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At least 1,423 records · Page 79Linked to original sources
PubMed1988

Simulation of genetic control of reproduction in beef cows. IV. Within-herd breeding value estimation with pasture mating.

Procedures for breeding value estimation for reproductive traits under pasture mating conditions were developed and tested using a computer simulation model of genetic control of bovine reproduction. The model generated annual calving rates (BCR) (0 or 1) and calving dates (CD) for each cow as a function of underlying genetic variation in two independent traits: single-service conception rate, which was indicative of the ability to conceive when estrus occurs, and postpartum interval (PPI) from calving to first estrus. Observed values for BCR and CD were shown to be complex, nonlinear functions of breeding values for ability to conceive (CRG) and for postpartum interval (PPIG) and of the previous CD. Effects of CRG on BCR and CD were small at high values of CRG, but these effects increased as CRG declined. Effects of PPIG on BCR and CD were small for cows that previously calved within the first 21 d of the calving season, but these effects increased for cows that calved after d 21. Previous CD had substantial nongenetic carryover effects on both BCR and CD. Unbiased estimates of CRG and PPIG could not be derived in the absence of breeding information. However, CD were reasonably highly correlated with breeding values for ability to conceive, provided information on open cows was included in the evaluation. Calving dates were only weakly associated with breeding values for PPI, in part because of the relatively short mean PPI (70 d) that was simulated.

Animals↗
PubMed1992

Computer-generated titanium cranioplasty: report of a new technique for repairing skull defects.

A review of 40 cases of titanium cranioplasty fabricated from impressions taken of the defect through the patient's scalp in the conventional way showed that 23% were ill-fitting and 41% of frontal plates had a poor aesthetic result. Attributable factors were difficulty in defining the defect border accurately and limited information of the surrounding tissue architecture which led to strains produced during insertion. Inadequate communication between surgeon and prosthetist compounded these difficulties. A prospective study of six cases fabricated from CT computer-generated models of challenging cranial defects appears to show significant improvements in plate design, resulting in better plate adaptation, stability and aesthetic contour. Plate insertion was rapid (mean time 27 min) thereby minimizing operating time. This paper also discusses the advantages of the enhanced information derived from CT and describes the potential for pre-craniotomy template and matching cranioplasty, thereby permitting a one-stage procedure.

Computer Graphics↗
PubMed1993

Stereoscopic imaging and its role in medical illustration.

Stereoscopic imaging is becoming more widespread as developments in computer software and hardware allow for rapid manipulation of electronically gathered medical data, and of computer-generated models. This paper examines the current three-dimensional multimedia scene, evaluates its place in training, and examines stereoscopic imaging and viewing techniques as well as the availability of stereoscopic equipment.

Depth Perception↗
PubMed2005

Relationship between glucose transport and metabolism in isolated bovine mammary epithelial cells.

Glucose transport by isolated bovine mammary epithelial cells involves translocation across the cell membrane into a compartment that exchanges slowly with the bulk cytosol. The significance to glucose metabolism of this compartmentalization was examined by generation, modeling, and analysis of transport and metabolism data. Net uptake of 5 mM 3-O-methyl-d-glucose by isolated bovine mammary epithelial cells was measured at 37 degrees C. Time-course curves were better fitted by a double exponential equation than a single exponential equation and were subjected to compartmental analysis to obtain glucose transport model parameters. Lactose synthesis and glucose oxidation rates and cellular concentrations of intermediary metabolites, glucose-6-phosphate and glucose-1-phosphate, were measured at varied media glucose concentrations. A model that integrates both glucose transport and metabolism under-predicted the rates of lactose synthesis and glucose oxidation by a factor of 3. To account for the observed glucose use rates, glucose must be available for phosphorylation once translocated across the cell membrane (intermediate compartmentalization of translocated glucose does not exclude access to hexokinase). Metabolic control analysis indicated that, at physiological glucose concentrations, phosphorylation by hexokinase exerts 80% of the control of glucose metabolism to lactose and CO(2), and transport exerts the remaining 20%.

3-O-Methylglucose↗
PubMed2026

Mechanism-Driven Diagnostic Development: A Specimen-Aware Framework Illustrated by Colorectal Cancer and Solid Tumours.

