bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of the block in targeted retroviral-mediated gene transfer
Authors: Zhao Yi , Zhu Lunjian , Lee Sunyoung , Li Ling , Chang Eric , Soong Nay-Wei , Douer Dan , Anderson W. French
Published: July 2002

A chimeric retroviral vector (33E67) containing a CD33-specific single-chain antibody was generated in an attempt to target cells displaying the CD33 surface antigen. The chimeric envelope protein was translated, processed, and incorporated into viral particles as efficiently as wild-type envelope protein. The viral particles carrying the 33E67 envelope protein could bind efficiently to the CD33 receptor on target cells and were internalized, but no gene transfer occurred. A unique experimental approach was used to examine the basis for this postbinding block. Our data indicate that the chimeric envelope protein itself cannot participate in the fusion process, the most reasonable explanation being that this chimeric protein cannot undergo the appropriate conformational change that is thought to be triggered by receptor binding, a suggested prerequisite to subsequent fusion and core entry. These results indicate that the block to gene transfer in this system, and probably in most of the current chimeric retroviral vectors to date, is the inability of the chimeric envelope protein to undergo this obligatory conformational change.
Network Therapy for Cocaine Abuse: Use of Family and Peer Supports
Authors: Galanter Marc , Dermatis Helen , Keller Daniel , Trujillo Manuel
Published: July 2002

Cocaine‐dependent subjects were treated by psychiatric residents in a 24‐week sequence of Network Therapy. This approach, developed for practitioners in solo practice, employs a cognitive‐behavioral orientation in sessions with family and peers as well as in individual sessions. Of 47 subjects, 73% of all observed weekly urines were negative for cocaine, and 20 (45%) of the subjects had negative toxicologies in the last 3 scheduled samples. A positive outcome was associated with the number of network (but not individual) sessions attended and completion of the full treatment sequence. Results suggest the utility of Network Therapy, even in the hands of relatively naive therapists.
The inhibition of [3H] inositol 1,4,5‐trisphosphate binding by Ca2+ is modified after long‐term ethanol treatment and ethanol withdrawal
Authors: Rodríguez F. David
Published: July 2002

We have analysed the influence of long‐term ethanol exposure on the effect exerted by Ca 2+ on the binding of tritiated inositol 1,4,5‐trisphosphate to its receptors in rat cerebellar membranes. After 21 days of ethanol treatment the binding of the agonist was reduced in the absence of Ca 2+. The decrease was due to reduction in B max without any alteration of K d. In membranes from control animals Ca 2+ inhibited the binding of InsP 3 in a dose‐dependent manner by altering the affinity of the protein for the ligand. However, the inhibitory effect of Ca 2+ was abolished following chronic ethanol exposure. Five days after withdrawing ethanol, the B max recovered to control values, but the inhibitory effect of Ca 2+ was recovered at only 10 days after withdrawal. The results indicate that long‐term ethanol exposure may have differential effects on the InsP 3 binding site and on the Ca 2+ binding site, or alternatively on a Ca 2+ ‐related regulatory cycle.
Hans Adolf Krebs (1900‐1981)…His Life and Times
Authors: Stubbs Marion , Gibbons Geoff
Published: July 2002

A symposium to mark the centenary of the birth of Sir Hans Krebs was held in St. Catherine's College, University of Oxford, UK, during September 13‐15, 2000. It was organized by Marion Stubbs, a long‐time associate of Krebs, and Geoff Gibbons, the head of the Metabolic Research Laboratory that was established for Krebs after his retirement from the Chair of Biochemistry at the University of Oxford. The speakers, from all parts of the world, were Krebs' friends and associates, dating from all stages of his career in the UK, beginning with Reg Hems, who joined Krebs in the early 1940s. The three children of Hans and Margaret Krebs‐Helen, Paul, and John‐were present. Sir John Krebs, F.R.S., Royal Society Research Professor of Zoology at Oxford, gave the welcoming address. This article was adapted by Drs. Stubbs and Gibbons from one of the same title that appeared in the program book. We thank them for their kind cooperation. We also thank Mrs. Helen Lowell (née Krebs) for conveying the permission of the Krebs' children to reproduce the illustrations in this article. ‐ William Whelan, Editor‐in‐Chief
Differential Regulation of the Secretions of Matrix Metalloproteinase‐9 and Tissue Inhibitor of Metalloproteinases‐1 from Human Keratinocytes in Culture
Authors: Kobayashi Takashi , Hattori Shunji , Nagai Yutaka , Tajima Shingo
Published: July 2002

