Allometric analysis using the multivariate shifted exponential normal distribution

In allometric studies, the joint distribution of the log-transformed morphometric variables is typically elliptical and with heavy tails. To account for these peculiarities, we introduce the multivariate shifted exponential normal (MSEN) distribution , an elliptical heavy-tailed generalization of the multivariate normal (MN). The MSEN belongs to the family of MN scale mixtures (MNSMs) by choosing a convenient shifted exponential as mixing distribution. The probability density function of the MSEN has a simple closed-form characterized by only one additional parameter, with respect to the nested MN, governing the tail weight. The first four moments exist and the excess kurtosis can assume any positive value. The membership to the family of MNSMs allows us a simple computation of the maximum likelihood (ML) estimates of the parameters via the expectation-maximization (EM) algorithm; advantageously, the M-step is computationally simplified by closed-form updates of all the parameters. We also evaluate the existence of the ML estimates. Since the parameter governing the tail weight is estimated from the data, robust estimates of the mean vector of the nested MN distribution are automatically obtained by downweighting; we show this aspect theoretically but also by means of a simulation study. We fit the MSEN distribution to multivariate allometric data where we show its usefulness also in comparison with other well-established multivariate elliptical distributions.     

STUDY OF BULL SPERMATOZOA : Quantitative Electron Microscopy

The electron microscope has been used to determine the characteristic dimensions and the distribution of the dry mass in bull spermatozoa. The most important result is that all characteristic data are occurring in logarithmic distributions. Furthermore, no correlation between such parameters as head weight and tail weight or head length and tail length was found. The occurrence in logarithmic distributions and the non-correlation of parts in the assembly of a spermatozoon are considered to reflect significant biologic principles. Methodologically, a new procedure is added to quantitative electron microscopy permitting the recording of the mass cross-section (total mass per unit length) of an object. This approach makes possible determinations of the distribution and the total mass of very long and narrow structures.     

鼠尾胶原蛋白提取、分离、纯化方法的建立及鉴定

目的建立一种高效提取、分离、纯化鼠尾胶原蛋白的方法。方法通过对鼠尾进行剥离获得鼠尾腱,用Tris-HCl缓冲液、胃蛋白酶处理获得鼠尾胶原蛋白原液、反复使用氯化钠溶液进行分级盐析、醋酸溶液复溶进行鼠尾胶原蛋白的纯化。超纯水透析除去无机盐类获得纯化的鼠尾胶原蛋白。通过SDS-PAGE蛋白质电泳、氨基酸含量分析等技术手段鉴定。结果本研究建立的方法可以获得高纯度的鼠尾胶原蛋白,纯度达到电泳纯。与国外进口的商业化鼠尾胶原蛋白产品相比无差异。研究了提取、分离、纯化参数对得率、纯度的影响,建立了最优的鼠尾胶原蛋白提取条件,胃蛋白酶用量：1∶500,酶解时间：72 h,盐析浓度：2 mol/L,提取所用酸溶液：0.05mol/L醋酸溶液。结论为鼠尾胶原蛋白的扩大化生产提供了合适的工艺参数,为大量获得鼠尾胶原蛋白并进行更深层次的功效方面研究提供了理论支持和实践基础。     

