Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “programmed genetic variation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1988

Positional variations in germinal cell growth in pigment-chimeric eyes of Xenopus: posterior half of the developing eye studied in genetic chimerae and in computer simulations.

Growth of germinal cells at different angular positions within the posterior portion of the embryonic frog eye has been examined by orthotopically transplanting small groups of germinal cells from pigmented (stage 30-38) donor embryos into albino (stage 28-36) hosts and then serially photographing the polyclonal-cell progeny domain (typically a black sector) in the pigmented retinal epithelium of the living, growing eye. Far-ventral (6 o'clock) germinal cells formed a narrow sector along the ventral fissure, but ventral germinal cells at a position just posterior to the fissure (7 o'clock on a right eye) were seen to expand rapidly their angular territory on the germinal zone and formed huge sectors that widened toward the front of the older larval eye. Posterior (8, 9, and 10 o'clock) germinal cells were seen to shift their angular positions gradually toward dorsal and formed sectors that appeared to veer dorsalward nearing the front of the older eye. Dorsal (11 o'clock) germinal cells showed attenuative growth, forming sectors that narrowed approaching the front of the older eye. A simulation model of the growth dynamic was used to examine how expansive growth ventrally drives the positional variations in growth. When far-ventral germinal cells were programmed to retain the 6 o'clock position and ventral (7 o'clock) germinal cells were programmed to divide symmetrically at a high probability to produce two daughter germinal cells, not only were the observed ventral chimeric patterns simulated, but also simulated were the attenuative growth of dorsal transplants and the dorsal displacement and veering seen in the growth of posterior transplants.

Animals↗
PubMed1999

Effect of genetic variants of the heart fatty acid-binding protein gene on intramuscular fat and performance traits in pigs.

In order to find genetic markers to improve the meat quality of pigs by breeding we studied the relationship between variation in the heart fatty acid-binding protein (H-FABP) gene (FABP3) and intramuscular fat (IMF) content. To estimate the effect of H-FABP, pigs from two Duroc populations were selectively mated in such a way that at least two genotypes were present in each litter. In total, data from 983 pigs and pedigree information from three preceding generations were analyzed. Offspring were tested for IMF content as well as backfat thickness (BFT), BW, and drip loss of the meat (DRIP). All pigs were assigned to H-FABP RFLP genotype classes either by the assessed genotype (75%) or based on a probability score determined according to genotypic information of their relatives (25%). Contrasts were detected between homozygous H-FABP RFLP genotype classes for IMF content (.4%, P < .05), BFT (.6 mm, P < .01), and BW (2.4 kg, P < .10). No significant contrasts were detected for DRIP. Results for IMF content, BFT, and BW were confirmed when only genotyped animals were analyzed. Variation in BFT partially explained the effect on IMF content. Although other closely linked genes on porcine chromosome 6 might be responsible for the observed effect, interference of the halothane gene was excluded because all parental animals were noncarriers. In conclusion, H-FABP RFLP can be used as markers to select for increased IMF content and growth in breeding programs.

Adipose Tissue↗
PubMed2025

TaLAC129 is a negative regulator of arbuscular mycorrhizal symbiosis but enhanced the growth and yield of bread wheat.

Arbuscular mycorrhizal (AM) symbiosis enhances nutrient acquisition and stress resilience in plants, yet the genetic mechanisms regulating this interaction in wheat remain poorly understood. This study explores the variation in AM colonization rates across a diverse set of wheat varieties and aims to identify key genes that regulate the wheat-AM symbiosis. Understanding these molecular mechanisms is crucial for improving nutrient uptake efficiency and stress resistance in wheat breeding programs. Here, we conducted a genome-wide association study (GWAS) of 291 wheat varieties and integrated transcriptomic data to identify TaLAC129, a laccase (LAC)-encoding gene, as a critical negative regulator of AM colonization in wheat roots. Overexpression of TaLAC129 significantly increased root LAC activity and lignin content, concurrently suppressing AM colonization. While this suppression reduced nitrogen (N), phosphorus (P), and potassium (K) uptake in stems, leaves, and glumes, it markedly enhanced nutrient utilization efficiency (NUE) in grains. Furthermore, TaLAC129 overexpression improved agronomic traits, including grains per panicle, 1000-grain weight, and overall yield. Our findings reveal the dual role of TaLAC129 in balancing AM symbiosis and nutrient allocation, offering a novel genetic target for breeding wheat varieties with improved yield and nutrient efficiency. This study provides critical insights into the molecular coordination between symbiotic trade-offs and agricultural productivity in cereal crops.

