bluuebunny/crossref_metadata_2025 huggingface dataset:
An International Perspective on I&C Policies: Recent Developments and Future Prospects
Authors: Gassmann Hanspeter
Published: July 2002

The last few years have seen unprecedented growth in information and communication technologies (I&C) and products, which has led to a robust growth in the whole world, and especially in the United States. Euphoria was such that the term 'New Economy' was coined about 4 years ago, and was taken to mean almost the same as 'New Technologies', mostly information and communication technologies. These technologies are truly global. They are important instruments for further globalisation, and for reducing the international digital divide; they offer important opportunities for further world economic growth. There is increasing competition in their operation, which brings great benefits to customers in the form of reduced prices and new applications. International co-ordination of standards, trade and regulatory frameworks is increasingly necessary. PTOs and other operators need to keep constantly abreast of developments in various international fora, especially the ITU, the WTO and the OECD.
To which space do I belong? Imagining citizenship in one curriculum subject
Authors: Morgan John
Published: July 2002

According to some commentators, one consequence of the ever‐increasing levels of globalization and internationalization of everyday life in the developed world during the last decade is the growing disorientation in many people's sense of place. Indeed, David Harvey has asked: ‘To what space/place do we belong? Am I a citizen of the world, the nation, the locality?’ In the school curriculum, geography offers children an answer to these questions by providing stable representations or ‘maps of meaning’ with which to make sense of the world. This article draws on work in cultural geography that regards such representations as highly constructed and historically contingent versions of the ‘geographical imagination’. It follows that calls to develop citizenship through geography draw upon ‘imagined geographies of citizenship’ which can be read for their dominant ideologies and hidden geographies of inclusion and exclusion. The article critically examines a number of such ‘imagined geographies’. These include Mackinder's argument that geography should promote an ‘imperial gaze’, teaching British children about their rightful dominion over ‘less developed’ people, the geographies of post‐war reconstruction, and recent calls for school geographers to teach a distinctly ‘British geography’. The article offers critical interpretations of these ‘imagined geographies of citizenship’, suggesting that arguments over citizenship education in school subjects must be located in wider social, economic and political contexts.
Thresholds in Toxicology and Risk Assessment
Authors: Slob Wout
Published: July 2002

It is argued that dose-thresholds in a strict quantitative sense cannot exist in dose-response relationships that are studied by toxicologists. The biological, more qualitative, notion of thresholds can only be translated into quantitative terms by defining thresholds in the effect-size of continuous end-points: What size of an effect can the organism cope with and when is the effect adverse? These are key questions that toxicologists should address, for the various (continuous) end-points that may be observed in toxicological studies. Avoiding this question by resorting to a “formal” statistical test is deceptive and makes the outcome of a risk assessment fortuitous. There is no defendable rationale for different procedures of data analysis based upon assumed underlying mechanisms. The approach of data analysis should be determined by the nature and quality of the data. If the data allow for dose-response modelling, this should be done whatever the underlying biological mechanism. Quantal dose-response relationships (relating to noncancer end-points) are problematic, because their slopes are largely determined by the experimental noise. Therefore, the concept of “extra risk” is not well defined in this case. In the case of tumor incidence data, on the other hand, the definition and estimation of an extra risk level are defendable, if it can be assumed that the stochastic component of the carcinogenicity process itself is large compared to the interindividual variation and experimental noise.
T2 relaxometry in the central nervous system of solvent misusers
Authors: YAMANOUCHI NAOTO , OKADA SHIN‐ICHI , KODAMA KAZUHIRO , SAKAMOTO TADASHI , SEKINE HIROSHI , HIRAI SHINJI , MURAKAMI ATSUHIRO , KOMATSU NAOYA , MORIYAMA TOSHIHIRO , SATO TOSHIO
Published: July 2002

Abstract The purpose of this study was to investigate T2 changes in the central nervous system of solvent misusers and to validate a classification of white matter changes (restricted, intermediate and diffuse) proposed in our previous study by visual inspection of magnetic resonance images. T2 values were calculated from the intensity measurements at nine regions in the brain of eight solvent misusers, six of whom showed white matter changes on MRI (two patients for each type), compared with age and gender‐matched controls. The misusers with white matter changes on MRI showed significantly prolonged T2 in the centrum semiovale (p= 0.002), periventricular white matter (p= 0.016), internal capsule (p= 0.040), and cerebellar white matter surrounding the dentate nucleus (p= 0.001) and shortened T2 in the thalamus (p= 0.025) compared to controls by ANOVA with post hoc comparison of Scheffe. In addition, each type of white matter changes showed different distribution of T2 changes corresponding to the findings from visual inspection. These results confirmed T2 prolongation in the white matter with T2 shortening in the thalamus of solvent misusers with white matter changes, and provided further support for our classification of white matter changes.
Screening for Speech and Language Disorders: the reliability, validity and accuracy of the General Language Screen
Authors: Stott Carol M. , Merricks Melanie J. , Bolton Patrick F. , Goodyer Ian M.
Published: July 2002

