The assigned spectra and structural assignments will be presented.

Density-based clustering of small peptide conformations sampled from a molecular dynamics simulation.

PubMed

Kim, Minkyoung; Choi, Seung-Hoon; Kim, Junhyoung; Choi, Kihang; Shin, Jae-Min; Kang, Sang-Kee; Choi, Yun-Jaie; Jung, Dong Hyun

2009-11-01

This study describes the application of a density-based algorithm to clustering small peptide conformations after a molecular dynamics simulation. We propose a clustering method for small peptide conformations that enables adjacent clusters to be separated more clearly on the basis of neighbor density. Neighbor density means the number of neighboring conformations, so if a conformation has too few neighboring conformations, then it is considered as noise or an outlier and is excluded from the list of cluster members. With this approach, we can easily identify clusters in which the members are densely crowded in the conformational space, and we can safely avoid misclustering individual clusters linked by noise or outliers. Consideration of neighbor density significantly improves the efficiency of clustering of small peptide conformations sampled from molecular dynamics simulations and can be used for predicting peptide structures.

Stressors among Hispanic adults from immigrant families in the United States: Familismo as a context for ambivalence.

PubMed

Rojas, Sasha M; Grzywacz, Joseph G; Zapata Roblyer, Martha I; Crain, Rebecca; Cervantes, Richard C

2016-07-01

Ongoing exposure to social stressors is widely believed to undermine the health of Hispanic immigrant families. The current work aims to explore and interpret expressions of familismo as a framework through which postimmigration experiences are interpreted and potentially given meaning. Qualitative data were obtained from 16 focus groups in California and Massachusetts (N = 93). Fifty-two percent of the participants identified as male and 59% primarily spoke Spanish. Analyses revealed 3 distinct forms of ambivalence specific to familismo among Hispanic adults from immigrant families. Give and take described experiences wherein immigrants turn their backs on family in the short term to realize a better long-term future for the family. Negative change explained family misfortunes that arise in the pursuit of a better future for the family and creates doubts about the vision that motivated migration. Forced shifts suggests the navigation of daily life necessitates the inversion or abandonment of culturally idealized family roles and responsibilities. Hispanic adults from immigrant families described several situations in which competing views of familismo likely influenced the interpretation of unanticipated stressors. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Exploration of the conformational landscape in pregnane X receptor reveals a new binding pocket

PubMed Central

Chandran, Aneesh

2016-01-01

Abstract Ligand‐regulated pregnane X receptor (PXR), a member of the nuclear receptor superfamily, plays a central role in xenobiotic metabolism. Despite its critical role in drug metabolism, PXR activation can lead to adverse drug‐drug interactions and early stage metabolism of drugs. Activated PXR can induce cancer drug resistance and enhance the onset of malignancy. Since promiscuity in ligand binding makes it difficult to develop competitive inhibitors targeting PXR ligand binding pocket (LBP), it is essential to identify allosteric sites for effective PXR antagonism. Here, molecular dynamics (MD) simulation studies unravelled the existence of two different conformational states, namely “expanded” and “contracted”, in apo PXR ligand binding domain (LBD). Ligand binding events shifted this conformational equilibrium and locked the LBD in a single “ligand‐adaptable” conformational state. Ensemble‐based computational solvent mapping identified a transiently open potential small molecule binding pocket between α5 and α8 helices, named “α8 pocket”, whose opening‐closing mechanism directly correlated with the conformational shift in LBD. A virtual hit identified through structure‐based virtual screening against α8 pocket locks the pocket in its open conformation. MD simulations further revealed that the presence of small molecule at allosteric site disrupts the LBD dynamics and locks the LBD in a “tightly‐contracted” conformation. The molecular details provided here could guide new structural studies to understand PXR activation and antagonism. PMID:27515410

Exploration of the relationship between topology and designability of conformations

NASA Astrophysics Data System (ADS)

Leelananda, Sumudu P.; Towfic, Fadi; Jernigan, Robert L.; Kloczkowski, Andrzej

2011-06-01

Protein structures are evolutionarily more conserved than sequences, and sequences with very low sequence identity frequently share the same fold. This leads to the concept of protein designability. Some folds are more designable and lots of sequences can assume that fold. Elucidating the relationship between protein sequence and the three-dimensional (3D) structure that the sequence folds into is an important problem in computational structural biology. Lattice models have been utilized in numerous studies to model protein folds and predict the designability of certain folds. In this study, all possible compact conformations within a set of two-dimensional and 3D lattice spaces are explored. Complementary interaction graphs are then generated for each conformation and are described using a set of graph features. The full HP sequence space for each lattice model is generated and contact energies are calculated by threading each sequence onto all the possible conformations. Unique conformation giving minimum energy is identified for each sequence and the number of sequences folding to each conformation (designability) is obtained. Machine learning algorithms are used to predict the designability of each conformation. We find that the highly designable structures can be distinguished from other non-designable conformations based on certain graphical geometric features of the interactions. This finding confirms the fact that the topology of a conformation is an important determinant of the extent of its designability and suggests that the interactions themselves are important for determining the designability.

Conformational analysis by intersection: CONAN.

PubMed

Smellie, Andrew; Stanton, Robert; Henne, Randy; Teig, Steve

2003-01-15

As high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three-dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low-energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average <0.5 seconds/stereoisomer) a complete description of the low energy conformational space of a small molecule. The molecule is first decomposed into nonoverlapping nodes N (usually rings) and overlapping paths P with conformations (N and P) generated in an offline process. In a second step the node and path data are combined to form distinct conformers of the molecule. Finally, heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of approximately 97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low-energy conformational space. Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 24: 10-20, 2003

Two intermediate states of the conformational switch in dual specificity phosphatase 13a.

PubMed

Wei, Chun Hwa; Min, Hee Gyeong; Kim, Myeongbin; Kim, Gwan Hee; Chun, Ha-Jung; Ryu, Seong Eon

2018-02-01

Dual specificity phosphatases (DUSPs) include MAP kinase phosphatases and atypical dual specificity phosphatases and mediate cell growth and differentiation, brain function, and immune responses. They serve as targets for drug development against cancers, diabetes and depression. Several DUSPs have non-canonical conformation of the central β-sheet and active site loops, suggesting that they may have conformational switch that is related to the regulation of enzyme activity. Here, we determined the crystal structure of DUSP13a, and identified two different structures that represent intermediates of the postulated conformational switch. Amino acid sequence of DUSP13a is not significantly homologous to DUSPs with conformational switch, indicating that the conformational switch is not sequence-dependent, but rather determined by ligand interaction. The sequence-independency suggests that other DUSPs with canonical conformation may have the conformational switch during specific cellular regulation. The conformational switch leads to significant changes in the protein surface, including a hydrophobic surface and pockets, which can be exploited for development of allosteric modulators of drug target DUSPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Kind of a drag: gender, race, and ambivalence in The Birdcage and To Wong Foo, Thanks for Everything! Julie Newmar.

PubMed

Kirk, Mary

2004-01-01

This paper examines the ways in which two Hollywood films featuring drag queens, Too Wong Foo, Thanks for Everything! Julie Newmar and The Birdcage, offer a kind of "both/and" look at the complexities of gender, sexuality, race, and culture, simultaneously challenging some institutionalized attitudes (especially heterosexism) while reinforcing others (especially sexism and racism)--making the use of drag as a locus of discovery in both films, at best, ambivalent.

Exposing hidden alternative backbone conformations in X-ray crystallography using qFit

DOE PAGES

Keedy, Daniel A.; Fraser, James S.; van den Bedem, Henry; ...

2015-10-27

Proteins must move between different conformations of their native ensemble to perform their functions. Crystal structures obtained from high-resolution X-ray diffraction data reflect this heterogeneity as a spatial and temporal conformational average. Although movement between natively populated alternative conformations can be critical for characterizing molecular mechanisms, it is challenging to identify these conformations within electron density maps. Alternative side chain conformations are generally well separated into distinct rotameric conformations, but alternative backbone conformations can overlap at several atomic positions. Our model building program qFit uses mixed integer quadratic programming (MIQP) to evaluate an extremely large number of combinations of sidechainmore » conformers and backbone fragments to locally explain the electron density. Here, we describe two major modeling enhancements to qFit: peptide flips and alternative glycine conformations. We find that peptide flips fall into four stereotypical clusters and are enriched in glycine residues at the n+1 position. The potential for insights uncovered by new peptide flips and glycine conformations is exemplified by HIV protease, where different inhibitors are associated with peptide flips in the “flap” regions adjacent to the inhibitor binding site. Our results paint a picture of peptide flips as conformational switches, often enabled by glycine flexibility, that result in dramatic local rearrangements. Our results furthermore demonstrate the power of large-scale computational analysis to provide new insights into conformational heterogeneity. Furthermore, improved modeling of backbone heterogeneity with high-resolution X-ray data will connect dynamics to the structure-function relationship and help drive new design strategies for inhibitors of biomedically important systems.« less

Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

NASA Astrophysics Data System (ADS)

Dai, Jin; Niemi, Antti J.; He, Jianfeng

2016-07-01

The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of the Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.

Surveillance and Conformity in Competitive Youth Swimming

ERIC Educational Resources Information Center

Lang, Melanie

2010-01-01

Underpinned by a Foucauldian analysis of sporting practices, this paper identifies the disciplinary mechanism of surveillance at work in competitive youth swimming. It highlights the ways in which swimmers and their coaches are subject to and apply this mechanism to produce embodied conformity to normative behaviour and obedient, docile bodies.…

Additional conformer observed in the microwave spectrum of methyl vinyl ketone

NASA Astrophysics Data System (ADS)

Wilcox, David S.; Shirar, Amanda J.; Williams, Owen L.; Dian, Brian C.

2011-05-01

A chirped-pulse Fourier transform microwave spectrometer was used to record the rotational spectrum of methyl vinyl ketone (MVK, 3-butene-2-one). Two stable conformations were identified: the previously documented antiperiplanar (ap) conformer and synperiplanar (sp), which is reported for the first time in this microwave study. Methyl torsional analysis resulted in V3 barrier heights of 433.8(1) and 376.6(2) cm-1 for ap- and sp-MVK, respectively. Heavy atom isotopic species of both conformers were detected in natural abundance allowing bond lengths and angles of the molecular frames to be calculated through Kraitchman analysis. A comparison with ab initio calculations is included.

Conformational states and folding pathways of peptides revealed by principal-independent component analyses.

PubMed

Nguyen, Phuong H

2007-05-15

Principal component analysis is a powerful method for projecting multidimensional conformational space of peptides or proteins onto lower dimensional subspaces in which the main conformations are present, making it easier to reveal the structures of molecules from e.g. molecular dynamics simulation trajectories. However, the identification of all conformational states is still difficult if the subspaces consist of more than two dimensions. This is mainly due to the fact that the principal components are not independent with each other, and states in the subspaces cannot be visualized. In this work, we propose a simple and fast scheme that allows one to obtain all conformational states in the subspaces. The basic idea is that instead of directly identifying the states in the subspace spanned by principal components, we first transform this subspace into another subspace formed by components that are independent of one other. These independent components are obtained from the principal components by employing the independent component analysis method. Because of independence between components, all states in this new subspace are defined as all possible combinations of the states obtained from each single independent component. This makes the conformational analysis much simpler. We test the performance of the method by analyzing the conformations of the glycine tripeptide and the alanine hexapeptide. The analyses show that our method is simple and quickly reveal all conformational states in the subspaces. The folding pathways between the identified states of the alanine hexapeptide are analyzed and discussed in some detail. 2007 Wiley-Liss, Inc.

Conformal expansions and renormalons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rathsman, J.

2000-02-07

The coefficients in perturbative expansions in gauge theories are factorially increasing, predominantly due to renormalons. This type of factorial increase is not expected in conformal theories. In QCD conformal relations between observables can be defined in the presence of a perturbative infrared fixed-point. Using the Banks-Zaks expansion the authors study the effect of the large-order behavior of the perturbative series on the conformal coefficients. The authors find that in general these coefficients become factorially increasing. However, when the factorial behavior genuinely originates in a renormalon integral, as implied by a postulated skeleton expansion, it does not affect the conformal coefficients.more » As a consequence, the conformal coefficients will indeed be free of renormalon divergence, in accordance with previous observations concerning the smallness of these coefficients for specific observables. The authors further show that the correspondence of the BLM method with the skeleton expansion implies a unique scale-setting procedure. The BLM coefficients can be interpreted as the conformal coefficients in the series relating the fixed-point value of the observable with that of the skeleton effective charge. Through the skeleton expansion the relevance of renormalon-free conformal coefficients extends to real-world QCD.« less

Ethanol Dimer: Observation of Three New Conformers by Broadband Rotational Spectroscopy

NASA Astrophysics Data System (ADS)

Loru, Donatella; Peña, Isabel; Sanz, M. Eugenia

2017-06-01

The conformational behaviour of the hydrogen-bonded cluster ethanol dimer has been reinvestigated by chirped pulse Fourier transform microwave spectroscopy in the 2-8 GHz frequency region. Three new conformers ({tt}, {tg}+, and {g}-{g}+) have been identified together with the three ({g}+{g}+, {g}-{t}, and {g}+{t}) previously observed by Hearn et al. (J. Chem. Phys. 123, 134324, 2005) and their rotational and centrifugal distortion constants have been determined. By using different carrier gases in the supersonic expansion, the relative abundances of the observed conformers have been estimated. The monosubstituted ^{13}C species and some of the ^{18}O species of the most abundant conformers {g}+{g}+, {g}-{t}, and {tt} have been observed in their natural abundance, which led to the partial determination of their r_{s} structures, and the r_{0} structure for the {tt} conformer. The six observed conformers are stabilized by the delicate interplay of primary O-H...O and secondary C-H...O hydrogen bonds, and dispersion interactions between the methyl groups. Density functional and ab initio methods with different basis sets are benchmarked against the experimental data.

Engineering a hyper-catalytic enzyme by photo-activated conformation modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, Pratul K

2012-01-01

Enzyme engineering for improved catalysis has wide implications. We describe a novel chemical modification of Candida antarctica lipase B that allows modulation of the enzyme conformation to promote catalysis. Computational modeling was used to identify dynamical enzyme regions that impact the catalytic mechanism. Surface loop regions located distal to active site but showing dynamical coupling to the reaction were connected by a chemical bridge between Lys136 and Pro192, containing a derivative of azobenzene. The conformational modulation of the enzyme was achieved using two sources of light that alternated the azobenzene moiety in cis and trans conformations. Computational model predicted thatmore » mechanical energy from the conformational fluctuations facilitate the reaction in the active-site. The results were consistent with predictions as the activity of the engineered enzyme was found to be enhanced with photoactivation. Preliminary estimations indicate that the engineered enzyme achieved 8-52 fold better catalytic activity than the unmodulated enzyme.« less

Physical–chemical determinants of coil conformations in globular proteins

PubMed Central

Perskie, Lauren L; Rose, George D

2010-01-01

We present a method with the potential to generate a library of coil segments from first principles. Proteins are built from α-helices and/or β-strands interconnected by these coil segments. Here, we investigate the conformational determinants of short coil segments, with particular emphasis on chain turns. Toward this goal, we extracted a comprehensive set of two-, three-, and four-residue turns from X-ray–elucidated proteins and classified them by conformation. A remarkably small number of unique conformers account for most of this experimentally determined set, whereas remaining members span a large number of rare conformers, many occurring only once in the entire protein database. Factors determining conformation were identified via Metropolis Monte Carlo simulations devised to test the effectiveness of various energy terms. Simulated structures were validated by comparison to experimental counterparts. After filtering rare conformers, we found that 98% of the remaining experimentally determined turn population could be reproduced by applying a hydrogen bond energy term to an exhaustively generated ensemble of clash-free conformers in which no backbone polar group lacks a hydrogen-bond partner. Further, at least 90% of longer coil segments, ranging from 5- to 20 residues, were found to be structural composites of these shorter primitives. These results are pertinent to protein structure prediction, where approaches can be divided into either empirical or ab initio methods. Empirical methods use database-derived information; ab initio methods rely on physical–chemical principles exclusively. Replacing the database-derived coil library with one generated from first principles would transform any empirically based method into its corresponding ab initio homologue. PMID:20512968

Is non-conformity WEIRD? Cultural variation in adults' beliefs about children's competency and conformity.

PubMed

Clegg, Jennifer M; Wen, Nicole J; Legare, Cristine H

2017-03-01

Cross-cultural comparisons provide critical insight into variation in reasoning about intelligence. In two studies, the authors used a novel methodology based on multivocal ethnography to assess the role of conformity in U.S. and Ni-Vanuatu adults' judgments of children's intelligence and, as a comparison trait, good behavior. In Study 1, there were cultural differences in the impact of conformity on U.S. and Ni-Vanuatu adults' judgments of children's intelligence and good behavior. When evaluating U.S. children only, U.S. adults were less likely to endorse high conformity children as intelligent, often citing creativity as a justification for their judgments. In contrast, Ni-Vanuatu adults were more likely to endorse Ni-Vanuatu high conformity children as intelligent. Ni-Vanuatu adults were also more likely to endorse high conformity children as well-behaved than U.S. adults. In Study 2, there were no effects of socioeconomic status on U.S. adults' evaluations of conformity. U.S. adults were less likely to endorse high conformity children as intelligent than Ni-Vanuatu adults. Taken together, the data demonstrate that beliefs about the relations between intelligence, conformity, and creativity vary within and across cultures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Triple diagnostics for early detection of ambivalent necrotizing fasciitis.

PubMed

Hietbrink, Falco; Bode, Lonneke G; Riddez, Louis; Leenen, Luke P H; van Dijk, Marijke R

2016-01-01

Necrotizing fasciitis is an uncommon, rapidly progressive and potential lethal condition. Over the last decade time to surgery decreased and outcome improved, most likely due to increased awareness and more timely referral. Early recognition is key to improve mortality and morbidity. However, early referral frequently makes it a challenge to recognize this heterogeneous disease in its initial stages. Signs and symptoms might be misleading or absent, while the most prominent skin marks might be in discrepancy with the position of the fascial necrosis. Gram staining and especially fresh frozen section histology might be a useful adjunct. Retrospective analysis of 3 year period. Non-transferred patients who presented with suspected necrotizing fasciitis are included. ASA classification was determined. Mortality was documented. In total, 21 patients are included. Most patients suffered from severe comorbidities. In 11 patients, diagnoses was confirmed based on intra-operative macroscopic findings. Histology and/or microbiotic findings resulted in 6/10 remaining patients in a change in treatment strategy. In total, 17 patients proved to suffer necrotizing fasciitis. In the cohort series 2 patients died due to necrotizing fasciitis. In the early phases of necrotizing fasciitis, clinical presentation can be ambivalent. In the present cohort, triple diagnostics consisting of an incisional biopsy with macroscopic, histologic and microbiotic findings was helpful in timely identification of necrotizing fasciitis.

Clustering Suicide Attempters: Impulsive-Ambivalent, Well-Planned, or Frequent.

PubMed

Lopez-Castroman, Jorge; Nogue, Erika; Guillaume, Sebastien; Picot, Marie Christine; Courtet, Philippe

2016-06-01

Attempts to predict suicidal behavior within high-risk populations have so far shown insufficient accuracy. Although several psychosocial and clinical features have been consistently associated with suicide attempts, investigations of latent structure in well-characterized populations of suicide attempters are lacking. We analyzed a sample of 1,009 hospitalized suicide attempters that were recruited between 1999 and 2012. Eleven clinically relevant items related to the characteristics of suicidal behavior were submitted to a Hierarchical Ascendant Classification. Phenotypic profiles were compared between the resulting clusters. A decisional tree was constructed to facilitate the differentiation of individuals classified within the first 2 clusters. Most individuals were included in a cluster characterized by less lethal means and planning ("impulse-ambivalent"). A second cluster featured more carefully planned attempts ("well-planned"), more alcohol or drug use before the attempt, and more precautions to avoid interruptions. Finally, a small, third cluster included individuals reporting more attempts ("frequent"), more often serious or violent attempts, and an earlier age at first attempt. Differences across clusters by demographic and clinical characteristics were also found, particularly with the third cluster whose participants had experienced high levels of childhood abuse. Cluster analysis consistently supported 3 distinct clusters of individuals with specific features in their suicidal behaviors and phenotypic profiles that could help clinicians to better focus prevention strategies. © Copyright 2016 Physicians Postgraduate Press, Inc.

Conformations of n-butyl imidazole: matrix isolation infrared and DFT studies.

PubMed

Ramanathan, N; Sundararajan, K; Sankaran, K

2015-03-15

Conformations of n-butyl imidazole (B-IMID) were studied using matrix isolation infrared spectroscopy by trapping in argon, xenon and nitrogen matrixes using an effusive nozzle source. The experimental studies were supported by DFT computations performed at the B3LYP/6-311++G(d,p) level. Computations identified nine unique minima for B-IMID, corresponding to conformers with tg(±)tt, tg(±)g(∓)t, tg(±)g(±)t, tg(±)tg(±), tg(±)tg(∓), tg(±)g(∓)g(∓), tg(±)g(±)g(±), tg(±)g(∓)g(±) and tg(±)g(±)g(∓) structures, given in order of increasing energy. Computations of the transition state structures connecting the higher energy conformers to the global minimum, tg(±)tt structure were carried out. The barriers for the conformer inter-conversion were found to be ∼2 kcal/mol. Natural Bond Orbital (NBO) analysis was performed to understand the reasons for conformational preferences in B-IMID. Copyright © 2014 Elsevier B.V. All rights reserved.

Conformal superalgebras via tractor calculus

NASA Astrophysics Data System (ADS)

Lischewski, Andree

2015-01-01

We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature.

Conformational Preference and Spectroscopical Characteristics of the Active Pharmaceutical Ingredient Levetiracetam.

PubMed

Luchian, Raluca; Vinţeler, Emil; Chiş, Cosmina; Vasilescu, Mihai; Leopold, Nicolae; Prates Ramalho, João P; Chiş, Vasile

2017-12-01

The analysis of the possible conformers and the conformational change between solid and liquid states of a particular drug molecule are mandatory not only for describing reliably its spectroscopical properties but also for understanding the interaction with the receptor and its mechanism of action. Therefore, here we investigated the free-energy conformational landscape of levetiracetam (LEV) in gas phase as well as in water and ethanol, aiming to describe the 3-dimensional structure and energetic stability of its conformers. Twenty-two unique conformers were identified, and their energetic stability was determined at density functional theory B3LYP/6-31+G(2d,2p) level of theory. The 6 most stable monomers in water, within a relative free-energy window of 0.71 kcal mol -1 and clearly separated in energy from the remaining subset of 16 conformers, as well as the 3 most stable dimers were then used to compute the Boltzmann populations-averaged UV-Vis and NMR spectra of LEV. The conformational landscape in solution is distinctly different from that corresponding to gas phase, particularly due to the relative orientations of the butanamide group. Aiming to clarify the stability of the possible dimers of LEV, we also investigated computationally the structure of a set of 11 nonhydrated and hydrated homochiral hydrogen-bonded LEV dimers. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Modelling proteins' hidden conformations to predict antibiotic resistance

NASA Astrophysics Data System (ADS)

Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik; Gross, Michael L.; Bowman, Gregory R.

2016-10-01

TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM's specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models' prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.

Modelling proteins’ hidden conformations to predict antibiotic resistance

PubMed Central

Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik; Gross, Michael L.; Bowman, Gregory R.

2016-01-01

TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM’s specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models’ prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design. PMID:27708258

A Cryo-Electron Microscopy Study Identifies the Complete H16.V5 Epitope and Reveals Global Conformational Changes Initiated by Binding of the Neutralizing Antibody Fragment

PubMed Central

Lee, Hyunwook; Brendle, Sarah A.; Bywaters, Stephanie M.; Guan, Jian; Ashley, Robert E.; Yoder, Joshua D.; Makhov, Alexander M.; Conway, James F.; Christensen, Neil D.

2014-01-01

ABSTRACT Human papillomavirus 16 (HPV16) is a worldwide health threat and an etiologic agent of cervical cancer. To understand the antigenic properties of HPV16, we pursued a structural study to elucidate HPV capsids and antibody interactions. The cryo-electron microscopy (cryo-EM) structures of a mature HPV16 particle and an altered capsid particle were solved individually and as complexes with fragment of antibody (Fab) from the neutralizing antibody H16.V5. Fitted crystal structures provided a pseudoatomic model of the virus-Fab complex, which identified a precise footprint of H16.V5, including previously unrecognized residues. The altered-capsid–Fab complex map showed that binding of the Fab induced significant conformational changes that were not seen in the altered-capsid structure alone. These changes included more ordered surface loops, consolidated so-called “invading-arm” structures, and tighter intercapsomeric connections at the capsid floor. The H16.V5 Fab preferentially bound hexavalent capsomers likely with a stabilizing effect that directly correlated with the number of bound Fabs. Additional cryo-EM reconstructions of the virus-Fab complex for different incubation times and structural analysis provide a model for a hyperstabilization of the capsomer by H16.V5 Fab and showed that the Fab distinguishes subtle differences between antigenic sites. IMPORTANCE Our analysis of the cryo-EM reconstructions of the HPV16 capsids and virus-Fab complexes has identified the entire HPV.V5 conformational epitope and demonstrated a detailed neutralization mechanism of this clinically important monoclonal antibody against HPV16. The Fab bound and ordered the apical loops of HPV16. This conformational change was transmitted to the lower region of the capsomer, resulting in enhanced intercapsomeric interactions evidenced by the more ordered capsid floor and “invading-arm” structures. This study advances the understanding of the neutralization mechanism used

Watching Conformations of Biomolecules: a Microwave Spectroscopy Approach

NASA Astrophysics Data System (ADS)

Lopez, J. C.

2011-06-01

The combination of laser ablation with Fourier transform microwave spectroscopy in supersonic jets (LA-MB-FTMW) has made possible the gas-phase study of solid biomolecules with high melting points. In the experiment, solids are efficiently vaporized by a high-energy laser pulse, supersonically expanded into a evacuated Fabry-Perot cavity and characterised by their rotational spectra. Recent improvements such as the use of picosecond pulse lasers, new ablation nozzles and the extension of the range of the spectrometers to low frequecy have notably increased the sensitivity of our experimental setup. To date different α-, β- and γ-amino acids have been studied using this technique, making possible the characterization of their preferred conformations and gaining insight in the role of intramolecular interactions. Even in conformationally challenging systems the different rotamers of such biomolecules can be identified by rotational spectroscopy as can be illustrated by the assignment of six low-energy conformers in cysteine and aspartic acid, seven in serine and threonine,^a and nine in γ-amino butyric acid (GABA). In all cases the low-energy conformers have been conclusive identified from their experimental rotational and 14N quadrupole coupling constants. The spectra of neurotransmitters and of the nucleic acid bases uracil, thymine, cytosine and guanine have also been studied and their preferred conformers or tautomeric forms determined. The complexes between amino acids and nucleic acid bases with water have also been investigated to obtain information on the possible changes induced in the conformational or tautomeric preferences by the addition of solvent molecules. J. L. Alonso, C. Pérez, M. E. Sanz, J. C. López, S. Blanco, Phys. Chem. Chem. Phys. 11, 617-627 (2009) and references therein M. E. Sanz, J. C. López, J. L. Alonso, Phys. Chem. Chem. Phys., 12, 3573-3578 (2010) S. Blanco, J. C. López, S. Mata and J. L. Alonso, Angew. Chem. Int. Ed. 49, 9187

Conformational changes in matrix-isolated 6-methoxyindole: Effects of the thermal and infrared light excitations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopes Jesus, A. J.; CQC, Faculty of Pharmacy, University of Coimbra, 3004-295 Coimbra; Reva, I., E-mail: reva@qui.uc.pt

2016-03-28

Conformational changes induced thermally or upon infrared excitation of matrix-isolated 6-methoxyindole were investigated. Narrowband near-infrared excitation of the first overtone of the N–H stretching vibration of each one of the two identified conformers is found to induce a selective large-scale conversion of the pumped conformer into the other one. This easily controllable bidirectional process consists in the intramolecular reorientation of the methoxy group and allowed a full assignment of the infrared spectra of the two conformers. Matrices with different conformational compositions prepared by narrow-band irradiations were subsequently used to investigate the effects of both thermal and broadband infrared excitations onmore » the conformational mixtures. Particular attention is given to the influence of the matrix medium (Ar vs. Xe) and conformational effects of exposition of the sample to the spectrometer light source during the measurements.« less

Dissecting linear and conformational epitopes on the native thyrotropin receptor.

PubMed

Ando, Takao; Latif, Rauf; Daniel, Samira; Eguchi, Katsumi; Davies, Terry F

2004-11-01

The TSH receptor (TSHR) is the primary antigen in Graves' disease. In this condition, autoantibodies to the TSHR that have intrinsic thyroid-stimulating activity develop. We studied the epitopes on the native TSHR using polyclonal antisera and monoclonal antibodies (mAbs) derived from an Armenian hamster model of Graves' disease. Of 14 hamster mAbs analyzed, five were shown to bind to conformational epitopes including one mAb with potent thyroid-stimulating activity. Overlapping conformational epitopes were determined by cell-binding competition assays using fluorescently labeled mAbs. We identified two distinct conformational epitopes: epitope A for both stimulating and blocking mAbs and epitope B for only blocking mAbs. Examination of an additional three mouse-derived stimulating TSHR-mAbs also showed exclusive binding to epitope A. The remaining nine hamster-derived mAbs were neutral or low-affinity blocking antibodies that recognized linear epitopes within the TSHR cleaved region (residues 316-366) (epitope C). Serum from the immunized hamsters also recognized conformational epitopes A and B but, in addition, also contained high levels of TSHR-Abs interacting within the linear epitope C region. In summary, these studies indicated that the natively conformed TSHR had a restricted set of epitopes recognized by TSHR-mAbs and that the binding site for stimulating TSHR-Abs was highly conserved. However, high-affinity TSHR-blocking antibodies recognized two conformational epitopes, one of which was indistinguishable from the thyroid-stimulating epitope. Hence, TSHR-stimulating and blocking antibodies cannot be distinguished purely on the basis of their conformational epitope recognition.

Hypotrochoids in conformal restriction systems and Virasoro descendants

NASA Astrophysics Data System (ADS)

Doyon, Benjamin

2013-09-01

A conformal restriction system is a commutative, associative, unital algebra equipped with a representation of the groupoid of univalent conformal maps on connected open sets of the Riemann sphere, along with a family of linear functionals on subalgebras, satisfying a set of properties including conformal invariance and a type of restriction. This embodies some expected properties of expectation values in conformal loop ensembles CLEκ (at least for 8/3 < κ ≤ 4). In the context of conformal restriction systems, we study certain algebra elements associated with hypotrochoid simple curves (a family of curves including the ellipse). These have the CLE interpretation of being ‘renormalized random variables’ that are nonzero only if there is at least one loop of hypotrochoid shape. Each curve has a center w, a scale ɛ and a rotation angle θ, and we analyze the renormalized random variable as a function of u = ɛeiθ and w. We find that it has an expansion in positive powers of u and \\bar {u}, and that the coefficients of pure u (\\bar {u}) powers are holomorphic in w (\\bar {w}). We identify these coefficients (the ‘hypotrochoid fields’) with certain Virasoro descendants of the identity field in conformal field theory, thereby showing that they form part of a vertex operator algebraic structure. This largely generalizes works by the author (in CLE), and the author with his collaborators Riva and Cardy (in SLE8/3 and other restriction measures), where the case of the ellipse, at the order u2, led to the stress-energy tensor of CFT. The derivation uses in an essential way the Virasoro vertex operator algebra structure of conformal derivatives established recently by the author. The results suggest in particular the exact evaluation of CLE expectations of products of hypotrochoid fields as well as nontrivial relations amongst them through the vertex operator algebra, and further shed light onto the relationship between CLE and CFT.

Hartree-Fock and density functional theory study of alpha-cyclodextrin conformers.

PubMed

Jiménez, Verónica; Alderete, Joel B

2008-01-31

Herein, we report the geometry optimization of four conformers of alpha-cyclodextrin (alpha-CD) by means of PM3, HF/STO-3G, HF/3-21G, HF/6-31G(d), B3LYP/6-31G(d), and X3LYP/6-31G(d) calculations. The analysis of several geometrical parameters indicates that all conformers possess bond lengths, angles, and dihedrals that agree fairly well with the crystalline structure of alpha-CD. However, only three of them (1-3) resemble the polar character of CDs and show intramolecular hydrogen-bonding patterns that agree with experimental NMR data. Among them, conformer 3 appears to be the most stable species both in the gas phase and in solution; therefore, it is expected to be the most suitable representative structure for alpha-CD conformation. The purpose of selecting such a species is to identify an appropriate structure to be employed as a starting point for reliable computational studies on complexation phenomena. Our results indicate that the choice of a particular alpha-CD conformer should affect the results of ab initio computational studies on the inclusion complexation with this cyclodextrin since both the direction and the magnitude of the dipole moment depend strongly on the conformation of alpha-CD.

Computational ligand-based rational design: Role of conformational sampling and force fields in model development.

PubMed

Shim, Jihyun; Mackerell, Alexander D

2011-05-01

A significant number of drug discovery efforts are based on natural products or high throughput screens from which compounds showing potential therapeutic effects are identified without knowledge of the target molecule or its 3D structure. In such cases computational ligand-based drug design (LBDD) can accelerate the drug discovery processes. LBDD is a general approach to elucidate the relationship of a compound's structure and physicochemical attributes to its biological activity. The resulting structure-activity relationship (SAR) may then act as the basis for the prediction of compounds with improved biological attributes. LBDD methods range from pharmacophore models identifying essential features of ligands responsible for their activity, quantitative structure-activity relationships (QSAR) yielding quantitative estimates of activities based on physiochemical properties, and to similarity searching, which explores compounds with similar properties as well as various combinations of the above. A number of recent LBDD approaches involve the use of multiple conformations of the ligands being studied. One of the basic components to generate multiple conformations in LBDD is molecular mechanics (MM), which apply an empirical energy function to relate conformation to energies and forces. The collection of conformations for ligands is then combined with functional data using methods ranging from regression analysis to neural networks, from which the SAR is determined. Accordingly, for effective application of LBDD for SAR determinations it is important that the compounds be accurately modelled such that the appropriate range of conformations accessible to the ligands is identified. Such accurate modelling is largely based on use of the appropriate empirical force field for the molecules being investigated and the approaches used to generate the conformations. The present chapter includes a brief overview of currently used SAR methods in LBDD followed by a more

Conformational Flexibility of Metazoan Fatty Acid Synthase Enables Catalysis

PubMed Central

Brignole, Edward J.; Smith, Stuart; Asturias, Francisco J.

