bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting specific neuronal populations using adeno‐ and lentiviral vectors: applications for imaging and studies of cell function
Authors: Teschemacher A. G. , Wang S. , Lonergan T. , Duale H. , Waki H. , Paton J. F. R. , Kasparov S.
Published: November 2004

We employ viral vectors to address questions related to the function of specific types of neurones in the central control of blood pressure. Adenoviral vectors (AVVs) or lentiviral vectors (LVVs) can be used to visualize specifically living GABAergic or noradrenergic (NAergic) neurones or to interfere with intracellular signalling within these cell types. Here, we review recent in vitro, in situ and in vivo applications of these vectors in the rat brainstem as performed in our laboratories. In organotypic slice cultures prepared from defined cardiovascular brainstem areas, viral vectors were used to study the electrophysiological properties, intracellular signalling and gene expression in selected neuronal phenotypes. In vivo, vectors were microinjected into brainstem nuclei to inhibit specific aspects of cell signalling by expression of dominant negative proteins, for example. Outcomes for cardiovascular control were measured either acutely in situ or chronically in vivo with radio telemetry in freely moving rats. We showed that AVVs and LVVs have distinct properties that need to be considered prior to their application. For example, LVVs can be manufactured very quickly, have no immunogenicity and can be pseudotyped to display higher tropism for neurones than glia. However, comparatively lower production yields of LVVs may limit their use for some types of applications. In contrast, AVVs require a lengthy construction period, are easy to amplify to high yields at moderate cost but may trigger an immune response when used at high titres in vivo. These features make AVVs particularly suitable for in vitro applications. As the two vector types complement each other in several ways we generated a shuttle system that simplifies transfer of transgene cassettes between the backbones of AVVs and LVVs. Thus, AVVs and LVVs are powerful experimental tools that can be used in a variety of experimental designs in vivo, in situ and in vitro.
Differences in transductional tropism of adenoviral and lentiviral vectors in the rat brainstem
Authors: Duale Hanad , Kasparov Sergey , Paton Julian F. R. , Teschemacher Anja G.
Published: November 2004

Adenoviral vectors (AVVs) and lentiviral vectors (LVVs) are highly useful research tools which can be used to investigate the function of specific cell phenotypes in the brain. The transductional tropism of viral vectors has a critical impact upon the transgene expression in different brain areas. This largely depends on the properties of the viral particles, which for AVVs are most commonly analogous to the serotype 5 adenovirus and, in the case of LVVs, are determined by the envelope used for pseudotyping, for example the vesicular stomatitis virus coat (VSVG). We have created a matching set of shuttle plasmids that allow a one‐step transfer of an entire expression cassette between the backbones of AVVs and LVVs. This has permitted a fair assessment of the impact of the vector type on tropism for both AVVs and LVVs. Thus, the aims of this study were twofold: (i) to develop and demonstrate the validity of a transgene ‘swap’ system between AVVs and LVVs; and (ii) using this system, to assess the tropism of AVVs and LVVs for neuronal versus glial cell types. We have constructed AVVs and VSVG‐coated LVVs to express monomeric red fluorescent protein (mRFP) driven by the human cytomegalovirus promoter (hCMV). Transgene expression in neurones and glia in the hypoglossal and dorsal vagal motor nuclei of the rat brainstem was compared by determining the colocalization with immunostaining for the neuronal marker NeuN (neuronal nuclear antigen) and the glial marker GFAP (glial fibrillatory acidic protein). We found that 55% of mRFP‐expressing cells transduced with AVVs were immunopositive for GFAP, while only 38% were NeuN‐immunoreactive. In contrast, when the same expression cassette was delivered by VSVG‐coated LVVs, the neurone/glia ratio of mRFP expression was reversed with 56% of mRFP‐positive cells identified as neurones and 26% as glia. Thus, the present study provides compelling evidence that VSVG‐coated LVVs significantly shift transgene expression towards neurones while transduction with AVVs favours glia.
Modulation of body fluids and angiotensin II receptors in a rat model of intra‐uterine growth restriction
Authors: Bédard Sophie , Sicotte Benoit , St‐Louis Jean , Brochu Michèle
Published: November 2004

We previously reported that sodium restriction during pregnancy reduces plasma volume expansion and promotes intra‐uterine growth restriction (IUGR) in rats while it activates the renin–angiotensin–aldosterone system (RAAS). In the present study, we proceeded to determine whether expression of the two angiotensin II (ANGII) receptor subtypes (AT1 and AT2) change in relation to maternal water–electrolyte homeostasis and fetal growth. To this end, pregnant (gestation day 15) and non‐pregnant Sprague‐Dawley rats were randomly assigned to two groups fed either normal, or Na+‐restricted diets for 7 days. At the end of the treatment period, plasma aldosterone and renin activity as well as plasma and urine electrolytes were measured. Determinations for AT1 and AT2 mRNA and protein were made by RNase protection assay and photoaffinity labelling, respectively, using a number of tissues implicated in volume regulation and fetal growth. In non‐pregnant rats, Na+ restriction decreases Na+ excretion without altering plasma volume, plasma Na+ concentration or the expression of AT1 and AT2 mRNA or protein in the tissues examined. In normally fed pregnant rats when compared to non‐pregnant controls, AT1 mRNA increases in the hypothalamus as well as pituitary and declines in uterine arteries, while AT1 protein decreases in the kidney and AT2 mRNA declines in the adrenal cortex. In pregnant rats, Na+ restriction induces a decrease in plasma Na+, an increase in plasma urea, as well as a decline in renal urea and creatinine clearance rates. Protein levels for both AT1 and AT2 in the pituitary and AT2 mRNA in the adrenal cortex are lower in the Na+‐restricted pregnant group when compared to normally fed pregnant animals. Na+ restriction also induces a decrease in AT1 protein in the placenta. In conclusion, these results suggest that pregnancy may increase sensitivity to Na+ depletion by the tissue‐specific modulation of ANGII receptors. Finally, these receptors may be implicated in the IUGR response to low Na+.
Hippocampal gamma‐frequency oscillations: from interneurones to pyramidal cells, and back
Authors: Mann Edward O. , Radcliffe Catrin A. , Paulsen Ole
Published: November 2004

