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[Classical taxomomies].

The sequence of classic paradigms in taxonomy that partly replaced each other and partly co-exist is given as follows: the theory of "organ and organism similarity", the naturalistic theory, the descriptive theory, and the phylogenetic theory. The naturalistic classics accepted the notion of "the plan of creation". The rejection of appealing to this plan brought forth certain problems in the formulation of the purpose of taxonomy; these problems were differently solved by the descriptive and the phylogenetic classic traditions. The difficulties of the current paradigms arising from the loss of a "strong purpose", a problem to be solved by taxonomists that is to be clear and interesting to a wide range of non-professionals. The paradox of formalization led to the losing of content of the methods due to their formalization. To attract attention to taxonomy, a new "image of the results" of its work that would be interesting to the non-professionals is necessary. The co-existence of different methods of reseach applied to different groups of facts leads to the loss of integrity of the research. It is not only that the taxon becomes a hypothesis and such hypotheses multiply. The comparison of these hypotheses is problematic, because each of them is supported by its own independent scope of facts. Because of the existence of a fundamental meronotaxonomic discrepancy, taxonomic systems based on different groups of characters appear to be incomparable, being rather systems of characters than systems of taxa. Systems of characters are not directly comparable with each other; they can be compared only through appealing to taxa, but taxa themselves exist only in the form of a number of hypotheses. Consequently, each separate taxonomic approach creates its own nature, its own subject of research. Therefore, it is necessary to describe the subject of research correctly (and indicate the purpose of research), as well as to distinguish clearly between results achieved through different systems of characters. The diversity of current "classic" approaches calls for a unification within the frame of a more general theory. The development of such a theory can be achieved through the formulaiton of a substantial theory of organization that would reflect the formal unity of a taxon, i.e., a theory of meron organization that woud hepl establish the relationship of taxonomic systems developed for different merons.

Animals↗

Nanosuspensions as a new approach for the formulation for the poorly soluble drug tarazepide.

Poorly soluble drugs are often a challenging problem in drug formulation, especially when the drug is not soluble in either aqueous media or organic solvents. Attempts to overcome the solubility problem are, e.g. solubilisation with mixed micelles or forming a complex using cyclodextrines, but these approaches are of limited success. Another problem with new high potential drug is that these drugs often show bioavailability problems. One tried to improve the in vivo performance of poorly soluble drugs by reducing the particles size of the drug thus leading to an increased surface area and an increased dissolution velocity (Müller et al., 1994, 1999). Some of these problems occurred with tarazepide and therefore it was tried to create a formulation with this drug as nanosuspension which is suitable for intravenous administration.

Benzodiazepines↗

An integer programming approach to the phase problem for centrosymmetric structures.

The problem addressed in this paper is the determination of three-dimensional structures of centrosymmetric crystals from X-ray diffraction measurements. The 'minimal principle' that a certain quantity is minimized only by the crystal structure is employed to solve the phase problem. The mathematical formulation of the minimal principle is a nonconvex nonlinear optimization problem. To date, local optimization techniques and advanced computer architectures have been used to solve this problem, which may have a very large number of local optima. In this paper, the minimal principle model is reformulated for the case of centrosymmetric structures into an integer programming problem in terms of the missing phases. This formulation is solvable by well established combinatorial optimization techniques that are guaranteed to provide the global optimum in a finite number of steps without explicit enumeration of all possible combinations of phases. Computational experience with the proposed method on a number of structures of moderate complexity is provided and demonstrates that the approach yields a fast and reliable method that resolves the crystallographic phase problem for the case of centrosymmetric structures.

Journal Article↗

The boundary element method in the forward and inverse problem of electrical impedance tomography.

