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Results for “Step selection function”

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At least 19 recordsLinked to original sources
PubMed1991

Mean square error of estimates of HIV prevalence and short-term AIDS projections derived by backcalculation.

We simulated multinomial AIDS incidence counts from 27 'representative' AIDS epidemics that spanned a period corresponding to previous applications of backcalculation (1 January 1977 to 1 July 1987) and assessed mean square error for several back-calculated estimators of HIV prevalence and short-term AIDS projections. Estimators were based on flexible model selection procedures that chose the best-fitting non-negatively constrained model of the infection curve from a family of possible step-function models. Selection of the best-fitting model from a family of four-step models each with a long last step of width of 4 or 4.5 years offered a favourable tradeoff between bias and variance when compared with selection from families of models with three steps or from families with a short last step. Five-step models performed as well as four-step models. Three-step models had substantially larger mean square error in some epidemic situations. Percentage root mean square error (PRMSE) for estimates of cumulative HIV prevalence as of 1 January 1985 was less than 14 per cent over a range of hypothetical epidemics of N = 50,000 infected individuals. PRMSE for short-term projections was less than 18 per cent. Estimates of cumulative HIV prevalence as of 1 July 1987 were substantially more uncertain and had a PRMSE of 33 per cent in the unfavourable case of a rapidly rising HIV epidemic. Estimates of cumulative HIV prevalence as of 1 July 1987 were positively biased in HIV epidemics with a rapidly decreasing recent HIV incidence rate and negatively biased in rapidly increasing HIV epidemics. Despite these uncertainties, we obtained useful estimates even for HIV epidemics with as few as 5000 infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed2025

Migration strategies, connectivity and corridor features of the partial migrant little bustard (Tetrax tetrax) across the Iberian Peninsula.

The study of migration ecology is crucial for understanding the factors and pressures affecting migratory species. Here, we studied the migratory ecology of the little bustard (Tetrax tetrax), a steppe bird that has suffered a sharp decline over recent decades, mainly due to agricultural intensification. Using 105 adult birds tagged across the main Iberian regions where the species is present (Alentejo, Extremadura, Ebro Valley, Northern Plateau, Southern Plateau and Guadalquivir Valley), we analysed the ratio of migratory and resident birds in each population and assessed their connectivity during the three main migratory periods (summer, winter and pre-breeding). Additionally, we describe the features of the migrations recorded in terms of length, duration and day period. Our results corroborate that little bustards can be considered partial migrants across Iberia, although the proportion of residents versus migrants varied between populations: the Alentejo (94.74%) and Northern Plateau (93.75%) had the highest proportion of migrants, followed by Guadalquivir Valley (81.82%), Extremadura (65.38%), Southern Plateau (55.56%) and Ebro Valley (25.93%). Migratory connectivity varied between periods: the pre-breeding and summering migrations showed a trend to move northwards, while birds moved southwards for winter. Regarding the migratory corridors obtained from the 253 migrations identified, we found three main routes: one corridor that connects the Northern Plateau with the western part of the Southern Plateau and Extremadura, another one that connects the Southern Plateau, Extremadura, Alentejo and Guadalquivir Valley, and one corridor that concentrates migrations within the Ebro Valley, and between the Ebro Valley and the Southern Plateau. Finally, analyses showed that little bustards migrate at night through areas dominated by herbaceous cover (avoiding tree-covered land and water bodies) and of low elevation and terrain roughness. Our results highlight the importance of developing an international and inter-regional conservation strategy to protect not only the breeding and wintering quarters, but also this endangered species' migratory corridors, thus supporting the viability of the metapopulation.

Brownian bridge kernel↗
PubMed1986

Isolation of new types of dexamethasone-resistant variants from a cAMP-resistant lymphoma.

We have developed a sequential selection procedure for the isolation of novel steroid-resistant variants of the murine thymoma WEHI-7. The first step involves the isolation of cell lines with an altered cAMP-dependent protein kinase (cAPK) activity by selection for resistance to dibutyryl cAMP (dbcAMP). The second step involves the selection for resistance to dexamethasone (dex) which results in the isolation of variants with decreased receptor function and a cAMPrdexr phenotype. The initial selection, to cAMPr, serves as a permissive step since isolation of spontaneous glucocorticoid resistance from wild-type WEHI-7 does not occur at a measurable frequency. The results demonstrate a potential role for cAPK in regulating the functional levels of glucocorticoid receptor and suggest that mutations in other cellular functions that affect receptor activity could lead to steroid resistance in lymphoid cells.

