Trimodal Frequency Distribution Research Articles

Chimeras Unfolded

The instability of mixing in the Kuramoto model of coupled phase oscillators is the key to understanding a range of spatiotemporal patterns, which feature prominently in collective dynamics of systems ranging from neuronal networks, to coupled lasers, to power grids. In this paper, we describe a codimension–2 bifurcation of mixing whose unfolding, in addition to the classical scenario of the onset of synchronization, also explains the formation of clusters and chimeras. We use a combination of linear stability analysis and Penrose diagrams to identify and analyze a variety of spatiotemporal patterns including stationary and traveling coherent clusters and twisted states, as well as their combinations with regions of incoherent behavior called chimera states. Penrose diagrams are used to locate the bifurcation of mixing and to determine its type. The linear stability analysis, on the other hand, yields the velocity distribution of the pattern emerging from the bifurcation. Furthermore, we show that network topology can endow chimera states with nontrivial spatial organization. In particular, we present twisted chimera states, whose coherent regions are organized as stationary or traveling twisted states. The analytical results are illustrated with numerical bifurcation diagrams computed for the Kuramoto model with uni-, bi-, and trimodal frequency distributions and all-to-all and nonlocal nearest-neighbor connectivity.

Scale matters: fire–vegetation feedbacks are needed to explain tropical tree cover at the local scale

AbstractAt a broad (regional to global) spatial scale, tropical vegetation is controlled by climate; at the local scale, it is believed to be determined by interactions between disturbance, vegetation and local conditions (soil and topography) through feedback processes. It has recently been suggested that strong fire–vegetation feedback processes may not be needed to explain tree‐cover patterns in tropical ecosystems and that climate–fire determinism is an alternative possibility. This conclusion was based on the fact that it is possible to reproduce observed patterns in tropical regions (e.g. a trimodal frequency distribution of tree cover) using a simple model that does not explicitly incorporate fire–vegetation feedback processes. We argue that these two mechanisms (feedbacks versus fire–climate control) operate at different spatial and temporal scales; it is not possible to evaluate the role of a process acting at fine scales (e.g. fire–vegetation feedbacks) using a model designed to reproduce regional‐scale pattern (scale mismatch). While the distributions of forest and savannas are partially determined by climate, many studies are providing evidence that the most parsimonious explanation for their environmental overlaps is the existence of feedback processes. Climate is unlikely to be an alternative to feedback processes; rather, climate and fire–vegetation feedbacks are complementary processes at different spatial and temporal scales.

Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants.

The thiopurine S-methyltransferase (TPMT) genetic polymorphism has a significant clinical impact on the toxicity of thiopurine drugs. It has been proposed that the identification of patients who are at high risk for developing toxicity on the basis of genotyping could be used to individualize drug treatment. In the present study, phenotype-genotype correlation of 1214 healthy blood donors was investigated to determine the accuracy of genotyping for correct prediction of different TPMT phenotypes. In addition, the influence of gender, age, nicotine and caffeine intake was examined. TPMT red blood cell activity was measured in all samples and genotype was determined for the TPMT alleles *2 and *3. Discordant cases between phenotype and genotype were systematically sequenced. A clearly defined trimodal frequency distribution of TPMT activity was found with 0.6% deficient, 9.9% intermediate and 89.5% normal to high methylators. The frequencies of the mutant alleles were 4.4% (*3A), 0.4% (*3C) and 0.2% (*2). All seven TPMT deficient subjects were homozygous or compound heterozygous carriers for these alleles. In 17 individuals with intermediate TPMT activity discordant to TPMT genotype, four novel variants were identified leading to amino acid changes (K119T, Q42E, R163H, G71R). Taking these new variants into consideration, the overall concordance rate between TPMT genetics and phenotypes was 98.4%. Specificity, sensitivity and the positive and negative predictive power of the genotyping test were estimated to be higher than 90%. Thus, the results of this study provide a solid basis to predict TPMT phenotype in a Northern European Caucasian population by molecular diagnostics.

