bluuebunny/crossref_metadata_2025 huggingface dataset:
Live Salmonella Recruits N-Ethylmaleimide–Sensitive Fusion Protein on Phagosomal Membrane and Promotes Fusion with Early Endosome
Authors: Mukherjee Konark , Siddiqi Shadab A. , Hashim Shehla , Raje Manoj , Basu Sandip K. , Mukhopadhyay Amitabha
Published: July 2002

To understand intracellular trafficking modulations by live Salmonella, we investigated the characteristics of in vitro fusion between endosomes and phagosomes containing live (LSP) or dead Salmonella (DSP). We observed that fusion of both DSP and LSP were time, temperature and cytosol dependent. GTPγS and treatment of the phagosomes with Rab-GDI inhibited fusion, indicating involvement of Rab-GTPases. LSP were rich in rab5, α-SNAP, and NSF, while DSP mainly contained rab7. Fusion of endosomes with DSP was inhibited by ATP depletion, N-ethylmaleimide (NEM) treatment, and in NEM-sensitive factor (NSF)–depleted cytosol. In contrast, fusion of endosomes with LSP was not inhibited by ATP depletion or NEM treatment, and occurred in NSF-depleted cytosol. However, ATPγS inhibited both fusion events. Fusion of NEM-treated LSP with endosomes was abrogated in NSF- depleted cytosol and was restored by adding purified NSF, whereas no fusion occurred with NEM-treated DSP, indicating that NSF recruitment is dependent on continuous signals from live Salmonella. Binding of NSF with LSP required prior presence of rab5 on the phagosome. We have also shown that rab5 specifically binds with Sop E, a protein from Salmonella. Our results indicate that live Salmonella help binding of rab5 on the phagosomes, possibly activate the SNARE which leads to further recruitment of α-SNAP for subsequent binding with NSF to promote fusion of the LSP with early endosomes and inhibition of their transport to lysosomes.
Peripheral Expression of Jak3 Is Required to Maintain T Lymphocyte Function
Authors: Thomis Daniel C. , Berg Leslie J.
Published: July 2002

The Jak family tyrosine kinase, Jak3, is involved in signaling through cytokine receptors that utilize the common γ chain (γc), such as those for IL-2, IL-4, IL-7, IL-9, and IL-15. Recent studies of Jak3-deficient mice and humans have demonstrated that Jak3 plays a critical role in B and T lymphocyte maturation and function. The T lymphocyte defects in Jak3-deficient mice include a small thymus, a decrease in peripheral CD8+ cells, an increase in the surface expression of activation markers, and a severe reduction in proliferative and cytokine secretion responses to mitogenic stimuli. To determine whether the peripheral T lymphocyte defects result from aberrant maturation in the thymus or from the absence of Jak3 protein in peripheral T cells, we generated reconstituted mice that express normal levels of Jak3 protein in the thymus but lose Jak3 expression in peripheral T cells. Jak3 expression in the thymus restores normal T cell development, including CD8+, γδ, and natural killer cells. However, the loss of Jak3 protein in peripheral T cells leads to the Jak3−/− phenotype, demonstrating that Jak3 is constitutively required to maintain T cell function.
rho, a Small GTP-Binding Protein, Is Essential for Shigella Invasion of Epithelial Cells
Authors: Watarai Masahisa , Kamata Yoichi , Kozaki Shunji , Sasakawa Chihiro
Published: July 2002

Shigella, the causative agents of bacillary dysentery, are capable of invading mammalian cells that are not normally phagocytic. Uptake of bacteria by the mammalian cells is directed by bacterial factors named IpaB, IpaC, and IpaD invasins, in which Ipa invasins secreted into the bacterial environment can interact with α5β1 integrin. We report here that Shigella invasion of epithelial cells requires rho activity, a ras-related GTP-binding protein. The invasive capacity of Shigella flexneri for Chinese hamster ovary (CHO) cells and other epithelial cells were greatly reduced when treated with Clostridium botulinum exoenzyme C3 transferase. Conversely, uptake of bacteria by CHO cells was promoted upon microinjection of an activated rho variant, Val14RhoA. Attachment of S. flexneri to CHO cells can elicit tyrosine phosphorylation of pp125FAK and paxillin, localized accumulation of F-actin, vinculin, and talin, and activation of protein kinase C, which were all blocked by the treatment with C3 transferase. Our results indicate that cellular signal transduction regulated by rho is essential for Shigella invasion of epithelial cells.
Postnatally Induced Inactivation of gp130 in Mice Results in Neurological, Cardiac, Hematopoietic, Immunological, Hepatic, and Pulmonary Defects
Authors: Betz Ulrich A.K. , Bloch Wilhelm , van den Broek Maries , Yoshida Kanji , Taga Tetsuya , Kishimoto Tadamitsu , Addicks Klaus , Rajewsky Klaus , Müller Werner
Published: July 2002