GABAergic interneurones are necessary for the emergence of hippocampal gamma‐frequency network oscillations, during which they play a key role in the synchronization of pyramidal cell firing. However, it remains to be resolved how distinct interneurone subtypes contribute to gamma‐frequency oscillations, in what way the spatiotemporal pattern of interneuronal input affects principal cell activity, and by which mechanisms the interneurones themselves are synchronized. Here we summarize recent evidence from cholinergically induced gamma‐frequency network oscillations in vitro, showing that perisomatic‐targeting GABAergic interneurones provide prominent rhythmic inhibition in pyramidal cells, and that these interneurones are synchronized by recurrent excitation. We conclude by presenting a minimal integrate‐and‐fire network model which demonstrates that this excitatory‐inhibitory feedback loop is sufficient to explain the generation of intrahippocampal gamma‐frequency oscillations.
Class II Integrase Mutants with Changes in Putative Nuclear Localization Signals Are Primarily Blocked at a Postnuclear Entry Step of Human Immunodeficiency Virus Type 1 Replication
Authors: Lu Richard , Limón Ana , Devroe Eric , Silver Pamela A. , Cherepanov Peter , Engelman Alan
Published: November 2004

Integrase has been implicated in human immunodeficiency virus type 1 (HIV-1) nuclear import. Integrase analyses, however, can be complicated by the pleiotropic nature of mutations: whereas class I mutants are integration defective, class II mutants display additional assembly and/or reverse transcription defects. We previously determined that HIV-1
V165A
, originally reported as defective for nuclear import, was a class II mutant. Here we analyzed mutants containing changes in other putative nuclear localization signals, including
186
KRK
188
/
211
KELQKQITK
219
and Cys-130. Previous work established HIV-1
K186Q
, HIV-1
Q214L/Q216L
, and HIV-1
C130G
as replication defective, but phenotypic classification was unclear and nuclear import in nondividing cells was not addressed. Consistent with previous reports, most of the bipartite mutants studied here were replication defective. These mutants as well as HIV-1
V165A
synthesized reduced cDNA levels, but a normal fraction of mutant cDNA localized to dividing and nondividing cell nuclei. Somewhat surprisingly, recombinant class II mutant proteins were catalytically active, and class II Vpr-integrase fusion proteins efficiently complemented class I mutant virus. Since a class I Vpr-integrase mutant efficiently complemented class II mutant viruses under conditions in which class II Vpr-integrases failed to function, we conclude that classes I and II define two distinct complementation groups and suggest that class II mutants are primarily defective at a postnuclear entry step of HIV-1 replication. HIV-1
C130G
was also defective for reverse transcription, but Vpr-integrase
C130G
did not efficiently complement class I mutant HIV-1. Since HIV-1
C130A
grew like the wild type, we conclude that Cys-130 is not essential for replication and speculate that perturbation of integrase structure contributed to the pleiotropic HIV-1
C130G
phenotype.
Target Cell Cyclophilin A Modulates Human Immunodeficiency Virus Type 1 Infectivity
Authors: Sokolskaja Elena , Sayah David M. , Luban Jeremy
Published: November 2004

The peptidyl-prolyl isomerase cyclophilin A (CypA) increases the kinetics by which human immunodeficiency virus type 1 (HIV-1) spreads in tissue culture. This was conclusively demonstrated by gene targeting in human CD4+T cells, but the role of CypA in HIV-1 replication remains unknown. Though CypA binds to mature HIV-1 capsid protein (CA), it is also incorporated into nascent HIV-1 virions via interaction with the CA domain of the Gag polyprotein. These findings raised the possibility that CypA might act at multiple steps of the retroviral life cycle. Disruption of the CA-CypA interaction, either by the competitive inhibitor cyclosporine (CsA) or by mutation of CA residue G89 or P90, suggested that producer cell CypA was required for full virion infectivity. However, recent studies indicate that CypA within the target cell regulates HIV-1 infectivity by modulating Ref1- or Lv1-mediated restriction. To examine the relative contribution to HIV-1 replication of producer cell CypA and target cell CypA, we exploited multiple tools that disrupt the HIV-1 CA-CypA interaction. These tools included the drugs CsA, MeIle4-CsA, and Sanglifehrin; CA mutants exhibiting decreased affinity for CypA or altered CypA dependence; HeLa cells with CypA knockdown by RNA interference; and Jurkat T cells homozygous for a deletion of the gene encoding CypA. Our results clearly demonstrate that target cell CypA, and not producer cell CypA, is important for HIV-1 CA-mediated function. Inhibition of HIV-1 infectivity resulting from virion production in the presence of CsA occurs independently of the CA-CypA interaction or even of CypA.
Multiple Genotypes of Influenza B Virus Circulated between 1979 and 2003
Authors: McCullers Jonathan A. , Saito Takehiko , Iverson Amy R.
Published: November 2004

