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PubMed2004

Anisotropic ballistic deposition model with links to the Ulam problem and the Tracy-Widom distribution.

We compute exactly the asymptotic distribution of scaled height in a (1+1)-dimensional anisotropic ballistic deposition model by mapping it to the Ulam problem of finding the longest nondecreasing subsequence in a random sequence of integers. Using the known results for the Ulam problem, we show that the scaled height in our model has the Tracy-Widom distribution appearing in the theory of random matrices near the edges of the spectrum. Our result supports the hypothesis that various growth models in (1+1) dimensions that belong to the Kardar-Parisi-Zhang universality class perhaps all share the same universal Tracy-Widom distribution for the suitably scaled height variables.

Journal Article↗

PubMed2006

Orthonormal transform to decompose the variance of a life-history trait across a phylogenetic tree.

In recent years, there has been an increased interest in studying the variability of a quantitative life-history trait across a set of species sharing a common phylogeny. However, such studies have suffered from an insufficient development of statistical methods aimed at decomposing the trait variance with respect to the topological structure of the tree. Here we propose a new and generic approach that expresses the topological properties of the phylogenetic tree via an orthonormal basis, which is further used to decompose the trait variance. Such a decomposition provides a structure function, referred to as an "orthogram," which is relevant to characterize in both graphical and statistical aspects the dependence of trait values on the topology of the tree ("phylogenetic dependence"). We also propose four complementary test statistics to be computed from orthogram values that help to diagnose both the intensity and the nature of phylogenetic dependence. The relevance of the method is illustrated by the analysis of three phylogenetic data sets, drawn from the literature and typifying contrasted levels and aspects of phylogenetic dependence. Freely available routines which have been programmed in the R framework are also proposed.

Analysis of Variance↗

PubMedDate not supplied

Comparison of local grid refinement methods for MODFLOW.

Many ground water modeling efforts use a finite-difference method to solve the ground water flow equation, and many of these models require a relatively fine-grid discretization to accurately represent the selected process in limited areas of interest. Use of a fine grid over the entire domain can be computationally prohibitive; using a variably spaced grid can lead to cells with a large aspect ratio and refinement in areas where detail is not needed. One solution is to use local-grid refinement (LGR) whereby the grid is only refined in the area of interest. This work reviews some LGR methods and identifies advantages and drawbacks in test cases using MODFLOW-2000. The first test case is two dimensional and heterogeneous; the second is three dimensional and includes interaction with a meandering river. Results include simulations using a uniform fine grid, a variably spaced grid, a traditional method of LGR without feedback, and a new shared node method with feedback. Discrepancies from the solution obtained with the uniform fine grid are investigated. For the models tested, the traditional one-way coupled approaches produced discrepancies in head up to 6.8% and discrepancies in cell-to-cell fluxes up to 7.1%, while the new method has head and cell-to-cell flux discrepancies of 0.089% and 0.14%, respectively. Additional results highlight the accuracy, flexibility, and CPU time trade-off of these methods and demonstrate how the new method can be successfully implemented to model surface water-ground water interactions.

Computer Simulation↗

PubMed2006

Genomic islands and the ecology and evolution of Prochlorococcus.

Prochlorococcus ecotypes are a useful system for exploring the origin and function of diversity among closely related microbes. The genetic variability between phenotypically distinct strains that differ by less that 1% in 16S ribosomal RNA sequences occurs mostly in genomic islands. Island genes appear to have been acquired in part by phage-mediated lateral gene transfer, and some are differentially expressed under light and nutrient stress. Furthermore, genome fragments directly recovered from ocean ecosystems indicate that these islands are variable among cooccurring Prochlorococcus cells. Genomic islands in this free-living photoautotroph share features with pathogenicity islands of parasitic bacteria, suggesting a general mechanism for niche differentiation in microbial species.

Adaptation, Physiological↗

PubMed1987

Induction of lymphomas by the hamster papovavirus correlates with massive replication of nonrandomly deleted extrachromosomal viral genomes.

The hamster papovavirus isolated from skin epithelioma can induce lymphomas and leukemias after subcutaneous inoculation into newborn hamsters. The lymphoma cells are virus free but contain large amounts of extrachromosomal hamster papovavirus DNA. We have cloned and partly sequenced some of these DNA molecules from independent tumors. These genomes displayed overlapping deletions consistently sharing a common end within the noncoding regulatory sequences; the other end was variable but always extended into the sequence coding for the N-terminal part of the viral capsid VP2. This unique in vivo interaction between a polyomavirus and its cellular host, the genesis of these variant molecules, and their role in the lymphoma formation are discussed.