Triticum↗
PubMed2004

Incremental genetic K-means algorithm and its application in gene expression data analysis.

BACKGROUND: In recent years, clustering algorithms have been effectively applied in molecular biology for gene expression data analysis. With the help of clustering algorithms such as K-means, hierarchical clustering, SOM, etc, genes are partitioned into groups based on the similarity between their expression profiles. In this way, functionally related genes are identified. As the amount of laboratory data in molecular biology grows exponentially each year due to advanced technologies such as Microarray, new efficient and effective methods for clustering must be developed to process this growing amount of biological data. RESULTS: In this paper, we propose a new clustering algorithm, Incremental Genetic K-means Algorithm (IGKA). IGKA is an extension to our previously proposed clustering algorithm, the Fast Genetic K-means Algorithm (FGKA). IGKA outperforms FGKA when the mutation probability is small. The main idea of IGKA is to calculate the objective value Total Within-Cluster Variation (TWCV) and to cluster centroids incrementally whenever the mutation probability is small. IGKA inherits the salient feature of FGKA of always converging to the global optimum. C program is freely available at http://database.cs.wayne.edu/proj/FGKA/index.htm. CONCLUSIONS: Our experiments indicate that, while the IGKA algorithm has a convergence pattern similar to FGKA, it has a better time performance when the mutation probability decreases to some point. Finally, we used IGKA to cluster a yeast dataset and found that it increased the enrichment of genes of similar function within the cluster.

Algorithms↗
PubMedDate not supplied

Teaching a new dog old tricks: identifying quantitative trait loci using lessons from plants.

Locating quantitative trait loci (QTL) in mammalian systems has proven difficult due to the lack of genetic control and reproducibility, as well as the expense of maintaining sufficiently large populations for genotyping and phenotyping. In plants, populations of recombinant inbred lines (progeny bred to homozygosity from a single cross) do not have these problems. Methods developed to identify QTL in a recombinant inbred soybean population provide a basis for analysis of a suitable mammalian population, such as Portuguese water dogs in the United States. The more than 6,000 dogs have accurate pedigrees, available phenotypic data and samples for genotyping, as well as interesting quantitative trait variation. The computer program Georgie allows us to choose large subpopulations with desirable characteristics such as high degrees of consanguinity that capture some of the benefits of recombinant inbred lines in plants. Computer simulations extending methods developed for simpler plant populations indicate that QTL with realistic effects can be identified from such subpopulations. Currently we are developing markers and collecting phenotypic and genotypic data from this population to begin the process of unraveling the genetic basis of quantitative traits in dogs.

Animals↗
PubMed1997

The use of genetically resistant sheep to control nematode parasitism.

Research in the last 20 years has firmly established that it is possible to exploit genetic variation in resistance to the nematode parasites of sheep by selection. Selected sheep are more resistant to infection and commercial application of this research is under way in both Australia and in New Zealand. Not all the consequences of these breeding programs have been established, particularly long-term consequences for productivity and the interaction with other control measures, but the technology is available in the public domain with no commercial restrictions. Faecal worm egg count remains the most effective way of selecting sheep although many alternatives, such as DNA markers, host antibody and parasite antigen assays are being developed for use as selection criteria. Strategic nutritional supplementation is an immediate candidate for inclusion in worm control programs and although nematode vaccines remain elusive, it is likely that some will be field-tested in the next few years. For both of these approaches, nutritional and immunological, it is critical that the response of selected genotypes are assessed under commercial conditions and as components of worm control programs. There is evidence to support the possibility that selected sheep will be more responsive to vaccination while the long-term interaction between the effect of strategic nutritional supplements and resistant genotypes needs to be investigated.

Animal Nutritional Physiological Phenomena↗
PubMed2006

Determination of the genetic structure of remnant Morus boninensis Koidz. trees to establish a conservation program on the Bonin Islands, Japan.

