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Behavior of heuristics on large and hard satisfiability problems.

We study the behavior of a heuristic for solving random satisfiability problems by stochastic local search near the satisfiability threshold. The heuristic for average satisfiability (ASAT), is similar to the Focused Metropolis Search heuristic, and shares the property of being focused, i.e., only variables in unsatisfied clauses are updated in each step. It is significantly simpler than the benchmark WALKSAT heuristic. We show that ASAT solves instances as large as N=10(6) in linear time, on average, up to a ratio of 4.21 clauses per variable in random three-satisfiability. For K higher than 3, ASAT appears to solve instances of K -satisfiability up to the Montanari-Ricci-Tersenghi-Parisi full replica symmetry breaking (FSRB) threshold denoted alpha(s)(K) in linear time.

Journal Article↗

Species divergence in sexually selected traits: increase in song elaboration is related to decrease in plumage ornamentation in finches.

Elaborate plumage and complex songs of male birds are two of the best-known examples of sexually selected traits, yet the interaction between these traits is poorly understood. Theory suggests that among a suite of potential displays, animals will emphasize traits that are most conspicuous, least costly, or best signal condition and reduce display of other traits. Here we examined the relationship between song and plumage elaborations in cardueline finches, songbirds that are highly variable in plumage displays and songs, but that share a similar mating system. We statistically controlled for body mass, habitat characteristics, and phylogenetic relationships and found that across species song complexity was strongly negatively related to elaboration of plumage ornamentation. When plumage coloration was partitioned into carotenoid-based and melanin-based components, song complexity was negatively related to elaboration of male carotenoid-based coloration but unrelated to elaboration of melanin-based coloration. These observations support the idea that, for condition-dependent traits, animal species trade off trait expression in response to changes in the costs or the information content of these traits. We discuss several alternative explanations for the observed pattern.

Animals↗

Antigenicity of Campylobacter jejuni flagella.

We studied the antigenicity of a wild-type flagellate and motile (F+M+) Campylobacter jejuni strain (81116) and two daughter mutants, one flagellate and immotile (F+M-) and one aflagellate and immotile (F-M-). By sodium dodecyl sulfate-polyacrylamide gel electrophoresis of acid-extracted surface proteins, a 63-kilodalton (kDa) band identified from sheared flagella as the flagellar protein was present in the F+M+ and F+M- strains but not in the F-M- strain. No other differences in protein profile among the three strains were noted. By Western blotting, serum from rabbits immunized with either the F+M+ or F-M- strain detected a 63-kDa protein in the F+M+ and F+M- strains but not in the F-M- strain. That the F-M- antiserum recognized the 63-kDa band suggests that small amounts of this protein or a cross-reacting antigen is present on the F-M- strain. By counterimmunoelectrophoresis of the acid-extracted preparations with immune sera, all three strains were found to share three major antigens, but a fourth antigen with a net positive charge was present only in the F+M+ and F+M- strains. Antisera to five C. jejuni and two Campylobacter fetus strains recognized the 63-kDa protein of purified F+M+ flagella in Western blots, demonstrating a common antigen is present, but enzyme-linked immunosorbent assay results suggest that the sharing of this antigen among Campylobacter strains is variable.

Antigens, Bacterial↗

Assessment of evolution of pandemic Vibrio parahaemolyticus by multilocus sequence typing.

The genetic relatedness of 81 isolates of Vibrio parahaemolyticus was assessed by multilocus sequence typing. The strain with serotype O3:K6 emerged as a pandemic pathogen in 1996, with subsequent expansion to include strains having serotypes O1:KUT, O4:K68, and O1:K25. Sequence data from gyrB, recA, dnaE, and gnd revealed that 16 distinct serogroups isolated prior to the pandemic were highly variable and only isolates of serogroup O3:K6 shared two alleles with the pandemic strains. The pandemic strains regardless of serotype were clonal, with 51 of 54 isolates having the identical allelic profile (AP). Serotype alone did not adequately define a pandemic strain: among O1:KUT strains tested, seven strains with the identical pandemic AP carried previously described pandemic markers, while five nonpandemic strains had five distinct APs. Our sequence data provide strong molecular support for the clonal origin of pandemic V. parahaemolyticus O3:K6 and suggest that strains within such a clonal group may acquire previously identified serotypes.

Genes, Bacterial↗

Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in Southern Africa.

A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.

Gene Products, env↗

Sequence and expression of the chicken beta 5- and beta 4-tubulin genes define a pair of divergent beta-tubulins with complementary patterns of expression.