Animals↗
PubMed1989

Excitation of skinned muscle fibers by imposed ion gradients. IV. Effects of stretch and perchlorate ion.

Depolarizing ion gradients stimulate 45Ca release in skeletal muscle fibers skinned by microdissection. Several lines of indirect evidence suggest that sealed transverse (T) tubules rather than sarcoplasmic reticulum (SR) are the locus of such stimulatory depolarization. Two implications of this hypothesis were tested. (a) A requirement for signal transmission was evaluated from the stimulation of 45Ca efflux in fibers that had been highly stretched, an intervention that can impair the electrical stimulation of intact fibers. Length was increased over approximately 95-115 s, after loading with 45Ca and rinsing at normal length; prestimulus 45Ca loss due to stretch itself was very small. In the first study, stimulation of 45Ca release by KCl replacement of K propionate was inhibited completely in fibers stretched to twice slack length, compared with fibers at 1.05-1.1 times slack length. Identical protocols did not alter 45Ca release stimulated by caffeine or Mg2+ reduction, implying that SR Ca release per se was fully functional and inhibition was selective for a preceding step in ionic stimulation. In a second study, stimulation by choline Cl replacement of K methanesulfonate, at constant [K+] [Cl-] product, was inhibited strongly; total 45Ca release decreased 69%, and stimulation above control loss decreased 78%, in segments stretched to twice the length at which sarcomere spacing had been 2.2 micron, compared with paired controls from the same fibers kept at 2.3 micron. (b) Perchlorate potentiation of T tubule activation was evaluated in fibers stimulated at constant [K+] [Cl-] at normal length (2.3 micron); this anion shifts the voltage dependence of intramembrane charge movement and contractile activation in intact fibers. Perchlorate (8 mM) potentiated both submaximal stimulation of Ca2+-dependent 45Ca release by partial choline Cl replacement of K methanesulfonate and the small Ca2+-insensitive 45Ca efflux component stimulated by nearly full replacement in the presence of 5 mM EGTA. These results provide independent support for the hypothesis that the T tubules are the locus of stimulation by depolarizing ion gradients, with junctional transmission of this signal causing SR 45Ca release.

Animals↗
PubMed1985

Reliability of threshold, slope, and PB max for monosyllabic words.

The Auditec recordings of the CID W-22 monosyllables were used to generate test and retest intelligibility functions on normally hearing listeners and subjects with mild-to-moderate sensorineural hearing loss. The normally hearing subjects were tested with 50-word lists at SPLs ranging from 15 to 50 dB. Lists of 25 words were used with the hearing-impaired group. The functions were analyzed to assess the reliability of threshold (50% point), slope (20%-80% points), and maximum intelligibility (PB max). The 50% point was obtained at 28 dB SPL for the normally hearing listeners and at a sensation level (SL) of 12 dB respondaic thresholds for the hearing-impaired group. Very stable monosyllabic thresholds were found because 95% of the test-retest values were within 6 dB for both subject groups. Slopes of 4.9% per dB and 2.7% per dB were obtained for the normally hearing and hearing-impaired groups, respectively. Fair reliability was observed; 95% of the test-retest values encompassed a range of +/- 1.9% per dB for the normally hearing subjects and +/- 1.1% per dB for the hearing-impaired group. Although group slopes provide useful information for selecting the range and step size for generating psychometric functions, the value of routinely obtaining slope on an individual basis has not been demonstrated. Even though the same word lists were used for both test and retest measurements, reliability closely agreed with predicted results based on the binomial theorem. In contrast to the large variability for a single list of 25 words, very stable PB max scores were found when two or three scores were averaged on the plateau of the function.

Adult↗
PubMed1990

Protein engineering and the study of structure--function relationships in receptors.

Protein engineering is a powerful tool for studying relationships between receptor structure and function--providing that it is used and interpreted appropriately. Site-directed mutagenesis, deletion mutagenesis and construction of chimaeric proteins have all been used to characterize receptors. In this review, Walter Ward, David Timms and Alan Fersht describe the application of protein engineering, illustrating important concepts with experimental data. They explain that detailed study of function requires careful dissection of mechanistic steps. Care must also be taken when selecting replacement residues; mutation should not cause delocalized structural reorganization or else the true significance of functional change will remain unclear.