BACKGROUND: Morus boninensis, is an endemic plant of the Bonin (Ogasawara) Islands of Japan and is categorized as "critically endangered" in the Japanese red data book. However, little information is available about its ecological, evolutionary and genetic status, despite the urgent need for guidelines for the conservation of the species. Therefore, we adopted Moritz's MU concept, based on the species' current genetic structure, to define management units and to select mother tree candidates for seed orchards. RESULTS: Nearly all individuals of the species were genotyped on the basis of seven microsatellite markers. Genetic diversity levels in putative natural populations were higher than in putative man-made populations with the exception of those on Otouto-jima Island. This is because a limited number of maternal trees are likely to have been used for seed collection to establish the man-made populations. A model-based clustering analysis clearly distinguished individuals into nine clusters, with a large difference in genetic composition between the population on Otouto-jima Island, the putative natural populations and the putative man-made populations. The Otouto-jima population appeared to be genetically differentiated from the others; a finding that was also supported by pairwise FST and RST analysis. Although multiple clusters were detected in the putative man-made populations, the pattern of genetic diversity was monotonous in comparison to the natural populations. CONCLUSION: The genotyping by microsatellite markers revealed strong genetic structures. Typically, artificial propagation of this species has ignored the genetic structure, relying only on seeds from Otouto-jima for replanting on other islands, because of a problem with inter-specific hybridization on Chichi-jima and Haha-jima Islands. However, this study demonstrates that we should be taking into consideration the genetic structure of the species when designing a propagation program for the conservation of this species.

Conservation of Natural Resources↗
PubMed1977

Characterization of abnormal glucose-6-phosphate dehydrogenase variants.

For characterizing glucose-6-phosphate dehydrogenase variants 10 functional parameters are generally used. As additional tests the determination of Km and Ki at different pH values, the limiting Km for both substrates, isoelectric focusing and electrophoresis of enzyme subunits have been recommended. Most of the variants with favourable kinetic properties do not produce chronic haemolysis. As an exception G6PD Aarau is quoted. Sporadic cases and deficiency conditions with manifest chronic nonspherocytic haemolytic anaemia should be selected for complete enzyme characterization. Individual and public health aspects are of primary importance for screening programs. Among 28,367 blood samples 424 cases with G6PD deficiency have been found in Switzerland.

Electrophoresis↗
PubMed1997

Commercial approaches to genetic selection for growth and feed conversion in domestic poultry.

Tremendous genetic progress has been observed historically for growth and feed conversion through the efforts of the primary breeding companies. However, significant between-strain variation still exists due to differences in selection emphasis and selection techniques practiced by these organizations. This paper provides an overview of methods currently employed in commercial poultry breeding with reference to factors complicating program design and future challenges facing the industry. Mass selection for body weight has resulted in a significant reduction in the number of days required to grow bird to market weight with indirect improvements in feed conversion. Direct selection for feed conversion is accomplished through part record testing of males that have been preselected for body weight, conformation, and defect traits. Data are commonly subjected to complex statistical analysis both to correct feed conversion for variation in body weight and to improve the accuracy of breeding value estimates. Feed conversion breeding values of male sibs are sometimes used for the selection of female candidates as well. Selection for growth rate and efficiency has resulted in negative complications, such as ascites, reduced reproductive performance, skeletal abnormalities, and increased carcass fatness. Some of these factors may be partially ameliorated through modified selection practices. If not addressed by the breeding industry, the disruption of physiological homeostasis might ultimately represent economic and genetic barriers to further progress in improving growth and efficiency. Modern techniques in molecular genetics, utilized in conjunction with traditional quantitative genetic approaches, will provide additional opportunities to circumvent these physiological complications associated with genetic selection for growth and feed efficiency.

Animals↗
PubMed2006

Genetic variation at the perilipin locus is associated with changes in serum free fatty acids and abdominal fat following mild weight loss.

