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At least 739 records · Page 41Linked to original sources
PubMed1987

Theoretical model for the post-transcriptional regulation of the human c-myc gene expression, involving double-stranded RNA processing.

We propose that the human c-myc gene expression is regulated by a post-transcriptional mechanism based on the formation of a hairpin structure between c-myc mRNA exons 1 and 2. This structure could be rapidly processed by a hypothetical double stranded RNAse, removing the 5' end segment of the c-myc mRNA having the cap site. Removal of cap should propitiate exonucleolytic degradation of transcript.

Gene Amplification↗
PubMedDate not supplied

Cells behaving badly: a theoretical model for the Fas/FasL system in tumour immunology.

One proposed mechanism of tumour escape from immune surveillance is tumour up-regulation of the cell surface ligand FasL, which can lead to apoptosis of Fas receptor (Fas) positive lymphocytes. Based upon this 'counterattack', we have developed a mathematical model involving tumour cell-lymphocyte interaction, cell surface expression of Fas/FasL, and their secreted soluble forms. The model predicts that (a) the production of soluble forms of Fas and FasL will lead to the down-regulation of the immune response; (b) matrix metalloproteinase (MMP) inactivation should lead to increased membrane FasL and result in a higher rate of Fas-mediated apoptosis for lymphocytes than for tumour cells. Recent studies on cancer patients lend support for these predictions. The clinical implications are two-fold. Firstly, the use of broad spectrum MMP inhibitors as anti-angiogenic agents may be compromised by their adverse effect on tumour FasL up-regulation. Also, Fas/FasL interactions may have an impact on the outcome of numerous ongoing immunotherapeutic trials since the final common pathway of all these approaches is the transduction of death signals within the tumour cell.

Apoptosis↗
PubMed1982

The development of clinical tuberculosis following infection with tubercle bacilli. 1. A theoretical model for the development of clinical tuberculosis following infection, linking from data on the risk of tuberculous infection and the incidence of clinical tuberculosis in the Netherlands.

Information on the risk of tuberculous infection in the Netherlands has been linked with information on the incidence of tuberculosis, in an attempt to estimate the risks of developing the disease following infection or reinfection. It was postulated that: (a) those with a recent primary infection had a characteristic risk of developing progressive primary tuberculosis; (b) those with a distant (i.e. not recent) primary infection and a recent reinfection had a characteristic risk of developing exogenous tuberculosis; and (c) those with a distant primary infection but no recent reinfection had a characteristic risk of developing endogenous tuberculosis. The information on the risk of tuberculous infection was used to estimate the size of the population in each of these infection classes for different age-groups and calendar years in the Netherlands. Using multiple regression to link these population figures with the information on tuberculosis incidence in the same age group and calendar year, it was possible to estimate the above risks of developing tuberculosis. For Netherlands males aged 15-69 years during the period 1951-70 the three risks of developing pulmonary tuberculosis were estimated to be: (a) 5.06 per cent annually (for 5 years) following primary infection; (b) 1.91 per cent annually (for 5 years) following reinfection; (c) 0.0253 per cent annually, after the first 5 years following primary infection, in the absence of reinfection. The corresponding (and significantly different) estimated annual risks of development of pulmonary tuberculosis for females were 5.85, 1.10 and 0.0020 per cent respectively. From these risks, it may be estimated that the degree of protection conferred by a distant primary infection, against pulmonary tuberculosis arising from a recent reinfection, was 63 per cent for males and 81 per cent for females. The estimated relative proportions of cases of progressive primary, exogenous and endogenous tuberculosis varied considerably with age and calendar year. Progressive primary tuberculosis was dominant at the younger ages, exogenous and endogenous tuberculosis at older ages. At these older ages, the great majority of cases in the Netherlands in the early 1950s appeared to be exogenous in origin, but by 1970, with the decrease in the risk of infection, the exogenous contribution had dwindled substantially, especially among males.