The segmented genome of influenza B virus allows exchange of gene segments between cocirculating strains. Through this process of reassortment, diversity is generated by the mixing of genes between viruses that differ in one or more gene segments. Phylogenetic and evolutionary analyses of all 11 genes of 31 influenza B viruses isolated from 1979 to 2003 were used to study the evolution of whole genomes. All 11 genes diverged into two new lineages prior to 1987. All genes except the NS1 gene were undergoing linear evolution, although the rate of evolution and the degree to which nucleotide changes translated into amino acid changes varied between lineages and by gene. Frequent reassortment generated 14 different genotypes distinct from the gene constellation of viruses circulating prior to 1979. Multiple genotypes cocirculated in some locations, and a sequence of reassortment events over time could not be established. The surprising diversity of the viruses, unrestricted mixing of lineages, and lack of evidence for coevolution of gene segments do not support the hypothesis that the reassortment process is driven by selection for functional differences.
Two Modes of Pseudorabies Virus Neuroinvasion and Lethality in Mice
Authors: Brittle Elizabeth E. , Reynolds Ashley E. , Enquist L. W.
Published: November 2004

We describe two distinct modes of neuroinvasion and lethality after murine flank inoculation with virulent and attenuated strains of pseudorabies virus (PRV). Mice infected with virulent (e.g., PRV-Becker, PRV-Kaplan, or PRV-NIA3) strains self-mutilate their flank skin in response to virally induced pruritus, die rapidly with no identifiable symptoms of central nervous system (CNS) infection such as behavioral abnormalities, and have little infectious virus or viral antigen in the brain. In distinct contrast, animals infected with an attenuated PRV vaccine strain (PRV-Bartha) survive approximately three times longer than wild-type PRV-infected animals, exhibit severe CNS abnormalities, and have an abundance of infectious virus in the brain at the time of death. Interestingly, these animals have no skin lesions and do not appear pruritic at any time during infection. The severe pruritus and relatively earlier time until death induced by wild-type PRV infection may reflect the peripheral nervous system (PNS) and immune responses to infection rather than a fatal, virally induced CNS pathology. Based on previously characterized afferent (sensory) and efferent (motor) neuronal pathways that innervate the skin, we deduced that wild-type virulent strains transit through the PNS via both afferent and efferent routes, whereas PRV-Bartha travels by only efferent routes in the PNS en route to the brain.
CD4+CD25+T Cells Regulate Vaccine-Generated Primary and Memory CD8+T-Cell Responses against Herpes Simplex Virus Type 1
Authors: Toka Felix N. , Suvas Susmit , Rouse Barry T.
Published: November 2004

It has become evident that naturally occurring CD25+regulatory T cells (Tregcells) not only influence self-antigen specific immune response but also dampen foreign antigen specific immunity. This report extends our previous findings by demonstrating that immunity to certain herpes simplex virus (HSV) vaccines is significantly elevated and more effective if Tregcell response is curtailed during either primary or recall immunization. The data presented here show that removal of CD25+Tregcells prior to SSIEFARL-CpG or gB-DNA immunization significantly enhanced the resultant CD8+T-cell response to the immunodominant SSIEFARL peptide. The enhanced CD8+T-cell reactivity in Tregcell-depleted animals was between two- and threefold and evident in both acute and memory stages. Interestingly, removal of CD25+Tregcells during the memory recall response to plasmid immunization resulted in a twofold increase in CD8+T-cell memory pool. Moreover, in the challenge experiments, memory CD8+T cells generated with plasmid DNA in the absence of Tregcells cleared the virus more effectively compared with control groups. We conclude that CD25+Tregcells quantitatively as well as qualitatively affect the memory CD8+T-cell response generated by gB-DNA vaccination against HSV. However, it remains to be seen if all types of vaccines against HSV are similarly affected by CD25+Tregcells and if it is possible to devise means of limiting Tregcell activity to enhance vaccine efficacy.
Human Cytomegalovirus 5-Kilobase Immediate-Early RNA Is a Stable Intron
Authors: Kulesza Caroline A. , Shenk Thomas
Published: November 2004

Immediate-early viral gene products of human cytomegalovirus (HCMV) are derived from several genomic loci and largely serve to establish a cellular environment conducive to viral replication. We have further examined an unusual immediate-early transcript known as the 5-kb RNA, concluding that it is a stable intron encoded by HCMV. The 5-kb RNA is highly AT rich in sequence and lacks open reading frames likely to be translated into protein. We confirmed the absence of polyadenylation of the transcript and showed that it is primarily nuclear localized during viral infection. We mapped the 5′ end of the 5-kb RNA to a consensus splice donor site and localized the 3′ end in the vicinity of a splice acceptor site. In transfection studies, we showed that the 5-kb RNA can be spliced from a heterologous primary transcript. Using bacterial artificial chromosome technology, we constructed a viral recombinant containing a mutation in the 5′ splice donor site that defines the 5′ end of the RNA and found that this mutation eliminates expression of the 5-kb RNA during viral infection. This mutant grows in human fibroblasts without complementation. Taken together, these data support the conclusion that the 5-kb RNA is a stable intron expressed by HCMV.
Structural Requirements of Astrovirus Virus-Like Particles Assembled in Insect Cells
Authors: Caballero Santiago , Guix Susana , Ribes Enric , Bosch Albert , Pintó Rosa M.
Published: November 2004