Animals↗

PubMed2001

Contrast discrimination and choice reaction times at near-threshold pedestals.

Choice reaction times (CRTs) to contrast differences were measured and compared with contrast increment thresholds obtained from concurrently measured psychometric functions at pedestal contrasts in the vicinity of detection threshold. Contrast discrimination functions had a classical dipper shape. The main finding was that CRTs were shorter at low pedestal contrasts but longer at higher pedestal contrasts compared to detection, reflecting the behaviour of increment thresholds. Even when equalized for response accuracy, CRTs varied with pedestal contrast in a similar manner to the contrast increment thresholds. The finding that CRTs and contrast increment thresholds depended on pedestal contrast in a similar manner suggests that both share a common origin. This common origin is proposed to lie in the variability of the sensory effect which determines the variability of the information accumulation process, which in turn affects the response criterion and contrast increment thresholds. At low pedestals, a decrease in variability lowers thresholds and results in a lower response criterion, thereby accelerating reaction times. At high pedestals, increasing signal-dependent noise inflates variability and thus raises thresholds and the response criterion, which results in slower CRTs.

Contrast Sensitivity↗

PubMed1995

Negative, psychoticism, and disorganized dimensions in patients with familial schizophrenia or bipolar disorder: continuity and discontinuity between the major psychoses.

OBJECTIVE: This study aimed to answer the following questions: 1) Can we reliably measure the psychopathologic dimensions of schizophrenia by using a lifetime frame and by rating acute and interepisode periods separately? 2) Can we reproduce in subjects with familial schizophrenia the characteristic three-factor structure of schizophrenic symptoms that has been found previously in general groups of schizophrenic patients? 3) Is the factor structure also present in familial bipolar disorder? METHOD: Lifetime measures of psychotic symptoms were taken through a slightly modified version of the Comprehensive Assessment of Symptoms and History for 138 patients with highly familial DSM-III-R schizophrenia (N = 51), bipolar disorder (N = 44), or spectrum disorders (N = 43). Symptoms were rated separately in the acute episodes and in the stabilized interepisode intervals across the patients' lives. RESULTS: A satisfactory level of reliability was obtained. In this highly familial study group, the positive/negative factorial distinction was replicated, as was a three-factor model similar to that observed in prior general groups of schizophrenic patients. These factors were also present in bipolar affective disorder. The negative, psychoticism, and disorganized factor model applied more to the acute phase of illness than to the stabilized state. CONCLUSIONS: These findings offer an empirical basis for testing biological or genetic variables in relation to negative/positive symptom dimensions, rather than diagnoses. Observations of a shared structure for schizophrenia and bipolar disorder suggest some continuity in the causes of these disorders.

Acute Disease↗

PubMed2006

HCV and HIV infection and co-infection: injecting drug use and sexual behavior, AjUDE-Brasil I Project.

This study aimed to characterize sexual and drug-use behaviors in injecting drug users (IDUs) in relation to single hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection and HCV/HIV co-infection. The sample consisted of 272 IDUs enrolled in the AjUDE-Brasil I Project, a cross-sectional multi-center study conducted in five Brazilian cities in 1998. Data were collected with a structured questionnaire using self-reported risk behavior, and HCV and HIV serological status used ELISA on filter paper. IDUs were clustered in four distinct groups: HCV/HIV seronegative; HCV mono-infected; HIV mono-infected; and HCV/HIV co-infected. Active sharing of injecting equipment was associated with HCV infection (p = 0.001). Sexual behavior variables, especially male same-sex sexual relations, were consistently associated with HIV infection. HCV/HIV co-infection was associated with both sexual and drug use variables. It was possible to distinguish different behavioral indicators for HCV and HIV infection and co-infection in this population.

Brazil↗

PubMed2004

Impact of age at onset and duration of illness on the expression of comorbidities in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) patients usually experience comorbidities including tics, trichotillomania, body dysmorphic disorder, and mood and anxiety disorders. The present report verifies how age at onset of obsessive-compulsive symptoms and duration of illness are associated with comorbid diagnoses in OCD patients. METHOD: Psychiatric comorbidity was assessed using a structured clinical interview in 161 consecutive outpatients referred for treatment between 1996 and 2001 who met DSM-IV criteria for OCD. Age at onset and duration of illness were retrospectively assessed by direct interviews. RESULTS: An earlier age at onset of obsessive-compulsive symptoms was associated with tic disorders, while longer illness duration was associated with depressive disorder (major depressive disorder or dysthymia) and social phobia. CONCLUSION: Age at onset and duration of OCD illness are meaningful variables affecting the expression of comorbidities in OCD. Tic disorders and OCD may share common etiologic pathways. Depressive disorders, in contrast, may be secondary complications of OCD.