Calibrating E-values for hidden Markov models using reverse-sequence null models

MOTIVATION: Hidden Markov models (HMMs) calculate the probability that a sequence was generated by a given model. Log-odds scoring provides a context for evaluating this probability, by considering it in relation to a null hypothesis. We have found that using a reverse-sequence null model effectively removes biases owing to sequence length and composition and reduces the number of false positives in a database search. Any scoring system is an arbitrary measure of the quality of database matches. Significance estimates of scores are essential, because they eliminate model- and method-dependent scaling factors, and because they quantify the importance of each match. Accurate computation of the significance of reverse-sequence null model scores presents a problem, because the scores do not fit the extreme-value (Gumbel) distribution commonly used to estimate HMM scores' significance. RESULTS: To get a better estimate of the significance of reverse-sequence null model scores, we derive a theoretical distribution based on the assumption of a Gumbel distribution for raw HMM scores and compare estimates based on this and other distribution families. We derive estimation methods for the parameters of the distributions based on maximum likelihood and on moment matching (least-squares fit for Student's t-distribution). We evaluate the modeled distributions of scores, based on how well they fit the tail of the observed distribution for data not used in the fitting and on the effects of the improved E-values on our HMM-based fold-recognition methods. The theoretical distribution provides some improvement in fitting the tail and in providing fewer false positives in the fold-recognition test. An ad hoc distribution based on assuming a stretched exponential tail does an even better job. The use of Student's t to model the distribution fits well in the middle of the distribution, but provides too heavy a tail. The moment-matching methods fit the tails better than maximum-likelihood methods. AVAILABILITY: Information on obtaining the SAM program suite (free for academic use), as well as a server interface, is available at http://www.soe.ucsc.edu/research/compbio/sam.html and the open-source random sequence generator with varying compositional biases is available at http://www.soe.ucsc.edu/research/compbio/gen_sequence     

绵羊X染色体59383635位点多态性与脂尾性状的相关性分析

脂尾(臀)性状是绵羊逆境生存的必要性状, 其脂肪在尾臀部大量沉积的遗传特性与分子机制仍不明晰。为此, 文章以筛选的X染色体59383635位点SNP为候选分子标记, 利用PCR-SSCP技术检测该位点在我国尾型极端差异的阿勒泰羊、小尾寒羊、湖羊、中国美利奴细毛羊以及引入品种萨福克羊群体中的多态性, 并采用模型分析其与尾(臀)性状的相关性。结果表明, X染色体59383635位点T等位基因高频出现在表型分值较高的阿勒泰群体中, 而C等位基因则在瘦尾型绵羊品种中高频出现; 等位基因频率T/C的比值与尾臀表型分值相关性模型表明T/C比值随着尾臀表型分值增加呈指数倍增长。以上结果提示, 绵羊X染色体59383635位点多态性在脂尾(臀)与瘦尾绵羊群体中分布存在较大差异, 该SNP可作为一个理想的分子标记应用于高、低脂绵羊品种选育, 但其生物功能仍有待进一步深入研究。     

Statistical Analysis of the Comet Assay Using a Mixture of Gamma Distributions

Tail moments in the single cell gel electrophoresis (comet) assay usually do not follow a normal distribution, making the statistical analysis complicated. Researchers have used a wide variety of statistical techniques in an attempt to overcome this problem. In many cases, the tail moments follow a bimodal distribution that can be modeled with a mixture of gamma distributions. This bimodality may be due to cells being in two different stages of the cell cycle at the time of treatment. Maximum likelihood, modified to accommodate censored data, can be used to estimate the five parameters of the gamma mixture distribution for each slide. A weighted analysis of variance on the parameter estimates for the gamma mixtures can be performed to determine differences in DNA damage between treatments. These methods were applied to an experiment on the effect of thymidine kinase in DNA damage and repair. Analysis based on the mixture of gamma distributions was found to be more statistically valid, more powerful, and more informative than analysis based on log-transformed tail moments.     

The distribution of beneficial and fixed mutation fitness effects close to an optimum

The distribution of the selection coefficients of beneficial mutations is pivotal to the study of the adaptive process, both at the organismal level (theories of adaptation) and at the gene level (molecular evolution). A now famous result of extreme value theory states that this distribution is an exponential, at least when considering a well-adapted wild type. However, this prediction could be inaccurate under selection for an optimum (because fitness effect distributions have a finite right tail in this case). In this article, we derive the distribution of beneficial mutation effects under a general model of stabilizing selection, with arbitrary selective and mutational covariance between a finite set of traits. We assume a well-adapted wild type, thus taking advantage of the robustness of tail behaviors, as in extreme value theory. We show that, under these general conditions, both beneficial mutation effects and fixed effects (mutations escaping drift loss) are beta distributed. In both cases, the parameters have explicit biological meaning and are empirically measurable; their variation through time can also be predicted. We retrieve the classic exponential distribution as a subcase of the beta when there are a moderate to large number of weakly correlated traits under selection. In this case too, we provide an explicit biological interpretation of the parameters of the distribution. We show by simulations that these conclusions are fairly robust to a lower adaptation of the wild type and discuss the relevance of our findings in the context of adaptation theories and experimental evolution.     