Translational oncology has moved rapidly from histopathology and single-analyte biomarkers toward multi-dimensional molecular profiling. Yet many clinically deployed tests still use reductionist biomarker strategies that under-represent cancer complexity. This review examines whether a mechanistic, multi-layered, and specimen-aware approach can improve cancer detection, classification, prognosis, minimal residual disease (MRD) assessment, and therapeutic selection. Evidence across solid tumours shows that genomic alterations alone incompletely explain tumour state, metastatic behaviour, immune evasion, or therapeutic vulnerability. Integrated genome and transcriptome analyses, proteogenomics, single-cell atlases, fragmentomic, methylation based cell-free DNA assays, metabolomics and microbiome assessments reveal clinically relevant biology that single modality tests cannot determine. Minimally invasive collected specimens can extend access to screening, diagnosis and longitudinal monitoring, but the choice of specimen should be matched to disease biology and analytes that represent mechanisms of oncogenesis. However, translation remains constrained by pre-analytical variability, contamination, differences in tumour shedding behaviour, clonal haematopoiesis, translation of generated models, incomplete external validation and uncertain downstream clinical utility for emerging platforms. This review provides a commentary on the future of cancer diagnostics, the considerations and barriers to clinical translation, the relationship between utility and dimensionality of biomarkers assessed and the emerging rationale towards mechanistically grounded integrated models.

biomarkers↗
PubMed2005

Predictors of common bile duct lithiasis in laparoscopic era.

AIM: To analyze retrospectively the records of 294 consecutive patients operated upon for gallbladder stones, to determine the predictive factors of synchronous common bile duct (CBD) stones and validate prospectively the generated model. METHODS: The prognostic estimation of a biochemical test and ultrasonography alone to differentiate between the absence and presence of choledocholithiasis was assessed using receiver operating characteristics curve analysis. Multivariate analysis was employed using discriminant analysis for establishment of a best model. Prospective validation of the model was made. RESULTS: Discriminant forward stepwise analysis disclosed that high values (> or = 2 x normal) of SGOT, ALP, conjugated bilirubin and CBD diameter on ultrasound > or = 10 mm were all prognostic factors of CBD lithiasis in univariate and multivariate analysis, P< 0.01. History was not included in the model. Prospective validation of the model was performed by multivariate analysis using Visual General Stepwise Regression. Positive predictive value, when considering all these predictors, was 93.3%, while the negative predictive value was 88.8%. Sensitivity of the model was 96.5% and specificity 80%. CONCLUSION: The above model can be objectively applied to predict the presence of CBD stones.

Adult↗
PubMed1994

When does a different environmental context make a difference in recognition? A global activation model.

The effects on recognition of changes in environmental context between learning and test are examined. A context effect occurs when memory tests that take place in an environmental context that is different from the learning context produce consistent differences in performance. A formal model of context-dependent recognition within a global activation framework is presented. The model generates the predictions that (1) context effects will be present when items are tested in a new context that was not seen during learning and (2) context effects will be absent or very small when items are tested in a context that was experienced during learning but that differs from the context in which the test item was learned. Both predictions were verified in an experiment that varied the nature of the different-context test within subjects. Implications for research concerned with context-dependent recognition are discussed.

Adult↗
PubMed2000

Granulysin, a T cell product, kills bacteria by altering membrane permeability.

Granulysin, a protein located in the acidic granules of human NK cells and cytotoxic T cells, has antimicrobial activity against a broad spectrum of microbial pathogens. A predicted model generated from the nuclear magnetic resonance structure of a related protein, NK lysin, suggested that granulysin contains a four alpha helical bundle motif, with the alpha helices enriched for positively charged amino acids, including arginine and lysine residues. Denaturation of the polypeptide reduced the alpha helical content from 49 to 18% resulted in complete inhibition of antimicrobial activity. Chemical modification of the arginine, but not the lysine, residues also blocked the antimicrobial activity and interfered with the ability of granulysin to adhere to Escherichia coli and Mycobacterium tuberculosis. Granulysin increased the permeability of bacterial membranes, as judged by its ability to allow access of cytosolic ss-galactosidase to its impermeant substrate. By electron microscopy, granulysin triggered fluid accumulation in the periplasm of M. tuberculosis, consistent with osmotic perturbation. These data suggest that the ability of granulysin to kill microbial pathogens is dependent on direct interaction with the microbial cell wall and/or membrane, leading to increased permeability and lysis.

Amino Acid Sequence↗
PubMed2001

Mutation of a single conserved residue in VH complementarity-determining region 2 results in a severe Ig secretion defect.