The pleiotrophic but overlapping functions of the cytokine family that includes interleukin (IL)-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1 are mediated by the cytokine receptor subunit gp130 as the common signal transducer. Although mice lacking individual members of this family display only mild phenotypes, animals lacking gp130 are not viable. To assess the collective role of this cytokine family, we inducibly inactivated gp130 via Cre-loxP–mediated recombination in vivo. Such conditional mutant mice exhibited neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects, demonstrating the widespread importance of gp130-dependent cytokines.
Essential and Partially Overlapping Role of CD3γ and CD3δ for Development of αβ and γδ T Lymphocytes
Authors: Wang Baoping , Wang Ninghai , Salio Mariolina , Sharpe Arlene , Allen Deborah , She Jian , Terhorst Cox
Published: July 2002

CD3γ and CD3δ are two highly related components of the T cell receptor (TCR)–CD3 complex which is essential for the assembly and signal transduction of the T cell receptor on mature T cells. In gene knockout mice deficient in either CD3δ or CD3γ, early thymic development mediated by pre-TCR was either undisturbed or severely blocked, respectively, and small numbers of TCR-αβ+ T cells were detected in the periphery of both mice. γδ T cell development was either normal in CD3δ−/− mice or partially blocked in CD3γ−/− mice. To examine the collective role of CD3γ and CD3δ in the assembly and function of pre-TCR and in the development of γδ T cells, we generated a mouse strain with a disruption in both CD3γ and CD3δ genes (CD3γδ−/−). In contrast to mice deficient in either CD3γ or CD3δ chains, early thymic development mediated by pre-TCR is completely blocked, and TCR-αβ+ or TCR-γδ+ T cells were absent in the CD3γδ−/− mice. Taken together, these studies demonstrated that CD3γ and CD3δ play an essential, yet partially overlapping, role in the development of both αβ and γδ T cell lineages.
CD8+ T Cells Mediate CD40-independent Maturation of Dendritic Cells In Vivo
Authors: Ruedl Christiane , Kopf Manfred , Bachmann Martin F.
Published: July 2002

Induction of cytotoxic T lymphocyte (CTL) responses against minor histocompatibility antigens is dependent upon the presence of T cell help and requires the interaction of CD40 on dendritic cells (DCs) with CD40 ligand on activated T helper cells (Th). This study demonstrates that CD40 is neither involved in Th-dependent nor Th-independent antiviral CTL responses. Moreover, the data show that DC maturation occurs in vivo after viral infection in the absence of CD40 and Th. This maturation did not require viral infection of  DCs but was mediated by peptide-specific CD8+ T cells. Surprisingly, naive CD8+ T cells were able to trigger DC maturation within 24 h after activation in vivo and in vitro. Moreover, peptide-activated CD8+ T cells were able to induce maturation in trans, as DCs that failed to present the relevant antigen in vivo also underwent maturation. Upon isolation, the in vivo–stimulated DCs were able to convert a classically Th-dependent CTL response (anti-HY) into a Th-independent response in vitro. Thus, antiviral CD8+ T cells are sufficient for the maturation of DCs in the absence of CD40.
Cd40 Ligand (Cd154) Triggers a Short-Term Cd4+ T Cell Activation Response That Results in Secretion of Immunomodulatory Cytokines and Apoptosis
Authors: Blair Patrick J. , Riley James L. , Harlan David M. , Abe Ryo , Tadaki Douglas K. , Hoffmann Steven C. , White Leonard , Francomano Tara , Perfetto Stephen J. , Kirk Allan D. , June Carl H.
Published: July 2002

Signals generated through CD28–B7 and CD40 ligand (CD40L)–CD40 interactions have been shown to be crucial for the induction of long-term allograft survivability. We have recently demonstrated that humanized anti-CD40L (hu5C8) prevents rejection of mismatched renal allografts in primates. To investigate potential mechanisms of CD40L–induced allograft acceptance, we coimmobilized hu5C8 with suboptimal amounts of anti-CD3 to stimulate CD4+ T cells. We now report that anti-CD3/CD40L costimulation results in CD28-independent activation and subsequent deletion of resting T cells. Coligation of CD3 and CD40L increased expression of CD69, CD25, and CD54 on CD4+ T cells. We also found that costimulation with anti-CD3/CD40L resulted in enhanced production of interleukin (IL)-10, interferon γ, and tumor necrosis factor α but not IL-2 or IL-6. Interestingly, after several days, anti-CD3/CD40L–mediated activation was followed by apoptosis in a significant population of cells. Consistent with that observation, anti-CD3/CD40L did not enhance the antiapoptotic proteins Bcl-2 and Bcl-xL. Further, the addition of CD28 at 24 h failed to rescue those cells induced to die after costimulation with anti-CD3/CD40L. Together, these data suggest that the graft-sparing effect of hu5C8 in vivo may result in part from early and direct effects on CD4+ T cells, including a vigorous induction of immunomodulatory cytokines and/or apoptosis of allograft-specific T cells.
Calcium-induced Transitions between the Spontaneous Miniature Outward and the Transient Outward Currents in Retinal Amacrine Cells
Authors: Mitra Pratip , Slaughter Malcolm M.
Published: July 2002