OBJECTIVE: Perilipin (PLIN) is a class of protein-coating lipid droplets in adipocytes. We aimed to examine the association between common single-nucleotide polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and abdominal fat distribution in response to weight loss. METHODS: Non-diabetic/overweight-obese Koreans (n=177) participated in a 12-week calorie restriction (-300kcal/day) program. Seven SNPs (6209T>C, 10076C>G, 10171A>T, 11482G>A, 13042A>G, 13048C>T and 14995A>T), abdominal fat areas (visceral/subcutaneous fat areas at 1st lumbar and 4th lumbar levels), serum lipids, glucose, insulin, FFA, oxidized low-density lipoprotein (LDL) and urinary 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) were examined. RESULTS: Single-nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage disequilibrium (LD) (D'=0.923, R (2)=0.839, P<0.001) and SNPs11482G>A/14995A>T showed moderate positive LD (D'=0.824, R (2)=0.578, P<0.001). Calorie restriction induced 4.6% weight loss with significant abdominal fat reduction. In response to weight loss, subjects with nCA/nCA haplotypes at SNPs 10076C>G/10171A>T showed greater reduction in FFA levels than those with CA/CA haplotype (CA/CA: C/C at SNP 10076 and A/A at SNP 10171, nCA: non-CA haplotype carrier). On the other hand, subjects with nGA/nGA haplotype at SNPs 11482G>A/14995A>T had increased FFA levels with a rapid loss in abdominal fat, whereas GA/GA haplotype carriers had reduction in FFA levels. These results still remained significant after adjusting for age, gender and BMI. Prostaglandin F(2alpha) and oxidized LDL were also more reduced in GA/GA haplotype carriers than in nGA haplotype carriers. This effect remained significant after adjusting for baseline level, age, gender and BMI. Paradoxically, nGA haplotype carriers had increased levels of urinary PGF(2alpha) after weight reduction. CONCLUSION: Fasting plasma FFA changes following a modest weight loss in overweight-obese subjects are influenced by the genetic variability at the PLIN locus. Furthermore, circulating FFA changes rather than body fat itself may determine changes in lipid peroxides such as urinary PGF(2alpha) and oxidized LDL.

Adult↗
PubMed2004

A new model for understanding the role of environmental factors in the origins of chronic illness: a case study of type 1 diabetes mellitus.

There is a need for a new pathophysiological model explaining and linking the role of numerous non-genetic factors believed to contribute to origins of many chronic physical diseases. This article presents a theoretical model for explaining the confusing and often contradictory findings regarding the role of environmental influences in type 1 diabetes, a disease that has been widely studied, for which clear diagnostic criteria exist, and for which development of effective prevention strategies represents significant challenges. The model is formulated from the large database of research regarding increasing understanding of the interaction between environmental factors, physiology, and autonomic regulatory function. Data is integrated from research in the fields of the experience-dependent maturation of the nervous system and the neurophysiology of traumatic stress to demonstrate how disruptions in early bonding and attachment, including adverse events such as traumatic stress, are capable of causing: (1) long-term imbalances in autonomic regulatory function and (2) relative dominance of sympathetic or parasympathetic activity. The proposed model of autonomic dysfunction suggests that ongoing mechanisms promoting high glucose in the context of decreasing insulin production in type 1 diabetes represent a state of relative sympathetic dominance influenced by environmental factors affecting autonomic, immune and endocrine systems during critical period programming. The model further identifies a link between the many seemingly unrelated non-genetic risk factors, and appears capable of explaining contradictions and enigmas in epidemiological and clinical studies regarding non-genetic origins of type 1 diabetes, including the role of stress, variation in age of onset, and duration of the preclinical phase.

Age Distribution↗
PubMed2005

Mating patterns of a subdivided population of the andean oak (Quercus humboldtii Bonpl., Fagaceae).

Mating patterns play a critical role in the maintenance of genetic variation. We analyzed the mating system in a recently fragmented population of the Andean oak (Quercus humboldtii) using four microsatellite loci. Five fragments in northeastern Colombia, South America, were selected consisting of 30.4 trees on average. We sampled about 30 seeds from three target trees in each fragment and genotyped them with four microsatellite loci with a total of 40 alleles across loci. Progenies were analyzed under the mixed mating system model (MLTR program) and the TwoGener pollen pool structure analyses. The number of unshared pollen donors per family (Nu) was estimated using gametotypic counts with the program HAPLOTYPES. Low selfing (3%) is occurring at the population and fragment level. Biparental inbreeding is present (4.9%), but reduced, in the largest fragment. The average pollen neighborhood size (Nep = 5.1 to 6.1) appears comparable to other oak species in sparse landscapes. In contrast, Nu consists of 2 to 4 main donors, although up to 12 are possible, with the mode positively correlated with fragment size. The Andean oak appears to be a resilient species capable of tolerating population subdivision, provided landscapes include large fragments.

