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PubMed1990

Tertiary structural constraints on protein evolutionary diversity: templates, key residues and structure prediction.

The pattern of residue substitution in divergently evolving families of globular proteins is highly variable. At each position in a fold there are constraints on the identities of amino acids from both the three-dimensional structure and the function of the protein. To characterize and quantify the structural constraints, we have made a comparative analysis of families of homologous globular proteins. Residues are classified according to amino acid type, secondary structure, accessibility of the sidechain, and existence of hydrogen bonds from sidechain to other sidechains or peptide carbonyl or amide functions. There are distinct patterns of substitution especially where residues are both solvent inaccessible and hydrogen bonded through their sidechains. The patterns of residue substitution can be used to construct templates or to identify 'key' residues if one or more structures are known. Conversely, analysis of conversation and substitution across a large family of aligned sequences in terms of substitution profiles can allow prediction of tertiary environment or indicate a functional role. Similar analyses can be used to test the validity of putative structures if several homologous sequences are available.

Amino Acid Sequence↗

PubMedDate not supplied

Prosody as an interactional resource: turn-projection and overlap.

One aim of current research into talk-in-interaction is to identify the resources that enable recipients to monitor the course of a turn in progress in order to project its upcoming completion. This issue is addressed through analysis of instances of overlapping talk, focusing on their design--that is, their particular prosodic and other linguistic characteristics; their placement--in other words, where precisely they occur in relation to the turn being overlapped; and the subsequent behavior of the coparticipants. Phonetic analysis is combined with interactional techniques developed within Conversation Analysis, to warrant the relevance of categories by reference to the behavior of the participants themselves. As French and Local (1983) found, for an incoming to be treated as turn-competitive, it has to be designed with relatively high pitch and loud volume. These turn-competitive incomings are positioned within the turn in progress, and before the final major accent. By contrast, overlapping incomings positioned after the major accent are not designed as or treated as turn-competitive. On the basis of this analysis, we can define transition relevance place (TRP) as the space between the TRP-projecting accent of the current turn and the onset of the next turn. TRP-projecting accents are identifiable on independent grounds, being phonetically distinct from non-TRP-projecting accents. They thus provide a robust resource for participants to monitor the upcoming completion of the turn.

Adult↗

PubMed2006

The applicability of a material-treatment laser pulse in non-destructive evaluations.

A practical optodynamic study was performed to determine the usability of different lengths of laser pulses for the generation of ultrasonic transients in a solid material. The aim of the study was to evaluate the possibility of a dual use for a laser pulse-for laser material processing, on the one hand, and for the ultrasonic wave generation on the other-with both processes being combined on the same production line. The propagation of the laser-generated ultrasonic waves is evaluated by detecting and measuring with a PID-controlled stabilized interferometer. Thus, both systems provided the basic tools, the generation and detection of ultrasonic waves, for an ultrasonic, laser-based, non-destructive material evaluation. The ultrasonic transients generated by 'classical' nanosecond laser pulses were compared with the transients generated by industrial laser pulses with a duration of a few tenths of a microsecond. The experimental results are compared with the results of a time-of-flight analysis that also involved part of a mode-conversion analysis for both regimes in a layered material structure. The differences between the two waveforms were assessed in terms of their visibility, wavelength and resolution. The limit values were calculated and estimated for the laser-pulse parameters, when such pulses are intended for use in an ultrasonic, laser-based, non-destructive evaluation. The possibility of using an industrial marking laser for laser ultrasound generation is thus demonstrated.

Journal Article↗

PubMed1984

[Possibilities of standardized qualitative content analysis].

This paper aims to develop further content analysis with reference to recent models of communication (pragmalinguistics, conversational analysis, and theory of texts). The central thesis is that any content analysis of linguistic symbols must include the conditions of their realization in the spoken discourse. Accordingly, the concepts for analyzing discourse are introduced which serve as the basis for the critique of traditional content analysis in psychotherapeutic research and indicate future perspectives. The first part presents concepts for analyzing spoken language: a model of the formal organization of speech, speech act theory, and a model for analyzing macrostructures in texts. In the second part the discoveries and problems of content analysis are discussed and evaluated with reference to these concepts.