During an immune response, somatic mutations are introduced into the VH and VL regions of Ig chains. The consequences of somatic mutation in highly conserved residues are poorly understood. Ile51 is present in 91% of murine VH complementarity-determining region 2 sequences, and we demonstrate that single Ile51-->Arg or Lys substitutions in the PCG1-1 Ab are sufficient to severely reduce Ig secretion (1-3% of wild-type (WT) levels). Mutant H chains, expressed in the presence of excess L chain, associate with Ig binding protein (BiP) and GRP94 and fail to form HL and H2L assembly intermediates efficiently. The mutations do not irreversibly alter the VH domain as the small amount of mutant H chain, which assembles with L chain as H2L2, is secreted. The secreted mutant Ab binds phosphocholine-protein with avidity identical with that of WT Ab, suggesting that the combining site adopts a WT conformation. A computer-generated model of the PCG1-1 variable region fragment of Ig (Fv) indicates that Ile51 is buried between complementarity-determining region 2 and framework 3 and does not directly contact the L chain. Thus, the Ile51-->Arg or Ile51-->Lys mutations impair association with the PCG1-1 L chain via indirect interactions. These interactions are in part dependent on the nature of the L chain as the PCG1-1 VH single Ile51-->Arg or Ile51-->Lys mutants were partially rescued when expressed with the J558L lambda1 L chain. These results represent the first demonstration that single somatic mutations in V(H) residues can impair Ig secretion and suggest one reason for the conservation of Ile51 in so many Ig VH.

Amino Acid Sequence↗
PubMed2005

Suppressive effect of 1alpha,25-dihydroxyvitamin D3 on type I IFN-mediated monocyte differentiation into dendritic cells: impairment of functional activities and chemotaxis.

Dendritic cells (DCs) generated by a single-step exposure of human monocytes to type I IFN and GM-CSF (IFN-DCs) are endowed with potent immunostimulatory activities and a distinctive migratory response to specific chemokines. In this study, we evaluated the effects of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the biologically active metabolite of vitamin D(3), on the DC differentiation/activation induced by type I IFN. We found that 1,25(OH)(2)D(3) prevented the generation of IFN-DCs when added to freshly isolated monocytes, and was capable of redirecting already differentiated IFN-DCs toward a more immature stage, as revealed by their immunophenotype, reduced allostimulatory activity, and impaired LPS-induced production of Th1-polarizing cytokines. Control and 1,25(OH)(2)D(3)-treated IFN-DCs exhibited a similar expression of vitamin D receptor, as well as comparable cell death rates. Furthermore, the chemotactic response of IFN-DCs to CCL4 and CCL19 was markedly reduced or completely abrogated by 1,25(OH)(2)D(3). Despite these changes in the IFN-DC migratory behavior, the expression of CCR5 and CCR7 and the calcium fluxes triggered by CCL4 and CCL19 were not affected. These findings indicate that, in this innovative single-step DC generation model from monocytes, the suppressive effect of 1,25(OH)(2)D(3) is associated with a potent impairment of DC migration in response to inflammatory and lymph node-homing chemokines, thus unraveling a novel mechanism involved in 1,25(OH)(2)D(3)-mediated immunomodulation.

Cell Differentiation↗
PubMed1998

Heat resistance of Alicyclobacillus acidoterrestris spores as affected by various pH values and organic acids.

Alicyclobacillus acidoterrestris, a thermoacidophilic sporeformer, has caused spoilage of fruit juices which had been treated with thermal processes intended to commercially sterilize the juice. The objective of this research was to document the effect of pH, acid, and temperature on the heat resistance of spores of three fruit-juice isolates of A. acidoterrestris. The thermal resistance of spores of A. acidoterrestris strains VF, WAC, and IP were studied in a model fruit-juice system composed of 12% glucose and 30 mM of either citric, malic, or tartaric acid, adjusted to selected pH values ranging from 2.8 to 4.0. Decimal reduction times (D values) and inactivation rates were determined. Spores of strains VF and WAC were similarly resistant to heat under acidic conditions, while strain IP spores were less resistant. In the range of pH 2.8 to 4.0, a statistically effect of hydrogen ion concentration on heat resistance was observed at lower temperatures, but not at the higher temperatures, but not at the higher temperatures. For examples, at 91 degrees C and pH 3.1 and 3.7, D values were 31.3 and 54.3 min, respectively, while at 97 degrees C D values at pH 3.1 and 3.7 were 7.9 and 8.8 min, respectively. The type of acid did not significantly affect the heat resistance. The zd values ranged from 5.9 to 10 degrees C, depending on the acid, pH, and the strain. The models generated from this research can be used to determine adequate thermal processes, accounting for the acid type, pH, and temperature, to destroy A. acidoterrestris spores in beverages, since this organism is able to survive the typical hot-fill and hold process (2 min at 88 to 96 degrees C) currently used to process fruit juice.

