bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of Sequence Variation of Dengue Type 3 Virus in Naturally Infected Mosquitoes and Human Hosts: Implications for Transmission and Evolution
Authors: Lin Su-Ru , Hsieh Szu-Chia , Yueh Yi-Yuan , Lin Ting-Hsiang , Chao Day-Yu , Chen Wei-June , King Chwan-Chuen , Wang Wei-Kung
Published: October 2004

Dengue virus is an arbovirus that replicates alternately in the mosquito vector and human host. We investigated sequences of dengue type 3 virus in naturally infected
Aedes aegypti
mosquitoes and in eight patients from the same outbreak and reported that the extent of sequence variation seen with the mosquitoes was generally lower than that seen with the patients (mean diversity, 0.21 versus 0.38% and 0.09 versus 0.23% for the envelope [E] and capsid [C] genes, respectively). This was further verified with five experimentally infected mosquitoes (mean diversity, 0.09 and 0.10% for the E and C genes, respectively). Examination of the quasispecies structures of the E sequences of the mosquitoes and of the patients revealed that the sequences of the major variants were the same, suggesting that the major variant was transmitted. These findings support our hypothesis that mosquitoes contribute to the evolutionary conservation of dengue virus by maintaining a more homogenous viral population and a dominant variant during transmission.
A RESOURCE BASED THREE COMPARTMENT MODEL
Authors: CHATTOPADHYAY J. , SARKAR A.K.
Published: October 2004

This paper examines a three compartment model which represents a resource-plant-herbivore system. It establishes that under certain conditions the system has a single interior (all positive) equilibrium and that when it exists is locally asymptotically stable. It has been shown that the reproduction rate of herbivore plays an important role in shaping the dynamics of the model.
SIMPLICITY VS COMPLEXITY IN DETERMINISTIC MODELS: AN APPLICATION TO AIDS DATA
Authors: SANDBERG SONJA , AWERBUCH TAMARA , GONIN RENÉ
Published: October 2004

This paper addresses the issue of how much complexity can be added to an AIDS model and still be supported by the data. Attention focuses on three models for a particular risk group in a particular geographic location to explain the AIDS epidemic. Statistical analysis shows that the simplest of models perform as well as the more complex ones in explaining the observed patterns in available data. Fitted parameters (risk group size, transmission parameter) are approximately equal for the three models. The models also produce similar predictions for the number of infected and diagnosed AIDS cases. Statistical curvature measures indicate that the simple three-compartment model is sufficiently close to “linear” for statistical inference to be adequate. We conclude that for the purpose of predicting trends of spread, simple models are as appropriate as the more complex ones.
THE EFFECT OF RESIDUAL STRESSES ON WAVE SPEED IN ARTERIES
Authors: CHAUDHRY H.R. , BUKIET B. , LACKER M.
Published: October 2004

The traditional approach to calculating stress distribution in arteries has been to assume (incorrectly) that the unloaded intact artery is stress-free. We consider the unloaded intact artery to have initial (i.e. residual) stresses and study how this affects the calculated wave speed of the arterial pulse. We use a set of equations that describe, in a simplified way, the blood flow in arteries and apply nonlinear elasticity theory to derive a formula for wave speed. We compare wave speed calculations under two assumptions (considering unloaded intact arteries as stress-free and considering these arteries to have residual stresses). We find that wave speeds calculated assuming residual stresses are more realistic. Clinical applications of this work are suggested.
A MINIMAL LATTICE MODEL RELATED TO PHYLLOTAXY
Authors: FAN X.D.
Published: October 2004

Structures in phyllotaxy are generalized using some concepts from lattice theory. A minimal lattice model is introduced to simulate the dynamics of the morphology of phyllotaxis. Numerical results indicate that the lattice divergences, which are equivalent to the divergence angle as used in phyllotaxy, converge to constant numbers for most of the growth rate and initial conditions. These numbers are associated with the noble numbers which are related to the general Fibonacci sequence. A method is developed to derive the lattice divergence as a sequence expressed in a recurrence formula. An analytical solution of the latter is obtained which reveals the convergence and asymptotic values of the sequence.
MATHEMATICAL MODEL FOR HEAT DEPOSITION IN TISSUE DURING PHOTODYNAMICAL THERAPY
Authors: ŠVARC ALFRED , JURIN MISLAV , BOROVIĆ SUZANA , ZORC HRVOJE , DOKO MARKO
Published: October 2004

A mathematical model for the heat deposition in tissue during the exposition to the red light, essential for the phototherapy, is presented. The comparison of model predictions with in vivo experimental data for the normal CBA/HZgr mice hind leg tissue is done in order to illustrate the domain of confidence of the theoretical model. The highest usable power of the light source, and consequently the lowest phototherapy treatment time with no influence upon normal tissue is determined.
COMPUTER SIMULATION OF TUMOR RECURRENCE
Authors: IVANKOV A. , TSODIKOV A. , YAKOVLEV A.
Published: October 2004

Computer simulations have been conducted to provide a realistic model of tumor recurrence in a cancer patient, following treatment. The simulation model incorporates description of the temporal organization of various biological processes underlying tumor development at the cellular level: proliferation, differentiation, death of tumor cells, growth control in neoplastic tissues along with the tumor treatment effect. The prime object of our concern is whether the simple parametric model of tumor recurrence proposed by Hoang et al. [6] allows estimation of actual value of the tumor growth potential. A good fit has been demonstrated of the parametric model when applied to the samples of simulated tumor recurrence times as well as to real data samples of tumor recurrence in breast cancer patients with various regimen of radiotherapy.
TOPOLOGICAL AND NONLINEAR PROPERTIES OF LIGAND-RECEPTOR SYSTEMS
Authors: BOUNIAS M. , BONALY A.
Published: October 2004

