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PubMed1975

Effects of truncal, selective, and highly selective vagotomy on glucose tolerance and insulin secretion in patients with duodenal ulcer. Part II-Comparison of response to oral and intravenous glucose.

Paired oral and intravenous glucose tolerance tests were carried out in patients who had undergone truncal vagotomy and pyloroplasty, selective vagotomy and pyloroplasty, or highly selective vagotomy at least six months earlier. Intravenous glucose tolerance was similar in all three groups. Oral glucose elicited significantly higher concentrations of plasma insulin in patients who had undergone selective and highly selective vagotomy than in those treated by truncal vagotomy. When the same amount of glucose was given intravenously, however, plasma insulin concentrations were similar in all three groups of patients. The insulin secreted in response to intravenous glucose expressed as a percentage of that secreted in response to oral glucose was 112% for truncal vagotomy, 51% for selective vagotomy, and 52% for highly selective vagotomy. Truncal vagotomy thus led to a diminished insulin response to oral glucose, which was probably due to impaired release of small-bowel hormones.

Administration, Oral↗

PubMed2005

An integrated feature selection and classification method to select minimum number of variables on the case study of gene expression data.

This paper introduces a novel generic approach for classification problems with the objective of achieving maximum classification accuracy with minimum number of features selected. The method is illustrated with several case studies of gene expression data. Our approach integrates filter and wrapper gene selection methods with an added objective of selecting a small set of non-redundant genes that are most relevant for classification with the provision of bins for genes to be swapped in the search for their biological relevance. It is capable of selecting relatively few marker genes while giving comparable or better leave-one-out cross-validation accuracy when compared with gene ranking selection approaches. Additionally, gene profiles can be extracted from the evolving connectionist system, which provides a set of rules that can be further developed into expert systems. The approach uses an integration of Pearson correlation coefficient and signal-to-noise ratio methods with an adaptive evolving classifier applied through the leave-one-out method for validation. Datasets of gene expression from four case studies are used to illustrate the method. The results show the proposed approach leads to an improved feature selection process in terms of reducing the number of variables required and an increased in classification accuracy.

Artificial Intelligence↗

PubMed1986

Motion selectivity in macaque visual cortex. I. Mechanisms of direction and speed selectivity in extrastriate area MT.

Mechanisms of direction selectivity and speed selectivity were studied in single neurons of the middle temporal visual area (MT) of behaving macaque monkeys. Visual stimuli were presented in both smooth and stroboscopic motion within a neuron's receptive field as the monkey fixated a stationary point of light. Direction selectivity, speed selectivity, and the spontaneous discharge characteristics of MT neurons in behaving monkeys were similar to those reported in previous studies in anesthetized monkeys. Stroboscopic motion stimuli were sequences of flashes characterized by the spatial and temporal intervals between each flash. The spatial and temporal intervals were systematically varied so that suppressive and facilitatory interactions could be studied in both the preferred and null directions. Suppression and facilitation were measured by subtracting the peak discharge rate elicited by a single flash from the peak discharge rate elicited by a stroboscopic train of flashes. The dominant mechanism of direction selectivity in MT was a pronounced suppression of discharge for motion in the null direction which we interpreted as inhibition. The inhibition was sufficiently potent to abolish the responses to single flashed stimuli when they were embedded in a series of flashes in the null direction, and it frequently reduced the neuronal discharge to a level below the spontaneous firing rate. Facilitation in the preferred direction was a prominent feature of the responses of some, but not all, MT neurons. The peak discharge rate for stroboscopic motion in the preferred direction was more than twice the peak rate to a single flash for approximately 50% of the neurons in our sample. The direction selectivity of most MT neurons showed the effects of both inhibitory and facilitatory mechanisms, and it was not possible to segregate MT neurons into distinct groups on the basis of these measures. Suppressive mechanisms contributed to speed tuning as well as direction tuning. The low-speed cutoff for motion in the preferred direction resulted from suppression in 82% of the neurons tested. The high-speed cutoff resulted from suppression in 32% of the neurons tested. The latter mechanism appeared to be distinct from the inhibitory mechanism which acted in the null direction in that large spatial intervals were required for its activation.