Colombia↗
PubMed1996

Familial correlations, cohabitation effects, and heritability for cardiovascular risk factors.

Familial correlations in cardiovascular risk factors were investigated with use of data from a community-based sample of 1319 nuclear families involving 4178 adult persons collected in the Busselton Population Health Surveys over the period 1966 to 1981. The risk factors considered were systolic blood pressure, diastolic blood pressure, body mass index, triceps fatfold, and cholesterol. All risk factors showed positive familial correlations, with correlations generally being lower for spouses than for parent-offspring pairs or for siblings. Spouse correlations showed little variation with age, suggesting that observed correlations are primarily due to assortative mating and not to cohabitation. The parent-offspring correlations tended to decline with age of (adult) offspring; this observation suggests that the effect of a shared household environment during childhood and adolescence diminishes over time when living apart during adulthood. The sibling correlations decreased with age for blood pressure and serum cholesterol and increased with age for body mass index and triceps fatfold. The estimated heritabilities were 27% for systolic and diastolic blood pressure, 37% for serum cholesterol, 52% for body mass index, and 23% for triceps fatfold. These results confirm that substantial familial aggregation of cardiovascular risk factors occurs and that much of this aggregation has a genetic basis, although assortative mating (in spouses) and environmental influences (in offspring and siblings) are also present. The nuclear family should be considered as a point of intervention in cardiovascular disease prevention programs.

Adult↗
PubMed1999

Linkage analysis of endothelial nitric oxide synthase gene with human blood pressure.

OBJECTIVE: Endothelial nitric oxide exerts important effects on the regulation of vascular tone and structure. Variants of the endothelial nitric oxide synthase gene (eNOS) have been associated with hypertension and myocardial infarction, although some reports have shown negative linkage with hypertension. To examine whether the region encoding the eNOS gene is linked with physiological blood pressure variation, we undertook a linkage analysis of this region in the general population. DESIGN: In healthy volunteer families, we used two independent quantitative linkage analyses to examine the relationship between genotypes and phenotypes, with both parametric and non-parametric and single-locus and multi-point methods. METHODS: We selected 260 families comprising mother and father (aged 40-70 years) and two natural offspring (aged 18-30 years) from the Victorian Family Heart Study. After standardized measurement of clinical data and extraction of DNA, all family members were genotyped at five microsatellite loci including the CA repeat in the eNOS gene by a PCR method. The quantitative linkage analyses were conducted according to two different analysis programs, the Genetic Analysis System (GAS) and the MAPMAKER/SIBS. RESULTS: With both linkage analyses, we found no linkage between any of the loci on chromosome 7q35-36 and the phenotypes systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, pulse rate, weight, height and body mass index. CONCLUSION: Based on these results, we conclude that in this population the eNOS gene is not linked to the physiological variation of blood pressure and other related phenotypes.

Adult↗
PubMed2005

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci.

Experimental evidence implicates interferon gamma (IFNgamma) in protection from and resolution of chlamydial infection. Conversely, interleukin 10 (IL10) is associated with susceptibility and persistence of infection and pathology. We studied genetic variation within the IL10 and IFNgamma loci in relation to the risk of developing severe complications of human ocular Chlamydia trachomatis infection. A total of 651 Gambian subjects with scarring trachoma, of whom 307 also had potentially blinding trichiasis and pair-matched controls with normal eyelids, were screened for associations between single-nucleotide polymorphisms (SNPs), SNP haplotypes and the risk of disease. MassEXTEND (Sequenom) and MALDI-TOF mass spectrometry were used for detection and analysis of SNPs and the programs PHASE and SNPHAP used to infer haplotypes from population genetic data. Multivariate conditional logistic regression analysis identified IL10 and IFNgamma SNP haplotypes associated with increased risk of both trachomatous scarring and trichiasis. SNPs in putative IFNgamma and IL10 regulatory regions lay within the disease-associated haplotypes. The IFNgamma +874A allele, previously linked to lower IFNgamma production, lies in the IFNgamma risk haplotype and was more common among cases than controls, but not significantly so. The promoter IL10-1082G allele, previously associated with high IL10 expression, is in both susceptibility and resistance haplotypes.

