bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE VERIFICATION OF FUNCTION EQUIVALENCE WITH UNKNOWN INPUT CORRESPONDENCE
Authors: CHENG DAVID IHSIN , MAREK-SADOWSKA MALGORZATA
Published: November 2004

A method that verifies the equivalence of functions with unknown input correspondence is proposed in this paper. The key to our method is to associate a new signature with each input variable, thereby effectively establishing partial (sometimes total) correspondence between two sets of input variables. The descriptive power of our new signature appears to be very effective. In addition to the strong descriptive power, our proposed signature also provides information for pruning when exhaustive search has to be used finally on variables that cannot be matched in two input functions. We have implemented and tested an algorithm based on our approach. The experimental results are encouraging.
APPLYING CONVENTIONAL UNIT TESTING TECHNIQUES TO ABSTRACT DATA TYPE OPERATIONS
Authors: PARRISH ALLEN , CORDES DAVID
Published: November 2004

Abstract data types (ADTs) represent the fundamental building blocks of object-oriented software development. There have been a variety of techniques in the literature for testing ADT modules. Virtually all of the proposed techniques have involved testing sequences of ADT operations (e.g., for a stack ADT, test the sequence PUSH; PUSH; POP) to discover defects in their interactions. However, the operations inside an ADT module are really nothing more than conventional procedures and functions. Consequently, it is conceivable that conventional subprogram unit testing techniques can be adapted to test ADT operations.

To support such testing techniques, test cases are best designed and expressed in terms of data values. When test cases are integers, for example, expressing a test case is trivial (e.g., ‘253’). However, when test cases are data abstractions (such as stacks), this problem is much more difficult due to the variety of different formats in which a single data abstraction can be legitimately viewed. In this paper, we provide a conceptual framework for applying classical white-box and black-box unit testing techniques to ADT operations. We then use this framework to develop a collection of guidelines for determining the best format for test case design, given different module characteristics and testing techniques.
COMPARING TWO HYBRID EXPERT SYSTEM SHELLS
Authors: VANHOOF K. , SURMA J.
Published: November 2004

This paper describes in full detail an analysis of two expert system shells: Level 5 Object and Kappa PC. The major components of these tools (knowledge representation, inference and control, developer interface, user interface and explanation facility, interface to external data sources, support and documentation) were studied and tested by means of small prototypes. Results and experiences of this work are given together with some software engineering remarks.
COMPUTING SHORTEST PATHS ON POLYHEDRA: APPLICATIONS IN GEOMETRIC MODELING AND SCIENTIFIC VISUALIZATION
Authors: OPITZ KARSTEN , POTTMANN HELMUT
Published: November 2004

The application of shortest path calculations on polyhedra in different problem domains is discussed. A technique is introduced which allows to transfer problems defined on a curved domain surface into a plane. The technique is based on an approximation to the inverse exponential map. It is applied to gradient estimation for scattered data on surfaces and for the construction of local surface approximations from unorganized points.
REGION COLORING, EDGE COLORING, AND SCAN-CONVERSION OF MAPS
Authors: McCROAN KEITH D. , LACHER R. C.
Published: November 2004

A theory is introduced relating extrinsic colorings of complementary regions of an embedded graph to certain intrinsic colorings of the edges of the graph, called color cycles, that satisfy a certain self-consistency condition. A region coloring is lifted to an edge coloring satisfying the cycle condition, and a dual construction builds a region coloring from any color cycle and any embedding of the graph. Both constructs are canonical, and the constructions are information-conservative in the sense that lifting an arbitrary region coloring to a color cycle and then reconstructing a region coloring from the cycle, using the same embedding, results in the original region coloring. The theory is motivated by, and provides the proof of correctness of, new scan-conversion algorithms that are useful in settings where region boundaries have very high complexity. These algorithms have been implemented and provide useful display functionality previously unavailable on certain rastor devices.
DETERMINING THE SEPARATION OF SIMPLE POLYGONS
Authors: AMATO NANCY M.
Published: November 2004

Given simple polygons P and Q, their separation, denoted by σ(P, Q), is defined to be the minimum distance between their boundaries. We present a parallel algorithm for finding a closest pair among all pairs (p, q), p ∈ P and q ∈ Q. The algorithm runs in O ( log n) time using O(n) processors on a CREW PRAM, where n = |P| + |Q|. This algorithm is time-optimal and improves by a factor of O ( log n) on the time complexity of previous parallel methods. The algorithm can be implemented serially in Θ (n) time, which gives the first optimal sequential algorithm for determining the separation of simple polygons. Our results are obtained by providing a unified treatment of the separation and the closest visible vertex problems for simple polygons.
ON THE STAR HEIGHT OF RATIONAL LANGUAGES
Authors: MONTALBANO ROSA , RESTIVO ANTONIO
Published: November 2004