To investigate the pathophysiological roles of matrix metalloproteinase (MMP)‐9 and tissue inhibitor of metalloproteinases (TIMP)‐1 in the differentiation of keratinocytes, we used human keratinocytes in culture to examine the gelatinolytic activity of MMP‐2 and MMP‐9 by zymographic analysis, MMP‐9 mRNA by reverse transcriptase‐polymerase chain reaction, and TIMP‐1 mRNA by Northern blot analysis. Adding of calcium (1 mM) to the culture medium increased the activity of MMP‐9 and MMP‐9 mRNA without affecting MMP‐2 activity or the expression of TIMP‐1 mRNA. These results suggest that keratinocytes regulate the expressions of MMP‐9 and TIMP‐1 differently during the process of differentiation.
Vanadium‐Binding Protein Excreted by Vanadate‐Reducing Bacteria
Authors: Antipov Alexey N. , Lyalikova Natalia N. , L'vov Nikolay P.
Published: July 2002

A vanadium‐binding protein was isolated from the culture medium of the vanadium‐reducing bacterium Pseudomonas isachenkovii by utilizing vanadate as the terminal electron acceptor upon anaerobic respiration. The protein was associated with vanadium at a molar ratio of approximately 1:20. It was purified to homogeneity and separated into three components by treatment with 1 M HCl followed by gel filtration: a protein, a vanadium‐binding ligand, and inorganic vanadium. Electron paramagnetic resonance analysis showed that vanadium was associated with the protein in the 4+ oxidation state. The distribution of vanadium within the cell was studied by electron microscopy and x‐ray microanalysis of P. isachenkovii cells. The results suggest that vanadium, accumulated in special swells on the surface of the cell membranes, is reduced and excreted to the medium.
Epitope‐Tagged Constructs of the Yeast Plasma‐Membrane H+‐ATPase
Authors: Santos Carlos F. Tourinho dos , Dewitt Natalie D. , Gupta Soma Sen , Allen Kenneth E. , Slayman Carolyn W.
Published: July 2002

In this study, two different epitope tags (HA, c‐myc) were introduced near the N terminus of the yeast PMA1 H+‐ATPase. The resulting proteins were indistinguishable from the wild‐type ATPase in their ability to travel through the secretory pathway, as judged by quantitative immunoblotting of isolated secretory vesicles. Furthermore, there were no significant abnormalities in ATPase activity (including Km for MgATP, Vmax, pH optimum, and IC50 for inhibition by vanadate) or in ATP‐dependent proton pumping. Finally, the epitope‐tagged ATPases could support normal growth and displayed the expected activation by glucose.
Effect of Streptozotocin‐Induced Diabetes on Activities of Cholinesterases in the Rat Retina
Authors: Sánchez‐Chávez Gustavo , Salceda Rocío
Published: July 2002

The effect of streptozotocin‐induced diabetes on cholinesterases activities was studied in the retina and, for comparison, in other nervous and nonnervous tissues. Streptozotocin diabetes did not affect acetylcholinesterase activity in the retina but increased its activity in the cerebral cortex (100%) and in serum (55%), and decreased it by 30‐40% in erythrocytes. The butyrylcholinesterase activity was decreased by 30‐50% in retina and hippocampus and to a lesser extent in retinal pigment epithelium from rats treated with streptozotocin for one week. Changes observed in cholinesterase activities were not correlated with the fasting blood glucose concentration. The results suggest that diabetes might influence a specific subset of cells and isoforms of cholinesterases. This, in turn, could lead to alterations associated with diabetes complications.
Studies on Insulin/IGF‐1 Hybrid and IGF‐1 Growth‐Promoting Functional Region
Authors: Wang Ping , Cai Ruo‐Rong , Feng You‐Min , Zhang You‐Shang
Published: July 2002