Spontaneous miniature outward currents (SMOCs) occur in a subset of retinal amacrine cells at membrane potentials between −60 and −40 mV. At more depolarized potentials, a transient outward current (Ito) appears and SMOCs disappear. Both SMOCs and the Ito are K+ currents carried by BK channels. They both arise from Ca2+ influx through high voltage–activated (HVA) Ca2+ channels, which stimulates release of internal Ca2+ from caffeine- and ryanodine-sensitive stores. An increase in Ca2+ influx resulted in an increase in SMOC frequency, but also led to a decline in SMOC mean amplitude. This reduction showed a temporal dependence: the effect being greater in the latter part of a voltage step. Thus, Ca2+ influx, although required to generate SMOCs, also produced a negative modulation of their amplitudes. Increasing Ca2+ influx also led to a decline in the first latency to SMOC occurrence. A combination of these effects resulted in the disappearance of SMOCs, along with the concomitant appearance of the Ito at high levels of Ca2+ influx. Therefore, low levels of Ca2+ influx, arising from low levels of activation of the HVA Ca2+ channels, produce randomly occurring SMOCs within the range of −60 to −40 mV. Further depolarization leads to greater activation of the HVA Ca2+ channels, larger Ca2+ influx, and the disappearance of discontinuous SMOCs, along with the appearance of the Ito. Based on their characteristics, SMOCs in retinal neurons may function as synaptic noise suppressors at quiescent glutamatergic synapses.
Putting journals out to tender: guidelines for societies and other sponsors
Authors: Page Gillian
Published: July 2002

Many journals are sponsored by one body and published by another. These notes are intended to guide sponsors by outlining the stages, processes, and timetable involved in obtaining and comparing tenders. Sponsors are advised that detailed analysis and open communication are more likely to result in satisfactory long‐term publishing arrangements.
Just one more 'zine? Maintaining and improving the scholarly journal in the electronic present: a view from the humanities
Authors: Tomlins Christopher L.
Published: July 2002

Humanities journals have been laggards in exploration of opportunities that the online environment offers, and such attention as editors have given the matter has focused on distribution. This article describes how history journals in the USA are moving to establish a collective presence for scholarly history online. It suggests that editors should give equal attention to current opportunities to improve journals' operational efficiencies through full exploitation of desktop publishing in production and the reorganization of manuscript management (submissions, peer review, and author–editor interactions) as online processes. It concludes that cooperation in online distribution of journal scholarship could well lead on to cooperative use of online production and management tools.
Book reviews
Authors: Mabe Michael
Published: July 2002

Communicating Research by A. J. Meadows Academic Press, 1998. Pp. 256. Hardback, £39.95. ISBN 0.12487415‐0
The evaluation of peer‐review quality
Authors: van Rooyen Susan
Published: July 2002

This paper discusses the role of peer review in the decision‐making processes of scientific journals. It outlines the objectives of peer review and some of the problems. It then goes on to describe research into the quality of peer review, in particular the BMJ's programme of research to date, the results obtained, and consequent changes in practice. It also looks briefly at future possibilities for research into the peer‐review process.
Never mind the textbook — here's the chapters
Authors: Taylor David
Published: July 2002

This paper first looks at the current supply model for the paper textbook in the UK market and its peculiar vulnerability not only to the new internet‐based entrants, but also to the changing nature of the very product itself. It then looks at the emerging supply model for the electronic version of the textbook – the e‐book – and why that mode of delivery is especially appropriate to the UK student market. It concludes by describing what the future supply model might look like for this material: the delivery of the electronic chapter.
From herbals to Hotbot: the development of journal indexing
Authors: Bell Hazel K.
Published: July 2002

The development of journal indexing since the early alphabetical tables to scientific works, culminating in current sophisticated cumulations, is traced. Standards for preparing indexes which have gradually evolved to cope with the increase in volume and complexity of the literature are described.
Virtual and non‐virtual realities: the changing roles of libraries and librarians
Authors: Klugkist Alex C.
Published: July 2002

What is the future for libraries and their librarians? In trying to give an answer to this pressing question we do not deal with utopian libraries of the next century, but with the library and the librarian of the next decade. The emphasis is on libraries within educational and research institutions, especially university libraries. We examine the changes confronting the library of the future and identify four key aspects of the library of the future. It will be (i) a gateway to information, whatever format this information comes in and wherever it is located; (ii) an expertise centre; (iii) a physical entity, not only in the sense of being a social meeting place and place of scholarly interaction, but also as a place where students and other users are provided with modern study facilities and adequate user support; and (iv) a collection centre of printed material. Such libraries can only take on an appropriate shape and will only survive if the institutions that librarians serve in meet the four criteria outlined above. We look at the demands that will be made on professional library knowledge and skills and the new job responsibilities and job attitudes required.
The new Directive on copyright and related rights
Authors: Oppenheim Charles
Published: July 2002

In February 2001, the Directive on ‘the harmonisation of certain aspects of copyright and related rights in the information society’ was approved by the European Parliament and therefore takes effect. This article highlights the changes introduced by the European Parliament in the Directive and comments on the implications of the change.
There is no such thing as a product
Authors: Dryburgh Alastair
Published: July 2002

How do you manage, or even think seriously about, profitability in an online business? Traditionally you tracked profitability by product, but in the online world this may simply not be possible. The article looks at why this is so, and how the same factors which create the problem also create new opportunities.
A year without print at Princeton, and what we plan next
Authors: Goodman David
Published: July 2002