This paper reports the reliability, validity and accuracy of the General Language Screen (GLS) as the first stage in its development as a potential screening instrument for the identification of speech and language disorder (SLD) in the primary care setting. Data reported were obtained during the Cambridge Language and Speech Project (CLASP) a longitudinal epidemiological study of primary SLD. The GLS was originally used in initial CLASP sample ascertainment when children were aged 36 months. This report utilises speech and language data collected at subsequent stages of this study (37‐months, 45‐months and 8‐years) to determine the reliability, validity and accuracy of the GLS. The GLS demonstrated sufficient levels of reliability (internal consistency f =0.74) and validity (criterion validity r =−0.55). Adequate construct validity was demonstrated by a factor analysis in which two language related factors were identified. These data therefore justified exploration of the accuracy of the GLS as a screening instrument. Analysis of accuracy in this context is complicated by lack of a generally accepted method of defining SLD case status. This report utilises data on language function at different stages of development to provide measures of GLS accuracy over time. Concurrent accuracy, measured against parental report of language function at 37‐months, was good (ROC area under the curve=0.93). Predictive accuracy measured against direct assessment of speech and language at 45‐months and 8‐years was, as expected, somewhat less (ROC=0.77 and 0.68 respectively). The implications for the use of the GLS as a screening instrument are discussed. The data indicate that the GLS would function most usefully as the first stage of a two‐stage screen for SLD in the primary care setting. Recommendations are made as to the nature of the second stage of such a screen and plans for future research are outlined.
An Investigation Into The Effectiveness Of An Early Intervention Method For Delayed Language Development In Young Children
Authors: Ward Sally
Published: July 2002

Delayed language development is common and has serious sequelae into adulthood in terms of educational, social and emotional development. The objective of this study was to test the hypothesis that a group of language‐delayed infants detected in the first year of life by the screen developed in the author's previous study, and receiving intervention at that stage, would not show language impairment at the age at which children are usually referred for speech and language therapy, whereas an untreated control group would do so. A sample (n 122), of very young language‐delayed children was divided into matched experimental and control groups. The mean (range) age of the sample was 10.6 (8‐21) months. The experimental group received intervention, and both groups were followed up until they were 3 years of age to determine whether there were differences in language development at that stage. The results showed that at 3 years, 85% of controls showed language delay while only 5% of the experimental group did so. The differences in mean language quotient in experimental and control groups were statistically significant (t 2.701, p 0.01). At this stage, 30% of the controls had been referred for speech and language therapy, while none of the experimental group had so been. The intervention was found to take relatively little resource and the low dropout rate and high take‐up indicated that it was popular with carers.
Specific Uptake of Tumor Necrosis Factor-α Is Involved in Growth Control of Trypanosoma brucei
Authors: Magez Stefan , Geuskens Maurice , Beschin Alain , Favero Herwig del , Verschueren Hendrik , Lucas Ralf , Pays Etienne , Baetselier Patrick de
Published: July 2002

Trypanosoma brucei is lysed by tumor necrosis factor-α (TNF-α) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF-α–gold particles are endocytosed via coated pits and vesicles and are directed towards lysosome-like digestive organelles. The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity. TNF-α specific lysis is prevented when lysis assays are performed at a temperature <26°C, despite uptake of the cytokine. Inhibition of lysis is also observed when a lysosomotropic agent is added during the first 2 h of incubation. Both monomorphic and pleomorphic trypanosomes are lysed but only when isolated during the peak of parasitaemia. Lysis is not observed with early infection stage parasites or procyclic (insect-specific) forms. Anti– TNF-α treatment of T. brucei-infected mice reveals a dramatic increase in parasitaemia in the blood circulation, the spleen, the lymph nodes, and the peritoneal cavity. These data suggest that in the mammalian host, TNF-α is involved in the growth control of T. brucei.
Dynamic Distribution of Chemoattractant Receptors in Living Cells During Chemotaxis and Persistent Stimulation
Authors: Xiao Zhan , Zhang Ning , Murphy Douglas B. , Devreotes Peter N.
Published: July 2002

While the localization of chemoattractant receptors on randomly oriented cells has been previously studied by immunohistochemistry, the instantaneous distribution of receptors on living cells undergoing directed migration has not been determined. To do this, we replaced cAR1, the primary cAMP receptor of Dictyostelium, with a cAR1-green fluorescence protein fusion construct. We found that this chimeric protein is functionally indistinguishable from wild-type cAR1. By time-lapse imaging of single cells, we observed that the receptors remained evenly distributed on the cell surface and all of its projections during chemotaxis involving turns and reversals of polarity directed by repositioning of a chemoattractant-filled micropipet. Thus, cell polarization cannot result from a gradient-induced asymmetric distribution of chemoattractant receptors. Some newly extended pseudopods at migration fronts showed a transient drop in fluorescence signals, suggesting that the flow of receptors into these zones may slightly lag behind the protrusion process. Challenge with a uniform increase in chemoattractant, sufficient to cause a dramatic decrease in the affinity of surface binding sites and cell desensitization, also did not significantly alter the distribution profile. Hence, the induced reduction in binding activity and cellular sensitivity cannot be due to receptor relocalization. The chimeric receptors were able to “cap” rapidly during treatment with Con A, suggesting that they are mobile in the plane of the cell membrane. This capping was not influenced by pretreatment with chemoattractant.
Phosphoinositide–Ap-2 Interactions Required for Targeting to Plasma Membrane Clathrin-Coated Pits
Authors: Gaidarov Ibragim , Keen James H.
Published: July 2002