2008-01-01

The metazoan cytosolic fatty acid synthase (FAS) contains all of the enzymes required for de novo fatty acid biosynthesis covalently linked around two reaction chambers. While the 3D architecture of FAS has been mostly defined, it is unclear how reaction intermediates can transfer between distant catalytic domains. Using single-particle electron microscopy we have identified a near continuum of conformations consistent with remarkable flexibility of FAS. The distribution of conformations was influenced by the presence of substrates and altered by different catalytic mutations suggesting a direct correlation between conformation and specific enzymatic activities. 3D reconstructions were interpreted by docking high-resolution structures of individual domains and illustrate that the substrate loading and condensation domains dramatically swing and swivel to access substrates within either reaction chamber. Concomitant rearrangement of the β-carbon processing domains synchronizes acyl-chain reduction in one chamber with acyl-chain elongation in the other. PMID:19151726

Ambivalence over emotional expression, intrusive thoughts, and posttraumatic stress symptoms among Chinese American breast cancer survivors.

PubMed

Lu, Qian; Yeung, Nelson; Man, Jenny; Gallagher, Matthew W; Chu, Qiao; Deen, Sidra H

2017-10-01

Posttraumatic stress symptoms (PTSS) are common among breast cancer survivors. However, the association and the underlying mediating mechanism between psychosocial factors and PTSS were rarely investigated among breast cancer survivors. Previous studies have suggested the importance of emotional expression in cancer survivors' PTSS. This study examined the association between ambivalence over emotional expression (AEE; defined as the conflict between the desire to express feelings and the fear of its consequences) and PTSS, and proposed intrusive thoughts as the mediators in such an association. We tested this proposed mediation model among Chinese breast cancer survivors whose culture discourages emotional expression. Participants were 118 Chinese-speaking breast cancer survivors in the USA, who were diagnosed with breast cancer of stages 0-III within the past 5 years. They completed questionnaires measuring their levels of AEE, PTSS, and intrusive thoughts. AEE was positively associated with intrusive thoughts (r = 0.43, p < 01), which were positively associated with the arousal and avoidance subscales of PTSS (r = 0.68 and r = 0.62, respectively, p < .01). Path analysis supported a partial mediation model with an indirect effect from AEE to the latent variable of PTSS (with both arousal and avoidance as indicators) via intrusive thoughts (β = 0.29; 95% CI= 0.18, 0.42) and the direct effect from AEE to the latent variable of PTSS (β = 0.21, 95% CI = 0.07, 0.35), all p < .001. Those who are highly ambivalent about emotion expression tend to have higher PTSS, and this may be partially due to the lack of opportunities to discuss emotional events, thereby increasing the repetitive cancer-related negative thoughts. Intervention for PTSS should consider helping cancer patients to develop adaptive emotional regulation strategies to reduce the detrimental effects of cancer-related intrusive thoughts.

Fermion-scalar conformal blocks

DOE PAGES

Iliesiu, Luca; Kos, Filip; Poland, David; ...

2016-04-13

In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. In addition, conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

OSI Conformance Testing for Bibliographic Applications.

ERIC Educational Resources Information Center

Arbez, Gilbert; Swain, Leigh

1990-01-01

Describes the development of Open Systems Interconnection (OSI) conformance testing sites, conformance testing tools, and conformance testing services. Discusses related topics such as interoperability testing, arbitration testing, and international harmonization of conformance testing. A glossary is included. (24 references) (SD)

PubChem3D: Conformer generation

PubMed Central

2011-01-01

Background PubChem, an open archive for the biological activities of small molecules, provides search and analysis tools to assist users in locating desired information. Many of these tools focus on the notion of chemical structure similarity at some level. PubChem3D enables similarity of chemical structure 3-D conformers to augment the existing similarity of 2-D chemical structure graphs. It is also desirable to relate theoretical 3-D descriptions of chemical structures to experimental biological activity. As such, it is important to be assured that the theoretical conformer models can reproduce experimentally determined bioactive conformations. In the present study, we investigate the effects of three primary conformer generation parameters (the fragment sampling rate, the energy window size, and force field variant) upon the accuracy of theoretical conformer models, and determined optimal settings for PubChem3D conformer model generation and conformer sampling. Results Using the software package OMEGA from OpenEye Scientific Software, Inc., theoretical 3-D conformer models were generated for 25,972 small-molecule ligands, whose 3-D structures were experimentally determined. Different values for primary conformer generation parameters were systematically tested to find optimal settings. Employing a greater fragment sampling rate than the default did not improve the accuracy of the theoretical conformer model ensembles. An ever increasing energy window did increase the overall average accuracy, with rapid convergence observed at 10 kcal/mol and 15 kcal/mol for model building and torsion search, respectively; however, subsequent study showed that an energy threshold of 25 kcal/mol for torsion search resulted in slightly improved results for larger and more flexible structures. Exclusion of coulomb terms from the 94s variant of the Merck molecular force field (MMFF94s) in the torsion search stage gave more accurate conformer models at lower energy windows. Overall

Fake conformal symmetry in unimodular gravity

NASA Astrophysics Data System (ADS)

Oda, Ichiro

2016-08-01

We study Weyl symmetry (local conformal symmetry) in unimodular gravity. It is shown that the Noether currents for both Weyl symmetry and global scale symmetry vanish exactly as in conformally invariant scalar-tensor gravity. We clearly explain why in the class of conformally invariant gravitational theories, the Noether currents vanish by starting with conformally invariant scalar-tensor gravity. Moreover, we comment on both classical and quantum-mechanical equivalences in Einstein's general relativity, conformally invariant scalar-tensor gravity, and the Weyl-transverse gravity. Finally, we discuss the Weyl current in the conformally invariant scalar action and see that it is also vanishing.

Emulating proton-induced conformational changes in the vesicular monoamine transporter VMAT2 by mutagenesis.

PubMed

Yaffe, Dana; Vergara-Jaque, Ariela; Forrest, Lucy R; Schuldiner, Shimon

2016-11-22

Neurotransporters located in synaptic vesicles are essential for communication between nerve cells in a process mediated by neurotransmitters. Vesicular monoamine transporter (VMAT), a member of the largest superfamily of transporters, mediates transport of monoamines to synaptic vesicles and storage organelles in a process that involves exchange of two H + per substrate. VMAT transport is inhibited by the competitive inhibitor reserpine, a second-line agent to treat hypertension, and by the noncompetitive inhibitor tetrabenazine, presently in use for symptomatic treatment of hyperkinetic disorders. During the transport cycle, VMAT is expected to occupy at least three different conformations: cytoplasm-facing, occluded, and lumen-facing. The lumen- to cytoplasm-facing transition, facilitated by protonation of at least one of the essential membrane-embedded carboxyls, generates a binding site for reserpine. Here we have identified residues in the cytoplasmic gate and show that mutations that disrupt the interactions in this gate also shift the equilibrium toward the cytoplasm-facing conformation, emulating the effect of protonation. These experiments provide significant insight into the role of proton translocation in the conformational dynamics of a mammalian H + -coupled antiporter, and also identify key aspects of the mode of action and binding of two potent inhibitors of VMAT2: reserpine binds the cytoplasm-facing conformation, and tetrabenazine binds the lumen-facing conformation.

Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble

NASA Astrophysics Data System (ADS)

Yongye, Austin B.; Bender, Andreas; Martínez-Mayorga, Karina

2010-08-01

Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged- RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged- RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 Å). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1-4), medium (5-9) and high (10-15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening experiments.

The conformal characters

NASA Astrophysics Data System (ADS)

Bourget, Antoine; Troost, Jan

2018-04-01

We revisit the study of the multiplets of the conformal algebra in any dimension. The theory of highest weight representations is reviewed in the context of the Bernstein-Gelfand-Gelfand category of modules. The Kazhdan-Lusztig polynomials code the relation between the Verma modules and the irreducible modules in the category and are the key to the characters of the conformal multiplets (whether finite dimensional, infinite dimensional, unitary or non-unitary). We discuss the representation theory and review in full generality which representations are unitarizable. The mathematical theory that allows for both the general treatment of characters and the full analysis of unitarity is made accessible. A good understanding of the mathematics of conformal multiplets renders the treatment of all highest weight representations in any dimension uniform, and provides an overarching comprehension of case-by-case results. Unitary highest weight representations and their characters are classified and computed in terms of data associated to cosets of the Weyl group of the conformal algebra. An executive summary is provided, as well as look-up tables up to and including rank four.

Conformational Phase Diagram for Polymers Adsorbed on Ultrathin Nanowires

NASA Astrophysics Data System (ADS)

Vogel, Thomas; Bachmann, Michael

2010-05-01

We study the conformational behavior of a polymer adsorbed at an attractive stringlike nanowire and construct the complete structural phase diagram in dependence of the binding strength and effective thickness of the nanowire. For this purpose, Monte Carlo optimization techniques are employed to identify lowest-energy structures for a coarse-grained model of a polymer in contact with the nanowire. Among the representative conformations in the different phases are, for example, compact droplets attached to the wire and also nanotubelike monolayer films wrapping it in a very ordered way. We here systematically analyze low-energy shapes and structural order parameters to elucidate the transitions between the structural phases.

Conformational phase diagram for polymers adsorbed on ultrathin nanowires.

PubMed

Vogel, Thomas; Bachmann, Michael

2010-05-14

We study the conformational behavior of a polymer adsorbed at an attractive stringlike nanowire and construct the complete structural phase diagram in dependence of the binding strength and effective thickness of the nanowire. For this purpose, Monte Carlo optimization techniques are employed to identify lowest-energy structures for a coarse-grained model of a polymer in contact with the nanowire. Among the representative conformations in the different phases are, for example, compact droplets attached to the wire and also nanotubelike monolayer films wrapping it in a very ordered way. We here systematically analyze low-energy shapes and structural order parameters to elucidate the transitions between the structural phases.

Impact of mutations on the allosteric conformational equilibrium

PubMed Central

Weinkam, Patrick; Chen, Yao Chi; Pons, Jaume; Sali, Andrej

2012-01-01

Allostery in a protein involves effector binding at an allosteric site that changes the structure and/or dynamics at a distant, functional site. In addition to the chemical equilibrium of ligand binding, allostery involves a conformational equilibrium between one protein substate that binds the effector and a second substate that less strongly binds the effector. We run molecular dynamics simulations using simple, smooth energy landscapes to sample specific ligand-induced conformational transitions, as defined by the effector-bound and unbound protein structures. These simulations can be performed using our web server: http://salilab.org/allosmod/. We then develop a set of features to analyze the simulations and capture the relevant thermodynamic properties of the allosteric conformational equilibrium. These features are based on molecular mechanics energy functions, stereochemical effects, and structural/dynamic coupling between sites. Using a machine-learning algorithm on a dataset of 10 proteins and 179 mutations, we predict both the magnitude and sign of the allosteric conformational equilibrium shift by the mutation; the impact of a large identifiable fraction of the mutations can be predicted with an average unsigned error of 1 kBT. With similar accuracy, we predict the mutation effects for an 11th protein that was omitted from the initial training and testing of the machine-learning algorithm. We also assess which calculated thermodynamic properties contribute most to the accuracy of the prediction. PMID:23228330

Conformity-driven agents support ordered phases in the spatial public goods game

NASA Astrophysics Data System (ADS)

Javarone, Marco Alberto; Antonioni, Alberto; Caravelli, Francesco

2016-05-01

We investigate the spatial Public Goods Game in the presence of fitness-driven and conformity-driven agents. This framework usually considers only the former type of agents, i.e., agents that tend to imitate the strategy of their fittest neighbors. However, whenever we study social systems, the evolution of a population might be affected also by social behaviors as conformism, stubbornness, altruism, and selfishness. Although the term evolution can assume different meanings depending on the considered domain, here it corresponds to the set of processes that lead a system towards an equilibrium or a steady state. We map fitness to the agents' payoff so that richer agents are those most imitated by fitness-driven agents, while conformity-driven agents tend to imitate the strategy assumed by the majority of their neighbors. Numerical simulations aim to identify the nature of the transition, on varying the amount of the relative density of conformity-driven agents in the population, and to study the nature of related equilibria. Remarkably, we find that conformism generally fosters ordered cooperative phases and may also lead to bistable behaviors.

Identification of small molecules capable of regulating conformational changes of telomeric G-quadruplex

NASA Astrophysics Data System (ADS)

Chen, Shuo-Bin; Liu, Guo-Cai; Gu, Lian-Quan; Huang, Zhi-Shu; Tan, Jia-Heng

2018-02-01

Design of small molecules targeted at human telomeric G-quadruplex DNA is an extremely active research area. Interestingly, the telomeric G-quadruplex is a highly polymorphic structure. Changes in its conformation upon small molecule binding may be a powerful method to achieve a desired biological effect. However, the rational development of small molecules capable of regulating conformational change of telomeric G-quadruplex structures is still challenging. In this study, we developed a reliable ligand-based pharmacophore model based on isaindigotone derivatives with conformational change activity toward telomeric G-quadruplex DNA. Furthermore, virtual screening of database was conducted using this pharmacophore model and benzopyranopyrimidine derivatives in the database were identified as a strong inducer of the telomeric G-quadruplex DNA conformation, transforming it from hybrid-type structure to parallel structure.

Anharmonic Vibrational Analyses of Pentapeptide Conformations Explored with Enhanced Sampling Simulations.

PubMed

Otaki, Hiroki; Yagi, Kiyoshi; Ishiuchi, Shun-Ichi; Fujii, Masaaki; Sugita, Yuji

2016-10-06

An accurate theoretical prediction of the vibrational spectrum of polypeptides remains to be a challenge due to (1) their conformational flexibility and (2) non-negligible anharmonic effects. The former makes the search for conformers that contribute to the spectrum difficult, and the latter requires an expensive, quantum mechanical calculation for both electrons and vibrations. Here, we propose a new theoretical approach, which implements an enhanced conformational sampling by the replica-exchange molecular dynamics method, a structural clustering to identify distinct conformations, and a vibrational structure calculation by the second-order vibrational quasi-degenerate perturbation theory (VQDPT2). A systematic mode-selection scheme is developed to reduce the cost of VQDPT2 and the generation of a potential energy surface by the electronic structure calculation. The proposed method is applied to a pentapeptide, SIVSF-NH 2 , for which the infrared spectrum has recently been measured in the gas phase with high resolution in the OH and NH stretching region. The theoretical spectrum of the lowest energy conformer is obtained with a mean absolute deviation of 11.2 cm -1 from the experimental spectrum. Furthermore, the NH stretching frequencies of the five lowest energy conformers are found to be consistent with the literature values measured for small peptides with a similar secondary structure. Therefore, the proposed method is a promising way to analyze the vibrational spectrum of polypeptides.

Benchmarking Commercial Conformer Ensemble Generators.

PubMed

Friedrich, Nils-Ole; de Bruyn Kops, Christina; Flachsenberg, Florian; Sommer, Kai; Rarey, Matthias; Kirchmair, Johannes

2017-11-27

We assess and compare the performance of eight commercial conformer ensemble generators (ConfGen, ConfGenX, cxcalc, iCon, MOE LowModeMD, MOE Stochastic, MOE Conformation Import, and OMEGA) and one leading free algorithm, the distance geometry algorithm implemented in RDKit. The comparative study is based on a new version of the Platinum Diverse Dataset, a high-quality benchmarking dataset of 2859 protein-bound ligand conformations extracted from the PDB. Differences in the performance of commercial algorithms are much smaller than those observed for free algorithms in our previous study (J. Chem. Inf. 2017, 57, 529-539). For commercial algorithms, the median minimum root-mean-square deviations measured between protein-bound ligand conformations and ensembles of a maximum of 250 conformers are between 0.46 and 0.61 Å. Commercial conformer ensemble generators are characterized by their high robustness, with at least 99% of all input molecules successfully processed and few or even no substantial geometrical errors detectable in their output conformations. The RDKit distance geometry algorithm (with minimization enabled) appears to be a good free alternative since its performance is comparable to that of the midranked commercial algorithms. Based on a statistical analysis, we elaborate on which algorithms to use and how to parametrize them for best performance in different application scenarios.

Static models with conformal symmetry

NASA Astrophysics Data System (ADS)

Manjonjo, A. M.; Maharaj, S. D.; Moopanar, S.

2018-02-01

We study static spherically symmetric spacetimes with a spherical conformal symmetry and a nonstatic conformal factor associated with the conformal Killing field. With these assumptions we find an explicit relationship relating two metric components of the metric tensor field. This leads to the general solution of the Einstein field equations with a conformal symmetry in a static spherically symmetric spacetime. For perfect fluids we can find all metrics explicitly and show that the models always admit a barotropic equation of state. Contained within this class of spacetimes are the well known metrics of (interior) Schwarzschild, Tolman, Kuchowicz, Korkina and Orlyanskii, Patwardhan and Vaidya, and Buchdahl and Land. The isothermal metric of Saslaw et al also admits a conformal symmetry. For imperfect fluids an infinite family of exact solutions to the field equations can be generated.

Conformal and Nearly Conformal Theories at Large N

NASA Astrophysics Data System (ADS)

Tarnoplskiy, Grigory M.

In this thesis we present new results in conformal and nearly conformal field theories in various dimensions. In chapter two, we study different properties of the conformal Quantum Electrodynamics (QED) in continuous dimension d. At first we study conformal QED using large Nf methods, where Nf is the number of massless fermions. We compute its sphere free energy as a function of d, ignoring the terms of order 1/Nf and higher. For finite Nf we use the epsilon-expansion. Next we use a large Nf diagrammatic approach to calculate the leading corrections to CT, the coefficient of the two-point function of the stress-energy tensor, and CJ, the coefficient of the two-point function of the global symmetry current. We present explicit formulae as a function of d and check them versus the expectations in 2 and 4 - epsilon dimensions. In chapter three, we discuss vacuum stability in 1 + 1 dimensional conformal field theories with external background fields. We show that the vacuum decay rate is given by a non-local two-form. This two-form is a boundary term that must be added to the effective in/out Lagrangian. The two-form is expressed in terms of a Riemann-Hilbert decomposition for background gauge fields, and is given by its novel "functional'' version in the gravitational case. In chapter four, we explore Tensor models. Such models possess the large N limit dominated by the melon diagrams. The quantum mechanics of a real anti-commuting rank-3 tensor has a large N limit similar to the Sachdev-Ye-Kitaev (SYK) model. We also discuss the quantum mechanics of a complex 3-index anti-commuting tensor and argue that it is equivalent in the large N limit to a version of SYK model with complex fermions. Finally, we discuss models of a commuting tensor in dimension d. We study the spectrum of the large N quantum field theory of bosonic rank-3 tensors using the Schwinger-Dyson equations. We compare some of these results with the 4 - epsilon expansion, finding perfect agreement. We

Insights into the conformational switching mechanism of the human vascular endothelial growth factor receptor type 2 kinase domain.

PubMed

Chioccioli, Matteo; Marsili, Simone; Bonaccini, Claudia; Procacci, Piero; Gratteri, Paola

2012-02-27

Human vascular endothelial growth factor receptor type 2 (h-VEFGR2) is a receptor tyrosine kinase involved in the angiogenesis process and regarded as an interesting target for the design of anticancer drugs. Its activation/inactivation mechanism is related to conformational changes in its cytoplasmatic kinase domain, involving first among all the αC-helix in N-lobe and the A-loop in C-lobe. Affinity of inhibitors for the active or inactive kinase form could dictate the open or closed conformation of the A-loop, thus making the different conformations of the kinase domain receptor (KDR) domain different drug targets in drug discovery. In this view, a detailed knowledge of the conformational landscape of KDR domain is of central relevance to rationalize the efficiency and selectivity of kinase inhibitors. Here, molecular dynamics simulations were used to gain insight into the conformational switching activity of the KDR domain and to identify intermediate conformations between the two limiting active and inactive conformations. Specific energy barriers have been selectively removed to induce, and hence highlight at the atomistic level, the regulation mechanism of the A-loop opening. The proposed strategy allowed to repeatedly observe the escape of the KDR domain from the DFG-out free energy basin and to identify rare intermediate conformations between the DFG-out and the DFG-in structures to be employed in a structure-based drug discovery process.

Conformational selection in protein binding and function

PubMed Central

Weikl, Thomas R; Paul, Fabian

2014-01-01

Protein binding and function often involves conformational changes. Advanced nuclear magnetic resonance (NMR) experiments indicate that these conformational changes can occur in the absence of ligand molecules (or with bound ligands), and that the ligands may “select” protein conformations for binding (or unbinding). In this review, we argue that this conformational selection requires transition times for ligand binding and unbinding that are small compared to the dwell times of proteins in different conformations, which is plausible for small ligand molecules. Such a separation of timescales leads to a decoupling and temporal ordering of binding/unbinding events and conformational changes. We propose that conformational-selection and induced-change processes (such as induced fit) are two sides of the same coin, because the temporal ordering is reversed in binding and unbinding direction. Conformational-selection processes can be characterized by a conformational excitation that occurs prior to a binding or unbinding event, while induced-change processes exhibit a characteristic conformational relaxation that occurs after a binding or unbinding event. We discuss how the ordering of events can be determined from relaxation rates and effective on- and off-rates determined in mixing experiments, and from the conformational exchange rates measured in advanced NMR or single-molecule fluorescence resonance energy transfer experiments. For larger ligand molecules such as peptides, conformational changes and binding events can be intricately coupled and exhibit aspects of conformational-selection and induced-change processes in both binding and unbinding direction. PMID:25155241

Intramolecular BSSE and dispersion affect the structure of a dipeptide conformer

NASA Astrophysics Data System (ADS)

Hameed, Rabia; Khan, Afsar; van Mourik, Tanja

2018-05-01

B3LYP and MP2 calculations with the commonly-used 6-31+G(d) basis set predict qualitatively different structures for the Tyr-Gly conformer book1, which is the most stable conformer identified in a previous study. The structures differ mainly in the ψtyr Ramachandran angle (138° in the B3LYP structure and 120° in the MP2 structure). The causes for the discrepant structures are attributed to missing dispersion in the B3LYP calculations and large intramolecular BSSE in the MP2 calculations. The correct ψtyr value is estimated to be 130°. The MP2/6-31+G(d) profile identified an additional conformer, not present on the B3LYP surface, with a ψtyr value of 96° and a more folded structure. This minimum is, however, likely an artefact of large intramolecular BSSE values. We recommend the use of basis sets of at least quadruple-zeta quality in density functional theory (DFT), DFTaugmented with an empirical dispersion term (DFT-D) and second-order Møller-Plesset perturbation theory (MP2 ) calculations in cases where intramolecular BSSE is expected to be large.

Sialyldisaccharide conformations: a molecular dynamics perspective

NASA Astrophysics Data System (ADS)

Selvin, Jeyasigamani F. A.; Priyadarzini, Thanu R. K.; Veluraja, Kasinadar

2012-04-01

Sialyldisaccharides are significant terminal components of glycoconjugates and their negative charge and conformation are extensively utilized in molecular recognition processes. The conformation and flexibility of four biologically important sialyldisaccharides [Neu5Acα(2-3)Gal, Neu5Acα(2-6)Gal, Neu5Acα(2-8)Neu5Ac and Neu5Acα(2-9)Neu5Ac] are studied using Molecular Dynamics simulations of 20 ns duration to deduce the conformational preferences of the sialyldisaccharides and the interactions which stabilize the conformations. This study clearly describes the possible conformational models of sialyldisaccharides deduced from 20 ns Molecular Dynamics simulations and our results confirm the role of water in the structural stabilization of sialyldisaccharides. An extensive analysis on the sialyldisaccharide structures available in PDB also confirms the conformational regions found by experiments are detected in MD simulations of 20 ns duration. The three dimensional structural coordinates for all the MD derived sialyldisaccharide conformations are deposited in the 3DSDSCAR database and these conformational models will be useful for glycobiologists and biotechnologists to understand the biological functions of sialic acid containing glycoconjugates.

Conformations of Substituted Ethanes.

ERIC Educational Resources Information Center

Kingsbury, Charles A.

1979-01-01

Reviews state-of-the-art of conformational analysis and factors which affect it. Emphasizes sp-3 hybridized acrylic molecules. Provides examples on the importance of certain factors in determining conformation. Purpose, is to provide examples for examination questions. (Author/SA)

Towards conformal loop quantum gravity

NASA Astrophysics Data System (ADS)

H-T Wang, Charles

2006-03-01

A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and Diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the canonical generators for spin-gauge and conformorphism transformations. The formulation has a remarkable feature of being parameter-free. Indeed, it is shown that a conformal parameter of the Barbero-Immirzi type can be absorbed by the conformal symmetry of the extended phase space. This gives rise to an alternative approach to loop quantum gravity that addresses both the conceptual problem of time and the technical problem of functional calculus in quantum gravity.

Raman spectral signatures as conformational probes of gas phase flexible molecules

NASA Astrophysics Data System (ADS)

Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman; Bar, Ilana

2009-07-01

A novel application of ionization-loss stimulated Raman spectroscopy (ILSRS) for monitoring the spectral features of four conformers of a gas phase flexible molecule is reported. The Raman spectral signatures of four conformers of 2-phenylethylamine are well matched by the results of density functional theory calculations, showing bands uniquely identifying the structures. The measurement of spectral signatures by ILSRS in an extended spectral range, with a conventional laser source, is instrumental in facilitating the unraveling of intra- and intermolecular interactions that are significant in biological structure and activity.

Enhanced conformational sampling technique provides an energy landscape view of large-scale protein conformational transitions.

PubMed

Shao, Qiang

2016-10-26

Large-scale conformational changes in proteins are important for their functions. Tracking the conformational change in real time at the level of a single protein molecule, however, remains a great challenge. In this article, we present a novel in silico approach with the combination of normal mode analysis and integrated-tempering-sampling molecular simulation (NMA-ITS) to give quantitative data for exploring the conformational transition pathway in multi-dimensional energy landscapes starting only from the knowledge of the two endpoint structures of the protein. The open-to-closed transitions of three proteins, including nCaM, AdK, and HIV-1 PR, were investigated using NMA-ITS simulations. The three proteins have varied structural flexibilities and domain communications in their respective conformational changes. The transition state structure in the conformational change of nCaM and the associated free-energy barrier are in agreement with those measured in a standard explicit-solvent REMD simulation. The experimentally measured transition intermediate structures of the intrinsically flexible AdK are captured by the conformational transition pathway measured here. The dominant transition pathways between the closed and fully open states of HIV-1 PR are very similar to those observed in recent REMD simulations. Finally, the evaluated relaxation times of the conformational transitions of three proteins are roughly at the same level as reported experimental data. Therefore, the NMA-ITS method is applicable for a variety of cases, providing both qualitative and quantitative insights into the conformational changes associated with the real functions of proteins.

Acculturation matters in the relation between ambivalence over emotional expressions and well-being among Chinese American breast cancer survivors.

PubMed

Tsai, William; Lu, Qian

2017-10-01

Ambivalence over emotional expression (AEE) is the inner conflict of desiring emotion expression and fearing consequence of emotion expression. Few studies to date have examined the effects of AEE within an ethnic group that prioritizes emotional self-control. The present study examined the associations between AEE and well-being (viz., quality of life and depressive symptoms) as a function of acculturation among a sample of Chinese American breast cancer survivors. Ninety-six Chinese breast cancer survivors (M age  = 54.64 years old, SD = 7.98) were recruited from Southern California. Participants filled out a paper-pen questionnaire containing the Ambivalence over Emotional Expression Questionnaire (AEQ), the Functional Assessment of Cancer Therapy-Breast (FACT-B), and the Center for Epidemiologic Studies Depression Scale-Short Form (CESD-10). Acculturation was a statistically significant moderator of the relations between AEE and depressive symptoms, and a statistically marginally significant moderator of the relations between AEE and quality of life. Simple slopes revealed that AEE was negatively associated with quality of life (B = -.45, p < .001) and depressive symptoms (B = .20, p < .001) for women with high acculturation, but not associated for women with low acculturation (Bs = -.15 and .04, ps > .05, for quality of life and depressive symptoms, respectively). These results suggest that less acculturated Chinese breast cancer survivors are protected by Chinese cultural values of emotional self-control and restraint, and thus do not experience the detrimental effects of AEE on their depressive symptoms and quality of life. Implications are discussed.

Leap-dynamics: efficient sampling of conformational space of proteins and peptides in solution.

PubMed

Kleinjung, J; Bayley, P; Fraternali, F

2000-03-31

A molecular simulation scheme, called Leap-dynamics, that provides efficient sampling of protein conformational space in solution is presented. The scheme is a combined approach using a fast sampling method, imposing conformational 'leaps' to force the system over energy barriers, and molecular dynamics (MD) for refinement. The presence of solvent is approximated by a potential of mean force depending on the solvent accessible surface area. The method has been successfully applied to N-acetyl-L-alanine-N-methylamide (alanine dipeptide), sampling experimentally observed conformations inaccessible to MD alone under the chosen conditions. The method predicts correctly the increased partial flexibility of the mutant Y35G compared to native bovine pancreatic trypsin inhibitor. In particular, the improvement over MD consists of the detection of conformational flexibility that corresponds closely to slow motions identified by nuclear magnetic resonance techniques.

A pH-induced conformational switch in a tyrosine kinase inhibitor identified by electronic spectroscopy and quantum chemical calculations.

PubMed

Khattab, Muhammad; Wang, Feng; Clayton, Andrew H A

2017-11-24

Tyrosine kinase inhibitors (TKIs) are a major class of drug utilised in the clinic. During transit to their cognate kinases, TKIs will encounter different pH environments that could have a major influence on TKI structure. To address this, we report UV-Vis spectroscopic and computational studies of the TKI, AG1478, as a function of pH. The electronic absorption spectrum of AG1478 shifted by 10 nm (from 342 nm to 332 nm) from acid to neutral pH and split into two peaks (at 334 nm and 345 nm) in highly alkaline conditions. From these transitions, the pKa value was calculated as 5.58 ± 0.01. To compute structures and spectra, time-dependent density functional theory (TD-DFT) calculations were performed along with conductor-like polarizable continuum model (CPCM) to account for implicit solvent effect. On the basis of the theoretical spectra, we could assign the AG1478 experimental spectrum at acidic pH to a mixture of two twisted conformers (71% AG1478 protonated at quinazolyl nitrogen N(1) and 29% AG1478 protonated at quinazolyl nitrogen N(3)) and at neutral pH to the neutral planar conformer. The AG1478 absorption spectrum (pH 13.3) was fitted to a mixture of neutral (70%) and NH-deprotonated species (30%). These studies reveal a pH-induced conformational transition in a TKI.

Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble

PubMed Central

Yongye, Austin B.; Bender, Andreas

2010-01-01

Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged-RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged-RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 Å). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1–4), medium (5–9) and high (10–15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening

Conformable derivative approach to anomalous diffusion

NASA Astrophysics Data System (ADS)

Zhou, H. W.; Yang, S.; Zhang, S. Q.

2018-02-01

By using a new derivative with fractional order, referred to conformable derivative, an alternative representation of the diffusion equation is proposed to improve the modeling of anomalous diffusion. The analytical solutions of the conformable derivative model in terms of Gauss kernel and Error function are presented. The power law of the mean square displacement for the conformable diffusion model is studied invoking the time-dependent Gauss kernel. The parameters related to the conformable derivative model are determined by Levenberg-Marquardt method on the basis of the experimental data of chloride ions transportation in reinforced concrete. The data fitting results showed that the conformable derivative model agrees better with the experimental data than the normal diffusion equation. Furthermore, the potential application of the proposed conformable derivative model of water flow in low-permeability media is discussed.

Weight shifting operators and conformal blocks

NASA Astrophysics Data System (ADS)

Karateev, Denis; Kravchuk, Petr; Simmons-Duffin, David

2018-02-01

We introduce a large class of conformally-covariant differential operators and a crossing equation that they obey. Together, these tools dramatically simplify calculations involving operators with spin in conformal field theories. As an application, we derive a formula for a general conformal block (with arbitrary internal and external representations) in terms of derivatives of blocks for external scalars. In particular, our formula gives new expressions for "seed conformal blocks" in 3d and 4d CFTs. We also find simple derivations of identities between external-scalar blocks with different dimensions and internal spins. We comment on additional applications, including deriving recursion relations for general conformal blocks, reducing inversion formulae for spinning operators to inversion formulae for scalars, and deriving identities between general 6 j symbols (Racah-Wigner coefficients/"crossing kernels") of the conformal group.

On The Evidence For Large-Scale Galactic Conformity In The Local Universe

NASA Astrophysics Data System (ADS)

Sin, Larry P. T.; Lilly, Simon J.; Henriques, Bruno M. B.

2017-10-01

We re-examine the observational evidence for large-scale (4 Mpc) galactic conformity in the local Universe, as presented in Kauffmann et al. We show that a number of methodological features of their analysis act to produce a misleadingly high amplitude of the conformity signal. These include a weighting in favour of central galaxies in very high density regions, the likely misclassification of satellite galaxies as centrals in the same high-density regions and the use of medians to characterize bimodal distributions. We show that the large-scale conformity signal in Kauffmann et al. clearly originates from a very small number of central galaxies in the vicinity of just a few very massive clusters, whose effect is strongly amplified by the methodological issues that we have identified. Some of these 'centrals' are likely misclassified satellites, but some may be genuine centrals showing a real conformity effect. Regardless, this analysis suggests that conformity on 4 Mpc scales is best viewed as a relatively short-range effect (at the virial radius) associated with these very large neighbouring haloes, rather than a very long-range effect (at tens of virial radii) associated with the relatively low-mass haloes that host the nominal central galaxies in the analysis. A mock catalogue constructed from a recent semi-analytic model shows very similar conformity effects to the data when analysed in the same way, suggesting that there is no need to introduce new physical processes to explain galactic conformity on 4 Mpc scales.