We have determined the nucleotide sequence of the chicken beta 5 (c beta 5)-tubulin gene. The gene displayed the coding structure common to all previously studied vertebrate beta-tubulin genes and was divided into four exon sequences interrupted by three intervening sequences (located between codons 19 and 20, within codon 56, and within codon 93). Comparison of the predicted polypeptide sequence encoded by c beta 5 with those of four other available chicken beta-tubulin sequences revealed that c beta 5 encoded a highly divergent beta-tubulin polypeptide isotype which was distinguished from previously known sequences primarily by two discrete variable sequence domains. However, c beta 5 uniquely shared identity in 16 residue positions with another divergent chicken beta-tubulin gene, c beta 4. These common sequences distinguished c beta 4 and c beta 5 from the remaining three chicken beta-tubulin genes. Analysis of the expression of c beta 5 and c beta 4 revealed a strikingly complementary pattern of gene expression: c beta 5 was expressed in a wide variety of cell and tissue types but not in neurons, whereas c beta 4 expression was detected uniquely in neuronal cells. Overall, these findings suggest the existence of two divergent families of beta-tubulin sequences in the chicken and further raise the possibility that the complementary expression of the c beta 4 and c beta 5 genes may fulfill a requirement for the presence of a divergent beta-tubulin polypeptide isotype in all cell types.

Amino Acid Sequence↗

Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.

Accumulated sequence analyses of the antibody repertoire have revealed that most autoantibodies and developmentally regulated antibodies share a small set of germline Ig-variable region (V) genes. The findings have prompted speculation that certain autoantibodies are of developmental importance and may be instrumental in maintaining homeostasis of the adult antibody repertoire. In order to evaluate this hypothesis critically, it is first necessary to determine the V gene usage in human antibodies against foreign substances. Unfortunately, only a few such antibodies have had their heavy and light chains characterized. To rectify the situation, we adapted the anchored polymerase chain reaction to clone and analyze rapidly the expressed V genes for three anti-virus IgG antibodies. The results show that all three heavy chain V (Vh) genes are highly homologous to the known autoantibody-related Vh genes. In contrast, two light chain V (VL) genes of the V lambda 1 subgroup are similar to a non-autoantibody-related germline V lambda 1 gene. Taken together with the reported Vh and VL sequences of several antibodies against viruses and bacteria, the data show that many antipathogen antibodies may use the same small set of Vh genes that encode autoantibodies, but diverse VL genes that are distinct from autoantibody-related VL genes. Thus, only a small portion of the potentially functional germline Vh genes are used recurrently to generate most antibodies in a normal antibody repertoire, regardless of their reactivities with either self or non-self.

Amino Acid Sequence↗

Relationships between cognitive and neurological performance in neuroleptic-naïve psychosis.

The authors explored relationships between neuropsychological performance and neurological exam abnormalities in 86 never-medicated patients with nonorganic psychosis (59 with schizophrenia or schizoaffective disorder) and 51 healthy subjects. Assessments include a reliable subset of the Neurological Evaluation Scale (rNES) and several neuropsychological tests of attention, executive function, memory, and current and premorbid intelligence. Principal components analysis of the rNES yielded two main factors. Of these, CogPer (consisting of more cognitively demanding perceptual tasks) showed stronger relationships than RepMot (consisting of repetitive manual motor tasks) to neuropsychological measures. Customarily, frontal neuropsychological tasks also relate more strongly to CogPer than to RepMot. Approximately one-half of the variability in these cognitive and neurological assessments is shared.

Adult↗

Genetic and environmental influences on body fat distribution, fasting insulin levels and CVD: are the influences shared?

Central body fat distribution has been shown to be related to hyperinsulinemia, insulin resistance, hypertriglyceridemia, and atherosclerosis to a greater degree than general obesity. There are known to be both genetic and environmental effects on all components of this clustering. Whether these genetic effects are due to one set of genes in common to the components or whether genetic influences on insulin resistance and/or general/abdominal fatness 'turn on' other genes that affect other components of the syndrome is not clear. We analyzed data from the Swedish Adoption/Twin Study of Aging (60% female; monozygotic = 116, dizygotic = 202; average age 65 years) to determine whether there were genetic and/or environmental factors shared among general body fat distribution, abdominal body fat distribution, fasting insulin levels and cardiovascular disease. We found additive genetic effects in males to be significantly different from those in females with genetic effects accounting for variance in waist-hip ratio (males = 28%; females = 49%), body mass index (males = 58%; females = 73%), fasting insulin levels (FI) (males = 27%; females = 49%), and cardiovascular disease (CVD) (males = 18%; females = 37%). There were also shared genetic and environmental effects among all the variables except CVD, but a majority of the genetic variance for these measures was trait specific.

Abdomen↗

Molecular characterization and chromosomal distribution of Galileo, Kepler and Newton, three foldback transposable elements of the Drosophila buzzatii species complex.