Humans↗
PubMed1990

Identified primary motoneurons in embryonic zebrafish select appropriate pathways in the absence of other primary motoneurons.

Accurate pathfinding is a crucial step in formation of a functional nervous system. Individually identified zebrafish primary motoneurons undergo a stereotyped temporal sequence of axonal outgrowth and pathway selection during which their growth cones follow a common pathway to a "choice point" and then select divergent cell-specific pathways that lead to separate muscle territories. The characteristic sequence of cell-specific pathway selection raises the possibility that the sequence of growth cone arrival at the choice point might determine pathway selection. To test this idea, we ablated identified primary motoneurons by laser irradiation, labeled the remaining primary motoneuron in the same hemisegment with a fluorescent dye, and followed its development through the end of embryogenesis. We found that the growth cone of each primary motoneuron has an independent ability to pioneer the common pathway and select its appropriate cell-specific pathway, even in the absence of all other primary motoneurons in the same hemisegment.

Animals↗
PubMed1992

Functional evaluation by gait analysis of various ankle-foot assemblies used by below-knee amputees.

Twelve different prosthetic feet were tested by 10 male subjects with right below-knee amputations. Level walking with each prosthetic foot was investigated using a pair of force plates. Five parameters were selected to compare the functional characteristics of the feet: 1) step length, 2) walking velocity on the sound side in relation to the prosthetic side, 3) depth of valley in the pattern of the vertical component of the floor reaction force, 4) efficiency of the deceleration and acceleration by the prosthetic foot, and 5) irregular patterns in the wave form of the fore and aft components of the floor reaction force. Each of the above parameters was rated numerically. The total score of the objective evaluation attained by analysing the five parameters showed some coincidence to the results of subjective evaluation. However, a good correlation existed between the objective negative score and the subjective negative rating (p < 0.05). Non-axial feet developed recently, such as the SAFE II and Seattle Light feet achieved higher scores in the older age group, while single-axis feet, such as the LAPOC and Otto Bock feet achieved higher scores in the younger age group (p < 0.05).

Adult↗
PubMed1988

Efficient one-step selection of hepatoma cell variants of a variety of phenotypes by use of aflatoxin B1.

We have developed a method to select for rat hepatoma cells that fail to express hepatocyte-specific functions. Well-differentiated cells descended from the H4IIEC3 hepatoma line express aldrin epoxidase (AE) activity, an indicator of the liver-specific forms of cytochromes P450 and, concurrently, are able to activate the procarcinogen aflatoxin B1 (AFB1) into highly toxic metabolites. Thus, differentiated hepatoma cells are highly sensitive to AFB1, while dedifferentiated derivatives, which fail to express AE activity, are resistant. Exposure of differentiated Fao cells to 10 microM AFB1 for 24 h permits the isolation, at a frequency of 5 x 10(-5), of resistant colonies that exhibit strongly reduced AE activity. Strikingly, various morphological types can be observed. In more than 90% of the colonies, cells are morphologically similar to the original differentiated cells and accumulate all liver-specific mRNAs examined in amounts comparable to Fao cells. Moreover, they are able to carry out gluconeogenesis, as judged by their capacity to grow in glucose-free medium. For a minor fraction of colonies, the cells exhibit nonhepatic morphology. These cells fail to express three or more of the liver functions and are not able to proliferate in glucose-free medium. Our results demonstrate that the use of AFB1 constitutes a simple and efficient single-step selective method for obtaining variant hepatoma cells of a wide variety of phenotypes.

Aflatoxin B1↗
PubMed1976

Responses of complex cells in the visual cortex of the cat as a function of the length of moving slits.

(1) As a step towards specifying the spatial selectivity characteristics of complex cells with spatially periodic substructures, we have studied single cell responses to narrow slits of variable length moved across the receptive field in the preferred direction. In general, the length-response curves were linear over a considerable and sometimes full range until an optimal slit length was reached. (2) In those cells in which the rate of rise of the slit length-response functions decreased before the optimal length was reached, at least 3 factors contribute to the shape of the curve. First, the receptive field shapes of some complex cells are more ovoid or rounded than rectangular, and the summation of responses from excitatory zones of varying optimal lengths itself results in a nonlinear slit length-response function at long slit lengths. Second, central regions may contribute more to cell response than do more lateral regions along the length dimension. Third, a nonlinearity in the slit length-response curve may occur in the upper range of slit lengths as a saturation effect because discharge rates may reach 600/sec, which appears to be close to a limiting firing rate. (3) Some cells believed to be complex during preliminary receptive field testing showed weak inhibitory regions beyond the region of the optimal slit length. Many of these cells also displayed periodic average response histograms to moving slits. The extent and magnitude of the inhibition were variable from cell to cell. In terms of receptive field properties, these cells and 'regular' complex cells seem part of a continuum.