Ligand-receptor (L-R) interactions involving substrate-enzyme and hormone-receptor systems, obey complex processes. Many parameters are not easily addressed in classical kinetic approaches; most are generally based on the probabilistic mass-action law and equilibrium constants. We describe the system in terms of tessellation of the reactional space with balls B(x, Γ) centered on the reactive species and whose radius (Γ), used as a scaling unit, is derived from the Hausdorff distance η=dist(L, R). This value is altered by a set of corrective terms representing interactions with inert and non-reactive species present in the medium, the influence of particular cell factors including heterogeneous phase conditions, and metabolic dissipation of the product. Topological properties have been studied for nonlinear pairing function governing the distance between two species, and the fractal dimension of the system is linked with its Bouligand-Minkowski dimension. The set of instant state equations of the system includes a chain of transfer matrices accounting for the linear phase of catalytic functions. An alternative set of iterative functions providing a complete metric description of the system in its topological definition space, exhibits similarities with the equations of the Mandelbrot sets family. Experimental confirmation that the major parameters (Vmax, S50 and Hill coefficient) are polyphasic functions of time rather than constants was obtained for honeybees haemolymph α-glucosidases.
A PARAMETRIC ANALYSIS OF TUMOR RECURRENCE DATA
Authors: HOANG T. , TSODIKOV A. , ASSELAIN B. , YAKOLEV A.
Published: October 2004

The evaluation of cancer treatment efficiency is often based on the risk of local recurrence. When applied to the statistical analysis of tumor recurrence data, a pertinent parametric method has the following distinct advantages: (1) it allows a natural interpretation in terms of parameters bearing clear biological meaning, (2) it provides a prediction of the recurrence risk forward in time beyond the follow-up period, (3) it offers a means of estimating survival fraction (probability of tumor cure) from the time-to-recurrence observations. This paper discusses a stochastic model of tumor recurrence based on the consideration of biological processes of tumor latency within the random minima framework. A parametric family of distributions is obtained that allows for a survival fraction, thereby providing an estimate of the probability of tumor cure. When applying the model to data on breast cancer, we estimate the expected number of clonogens which give rise to early and late recurrences and their progression rate parameters. The prime object of our concern is discrimination between true recurrence and spontaneuos carcinogenesis on the basis of the temporal characteristics of the tumor latency. As evidenced by the data analysis, such a discrimination is feasible and allows to conclude that the contralateral breast cancer may be interpreted as a preexisting subclinical tumor at the time of treatment.
FLEXIBILITY AND THERMAL DENATURATION (MELTING) OF IRRADIATED DNA
Authors: KALFAS C.A. , LOUKAKIS G.K. , GEORGAKILAS A.G. , SIDERIS E.G. , ANAGNOSTOPOULOU-KONSTA A.
Published: October 2004

The study of the melting transition for large molecular weight DNA which had been irradiated with various doses of γ-rays can yield information on the structural and dynamical behaviour of DNA, leading to a better understanding of changes induced by external agents. In order to interpret the accumulated experimental data, a theoretical description capable of correlating thermal changes to those induced by ionizing radiation, is required. The theoretical ideas proposed here, based on first principles and certain assumptions, allow for a quantitative analysis of the melting data and the subsequent evaluation of a very small number of parameters which can be used to interpret the observed variations in experimental quantities (such as UV absorbance) which are related to structural variations.
ON A KINETIC (CELLULAR) THEORY FOR COMPETITION BETWEEN TUMORS AND THE HOST IMMUNE SYSTEM
Authors: BELLOMO N. , PREZIOSI L. , FORNI G.
Published: October 2004

This paper deals with a kinetic modelling of the cellular dynamics of tumors interacting with an active immune defence system. The analysis starts from a detailed modelling of the cellular interactions and follows with the derivation of evolution equations in a framework similar to the one of nonlinear statistical mechanics. A discussion about the qualitative properties of the model and on the possibility of its application in immunology is proposed in the last part of the paper.
WHY DOES THE CHEMICAL COMPOSITION OF LIVING THINGS ADAPT TO THE ENVIRONMENT?
Authors: GLADYSHEV G.P. , KITAEVA D.KH. , OVCHARENKO E.N.
Published: October 2004

It is shown, using the example of fatty acids contained in living things, that the temperature adaptation of the living things chemical composition is a consequence of the second principle of thermodynamics in its classical form. The obtained result is interesting since the application of equilibrium thermodynamics to living organisms was being rejected for a long time because of the complexity and open nature of these organisms.
LIVING BEINGS AS INFORMED SYSTEMS: TOWARDS A PHYSICAL THEORY OF INFORMATION
Authors: LEÓN ANTONIO
Published: October 2004

I propose here a new concept of information based on two relevant aspects of its expression. The first refers to the undeniable fact that the expression of information modifies the physical state of its receiver. The second, to that the said changes are arbitrary, not deducible from physical laws but from a code established arbitrarily. Thus, physical information is proposed here as the capacity of producing arbitrary changes. Once defined information from this physical point of view, I deduce some basic physical properties of informed systems. These properties (renewal, self-reproducing, evolution, diversification) are immediately recognisable as the attributes most characteristic of living beings, the only natural informed systems we know. Although no new attribute of living beings has been discovered here, the formal way used to obtain them is a significant novelty. I also propose here a double evaluation of information. The former is an absolute measure of the physical effects of its expression based on Einstein’s probability. The latter is a functional measure based on the probability that an informed system attain a given objective as consequence of the expression of its information.
COMPLEXITY
Authors: SILVERT WILLIAM
Published: October 2004