Princeton began to receive some major titles as electronic only, starting with the 2000 subscription year. We are expanding this in appropriate cases where we have confidence in the publisher, and the financial advantage is significant. There have been no complaints, and also almost no comments. Apparently users now look for current journal articles online, using the paper versions only if online is not available. We plan further developments to facilitate user convenience.
Rights acquisition in the electronic era
Authors: McCracken Richard
Published: July 2002

Considers how the licensing‐in of rights in the electronic era may evolve and develop as a working tool
Calculation of Manin’s invariant for Del Pezzo surfaces
Authors: Urabe Tohsuke
Published: July 2002

For

r
=
7

r=7

and 8 we consider an action of the Weyl group of type

E

r

E_{\,r}

on a unimodular lattice of rank

r
+
1

r+1

. We give the tables of the first cohomology groups for all cyclic subgroups of the Weyl group with respect to this action. These are important in the arithmetic theory of Del Pezzo surfaces.
Fast solvers of integral and pseudodifferential equations on closed curves
Authors: Saranen J. , Vainikko G.
Published: July 2002

On the basis of a fully discrete trigonometric Galerkin method and two grid iterations we propose solvers for integral and pseudodifferential equations on closed curves which solve the problem with an optimal convergence order
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u
N

−
u

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λ

≤

c

λ
,
μ

N

λ
−
μ

‖
u

‖
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\|u_N-u\|_\lambda \leq c_{\lambda ,\mu }N^{\lambda -\mu }\|u\|_\mu

,

λ
≤
μ

\lambda \leq \mu

(Sobolev norms of periodic functions) in

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(
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arithmetical operations.
Non-axial self-similar hole filling for the porous medium equation
Authors: Angenent S. , Aronson D.
Published: July 2002

We construct non-axially symmetric self-similar solutions to the porous medium equation by showing that the family of radial self-similar solutions found by Aronson and Graveleau (1993) undergoes a sequence of symmetry breaking bifurcations as the parameter

m
m

decreases from

m
=
∞

m=\infty

to

m
=
1

m=1

.
On Hitchin’s connection
Authors: van Geemen Bert , de Jong Aise Johan
Published: July 2002

The aim of the paper is to give an explicit expression for Hitchin’s connection in the case of stable rank 2 bundles on genus 2 curves. Some general theory (in the algebraic geometric setting) concerning heat operators is developed. In particular the notion of compatibility of a heat operator with respect to a closed subvariety is introduced. This is used to compare the heat operator in the nonabelian rank 2 genus 2 case to the abelian heat operator (on theta functions) for abelian surfaces. This relation allows one to perform the computation; the resulting differential equations are similar to the Knizhnik-Zalmolodshikov equations.
Asymptotic results for super-Brownian motions and semilinear differential equations
Authors: Lee Tzong-Yow
Published: July 2002

Limit laws for three-dimensional super-Brownian motion are derived, conditioned on survival up to a large time. A large deviation principle is proved for the joint behavior of occupation times and their difference. These are done via analyzing the generating function and exploiting a connection between probability and differential/integral equations.
Stable nilpotent orbital integrals on real reductive Lie algebras
Authors: Kottwitz Robert
Published: July 2002

This paper proves a stable analog of Rossmann’s formula for the number of

G
(

R

)

G(\mathbb {R})

-orbits in

g

∩

O

\mathfrak g \cap \mathbf {O}

, where

O

\mathbf {O}

is a nilpotent orbit in

g

C

\mathfrak {g}_{\mathbf {C}}

.
Application of constraint programming techniques for structure prediction of lattice proteins with extended alphabets.
Authors: Backofen R , Will S , Bornberg-Bauer E
Published: July 2002

MOTIVATION: Predicting the ground state of biopolymers is a notoriously hard problem in biocomputing. Model systems, such as lattice proteins, are simple tools and valuable to test and improve new methods. Best known are models with sequences composed from a binary (hydrophobic and polar) alphabet. The major drawback is the degeneracy, i.e. the number of different ground state conformations. RESULTS: We show how recently developed constraint programming techniques can be used to solve the structure prediction problem efficiently for a higher order alphabet. To our knowledge it is the first report of an exact and computationally feasible solution to model proteins of length up to 36 and without resorting to maximally compact states. We further show that degeneracy is reduced by more than one order of magnitude and that ground state conformations are not necessarily compact. Therefore, more realistic protein simulations become feasible with our model.
Investigating extended regulatory regions of genomic DNA sequences.
Authors: Babenko V N , Kosarev P S , Vishnevsky O V , Levitsky V G , Basin V V , Frolov A S
Published: July 2002

