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At least 1,225 records · Page 68Linked to original sources
PubMed2004

Category number impacts rule-based but not information-integration category learning: further evidence for dissociable category-learning systems.

Category number effects on rule-based and information-integration category learning were investigated. Category number affected accuracy and the distribution of best-fitting models in the rule-based task but had no effect on accuracy and little effect on the distribution of best-fining models in the information-integration task. In the 2 category conditions, rule-based learning was better than information-integration learning, whereas in the 4 category conditions, unidimensional and conjunctive rule-based learning was worse than information-integration learning. Rule-based strategies were used in the 2-category/rule-based condition, but about half of the observers used rule-based strategies in the 4-category unidimensional and conjunctive rule-based conditions. Information-integration strategies were used in the 4-category/ information-integration condition and by the end of training were used in the 2-category/information-integration condition.

Adult↗
PubMed2005

Information-integration category learning in patients with striatal dysfunction.

Information-integration category learning was examined in patients with Parkinson's disease (PD) and in healthy control participants in 2 different conditions. In the linear condition, optimal categorization required a nonverbalizable linear integration of information from the 2 stimulus dimensions, whereas in the nonlinear condition, a nonlinear integration of information was required. Each participant completed 600 trials in each condition and was given corrective feedback following each trial. Results indicated that PD patients were not impaired in the linear condition across all trials, whereas the same patients were impaired in the nonlinear condition, but only later in training. The authors conducted model-based analyses to identify participants who used an information-integration approach, and a comparison of the accuracy rates of those individuals further revealed a specific deficit in information-integration category learning in patients with PD. These findings suggest that the striatum may be particularly involved in information-integration category learning when the rule is highly complex.

Aged↗
PubMedDate not supplied

Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells.

Human T-cell leukaemia virus (HTLV), previously also reported as ATLV, is a recently identified retrovirus which is closely associated with adult T-cell leukaemia (ATL) endemic in southwestern Japan and the Caribbean. Determination of the total nucleotide sequence of the HTLV genome has revealed no typical onc gene acquired from the cellular sequence. Screening of the HTLV provirus genome in tumour cells has shown that in all cases of ATL examined, the primary tumour cells contained the provirus genome and were monoclonal with respect to the integration site of the provirus. These findings suggest that ATL leukaemogenesis may be due to insertional mutagenesis in which the provirus genome is integrated into a specific locus on the chromosomal DNA and then activates an adjacent cellular onc gene, a mechanism already demonstrated in avian lymphoma and erythroblastosis induced by avian leukosis viruses. A common site of HTLV provirus integration in leukaemic cells among some ATL patients was reported by Hahn et al. but subsequently retracted. However, this retraction does not imply the random integration of the proviruses. Independently, we have been testing this insertional mutagenesis model in ATL and report here that the provirus did not have a common locus of integration in 35 ATL patients and did not integrate on the same chromosome in 2 ATL patients.

Adult↗
PubMedDate not supplied

Hepatitis B virus DNA integration in a sequence homologous to v-erb-A and steroid receptor genes in a hepatocellular carcinoma.

Hepatitis B virus (HBV) is clearly involved in the aetiology of human hepatocellular carcinoma (HCC) and the finding of HBV DNA integration into human liver DNA in almost all HCCs studied suggested that these integrated viral sequences may be involved in liver oncogenesis. Several HBV integrations in different HCCs and HCC-derived cell lines have been analysed after molecular cloning without revealing any obvious role for HBV. From a comparison of a HBV integration site present in a particular HCC with the corresponding unoccupied site in the non-tumorous tissue of the same liver, we now report that HBV integration places the viral sequence next to a liver cell sequence which bears a striking resemblance to both an oncogene (v-erb-A) and the supposed DNA-binding domain of the human glucocorticoid receptor and human oestrogen receptor genes. We suggest that this gene, usually silent or transcribed at a very low level in normal hepatocytes, becomes inappropriately expressed as a consequence of HBV integration, thus contributing to the cell transformation.

Amino Acid Sequence↗
PubMed1990

The preS2/S region of integrated hepatitis B virus DNA encodes a transcriptional transactivator.