Complexity is a property of models, not of systems. It is shown that the complexity of a system is not a well-defined quantity, and that the complexity implicit in a model is connected to the amount of information about the system (in an information-theoretic sense) that the model is able to process.
QUALITATIVE MODALITIES
Authors: HOEK WIEBE VAN DER
Published: October 2004

We add a binary operator ≥ to the logical language, with intended meaning of φ<ψ: ‘φ is at least as likely, probable, or trustworthy, as ψ’. The operator ≥ is interpreted on Kripke structures, making it possible to define the standard necessity operator □ in terms of ≥. The operator ≥ provides us with an intermediate for the K-axiom, in the sense that we have both □(p→q)→(q≥p) and (q≥p)→(□p→□q). We discuss two semantics for this binary modal operator. It turns out that, as shown by Gärdenfors and Segerberg, ≥ is not only too weak to distinguish finite models from infinite ones or to distinguish countable additivity from finite additivity, ≥ also cannot distinguish sophisticated ways of assigning exact probabilities to events (‘measuring’) from the conceptually simpler task of just counting them.
COMPUTING THE WELL-FOUNDED MODEL OF DEDUCTIVE DATABASES
Authors: BAGAI RAJIV , SUNDERRAMAN RAJSHEKHAR
Published: October 2004

The well-founded model is one of the most popular models of general logic programs, i.e. logic programs with negation in the bodies of clauses. We present a method for constructing this model for general deductive databases, which are logic programs without any function symbols. The method adopts paraconsistent relations as the semantic objects associated with the predicate symbols of the database. Paraconsistent relations are a generalization of ordinary relations in that they allow manipulation of incomplete as well as inconsistent information. The first step in the model construction method is to transform the database clauses into paraconsistent relation definitions involving these operators. The second step is to build the well-founded model iteratively. Algorithms for both steps are presented and their termination and correctness is also established.
DEALING WITH DISJUNCTIVE AND MISSING INFORMATION IN LOGIC FUZZY DATABASES
Authors: PONS O. , CUBERO J.C. , MEDINA J.M. , VILA M.A.
Published: October 2004

This work is concerned with the problem of representing and handling disjunctive and missing information in the framework of logic fuzzy databases. We use the general term of incomplete information to refer both disjunctive or missing information. To pose the problem, we firstly give a brief summary about the underlying Logic Fuzzy Database Model. Starting from the concept of logic fuzzy database, which is a general fuzzy database that can be represented in a logic framework, we see how disjunctive and missing information can be represented and handled.
VANISHING TETRAD DIFFERENCES AND MODEL STRUCTURE
Authors: SHAFER GLENN , KOGAN ALEXANDER , SPIRTES PETER
Published: October 2004

The tetrad representation theorem, due to Spirtes, Glymour, and Scheines (1993), gives a graphical condition necessary and sufficient for the vanishing of an individual tetrad difference in a recursive path model with uncorrelated errors. In this paper, we generalize their result from individual tetrad differences to sets of tetrad differences of a certain form, and we simplify their proof. The generalization allows tighter constraints to be placed on the set of models compatible with given data and thereby facilitates the search for parsimonious models for large data sets.
ON THE EQUIVALENCE BETWEEN FUZZY AND STATISTICAL CLASSIFIERS
Authors: KUNCHEVA LUDMILA I.
Published: October 2004

In this paper the equivalence between fuzzy systems and two nonparametric techniques for pattern recognition is considered. The conditions under which a fuzzy system coincides with the nearest neighbor rule, and with the Parzen’s classifier have been formulated.
AGGREGATION AND COMPLETION OF RANDOM SETS WITH DISTRIBUTIONAL FUZZY MEASURES
Authors: JOSLYN CLIFF
Published: October 2004

The two known information theories, probability and possibility theory, are based on t-conorm decomposable fuzzy measures, so that bijective mappings exist between their set-valued measures and their point-valued distributions. Further, their random set (Dempster-Shafer evidence theoretical) interpretations have simple topological structures, with bijective mappings between the subset focal elements and the point singletons. We introduce the concepts of distributional and aggregable random sets and random set completion, and first use them as a model in which to cast probability and possibility measures and distributions. Then, towards the goal of deriving new forms of information theory, general Sugeno conorm decomposable fuzzy measures and ring-like aggregable random sets with set-intersection structural aggregation are examined, but it is shown that in these two cases no new information theories are forthcoming.
ON THE INCLUSION OF VARIANCE IN DECISION MAKING UNDER UNCERTAINTY
Authors: YAGER RONALD R.
Published: October 2004

The basic paradigm for decision making under uncertainty is introduced. A methodology is suggested for the calculation of the variance associated with each of the alternatives in the case when the uncertainty is not necessarily of a probabilistic nature.
SECOND ORDER LOGICAL SYSTEM FOR RISK CLASSIFICATION IN A NEWLY DEVELOPED COUNTRY
Authors: WHALEN THOMAS , GIM GWANGYONG
Published: October 2004

Modern financial institutions require sophisticated risk assessment tools to integrate human expertise and historical data in a market that is changing and broadening qualitatively, quantitatively, and geographically. The need is especially acute in newly developed countries where expertise and data are scarce, and knowledge bases and assumptions imported from the West may be of limited applicability.

