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PubMed2004

The impact of thymic antigen diversity on the size of the selected T cell repertoire.

The TCR repertoire of a normal animal is shaped in the thymus by ligand-specific positive- and negative-selection events. These processes are believed to be determined at the single-cell level primarily by the affinity of the TCR-ligand interactions. The relationships among all the variables involved are still unknown due to the complexity of the interactions and the lack of quantitative analysis of those parameters. In this study, we developed a quantitative model of thymic selection that provides estimates of the fractions of positively and negatively selected thymocytes in the cortex and in the medulla, as well as upper-bound ranges for the number of selecting ligands required for the generation of a normal diverse TCR repertoire. Fitting the model to current estimates of positive- and negative-selected thymocytes leads to specific predictions. The results indicate the following: 1) the bulk of thymocyte death takes place in the cortex, and it is due to neglect; 2) the probability of a thymocyte to be negatively selected in the cortex is at least 10-fold lower than in the medulla; 3) <60 ligands are involved in cortical positive selection; and 4) negative selection in the medulla is constrained by a large diversity of selecting ligands on medullary APCs.

Animals↗

PubMed2006

Detection of biofilm formation among the clinical isolates of Staphylococci: an evaluation of three different screening methods.

PURPOSE: The purpose of this study was to evaluate three methods for detection of biofilm formation in staphylococci. METHODS: For detection of biofilm formation, 152 clinical isolates of Staphylococcus spp. were screened by tissue culture plate (TCP), Tube method (TM) and Congo red agar (CRA) method. RESULTS: Of the 152 Staphylococcus spp. 88(57.8%) displayed a biofilm-positive phenotype under the optimized conditions in the TCP method and strains were further classified as high 22 (14.47 %) and moderate 60 (39.4 %) while in 70 (46.0 %) isolates weak or no biofilm was detected. Though TM correlated well with the TCP test for 18 (11.8 %) strongly biofilm producing strains, weak producers were difficult to discriminate from biofilm negative isolates. Screening on CRA does not correlate well with either of the two methods for detecting biofilm formation in staphylococci. CONCLUSION: The TCP method was found to be most sensitive, accurate and reproducible screening method for detection of biofilm formation by staphylococci and has the advantage of being a quantitative model to study the adherence of staphylococci on biomedical devices.

Agar↗

PubMed1993

Some computer-based decision support tools for the rehabilitation manager.

The recent introduction of the Management Information System (MIS) guidelines has sparked much interest among health care institutions across Canada regarding proper approaches to the recording and interpretation of various financial and workload indicators. While the benefits of the MIS guidelines are widely acknowledged, much less attention has been directed to how departmental managers can analyze and make use of the vast amount of information generated. In this paper we attempt to review some of the computer-based decision-support tools that may be useful to the manager of the rehabilitation services department in analyzing the various MIS data that are collected. The data are assumed to be available through a computerized rehabilitation information system which includes workload measures. The quantitative models reviewed in this paper include basic descriptive statistics, deviation, trend and what-if-analysis and graph-plotting. Although the use of such tools can assist the rehabilitation manager in the routine decision-making process, it is very important that we ask the right questions and employ the proper model to make the most rational and best decision. In this respect, ongoing training in general problem-solving skills, decision-making processes, and use of computer-based decision-support tools may be very beneficial.

Canada↗

PubMed1999

Aspartate-27 and glutamate-473 are involved in catalysis by Zymomonas mobilis pyruvate decarboxylase.

Zymomonas mobilis pyruvate decarboxylase (EC 4.1.1.1) was subjected to site-directed mutagenesis at two acidic residues near the thiamin diphosphate cofactor in the active site. Asp-27 was changed to Glu or Asn, and Glu-473 was mutated to Asp (E473D) or Gln (E473Q). Each mutant protein was purified to near-homogeneity, and the kinetic and cofactor-binding properties were compared with those of the wild-type protein. Despite the very conservative nature of these alterations, all mutants had a very low, but measurable, specific activity ranging from 0.025% (E473Q) to 0.173% (E473D) of the wild type. With the exception of E473Q, the mutants showed small decreases in the affinity for thiamin diphosphate, and binding of the second cofactor (Mg2+) was also weakened somewhat. With E473Q, both cofactors seemed to be very tightly bound so that they were not removed by the treatment that was effective for the wild-type enzyme and other mutant forms. All mutants showed minor changes in the Km for substrate, but these alterations did not account for the low activities. These low specific activities, accompanied by little change in the Km for pyruvate, are consistent with a quantitative model of the catalytic cycle in which the main effect of the mutations is to slow the decarboxylation step with a minor change in the rate constant for pyruvate binding.