Statistical assessment of geochemical pattern in overbank sediments of the river Sava, Croatia

Four overbank profiles from the three terraces of different age were sampled in 10 to 20 cm intervals for the bulk content of major and minor (Ca, Mg, Fe, Ti, Al, Na, K and P) and trace (Mo, Cu, Pb, Zn, Ni, Co, Mn, As, U, Th, Sr, Cd, Sb, V, La, Cr, Ba, W, Zr, Ce, Sn, Y, Nb, Ta, Sc, Li, Rb and Hf) elements in the minus 0.125 mm fraction. Univariate statistics together with analysis of variance discriminated between the lower-lying carbonate (CA) population dominantly composed of carbonates and the overlying silicate (SI) population being dominantly of silicate mineralogy. This stratified pattern resulted from the intensive erosive action of melting glaciers exerted on limestones and dolomites in the alpine region, followed by local inputs mainly of silicate composition. Elements exhibiting the greatest between-population variability are Ca and Mg being enriched in the CA population and Fe, Mn, P, Sr, Al, Na, K, Li, Rb, Y, Zr, Ni, Cr and Ti being enriched in the SI population. Anomalously high Hg, Pb and Ba concentrations (maximum values: 6,500±2,860 ppb, 225±13 ppm and 1,519±91 ppm, respectively) in the lowermost part of the profile S7, which is nearest to the Croatian-Slovenian border, derive from the mineralized Slovenian catchment area. This profile also contains trimodal frequency distributions of Fe, Mn and P whose highest concentrations coincide with increased values of Zn and Cu which are bimodally distributed. Geochemical patterns of majority of elements in all four profiles consistently reflect the average compositions of the upstream drainage basins.

Bifurcations and global stability of synchronized stationary states in the Kuramoto model for oscillator populations

Bistability between synchronized stationary states is shown to occur in large populations of nonlinearly coupled random oscillators (Kuramoto model), governed by trimodal natural frequency distributions. Numerical simulations and a numerical investigation of bifurcating states provide evidence of global stability of such states, subject to unimodal, bimodal, and trimodal frequency distributions. All this may be important in the framework of large superconducting Josephson junctions arrays, as well as of neural networks.

Genetic Characteristics of the Breaking Strength of the Basal Culm Related to Lodging Resistance in a Cross between Koshihikari and Chugoku 117.

水稲の耐倒伏性に関与する程基部の挫折強度が著しく異なる中国117号およびコシヒカリとを用いて, 耐倒伏性に関与する形質が後代にどのように分離し遺伝する特徴があるかを検討した. F1は両親に比べ稈長が長く地上部が重かったが, 稈の挫折時モーメントが大きいため倒伏しなかった. F1の稈の挫折時モーメントが大きいのは, 中国117号の断面係数が大きい性質とコシヒカリの曲げ応力の大きい性質が組合さった結果であった. 断面係数についてのF2 150個体の頻度分布は3頂分布を示し, この形質は単一遺伝子ではなく2つ以上の遺伝子が関与している可能性があること, また遺伝率は0.69とやや大きく, 断面係数は選抜の可能性のある形質と考えられた. F2における断面係数と曲げ応力との間の遣伝相関係数は-0.70で, 両方の形質を育種目標として選抜することは困難であると考えられた. しかしながら, F2個体の中には, 中国117号と同様に断面係数が大きく, 曲げ応力も中国117号より約1.5倍大きい結果, 稈の挫折時モーメントが著しく大きい個体が3個体見い出された. さらに, これらの個体から得たF3個体は, 断面係数および曲げ応力の大きい性質を備えていた. 以上の結果から, 挫折強度の大きい品種・系統との交配を通じて, 断面係数および曲げ応力がともに大きく, 耐倒伏性の大きい性質を付与できる可能性のあることが示唆された.

Dynamic Organization of Endocytic Pathways in Axons of Cultured Sympathetic Neurons

Despite the wealth of information about endocytic pathways in non-neuronal cells, little is known about these crucial sorting, recycling, and degradative pathways in neurons. In this report, we analyzed in detail the dynamic steady-state organization of endocytically derived organelles as they progress through the endosomal-lysosomal pathway in axons of live cultured sympathetic neurons. By ratiometric imaging of neurons endocytically labeled with the pH indicator 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS), we demonstrate a trimodal frequency distribution of endocytic organelle pH in axon shafts, indicating two rapid acidification steps in the progression from endocytosis to the lysosome. Axonal branch points display a unimodal organelle pH distribution (mean 6.4), implicating them as meeting places for endocytic organelles and Golgi-derived vesicles or as sorting sites. By following endocytic organelle traffic retrogradely from growth cone to soma, we identified significant transition points in the pathway. Growth cones exhibit a unimodal pH distribution comprised mainly of acidified recycling/sorting endosomes (mean 6.3). However, organelles in the axon shaft immediately adjacent to the growth cone display the distinct trimodal pH distribution of the axon, suggesting that important sorting events occur between these domains. An abrupt increase in organelle acidification occurs in the distal axon 50-150 microns from the growth cone, demonstrating a discontinuous spatial gradient of acidification along axons. Immunofluorescence microscopy reveals that the lysosomal glycoprotein LEP100 is present in axons and is concentrated in two important regions: the proximal axon where the endocytic organelle population is largely acidified, and the same region of the distal axon where substantial acidification occurs.