Hepatitis B virus (HBV) is regarded as the main aetiologic factor in the development of human hepatocellular carcinoma (HCC), one of the most frequent fatal malignancies worldwide. Detection of integrated HBV sequences in the cellular DNA of almost all HCCs studied, and the recent finding that the integrated HBV open reading frame (orf) X encodes a transactivating activity, supports the notion that integrated HBV DNA could contribute to liver carcinogenesis by activation of cellular genes in trans. But not all HCCs seem to harbour a functional orf X. We report here that 3'-truncated preS2/S sequences in integrated HBV DNA of liver cell carcinomas encode a so far unidentified transcriptional trans-activation activity. This activity is also produced by an artificially 3'-truncated preS2/S gene of the wild-type HBV genome. Besides the simian virus 40 promoter of the reporter plasmid pSV2CAT, the promoter of the human c-myc oncogene can also be activated. These results, taken together with the fact that preS/S is the only HBV gene found to be integrated in almost every HBV-related HCC analysed so far, indicate that trans-activation by integrated preS2/S sequences is a possible mechanism for HBV-associated oncogenesis.

Amino Acid Sequence↗
PubMed1986

Weighted integration method for local cerebral blood flow measurements with positron emission tomography.

A new technique called the weighted integration method for the measurement of local CBF (LCBF) in humans with positron emission tomography (PET) is presented. LCBF is calculated from weighted time integrals of the blood and tissue radioactivity curves. This method is computationally efficient and achieves nearly optimal statistical estimation of LCBF. The predicted root mean squared error of the weighted integration method is verified by simulation studies and is only 1-2% larger than the minimum possible error that can be achieved by an ideal estimation algorithm. For LCBF of greater than 30 ml/min/100 g, the weighted integration method provides reduced noise compared with the integrated projection technique, the PET autoradiographic method, and the steady-state technique. In addition, an error analysis is performed to study the sensitivity of the weighted integration method to tissue mixtures, blood sample timing errors, and changes in LCBF during the data collection period.

Brain↗
PubMed2002

Site-specific genomic integration produces therapeutic Factor IX levels in mice.

We used the integrase from phage phiC31 to integrate the human Factor IX (hFIX) gene permanently into specific sites in the mouse genome. A plasmid containing attB and an expression cassette for hFIX was delivered to the livers of mice by using high-pressure tail vein injection. When an integrase expression plasmid was co-injected, hFIX serum levels increased more than tenfold to approximately 4 microg/ml, similar to normal FIX levels, and remained stable throughout the more than eight months of the experiment. hFIX levels persisted after partial hepatectomy, suggesting genomic integration of the vector. Site-specific integration was proven by characterizing and quantifying genomic integration in the liver at the DNA level. Integration was documented at two pseudo-attP sites, native sequences with partial identity to attP, with one site highly predominant. This study demonstrates in vivo gene transfer in an animal by site-specific genomic integration.

Animals↗
PubMed1998

Membrane integration of Sec61alpha: a core component of the endoplasmic reticulum translocation complex.

The Sec61 complex is a central component of the endoplasmic reticulum (ER) translocation site. The complex consists of three subunits: Sec61alpha, Sec61beta and Sec61gamma, at least two of which (alpha and beta) are adjacent to nascent proteins during membrane insertion. Another component of the translocation machinery is the translocating chain-associating membrane (TRAM) protein, which is also adjacent to many nascent proteins during membrane insertion. Sec61alpha functions as the major component of a transmembrane channel formed by oligomers of the Sec61 complex. This channel is the site of secretory protein translocation and membrane protein integration at the ER membrane. Sec61alpha is a polytopic integral membrane protein, and we have studied its biosynthesis and membrane integration in vitro. Using a cross-linking approach to analyse the environment of a series of discrete Sec61alpha membrane-integration intermediates, we find: (i) newly synthesized Sec61alpha is adjacent to known components of the ER membrane-insertion site, namely Sec61alpha, Sec61beta and TRAM, and thus the integration of Sec61alpha appears to require a pre-existing Sec61 complex; (ii) a site-specific cross-linking analysis indicates that the first transmembrane domain of Sec61alpha remains adjacent to protein components of the ER-insertion site (specifically TRAM and Sec61beta) during the insertion of at least three subsequent transmembrane domains; and (iii) the membrane integration of Sec61alpha requires ER targeting by the signal-recognition particle.

Animals↗
PubMed2004

Autonomy and integrity: upholding older adult patients' dignity.