Galileo is a foldback transposable element that has been implicated in the generation of two polymorphic chromosomal inversions in Drosophila buzzatii. Analysis of the inversion breakpoints led to the discovery of two additional elements, called Kepler and Newton, sharing sequence and structural similarities with Galileo. Here, we describe in detail the molecular structure of these three elements, on the basis of the 13 copies found at the inversion breakpoints plus 10 additional copies isolated during this work. Similarly to the foldback elements described in other organisms, these elements have long inverted terminal repeats, which in the case of Galileo possess a complex structure and display a high degree of internal variability between copies. A phylogenetic tree built with their shared sequences shows that the three elements are closely related and diverged approximately 10 million years ago. We have also analyzed the abundance and chromosomal distribution of these elements in D. buzzatii and other species of the repleta group by Southern analysis and in situ hybridization. Overall, the results suggest that these foldback elements are present in all the buzzatti complex species and may have played an important role in shaping their genomes. In addition, we show that recombination rate is the main factor determining the chromosomal distribution of these elements.

Animals↗

Psychological mechanisms in hyperactivity: II. The role of genetic factors.

The main aim of this study was to combine two research approaches to hyperactivity: the behaviour genetic approach and the testing of psychological theories of hyperactivity. For a sample of 268 twin pairs aged 7-11 years we obtained ratings on the Conners' scales from both teachers (CTRS-28) and parents (CPRS-48). Forty-six hyperactive twin pairs (pairs in which at least one twin was pervasively hyperactive) and 47 control twin pairs were assessed on a psychological test battery. Confirming findings from previous twin studies, a substantial proportion of the variance in hyperactivity considered as a dimension was due to genetic effects. There was significant evidence of genetic effects also on extreme hyperactivity, although the present group heritability estimates were somewhat lower than those reported in most previous studies. We investigated the possibility that the psychological mechanisms we reported to be associated with hyperactivity (Kuntsi, Oosterlaan, & Stevenson, 2001) share common genetic factors with hyperactive behaviour. The data produced significant evidence of such shared genetic effects only on hyperactivity and the variability of reaction times. Given that the high variability in speed of responding would indicate a state-regulation problem, this is the psychological mechanism that could possibly be the "link" between genetic effects and hyperactive behaviour.

Attention Deficit Disorder with Hyperactivity↗

Determinants of hospital utilization: the situation in Israel and selected countries.

BACKGROUND: In 1995 hospital costs constituted about 42% of the health expenditures in Israel. Although this proportion remained stable over the last decade, hospital discharge rates per 1,000 population increased, while hospitalization days per 1,000 population and average length of stay declined. OBJECTIVE: To gain an insight into the forces behind these changes, we compared the trends in hospital utilization in Israel with those in 21 developed countries with available data. MATERIALS AND METHODS: Our data were derived from The "Hospitals and Day Care Units, 1995" report by the Health Information and Computer Services of the Israel Ministry of Health, and the Organization for Economic Cooperation and Development Health Data, 98. We examined the numbers of acute care hospital beds, of patients on dialysis and of doctors' consultations, health expenditures and age structure of the population in 1995 or closest year with available data, as well as changes in DRs, HDs and ALOS between 1976 and 1995. RESULTS: In Israel the DRs increased from 130 in 1976 to 177 in 1995 (36%), HDs declined from 992 to 818 (18%), and ALOS declined from 7.60 to 4.51 days (41%). Relative to other countries, in 1995 Israel had the lowest ALOS; low HDs similar to those in the UK, Portugal, Spain, the USA and Sweden; and intermediate DRs similar to those in Belgium, Germany, Sweden and Australia. The number of acute care beds per 1,000 population was directly related to HDs (r = 0.954, P = 0.000) and to DRs (r = 0.419, P = 0.052). Health expenditures (% of the gross national product) correlated with the number of patients on dialysis per 1,000,000 population (r = 0.743, P = 0.000). Between 1976 and 1995, HDs and ALOS declined in most countries, however the trends in DRs varied from an increase by 119% in the UK to a decline by 29% in Canada. CONCLUSIONS AND HYPOTHESES: The increase in DRs in Israel from 1976 to 1995 was shared by many but not all countries. This variability may be related to differences in trends in local practice norms and in available hospital beds. If the number of patients on dialysis is a valid index for use of expensive treatment modalities, the correlation of health expenditures with the number of patients on dialysis suggests that the use of expensive technology is a more important determinant of health care costs than the age of the population or hospital utilization. Since the use of expensive technology is highest during the first few days in hospital, decisions about health care policy should consider the possibility that the savings incurred by a further decline in HDs and ALOS may be offset by a possible increase in per diem hospital costs and in health care expenditures after discharge from hospital.

Australia↗

Meeting the challenges in cancer pain management.

Cancer pain, caused by the disease itself or its treatments, is common. This session discussed pain management strategies that nurses can share with patients experiencing pain. The program covered variables that must be considered when selecting an initial opioid for managing pain, the concept of opioid rotation for patients experiencing severe pain, neuropathy assessment and treatment, and the future of cancer pain management.