Animals↗

PubMed2006

Ovulation-selective genes: the generation and characterization of an ovulatory-selective cDNA library.

Ovulation-selective/specific genes, that is, genes preferentially or exclusively expressed during the ovulatory process, have been the subject of growing interest. We report herein studies on the use of suppression subtractive hybridization (SSH) to construct a 'forward' ovulation-selective/specific cDNA library. In toto, 485 clones were sequenced and analyzed for homology to known genes with the basic local alignment tool (BLAST). Of those, 252 were determined to be nonredundant. Of these 252 nonredundant clones, 98 were analyzed by probing mouse preovulatory and postovulatory ovarian cDNA. Twenty-five clones (26%) failed to show any signal, and 43 cDNAs tested thus far display a true ovulation-selective/specific expression pattern. In this communication, we focus on one such ovulation-selective gene, the fatty acid elongase 1 (FAE-1) homolog, found to be localized to the inner periantral granulosa and to the cumulus granulosa cells of antral follicles. The FAE-1 gene is a beta-ketoacyl-CoA synthase belonging to the fatty acid elongase (ELO) family, which catalyzes the initial step of very long-chain fatty acid synthesis. All in all, the present study accomplished systematic identification of those hormonally regulated genes that are expressed in the ovary in an ovulation-selective/specific manner. These ovulation-selective/specific genes may have significant implications for the understanding of ovarian function in molecular terms and for the development of innovative strategies for both the promotion of fertility and its control.

Acetyltransferases↗

PubMed1998

Comparison of selection by independent culling levels for below-average birth weight and high yearling weight with mass selection for high yearling weight in line 1 Hereford cattle.

Mass selection by independent culling levels (YB subline) for below-average birth weight (BWT) and high yearling weight (YWT) was compared with single-trait mass selection (YW subline) for high YWT in the inbred population of Line 1 Hereford cattle at Miles City, Montana. There were 4.2 generations of selection in YB and YW. Heritability estimates for the base population derived from multiple-trait REML were .28 and .31 for direct effects and .16 and .06 for maternal effects on BWT and YWT, respectively. Mid-parent cumulative selection differentials for BWT of YB and YW diverged (-2.9 vs 8.2 kg, respectively), as did the associated genetic trends for direct effects (-.014 kg/yr vs .105 kg/yr, respectively). Mid-parent cumulative selection differential for YWT of YB (102.1 kg) was 64% of that attained in YW (160.7 kg). Likewise, response in YWT of YB (.91 kg/yr) was 61% of response attained in YW (1.5 kg/yr). For BWT and YWT, maternal genetic trends were similar across selection lines. Assistance at parturition of first-parity 2-yr-old heifers was consistently less frequent in YB than in YW.

Aging↗

PubMed1991

Selection for high and low threshold body weight at first egg in broiler strain females. 1. Direct response to selection and correlated effects on juvenile growth rate and age at first egg.

A selection program for high and low threshold body weight at first egg was carried out in a broiler line. Selection was on the basis of weight at first egg, following gradual release from feed restriction at a relatively advanced age. After six generations of selection, the lines differed by 862 g in the trait under selection. In addition, 6-wk body weight of high-line (HL) birds was 91 g greater, and age at first egg was 32 days greater than in low-line (LL) birds. When raised under an ad libitum feeding regimen from hatch, HL birds entered lay 20 days later than LL birds. When onset of lay was markedly delayed by maintaining feed restriction until 29 wk of age, body weight at first egg of HL birds was greater by 645 g than that of LL birds. Similarly, when birds of the two lines were subjected to forced molt and brought to a body weight well below that of initial body weight at first egg, and then allowed to gain weight and reenter lay, body weight difference at first egg of HL and LL birds following rehabilitation was similar to that found on original entry into lay. It is proposed that the results may most plausibly be explained as resulting from a primary effect of the selection procedure on the time required to first egg from onset of sexual competence, defined as onset of responsiveness to lay-inducing factors such as light. Alternative explanations involve effects of the selection procedure on threshold weight or threshold age requirements for sexual competence.

