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PubMed2000

Random effects modeling of multiple binomial responses using the multivariate binomial logit-normal distribution.

The multivariate binomial logit-normal distribution is a mixture distribution for which, (i) conditional on a set of success probabilities and sample size indices, a vector of counts is independent binomial variates, and (ii) the vector of logits of the parameters has a multivariate normal distribution. We use this distribution to model multivariate binomial-type responses using a vector of random effects. The vector of logits of parameters has a mean that is a linear function of explanatory variables and has an unspecified or partly specified covariance matrix. The model generalizes and provides greater flexibility than the univariate model that uses a normal random effect to account for positive correlations in clustered data. The multivariate model is useful when different elements of the response vector refer to different characteristics, each of which may naturally have its own random effect. It is also useful for repeated binary measurement of a single response when there is a nonexchangeable association structure, such as one often expects with longitudinal data or when negative association exists for at least one pair of responses. We apply the model to an influenza study with repeated responses in which some pairs are negatively associated and to a developmental toxicity study with continuation-ratio logits applied to an ordinal response with clustered observations.

Abnormalities, Drug-Induced↗

PubMed2006

Building multiclass classifiers for remote homology detection and fold recognition.

BACKGROUND: Protein remote homology detection and fold recognition are central problems in computational biology. Supervised learning algorithms based on support vector machines are currently one of the most effective methods for solving these problems. These methods are primarily used to solve binary classification problems and they have not been extensively used to solve the more general multiclass remote homology prediction and fold recognition problems. RESULTS: We present a comprehensive evaluation of a number of methods for building SVM-based multiclass classification schemes in the context of the SCOP protein classification. These methods include schemes that directly build an SVM-based multiclass model, schemes that employ a second-level learning approach to combine the predictions generated by a set of binary SVM-based classifiers, and schemes that build and combine binary classifiers for various levels of the SCOP hierarchy beyond those defining the target classes. CONCLUSION: Analyzing the performance achieved by the different approaches on four different datasets we show that most of the proposed multiclass SVM-based classification approaches are quite effective in solving the remote homology prediction and fold recognition problems and that the schemes that use predictions from binary models constructed for ancestral categories within the SCOP hierarchy tend to not only lead to lower error rates but also reduce the number of errors in which a superfamily is assigned to an entirely different fold and a fold is predicted as being from a different SCOP class. Our results also show that the limited size of the training data makes it hard to learn complex second-level models, and that models of moderate complexity lead to consistently better results.

Algorithms↗

PubMed1984

Construction of a gene bank of Rhodopseudomonas capsulata using a broad host range DNA cloning system.

A gene bank of the phototrophic bacterium Rhodopseudomonas capsulata was constructed using the binary plasmid system pRK290/pRK2013. Fragments of about 20 kb of chromosomal DNA of R. capsulata strain 37b4 were inserted into the cloning vector pRK290. The hybrid plasmids of the gene bank, maintained in Escherichia coli HB101 were transferred by conjugation to R. capsulata strains defective in the photosynthetic apparatus with frequencies of 5 X 10(-4) to 5 X 10(-2). Phototrophically growing transconjugants occurred with frequencies of 5 X 10(-7) to 5 X 10(-6). Recombination between the hybrid plasmids and the R. capsulata chromosome was shown. The hybrid plasmid pRCF1002, carrying a 25 kb insert of R. capsulata wild type DNA, was isolated from one E. coli clone of the gene bank. It reconstituted some bacteriochlorophyll- and photosynthetic negative mutants to phototrophic growth.

Cloning, Molecular↗

PubMed2001

Neutron Brillouin scattering study of collective dynamics in a dense He-Ne gaseous mixture.

The dynamic structure factor S(k,omega) of a 77% He and 23% Ne gaseous mixture at T = 39.3 K and total number density n = 15.8 nm(-3) has been measured by inelastic neutron scattering at small angles. In the range of wave vectors studied, 0.7<k/nm(-1)<1.8, we find clear side peaks at frequencies following the hydrodynamic sound dispersion c k of the binary mixture (with c the adiabatic sound speed in the mixture). Surprisingly, neither fast modes nor a transition from normal to fast sound are observed in the above low- k region, indicating that hydrodynamic behavior persists up to k values which are larger than those predicted by theories and computer simulations.