Animals↗
PubMed1991

Centromere formation in mouse cells cotransformed with human DNA and a dominant marker gene.

A 13,863-base-pair (bp) putative centromeric DNA fragment has been isolated from a human genomic library by using a probe obtained from metaphase chromosomes of human colon carcinoma cells. The abundance of this DNA was estimated to be 16-32 copies per genome. Cotransfection of mouse cells with this sequence and a selectable marker gene (aminoglycoside 3'-phosphotransferase type II, APH-II) resulted in a transformed cell line carrying an additional centromere in a dicentric chromosome. This centromere was capable of binding an anti-centromere antibody. In situ hybridization demonstrated that the human DNA sequence as well as the APH-II gene and vector DNA sequences were located only in the additional centromere of the dicentric chromosome. The extra centromere separated from the dicentric chromosome, forming a stable minichromosome. This functional centromere linked to a dominant selectable marker may be a step toward the construction of an artificial mammalian chromosome.

Animals↗
PubMed1978

Distinguishing between malignant and cirrhotic ascites by computerized step-wise discriminant functional analysis of its biochemistry.

This study was designed to evaluate the ability of a specifically programmed computer to select those biochemical substances most capable of distinguishing "cirrhotic ascites" from "malignant ascites". After simultaneously performing selected biochemical and electrophoretic studies on fresh unstored serum and ascites of 23 patients with documented cirrhosis and 18 patients with proven malignancies, computerized step-wise discriminant analysis of the multiple input revealed that the serum-to-ascites LDH ratio was able to distinguish "cirrhotic ascites" from "malignant ascites" with greater than 86% accuracy. Assignment to proper groups was increased to 89% with the addition of the ratio to serum total protein-to-ascites total protein. The predictive value of a positive result was 100%; specificity was 100%; the predictive value of a negative result was 85%. This type of computer analysis also permits incorporation of both additional cases and new substances thus increasing predictability and reducing type II statistical errors.

Albumins↗
PubMed1977

Effect of microtubular or translational inhibitors on general cell protein degradation. Evidence for a dual catabolic pathway.

Rat embryo fibroblasts were grown in Eagle's minimal essential medium with 10% serum and cell proteins prelabelled with L-[1-(14)C]leucine, followed by a 24h chase. When transferred to medium deprived of serum these cells showed a 2--3-fold increase in the production of trichloroacetic acid-soluble radioactivity during a 4h observation period. The microtubular poisons vinblastine, vincristine and colchicine partially inhibited this induced proteolysis, but had no effect on the proteolytic rate of cells maintained in medium with 10% serum. A similar discriminating effect on induced proteolysis was observed with cycloheximide, puromycin and insulin. The inhibitory effects of cycloheximide and vinblastine were not additive. These data support the hypothesis that, in addition to the basal turnover of cell proteins, a second mechanism of protein degradation involving cytoplasmic autophagy can be activated by nutritional step-down and is selectively inhibited by agents that interfere with microtubular function and protein synthesis.

Animals↗
PubMed1989

[Nuclear medicine in Germany: a look back at the beginning].

The development of nuclear medicine in Germany from early approaches with 32P and 131I to the first radioiodine therapy of thyroid cancer up to the clarification of basic principles for current thyroid diagnostics and for functional scintigraphic imaging are presented. Selected references are used in portraying scientific stepping stones of our speciality as well as its establishment in clinical practice during the first two decades. Researchers, places, and facts are specified and interpreted in their relation to the state-of-the-art of nuclear medicine.

Germany↗
PubMed1992

Discriminant analysis when all variables are ordered.

Determination of the equation that relates an ordered dependent variable to ordered independent variables is sought. One solution, non-parametric discriminant analysis (NPD), involves obtaining the best monotonic step function by means of a computer search procedure. Although one can use alternative selection criteria in obtaining the equation, the illustrative examples use absolute distance. This paper compares the prediction procedures obtained from NPD with those from linear discriminant analysis, linear regression (with and without transformed variables), and logistic regression. We show that NPD is analogous to regression tree analysis with incorporation of ordered variables and monotonicity. We use various prediction functions to predict the example data, the data using the leave-one-out technique, and a verification set. Consistently, non-parametric discriminant analysis performs as good as or better than the tested alternatives.