Second order logical models can be a valuable tool in such situations. They integrate the robustness of neural or statistical modeling of data, the perspicuity of logical rule induction, and the experience and understanding of skilled human experts. The approach is illustrated in the context of risk assessment in the Korean surety insurance industry.
PRINCIPAL COMPONENTS, B-SPLINES, AND FUZZY SYSTEM REDUCTION
Authors: YEN JOHN , LANGARI REZA , WANG LIANG
Published: October 2004

This paper proposes to use the method of principal components to reduce the dimensionality of input space and the B-splines to represent the membership functions of input variables. A model reduction strategy, which is based on Johansen’s optimality theorem, also suggested. The utility of this approach is illustrated using a fuzzy system modeling example.
A PRECEDENT-BASED LEGAL JUDGEMENT SYSTEM USING FUZZY DATABASE
Authors: HIROTA KAORU , KURISU HIROTERU , YOSHINO HAJIME
Published: October 2004

In the domain of law, various real situations are expressed as relations and/or combinations of legal knowledge items (legal concepts, articles of law, etc). Such knowledge items (legal facts, events) cannot be precisely defined. Legal judgement is performed based on resemblance of legal knowledge and facts. In our system, vague legal knowledge is saved in the fuzzy relational database, and legal inference is realized as fuzzy inference. The target law for this system is the United Nations Convention on Contracts for the International Sale of Goods (CISG).
A NEURAL NETWORK THAT LEARNS FROM FUZZY DATA FOR LANGUAGE ACQUISITION
Authors: LIN CHIN-TENG , KAN MING-CHIH , CHUNG I-FANG
Published: October 2004

This paper proposes a four-layered fuzzy language acquisition network (FLAN) for acquiring fuzzy language. It can catch the intended information from a sentence (command) spoken in natural language with fuzzy terms. The intended information includes a meaningful semantic action and the fuzzy linguistic information of that action (for example, the phrase “move forward” represents the meaningful semantic action and the phrase “very high speed” represents the linguistic information in the fuzzy command “Move forward in a very high speed.”). The proposed FLAN has two important features. First, we can make no restrictions whatever on the fuzzy language input which is used to specify the desired information, and the network requires no acoustic, prosodic, grammar and syntactic structure. Second, the linguistic information of an action is learned automatically and it is represented by fuzzy numbers based on α-level sets. A supervised learning scheme is proposed to train the FLAN on fuzzy training data. This learning scheme consists of the mutual-information (MI) supervised learning algorithm for learning meaningful semantic actions, and the fuzzy backpropagation (FBP) learning algorithm for learning linguistic information. An experimental system is constructed to illustrate the performance and applicability of the proposed FLAN.
INTERVAL METHODS IN KNOWLEDGE REPRESENTATION
Authors: Kreinovich Vladik
Published: October 2004

This section is maintained by Vladik Kreinovich. Please send your abstract or copies of papers that you want to see reviewed here to vladik@cs.utep.edu, or by regular mail to: Vladik Kreinovich, Department of Computer Science, University of Texas at El Paso, El Paso, TX 79968, USA.
Renal Stone Disease: The Urological Perspective
Authors: Amiel Jean , Choong Simon
Published: October 2004

Percutaneous nephrolithotomy, extracorporeal lithotripsy and ureteroscopy have changed the face of urolithiasis. Open surgery is becoming extremely rare today. Nevertheless, the cooperation between nephrologist and urologist remains essential and is the only way to prevent recurrence.
Molecular Aetiology of Primary Hyperoxaluria Type 1
Authors: Danpure Christopher J.
Published: October 2004

Primary hyperoxaluria type 1 (PH1) is a rare autosomal-recessive disorder, caused by a deficiency of the liver-specific intermediary-metabolic enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in increased synthesis and excretion of the metabolic end-product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. Numerous mutations and polymorphisms have been identified in the gene (AGXT) that encodes AGT, some of which interact synergistically to cause a variety of complex enzyme phenotypes, including AGT intraperoxisomal aggregation, accelerated degradation, and peroxisome-to-mitochondrion mistargeting. The latter is the single most common cause of PH1 and results from the functional interaction between a common Pro11Leu polymorphism and a disease-specific Gly170Arg mutation. The recent solution of the crystal structure of AGT has enabled the effects of several mutations and polymorphisms to be rationalised in terms of their likely effects on AGT conformation. Increased understanding of the molecular aetiology of PH1 has led to significant improvements in all aspects of the clinical management of the disorder, including diagnosis (by enzyme assay of percutaneous needle liver biopsies), prenatal diagnosis (by DNA analysis of chorionic villus samples) and treatment (by liver transplantation as a form of enzyme replacement therapy).
The Molecular Basis of Cystinuria
Authors: Goodyer P.
Published: October 2004

Cystinuria is an inherited form of nephrolithiasis due to failure of reabsorptive transport in the proximal tubule. Patients with classical recessive cystinuria have inherited two mutations of the SLC3A1 gene, encoding a subunit of the transport mechanism. Patients with the dominant form of cystinuria have inherited two mutations of the SLC7A9 gene, encoding the transport channel itself. A smaller subset of patients have mixed-type cystinuria, combining recessive and dominant mutant alleles. Children at risk for nephrolithiasis can be identified by the level of urinary cystine only after tubular transport has matured (age 2 years). Conservative therapy with high urine volume and urinary alkalinization is sufficient for some, but recurrent stone formation may cause renal damage and warrants prophylaxis with agents that form mixed disulfides with cystine.
Role of Renal Epithelial Cells in the Initiation of Calcium Oxalate Stones
Authors: Khan Saeed R.
Published: October 2004