Aspartic Acid↗

PubMed1986

An innovative approach to public health research: the case of a new center in Mexico.

This paper presents the conceptual and organizational elements that have guided the development of the Center for Public Health Research (CPHR) in Mexico. The CPHR was established in August 1984, in the midst of the most profound health care reform in Mexico in the last 40 years. The reform has included, among other measures, a Constitutional amendment recognizing the social right to health care, an energetic effort to decentralize the system so that each state will run its own services, an ambitious drive to extend primary health care coverage to all the population, and a strong promotion of research as the basis for strategic planning and for the development of standards of care. The creation of the CPHR is a response to the need for a firm base of epidemiologic and health systems research in Mexico. This need arises from the increasing complexity of the country's organizational arrangements for health care. In addition, the patterns of morbidity and mortality are also becoming more intricate, as Mexico is experiencing an epidemiologic transition whereby chronic diseases, mental ailments, and accidents are on the rise even as the incidence of infectious diseases and malnutrition continues to be high. As a unit of the Ministry of Health, the CPHR must strike a balance between relevance to decision making and excellence in the strict adherence to the norms of scientific research. To do so, it has developed a conceptual framework based on a tridimensional matrix. The dimensions of the matrix include substantive areas (i.e., the phenomena to be researched), knowledge areas (i.e., the disciplines pertinent to public health), and methodological areas (i.e., the methods to be applied in each project). The intersection of these dimensions produces different configurations of "research modules" that can be adapted to changing priorities. Current priorities of the CPHR include epidemiologic studies of the emerging conditions in the transition, migration and health, child survival, social organization and primary health care, health systems management, quality of care, and the development of information systems and quantitative models for public health research. Research projects are undertaken in a matrix type of organization in which academic departments are structured according to problems rather than disciplines. The analysis of Mexico's Center for Public Health Research may contribute to similar endeavors in other countries and also to the wider development of comparative studies on research organizations.

Mexico↗

PubMed1999

Computer-aided diagnostic system in dentistry.

A dental diagnostic system for patient database management, automated measurements, diagnostics and statistical estimation of health conditions is described. To increase the diagnosis quality various diagnostic tools are developed using several statistical methods. The analysis provides information about the importance of particular general, dental, and periodontal data which are further used in quantitative modeling of healing process in the oral cavity. The system supports clinician's diagnostic process and leads to improvement of decisions obtained by a conventional routine. Increased control and evaluation of different therapy types is enabled.

Computer Communication Networks↗

PubMed2000

Spatial convergence and divergence between cutaneous afferent axons and dorsal horn cells are not constant.

We have proposed a quantitative model of the development of dorsal horn cell receptive fields (RFs) and somatotopic organization (Brown et al. [1997] Somatosens. Motor Res. 14:93-106). One component of that model is a hypothesis that convergence and divergence of connections between low-threshold primary afferent mechanoreceptive axons and dorsal horn cells are invariant over skin location and dorsal horn location. The more limited, and more easily tested, hypothesis that spatial convergence and divergence between cutaneous mechanoreceptors and dorsal horn cell are constant was examined. Spatial divergence is the number of dorsal horn cells whose RFs overlap the RF center of a primary afferent, and spatial convergence is the number of afferent RF centers that lie within the RF of a dorsal horn cell. Innervation density was determined as a function of location on the hindlimb by using peripheral nerve recording and axon counting. A descriptive model of dorsal horn cell receptive fields (Brown et al. [1998] J. Neurophysiol. 31:833-848) was used to simulate RFs of the entire dorsal horn cell population in order to estimate RF area and map scale as a function of location on the hindlimb. Previously reported correlations among innervation density, map scale, and RF size were confirmed. However, these correlations were not linear. The hypothesis that spatial convergence and divergence are constant was rejected. The previously proposed model of development of dorsal horn cell somatotopy and RF geometries must be revised to take variable spatial convergence and divergence into account.

Afferent Pathways↗

PubMed2000

Validation of an analytic method of calculating cerebral glucose metabolism using PET.