Numerical Study of Propulsion Mechanism for Oscillating Rigid and Flexible Tuna-Tails

Numerical study on the unsteady hydrodynamic characteristics of oscillating rigid and flexible tuna-tails in viscous flow-field is performed.Investigations are conducted using Reynolds-Averaged Navier-Stokes (RANS) equations with a moving adaptive mesh.The effect of swimming speed,flapping amplitude,frequency and flexure amplitude on the propulsion performance of the rigid and flexible tuna-tails are investigated.Computational results reveal that a pair of leading edge vortices develop along the tail surface as it undergoes an oscillating motion.The propulsive efficiency has a strong correlation with various locomotive parameters.Peak propulsive efficiency can be obtained by adjusting these parameters.Particularly,when input power coefficient is less than 2.8,the rigid tail generates larger thrust force and higher propulsive efficiency than flexible tail.However,when input power coefficient is larger than 2.8,flexible tail is superior to rigid tail.     

Distribution of halothane in a dipalmitoylphosphatidylcholine bilayer from molecular dynamics calculations

We report a 2-ns constant pressure molecular dynamics simulation of halothane, at a mol fraction of 50%, in the hydrated liquid crystal bilayer phase of dipalmitoylphosphatidylcholine. Halothane molecules are found to preferentially segregate to the upper part of the lipid acyl chains, with a maximum probability near the C(5) methylene groups. However, a finite probability is also observed along the tail region and across the methyl trough. Over 95% of the halothane molecules are located below the lipid carbonyl carbons, in agreement with photolabeling experiments. Halothane induces lateral expansion and a concomitant contraction in the bilayer thickness. A decrease in the acyl chain segment order parameters, S(CD), for the tail portion, and a slight increase for the upper portion compared to neat bilayers, are in agreement with several NMR studies on related systems. The decrease in S(CD) is attributed to a larger accessible volume per lipid in the tail region. Significant changes in the electric properties of the lipid bilayer result from the structural changes, which include a shift and broadening of the choline headgroup dipole (P-N) orientation distribution. Our findings reconcile apparent controversial conclusions from experiments on diverse lipid systems.     

Robust Joint Modeling of Longitudinal Measurements and Competing Risks Failure Time Data

Existing methods for joint modeling of longitudinal measurements and survival data can be highly influenced by outliers in the longitudinal outcome. We propose a joint model for analysis of longitudinal measurements and competing risks failure time data which is robust in the presence of outlying longitudinal observations during follow‐up. Our model consists of a linear mixed effects sub‐model for the longitudinal outcome and a proportional cause‐specific hazards frailty sub‐model for the competing risks data, linked together by latent random effects. Instead of the usual normality assumption for measurement errors in the linear mixed effects sub‐model, we adopt a t ‐distribution which has a longer tail and thus is more robust to outliers. We derive an EM algorithm for the maximum likelihood estimates of the parameters and estimate their standard errors using a profile likelihood method. The proposed method is evaluated by simulation studies and is applied to a scleroderma lung study (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Modeling menstrual cycle length using a mixture distribution

In reproductive health studies, epidemiologists are often interested in examining the effects of covariates on menstrual cycle length which is a convenient, noninvasive measure of women's ovarian and reproductive function. Previous literature (Harlow and Zeger, 1991) suggests that the distribution of cycle length is a mixture of a major symmetric distribution and a component featuring a long right tail. Motivated by the shape of this marginal distribution, we propose a mixture distribution for cycle length, representing standard cycles from a Normal distribution and nonstandard cycles from a shifted Weibull distribution. The parameters are estimated using an estimating equation derived from the score function of an independence working model. The fitted mixture distribution agrees well with the distribution estimated using nonparametric approaches. We propose two measures to help determine whether a cycle is standard or nonstandard, developing tools necessary to identify characteristics of the menstrual cycles that are biologically indicative of ovarian dysfunction. We model the effect of a woman's age on the mean and variation of both standard and nonstandard cycle lengths using multiple measurements of women.     