Thiopurine methyltransferase activity in a Korean population sample of children*

Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that catalyzes the S-methylation of the cytotoxic drugs 6-mercaptopurine and azathioprine. Red blood cell (RBC) TPMT activity is subject to genetic polymorphism, and we have previously demonstrated an interethnic difference in TPMT activity. To investigate whether there was a race-related difference in RBC TPMT activity, TPMT was measured in a Korean population sample of 309 healthy children. Mean TPMT activity in healthy Korean children was 12.4 +/- 2.4 units/ml RBC, which is similar to the earlier reported TPMT activities in white populations. In contrast to the bimodal or trimodal frequency distributions of RBC TPMT activity in most other population samples, the frequency distribution histogram, the probit plot, and the Shapiro-Wilk test supported a normal distribution of TPMT activity in this Korean population sample of healthy children. Mean RBC TPMT activity showed a tendency to decrease with age, but it was not statistically significant. No gender-related difference in RBC TPMT activity was found.

Linkage of Chromosomal Markers on 4q With a Putative Gene Determining Maximal Insulin Action in Pima Indians

Insulin action in vivo varies widely in nondiabetic Pima Indians. Not all of this variance is attributable to individual differences in obesity, physical fitness, sex, or age, and after correcting for these co-variates, measures of insulin action aggregate in families. Insulin action at maximally stimulating insulin concentrations has a trimodal frequency distribution, particularly among obese individuals. This is consistent with the hypothesis that a codominantly inherited autosomal gene, unrelated to obesity, determines MaxM in the population. Preliminary sib-pair linkage analyses indicated the possibility of linkage between MaxM and the GYPA/B locus (encoding the MNSs red cell surface antigens) on chromosome 4q. To confirm and extend these findings, 10 additional loci on 4q were typed in 123 siblings and many of their parents from 46 nuclear families. The results indicate significant (P < 0.001) linkage of the FABP2 and ANX5 loci on 4q with MaxM, and of FABP2 with fasting insulin concentration. No linkage was found between the 4q markers and obesity. Our findings indicate that a gene on 4q, near the FABP2 and ANX5 loci, contributes to in vivo insulin action in Pima Indians.

Attachment level changes in destructive periodontal diseases.

The present communication attempts to summarize some of the features of attachment loss which are of interest to the clinician and the statistician analyzing data from clinical trials. These include the measurements employed to detect changes in attachment level, the nature of the destructive disease process and the effects of therapy on the attachment level measurements. Although there are several difficulties associated with the attachment level measurement, at the present time it appears to be the best estimator of periodontal attachment available. The overall standard deviation of this measurement in greater than 46,000 replicate measurements at periodontal sites in 58 subjects was 0.78 mm (range 0.4 to 1.2 mm). In the periodontally healthy subject, the length of the attachment measured around 28 teeth is approximately 700 mm. Therefore, there are approximately 1400 adjacent points along the periodontal attachment where a measurement could be made using a periodontal probe with a 0.5 mm diameter tip. If 6 measurements were recorded per tooth, then approximately 12% of the possible probable points would be evaluated. Recent data indicate that destructive periodontal diseases progress with acute bursts of activity rather than as slowly progressive, continual processes. Such findings suggest new models of attachment loss progression. In one likely model, destructive periodontal diseases would progress by asynchronous bursts of activity at individual sites which occur with greater frequency during a finite period of time in an individual's life. 3 major patterns of attachment loss could be distinguished when frequency distributions of attachment level measurements were constructed for 61 destructive periodontal disease subjects. Pattern I (30 subjects) exhibited a bimodal distribution with localized destruction occurring at less than 34% of sites. Pattern II (14 subjects) exhibited more widespread disease (greater than 33% of sites affected) with a trimodal frequency distribution. Pattern III (17 subjects) exhibited a unimodal distribution in which virtually all sites were affected. The proportions of Fusobacterium nucleatum, Streptococcus intermedius and Eikenella corrodens in subgingival plaque samples were significantly elevated in sites of subjects with patterns II and III (the widespread disease groups). Bacteroides intermedius, Streptococcus uberis and Actinobacillus actinomycetemcomitans were elevated in sampled sites of localized disease subjects (pattern I). The effects of therapy by Widman flap surgery and systemic tetracycline were examined by several statistical analyses.(ABSTRACT TRUNCATED AT 400 WORDS)

Corticosteroid-Induced Ocular Hypertension

AbstractTopical corticosteroids produce adverse effects, including an elevation in intraocular pressure. Initial observations suggested that the pressure response was genetically determined and that inheritance of this response was closely associated with that of primary open-angle glaucoma. The response would have been useful in screening the normal population or those at risk for glaucoma, and also for identifying those ocular hypertensives likely to progress to glaucoma, but this was never realized. Other workers were unable to demonstrate the trimodal frequency distribution that formed the basis of the concept of corticosteroid pressure response as a prognostic indicator and later evidence was produced to show that corticosteroid-induced ocular hypertension can be acquired. This pressure response therefore has no clinical role in glaucoma practice but its significance as an adverse reaction to prolonged use of topical corticosteroids is stressed. A hypothesis is postulated for the response's mechanism.