Journal Article↗

PubMed2005

Closed-loop cortical control of direction using support vector machines.

Motor neuroprosthetics research has focused on reproducing natural limb motions by correlating firing rates of cortical neurons to continuous movement parameters. We propose an alternative system where specific spatial-temporal spike patterns, emerging in tasks, allow detection of classes of behavior with the aid of sophisticated nonlinear classification algorithms. Specifically, we attempt to examine ensemble activity from motor cortical neurons, not to reproduce the action this neural activity normally precedes, but rather to predict an output supervisory command to potentially control a vehicle. To demonstrate the principle, this design approach was implemented in a discrete directional task taking a small number of motor cortical signals (8-10 single units) fed into a support vector machine (SVM) to produce the commands Left and Right. In this study, rats were placed in a conditioning chamber performing a binary paddle pressing task mimicking the control of a wheelchair turning left or right. Four animal subjects (male Sprague-Dawley rats) were able to use such a brain-machine interface (BMI) with an average accuracy of 78% on their first day of exposure. Additionally, one animal continued to use the interface for three consecutive days with an average accuracy over 90%.

Algorithms↗

PubMed2000

Variegation of retroviral vector gene expression in myeloid cells.

We have comparatively evaluated the efficiency of a series of retroviral vectors transducing the gp91-phox gene, whose defects are responsible for impaired production of superoxide anion (O2-) by phagocytic cells and lead to the X-linked form of chronic granulomatous disease (X-CGD). These vectors included four constructs based on the MoMuLV backbone and expressing gp91-phox from the viral long terminal repeat (LTR) or from internal promoters, and one construct based on the myelotropic FMEV vector. Expression of the therapeutic gene from the MoMuLV LTR was unsatisfactory after transduction of the PLB985 X-CGD knockout cell line and of primary CD34+ hematopoietic progenitors from X-CGD patients. The presence of either constitutive or inducible internal promoters did not result in important improvements in the efficiency of O2- production and lowered the titers of the viral preparations. In contrast, sustained levels of superoxide generation were obtained upon transduction with the FMEV vector. To analyze the efficiency of transgene expression at the single cell level, over 150 cellular clones were generated from bulk cultures of PLB985 X-CGD cells transduced with this vector, each one representative of an individual transduction event. These clones revealed a markedly heterogeneous pattern of gp91-phox expression, ranging from complete silencing to full restoration of superoxide production. Within each clone, expression of the therapeutic gene correlated with the number of expressing cells rather than with the average levels of expression from each cell, indicating that at the single cell level, the proviral promoter is regulated by a binary, on/off mechanism. Moreover, both transduced bulk and clonal cell populations displayed a tendency to a progressive extinction of expression over time, with a mechanism involving LTR methylation. The design of novel retroviral vectors escaping silencing is highly desirable for efficient gene therapy.

Gene Expression↗

PubMed1990

Growth, morphology and division of flagellates of the genus Trypanoplasma (Protozoa, Kinetoplastida) in vitro.

Nine strains of trypanoplasms were grown in axenic culture. Cultures of Trypanoplasma borreli Laveran and Mesnil, 1901 from fish hosts Blicca bjoerkna, Cyprinus carpio, Scardinius erythrophthalmus and Tinca tinca and of T. guerneyorum Minchin, 1909 from Esox lucius and Trypanoplasma spp. from the leech Piscicola geometra were maintained in biphasic blood-agar medium SNB-9 supplemented with vitamins and antibiotics. In culture, the flagellates transformed into smaller, elongated stages with a little-developed undulating membrane and into short flagella that were morphologically similar to stages in the leech vector. The cultures were passaged weekly at 17-20 degrees C, but they also grew at 4 degrees C. The flagellates divided by binary fission, which was initiated by the formation of two new anterior flagella. The original anterior flagellum of the mother individual was gradually apposed to the cell surface and became the recurrent flagellum of one of the daughter individuals. In the meantime, nuclear division took place, followed by transverse cleavage of the kinetoplast. The division was completed by longitudinal fission of the mother individual into two offspring. Multiple fission that resulted in rosettes, which then cleaved into several daughter cells, was also observed, as well as some dyskinetoplastic and other anomalous forms. In cultures isolated from tenches with high parasitaemia, non-dividing, long filiform stages were observed. Culture stages were not infective for susceptible fishes.