Communication↗

PubMed2005

Conversational strategies with parents of newly diagnosed leukaemic children: an analysis of 4880 conversational turns.

GOALS OF WORK: Communication with parents of children newly diagnosed with cancer poses a number of problems, mostly due to the psychological effects of parental trauma. This study was designed to answer the following questions: How can we sustain the flow of communication with parents of children newly diagnosed with leukaemia so that it may become easier and more effective? What should we say to gather more reliable information from parents? How can we help empower their coping strategies? PATIENTS AND METHODS: We analysed 4880 conversational turns in individual conversations carried out between psychologists and 21 parents of children with leukaemia. The conversations were aimed at gathering information of the families' daily routines. Dialogues were audiotaped and fully transcribed. The type and frequency of speech acts present in each turn were coded along 18 categories by two independent judges (inter-rater agreement, Cohen Kappa =0.73). MAIN RESULTS: The parental speech acts expressing emotion in various ways go up to 58% of the total number of their speech acts. The lag-sequential analysis showed that such expressions are not associated with any of the interviewer's speech act. The same analysis showed that, by contrast, the interviewer's style has an effect upon the cognitive aspects of parents' conversation. Support of hope favoured parental ability to identify their coping strategies. Explicit requests, confirmations such as "sure" and key words summarizing parents' viewpoints are followed by parental factual and objective narratives. CONCLUSIONS: Based on these results, a few practical recommendations for health care professionals are given in order to better communicate with parents of children newly diagnosed with cancer.

Adolescent↗

PubMed1998

Validation of the three-dimensional acquisition mode in positron emission tomography for the quantitation of [18F]fluoro-DOPA uptake in the human striata.

Three-dimensional (3D) positron emission tomography (PET) is attractive for [18F]fluoro-DOPA studies, since the sensitivity improvement is maximal for radioactive sources located in central planes, which is usually the case for the human striata. However, the image quantitation in that mode must be assessed because of the nearly threefold increase in scattered coincidences. We report the results of [18F]fluoro-DOPA studies performed on six normal volunteers. Each one was scanned in the 3D and two-dimensional (2D) modes on the same tomograph. The quantitation in the 3D and 2D modes was compared for a Patlak graphical analysis with the occipital counts as the input function (Ki) and a striatooccipital ratio analysis. We find that, in 3D PET, a scatter correction is required to preserve the same quantitation as in 2D PET. When the 3D data sets are corrected for scatter, the quantitation of the [18F]fluoro-DOPA uptake, using the Patlak analysis, is similar in the 2D and 3D acquisition modes. Conversely, analysis of the striatooccipital ratio leads to higher values in 3D PET because of a better in-plane resolution. Finally, using the 3D mode, the dose injected to the subjects can be reduced by a factor greater than 1.5 without any loss in accuracy compared to the 2D mode.

Adult↗

PubMed1994

Issues in the analysis of psychotic speech.

Debate on the locus of dysfunction in psychotic speech or thought disorder continues. Research in the area tends to reflect researchers' assumptions about the relationship between language and thought, and these determine the nature of the methodologies used. The circularity of argument produced in this way is inevitable, while fully contextualized comprehensive descriptions of interactions with psychotic patients are lacking. This article outlines a method of analysis which will yield basic descriptions, and produce data readily comparable to naturally occurring conversation. It includes consideration of context, conversation analysis, cohesion analysis, and tone-unit analysis. A crucial feature of the method is serious attention paid to the role of the listener in the creation of misunderstandings in conversations with psychotic speakers.

Antisocial Personality Disorder↗

PubMed2003

Real-time independent component analysis of fMRI time-series.

