Focused antithrombotic therapy: Novel anti-platelet salicylates with reduced ulcerogenic potential and higher first-pass detoxification than aspirin in rats

The use of aspirin as an anti-platelet drug is limited by its propensity to induce gastric injury and by its adverse effect on vascular prostacyclin formation. Two phenolic non-steroidal anti-inflammatory drugs (salicyclic acid and diflunisal) were modified by esterification with a series of O-acyl moieties. The short-term ulcerogenic in vitro and in vivo anti-platelet properties, pharmacodynamic profiles, and extent of hepatic extraction of these phenolic esters were compared with aspirin (acetylsalicylic acid). The more lipophilic esters (longer carbon chain length in O-acyl group) show significantly less gastrotoxicity in stressed rats than does aspirin after a single oral dose. The in vitro and in vivo anti-platelet studies show that these phenolic esters inhibited (1) arachidonate-triggered human platelet aggregation and (2) thrombin-stimulated rat serum thromboxane Ag production by platelets in the clotting process almost as effectively as aspirin. The hepatic extractions of these O-acyl derivatives are significantly higher than those of aspirin. The pharmacodynamic studies show that these O-acyl derivatives of salicylic acid and diflunisal probably bind to, or combine with, the same site on the platelet cyclooxygenase as aspirin. Replacing the O-acetyl group with longer chain O-acyl moiety in this series of phenolic esters markedly reduced the potential of these agents to induce short-term gastric injury but did not lessen their activity as inhibitors of platelet aggregation. These non-acetyl salicylates may therefore represent a novel class of anti-platelet drugs with less ulcerogenic potential.

Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity

Previous studies have demonstrated that 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and several other aroylhydrazone chelators possess anti-neoplastic activity due to their ability to bind intracellular iron. In this study we have examined the structure and properties of NIH and its Fe-III complex in order to obtain further insight into its anti-tumour activity. Two tridentate NIH ligands deprotonate upon coordination to Fe-III in a meridional fashion to form a distorted octahedral, high-spin complex. Solution electrochemistry of [Fe(NIH-H)(2)](+) shows that the trivalent oxidation state is dominant over a wide potential range and that the Fe-II analogue is not a stable form of this complex. The fact that [Fe(NIH-H)(2)](+) cannot-cycle between the Fe-II and Fe-III states suggests that the production of toxic free- radical species, e.g. OH. or O2(.-),is not part of this ligand's cytotoxic action. This suggestion is supported by cell culture experiments demonstrating that the addition of Fe-III to NIH prevents its anti-proliferative effect. The chemistry of this chelator and its Fe-III complex are discussed in the context of understanding its anti-tumour activity.

Protein fold recognition score functions: Unusual construction strategies

We describe two ways of optimizing score functions for protein sequence to structure threading. The first method adjusts parameters to improve sequence to structure alignment. The second adjusts parameters so as to improve a score function's ability to rank alignments calculated in the first score function. Unlike those functions known as knowledge-based force fields, the resulting parameter sets do not rely on Boltzmann statistics, have no claim to representing free energies and are purely constructions for recognizing protein folds. The methods give a small improvement, but suggest that functions can be profitably optimized for very specific aspects of protein fold recognition, Proteins 1999;36:454-461. (C) 1999 Wiley-Liss, Inc.

U-q[(sl(2)over-cap vertical bar 1)] vertex operators, screen currents, and correlation functions at an arbitrary level

Bosonized q-vertex operators related to the four-dimensional evaluation modules of the quantum affine superalgebra U-q[sl((2) over cap\1)] are constructed for arbitrary level k=alpha, where alpha not equal 0,-1 is a complex parameter appearing in the four-dimensional evaluation representations. They are intertwiners among the level-alpha highest weight Fock-Wakimoto modules. Screen currents which commute with the action of U-q[sl((2) over cap/1)] up to total differences are presented. Integral formulas for N-point functions of type I and type II q-vertex operators are proposed. (C) 2000 American Institute of Physics. [S0022-2488(00)00608-3].