Effects of Message Framing on Influenza Vaccination: Understanding the Role of Risk Disclosure, Perceived Vaccine Efficacy, and Felt Ambivalence.

PubMed

Kim, Sungsu; Pjesivac, Ivanka; Jin, Yan

2017-10-20

The current study examined the effects of framing in promotional health messages on intention to vaccinate against seasonal influenza virus. The findings of an experimental study (N = 86) indicated that exposure to both benefits and side effects of vaccination (gain-framed with risk disclosure message) led to lower intention to receive the flu vaccine. This relationship was mediated by both perceived vaccine efficacy and felt ambivalence in a serial order, revealing the underlying psychological mechanisms important for understanding health-related behaviors. Theoretical implications of constructing sub-framed messages are discussed and the concept of second-order framing is introduced.

Conformational analysis of a modified RGD adhesive sequence.

PubMed

Triguero, Jordi; Zanuy, David; Alemán, Carlos

2017-02-01

The conformational preferences of the Arg-GlE-Asp sequence, where GlE is an engineered amino acid bearing a 3,4-ethylenedioxythiophene (EDOT) ring as side group, have been determined combining density functional theory calculations with a well-established conformational search strategy. Although the Arg-GlE-Asp sequence was designed to prepare a conducting polymer-peptide conjugate with excellent electrochemical and bioadhesive properties, the behavior of such hybrid material as adhesive biointerface is improvable. Results obtained in this work prove that the bioactive characteristics of the parent Arg-Gly-Asp sequence become unstable in Arg-GlE-Asp because of both the steric hindrance caused by the EDOT side group and the repulsive interactions between the oxygen atoms belonging to the backbone amide groups and the EDOT side group. Detailed analyses of the conformational preferences identified in this work have been used to re-engineer the Arg-GlE-Asp sequence for the future development of a new electroactive conjugate with improved bioadhesive properties. The preparation of this new conjugate is in progress. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Conformal higher spin theory and twistor space actions

NASA Astrophysics Data System (ADS)

Hähnel, Philipp; McLoughlin, Tristan

2017-12-01

We consider the twistor description of conformal higher spin theories and give twistor space actions for the self-dual sector of theories with spin greater than two that produce the correct flat space-time spectrum. We identify a ghost-free subsector, analogous to the embedding of Einstein gravity with cosmological constant in Weyl gravity, which generates the unique spin-s three-point anti-MHV amplitude consistent with Poincaré invariance and helicity constraints. By including interactions between the infinite tower of higher-spin fields we give a geometric interpretation to the twistor equations of motion as the integrability condition for a holomorphic structure on an infinite jet bundle. Finally, we conjecture anti-self-dual interaction terms which give an implicit definition of a twistor action for the full conformal higher spin theory.

Pilot Non-Conformance to Alerting System Commands During Closely Spaced Parallel Approaches

NASA Technical Reports Server (NTRS)

Pritchett, Amy Ruth; Hansman, R. John; Corker, Kevin (Technical Monitor)

1997-01-01

Cockpit alerting systems monitor potentially hazardous situations, both inside and outside the aircraft. When a hazard is projected to occur, the alerting system displays alerts and/or command decisions to the pilot. However, pilots have been observed to not conform to alerting system commands by delaying their response or by not following the automatic commands exactly. This non-conformance to the automatic alerting system can reduce its benefit. Therefore, a need exists to understand the causes and effects of pilot non-conformance in order to develop automatic alerting systems whose commands the pilots are more likely to follow. These considerations were examined through flight simulator evaluations of the collision avoidance task during closely spaced parallel approaches. This task provided a useful case-study because the effects of non-conformance can be significant, given the time-critical nature of the task. A preliminary evaluation of alerting systems identified non-conformance in over 40% of the cases and a corresponding drop in collision avoidance performance. A follow-on experiment found subjects' alerting and maneuver selection criteria were consistent with different strategies than those used by automatic systems, indicating the pilot may potentially disagree with the alerting system if the pilot attempts to verify automatic alerts and commanded avoidance maneuvers. A final experiment found supporting automatic alerts with the explicit display of its underlying criteria resulted in more consistent subject reactions. In light of these experimental results, a general discussion of pilot non-conformance is provided. Contributing factors in pilot non-conformance include a lack of confidence in the automatic system and mismatches between the alerting system's commands and the pilots' own decisions based on the information available to them. The effects of non-conformance on system performance are discussed. Possible methods of reconciling mismatches are

Conformity and statistical tolerancing

NASA Astrophysics Data System (ADS)

Leblond, Laurent; Pillet, Maurice

2018-02-01

Statistical tolerancing was first proposed by Shewhart (Economic Control of Quality of Manufactured Product, (1931) reprinted 1980 by ASQC), in spite of this long history, its use remains moderate. One of the probable reasons for this low utilization is undoubtedly the difficulty for designers to anticipate the risks of this approach. The arithmetic tolerance (worst case) allows a simple interpretation: conformity is defined by the presence of the characteristic in an interval. Statistical tolerancing is more complex in its definition. An interval is not sufficient to define the conformance. To justify the statistical tolerancing formula used by designers, a tolerance interval should be interpreted as the interval where most of the parts produced should probably be located. This tolerance is justified by considering a conformity criterion of the parts guaranteeing low offsets on the latter characteristics. Unlike traditional arithmetic tolerancing, statistical tolerancing requires a sustained exchange of information between design and manufacture to be used safely. This paper proposes a formal definition of the conformity, which we apply successively to the quadratic and arithmetic tolerancing. We introduce a concept of concavity, which helps us to demonstrate the link between tolerancing approach and conformity. We use this concept to demonstrate the various acceptable propositions of statistical tolerancing (in the space decentring, dispersion).

Dissecting the large-scale galactic conformity

NASA Astrophysics Data System (ADS)

Seo, Seongu

2018-01-01

Galactic conformity is an observed phenomenon that galaxies located in the same region have similar properties such as star formation rate, color, gas fraction, and so on. The conformity was first observed among galaxies within in the same halos (“one-halo conformity”). The one-halo conformity can be readily explained by mutual interactions among galaxies within a halo. Recent observations however further witnessed a puzzling connection among galaxies with no direct interaction. In particular, galaxies located within a sphere of ~5 Mpc radius tend to show similarities, even though the galaxies do not share common halos with each other ("two-halo conformity" or “large-scale conformity”). Using a cosmological hydrodynamic simulation, Illustris, we investigate the physical origin of the two-halo conformity and put forward two scenarios. First, back-splash galaxies are likely responsible for the large-scale conformity. They have evolved into red galaxies due to ram-pressure stripping in a given galaxy cluster and happen to reside now within a ~5 Mpc sphere. Second, galaxies in strong tidal field induced by large-scale structure also seem to give rise to the large-scale conformity. The strong tides suppress star formation in the galaxies. We discuss the importance of the large-scale conformity in the context of galaxy evolution.

Entanglement evolution across a conformal interface

NASA Astrophysics Data System (ADS)

Wen, Xueda; Wang, Yuxuan; Ryu, Shinsei

2018-05-01

For two-dimensional conformal field theories (CFTs) in the ground state, it is known that a conformal interface along the entanglement cut can suppress the entanglement entropy from to , where L is the length of the subsystem A, and is the effective central charge which depends on the transmission property of the conformal interface. In this work, by making use of conformal mappings, we show that a conformal interface has the same effect on entanglement evolution in non-equilibrium cases, including global, local and certain inhomogeneous quantum quenches. I.e. a conformal interface suppresses the time evolution of entanglement entropy by effectively replacing the central charge c with , where is exactly the same as that in the ground state case. We confirm this conclusion by a numerical study on a critical fermion chain. Furthermore, based on the quasi-particle picture, we conjecture that this conclusion holds for an arbitrary quantum quench in CFTs, as long as the initial state can be described by a regularized conformal boundary state.

Behavioral responses of wolves to roads: scale-dependent ambivalence

PubMed Central

Nelson, Lindsey; Wabakken, Petter; Sand, Håkan; Liberg, Olof

2014-01-01

Throughout their recent recovery in several industrialized countries, large carnivores have had to cope with a changed landscape dominated by human infrastructure. Population growth depends on the ability of individuals to adapt to these changes by making use of new habitat features and at the same time to avoid increased risks of mortality associated with human infrastructure. We analyzed the summer movements of 19 GPS-collared resident wolves (Canis lupus L.) from 14 territories in Scandinavia in relation to roads. We used resource and step selection functions, including >12000 field-checked GPS-positions and 315 kill sites. Wolves displayed ambivalent responses to roads depending on the spatial scale, road type, time of day, behavioral state, and reproductive status. At the site scale (approximately 0.1 km2), they selected for roads when traveling, nearly doubling their travel speed. Breeding wolves moved the fastest. At the patch scale (10 km2), house density rather than road density was a significant negative predictor of wolf patch selection. At the home range scale (approximately 1000 km2), breeding wolves increased gravel road use with increasing road availability, although at a lower rate than expected. Wolves have adapted to use roads for ease of travel, but at the same time developed a cryptic behavior to avoid human encounters. This behavioral plasticity may have been important in allowing the successful recovery of wolf populations in industrialized countries. However, we emphasize the role of roads as a potential cause of increased human-caused mortality. PMID:25419085

Behavioral responses of wolves to roads: scale-dependent ambivalence.

PubMed

Zimmermann, Barbara; Nelson, Lindsey; Wabakken, Petter; Sand, Håkan; Liberg, Olof

2014-11-01

Throughout their recent recovery in several industrialized countries, large carnivores have had to cope with a changed landscape dominated by human infrastructure. Population growth depends on the ability of individuals to adapt to these changes by making use of new habitat features and at the same time to avoid increased risks of mortality associated with human infrastructure. We analyzed the summer movements of 19 GPS-collared resident wolves ( Canis lupus L.) from 14 territories in Scandinavia in relation to roads. We used resource and step selection functions, including >12000 field-checked GPS-positions and 315 kill sites. Wolves displayed ambivalent responses to roads depending on the spatial scale, road type, time of day, behavioral state, and reproductive status. At the site scale (approximately 0.1 km 2 ), they selected for roads when traveling, nearly doubling their travel speed. Breeding wolves moved the fastest. At the patch scale (10 km 2 ), house density rather than road density was a significant negative predictor of wolf patch selection. At the home range scale (approximately 1000 km 2 ), breeding wolves increased gravel road use with increasing road availability, although at a lower rate than expected. Wolves have adapted to use roads for ease of travel, but at the same time developed a cryptic behavior to avoid human encounters. This behavioral plasticity may have been important in allowing the successful recovery of wolf populations in industrialized countries. However, we emphasize the role of roads as a potential cause of increased human-caused mortality.

Ligand Induced Conformational Changes of the Human Serotonin Transporter Revealed by Molecular Dynamics Simulations

PubMed Central

Grouleff, Julie; Schiøtt, Birgit

2013-01-01

The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design. PMID:23776432

Conformer-specific hydrogen atom tunnelling in trifluoromethylhydroxycarbene

NASA Astrophysics Data System (ADS)

Mardyukov, Artur; Quanz, Henrik; Schreiner, Peter R.

2017-01-01

Conformational control of organic reactions is at the heart of the biomolecular sciences. To achieve a particular reactivity, one of many conformers may be selected, for instance, by a (bio)catalyst, as the geometrically most suited and appropriately reactive species. The equilibration of energetically close-lying conformers is typically assumed to be facile and less energetically taxing than the reaction under consideration itself: this is termed the 'Curtin-Hammett principle'. Here, we show that the trans conformer of trifluoromethylhydroxycarbene preferentially rearranges through a facile quantum-mechanical hydrogen tunnelling pathway, while its cis conformer is entirely unreactive. Hence, this presents the first example of a conformer-specific hydrogen tunnelling reaction. The Curtin-Hammett principle is not applicable, due to the high barrier between the two conformers.

40 CFR 52.799 - Transportation conformity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting of...

40 CFR 52.799 - Transportation conformity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting of...

40 CFR 52.799 - Transportation conformity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting of...

40 CFR 52.799 - Transportation conformity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting of...

Lattice Simulations and Infrared Conformality

DOE PAGES

Appelquist, Thomas; Fleming, George T.; Lin, Meifeng; ...

2011-09-01

We examine several recent lattice-simulation data sets, asking whether they are consistent with infrared conformality. We observe, in particular, that for an SU(3) gauge theory with 12 Dirac fermions in the fundamental representation, recent simulation data can be described assuming infrared conformality. Lattice simulations include a fermion mass m which is then extrapolated to zero, and we note that this data can be fit by a small-m expansion, allowing a controlled extrapolation. We also note that the conformal hypothesis does not work well for two theories that are known or expected to be confining and chirally broken, and that itmore » does work well for another theory expected to be infrared conformal.« less

Large-Scale Conformational Changes of Trypanosoma cruzi Proline Racemase Predicted by Accelerated Molecular Dynamics Simulation

PubMed Central

McCammon, J. Andrew

2011-01-01

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life-threatening illness affecting 11–18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR) as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery. PMID:22022240

Large-scale conformational changes of Trypanosoma cruzi proline racemase predicted by accelerated molecular dynamics simulation.

PubMed

de Oliveira, César Augusto F; Grant, Barry J; Zhou, Michelle; McCammon, J Andrew

2011-10-01

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life-threatening illness affecting 11-18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR) as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery.

Conformers, infrared spectrum, UV-induced photochemistry, and near-IR-induced generation of two rare conformers of matrix-isolated phenylglycine.

PubMed

Borba, Ana; Gómez-Zavaglia, Andrea; Fausto, Rui

2014-10-21

The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N-H···O=C, type II by a strong O-H···N hydrogen bond, type III by weak N-H···O-H hydrogen bonds, and type IV by a C=O···H-C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the case of conformers of type II, where the strong intramolecular O-H···N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N2 matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm(-1), respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix revealed that PG undergoes facile

Conformers, infrared spectrum, UV-induced photochemistry, and near-IR-induced generation of two rare conformers of matrix-isolated phenylglycine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borba, Ana, E-mail: anaborba@ci.uc.pt; Fausto, Rui; Gómez-Zavaglia, Andrea

The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N–H···O=C, type II by a strong O–H···N hydrogen bond, type III by weak N–H···O–H hydrogen bonds, and type IV by a C=O···H–C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the casemore » of conformers of type II, where the strong intramolecular O–H···N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N{sub 2} matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm{sup −1}, respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix

Conformers of CL-20 explosive and ab initio refinement using perturbation theory: implications to detonation mechanisms.

PubMed

Molt, Robert W; Bartlett, Rodney J; Watson, Thomas; Bazanté, Alexandre P

2012-12-13

We have identified the major conformers of CL-20 explosive, otherwise known as 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane, more formally known as 2,4,6,8,10,12-hexanitrohexaazatetracyclo[5.5.0.0]-dodecane, via Monte Carlo search in conformational space through molecular mechanics and subsequent quantum mechanical refinement using perturbation theory. Our search produced enough conformers to account for all of the various forms of CL-20 found in crystals. This suggests that our methodology will be useful in studying the conformational landscape of other nitramines. The energy levels of the conformers found are all within 0.25 eV of one another based on MBPT(2)/6-311G(d,p); consequently, without further refinement from a method such as coupled cluster theory, all conformers may reasonably be populated at STP in the gas phase. We also report the harmonic vibrational frequencies of conformers, including the implications on the mechanism of detonation. In particular, we establish that the weakest N-N nitramine of CL-20 is the cyclohexane equatorial nitramine. This preliminary mapping of the conformers of CL-20 makes it possible to study the mechanism of detonation of this explosive rigorously in future work.

Deciphering the shape and deformation of secondary structures through local conformation analysis

PubMed Central

2011-01-01

Background Protein deformation has been extensively analysed through global methods based on RMSD, torsion angles and Principal Components Analysis calculations. Here we use a local approach, able to distinguish among the different backbone conformations within loops, α-helices and β-strands, to address the question of secondary structures' shape variation within proteins and deformation at interface upon complexation. Results Using a structural alphabet, we translated the 3 D structures of large sets of protein-protein complexes into sequences of structural letters. The shape of the secondary structures can be assessed by the structural letters that modeled them in the structural sequences. The distribution analysis of the structural letters in the three protein compartments (surface, core and interface) reveals that secondary structures tend to adopt preferential conformations that differ among the compartments. The local description of secondary structures highlights that curved conformations are preferred on the surface while straight ones are preferred in the core. Interfaces display a mixture of local conformations either preferred in core or surface. The analysis of the structural letters transition occurring between protein-bound and unbound conformations shows that the deformation of secondary structure is tightly linked to the compartment preference of the local conformations. Conclusion The conformation of secondary structures can be further analysed and detailed thanks to a structural alphabet which allows a better description of protein surface, core and interface in terms of secondary structures' shape and deformation. Induced-fit modification tendencies described here should be valuable information to identify and characterize regions under strong structural constraints for functional reasons. PMID:21284872

Deciphering the shape and deformation of secondary structures through local conformation analysis.

PubMed

Baussand, Julie; Camproux, Anne-Claude

2011-02-01

Protein deformation has been extensively analysed through global methods based on RMSD, torsion angles and Principal Components Analysis calculations. Here we use a local approach, able to distinguish among the different backbone conformations within loops, α-helices and β-strands, to address the question of secondary structures' shape variation within proteins and deformation at interface upon complexation. Using a structural alphabet, we translated the 3 D structures of large sets of protein-protein complexes into sequences of structural letters. The shape of the secondary structures can be assessed by the structural letters that modeled them in the structural sequences. The distribution analysis of the structural letters in the three protein compartments (surface, core and interface) reveals that secondary structures tend to adopt preferential conformations that differ among the compartments. The local description of secondary structures highlights that curved conformations are preferred on the surface while straight ones are preferred in the core. Interfaces display a mixture of local conformations either preferred in core or surface. The analysis of the structural letters transition occurring between protein-bound and unbound conformations shows that the deformation of secondary structure is tightly linked to the compartment preference of the local conformations. The conformation of secondary structures can be further analysed and detailed thanks to a structural alphabet which allows a better description of protein surface, core and interface in terms of secondary structures' shape and deformation. Induced-fit modification tendencies described here should be valuable information to identify and characterize regions under strong structural constraints for functional reasons.

Lie algebra of conformal Killing-Yano forms

NASA Astrophysics Data System (ADS)

Ertem, Ümit

2016-06-01

We provide a generalization of the Lie algebra of conformal Killing vector fields to conformal Killing-Yano forms. A new Lie bracket for conformal Killing-Yano forms that corresponds to slightly modified Schouten-Nijenhuis bracket of differential forms is proposed. We show that conformal Killing-Yano forms satisfy a graded Lie algebra in constant curvature manifolds. It is also proven that normal conformal Killing-Yano forms in Einstein manifolds also satisfy a graded Lie algebra. The constructed graded Lie algebras reduce to the graded Lie algebra of Killing-Yano forms and the Lie algebras of conformal Killing and Killing vector fields in special cases.

Extraction of conformal data in critical quantum spin chains using the Koo-Saleur formula

NASA Astrophysics Data System (ADS)

Milsted, Ashley; Vidal, Guifre

2017-12-01

We study the emergence of two-dimensional conformal symmetry in critical quantum spin chains on the finite circle. Our goal is to characterize the conformal field theory (CFT) describing the universality class of the corresponding quantum phase transition. As a means to this end, we propose and demonstrate automated procedures which, using only the lattice Hamiltonian H =∑jhj as an input, systematically identify the low-energy eigenstates corresponding to Virasoro primary and quasiprimary operators, and assign the remaining low-energy eigenstates to conformal towers. The energies and momenta of the primary operator states are needed to determine the primary operator scaling dimensions and conformal spins, an essential part of the conformal data that specifies the CFT. Our techniques use the action, on the low-energy eigenstates of H , of the Fourier modes Hn of the Hamiltonian density hj. The Hn were introduced as lattice representations of the Virasoro generators by Koo and Saleur [Nucl. Phys. B 426, 459 (1994), 10.1016/0550-3213(94)90018-3]. In this paper, we demonstrate that these operators can be used to extract conformal data in a nonintegrable quantum spin chain.

Conformation of repaglinide: A solvent dependent structure

NASA Astrophysics Data System (ADS)

Chashmniam, Saeed; Tafazzoli, Mohsen

2017-09-01

Experimental and theoretical conformational study of repaglinide in chloroform and dimethyl sulfoxide was investigated. By applying potential energy scanning (PES) at B3LYP/6-311++g** and B3LYP-D3/6-311++g** level of theory on rotatable single bonds, four stable conformers (R1-R4) were identified. Spin-spin coupling constant values were obtained from a set of 2D NMR spectra (Hsbnd H COSY, Hsbnd C HMQC and Hsbnd C HMBC) and compared to its calculated values. Interestingly, from 1HNMR and 2D-NOESY NMR, it has been found that repaglinide structure is folded in CDCl3 and cause all single bonds to rotate at an extremely slow rate. On the other hand, in DMSO-d6, with strong solvent-solute intermolecular interactions, the single bonds rotate freely. Also, energy barrier and thermodynamic parameters for chair to chair interconversion was measured (13.04 kcal mol-1) in CDCl3 solvent by using temperature dynamic NMR.

A new fundamental type of conformational isomerism

NASA Astrophysics Data System (ADS)

Canfield, Peter J.; Blake, Iain M.; Cai, Zheng-Li; Luck, Ian J.; Krausz, Elmars; Kobayashi, Rika; Reimers, Jeffrey R.; Crossley, Maxwell J.

2018-06-01

Isomerism is a fundamental chemical concept, reflecting the fact that the arrangement of atoms in a molecular entity has a profound influence on its chemical and physical properties. Here we describe a previously unclassified fundamental form of conformational isomerism through four resolved stereoisomers of a transoid (BF)O(BF)-quinoxalinoporphyrin. These comprise two pairs of enantiomers that manifest structural relationships not describable within existing IUPAC nomenclature and terminology. They undergo thermal diastereomeric interconversion over a barrier of 104 ± 2 kJ mol-1, which we term `akamptisomerization'. Feasible interconversion processes between conceivable synthesis products and reaction intermediates were mapped out by density functional theory calculations, identifying bond-angle inversion (BAI) at a singly bonded atom as the reaction mechanism. We also introduce the necessary BAI stereodescriptors parvo and amplo. Based on an extended polytope formalism of molecular structure and stereoisomerization, BAI-driven akamptisomerization is shown to be the final fundamental type of conformational isomerization.

"Voices of fear and safety" women's ambivalence towards breast cancer and breast health: a qualitative study from Jordan.

PubMed

Taha, Hana; Al-Qutob, Raeda; Nyström, Lennarth; Wahlström, Rolf; Berggren, Vanja

2012-07-26

Breast cancer is the leading cause of cancer mortality among Jordanian women. Breast malignancies are detected at late stages as a result of deferred breast health-seeking behaviour. The aim of this study was to explore Jordanian women's views and perceptions about breast cancer and breast health. We performed an explorative qualitative study with purposive sampling. Ten focus groups were conducted consisting of 64 women (aged 20 to 65 years) with no previous history and no symptoms of breast cancer from four governorates in Jordan. The transcribed data was analysed using latent content analysis. Three themes were constructed from the group discussions: a) Ambivalence in prioritizing own health; b) Feeling fear of breast cancer; and c) Feeling safe from breast cancer. The first theme was seen in women's prioritizing children and family needs and in their experiencing family and social support towards seeking breast health care. The second theme was building on women's perception of breast cancer as an incurable disease associated with suffering and death, their fear of the risk of diminished femininity, husband's rejection and social stigmatization, adding to their apprehensions about breast health examinations. The third theme emerged from the women's perceiving themselves as not being in the risk zone for breast cancer and in their accepting breast cancer as a test from God. In contrast, women also experienced comfort in acquiring breast health knowledge that soothed their fears and motivated them to seek early detection examinations. Women's ambivalence in prioritizing their own health and feelings of fear and safety could be better addressed by designing breast health interventions that emphasize the good prognosis for breast cancer when detected early, involve breast cancer survivors in breast health awareness campaigns and catalyse family support to encourage women to seek breast health care.

Conformal Galilei algebras, symmetric polynomials and singular vectors

NASA Astrophysics Data System (ADS)

Křižka, Libor; Somberg, Petr

2018-01-01

We classify and explicitly describe homomorphisms of Verma modules for conformal Galilei algebras cga_ℓ (d,C) with d=1 for any integer value ℓ \\in N. The homomorphisms are uniquely determined by singular vectors as solutions of certain differential operators of flag type and identified with specific polynomials arising as coefficients in the expansion of a parametric family of symmetric polynomials into power sum symmetric polynomials.

Conformational Clusters of Phosphorylated Tyrosine.

PubMed

Abdelrasoul, Maha; Ponniah, Komala; Mao, Alice; Warden, Meghan S; Elhefnawy, Wessam; Li, Yaohang; Pascal, Steven M

2017-12-06

Tyrosine phosphorylation plays an important role in many cellular and intercellular processes including signal transduction, subcellular localization, and regulation of enzymatic activity. In 1999, Blom et al., using the limited number of protein data bank (PDB) structures available at that time, reported that the side chain structures of phosphorylated tyrosine (pY) are partitioned into two conserved conformational clusters ( Blom, N.; Gammeltoft, S.; Brunak, S. J. Mol. Biol. 1999 , 294 , 1351 - 1362 ). We have used the spectral clustering algorithm to cluster the increasingly growing number of protein structures with pY sites, and have found that the pY residues cluster into three distinct side chain conformations. Two of these pY conformational clusters associate strongly with a narrow range of tyrosine backbone conformation. The novel cluster also highly correlates with the identity of the n + 1 residue, and is strongly associated with a sequential pYpY conformation which places two adjacent pY side chains in a specific relative orientation. Further analysis shows that the three pY clusters are associated with distinct distributions of cognate protein kinases.

Detection of Mutant Huntingtin Aggregation Conformers and Modulation of SDS-Soluble Fibrillar Oligomers by Small Molecules

PubMed Central

Sontag, Emily Mitchell; Lotz, Gregor P.; Yang, Guocheng; Sontag, Christopher J.; Cummings, Brian J.; Glabe, Charles G.; Muchowski, Paul J.; Thompson, Leslie Michels

2012-01-01

The Huntington’s disease (HD) mutation leads to a complex process of Huntingtin (Htt) aggregation into multimeric species that eventually form visible inclusions in cytoplasm, nuclei and neuronal processes. One hypothesis is that smaller, soluble forms of amyloid proteins confer toxic effects and contribute to early cell dysfunction. However, analysis of mutant Htt aggregation intermediates to identify conformers that may represent toxic forms of the protein and represent potential drug targets remains difficult. We performed a detailed analysis of aggregation conformers in multiple in vitro, cell and ex vivo models of HD. Conformation-specific antibodies were used to identify and characterize aggregation species, allowing assessment of multiple conformers present during the aggregation process. Using a series of assays together with these antibodies, several forms could be identified. Fibrillar oligomers, defined as having a β-sheet rich conformation, are observed in vitro using recombinant protein and in protein extracts from cells in culture or mouse brain and shown to be globular, soluble and non-sedimentable structures. Compounds previously described to modulate visible inclusion body formation and reduce toxicity in HD models were also tested and consistently found to alter the formation of fibrillar oligomers. Interestingly, these compounds did not alter the rate of visible inclusion formation, indicating that fibrillar oligomers are not necessarily the rate limiting step of inclusion body formation. Taken together, we provide insights into the structure and formation of mutant Htt fibrillar oligomers that are modulated by small molecules with protective potential in HD models. PMID:24086178

Conformer-specific microwave spectroscopy of 3-phenylpropionitrile by strong field coherence breaking

NASA Astrophysics Data System (ADS)

Fritz, Sean M.; Hernandez-Castillo, A. O.; Abeysekera, Chamara; Hays, Brian M.; Zwier, Timothy S.

2018-07-01

Strong field coherence breaking (SFCB) was used with a chirped-pulse Fourier Transform microwave spectrometer to obtain conformer-specific rotational spectra of 3-phenylpropionitrile in the 8-18 GHz region. Transitions belonging to anti and gauche conformers were identified and assigned and accurate experimental rotational constants were determined to provide insight to the molecular structure. Experimental rotational transitions provided relative abundances in the supersonic expansion. A modified line picking scheme was developed in the process to modulate more transitions and improve the overall efficiency of the SFCB multiple selective excitation technique.

Thickenings and conformal gravity

NASA Astrophysics Data System (ADS)

Lebrun, Claude

1991-07-01

A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason [B-M].

Laboratory evolution of protein conformational dynamics.

PubMed

Campbell, Eleanor C; Correy, Galen J; Mabbitt, Peter D; Buckle, Ashley M; Tokuriki, Nobuhiko; Jackson, Colin J

2017-11-08

This review focuses on recent work that has begun to establish specific functional roles for protein conformational dynamics, specifically how the conformational landscapes that proteins can sample can evolve under laboratory based evolutionary selection. We discuss recent technical advances in computational and biophysical chemistry, which have provided us with new ways to dissect evolutionary processes. Finally, we offer some perspectives on the emerging view of conformational dynamics and evolution, and the challenges that we face in rationally engineering conformational dynamics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transportation Conformity

EPA Pesticide Factsheets

This section provides information on: current laws, regulations and guidance, policy and technical guidance, project-level conformity, general information, contacts and training, adequacy review of SIP submissions

Coexisting stable conformations of gaseous protein ions.

PubMed Central

Suckau, D; Shi, Y; Beu, S C; Senko, M W; Quinn, J P; Wampler, F M; McLafferty, F W

1993-01-01

For further insight into the role of solvent in protein conformer stabilization, the structural and dynamic properties of protein ions in vacuo have been probed by hydrogen-deuterium exchange in a Fourier-transform mass spectrometer. Multiply charged ions generated by electrospray ionization of five proteins show exchange reactions with 2H2O at 10(-7) torr (1 torr = 133.3 Pa) exhibiting pseudo-first-order kinetics. Gas-phase compactness of the S-S cross-linked RNase A relative to denatured S-derivatized RNase A is indicated by exchange of 35 and 135 hydrogen atoms, respectively. For pure cytochrome c ions, the existence of at least three distinct gaseous conformers is indicated by the substantially different values--52, 113, and 74--of reactive H atoms; the observation of these same values for ions of a number--2, 7, and 5, respectively--of different charge states indicates conformational insensitivity to coulombic forces. For each of these conformers, the compactness in vacuo indicated by these values corresponds directly to that of a known conformer structure in the solution from which the conformer ions are produced by electrospray. S-derivatized RNase A ions also exist as at least two gaseous conformers exchanging 50-140 H atoms. Gaseous conformer ions are isometrically stable for hours; removal of solvent greatly increases conformational rigidity. More specific ion-molecule reactions could provide further details of conformer structures. Images PMID:8381533

PubChem3D: conformer ensemble accuracy

PubMed Central

2013-01-01

Background PubChem is a free and publicly available resource containing substance descriptions and their associated biological activity information. PubChem3D is an extension to PubChem containing computationally-derived three-dimensional (3-D) structures of small molecules. All the tools and services that are a part of PubChem3D rely upon the quality of the 3-D conformer models. Construction of the conformer models currently available in PubChem3D involves a clustering stage to sample the conformational space spanned by the molecule. While this stage allows one to downsize the conformer models to more manageable size, it may result in a loss of the ability to reproduce experimentally determined “bioactive” conformations, for example, found for PDB ligands. This study examines the extent of this accuracy loss and considers its effect on the 3-D similarity analysis of molecules. Results The conformer models consisting of up to 100,000 conformers per compound were generated for 47,123 small molecules whose structures were experimentally determined, and the conformers in each conformer model were clustered to reduce the size of the conformer model to a maximum of 500 conformers per molecule. The accuracy of the conformer models before and after clustering was evaluated using five different measures: root-mean-square distance (RMSD), shape-optimized shape-Tanimoto (STST-opt) and combo-Tanimoto (ComboTST-opt), and color-optimized color-Tanimoto (CTCT-opt) and combo-Tanimoto (ComboTCT-opt). On average, the effect of clustering decreased the conformer model accuracy, increasing the conformer ensemble’s RMSD to the bioactive conformer (by 0.18 ± 0.12 Å), and decreasing the STST-opt, ComboTST-opt, CTCT-opt, and ComboTCT-opt scores (by 0.04 ± 0.03, 0.16 ± 0.09, 0.09 ± 0.05, and 0.15 ± 0.09, respectively). Conclusion This study shows the RMSD accuracy performance of the PubChem3D conformer models is operating as designed. In addition, the effect of PubChem3D

The Role of Social Context in Gifted and Talented Education.

ERIC Educational Resources Information Center

Fetterman, David

1999-01-01

The dichotomy between individualism and conformity, the myth that gifted children will make it on their own, and the fallacy of equating equal opportunity with equal potential, ability, and results has fostered a climate in which simplistic thinking, ambivalence, and neglect is prevalent. Awareness of this larger social context can allow for new…

Conformer-Specific IR Spectroscopy of Laser-Desorbed Sulfonamide Drugs: Tautomeric and Conformational Preferences of Sulfanilamide and its Derivatives

NASA Astrophysics Data System (ADS)

Uhlemann, Thomas; Seidel, Sebastian; Müller, Christian W.