Normal urinary environment is inhibitory to crystallization. Occasional crystals are internalized by the renal epithelial cells and sequestered to lysosomes or externalized into the interstitium to be handled by the inflammatory cells. Elevated levels of oxalate and calcium oxalate crystals, however, provoke renal cells to increase the synthesis of osteopontin, bikunin, heparan sulfate proteoglycan, monocyte chemoattractant protein-1, and prostaglandin E2, which are known mediators of the inflammatory processes and extracellular matrix production. Osteopontin and bikunin are also modulators of crystallization. Exposed renal epithelial cells are often injured and go through apoptosis and/or necrosis initiating a cascade of events leading to further crystallization, crystal retention and development of stone nidi. Reactive oxygen species are produced during the interactions between the oxalate/crystals and renal cells and are responsible for the various cellular responses. Calcium oxalate crystal deposition in the rat kidneys also activates the renin-angiotensin system. Both oxalate and calcium oxalate crystals selectively activate p38 mitogen-activated protein kinase in the exposed tubular cells. Extracellular environment changes from one that inhibits crystal nucleation, growth, aggregation and retention to that, which promotes these processes.
Microorganisms and Calcium Oxalate Stone Disease
Authors: Goldfarb David S.
Published: October 2004

Microorganisms may have a role in the pathogenesis and prevention of kidney stones. The subjects of this review include nanobacteria, Oxalobacter formigenes, and lactic acid bacteria. Not reviewed here is the well-described role of infections of the urinary tract with Proteus species and other urease-producing organisms associated with struvite stone formation. Nanobacteria have been proposed to be very small (0.08–0.5 nm), ubiquitous organisms that could play a role in stone formation. The theory is that nanobacteria can nucleate carbonate apatite on their surfaces and thereby provide the nidus for stone formation. However, their existence remains uncertain and many investigators are openly skeptical. Recent investigations suggest that they are artifacts, and not actually living organisms, but their proponents continue to study them. O. formigenes is an obligate anaerobe which may be important in the prevention of stone formation. Its sole substrate for generation of ATP is oxalate. It may thereby metabolize its human host’s dietary oxalate and diminish intestinal absorption and subsequent urinary excretion of oxalate. There is evidence that the organism’s absence, perhaps sometimes due to courses of antibiotics, may be a cause of hyperoxaluria and stone formation. In early investigations, patients not colonized with the organism can be recolonized. Urinary oxalate can be diminished by accompanying an oxalate-containing meal with the organism. One study demonstrated that a preparation of lactic acid bacteria successfully reduced urinary oxalate excretion in 6 patients with calcium oxalate stones and hyperoxaluria. The mechanism of this effect is uncertain since these bacteria lacked the gene possessed by O. formigenes which codes for that organism’s oxalate uptake mechanism. The author is currently completing a small randomized controlled clinical trial with this preparation in calcium stone-forming patients with idiopathic hyperoxaluria.
Role of Dietary Intake and Intestinal Absorption of Oxalate in Calcium Stone Formation
Authors: Jaeger Ph. , Robertson W.G.
Published: October 2004

The factors affecting the urinary excretion of oxalate are critical to the risk of forming calcium oxalate stones. This article reviews the role of dietary and intestinal oxalate in determining the level of oxalate excreted in urine. The amount of oxalate available for absorption throughout the intestine is highly dependent on the state of oxalate (a) in the food ingested, and (b) in the intestinal contents at each section of the intestinal tract since only the soluble form of oxalate can be absorbed. In this respect, the solubility of calcium oxalate (CaOx) under the prevailing conditions is paramount in determining the amount of oxalate available for absorption at any particular site. In turn, the main factors that control how much oxalate is in the soluble form are pH and the concentrations of calcium, magnesium and (indirectly) phosphate. Based on these parameters, a model of the intestine has been constructed which brings together the available evidence on the prevailing concentrations of these various factors at different sites in the intestine after allowing for dietary intake and the concentration of the above ions in intestinal secretions. The model then calculates the likely concentration of oxalate that is in the soluble form at each site and therefore available for passive absorption at that site. The model shows that oxalate is likely to be absorbed in the stomach, although it can be also absorbed in the small intestine, particularly at the distal end (after the absorption of calcium), and in the colon, since, on a normal intake of calcium and phosphate, most of the calcium in the large bowel would be anticipated to be precipitated as calcium phosphate under the prevailing alkaline conditions and high concentration of phosphate. The amount of free oxalate in the colon is also controlled by the presence or absence of Oxalobacter formigenes, an anaerobe that has an obligate requirement for oxalate as a source of energy and cellular carbon.
Microglia in Culture: What Genes Do They Express?
Authors: Duke D.C. , Moran L.B. , Turkheimer F.E. , Banati R. , Graeber M.B.
Published: October 2004