Commentary: Using the convection-dispersion model and transit time density functions in the analysis of organ distribution kinetics

The convection-dispersion model and its extended form have been used to describe solute disposition in organs and to predict hepatic availabilities. A range of empirical transit-time density functions has also been used for a similar purpose. The use of the dispersion model with mixed boundary conditions and transit-time density functions has been queried recently by Hisaka and Sugiyanaa in this journal. We suggest that, consistent with soil science and chemical engineering literature, the mixed boundary conditions are appropriate providing concentrations are defined in terms of flux to ensure continuity at the boundaries and mass balance. It is suggested that the use of the inverse Gaussian or other functions as empirical transit-time densities is independent of any boundary condition consideration. The mixed boundary condition solutions of the convection-dispersion model are the easiest to use when linear kinetics applies. In contrast, the closed conditions are easier to apply in a numerical analysis of nonlinear disposition of solutes in organs. We therefore argue that the use of hepatic elimination models should be based on pragmatic considerations, giving emphasis to using the simplest or easiest solution that will give a sufficiently accurate prediction of hepatic pharmacokinetics for a particular application. (C) 2000 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 89:1579-1586, 2000.

Determining complicated winding patterns for shim coils using stream functions and the target-field method

In a magnetic resonance imaging equipment, gradient and shim coils are needed to produce a spatially varying magnetic field throughout the sample being imaged. Such coils consist of turns of wire wound on the surface of a cylindrical tube. Shim coils in particular, must sometimes be designed to produce complicated magnetic fields to correct for impurities. Streamline patterns for shim coils are much more complicated than those for gradient coils, In this work we present a detailed analysis of streamline methods and their application to shim coil design, A method is presented for determining the winding patterns to generate these complicated fields. (C) 2002 John Wiley & Sons, Inc.

A method for the design of MRI radiofrequency coils based on triangular and pulse basis functions

This paper presents a numerical technique for the design of an RF coil for asymmetric magnetic resonance imaging (MRI) systems. The formulation is based on an inverse approach where the cylindrical surface currents are expressed in terms of a combination of sub-domain basis functions: triangular and pulse functions. With the homogeneous transverse magnetic field specified in a spherical region, a functional method is applied to obtain the unknown current coefficients. The current distribution is then transformed to a conductor pattern by use of a stream function technique. Preliminary MR images acquired using a prototype RF coil are presented and validate the design method. (C) 2002 Elsevier Science B.V. All rights reserved.

Group theory and quasiprobability integrals of Wigner functions

The integral of the Wigner function of a quantum-mechanical system over a region or its boundary in the classical phase plane, is called a quasiprobability integral. Unlike a true probability integral, its value may lie outside the interval [0, 1]. It is characterized by a corresponding selfadjoint operator, to be called a region or contour operator as appropriate, which is determined by the characteristic function of that region or contour. The spectral problem is studied for commuting families of region and contour operators associated with concentric discs and circles of given radius a. Their respective eigenvalues are determined as functions of a, in terms of the Gauss-Laguerre polynomials. These polynomials provide a basis of vectors in a Hilbert space carrying the positive discrete series representation of the algebra su(1, 1) approximate to so(2, 1). The explicit relation between the spectra of operators associated with discs and circles with proportional radii, is given in terms of the discrete variable Meixner polynomials.

Stakeholders Theory and Theory of the Firm: a study on the hierarchy of objective-functions in Brazilian companies