The clathrin-associated AP-2 adaptor protein is a major polyphosphoinositide-binding protein in mammalian cells. A high affinity binding site has previously been localized to the NH2-terminal region of the AP-2 α subunit (Gaidarov et al. 1996. J. Biol. Chem. 271:20922–20929). Here we used deletion and site- directed mutagenesis to determine that α residues 21–80 comprise a discrete folding and inositide-binding domain. Further, positively charged residues located within this region are involved in binding, with a lysine triad at positions 55–57 particularly critical. Mutant peptides and protein in which these residues were changed to glutamine retained wild-type structural and functional characteristics by several criteria including circular dichroism spectra, resistance to limited proteolysis, and clathrin binding activity. When expressed in intact cells, mutated α subunit showed defective localization to clathrin-coated pits; at high expression levels, the appearance of endogenous AP-2 in coated pits was also blocked consistent with a dominant-negative phenotype. These results, together with recent work indicating that phosphoinositides are also critical to ligand-dependent recruitment of arrestin-receptor complexes to coated pits (Gaidarov et al. 1999. EMBO (Eur. Mol. Biol. Organ.) J. 18:871–881), suggest that phosphoinositides play a critical and general role in adaptor incorporation into plasma membrane clathrin-coated pits.
Mutations in Synaptojanin Disrupt Synaptic Vesicle Recycling
Authors: Harris Todd W. , Hartwieg Erika , Horvitz H. Robert , Jorgensen Erik M.
Published: July 2002

Synaptojanin is a polyphosphoinositide phosphatase that is found at synapses and binds to proteins implicated in endocytosis. For these reasons, it has been proposed that synaptojanin is involved in the recycling of synaptic vesicles. Here, we demonstrate that the unc-26 gene encodes the Caenorhabditis elegans ortholog of synaptojanin. unc-26 mutants exhibit defects in vesicle trafficking in several tissues, but most defects are found at synaptic termini. Specifically, we observed defects in the budding of synaptic vesicles from the plasma membrane, in the uncoating of vesicles after fission, in the recovery of vesicles from endosomes, and in the tethering of vesicles to the cytoskeleton. Thus, these results confirm studies of the mouse synaptojanin 1 mutants, which exhibit defects in the uncoating of synaptic vesicles (Cremona, O., G. Di Paolo, M.R. Wenk, A. Luthi, W.T. Kim, K. Takei, L. Daniell, Y. Nemoto, S.B. Shears, R.A. Flavell, D.A. McCormick, and P. De Camilli. 1999. Cell. 99:179–188), and further demonstrate that synaptojanin facilitates multiple steps of synaptic vesicle recycling.
Ran-Binding Protein 3 Is a Cofactor for Crm1-Mediated Nuclear Protein Export
Authors: Lindsay Mark E. , Holaska James M. , Welch Katie , Paschal Bryce M. , Macara Ian G.
Published: July 2002

Crm1 is a member of the karyopherin family of nucleocytoplasmic transport receptors and mediates the export of proteins from the nucleus by forming a ternary complex with cargo and Ran:GTP. This complex translocates through the nuclear pores and dissociates in the cytosol. The yeast protein Yrb2p participates in this pathway and binds Crm1, but its mechanism of action has not been established. We show that the human orthologue of Yrb2p, Ran-binding protein 3 (RanBP3), acts as a cofactor for Crm1-mediated export in a permeabilized cell assay. RanBP3 binds directly to Crm1, and the complex posseses an enhanced affinity for both Ran:GTP and cargo. RanBP3 shuttles between the nucleus and the cytoplasm by a Crm1-dependent mechanism, and the Crm1–RanBP3-NES-Ran:GTP quarternary complex can associate with nucleoporins. We infer that this complex translocates through the nuclear pore to the cytoplasm where it is disassembled by RanBP1 and Ran GTPase–activating protein.
Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p
Authors: Gladfelter Amy S. , Bose Indrani , Zyla Trevin R. , Bardes Elaine S.G. , Lew Daniel J.
Published: July 2002

At the beginning of the budding yeast cell cycle, the GTPase Cdc42p promotes the assembly of a ring of septins at the site of future bud emergence. Here, we present an analysis of cdc42 mutants that display specific defects in septin organization, which identifies an important role for GTP hydrolysis by Cdc42p in the assembly of the septin ring. The mutants show defects in basal or stimulated GTP hydrolysis, and the septin misorganization is suppressed by overexpression of a Cdc42p GTPase-activating protein (GAP). Other mutants known to affect GTP hydrolysis by Cdc42p also caused septin misorganization, as did deletion of Cdc42p GAPs. In performing its roles in actin polarization and transcriptional activation, GTP-Cdc42p is thought to function by activating and/or recruiting effectors to the site of polarization. Excess accumulation of GTP-Cdc42p due to a defect in GTP hydrolysis by the septin-specific alleles might cause unphysiological activation of effectors, interfering with septin assembly. However, the recessive and dose-sensitive genetic behavior of the septin-specific cdc42 mutants is inconsistent with the septin defect stemming from a dominant interference of this type. Instead, we suggest that assembly of the septin ring involves repeated cycles of GTP loading and GTP hydrolysis by Cdc42p. These results suggest that a single GTPase, Cdc42p, can act either as a ras-like GTP-dependent “switch” to turn on effectors or as an EF-Tu–like “assembly factor” using the GTPase cycle to assemble a macromolecular structure.
Induction of maturation-promoting factor during Xenopus oocyte maturation uncouples Ca2+ store depletion from store-operated Ca2+ entry
Authors: Machaca Khaled , Haun Shirley
Published: July 2002