Single‐chain insulin/IGF‐1 hybrid‐[Ins/IGF‐1(C)], single‐chain porcine insulin precursor‐(PIP), and B10Asp PIP were prepared by protein engineering. Their growth‐promoting activities in mouse breast cancer cell line GR2H6 are 10, 0.2, and 2 times that of insulin, respectively, and 29%, 0.6%, and 6% of that of IGF‐1, indicating that the C domain and 9Glu of IGF‐1 are important for its growth‐promoting activity. Given these results and previous reports, we propose that the C domain, 9Glu, and 23Phe‐26Asn beta bend are involved in the growth‐promoting functional region of IGF‐1.
Effects of Epitope Modification on T Cell Receptor–Ligand Binding and Antigen Recognition by Seven H-2Kd–restricted Cytotoxic T Lymphocyte Clones Specific for a Photoreactive Peptide Derivative
Authors: Kessler Benedikt M. , Bassanini Paolo , Cerottini Jean-Charles , Luescher Immanuel F.
Published: July 2002

We tested for antigen recognition and T cell receptor (TCR)–ligand binding 12 peptide derivative variants on seven H-2Kd–restricted cytotoxic T lymphocytes (CTL) clones specific for a bifunctional photoreactive derivative of the Plasmodium berghei circumsporozoite peptide 252– 260 (SYIPSAEKI). The derivative contained iodo-4-azidosalicylic acid in place of PbCS S-252 and 4-azidobenzoic acid on PbCS K-259. Selective photoactivation of the N-terminal photoreactive group allowed crosslinking to Kd molecules and photoactivation of the orthogonal group to TCR. TCR photoaffinity labeling with covalent Kd–peptide derivative complexes allowed direct assessment of TCR–ligand binding on living CTL. In most cases (over 80%) cytotoxicity (chromium release) and TCR–ligand binding differed by less than fivefold. The exceptions included (a) partial TCR agonists (8 cases), for which antigen recognition was fivetenfold less efficient than TCR–ligand binding, (b) TCR antagonists (2 cases), which were not recognized and capable of inhibiting recognition of the wild-type conjugate, (c) heteroclitic agonists (2 cases), for which antigen recognition was more efficient than TCR–ligand binding, and (d) one partial TCR agonist, which activated only Fas (CD95), but not perforin/granzymemediated cytotoxicity. There was no correlation between these divergences and the avidity of TCR–ligand binding, indicating that other factors than binding avidity determine the nature of the CTL response. An unexpected and novel finding was that CD8-dependent clones clearly incline more to TCR antagonism than CD8-independent ones. As there was no correlation between CD8 dependence and the avidity of TCR–ligand binding, the possibility is suggested that CD8 plays a critical role in aberrant CTL function.
HIV-1 Selection by Epidermal Dendritic Cells during Transmission across Human Skin
Authors: Reece Jeanette C. , Handley Amanda J. , Anstee E. John , Morrison Wayne A. , Crowe Suzanne M. , Cameron Paul U.
Published: July 2002

Macrophage tropic HIV-1 is predominant during the initial viremia after person to person transmission of HIV-1 (Zhu, T., H. Mo, N. Wang, D.S. Nam, Y. Cao, R.A. Koup, and D.D. Ho. 1993. Science. 261:1179–1181.), and this selection may occur during virus entry and carriage to the lymphoid tissue. Human skin explants were used to model HIV-1 selection that may occur at the skin or mucosal surface. Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the abraded epidermis were recovered from the cells emigrating from the skin explants. Dermis and epidermis were separated by dispase digestion after virus exposure to determine the site of viral selection within the skin. Uptake and transmission to T cells of all HIV-1 isolates was found with the dermal emigrant cells, but only macrophage tropic virus was transferred by emigrants from the epidermis exposed to HIV-1, indicating selection only within the epidermis. CD3+, CD4+ T cells were found in both the dermal and epidermal emigrant cells. After cell sorting to exclude contaminating T cells, macrophage tropic HIV-1 was found in both the dermal emigrant dendritic cells and in dendritic cells sorted from the epidermal emigrants. These observations suggest that selective infection of the immature epidermal dendritic cells represents the cellular mechanism that limits the initial viremia to HIV-1 that can use the CCR5 coreceptor.
The Activated Type 1–Polarized Cd8+ T Cell Population Isolated from an Effector Site Contains Cells with Flexible Cytokine Profiles
Authors: Doyle Anthony G. , Buttigieg Kathy , Groves Penny , Johnson Barbara J. , Kelso Anne
Published: July 2002