Animals↗

PubMed1990

Calculation of site affinity constants and cooperativity coefficients for binding of ligands and/or protons to macromolecules. I. Generation of partition functions and mass balance equations.

The thermodynamics of binding of a ligand A and/or proton H to a macromolecule M is treated by the partition function method. In complex systems, the representation of the equilibria by means of cumulative constants beta PQR used as coefficients in partition functions ZM, ZA, and ZH is ill-suited to least-squares refinement procedures because the cumulative constants are interrelated by common cooperativity functions gamma j(i) and common site affinity constants kappa j. There is therefore the need to express ZM, ZA, ZH as functions of site constants kappa j and cooperativity coefficients bj. This is done by developing an algebra of partition functions based on the following concepts: (i) factorability of partition functions; (ii) binary generating function Jj = (1 + kappa j[Y])i tau for each class j of sites, represented by column (Jj) and row (Jj) vectors; (iii) cooperativity between sites of one class described by functions gamma j(i), represented by diagonal matrices gamma j; (iv) probability of finding microspecies represented by elements of tensor product matrix Ll = (J1)[J2]; (v) statistical factors mij obtained from Newton polynomials, Jj; (vi) power operators Oi', O(i-l)', and O(i tau-l)', transforming vectors Jj; and (vii) operators Oi or O(i-l) indicating tensor products of i or (i-l) vectors Jj. Vectors Jj combined in tensors Ll give rise to both an affinity/cooperativity space and a parallel index space. The partition functions ZM, ZA, and ZH and the total amounts TM, TA, and TH can be obtained as an appropriate sum of elements of matrices Ll, each of which is represented in an index space by a combination p1, p2,...q1, q2,...r1, r2,... of indices ij. From these indices the contribution of that element to partition function ZM, ZA, or ZH and to total amount TM, TA, or TH is calculated in the affinity/cooperativity space as product of factors: [i tau !/i !(i tau-i)!]kappa ij(exp[bj (i-1)i])[X]i, i being any index p, q, r and X any component M, A, or H. Future applications of this algorithm to practical problems of macromolecule-ligand-proton equilibria are outlined.

Binding Sites↗

PubMedDate not supplied

Ensemble methods for classification in cheminformatics.

We describe the application of ensemble methods to binary classification problems on two pharmaceutical compound data sets. Several variants of single and ensembles models of k-nearest neighbors classifiers, support vector machines (SVMs), and single ridge regression models are compared. All methods exhibit robust classification even when more features are given than observations. On two data sets dealing with specific properties of drug-like substances (cytochrome P450 inhibition and "Frequent Hitters", i.e., unspecific protein inhibition), we achieve classification rates above 90%. We are able to reduce the cross-validated misclassification rate for the Frequent Hitters problem by a factor of 2 compared to previous results obtained for the same data set with different modeling techniques.

Journal Article↗

PubMed2006

Family-specific approaches to the analysis of case-control family data.

Case-control studies augmented by the values of responses and covariates from family members allow investigators to study the association between the response and genetics and environment by relating differences in the response directly to within-family differences in covariates. However, existing approaches for case-control family data parameterize covariate effects in terms of the marginal probability of response, the same effects that one estimates from standard case-control studies. This article focuses on the estimation of family-specific covariate effects and develops efficient methods to fit family-specific models such as binary mixed-effects models. We also extend the approach to cover any setting where one has a fully specified model for the vector of responses in a family. We illustrate our approach using data from a case-control family study of brain cancer and consider the use of weighted and conditional likelihood methods as alternatives.