Adolescent↗

PubMed1976

The mortality component of health status indexes.

The mortality component of contemporary health indexes is discussed. Since these indexes reduce to mortality indexes when only life and death states enter the analysis, they share the conceptual weaknesses of mortality indexes. Also, they do not incorporate consumption variables explicity and therefore provide no structure for relating health status and living standard. Some attention is devoted to methodological problems of assessing survival probabilities, either from survey or experimental data or from beliefs of experts or individuals who are affected directly. The final section deals with individual preferences for survival lotteries. Conceptual weaknesses of common indexes are discussed, several canonical models for survival preferences are presented, the interdependence of individual utilities is discussed, and methods for eliciting individual survival preferences are considered, along with some illustrative empirical results.

Choice Behavior↗

PubMed1999

Identification of pathogenic T cells in patients with beryllium-induced lung disease.

Chronic beryllium disease (CBD) is caused by beryllium exposure and is characterized by granulomatous inflammation with accumulation of CD4+ T cells in the lung. We analyzed TCR beta-chain and alpha-chain genes expressed by these CD4+ T cells. In the lungs of individual patients, as well as among four of five CBD patients studied, different oligoclonal expansions within the Vbeta3 subset were found to express homologous or even identical CDR3 amino acid sequences. These related expansions were specific for CBD patients, were compartmentalized to lung, and persisted at high frequency in patients with active disease. Limiting dilution cloning and analysis of coexpressed TCR alpha-chain genes confirmed that these TCRs were selectively expanded by a common Ag involving beryllium. Overall, homologous TCR beta- and alpha-chains showed identical V regions and invariant charged residues within the CDR3 but considerable variability in TCRJ usage. Remarkably, CBD patients expressing nearly identical TCRs did not share common HLA-DRB1 or DQ alleles. These results implicate particular CD4+ cells in the pathogenesis of CBD and provide insight into how beryllium is recognized in human disease.

Amino Acid Sequence↗

PubMed1999

Hot and cold nociception are genetically correlated.

Recent experiments in our laboratory have revealed a genetic correlation of the sensitivity of inbred mouse strains to different assays of nociception using noxious heat stimuli. An open question is whether the property of the noxious stimulus underlying the genetic correlation is heat specifically or simply a temperature (hot or cold) in the noxious range. The existing electrophysiological, psychophysical, neurochemical, and functional imaging literatures regarding the relationship of heat pain and cold pain are quite contentious, with a number of similarities and dissociations being documented. In the present study, we tested 12 inbred mouse strains (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C57BL/10J, C58/J, CBA/J, DBA/2J, RIIIS/J, and SM/J) for their reflexive withdrawal sensitivity to immersion of the tail in hot (47. 5 degrees C) and cold (-15 degrees C) water and compared the observed latencies with those obtained previously, using a 49 degrees C stimulus. All three traits displayed substantial heritabilities, ranging from 0.41 to 0.50. Strain means on these nociceptive traits displayed a high degree of cross-correlation (r = 0.49-0.77). Genetic correlation of hot and cold nociception implies that similar genes underlie interindividual variability in both traits in mice and further suggests that these nociceptive types share physiological mediation. This finding is discussed in relation to existing data in other mammals including humans.

Animals↗

PubMed2000

Structure and function of the Groucho gene family and encoded transcriptional corepressor proteins from human, mouse, rat, Xenopus, Drosophila and nematode.

A gene family of the Groucho, TLE, ESG and AES proteins has been characterized from Drosophila, nematode, Xenopus, mouse, rat and human, and their structural relationships have been analyzed. The genomic organization of nematode ESG, human and mouse AES genes has been determined, and the expression of ESG and AES genes from Xenopus and human has been analyzed. The Groucho, TLE and ESG proteins all share a similar structure, consisting of a conserved amino-terminal domain, a variable middle region, and highly conserved carboxyl-terminal WD-40 repeats. The Drosophila Groucho transcriptional corepressor protein has been shown to interact with the DNA-binding bHLH domain of Enhancer of split, Hairy and Deadpan proteins, which proteins are involved in neurogenesis, segmentation and sex-determination, respectively. Human TLE1 protein has been demonstrated to interact with mammalian AML1 protein, which regulates hematopoiesis and osteoblast differentiation. The AES proteins from human, mouse, rat and Xenopus exhibit strong similarity to the amino-terminal domain of Groucho proteins; however, the biological function remains to be elucidated.