Two problems concerning the star height of a rational language are investigated: the star height one problem and the relationships between the unambiguity of an expression and its star height. For this purpose we consider the class of factorial, transitive and rational (FTR) languages. From the algebraic point of view a FTR language is the set of factors of a rational submonoid M. Two subclasses of FTR languages are introduced: renewal languages, corresponding to the case of M finitely generated, and unambiguous renewal languages, corresponding to the case of M finitely generated and free. We prove that a FTR language has star height one if and only if it is renewal. This gives a simple decision procedure for the star height one problem for this class of languages. As concerns the relationships with the ambiguity, we introduce the notion of unambiguous star height of a rational language and prove that it can be strictly greater than the star height. This is a consequence of the following results: i) a FTR language of unambiguous star height one is unambiguous renewal; ii) there exist renewal languages which are not unambiguous renewal. This last result is obtained by using arguments involving the entropy of a language.
POLYMERS FOR PHOTONICS
Authors: PRASAD P.N.
Published: November 2004

Polymers have emerged as an important class of materials for applications in photon-ics. In this review, a brief background is presented on photonics and nonlinear optical processes, the latter providing many of the operational functions for the photonics technology. Nonlinear optical processes in polymeric materials are discussed along with the needed structural requirements. The three types of nonlinear polymeric systems discussed are: (i) χ(2) materials; (ii) χ(3) materials and (iii) photorefractive polymers. The photorefractive polymeric systems utilize the combined action of photoconductivity and nonlinear optical effect. New developments using sol-gel processed inorganic glass: polymer composites for nonlinear optics are discussed.
CASE-BASED REASONING FOR KNOWLEDGE ACQUISITION SUGGESTIONS
Authors: BECKER LEE , GUAY TODD
Published: November 2004

Case-based suggestion (CBS) is a general mechanism for system-driven interactive knowledge acquisition. CBS applies case-based reasoning to the task of knowledge acquisition. It utilizes previously acquired knowledge embodied in cases to assist the expert during the current knowledge acquisition session. In this work we describe the general CBS technique and illustrate its use during the acquisition of a specific kind of knowledge. A system utilizing CBS was implemented in the acquisition module of a prototype system called ODS, which structures acquired diagnostic knowledge in decision trees. The algorithm used for case-based suggestion by the ODS system and a description of how the decision tree knowledge was represented in the case base is presented. Several evaluation metrics are introduced, and the application of these measures to several experiences of acquiring knowledge with ODS is discussed.
ACCELERATING TRAINING OF FEEDFORWARD NEURAL NETWORKS
Authors: LOONEY CARL G.
Published: November 2004

We review methods and techniques for training feedforward neural networks that avoid problematic behavior, accelerate the convergence, and verify the training. Adaptive step gain, bipolar activation functions, and conjugate gradients are powerful stabilizers. Random search techniques circumvent the local minimum trap and avoid specialization due to overtraining. Testing assures quality learning.
SHASTRA — AN ARCHITECTURE FOR DEVELOPMENT OF COLLABORATIVE APPLICATIONS
Authors: ANUPAM VINOD , BAJAJ CHANDRAJIT
Published: November 2004

We address the issue of architectures and abstractions to implement multimedia scientific manipulation systems in a Concurrent Engineering setting, where experts in a cooperating group communicate and interact to solve problems. We propose a model for the integration of software tools into a multi-user distributed and collaborative environment on the multimedia desktop, and describe a prototype CSCW infrastructure which we have used to implement scientific problem solving tools. Finally, we briefly describe a prototype CE system built on this infrastructure. Shastra presents a unified prototype for some crucial enabling technologies for Concurrent Engineering — Multimedia Communication, Framework Integration, Coordination, and Enterprise Integration.
LINKS IN A SOLID TORUS AND DICHROMATIC LINK INVARIANTS DERIVED FROM QUANTUM GROUPS
Authors: NAKABO SHIGEKAZU
Published: November 2004

We give an algorithm to simplify the calculation of the inavriants of links in a solid torus, which are defined by means of the representations of [Formula: see text] and the height function. The explicit formula of the initial data for this procedure is presented. Lastely, we observe that the invariant in the simplest level gives an example belonging to a class of 1-trivial dichromatic link invariants different from that defined by Hoste and Kidwell.
ON THE REALIZATION OF WIRTINGER PRESENTATIONS AS KNOT GROUPS
Authors: ROSEBROCK STEPHAN
Published: November 2004

The weight test of Gersten and Pride is modified, to test whether a given abstract Wirtinger presentation occurs as the geometric Wirtinger presentation of a knot. A more refined version of this test then shows that the groups presented by certain abstract Wirtinger presentations are hyperbolic and so do not occur as knot groups. We give an infinite class of examples of such groups with symmetric Alexander polynomial.
GRAPH INVARIANTS AND THE TOPOLOGY OF RNA FOLDING
Authors: KAUFFMAN LOUIS H. , MAGARSHAK YURI
Published: November 2004