In this paper, a new formulation of the reconstruction problem of electrical impedance tomography (EIT) is proposed. Instead of reconstructing a complete two-dimensional picture, a parameter representation of the gross anatomy is formulated, of which the optimal parameters are determined by minimizing a cost function. The two great advantages of this method are that the number of unknown parameters of the inverse problem is drastically reduced and that quantitative information of interest (e.g., lung volume) is estimated directly from the data, without image segmentation steps. The forward problem of EIT is to compute the potentials at the voltage measuring electrodes, for a given set of current injection electrodes and a given conductivity geometry. In this paper, it is proposed to use an improved boundary element method (BEM) technique to solve the forward problem, in which flat boundary elements are replaced by polygonal ones. From a comparison with the analytical solution of the concentric circle model, it appears that the use of polygonal elements greatly improves the accuracy of the BEM, without increasing the computation time. In this formulation, the inverse problem is a nonlinear parameter estimation problem with a limited number of parameters. Variants of Powell's and the simplex method are used to minimize the cost function. The applicability of this solution of the EIT problem was tested in a series of simulation studies. In these studies, EIT data were simulated using a standard conductor geometry and it was attempted to find back this geometry from random starting values. In the inverse algorithm, different current injection and voltage measurement schemes and different cost functions were compared. In a simulation study, it was demonstrated that a systematic error in the assumed lung conductivity results in a proportional error in the lung cross sectional area. It appears that our parametric formulation of the inverse problem leads to a stable minimization problem, with a high reliability, provided that the signal-to-noise ratio is about ten or higher.

Algorithms↗

Network flow problems with fuzzy arc lengths.

Network flow problems cover a wide range of engineering and management applications. Many streamlined solution methods have been devised for solving different types of the problems. This paper investigates the network flow problems in that the arc lengths of the network are fuzzy numbers. Based on the integer-solution property of the network flow problem, the Yager ranking indices can be calculated for the fuzzy arcs to change the fuzzy formulation of the problem to a crisp formulation. Consequently, the conventional streamlined solution methods can still be applied to find an optimal solution. This optimal solution is proved to be the same as that derived from an exhaustive comparison of all possible solutions. Two examples, one shortest path and one transshipment, discussed in some previous studies illustrate that the method proposed in this paper is able to find the optimal solution. To show that the proposed method is useful in solving real-world problems, the problem of multimedia transmission over the Internet is exemplified.

Journal Article↗

Analysis of the force-sharing problem using an optimization model.

In biomechanics, one frequently used approach for finding a unique set of muscle forces in the 'force-sharing problem' is to formulate and solve a non-linear optimization problem of the form: min phi(f)= summation operator (f(i)/omega(i))(alpha) subject to Af = b and f > or = 0. Solutions to this problem have typically been obtained numerically for complex models, or analytically for specific musculoskeletal geometries. Here, we present simple geometrical methods for analyzing the solution to this family of optimization problems for a general n-degrees-of-freedom musculoskeletal system. For example, it is shown that the moment-arm vectors of active (f(i) > 0) and passive (f(i) = 0) muscles are separated by a hyperplane through the origin of the moment-arm vector space. For the special case of a system with two degrees-of-freedom, solutions can be readily represented in graphical form. This allows for powerful interpretations of force-sharing calculated using optimization.

Animals↗

Nanomachines: methods to induce a directed motion at nanoscale.

The motion of bodies in a periodic potential with weak damping is discussed. A spontaneous directed motion of particles is shown to be possible in the presence of external periodic forces at a velocity unambiguously defined by the frequency of the periodic action and the spatial period of the potential. The principle of inducing the directed motion at a precisely controlled velocity can be used to develop (i) means of handling individual molecules or molecular clusters on crystalline surfaces; (ii) "nanomachines"-objects capable of spontaneous motion not only in the absence of an external force but also under the action of a force opposite to the direction of motion (and thereby capable of carrying other particles); (iii) drives providing precisely controlled velocity of motion; (iv) controllable tribological systems constructed by profiling friction surfaces in a specified manner and applying an ultrasonic excitation. The dependence of the average system velocity on the average applied force is shown to have plateaus of constant velocity at zero velocity and a set of equidistant discrete velocities in the presence of periodic external perturbations. The problem of developing fully controlled nanomachines can be formulated as the problem of controlling the width and position of the plateaus.

Journal Article↗

Fast de novo peptide sequencing and spectral alignment via tree decomposition.

De novo sequencing and spectral alignment are computationally important for the prediction of new protein peptides via tandem mass spectrometry (MS/MS). Both approaches are established upon the problem of finding the longest antisymmetric path on formulated graphs. The problem is of high computational complexity and the prediction accuracy is compromised when given spectra involve noisy data, missing mass peaks, or post translational modifications (PTMs) and mutations. This paper introduces a graphical mechanism to describe relationships among mass peaks that, through graph tree decomposition, yields linear and quadratic time algorithms for optimal de novo sequencing and spectral alignment respectively. Our test results show that, in addition to high efficiency, the new algorithms can achieve desired prediction accuracy on spectra containing noisy peaks and PTMs while allowing the presence of both b-ions and y-ions.