Erythrocyte catechol-O-methyltransferase activity in a Swedish population.

Erythrocyte catechol-O-methyltransferase (COMT) activity has been analyzed in 185 individuals. The activities showed a trimodal frequency distribution. This suggests an autosomal codominant inheritance of the human erythrocyte COMT activity. The mean male COMT activity was 18.9 +/- 7.0 (S.D.) nmol/ml RBC/h. The mean female activity was 16.1 +/- 6.3 nmol/ml RBC/h and the frequency distribution pattern for women was shifted towards lower values.

Pharmacogenetics of Tolbutamide Metabolism in Humans

This study was designed to focus on the genetic control of tolbutamide dispositon in humans and to provide insight into the potential for high accrued blood levels in individuals receiving fixed dosage regimens. Tolbutamide was administered intravenously to 42 nondiabetic subjects, eight of their relatives, and to five sets of twins. A ninefold variation in the rate of tolbutamide disappearance from plasms (Kd) was found. This variation was characterized by a trimodal frequency distribution, suggestive of monogenic inheritance and consistent with pedigree analysis, indicating autosomal transmission of rapid and slow inactivation of tolbutamide. A heritability value of 0.995 for Kd indicated little influence of environmental factors on variation of this rate. Interindividual differences in the binding of 35S-tolbutamide to serum proteins were also assessed. No correlation was found between tolbutamide serum protein binding affinity and Kd. Analysis of the metabolites of tolbutamide in urine samples provided evidence for the microsomal oxidation of the drug to hydroxytolbutamide as the primary site of genetic control. In conclusion, this study provides evidence for monogenic control of tolbutamide metabolism in man. The results suggest that fixed dosage regimens of this drug, as were prescribed in the controversial University Group Diabetes Program study, might lead to higher accrued blood levels in slow inactivators.

Comparative Pharmacokinetics of Coumarin Anticoagulants XXXIII: Frequency Distribution of Dicumarol Total Clearance in Rats

The total clearance of dicumarol was determined in 172 adult male Sprague-Dawley rats. Clearance values ranged from 1.46 to 27.0 ml/hr/kg. Statistical analysis of a histogram of the total clearance values indicated a trimodal distribution, with modes at 6.28, 14.8, and 23.7 ml/hr/kg. The percentage of animals in each of these components was 60.5 33.7, and 5.8. A previous study had shown that the total clearance of dicumarol was proportional to the fraction of nonprotein-bound drug in serum (serum free fraction) and that interindividual differences in total clearance of dicumarol in rats were due almost entirely to corresponding differences in the serum free fraction. Therefore, it is likely that the observed trimodal frequency distribution of total clearance values reflects a similar distribution of serum free fraction values of dicumarol. The frequency distribution curve for dicumarol total clearance is very similar to the trimodal frequency distribution curve for warfarin serum free fraction values in rats. This observation is consistent with the previously demonstrated strong correlation of serum free fraction values of dicumarol and warfarin in individual animals.

Normal IQ distributions of early-treated phenylketonuric children and their unaffected siblings: failure to replicate a trimodal response or negative skew.

PHENYLKETONURIA, an inherited metabolic disorder associated with mental retardation, has been generally considered a single gene defect. Fuller and Schuman1, however, have argued for a more complex genetic model, citing a trimodal frequency distribution of IQ scores for a sample of treated phenylketonurics (PKUs) and a negative skew in the IQ distributions of unaffected siblings as evidence for their model. We have analysed data collected by Hudson2 to test the basis of Fuller's findings. Evidence was found for neither a trimodal response to treatment of phenylketonuria nor a negative skew in the IQ distribution of their unaffected siblings. Both groups showed IQ distributions which were not significantly different from the expected, normal, curve for that sample.

Genetics of Isoniazid Metabolism in Caucasian, Negro, and Japanese Populations

Trimodal frequency distributions for isoniazid inactivation were found in Caucasian and Negro populations. The frequency of "rapid" and "slow" alleles in Caucasian and Negro populations was similar and differed from that of a Japanese population.