Animal Feed↗

PubMed1993

Divergent selection for growth in Japanese quail under split and complete nutritional environments. 7. Heterosis and combining ability among diallel crosses following twenty-seven generations of selection.

Growth patterns of quail lines divergently selected for 4-wk BW under split and complete nutrition environments were investigated utilizing a diallel mating scheme. The design, involving 16 mating combinations, allowed investigation of heterotic effects, reciprocal cross effects, and combining ability. Progeny from Generation 27 breeders were evaluated in two hatches under both selection diets. Heterosis for hatch weight was essentially zero; however, percentage heterosis from High x High crosses and Low x Low crosses ranged from 5 to 18% after 1 wk of age. Quail progeny from Low x High crosses were consistently larger than quail from reciprocal High x Low crosses under both selection diets. Reciprocal differences were greatest immediately posthatch and declined with age. However, in crosses involving males from High and Low split diet lines mated to females from High and Low complete diet lines, large reciprocal differences in BW remained at 8 wk. Mean heterosis values for BW across ages from crossing High and Low lines both within and across selection environments were negative in six of eight comparisons. Mean values ranged from +3 to -11% and indicated that greater selection responses may have been made in divergent selection for low 4-wk BW than for high BW. General combining ability of lines was greater when transmitted via females as opposed to males, and was similar under the two diets (split and complete). There was evidence that high-BW lines exhibited greater general combining ability under both dietary environments than did low-BW lines.

Animal Nutritional Physiological Phenomena↗

PubMed2000

Opening a window on thymic positive selection: developmental changes in the influence of cosignaling by integrins and CD28 on selection events induced by TCR engagement.

How TCR and non-TCR signals are integrated by thymocytes to generate a decision to undergo either positive or negative selection remains incompletely understood. Recent evidence suggests that TCR signal transduction changes its quality during thymocyte maturation, but whether the contributions of various cosignaling or costimulatory pathways to thymocyte selection also are modified during development is unclear. Questions also remain about the possible selective roles of specific costimulatory pathways in induction of differentiation vs death among thymocytes at any given stage of maturity. To address these issues, a quantitative in vitro analysis of initiation of CD4+CD8+ thymocyte differentiation as measured by CD69 up-regulation/coreceptor down-modulation was conducted in parallel with an analysis of induction of death. Using transfected cells varying in their surface display of ICAM-1 or B7.1 along with antibody blocking experiments, we demonstrate here that ICAM-1 provides a selective boost to signaling for differentiation without substantially affecting induction of death among CD4+CD8+ cells, a property that is lost as thymocytes mature further. In contrast, B7 engagement enhances both cell activation and death in parallel. Based on these data, we propose that the high level of ICAM-1 on cortical epithelial cells plays a special role in opening a window between TCR signaling for differentiation vs death, permitting efficient initiation of positive selection on epithelial ligands. In contrast, late CD28-dependent cosignaling on hemopoietic cells in the medulla would help enforce negative selection by augmenting the effects of TCR engagement by low levels of high affinity ligands.

Amino Acid Sequence↗

PubMed2004

Thymocytes between the beta-selection and positive selection checkpoints are nonresponsive to IL-7 as assessed by STAT-5 phosphorylation.

Interleukin-7 is widely accepted as a major homeostatic factor involved in T cell development. To assess the IL-7 responsiveness of thymocytes involved in selection processes, we used a new sensitive flow cytometry-based assay to detect intracellular phosphorylation of STAT-5 induced by IL-7 in defined mouse thymocyte subsets. Using this method, we found the earliest thymocyte subset (CD4(-)CD8(-)CD25(-)CD44(+)) to contain both IL-7-responsive and nonresponsive cells. Transition through the next stages of development (CD4(-)CD8(-)CD25(+)CD44(+ and -)) was associated with responsiveness of all thymocytes within these populations. Passage of thymocytes through beta-selection resulted in a significant reduction in IL-7 sensitivity. In the next phases of development (TCR(-) and TCR(low)CD69(-)), thymocytes were completely insensitive to the effects of IL-7. STAT-5 phosphorylation in response to IL-7 was again observed, however, in thymocytes involved in the positive selection process (TCR(low)CD69(+) and TCR(intermediate)). As expected, CD4 and CD8 single-positive thymocytes were responsive to IL-7. These findings delineate an IL-7-insensitive population between the beta-selection and positive selection checkpoints encompassing thymocytes predicted to die by neglect due to failure of positive selection. This pattern of sensitivity suggests a two-signal mechanism by which survival of thymocytes at these checkpoints is governed.