Algorithms↗

First-order system least squares for elastohydrodynamics with application to flow in compliant blood vessels.

Mathematical modeling of compliant blood vessels generally involves the Navier-Stokes equations on the evolving fluid domain and constitutive structural equations on the tissue domain. Coupling these systems while accounting for the changing shape of the fluid domain is a major challenge in numerical simulation. Many techniques have been developed to model compliant vessels, but all suffer from disproportionate increase in computational cost as problem complexity increases (i.e., larger domains, more dimensions, and more variables.). Even the best standard methods result in computational cost that typically grows quadratically with the degrees of freedom. Using a least-squares formulation of the problem, elliptic grid generation for the changing fluid domain, and an algebraic multigrid solver for the linear system can overcome many shortcomings of standard techniques. Most notably, the computational cost of solving the problem increases linearly with the degrees of freedom and the associated functional provides an a posteriori error measurement. Least squares represents a systematic approach for formulating the original problem so that the numerical process becomes straightforward and optimal, and it avoids restrictions that often limit other methods. Results are presented for a two-dimensional test problem consisting of a Newtonian fluid with properties of blood in a linear-elastic vessel with properties of smooth muscle.

Computer Simulation↗

An improved collocation method for solving the Henry problem.

The original Henry problem is characterized with severe (albeit unphysical) sea boundary condition difficult to handle with numerical methods. In this paper, we present an improved numerical solution of the Henry problem. Presented numerical model solves the steady-state dimensionless equations by the collocation method named Fup Fragment Collocation Method (FFCM) and uses R(bf) basis functions of Fup(2) (x, y) type. This method enables application of the classical formulation and high approximation accuracy as proven in comparison with published solutions. Particular difficulty in solving the original Henry problem is in the accurate representation of the seepage face due to the fixed sea concentration at the sea boundary. The results of the original Henry problem formulation and problem with modified boundary conditions indicate the accuracy and robustness of the FFCM in describing the discharge area of the considered problem.

Humans↗

Neural networks and linear programming for the satisfiability problem.

First a Linear Programming formulation is considered for the satisfiability problem, in particular for the satisfaction of a Conjunctive Normal Form in the Propositional Calculus and the Simplex algorithm for solving the optimization problem. The use of Recurrent Neural Networks is then described for choosing the best pivot positions and greatly improving the algorithm performance. The result of hard cases testing is reported and shows that the technique can be useful even if it requires a huge amount of size for the constraint array and Neural Network Data Input.

Algorithms↗

The implausibility of Mendel's theory before 1900.

Attention is paid to the category of the plausibility of Mendel's terminology in formulating the research problem, in describing experimental model and research method and in explaining his theory in the historical context of the long lasting enigma of generation, hybridization and heredity. The new research problem of heredity derived from the enigma of generation was plausible for the sheep breeders in Brno in 1836-1837 who also formulated the research question: what and how is inherited? But they did not find an approach to the experimental investigation. Later in 1852 the research problem of heredity was formulated by the physiologist of the Göttingen University, R. Wagner, who also outlined the method of crossing animals or artifical fertilization of plants for the investigation of the enigma of generation and heredity. But he could not carry out the recommended experiments at the University. His proposal remained without echo. Mendel first mentioned the motivation for his research arising from plant breeding experience and then from the experiments with plant crossing by botanists. He delivered his lectures in Brno to the community of naturalists, who paid attention to the appearance of hybrids in nature, but were not interested in plant breeding. After describing research model and experimental method Mendel presented the sequence of hypotheses proved in experiments and explained the origin and development of hybrids and at the same time also the mechanism of fertilization and of transmission of traits, what was heredity without using the term. The listeners of his lectures and later the readers of his paper did not understand his explanation. ...

Austria↗

Application of mathematical tools to improve the design and operation of activated sludge plants. Case study: the new WWTP of Galindo-Bilbao. Part I: Optimum design.

This paper presents a mathematical formulation for the optimum design of a new activated sludge WWTP. The WWTP optimum design problem has been formulated as a Mathematical Programming problem, which is solved through a nonlinear optimisation method. The plant model has been based on the ASM1. The minimum volume of the biological reactors and the minimum total cost (including construction and exploitation costs) have been considered as optimisation criteria. Some practical results are also included, using as a case study the design of the second stage of the Galindo-Bilbao WWTP.

Algorithms↗

Development of a lyophilized formulation of interleukin-2.