Biometry↗

PubMed2005

Synergistic efficacy of botanical blends with and without synthetic insecticides against Aedes aegypti and Culex annulirostris mosquitoes.

Increasing insecticide resistance requires strategies to prolong the use of highly effective vector control compounds. The use of combinations of insecticides with other insecticides and phytochemicals is one such strategy that is suitable for mosquito control. In bioassays with Aedes aegypti and Culex annulirostris mosquitoes, binary mixtures of phytochemicals with or without synthetic insecticides produced promising results when each was applied at a LC25 dose. All mixtures resulted in 100% mortality against Cx. annulirostris larvae within 24 h rather than the expected mortality of 50%. All mixtures acted synergistically against Ae. aegypti larvae within the first 24 h except for one mixture that showed an additive effect. We conclude that mixtures are more effective than insecticides or phytochemicals alone and that they enable a reduced dose to be applied for vector control potentially leading to improved resistance management and reduced costs.

Aedes↗

PubMed1975

Kinetic theory of viscosity of compressed fluids.

THE VISCOSITY OF A COMPRESSED GAS IS A FUNCTION OF THREE VARIABLES: (1) the degree of crowding of the molecules; (2) their capacity, by reason of softness, flexibility, or rotational inertia, to absorb the vector momentum applied to cause flow; (3) the resistance to this vector momentum offered by the randomly oriented thermal momenta, which becomes significant when the liquid expands sufficiently to permit molecular mean free paths between binary collisions to be long enough for thermal momenta to acquire fractions of their thermal momentum in free space.The fluidity varphi of simple liquids obeys the linear equation varphi = B(V - V(0))/V(0) and its viscosity is, therefore, eta(a) = V(0)/B(V - V(0)); this accounts for components 1 and 2. The contribution of random thermal momenta, 3, obeys the equation, eta(b) = eta(0)(1 - V(t)/V). eta(0) is the viscosity of the dilute gas; V(t) is the molal volume at which the thermal contribution begins. The total momentum, eta = eta(a) + eta(b).Values of eta(0) vary linearly with T(1/2). Values of V(t) are related to heat capacities.

Journal Article↗

PubMed1981

Babesia crassa n.sp. (Sporozoa, Babesiidae) of domestic sheep in Iran.

A large Babesia sp., isolated from a sheep in Iran, provided to be serologically and morphologically different from B, motasi and B. ovis. The parasite, designated B. crassa n. sp., is characterized by the frequent occurrence of four organisms in one erythrocyte, which is the result of quadruple division and, in other cases, of two successive binary divisions. Parasited resulting from the first of two successive binary divisions are exceptionally broad. B. crassa appears to be of low pathogenicity for sheep and goats, to which it is also infective. The vector is unknown.

Animals↗

PubMed2005

Crystallization kinetics of polydisperse colloidal hard spheres. II. Binary mixtures.

In this paper we present measurements of the crystallization kinetics of binary mixtures of two different sized hard sphere particles. The growth of the Bragg reflections over time were analyzed to yield the crystallite scattering vector, the total amount of crystal, and the average linear crystal size. It was observed that a particle size distribution skewed to higher sized particles has a less detrimental effect on the crystal structure than a skew to smaller sized particles. In the latter case we observe that initial crystallite growth occurs at only a small number of sites, with further crystallization sites developing at later times. Based on these measurements we elaborate further on the previously proposed growth mechanism whereby crystallization occurs in conjunction with a local fractionation process in the fluid, which significantly affects the kinetic growth of crystallites in polydisperse systems.

Journal Article↗

PubMed2005

Agrobacterium-mediated gene transfer and enhanced green fluorescent protein visualization in the mycorrhizal ascomycete Tuber borchii: a first step towards truffle genetics.