Collagen fibril diameter distribution does not reflect changes in the mechanical properties of in vitro stress-deprived tendons

The purpose of this study was to determine if an association exists between the tensile properties and the collagen fibril diameter distribution in in vitro stress-deprived rat tail tendons. Rat tail tendons were paired into two groups of 21 day stress-deprived and 0 time controls and compared using transmission electron microscopy (n = 6) to measure collagen fibril diameter distribution and density, and mechanical testing (n =6) to determine ultimate stress and tensile modulus. There was a statistically significant decrease in both ultimate tensile strength (control: 17.95+/-3.99 MPa, stress-deprived: 6.79+/-3.91 MPa) and tensile modulus (control: 312.8+/-89.5 MPa, stress-deprived: 176.0+/-52.7 MPa) in the in vitro stress-deprived tendons compared to controls. However, there was no significant difference between control and stress-deprived tendons in the number of fibrils per tendon counted, mean fibril diameter, mean fibril density, or fibril size distribution. The results of this study demonstrate that the decrease in mechanical properties observed in in vitro stress-deprived rat tail tendons is not correlated with the collagen fibril diameter distribution and, therefore, the collagen fibril diameter distribution does not, by itself, dictate the decrease in mechanical properties observed in in vitro stress-deprived rat tail tendons.     

Changes in activity and object manipulation before tail damage in finisher pigs as an early detector of tail biting

Tail damage within the production of finisher pigs is an animal welfare problem. Recent research suggests that removal of known risk factors may not be enough to eliminate tail biting, especially in undocked pigs, thus a different strategy is worth investigating. This could be early detection of tail biting, using behavioural changes observed before tail damage. If these early stages of tail biting can be detected before tail damage occurs, then tail damage could be prevented by early interventions. The first step in developing such a strategy is to identify the types of behaviour changes that emerge during early stages of tail biting. Thus, the aim of the current study was to investigate whether pen level activity and object manipulation evolved differently during the last 7 days before the scoring of tail damage (day 0) for pens scored with tail damage (tail damage pens) and pens not scored with tail damage (matched control pens). The study included video recordings for twenty-four tail damage pens and thirty-two matched control pens. Activity level and object manipulation were observed the last 7 days before day 0 during the morning (0600 to 0800 h), afternoon (1600 to 1800 h) and evening (2200 to 2400 h, only activity level). Both activity level and object manipulation were analysed using generalised linear mixed effects models with a binomial distribution for activity level and a negative binomial distribution for object manipulation. The probability of being active was higher in tail damage pens compared to control pens during the afternoon the last 5 days before day 0 (P<0.001). This was seen due to a decrease in activity level in the control pens, which makes it difficult to identify future tail damage pens from this difference. Object manipulation was lower in tail damage pens compared to the control pens on all 7 days before day 0, but only in pens with undocked pigs (P<0.01). Thus, it is still unknown when this difference in object manipulation initiated. It was concluded that both activity level and object manipulation seemed related to ongoing tail biting and should be investigated through more detailed observations and for a longer time to establish the normal behaviour pattern for a particular pen. Thus, it is suggested that future research focusses on developing automatic monitoring methods for pen level activity and object manipulation and applies algorithms that establish and detect deviations from the normal behaviour pattern of the pen before tail damage.     

Kinetics of sickle hemoglobin polymerization. III. Nucleation rates determined from stochastic fluctuations in polymerization progress curves

The polymerization kinetics of sickle cell hemoglobin are found to exhibit stochastic variations when observed in very small volumes (approximately 10(-10) cm3). The distribution of progress curves has been measured at several temperatures for a 4.50 mM-hemoglobin S sample using a laser-photolysis, light-scattering technique. The progress curves at a given temperature are superimposable when translated along the time axis, showing that the variability of the kinetic progress curves results primarily from fluctuations in the time at which polymerization is initiated. The shapes of the initial part of the progress curves are well-fitted using the functional form I(t) = Io + As exp (Bt), derived from a dual nucleation model. When the distribution of the measured tenth times is broad, the rate of homogeneous nucleation can be obtained by fitting the exponential tail of the distribution. As the distribution sharpen, the rate of homogeneous nucleation can be estimated by modelling the width of the distribution function using a simple Monte-Carlo simulation of the polymerization kinetics. Using the rates of homogeneous nucleation obtained from the distributions, the rates of heterogeneous nucleation and polymer growth can be obtained from the experimental parameters As and B. The resulting nucleation rates are roughly 1000 times greater than those obtained from an analysis of bulk kinetic data. The results provide strong support for the dual-nucleation mechanism and show that the distribution of progress curves provides a powerful independent method for measuring the rate of homogeneous nucleation and thereby obtaining values for the other principal rates of the mechanism.     