AIM: The aim of this study was to deepen understanding of the relationship between autonomy and integrity in interactions between patients and individual health care workers in real-life care situations. METHOD: The data reported here are from a 6- and 12-month follow-up of the teaching of ethics to health care professionals working with older people. The data collection method used was participant observation. Health professionals' caring behaviour in everyday situations was observed from the point of view of patients' autonomy and integrity. Theoretical frameworks relating to autonomy and integrity were used to analyse the data. FINDINGS: The structural framework was useful for identifying the two concepts and their relationship in everyday situations. The data suggest that the two concepts are ethically complex. Autonomy is grounded in respect for patients' ability to choose, decide and take responsibility for their own lives. Autonomy varies within and between individuals and is dependent on context and on those involved. It stresses the intrinsic value of patients, which marks their worth independently of others. Integrity, however, is bound to patients' very existence, no matter what their physical and mental conditions, and must be respected regardless of their ability to act autonomously. CONCLUSION: The concepts of autonomy and integrity appear to presuppose one another and to be indivisible if older adult patients' dignity is to be maintained. This implies that when patients' autonomy is supported their integrity is protected and, consequently, their dignity upheld.

Adult↗
PubMed2002

Child health and obstetrics-gynaecology in a problem-based learning curriculum: accepting the limits of integration and the need for differentiation.

BACKGROUND AND OBJECTIVES: The University of Manchester's undergraduate curriculum was reorganised in 1994. Problem-based learning (PBL) was chosen as the central educational method throughout the 5 years. A thematic interdisciplinary style provided a framework around which to select and integrate content. The theme for family, reproductive and child health for the 14-week Families and Children Module (FCM) in year 4 integrated content from obstetrics-gynaecology, paediatrics (including child psychiatry), genetics and public health. This paper focuses on the FCM which has put to test some of the principles of integration. METHODS: The educational process and outcome of the FCM was evaluated with information from (1) Open Forum feedback sessions (2) student questionnaires and (3) students' performance in an objective structured clinical examination (OSCE). RESULTS: Significant problems were encountered during the first year of the FCM (1997--98). An Open Forum for all students and staff was convened after each module in order to address the level of concern. Students' responses to questionnaires reflected the overall impression obtained from the Open Forum. Difficulties appeared to be more than the anxieties and challenges inherent in organisational change and were not simple practical timetabling problems. Tutors perceived a loss of coherence and student contact; students reported difficulties maintaining sufficient continuity of focus in clinical and academic learning experiences. The intended level of integration of paediatrics and obstetrics-gynaecology was unmanageable. Consequently, the FCM (1998-99) was divided into separate attachments for clinical learning and experience in paediatrics and obstetrics-gynaecology, each of 7 weeks' duration. Further open feedback sessions revealed that the modifications implemented in 1998-99 were associated with positive experiences for students and tutors. Comparison of responses to the evaluation questionnaires showed that students' overall rating of the module was higher (P=0.002) for 1998-99 (mean 3.4, SD 0.9) than for 1997-98 (mean 3.0, SD 1.1). CONCLUSIONS: We emphasise that horizontal integration can result in an experience of disintegration for students and tutors. Certain disciplines, such as paediatrics and obstetrics-gynaecology, may not have enough in common for full curriculum integration.

Curriculum↗
PubMed2003

The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function.

Cell wall integrity is crucial for fungal growth, development and stress survival. In the model yeast Saccharomyces cerevisiae, the cell integrity Mpk1/Slt2 MAP kinase and calcineurin pathways monitor cell wall integrity and promote cell wall remodelling under stress conditions. We have identified the Cryptococcus neoformans homologue of the S. cerevisiae Mpk1/Slt2 MAP kinase and have characterized its role in the maintenance of cell integrity in response to elevated growth temperature and in the presence of cell wall synthesis inhibitors. C. neoformans Mpk1 is required for growth at 37 degrees C in vitro, and this growth defect is suppressed by osmotic stabilization. C. neoformans mutants lacking Mpk1 are attenuated for virulence in the mouse model of cryptococcosis. Phosphorylation of Mpk1 is induced in response to perturbations of cell wall biosynthesis by the antifungal drugs nikkomycin Z (a chitin synthase inhibitor), caspofungin (a beta-1,3-glucan synthase inhibitor), or FK506 (a calcineurin inhibitor), and mutants lacking Mpk1 display enhanced sensitivity to nikkomycin Z and caspofungin. Lastly, we show that calcineurin and Mpk1 play complementing roles in regulating cell integrity in C. neoformans. Our studies demonstrate that pharmacological inhibition of the cell integrity pathway would enhance the activity of antifungal drugs that target the cell wall.