Expression of the complete ORF2 of human astrovirus serotype 1 (HAstV-1) in the baculovirus system led to the formation of virus-like particles (VLPs) of around 38 nm. The same kind of VLPs were also obtained either with the expression of a truncated form of ORF2 lacking the first 70 amino acids (aa), or with the same truncated form in which those 70 aa were replaced by the green fluorescent protein. All three kinds of VLPs were equally recognized by an anti-HAstV-1 polyclonal antibody and by two monoclonal antibodies (MAbs; 8E7 and 5B7), indicating a nonessential role of those amino acids neither in the capsid assembly nor in the antigen structure. A second type of structure consisting of 16-nm ring-like units was observed in all of the cases, mostly after disassembling the 38-nm VLPs through the addition of EDTA. The removal of the EDTA and the addition of Mg
2+
ions promoted the reassembly of the 38-nm VLPs. The nature of these 16-nm ring-like structures, capsomers or T = 1 VLPs, still remains unclear. Biochemical analysis revealed no differences between the 38-nm VLPs and the 16-nm structures, whereas antigenically, they shared the 8E7 MAb epitope but differed in the 5B7 MAb epitope, with the latter structures being more readily recognized.
Differential Requirement for Cell Fusion and Virion Formation in the Pathogenesis of Varicella-Zoster Virus Infection in Skin and T Cells
Authors: Besser Jaya , Ikoma Minako , Fabel Konstanze , Sommer Marvin H. , Zerboni Leigh , Grose Charles , Arvin Ann M.
Published: November 2004

The protein product of varicella-zoster virus (VZV) ORF47 is a serine/threonine protein kinase and tegument component. Evaluation of two recombinants of the Oka strain, rOka47ΔC, with a C-terminal truncation of ORF47, and rOka47D-N, with a point mutation in the conserved kinase motif, showed that ORF47 kinase function was necessary for optimal VZV replication in human skin xenografts in SCID mice but not in cultured cells. We now demonstrate that rOka47ΔC and rOka47D-N mutants do not infect human T-cell xenografts. Differences in the growth of kinase-defective ORF47 mutants allowed an examination of requirements for VZV pathogenesis in skin and T cells in vivo. Although virion assembly was reduced and no virion transport to cell surfaces was observed, epidermal cell fusion persisted, and VZV polykaryocytes were generated by rOka47ΔC and rOka47D-N in skin. Virion assembly was also impaired in vitro, but VZV-induced cell fusion continued to cause syncytia in cultured cells infected with rOka47ΔC or rOka47D-N. Intracellular trafficking of envelope glycoprotein E and the ORF47 and IE62 proteins, components of the tegument, was aberrant without ORF47 kinase activity. In summary, normal VZV virion assembly appears to require ORF47 kinase function. Cell fusion was induced by ORF47 mutants in skin, and cell-cell spread occurred even though virion formation was deficient. VZV-infected T cells do not undergo cell fusion, and impaired virion assembly by ORF47 mutants was associated with a complete elimination of T-cell infectivity. These observations suggest a differential requirement for cell fusion and virion formation in the pathogenesis of VZV infection in skin and T cells.
REASONING ABOUT OBJECT SYSTEMS IN VTLoE
Authors: MASON IAN , TALCOTT CAROLYN
Published: November 2004

VTLoE (Variable Type Logic of Effects) is a logic for reasoning about imperative functional programs inspired by the variable type systems of Feferman. The underlying programming language, λ mk , extends the call-by-value lambda calculus with primitives for arithmetic, pairing, branching, and reference cells (mutable data). In VTLoE one can reason about program equivalence and termination, input/output relations, program contexts, and inductively (and co-inductively) define data structures. In this paper we present a refinement of VTLoE. We then introduce a notion of object specification and establish formal principles for reasoning about object systems within VTLoE. Objects are self-contained entities with local state. The local state of an object can only be changed by action of that object in response to a message. In λ mk objects are represented as closures with mutable data bound to local variables. A semantic principle called simulation induction was introduced in our earlier work as a means of establishing equivalence relations between streams, object behaviors, and other potentially infinite structures. These are formulated in VTLoE using the class apparatus. The use of these principles is illustrated by validating a variety of basic tranformation rules.
EFFECTS OF SURFACE TOPOLOGY ON TITANIUM RELEASE FROM IMPLANTS INTO RABBIT BONE AFTER 1-YEAR FOLLOW-UP
Authors: Ektessabi Ali , Wennerberg Ann
Published: November 2004