The capacity of activated T cells to alter their cytokine expression profiles after migration into an effector site has not previously been defined. We addressed this issue by paired daughter analysis of a type 1–polarized CD8+ effector T cell population freshly isolated from lung parenchyma of influenza virus–infected mice. Single T cells were activated to divide in vitro; individual daughter cells were then micromanipulated into secondary cultures with and without added IL-4 to assess their potential to express type 2 cytokine genes. The resultant subclones were analyzed for type 1 and 2 cytokine mRNAs at day 6–7. When the most activated (CD44highCD11ahigh) CD8+ subpopulation from infected lung was compared with naive or resting (CD44lowCD11alow) CD8+ cells from infected lung and from normal lymph nodes (LNs), both clonogenicity and plasticity of the cytokine response were highest in the LN population and lowest in the activated lung population, correlating inversely with effector function. Multipotential cells were nevertheless detected among clonogenic CD44highCD11ahigh lung cells at 30–50% of the frequency in normal LNs. The data indicate that activated CD8+ T cells can retain the ability to proliferate and express new cytokine genes in response to local stimuli after recruitment to an effector site.
Independence of Herpesvirus-Induced T Cell Lymphoma from Viral Cyclin D Homologue
Authors: Ensser Armin , Glykofrydes Diana , Niphuis Henk , Kuhn Eva M. , Rosenwirth Brigitte , Heeney Jonathan L. , Niedobitek Gerald , Müller-Fleckenstein Ingrid , Fleckenstein Bernhard
Published: July 2002

Cyclin D family members are cellular protooncogenes, and their viral homologues in the Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus type 8 [HHV-8]) and the closely related Herpesvirus saimiri have been implicated as putative cofactors of viral transformation and pathogenesis. KSHV is regularly found in Kaposi's sarcoma and in the primary effusion B cell lymphoma and Castleman's disease associated with immunosuppression and AIDS. H. saimiri strain C488 transforms human and marmoset T cells in vitro and causes polyclonal T cell lymphoma in New World monkeys. The viral cyclins stimulate cell cycle progression of quiescent fibroblasts, and they form active cyclin-dependent kinase (CDK)6 complexes of broad substrate specificity that can resist and downregulate cellular CDK inhibitors. This study shows that the viral cyclin of H. saimiri strain C488 is not required for viral replication, T cell transformation, and pathogenicity in New World primates.
Identification of Cyclin B1 as a Shared Human Epithelial Tumor-Associated Antigen Recognized by T Cells
Authors: Kao Henry , Marto Jarrod A. , Hoffmann Thomas K. , Shabanowitz Jeffrey , Finkelstein Sydney D. , Whiteside Theresa L. , Hunt Donald F. , Finn Olivera J.
Published: July 2002

We eluted peptides from class I molecules of HLA-A2.1+ breast adenocarcinoma and loaded reverse phase high-performance liquid chromatography (HPLC) fractions onto dendritic cells to prime naive CD8+ T cells. Fractions that supported growth of tumor-specific cytotoxic T lymphocytes were analyzed by nano-HPLC micro-ESI tandem mass spectrometry. Six HLA-A2.1-binding peptides, four 9-mers (P1-P4) differing in the COOH-terminal residue, and two 10-mers (P5 and P6) with an additional COOH-terminal alanine, were identified in one fraction. Peptide sequences were homologous to cyclin B1. We primed CD8+ T cells from another HLA-A2.1+ healthy donor with synthetic peptides and generated P4-specific responses. We also detected memory T cells specific for one or more of these peptides in patients with breast cancer and squamous cell carcinomas of the head and neck (SCCHN). T cells from one patient, restimulated once in vitro, could kill the tumor cell line from which the peptides were derived. Immunohistochemical analysis of tumor lines and tissue sections showed cyclin B1 overexpression and aberrant localization in the cytoplasm instead of the nucleus. Sequencing genomic DNA and cDNA corresponding to P1–P6 region showed that differences in COOH-terminal residues were not due to either DNA mutations or errors in transcription, suggesting a high error rate in translation of cyclin B1 protein in tumors.
Isolation of a Single Carboxyl-Carboxylate Proton Binding Site in the Pore of a Cyclic Nucleotide–Gated Channel
Authors: Morrill James A. , MacKinnon Roderick
Published: July 2002