Animals↗

PubMed1991

[The influence of between-channel selection on the brain potentials related to within-channel selection in auditory attention].

Event-related potentials (ERPs) were recorded during a selective listening paradigm similar to a previous study (Okita, 1989). Stimuli were random sequences of five vowels and a tone pip in two "channels' (separated by location, left and right). The difficulty of between-channel selection was varied in discriminability of location, easy (EL) or hard (HL), whereas within-channel selection was manipulated by designating either tone (T), one vowel (1V), or two vowels (2V) as targets. Subjects were required to attend to one channel and detect targets therein. ERPs for the EL condition replicating the earlier study, confirmed the effects of within-channel selection on the early phase of attention-related negativity (Nd): the early Nd being larger, the higher the target/nontarget selection load. In the HL condition, however, the 1V/2V difference disappeared: the early Nd effect was reduced for 2V, but prolonged in duration for 1V. The interaction between selection processes of the between- and within-channel was discussed in relation to the allocation of limited attentional capacity for operations rechecking outcomes of a preattentive target-classification stage.

Adult↗

PubMed1999

Functional similarity and differences between selection-independent CD4-CD8- alphabeta T cells and positively selected CD8 T cells expressing the same TCR and the induction of anergy in CD4-CD8- alphabeta T cells in antigen-expressing mice.

In TCR-alphabeta transgenic mice, CD4-CD8- TCR-alphabeta+ (alphabeta DN) cells arise in the absence of positively selecting MHC molecules and are resistant to clonal deletion in Ag-expressing mice. In this study the activation requirements and functional properties of alphabeta double-negative (DN) cells were compared with those of positively selected CD8+ cells expressing equivalent levels of the same MHC class I-restricted transgenic TCR. We found that positively selected CD8+ cells required a lower density of the antigenic ligand for optimal proliferative responses compared with alphabeta DN cells derived from nonpositively selecting mice. However, when the CD8 coreceptor on CD8+ cells was blocked with an anti-CD8 mAb, both alphabeta DN and CD8+ cells exhibited the same dose-response curve to the antigenic ligand and the same dependence on CD28/B7 costimulation. Positively selected CD8+ cells also differed from alphabeta DN cells in that they differentiated into more efficient killers and IL-2 producers after Ag stimulation, even after CD8 blockade. However, Ag-activated alphabeta DN and CD8+ cells were equally efficient in producing IFN-gamma, suggesting that this functional property is independent of positive selection. We also found that alphabeta DN cells recovered from the lymph nodes of Ag-expressing mice were functionally anergic. This anergic state was associated with defective proliferation and IL-2 production in response to Ag stimulation. These observations indicate that alphabeta DN cells can be anergized in vivo by physiological levels of the antigenic ligand.

Animals↗

PubMed1998

Clinical comparison of selective and non-selective alpha 1A-adrenoceptor antagonists for bladder outlet obstruction associated with benign prostatic hyperplasia: studies on tamsulosin and terazosin in Chinese patients. The Chinese Tamsulosin Study Group.