2017-06-01

Molecules containing the sulfonamide group R^{1}-SO_2-NHR^{2} have a longstanding history as antimicrobial agents. Even though nowadays they are not commonly used in treating humans anymore, they continue to be studied as effective inhibitors of metalloenzyme carbonic anhydrases. These enzymes are important targets for a variety of diseases, such as, for instance, breast cancer, glaucoma, and obesity. Here we present the results of our laser desorption single-conformation UV and IR study of sulfanilamide (NH_2Ph-SO_2-NHR, R=H), a variety of singly substituted derivatives, and their monohydrated complexes. Depending on the substituent, the sulfonamide group can either adopt an amino or an imino tautomeric form. The form prevalent in the crystal is not necessarily also the tautomeric form we identified in the molecular beam after laser desorbing the sample. Furthermore, we explored the effect of complexation with a single water molecule on the tautomeric and conformational preferences of the sulfonamides. Our conformer-specific IR spectra in the NH and OH stretch region (3200-3750 \\wn) suggest that the intra- and intermolecular interactions governing the structures of the monomers and water complexes are surprisingly diverse. We have undertaken both Quantum Theory of Atoms in Molecules (QTAIM) and Interacting Quantum Atoms (IQA) analyses of calculated electron densities to quantitatively characterize the nature and strengths of the intra- and intermolecular interactions prevalent in the monomer and water complex structures.

Preferred Conformers of Non-Proteinogenic Amino Acids Homoserine and Homocysteine

NASA Astrophysics Data System (ADS)

Díez, Verónica; Rodríguez, Miguel A.; Mata, Santiago; Alonso, E. R.; Cabezas, Carlos; Alonso, José L.

2016-06-01

Vaporization of solid homoserine and homocysteine by laser ablation in combination with Fourier transform microwave spectroscopy techniques made possible the detection of their most stable structures in a supersonic expansion. All detected conformers have been identified through their rotational and 14N quadrupole coupling constants. They show hydrogen bonds linking the amino and carboxylic group through N-H\\cdot\\cdot\\cdotO=C (type I) or N\\cdot\\cdot\\cdotH-O (type II) interactions. In some of them there are additional hydrogen bonds established between the amino group and the hydroxyl/thiol groups in the gamma position. Entropic effects related to the side chain have been found to be significant in determining the most populated conformations.

Epoxide Hydrolase Conformational Heterogeneity for the Resolution of Bulky Pharmacologically Relevant Epoxide Substrates.

PubMed

Serrano-Hervás, Eila; Casadevall, Guillem; Garcia-Borràs, Marc; Feixas, Ferran; Osuna, Sílvia

2018-04-06

The conformational landscape of Bacillus megaterium epoxide hydrolase (BmEH) and how it is altered by mutations that confer the enzyme the ability to accept bulky epoxide substrates has been investigated. Extensive molecular dynamics (MD) simulations coupled to active site volume calculations have unveiled relevant features of the enzyme conformational dynamics and function. Our long-timescale MD simulations identify key conformational states not previously observed by means of X-ray crystallography and short MD simulations that present the loop containing one of the catalytic residues, Asp239, in a wide-open conformation, which is likely involved in the binding of the epoxide substrate. Introduction of mutations M145S and F128A dramatically alters the conformational landscape of the enzyme. These singly mutated variants can accept bulky epoxide substrates due to the disorder induced by mutation in the α-helix containing the catalytic Tyr144 and some parts of the lid domain. These changes impact the enzyme active site, which is substantially wider and more complementary to the bulky pharmacologically relevant epoxide substrates. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mapping the temperature-dependent conformational landscapes of the dynamic enzymes cyclophilin A and urease

NASA Astrophysics Data System (ADS)

Thorne, Robert; Keedy, Daniel; Warkentin, Matthew; Fraser, James; Moreau, David; Atakisi, Hakan; Rau, Peter

Proteins populate complex, temperature-dependent ensembles of conformations that enable their function. Yet in X-ray crystallographic studies, roughly 98% of structures have been determined at 100 K, and most refined to only a single conformation. A combination of experimental methods enabled by studies of ice formation and computational methods for mining low-density features in electron density maps have been applied to determine the evolution of the conformational landscapes of the enzymes cyclophilin A and urease between 300 K and 100 K. Minority conformations of most side chains depopulate on cooling from 300 to ~200 K, below which subsequent conformational evolution is quenched. The characteristic temperatures for this depopulation are highly heterogeneous throughout each enzyme. The temperature-dependent ensemble of the active site flap in urease has also been mapped. These all-atom, site-resolved measurements and analyses rule out one interpretation of the protein-solvent glass transition, and give an alternative interpretation of a dynamical transition identified in site-averaged experiments. They demonstrate a powerful approach to structural characterization of the dynamic underpinnings of protein function. Supported by NSF MCB-1330685.

Visualization of SV2A conformations in situ by the use of Protein Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lynch, Berkley A.; Matagne, Alain; Braennstroem, Annika

2008-10-31

The synaptic vesicle protein 2A (SV2A), the brain-binding site of the anti-epileptic drug levetiracetam (LEV), has been characterized by Protein Tomography{sup TM}. We identified two major conformations of SV2A in mouse brain tissue: first, a compact, funnel-structure with a pore-like opening towards the cytoplasm; second, a more open, V-shaped structure with a cleft-like opening towards the intravesicular space. The large differences between these conformations suggest a high degree of flexibility and support a valve-like mechanism consistent with the postulated transporter role of SV2A. These two conformations are represented both in samples treated with LEV, and in saline-treated samples, which indicatesmore » that LEV binding does not cause a large-scale conformational change of SV2A, or lock a specific conformational state of the protein. This study provides the first direct structural data on SV2A, and supports a transporter function suggested by sequence homology to MFS class of transporter proteins.« less

Galilean field theories and conformal structure

NASA Astrophysics Data System (ADS)

Bagchi, Arjun; Chakrabortty, Joydeep; Mehra, Aditya

2018-04-01

We perform a detailed analysis of Galilean field theories, starting with free theories and then interacting theories. We consider non-relativistic versions of massless scalar and Dirac field theories before we go on to review our previous construction of Galilean Electrodynamics and Galilean Yang-Mills theory. We show that in all these cases, the field theories exhibit non-relativistic conformal structure (in appropriate dimensions). The surprising aspect of the analysis is that the non-relativistic conformal structure exhibited by these theories, unlike relativistic conformal invariance, becomes infinite dimensional even in spacetime dimensions greater than two. We then couple matter with Galilean gauge theories and show that there is a myriad of different sectors that arise in the non-relativistic limit from the parent relativistic theories. In every case, if the parent relativistic theory exhibited conformal invariance, we find an infinitely enhanced Galilean conformal invariance in the non-relativistic case. This leads us to suggest that infinite enhancement of symmetries in the non-relativistic limit is a generic feature of conformal field theories in any dimension.

The Dynameomics Entropy Dictionary: A Large-Scale Assessment of Conformational Entropy across Protein Fold Space.

PubMed

Towse, Clare-Louise; Akke, Mikael; Daggett, Valerie

2017-04-27

Molecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing data set of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain size are not strictly coupled. An outcome of these analyses is the Dynameomics Entropy Dictionary, the contents of which have been compared with entropies derived by other theoretical approaches and experiment. As might be expected, the conformational entropies scale linearly with the number of residues, demonstrating that conformational entropy is an extensive property of proteins. The calculated conformational entropies of folding agree well with previous estimates. Detailed analysis of specific cases identifies deviations in conformational entropy from the average values that highlight how conformational entropy varies with sequence, secondary structure, and tertiary fold. Notably, α-helices have lower entropy on average than do β-sheets, and both are lower than coil regions.

Meta-analyses of the relationship between conformity to masculine norms and mental health-related outcomes.

PubMed

Wong, Y Joel; Ho, Moon-Ho Ringo; Wang, Shu-Yi; Miller, I S Keino

2017-01-01

Despite theoretical postulations that individuals' conformity to masculine norms is differentially related to mental health-related outcomes depending on a variety of contexts, there has not been any systematic synthesis of the empirical research on this topic. Therefore, the authors of this study conducted meta-analyses of the relationships between conformity to masculine norms (as measured by the Conformity to Masculine Norms Inventory-94 and other versions of this scale) and mental health-related outcomes using 78 samples and 19,453 participants. Conformity to masculine norms was modestly and unfavorably associated with mental health as well as moderately and unfavorably related to psychological help seeking. The authors also identified several moderation effects. Conformity to masculine norms was more strongly correlated with negative social functioning than with psychological indicators of negative mental health. Conformity to the specific masculine norms of self-reliance, power over women, and playboy were unfavorably, robustly, and consistently related to mental health-related outcomes, whereas conformity to the masculine norm of primacy of work was not significantly related to any mental health-related outcome. These findings highlight the need for researchers to disaggregate the generic construct of conformity to masculine norms and to focus instead on specific dimensions of masculine norms and their differential associations with other outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Ambivalence in the Christian attitude to war and peace.

PubMed

Wille, Wilhelm

2007-06-01

In this paper it will be argued that the basic document of Christianity, the Bible, contains a unique potential for accepting the other and solving conflicts by non-violent means, but that this potential has never been available in pure form. The history of Christianity from the very beginnings in the New Testament period up to the present has been one of great ambiguity, an amalgam of attempts to live out the fundamental values as well as of compromise and open betrayal. This process will be outlined, illustrated and the factors will be pointed at, which in different situations bring to the fore the conflicting elements of Christian tradition. Examples of Christian pacifism, the ethical compromise of the just-war doctrine throughout the centuries will be commented on. The emphasis, however, is on developments in the twentieth century with the great regression of fascism. Finally, the focus is on more recent developments in reflection and action, when Christians begin to transcend the just-war doctrine and struggle to overcome the institution of war responding to the threat posed by weapons of mass destruction. Concrete examples of decisions are discussed and the shadow of a powerful Christian fundamentalism is critically assessed. Nevertheless, it is argued that despite all the failures of historic and contemporary Christianity the basic values of Christian tradition could serve as a motivating force to meet the challenges of a historical situation when violence is dangerously increasing on a global scale. However, these values will only become effective if people relate personally and practically to the ambivalent historical process, critically and responsibly.

Transportation Conformity Training and Presentations

EPA Pesticide Factsheets

EPA's OTAQ has provided multiple conformity training sessions in the past to assist state and local governments in implementing conformity requirements. As training information is prepared for other venues, it will be posted on this page.

Conformal Dimensions via Large Charge Expansion

NASA Astrophysics Data System (ADS)

Banerjee, Debasish; Chandrasekharan, Shailesh; Orlando, Domenico

2018-02-01

We construct an efficient Monte Carlo algorithm that overcomes the severe signal-to-noise ratio problems and helps us to accurately compute the conformal dimensions of large-Q fields at the Wilson-Fisher fixed point in the O (2 ) universality class. Using it, we verify a recent proposal that conformal dimensions of strongly coupled conformal field theories with a global U (1 ) charge can be obtained via a series expansion in the inverse charge 1 /Q . We find that the conformal dimensions of the lowest operator with a fixed charge Q are almost entirely determined by the first few terms in the series.

Neural signatures of social conformity: A coordinate-based activation likelihood estimation meta-analysis of functional brain imaging studies.

PubMed

Wu, Haiyan; Luo, Yi; Feng, Chunliang

2016-12-01

People often align their behaviors with group opinions, known as social conformity. Many neuroscience studies have explored the neuropsychological mechanisms underlying social conformity. Here we employed a coordinate-based meta-analysis on neuroimaging studies of social conformity with the purpose to reveal the convergence of the underlying neural architecture. We identified a convergence of reported activation foci in regions associated with normative decision-making, including ventral striatum (VS), dorsal posterior medial frontal cortex (dorsal pMFC), and anterior insula (AI). Specifically, consistent deactivation of VS and activation of dorsal pMFC and AI are identified when people's responses deviate from group opinions. In addition, the deviation-related responses in dorsal pMFC predict people's conforming behavioral adjustments. These are consistent with current models that disagreement with others might evoke "error" signals, cognitive imbalance, and/or aversive feelings, which are plausibly detected in these brain regions as control signals to facilitate subsequent conforming behaviors. Finally, group opinions result in altered neural correlates of valuation, manifested as stronger responses of VS to stimuli endorsed than disliked by others. Copyright © 2016 Elsevier Ltd. All rights reserved.

Harmony of spinning conformal blocks

NASA Astrophysics Data System (ADS)

Schomerus, Volker; Sobko, Evgeny; Isachenkov, Mikhail

2017-03-01

Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

Conformational Map of Phenolic Acids.

PubMed

Cortijo, Vanessa; Alonso, Elena R; Mata, Santiago; Alonso, José L

2018-01-18

The benefits of vaporization by laser ablation and the high resolution and sensitivity attained by the chirped pulse Fourier transform microwave spectroscopy CP-FTMW have provided the first conformational map of the simplest phenolic acids of trans-cinnamic and p-coumaric. Two conformers of trans-cinnamic acid and four conformers of trans-p-coumaric acid have been characterized under the isolation conditions of a supersonic expansion. The spectroscopic constants derived from the analysis of the rotational spectra compared with those predicted theoretically provide an unmatched means to achieve an unambiguous identification of the observed species.

Conformations of eight-membered cyclosiloxanes

NASA Astrophysics Data System (ADS)

Palyulin, V. A.; Zefirov, N. S.; Shklover, V. E.; Struchkov, Yu. T.

1981-01-01

Using the Cremer—Pople approach the classification and quantitative description of the conformations of eight-membered rings has been accomplished. The conformations of eight-membered cyclosiloxanes are considered and classified on the basis of available X-ray structural data.

Rapid Fine Conformational Epitope Mapping Using Comprehensive Mutagenesis and Deep Sequencing*

PubMed Central

Kowalsky, Caitlin A.; Faber, Matthew S.; Nath, Aritro; Dann, Hailey E.; Kelly, Vince W.; Liu, Li; Shanker, Purva; Wagner, Ellen K.; Maynard, Jennifer A.; Chan, Christina; Whitehead, Timothy A.

2015-01-01

Knowledge of the fine location of neutralizing and non-neutralizing epitopes on human pathogens affords a better understanding of the structural basis of antibody efficacy, which will expedite rational design of vaccines, prophylactics, and therapeutics. However, full utilization of the wealth of information from single cell techniques and antibody repertoire sequencing awaits the development of a high throughput, inexpensive method to map the conformational epitopes for antibody-antigen interactions. Here we show such an approach that combines comprehensive mutagenesis, cell surface display, and DNA deep sequencing. We develop analytical equations to identify epitope positions and show the method effectiveness by mapping the fine epitope for different antibodies targeting TNF, pertussis toxin, and the cancer target TROP2. In all three cases, the experimentally determined conformational epitope was consistent with previous experimental datasets, confirming the reliability of the experimental pipeline. Once the comprehensive library is generated, fine conformational epitope maps can be prepared at a rate of four per day. PMID:26296891

Conformational stability, r(0) structural parameters, vibrational assignments and ab initio calculations of ethyldichlorophosphine.

PubMed

Darkhalil, Ikhlas D; Paquet, Charles; Waqas, Mohammad; Gounev, Todor K; Durig, James R

2015-02-05

Variable temperature (-60 to -100 °C) studies of ethyldichlorophosphine, CH3CH2PCl2, of the infrared spectra (4000-400 cm(-1)) dissolved in liquid xenon have been carried out. From these data, the two conformers have been identified and the enthalpy difference has been determined between the more stable trans conformer and the less stable gauche form to be 88±9 cm(-1) (1.04±0.11 kJ/mol). The percentage of abundance of the gauche conformer is estimated to be 57% at ambient temperature. The conformational stabilities have been predicted from ab initio calculations by utilizing many different basis sets up to aug-cc-pVTZ for both MP2(full) and density functional theory calculations by the B3LYP method. Vibrational assignments have been provided for both conformers which have been predicted by MP2(full)/6-31G(d) ab initio calculations to predict harmonic force fields, wavenumbers of the fundamentals, infrared intensities, Raman activities and depolarization ratios for both conformers. Estimated r0 structural parameters have been obtained from adjusted MP2(full)/6-311+G(d,p) calculations. The results are discussed and compared to the corresponding properties of some related molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

Proper Conformal Killing Vectors in Kantowski-Sachs Metric

NASA Astrophysics Data System (ADS)

Hussain, Tahir; Farhan, Muhammad

2018-04-01

This paper deals with the existence of proper conformal Killing vectors (CKVs) in Kantowski-Sachs metric. Subject to some integrability conditions, the general form of vector filed generating CKVs and the conformal factor is presented. The integrability conditions are solved generally as well as in some particular cases to show that the non-conformally flat Kantowski-Sachs metric admits two proper CKVs, while it admits a 15-dimensional Lie algebra of CKVs in the case when it becomes conformally flat. The inheriting conformal Killing vectors (ICKVs), which map fluid lines conformally, are also investigated.

Perceived Social Support Mediates the Longitudinal Relations between Ambivalence over Emotional Expression and Quality of Life among Chinese American Breast Cancer Survivors.

PubMed

Tsai, William; Lu, Qian

2018-06-01

The present study examined perceived social support as a mediator of the longitudinal link between ambivalence over emotional expression (AEE) and quality of life among a sample of Chinese breast cancer survivors. Ninety-six Chinese breast cancer survivors recruited from Southern California completed four surveys in total: (1) a baseline survey (T1), 1-month follow-up (T2), 3-month follow-up (T3), and 6-month follow-up (T4). Participants filled out a paper-pen questionnaire containing the Ambivalence over Emotional Expression Questionnaire (AEQ), the Functional Assessment of Cancer Therapy-General (FACT-G), and the Medical Outcomes Study Social Support Scale (MOS-SSS). Higher T1 AEE was associated with lower T1 social support (B = -0.01, SE = 0.004, p < 0.01) which in turn was associated with lower quality of life at T2 (B = 2.98, SE = 0.64, p < 0.01), T3 (B = 2.14, SE = 0.54, p < 0.01), and T4 (B = 2.08, SE = 0.68, p < 0.01). These results suggest that the harmful effect of AEE on quality of life is explained by reduced social support. Given the detrimental effects of AEE on social support and quality of life, future research on interventions that facilitate emotional disclosure is needed. Implications for the effects of Chinese culture on AEE are discussed.

General Conformity

EPA Pesticide Factsheets

The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

CCProf: exploring conformational change profile of proteins

PubMed Central

Chang, Che-Wei; Chou, Chai-Wei; Chang, Darby Tien-Hao

2016-01-01

In many biological processes, proteins have important interactions with various molecules such as proteins, ions or ligands. Many proteins undergo conformational changes upon these interactions, where regions with large conformational changes are critical to the interactions. This work presents the CCProf platform, which provides conformational changes of entire proteins, named conformational change profile (CCP) in the context. CCProf aims to be a platform where users can study potential causes of novel conformational changes. It provides 10 biological features, including conformational change, potential binding target site, secondary structure, conservation, disorder propensity, hydropathy propensity, sequence domain, structural domain, phosphorylation site and catalytic site. All these information are integrated into a well-aligned view, so that researchers can capture important relevance between different biological features visually. The CCProf contains 986 187 protein structure pairs for 3123 proteins. In addition, CCProf provides a 3D view in which users can see the protein structures before and after conformational changes as well as binding targets that induce conformational changes. All information (e.g. CCP, binding targets and protein structures) shown in CCProf, including intermediate data are available for download to expedite further analyses. Database URL: http://zoro.ee.ncku.edu.tw/ccprof/ PMID:27016699

Conformal Dimensions via Large Charge Expansion.

PubMed

Banerjee, Debasish; Chandrasekharan, Shailesh; Orlando, Domenico

2018-02-09

We construct an efficient Monte Carlo algorithm that overcomes the severe signal-to-noise ratio problems and helps us to accurately compute the conformal dimensions of large-Q fields at the Wilson-Fisher fixed point in the O(2) universality class. Using it, we verify a recent proposal that conformal dimensions of strongly coupled conformal field theories with a global U(1) charge can be obtained via a series expansion in the inverse charge 1/Q. We find that the conformal dimensions of the lowest operator with a fixed charge Q are almost entirely determined by the first few terms in the series.

A Projective-to-Conformal Fefferman-Type Construction

NASA Astrophysics Data System (ADS)

Hammerl, Matthias; Sagerschnig, Katja; Šilhan, Josef; Taghavi-Chabert, Arman; Zádník, Vojtĕch

2017-10-01

We study a Fefferman-type construction based on the inclusion of Lie groups SL(n+1) into Spin(n+1,n+1). The construction associates a split-signature (n,n)-conformal spin structure to a projective structure of dimension n. We prove the existence of a canonical pure twistor spinor and a light-like conformal Killing field on the constructed conformal space. We obtain a complete characterisation of the constructed conformal spaces in terms of these solutions to overdetermined equations and an integrability condition on the Weyl curvature. The Fefferman-type construction presented here can be understood as an alternative approach to study a conformal version of classical Patterson-Walker metrics as discussed in recent works by Dunajski-Tod and by the authors. The present work therefore gives a complete exposition of conformal Patterson-Walker metrics from the viewpoint of parabolic geometry.

"Doctor, are you trying to kill me?": ambivalence about the patient package insert for estrogen.

PubMed

Watkins, Elizabeth Siegel

2002-01-01

In 1976, the U.S. Food and Drug Administration proposed new requirements for patient labeling for estrogens prescribed for menopausal and postmenopausal women. This paper explores the variety of responses to this proposal from women and their husbands, feminist and consumer activists, physicians, pharmacists, and pharmaceutical manufacturers, as represented in letters written to the FDA. The drug industry and the medical profession opposed patient labeling on the grounds of cost and a resentment of governmental intrusion. Feminists and consumer advocates were in favor of the idea, but the response from current estrogen users was mixed: most women wished to be better informed, but many expressed concern that estrogen would be removed from the market. This ambivalence suggests unresolved tensions regarding conceptions of female aging, the medical management of menopause and aging, informed consent in medicine, and governmental regulation of medical practice. The debate thus represents an important moment in the history of women's health care.

[Affective bipolar disorder and ambivalence in relation to the drug treatment: analyzing the causal conditions].

PubMed

Miasso, Adriana Inocenti; Cassiani, Silvia Helena De Bortoli; Pedrão, Luiz Jorge

2011-04-01

This study was performed with an aim to understand the conditions causing the ambivalence of the person with bipolar affective disorder (BAD) regarding following the drug treatment. A qualitative approach was used, with the Grounded Theory as the methodology framework, under the light of Symbolic Interactionism. Participants were 14 individuals with BAD who were being followed at an Outpatient Clinic for Mood Disorders of a university hospital and 14 relatives they indicated. Interviews and observation were the main forms of obtaining data. Results revealed three categories that described the referred causal conditions: experiencing the crises of the disorder; needing the drug; and living with the side effects of the drugs. It was found that there is a need to change the attitude of some health professionals from blaming the patient for interrupting the treatment to one of listening, valuing their symbolic and affective universe as well as the partnership in the treatment.

Conformational effects in photoelectron circular dichroism

NASA Astrophysics Data System (ADS)

Turchini, S.

2017-12-01

Photoelectron circular dichroism (PECD) is a novel type of spectroscopy, which presents surprising sensitivity to conformational effects in chiral systems. While classical photoelectron spectroscopy mainly responds to conformational effects in terms of energy level shifts, PECD provides a rich and detailed response to tiny changes in electronic and structural properties by means of the intensity dispersion of the circular dichroism as a function of photoelectron kinetic energy. In this work, the basics of PECD will be outlined, emphasizing the role of interference from the l,l+/- 1 outgoing partial wave of the photoelectron in the PECD transition matrix element, which is responsible for the extreme sensitivity to conformational effects. Examples using molecular systems and interfaces will shed light on the powerful application of PECD to classical conformational effects such as group substitution, isomerism, conformer population and clustering. Moreover, the PECD results will be reported in challenging new fields where conformations play a key role, such as vibrational effects, transient chirality and time- resolved experiments. To date, PECD has mostly been based on synchrotron radiation facilities, but it also has a future as a table-top lab experiment by means of multiphoton ionization. An important application of PECD as an analytical tool will be reported. The aim of this review is to illustrate that in PECD, the presence of conformational effects is essential for understanding a wide range of effects from a new perspective, making it different from classical spectroscopy.

The effects of dog breed development on genetic diversity and the relative influences of performance and conformation breeding.

PubMed

Pedersen, N; Liu, H; Theilen, G; Sacks, B

2013-06-01

Genetic diversity was compared among eight dog breeds selected primarily for conformation (Standard Poodle, Italian Greyhound and show English Setter), conformation and performance (Brittany), predominantly performance (German Shorthaired and Wirehaired Pointers) or solely performance (field English Setter and Red Setter). Modern village dogs, which better reflect ancestral genetic diversity, were used as the standard. Four to seven maternal and one to two Y haplotypes were found per breed, with one usually dominant. Diversity of maternal haplotypes was greatest in village dogs, intermediate in performance breeds and lowest in conformation breeds. Maternal haplotype sharing occurred across all breeds, while Y haplotypes were more breed specific. Almost all paternal haplotypes were identified among village dogs, with the exception of the dominant Y haplotype in Brittanys, which has not been identified heretofore. The highest heterozygosity based on 24 autosomal microsatellites was found in village dogs and the lowest in conformation (show) breeds. Principal coordinate analysis indicated that conformation-type breeds were distinct from breeds heavily used for performance, the latter clustering more closely with village dogs. The Brittany, a well-established dual show and field breed, was also genetically intermediate between the conformation and performance breeds. The number of DLA-DRB1 alleles varied from 3 to 10 per breed with extensive sharing. SNPs across the wider DLA region were more frequently homozygous in all pure breeds than in village dogs. Compared with their village dog relatives, all modern breed dogs exhibit reduced genetic diversity. Genetic diversity was even more reduced among breeds under selection for show/conformation. © 2012 Blackwell Verlag GmbH.

Local conformity induced global oscillation

NASA Astrophysics Data System (ADS)

Li, Dong; Li, Wei; Hu, Gang; Zheng, Zhigang

2009-04-01

The game ‘rock-paper-scissors’ model, with the consideration of the effect of the psychology of conformity, is investigated. The interaction between each two agents is global, but the strategy of the conformity is local for individuals. In the statistical opinion, the probability of the appearance of each strategy is uniform. The dynamical analysis of this model indicates that the equilibrium state may lose its stability at a threshold and is replaced by a globally oscillating state. The global oscillation is induced by the local conformity, which is originated from the synchronization of individual strategies.

Exploration of the kinetic and thermochemical abilities for the free radical scavenging of two quercetin conformers

NASA Astrophysics Data System (ADS)

Mendoza-Wilson, Ana María; Sotelo-Mundo, Rogerio R.; Balandrán-Quintana, René R.; Glossman-Mitnik, Daniel; Sántiz-gómez, Marco a.; García-orozco, karina D.

2010-09-01

Quercetin has a great antioxidant potential due to its large capacity for free radical scavenging. Although it has been found that conformational changes have a profound effect on its chemical properties, there are few studies where conformation is associated with the antioxidant activity. The aim of this investigation was to explore the kinetic and the thermochemical abilities of two quercetin conformers for the free radical scavenging. Quercetin unhydrate (QUH) and quercetin dihydrate (QDH) conformers were studied employing 2,2-diphenyl-1-picrylhydrazyl (DPPH rad ) as in vitro radical model, and catechol and 4-hexyl-resorcinol as reference systems, for identifying the oxidation products. QDH showed to be most effective under conditions of free radical excess, while QUH was most effective when the flavonoid far exceeds the concentration of free radical. It was found, by means of experimental and computational methods, that 4'-OH, 3-OH and 3'-OH are the main reactive sites of both conformers.

14 CFR 21.53 - Statement of conformity.

Code of Federal Regulations, 2011 CFR

2011-01-01

... each aircraft engine and propeller presented to the Administrator for type certification. This statement of conformity must include a statement that the aircraft engine or propeller conforms to the type... aircraft engine or propeller presented for type certification conforms to its type design. ...

Conformational adaptation and manipulation of manganese tetra(4-pyridyl)porphyrin molecules on Cu(111)

NASA Astrophysics Data System (ADS)

Chen, Xianwen; Lei, Shulai; Lotze, Christian; Czekelius, Constantin; Paulus, Beate; Franke, Katharina J.

2017-03-01

Porphyrins are highly flexible molecules and well known to adapt to their local environment via conformational changes. We studied the self-assembly of manganese meso-tetra(4-pyridyl)porphyrin (Mn-TPyP) molecules on a Cu(111) surface by low temperature scanning tunneling microscopy (STM) and atomic force microscopy (ATM). We observe molecular chains along the ⟨1 1 ¯ 0 ⟩ direction of the substrate. Within these chains, we identify two molecular conformations, which differ by the orientation of the upward bending of the macrocycle. Using density functional theory, we show that this saddle shape is a consequence of the rotation and inclination of the pyridyl groups towards Cu adatoms, which stabilize the metal-organic chains. The molecular conformations obey a strict alternation, reflecting the mutual enforcement of conformational adaptation in densely packed structures. Tunneling electrons from the STM tip can induce changes in the orientation of the pyridyl endgroups. The switching behaviour varies with the different adsorption configurations.

Gluon amplitudes as 2 d conformal correlators

NASA Astrophysics Data System (ADS)

Pasterski, Sabrina; Shao, Shu-Heng; Strominger, Andrew

2017-10-01

Recently, spin-one wave functions in four dimensions that are conformal primaries of the Lorentz group S L (2 ,C ) were constructed. We compute low-point, tree-level gluon scattering amplitudes in the space of these conformal primary wave functions. The answers have the same conformal covariance as correlators of spin-one primaries in a 2 d CFT. The Britto-Cachazo-Feng-Witten (BCFW) recursion relation between three- and four-point gluon amplitudes is recast into this conformal basis.

Multichannel conformal blocks for scattering amplitudes

NASA Astrophysics Data System (ADS)

Belitsky, A. V.

2018-05-01

By performing resummation of small fermion-antifermion pairs within the pentagon form factor program to scattering amplitudes in planar N = 4 superYang-Mills theory, we construct multichannel conformal blocks within the flux-tube picture for N-sided NMHV polygons. This procedure is equivalent to summation of descendants of conformal primaries in the OPE framework. The resulting conformal partial waves are determined by multivariable hypergeometric series of Lauricella-Saran type.

Estimation of the rotamerization constants of different conformations of N-acetylalanine: a theoretical and matrix-isolation FT-IR study.

PubMed

Boeckx, Bram; Maes, Guido

2012-02-01

The conformational landscape of N-acetylalanine has been investigated by a theoretical and matrix-isolation FT-IR study. Optimizations of N-acetylalanine structures has been conducted at successive higher levels of theory HF/3-21G, DFT(B3LYP)/6-31++G** and MP2/6-31++G**. This resulted in three stable conformations. Among these, one conformation contains an intramolecular H-bond. The vibrational properties of these conformations were calculated and used to identify the conformations in a cryogenic argon matrix. The intensities of some bands assigned to a particular conformation were used to estimate the rotamerization constants K(r12) and K(r13) for the equilibria NAA1 NAA2 and NAA1 NAA3, respectively. The obtained experimental values were in agreement with the theoretical predictions. Copyright © 2011 Elsevier B.V. All rights reserved.

Diagnostic ambivalence: psychiatric workarounds and the Diagnostic and Statistical Manual of Mental Disorders.

PubMed

Whooley, Owen

2010-03-01

In 1980 the American Psychiatric Association (APA), faced with increased professional competition, revised the Diagnostic and Statistical Manual of Mental Disorders (DSM). Psychiatric expertise was redefined along a biomedical model via a standardised nosology. While they were an integral part of capturing professional authority, the revisions demystified psychiatric expertise, leaving psychiatrists vulnerable to infringements upon their autonomy by institutions adopting the DSM literally. This research explores the tensions surrounding standardisation in psychiatry. Drawing on in-depth interviews with psychiatrists, I explore the 'sociological ambivalence' psychiatrists feel towards the DSM, which arises from the tension between the desire for autonomy in practice and the professional goal of legitimacy within the system of mental health professions. To carve a space for autonomy for their practice, psychiatrists develop 'workarounds' that undermine the DSM in practice. These workarounds include employing alternative diagnostic typologies, fudging the numbers (or codes) on official paperwork and negotiating diagnoses with patients. In creating opportunities for patient input and resistance to fixed diagnoses, the varied use of the DSM raises fundamental questions for psychiatrists about the role of the biomedical model of mental illness, especially its particular manifestation in the DSM.

Conformational Transition Pathway in the Activation Process of Allosteric Glucokinase

PubMed Central

Shi, Ting; Zhao, Yaxue; Chen, Yingyi; Li, Xiaobai; Liu, Xinyi; Huang, Zhimin; Zhang, Jian

2013-01-01

Glucokinase (GK) is a glycolytic enzyme that plays an important role in regulating blood glucose level, thus acting as a potentially attractive target for drug discovery in the treatment of diabetes of the young type 2 and persistent hyperinsulinemic hypoglycemia of infancy. To characterize the activation mechanism of GK from the super-open state (inactive state) to the closed state (active state), a series of conventional molecular dynamics (MD) and targeted MD (TMD) simulations were performed on this enzyme. Conventional MD simulation showed a specific conformational ensemble of GK when the enzyme is inactive. Seven TMD simulations depicted a reliably conformational transition pathway of GK from the inactive state to the active state, and the components important to the conformational change of GK were identified by analyzing the detailed structures of the TMD trajectories. In combination with the inactivation process, our findings showed that the whole conformational pathway for the activation-inactivation-activation of GK is a one-direction circulation, and the active state is less stable than the inactive state in the circulation. Additionally, glucose was demonstrated to gradually modulate its binding pose with the help of residues in the large domain and connecting region of GK during the activation process. Furthermore, the obtained energy barriers were used to explain the preexisting equilibrium and the slow binding kinetic process of the substrate by GK. The simulated results are in accordance with the recent findings from the mutagenesis experiments and kinetic analyses. Our observations reveal a complicated conformational process in the allosteric protein, resulting in new knowledge about the delicate mechanisms for allosteric biological macromolecules that will be useful in drug design for targeting allosteric proteins. PMID:23409066

Inverse bootstrapping conformal field theories

NASA Astrophysics Data System (ADS)

Li, Wenliang

2018-01-01

We propose a novel approach to study conformal field theories (CFTs) in general dimensions. In the conformal bootstrap program, one usually searches for consistent CFT data that satisfy crossing symmetry. In the new method, we reverse the logic and interpret manifestly crossing-symmetric functions as generating functions of conformal data. Physical CFTs can be obtained by scanning the space of crossing-symmetric functions. By truncating the fusion rules, we are able to concentrate on the low-lying operators and derive some approximate relations for their conformal data. It turns out that the free scalar theory, the 2d minimal model CFTs, the ϕ 4 Wilson-Fisher CFT, the Lee-Yang CFTs and the Ising CFTs are consistent with the universal relations from the minimal fusion rule ϕ 1 × ϕ 1 = I + ϕ 2 + T , where ϕ 1 , ϕ 2 are scalar operators, I is the identity operator and T is the stress tensor.