Department of Physiology and Biophysics, University of Arkansas Medical Science, Little Rock, AR 72205

During oocyte maturation, eggs acquire the ability to generate specialized Ca2+ signals in response to sperm entry. Such Ca2+ signals are crucial for egg activation and the initiation of embryonic development. We examined the regulation during Xenopus oocyte maturation of store-operated Ca2+ entry (SOCE), an important Ca2+ influx pathway in oocytes and other nonexcitable cells. We have previously shown that SOCE inactivates during Xenopus oocyte meiosis. SOCE inactivation may be important in preventing premature egg activation. In this study, we investigated the correlation between SOCE inactivation and the Mos–mitogen-activated protein kinase (MAPK)–maturation-promoting factor (MPF) kinase cascade, which drives Xenopus oocyte maturation. SOCE inactivation at germinal vesicle breakdown coincides with an increase in the levels of MAPK and MPF. By differentially inducing Mos, MAPK, and MPF, we demonstrate that the activation of MPF is necessary for SOCE inactivation during oocyte maturation. In contrast, sustained high levels of Mos kinase and the MAPK cascade have no effect on SOCE activation. We further show that preactivated SOCE is not inactivated by MPF, suggesting that MPF does not block Ca2+ influx through SOCE channels, but rather inhibits coupling between store depletion and SOCE activation.
Galectin-1, an Endogenous Lectin Produced by Thymic Epithelial Cells, Induces Apoptosis of Human Thymocytes
Authors: Perillo Nancy L. , Uittenbogaart Christel H. , Nguyen Julie T. , Baum Linda G.
Published: July 2002

Galectin-1, a β-galactoside binding protein, is produced by thymic epithelial cells and binds to human thymocytes. We have previously reported that galectin-1 induces the apoptosis of activated T lymphocytes. Because the majority of thymocytes die via apoptosis while still within the thymus, we tested whether galectin-1 could induce the apoptosis of these cells. We now report that in vitro exposure to galectin-1 induced apoptosis of two subsets of CD4lo CD8lo thymocytes. The phenotypes of susceptible thymocytes were consistent with that of both negatively selected and nonselected cells. Galectin-1–induced apoptosis was enhanced by preexposure of thymocytes to antibody to CD3, suggesting that galectin-1 may be a participant in T-cell– receptor mediated apoptosis. In contrast, pretreatment of thymocytes with dexamethasone had no effect on galectin-1 susceptibility. We noted that 71% of the cells undergoing apoptosis after galectin-1 treatment had a DNA content greater than 2N, indicating that proliferating thymocytes were most sensitive to galectin-1. We propose that galectin-1 plays a role in the apoptosis of both negatively selected and nonselected thymocytes, and that the susceptibility of thymocytes to galectin-1 is regulated, in part, by entry or exit from the cell cycle.
Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin
Authors: Ferrari Davide , Chiozzi Paola , Falzoni Simonetta , Hanau Stefania , Di  Virgilio Francesco
Published: July 2002

Microglial cells express a peculiar plasma membrane receptor for extracellular ATP, named P2Z/P2X7 purinergic receptor, that triggers massive transmembrane ion fluxes and a reversible permeabilization of the plasma membrane to hydrophylic molecules of up to 900 dalton molecule weight and eventual cell death (Di Virgilio, F. 1995. Immunol. Today. 16:524–528). The physiological role of this newly cloned (Surprenant, A., F. Rassendren, E. Kawashima, R.A. North and G. Buell. 1996. Science (Wash. DC). 272:735–737) cytolytic receptor is unknown. In vitro and in vivo activation of the macrophage and microglial cell P2Z/P2X7 receptor by exogenous ATP causes a large and rapid release of mature IL-1β. In the present report we investigated the role of microglial P2Z/P2X7 receptor in IL-1β release triggered by LPS. Our data suggest that LPS-dependent IL-1β release involves activation of this purinergic receptor as it is inhibited by the selective P2Z/P2X7 blocker oxidized ATP and modulated by ATP-hydrolyzing enzymes such as apyrase or hexokinase. Furthermore, microglial cells release ATP when stimulated with LPS. LPS-dependent release of ATP is also observed in monocyte-derived human macrophages. It is suggested that bacterial endotoxin activates an autocrine/paracrine loop that drives ATP-dependent IL-1β secretion.
Early T Cell Receptor β Gene Expression Is Regulated by the Pre-T Cell Receptor–CD3 Complex
Authors: Aifantis Iannis , Feinberg Jacqueline , Fehling Hans Jörg , Di Santo James P. , von Boehmer Harald
Published: July 2002

We have examined the question of whether there is an additional checkpoint in T cell development that regulates T cell receptor (TCR)-β expression in CD25+44− thymocytes by mechanisms that are independent of the pre-TCR. Our analysis in various mutant mice indicates that all changes in cytoplasmic TCR-β expression can be accounted for by pre-TCR–dependent signal mediation, putting into question the function of a putative pro-TCR.
Pim1 Reconstitutes Thymus Cellularity in Interleukin 7–And Common γ Chain–Mutant Mice and Permits Thymocyte Maturation in Rag- but Not Cd3γ-Deficient Mice
Authors: Jacobs Heinz , Krimpenfort Paul , Haks Mariëlle , Allen John , Blom Bianca , Démollière Corinne , Kruisbeek Ada , Spits Hergen , Berns Anton
Published: July 2002