MOTIVATION: Despite the growing volume of data on primary nucleotide sequences, the regulatory regions remain a major puzzle with regard to their function. Numerous recognising programs considering a diversity of properties of regulatory regions have been developed. The system proposed here allows the specific contextual, conformational and physico-chemical properties to be revealed based on analysis of extended DNA regions. RESULTS: The Internet-accessible computer system RegScan, designed to analyse the extended regulatory regions of eukaryotic genes, has been developed. The computer system comprises the following software: (i) programs for classification dividing a set of promoters into TATA-containing and TATA-less promoters and promoters with and without CpG islands; (ii) programs for constructing (a) nucleotide frequency profiles, (b) sequence complexity profiles and (c) profiles of conformational and physico-chemical properties; (iii) the program for constructing the sets of degenerate oligonucleotide motifs of a specified length; and (iv) the program searching for and visualising repeats in nucleotide sequences. The system has allowed us to demonstrate the following characteristic patterns of vertebrate promoter regions: the TATA box region is flanked by regions with an increased G+C content and increased bending stiffness, the TATA box content is asymmetric and promoter regions are saturated with both direct and inverted repeats. AVAILABILITY: The computer system RegScan is available via the Internet at http://www.mgs.bionet.nsc. ru/Systems/RegScan, http://www.cbil.upenn.edu/mgs/systems/r egscan/.
Functional and structural genomics using PEDANT
Authors: Frishman Dmitrij , Albermann Kaj , Hani Jean , Heumann Klaus , Metanomski Agnes , Zollner Alfred , Mewes Hans-Werner
Published: July 2002

Motivation: Enormous demand for fast and accurate analysis of biological sequences is fuelled by the pace of genome analysis efforts. There is also an acute need in reliable up-to-date genomic databases integrating both functional and structural information. Here we describe the current status of the PEDANT software system for high-throughput analysis of large biological sequence sets and the genome analysis server associated with it.

Results: The principal features of PEDANT are: (i) completely automatic processing of data using a wide range of bioinformatics methods, (ii) manual refinement of annotation, (iii) automatic and manual assignment of gene products to a number of functional and structural categories, (iv) extensive hyperlinked protein reports, and (v) advanced DNA and protein viewers. The system is easily extensible and allows to include custom methods, databases, and categories with minimal or no programming effort. PEDANT is actively used as a collaborative environment to support several on-going genome sequencing projects. The main purpose of the PEDANT genome database is to quickly disseminate well-organized information on completely sequenced and unfinished genomes. It currently includes 80 genomic sequences and in many cases serves as the only source of exhaustive information on a given genome. The database also acts as a vehicle for a number of research projects in bioinformatics. Using SQL queries, it is possible to correlate a large variety of pre-computed properties of gene products encoded in complete genomes with each other and compare them with data sets of special scientific interest. In particular, the availability of structural predictions for over 300 000 genomic proteins makes PEDANT the most extensive structural genomics resource available on the web.

Availability: The PEDANT genome analysis server is available at http://pedant.mips.biochem.mpg.de.

Contact: Genome sequencing centres interested in inclusion of their sequences in the PEDANT database should contact Dmitrij Frishman (frishman@mips.biochem.mpg.de).

* To whom correspondence should be addressed.
Tip cell‐derived RTK signaling initiates cell movements in the Drosophila stomatogastric nervous system anlage
Authors: González‐Gaitán Marcos , Jäckle Herbert
Published: July 2002

The stomatogastric nervous system (SNS) of Drosophila is a simply organized neural circuitry that innervates the anterior enteric system. Unlike the central and the peripheral nervous systems, the SNS derives from a compact epithelial anlage in which three invagination centers, each giving rise to an invagination fold headed by a tip cell, are generated. Tip cell selection involves lateral inhibition, a process in which Wingless (Wg) activity adjusts the range of Notch signaling. Here we show that RTK signaling mediated by the Drosophila homolog of the epidermal growth factor receptor, DER, plays a key role in two consecutive steps during early SNS development. Like Wg, DER signaling participates in adjusting the range of Notch‐dependent lateral inhibition during tip cell selection. Subsequently, tip cells secrete the DER ligand Spitz and trigger local RTK signaling, which initiates morphogenetic movements resulting in the tip cell‐directed invaginations within the SNS anlage.
DNA conformation driven by AP‐1 triggers cell‐specific expression via a strong epithelial enhancer
Authors: Virolle Thierry , Djabari Zied , Ortonne Jean‐Paul , Aberdam Daniel
Published: July 2002

We report here the characterization of the regulatory region of the human LAMA3 gene, coding for the α3A chain of laminin‐5. A 202 bp fragment is sufficient to confer epithelial‐specific expression to a thymidine kinase promoter through the cooperative effect of three AP‐1 binding sites. Remarkably, removal of the sequences located between the AP‐1 sites does not modify the promoter activity in keratinocytes but allows strong expression in fibroblasts. Replacement of the deleted sequences by non‐homologous ones fully restores the restricted enhancement in keratinocytes. Functional analysis and mutagenesis experiments demonstrate that a minimal distance between the AP‐1 sites is required for the enhancer DNA fragment to adopt a particular conformation driven by the binding of Jun–Fos heterodimers. In non‐permissive cells, this conformation leads to the anchorage of non‐DNA‐binding fibroblastic cofactors to form an inhibitory ternary complex. Therefore, our results describe for the first time an unusual conformation‐dependent epithelial‐specific enhancer.
Efficient biallelic mutagenesis with Cre/loxP‐mediated inter‐chromosomal recombination
Authors: Koike Hiroko , Horie Kyoji , Fukuyama Hidehiro , Kondoh Gen , Nagata Shigekazu , Takeda Junji
Published: July 2002