The cell culture model utilized in this study represents one of the most widely used paradigms of microglia in vitro. After 14 days, microglia harvested from the neonatal rat brain are considered ‘mature’. However, it is clear that this represents a somewhat arbitrary definition. In this paper, we provide a transcriptome definition of such microglial cells. More than 7,000 known genes and 1,000 expressed sequence tag clusters were analysed. ‘Microglia genes’ were defined as sequences consistently expressed in all microglia samples tested. Accordingly, 388 genes were identified as microglia genes. Another 1,440 sequences were detected in a subset of the cultures. Genes consistently expressed by microglia included genes known to be involved in the cellular immune response, brain tissue surveillance, microglial migration as well as proliferation. The expression profile reported here provides a baseline against which changes of microglia in vitro can be examined. Importantly, expression profiling of normal microglia will help to provide the presently purely operational definition of ‘microglial activation’ with a molecular biological correlate. Furthermore, the data reported here add to our understanding of microglia biology and allow projections as to what functions microglia may exert in vivo, as well as in vitro.
Expression of ARVCF in the Human Ganglionic Eminence during Fetal Development
Authors: Ulfig Norbert , Chan Wood Yee
Published: October 2004

ARVCF (armadillo repeat gene deleted in velocardiofacial syndrome) is a recently characterized member of the catenin p120 (ctn) subfamily of the armadillo repeat proteins. It is involved in modulation of cell-cell adhesion essential to many developmental processes including cellular rearrangement and migration. In the present study, by using specific immunohistochemical methods, strongly ARVCF-immunoreactive cells in a high packing density were found in the human ganglionic eminence (GE), a telencephalic structure which gives rise to precursor neurons of the striatum, the amygdala and the basal nucleus of Meynert. From 20 to 25 weeks of gestation, stripes of immunoreactive cells were found to extend from both the superior part of the GE towards the intermediate zone of the neocortex and from the inferior part of the GE either towards the amygdaloid complex or more laterally towards the intermediate zone. Bands of ARVCF-positive cells were also identified in the gangliothalamic body, a transient target for the migrating neurons from the GE to the thalamus. Double immunolabelling with ARVCF and calretinin antibodies, which mark the GE neurons migrating towards the cerebral cortex, revealed that a majority of ARVCF-positive neurons at the periphery of the GE and the cellular extensions from the GE also expressed calretinin. Our results implicate a very close association of ARVCF with migrating neurons from the GE.
Isolation of Cystatin C via Functional Cloning of Astrocyte Differentiation Factors
Authors: Kumada Tatsuro , Hasegawa Akiko , Iwasaki Yasuno , Baba Hiroko , Ikenaka Kazuhiro
Published: October 2004

We screened for factors upregulating glial fibrillary acidic protein (GFAP) promoter activity by functional cloning with an immature astrocyte cell line (HB108-10) harboring a GFAP-lacZ construct. One cDNA clone that repeatedly upregulated lacZ expression encoded cystatin C (CysC), a cysteine protease inhibitor. TGF-β induced CysC and GFAP expression in AP-16 cells, an astrocyte progenitor-like cell line expressing GLAST (a glutamate transporter subtype specifically expressed in immature astrocytes). CysC gene expression started earlier than that of GFAP in the mouse forebrain. It started in the ventricular zone at a similar period as (or slightly after) GLAST expression, but before GFAP expression. Although previous data showed that CysC is involved in the maintenance of adult neural stem cells, our data indicate that it is involved in astrocyte differentiation during mouse brain development.
Interleukin-1 Balance in the Lungs of Preterm Infants Who Develop Bronchopulmonary Dysplasia
Authors: Kakkera Deepika K. , Siddiq Mustafa M. , Parton Lance A.
Published: October 2004

Background: The local pulmonary balance between the agonist and antagonist of interleukin-1 (IL-1) may influence the development of inflammatory disease and resultant structural damage in a variety of human diseases including adult respiratory distress syndrome and asthma. Objectives: We tested the hypothesis that IL-1 cytokines are early markers for bronchopulmonary dysplasia (BPD), when measured in tracheal aspirates (TAs) obtained from premature infants being ventilated for respiratory distress syndrome during the first week of life. Methods: Serial TAs were collected on days 1, 3, 5 and 7 from 35 preterm infants (16 BPD, 19 non-BPD) in the absence of chorioamnionitis, and were assayed for IL-1 cytokines and leukocytes. Results: In spite of comparable maternal demographic and clinical characteristics, premature infants who developed BPD had higher levels of IL-1 receptor antagonist (Ra) in their airways on the first day of life. This antagonist IL-1Ra was an early and persistent marker for BPD during the first week of life. The agonist IL-1β also increased significantly for BPD patients early, both compared to non-BPD patients, and also within the BPD group. While the early (day 1) IL-1 antagonist/agonist molar balance offered protection, by days 5 and 7, a threshold for IL-1Ra in the presence of increasing IL-1β expression-favored pro-inflammation in the BPD group. Conclusions: We conclude that a strong and early expression of airway antagonist (IL-1Ra) proves ultimately to be sub-optimal and non-protective due to the robust expression of airway agonist (IL-1β) seen by day 5 in premature infants who develop BPD.
Detection of Acute Brainstem Infarction by Using DWI/MRI
Authors: Etgen Thorleif , Gräfin von Einsiedel Helga , Röttinger Michael , Winbeck Kerstin , Conrad Bastian , Sander Dirk
Published: October 2004