Native human interleukin-2 (IL-2) comprises a group of glycoproteins of MW 13,000-17,500. Recombinant human IL-2 (rhIL-2) (Cetus) is derived from E. coli and is not glycosylated. We have evaluated several processes for manufacturing rhIL-2, based on different chaotropic agents for solubilization of insoluble protein pastes. Formulation work carried out with material purified by one of these processes is reported here. Our studies have indicated that the presence of a stabilizer in the form of an amorphous excipient, such as amino acids, a non-ionic surfactant (polysorbate 80), hydroxypropyl-beta-cyclodextrin or human serum albumin was essential for preservation of rhIL-2 during lyophilization. Each of these formulations exhibited its own unique problems. We have overcome these problems through a systematic formulation development program and have been successful in developing several lyophilized formulations of rhIL-2 with optimum properties and performance.

2-Hydroxypropyl-beta-cyclodextrin↗

Enrichment or depletion of a GO category within a class of genes: which test?

MOTIVATION: A number of available program packages determine the significant enrichments and/or depletions of GO categories among a class of genes of interest. Whereas a correct formulation of the problem leads to a single exact null distribution, these GO tools use a large variety of statistical tests whose denominations often do not clarify the underlying P-value computations. SUMMARY: We review the different formulations of the problem and the tests they lead to: the binomial, chi2, equality of two probabilities, Fisher's exact and hypergeometric tests. We clarify the relationships existing between these tests, in particular the equivalence between the hypergeometric test and Fisher's exact test. We recall that the other tests are valid only for large samples, the test of equality of two probabilities and the chi2-test being equivalent. We discuss the appropriateness of one- and two-sided P-values, as well as some discreteness and conservatism issues. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Data Interpretation, Statistical↗

An automated quantitation of short echo time MRS spectra in an open source software environment: AQSES.

This paper describes a new quantitation method called AQSES for short echo time magnetic resonance spectra. This method is embedded in a software package available online from www.esat.kuleuven.be/sista/members/biomed/new/ with a graphical user interface, under an open source license, which means that the source code is freely available and easy to adapt to specific needs of the user. The quantitation problem is mathematically formulated as a separable nonlinear least-squares fitting problem, which is numerically solved using a modified variable-projection procedure. A macromolecular baseline is incorporated into the fit via nonparametric modelling, efficiently implemented using penalized splines. Unwanted components such as residual water are removed with a maximum-phase FIR filter. Constraints on the phases, dampings and frequencies of the metabolites can be imposed. AQSES has been tested on simulated MR spectra with several types of disturbance and on short echo time in vivo proton MR spectra. Results show that AQSES is robust, easy to use and very flexible.

Humans↗

[The conduct of deaconesses during the NS-dictatorship and the efforts to overcome these experiences. A case study on historical research].

The article is an approach to the conduct of nurses organisations and their members during the time of National Socialism as well as the following attempts to come to terms with these events. Both themes are dealt with rarely. The present state of research is outlined. In a case-study, which relies on source material from an archive of a deaconesses mother house and covers the period from 1943 to 1990, central problems are discussed exemplarily. Questions for further research are formulated and methodological problems are discussed. In this connection the special relevance of the analysis of personal files of the nurses is emphasized.

Attitude of Health Personnel↗

[Plans for the training of health personnel: basic considerations for its formulation].

This article presents the problem of "plans for human resources development"--formulated by some countries, but not always utilized. Although the term "development of human resources" has an ample, comprehensive meaning, the authors limit the discussion to the formative phase, leaving the utilization aspects for a future paper. The reasons for preparing such plans are analyzed within the context of the health strategies to reach the goal of HFA/2000, and the article brings up-to-date the meaning and interpretation, within that context, of some commonly used definitions and planning concepts. The authors establish a frame of reference for these plans, examining the influence of different factors in determining the course a plan may follow in its implementation. Included among these factors are: human resources policies; governmental priorities and planning measures; professional practices and how they influence the development and structure of the work force; teaching capacity, and availability of funds and of other resources. The process of formulating a plan comes next, outlining some premises and detailing the different components. The article concludes pointing out that a plan for the development of human resources is not a solution to existing problems, but should rather be used as a guideline. The authors insist as well on the flexibility of objectives and purpose, and the reason for this characteristic. Perhaps the most important conclusion is the warning that a plan for human resources development is not an isolated, independent instrument, but should be considered as an integral part of more comprehensive development plans within the health services infrastructure, and within the political, social and economic framework of a concrete reality.

Health Occupations↗