Real-time functional magnetic resonance imaging (fMRI) enables one to monitor a subject's brain activity during an ongoing session. The availability of online information about brain activity is essential for developing and refining interactive fMRI paradigms in research and clinical trials and for neurofeedback applications. Data analysis for real-time fMRI has traditionally been based on hypothesis-driven processing methods. Off-line data analysis, conversely, may be usefully complemented by data-driven approaches, such as independent component analysis (ICA), which can identify brain activity without a priori temporal assumptions on brain activity. However, ICA is commonly considered a time-consuming procedure and thus unsuitable to process the high flux of fMRI data while they are acquired. Here, by specific choices regarding the implementation, we exported the ICA framework and implemented it into real-time fMRI data analysis. We show that, reducing the ICA input to a few points within a time-series in a sliding-window approach, computational times become compatible with real-time settings. Our technique produced accurate dynamic readouts of brain activity as well as a precise spatiotemporal history of quasistationary patterns in the form of cumulative activation maps and time courses. Results from real and simulated motor activation data show comparable performances for the proposed ICA implementation and standard linear regression analysis applied either in a sliding-window or in a cumulative mode. Furthermore, we demonstrate the possibility of monitoring transient or unexpected neural activities and suggest that real-time ICA may provide the fMRI researcher with a better understanding and control of subjects' behaviors and performances.

Algorithms↗

PubMed1997

Static image analysis of skin specimens: the application of telepathology to frozen section evaluation.

Although the ability to transmit high-resolution images of histopathological sections could have a profound impact on the practice of pathology, the application of video microscopy to the daily activities of surgical pathology has not been rigorously evaluated. In particular, certain aspects of video microscopy relating to frozen section evaluation have not been adequately assessed. We conducted a retrospective analysis of 48 excisional skin biopsy specimens encompassing a spectrum of benign and malignant lesions. To simulate an actual frozen section evaluation, only original frozen section slides were evaluated. Fields were selected and digitized (Roche Image Analysis System) by a pathology resident. Two sets of diagnoses were subsequently rendered by a surgical pathologist, the first set based on the digitized images and the second based on direct microscopic examination of the histological slides. The two sets of diagnoses were compared, and the concordance rates were as follows: malignant diagnoses, 100%; benign diagnoses, 100%; positive margins, 96%; negative margins, 99%. One (4%) of the 25 positive margins was indexed as negative by image analysis. Conversely, one (1%) of the 121 negative margins was indexed as positive by image analysis. In both of these cases, error was attributable to selection and digitization of an inappropriate field. We conclude that telepathology of static images is an accurate method of evaluating frozen sections of skin lesions. Potentially, this technology could be applied to the frozen section evaluation of other lesions as well. Static image analysis is, however, susceptible to errors induced by inappropriate field selection, emphasizing the need for trained and skillful personnel on both sides of the video camera.

Frozen Sections↗

PubMed1997

Co-determination of the angiogenic factors thymidine phosphorylase and vascular endothelial growth factor in node-negative breast cancer: prognostic implications.