The pore of the catfish olfactory cyclic nucleotide–gated (CNG) channel contains four conserved glutamate residues, one from each subunit, that form a high-affinity binding site for extracellular divalent cations. Previous work showed that these residues form two independent and equivalent high-pKa (∼7.6) proton binding sites, giving rise to three pH-dependent conductance states, and it was suggested that the sites were formed by pairing of the glutamates into two independent carboxyl-carboxylates. To test further this physical picture, wild-type CNG subunits were coexpressed in Xenopus oocytes with subunits lacking the critical glutamate residue, and single channel currents through hybrid CNG channels containing one to three wild-type (WT) subunits were recorded. One of these hybrid channels had two pH-dependent conductance states whose occupancy was controlled by a single high-pKa protonation site. Expression of dimers of concatenated CNG channel subunits confirmed that this hybrid contained two WT and two mutant subunits, supporting the idea that a single protonation site is made from two glutamates (dimer expression also implied the subunit makeup of the other hybrid channels). Thus, the proton binding sites in the WT channel occur as a result of the pairing of two glutamate residues. This conclusion places these residues in close proximity to one another in the pore and implies that at any instant in time detailed fourfold symmetry is disrupted.
Boundedness of the fractional integral on weighted Lebesgue and Lipschitz spaces
Authors: Harboure Eleonor , Salinas Oscar , Viviani Beatriz
Published: July 2002

Necessary and sufficient conditions are given for the fractional integral operator

I
α

I_\alpha

to be bounded from weighted strong and weak

L
p

L^p

spaces within the range

p
≥
n

/

α

p\geq n/\alpha

into suitable weighted

B
M
O

BMO

and Lipschitz spaces. We also characterize the weights for which

I
α

I_\alpha

can be extended to a bounded operator from weighted

B
M
O

BMO

into a weighted Lipschitz space of order

α
\alpha

. Finally, under an additional assumption on the weight, we obtain necessary and sufficient conditions for the boundedness of

I
α

I_\alpha

between weighted Lipschitz spaces.
Improved error bounds for scattered data interpolation by radial basis functions
Authors: Schaback R.
Published: July 2002

If additional smoothness requirements and boundary conditions are met, the well–known approximation orders of scattered data interpolants by radial functions can roughly be doubled.
A strategy for finding regions of similarity in complete genome sequences.
Authors: Vincens P , Buffat L , Andr√© C , Chevrolat J P , Boisvieux J F , Hazout2 S
Published: July 2002

MOTIVATION: Complete genomic sequences will become available in the future. New methods to deal with very large sequences (sizes beyond 100 kb) efficiently are required. One of the main aims of such work is to increase our understanding of genome organization and evolution. This requires studies of the locations of regions of similarity. RESULTS: We present here a new tool, ASSIRC ('Accelerated Search for SImilarity Regions in Chromosomes'), for finding regions of similarity in genomic sequences. The method involves three steps: (i) identification of short exact chains of fixed size, called 'seeds', common to both sequences, using hashing functions; (ii) extension of these seeds into putative regions of similarity by a 'random walk' procedure; (iii) final selection of regions of similarity by assessing alignments of the putative sequences. We used simulations to estimate the proportion of regions of similarity not detected for particular region sizes, base identity proportions and seed sizes. This approach can be tailored to the user's specifications. We looked for regions of similarity between two yeast chromosomes (V and IX). The efficiency of the approach was compared to those of conventional programs BLAST and FASTA, by assessing CPU time required and the regions of similarity found for the same data set. AVAILABILITY: Source programs are freely available at the following address: ftp://ftp.biologie.ens. fr/pub/molbio/assirc.tar.gz CONTACT: vincens@biologie.ens.fr, hazout@urbb.jussieu.fr
KIND-a non-redundant protein database.
Authors: Kallberg Y , Persson B
Published: July 2002