Craniocerebral Trauma↗
PubMed2026

Large-scale benchmarking of prokaryotic annotation tools across thousands of species.

BACKGROUND: Genome annotation is an important step in deriving functional meaning from prokaryotic sequencing data, yet systematic evaluations guiding tool selection are lacking. We present the first large-scale investigation of four prominent open-source annotation tools (Prokka, Bakta, EggNOG-mapper, and PGAP) across 156,033 diverse genomes. This includes Escherichia coli strains for baseline performance, thousands of archaea and bacteria genomes, as well as frameshifted and metagenome-assembled genomes. RESULTS: Bakta excels in annotating high-quality bacterial genomes, while PGAP was better for archaeal genomes and challenging bacterial assemblies, including metagenome-assembled, fragmented, or contaminated samples. For Gene Ontology annotation, PGAP consistently provides broader term coverage, whereas EggNOG-mapper offers more terms per feature. CONCLUSIONS: Our findings highlight tool-specific strengths crucial for selecting optimal solutions based on genome quality, taxonomy, and origin (e.g. MAGs). This study provides an evidence-based guide for users and informs future tool development.

Molecular Sequence Annotation↗
PubMed1988

[Genetics and phenogenetics of hormonal characteristics of animals. VIII. Analysis of the variability of the corticosteroid function of the adrenal cortex of silver foxes during their domestication].

The contribution of genetic and environmental components in phenotype variety of corticosteroid adrenal function was studied in undomesticated and domesticated silver foxes during postnatal ontogenesis. The variation of basal and stress plasma corticosteroid level in animals aged 2, 4, 6, 8 months and in vitro secretion of the adrenal gland at the age 8 months was analysed. Significant genotype-depended variability was only demonstrated in undomesticated foxes under stress stimulation conditions. This phenomenon is manifested from the fourth month of life. However, significant genotype-depended variability was already revealed under basal conditions in domesticated foxes, on initial steps of postnatal ontogenesis. The peculiarities of genetic variability of adrenocortical function in foxes selected for domestication are discussed.

Adrenal Cortex↗
PubMed1988

Benzothiopyranoindazoles, a new class of chromophore modified anthracenedione anticancer agents. Synthesis and activity against murine leukemias.

The synthesis of the benzothiopyranoindazoles, a new class of chromophore modified anthracenediones related to mitoxantrone, is described. In this structural class the quinone moiety, which is believed to be responsible for the cardiotoxicity of the anthracyclines, has been designed out. The synthesis of the benzothiopyranoindazoles was carried out by a multistep sequence from requisite 1-chloro-4-nitro-9H-thioxanthen-9-one precursors. Reaction with a monoalkylhydrazine gave a 5-nitrobenzothiopyranoindazole adduct, which was catalytically reduced to a corresponding C-5 anilino intermediate. Alkylation of 7 with a requisite X(CH2)nNR1R2 (X = Cl, Br; R1, R2 = H, alkyl, acyl; n = 2,3) provided target "two-armed" benzothiopyranoindazoles or A-ring methoxy and/or side chain acyl intermediates, which could be converted to 3 by appropriate deprotection methodologies. Alternatively, certain target compounds 3 were synthesized by reaction of 7 with appropriately functionalized glycine precursors under Schotten-Bauman or BOP chloride condensation conditions to provide C-5 acylamino intermediates, followed by Red-Al reduction and deprotection steps. Described also is the synthesis of selected benzothiopyranoindazole congeners with proximal acylamino side chains at C-5 and B-ring sulfone functionality at S-6. Potent activity was demonstrated against murine L1210 leukemia in vitro (IC50 = 10(-7)-10(-9) M) as well as against P388 leukemia in vivo over a wide range of structural variants. In general, activity against the P388 line was maximized by (a) a basic side chain at N-2 and a dibasic side chain at C-5 with primary or secondary distal amine substitution, (b) certain patterns of A-ring hydroxylation with 8-OH and 9-OH most favorable, and (c) sulfide oxidation state at S-6. Besides having curative activity against the P388 line, the more active compounds were curative against murine B-16 melanoma in vivo. On the basis of their exceptional broad-spectrum in vivo anticancer activity, selected compounds in this series have been chosen for development toward clinical trials.

Animals↗