The material composition and surface structure of dental and orthopaedic implants have important effects on integration of the implants with the surrounding bone, and at the same time, the release of the constituent elements of the implants into the surrounding tissues. It is the aim of this paper to study the degree of release of Ti in relation to the surface roughness of the implants. For this purpose, screw shaped implants were prepared with two different surface topographies; one group was left as-machined, i.e. as machine-turned surface, and the second group was blasted with 25 µm Al2O3 particles. The surface topography was measured with a confocal laser scanning profilometer and the surface roughness was characterized using height and spatial descriptive parameters. The as-machined surfaces had an average surface roughness (Sa) of 0.96 µm and the blasted surfaces had an Sa value of 1.16 µm. The implants were inserted into rabbit bone for 1 year. Six samples (three of each type) were prepared for PIXE analysis. The PIXE analysis was done using proton beams from a tandem type accelerator. with an energy of 2 MeV. The results show that at distances of about 2 mm from implant surface, titanium release into hard tissues was found at similar amounts for the as-machined and the blasted implants inserted in the tibia.
EXTERNAL BEAM PIXE ANALYSIS OF GOLD PRE-HISPANIC MEXICAN JEWELRY
Authors: RUVALCABA-SIL J.L. , DEMORTIER G. , OLIVER A.
Published: November 2004

Pre-Hispanie funerary gold jewelry artefacts (900–1325 A.D.) from Mexico (Oaxaca) were studied by PIXE. A 2,7 MeV proton beam was used in an external beam set-up to determine the elemental composition in various regions of each item. Some of the flattest regions were analyzed at normal and grazing beam incidence to determine whether elemental compositions are different in the bulk by comparison with the surface. The results provide relevant information about the metallurgical techniques, like alloy casting, gilding and soldering processes used by ancient mesoamerican goldsmiths.
FROM SUBFACTORS TO 3-DIMENSIONAL TOPOLOGICAL QUANTUM FIELD THEORIES AND BACK: A detailed account of Ocneanu’s theory
Authors: EVANS DAVID E. , KAWAHIGASHI YASUYUKI
Published: November 2004

A full proof of Ocneanu’s theorem is given that one can produce a rational unitary polyhedral 3-dimensional topological quantum field theory of Turaev-Viro type from a subfactor with finite index and finite depth, and vice versa. The key argument is an equivalence between flatness of a connection in paragroup theory and invariance of a state sum under one of the three local moves of tetrahedra. This was announced by A. Ocneanu and he gave a proof of Frobenius reciprocity and the pentagon relation, which produces a 3-dimensional TQFT via the Turaev-Viro machinery, but he has not published a proof of the converse direction of the equivalence. Details are given here along the lines suggested by him.
A NOTE ON A TREE-TO-TREE EDITING PROBLEM
Authors: TANAKA EIICHI
Published: November 2004

In the previous paper on a tree-to-tree editing problem some errors were included. This letter describes the corrected definition of a structure preserving mapping between rooted and ordered trees and a computing method of the tree distance based on the mapping.
A VLSI IMPLEMENTATION OF THE INVERSE DISCRETE COSINE TRANSFORM
Authors: BHATTACHARYA ARUP K. , HAIDER SYED S.
Published: November 2004

The Inverse Discrete Cosine Transform (IDCT) is an important function in HDTV, digital TV and multimedia systems complying with JPEG or MPEG standards for video compression. However, the IDCT is computationally intensive and therefore very expensive to implement in VLSI using direct matrix multiplication. By properly arranging the input coefficient sequence and the output data, the rows and columns of the transform matrix can be reordered to build modular regularity suitable for custom implementation in VLSI. This regularity can be exploited, so that a single permutation can be used to derive each output column from the previous one using a circular shift of an accumulator’s input data multiplied in a special sequence. This technique, using only one 1-dimensional IDCT processor and seven constant multipliers, and its implementation are presented. Operation of 58 MHz under worst case conditions is easily achieved, thus making the design applicable to a wide range of video and real time image processing applications. Fabricated in 0.5 micron triple metal CMOS technology, the IDCT contains 70,000 transistors occupying 7 mm2 square silicon. The design has been used on an AT&T MPEG video decoder chip.
QUADTREE ALGORITHMS FOR TEMPLATE MATCHING ON MESH CONNECTED COMPUTER
Authors: SENOUSSI H. , SAOUDI A.
Published: November 2004

We present four algorithms to perform template matching of an N×N image with an M×M template. The first algorithm is sequential, and the others are based on a SIMD mesh connected computer with N×N processors. In the first three algorithms, both the image and the template are represented by quadtrees, whereas in the last one, the template is represented by a quadtree, and the image is represented by a matrix. The time complexities of the four algorithms are respectively upper-bounded by α1N2M2, α2N+β2M2, α3N+β3M2, and β4M2, where α1, α2, β2, α3, β3, and β4 are constants.
DATA ALLOCATION STRATEGIES FOR PARALLEL IMAGE PROCESSING ALGORITHMS
Authors: MARION-POTY VIRGINIE , MIGUET SERGE
Published: November 2004

This paper discusses several data allocation strategies used for the parallel implementation of basic imaging operators. It shows that depending on the operator (sequential or parallel, with regular or irregular execution time), the image data must be partitioned in very different manners: The square sub-domains are best adapted for minimizing the communication volume, but rectangles can perform better when we take into account the time for constructing messages. Block allocations are well adapted for inherently parallel operators since they minimize interprocessor interactions, but in the case of recursive operators, they lead to nearly sequential executions. In this framework, we show the usefulness of block-cyclic allocations. Finally, we illustrate the fact that allocating the same amount of image data to each processor can lead to severe load imbalance in the case of some operators with data-dependant execution times.
THE COMBINATION OF MULTIPLE CLASSIFIERS BY A NEURAL NETWORK APPROACH
Authors: HUANG YEA S. , LIU KE , SUEN CHING Y.
Published: November 2004