Mycorrhizal ascomycetes are ecologically and commercially important fungi that have proved impervious to genetic transformation so far. We report here on the successful transient transformation of Tuber borchii, an ectomycorrhizal ascomycete that colonizes a variety of trees and produces highly prized hypogeous fruitbodies known as "truffles". A hypervirulent Agrobacterium tumefaciens strain bearing the binary plasmid pBGgHg was used for transformation. The genes for hygromycin resistance and the enhanced green fluorescent protein (EGFP), both under the control of vector-borne promoters, were employed as selection markers. Patches of dark and fluorescent hyphae were observed upon fluorescence microscopic examination of hygromycin-resistant mycelia. The presence of EGFP was confirmed by both confocal microscopy and PCR analysis. The lack in the transformed mycelia of the DNA coding for kanamicin resistance (a trait encoded by a vector-borne gene located outside of the T-DNA region) indicates that Agrobacterium-mediated gene transfer correctly occurred in T. borchii.

Agrobacterium tumefaciens↗

PubMed1977

Profiling of odor components and their mixtures.

Observers evaluated five odors and their 26 mixtures (two, three, four, and five components) by magnitude estimation. Estimates revealed that in mixtures there is moderate suppression of perceived intensity; a vector model proposed by Berglund (Annals of the New York Academy of Sciences, 1974, 237, 35-51) provides a good prediction of the intensity of binary mixtures, but overpredicts the intensity of three, four, and five component mixtures. Hedonic tones of mixtures were difficult to predict from hedonic tones of components. Qualities of mixtures were difficult to predict from quality of components. Intermediacy, of quality and hedonic values, was often observed.

Adult↗

PubMed2000

High-resolution electron microscopy observation of a new crystalline approximant W' of Mg-Zn-Y icosahedral quasicrystal

A new ordered structure W' with a lattice parameter (a = 2.05 nm) about three times as large as that of the fundamental face-centered cubic W phase (a = 0.6848 nm) has been found in the Mg-Zn-Y system by means of transmission electron microscopy. The W' and W phases have the cube-to-cube orientation relationship. Moreover, the strong electron diffraction spots of the W' phase showed pseudoicosahedral symmetry, implying that it is a crystalline approximant of the Mg-Zn-Y icosahedral quasicrystal. In the high-resolution electron microscopic images of the W' phase, Penrose tiles of pentagons and boats with an edge length of a(p) = 0.481 nm can be identified. A binary tile of crown subunit has also been deduced from such a tiling. Translation domains of the W' phase have also been observed and the translation vectors at the domain boundary are: a(p), tau x a(p) and (1 + tau) x a(p), respectively, where (1 + tau) x a(p) equals to the edge length a(r) of the big obtuse rhombus of the W' phase and tau = (1 + square root of 5)/2, is the golden ratio.

Journal Article↗

PubMed2005

Simple decision rules for classifying human cancers from gene expression profiles.

MOTIVATION: Various studies have shown that cancer tissue samples can be successfully detected and classified by their gene expression patterns using machine learning approaches. One of the challenges in applying these techniques for classifying gene expression data is to extract accurate, readily interpretable rules providing biological insight as to how classification is performed. Current methods generate classifiers that are accurate but difficult to interpret. This is the trade-off between credibility and comprehensibility of the classifiers. Here, we introduce a new classifier in order to address these problems. It is referred to as k-TSP (k-Top Scoring Pairs) and is based on the concept of 'relative expression reversals'. This method generates simple and accurate decision rules that only involve a small number of gene-to-gene expression comparisons, thereby facilitating follow-up studies. RESULTS: In this study, we have compared our approach to other machine learning techniques for class prediction in 19 binary and multi-class gene expression datasets involving human cancers. The k-TSP classifier performs as efficiently as Prediction Analysis of Microarray and support vector machine, and outperforms other learning methods (decision trees, k-nearest neighbour and naïve Bayes). Our approach is easy to interpret as the classifier involves only a small number of informative genes. For these reasons, we consider the k-TSP method to be a useful tool for cancer classification from microarray gene expression data. AVAILABILITY: The software and datasets are available at http://www.ccbm.jhu.edu CONTACT: actan@jhu.edu.

Algorithms↗