A latent class regression analysis of men's conformity to masculine norms and psychological distress.

PubMed

Wong, Y Joel; Owen, Jesse; Shea, Munyi

2012-01-01

How are specific dimensions of masculinity related to psychological distress in specific groups of men? To address this question, the authors used latent class regression to assess the optimal number of latent classes that explained differential relationships between conformity to masculine norms and psychological distress in a racially diverse sample of 223 men. The authors identified a 2-class solution. Both latent classes demonstrated very different associations between conformity to masculine norms and psychological distress. In Class 1 (labeled risk avoiders; n = 133), conformity to the masculine norm of risk-taking was negatively related to psychological distress. In Class 2 (labeled detached risk-takers; n = 90), conformity to the masculine norms of playboy, self-reliance, and risk-taking was positively related to psychological distress, whereas conformity to the masculine norm of violence was negatively related to psychological distress. A post hoc analysis revealed that younger men and Asian American men (compared with Latino and White American men) had significantly greater odds of being in Class 2 versus Class 1. The implications of these findings for future research and clinical practice are examined. (c) 2012 APA, all rights reserved.

The interaction with gold suppresses fiber-like conformations of the amyloid β (16-22) peptide

NASA Astrophysics Data System (ADS)

Bellucci, Luca; Ardèvol, Albert; Parrinello, Michele; Lutz, Helmut; Lu, Hao; Weidner, Tobias; Corni, Stefano

2016-04-01

Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution.Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution. Electronic supplementary information (ESI

Fungal disease dynamics in insect societies: optimal killing rates and the ambivalent effect of high social interaction rates.

PubMed

Novak, Sebastian; Cremer, Sylvia

2015-05-07

Entomopathogenic fungi are potent biocontrol agents that are widely used against insect pests, many of which are social insects. Nevertheless, theoretical investigations of their particular life history are scarce. We develop a model that takes into account the main distinguishing features between traditionally studied diseases and obligate killing pathogens, like the (biocontrol-relevant) insect-pathogenic fungi Metarhizium and Beauveria. First, obligate killing entomopathogenic fungi produce new infectious particles (conidiospores) only after host death and not yet on the living host. Second, the killing rates of entomopathogenic fungi depend strongly on the initial exposure dosage, thus we explicitly consider the pathogen load of individual hosts. Further, we make the model applicable not only to solitary host species, but also to group living species by incorporating social interactions between hosts, like the collective disease defences of insect societies. Our results identify the optimal killing rate for the pathogen that minimises its invasion threshold. Furthermore, we find that the rate of contact between hosts has an ambivalent effect: dense interaction networks between individuals are considered to facilitate disease outbreaks because of increased pathogen transmission. In social insects, this is compensated by their collective disease defences, i.e., social immunity. For the type of pathogens considered here, we show that even without social immunity, high contact rates between live individuals dilute the pathogen in the host colony and hence can reduce individual pathogen loads below disease-causing levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

NASA Astrophysics Data System (ADS)

Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian

2016-07-01

The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of peptide conformations. These findings are consistent with experimental results, and give a molecular level interpretation for the reduced cytotoxicity of Vpr13-33 to some extent upon graphene exposure. Meanwhile, this study provides some significant insights into the detailed mechanism of graphene-induced protein conformation transition.

Measuring the mechanical properties of molecular conformers

NASA Astrophysics Data System (ADS)

Jarvis, S. P.; Taylor, S.; Baran, J. D.; Champness, N. R.; Larsson, J. A.; Moriarty, P.

2015-09-01

Scanning probe-actuated single molecule manipulation has proven to be an exceptionally powerful tool for the systematic atomic-scale interrogation of molecular adsorbates. To date, however, the extent to which molecular conformation affects the force required to push or pull a single molecule has not been explored. Here we probe the mechanochemical response of two tetra(4-bromophenyl)porphyrin conformers using non-contact atomic force microscopy where we find a large difference between the lateral forces required for manipulation. Remarkably, despite sharing very similar adsorption characteristics, variations in the potential energy surface are capable of prohibiting probe-induced positioning of one conformer, while simultaneously permitting manipulation of the alternative conformational form. Our results are interpreted in the context of dispersion-corrected density functional theory calculations which reveal significant differences in the diffusion barriers for each conformer. These results demonstrate that conformational variation significantly modifies the mechanical response of even simple porpyhrins, potentially affecting many other flexible molecules.

A coupling of homology modeling with multiple molecular dynamics simulation for identifying representative conformation of GPCR structures: a case study on human bombesin receptor subtype-3.

PubMed

Nowroozi, Amin; Shahlaei, Mohsen

2017-02-01

In this study, a computational pipeline was therefore devised to overcome homology modeling (HM) bottlenecks. The coupling of HM with molecular dynamics (MD) simulation is useful in that it tackles the sampling deficiency of dynamics simulations by providing good-quality initial guesses for the native structure. Indeed, HM also relaxes the severe requirement of force fields to explore the huge conformational space of protein structures. In this study, the interaction between the human bombesin receptor subtype-3 and MK-5046 was investigated integrating HM, molecular docking, and MD simulations. To improve conformational sampling in typical MD simulations of GPCRs, as in other biomolecules, multiple trajectories with different initial conditions can be employed rather than a single long trajectory. Multiple MD simulations of human bombesin receptor subtype-3 with different initial atomic velocities are applied to sample conformations in the vicinity of the structure generated by HM. The backbone atom conformational space distribution of replicates is analyzed employing principal components analysis. As a result, the averages of structural and dynamic properties over the twenty-one trajectories differ significantly from those obtained from individual trajectories.

Renormalization, conformal ward identities and the origin of a conformal anomaly pole

NASA Astrophysics Data System (ADS)

Corianò, Claudio; Maglio, Matteo Maria

2018-06-01

We investigate the emergence of a conformal anomaly pole in conformal field theories in the case of the TJJ correlator. We show how it comes to be generated in dimensional renormalization, using a basis of 13 form factors (the F-basis), where only one of them requires renormalization (F13), extending previous studies. We then combine recent results on the structure of the non-perturbative solutions of the conformal Ward identities (CWI's) for the TJJ in momentum space, expressed in terms of a minimal set of 4 form factors (A-basis), with the properties of the F-basis, and show how the singular behaviour of the corresponding form factors in both basis can be related. The result proves the centrality of such massless effective interactions induced by the anomaly, which have recently found realization in solid state, in the theory of topological insulators and of Weyl semimetals. This pattern is confirmed in massless abelian and nonabelian theories (QED and QCD) investigated at one-loop.

Shrug Ambivalence and Disagreement; Search Commonalities in Psychiatric Phenomena**

PubMed Central

Singh, Ajai R.

2014-01-01

Holistic understanding is necessary to study intimate nuances of psychological/psychopathological processes; also, individual manifestations and individual approach are laudable goals in treatment and approach. But we cannot forget that major therapeutic advances result when we are able to delineate commonalities and stable symptom clusters that cut across geo-cultural boundaries and are amenable to study and intervention. Even though the purpose and approach of psychiatry, as of all medicine, has to be humane and caring, major therapeutic advancements and aetiologic understandings result only from a scientific methodology that stresses and figures out the commonalities of psychopathological phenomena. It is a mistake to stress individuality so much that commonalities are obliterated. Although stress on the individual's needs has helped psychiatry at times become more humane, it has hurt the task enormously by making some very bright minds question the very scientific basis of psychiatry and its status as a medical discipline. Hence, even as it is necessary to promote holistic and individualistic caring, it is equally necessary to shrug ambivalence and crippling disagreements that can result if individualism in therapy is carried beyond limits. Psychiatry's tradition, and field, will always allow for diversity in its practice, even in its theorising. For, psychopathology has both a personal, deep inner dimension — due to biogenetic and personality factors - and social, manifest/unmanifest, outer dimension — due to the environment. And the practice, and theory, of both are likely to be different, although we do try to amalgamate them in our ‘bio-psycho-social’ model. Such differences are only manifestations of an intricate network of influences that make for the human condition in health and disease. Psychiatry is the one branch which realises this diversity the most, but equally important for it is to stress its unity: Of purpose – that of reducing

Conformational dynamics of the molecular chaperone Hsp90

PubMed Central

Krukenberg, Kristin A.; Street, Timothy O.; Lavery, Laura A.; Agard, David A.

2016-01-01

The molecular chaperone Hsp90 is an essential eukaryotic protein that makes up 1–2% of all cytosolic proteins. Hsp90 is vital for the maturation and maintenance of a wide variety of substrate proteins largely involved in signaling and regulatory processes. Many of these substrates have also been implicated in cancer and other diseases making Hsp90 an attractive target for therapeutics. Hsp90 is a highly dynamic and flexible molecule that can adapt its conformation to the wide variety of substrate proteins with which it acts. Large conformational rearrangements are also required for the activation of these client proteins. One driving force for these rearrangements is the intrinsic ATPase activity of Hsp90, as seen with other chaperones. However, unlike other chaperones, studies have shown that the ATPase cycle of Hsp90 is not conformationally deterministic. That is, rather than dictating the conformational state, ATP binding and hydrolysis shifts the equilibrium between a pre-existing set of conformational states in an organism-dependent manner. In vivo Hsp90 functions as part of larger heterocomplexes. The binding partners of Hsp90, co-chaperones, assist in the recruitment and activation of substrates, and many co-chaperones further regulate the conformational dynamics of Hsp90 by shifting the conformational equilibrium towards a particular state. Studies have also suggested alternative mechanisms for the regulation of Hsp90’s conformation. In this review, we discuss the structural and biochemical studies leading to our current understanding of the conformational dynamics of Hsp90 and the role that nucleotide, co-chaperones, post-translational modification and clients play in regulating Hsp90’s conformation. We also discuss the effects of current Hsp90 inhibitors on conformation and the potential for developing small molecules that inhibit Hsp90 by disrupting the conformational dynamics. PMID:21414251

tRNA Shifts the G-quadruplex-Hairpin Conformational Equilibrium in RNA towards the Hairpin Conformer.

PubMed

Rode, Ambadas B; Endoh, Tamaki; Sugimoto, Naoki

2016-11-07

Non-coding RNAs play important roles in cellular homeostasis and are involved in many human diseases including cancer. Intermolecular RNA-RNA interactions are the basis for the diverse functions of many non-coding RNAs. Herein, we show how the presence of tRNA influences the equilibrium between hairpin and G-quadruplex conformations in the 5' untranslated regions of oncogenes and model sequences. Kinetic and equilibrium analyses of the hairpin to G-quadruplex conformational transition of purified RNA as well as during co-transcriptional folding indicate that tRNA significantly shifts the equilibrium toward the hairpin conformer. The enhancement of relative translation efficiency in a reporter gene assay is shown to be due to the tRNA-mediated shift in hairpin-G-quadruplex equilibrium of oncogenic mRNAs. Our findings suggest that tRNA is a possible therapeutic target in diseases in which RNA conformational equilibria is dysregulated. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

14 CFR 21.53 - Statement of conformity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... conformity (FAA Form 317) to the Administrator for each aircraft engine and propeller presented to the... engine or propeller conforms to the type design therefor. (b) Each applicant must submit a statement of... statement that each aircraft engine or propeller presented for type certification conforms to its type...

SCit: web tools for protein side chain conformation analysis.

PubMed

Gautier, R; Camproux, A-C; Tufféry, P

2004-07-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit.

SCit: web tools for protein side chain conformation analysis

PubMed Central

Gautier, R.; Camproux, A.-C.; Tufféry, P.

2004-01-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit. PMID:15215438

Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations

PubMed Central

Skjaerven, Lars; Grant, Barry; Muga, Arturo; Teigen, Knut; McCammon, J. Andrew; Reuter, Nathalie; Martinez, Aurora

2011-01-01

GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observed conformations and the mechanisms involved in the allosteric response to ATP and the nucleotide-driven reaction cycle are not completely established. Here we describe extensive (in total long) unbiased molecular dynamics (MD) simulations that probe the response of GroEL subunits to ATP binding. We observe nucleotide dependent conformational transitions, and show with multiple 100 ns long simulations that the ligand-induced shift in the conformational populations are intrinsically coded in the structure-dynamics relationship of the protein subunit. Thus, these simulations reveal a stabilization of the equatorial domain upon nucleotide binding and a concomitant “opening” of the subunit, which reaches a conformation close to that observed in the crystal structure of the subunits within the ADP-bound oligomer. Moreover, we identify changes in a set of unique intrasubunit interactions potentially important for the conformational transition. PMID:21423709

Conformal Killing horizons and their thermodynamics

NASA Astrophysics Data System (ADS)

Nielsen, Alex B.; Shoom, Andrey A.

2018-05-01

Certain dynamical black hole solutions can be mapped to static spacetimes by conformal metric transformations. This mapping provides a physical link between the conformal Killing horizon of the dynamical black hole and the Killing horizon of the static spacetime. Using the Vaidya spacetime as an example, we show how this conformal relation can be used to derive thermodynamic properties of such dynamical black holes. Although these horizons are defined quasi-locally and can be located by local experiments, they are distinct from other popular notions of quasi-local horizons such as apparent horizons. Thus in the dynamical Vaidya spacetime describing constant accretion of null dust, the conformal Killing horizon, which is null by construction, is the natural horizon to describe the black hole.

Molecular dynamics studies of the conformation of sorbitol

PubMed Central

Lerbret, A.; Mason, P.E.; Venable, R.M.; Cesàro, A.; Saboungi, M.-L.; Pastor, R.W.; Brady, J.W.

2009-01-01

Molecular dynamics simulations of a 3 m aqueous solution of D-sorbitol (also called D-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data supports a more bent structure. PMID:19744646

Conformal Robotic Stereolithography

PubMed Central

Stevens, Adam G.; Oliver, C. Ryan; Kirchmeyer, Matthieu; Wu, Jieyuan; Chin, Lillian; Polsen, Erik S.; Archer, Chad; Boyle, Casey; Garber, Jenna

2016-01-01

Abstract Additive manufacturing by layerwise photopolymerization, commonly called stereolithography (SLA), is attractive due to its high resolution and diversity of materials chemistry. However, traditional SLA methods are restricted to planar substrates and planar layers that are perpendicular to a single-axis build direction. Here, we present a robotic system that is capable of maskless layerwise photopolymerization on curved surfaces, enabling production of large-area conformal patterns and the construction of conformal freeform objects. The system comprises an industrial six-axis robot and a custom-built maskless projector end effector. Use of the system involves creating a mesh representation of the freeform substrate, generation of a triangulated toolpath with curved layers that represents the target object to be printed, precision mounting of the substrate in the robot workspace, and robotic photopatterning of the target object by coordinated motion of the robot and substrate. We demonstrate printing of conformal photopatterns on spheres of various sizes, and construction of miniature three-dimensional objects on spheres without requiring support features. Improvement of the motion accuracy and development of freeform toolpaths would enable construction of polymer objects that surpass the size and support structure constraints imparted by traditional SLA systems. PMID:29577062

On Feeling Torn About One’s Sexuality

PubMed Central

Windsor-Shellard, Ben

2014-01-01

Three studies offer novel evidence addressing the consequences of explicit–implicit sexual orientation (SO) ambivalence. In Study 1, self-identified straight females completed explicit and implicit measures of SO. The results revealed that participants with greater SO ambivalence took longer responding to explicit questions about their sexual preferences, an effect moderated by the direction of ambivalence. Study 2 replicated this effect using a different paradigm. Study 3 included self-identified straight and gay female and male participants; participants completed explicit and implicit measures of SO, plus measures of self-esteem and affect regarding their SO. Among straight participants, the response time results replicated the findings of Studies 1 and 2. Among gay participants, trends suggested that SO ambivalence influenced time spent deliberating on explicit questions relevant to sexuality, but in a different way. Furthermore, the amount and direction of SO ambivalence was related to self-esteem. PMID:24972940

Elucidation of the conformational free energy landscape in H.pylori LuxS and its implications to catalysis.

PubMed

Bhattacharyya, Moitrayee; Vishveshwara, Saraswathi

2010-08-12

One of the major challenges in understanding enzyme catalysis is to identify the different conformations and their populations at detailed molecular level in response to ligand binding/environment. A detail description of the ligand induced conformational changes provides meaningful insights into the mechanism of action of enzymes and thus its function. In this study, we have explored the ligand induced conformational changes in H.pylori LuxS and the associated mechanistic features. LuxS, a dimeric protein, produces the precursor (4,5-dihydroxy-2,3-pentanedione) for autoinducer-2 production which is a signalling molecule for bacterial quorum sensing. We have performed molecular dynamics simulations on H.pylori LuxS in its various ligand bound forms and analyzed the simulation trajectories using various techniques including the structure network analysis, free energy evaluation and water dynamics at the active site. The results bring out the mechanistic details such as co-operativity and asymmetry between the two subunits, subtle changes in the conformation as a response to the binding of active and inactive forms of ligands and the population distribution of different conformations in equilibrium. These investigations have enabled us to probe the free energy landscape and identify the corresponding conformations in terms of network parameters. In addition, we have also elucidated the variations in the dynamics of water co-ordination to the Zn2+ ion in LuxS and its relation to the rigidity at the active sites. In this article, we provide details of a novel method for the identification of conformational changes in the different ligand bound states of the protein, evaluation of ligand-induced free energy changes and the biological relevance of our results in the context of LuxS structure-function. The methodology outlined here is highly generalized to illuminate the linkage between structure and function in any protein of known structure.

Operator product expansion for conformal defects

NASA Astrophysics Data System (ADS)

Fukuda, Masayuki; Kobayashi, Nozomu; Nishioka, Tatsuma

2018-01-01

We study the operator product expansion (OPE) for scalar conformal defects of any codimension in CFT. The OPE for defects is decomposed into "defect OPE blocks", the irreducible representations of the conformal group, each of which packages the contribution from a primary operator and its descendants. We use the shadow formalism to deduce an integral representation of the defect OPE blocks. They are shown to obey a set of constraint equations that can be regarded as equations of motion for a scalar field propagating on the moduli space of the defects. By employing the Radon transform between the AdS space and the moduli space, we obtain a formula of constructing an AdS scalar field from the defect OPE block for a conformal defect of any codimension in a scalar representation of the conformal group, which turns out to be the Euclidean version of the HKLL formula. We also introduce a duality between conformal defects of different codimensions and prove the equivalence between the defect OPE block for codimension-two defects and the OPE block for a pair of local operators.

Identification of Relevant Conformational Epitopes on the HER2 Oncoprotein by Using Large Fragment Phage Display (LFPD)

PubMed Central

Gabrielli, Federico; Salvi, Roberto; Garulli, Chiara; Kalogris, Cristina; Arima, Serena; Tardella, Luca; Monaci, Paolo; Pupa, Serenella M.; Tagliabue, Elda; Montani, Maura; Quaglino, Elena; Stramucci, Lorenzo; Curcio, Claudia

2013-01-01

We developed a new phage-display based approach, the Large Fragment Phage Display (LFPD), that can be used for mapping conformational epitopes on target molecules of immunological interest. LFPD uses a simplified and more effective phage-display approach in which only a limited set of larger fragments (about 100 aa in length) are expressed on the phage surface. Using the human HER2 oncoprotein as a target, we identified novel B-cell conformational epitopes. The same homologous epitopes were also detected in rat HER2 and all corresponded to the epitopes predicted by computational analysis (PEPITO software), showing that LFPD gives reproducible and accurate results. Interestingly, these newly identified HER2 epitopes seem to be crucial for an effective immune response against HER2-overexpressing breast cancers and might help discriminating between metastatic breast cancer and early breast cancer patients. Overall, the results obtained in this study demonstrated the utility of LFPD and its potential application to the detection of conformational epitopes on many other molecules of interest, as well as, the development of new and potentially more effective B-cell conformational epitopes based vaccines. PMID:23555577

40 CFR 51.854 - Conformity analysis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Federal Government taking an action subject to this subpart must make its own conformity determination... agency or develop its own analysis in order to make its conformity determination. Effective Date Note: At...

21 CFR 26.70 - Conformity assessment bodies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Conformity assessment bodies. 26.70 Section 26.70...Frameworkâ Provisions § 26.70 Conformity assessment bodies. Each party recognizes that the conformity assessment bodies (CAB's) listed in subpart B of this part fulfill the conditions of eligibility to assess...

Towards an Uncertain Politics of Professionalism: Teacher and Nurse Identifies in Flux.

ERIC Educational Resources Information Center

Stronach, Ian; Corbin, Brian; Stark, Sheila; McNamara, Olwen; Warne, Tony

2002-01-01

Discusses nature of professional identity, focusing on teachers and nurses, and articulates view of "professional" as "caught between an 'economy of performance' and various 'ecologies of practice'." Rejects over-simplified understanding of "professional" identity and advocates embracing "ambivalence and…

Analytical halo model of galactic conformity

NASA Astrophysics Data System (ADS)

Pahwa, Isha; Paranjape, Aseem

2017-09-01

We present a fully analytical halo model of colour-dependent clustering that incorporates the effects of galactic conformity in a halo occupation distribution framework. The model, based on our previous numerical work, describes conformity through a correlation between the colour of a galaxy and the concentration of its parent halo, leading to a correlation between central and satellite galaxy colours at fixed halo mass. The strength of the correlation is set by a tunable 'group quenching efficiency', and the model can separately describe group-level correlations between galaxy colour (1-halo conformity) and large-scale correlations induced by assembly bias (2-halo conformity). We validate our analytical results using clustering measurements in mock galaxy catalogues, finding that the model is accurate at the 10-20 per cent level for a wide range of luminosities and length-scales. We apply the formalism to interpret the colour-dependent clustering of galaxies in the Sloan Digital Sky Survey (SDSS). We find good overall agreement between the data and a model that has 1-halo conformity at a level consistent with previous results based on an SDSS group catalogue, although the clustering data require satellites to be redder than suggested by the group catalogue. Within our modelling uncertainties, however, we do not find strong evidence of 2-halo conformity driven by assembly bias in SDSS clustering.

Rapid roll inflation with conformal coupling

NASA Astrophysics Data System (ADS)

Kofman, Lev; Mukohyama, Shinji

2008-02-01

Usual inflation is realized with a slow rolling scalar field minimally coupled to gravity. In contrast, we consider dynamics of a scalar with a flat effective potential, conformally coupled to gravity. Surprisingly, it contains an attractor inflationary solution with the rapidly rolling inflaton field. We discuss models with the conformal inflaton with a flat potential (including hybrid inflation). There is no generation of cosmological fluctuations from the conformally coupled inflaton. We consider realizations of modulated (inhomogeneous reheating) or curvaton cosmological fluctuations in these models. We also implement these unusual features for the popular string-theoretic warped inflationary scenario, based on the interacting D3-D¯3 branes. The original warped brane inflation suffers a large inflaton mass due to conformal coupling to 4-dimensional gravity. Instead of considering this as a problem and trying to cure it with extra engineering, we show that warped inflation with the conformally coupled, rapidly rolling inflaton is yet possible with N=37 efoldings, which requires low-energy scales 1 100 TeV of inflation. Coincidentally, the same warping numerology can be responsible for the hierarchy. It is shown that the scalars associated with angular isometries of the warped geometry of compact manifold (e.g. S3 of Klebanov-Strassler (KS) geometry) have solutions identical to conformally coupled modes and also cannot be responsible for cosmological fluctuations. We discuss other possibilities.

Target dose conformity in 3-dimensional conformal radiotherapy and intensity modulated radiotherapy.

PubMed

Wu, Vincent W C; Kwong, Dora L W; Sham, Jonathan S T

2004-05-01

Dose conformity to the planning target volume is an important criterion in radiotherapy treatment planning, for which the conformity index is a useful assessment tool. The purpose of this study is to compare the differences in CI for the treatment planning of four cancers including the nasopharynx, oesophagus, lung and prostate. Seventy patients with cancers of nasopharynx (30), oesophagus (15), lung (15) and prostate (10) were recruited. Each of these patients was planned with three sets of treatment plans using the FOCUS treatment planning system: the forward and inverse 3DCRT plans and the IMRT plan. The CI was generated for each treatment plan. The mean CI from each cancer patient group was calculated and compared with the other three cancer groups. The mean value of CI was also compared among the three planning methods. The oesophageal and lung cancers demonstrated relatively higher overall mean CI values (0.64 and 0.62, respectively), whereas that of the nasopharynx and prostate were lower (0.54 and 0.50, respectively). With regards to the planning method groups, the IMRT plans produced the highest overall mean CI (0.62), while those for the forward and inverse 3DCRT were similar (0.57 and 0.55, respectively). For the four selected cancers, oesophageal and lung cancers were easier to conform than the nasopharyngeal and prostate cancers. The IMRT plans were more effective in achieving better dose conformity than that of the 3DCRT.

Cis-dicarbonyl binding at cobalt and iron porphyrins with saddle-shape conformation.

PubMed

Seufert, Knud; Bocquet, Marie-Laure; Auwärter, Willi; Weber-Bargioni, Alexander; Reichert, Joachim; Lorente, Nicolás; Barth, Johannes V

2011-02-01

Diatomic molecules attached to complexed iron or cobalt centres are important in many biological processes. In natural systems, metallotetrapyrrole units carry respiratory gases or provide sensing and catalytic functions. Conceiving synthetic model systems strongly helps to determine the pertinent chemical foundations for such processes, with recent work highlighting the importance of the prosthetic groups' conformational flexibility as an intricate variable affecting their functional properties. Here, we present simple model systems to investigate, at the single molecule level, the interaction of carbon monoxide with saddle-shaped iron- and cobalt-porphyrin conformers, which have been stabilized as two-dimensional arrays on well-defined surfaces. Using scanning tunnelling microscopy we identified a novel bonding scheme expressed in tilted monocarbonyl and cis-dicarbonyl configurations at the functional metal-macrocycle unit. Modelling with density functional theory revealed that the weakly bonded diatomic carbonyl adduct can effectively bridge specific pyrrole groups with the metal atom as a result of the pronounced saddle-shape conformation of the porphyrin cage.

Voltage-dependent conformational changes in connexin channels.

PubMed

Bargiello, Thaddeus A; Tang, Qingxiu; Oh, Seunghoon; Kwon, Taekyung

2012-08-01

Channels formed by connexins display two distinct types of voltage-dependent gating, termed V(j)- or fast-gating and loop- or slow-gating. Recent studies, using metal bridge formation and chemical cross-linking have identified a region within the channel pore that contributes to the formation of the loop-gate permeability barrier. The conformational changes are remarkably large, reducing the channel pore diameter from 15 to 20Å to less than 4Å. Surprisingly, the largest conformational change occurs in the most stable region of the channel pore, the 3(10) or parahelix formed by amino acids in the 42-51 segment. The data provide a set of positional constraints that can be used to model the structure of the loop-gate closed state. Less is known about the conformation of the V(j)-gate closed state. There appear to be two different mechanisms; one in which conformational changes in channel structure are linked to a voltage sensor contained in the N-terminus of Cx26 and Cx32 and a second in which the C-terminus of Cx43 and Cx40 may act either as a gating particle to block the channel pore or alternatively to stabilize the closed state. The later mechanism utilizes the same domains as implicated in effecting pH gating of Cx43 channels. It is unclear if the two V(j)-gating mechanisms are related or if they represent different gating mechanisms that operate separately in different subsets of connexin channels. A model of the V(j)-closed state of Cx26 hemichannel that is based on the X-ray structure of Cx26 and electron crystallographic structures of a Cx26 mutation suggests that the permeability barrier for V(j)-gating is formed exclusively by the N-terminus, but recent information suggests that this conformation may not represent a voltage-closed state. Closed state models are considered from a thermodynamic perspective based on information from the 3.5Å Cx26 crystal structure and molecular dynamics (MD) simulations. The applications of computational and experimental

Bioactive focus in conformational ensembles: a pluralistic approach

NASA Astrophysics Data System (ADS)

Habgood, Matthew

2017-12-01

Computational generation of conformational ensembles is key to contemporary drug design. Selecting the members of the ensemble that will approximate the conformation most likely to bind to a desired target (the bioactive conformation) is difficult, given that the potential energy usually used to generate and rank the ensemble is a notoriously poor discriminator between bioactive and non-bioactive conformations. In this study an approach to generating a focused ensemble is proposed in which each conformation is assigned multiple rankings based not just on potential energy but also on solvation energy, hydrophobic or hydrophilic interaction energy, radius of gyration, and on a statistical potential derived from Cambridge Structural Database data. The best ranked structures derived from each system are then assembled into a new ensemble that is shown to be better focused on bioactive conformations. This pluralistic approach is tested on ensembles generated by the Molecular Operating Environment's Low Mode Molecular Dynamics module, and by the Cambridge Crystallographic Data Centre's conformation generator software.

Probing RNA Native Conformational Ensembles with Structural Constraints.

PubMed

Fonseca, Rasmus; van den Bedem, Henry; Bernauer, Julie

2016-05-01

Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of cellular processes, ranging from regulating gene expression to post-translational modification and protein synthesis. Their activity is modulated by highly dynamic exchanges between three-dimensional conformational substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined by distance constraints in the tertiary structure. The dimensionality reduction enables efficient exploration of conformational space. We show that the conformational distributions obtained with our method broadly sample the conformational landscape observed in NMR experiments. Compared to normal mode analysis-based exploration, our procedure diffuses faster through the experimental ensemble while also accessing conformational substates to greater precision. Our results suggest that conformational sampling with a highly reduced but fully atomistic representation of noncoding RNA expresses key features of their dynamic nature.

The research of conformal optical design

NASA Astrophysics Data System (ADS)

Li, Lin; Li, Yan; Huang, Yi-fan; Du, Bao-lin

2009-07-01

Conformal optical domes are characterized as having external more elongated optical surfaces that are optimized to minimize drag, increased missile velocity and extended operational range. The outer surface of the conformal domes typically deviate greatly from spherical surface descriptions, so the inherent asymmetry of conformal surfaces leads to variations in the aberration content presented to the optical sensor as it is gimbaled across the field of regard, which degrades the sensor's ability to properly image targets of interest and then undermine the overall system performance. Consequently, the aerodynamic advantages of conformal domes cannot be realized in practical systems unless the dynamic aberration correction techniques are developed to restore adequate optical imaging capabilities. Up to now, many optical correction solutions have been researched in conformal optical design, including static aberrations corrections and dynamic aberrations corrections. There are three parts in this paper. Firstly, the combination of static and dynamic aberration correction is introduced. A system for correcting optical aberration created by a conformal dome has an outer surface and an inner surface. The optimization of the inner surface is regard as the static aberration correction; moreover, a deformable mirror is placed at the position of the secondary mirror in the two-mirror all reflective imaging system, which is the dynamic aberration correction. Secondly, the using of appropriate surface types is very important in conformal dome design. Better performing optical systems can result from surface types with adequate degrees of freedom to describe the proper corrector shape. Two surface types and the methods of using them are described, including Zernike polynomial surfaces used in correct elements and user-defined surfaces used in deformable mirror (DM). Finally, the Adaptive optics (AO) correction is presented. In order to correct the dynamical residual aberration

New open conformation of SMYD3 implicates conformational selection and allostery

PubMed Central

Spellmon, Nicholas; Sun, Xiaonan; Xue, Wen; Holcomb, Joshua; Chakravarthy, Srinivas; Shang, Weifeng; Edwards, Brian; Sirinupong, Nualpun; Li, Chunying; Yang, Zhe

2016-01-01

SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly “closed” substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an “open” conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics. The two states are characterized by many distinct structural and dynamical differences and the conformational transition pathway is mediated by a reversible twisting motion of the C-terminal domain (CTD). The spontaneous transition from the closed to open states suggests two possible, mutually non-exclusive models for SMYD3 functional regulation and the conformational selection mechanism and allostery may regulate the catalytic or ligand binding competence of SMYD3. This study provides an immediate clue to the puzzling role of SMYD3 in epigenetic gene regulation. PMID:28050603

Reciprocity Outperforms Conformity to Promote Cooperation.

PubMed

Romano, Angelo; Balliet, Daniel

2017-10-01

Evolutionary psychologists have proposed two processes that could give rise to the pervasiveness of human cooperation observed among individuals who are not genetically related: reciprocity and conformity. We tested whether reciprocity outperformed conformity in promoting cooperation, especially when these psychological processes would promote a different cooperative or noncooperative response. To do so, across three studies, we observed participants' cooperation with a partner after learning (a) that their partner had behaved cooperatively (or not) on several previous trials and (b) that their group members had behaved cooperatively (or not) on several previous trials with that same partner. Although we found that people both reciprocate and conform, reciprocity has a stronger influence on cooperation. Moreover, we found that conformity can be partly explained by a concern about one's reputation-a finding that supports a reciprocity framework.

Conformational Transitions and Convergence of Absolute Binding Free Energy Calculations

PubMed Central

Lapelosa, Mauro; Gallicchio, Emilio; Levy, Ronald M.