Amino Acid Sequence↗

PubMed2004

[Prognosis after acute coronary syndrome. Lack of difference according to the sex].

Acute coronary syndromes (ACS) represent a continuum from unstable angina to non-ST-elevation myocardial infarction. ACS is the preferred diagnostic term for non transmural myocardial infarction. The different forms of ACS share a common anatomic substrate consisting of atherosclerotic plaque rupture or erosion, with variable degrees of thrombus formation and compromised blood flow to viable myocardium. Patients with ACS have a heterogeneous profile of short- and mid-term adverse outcomes and require a tailored approach. Recent major advances in the management of ACS have emphasized the importance of earlier identification of higher-risk patients, whose outcome might be improved by aggressive revascularization. However, during the past several years, numerous studies have shown a significant difference in the prognosis of women and men with ACS. Some reports have concluded that women have a worse prognosis than men after thrombolytic therapy and/or coronary angioplasty with stenting for myocardial reperfusion. The aim of our retrospective study was to determine sex differences in outcomes after early percutaneous intervention (PCI) in high-risk patients with acute coronary syndromes (ACS). A total of 694 consecutive patients (151 women with 233 treated lesions and 543 men with 850 treated lesions) were included. Enrollments were limited to ACS patients judged to be at high risk [unstable angina/non ST-elevation myocardial infarction with recurrent ischemia/dynamic ST segment changes (53.6% vs 52.4%) or post-infarction unstable angina (46.4% vs 47.6%)] who underwent PCI within 24 hours of admission if the coronary anatomy was deemed suitable. The two groups were well matched for clinical and lesion characteristics, except that the women, as in other studies, were older (67.9 +/- 11.3 vs 62.3 +/- 12.3 years) and had a higher prevalence of hypertension. All the lesions were treated by stent implantation, and glycoprotein IIb/IIIa inhibitors were used similarly in the two sexes (27.1% of women, 30.5% of men). The success rates were similar (94% and 93.7%), with a similar incidence of in-hospital MACE (4% vs 3.8%, p = 0.56). After a mean follow-up of 564 +/- 294 days, the two groups had similar rates of mortality (2% vs 3.2%), myocardial infarction (6.7% vs 7.1%) and repeated revascularization (7.2% vs 8.3%). The respective event-free survival rates were 88 +/- 60.3% and 83 +/- 0.3% at 1 year and 87% vs 78 +/- 0.2% at 2 years (p = 0.58). Previous studies have shown increased morbidity and mortality associated with recurrent ischemia and myocardial infarction in women after acute revascularization for ACS. Our study confirms that aggressive revascularization offers a comparable survival benefit in the two sexes. Women with ACS who are at high risk derive the same benefit as men from early angioplasty and coronary stenting of the culprit lesion, with satisfactory in-hospital and mid-term outcomes.

Acute Disease↗

PubMed1991

[4p trisomy secondary to paternal translocation t(4p-;15q+)].

A new case of trisomy 4p is reported. The patient was a boy with dysmorphism, growth failure and developmental retardation. Craniofacial features included microcephaly with a flat forehead, a prominent glabella, hyperteleorism, a broad, concave nasal bridge, a bulb-shaped nose, a wide mouth with a prominent upper lip and a short philtrum, low-set ears, a low hairline, micrognathia, and a short neck. Abdominal muscles were normal. Cryptorchidism with a hypoplastic scrotum and a micropenis were found, as well as forced flexion of the fingers and talipes equinus. The intravenous urogram disclosed ptosis of the right kidney. Developmental retardation was severe with an IQ under 50. RHG banding techniques on peripheral lymphocytes disclosed 4p14 pter duplication. The karyotype was 46,XY inv dup(4-p) (p14----pter). The mother's karyotype was normal. The father had a translocation between the short arm of chromosome 4 and the long arm of chromosome 15; his karyotype was 46,XY, t(4;15) (p14;q26). Thus, the child had trisomy for a segment of the short arm of chromosome 4 (p14----pter) and monosomy for the terminal band of the long arm of chromosome 15 (15q26). The first case of trisomy 4p was reported in 1970 by Wilson et al. Since then, there have been 46 additional reports in the medical literature. Although children with trisomy 4p share a number of features, the phenotypic manifestations of this chromosomal abnormality are variable and nonspecific, making clinical diagnosis difficult.

Child, Preschool↗

PubMed1987

Sporadic idiotypic cross-reactivities between antibodies and T helper cells: one example of aleatory expression of T cell idiotypes.