UNLABELLED: Quantitative modeling of cerebral metabolic rate for glucose (CMRglc) using PET with the FDG method requires calculation of the integral of the time course of radioactivity in arterial plasma. Numeric integration has typically been used but requires 30 or more blood samples taken between 15 s and 100 min after injection of the radiotracer. Our laboratory has developed an alternative integration method that fits the values of the plasma samples to an analytically integrable function using only 4-6 samples taken between 40 and 110 min after radiotracer injection. METHODS: The plasma integrals were calculated by both the analytic and the numeric methods with data from FDG PET studies that were not used in the development of the analytic method. In 39 PET studies from 22 healthy volunteers, 30 plasma samples were taken over 110 min. RESULTS: The plasma integrals determined by the analytic and numeric methods yielded a within-subject correlation coefficient of >0.95 and differences of <10%. CONCLUSION: Because the analytic method requires less blood sampling and does not require sampling immediately after radiotracer injection, the experimental procedure is simplified without loss of accuracy in CMRglc computation, and the effect of missing or incorrect samples is reduced.

Adult↗

PubMed2000

Horizontal Distribution Patterns of Testate Amoebae (Protozoa) in a Sphagnum magellanicum Carpet.

The distribution of soil microorganisms is generally believed to be patchy and to reflect habitat heterogeneity. Despite this general rule, the amount of existing data on species distribution patterns is scarce. Testate amoebae (Protozoa; Rhizopoda) are an important component of soil microbial communities and are increasingly used in ecological and paleoecological studies of Sphagnum-dominated peatlands, but data on the spatial structure of communities are completely lacking. This is an important aspect since quantitative models used for paleoecological reconstruction and monitoring are based on species assemblages. We explored the distribution patterns of testate amoebae distribution in a macroscopically homogeneous Sphagnum carpet, down to a scale of several centimeters. Distributions maps of the species and spatially constrained sample groups were produced. Multivariate and individual spatial autocorrelations were calculated. The importance of spatial structure was quantified by canonical correspondence analysis. Our ultimate goal is to find the finest resolution of environmental monitoring using testate amoebae. The distribution patterns differed among species, resulting in a complex spatial structure of the species assemblage in a whole. Spatial structure accounted for 36% of the total variation of species abundance in a canonical correspondence analysis constrained by spatial variables. This structure was partly correlated to altitude (microtopography) at a very fine scale. These results confirmed the existence of significant broad- and fine-scale spatial structures within testate amoebae communities that could in part be interpreted as effects of ecological gradients. This shows that, on a surface area of 0.25 m(2), ecological conditions which look uniform from a macroscopic point of view are not perceived as such by Sphagnum-inhabiting organisms. Therefore, testate amoebae could prove very useful to monitor fine-scale ecological processes or disturbances. Studies of the species' spatial distribution patterns in combination with autoecological studies are needed and should be included in the toolbox of biomonitoring itself.

Journal Article↗

PubMed2000

[RFLP analysis on wide compatibility genes in rice variety dular of ecotype aus].

Dular is one of the typical wide compatibility varieties in ecotype Aus of rice. Genetic analysis on wide compatibility genes (WCG) from Dular based on triple crosses (indica//++Dular/japonica) was conducted. In the condition of being shaded for 7 days, the individual spikelet fertility segregated obviously, and the continuous distributions of spikelet fertility with a handful of peaks were observed. This suggested that the segregation of spikelet fertility in triple cross populations was controlled by one or more major genes, also modified by some minor genes. Based on 109 individuals of triple cross Nanjing 11 (indica)//++Dular/2533(japonica, a marker gene line, Rc and g), fertile and semisterile pools were set up by bulked segregant analysis, the RFLP analysis of the two pools led to the discovery of three chromosomal segments co-segregating with fertility. The one is on the interval RG213-C235 on chromosome 6. According to the previous studies, it may be the wide compatibility gene S5n. The other two were on the interval RG901-RG413 and G402-RG651 on chromosome 12, temporarily designated as Sd1(t)n and Sd2(t)n, respectively. Because of the continuous distribution for spikelet fertility, we also used a quantitative model to evaluate the effects of those three loci. On the basis of interval analysis with Mapmaker/QTL, 32.3% of the phenotypic variance associated with spikelet fertility was explained by the S5n (LOD = 9.03), and the other two chromosomal segments were responsible for 10.5%(LOD = 2.61) and 10.9%(LOD = 2.14) phenotypic variance, respectively. The results demonstrated that the wide compatibility variety Dular contained three WCGs. To introgress the three WCGs into a restorer line or an abortive line will overcome the hybrid sterility barrier of indica/japonica crosses, and the precise RFLP mapping will be useful for breeders to accumulate a few genes of interest into one cultivar by means of molecular marker assisted selection.

Chromosome Mapping↗

PubMed2001

Estimating near-infrared leaf reflectance from leaf structural characteristics.