To examine the clinical usefulness of selective and non-selective alpha 1-adrenoceptor antagonists, we compared a selective (tamsulosin) and non-selective (terazosin) alpha 1-adrenoceptor antagonists in the treatment of Chinese patients with benign prostatic hyperplasia (BPH). The study was a single-blind, randomized, multicenter design to compare a fixed dose of tamsulosin (0.2 mg) or terazosin (2 mg) given once daily after breakfast for four weeks. A total of 212 patients were enrolled with 201 patients included in the analysis. The primary variables assessed were changes in total International Prostatic Symptom Score (IPSS), maximum urinary flow rate (Qmax), and average urinary flow rate (AFR) four weeks after dosing. Adverse events were recorded through the treatment period. Both tamsulosin and terazosin produced significant improvements in total IPSS (total score of 11.8 +/- 4.5; decrease in 45.1% and total score of 13.3 +/- 5.3; decrease in 39.0%, respectively) (p < 0.001), Qmax (13.2 +/- 4.1 mL/s, 37.5% increase and 13.6 +/- 3.6 mL/s, 30.8% increase, respectively) (p < 0.001) and AFR (7.7 +/- 3.3 mL/s, 37.5% increase and 7.8 +/- 3.1 mL/s, 25.8% increase, respectively) (p < 0.001) at endpoint. Tamsulosin was superior to terazosin in improvement of total IPSS (p < 0.05) and AFR (p < 0.05). The incidence of adverse events by administration of tamsulosin was less than that by terazosin (13 and 50, respectively; p < 0.01). Among the adverse event, incidence of dizziness (p < 0.001) and hypotension (p < 0.01) by administration of terazosin were significantly greater than that by tamsulosin. Both systolic and diastolic blood pressure of sitting position decreased significantly in patients treated with terazosin (p < 0.01). These results suggest that tamsulosin, a selective alpha 1A-adrenoceptor antagonist, was superior to terazosin, a non-selective alpha 1-adrenoceptor antagonist, in efficacy and adverse events in patients with symptomatic BPH.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2002

Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooxygenase-2 inhibitor.

The inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) are overexpressed in colonic tumors of humans, as well as in colon tumors that develop in rats after the administration of the colon-specific carcinogen, azoxymethane (AOM). iNOS may regulate COX-2 production of proinflammatory prostaglandins, which are known to play a key role in colon tumor development. Experiments were designed to assess the potential chemopreventive properties of highly selective iNOS inhibitors, administered individually and in combination with a selective COX-2 inhibitor, on the development of AOM-induced colonic aberrant crypt foci (ACF). F344 rats were fed experimental diets containing one of the following: 0, 10, 30, or 100 parts/million (ppm) of the selective iNOS inhibitor L-N(6)-(1-iminoethyl)lysine tetrazole-amide (SC-51); 1800 ppm of the less potent, selective iNOS inhibitor aminoguanidine (AG); 500 ppm of the COX-2 inhibitor celecoxib; 320 ppm of the nonsteroidal anti-inflammatory sulindac (positive control); or 30 ppm of SC-51 with 500 ppm of celecoxib, and 100 ppm of SC-51 with 500 ppm of celecoxib. One and 2 weeks later, rats received s.c. injections of AOM at a dose of 15 mg/kg of body weight. At 17 weeks of age, all rats were sacrificed. Colons were evaluated for ACF, and colonic mucosae were assayed for COX and NOS isoform enzyme activities. Samples of venous blood, collected at various time points, were analyzed for these agents. SC-51, administered alone, demonstrated dose-dependent inhibition of the incidence of colonic ACF. The highest doses of SC-51 (100 ppm) and AG (1800 ppm) significantly suppressed the incidence of colonic ACF (P < 0.01 and < 0.001, respectively) and crypt multiplicity in terms of numbers of aberrant crypts/focus (P < 0.0001). Importantly, the combination of either low or high effective doses of SC-51 (30 or 100 ppm) and celecoxib (500 ppm) suppressed AOM-induced colonic ACF formation (P < 0.05 and < 0.001, respectively) and reduced multiplicity of four or more aberrant crypts/focus (P < 0.0001) to a greater extent than did these agents administered individually. As expected, sulindac inhibited colonic ACF formation (P < 0.001) and reduced the multiplicity of four or more aberrant crypts (P < 0.0001) to approximately 45%. The enzymatic activities of COX-2 and iNOS were significantly induced in the AOM-treated animals, and administration of the iNOS inhibitors, SC-51 and AG, significantly inhibited the activities of both iNOS and COX-2 in the colonic mucosa. The combined administration of SC-51 and celecoxib inhibited the COX-2 activity to a greater extent than did either of these agents administered alone. These findings support the hypothesis that selective iNOS inhibitors may have chemopreventive properties and that coadministration with a selective COX-2 inhibitor may have additional chemopreventive potential.