Even using diffusion-weighted images (DWI) detection of acute brainstem infarction (BI) is still a challenge. To evaluate the clinical efficacy of a DWI protocol with improved spatial resolution all images of 44 patients with clinically possible BI on admission (24 patients with definite BI and 20 patients with other etiologies) and first DWI within 24 h after symptom onset were blindly reanalyzed for visibility and detection of BI on the first DWI by reviewers with different expertise levels. Neuroradiologists identified definite BI in 21 out of 24 patients (sensitivity 90%, specificity 100%); neurologists and junior house officers achieved similar results (sensitivity 86 and 83%, specificity 98 and 97%). The use of DWI allows a definite diagnosis of BI, even if raters have limited experience.
Pharmacodynamic Equivalence of a Decapeptyl 3-Month SR Formulation with the 28-Day SR Formulation in Patients with Advanced Prostate Cancer
Authors: Teillac Pierre , Heyns Christiaan F. , Kaisary Amir V. , Bouchot Olivier , Blumberg Joëlle
Published: October 2004

Aims: The objective of the study was to assess the pharmacodynamic equivalence of LHRH analogue triptorelin 3-month and 28-day SR formulations. Methods: Patients with documented locally advanced or metastatic prostate cancer were randomized to receive one injection of the 3-month formulation (n = 63) or three injections at 28-day intervals of the 28-day formulation (n = 68). Group-chemical castration rates defined as the percentage of patients reaching a testosterone plasma level ≤0.5 ng/ml were compared at D84 (i.e., 3 × 28 days). Testosterone, LH and triptorelin plasma profiles, and change from baseline in plasma PSA were assessed over 3 months (from baseline to D91). Results: Chemical castration rates were 98 and 96% in the 3-month and 28-day formulation groups, respectively, with confidence interval (two-sided 94.2% CI) of [–8.1%; 9.6%]. Median times to reach chemical castration were 18.8 and 18.5 days (p = 0.86, log rank), respectively. Ratios for mean peak plasma levels and AUC91 of the two formulations for both testosterone and LH fell within the [0.80; 1.25] equivalence interval. Mean PSA decreases from baseline at D91 were 91.0 and 91.7%, respectively (p = 0.73). Conclusion: Treatments with the two triptorelin formulations over 3 months are pharmacologically equivalent.
Effects of Trifolium alexandrinum Extracts on Streptozotocin-Induced Diabetes in Male Rats
Authors: Amer Maher , El-Habibi El-Sayed , El-Gendy Ahkam
Published: October 2004

The effects of (water, hexane and ethanolic) extracts prepared from the flower head of Trifolium alexandrinum (Leguminosae) were examined in the treatment of diabetes induced experimentally by streptozotocin (STZ) in rats. A single dose of STZ (50 mg/kg) produced a hyperglycemia, decrease in insulin level and elevation in glycosylated hemoglobin of RBCs as well as elevated serum total lipids, triglycerides and cholesterol levels. Also, a decreased serum high-density lipoprotein and in hepatic glycogen and glutathione GSH contents, concurrent with an increase in the concentration of malondialdehyde in the liver was observed. Daily intake of (water, hexane and ethanolic) extracts of T. alexandrinum in drinking water for 4 weeks immediately after diabetes induction caused significant decreases in glucose and glycated hemoglobin levels and increase in insulin level. It also greatly improved the levels of serum lipid parameters and significantly decreased lipid peroxidation in addition to increase the hepatic GSH content significantly. Conclusion: Extracts of T. alexandrinum improved hyperglycemia and other biochemical alterations noticed in STZ-diabetic rats. These effects may be due to the presence of a high content of flavonoids which acts synergistically as antioxidants.
Special Management of Insulin Lispro in Continuous Subcutaneous Insulin Infusion in Young Diabetic Children: A Randomized Cross-Over Study
Authors: Tubiana-Rufi Nadia , Coutant Regis , Bloch Juliette , Munz-Licha Geraldine , Delcroix Christine , Montaud-Raguideau Nathalie , Ducrocq Rolande , Limal Jean-Marie , Czernichow Paul
Published: October 2004

Objective: To compare the safety, efficacy and management of insulin lispro (LP) with regular human insulin (RH) in young diabetic children treated with continuous subcutaneous insulin infusion (CSII). Study Design: 27 very young diabetic children (age 4.6 ± 2.2 years) treated with CSII participated in an open-label, randomized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH. Results: Mean daily basal rate was significantly higher during the LP period (p = 0.04). No differences were seen in changes in HbA1c levels, number of hypoglycemic events, cutaneous infections and catheter occlusions. There was no significant difference between the two treatments for preprandial and postprandial glucose values, although prandial glucose excursions tended to be lower with LP (significant at dinner, p = 0.01). Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy (p < 0.05). No episode of ketoacidosis occurred during LP treatment. More parents indicated that LP made their own and the child’s daily life easier (p = 0.02) and preferred LP (p = 0.01). Conclusions: LP in CSII therapy in children is safe, as effective as RH, improved postprandial excursions, met the needs of young children in their daily life well, and gained their parents’ satisfaction and preference. However, a shorter duration of LP resulted in hyperglycemia during the first part of the night, which must be compensated for by increasing nocturnal basal rates during this time.
Serum Malondialdehyde and Coronary Artery Disease in Hemodialysis Patients
Authors: Jung Hae Hyuk , Choi Dae Hee , Lee Sang Hyun
Published: October 2004