Adolescent↗
PubMed2000

The Biological System of the Elements (BSE). Part II: a theoretical model for establishing the essentiality of chemical elements. The application of stoichiometric network analysis to the biological system of the elements

Stoichiometric Network Analysis (SNA), originally developed by the Canadian chemist Bruce L. Clarke during the 1970s, provides a most efficient means of reducing the background topology of complex interaction networks to some skeleton topology around which systems dynamics can be understood without jeopardising insight into complex dynamics by over- or miss-simplification. Since it focuses on the corresponding autocatalytic (AC) features of a feedback system as those which control overall behaviour to some extent, SNA deals with reaction kinetics in and beyond chemistry, e.g. with nuclear reactions. It is therefore quite straightforward to apply this manner of simplification, which in turn is supported by a number of mathematical theorems on systems behaviour and properties of AC cycles, to biological systems although their 'full' complexity may not even be assessed in the yet rare cases of complete genetic sequencing. Assuming there is a relationship between the kinds of metal or metalloid species and key biological/biochemical transformations to be promoted with their aid--this relationship being the subject of bio-inorganic chemistry--and that biochemistry is, in effect, about systems which can reproduce and thus behave autocatalytically, one can expect SNA to yield formally sound statements on basic features of biology and biochemistry too. If we sum up the facts and considerations concerning essentiality or possible essentiality in a biological system of elements (Markert, 1994), this means joining the triangular representation of BSE, including statements on (the degree of biological) evolution and aggregation levels, to SNA treatment of autocatalysis within hierarchical systems from metalloenzymes to entire biocoenoses. Arguments using preferred cluster sizes and aggregation tendencies from coordination chemistry are then employed to circumscribe possible functions within the BSE. They are also extended to metals hitherto not known to be essential, such as tellurium or scandium.

Journal Article↗
PubMedDate not supplied

Cognition in Alzheimer's disease: theoretic models and clinical implications.

Riege and Metter review studies of cognitive functioning in probable Alzheimer's disease (pAD), representative of three distinguishable models: severity or staging, heterogeneity or subtyping, and information processing. As Riege and Metter point out, apparent differences in both disease description and implications for diagnostic assessment are dependent upon the model employed. The present commentary examines clinical and research implications derived from consideration of interactions between these three models, drawing upon recent cross-sectional and longitudinal studies of information processing in pAD.

Alzheimer Disease↗
PubMed1996

Promoting reflection in postgraduate nursing: a theoretical model.

Reflection is a method of learning and teaching professional maturity through critical analysis of experience. Illuminative research approach is used in collaboration with students on a palliative care course to investigate the effects of reflective learning 1 year after the course. Questionnaire and interview methods were used to collect data. This study concludes that (1) critical thinking is notably augmented, (2) listening and observation skills are enhanced and (3) gaining insight into clinical situations and personal nursing philosophy and approaches are essential for discovery of theories of nursing.

Clinical Competence↗
PubMed2002

Analysis of DNA curvature distribution in mycobacterial promoters using theoretical models.

In this paper, 125 different mycobacterial promoters are analyzed for their DNA curvature distribution using several di- and tri-nucleotide dependent models of DNA curvature. Different models give similar behavior and therefore qualitative validation of the results. Mycobacterial promoters resembling the E. coli sigma(70) type have almost 81% (85%) sequences having medium and high curvature profiles using dinucleotide-dependent models. Non-E. coli sigma(70) type mycobacterial promoters have comparatively higher percent of low curvature profiles. Very few extended -10 promoters have low curvature profiles. Mycobacterial promoters having A(n)T(m) (n+m > or =3) tract in the upstream region of -35 box and repeated in phase with each other have high curvature profiles. M. smegmatis promoters have high curvature profiles compared to M. tuberculosis promoters.

Base Sequence↗
PubMed2000

Theoretical modeling of the effects of shock duration, frequency, and strength on the degree of electroporation.

Electroporation is becoming an increasingly important tool for introducing biologically active compounds into living cells, yet the effectiveness of this technique can be low, particularly in vivo. One way to improve the success rate is to optimize the shock protocols, but experimental studies are costly, time consuming, and yield only an indirect measurement of pore creation. Alternatively, this study models electroporation in two geometries, a space-clamped membrane and a single cell, and investigates the effects of pulse duration, frequency, shape, and strength. The creation of pores is described by a first order differential equation derived from the Smoluchowski equation. Both the membrane and the cell are exposed to monophasic and biphasic shocks of varying duration (membrane, 10 micros-100 s; cell, 0.1 micros-200 ms) and to trains of monophasic and biphasic pulses of varying frequency (membrane, 50 Hz-4 kHz; cell, 200 kHz-6 MHz). The effectiveness of each shock is measured by the fractional pore area (FPA). The results indicate that FPA is sensitive to shock duration only in a very narrow range (membrane, approximately 1 ms; cell, approximately 0.25 micros). In contrast, FPA is sensitive to shock strength and frequency of the pulse train, increasing linearly with shock strength and decreasing slowly with frequency. In all cases, monophasic shocks were at least as effective as biphasic shocks, implying that varying the strength and frequency of a monophasic pulse train is the most effective way to control the creation of pores.