A new general method is described for obtaining ambient isotopy or regular isotopy invariants of even valence rigid vertex graphs embedded in three-dimensional space. The paper concentrates on the case of 4-valent vertices and defines an RNA vertex in analogy to the structure of a folded molecule. Examples are given to show how these methods can discriminate graph embeddings that are indistinguishable via Vassiliev invariants. Applications to molecular folding are discussed.
P. L. PROPER KNOT EQUIVALENCE CLASSES ARE GENERATED BY LOCALLY FLAT ISOTOPIES
Authors: NANYES OLLIE
Published: November 2004

A p. 1. proper knot is a proper p. 1. embedding of the real line into a p. 1. open 3-manifold. Two p. 1. proper knots are said to be equivalent if there is a p. 1. proper isotopy (possibly non-ambient) connecting them. A priori such an isotopy need not be locally flat: for example a local knot in the range could be shrunk to a point within a 3-cell. In this paper we show that, in essence, this is the only type of non-locally flat phenomena. We show that such a local knot can always be "combed to infinity". Thus if two p. 1. proper knots are connected by a p. 1. proper isotopy then the connecting isotopy can be modified to be a locally flat p. 1. proper isotopy. Hence, in proper knot theory, the smooth category and the p. 1. category are similar.
Remarks on Braid Theory and the characterisation of periodic orbits
Authors: Natiello Mario A. , Solari Hernán G.
Published: November 2004

The relationship between Braid Theory and the organisation of periodic orbits of dynamical systems is considered.

It is shown that for some (physically relevant) 3-d flows the characterisation of periodic orbits by means of Braid Theory can be done on the Poincaré surface in an efficient way. The result is a thread-less graphical presentation of a braid class.

We discuss extensions of this approach to (adequate) dynamical systems of dimension higher than three, using results from Central Manifold Theory.
CONNECTIVITY AND THE EVOLUTION OF BIOLOGICAL SYSTEMS
Authors: GREEN DAVID G.
Published: November 2004

Here I show that digraphs (directed graphs) are inherent both in the relationships between elements of biological systems and in transitions between different system states. Properties of digraphs therefore underlie many biological phenomena, especially criticality and phase changes. Examples include epidemics, development, vegetation change and evolution. An important source of variety in biological systems is the extreme variability in digraph patterns that occurs when levels of connectivity are critical. Many biological processes, including evolution, appear to exploit this variety via a mechanism in which the connectivity of a system flips back and forth across the critical level.
ANALYSIS OF CATEGORICAL TIME-SERIES TEXT RECALL DATA USING A CONNECTIONIST MODEL
Authors: GOLDEN R.M.
Published: November 2004

Categorical time-series are generated by discrete-time probabilistic dynamical systems which can only be in one of a small number of finite states at any given instant in time. A novel statistical methodology based upon log-linear modelling is proposed for analyzing categorical time-series data which allows one to incorporate a considerable amount of prior knowledge directly into the data analysis. The statistical model can be shown to be formally equivalent to a connectionist (i.e., artificial neural network) model, Methods for model selection and hypothesis testing using the new statistical model for samples with large numbers of observations are then developed using asymptotic statistical theory. To illustrate this new method of categorical time-series data analysis, the model is applied to the analysis of text free recall data from children and adults. These analyses indicated that the model can successfully use the order of recalled text propositions to discriminate among alternative theories of prior knowledge and alternative treatment conditions. The reliability of the large sample statistical tests were also checked using a boot-strap methodology and found to be acceptable.
CATEGORIZATION AND IDENTIFICATION OF HUMAN FACE IMAGES BY NEURAL NETWORKS: A REVIEW OF THE LINEAR AUTOASSOCIATIVE AND PRINCIPAL COMPONENT APPROACHES
Authors: VALENTIN D. , ABDI H. , O’TOOLE A.J.
Published: November 2004

Recent statistical/neural network models of face processing suggest that faces can be efficiently represented in terms of the eigendecomposition of a matrix storing pixel-based descriptions of a set of face images. The studies presented here support the idea that the information useful for solving seemingly complex tasks such as face categorization or identification can be described using simple linear models (linear autoassociator or principal component analysis) in conjunction with a pixel-based coding of the faces.
A PROTOTYPE INFORMATION SYSTEM FOR WATERSHED MANAGEMENT AND PLANNING
Authors: LAM D.C.L. , MAYFIELD C.I. , SWAYNE D.A. , HOPKINS K.
Published: November 2004

Watershed management and planning requires a reliable information system for the storage and manipulation of data and knowledge for an integrative approach to solve environmental problems. An approach to develop such an information system is described, with the focus on the requirements both for data analysis and for knowledge processing. Examples based on the results of a prototype system for three different watershed studies are presented to demonstrate the representation and visualization of data and knowledge. While the prototype system is found to be viable, its usefulness depends on the ability to link with existing software systems and on the commitment of expert partners in the formulation of an accurate knowledge base for watershed management and planning.
FUZZY SENSORS FOR FUZZY CONTROL
Authors: FOULLOY LAURENT , GALICHET SYLVIE
Published: November 2004