Discussion opposing the Theory of the Firm to the Theory of Stakeholders are contemporaneous and polemical. One focal point of such debates refers to which objective-function companies, should choose, whether that of the shareholders or that of the stakeholders, and whether it is possible to opt for both simultaneously. Several empirical studies. have attempted-to test a possible correlation between both functions, and there has not been any consensus-so far. The objective of the present research is to examine a gap in such discussions: is there (or not) a subordination of the stakeholders` objective-function to that of the shareholders? The research is empirical,and analytical and employs quantitative methods. Hypotheses were tested and data analyzed by using non-parametrical (chi-square test) and parametrical procedures (frequency. correlation `coefficient). Secondary data was collected from he Economitica database and from the Brazilian Institute of Social and-Economic Analyses (IBASE) website, relative to public companies that have published their Social Balance Statements following the IBASE model from 1999 to 2006, whose sample amounted to 65 companies; In order to assess the objective-function of shareholders a proxy was created based on the following three indices: ROE (return on equity), EnterpriseValue and Tobin`s Q. In order to assess the objective-function of stakeholders a proxy was created by employing the following IBASE social balance indices: internal ones (ISI), external ones (ISE), and environmental ones (IAM). The results have shown no evidence of subordination of stakeholders` objective-function to that of the shareholders in analyzed companies, negating initial expectations and calling for deeper investigation of results. Its main conclusion, which states that the attempted subordination does not take place, is limited to the sample herein investigated and calls for ongoing research aiming at improvements which may lead to sample enlargement and, as a consequence, may make feasible the application of other statistical techniques which may yield a more thorough, analysis of the studied phenomehon.

On S-asymptotically omega-periodic functions on Banach spaces and applications

This paper is devoted to the study of the class of continuous and bounded functions f : [0, infinity] -> X for which exists omega > 0 such that lim(t ->infinity) (f (t + omega) - f (t)) = 0 (in the sequel called S-asymptotically omega-periodic functions). We discuss qualitative properties and establish some relationships between this type of functions and the class of asymptotically omega-periodic functions. We also study the existence of S-asymptotically omega-periodic mild solutions of the first-order abstract Cauchy problem in Banach spaces. (C) 2008 Elsevier Inc. All rights reserved.

A note on S-asymptotically periodic functions

In [Haiyin Gao, Ke Wang, Fengying Wei, Xiaohua Ding, Massera-type theorem and asymptotically periodic Logistic equations, Nonlinear Analysis: Real World Applications 7 (2006) 1268-1283, Lemma 2.1] it is established that a scalar S-asymptotically to-periodic function (that is, a continuous and bounded function f : [0, infinity) -> R such that lim(t ->infinity)(f (t + omega) - f (t)) = 0) is asymptotically omega-periodic. In this note we give two examples to show that this assertion is false. (C) 2008 Elsevier Ltd. Ail rights reserved.

Observations of anti-winds in a deep alpine valley, Lake Tekapo, New Zealand

This paper presents observations of summertime anti-winds monitored under ideal conditions in the Lake Tekapo hydro-catchment situated in the central Southern Alps, New Zealand. Onset and cessation of anti-winds was observed to coincide with the change in phase of the surface limbs of thermally generated valley and mountain winds under settled anti-cyclonic conditions. Anti-winds were best developed in the early morning before surface heating and associated convective mixing of the valley atmosphere began to mask the boundaries between the surface based limb of the mountain-valley wind and the corresponding anti-wind. By mid-day, the anti-valley wind exceeded the height of the surrounding ridgeline and became embedded in the topographically channeled gradient wind. Observations presented here have both theoretical and applied implications with regard to the development of thermally generated wind systems in deep alpine valleys, and their role in the dispersion of air pollution.

A New Family of Distance Functions for Perceptual Similarity Retrieval of Medical Images

A long-standing challenge of content-based image retrieval (CBIR) systems is the definition of a suitable distance function to measure the similarity between images in an application context which complies with the human perception of similarity. In this paper, we present a new family of distance functions, called attribute concurrence influence distances (AID), which serve to retrieve images by similarity. These distances address an important aspect of the psychophysical notion of similarity in comparisons of images: the effect of concurrent variations in the values of different image attributes. The AID functions allow for comparisons of feature vectors by choosing one of two parameterized expressions: one targeting weak attribute concurrence influence and the other for strong concurrence influence. This paper presents the mathematical definition and implementation of the AID family for a two-dimensional feature space and its extension to any dimension. The composition of the AID family with L (p) distance family is considered to propose a procedure to determine the best distance for a specific application. Experimental results involving several sets of medical images demonstrate that, taking as reference the perception of the specialist in the field (radiologist), the AID functions perform better than the general distance functions commonly used in CBIR.