Idiotypic cross-reactivities between T and B cell receptors have been taken in the past to suggest VH-gene expression by both types of lymphocytes. More recently, after the molecular characterization of TcR, those observations were reinterpreted to indicate idiotypic network regulation, operating to select cross-reactive idiotypes in both B and T cell compartments. In support of these views, it has been shown that T cell expression of idiotypes is controlled by IgH-linked genes and markedly altered in B cell-deprived mice, and that T cells "learn" idiotype expression from the B cell compartment in the first few weeks of life. In most of these studies, aleatory idiotype cross-reactivities have not been sufficiently considered. Given the large diversity of antibodies and TcR, and the degeneracy of antibody-ligand interactions, it could be expected that a (monoclonal) anti-idiotypic reagent prepared against an antibody idiotope will always "cross-react" with some TcR variable regions. If these will be "major" T cell clonotypes, situations of idiotype sharing by B and T cells can be found which indicate neither VH-gene expression by T cells nor idiotypic network regulation. We report here one example of such aleatory expression of antibody idiotypes by T lymphocytes. A monoclonal anti-idiotypic antibody directed to anti-TNP antibodies of BALB/c mice specifically inhibits the growth and effector activity of C57BL/6 anti-NP-self helper T cells, while failing to interact with either BALB/c anti-NP-self or C57BL/6 anti-TNP-self helper cells. The clonotypic nature of these interactions could also be demonstrated by the specific induction of IL-2 production in the appropriate helper T cells by the anti-idiotypic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Two Ia.17-specific monoclonal antibodies detect the same epitope but do not share idiotype.

The clonal diversity of anti-Ia antibodies was studied by using heterologous anti-idiotypic reagents generated against two Ia.17-specific monoclonal antibodies (Mab). The Mab 10-2.16 and 10-3.6 are specific for the Ia.17 public specificity expressed on I-A molecules of the k, s, f, u, r, and j haplotypes. Competitive inhibition experiments demonstrated that 10-2.16 and 10-3.6 inhibited the binding of each other to Ia.17-positive cell targets, indicating that they detected the same or overlapping epitope(s). Identical inhibition patterns of 125I-10-2.16 binding by 10-3.6 by using Ia.17-positive target cells of four different strains indicated that inhibition was not due to steric hindrance from binding to spatially related epitopes. Rabbit anti-10-2.16 serum detected both site-specific and framework-specific 10-2.16 idiotypic determinants not shared by 10-3.6. Conversely, rabbit anti-10-3.6 serum detected 10-3.6 idiotypic determinants not shared by 10-2.16. C3H/J (I-Ak) anti-10-2.16 serum detected only 10-2.16 framework-specific idiotypes, suggesting that 10-2.16 site-specific determinants represent cellular determinants for syngeneic Ia antigens. Furthermore, anti-Ia.17 immune serum from three of 10 mice with the Igh-Cb allotype expressed the 10-2.16 framework-specific idiotype. We have demonstrated that two anti-Ia.17 Mab, 10-2.16 and 10-3.6, lack a shared idiotype, even though they detect a similar epitope. This observation and the variable expression of 10-2.16 idiotypic determinants in immune sera indicate that the B cell response to the Ia.17 epitope detected by 10-2.16 and 10-3.6 is diverse.

Animals↗

PubMed1996

Functional dyspepsia: how could a biliary dyspepsia sub-group be recognized? A methodological approach.

Functional dyspepsia (FD) includes a heterogeneous group of patients suffering from a variety of different conditions. The Dyspepsia Project has been implemented in 14 GI Units since 1984, in order to epidemiologically test the discriminating power of the Working Teams definitions and of standardized questionnaires. Five per cent of admitted subjects were subclassified as sphincter of Oddi dysfunction or biliary dyspepsia (BD), defined as biliary pain associated or not to bilirubin or alkaline phosphatase elevation, in the abscence of ultrasonographic evidence of gallstone disease or bile duct dilatation. The more useful symptoms in favour of the diagnosis of biliary dyspepsia were found to be pain in the right hypochondrium, radiating to the shoulder, or to the back, initiated by food, and eventually associated with constipation, or epigastric postprandial discomfort. Interestingly, symptoms suggesting biliary dyspepsia are partially shared by dysmotility-like dyspepsia. The placebo response in functional dyspepsia is variable, between 6 and 80% of patients, reflecting variations in the kind and severity of the diseases in different studies. That represents a considerable difficulty in evaluating drug efficacy, even in the case of biliary dyspepsia. A therapeutic double-blind trial in functional dyspepsia using tauro-ursodeoxycholic acid is discussed.

Adult↗