Electroporation↗
PubMed2002

Ligand-receptor interaction at the neural nicotinic acetylcholine binding site: a theoretical model.

Recent mutagenesis experiments have identified some of the functional amino acids that are essential in the interaction of nicotinic agents with the binding site of the neural nicotinic acetylcholine receptor (nAChR). Although this receptor is one of the best studied and characterized the lack of detailed experimental information regarding its quaternary structure has turned it into a challenge for computational chemistry. We have previously reported [J. Comput. Aided Mol. Design 13 (1999) 57-68] a computational protocol based on molecular mechanics and molecular dynamics (MD) where SER82, ASP83, TRP86, ASP89, TYR93, TYR190, TYR198 and ARG209 were placed around selected agonists and antagonists aided by stereoelectronic criteria. Explicit water molecules were used with the double goal of simulating aqueous environment and keeping the system from falling apart. The protocol was stable enough to allow the ligands to evolve to their thermodynamically most probable structure while maintaining the key interactions. In this communication we use the average model for the agonists (one average structure for each agonist) to calculate quantum mechanically the interactions of the binding site with one neurotransmitter acetylcholine (ACh, 1), as well as with two of the most potent agonists described so far [nicotine (2) and epibatidine (3)] and the modeled binding site. A wide variety of methods as well as basis sets were used in order to rationalise the best way to treat the problem. In this limited set of compounds, a good correlation between total interaction energies and biological affinity is observed.

Acetylcholine↗
PubMed1994

Individual perception of education and treatment versus actual outcome. A theoretical model exemplified by an interventional study on patients with insulin-dependent diabetes mellitus.

An educational model is presented that stresses the importance of the interaction between individual characteristics and intentional educational influences on outcome variation. This model is exemplified by an interventional study of patients with insulin-dependent diabetes mellitus who, despite long-term conventional medical treatment, had been unable to achieve satisfactory hemoglobin Alc levels. Treatment modes and their importance for understanding variations in outcomes are discussed from the interactional perspective suggested in the model.

Adult↗
PubMed2002

Contextual social-cognitive mediators and child outcome: a test of the theoretical model in the Coping Power program.

This study tests the contextual social-cognitive model, which has served as the basis for the Coping Power program, an indicated preventive intervention with at-risk preadolescent boys at the time of transition from elementary to middle school. The contextual social-cognitive model assumes that aggressive children have distortions in their social-cognitive appraisals and deficiencies in their social problem solving skills and that their parents have deficiencies in their parenting behaviors. To test this model, boys were identified as being at risk on the basis of fourth grade and fifth grade teachers' ratings of children's aggressive and disruptive behaviors, and interventions were delivered at the end of elementary school and the beginning of middle school. The intervention effect on delinquency, substance use, and school behavior outcomes was at least partially mediated through intervention-produced changes in child and parent variables that were targets for the intervention. These analyses provided unique support for the assumptions in the contextual social-cognitive model that changes in these mediating processes, even among high-risk boys, can have a meaningful impact on later negative outcomes.

Adaptation, Psychological↗
PubMed2002

Examination of theoretical models in external voltage control of capillary electrophoresis.

Control of electroosmosis by an external voltage in capillaries of varying geometry was examined and investigated. Controlled geometric factors included inner and outer radii, external electrode coverage area, and the method of voltage application. The behavior of the flow in response to the external voltage from earlier work and this study were compared to existing literature models. A noticeable lack of correlation between the current modeling theories and the published data is noted. In light of these results, suggestions for further areas of investigation of a description of external voltage flow control mechanism are suggested.

Journal Article↗