Background/Aims: It has been suggested that enhanced oxidative stress participates in the acceleration of coronary artery disease (CAD) in patients with end-stage renal disease (ESRD). The aim of this study was to investigate the relationship between the level of malondialdehyde (MDA), which is a marker of lipid peroxidation, and the severity of CAD in ESRD patients. Methods: We conducted a study of 39 hemodialysis patients (median age 58 years; 27 males and 12 females; diabetics 44%). In these patients, the predialysis serum concentrations of MDA and C-reactive protein (CRP) were measured. We performed multirow spiral computed tomography to derive coronary artery calcification (CAC) scores, as a marker of CAD severity. Results: Eleven of the 39 patients had minimal CAC (28%, CAC score <10), 10 patients had mild to moderate CAC (26%, 10–400), and 18 patients had severe CAC (46%, >400). The MDA levels increased (p < 0.05) with increasing CAC category and were correlated (r = 0.35, p < 0.05) with the CAC scores. The levels of MDA also correlated with the serum concentrations of CRP and albumin (r = 0.34, p < 0.05 and r = –0.32, p < 0.05, respectively). Patients in the highest tertile of MDA compared with the other patients were over four times as likely to have severe CAC, and the highest tertile of MDA was an independent predictor of severe CAC, along with a previous cardiovascular event. Conclusion: An increased level of MDA, which was associated with inflammatory markers, was a predictive factor for severe CAC in ESRD patients.
Excessive Sarcoplasmic/Endoplasmic Reticulum Ca
2+
-ATPase Expression Causes Increased Sarcoplasmic Reticulum Ca
2+
Uptake but Decreases Myocyte Shortening
Authors: Teucher Nils , Prestle Juergen , Seidler Tim , Currie Susan , Elliott Elspeth B. , Reynolds Deborah F. , Schott Peter , Wagner Stefan , Kogler Harald , Inesi Giuseppe , Bers Donald M. , Hasenfuss Gerd , Smith Godfrey L.
Published: October 2004

Background—

Increasing sarcoplasmic/endoplasmic reticulum (SR) Ca
2+
-ATPase (SERCA) uptake activity is a promising therapeutic approach for heart failure. We investigated the effects of different levels of SERCA1a expression on contractility and Ca
2+
cycling. We tested whether increased SERCA1a expression levels enhance myocyte contractility in a gene-dose–dependent manner.

Methods and Results—

Rabbit isolated cardiomyocytes were transfected at different multiplicities of infection (MOIs) with adenoviruses encoding SERCA1a (or β-galactosidase as control). Myocyte relaxation half-time was decreased by 10% (
P
=0.052) at SERCA1a MOI 10 and by 28% at MOI 50 (
P
<0.05). Myocyte fractional shortening was increased by 12% at MOI 10 (
P
<0.05) but surprisingly decreased at MOI 50 (−22%,
P
<0.05) versus control. SR Ca
2+
uptake (in permeabilized myocytes) demonstrated a gene-dose–dependent decrease in
K
m
by 29% and 46% and an increase in V
max
by 37% and 72% at MOI 10 and MOI 50, respectively (all
P
<0.05 versus control). Ca
2+
transient amplitude was increased in Ad-SERCA1a–infected myocytes at MOI 10 (by 121%,
P
<0.05), but at MOI 50, the Ca
2+
transient amplitude was not significantly changed. Caffeine-induced Ca
2+
transients indicated significantly increased SR Ca
2+
content in Ad-SERCA1a–infected cells, by 72% at MOI 10 and by 87% at MOI 50. Mathematical simulations demonstrate that the functional increase in SR Ca
2+
-ATPase uptake activity at MOI 50 (and increased cytosolic Ca
2+
buffering) is sufficient to curtail the Ca
2+
transient amplitude and explain the reduced contraction.

Conclusions—

Moderate SERCA1a gene transfer and expression improve contractility and Ca
2+
cycling. However, higher SERCA1a expression levels can impair myocyte shortening because of higher SERCA activity and Ca
2+
buffering.
Acute β-Blockade Increases Muscle Sympathetic Activity and Modifies Its Frequency Distribution
Authors: Cogliati Chiara , Colombo Simona , Ruscone Tomaso Gnecchi , Gruosso Domenico , Porta Alberto , Montano Nicola , Malliani Alberto , Furlan Raffaello
Published: October 2004

Background—

The possible mechanisms by which β-adrenergic antagonists may act on the neural regulation of the cardiovascular system are still elusive. Recent studies reported a marked increase of postganglionic muscle sympathetic nerve activity (MSNA) after acute β-blockade associated with unchanged values of arterial blood pressure and baroreflex sensitivity. We tested the hypothesis that acute β-blockade might also alter the oscillatory characteristics of MSNA, thus decreasing its effectiveness on peripheral vasoconstriction.

Methods and Results—

In 11 healthy volunteers, ECG, MSNA, arterial pressure, and respiration were recorded before and after atenolol (0.05 mg/kg IV bolus) administration. The frequency distribution of RR interval, MSNA, systolic arterial pressure (SAP), and respiratory variability was assessed by spectrum and cross-spectrum analysis. Spontaneous baroreflex sensitivity (α-index) and plasma catecholamines (high-performance liquid chromatography) were measured. Atenolol induced a significant increase in RR interval (14.3±1.6%) with no changes in systolic and diastolic arterial pressure. MSNA increased (42±13% from 18±2 bursts per minute). The low-frequency (LF) component of RR and MSNA variability decreased (−44±7% and −24±5%, respectively), whereas the high-frequency (HF) component increased (163±55% and 34±11%, respectively), expressed in normalized units. Spectral coherence, an index of oscillatory coupling, decreased between LF
RR
and LF
MSNA
, whereas it increased between HF
MSNA
and HF
Resp
. SAP variability, α-index, and plasma catecholamines remained unchanged.

Conclusions—

Atenolol induced a change in MSNA frequency distribution reflecting a stronger respiratory coupling. This shift toward high frequency, despite an increase in MSNA, may lead to a less efficient sympathetic vasomotor modulation.