Alleles↗
PubMed2026

Longitudinal whole-genome analysis of bluetongue virus identifies conserved serotype-specific genomes and distinct genomic constellations within a Colorado sheep flock (2021-2023).

Bluetongue virus (BTV) is a segmented double-stranded RNA virus of ruminants transmitted by Culicoides spp. biting midges. Although the genome consists of ten segments, classification into serotypes is primarily based on genome segment 2. However, reassortment among genomic segments is a major driver of BTV evolution and diversity. This study used longitudinal whole-genome sequencing to characterize BTV genomes collected from 2021 to 2023 within a single sheep flock in Colorado, where multiple serotypes co-circulate. Whole-genome sequences were generated from fourteen blood samples representing four serotypes: BTV-6, -11, -13, and -17. Longitudinal sampling identified multiple BTV serotypes within individual sheep across consecutive years. Tanglegram analysis comparing segment phylogenies to the segment 2 tree demonstrated incongruent topologies across all genomic segments, suggestive of reassortment or the circulation of distinct genomic constellations. Nucleotide-level comparisons revealed high sequence homology among same-serotype samples from the same year, while the greatest genetic divergence was observed among BTV-17 genomes collected in different years. Additionally, all BTV-13 genomes contained a previously undescribed nonsynonymous substitution in segment 10 predicted to extend the encoded protein by three amino acids. Together, these findings demonstrate that highly conserved BTV genomes and distinct genomic constellations can be detected at the flock level across multiple years. This longitudinal whole-genome approach reveals the genetic complexity of endemic BTV populations, including novel variants and genomic patterns consistent with reassortment that are lost with conventional serotyped-based approaches, highlighting the need to integrate whole-genome characterization into endemic BTV monitoring programs.

Animals↗
PubMed2002

Detecting cryptically simple protein sequences using the SIMPLE algorithm.

MOTIVATION: Low-complexity or cryptically simple sequences are widespread in protein sequences but their evolution and function are poorly understood. To date methods for the detection of low complexity in proteins have been directed towards the filtering of such regions prior to sequence homology searches but not to the analysis of the regions per se. However, many of these regions are encoded by non-repetitive DNA sequences and may therefore result from selection acting on protein structure and/or function. RESULTS: We have developed a new tool, based on the SIMPLE algorithm, that facilitates the quantification of the amount of simple sequence in proteins and determines the type of short motifs that show clustering above a certain threshold. By modifying the sensitivity of the program simple sequence content can be studied at various levels, from highly organised tandem structures to complex combinations of repeats. We compare the relative amount of simplicity in different functional groups of yeast proteins and determine the level of clustering of the different amino acids in these proteins. AVAILABILITY: The program is available on request or online at http://www.biochem.ucl.ac.uk/bsm/SIMPLE.

Algorithms↗
PubMed2006

A greedier approach for finding tag SNPs.

MOTIVATION: Recent studies have shown that a small subset of Single Nucleotide Polymorphisms (SNPs) (called tag SNPs) is sufficient to capture the haplotype patterns in a high linkage disequilibrium region. To find the minimum set of tag SNPs, exact algorithms for finding the optimal solution could take exponential time. On the other hand, approximation algorithms are more efficient but may fail to find the optimal solution. RESULTS: We propose a hybrid method that combines the ideas of the branch-and-bound method and the greedy algorithm. This method explores larger solution space to obtain a better solution than a traditional greedy algorithm. It also allows the user to adjust the efficiency of the program and quality of solutions. This algorithm has been implemented and tested on a variety of simulated and biological data. The experimental results indicate that our program can find better solutions than previous methods. This approach is quite general since it can be used to adapt other greedy algorithms to solve their corresponding problems. AVAILABILITY: The program is available upon request.

Algorithms↗