The isolation of mutant cells with phenotypes caused by random mutagenesis has been hampered in mammalian cells because there are two alleles per gene and the disruption of both alleles is extremely rare. We describe a method for the efficient biallelic mutagenesis in embryonic stem cells. loxP sites were introduced near the centromeric regions of a pair of chromosome 1s. A mutant neo gene was inserted at the distal part of one of the loxP sites so that biallelic mutants would be selected by high‐dose G418. Expression of Cre induced the recombination between homologous chromosomes and led to an elevation in the number of biallelic mutants. This system will facilitate phenotype‐driven gene function study in the mammalian system.
Influence of respiration‐induced organ motion on dose distributions in treatments using enhanced dynamic wedges
Authors: Pemler P. , Besserer J. , Lombriser N. , Pescia R. , Schneider U.
Published: July 2002

The mean velocity of respiration‐induced organ motion in cranio‐caudal direction is of the same magnitude as the velocity of the moving jaw during a treatment with an enhanced dynamic wedge. Therefore, if organ motion is present during collimator movement, the resulting dose distribution in wedge direction may differ from that obtained for the static case, i.e., without organ motion. The position as a function of time of the moving jaw has been derived from a log‐file generated during each treatment. Parameters for the respiratory cycle and information about respiration‐induced motion for organs in the upper abdomen were taken from the literature. Both movements were superimposed and the resulting monitor unit distribution has been calculated in the intrinsic coordinate system of the organ. The deviations from the static case have been studied as a function of wedge angle, amplitude of organ motion, respiratory rate, asymmetry of the respiratory cycle, beam energy, and the dose rate. If an amplitude of 30 mm and a respiratory rate of 10 are assumed, the maximum deviation in monitor units is 2.5% for a 10° wedge, 7% for a 30° wedge, and 16% for a 60° wedge. Furthermore, a dose distribution for an organ undergoing respiration‐induced motion has been generated and we found dose deviations of the same magnitude as calculated with the monitor unit distribution.
Calculating dose and output factors for wedged photon radiotherapy fields using a convolution/superposition method
Authors: Liu H. Helen , Mackie T. Rock , McCullough Edwin C.
Published: July 2002

We have developed a convolution/superposition method to calculate dose distributions in photon treatment fields with beam modifiers such as physical wedges. The dose component due to wedge generated radiation was accounted for by using an extended phantom model, which integrated a wedge, an air gap, and a patient phantom as the calculation phantom. The inhomogeneities in the extended phantom and the effect of beam hardening by the wedge were both corrected for in the convolution dose calculation. The calculated dose was verified by Monte Carlo simulation of the same extended phantom. A new dual photon source model was also used in the convolution method to account for both primary photons from the target and extra‐focal photons from the primary collimator and flattening filter. Thus, realistic photon energy fluence distributions in the extended phantom were used for the dose calculation. The calculated dose distributions and the wedge factors agreed with the measured data within 2% for a variety of treatment fields including asymmetric fields. Our results showed that the wedge‐generated radiation could contribute a significant fraction of the total dose in patients. This dose component depends on a specific field configuration, thus wedge factor changes with photon energy, wedge angle, field size, depth, and patient phantom SSD. The variation of the wedge factor can be predicted accurately by our convolution approach with the extended phantom model, which allows for more accurate dose or monitor unit computation for photon fields with beam modifiers.
The CT's sample volume as an approximate, instrumental measure for density resolution in densitometry of the lung
Authors: Kemerink Gerrit J. , Kruize Han H. , Lamers Rob J. S.
Published: July 2002

Ultimately CT‐densitometry of the lung should give comparable results on all scanners. One prerequisite for this is the use of the same density resolution. Unfortunately, density resolution is impractical as a performance specifying parameter because it depends on the cellular material scanned. Therefore, another parameter that can be used for scanner and protocol characterization, and that does not depend on a special phantom, would be highly preferable. We investigated how well the CT's nominal sample volume , calculated from section thickness and in‐plane spatial resolution as specified by the CT manufacturer, can serve as a simple measure for density resolution. Six CT scanners were studied using foam and lung phantoms. On all scanners we observed for foam an approximately linear relation between density resolution and . Density resolution on different scanners varied to some extent. These differences can be interpreted as being caused by deviations of the true sample volume from the nominal value: the 95%‐confidence interval runs for instance for from 4.6 to 16.9 . Acceptability of this spread depends on the consequences for parameters of clinical interest, like percentiles and pixel indexes. To evaluate this we used data from a previous patient study on the dependence of histogram parameters on sample volume. With these data it is found that large interscanner differences in histogram parameters are possible for small values of , as used in thin‐section densitometry. For larger values of , as required for a more adequate density resolution, the differences are much smaller and probably acceptable when compared to other sources of variability in lung densitometry. In conclusion, for sections of at least 2 mm and smooth reconstruction filters, corresponding to , the CT's nominal sample volume might be used for interscanner and interprotocol comparison of density resolution.
Source placement error for permanent implant of the prostate
Authors: Roberson Peter L. , Narayana Vrinda , McShan Daniel L. , Winfield Raymond J. , McLaughlin P. William
Published: July 2002