Bacillaceae↗
PubMed2001

Malignant melanoma.

CONTEXT: The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches. OBJECTIVES: To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches. METHODS: Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center. RESULTS: Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches. CONCLUSIONS: (1) Melanoma is not genetically homogeneous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy.

Chromosome Aberrations↗
PubMed1999

Prediction of the systemic exposure to oral 9-amino-20(S)-camptothecin using single-sample analysis.

The purpose of this study was to develop and validate limited-sampling strategies for prediction of the area under the plasma-concentration time curves (AUCs) of the lactone and total (i. e., lactone plus carboxylate) forms of the novel topoisomerase-I inhibitor 9-amino-20(S)-camptothecin (9-AC). Complete pharmacokinetic curves for both drug species were obtained from 32 patients who received the drug orally in a clinical phase I setting at dose levels ranging from 0.25 to 1.10 mg/m2. The concentrations of the lactone and carboxylate forms of 9-AC in plasma were measured by HPLC. Using data from 20 randomly selected patients, forward-stepwise multivariate regression analysis was used to generate modeling strategies incorporating data from one, two, or three plasma samples. The simultaneous optimal prediction of both 9-AC lactone and 9-AC total AUCs was obtained with sample time points at 0.33, 3.0, and 11.0 h after drug dosing. Validation of the models on an independent data set comprising data of the remaining 12 patients demonstrated that 9-AC lactone and 9-AC total AUCs could be predicted sufficiently unbiased and precise using one and two time points: [AUC (ng. h/ml) = 7.103*C3 + 4.333] for 9-AC lactone and [AUC (ng. h/ml) = 9.612*C3 + 13.77*C11 - 44.11] for 9-AC total, where C3 and C11 represent the 9-AC plasma concentrations in ng/ml at 3 and 11 h after drug dosing. Application of the proposed models will be valuable in the determination of 9-AC population pharmacokinetics and permits treatment optimization for patients on the basis of individual pharmacokinetic characteristics through restricted drug monitoring in clinical routines.

Adolescent↗
PubMed1999

Expression of cyclins and cdks throughout murine carcinogenesis.

The overexpression and/or amplification of cell cycle regulating genes is an important factor in the progression of cancer. Recent attention has been focused on several cyclin and cdks genes whose expression were increased in many types of tumor. In this study, we investigated the expression kinetics of cyclins A, B, D1, E and cdks 1, 2, 4, 6 by RT-PCR coupled with densitometry and correlated to the growth fraction (percentage of S cells). This analysis was performed using an experimental murine leukemic model, generated by in vivo administration of murine clonogenic cells Wehi-3b injected into balb-c mice. Differential expression of cyclins and cdks was observed between normal and tumoral cells with different patterns of expression between G1 and G2M cyclins-cdks. G1 cyclins cdks expression was significantly increased in tumor cells when compared to normal cells. In the same manner, G2M cyclins cdks expression was only observed in tumor cells at a lower level than for G1 cyclins cdks, but not detected in normal cells. These differences correlated with the growth fraction for both the G1 cyclins cdks (r = 0.91, 0.94, 0.85, 0.90 and 0.96 for cyclin D1, cyclin E, cdk2, cdk4 and cdk6, respectively) and the G2M cyclins cdks (r = 0.96, 0.97 and 0.93 for cyclins A, B and cdkl respectively). Analysis of cyclins cdks expression kinetics during tumoral progression shows that cyclins A, B and cdkl were expressed from the 12th day on of disease, increased until the death of the animals and correlated with the growth fraction (r = 0.94, 0.95 and 0.97 for cyclins A, B and cdk1 respectively) (n = 20). Overexpression of other cyclins cdks were observed, from the 6th day on for cyclin D1, the 12th day for cdk2 and cdk4, the 15th day for cdk6 and the 20th day for cyclin E. These increases persisted during tumoral progression and correlated with the growth fraction (r = 0.85, 0.94, 0.93, 0.96, and 0.98 for cyclin D1, cyclin E, cdk2, cdk4 and cdk6, respectively) (n = 20). Our results demonstrated that G1 and G2-M cyclins cdks mRNA levels were increased at approximately the same time of maximal tumor growth. Only cyclin D1 overexpression occured at the initiation of tumoral development, and could therefore be considered as an early marker of cell proliferation.

Animals↗
PubMed2000

Scene dependence of the non-Gaussian scaling properties of natural images.