Animals↗

PubMed1995

Differences in the avidity of TCR interactions with a superantigenic ligand affect negative selection but do not allow positive selection.

The products of the sag genes of the exogenous mouse mammary tumor virus (MMTV) genome and of endogenous Mtv integrants have been demonstrated to affect the T cell repertoire in mice by causing the deletion of T cells expressing receptors encoded by particular V beta gene segments. Since these deletions affect large populations of T cells with receptors of heterogeneous specificity, they serve as an important model for the study of T cell development in normal mice. Using several C3H/HeN-based strains that express different MMTV(C3H) transgenes, we demonstrate here that the stage of development at which T cell deletion occurs is determined by the level of ligand expression. Although at low levels of ligand expression in the thymus some signs of activation were observed in immature thymocytes, we were unable to detect a level of Sag expression that led to net positive selection. Moreover, we detected a level of Sag-transgene expression that did not cause negative selection in the thymus; no signs of positive selection were observed either. Inclusion of the env gene in the construct, earlier shown to markedly potentiate stimulation by Sag in mixed lymphocyte reactions, also markedly increased the ability of Sag to drive negative selection. These data are interpreted as showing that marked quantitative differences in expression of superantigens does not reveal a level at which only positive selection occurs. This, in turn, suggests that positive selection will occur on ligands distinct from those that drive clonal deletion.

Aging↗

PubMed2005

Selection of high-producing CHO cells using NPT selection marker with reduced enzyme activity.

We developed an expression system that aimed to increase the proportion of high producers in a transfected cell population in order to reduce the effort in clone screening. The principle is based on the impairment of the selection marker. Twelve single-point mutations in more or less conserved domains of the resistance marker gene neomycin-phosphotransferase (NPT) resulted in different degrees of reduced enzyme activity, depending on the amino acid conservation and the kind of amino acid exchange. In all transfected, mutant-NPT bearing CHO-DG44 cell pools surviving the selection with G418, the ratio of high-producing cells to total cell number was higher than in pools selected with wildtype-NPT. Furthermore, these pools showed, in comparison to wildtype-NPT selected pools, not only higher NPT-RNA levels but also increased specific productivities and higher titers of a coexpressed biopharmaceutically relevant product. Elevated productivity could be ascribed to higher gene copy numbers, integration into chromatin regions with higher transcriptional activity, or a combination of both effects. Thus, the use of NPT-mutants as selection markers is suitable for the enrichment of high producers in a transfected CHO-DG44 cell population, since cell survival is achieved only if the enzymatic impairment of the cointegrated resistance marker is compensated by a higher expression level.

Amino Acid Motifs↗

PubMed2002

Safe, highly selective use of pulmonary artery catheters in coronary artery bypass grafting: an objective patient selection method.