Review of Dinosaur Tail Traces

Since 1858, when Hitchcock first recorded dinosaur tail traces from the Jurassic of Massachusetts, USA, a number of dinosaur tail traces have been reported. Although considered rare, at least 38 records of dinosaur tail traces have previously been reported in the literature. These occurrences are herein reviewed in order to understand their geographic and stratigraphic distribution, types of tail trace makers, and characteristics of dinosaur tail traces. Several terms for dinosaur tail traces have been employed and they are divided into tail impressions (TIs) for resting traces, and tail drag impressions (TDIs) for locomotion traces. Possible criteria for distinguishing, measuring and comparing TIs and TDIs are suggested. In addition, herringbone structures, one of the characteristic features of tail traces associated with ornithopod and theropod tracks, are discussed. Estimated speeds of tail trace makers are shown to be rather low. Finally, the abundance of tail traces associated with bipedal, rather than quadrupedal, dinosaurs is considered a reflection of behavior.     

Comet assay: rapid processing of multiple samples

The present study describes modifications to the basic comet protocol that increase productivity and efficiency without sacrificing assay reliability. A simple technique is described for rapidly preparing up to 96 comet assay samples simultaneously. The sample preparation technique allows thin layers of agarose-embedded cells to be prepared in multiple wells attached to a flexible film of Gelbond, which improves the ease of manipulating and processing samples. To evaluate the effect of these modifications on assay sensitivity, dose-response curves are presented for DNA damage induced by exposure of TK6 cells to low concentrations of hydrogen peroxide (0-10 microM) and for exposure of human lymphocytes to X-irradiation (0-100 cGy). The limit of detection of DNA damage induced by hydrogen peroxide in TK6 cells was observed to be 1 uM for all parameters (tail ratio, tail moment, tail length and comet length) while the limit of detection of DNA damage in human lymphocytes was 10 cGy for tail and comet length parameters, but 50 cGy for tail ratio and tail moment parameters. These results are similar to those previously reported using the conventional alkaline comet assay. The application of SYBR Gold for detection of DNA damage was compared to that of propidium iodide. Measurements of matching samples for tail length and comet length were similar using both stains. However, comets stained with SYBR Gold persisted longer and were much brighter than those obtained with propidium iodide. SYBR Gold was found to be ideal for measuring tail length and comet length but, under present assay conditions, impractical for measuring tail ratio or tail moment due to saturation of staining in the head region of the comets.     

Distribution of the number of false discoveries in large-scale family-based association testing with application to the association between <Emphasis Type="Italic">PTPN1</Emphasis> and hypertension and obesity

We present a model-free approach to the study of the number of false discoveries for large-scale simultaneous family-based association tests (FBATs) in which the set of discoveries is decided by applying a threshold to the test statistics. When the association between a set of markers in a candidate gene and a group of phenotypes is studied by a class of FBATs, we indicate that a joint null hypothesis distribution for these statistics can be obtained by the fundamental statistical method of conditioning on sufficient statistics for the null hypothesis. Based on the joint null distribution of these statistics, we can obtain the distribution of the number of false discoveries for the set of discoveries defined by a threshold; the size of this set is referred to as its tail count. Simulation studies are presented to demonstrate that the conditional, not the unconditional, distribution of the tail count is appropriate for the study of false discoveries. The usefulness of this approach is illustrated by re-examining the association between PTPN1 and a group of blood-pressure-related phenotypes reported by Olivier et al. (Hum Mol Genet 13:1885–1892, 2004); our results refine and reinforce this association.