This paper introduces sensors employing a fuzzy numeric to symbolic interface. The fundamental design considerations for this kind of fuzzy symbolic sensor, or fuzzy sensor, are formally presented. Then, the use of these components for fuzzy control is discussed and illustrated.
Galileo and the Mountains of the Moon: Analogical Reasoning, Models and Metaphors in Scientific Discovery
Authors: Spranzi Marta
Published: November 2004

This paper is about the use of analogical reasoning, models and metaphors in Galileo's discovery of the mountains of the moon, which he describes in the Starry Messenger, a short but groundbreaking treatise published in 1610. On the basis of the observations of the Moon he has made with the newly invented telescope, Galileo shows that the Moon has mountains and that therefore it shares the same solid, opaque and rugged nature of the Earth. I will first reconstruct Galileo's reasoning, and illustrate the counterintuitive and quasi-circular way in which discovery depends on analogy: in order for analogical reasoning to succeed in bridging ontological gaps and thus serve as a discovery tool, a certain similarity between what are considered as radically different domains has to be presupposed. More particularly, in order for analogical reasoning to lead to genuine discoveries, salient features have to be selected in the source domain that will be mapped onto the target domain. There is disagreement as to how this mapping is successfully carried out: the syntactical (Dedre Gentner), pragmatic (Paul Thagard) and ontological-categorical (Rom Harré) approaches, all illuminate some features of this selection in the mapping process. On the basis of an analysis of Galileo's discovery, I will argue that we need a different "bootstrapping" approach which involves the construction of an imaginary temporary model encompassing both the source and the target domains, and which is occasionally strengthened by metaphors which serve as incomplete transitional models.
What Has History to Do with Cognition? Interactive Methods for Studying Research Laboratories
Authors: Kurz-Milcke Elke , Nersessian Nancy , Newstetter Wendy
Published: November 2004

We have been studying cognition and learning in research laboratories in the field of biomedical engineering (Nersessian, Kurz-Milcke, Newstetter & Davies 2003; Newstetter, Kurz-Milcke & Nersessian, in press[a]). Through our combining of ethnography and cognitive-historical analysis in studying these settings we have been led to understand these labs as comprising evolving distributed cognitive systems and as furnishing agentive learning environments. For this paper we develop the theme of 'models-in-action,' a variant of what Knorr Cetina (1999) has called 'knowledge-in-action.' Among the epistemically most salient objects in these labs are so called "model systems," which are designs that blend engineering with the study and use of biological systems for purposes of simulative model-based reasoning. We portray the prevalent design-orientation in this engineering specialty and how the prevailing activity of cell-culturing in these labs transitions into a design activity for the bio-medical engineers, leading them to work with 'wet' devices. We discuss how devices, 'wet' and 'dry,' situate model-based understandings and how they participate in model systems in these labs. Models tend to come in clusters or configurations, and the model systems in these labs are epistemically salient junctures of interlocking models. Model systems in these labs evolve thereby consolidating what we want to call a 'fabric of interlocking models,' which functions as point of stability and departure in these labs. We convey a taste of such a 'fabric' for a tissue-engineering lab. We conjecture that through this 'fabric' extended developments in technology and methodology have a 'situated' presence in the workings of these labs.
Putative chemical signals of leopard
Authors: Poddar-Sarkar Mousumi , Brahmachary
Published: November 2004

A study of marking fluid (MF) of Indian male leopard has been undertaken as a continuation of the earlier work on tiger and cheetah pheromones. The behavioural observations reveal that MF is presumably the primary means of communication in leopard. The chemical analyses reveal the presence of acetic, propionic, isobutyric, butyric, isovarleric, valeric, isohexanoic, hexanoic, isoheptanoic, heptanoic, isooctanoic, octanoic and nonanoic acid in the acidic fraction of steam distillate of MF. Amines like etylenediamine, putrescine, cadaverine and phenylethylamine, dimethylamine and trimethylamine were also detected in the basic fraction of MF. The amount of lipid extracted from MF is 1.15 mg/ml.
Continuing Professional Development in School Psychology
Authors: Lam Shui-Fong , Yuen Mantak
Published: November 2004

A questionnaire survey was conducted in Hong Kong to investigate the types, frequency, popularity and quality of continuing professional development (CPD) in school psychology. The results indicated that 60 percent of the 32 respondents received regular supervision, however, the majority met their supervisors less than once a month. The characteristics of their supervisors also suggested that the supervision tended to be administrative instead of professional in nature. The most popular CPD activities were attending conferences/seminars, self-study and individual supervision. Large variation was found among the school psychologists from different work settings. The few school psychologists in private practice reported the least amount of CPD activities. The results are discussed with reference to the need to establish regulatory systems with mandatory CPD.
Cost Model Based Optimisation of Carburising Operation
Authors: Sahay S.S. , Mitra K.
Published: November 2004