The relationship between near-infrared reflectance at 800 nm (NIRR) from leaves and characteristics of leaf structure known to affect photosynthesis was investigated in 48 species of alpine angiosperms. This wavelength was selected to discriminate the effects of leaf structure vs. chemical or water content on leaf reflectance. A quantitative model was first constructed correlating NIRR with leaf structural characteristics for six species, and then validated using all 48 species. Among the structural characteristics tested in the reflectance model were leaf trichome density, the presence or absence of both leaf bicoloration and a thick leaf cuticle (>1 μm), leaf thickness, the ratio of palisade mesophyll to spongy mesophyll thickness (PM/SM), the proportion of the mesophyll occupied by intercellular air spaces (%IAS), and the ratio of mesophyll cell surface area exposed to IAS (A(mes)) per unit leaf surface area (A), or A(mes)/A. Multiple regression analysis showed that measured NIRR was highly correlated with A(mes)/A, leaf bicoloration, and the presence of a thick leaf cuticle (r = 0.93). In contrast, correlations between NIRR and leaf trichome density, leaf thickness, the PM/SM ratio, or %IAS were relatively weak (r < 0.25). A model incorporating A(mes)/A, leaf bicoloration, and cuticle thickness predicted NIRR accurately for 48 species (r = 0.43; P < 0.01) and may be useful for linking remotely sensed data to plant structure and function.

Journal Article↗

PubMed2001

Reducing the risk of breast cancer with tamoxifen in women at increased risk.

Validated quantitative models are available that permit the accurate estimation of a woman's risk of developing invasive breast cancer during a specified period of time. Data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial indicate that tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. All premenopausal women whose 5-year risk of developing breast cancer is 1.67% or greater derive a net benefit from taking tamoxifen for risk reduction. Women who have either lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia derive an even greater net benefit. Women who carry mutations in either the BRCA1 or BRCA2 gene will also experience reduced incidence of breast cancer with tamoxifen. Although postmenopausal women derive a net benefit from tamoxifen through the reduction of both breast cancer and bone fracture event rates, the risks of both invasive endometrial cancer and thromboembolic events must be balanced in older women. Physicians should identify appropriate candidates with whom to discuss the possible benefits of tamoxifen for reducing the risk of breast cancer.

Adult↗

PubMed2001

Health behavior in a kibbutz population: correlations among different modalities of healthcare utilization.

BACKGROUND: Alternative medicine use is increasing worldwide and the associated expenditures are significant. In Israel 19% of patients who consulted their family physician had also sought treatment by an alternative medicine practitioner. OBJECTIVES: To explore the correlation between different modalities of healthcare utilization, health behavior, and health belief among adult members of a kibbutz (rural communal settlement). This unique study population enabled the use of a simplified quantitative model due to the minimal individual differences in cost and access. METHODS: Healthcare utilization data were obtained for 220 kibbutz members aged 15-70 years from patient medical files and self-administered questionnaires over a 45 month period. Patient visits to the family practitioner and other specialist physicians were tallied, and individuals reported alternative medicine consultations during the previous year. Multiple regression analysis was used to control for age, chronic disease, and other background characteristics. RESULTS: The mean number of patient FP visits was 3.6 per patient per year. Women and chronic disease sufferers visited the doctor more frequently. A patient's number of FP visits and other specialist physician visits were closely correlated, with each specialist physician consult resulting in an additional 0.64 FP visit for a given individual (P = 0.007). Our analysis indicated that self-reported alternative therapy utilization was positively associated with the number of FP visits; patients reporting alternative therapy use visited their primary care physician once additionally per year (P = 0.03). Low self-rated health status was correlated with increased likelihood of alternative therapy use (borderline significance). CONCLUSION: These results suggest that a patient who seeks treatment from one type of healthcare practitioner will seek out other practitioners as well. This study supports the notion that unconventional therapies are used in conjunction with, rather than instead of, mainstream medical care.

Adolescent↗

PubMed2001

High gene flow levels lead to gamete wastage in a desert spider system.

Field censuses, breeding experiments, and a quantitative model are used to obtain insight into the extent and consequences of genetic mixing between locally adapted populations of a desert spider. Typically, 9% of the matings of desert riparian spiders (non-aggressive phenotype) in native habitat involve an arid-land partner (aggressive phenotype). Mating was found to be random with respect to behavioral phenotype, but linearly related to both the rate of immigration and survival of immigrants from surrounding arid habitats in the riparian area. Genetic mixing between riparian and arid-land spiders produces offspring that exhibit lower rates of survival in riparian habitat. Two extreme behavioral phenotypes were also observed in the field studies: approximately 5% of the female spiders attacked all males they encountered while another 22% ran from all potential mates. Punnett square analyses of the potential genotypes produced by introgression between arid- and riparian-adapted spiders indicate that these extreme phenotypes appear in F2 generation hybrids and backcrosses. Because there is a costly wastage of gametes in the case of mixed phenotype mating, model results indicate that within three generations of the cessation of gene flow, the riparian population would be free of mixed genotypes and moving towards genetic differentiation.