Due to different writing styles and various kinds of noise, the recognition of handwritten numerals is an extremely complicated problem. Recently, a new trend has emerged to tackle this problem by the use of multiple classifiers. This method combines individual classification decisions to derive the final decisions. This is called "Combination of Multiple Classifiers" (CME). In this paper, a novel approach to CME is developed and discussed in detail. It contains two steps: data transformation and data classification. In data transformation, the output values of each classifier are first transformed into a form of likeness measurement. The larger a likeness measurement is, the more probable the corresponding class has the input. In data classification, neural networks have been found very suitable to aggregate the transformed output to produce the final classification decisions. Some strategies for further improving the performance of neural networks have also been proposed in this paper. Experiments with several data transformation functions and data classification approaches have been performed on a large number of handwritten samples. The best result among them is achieved by using both the proposed data transformation function and the multi-layer perceptron neural net, which increased the recognition rate of three individual classifications considerably.
THE CONCEPT OF A HIGH PERFORMANCE ALL-ROUND ENERGY EFFICIENT MECHATRONICALLY-CONTROLLED TRI-MODE SUPERCAR
Authors: FIJALKOWSKI BOGDAN T.
Published: November 2004

Automotive designers' long-term ambition of combining high performance and excellent liquid and gas fuel economy in the same automotive vehicle, seems to be on the verge of fruition by Cracow University of Technology's Automotive Mechatronics Research-and-Development (R&D) Team with their revolutionary concept of new all-round energy efficient tri-mode supercars (advanced ultralight hybrids). This all-round, energy efficient, tri-mode supercar concept had been conceived shortly before October 1993 when the US President Bill Clinton's Clean Car Initiative launched a commitment by America's Big Three automotive manufacturers in Detroit that are to be assisted by America's national weapons laboratories in a 10-year program to develop environmentally-friendly supercars. Reporting this, the New York Times named President Clinton's teenage dream car as a 1952 Buick "Kaiser Henry J" gas guzzler. The development of the tri-mode supercars at Cracow University of Technology began in the early 1990s on a very much restricted budget, compared with similar projects in other countries, with emphasis on lengthening the operating distance and enhancing the image of them. Longer running distance will be achieved by designing an energy-saving full-time Four-Wheel Driveable (4WD) propulsion, Four-Wheel Brakeable (4WB) dispulsion, Four-Wheel Absorbable (4WA) suspension, Four-Wheel Steerable (4WS) conversion and ultralight chassis and body with an aerodynamic drag of around 0.2, as well as the use of high-performance unconventional combustion engines, modern electronically-controlled electromechanical/ mechanoelectrical Steer-, Autodrive- and Autoabsorbable Wheels ( SA 2 W ) with the AC-AC, AC-DC-AC and/or DC-AC/AC-DC macroelectronic converter commutator (macrocommutator) wheel-hub motors/generators and high-density mechanical energy-storing high-speed Autodrive- and Autoabsorbable Flywheel ( A 2 F ) with the brushless AC-AC, AC-DC-AC and/or DC-AC/AC-DC macrocommutator twin composite-flywheel-hub motors/generators and chemical energy-storing advanced chemoelectrical storage battery. Called the Poly-Supercar (or Polytechnic all-round energy efficient tri-mode supercar), i.e. the advanced ultralight hybrid, it will be the product of four year's R&D to design an experimental four-seat supercar of advanced specification, performance and economy, and with functions which include lane keeping, adaptive cruise control, traffic sign recognition, obstacle detection, collision avoidance, blind spot detection, and day/night vision enhancement.
NEW RESONANT DC/DC CONVERTER WITH CLASS DE INVERTER AND CLASS E RECTIFIER
Authors: KOIZUMI HIROTAKA , FUJII MOTOKI , SUETSUGU TADASHI , MORI SHINSAKU
Published: November 2004

A new resonant dc/dc converter is proposed. It consists of a Class DE inverter and a Class E rectifier. Class E switching conditions are achieved for both the inverter and rectifier. Therefore, the efficiency of the converter is very high at switching frequencies in the megahertz range. In this paper, we give an analysis, design equations and experimental results for the proposed circuit. Experimental waveforms were in good agreement with the theory. The measured dc/dc power conversion efficiency was over 83% at 1 MHz 2.3 W.
SLIDING MODE CONTROLLER FOR PARALLEL RESONANT DUAL CONVERTERS
Authors: KORONDI PÉTER , YANG SENUG HAK , HASHIMOTO HIDEKI , HARASHIMA FUMIO
Published: November 2004

The classical DC drive control structure (outer speed control loop and fast inner current control loop) is applied for induction motors. This paper focuses on the inner current control (indirect current control) loop. Three Park vector based VSC (Variable Structure Control) methods (one for input rectifier two for the output inverter) are studied. In the three cases, a complex error vector, a complex sliding surface and a complex distance vector (which indicates the distance of the actual state from the sliding surface) are defined. The inverter is switched in such a way that the system trajectory gets as close to the sliding surface as possible. In spite of the fact that the error vectors have different physical meanings, similar switching strategies can be applied to all cases due to the similarity of mathematical equations. By the proposed method both the low-order harmonics and the audio noise can be reduced.
ENTREPRENEURSHIP IN A TRANSITION ECONOMY: AN EXAMINATION OF VENTURE CREATION IN HUNGARY
Authors: LYLES MARJORIE A , BAIRD INGA S , ORRIS J B
Published: November 2004