Animals↗
PubMed1992

The methylation patterns of chromosomal integration regions influence gene activity of transferred DNA in Petunia hybrida.

The regions of integration of a transferred DNA-fragment from three transgenic Petunia hybrida plants were analysed for their influence on the expression of the foreign DNA. Each of the three transformants, lines 16, 17 and 24, contained a fragment of a plasmid on which two genes were located, an npt-II gene which renders the plants resistant to kanamycin and the A1 gene from Zea mays, a visible marker gene that leads to the production of a brick red anthocyanin pigment in the flowers. Inactivation of both genes in line 16 is associated with integration into a region of highly repetitive DNA, while the integration sites of the other two lines were essentially unique. The integration regions of lines 17 and 24, both of which show expression of the foreign genes at characteristically different intensities, showed a distinct methylation pattern that was stably conserved for these regions in both transgenic and wild-type plants. The characteristic methylation pattern of the two integration regions was also imposed on the border region of the integrated fragments and might thus be responsible for the differences in the intensity of gene expression observed among the two lines.

Base Sequence↗
PubMed2003

Atrial evoked response integral for automatic capture verification in atrial pacing.

Beat-by-beat Autocapture is currently limited to operation in the ventricle with bipolar leads. The authors investigated the integral of the negative-going portion of the atrial evoked response integral (AERI) as a potential resource for verification of atrial capture. Intracardiac electrogram signals were collected from 59 patients (ages 67.8 +/- 15.1 years) with bipolar, low polarization atrial leads. The signals were collected over a mean period of 6.1 months (minimum 4 days) after lead implantation. St. Jude Medical Affinity pulse generators were used to perform automatic capture threshold tests while the electrogram signals were recorded by a Model 3510 programming device. These signals were transferred to a personal computer in digital form for later analysis. The AERI was calculated at each programmable pacing voltage until capture was lost. The difference between the polarization integral at loss of capture and evoked response integral with successful capture was sufficient to justify enabling the atrial Autocapture feature in 53 of 59 patients in whom bipolar pacing and unipolar sensing was performed. The authors developed a calibration routine to identify automatically those patients in whom atrial Autocapture could be programmed On, based on the polarization integral at loss of capture, the estimated maximum polarization integral, and the AERI. Preliminary analysis indicated that the AERI is a practical resource for beat-by-beat atrial capture detection when used with low polarization leads.

Aged↗
PubMed2006

Intraepithelial gammadelta+ lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection.

BACKGROUND & AIMS: Intestinal epithelial integrity and permeability is dependent on intercellular tight junction (TJ) complexes. How TJ integrity is regulated remains unclear, although phosphorylation and dephosphorylation of the integral membrane protein occludin is an important determinant of TJ formation and epithelial permeability. We have investigated the role intestinal intraepithelial lymphocytes (iIELs) play in regulating epithelial permeability in response to infection. METHODS: Recombinant strains of Toxoplasma gondii were used to assess intestinal epithelial barrier function and TJ integrity in mice with intact or depleted populations of iIELs. Alterations in epithelial permeability were correlated with TJ structure and the state of phosphorylation of occludin. iIEL in vivo reconstitution experiments were used to identify the iIELs required to maintain epithelial permeability and TJ integrity. RESULTS: In the absence of gammadelta+ iIELs, intestinal epithelial barrier function and the ability to restrict epithelial transmigration of Toxoplasma and the unrelated intracellular bacterial pathogen Salmonella typhimurium was severely compromised. Leaky epithelium in gammadelta+ iIEL-deficient mice was associated with the absence of phosphorylation of serine residues of occludin and lack of claudin 3 and zona occludens-1 proteins in TJ complexes. These deficiencies were attributable to the absence of a single subset of gammadelta T-cell receptor (TCR-Vgamma7+) iIELs that, after reconstituting gammadelta iIEL-deficient mice, restored epithelial barrier function and TJ complexes, resulting in increased resistance to infection. CONCLUSIONS: These findings identify a novel role for gammadelta+ iIELs in maintaining TJ integrity and epithelial barrier function that have implications for understanding the pathogenesis of intestinal inflammatory diseases associated with disruption of TJ complexes.

Animals↗
PubMed1981

Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue specimens.