Alleles↗

PubMed2002

Interference in implicit memory caused by processing of interpolated material.

This study addresses the susceptibility of implicit memory to interference. Interference is manipulated by presenting interpolated lists of words that do or do not have word stems in common with previously studied target words (e.g., target word paragraph followed by interpolated words such as paradise or vicinity). Interference in a word stem completion task occurred only when words had similar word stems (Experiment 1). Increasing the number of interpolated words with corresponding word stems (e.g., not only paradise but also parking, pardon, and parliament) produced increasing amounts of interference (Experiment 2). Interference in implicit memory appears to be a simple response competition phenomenon that occurs when cues simultaneously activate primed targets and primed competing responses. The amount of interference can be explained by a quantitative model of the relative strengths of target and competing responses.

Adult↗

PubMed2002

n-3 fatty acid deficiency alters recovery of the rod photoresponse in rhesus monkeys.

PURPOSE: Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid within rod outer segments. Varying the dietary content of DHA or its precursor, alpha-linolenic acid (ALA), can alter retinal DHA levels. The purpose of the present study was to assess rod phototransduction and recovery in rhesus monkeys raised on diets with different DHA and ALA content. METHODS: Adult rhesus monkeys had consumed from birth a diet low in ALA (0.3%) and known to induce an 80% reduction in retinal DHA. They were compared with groups receiving 8% ALA or 0.6% DHA, both of which support normal retinal DHA levels. Rod recovery was assessed with a double-flash protocol using a-wave saturating test flashes. The recovery of rod-isolated ERG a-wave amplitude was analyzed to determine Tc, the time to initiation of rod recovery, and T50, the time from initiation to 50% of full recovery. Phototransduction was assessed from the fit of a quantitative model to the leading edges of rod-isolated ERG a-waves. ERG a- and b-wave amplitudes and implicit times were also measured. RESULTS: Rod recovery (T50) was delayed by 30% and ERG implicit times by 5% in monkeys in the low ALA group compared with the other groups. There was no significant effect of diet on ERG amplitudes, the time to initiation of rod recovery, or the parameters describing phototransduction. CONCLUSIONS: The results indicate that mechanisms involved in deactivation and rod recovery are selectively altered in monkeys raised on a low-ALA diet whereas, at the flash intensities used, the mechanisms underlying phototransduction remain unaffected.

Animals↗

PubMed1990

[The impact of demographic variables on the quality of the environment].

"This paper discusses the impact of changes in the [size] of population on [the] natural environment. The discussion includes a quantitative model on the mechanism of the demographic impact on population pressure. The paper concludes that population growth is not the main 'villain' of the deterioration of natural environment. Rather, high population growth will worsen the already bad condition of [the] natural environment. Therefore, efforts in reducing population rate will...[curb environmental] problems...." The geographical scope is worldwide. (SUMMARY IN ENG)

Demography↗

PubMed2002

Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands.

Cytosolic long-chain fatty acid binding proteins (FABPs) are found in tissues that metabolize fatty acids. Like most lipid binding proteins, their specific functions remain unclear. Two classes have been described. Membrane-active FABPs interact directly with membranes during exchange of fatty acids between the protein binding site and the membrane, while membrane-inactive FABPs bind only to fatty acids that are already in aqueous solution. Despite these binding proteins, most fatty acids in cell cytoplasm appear to be bound to membranes. This paper reviews data suggesting that FABPs catalyze transfer of fatty acids between intracellular membranes, often across considerable intracellular distances. This process occurs in three distinct steps: dissociation of the fatty acid from a 'donor' membrane, diffusion of the fatty acid across the intervening water layer, and binding to an 'acceptor' membrane. Membrane-active FABPs catalyze dissociation of the fatty acid from the donor membrane and binding to the acceptor membrane, while membrane-inactive FABPs catalyze diffusion of fatty acids across the aqueous cytosol. Thus, FABPs catalyze all three steps in intracellular transport. A simple quantitative model has been developed that predicts the rate of intracellular transport as a function of the concentration, affinity and diffusional mobility of the binding protein. Different FABPs may have evolved to match the specific transport requirements of the cell type within which they are found.

Animals↗