This study examines entrepreneurs and new ventures in a transition economy, Hungary, and identifies what variables distinguish between Hungarian entrepreneurs and their new ventures in the pre-1988 transition period from that which followed. The variables that discriminate most strongly are their business strategies. The newer firms had a concentration strategy while the older firms had a new product development strategy. Other variables that discriminated between the groups include reacting to the political environment, satisfaction with firm performance, encouragement from investors, recent investment in building improvement, and family history of entrepreneurship. The newer entrepreneurs had more family role models of entrepreneurship.
Hyperoxia alters the expression and phosphorylation of multiple factors regulating translation initiation
Authors: Shenberger Jeffrey S. , Myers Jennifer L. , Zimmer Stephen G. , Powell Richard J. , Barchowsky Aaron
Published: November 2004

Hyperoxia is cytotoxic and depresses many cellular metabolic functions including protein synthesis. Translational control is exerted primarily during initiation by two mechanisms: 1) through inhibition of translation initiation complex formation via sequestration of the cap-binding protein, eukaryotic initiation factor (eIF) 4E, with inhibitory 4E-binding proteins (4E-BP); and 2) by prevention of eIF2-GTP-tRNA[Formula: see text] formation and eIF2B activity by phosphorylated eIF2α. In this report, exposure of human lung fibroblasts to 95% O2decreased the incorporation of thymidine into DNA at 6 h and the incorporation of leucine into protein beginning at 12 h. The reductions in DNA and protein synthesis were accompanied by increased phosphorylation of eIF4E protein and reduced phosphorylation of 4E-BP1. At 24 h, hyperoxia shifted 4E-BP1 phosphorylation to lesser-phosphorylated isoforms, increased eIF4E expression, and increased the association of eIF4E with 4E-BP1. Although hyperoxia did not change eIF2α expression, it increased its phosphorylation at Ser51, but not until 48 h. In addition, the activation of eIF2α was not accompanied by the formation of stress granules. These findings suggest that hyperoxia diminishes protein synthesis by increasing eIF4E phosphorylation and enhancing the affinity of 4E-BP1 for eIF4E.
A fractal analysis of the radial distribution of bronchial capillaries around large airways
Authors: Anderson Joseph C. , Babb Albert L. , Hlastala Michael P.
Published: November 2004

We analyzed published measurements of the bronchial circulation and airway wall (Anderson JC, Bernard SL, Luchtel DL, Babb AL, and Hlastala MP. Respir Physiol Neurobiol 132: 329–339, 2002) and determined that the radial distribution of bronchial capillary cross-sectional area was fractal. We limited our analysis to bronchial capillaries, diameter ≤10 μm, that resided between the epithelial basement membrane and adventitia-alveolar boundary, the airway wall tissue. Thirteen different radial distributions of capillary-to-tissue area were constructed simply by changing the number of annuli (i.e., the annular size) used to form each distribution. For the 13 distributions created, these annuli ranged in size from to of the size of the airway wall area. Radial distributions were excluded from the fractal analysis if the sectioning procedure resulted in an annulus with a radial thickness less than the diameter of a capillary. To determine the fractal dimension for a given airway, the coefficient of variation (CV) for each distribution was calculated, and ln(CV) was plotted against the logarithm of the relative piece area. For airways with diameter >2.4 mm, this relationship was linear, which indicated the radial distribution of bronchial capillary cross-sectional area was fractal with an average fractal dimension of 1.27. The radial distribution of bronchial capillary cross-sectional area was not fractal around airways with diameter <1.5 mm. We speculated on how the fractal nature of this circulation impacts the distribution of bronchial blood flow and the efficiency of mass transport during health and disease. A fractal analysis can be used as a tool to quantify and summarize investigations of the bronchial circulation.
Conduction velocity of low-threshold motor units during ischemic contractions performed with surface EMG feedback
Authors: Farina Dario , Gazzoni Marco , Camelia Federico
Published: November 2004

The aim of this study was to analyze the effect of ischemia on low-threshold motor unit conduction velocity. Nine subjects were trained to isolate the activity of a single motor unit (target motor unit) in the abductor pollicis brevis muscle with feedback on surface EMG signals recorded with a 16-electrode linear array. After training, the subjects activated the target motor unit at ∼8 pulses per second (pps) for five 3-min-long contractions. During the third and fourth contractions, a cuff inflated at 180 mmHg around the forearm induced ischemia of the hand. The exerted force (mean ± SE, 4.6 ± 2.1% of the maximal voluntary contraction force), discharge rate (8.6 ± 0.4 pps), interpulse interval variability (34.8 ± 2.5%), and peak-to-peak amplitude of the target motor unit action potentials (176.6 ± 18.2 μV) were not different among the five contractions. Conduction velocity, mean power spectral frequency, and action potential duration were the same in the beginning of the five contractions (2.8 ± 0.2 m/s, 195.2 ± 10.5 Hz, and 5.4 ± 0.3 ms, respectively) and changed over the 3 min of sustained activation only during the fourth contraction. Conduction velocity and mean power spectral frequency decreased (10.05 ± 1.8% and 8.50 ± 2.18% during the 3 min, respectively) and action potential duration increased (8.2 ± 4.6% in the 3 min) during the fourth contraction. In conclusion, 1) subjects were able to isolate the activity of a single motor unit with surface EMG visual feedback in ischemic conditions maintained for 16 min, and 2) the activation-induced decrease in single motor unit conduction velocity was significantly larger with ischemia than with normal circulation, probably due to the alteration of mechanisms of ion exchange across the fiber membrane.
Molecular Mechanisms of Thyroid Dysgenesis
Authors: Polak Michel , Sura-Trueba Sylvia , Chauty Anne , Szinnai Gabor , Carré Aurore , Castanet Mireille
Published: November 2004