Experimental and clinical studies have shown that human breast cancer is an angiogenesis-dependent neoplasm. In fact, several authors have demonstrated that the determination in primary tumors of the degree of vascularization (microvessel counts) as well as of some angiogenic peptides is of prognostic value. However, which are the most important mediators of angiogenesis and their relationship with other relevant biological markers needs further investigation. In the series of 260 women with node-negative breast cancer (NNBC) on which we previously assessed vascular endothelial growth factor (VEGF), we have now also determined thymidine phosphorylase (TP) protein as well as p53 protein and Cathepsin-D cytosolic levels using immunometric methods. The median concentrations of TP, p53 and Cathepsin-D were 105.4U/mg (range 1.2-843.1), 0.22 ng/mg (range 0.0-41.65) and 33.80nmol/mg (range 4.20-216.0), respectively. We found that TP concentrations were associated with Cathepsin-D and p53, but not with VEGF. VEGF (p<0.0001) and p53 (p = 0.03 and p = 0.012, respectively) were found to be statistically significant prognostic variables for both relapse-free survival (RFS) and overall survival in univariate analysis. Conversely, TP and Cathepsin-D levels did not correlate with prognosis. In multivariate analysis for RFS, VEGF levels (p<0.0001), TP levels (p = 0.050) and their first-order interaction terms (p = 0.027) were statistically significant prognostic indicators. Cathepsin-D and p53 protein levels did not retain significance in the model inclusive of all the above variables. The predictive capability of the complete model was satisfactory (Harrell c statistic = 0.72). Moreover, these results suggest a possible potentiation of the capability of predicting the likelihood of recurrence by the co-determination of TP and VEGF. The probability of recurrence was particularly high in the patients with primary tumors characterized by elevated levels of both angiogenic factors. This is the first study showing in vivo that two different angiogenic peptides concur in the progression of human breast cancer. The biology and possible therapeutic implications of this observation are discussed.

Journal Article↗

PubMed2001

Supporting Partners of People with Aphasia in Relationships and Cconversation (SPPARC).

This paper reviews new theoretical and practical developments in working with partners of people with aphasia and describes the development of a clinician's resource entitled 'SPPARC: Supporting Partners of People with Aphasia in Relationships and Conversation'. It focuses particularly on one part of that resource: the SPPARC Conversation Training Programme, which adapts conversation analysis for clinical use. The paper describes the stages involved in assessing and working on conversation in everyday life.

Aphasia↗

PubMed1991

Site-directed mutagenesis of ricin A-chain and implications for the mechanism of action.

Ricin A-chain is an N-glycosidase that attacks ribosomal RNA at a highly conserved adenine residue. The enzyme is representative of a large family of medically significant proteins used in the design of anticancer agents and in the treatment of HIV infection. The x-ray structure has been used as a guide to create several active site mutations by directed mutagenesis of the cloned gene. Glu177 is a key catalytic residue, and conversion to Gln reduces activity 180-fold. Asn209 is shown to participate in substrate binding by kinetic analysis. Conversion to Ser increases Km sixfold but has no effect on kcat. Conversion of Tyr80 and Tyr123 to Phe decreases activity by 15- and 7-fold respectively. A mechanism of action is proposed that involves binding of the substrate adenine in a syn configuration that resembles the transition state; the putative oxycarbonium ion is probably stabilized by interaction with Glu177.

Base Sequence↗

PubMed2003

Expressions of power and powerlessness in discharge planning: a case study of an older woman on her way home.

The aim of this case study was to illuminate and describe the phenomenon of power as it appeared in a discharge planning conference. The patient was an older woman who needed long-term care as a result of stroke and heart failure. Data comprised transcriptions of a video-recorded discharge planning conference and two audio-recorded interviews focusing on the patient's experience of the discharge planning conference. The findings reveal that the content of the discharge planning conference focused on the patient's medical state and routine administrative protocols. Analysis of the participants' activities, strategies and attitudes during the conference indicate that the professional carers dominated the conversation. Analysis further reveals that the patient experienced a feeling of powerlessness and of being treated as an object. The findings are interpreted and discussed based on the concepts of 'institutional frame' and 'client's frame', derived from Agar's theory of institutional discourse.

Adult↗

PubMed1993

Functional analysis of petunia floral homeotic MADS box gene pMADS1.