The performance of ultrasound (US) and fluoroscopic‐guided permanent 125I source implant of the prostate using CT identification of the source positions has been evaluated. Marker seeds were implanted during the planning study to assist in the alignment of the US and CT prostate volumes for treatment planning and to guide the placement of needles. The relative positions of the needles and marker seeds were checked by fluoroscopy. A postimplant CT study was used to input the radioactive source positions and to register the sources relative to the preimplant CT and US prostate volumes and the planned source distribution. Source placement errors observed were categorized as: (1) source‐to‐source spacing differences; (2) needle placement error, both depth and position; and (3) seed splaying, particularly near the prostate periphery. Errors due to source splaying and spacing were in part attributed to prostate motion. Later refinements included fixed‐spaced string sources, for which placement errors were smaller than for unattached sources. However, source placement errors due to needle placement error and prostate motion remained unchanged.
Linear accelerator photon beam quality at off‐axis points
Authors: Yu M. K. , Sloboda R. S. , Murray B.
Published: July 2002

Transmitted intensity through water was measured in a narrow‐beam geometry for different energy x‐ray beams from commercial accelerators. In order to accurately obtain the attenuation coefficient of the incident beam using transmission data, a novel formula was developed based on consideration of beam hardening in phantom. The value of the attenuation coefficient obtained by fitting transmission data to this formula was found to be independent of the absorber thickness used in experiments, whereas the attenuation coefficient obtained from the traditional formula, I(x)=I0 exp(−μx), changed by up to 7% with absorber thickness for a given beam. The beam hardening coefficient obtained from our formula indicates that the attenuation coefficient in water changes by about 0.33% per cm near the surface for the high‐energy photon beams studied. Variations in beam quality with off‐axis distance were subsequently investigated using the new formula. Results show that the attenuation coefficient at the water surface increased by about 15% for 15 and 18 MV beams, and by 11%–13% for 6 MV beams, when the off‐axis distance at 100 cm from the source was changed from 0 to 18 cm. Consideration of the physics of bremsstrahlung production suggests that these variations should be mainly determined by the shape of the flattening filter, i.e., by the path length of rays traversing the filter in different directions. This expectation was confirmed by observing that the attenuation coefficient at the phantom surface can be related to the ray path of the beam in the flattening filter using the new transmission formula.
Effect of using an initial polyenergetic spectrum with the pencil‐beam redefinition algorithm for electron‐dose calculations in water
Authors: Boyd Robert A. , Hogstrom Kenneth R. , Rosen Isaac I.
Published: July 2002

This work compares the accuracy of dose distributions computed using an incident polyenergetic (PE) spectrum and a monoenergetic (ME) spectrum in the electron pencil‐beam redefinition algorithm (PBRA). It also compares the times required to compute PE and ME dose distributions. This has been accomplished by comparing PBRA calculated dose distributions with measured dose distributions in water from the National Cancer Institute electron collaborative working group (ECWG) data set. Comparisons are made at 9 and 20 MeV for the and fields at 100‐ and 110‐cm SSD. The incident PE spectrum is determined by a process that best matches the weighted sum of monoenergetic PBRA calculated central‐axis depth doses, each calculated with the energy correction factor, equal to unity, to the ECWG measured depth dose for the field at 100‐cm SSD. is determined by a least square fit to central‐axis depth dose for the PE PBRA. Results show that both the PE and ME PBRA accurately calculate central‐axis depth dose at 100‐cm SSD for the and field sizes and also at 110‐cm SSD for the field size. In the penumbral region, the PE PBRA calculation is significantly more accurate than the ME PBRA for all measurement conditions. Both the PE and ME PBRA exhibit significant dose errors (>4%) outside the penumbra at shallow depths for the and fields at 100‐cm SSD and inside the penumbra at shallow depths for the field size at 110‐cm SSD. These errors are attributed to the fact that the PBRA does not model collimator scatter in the incident beam. Calculation times for the PE PBRA are approximately 70%–140% greater than those for the ME PBRA. We conclude that the PE PBRA is significantly more accurate than the ME PBRA, and we believe that the increase in time for the PE PBRA will not significantly impact the clinical utility of the PBRA.
Experimental determination of the thermal neutron flux around two different types of high intensity sources
Authors: Schmidt R. , Maughan R. L. , Yudelev M. , Kota C. , Wanwilairat S.
Published: July 2002

The application of neutron emitting radioisotopes in brachytherapy facilitates the use of the higher biological effectiveness of neutrons compared to photons in treating some cancers. Different types of high intensity sources are in use for the treatment of different cancers. To improve the therapy of bulky tumors the dose can be augmented by the additional use of the boron capture reaction of thermal neutrons. This requires information about the thermal neutron dose component around the Cf source. In this work, a Mg/Ar‐ionization chamber internally coated with was used to measure the thermal neutrons. These measurements were performed on two different sources, one in use in the Gershenson Radiation Oncology Center at Harper Hospital in Detroit, MI, and one at the University Hospital of Chiang Mai in Chiang Mai, Thailand. The results of these measurements are compared and indicate that the differences in the construction of the sources influence the thermal dose component.
Multileaf collimator interleaf transmission
Authors: Balog J. P. , Mackie T. R. , Wenman D. L. , Glass M. , Fang G. , Pearson D.
Published: July 2002