Cost modelling provides a unified framework for optimising industrial processes by simultaneously considering all the key metrics that characterise the performance of a process. The broad scope of cost modelling is to correlate the process parameters with the plant performance metrics and, in turn, relate these to the overall process cost. In the present paper, the concept of cost modelling will be elaborated in a case study on the gas carburising operation. The cost model for the case carburisation process relates the controllable parameters (carbon potential and T–t set points) to the relevant cost drivers (energy, productivity, gas consumption, emissions) and quality parameters (case depth, grain size and distortion). These cost drivers and quality parameters are transformed to obtain the overall normalised production cost using appropriate cost functions. The cost model is subsequently used to optimise the carburisation cycle by the exhaustive search method for boost stage optimisation and by the differential evolution method, a genetic algorithm based technique, for the entire cycle optimisation, with the objective of minimising the production cost. This approach resulted in significant energy reduction (14%) and productivity enhancement (20%) in an industrial carburising operation.
Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials
Authors: Spina Michele , Jaeger Ulrich , Sparano Joseph A. , Talamini Renato , Simonelli Cecilia , Michieli Mariagrazia , Rossi Giuseppe , Nigra Ezio , Berretta Massimiliano , Cattaneo Chiara , Rieger Armin C. , Vaccher Emanuela , Tirelli Umberto
Published: November 2004

Evidence suggests that infusional therapy is a more effective means for administering cytotoxic therapy than intravenous bolus therapy for lymphoma and offers greater potential for therapeutic synergy with rituximab, which has a long half-life. We pooled the results of 3 prospective phase 2 trials evaluating rituximab in combination with 96-hour infusion of cyclophosphamide (187.5-200 mg/m2 per day), doxorubicin (12.5 mg/m2 per day), and etoposide (60 mg/m2 per day) (R-CDE) plus granulocyte–colony-stimulating factor (G-CSF) in 74 patients with HIV-associated, B-cell non-Hodgkin lymphoma, of whom 56 (76%) patients received concurrent highly active antiretroviral therapy (HAART). The complete remission (CR) rate was 70% (95% confidence interval [CI], 59%-81%), and the estimated 2-year failure-free survival and overall survival rates were 59% (95% CI, 47%-71%) and 64% (95% CI, 52%-76%), respectively. Ten (14%) patients had opportunistic infections during or within 3 months of the end of R-CDE, and 17 (23%) patients developed nonopportunistic infections after that time. Six (8%) patients died because of infection; 2 (3%) of those infections were bacterial sepsis during R-CDE, and 4 (5%) were opportunistic infections that occurred between 2 and 8 months after the completion of R-CDE. R-CDE produced a 70% CR rate and a 59% 2-year failure-free survival rate in patients with HIV-associated lymphoma. Consistent with other reports, adding rituximab to cytotoxic therapy in this population may increase the risk for life-threatening infection. Further studies evaluating rituximab in combination with infusional chemotherapy are warranted, but caution is advised.
Calibration and assessment of channel-specific biases in microarray data with extended dynamical range
Authors: Bengtsson Henrik , Jönsson Göran , Vallon-Christersson Johan
Published: November 2004

Background

Non-linearities in observed log-ratios of gene expressions, also known as intensity dependent log-ratios, can often be accounted for by global biases in the two channels being compared. Any step in a microarray process may introduce such offsets and in this article we study the biases introduced by the microarray scanner and the image analysis software.

Results

By scanning the same spotted oligonucleotide microarray at different photomultiplier tube (PMT) gains, we have identified a channel-specific bias present in two-channel microarray data. For the scanners analyzed it was in the range of 15–25 (out of 65,535). The observed bias was very stable between subsequent scans of the same array although the PMT gain was greatly adjusted. This indicates that the bias does not originate from a step preceding the scanner detector parts. The bias varies slightly between arrays. When comparing estimates based on data from the same array, but from different scanners, we have found that different scanners introduce different amounts of bias. So do various image analysis methods. We propose a scanning protocol and a constrained affine model that allows us to identify and estimate the bias in each channel. Backward transformation removes the bias and brings the channels to the same scale. The result is that systematic effects such as intensity dependent log-ratios are removed, but also that signal densities become much more similar. The average scan, which has a larger dynamical range and greater signal-to-noise ratio than individual scans, can then be obtained.

Conclusions

The study shows that microarray scanners may introduce a significant bias in each channel. Such biases have to be calibrated for, otherwise systematic effects such as intensity dependent log-ratios will be observed. The proposed scanning protocol and calibration method is simple to use and is useful for evaluating scanner biases or for obtaining calibrated measurements with extended dynamical range and better precision. The cross-platform R package aroma, which implements all described methods, is available for free from http://www.maths.lth.se/bioinformatics/.
Density-dependence and within-host competition in a semelparous parasite of leaf-cutting ants
Authors: Hughes William OH , Petersen Klaus S , Ugelvig Line V , Pedersen Dorthe , Thomsen Lene , Poulsen Michael , Boomsma Jacobus J
Published: November 2004

Background

Parasite heterogeneity and within-host competition are thought to be important factors influencing the dynamics of host-parasite relationships. Yet, while there have been many theoretical investigations of how these factors may act, empirical data is more limited. We investigated the effects of parasite density and heterogeneity on parasite virulence and fitness using four strains of the entomopathogenic fungus, Metarhizium anisopliae var. anisopliae, and its leaf-cutting ant host Acromyrmex echinatior as the model system.