BACKGROUND: Routine versus selective use of pulmonary artery catheter (PAC) monitoring in coronary artery bypass grafting operations is a topic of significant debate. Accordingly, we retrospectively examined operative outcomes in 2,685 consecutive (1994 to 1998) coronary artery bypass grafting patients in whom PAC use was highly selective. Next, we developed a quantitative model of PAC use in terms of its multivariate predictors as a means of providing an objective criterion for patient PAC use selection. METHODS: Safety of the implemented selective PAC use was assessed by comparisons to contemporaneous coronary artery bypass grafting outcome reported by The Society of Thoracic Surgeons' national data. Continuous relations describing PAC use in terms of continuous univariate predictors were obtained using overlapping-range patient cohorts. Next, independent predictors of PAC use were derived by multivariate regression to best fit the categorical variable PAC (Yes = 1, No = 0). Model estimates were a continuous variable (PAC score) with values between 0 and 1. RESULTS: Planned use of PAC was based on collective consideration of preoperative patient variables, and was not limited to low-risk or preserved ejection fraction patients. Planned and unplanned use of PAC was limited to 176 (planned, 6.6%) and 66 (unplanned, 2.4%) patients, respectively, whereas no PAC was used in 2,443 (91%). Overall patient characteristics and risk factors in this series were comparable to contemporaneous Society of Thoracic Surgeons data, and the incidence of operative deaths was 2.31% (n = 61; observed-to-expected [Society of Thoracic Surgeons risk] mortality = 0.73). Independent predictors of PAC use were ejection fraction, Society of Thoracic Surgeons risk, intraaortic balloon pump, congestive heart failure, reoperative surgery, and New York Heart Association class IV. Expectedly, PAC scores were substantially different for PAC (mean +/- standard deviation, 0.37 +/- 0.20; median, 0.38) and no PAC (0.14 +/- 0.11; median, 0.10) patients (p < 0.001). Area under the receiver operating characteristic curve derived for PAC score was relatively high (area, 0.85). Moreover, the corresponding summed sensitivity (0.68 to 0.91) and specificity (0.85 to 0.62) was maximized at 1.53 for PAC score between 0.15 and 0.31. CONCLUSIONS: Our results indicate that highly selective use of PAC in coronary artery bypass grafting can be accomplished safely, and it need not be limited to patients with preserved ejection fractions or low operative risk. Indeed, coronary artery bypass grafting without PAC may be preferable in the vast majority of patients as it reduces catheter-associated risks and resource utilization without incurring an increased operative risk. Also, pending further prospective confirmation, our analysis suggests that collective consideration of PAC use predictors to derive a PAC score provides an objective criterion to minimize unnecessary use of PAC with an acceptably low probability of error.

Aged↗

PubMed1990

Selection during a selfing programme. I. The effects of a single round of selection.

Theory is presented to describe the effects of a single round of selection during a selfing programme in terms of both the mean and the genetical variance of the inbred lines produced. Response equations describing the effect on the inbred means are used to determine optimum breeding designs in a limited set of circumstances. These theoretical arguments are supported by computer simulations, and good agreement with expectation is found. The magnitude and direction of dominance is shown to be unimportant even in the case of early generation selection. A description of the reduction in genetic variance between selected lines is also presented and supported by simulation. Unlike the effects described by Bulmer in outbreeding populations, this reduction is fixed during a selfing programme. The simulation studies show that the additional variance generated by further segregation after selection may also be affected by selection, but the assumption that it is unaffected is found to be adequate.

Breeding↗

PubMed2006

Can biochemical properties serve as selective pressure for gene selection during inter-species and endosymbiotic lateral gene transfer?

During the evolution of endosymbiosis, only one orthologous gene, either from the invader or the invaded genome, is preserved. Genetic and environmental factors are usually invoked to explain this gene preference. How biochemical parameters can play a role in the selection of genes that code for enzymes that constitute a metabolic pathway is explored. Simple Michaelis-Menten-like enzymes are considered whose kinetic parameters are randomly generated to construct two parallel homologous pathways to account for the contributions of the invaded and the invader. Steady-state fluxes as targets of natural selection are focused. Enzymes are eliminated one by one so that the total flux through the pathway is least disturbed. Analysis of the results, done by different criteria, indicate that the maximal velocities, both forward and backward, are more influential in selection than the respective Michaelis constants. This inclination disappears as metabolite concentrations are increased. It is shown that kinetic selection criteria can result in a mosaicism of enzymes in the same pathway in terms of their genetic origin. Analysis of the results using the control coefficient paradigm disclosed an expected robust correlation between flux control coefficients of enzymes and their selective elimination. Similar analyses, performed for the case of single gene transfer or for gene replication with subsequent mutation, yielded essentially similar results. The results conform with the phenomenon of genetic mosaicism found in phylogenetic analyses of single or double endosymbioses and lateral gene transfer.

Animals↗