Multileaf collimators (MLCs) have advanced past their original design purpose as a replacement for field shaping cerrobend blocks. Typically, MLCs incorporate an interlocking tongue‐and‐groove design between adjacent leaves to minimize leakage between leaves. They are beginning to be used to provide intensity modulation for conformal three‐dimensional radiation therapy. It is possible that a critical target volume may receive an underdose due to the region of overlap if adjacent leaves are allowed to alternate between the open and closed positions, as they might if intensity modulation is employed. This work demonstrates the magnitude of that effect for a commercially available one‐dimensional temporally modulated MLC. The magnitude of the transmission between leaves as a function of leaf separation was also studied, as well as the transmission as a function of leaf rotation away from the source. The results of this work were used for the design of a tomotherapy MLC. The radiation leakage considerations for a tomotherapy MLC are discussed.
Measured overall perturbation factors at depths greater than for ionization chambers in electron beams
Authors: Reft Chester S. , Kuchnir Franca T.
Published: July 2002

In electron beam dosimetry the perturbation effect in the medium by the ionization chamber cavity is accounted for by introducing a replacement correction factor, Another perturbation correction factor, denoted as is due to the materials of the walls of the parallel‐plate chamber differing from the phantom material. Because of the difficulties in separating these two components, we measure the overall perturbation factor, A distinct advantage of parallel‐plate ionization chambers over cylindrical chambers is that has been shown to be close to unity at the standard calibration depth, However, for many dosimetry applications it is necessary to know the overall perturbation factor at depths greater than We measured the overall perturbation factor at depths greater than (approximating the 95%, 90% and 50% depth dose) for a Farmer‐type cylindrical ionization chamber and three parallel‐plate ionization chambers. We assumed that for the NACP chamber is unity at these measurement depths. The depth dependence for the other chambers was then measured relative to the NACP chamber. The mean energy at depth, and percentage depth dose gradient ranges studied were 1.9–18.5 MeV and 0 to 4.5%/mm, respectively. For the other two parallel‐plate chambers, we find to be unity at depths where the percent depth dose is greater than 90%, but it deviates from unity at deeper depths, where the dose gradients exceed about 2.5%/mm. For the cylindrical chamber, values at depths greater than were found to be in good agreement with those in TG 21, where the energy at depth, is used to evaluate
New low‐contrast resolution phantoms for computed tomography
Authors: Suess Christoph , Kalender Willi A. , Coman Johannes M.
Published: July 2002

Computed tomography (CT) has been established as a major imaging modality in diagnostic radiology. Accordingly, acceptance testing and quality control of CT scanners is of great importance. While most procedures and phantoms for testing are widely accepted, there is still discussion and uncertainty about low‐contrast (LC) sensitivity. In our opinion this unsatisfactory situation is caused at least in part by the lack of suitable phantoms for LC resolution measurements. We investigated the commonly used phantoms for LC detectability, the Catphan, and for LC resolution, the ATS phantom. While the Catphan showed stable object contrasts, the ATS phantom's measured contrast exhibited a strong dependence on temperature and x‐ray quality. Based on newly developed polyurethane resin materials, we designed and tested a LC resolution phantom with several different contrast steps. The object contrasts showed no dependence on temperature and beam quality. The new LC resolution phantom proved to be very suitable for measuring a scanner's low‐contrast sensitivity in the image plane, one of the most important image quality parameters. To assess LC resolution in three dimensions we designed an additional phantom with rows of spherical objects. A first prototype was evaluated in a multicenter study. The setup proved to be very helpful to quantify the in‐plane and axial LC sensitivity of spiral CT scan modes.
Verification of segmented beam delivery using a commercial electronic portal imaging device
Authors: Curtin‐Savard Arthur J. , Podgorsak Ervin B.
Published: July 2002

In modern radiotherapy, three‐dimensional conformal dose distributions are achieved through the delivery of beam ports having precalculated planar distributions of photon beam intensity. Although sophisticated means to calculate and deliver these spatially modulated beams have been developed, means to verify their actual delivery are relatively cumbersome, making equipment and treatment quality assurance difficult to enforce. An electronic portal imaging device of the scanning liquid ionization chamber type yields images which, once calibrated from a previously determined calibration curve, provide highly precise planar maps of the incident dose rate. For verification of an intensity‐modulated beam delivered in the segmented approach with a multileaf collimator, a portal image is acquired for each subfield of the leaf sequence. Subsequent to their calibration, the images are multiplied by their respective associated monitor unit settings, and summed to produce a planar dose distribution at the measurement depth in phantom. The excellent agreement of our portal imager measurements with calculations of our treatment planning system and measurements with a one‐dimensional beam profiler attests to the usefulness of this method for the planar verification of intensity‐modulated fields produced in the segmented approach on a computerized linear accelerator equipped with a multileaf collimator.