SUMMARY: KIND (Karolinska Institutet Nonredundant Database) is a protein database where identical sequences, both full length and partial, have been removed. The database contains nearly 274 900 sequences, half of which originate from the protein sequence databases Swissprot and PIR, while the other half come from translated open reading frames in GenPept and TrEMBL. AVAILABILITY: KIND is downloadable from ftp://ftp.mbb.ki.se/pub/KIND.
THE END OF CONSCRIPTION IN EUROPE?
Authors: Jehn Christopher , Selden Zachary
Published: July 2002

The end of the cold war prompted a number of European countries to phase out conscription and construct all‐volunteer forces (AVFs). Despite this trend, many European countries plan to retain some level of conscription. The disparity between those countries eliminating conscription and those retaining it cannot be accounted for by any single factor, and each country is responding to the particular international and domestic pressures it faces. In general, however, those countries retaining conscription fall into two categories: (1) countries that stood outside the cold war alliance structure and consequently built the ability to mobilize a large proportion of the male population in the event of war, and (2) those countries that are new political entities still attempting to construct viable armed forces. Although the practice of conscription has declined in Europe, it is unlikely to be eliminated in the near future.
Comparative in-vitro activity of levofloxacin, other fluoroquinolones, doxycycline and erythromycin against Ureaplasma urealyticum and Mycoplasma hominis
Authors: Ullmann U. , Schubert S. , Krausse R.
Published: July 2002

The susceptibility of 56 Ureaplasma urealyticum and 57 Mycoplasma hominis strains to levofloxacin, ofloxacin, ciprofloxacin, fleroxacin, doxycycline and erythromycin was determined by an agar dilution method. The reference strain used was M. hominis PG 21. Agar plates containing serial dilutions of antibiotics (range 0.03-16 mg/L), and control plates (without antibiotics) were inoculated with bacteria suspended in modified Shepard's broth using a multipoint inoculator. Levofloxacin showed greater activity against all U. urealyticum and M. hominis strains compared with all other antibiotics tested. The MIC 90 values for U. urealyticum were as follows: levofloxacin, 1 mg/L; ofloxacin, 2 mg/L; ciprofloxacin, 4 mg/L; fleroxacin, 4 mg/L; doxycycline, 1 mg/L; erythromycin, 8 mg/L. The MIC 90 s for M. hominis were: levofloxacin, 1 mg/L; ofloxacin, 2 mg/L; ciprofloxacin, 4 mg/L; fleroxacin, 4 mg/L; doxycycline, 4 mg/L; erythromycin, ≥16 mg/L. In conclusion, the results of this study suggest that levofloxacin may be useful in the treatment of mycoplasma genital infections.
Calculation of diffraction coefficients for a semi-infinite crack embedded in an infinite anisotropic linearly elastic body
Authors: Lewis P. A. , Temple J. A. G. , Walker E. J. , Wickham G. R.
Published: July 2002

In this paper we consider the diffraction of sound by a semi–infinite planar crack arbitrarily oriented in a homogeneous anisotropic linearly elastic solid. The problem is formulated exactly as an integro–differential equation with a difference kernel which is the stress tensor corresponding to the fundamental point force solution for the uncracked solid. The solution of this equation is the crack opening displacement (COD) induced by the incident field, and this may be expressed in terms of the Wiener–Hopf factors of the Fourier symbol of the kernel. The quantity of physical interest is the so–called diffraction coefficient which is proportional to the Fourier transform of the COD and relates the vector amplitude on an incident ray to the crack edge to the amplitudes on the diffracted rays. In the general case, the necessary Wiener–Hopf factorization cannot be found explicitly, but it is possible to construct an iterative procedure which enables a numerical evaluation. In this, the first of two papers, we give a general formal solution of the diffraction problem and show how it reproduces known results with special material symmetries. In the second paper we shall discuss the numerical procedure in detail and provide some new tabulations of diffraction coefficients.
Insect resistance to Bacillus thuringiensis: uniform or diverse?
Authors: Tabashnik B. E. , Liu Y. , Malvar T. , Heckel D. G. , Masson L. , Ferré J.
Published: July 2002