2011-01-01

The Binding Energy Distribution Analysis Method (BEDAM) is employed to compute the standard binding free energies of a series of ligands to a FK506 binding protein (FKBP12) with implicit solvation. Binding free energy estimates are in reasonably good agreement with experimental affinities. The conformations of the complexes identified by the simulations are in good agreement with crystallographic data, which was not used to restrain ligand orientations. The BEDAM method is based on λ -hopping Hamiltonian parallel Replica Exchange (HREM) molecular dynamics conformational sampling, the OPLS-AA/AGBNP2 effective potential, and multi-state free energy estimators (MBAR). Achieving converged and accurate results depends on all of these elements of the calculation. Convergence of the binding free energy is tied to the level of convergence of binding energy distributions at critical intermediate states where bound and unbound states are at equilibrium, and where the rate of binding/unbinding conformational transitions is maximal. This finding mirrors similar observations in the context of order/disorder transitions as for example in protein folding. Insights concerning the physical mechanism of ligand binding and unbinding are obtained. Convergence for the largest FK506 ligand is achieved only after imposing strict conformational restraints, which however require accurate prior structural knowledge of the structure of the complex. The analytical AGBNP2 model is found to underestimate the magnitude of the hydrophobic driving force towards binding in these systems characterized by loosely packed protein-ligand binding interfaces. Rescoring of the binding energies using a numerical surface area model corrects this deficiency. This study illustrates the complex interplay between energy models, exploration of conformational space, and free energy estimators needed to obtain robust estimates from binding free energy calculations. PMID:22368530

Irreversibility and higher-spin conformal field theory

NASA Astrophysics Data System (ADS)

Anselmi, Damiano

2000-08-01

I discuss the properties of the central charges c and a for higher-derivative and higher-spin theories (spin 2 included). Ordinary gravity does not admit a straightforward identification of c and a in the trace anomaly, because it is not conformal. On the other hand, higher-derivative theories can be conformal, but have negative c and a. A third possibility is to consider higher-spin conformal field theories. They are not unitary, but have a variety of interesting properties. Bosonic conformal tensors have a positive-definite action, equal to the square of a field strength, and a higher-derivative gauge invariance. There exists a conserved spin-2 current (not the canonical stress tensor) defining positive central charges c and a. I calculate the values of c and a and study the operator-product structure. Higher-spin conformal spinors have no gauge invariance, admit a standard definition of c and a and can be coupled to Abelian and non-Abelian gauge fields in a renormalizable way. At the quantum level, they contribute to the one-loop beta function with the same sign as ordinary matter, admit a conformal window and non-trivial interacting fixed points. There are composite operators of high spin and low dimension, which violate the Ferrara-Gatto-Grillo theorem. Finally, other theories, such as conformal antisymmetric tensors, exhibit more severe internal problems. This research is motivated by the idea that fundamental quantum field theories should be renormalization-group (RG) interpolations between ultraviolet and infrared conformal fixed points, and quantum irreversibility should be a general principle of nature.

Essential role of conformational selection in ligand binding.

PubMed

Vogt, Austin D; Pozzi, Nicola; Chen, Zhiwei; Di Cera, Enrico

2014-02-01

Two competing and mutually exclusive mechanisms of ligand recognition - conformational selection and induced fit - have dominated our interpretation of ligand binding in biological macromolecules for almost six decades. Conformational selection posits the pre-existence of multiple conformations of the macromolecule from which the ligand selects the optimal one. Induced fit, on the other hand, postulates the existence of conformational rearrangements of the original conformation into an optimal one that are induced by binding of the ligand. In the former case, conformational transitions precede the binding event; in the latter, conformational changes follow the binding step. Kineticists have used a facile criterion to distinguish between the two mechanisms based on the dependence of the rate of relaxation to equilibrium, kobs, on the ligand concentration, [L]. A value of kobs decreasing hyperbolically with [L] has been seen as diagnostic of conformational selection, while a value of kobs increasing hyperbolically with [L] has been considered diagnostic of induced fit. However, this simple conclusion is only valid under the rather unrealistic assumption of conformational transitions being much slower than binding and dissociation events. In general, induced fit only produces values of kobs that increase with [L] but conformational selection is more versatile and is associated with values of kobs that increase with, decrease with or are independent of [L]. The richer repertoire of kinetic properties of conformational selection applies to kinetic mechanisms with single or multiple saturable relaxations and explains the behavior of nearly all experimental systems reported in the literature thus far. Conformational selection is always sufficient and often necessary to account for the relaxation kinetics of ligand binding to a biological macromolecule and is therefore an essential component of any binding mechanism. On the other hand, induced fit is never necessary and

“Voices of Fear and Safety” Women’s ambivalence towards breast cancer and breast health: a qualitative study from Jordan

PubMed Central

2012-01-01

Background Breast cancer is the leading cause of cancer mortality among Jordanian women. Breast malignancies are detected at late stages as a result of deferred breast health-seeking behaviour. The aim of this study was to explore Jordanian women’s views and perceptions about breast cancer and breast health. Methods We performed an explorative qualitative study with purposive sampling. Ten focus groups were conducted consisting of 64 women (aged 20 to 65 years) with no previous history and no symptoms of breast cancer from four governorates in Jordan. The transcribed data was analysed using latent content analysis. Results Three themes were constructed from the group discussions: a) Ambivalence in prioritizing own health; b) Feeling fear of breast cancer; and c) Feeling safe from breast cancer. The first theme was seen in women’s prioritizing children and family needs and in their experiencing family and social support towards seeking breast health care. The second theme was building on women’s perception of breast cancer as an incurable disease associated with suffering and death, their fear of the risk of diminished femininity, husband’s rejection and social stigmatization, adding to their apprehensions about breast health examinations. The third theme emerged from the women’s perceiving themselves as not being in the risk zone for breast cancer and in their accepting breast cancer as a test from God. In contrast, women also experienced comfort in acquiring breast health knowledge that soothed their fears and motivated them to seek early detection examinations. Conclusions Women’s ambivalence in prioritizing their own health and feelings of fear and safety could be better addressed by designing breast health interventions that emphasize the good prognosis for breast cancer when detected early, involve breast cancer survivors in breast health awareness campaigns and catalyse family support to encourage women to seek breast health care. PMID:22834874

A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers

PubMed Central

Noble, Geoffrey P.; Wang, Daphne W.; Walsh, Daniel J.; Barone, Justin R.; Miller, Michael B.; Nishina, Koren A.; Li, Sheng; Supattapone, Surachai

2015-01-01

Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS) studies revealed that solvent accessibility profiles of infectious and non-infectious autocatalytic recombinant PrP conformers are remarkably similar throughout their protease-resistant cores, except for two domains encompassing residues 91-115 and 144-163. Raman spectroscopy and immunoprecipitation studies confirm that these domains adopt distinct conformations within infectious versus non-infectious autocatalytic recombinant PrP conformers. Functionally, in vitro prion propagation experiments show that the non-infectious conformer is unable to seed mouse PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor, including native PrPC. Taken together, these results indicate that having a conformation that can be specifically adopted by post-translationally modified PrPC molecules is an essential determinant of biological infectivity for recombinant prions, and suggest that this ability is associated with discrete features of PrPSc structure. PMID:26125623

Conformational landscape, photochemistry, and infrared spectra of sulfanilamide.

PubMed

Borba, Ana; Gómez-Zavaglia, Andrea; Fausto, Rui

2013-01-31

A combined matrix isolation FTIR and theoretical DFT(B3LYP)/6-311++G(3df,3pd) study of sulfanilamide (SA) was performed. The full conformational search on the potential energy surface of the compound allowed the identification of four different minima, all of them bearing the sulfamide nitrogen atom placed in the perpendicular orientation relatively to the aromatic ring and differing from each other in the orientation of the hydrogen atoms connected to the two nitrogen atoms of the molecule. All conformers were predicted to be significantly populated in the gas phase (at 100 °C, their relative populations were estimated as being 1:0.9:0.3:0.2). However, in agreement with the theoretically calculated low-energy barriers for conformational isomerization, in the low-temperature matrices, only the most stable conformer could be observed, with the remaining forms being converted into this form during matrix deposition (conformational cooling). The unimolecular photochemistry of matrix-isolated SA (in both argon and xenon) was also investigated. Upon broadband UV irradiation (λ > 215 nm), two photofragmentation pathways were observed: the prevalent pathway (A), leading to extrusion of sulfur dioxide and simultaneous formation of benzene-1,4-diamine, which then converts to 2,5-cyclohexadiene-1,4-diimine, and the minor pathway (B), conducting an γ-cleavage plus [1,3] H-atom migration from the sulfamide group to the aromatic ring, which leads to formation of iminosulfane dioxide and aniline, the latter undergoing subsequent phototransformation into cyclohexa-2,5-dien-1-imine. Finally, the crystalline polymorph of SA resulting from warming (265 K) the amorphous solid obtained from fast cooling of the vapor of the compound onto the cold (13 K) substrate of the cryostat was identified spectroscopically, and found to be the γ-crystalline phase, the one exhibiting in average longer H-bonds and an infrared spectrum resembling more that of the low temperature SA glass. Full

Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline

NASA Astrophysics Data System (ADS)

Cabezas, C.; Cortijo, V.; Mata, S.; Lopez, J. C.; Alonso, J. L.

2013-06-01

Recent improvements in our LA-MB-FTMW instrumentation have allowed the characterization of eleven and eight conformers for the neurotransmitters adrenaline and noradrenaline respectively. The observation of this rich conformational behavior is in accordance with the recent observation of seven conformers for dopamine and in sharp contrast with the conformational reduction proposed for catecholamines. C. Cabezas, I. Peña, J. C. López, J. L. Alonso J. Phys. Chem. Lett. 2013, 4, 486. H. Mitsuda, M. Miyazaki, I. B. Nielsen, P. Carcabal,C. Dedonder, C. Jouvet, S. Ishiuchi, M. Fujii J. Phys. Chem. Lett. 2010, 1, 1130.

[Psychometric properties of the French versions of the Cognitive Slippage Scale and Schizotypal Ambivalence Scale in 340 subjects].

PubMed

Yon, V; Loas, G; Monestes, J-L; Verrier, A; Deligne, H

2007-01-01

The aim of this article is firstly to present the French translations of the Cognitive Slippage (Miers and Raulin, 1987) and the Schizotypal Ambivalence Scales (Raulin, 1986), and secondly to determine their psychometric properties in different samples of non-clinical and clinical subjects. Chapman et al. have developed trait-oriented scales based on Meehl's manual of schizotypy, such as the Physical and Social Anhedonia Scales, the Perceptual Aberration Scale, the Magical Ideation Scale, the Impulsive Nonconformity Scale, the Cognitive Slippage Scale (CSS), and the Schizotypal Ambivalence Scale (SAS). The Chapman scales of psychosis proneness are the most internationally used instruments for the assessment of schizotypy and some of them such as the Cognitive Slippage and Schizotypal Ambivalence Scales were still not available in French. The study was conducted in three different samples: the non-clinical sample (n=158) comprised firstly 128 university students (113 females, 15 males) with a mean age of 24.67 years (sd=5.18) and secondly 30 healthy subjects (12 males, 18 females) with a mean age of 33.26 years (sd=7.35); the clinical sample (n=167) comprised firstly 106 psychiatric patients hospitalized in a general hospital (73 males, 33 females) with a mean age of 38.35 years (sd=11.60) and 61 (35 males, 26 females) in or outpatients of a psychiatric department with a mean age of 37.75 years (sd=10.72); 15 schizotypal university students presenting high score of the Revised Social Anhedonia Scale (1 male, 14 females) with a mean age of 21.26 years (sd=1.1). Using the ICD-10, the diagnoses for the general hospital sample were neurotic or anxious disorders (47%) and depressive disorders (24%). For the psychiatric department sample, the diagnoses were schizophrenic disorders (29%), mood disorders (16%), neurotic disorders (18%) and personality disorders (15%). The internal consistency was determined by the Kuder-Richardson coefficient (KR 20) (CSS: KR 20=0.85 in the

Conformity and Psychopathology: A Comparative Study of Conformity Behaviors in Manic-depressive, Paranoid Schizophrenic and Normal Populations

ERIC Educational Resources Information Center

Marsella, Anthony J.

1975-01-01

The present study investigated the relationship between conformity and psychopathology in male and female manic-depressive (MD), paranoid schizophrenics (PS), and normals (N) on two conformity tasks under conditions of live social pressure. (Author)

The Inherent Conformational Preferences of Glutamine-Containing Peptides: the Role for Side-Chain Backbone Hydrogen Bonds

NASA Astrophysics Data System (ADS)

Walsh, Patrick S.; McBurney, Carl; Gellman, Samuel H.; Zwier, Timothy S.

2015-06-01

Glutamine is widely known to be found in critical regions of peptides which readily fold into amyloid fibrils, the structures commonly associated with Alzheimer's disease and glutamine repeat diseases such as Huntington's disease. Building on previous single-conformation data on Gln-containing peptides containing an aromatic cap on the N-terminus (Z-Gln-OH and Z-Gln-NHMe), we present here single-conformation UV and IR spectra of Ac-Gln-NHBn and Ac-Ala-Gln-NHBn, with its C-terminal benzyl cap. These results point towards side-chain to backbone hydrogen bonds dominating the structures observed in the cold, isolated environment of a molecular beam. We have identified and assigned three main conformers for Ac-Gln-NHBn all involving primary side-chain to backbone interactions. Ac-Ala-Gln-NHBn extends the peptide chain by one amino acid, but affords an improvement in the conformational flexibility. Despite this increase in the flexibility, only a single conformation is observed in the gas-phase: a structure which makes use of both side-chain-to-backbone and backbone-to-backbone hydrogen bonds.

Spacer conformation in biologically active molecules. Part 1. Structure and conformational preferences of 2-substituted benzoxazoles

NASA Astrophysics Data System (ADS)

Czylkowski, R.; Karolak-Wojciechowska, J.; Mrozek, A.; Yalçin, I.; Aki-Şener, E.

2001-12-01

The mutual position of two pharmacophoric elements in flexible biologically active molecules depends on the spacer conformation. This is true even for a two-atomic chain put to use as a spacer. It was established for 2-substituted-benzoxazoles containing two aromatic centres joined by -CH2-X- (X=S or O). From crystallographic studies of four molecules it was found that the role of heteroatom is essential for the whole molecule conformation. The spacer with X=S adopts the (-)synclinal conformation while for X=O the (+)antiperiplanar one. Such preferences were also found in the statistical data from Cambridge Structural Database (CSD).

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis*

PubMed Central

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.; Cohen, Itay; Henin, Rachel D.; Hockla, Alexandra; Soares, Alexei S.; Papo, Niv; Caulfield, Thomas R.; Radisky, Evette S.

2016-01-01

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4-Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals a dramatic conformational change in the substrate upon proteolysis. By using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning 3 orders of magnitude, we identify global and local dynamic features of substrates on the nanosecond-microsecond time scale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substrate-like and product-like states, linking substrate dynamics on the nanosecond-microsecond time scale with large collective substrate motions on the much slower time scale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis. PMID:27810896

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis

DOE PAGES

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.; ...

2016-11-03

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. While considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here in this paper, we examine the importance of substrate dynamics in the cleavage of Kunitz-BPTI protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4 Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals amore » dramatic conformational change in the substrate upon proteolysis. Using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning three orders of magnitude, we identify global and local dynamic features of substrates on the ns-μs timescale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substratelike and product-like states, linking substrate dynamics on the ns-μs timescale with large collective substrate motions on the much slower timescale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis.« less

Conformation-Specific Infrared and Ultraviolet Spectroscopy of Cold [YAPAA +H]+ and [YGPAA +H]+ Ions

NASA Astrophysics Data System (ADS)

Deblase, Andrew; Harrilal, Christopher; Lawler, John; Burke, Nicole; McLuckey, Scott; Timothy, Zwier

Incorporation of the unnatural D-proline stereoisomer into a peptide sequence is a typical strategy to synthesize model β-hairpin loops. Using conformation-specific IR and UV spectroscopy of cold ( 10 K) gas-phase ions, we unravel the inherent conformational preferences of the DP and LP diastereomers in the protonated peptide [YAPAA +H]+ because only intramolecular interactions are possible in this isolated regime. Consistent with the solution phase studies, one of the conformers of [YADPAA +H]+ is folded into a β-hairpin turn. However, a second predominant γ-turn conformer family is identified. The [YALPAA +H]+ stereoisomer discourages β-hairpin formation. We show that the trans(DP) ->cis (LP) isomerization is sterically driven and can be reversed by substituting [YGLPAA +H]+ for [YALPAA +H]+. Therefore, we provide a basis for understanding residue-specific alterations in the potential energy surface and reveal new insights into the origin of β-hairpin formation from the bottom-up. National Science Foundation (NSF CHE 1213289) and the U.S. Department of Energy (Office of Basic Energy Sciences under Award Number FG02-00ER15105).

Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers.

PubMed

Satoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, Koichi

2016-11-08

This paper describes our approach that is built upon the potential energy surface (PES)-based conformational analysis. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search has been achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the minima and TS structures by simply taking into account the mathematical feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equilibrium (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalculation analysis of the deduced r-map is interactively carried out using the RMapViewer software we have developed. This paper presents computational details of the PES-based conformational analysis and its application to d-glucose. The calculations have been performed for an isolated glucose molecule in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-d-glucose is composed of 201 EQ and 435 TS conformers and that for β-d-glucose is composed of 202 EQ and 371 TS conformers. For the postcalculation analysis of the conformational r-maps by using the RMapViewer software program we have found multiple minimum energy paths (MEPs) between global minima of 1 C 4 and 4 C 1 chair conformations. The analysis using RMapViewer allows us to confirm the thermodynamic and kinetic predominance of 4 C 1 conformations; that is, the potential energy of the global minimum of 4 C 1 is lower than that of 1 C 4 (thermodynamic predominance

Linear Response Path Following: A Molecular Dynamics Method To Simulate Global Conformational Changes of Protein upon Ligand Binding.

PubMed

Tamura, Koichi; Hayashi, Shigehiko

2015-07-14

Molecular functions of proteins are often fulfilled by global conformational changes that couple with local events such as the binding of ligand molecules. High molecular complexity of proteins has, however, been an obstacle to obtain an atomistic view of the global conformational transitions, imposing a limitation on the mechanistic understanding of the functional processes. In this study, we developed a new method of molecular dynamics (MD) simulation called the linear response path following (LRPF) to simulate a protein's global conformational changes upon ligand binding. The method introduces a biasing force based on a linear response theory, which determines a local reaction coordinate in the configuration space that represents linear coupling between local events of ligand binding and global conformational changes and thus provides one with fully atomistic models undergoing large conformational changes without knowledge of a target structure. The overall transition process involving nonlinear conformational changes is simulated through iterative cycles consisting of a biased MD simulation with an updated linear response force and a following unbiased MD simulation for relaxation. We applied the method to the simulation of global conformational changes of the yeast calmodulin N-terminal domain and successfully searched out the end conformation. The atomistically detailed trajectories revealed a sequence of molecular events that properly lead to the global conformational changes and identified key steps of local-global coupling that induce the conformational transitions. The LRPF method provides one with a powerful means to model conformational changes of proteins such as motors and transporters where local-global coupling plays a pivotal role in their functional processes.

Galactic conformity measured in semi-analytic models

NASA Astrophysics Data System (ADS)

Lacerna, I.; Contreras, S.; González, R. E.; Padilla, N.; Gonzalez-Perez, V.

2018-03-01

We study the correlation between the specific star formation rate of central galaxies and neighbour galaxies, also known as `galactic conformity', out to 20 h^{-1} {Mpc} using three semi-analytic models (SAMs, one from L-GALAXIES and other two from GALFORM). The aim is to establish whether SAMs are able to show galactic conformity using different models and selection criteria. In all the models, when the selection of primary galaxies is based on an isolation criterion in real space, the mean fraction of quenched (Q) galaxies around Q primary galaxies is higher than that around star-forming primary galaxies of the same stellar mass. The overall signal of conformity decreases when we remove satellites selected as primary galaxies, but the effect is much stronger in GALFORM models compared with the L-GALAXIES model. We find this difference is partially explained by the fact that in GALFORM once a galaxy becomes a satellite remains as such, whereas satellites can become centrals at a later time in L-GALAXIES. The signal of conformity decreases down to 60 per cent in the L-GALAXIES model after removing central galaxies that were ejected from their host halo in the past. Galactic conformity is also influenced by primary galaxies at fixed stellar mass that reside in dark matter haloes of different masses. Finally, we explore a proxy of conformity between distinct haloes. In this case, the conformity is weak beyond ˜3 h^{-1} {Mpc} (<3 per cent in L-GALAXIES, <1-2 per cent in GALFORM models). Therefore, it seems difficult that conformity is directly related with a long-range effect.

Vapor deposition routes to conformal polymer thin films

PubMed Central

Moni, Priya; Al-Obeidi, Ahmed

2017-01-01

Vapor phase syntheses, including parylene chemical vapor deposition (CVD) and initiated CVD, enable the deposition of conformal polymer thin films to benefit a diverse array of applications. This short review for nanotechnologists, including those new to vapor deposition methods, covers the basic theory in designing a conformal polymer film vapor deposition, sample preparation and imaging techniques to assess film conformality, and several applications that have benefited from vapor deposited, conformal polymer thin films. PMID:28487816

Finite conformal quantum gravity and spacetime singularities

NASA Astrophysics Data System (ADS)

Modesto, Leonardo; Rachwał, Lesław

2017-12-01

We show that a class of finite quantum non-local gravitational theories is conformally invariant at classical as well as at quantum level. This is actually a range of conformal anomaly-free theories in the spontaneously broken phase of the Weyl symmetry. At classical level we show how the Weyl conformal invariance is able to tame all the spacetime singularities that plague not only Einstein gravity, but also local and weakly non-local higher derivative theories. The latter statement is proved by a singularity theorem that applies to a large class of weakly non-local theories. Therefore, we are entitled to look for a solution of the spacetime singularity puzzle in a missed symmetry of nature, namely the Weyl conformal symmetry. Following the seminal paper by Narlikar and Kembhavi, we provide an explicit construction of singularity-free black hole exact solutions in a class of conformally invariant theories.

Conformal and projective symmetries in Newtonian cosmology

NASA Astrophysics Data System (ADS)

Duval, C.; Gibbons, G. W.; Horváthy, P. A.

2017-02-01

Definitions of non-relativistic conformal transformations are considered both in the Newton-Cartan and in the Kaluza-Klein-type Eisenhart/Bargmann geometrical frameworks. The symmetry groups that come into play are exemplified by the cosmological, and also the Newton-Hooke solutions of Newton's gravitational field equations. It is shown, in particular, that the maximal symmetry group of the standard cosmological model is isomorphic to the 13-dimensional conformal-Newton-Cartan group whose conformal-Bargmann extension is explicitly worked out. Attention is drawn to the appearance of independent space and time dilations, in contrast with the Schrödinger group or the Conformal Galilei Algebra.

Modeling the Conformation-Specific Infrared Spectra of N-Alkylbenzenes

NASA Astrophysics Data System (ADS)

Tabor, Daniel P.; Sibert, Edwin; Hewett, Daniel M.; Korn, Joseph A.; Zwier, Timothy S.

2016-06-01

Conformation-specific UV-IR double resonance spectra are presented for n-alkylbenzenes. With the aid of a local mode Hamiltonian that includes the effects of stretch-bend Fermi coupling, the spectra of ethyl, n-propyl, and n-butylbenzene are assigned to individual conformers. These molecules allow for further development of the work on a first principles method for calculating alkyl stretch spectra. Due to the consistency of the anharmonic couplings from conformer to conformer, construction of the model Hamiltonian for a given conformer only requires a harmonic frequency calculation at the conformer's minimum geometry as an input. The model Hamiltonian can be parameterized with either density functional theory or MP2 electronic structure calculations. The relative strengths and weaknesses of these methods are evaluated, including their predictions of the relative energetics of the conformers. Finally, the IR spectra for conformers that have the alkyl chain bend back and interact with the π cloud of the benzene ring are modeled.

Side-chain conformational space analysis (SCSA): A multi conformation-based QSAR approach for modeling and prediction of protein-peptide binding affinities

NASA Astrophysics Data System (ADS)

Zhou, Peng; Chen, Xiang; Shang, Zhicai

2009-03-01

In this article, the concept of multi conformation-based quantitative structure-activity relationship (MCB-QSAR) is proposed, and based upon that, we describe a new approach called the side-chain conformational space analysis (SCSA) to model and predict protein-peptide binding affinities. In SCSA, multi-conformations (rather than traditional single-conformation) have received much attention, and the statistical average information on multi-conformations of side chains is determined using self-consistent mean field theory based upon side chain rotamer library. Thereby, enthalpy contributions (including electrostatic, steric, hydrophobic interaction and hydrogen bond) and conformational entropy effects to the binding are investigated in terms of occurrence probability of residue rotamers. Then, SCSA was applied into the dataset of 419 HLA-A*0201 binding peptides, and nonbonding contributions of each position in peptide ligands are well determined. For the peptides, the hydrogen bond and electrostatic interactions of the two ends are essential to the binding specificity, van der Waals and hydrophobic interactions of all the positions ensure strong binding affinity, and the loss of conformational entropy at anchor positions partially counteracts other favorable nonbonding effects.

Critical Nexus or Pluralist Discipline? Institutional Ambivalence and the Future of Canadian Sociology.

PubMed

Puddephatt, Antony J; McLaughlin, Neil

2015-08-01

While some scholars believe in a transdisciplinary future for the social sciences and humanities, we argue that sociology would do well to maintain its disciplinary borders, while celebrating the plurality of its intellectual, social, and political content. Although a pluralist position can threaten disciplinary coherence and increase fragmentation, we argue the counterbalance ought to be convergence around shared institutional norms of knowledge production. Establishing these norms is not easy, since there is a great deal of institutional ambivalence at play in the field of sociology. As such, sociology is pushed and pulled between two poles of at least four major continuums of knowledge production, which include the following: (1) interdisciplinary versus discipline-based research; (2) political versus analytical scholarship; (3) professional versus public/policy sociology; and (4) local/national versus global audiences. Since both sides of these ideal-typical continuums contain their own pathologies, we propose adopting a balanced position to correct for the shortcomings of each. Rather than imposing one philosophical or theoretical paradigm for the field, we suggest that embracing the "chaos" of our diverse forms of knowledge and centralizing and integrating findings will serve to strengthen our collective efforts in the long term. © 2015 Canadian Sociological Association/La Société canadienne de sociologie.

Conformal mapping for multiple terminals

PubMed Central

Wang, Weimin; Ma, Wenying; Wang, Qiang; Ren, Hao

2016-01-01

Conformal mapping is an important mathematical tool that can be used to solve various physical and engineering problems in many fields, including electrostatics, fluid mechanics, classical mechanics, and transformation optics. It is an accurate and convenient way to solve problems involving two terminals. However, when faced with problems involving three or more terminals, which are more common in practical applications, existing conformal mapping methods apply assumptions or approximations. A general exact method does not exist for a structure with an arbitrary number of terminals. This study presents a conformal mapping method for multiple terminals. Through an accurate analysis of boundary conditions, additional terminals or boundaries are folded into the inner part of a mapped region. The method is applied to several typical situations, and the calculation process is described for two examples of an electrostatic actuator with three electrodes and of a light beam splitter with three ports. Compared with previously reported results, the solutions for the two examples based on our method are more precise and general. The proposed method is helpful in promoting the application of conformal mapping in analysis of practical problems. PMID:27830746

Mapping Conformational Dynamics of Proteins Using Torsional Dynamics Simulations

PubMed Central

Gangupomu, Vamshi K.; Wagner, Jeffrey R.; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-01-01

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein’s experimentally established conformational substates. Conformational transition of calmodulin from the Ca2+-bound to the Ca2+-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in

Research on conformal dome of Karman-curve shape

NASA Astrophysics Data System (ADS)

Zhang, Yunqiang; Chang, Jun; Niu, Yajun

2018-01-01

Because the conformal optical technology can obviously improve the aerodynamic performance of the infrared guidance missile, it has been studied deeply in recent years. By comparing the performance of the missiles with conformal dome and conventional missiles, the advantages of the conformal optical technology are demonstrated in the maneuverability and stealth of the missile. At present, the study of conformal optical systems focuses on ellipsoid or quadratic curve types. But in actual use, the dome using these curves is not the best choice. In this paper, the influence of different shape of the dome on aerodynamic performance, aerodynamic heating, internal space volume and other properties is discussed. The result shows infrared optical system with conformal dome of Karman-curve shape has a good application prospect, is the future direction of development. Finally, the difficult problems of conformal dome of Karman-curve shape are discussed.

Molecular Clustering Interrelationships and Carbohydrate Conformation in Hull and Seeds Among Barley Cultivars

DOE Office of Scientific and Technical Information (OSTI.GOV)

N Liu; P Yu

2011-12-31

The objective of this study was to use molecular spectral analyses with the diffuse reflectance Fourier transform infrared spectroscopy (DRIFT) bioanlytical technique to study carbohydrate conformation features, molecular clustering and interrelationships in hull and seed among six barley cultivars (AC Metcalfe, CDC Dolly, McLeod, CDC Helgason, CDC Trey, CDC Cowboy), which had different degradation kinetics in rumen. The molecular structure spectral analyses in both hull and seed involved the fingerprint regions of ca. 1536-1484 cm{sup -1} (attributed mainly to aromatic lignin semicircle ring stretch), ca. 1293-1212 cm{sup -1} (attributed mainly to cellulosic compounds in the hull), ca. 1269-1217 cm{sup -1}more » (attributed mainly to cellulosic compound in the seeds), and ca. 1180-800 cm{sup -1} (attributed mainly to total CHO C-O stretching vibrations) together with an agglomerative hierarchical cluster (AHCA) and principal component spectral analyses (PCA). The results showed that the DRIFT technique plus AHCA and PCA molecular analyses were able to reveal carbohydrate conformation features and identify carbohydrate molecular structure differences in both hull and seeds among the barley varieties. The carbohydrate molecular spectral analyses at the region of ca. 1185-800 cm{sup -1} together with the AHCA and PCA were able to show that the barley seed inherent structures exhibited distinguishable differences among the barley varieties. CDC Helgason had differences from AC Metcalfe, MeLeod, CDC Cowboy and CDC Dolly in carbohydrate conformation in the seed. Clear molecular cluster classes could be distinguished and identified in AHCA analysis and the separate ellipses could be grouped in PCA analysis. But CDC Helgason had no distinguished differences from CDC Trey in carbohydrate conformation. These carbohydrate conformation/structure difference could partially explain why the varieties were different in digestive behaviors in animals. The molecular spectroscopy

He loves her, he loves her not: attachment style as a personality antecedent to men's ambivalent sexism.

PubMed

Hart, Joshua; Hung, Jacqueline A; Glick, Peter; Dinero, Rachel E

2012-11-01

The authors present an integrative account of how attachment insecurities relate to sexism. Two studies showed that attachment avoidance predisposes men to endorse hostile but to reject benevolent sexism (BS), whereas attachment anxiety predisposes men toward ambivalent (both hostile and benevolent) sexism. The authors also tested predicted mediators, finding that men's social dominance orientation (a competitive intergroup ideology) mediated the avoidance to hostile sexism link. In addition, romanticism (an idealized interpersonal ideology) mediated attachment insecurity to BS links: (a) Avoidant men tended to reject romanticism (i.e., were cynical about romance) and, in turn, were likely to reject BS, whereas (b) anxious men tended to endorse romanticism (i.e., were idealistic about romance) and, in turn, likely to endorse BS. The authors conclude that men's sexism stems in part from dispositional attachment working models, both directly and through the interpersonal and intergroup ideologies they generate.

UV conformal window for asymptotic safety

NASA Astrophysics Data System (ADS)

Bond, Andrew D.; Litim, Daniel F.; Vazquez, Gustavo Medina; Steudtner, Tom

2018-02-01

Interacting fixed points in four-dimensional gauge theories coupled to matter are investigated using perturbation theory up to three loop order. It is shown how fixed points, scaling exponents, and anomalous dimensions are obtained as a systematic power series in a small parameter. The underlying ordering principle is explained and contrasted with conventional perturbation theory and Weyl consistency conditions. We then determine the conformal window with asymptotic safety from the complete next-to-next-to-leading order in perturbation theory. Limits for the conformal window arise due to fixed point mergers, the onset of strong coupling, or vacuum instability. A consistent picture is uncovered by comparing various levels of approximation. The theory remains perturbative in the entire conformal window, with vacuum stability dictating the tightest constraints. We also speculate about a secondary conformal window at strong coupling and estimate its lower limit. Implications for model building and cosmology are indicated.

Characterizing highly dynamic conformational states: The transcription bubble in RNAP-promoter open complex as an example

NASA Astrophysics Data System (ADS)

Lerner, Eitan; Ingargiola, Antonino; Weiss, Shimon

2018-03-01

Bio-macromolecules carry out complicated functions through structural changes. To understand their mechanism of action, the structure of each step has to be characterized. While classical structural biology techniques allow the characterization of a few "structural snapshots" along the enzymatic cycle (usually of stable conformations), they do not cover all (and often fast interconverting) structures in the ensemble, where each may play an important functional role. Recently, several groups have demonstrated that structures of different conformations in solution could be solved by measuring multiple distances between different pairs of residues using single-molecule Förster resonance energy transfer (smFRET) and using them as constrains for hybrid/integrative structural modeling. However, this approach is limited in cases where the conformational dynamics is faster than the technique's temporal resolution. In this study, we combine existing tools that elucidate sub-millisecond conformational dynamics together with hybrid/integrative structural modeling to study the conformational states of the transcription bubble in the bacterial RNA polymerase-promoter open complex (RPo). We measured microsecond alternating laser excitation-smFRET of differently labeled lacCONS promoter dsDNA constructs. We used a combination of burst variance analysis, photon-by-photon hidden Markov modeling, and the FRET-restrained positioning and screening approach to identify two conformational states for RPo. The experimentally derived distances of one conformational state match the known crystal structure of bacterial RPo. The experimentally derived distances of the other conformational state have characteristics of a scrunched RPo. These findings support the hypothesis that sub-millisecond dynamics in the transcription bubble are responsible for transcription start site selection.

Direct observation of fast protein conformational switching.