The majority of lymphomas induced in Rag-deficient mice by Moloney murine leukemia virus (MoMuLV) infection express the CD4 and/or CD8 markers, indicating that proviral insertions cause activation of genes affecting the development from CD4−8− pro-T cells into CD4+8+ pre-T cells. Similar to MoMuLV wild-type tumors, 50% of CD4+8+ Rag-deficient tumors carry a provirus near the Pim1 protooncogene. To study the function of PIM proteins in T cell development in a more controlled setting, a Pim1 transgene was crossed into mice deficient in either cytokine or T cell receptor (TCR) signal transduction pathways. Pim1 reconstitutes thymic cellularity in interleukin (IL)-7– and common γ chain–deficient mice. In Pim1-transgenic Rag-deficient mice but notably not in CD3γ-deficient mice, we observed slow expansion of the CD4+8+ thymic compartment to almost normal size. Based on these results, we propose that PIM1 functions as an efficient effector of the IL-7 pathway, thereby enabling Rag-deficient pro-T cells to bypass the pre-TCR–controlled checkpoint in T cell development.
Distinct Cytokine Profiles of Neonatal Natural Killer T Cells after Expansion with Subsets of Dendritic Cells
Authors: Kadowaki Norimitsu , Antonenko Svetlana , Ho Stephen , Rissoan Marie-Clotilde , Soumelis Vassili , Porcelli Steven A. , Lanier Lewis L. , Liu Yong-Jun
Published: July 2002

Natural killer T (NKT) cells are a highly conserved subset of T cells that have been shown to play a critical role in suppressing T helper cell type 1–mediated autoimmune diseases and graft versus host disease in an interleukin (IL)-4–dependent manner. Thus, it is important to understand how the development of IL-4– versus interferon (IFN)-γ–producing NKT cells is regulated. Here, we show that NKT cells from adult blood and those from cord blood undergo massive expansion in cell numbers (500–70,000-fold) during a 4-wk culture with IL-2, IL-7, phytohemagglutinin, anti-CD3, and anti-CD28 mAbs. Unlike adult NKT cells that preferentially produce both IL-4 and IFN-γ, neonatal NKT cells preferentially produce IL-4 after polyclonal activation. Addition of type 2 dendritic cells (DC2) enhances the development of neonatal NKT cells into IL-4+IFN-γ− NKT2 cells, whereas addition of type 1 dendritic cells (DC1) induces polarization towards IL-4−IFN-γ+ NKT1 cells. Adult NKT cells display limited plasticity for polarization induced by DC1 or DC2. Thus, newly generated NKT cells may possess the potent ability to develop into IL-4+IFN-γ− NKT2 cells in response to appropriate stimuli and may thereafter acquire the tendency to produce both IL-4 and IFN-γ.
Nilpotent ideals in a class of Banach algebras
Authors: Zhang Yong
Published: July 2002

We introduce the concepts of approximately complemented subspaces of normed spaces and approximately biprojective algebras. We prove that any approximately biprojective Banach algebra with left and right approximate identities does not have a nontrivial nilpotent ideal whose closure is approximately complemented.
The integer Chebyshev problem
Authors: Borwein Peter , Erdélyi Tamás
Published: July 2002

We are concerned with the problem of minimizing the supremum norm on an interval of a nonzero polynomial of degree at mostnnwith integer coefficients. This is an old and hard problem that cannot be exactly solved in any nontrivial cases. We examine the case of the interval[0,1][0,1]in most detail. Here we improve the known bounds a small but interesting amount. This allows us to garner further information about the structure of such minimal polynomials and their factors. This is primarily a (substantial) computational exercise. We also examine some of the structure of such minimal “integer Chebyshev” polynomials, showing for example that on small intevals[0,δ][0, \delta ]and for small degreesdd,xdx^{d}achieves the minimal norm. There is a natural conjecture, due to the Chudnovskys and others, as to what the “integer transfinite diameter” of[0,1][0,1]should be. We show that this conjecture is false. The problem is then related to a trace problem for totally positive algebraic integers due to Schur and Siegel. Several open problems are raised.
On searching for solutions of the Diophantine equation 𝑥³+𝑦³+𝑧³=𝑛
Authors: Koyama Kenji , Tsuruoka Yukio , Sekigawa Hiroshi
Published: July 2002

We propose a new search algorithm to solve the equation

x
3

+

y
3

+

z
3

=
n

x^3+y^3+z^3=n

for a fixed value of

n
>
0

n>0

. By parametrizing

|

x

|

=

|x|=

min

(

|

x

|

,

|

y

|

,

|

z

|

)

(|x|, |y|, |z|)

, this algorithm obtains

|

y

|

|y|

and

|

z

|

|z|

(if they exist) by solving a quadratic equation derived from divisors of

|

x

|

3

±
n

|x|^3 \pm n

. By using several efficient number-theoretic sieves, the new algorithm is much faster on average than previous straightforward algorithms. We performed a computer search for 51 values of

n
n

below 1000 (except

n
≡
±
4
(
mod
⁡
9
)

n\equiv \pm 4 (\operatorname {mod}9)

) for which no solution has previously been found. We found eight new integer solutions for

n
=
75
,
435
,
444
,
501
,
600
,
618
,
912
,

n=75, 435, 444, 501, 600, 618, 912,

and

969
969

in the range of

|

x

|

≤
2
⋅

10
7

|x| \le 2 \cdot 10^7

.
A general mixed covolume framework for constructing conservative schemes for elliptic problems
Authors: Chou So-Hsiang , Vassilevski Panayot
Published: July 2002