We report results on the scaling properties of changes in contrast of natural images in different visual environments. This study confirms the existence, in a vast class of images, of a multiplicative process relating the variations in contrast seen at two different scales, as was found in Turiel et al (Turiel A, Mato G, Parga N and Nadal J-P 1998 Self-Similarity Properties of Natural Images: Proc. NIPS'97 (Cambridge, MA: MIT Press), Turiel A, Mato G, Parga N and Nadal J-P 1998 Phys. Rev. Lett. 80 1098-101). But it also shows that the scaling exponents are not universal: even if most images follow the same type of statistics, they do it with different values of the distribution parameters. Motivated by these results, we also present the analysis of a generative model of images that reproduces those properties and that has the correct power spectrum. Possible implications for visual processing are also discussed.

Animals↗
PubMedDate not supplied

Nonlinear discriminant analysis and prognostic factor classification in node-negative primary breast cancer using probabilistic neural networks.

BACKGROUND: We used non-linear kernel discriminant analysis (KDA) to predict the outcome of 134 axillary node-negative primary breast cancer patients not treated with adjuvant therapy in a non censored database. MATERIAL: Posterior probabilities of relapse at 5 years were estimated using probabilistic neural networks (PNN) and a cross-validation (leave-one-out) technique to avoid overfitting the data. A stepwise method was used to construct the models to define the best combination of risk factors among eleven prognostic factors: age, menopausal status, Scarff-Bloom-Richardson grade, clinical tumor size, pathological tumor size, estrogen and progesterone receptor status, urokinase-type plasminogen activator, p53 protein level, c-erbB-2 protein and epidermal growth factor receptor. The different variables were tested individually and in combination to determine their prognostic power using a ROC indicator, which measures the separation between the probability distributions of the output neuron activations under the null hypothesis (no recurrence at 5 years) and under the alternative hypothesis (recurrence at 5 years). RESULTS: The best predictive one-dimensional model was obtained with uPA (ROC indicator = 0.75). A two-factor model including uPA and clinical tumor size (T) gave the best discrimination between recurrence and non recurrence at 5 years (ROC indicator = 0.84). Additional variables did not improve the accuracy of the prediction. The uPA-T model generated a map useful in predicting the posterior probability of cancer recurrence in a given patient. This representation allows the entire database to be easily visualized and each patient can be compared with the entire database. CONCLUSION: This is a powerful approach to analyze the impact of prognostic factors and it could find clinical applications in breast cancer.

Age Factors↗
PubMed2000

Anaerobic batch degradation of solid poultry slaughterhouse waste.

We studied anaerobic batch degradation of solid poultry slaughterhouse wastes with different initial waste and inoculum concentrations and waste-to-inoculum ratios and simulated the dynamics of the process with a new generation model. Our modelling results suggest that inhibited propionate degradation by long-chain fatty acids (LCFA) and inhibited hydrolysis by a high propionate concentration constituted the rate-limiting step in the waste degradation. Palmitate was the most abundant LCFA in the assays. Within 27 days of incubation, up to 0.55 to 0.67 m3 of methane (STP)/kg VS added was produced under the studied conditions. Lower waste-to-inoculum ratios exhibited a faster onset and rate of specific methane production. In all the assays, ammonification occurred within 3 to 6 days and accounted for 50 to 60% of total nitrogen.

Abattoirs↗
PubMed2001

Simulation studies of detection of a complex disease in a partially isolated population.

Simulation studies were undertaken with POPGEN, a new population simulation program, to explore strategies for detecting loci underlying rare and common disorders in a small population that has been partially isolated for 10 generations. Haplotype-sharing analysis (HSA) and non-parametric linkage analysis (NPL) were applied to the simulated haplotype and pedigree data for 100 cases, 100 controls, and an average of 28 multiplex pedigrees from cases' families, for a 2-5 cM map of markers. When identity by descent (IBD) status was known (using unique founder marker allele designations assigned during simulation), a linkage disequilibrium (LD) signal could be detected under disease-generating models predicting relative risk to sibs of 11.8 (high-RR) or 2.67 (mod-RR). Detection was more difficult when marker alleles were down-coded to resemble microsatellites (heterozygosities 0.75-0.80). False-positive peaks on nondisease chromosomes were uncommon. NPL analysis was more powerful than HSA at this marker density using down-coded alleles and assuming availability of all affected relatives. LD mapping of common disorders is likely to require denser maps of highly polymorphic markers to approximate full IBD information. LD and linkage mapping provide independent information, and strategies that combine these two methods could be useful in studies of small isolated populations.

Computer Simulation↗