PubMed

Ishikawa, Haruto; Kwak, Kyungwon; Chung, Jean K; Kim, Seongheun; Fayer, Michael D

2008-06-24

Folded proteins can exist in multiple conformational substates. Each substate reflects a local minimum on the free-energy landscape with a distinct structure. By using ultrafast 2D-IR vibrational echo chemical-exchange spectroscopy, conformational switching between two well defined substates of a myoglobin mutant is observed on the approximately 50-ps time scale. The conformational dynamics are directly measured through the growth of cross peaks in the 2D-IR spectra of CO bound to the heme active site. The conformational switching involves motion of the distal histidine/E helix that changes the location of the imidazole side group of the histidine. The exchange between substates changes the frequency of the CO, which is detected by the time dependence of the 2D-IR vibrational echo spectrum. These results demonstrate that interconversion between protein conformational substates can occur on very fast time scales. The implications for larger structural changes that occur on much longer time scales are discussed.

Performance of Conformable Ablators in Aerothermal Environments

NASA Technical Reports Server (NTRS)

Thornton, J.; Fan, W.; Skokova, K.; Stackpoole, M.; Beck, R.; Chavez-Garcia, J.

2012-01-01

Conformable Phenolic Impregnated Carbon Ablator, a cousin of Phenolic Impregnated Carbon Ablator (PICA), was developed at NASA Ames Research Center as a lightweight thermal protection system under the Fundamental Aeronautics Program. PICA is made using a brittle carbon substrate, which has a very low strain to failure. Conformable PICA is made using a flexible carbon substrate, a felt in this case. The flexible felt significantly increases the strain to failure of the ablator. PICA is limited by its thermal mechanical properties. Future NASA missions will require heatshields that are more fracture resistant than PICA and, as a result, NASA Ames is working to improve PICAs performance by developing conformable PICA to meet these needs. Research efforts include tailoring the chemistry of conformable PICA with varying amounts of additives to enhance mechanical properties and testing them in aerothermal environments. This poster shows the performance of conformable PICA variants in arc jets tests. Some mechanical and thermal properties will also be presented.

Perspectives on electrostatics and conformational motions in enzyme catalysis.

PubMed

Hanoian, Philip; Liu, C Tony; Hammes-Schiffer, Sharon; Benkovic, Stephen

2015-02-17

. Complementary molecular dynamics simulations in conjunction with mixed quantum mechanical/molecular mechanical calculations accurately reproduced the vibrational frequency shifts in these probes and provided atomic-level insight into the residues influencing these changes. Our findings indicate that conformational and electrostatic changes are intimately related and functionally essential. This approach can be readily extended to the study of other enzyme systems to identify more general trends in the relationship between conformational fluctuations and electrostatic interactions. These results are relevant to researchers seeking to design novel enzymes as well as those seeking to develop therapeutic agents that function as enzyme inhibitors.

Perspectives on Electrostatics and Conformational Motions in Enzyme Catalysis

PubMed Central

2016-01-01

. Complementary molecular dynamics simulations in conjunction with mixed quantum mechanical/molecular mechanical calculations accurately reproduced the vibrational frequency shifts in these probes and provided atomic-level insight into the residues influencing these changes. Our findings indicate that conformational and electrostatic changes are intimately related and functionally essential. This approach can be readily extended to the study of other enzyme systems to identify more general trends in the relationship between conformational fluctuations and electrostatic interactions. These results are relevant to researchers seeking to design novel enzymes as well as those seeking to develop therapeutic agents that function as enzyme inhibitors. PMID:25565178

Incompleteness of Bluetooth protocol conformance test cases

NASA Astrophysics Data System (ADS)

Wu, Peng; Gao, Qiang

2001-10-01

This paper describes a formal method to verify the completeness of conformance testing, in which not only Implementation Under Test (IUT) is formalized in SDL, but also conformance tester is described in SDL so that conformance testing can be performed in simulator provided with CASE tool. The protocol set considered is Bluetooth, an open wireless communication technology. Our research results show that Bluetooth conformance test specification is not complete in that it has only limited coverage and many important capabilities defined in Bluetooth core specification are not tested. We also give a detail report on the missing test cases against Bluetooth core specification, and provide a guide on further test case generation in the future.

Mapping conformational dynamics of proteins using torsional dynamics simulations.

PubMed

Gangupomu, Vamshi K; Wagner, Jeffrey R; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-05-07

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein's experimentally established conformational substates. Conformational transition of calmodulin from the Ca(2+)-bound to the Ca(2+)-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in

Lessons in ambivalence: The Shanghai Municipal Council's opium policies, 1906-1917.

PubMed

Zhang, Yong-An; Du, Yilun

2016-11-01

Shanghai was considered to be a "capital of opium" in modern China, hence the history of opium in the city has received significant attention. In the Shanghai International Settlement, where Chinese and foreigners lived as neighbours, drugs were considered by the administration as both "trouble maker", and important financial resource. This paper explores how the Shanghai Municipal Council (SMC), the most senior governing body in the settlement, used its position to maximize political and economic profit from the trade and consumption of opium. The paper is based on documentary analysis of records of the SMC board meetings and other related material stored at Shanghai Municipal Archives. Interpretive approaches were used to analyze the shifting SMC strategies on opium consumption, the competing power relations and the way they were negotiated between actors with a stake in the region, including semi-colonialism and world systems analysis. With the dual purpose of preventing damage and enhancing municipal management, the SMC introduced a licensing system permitting the consumption and trade of drugs. However, the anti-opium policies of the late Qing government and the Anglo-Chinese 10 Year Agreement meant SMC had to shut down opium "houses" (opium dens) and "shops" (for the sale of opium to be consumed off the premises). Over almost a decade, the SMC shifted emphasis from political regulation of a social, recreational practice to maximizing financial benefit. In the process, SMC made full use of the opportunities it gained from a period of ambivalent Chinese and British power relations and local community rule. Copyright © 2016 Elsevier B.V. All rights reserved.

Intrinsic Conformational Preferences of Cα,α-Dibenzylglycine

PubMed Central

Casanovas, Jordi; Nussinov, Ruth; Alemán, Carlos

2009-01-01

The intrinsic conformational preferences of Cα,α-dibenzylglycine, a symmetric α,α-dialkylated amino acid bearing two benzyl substituents on the α-carbon atom, have been determined using quantum chemical calculations at the B3LYP/6-31+G(d,p) level. A total of 46 minimum energy conformations were found for the N-acetyl-N'-methylamide derivative, even though only 9 of them showed a relative energy lower than 5.0 kcal/mol. The latter involves C7, C5 and α' backbone conformations stabilized by intramolecular hydrogen bonds and/or N-H…π interactions. Calculation of the conformational free energies in different environments (gas-phase, carbon tetrachloride, chloroform, methanol and water solutions) indicates that four different minima (two C5 and two C7) are energetically accessible at room temperature in the gas-phase, while in methanol and aqueous solutions one such minimum (C5) becomes the only significant conformation. Comparison with results recently reported for Cα,α-diphenylglycine indicates that substitution of phenyl side groups by benzyl enhances the conformational flexibility leading to (i) a reduction of the strain of the peptide backbone; and (ii) alleviating the repulsive interactions between the π electron density of the phenyl groups and the lone pairs of the carbonyl oxygen atoms. PMID:18465898

Conformations of organophosphine oxides

DOE PAGES

De Silva, Nuwan; Zahariev, Federico; Hay, Benjamin P.; ...

2015-07-17

The conformations of a series of organophosphine oxides, OP(CH 3) 2R, where R = methyl, ethyl, isopropyl, tert-butyl, vinyl, and phenyl, are predicted using the MP2/cc-pVTZ level of theory. Comparison of potential energy surfaces for rotation about P–C bonds with crystal structure data reveals a strong correlation between predicted location and energetics of minima and histograms of dihedral angle distributions observed in the solid state. In addition, the most stable conformers are those that minimize the extent of steric repulsion between adjacent rotor substituents, and the torsional barriers tend to increase with the steric bulk of the rotating alkyl group.more » MM3 force field parameters were adjusted to fit the MP2 results, providing a fast and accurate model for predicting organophosphine oxides shapes—an essential part of understanding the chemistry of these compounds. As a result, the predictive power of the modified MM3 model was tested against MP2/cc-pVTZ conformations for triethylphosphine oxide, OP(CH 2CH 3) 3, and triphenylphosphine oxide, OP(Ph) 3.« less

Self-limiting atomic layer deposition of conformal nanostructured silver films

NASA Astrophysics Data System (ADS)

Golrokhi, Zahra; Chalker, Sophia; Sutcliffe, Christopher J.; Potter, Richard J.

2016-02-01

The controlled deposition of ultra-thin conformal silver nanoparticle films is of interest for applications including anti-microbial surfaces, plasmonics, catalysts and sensors. While numerous techniques can produce silver nanoparticles, few are able to produce highly conformal coatings on high aspect ratio surfaces, together with sub-nanometre control and scalability. Here we develop a self-limiting atomic layer deposition (ALD) process for the deposition of conformal metallic silver nanoparticle films. The films have been deposited using direct liquid injection ALD with ((hexafluoroacetylacetonato)silver(I)(1,5-cyclooctadiene)) and propan-1-ol. An ALD temperature window between 123 and 128 °C is identified and within this range self-limiting growth is confirmed with a mass deposition rate of ∼17.5 ng/cm2/cycle. The effects of temperature, precursor dose, co-reactant dose and cycle number on the deposition rate and on the properties of the films have been systematically investigated. Under self-limiting conditions, films are metallic silver with a nano-textured surface topography and nanoparticle size is dependent on the number of ALD cycles. The ALD reaction mechanisms have been elucidated using in-situ quartz crystal microbalance (QCM) measurements, showing chemisorption of the silver precursor, followed by heterogeneous catalytic dehydrogenation of the alcohol to form metallic silver and an aldehyde.

Rotational Spectrum of the Methyl Salicylate-Water Complex: the Missing Conformer and the Tunneling Motions

NASA Astrophysics Data System (ADS)

Ghosh, Supriya; Thomas, Javix; Xu, Yunjie; Jäger, Wolfgang

2015-06-01

Methyl salicylate is a naturally occurring organic ester produced by wintergreen and other plants. It is also found in many over-the-counter remedies, such as muscle ache creams. The rotational spectrum of the methyl salicylate monomer was reported previously, where the most stable, dominant conformer was identified. The methyl salicylate-water complex was first studied using fluorescence-detected infrared spectroscopy; only one monohydrate conformer was found in that work. In the present study, we employed both broadband chirped and cavity based Fourier transform microwave spectroscopy to examine the competition between intra- and intermolecular hydrogen-bonding interactions and possible large amplitude motions associated with the methyl group and the water subunit. In contrast to the previous infrared study, two monohydrate conformers were identified, with carbonyl O or hydroxyl O as the hydrogen bond acceptors. Detailed analyses of the observed hyperfine structures will be presented, as well as our efforts to extend the study to larger methyl salicylate hydration clusters. S. Melandri, B. M. Giuliano, A. Maris, L. B. Favero, P. Ottaviani, B. Velino, W. Caminati, J. Phys. Chem. A. 2007, 111, 9076. A. Mitsuzuka, A. Fujii, T. Ebata, N. Mikami, J. Phys. Chem. A 1998, 102, 9779.

Mapping the conformational free energy of aspartic acid in the gas phase and in aqueous solution.

PubMed

Comitani, Federico; Rossi, Kevin; Ceriotti, Michele; Sanz, M Eugenia; Molteni, Carla

2017-04-14

The conformational free energy landscape of aspartic acid, a proteogenic amino acid involved in a wide variety of biological functions, was investigated as an example of the complexity that multiple rotatable bonds produce even in relatively simple molecules. To efficiently explore such a landscape, this molecule was studied in the neutral and zwitterionic forms, in the gas phase and in water solution, by means of molecular dynamics and the enhanced sampling method metadynamics with classical force-fields. Multi-dimensional free energy landscapes were reduced to bi-dimensional maps through the non-linear dimensionality reduction algorithm sketch-map to identify the energetically stable conformers and their interconnection paths. Quantum chemical calculations were then performed on the minimum free energy structures. Our procedure returned the low energy conformations observed experimentally in the gas phase with rotational spectroscopy [M. E. Sanz et al., Phys. Chem. Chem. Phys. 12, 3573 (2010)]. Moreover, it provided information on higher energy conformers not accessible to experiments and on the conformers in water. The comparison between different force-fields and quantum chemical data highlighted the importance of the underlying potential energy surface to accurately capture energy rankings. The combination of force-field based metadynamics, sketch-map analysis, and quantum chemical calculations was able to produce an exhaustive conformational exploration in a range of significant free energies that complements the experimental data. Similar protocols can be applied to larger peptides with complex conformational landscapes and would greatly benefit from the next generation of accurate force-fields.

Mapping the conformational free energy of aspartic acid in the gas phase and in aqueous solution

NASA Astrophysics Data System (ADS)

Comitani, Federico; Rossi, Kevin; Ceriotti, Michele; Sanz, M. Eugenia; Molteni, Carla

2017-04-01

The conformational free energy landscape of aspartic acid, a proteogenic amino acid involved in a wide variety of biological functions, was investigated as an example of the complexity that multiple rotatable bonds produce even in relatively simple molecules. To efficiently explore such a landscape, this molecule was studied in the neutral and zwitterionic forms, in the gas phase and in water solution, by means of molecular dynamics and the enhanced sampling method metadynamics with classical force-fields. Multi-dimensional free energy landscapes were reduced to bi-dimensional maps through the non-linear dimensionality reduction algorithm sketch-map to identify the energetically stable conformers and their interconnection paths. Quantum chemical calculations were then performed on the minimum free energy structures. Our procedure returned the low energy conformations observed experimentally in the gas phase with rotational spectroscopy [M. E. Sanz et al., Phys. Chem. Chem. Phys. 12, 3573 (2010)]. Moreover, it provided information on higher energy conformers not accessible to experiments and on the conformers in water. The comparison between different force-fields and quantum chemical data highlighted the importance of the underlying potential energy surface to accurately capture energy rankings. The combination of force-field based metadynamics, sketch-map analysis, and quantum chemical calculations was able to produce an exhaustive conformational exploration in a range of significant free energies that complements the experimental data. Similar protocols can be applied to larger peptides with complex conformational landscapes and would greatly benefit from the next generation of accurate force-fields.

Picosecond to nanosecond dynamics provide a source of conformational entropy for protein folding.

PubMed

Stadler, Andreas M; Demmel, Franz; Ollivier, Jacques; Seydel, Tilo

2016-08-03

Myoglobin can be trapped in fully folded structures, partially folded molten globules, and unfolded states under stable equilibrium conditions. Here, we report an experimental study on the conformational dynamics of different folded conformational states of apo- and holomyoglobin in solution. Global protein diffusion and internal molecular motions were probed by neutron time-of-flight and neutron backscattering spectroscopy on the picosecond and nanosecond time scales. Global protein diffusion was found to depend on the α-helical content of the protein suggesting that charges on the macromolecule increase the short-time diffusion of protein. With regard to the molten globules, a gel-like phase due to protein entanglement and interactions with neighbouring macromolecules was visible due to a reduction of the global diffusion coefficients on the nanosecond time scale. Diffusion coefficients, residence and relaxation times of internal protein dynamics and root mean square displacements of localised internal motions were determined for the investigated structural states. The difference in conformational entropy ΔSconf of the protein between the unfolded and the partially or fully folded conformations was extracted from the measured root mean square displacements. Using thermodynamic parameters from the literature and the experimentally determined ΔSconf values we could identify the entropic contribution of the hydration shell ΔShydr of the different folded states. Our results point out the relevance of conformational entropy of the protein and the hydration shell for stability and folding of myoglobin.

Conformable apparatus in a drill string

DOEpatents

Hall, David R [Provo, UT; Hall, Jr., H. Tracy; Pixton, David S [Lehi, UT; Fox, Joe [Spanish Fork, UT

2007-08-28

An apparatus in a drill string comprises an internally upset drill pipe. The drill pipe comprises a first end, a second end, and an elongate tube intermediate the first and second ends. The elongate tube and the ends comprising a continuous an inside surface with a plurality of diameters. A conformable metal tube is disposed within the drill pipe intermediate the ends thereof and terminating adjacent to the ends of the drill pipe. The conformable metal tube substantially conforms to the continuous inside surface of the metal tube. The metal tube may comprise a non-uniform section which is expanded to conform to the inside surface of the drill pipe. The non-uniform section may comprise protrusions selected from the group consisting of convolutions, corrugations, flutes, and dimples. The non-uniform section extends generally longitudinally along the length of the tube. The metal tube may be adapted to stretch as the drill pipes stretch.

Conformal Electromagnetic Particle in Cell: A Review

DOE PAGES

Meierbachtol, Collin S.; Greenwood, Andrew D.; Verboncoeur, John P.; ...

2015-10-26

We review conformal (or body-fitted) electromagnetic particle-in-cell (EM-PIC) numerical solution schemes. Included is a chronological history of relevant particle physics algorithms often employed in these conformal simulations. We also provide brief mathematical descriptions of particle-tracking algorithms and current weighting schemes, along with a brief summary of major time-dependent electromagnetic solution methods. Several research areas are also highlighted for recommended future development of new conformal EM-PIC methods.

Conformational sampling with stochastic proximity embedding and self-organizing superimposition: establishing reasonable parameters for their practical use.

PubMed

Tresadern, Gary; Agrafiotis, Dimitris K

2009-12-01

Stochastic proximity embedding (SPE) and self-organizing superimposition (SOS) are two recently introduced methods for conformational sampling that have shown great promise in several application domains. Our previous validation studies aimed at exploring the limits of these methods and have involved rather exhaustive conformational searches producing a large number of conformations. However, from a practical point of view, such searches have become the exception rather than the norm. The increasing popularity of virtual screening has created a need for 3D conformational search methods that produce meaningful answers in a relatively short period of time and work effectively on a large scale. In this work, we examine the performance of these algorithms and the effects of different parameter settings at varying levels of sampling. Our goal is to identify search protocols that can produce a diverse set of chemically sensible conformations and have a reasonable probability of sampling biologically active space within a small number of trials. Our results suggest that both SPE and SOS are extremely competitive in this regard and produce very satisfactory results with as few as 500 conformations per molecule. The results improve even further when the raw conformations are minimized with a molecular mechanics force field to remove minor imperfections and any residual strain. These findings provide additional evidence that these methods are suitable for many everyday modeling tasks, both high- and low-throughput.

Dissecting the dynamic conformations of the metamorphic protein lymphotactin.

PubMed

Harvey, Sophie R; Porrini, Massimiliano; Konijnenberg, Albert; Clarke, David J; Tyler, Robert C; Langridge-Smith, Patrick R R; MacPhee, Cait E; Volkman, Brian F; Barran, Perdita E

2014-10-30

A mass spectrometer provides an ideal laboratory to probe the structure and stability of isolated protein ions. Interrogation of each discrete mass/charge-separated species enables the determination of the intrinsic stability of a protein fold, gaining snapshots of unfolding pathways. In solution, the metamorphic protein lymphotactin (Ltn) exists in equilibrium between two distinct conformations, a monomeric (Ltn10) and a dimeric (Ltn40) fold. Here, we use electron capture dissociation (ECD) and drift tube ion mobility-mass spectrometry (DT IM-MS) to analyze both forms and use molecular dynamics (MD) to consider how the solution fold alters in a solvent-free environment. DT IM-MS reveals significant conformational flexibility for the monomer, while the dimer appears more conformationally restricted. These findings are supported by MD calculations, which reveal how salt bridges stabilize the conformers in vacuo. Following ECD experiments, a distinctive fragmentation pattern is obtained for both the monomer and dimer. Monomer fragmentation becomes more pronounced with increasing charge state especially in the disordered regions and C-terminal α-helix in the solution fold. Lower levels of fragmentation are seen in the β-sheet regions and in regions that contain salt bridges, identified by MD simulations. The lowest charge state of the dimer for which we obtain ECD data ([D+9H](9+)) exhibits extensive fragmentation with no relationship to the solution fold and has a smaller collision cross section (CCS) than charge states 10-13+, suggesting a "collapsed" encounter complex. Other charge states of the dimer, as for the monomer, are resistant to fragmentation in regions of β-sheets in the solution fold. This study provides evidence for preservation and loss of global fold and secondary structural elements, providing a tantalizing glimpse into the power of the emerging field of native top-down mass spectrometry.

A Mediated Moderation Model of Conformative Peer Bullying

ERIC Educational Resources Information Center

Cho, Yoonju; Chung, Ock-Boon

2012-01-01

We investigated the relationship between conformative peer bullying and issues of peer conformity among adolescents. This relationship is examined through the establishment of a mediated moderation model for conformative peer bullying using structural equation modeling in a sample of 391 second-year middle school students in Seoul, South Korea. We…

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis.

PubMed

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F; Cohen, Itay; Henin, Rachel D; Hockla, Alexandra; Soares, Alexei S; Papo, Niv; Caulfield, Thomas R; Radisky, Evette S

2016-12-16

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4-Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals a dramatic conformational change in the substrate upon proteolysis. By using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning 3 orders of magnitude, we identify global and local dynamic features of substrates on the nanosecond-microsecond time scale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substrate-like and product-like states, linking substrate dynamics on the nanosecond-microsecond time scale with large collective substrate motions on the much slower time scale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

40 CFR 93.154 - Conformity analysis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... department, agency, or instrumentality of the Federal government taking an action subject to this subpart... conformity determination. Effective Date Note: At 75 FR 17275, Apr. 5, 2010, § 93.154 was revised, effective... government taking an action subject to this subpart must make its own conformity determination consistent...

The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains

DOE PAGES

Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida

2017-10-18

Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domainmore » 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.« less

The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida

Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domainmore » 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.« less

48 CFR 46.504 - Certificate of conformance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... MANAGEMENT QUALITY ASSURANCE Acceptance 46.504 Certificate of conformance. A certificate of conformance (see... acceptable and any defective work would be replaced, corrected, or repaired without contest. In no case shall...

Non-local Effects of Conformal Anomaly

NASA Astrophysics Data System (ADS)

Meissner, Krzysztof A.; Nicolai, Hermann

2018-03-01

It is shown that the nonlocal anomalous effective actions corresponding to the quantum breaking of the conformal symmetry can lead to observable modifications of Einstein's equations. The fact that Einstein's general relativity is in perfect agreement with all observations including cosmological or recently observed gravitational waves imposes strong restrictions on the field content of possible extensions of Einstein's theory: all viable theories should have vanishing conformal anomalies. It is shown that a complete cancellation of conformal anomalies in D=4 for both the C^2 invariant and the Euler (Gauss-Bonnet) invariant can only be achieved for N-extended supergravity multiplets with N ≥ 5.

Invariant classification of second-order conformally flat superintegrable systems

NASA Astrophysics Data System (ADS)

Capel, J. J.; Kress, J. M.

2014-12-01

In this paper we continue the work of Kalnins et al in classifying all second-order conformally-superintegrable (Laplace-type) systems over conformally flat spaces, using tools from algebraic geometry and classical invariant theory. The results obtained show, through Stäckel equivalence, that the list of known nondegenerate superintegrable systems over three-dimensional conformally flat spaces is complete. In particular, a seven-dimensional manifold is determined such that each point corresponds to a conformal class of superintegrable systems. This manifold is foliated by the nonlinear action of the conformal group in three dimensions. Two systems lie in the same conformal class if and only if they lie in the same leaf of the foliation. This foliation is explicitly described using algebraic varieties formed from representations of the conformal group. The proof of these results rely heavily on Gröbner basis calculations using the computer algebra software packages Maple and Singular.

Multiple conformations are a conserved and regulatory feature of the RB1 5′ UTR

PubMed Central

Kutchko, Katrina M.; Sanders, Wes; Ziehr, Ben; Phillips, Gabriela; Solem, Amanda; Halvorsen, Matthew; Weeks, Kevin M.; Moorman, Nathaniel

2015-01-01

Folding to a well-defined conformation is essential for the function of structured ribonucleic acids (RNAs) like the ribosome and tRNA. Structured elements in the untranslated regions (UTRs) of specific messenger RNAs (mRNAs) are known to control expression. The importance of unstructured regions adopting multiple conformations, however, is still poorly understood. High-resolution SHAPE-directed Boltzmann suboptimal sampling of the Homo sapiens Retinoblastoma 1 (RB1) 5′ UTR yields three distinct conformations compatible with the experimental data. Private single nucleotide variants (SNVs) identified in two patients with retinoblastoma each collapse the structural ensemble to a single but distinct well-defined conformation. The RB1 5′ UTRs from Bos taurus (cow) and Trichechus manatus latirostris (manatee) are divergent in sequence from H. sapiens (human) yet maintain structural compatibility with high-probability base pairs. SHAPE chemical probing of the cow and manatee RB1 5′ UTRs reveals that they also adopt multiple conformations. Luciferase reporter assays reveal that 5′ UTR mutations alter RB1 expression. In a traditional model of disease, causative SNVs disrupt a key structural element in the RNA. For the subset of patients with heritable retinoblastoma-associated SNVs in the RB1 5′ UTR, the absence of multiple structures is likely causative of the cancer. Our data therefore suggest that selective pressure will favor multiple conformations in eukaryotic UTRs to regulate expression. PMID:25999316

Generalized conformal structure, dilaton gravity and SYK

NASA Astrophysics Data System (ADS)

Taylor, Marika

2018-01-01

A theory admits generalized conformal structure if the only scale in the quantum theory is set by a dimensionful coupling. SYK is an example of a theory with generalized conformal structure and in this paper we investigate the consequences of this structure for correlation functions and for the holographic realization of SYK. The Ward identities associated with the generalized conformal structure of SYK are implemented holographically in gravity/multiple scalar theories, which always have a parent AdS3 origin. For questions involving only the graviton/running scalar sector, one can always describe the bulk running in terms of a single scalar but multiple running scalars are in general needed once one includes the bulk fields corresponding to all SYK operators. We then explore chaos in holographic theories with generalized conformal structure. The four point function explored by Maldacena, Shenker and Stanford exhibits exactly the same chaotic behaviour in any such theory as in holographic realizations of conformal theories i.e. the dimensionful coupling scale does not affect the chaotic exponential growth.

Conformal collineations and anisotropic fluids in general relativity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duggal, K.L.; Sharma, R.

1986-10-01

Recently, Herrera et al. (L. Herrera, J. Jimenez, L. Leal, J. Ponce de Leon, M. Esculpi, and V. Galino, J. Math. Phys. 25, 3274 (1984)) studied the consequences of the existence of a one-parameter group of conformal motions for anisotropic matter. They concluded that for special conformal motions, the stiff equation of state (p = ..mu..) is singled out in a unique way, provided the generating conformal vector field is orthogonal to the four-velocity. In this paper, the same problem is studied by using conformal collineations (which include conformal motions as subgroups). It is shown that, for a special conformalmore » collineation, the stiff equation of state is not singled out. Non-Einstein Ricci-recurrent spaces are considered as physical models for the fluid matter.« less

Conformational Changes in Orotidine 5-Monophosphate Decarboxylase: "Remote" Residues That Stabilize the Active Conformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, B.; Amyes, T; Fedorov, A

2010-01-01

The structural factors responsible for the extraordinary rate enhancement ({approx}10{sup 17}) of the reaction catalyzed by orotidine 5{prime}-monophosphate decarboxylase (OMPDC) have not been defined. Catalysis requires a conformational change that closes an active site loop and 'clamps' the orotate base proximal to hydrogen-bonded networks that destabilize the substrate and stabilize the intermediate. In the OMPDC from Methanobacter thermoautotrophicus, a 'remote' structurally conserved cluster of hydrophobic residues that includes Val 182 in the active site loop is assembled in the closed, catalytically active conformation. Substitution of these residues with Ala decreases k{sub cat}/K{sub m} with a minimal effect on k{sub cat},more » providing evidence that the cluster stabilizes the closed conformation. The intrinsic binding energies of the 5{prime}-phosphate group of orotidine 5{prime}-monophosphate for the mutant enzymes are similar to that for the wild type, supporting this conclusion.« less

Probing conformational dynamics by photoinduced electron transfer

NASA Astrophysics Data System (ADS)

Neuweiler, Hannes; Herten, Dirk P.; Marme, N.; Knemeyer, J. P.; Piestert, Oliver; Tinnefeld, Philip; Sauer, Marcus

2004-07-01

We demonstrate how photoinduced electron transfer (PET) reactions can be successfully applied to monitor conformational dynamics in individual biopolymers. Single-pair fluorescence resonance energy transfer (FRET) experiments are ideally suited to study conformational dynamics occurring on the nanometer scale, e.g. during protein folding or unfolding. In contrast, conformational dynamics with functional significance, for example occurring in enzymes at work, often appear on much smaller spatial scales of up to several Angströms. Our results demonstrate that selective PET-reactions between fluorophores and amino acids or DNA nucleotides represent a versatile tool to measure small-scale conformational dynamics in biopolymers on a wide range of time scales, extending from nanoseconds to seconds, at the single-molecule level under equilibrium conditions. That is, the monitoring of conformational dynamics of biopolymers with temporal resolutions comparable to those within reach using new techniques of molecular dynamic simulations. We present data about structural changes of single biomolecules like DNA hairpins and peptides by using quenching electron transfer reactions between guanosine or tryptophan residues in close proximity to fluorescent dyes. Furthermore, we demonstrate that the strong distance dependence of charge separation reactions on the sub-nanometer scale can be used to develop conformationally flexible PET-biosensors. These sensors enable the detection of specific target molecules in the sub-picomolar range and allow one to follow their molecular binding dynamics with temporal resolution.

Conformal Symmetry as a Template for QCD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brodsky, S

2004-08-04

Conformal symmetry is broken in physical QCD; nevertheless, one can use conformal symmetry as a template, systematically correcting for its nonzero {beta} function as well as higher-twist effects. For example, commensurate scale relations which relate QCD observables to each other, such as the generalized Crewther relation, have no renormalization scale or scheme ambiguity and retain a convergent perturbative structure which reflects the underlying conformal symmetry of the classical theory. The ''conformal correspondence principle'' also dictates the form of the expansion basis for hadronic distribution amplitudes. The AdS/CFT correspondence connecting superstring theory to superconformal gauge theory has important implications for hadronmore » phenomenology in the conformal limit, including an all-orders demonstration of counting rules for hard exclusive processes as well as determining essential aspects of hadronic light-front wavefunctions. Theoretical and phenomenological evidence is now accumulating that QCD couplings based on physical observables such as {tau} decay become constant at small virtuality; i.e., effective charges develop an infrared fixed point in contradiction to the usual assumption of singular growth in the infrared. The near-constant behavior of effective couplings also suggests that QCD can be approximated as a conformal theory even at relatively small momentum transfer. The importance of using an analytic effective charge such as the pinch scheme for unifying the electroweak and strong couplings and forces is also emphasized.« less

Ambivalent sexism and attitudes toward women in different stages of reproductive life: a semantic, cross-cultural approach.

PubMed

Chrisler, Joan C; Gorman, Jennifer A; Marván, Maria Luisa; Johnston-Robledo, Ingrid

2014-01-01

College students in southeastern Mexico (n = 185) and the northeastern United States (n = 96) utilized a semantic differential scale to rate subtypes of women: a menstruating woman, a menopausal woman, a pregnant woman, a premenstrual woman, a woman with a hysterectomy, a teenage girl, a woman in love, and a woman with a young baby. Americans reported significantly more negative attitudes than Mexicans did toward a menstruating woman, a premenstrual woman, a teenage girl, and a pregnant woman. Participants chose more positive words to describe a teenage girl, a woman in love, a pregnant woman, and a woman with a young baby, which is suggestive of a pronatal bias. Participants also completed the Ambivalent Sexism Inventory (ASI). Men scored significantly higher than women on hostile sexism. Mexicans scored significantly higher than Americans on both hostile and benevolent sexism. Sexism scores are related to attitudes toward premenstrual, menstruating, and menopausal women; women with a hysterectomy; and women with a young baby.

Network visualization of conformational sampling during molecular dynamics simulation.

PubMed

Ahlstrom, Logan S; Baker, Joseph Lee; Ehrlich, Kent; Campbell, Zachary T; Patel, Sunita; Vorontsov, Ivan I; Tama, Florence; Miyashita, Osamu

2013-11-01

Effective data reduction methods are necessary for uncovering the inherent conformational relationships present in large molecular dynamics (MD) trajectories. Clustering algorithms provide a means to interpret the conformational sampling of molecules during simulation by grouping trajectory snapshots into a few subgroups, or clusters, but the relationships between the individual clusters may not be readily understood. Here we show that network analysis can be used to visualize the dominant conformational states explored during simulation as well as the connectivity between them, providing a more coherent description of conformational space than traditional clustering techniques alone. We compare the results of network visualization against 11 clustering algorithms and principal component conformer plots. Several MD simulations of proteins undergoing different conformational changes demonstrate the effectiveness of networks in reaching functional conclusions. Copyright © 2013 Elsevier Inc. All rights reserved.

Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding.

PubMed

Danilov, Sergei M; Lünsdorf, Heinrich; Akinbi, Henry T; Nesterovitch, Andrew B; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V; Piegeler, Tobias; Golukhova, Elena Z; Schwartz, David E; Dull, Randal O; Minshall, Richard D; Kost, Olga A; Garcia, Joe G N

2016-10-13

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.

Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding

PubMed Central

Danilov, Sergei M.; Lünsdorf, Heinrich; Akinbi, Henry T.; Nesterovitch, Andrew B.; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V.; Piegeler, Tobias; Golukhova, Elena Z.; Schwartz, David E.; Dull, Randal O.; Minshall, Richard D.; Kost, Olga A.; Garcia, Joe G. N.

2016-01-01

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients. PMID:27734897

Gender conformity, self-objectification, and body image for sorority and nonsorority women: A closer look.

PubMed

Adams, David Francis; Behrens, Erica; Gann, Lianne; Schoen, Eva

2017-01-01

Sororities have been identified as placing young women at risk for body image concerns due to a focus on traditional gender role norms and objectification of women. This study assessed the relationship between conformity to feminine gender role norms, self-objectification, and body image surveillance among undergraduate women. In a random sample of undergraduates, the authors examined data from sorority and nonsorority women. In a random sample of undergraduate women, the authors assessed the impact of traditional feminine gender role norms on self-objectification, body image, and feedback regarding physical appearance for sorority and nonsorority undergraduate women. Three linear regressions were conducted, and only conformity to feminine gender role norms contributed significantly in each regression model. Regardless of sorority membership, conformity to feminine gender role norms was found to significantly contribute to increased body consciousness, negative body image, and feedback on physical appearance.