Resistance to the insecticidal proteins produced by the soil bacterium
Bacillus thuringiensis
(Bt) has been documented in more than a dozen species of insect. Nearly all of these cases have been produced primarily by selection in the laboratory, but one pest, the diamondback moth (
Plutella xylostella
), has evolved resistance in open–field populations. Insect resistance to Bt has immediate and widespread significance because of increasing reliance on Bt toxins in genetically engineered crops and conventional sprays. Furthermore, intense interest in Bt provides an opportunity to examine the extent to which evolutionary pathways to resistance vary among and within species of insect. One mode of resistance to Bt is characterized by more than 500–fold resistance to at least one Cry1A toxin, recessive inheritance, little or no cross–resistance to Cry1C, and reduced binding of at least one Cry1A toxin. Analysis of resistance to Bt in the diamondback moth and two other species of moth suggests that although this particular mode of resistance may be the most common, it is not the only means by which insects can attain resistance to Bt.
Hypermutation in bacteria and other cellular systems
Authors: Bridges Bryn A.
Published: July 2002

A temporary state of hypermutation can in principle arise through an increase in the rate of polymerase errors (which may or may not be triggered by template damage) and/or through abrogation of fidelity mechanisms such as proofreading and mismatch correction. In bacteria there are numerous examples of transient mutator states, often occurring as a consequence of stress. They may be targeted to certain regions of the DNA, for example by transcription or by recombination. The initial errors are made by various DNA polymerases which vary in their error–proneness: several are inducible and are under the control of the SOS system. There are several structurally related polymerases in mammals that have recently come to light and that have unusual properties, such as the ability to carry out ‘accurate’ translesion synthesis opposite sites of template damage or the possession of exceedingly high misincorporation rates. In bacteria the initial errors may be genuinely spontaneous polymerase errors or they may be triggered by damage to the template strand, for example as a result of attack by active oxidative species such as singlet oxygen. In mammalian cells, hypermutable states persisting for many generations have been shown to be induced by various agents, not all of them DNA damaging agents. A hypermutable state induced by ionizing radiation in male germ cells in the mouse results in a high rate of sequence errors in certain unstable minisatellite loci; the mechanism is unclear but believed to be associated with recombination events.
A variable resolution x‐ray detector for computed tomography: I. Theoretical basis and experimental verification
Authors: DiBianca F. A. , Gupta V. , Zeman H. D.
Published: July 2002

A computed tomography imaging technique called variable resolution x‐ray (VRX) detection provides detector resolution ranging from that of clinical body scanning to that of microscopy (1 cy/mm to 100 cy/mm). The VRX detection technique is based on a new principle denoted as “projective compression” that allows the detector resolution element to scale proportionally to the image field size. Two classes of VRX detector geometry are considered. Theoretical aspects related to x‐ray physics and data sampling are presented. Measured resolution parameters (line‐spread function and modulation‐transfer function) are presented and discussed. A VRX image that resolves a pair of 50μ tungsten hairs spaced 30μ apart is shown.
Impact of dose‐distribution uncertainties on rectal modeling I: Uncertainty estimates
Authors: Fenwick John D. , Nahum Alan E.
Published: July 2002