Results

The relationship between parasite density and infection was sigmoidal, with there being an invasion threshold for an infection to occur (an Allee effect). Although spore production was positively density-dependent, parasite fitness decreased with increasing parasite density, indicating within-host scramble competition. The dynamics differed little between the four strains tested. In mixed infections of three strains the infection-growth dynamics were unaffected by parasite heterogeneity.

Conclusions

The strength of within-host competition makes dispersal the best strategy for the parasite. Parasite heterogeneity may not have effected virulence or the infection dynamics either because the most virulent strain outcompeted the others, or because the interaction involved scramble competition that was impervious to parasite heterogeneity. The dynamics observed may be common for virulent parasites, such as Metarhizium, that produce aggregated transmission stages. Such parasites make useful models for investigating infection dynamics and the impact of parasite competition.
Identification of a panel of tumor-associated antigens from breast carcinoma cell lines, solid tumors and testis cDNA libraries displayed on lambda phage
Authors: Pavoni Emiliano , Vaccaro Paola , Pucci Andrea , Monteriù Giorgia , Beghetto Elisa , Barca Stefano , Dupuis Maria Luisa , De Pasquale Ceratti Adolfo , Lugini Antonio , Cianfriglia Maurizio , Cortesi Enrico , Felici Franco , Minenkova Olga
Published: November 2004

Background

Tumor-associated antigens recognized by humoral effectors of the immune system are a very attractive target for human cancer diagnostics and therapy. Recent advances in molecular techniques have led to molecular definition of immunogenic tumor proteins based on their reactivity with autologous patient sera (SEREX).

Methods

Several high complexity phage-displayed cDNA libraries from breast carcinomas, human testis and breast carcinoma cell lines MCF-7, MDA-MB-468 were constructed. The cDNAs were expressed in the libraries as fusion to bacteriophage lambda protein D. Lambda-displayed libraries were efficiently screened with sera from patients with breast cancer.

Results

A panel of 21 clones representing 18 different antigens, including eight proteins of unknown function, was identified. Three of these antigens (T7-1, T11-3 and T11-9) were found to be overexpressed in tumors as compared to normal breast. A serological analysis of the 21 different antigens revealed a strong cancer-related profile for at least five clones (T6-2, T6-7, T7-1, T9-21 and T9-27).

Conclusions

Preliminary results indicate that patient serum reactivity against five of the antigens is associated with tumor disease. The novel T7-1 antigen, which is overexpressed in breast tumors and recognized specifically by breast cancer patient sera, is potentially useful in cancer diagnosis.
Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression
Authors: Lagergren Anna , Manetopoulos Christina , Axelson Håkan , Sigvardsson Mikael
Published: November 2004

Background

Transcription factors are frequently involved in the process of cellular transformation, and many malignancies are characterized by a distinct genetic event affecting a specific transcription factor. This probably reflects a tissue specific ability of transcription factors to contribute to the generation of cancer but very little is known about the precise mechanisms that governs these restricted effects.

Methods

To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR. The presence of transcription factors in the different model cell lines was further investigated by EMSA analysis.

Results

In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins. We here show that neuroblastoma cells express these three, for B cell development crucial transcription factors, but nevertheless fail to express detectable levels of their known target genes. Expression of mb-1 could, however, be induced in neuroblastoma cells after disruption of the chromatin structure by treatment with 5-azacytidine and Trichostatin A.

Conclusion

These data suggest that transcription factors are able to selectively activate target genes in different tissues and that chromatin structure plays a key role in the regulation of this activity.
Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy – spatial and time dependent distribution
Authors: Cemazar Maja , Wilson Ian , Dachs Gabi U , Tozer Gillian M , Sersa Gregor
Published: November 2004

Background

Electroporation is currently receiving much attention as a way to increase drug and DNA delivery. Recent studies demonstrated the feasibility of electrogene therapy using a range of therapeutic genes for the treatment of experimental tumors. However, the transfection efficiency of electroporation-assisted DNA delivery is still low compared to viral methods and there is a clear need to optimize this approach. In order to optimize treatment, knowledge about spatial and time dependency of gene expression following delivery is of utmost importance in order to improve gene delivery. Intravital microscopy of tumors growing in dorsal skin fold window chambers is a useful method for monitoring gene transfection, since it allows non-invasive dynamic monitoring of gene expression in tumors in a live animal.

Methods

Intravital microscopy was used to monitor real time spatial distribution of the green fluorescent protein (GFP) and time dependence of transfection efficiency in syngeneic P22 rat tumor model. DNA alone, liposome-DNA complexes and electroporation-assisted DNA delivery using two different sets of electric pulse parameters were compared.

Results

Electroporation-assisted DNA delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz was superior to other methods and resulted in 22% increase in fluorescence intensity in the tumors up to 6 days post-transfection, compared to the non-transfected area in granulation tissue. Functional GFP was detected within 5 h after transfection. Cells expressing GFP were detected throughout the tumor, but not in the surrounding tissue that was not exposed to electric pulses.