Conformational diversity and computational enzyme design

PubMed Central

Lassila, Jonathan K.

2010-01-01

The application of computational protein design methods to the design of enzyme active sites offers potential routes to new catalysts and new reaction specificities. Computational design methods have typically treated the protein backbone as a rigid structure for the sake of computational tractability. However, this fixed-backbone approximation introduces its own special challenges for enzyme design and it contrasts with an emerging picture of natural enzymes as dynamic ensembles with multiple conformations and motions throughout a reaction cycle. This review considers the impact of conformational variation and dynamics on computational enzyme design and it highlights new approaches to addressing protein conformational diversity in enzyme design including recent advances in multistate design, backbone flexibility, and computational library design. PMID:20829099

Dissecting the conformational determinants of chitosan and chitlac oligomers.

PubMed

Esteban, Carmen; Donati, Ivan; Pantano, Sergio; Villegas, Myriam; Benegas, Julio; Paoletti, Sergio

2018-06-01

Chitosan and its highly hydrophilic 1-deoxy-lactit-1-yl derivative (Chitlac) are polysaccharides with increasing biomedical applications. Aimed to unravel their conformational properties we have performed a series of molecular dynamics simulations of Chitosan/Chitlac decamers, exploring different degrees of substitution (DS) of lactitol side chains. At low DS, two conformational regions with different populations are visited, while for DS ≥ 20% the oligomers remain mostly linear and only one main region of the glycosidic angles is sampled. These conformers are (locally) characterized by extended helical "propensities". Helical conformations 3 2 and 2 1, by far the most abundant, only develop in the main region. The accessible conformational space is clearly enlarged at high ionic strength, evidencing also a new region accessible to the glycosidic angles, with short and frequent interchange between regions. Simulations of neutral decamers share these features, pointing to a central role of electrostatic repulsion between charged moieties. These interactions seem to determine the conformational behavior of the chitosan backbone, with no evident influence of H-bond interactions. Finally, it is also shown that increasing temperature only slightly enlarges the available conformational space, but certainly without signs of a temperature-induced conformational transition. © 2018 Wiley Periodicals, Inc.

Testing of Advanced Conformal Ablative TPS

NASA Technical Reports Server (NTRS)

Gasch, Matthew; Agrawal, Parul; Beck, Robin

2013-01-01

In support of the CA250 project, this paper details the results of a test campaign that was conducted at the Ames Arcjet Facility, wherein several novel low density thermal protection (TPS) materials were evaluated in an entry like environment. The motivation for these tests was to investigate whether novel conformal ablative TPS materials can perform under high heat flux and shear environment as a viable alternative to rigid ablators like PICA or Avcoat for missions like MSL and beyond. A conformable TPS over a rigid aeroshell has the potential to solve a number of challenges faced by traditional rigid TPS materials (such as tiled Phenolic Impregnated Carbon Ablator (PICA) system on MSL, and honeycomb-based Avcoat on the Orion Multi Purpose Crew Vehicle (MPCV)). The compliant (high strain to failure) nature of the conformable ablative materials will allow better integration of the TPS with the underlying aeroshell structure and enable monolithic-like configuration and larger segments to be used in fabrication.A novel SPRITE1 architecture, developed by the researchers at NASA Ames was used for arcjet testing. This small probe like configuration with 450 spherecone, enabled us to test the materials in a combination of high heat flux, pressure and shear environment. The heat flux near the nose were in the range of 500-1000 W/sq cm whereas in the flank section of the test article the magnitudes were about 50 of the nose, 250-500W/sq cm range. There were two candidate conformable materials under consideration for this test series. Both test materials are low density (0.28 g/cu cm) similar to Phenolic Impregnated Carbon Ablator (PICA) or Silicone Impregnated Refractory Ceramic Ablator (SIRCA) and are comprised of: A flexible carbon substrate (Carbon felt) infiltrated with an ablative resin system: phenolic (Conformal-PICA) or silicone (Conformal-SICA). The test demonstrated a successful performance of both the conformable ablators for heat flux conditions between 50

On gravitational energy in conformal teleparallel gravity

NASA Astrophysics Data System (ADS)

da Silva, J. G.; Ulhoa, S. C.

2017-07-01

The paper deals with the definition of gravitational energy in conformal teleparallel gravity. The total energy is defined by means of the field equations which allow a local conservation law. Then such an expression is analyzed for a homogeneous and isotropic Universe. This model is implemented by the Friedmann-Robertson-Walker (FRW) line element. The energy of the Universe in the absence of matter is identified with the dark energy, however it can be expanded for curved models defining such an energy as the difference between the total energy and the energy of the perfect fluid which is the matter field in the FRW model.

Black holes in six-dimensional conformal gravity

NASA Astrophysics Data System (ADS)

Lü, H.; Pang, Yi; Pope, C. N.

2013-05-01

We study conformally invariant theories of gravity in six dimensions. In four dimensions, there is a unique such theory that is polynomial in the curvature and its derivatives, namely, Weyl-squared, and furthermore all solutions of Einstein gravity are also solutions of the conformal theory. By contrast, in six dimensions there are three independent conformally invariant polynomial terms one could consider. There is a unique linear combination (up to overall scale) for which Einstein metrics are also solutions, and this specific theory forms the focus of our attention in this paper. We reduce the equations of motion for the most general spherically symmetric black hole to a single fifth-order differential equation. We obtain the general solution in the form of an infinite series, characterized by five independent parameters, and we show how a finite three-parameter truncation reduces to the already known Schwarzschild-AdS metric and its conformal scaling. We derive general results for the thermodynamics and the first law for the full five-parameter solutions. We also investigate solutions in extended theories coupled to conformally invariant matter, and in addition we derive some general results for conserved charges in cubic-curvature theories in arbitrary dimensions.

Conformational phases of membrane bound cytoskeletal filaments

NASA Astrophysics Data System (ADS)

Quint, David A.; Grason, Gregory; Gopinathan, Ajay

2013-03-01

Membrane bound cytoskeletal filaments found in living cells are employed to carry out many types of activities including cellular division, rigidity and transport. When these biopolymers are bound to a membrane surface they may take on highly non-trivial conformations as compared to when they are not bound. This leads to the natural question; What are the important interactions which drive these polymers to particular conformations when they are bound to a surface? Assuming that there are binding domains along the polymer which follow a periodic helical structure set by the natural monomeric handedness, these bound conformations must arise from the interplay of the intrinsic monomeric helicity and membrane binding. To probe this question, we study a continuous model of an elastic filament with intrinsic helicity and map out the conformational phases of this filament for various mechanical and structural parameters in our model, such as elastic stiffness and intrinsic twist of the filament. Our model allows us to gain insight into the possible mechanisms which drive real biopolymers such as actin and tubulin in eukaryotes and their prokaryotic cousins MreB and FtsZ to take on their functional conformations within living cells.

Conformational profile of a proline-arginine hybrid

PubMed Central

Revilla-López, Guillermo; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos; Zanuy, David

2010-01-01

The intrinsic conformational preferences of a new non-proteinogenic amino acid have been explored by computational methods. This tailored molecule, named (βPro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the Cβ position of the five-membered pyrrolidine ring, either in a cis or a trans orientation with respect to the carboxylic acid. The conformational profile of the N-acetyl-N'-methylamide derivatives of the cis and trans isomers of (βPro)Arg has been examined in the gas phase and in solution by B3LYP/6–31+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen-bonds. Thus, both cis and trans (βPro)Arg exhibit a preference for the αL conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups. PMID:20886854

Conformational profile of a proline-arginine hybrid.

PubMed

Revilla-López, Guillermo; Jiménez, Ana I; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos; Zanuy, David

2010-10-25

The intrinsic conformational preferences of a new nonproteinogenic amino acid have been explored by computational methods. This tailored molecule, named ((β)Pro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the C(β) position of the five-membered pyrrolidine ring, in either a cis or a trans orientation with respect to the carboxylic acid. The conformational profiles of the N-acetyl-N'-methylamide derivatives of the cis and trans isomers of ((β)Pro)Arg have been examined in the gas phase and in solution by B3LYP/6-31+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen bonds. Thus, both cis- and trans-((β)Pro)Arg exhibit a preference for the α(L) conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups.

Structural alphabets derived from attractors in conformational space

PubMed Central

2010-01-01

Background The hierarchical and partially redundant nature of protein structures justifies the definition of frequently occurring conformations of short fragments as 'states'. Collections of selected representatives for these states define Structural Alphabets, describing the most typical local conformations within protein structures. These alphabets form a bridge between the string-oriented methods of sequence analysis and the coordinate-oriented methods of protein structure analysis. Results A Structural Alphabet has been derived by clustering all four-residue fragments of a high-resolution subset of the protein data bank and extracting the high-density states as representative conformational states. Each fragment is uniquely defined by a set of three independent angles corresponding to its degrees of freedom, capturing in simple and intuitive terms the properties of the conformational space. The fragments of the Structural Alphabet are equivalent to the conformational attractors and therefore yield a most informative encoding of proteins. Proteins can be reconstructed within the experimental uncertainty in structure determination and ensembles of structures can be encoded with accuracy and robustness. Conclusions The density-based Structural Alphabet provides a novel tool to describe local conformations and it is specifically suitable for application in studies of protein dynamics. PMID:20170534

Conformational analysis of oligosaccharides and polysaccharides using molecular dynamics simulations.

PubMed

Frank, Martin

2015-01-01

Complex carbohydrates usually have a large number of rotatable bonds and consequently a large number of theoretically possible conformations can be generated (combinatorial explosion). The application of systematic search methods for conformational analysis of carbohydrates is therefore limited to disaccharides and trisaccharides in a routine analysis. An alternative approach is to use Monte-Carlo methods or (high-temperature) molecular dynamics (MD) simulations to explore the conformational space of complex carbohydrates. This chapter describes how to use MD simulation data to perform a conformational analysis (conformational maps, hydrogen bonds) of oligosaccharides and how to build realistic 3D structures of large polysaccharides using Conformational Analysis Tools (CAT).

Influence of solvents on the conformation of benzoin

NASA Astrophysics Data System (ADS)

Pawełka, Z.; Czarnik-Matusewicz, B.; Zeegers-Huyskens, Th.

2010-01-01

The conformation of benzoin in several organic solvents is investigated by infrared spectrometry and dipolometry. The frequencies, intensities, and band shapes of the ν(OH), ν(C dbnd O), and aromatic ring vibrations indicate that in solvents of low proton acceptor ability, the cis conformer with intramolecular OH···O hydrogen bonding is preserved. In solvents of large proton acceptor ability there is equilibrium between the cis and trans conformers. The dipole moments are less sensitive to conformational changes, but indicate the same trends. The results are discussed as a function of the specific solvation of the O atoms or OH groups of benzoin.

Influence of solvents on the conformation of benzoin.

PubMed

Pawełka, Z; Czarnik-Matusewicz, B; Zeegers-Huyskens, Th

2010-01-01

The conformation of benzoin in several organic solvents is investigated by infrared spectrometry and dipolometry. The frequencies, intensities, and band shapes of the nu(OH), nu(C=O), and aromatic ring vibrations indicate that in solvents of low proton acceptor ability, the cis conformer with intramolecular OH...O hydrogen bonding is preserved. In solvents of large proton acceptor ability there is equilibrium between the cis and trans conformers. The dipole moments are less sensitive to conformational changes, but indicate the same trends. The results are discussed as a function of the specific solvation of the O atoms or OH groups of benzoin. Copyright 2009 Elsevier B.V. All rights reserved.

Thermally induced conformational changes in polyethylene studied by two-dimensional near-infrared infrared hetero-spectral correlation spectroscopy

NASA Astrophysics Data System (ADS)

Watanabe, Shin; Noda, Isao; Ozaki, Yukihiro

2008-07-01

The amount of nonplanar gauche bonds was monitored as a function of increasing temperature in three different polyethylene (PE) samples by means of mid-infrared (MIR) and near-infrared (NIR) spectroscopy. The hetero-spectral two-dimensional (2D) correlation analysis was carried out between the NIR spectral region of 4365-4235 cm -1 and the well-established MIR spectral region of 1375-1265 cm -1, where bands due to nonplanar conformer are detected. This approach allowed us to identify the NIR band at 4265 cm -1, which behaves in a way similar to MIR bands originating from conformational-defect sequences. By combining the result of our current study and that of our previous report obtained on different types of PE, it is suggested that the NIR band originates from conformational-defect sequences in PE. This finding opens up a unique and useful way to study the state of conformational disorder in PE crystal by NIR spectroscopy, monitoring the intensity of the NIR band at 4265 cm -1. The use of NIR spectroscopy allows researchers to directly probe the degree in the formation of conformational-defect sequences in thick, real-world PE samples that cannot be studied by conventional MIR spectroscopy. The 2D correlation spectroscopy analysis among the MIR CH 2 wagging conformational-defect-mode bands on linear low-density PE (LLDPE) and low-density PE (LDPE) revealed the formation of nonplanar conformer represented by the band at 1368 cm -1 proceeds prior to those by other band at 1308 cm -1. This result agrees well with our previous finding on high-density PE (HDPE). We therefore propose with strong confidence that the bands at 1368 and 1308 cm -1 arise from different conformational-defect sequences, even though both of the bands have been proposed to arise from the same conformer of gtg' ( kink) + gtg sequence.

Anomalous conformer dependent S 1 lifetime of L-phenylalanine

NASA Astrophysics Data System (ADS)

Hashimoto, Takayo; Takasu, Yuichi; Yamada, Yuji; Ebata, Takayuki

2006-04-01

The fluorescence lifetimes were measured for six conformers of L-phenylalanine cooled in a supersonic jet. It was found that the S 1 state lifetimes differ by a factor of three among the conformers. Especially, the most stable conformer (intramolecular hydrogen-bonded form) in S 0 had the shortest lifetime. Time-dependent DFT calculation suggested an importance of the mixing of the nπ ∗ character to S 1(ππ ∗) in this conformer dependent dynamics.

Conformational Transitions upon Ligand Binding: Holo-Structure Prediction from Apo Conformations

PubMed Central

Seeliger, Daniel; de Groot, Bert L.

2010-01-01

Biological function of proteins is frequently associated with the formation of complexes with small-molecule ligands. Experimental structure determination of such complexes at atomic resolution, however, can be time-consuming and costly. Computational methods for structure prediction of protein/ligand complexes, particularly docking, are as yet restricted by their limited consideration of receptor flexibility, rendering them not applicable for predicting protein/ligand complexes if large conformational changes of the receptor upon ligand binding are involved. Accurate receptor models in the ligand-bound state (holo structures), however, are a prerequisite for successful structure-based drug design. Hence, if only an unbound (apo) structure is available distinct from the ligand-bound conformation, structure-based drug design is severely limited. We present a method to predict the structure of protein/ligand complexes based solely on the apo structure, the ligand and the radius of gyration of the holo structure. The method is applied to ten cases in which proteins undergo structural rearrangements of up to 7.1 Å backbone RMSD upon ligand binding. In all cases, receptor models within 1.6 Å backbone RMSD to the target were predicted and close-to-native ligand binding poses were obtained for 8 of 10 cases in the top-ranked complex models. A protocol is presented that is expected to enable structure modeling of protein/ligand complexes and structure-based drug design for cases where crystal structures of ligand-bound conformations are not available. PMID:20066034

Conformational stability as a design target to control protein aggregation.

PubMed

Costanzo, Joseph A; O'Brien, Christopher J; Tiller, Kathryn; Tamargo, Erin; Robinson, Anne Skaja; Roberts, Christopher J; Fernandez, Erik J

2014-05-01

Non-native protein aggregation is a prevalent problem occurring in many biotechnological manufacturing processes and can compromise the biological activity of the target molecule or induce an undesired immune response. Additionally, some non-native aggregation mechanisms lead to amyloid fibril formation, which can be associated with debilitating diseases. For natively folded proteins, partial or complete unfolding is often required to populate aggregation-prone conformational states, and therefore one proposed strategy to mitigate aggregation is to increase the free energy for unfolding (ΔGunf) prior to aggregation. A computational design approach was tested using human γD crystallin (γD-crys) as a model multi-domain protein. Two mutational strategies were tested for their ability to reduce/increase aggregation rates by increasing/decreasing ΔGunf: stabilizing the less stable domain and stabilizing the domain-domain interface. The computational protein design algorithm, RosettaDesign, was implemented to identify point variants. The results showed that although the predicted free energies were only weakly correlated with the experimental ΔGunf values, increased/decreased aggregation rates for γD-crys correlated reasonably well with decreases/increases in experimental ΔGunf, illustrating improved conformational stability as a possible design target to mitigate aggregation. However, the results also illustrate that conformational stability is not the sole design factor controlling aggregation rates of natively folded proteins.

Homologous ligands accommodated by discrete conformations of a buried cavity

PubMed Central

Merski, Matthew; Fischer, Marcus; Balius, Trent E.; Eidam, Oliv; Shoichet, Brian K.

2015-01-01

Conformational change in protein–ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate benzene but, even with toluene, larger cavity conformations become observable in the electron density, and over the series two other major conformations are observed. These involve discrete changes in main-chain conformation, expanding the site; few continuous changes in the site are observed. In most structures, two discrete protein conformations are observed simultaneously, and energetic considerations suggest that these conformations are low in energy relative to the ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that these three conformations dominate the previously determined structures, largely modeled in a single conformation. An investigation of the few congeneric series in the PDB suggests that discrete changes are common adaptations to a series of growing ligands. The discrete, but relatively few, conformational states observed here, and their energetic accessibility, may have implications for anticipating protein conformational change in ligand design. PMID:25847998

Homologous ligands accommodated by discrete conformations of a buried cavity.

PubMed

Merski, Matthew; Fischer, Marcus; Balius, Trent E; Eidam, Oliv; Shoichet, Brian K

2015-04-21

Conformational change in protein-ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate benzene but, even with toluene, larger cavity conformations become observable in the electron density, and over the series two other major conformations are observed. These involve discrete changes in main-chain conformation, expanding the site; few continuous changes in the site are observed. In most structures, two discrete protein conformations are observed simultaneously, and energetic considerations suggest that these conformations are low in energy relative to the ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that these three conformations dominate the previously determined structures, largely modeled in a single conformation. An investigation of the few congeneric series in the PDB suggests that discrete changes are common adaptations to a series of growing ligands. The discrete, but relatively few, conformational states observed here, and their energetic accessibility, may have implications for anticipating protein conformational change in ligand design.

Cyclo-biphenalenyl Biradicaloid Molecular Materials: Conformation, Tautomerization, Magnetism, and Thermochromism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Jingsong; Meunier, Vincent; Tian, Yong-Hui

2010-01-01

Phenalenyl and its derivatives have recently attracted a great deal of interest as a result of a two-electron multicenter (2e/mc) - bonding between two -stacked phenalenyl units. The 2e/mc bonded -dimers are close in energy to the -dimers of phenalenyl and therefore fickle properties may emerge from bond fluctuation, yielding smart -functional materials. Here, we examine the valence tautomerization of two cyclo-biphenalenyl biradicaloid molecular materials with chair and boat conformations by spin-restricted (R) and unrestricted (U) DFT using the M06 and B3LYP functionals. We found that the chair conformation involves a 2e/4c - bonded structure, whereas the boat conformation involvesmore » a 2e/12c - bonded structure on their potential energy surfaces. The global minimum for the chair conformation is the -bonded structure, whereas it is the - bonded structure for the boat conformation. The chair conformation exhibits a stepwise [3,3]-sigmatropic rearrangement, and calculations predict a negligible paramagnetic susceptibility near room temperature. In comparison, the paramagnetism of the boat conformation should be observable by SQUID and ESR. According to the energy differences of the respective - and -dimers of the two conformations and the UV-vis calculations, the color of the chair conformation is expected to become darker, whereas that of the boat conformation should become lighter with increasing temperature.« less

Conformational flexibility of DENV NS2B/NS3pro: from the inhibitor effect to the serotype influence

NASA Astrophysics Data System (ADS)

Piccirillo, Erika; Merget, Benjamin; Sotriffer, Christoph A.; do Amaral, Antonia T.

2016-03-01

The dengue virus (DENV) has four well-known serotypes, namely DENV1 to DENV4, which together cause 50-100 million infections worldwide each year. DENV NS2B/NS3pro is a protease recognized as a valid target for DENV antiviral drug discovery. However, NS2B/NS3pro conformational flexibility, involving in particular the NS2B region, is not yet completely understood and, hence, a big challenge for any virtual screening (VS) campaign. Molecular dynamics (MD) simulations were performed in this study to explore the DENV3 NS2B/NS3pro binding-site flexibility and obtain guidelines for further VS studies. MD simulations were done with and without the Bz-nKRR-H inhibitor, showing that the NS2B region stays close to the NS3pro core even in the ligand-free structure. Binding-site conformational states obtained from the simulations were clustered and further analysed using GRID/PCA, identifying four conformations of potential importance for VS studies. A virtual screening applied to a set of 31 peptide-based DENV NS2B/NS3pro inhibitors, taken from literature, illustrated that selective alternative pharmacophore models can be constructed based on conformations derived from MD simulations. For the first time, the NS2B/NS3pro binding-site flexibility was evaluated for all DENV serotypes using homology models followed by MD simulations. Interestingly, the number of NS2B/NS3pro conformational states differed depending on the serotype. Binding-site differences could be identified that may be crucial to subsequent VS studies.

Memory, metamemory, and social cues: Between conformity and resistance.

PubMed

Zawadzka, Katarzyna; Krogulska, Aleksandra; Button, Roberta; Higham, Philip A; Hanczakowski, Maciej

2016-02-01

When presented with responses of another person, people incorporate these responses into memory reports: a finding termed memory conformity. Research on memory conformity in recognition reveals that people rely on external social cues to guide their memory responses when their own ability to respond is at chance. In this way, conforming to a reliable source boosts recognition performance but conforming to a random source does not impair it. In the present study we assessed whether people would conform indiscriminately to reliable and unreliable (random) sources when they are given the opportunity to exercise metamemory control over their responding by withholding answers in a recognition test. In Experiments 1 and 2, we found the pattern of memory conformity to reliable and unreliable sources in 2 variants of a free-report recognition test, yet at the same time the provision of external cues did not affect the rate of response withholding. In Experiment 3, we provided participants with initial feedback on their recognition decisions, facilitating the discrimination between the reliable and unreliable source. This led to the reduction of memory conformity to the unreliable source, and at the same time modulated metamemory decisions concerning response withholding: participants displayed metamemory conformity to the reliable source, volunteering more responses in their memory report, and metamemory resistance to the random source, withholding more responses from the memory report. Together, the results show how metamemory decisions dissociate various types of memory conformity and that memory and metamemory decisions can be independent of each other. PsycINFO Database Record (c) 2016 APA, all rights reserved.

On the Roles of Substrate Binding and Hinge Unfolding in Conformational Changes of Adenylate Kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brokaw, Jason B.; Chu, Jhih-wei

2010-11-17

We characterized the conformational change of adenylate kinase (AK) between open and closed forms by conducting five all-atom molecular-dynamics simulations, each of 100 ns duration. Different initial structures and substrate binding configurations were used to probe the pathways of AK conformational change in explicit solvent, and no bias potential was applied. A complete closed-to-open and a partial open-to-closed transition were observed, demonstrating the direct impact of substrate-mediated interactions on shifting protein conformation. The sampled configurations suggest two possible pathways for connecting the open and closed structures of AK, affirming the prediction made based on available x-ray structures and earlier worksmore » of coarse-grained modeling. The trajectories of the all-atom molecular-dynamics simulations revealed the complexity of protein dynamics and the coupling between different domains during conformational change. Calculations of solvent density and density fluctuations surrounding AK did not show prominent variation during the transition between closed and open forms. Finally, we characterized the effects of local unfolding of an important hinge near Pro177 on the closed-to-open transition of AK and identified a novel mechanism by which hinge unfolding modulates protein conformational change. The local unfolding of Pro177 hinge induces alternative tertiary contacts that stabilize the closed structure and prevent the opening transition.« less

Thermally evaporated conformal thin films on non-traditional/non-planar substrates

NASA Astrophysics Data System (ADS)

Pulsifer, Drew Patrick

female's elytra. As rearing EAB and then deploying dead females as decoys is both arduous and inconvenient, the development of an artificial decoy would be of great interest to entomologists and foresters. A dead female EAB was used to make a negative die of nickel and a positive die of epoxy. The process of fabricating the paired dies utilized thermally evaporated conformal thin films in several critical steps. In order to conformally coat the EAB with nickel, the substrate stage holding the female EAB was periodically rocked and rotated during the deposition. This process was designed to result in a uniform thin film of ˜ 500-nm thickness with dense morphology. The nickel film was then reinforced through an electroforming process and mounted in a fixture which allowed it to be heated electrically. The corresponding positive die was replicated from the negative die through a series of successive castings. The final EAB positive die was fabricated from a hard epoxy material and attached to a fixture which allowed it to be heated while being pressed into the negative die. Decoys were then made by first depositing a quarter-wave-stack Bragg reflector on a polymer sheet and then stamping it with the pair of matched negative and positive dies to take the shape of the upper surface of an EAB female. As nearly 100 decoys were fabricated from just one EAB female, this bioreplication process is industrially scalable. Preliminary results from field trapping tests are indicative of success. For the second setting, a method of developing latent fingermarks with thermally evaporated conformal thin films was developed. Fingermarks have long been used to identify the individual who left them behind when he/she touched an object with the friction ridges of his/her hands. In many cases the fingermark which is left behind consists of sebaceous secretions which are not clearly visible under normal conditions. In order to make the fingermarks visible and identifiable, they are

Methyl group conformation and hydrogen bonds in proteins determined by neutron protein crystallography

NASA Astrophysics Data System (ADS)

Yamaguchi, Atsushi; Shibata, Kouji; Tanaka, Ichiro; Niimura, Nobuo

2009-02-01

Using 'Hydrogen and Hydration in Proteins Data Base' (HHDB) that catalogs all H atom positions in biological macromolecules and in hydration water molecules that have been determined thus far by neutron macromolecular crystallography, methyl group conformation and hydrogen bonds (H.B.) in proteins are explored. It is found that most of the methyl groups belong to the stable staggered conformation but 11% of them seemed to be close to the eclipsed conformation. And geometrical consideration has been done for H.B. involved in α-helices. 125 H.B. were identified as donors for acceptor C dbnd O in the main chain α-helix. For these H.B., it is found that co-linear H.B. were rare, that hydrogen atoms seen from acceptors C dbnd O can localize upon certain arrangements, that H.B. are not parallel to the helix axis but rather inclined to C-terminal direction, and that hydrogen atoms except water are located inside, not outside of cylinders which the backbones of α-helices form.

Conformational Analysis of Retinoic Acids: Effects of Steric Interactions on Nonplanar Conjugated Polyenes.

PubMed

Cox, Bryan D; Muccio, Donald D; Hamilton, Tracy P

2013-05-01

Retinoic acids and other vitamin A analogs contain a trimethylcyclohexenyl ring in conjugation with a polyene chain joined at carbon-6 (C6) and carbon-7 (C7). A MP2-SCS/cc-pVDZ// B3LYP/6-31G(d) 2-D potential energy surface was computed for all- trans retinoic acid, which had 6 minima (3 enantiomeric pairs). The global minima were distorted s-gauche enantiomers ( 6-7 = 53°) with half-chair conformations of the ring. Distorted s-gauche enantiomers ( 6-7 = 55°) with inverted half-chair ring conformations were 1.7 kJ/mol above the global minima. The s-trans enantiomers ( 6-7 = 164°) were 11.3 kJ/mol above the global minima. Steric energies were computed by the method of Guo and Karplus to identify key structural elements in retinoic acids which determines their conformation. Small molecule crystal structures in the CCDC database with trimethylcyclohexenyl ring and exocyclic double bonds have ring-chain geometries near to one of the 6 energy minima of retinoic acids, except for retinaldehyde iminium cations.

Fluoxetine (Prozac) Binding to Serotonin Transporter Is Modulated by Chloride and Conformational Changes

PubMed Central

Tavoulari, Sotiria; Forrest, Lucy R.; Rudnick, Gary

2010-01-01

Serotonin transporter (SERT) is the main target for widely used antidepressant agents. Several of these drugs, including imipramine, citalopram, sertraline, and fluoxetine (Prozac), bound more avidly to SERT in the presence of Cl–. In contrast, Cl– did not enhance cocaine or paroxetine binding. A Cl– binding site recently identified in SERT, and shown to be important for Cl– dependent transport, was also critical for the Cl– dependence of antidepressant affinity. Mutation of the residues contributing to this site eliminated the Cl–-mediated affinity increase for imipramine and fluoxetine. Analysis of ligand docking to a single state of SERT indicated only small differences in the energy of interaction between bound ligands and Cl–. These differences in interaction energy cannot account for the affinity differences observed for Cl– dependence. However, fluoxetine binding led to a conformational change, detected by cysteine accessibility experiments, that was qualitatively different from that induced by cocaine or other ligands. Given the known Cl– requirement for serotonin-induced conformational changes, we propose that Cl– binding facilitates conformational changes required for optimal binding of fluoxetine and other antidepressant drugs. PMID:19641126

Investigating ion channel conformational changes using voltage clamp fluorometry.

PubMed

Talwar, Sahil; Lynch, Joseph W

2015-11-01

Ion channels are membrane proteins whose functions are governed by conformational changes. The widespread distribution of ion channels, coupled with their involvement in most physiological and pathological processes and their importance as therapeutic targets, renders the elucidation of these conformational mechanisms highly compelling from a drug discovery perspective. Thanks to recent advances in structural biology techniques, we now have high-resolution static molecular structures for members of the major ion channel families. However, major questions remain to be resolved about the conformational states that ion channels adopt during activation, drug modulation and desensitization. Patch-clamp electrophysiology has long been used to define ion channel conformational states based on functional criteria. It achieves this by monitoring conformational changes at the channel gate and cannot detect conformational changes occurring in regions distant from the gate. Voltage clamp fluorometry involves labelling cysteines introduced into domains of interest with environmentally sensitive fluorophores and inferring structural rearrangements from voltage or ligand-induced fluorescence changes. Ion channel currents are monitored simultaneously to verify the conformational status. By defining real time conformational changes in domains distant from the gate, this technique provides unexpected new insights into ion channel structure and function. This review aims to summarise the methodology and highlight recent innovative applications of this powerful technique. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Conformal invariants associated to a measure.

PubMed

Chang, Sun-Yung A; Gursky, Matthew J; Yang, Paul

2006-02-21

In this note, we study some conformal invariants of a Riemannian manifold (M(n), g) equipped with a smooth measure m. In particular, we show that there is a natural definition of the Ricci and scalar curvatures associated to such a space, both of which are conformally invariant. We also adapt the methods of Fefferman and Graham [Fefferman, C. & Graham, C. R. (1985) Astérisque, Numero Hors Serie, 95-116] and Graham, Jenne, Mason, and Sparling [Graham, C. R., Jenne, R., Mason, L. J., & Sparling, G. A. J. (1992) J. London Math. Soc. 46, 557-565] to construct families of conformally covariant operators defined on these spaces. Certain variational problems in this setting are considered, including a generalization of the Einstein-Hilbert action.

Conformational Explosion: Understanding the Complexity of the Para-Dialkylbenzene Potential Energy Surfaces

NASA Astrophysics Data System (ADS)

Mishra, Piyush; Hewett, Daniel M.; Zwier, Timothy S.

2017-06-01

This talk focuses on the single-conformation spectroscopy of small-chain para-dialkylbenzenes. This work builds on previous studies from our group on long-chain n-alkylbenzenes that identified the first folded structure in octylbenzene. The dialkylbenzenes are representative of a class of molecules that are common components of coal and aviation fuel and are known to be present in vehicle exhaust. We bring the molecules para-diethylbenzene, para-dipropylbenzene and para-dibutylbenzene into the gas phase and cool the molecules in a supersonic expansion. The jet-cooled molecules are then interrogated using laser-induced fluorescence excitation, fluorescence dip IR spectroscopy (FDIRS) and dispersed fluorescence. The LIF spectra in the S_{0}-S_{1} origin region show dramatic increases in the number of resolved transitions with increasing length of alkyl chains, reflecting an explosion in the number of unique low-energy conformations formed when two independent alkyl chains are present. Since the barriers to isomerization of the alkyl chain are similar in size, this results in an 'egg carton' shape to the potential energy surface. We use a combination of electronic frequency shift and alkyl CH stretch infrared spectra to generate a consistent set of conformational assignments.

48 CFR 46.315 - Certificate of conformance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Certificate of conformance. 46.315 Section 46.315 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Clauses 46.315 Certificate of conformance. The contracting officer...

48 CFR 246.504 - Certificate of conformance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Certificate of conformance. 246.504 Section 246.504 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT QUALITY ASSURANCE Acceptance 246.504 Certificate of conformance...

The detection of conformational disorder by thermal analysis

NASA Astrophysics Data System (ADS)

Wunderlich, B.

Conformational disorder in crystals is found in many molecules that possess a plurality of conformational isomers. Typical examples are linear macromolecules such as polyethylene, polytetrafluoroethylene and trans-1,4-polybutadiene; and small molecules such as paraffins, cycloparaffins, soaps, lipids and many liquid-crystal forming molecules. Conformational motion is often coupled with the cooperative creation of disorder. In this case a heat and entropy of transition is observed by thermal analysis. Levels of transition entropies can be estimated, assuming most of the disorder can be traced to conformational isomerism. In case there is conformational disorder frozen-in at low temperature, thermal analysis can be used to find the glass transition of a condis crystal. An Advanced Thermal Analysis System has been developed, and will be described that permits a detailed interpretation of the thermal analysis traces. It rests with the establishment of high quality heat capacity for the rigid solid state (vibration only) and the mobile liquid state (vibrations and large amplitude cooperative motion).