Thyroid dysgenesis (TD) is the most prevalent form of congenital hypothyroidism. Ttf-1, Ttf-2, Pax8 and the Tshr are expressed at early stages of thyroid development and are implicated in thyroid ontogeny. Mutations in these genes have been found in some cases of TD. The prevalence of familial forms of TD is significantly higher than expected if the disease was only sporadic, allowing to postulate a genetic basis of the disease. Linkage analysis and mutational screening of the four above-mentioned genes in familial forms of TD showed their exclusion as contributors to the disease in some families, implicating genetic heterogeneity and involving other genetic mechanisms. Strategies to uncover new genes involved in TD are therefore needed. We underscore differences in the temporal expression patterns during the human thyroid development with those in animal models. Further, the extrathyroid expression of these genes during human development enables to define the gene-specific malformations that may be present in patients bearing mutations. The data gathered on molecular thyroid development enable precise genetic counselling of affected families. By increasing our knowledge of thyroid development, we hope to uncover new perspectives of genetic screening and eventually of early in utero treatment.
Growth Hormone Treatment: Cancer Risk
Authors: Sklar Charles A.
Published: November 2004

There have been concerns that growth hormone (GH) therapy may be associated with an increased risk of cancer. Although data are limited and conflicting, one recent report on cancer risk in individuals with no cancer history or risk factors for cancer who were treated with pituitary GH demonstrated a small increased risk of colon cancer and deaths from colon cancer and Hodgkin disease. The data from cancer survivors have consistently shown no increased risk of recurrence of the primary tumor in survivors of all tumor types who are treated with GH. One recent study did show a small increased risk of second solid tumors in survivors previously treated with GH. Limited data suggest that GH therapy is not associated with excess cancer risk in individuals with Langerhans cell histiocytosis and neurofibromatosis type 1. Overall, the clinical data are reassuring, but continued surveillance is mandatory.
Genetics and Variation in Phenotype in Noonan Syndrome
Authors: Jongmans Marjolijn , Otten Barto , Noordam Kees , van der Burgt Ineke
Published: November 2004

Noonan syndrome is a well-known clinical entity comprising multiple congenital anomalies characterized by typical facial features, short stature and congenital heart defect. Approximately 50% of cases are sporadic. Familial cases are generally autosomal dominant. In 2001 a gene responsible for Noonan syndrome, PTPN11, encoding for the non-receptor protein tyrosine phosphatase SHP-2, was identified. Mutation analysis of the PTPN11 gene was carried out in Nijmegen in 150 patients with Noonan syndrome. Mutations were found in 68 patients (45%), the most common being A922G in exon 8. In exon 4 a mutation was found that encoded the C-SH2 domain of the PTPN11 gene in two unique patients who shared some uncommon features. A 218C→T mutation was found in exon 3 in one patient with Noonan syndrome and mild juvenile myelomonocytic leukaemia.
Treatment of Acromegaly
Authors: Holdaway Ian M.
Published: November 2004

Mortality is increased in individuals with acromegaly unless serum growth hormone (GH) levels are below 2 µg/l and serum insulin-like growth factor (IGF)-I levels are normal following treatment. These combined criteria have been used to define remission of the disorder in this review. Transsphenoidal surgery achieves remission targets in an average of 55% of patients. For those not in remission following surgery, options include repeat surgery or use of adjuvant therapy. Fractionated external beam pituitary radiotherapy achieves 10-year remission rates of 47% but leaves patients exposed to excess GH until remission occurs. Stereotactic radiotherapy and gamma knife radiosurgery achieve remission rates of 40% over 3 years, and dopamine agonists produce remission in about 20% of patients. Somatostatin analogues induce remission in 59% of patients within the first year of treatment. The GH receptor antagonist pegvisomant leads to remission in 90% of patients, using IGF-I levels for assessment. Optimal treatment for a patient with acromegaly thus depends on the likely efficacy of treatment, cost, surgical skill, severity of side effects, tolerability, control of tumour growth, and improvement in complications related to tumour mass. A primary surgical approach, followed by medical therapy for those not in remission, remains the preferred option in most centres.
Growth Hormone Treatment Strategy for Short Children Born Small for Gestational Age
Authors: Czernichow Paul
Published: November 2004

Several studies performed in the last 15 years have shown that growth hormone (GH) induces a profound catch-up in height in short children born small for gestational age (SGA). We know from more recent studies that final height can be normalized through GH treatment. In Europe, GH is now a recognized indication, enabling treatment of short children born SGA. Treatment is given to the most severe growth-retarded children after the age of 4 years. A dose of 0.035 mg/kg per day is recommended. However, in our opinion a higher dose would be more efficient in very short children, especially if they are treated later in childhood.