We present a general framework for the finite volume or covolume schemes developed for second order elliptic problems in mixed form, i.e., written as first order systems. We connect these schemes to standard mixed finite element methods via a one-to-one transfer operator between trial and test spaces. In the nonsymmetric case (convection-diffusion equation) we show one-half order convergence rate for the flux variable which is approximated either by the lowest order Raviart–Thomas space or by its image in the space of discontinuous piecewise constants. In the symmetric case (diffusion equation) a first order convergence rate is obtained for both the state variable (e.g., concentration) and its flux. Numerical experiments are included.
The Grothendieck duality theorem via Bousfield’s techniques and Brown representability
Authors: Neeman Amnon
Published: July 2002

Grothendieck proved that if

f
:
X
⟶
Y

f:X\longrightarrow Y

is a proper morphism of nice schemes, then

R

f
∗

Rf_*

has a right adjoint, which is given as tensor product with the relative canonical bundle. The original proof was by patching local data. Deligne proved the existence of the adjoint by a global argument, and Verdier showed that this global adjoint may be computed locally. In this article we show that the existence of the adjoint is an immediate consequence of Brown’s representability theorem. 1It follows almost as immediately, by “smashing” arguments, that the adjoint is given by tensor product with a dualising complex. Verdier’s base change theorem is an easy consequence.
Characterization of Signal That Directs C-Tail–anchored Proteins to Mammalian Mitochondrial Outer Membrane
Authors: Horie Chika , Suzuki Hiroyuki , Sakaguchi Masao , Mihara Katsuyoshi
Published: July 2002

We analyzed the signal that directs the outer membrane protein with the C-terminal transmembrane segment (TMS) to mammalian mitochondria by using yeast Tom5 as a model and green fluorescent protein as a reporter. Deletions or mutations were systematically introduced into the TMS or the flanking regions and their intracellular localization in COS-7 cells was examined using confocal microscopy and cell fractionation. 1) Three basic amino acid residues within the C-terminal five-residue segment (C-segment) contained the information required for mitochondrial-targeting. Reduction of the net positive charge in this segment decreased mitochondrial specificity, and the mutants were distributed throughout the intracellular membranes. 2) Elongation of the TMS interfered with the function of the C-segment and the mutants were delivered to the intracellular membranes. 3) Separation of the TMS and C-segment by linker insertion severely impaired mitochondrial targeting function, leading to mislocalization to the cytoplasm. 4) Mutations or small deletions in the region of the TMS flanking the C-segment also impaired the mitochondrial targeting. Therefore, the moderate length of the TMS, the positive charges in the C-segment, and the distance between or context of the TMS and C-segment are critical for the targeting signal. The structural characteristics of the signal thus defined were also confirmed with mammalian C-tail–anchored protein OMP25.
HEALTH INSURANCE COVERAGE AND ENTREPRENEURSHIP
Authors: Wellington Alison J.
Published: July 2002

This article estimates the importance of health insurance coverage on the probability of self‐employment. Using data from the 1993 Current Population Survey (CPS), the author focuses on the impact of having health insurance through one's spouse on the likelihood of self‐employment. The best estimates suggest that a guaranteed alternative source of health insurance would increase the probability of self‐employment between 2.3 and 4.4 percentage points for husbands and 1.2 and 4.6 percentage points for wives. The author's more conservative estimates suggest that universal coverage could increase the percentage of self‐employed in the workforce by 2 to 3.5 percentage points.
Activation of the Drosophila NF‐κB factor Relish by rapid endoproteolytic cleavage
Authors: Stöven Svenja , Ando Istvan , Kadalayil Latha , Engström Ylva , Hultmark Dan
Published: July 2002

The Rel/NF‐κB transcription factor Relish plays a key role in the humoral immune response in Drosophila. We now find that activation of this innate immune response is preceded by rapid proteolytic cleavage of Relish into two parts. An N‐terminal fragment, containing the DNA‐binding Rel homology domain, translocates to the nucleus where it binds to the promoter of the Cecropin A1 gene and probably to the promoters of other antimicrobial peptide genes. The C‐terminal IκB‐like fragment remains in the cytoplasm. This endoproteolytic cleavage does not involve the proteasome, requires the DREDD caspase, and is different from previously described mechanisms for Rel factor activation.
Investigating the biology of consciousness
Authors:   The American Association for Research into Nervous and Mental Diseases, Damasio A. R.
Published: July 2002

The fact that consciousness is a private, first–person phenomenon makes it more difficult to study than other cognitive phenomena that, although being equally private, also have characteristic behavioural signatures. Nonetheless, by combining cognitive and neurobiological methods, it is possible to approach consciousness, to describe its cognitive nature, its behavioural correlates, its possible evolutionary origin and functional role; last but not least, it is possible to investigate its neuroanatomical and neurophysiological underpinnings. In this brief essay I distinguish between two kinds of consciousness: core consciousness and extended consciousness. Core consciousness corresponds to the transient process that is incessantly generated relative to any object with which an organism interacts, and during which a transient core self and transient sense of knowing are automatically generated. Core consciousness requires neither language nor working memory, and needs only a brief short–term memory. Extended consciousness is a more complex process. It depends on the gradual build–up of an autobiographical self, a set of conceptual memories pertaining to both past and anticipated experiences of an individual, and it requires conventional memory. Extended consciousness is enhanced by language.
Phylogenetic reconstruction of parental–care systems in the ancestors of birds
Authors: Tullberg B. S. , Ah–King M. , Temrin H.
Published: July 2002