Conclusions

Intravital microscopy was demonstrated to be a suitable method for monitoring time and spatial distribution of gene expression in experimental tumors and provided evidence that electroporation-assisted gene delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz is an effective method, resulting in early onset and homogenous distribution of gene expression in the syngeneic P22 rat tumor model.
Use of interrupter technique in assessment of bronchial responsiveness in normal subjects
Authors: Panagou Panagiotis , Kottakis Ioannis , Tzouvelekis Argyris , Anevlavis Stavros , Bouros Demosthenes
Published: November 2004

Background

A number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD20 FEV1.

Methods

We studied 170 normal subjects, 100 male and 70 female (mean ± SD age, 38 ± 8.5 and 35 ± 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD100Rint, EI) as well as by percent dose response ratio (DRR).

Results

BHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthmatic range. The method was reproducible and showed good correlation with PD20FEV1 (r = 0.76, p < 0.005), with relatively narrow limits of agreement at -1.39 μmol and 1.27 μmol methacholine, respectively, but the interrupter methodology proved more sensitive than FEV1 in terms of reactivity (DRR).

Conclusions

Interrupter methodology is clinically useful and may be used to evaluate bronchial responsiveness in normal subjects and in situations when forced expirations cannot be performed.
Effects of heparin on the uptake of lipoprotein lipase in rat liver
Authors: Neuger Lucyna , Vilaró Senén , Lopez-Iglesias Carmen , Gupta Jitendra , Olivecrona Thomas , Olivecrona Gunilla
Published: November 2004

Background

Lipoprotein lipase (LPL) is anchored at the vascular endothelium through interaction with heparan sulfate. It is not known how this enzyme is turned over but it has been suggested that it is slowly released into blood and then taken up and degraded in the liver. Heparin releases the enzyme into the circulating blood. Several lines of evidence indicate that this leads to accelerated flux of LPL to the liver and a temporary depletion of the enzyme in peripheral tissues.

Results

Rat livers were found to contain substantial amounts of LPL, most of which was catalytically inactive. After injection of heparin, LPL mass in liver increased for at least an hour. LPL activity also increased, but not in proportion to mass, indicating that the lipase soon lost its activity after being bound/taken up in the liver. To further study the uptake, bovine LPL was labeled with 125I and injected. Already two min after injection about 33 % of the injected lipase was in the liver where it initially located along sinusoids. With time the immunostaining shifted to the hepatocytes, became granular and then faded, indicating internalization and degradation. When heparin was injected before the lipase, the initial immunostaining along sinusoids was weaker, whereas staining over Kupffer cells was enhanced. When the lipase was converted to inactive before injection, the fraction taken up in the liver increased and the lipase located mainly to the Kupffer cells.

Conclusions

This study shows that there are heparin-insensitive binding sites for LPL on both hepatocytes and Kupffer cells. The latter may be the same sites as those that mediate uptake of inactive LPL. The results support the hypothesis that turnover of endothelial LPL occurs in part by transport to and degradation in the liver, and that this transport is accelerated after injection of heparin.
The immunotherapy of Alzheimer's disease
Authors: Weksler Marc E
Published: November 2004

Only a small percentage of patients with Alzheimer's disease benefit from current drug therapy and for only a relatively short time. This is not surprising as the goal of these drugs is to enhance existing cerebral function in Alzheimer patients and not to block the progression of cognitive decline. In contrast, immunotherapy is directed at clearing the neurotoxic amyloid beta peptide from the brain that directly or indirectly leads to cognitive decline in patients with Alzheimer's disease. The single trial of active immunization with the amyloid beta peptide provided suggestive evidence of a reduction in cerebral amyloid plaques and of stabilization in cognitive function of half the patients who developed good antibody responses to the amyloid beta peptide. However, 6% of actively immunized Alzheimer patients developed sterile meningoencephalitis that forced the cessation of the clinical trial. Passive immunotherapy in animal models of Alzheimer's disease has provided similar benefits comparable to those seen with active immunotherapy and has the potential of being effective in the half of Alzheimer's disease patients who do not make a significant anti-amyloid beta peptide antibody response and without inducing T-cell-mediated encephalitis. Published studies of 5 patients with sporadic Alzheimer disease treated with intravenous immunoglobulin containing anti-amyloid beta peptide antibodies showed that amyloid beta peptide was mobilized from the brain and cognitive decline was interrupted. Further studies of passive immunotherapy are urgently required to confirm these observations.
The hydrology and hydrogeology of dambos: a review
Authors: von der Heyden Constantin J.
Published: November 2004