The petunia mutant green petal (gp, line PLV) shows a homeotic effect in one floral whorl, that is, the conversion of petal to sepal. We demonstrate that this mutant contains a chromosomal deletion, including the petunia MADS box gene pMADS1. Second whorl petal development in this null mutant can be restored with a CaMV 35S-pMADS1 transgene, demonstrating the essential role of pMADS1 in this process. Because gp (PLV) shows only a minor effect on stamen development, the homeotic effects of pMADS1 are different from those of B-type genes in Antirrhinum and Arabidopsis. Two other MADS box genes, pMADS2 and fbp1 (Angenent et al. 1992), require pMADS1 to maintain expression in the second whorl. However, in the absence of pMADS1 these two genes continue to be expressed in the third whorl. The functions assigned to pMADS1 are further supported by experiments in which we phenocopy gp by cosuppression of pMADS1 gene expression. The flowers, obtained through cosuppression and phenotype restoration, display different degrees of sepal to petal conversion. Analysis of these flowers indicate that pMADS1 controls growth under the zone of petal and stamen initiation, which causes the corolla tube and stamen filaments to emerge as a congenitally fused structure.

Gene Expression↗

PubMedDate not supplied

'I suppose' as a resource for the construction of turns at talk in agrammatic aphasia.

This paper uses the methodology and analytical findings of conversation analysis to investigate the use of a particular subject-verb construction within the context of turns at talk in conversation. An investigation of the conversation of an English speaking man with agrammatism reveals recurrent use of 'I suppose' to provide structure within turns at talk. The speaker's ability to produce subject-verb constructions is known to be generally poor. Thus, it is suggested that the use of a particular construction that can be produced with relative ease may be interactionally motivated by the need to take a reasonably unproblematic turn at talk despite the constraints of an agrammatic aphasia. Preliminary thoughts on the implications of this finding for the assessment of aphasia are presented.

Adaptation, Psychological↗

PubMed2000

PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.

Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.

Animals↗

PubMed1987

[Motivation, social support and depression].

The author proposes a new approach toward a systemic analysis of the value-motivational sphere of patients with manic-depressive psychosis. The study has involved semi-standardized psychological conversation, analysis of patients' autobiographies, as well as techniques of personality investigation. Examination of 35 patients during intermission has revealed significant structural and dynamic characteristics of motivation, including hypertrophy of the modal value level, a closed nature of the motivational system, rigidity, and retardation of value formations. It has been shown that the above characteristics make patients with manic-depressive psychosis particularly sensitive toward deprivation of social support. Recommendations as to the development of psychoprophylactic measures are presented.

Bipolar Disorder↗

PubMed1999

Psychosocial explanations of complaints in Dutch general practice.

BACKGROUND: Dutch GPs are frequently consulted by patients presenting physical complaints which have a psychosocial cause. Until now, this type of complaint has often been the subject of study, but the way in which psychosocial explanations for complaints are broached and discussed has not yet been studied. OBJECTIVE: We aimed to analyse the way in which GPs and patients relate physical complaints to psychosocial causes and whether this affects the advice or treatment given in the course of the consultation. We hoped to provide insight into the actual behaviour of GPs and patients concerning these issues. METHODS: From a corpus of 279 videotaped consultations, 24 consultations of eight GPs, four female and four male in different practices, were selected for analysis. The verbal behaviour of GPs and patients in the selected consultations was transcribed in detail and subsequently analysed, according to the qualitative methodology of conversation analysis. RESULTS: Patients present explicit, as well as implicit, psychosocial explanations. GPs respond confirmatively to the first kind and almost ignore the latter. GPs present two types of psychosocial cause-seeking questions. Verifying questions suggesting a psychosocial cause lead to an explicit response from patients; conversely, exploratory queries investigating potential psychosocial causes lead always to a denial. Subsequently, GPs initiate a checklist strategy to investigate potential psychosocial causes. This strategy hardly ever leads to establishing a psychosocial explanation. GPs nearly always focus on the somatic aspects of the complaint, notwithstanding the establishment of a psychosocial explanation. They will hardly ever give any psychosocial advice in the course of that same consultation. CONCLUSION: GPs and patients are cautious in relating physical complaints with psychosocial causes. Psychosocial explanations are formulated and treated as delicate activities in the context of the consultation. GPs and patients both contribute to psychosocial explanations, but GPs contribute more to this delicate topic than their patients do.

Communication↗