Due to the controversy surrounding incipient avian parental care, ancestral parental care systems were reconstructed in a phylogeny including major extant amniote lineages. Using two different resolutions for the basal avian branches, transitions between the states no care, female care, biparental care and male care were inferred for the most basal branches of the tree. Uniparental female care was inferred for the lineage to birds and crocodiles. Using a phylogeny where ratites and tinamous branch off early and an ordered character–state assumption, a transition to biparental care was inferred for the ancestor of birds. This ancestor could be any organism along the lineage leading from the crocodile–bird split up to modern birds, not necessarily the original bird. We discuss the support for alternative avian phylogenies and the homology in parental care between crocodiles and birds. We suggest that the phylogenetic pattern should be used as a starting point for a more detailed analysis of parental care systems in birds and their relatives.
Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord
Authors: Muroyama Yuko , Fujihara Motoyuki , Ikeya Makoto , Kondoh Hisato , Takada Shinji
Published: July 2002

In the developing spinal cord, signals from the roof plate are required for the development of three classes of dorsal interneuron: D1, D2, and D3, listed from dorsal to ventral. Here, we demonstrate that absence of Wnt1 and Wnt3a, normally expressed in the roof plate, leads to diminished development of D1 and D2 neurons and a compensatory increase in D3 neuron populations. This occurs without significantly altered expression of BMP and related genes in the roof plate. Moreover, Wnt3a protein induces expression of D1 and D2 markers in the isolated medial region of the chick neural plate, and Noggin does not interfere with this induction. Thus, Wnt signaling plays a critical role in the specification of cell types for dorsal interneurons.
A spiral phantom for IMRT and tomotherapy treatment delivery verification
Authors: Paliwal Bhudatt , Tomé Wolfgang , Richardson Susan , Mackie T. Rockwell
Published: July 2002

A solid water/cylindrical phantom is machined to create a spiral cavity for placing radiographic or radiochromatic film in a spiral configuration. This spiral phantom is used to sample, predict, and measure data in three‐dimension subspace. The predicted data are obtained by projecting the patient plan data on the spiral phantom in the treatment planning software. The measured data are obtained by irradiating the spiral phantom (with film in the spiral cavity) as per the treatment plan. The predicted and measured data are converted to a two‐dimensional matrix and plotted as a spiralogram. Comparison of these predicted and measured spiralograms provides a quantitative comparison and thus validation of treatment delivered as planned. The spiral phantom is a simple, cost‐effective approach to sample 3D data from complexly shaped, intensity modulated or compensated multiple beams. A software script is being written to automate the entire process of projection, data sampling, and comparison. Design aspects and some examples of dose verification are presented. The usefulness of the spiral phantom for intensity modulated radiation therapy and dynamic field shaping are discussed.
Technical note: Acquisition of CT models for radiotherapy applications with reduced tube heating
Authors: Balter James M. , Lam Kwok L.
Published: July 2002

The potential for changing computed tomography (CT) protocols to provide data sets that generate high quality digitally reconstructed radiographs (DRRs) from scans with very low tube currents is demonstrated. DRRs were generated from CT data acquired with slice thickness of 1, 3, and 5 mm, using high current to reduce noise in axial images. These DRRs were compared to one generated from a CT scan acquired using 1 mm aperture and very low (10 mA) current. The DRR generated via this technique is comparable to that generated with high current and 1 mm aperture, and higher resolution than from the 3 and 5 mm CT scans.
Analytical scatter kernels for portal imaging at 6 MV
Authors: Spies L. , Bortfeld T.
Published: July 2002

X‐ray photon scatter kernels for 6 MV electronic portal imaging are investigated using an analytical and a semi‐analytical model. The models are tested on homogeneous phantoms for a range of uniform circular fields and scatterer‐to‐detector air gaps relevant for clinical use. It is found that a fully analytical model based on an exact treatment of photons undergoing a single Compton scatter event and an approximate treatment of second and higher order scatter events, assuming a multiple‐scatter source at the center of the scatter volume, is accurate within 1% (i.e., the residual scatter signal is less than 1% of the primary signal) for field sizes up to 100 and air gaps over 30 cm, but shows significant discrepancies for larger field sizes. Monte Carlo results are presented showing that the effective multiple‐scatter source is located toward the exit surface of the scatterer, rather than at its center. A second model is therefore investigated where second and higher‐order scattering is instead modeled by fitting an analytical function describing a nonstationary isotropic point‐scatter source to Monte Carlo generated data. This second model is shown to be accurate to within 1% for air gaps down to 20 cm, for field sizes up to 900 and phantom thicknesses up to 50 cm.
Investigation of the slice sensitivity profile for step‐and‐shoot mode multi‐slice computed tomography
Authors: Hsieh Jiang
Published: July 2002