Dambos are shallow, seasonally waterlogged, tropical and subtropical African wetlands. Their importance, through their role in agriculture and water supply to downstream river networks, has been widely acknowledged. As a result, much research has been conducted on the hydrological functions of dambos and their hydrogeological structures, in an attempt to better understand, utilize and manage this regionally ubiquitous landform. However, these studies have resulted in little consensus regarding the geomorphology of dambos, their hydrological regimes and the hydrogeological model that drives those regimes. This review paper, focusing on dambo hydrology, hydrogeology and their primary determinants, highlights the key issues of the debate and draws some overriding conclusions from the divergent literature. Five hypotheses are proposed based on these conclusions, in an attempt to focus future dambo research efforts.
Receptor regulatory properties evident in the molecular similarity of serotonin receptor ligands and purine nucleotides
Authors: Williams W R , Pugh W J , Nicholls P J
Published: November 2004

Previous computational studies have explored the relative molecular similarity inherent in the ligands of neurotransmitter-regulated cell receptors and purine nucleotides. This study presents the results of an investigation of the major serotonin (5-HT) receptor classes, using molecular superimposition and fitting data. Ligands for 5HT1B/C/D and 5HT4/7 receptors identified pharmacophores in the adenine ring of ATP. 5-HT2 and 5-HT3 receptor ligands identified pharmacophores in the guanosine nucleotide and cyclic nucleotide, respectively. The described molecular similarity is consistent with the cyclic nucleotide responses observed during signal transduction events initiated by 5-HT, and the reported similarity between ligands of the 5-HT1B and 5-HT1D, 5-HT1A and 5-HT7, and 5-HT4 and 5-HT3 receptors. The results are discussed in terms of current pharmacophoric models and signal transduction events involving interaction between G-protein receptors and catalytic sites.
Whose TPMT activity is it anyway?
Authors: Ford Loretta , Prout Catherine , Gaffney Dairena , Berg Jonathan
Published: November 2004

Determination of thiopurine S-methyltransferase (TPMT) activity prior to starting azathioprine therapy is used to identify individuals with low or deficient TPMT activities who are at risk of severe complications and even death

This case describes a patient treated with azathioprine without prior knowledge of TPMT status. Pancytopaenia developed over several months and at this point TPMT activity was determined and found to be low at 16 nmol 6-methyl thioguanine (6-MTG)/g Hb/h, which is within the reference interval associated with heterozygosity for TPMT mutant alleles. On repeating the TPMT measurement 3 months later, the TPMT activity was 2 nmol 6-MTG/g Hb/h, consistent with deficient TPMT activity (homozygosity for TPMT mutant alleles), suggesting the patient is at high risk of myelosuppression if treated with thiopurine drugs.

Retrospectively, it was found that the patient had received transfusions of red blood cell and platelets 6 days before TPMT activity was first measured.

This case underlines the importance of determining TPMT activity status prior to azathioprine treatment, rather than taking a dose incrementation approach. It also highlights the caution that must be taken in interpreting TPMT activity in patients who have recently been transfused.
Down's syndrome risk estimates demonstrate considerable heterogeneity despite homogeneity of input
Authors: Reynolds Tim , Ellis Andy , Jones Rick
Published: November 2004

Background: Due to concerns about screening quality, Down's syndrome screening laboratories were surveyed to identify the range of variation in risk-calculation software.

Methods: All UK Down's syndrome screening laboratories were sent the confidential survey via the National External Quality Assessment Scheme. This covered the software used, its origin, the risk calculation methodology and the Gaussian population parameters. Laboratories were also given multiples of the median (MoM) data from five representative cases and asked to calculate Down's syndrome risks on their systems.

Results: Most parameter sets could be traced to published literature. The range of risk results for identical patient data was wide; the largest differences between lowest and highest risk for a test MoM set were: α-fetoprotein (AFP)+human chorionic gonadotrophin (hCG), 1:95 to 1:388 = 408%; AFP+hCG+urine estriol (UE3), 1:2011 to 1:7000 = 348%; AFP+free-β-hCG, 1:280 to 1:1681 = 600%; AFP+free-β-hCG+UE3, 1:340 to 1:13000 = 3823%. Two explanations for this variation - the prior age risk result (half-year correction) and the population parameters - are described.

Conclusions: (a) All laboratories should apply half-year correction for maternal age risk calculation. (b) Triple-test parameter variations result in huge variation of risk estimates, and a single national risk threshold of 1 in 250 will be unlikely to improve screening equity unless attention is also paid to standardizing population parameters. Down's syndrome screening has been controversial since it was introduced, and the possibility that more central control (including listing acceptable population parameters) may be necessary to ensure comparability of results is certain to ensure that this controversy continues.
Role of CO2 laser in the management of obstructive ectopic lingual thyroids
Authors: Hafidh Maky A. , Sheahan Patrick , Khan Naveed A. , Colreavy Michael , Timon Conrad
Published: November 2004

Ectopic lingual thyroid glands may occasionally undergo massive hypertrophyand be a source of airway obstruction. Securing the airway prior to surgery in such cases may be difficult. In the present paper, we report on two cases of obstructive ectopic lingual thyroids which were successfully managed endoscopically using CO2 laser. The use of CO2 laser for removal of ectopic lingual thyroid tissue offers advantages over traditionalsurgical techniques. In our opinion, removal of an appropriate amount of gland to secure an adequate airway is all that is required in most cases.