Analgesics↗

[The Human Genome Project, genetic viability and genetic epidemiology].

The goal of the Human Genome Project to elucidate the complete sequence of the human genome has been achieved. The aims of the "post-genome" era are explaining the genetic information, characterisation of functional elements encoded in the human genome and mapping the human genetic variability as well. Two unrelated human beings also share 99.9% of their genomic sequence. The difference of 0.1% is the result of genetic polymorphisms: single nucleotide polymorphisms, repetitive sequences and insertion/deletion. The genetic differences, coupled with environmental exposures will determine the phenotypic variation we observe in health or disease. The disease-causing genetic variants can be identified by linkage analysis or association studies. The knowledge of human genome and application of multiple biomarkers will improve our ability to identify individuals at risk, so that preventive interventions can be applied, earlier diagnosis can be made and treatment can be optimized.

Early Diagnosis↗

A novel DNMT3B subfamily, DeltaDNMT3B, is the predominant form of DNMT3B in non-small cell lung cancer.

De novo promoter DNA methylation represses gene transcription and is a common mechanism to inactivate tumor suppressor genes in tumorigenesis. DNMT3B plays an important role in de novo DNA methylation. We report here the identification of a novel DNMT3B subfamily, termed DeltaDNMT3B, whose expression is initiated through a promoter located at intron 4 and exon 5 of the DNMT3B gene. At least 7 transcriptional variants of DeltaDNMT3B have been observed as the result of alternative pre-mRNA splicing. Predicted proteins derived from these variants suggest that 4 of the variants share a conservative enzymatic domain but contain a variable PWWP motif, a putative DNA binding structure, whereas 3 of the variants lack the enzymatic domain due to predicted premature translational termination. In non-small cell lung cancer (NSCLC) cell lines, DeltaDNMT3B variants are frequently expressed and are the predominant forms of DNMT3B. Similarly, DeltaDNMT3B variants are frequently expressed in primary NSCLC but are not detectable or are expressed at low levels in corresponding normal lung tissue. Our results indicate that DeltaDNMT3B is the major expression form of DNMT3B in NSCLC and may play an important role in the development of aberrant promoter methylation during lung tumorigenesis.

Alternative Splicing↗

Susceptibility of clinical isolates to dactimicin and gentamicin.

Dactimicin is a new aminoglycoside and its in vitro activity has been compared with that of gentamicin against 100 recent clinical isolates. The minimum inhibitory concentrations were determined by agar dilution. Dactimicin was generally one two-fold dilution step less active or as equally active as gentamicin against enterobacteria and pseudomonas. Dactimicin was several times more active than gentamicin against Acinetobacter and staphylococci. Both compounds share poor activity against enterococci and have a variable effect on other streptococci. They are highly active against serogroup A streptococci and pneumococci.

Aminoglycosides↗

Clustering of cardiovascular risk factors in Australian adolescents: association with dietary excesses and deficiencies.

BACKGROUND: Effective cardiovascular disease prevention requires strategies aimed at those children and adolescents most at risk. This study was designed to identify adolescents with clustering of higher levels of cardiovascular risk factors related to diet, blood pressure, fitness, fatness and blood cholesterol. METHODS: A representative sample of 555 schoolchildren aged 15 years from the Perth, Australia metropolitan area, was included in a cross-sectional survey analysing relationships between nutrient intake, fitness, physical activity, percentage of body fat, blood pressure and heart rate. RESULTS: Cluster analysis identified 21.1% of boys and 20.7% of girls with significantly worse risk profiles. Higher cardiovascular risk was associated with both dietary excesses, particularly in fat, cholesterol and sodium intake, and deficiencies of a number of minerals, vitamins and dietary fibre. Socioeconomic status was inversely associated with cardiovascular risk and undernutrition in girls. CONCLUSIONS: The analysis has identified a subgroup of about 21% of 15-year-old schoolchildren who share features of a range of unhealthy lifestyle variables, putting them at substantial risk of cardiovascular disease and other ill health in later life.

Adolescent↗

The effect of HMOs on fee-for-service health care expenditures: evidence from Medicare.

This paper examines the relationship between HMO market share and fee-for-service health care expenditures using 1986-1990 county- and metropolitan statistical area-level data on Medicare expenditures and HMO market share. Fixed-effects estimates imply that fee-for-service expenditures are concave and decreasing in market share. Increases in market share from 20% to 30% are associated with 3-7% expenditure reductions. Instrumental variable estimates that exploit cross-sectional variation in HMO activity also indicate a concave relationship, with expenditures declining in market share for market shares above 15-18%, but imply larger expenditure responses to market share changes.

Catchment Area, Health↗