We used recombinant-DNA technology and gel electrophoresis to find hepatitis B virus DNA (HBV-DNA) in liver and tumor tissue from patients with hepatocellular carcinoma and chronic liver disease, and to study the integration of HBV-DNA into the genome of these tissues' cells. In 12 patients with hepatocellular carcinoma who had hepatitis B surface antigen (HBsAg) in their serum, integrated HBV-DNA was identified in the tumors; it was also found in tumors from three of eight patients who were seronegative for HBsAg but positive for antibody to HBsAg. In some cases, integrated HBV-DNA was also present in nontumorous liver tissue that had the same hybridization pattern or one different from that of the tumor. In five carriers of HBsAg who had evidence of the carrier state and chronic liver disease for less than two years, HBV-DNA was present but not integrated in liver tissue. In the two patients who had carried HBsAg for more than eight years, HBV-DNA was integrated into the host genome. These data suggest that integration of HBV-DNA into hepatocytes occurs during the course of persistent HBV infection and precedes development of gross neoplasm.

Biopsy↗
PubMed2005

Rigorous integral screening for electron correlation methods.

We derive rigorous multipole-based integral estimates (MBIE) in order to account for the distance dependence occurring in atomic-orbital (AO) formulations of electron correlation theory, where our focus is on AO-MP2 theory within a Laplace scheme. We find for the exact transformed integral products an extremely early onset of a linear-scaling behavior and a very small number of significant products. To preselect the significant integral products we adapt our MBIE method as rigorous upper bound. In this way it is possible to exploit the favorable scaling behavior observed and to reduce the scaling of estimated products asymptotically to linear, without sacrificing accuracy or reliability. By separating Coulomb- and exchange-type contractions only half-transformed integrals need to be computed. Furthermore, our scheme of rigorously preselecting transformed integral products via MBIE seems to offer particularly interesting perspectives for a direct formation of half- or fully transformed integrals by using multipole expansions and auxiliary basis sets.

Journal Article↗
PubMed1981

Does integration produce masking or protect from it?

To examine the role of integration in pattern masking, possible disruptive effects of integration were minimized by using a mask that overlaid completely all targets. Exposure durations were 10 ms, so under energy summation the target area was much darker than the rest. In another condition the mask was red and targets were blue, so under energy summation the target area could also be distinguished by hue. Masking magnitude increased with delay of mask onset, and it was established by four independent criteria that integration was negligible in the condition which produced most masking. It is deduced that integration is not necessary for masking; furthermore it is suggested that integration never produces masking, but rather may or may not protect from a disruptive effect of interruption. The argument is that were the visual system to have better visual resolution, it would suffer more given the same masking parameters. It is argued that type B masking functions arise from a combination of the facilitatory effect of integration and the detrimental effect of interruption.

Color Perception↗
PubMed1995

Integration of stereo, texture, and outline cues during pinhole viewing of real ridge-shaped objects and stereograms of ridges.

Three experiments are reported in which the possible role of blur cues as a factor needing to be taken into account in cue-integration studies involving conflicts between stereo and texture/outline cues was investigated. The earlier suggestion was tested that uncontrolled blur cues might have caused the quite different patterns of cue integration reported for real ridge-shaped objects oriented vertically and for stereograms depicting similar surfaces. Blur cues were manipulated by pinhole viewing intended to render accommodation open loop. The results for real ridges were as predicted by the blur-cue hypothesis: pinhole viewing strengthened texture/outline cues in vertically oriented ridges, thereby diminishing the pattern of stereo dominance hitherto observed for these stimuli (and as observed here in non-pinhole-viewing control conditions and in horizontally oriented ridges). The results for the stereograms did not conform to predictions: pinhole viewing, assumed to remove blur cues from the cue-integration process, still produced the pattern observed in control conditions in which a texture/outline cue for a shallow ridge overwhelmed stereo cues for a steep ridge. This result is against the hypothesis that perhaps blur cues for the stereogram projection surface differentially favoured the shallow texture/outline cues. A new variant of the blur-cue hypothesis is offered to account for this result. The main conclusion from the study is: beware drawing firm conclusions from stereograms about the pattern of cue integration that can be expected when real objects are being viewed. The two situations can produce very different results as far as cue integration is concerned. This is a conclusion with serious implications for the use of stereograms for studying the integration of stereo with other cues.

Adolescent↗