Multislice computed tomography (MCT) is one of the recent technology advancements in CT. Compared to single slice CT, MCT significantly improves examination time, x‐ray tube efficiency, and contrast material utilization. Although the scan mode of MCT is predominately helical, step‐and‐shoot (axial) scans continue to be an important part of routine clinical protocols. In this paper, we present a detailed investigation on the slice sensitivity profile (SSP) of MCT in the step‐and‐shoot mode. Our investigation shows that, unlike single slice CT, the SSP for MCT exhibits multiple peaks and valleys resulting from intercell gaps between detector rows. To fully understand the characteristics of the SSP, we developed an analytical model to predict the behavior of MCT. We propose a simple experimental technique that can quickly and accurately measure SSP. The impact of the SSP on image artifacts and low contrast detectability is also investigated.
A theoretical derivation of the nomograms for permanent prostate brachytherapy
Authors: Wang Xiao‐Hong , Potters Louis
Published: July 2002

This study calculates the required minimum radioactivity to deliver a prescribed dose of radiation to a target using radioisotopes in permanent prostate brachytherapy. Assuming the radioactivity to be in a continuous form, an integral equation — Fredholm equation of the first kind, can be formulated with the radioactivity density used as the variable. The density distribution to produce a uniform volume dose rate is determined using a quadrature method and the radial profile behaves smoothly from the zero radius, and peaks sharply approaching the volume boundary. The density for Pd‐103 is about 1.5 times that of I‐125 due to its higher spatial attenuation. A nomogram is the relationship between the total activity per unit dose and the dimension of the volume Expressing the nomogram as then [(0.0098, 2.09) I‐125] and [(0.031, 2.25) Pd‐103]. Compared with the Memorial nomogram, (c,n)=[(0.011,2.2) I‐125] and [(0.036,2.56) Pd‐103], or that quoted by AAPM TG64, (c,n)=[(0.014,2.05) I‐125] and [(0.056,2.22) Pd‐103], our calculation determined an average 33% and 35% decrease for I‐125, and 89% and 77% decrease for Pd‐103, respectively. Two reasons for the extra total activity found in the Memorial and AAPM nomograms are: (a) An imperfect clinical situation limited by the restraints of implant techniques (e.g., use of templates) associated with the presence of adjacent normal organs, and (b) source discretization into seeds. When radioactivity is clumped as discrete seeds, higher activity is needed because of “wastage” in two aspects: (a) Dose cold‐spots at intersource spaces, (b) hot‐spots around the sources. Thus in theory, use of lower activity seeds will require less total activity to deliver a prescribed dose. Based on our study, Pd‐103 delivers a higher therapeutic ratio and a lower integral dose to the patient compared to I‐125.
A study of the use of flat‐panel imagers for radiotherapy verification (in English)
Authors: Groh Burkhard
Published: July 2002

This thesis investigates the feasibility of the application of flat‐panel imagers (FPIs) based on amorphous silicon to radiotherapy verification. Intensity modulated radiotherapy imposes new demands on verification procedures. A contrast resolution of 1% may be required from portal imaging systems to resolve the target structure and the organs at risk (OAR). Furthermore a spatial resolution of 1 mm is desired. The imaging characteristics, spatial resolution, efficiency, and noise characteristics of the FPI for megavoltage imaging were investigated regarding these demands. Possible improvements from scatter rejection by a modified detector design were investigated by simulating the spectral response of the converter plates of these detectors to photons of different energies and the response to scattered photons. Since low contrast objects like the target structure and the OAR can be detected in radiographic transmission images only for some rare cases, tomographical imaging was tested for position verification. This was also done using an FPI and the megavoltage (MV) source of the treatment accelerator. A different approach to position verification is the integration of kilovoltage (kV) computed tomography (CT) into a clinical linear accelerator. Although this approach has higher demands on the hardware side, it will deliver higher contrast images at a lower dose. A comparison of MVCT and kVCT and an outlook to new possibilities using integrated CT therefore completes this thesis.
Interleaf leakage for 5 and 10 mm dynamic multileaf collimation systems incorporating patient motion
Authors: Klein Eric E. , Low Daniel A.
Published: July 2002

Use of dynamic multileaf collimation (DMLC) for intensity modulated radiation therapy (IMRT) is accelerating. Delivery systems have the ailment of interleaf leakage (IL). This is compounded by the inefficiency of IMRT delivery, estimated to be a factor of 5 for DMLC. With IL on the order of 4%, it is possible to deliver as much as 20% of the prescribed dose to nonprescribed regions. However, IL is characterized by narrow Gaussian peaks of ∼0.5–1.0 mm full‐width‐half‐maximum (FWHM). We performed a leakage study for 5 and 10 mm leaf systems, accounting for intratreatment and intertreatment motions. In solid phantoms, film was placed perpendicular to beams. DMLC patterns delivered step‐wedged distributions. The same field was duplicated using a collimating jaw in a segmented fashion to obtain baseline data of primary and scatter contributions. Longitudinal shifts up to 4 mm and angulations up to 4 degrees were introduced during beam delivery by running multiple patterns, to arrive at a composite delivery. The intent of these rigid body motion experiments was to replicate patient motion. Clinical IMRT fields using segmented MLC were also tested. Films were scanned and converted to dose. A microionization chamber confirmed film data at discrete points. In all cases shifts diminished IL peak values. In the step‐wedge case, the net 18 MV IL peaks diminished from 3.6% to 3.2% for the 10 mm system. The 5 mm system IL values decreased from 4.0% to 3.2% with a 2 mm shift but increased to 4.0% with 4 mm shifts. The clinical field data followed the same pattern with a washing out of peak values, but the overall transmission to shielded regions slightly increased. Therefore nonprescribed regions are influenced by an effective transmission value rather than discrete peak IL values. The 5 mm leaf system does not introduce increased IL and is an appropriate system for IMRT.