A trial of nonescalated conformal versus conventional radiotherapy treatment of prostate cancer has been carried out at the Royal Marsden NHS Trust (RMH) and Institute of Cancer Research (ICR), demonstrating a significant reduction in the rate of rectal bleeding reported for patients treated using the conformal technique. The relationship between planned rectal dose‐distributions and incidences of bleeding has been analyzed, showing that the rate of bleeding falls significantly as the extent of the rectal wall receiving a planned dose‐level of more than 57 Gy is reduced. Dose‐distributions delivered to the rectal wall over the course of radiotherapy treatment inevitably differ from planned distributions, due to sources of uncertainty such as patient setup error, rectal wall movement and variation in the absolute rectal wall surface area. In this paper estimates of the differences between planned and treated rectal dose‐distribution parameters are obtained for the RMH/ICR nonescalated conformal technique, working from a distribution of setup errors observed during the RMH/ICR trial, movement data supplied by Lebesque and colleagues derived from repeat CT scans, and estimates of rectal circumference variations extracted from the literature. Setup errors and wall movement are found to cause only limited systematic differences between mean treated and planned rectal dose‐distribution parameter values, but introduce considerable uncertainties into the treated values of some dose‐distribution parameters: setup errors lead to 22% and 9% relative uncertainties in the highly dosed fraction of the rectal wall and the wall average dose, respectively, with wall movement leading to 21% and 9% relative uncertainties. Estimates obtained from the literature of the uncertainty in the absolute surface area of the distensible rectal wall are of the order of 13%–18%. In a subsequent paper the impact of these uncertainties on analyses of the relationship between incidences of bleeding and planned rectal dose‐distributions is explored.
Impact of dose‐distribution uncertainties on rectal modeling II: Uncertainty implications
Authors: Fenwick John D.
Published: July 2002

A trial of nonescalated conformal versus conventional radiotherapy treatment of prostate cancer has been carried out at the Royal Marsden NHS Trust (RMH) and Institute of Cancer Research (ICR), demonstrating a significant reduction in the rate of rectal bleeding reported for patients treated using the conformal technique. The rate of bleeding has been shown to fall significantly as the extent of rectal wall receiving a planned dose‐level in excess of 57 Gy is reduced. Dose‐distributions delivered to the rectal wall over the course of radiotherapy treatment inevitably differ from planned distributions. In a previous paper estimates were obtained of the uncertainties in some planned rectal dose‐distribution parameters generated by patient setup error, rectal wall movement and the variable degree of rectal wall distension. Here these uncertainties are combined to obtain estimates of the total planning uncertainties in rectal dose‐distribution parameters thought likely, on the basis of mechanistic biological modeling, to correlate strongly with the complication rate. Working from these totaled uncertainty values, together with values of patient‐to‐patient and technique‐to‐technique differences in planned dose‐distribution parameters, it can be inferred that the rectal dose‐distribution uncertainties: (i) Have only a marginal impact on fits of a normal tissue complication probability (ntcp) model to RMH/ICR dose‐distribution and grade 1, 2, 3 bleeding data (slightly flattening observed volume‐response curves); (ii) only slightly reduce the power of a patient trial of conformal versus conventional prostate radiotherapy to detect a significantly lower rate of grade 1,2,3 rectal bleeding amongst conformally treated patients; (iii) do not diminish the information content of individual planned patient dose‐distribution data to the point where the fitting of technique‐averaged data would provide as sensitive a test of the existence of a volume effect as the fitting of individual patient data.
Dose rate table for a intravascular brachytherapy source from Monte Carlo calculations
Authors: Bohm Tim D. , Mourtada Firas A. , Das Rupak K.
Published: July 2002

Studies of intravascular brachytherapy to prevent restenosis following angioplasty have shown many promising results. Accurate dose rate tables based on detailed models of the brachytherapy sources are necessary for treatment planning. This work will present an away and along dose rate table for a 27 mm long catheter based beta source. MD‐55‐2 radiochromic film has been exposed at five different depths (0.5 mm–4 mm) in a polystyrene phantom using a 27 mm long Guidant beta source. The total dose to the active region of the film was determined using the absolute detector response of the MD‐55‐2 radiochromic film. The Monte Carlo code MCNP4B2 was also used to calculate the dose to the active region of the film using a detailed model of the source, encapsulation, and radiochromic film. The dose to film calculations showed good agreement with the measurements presented in this work with an average difference of 7%. The Monte Carlo calculations were also verified against previously published depth dose in water measurements determined using radiochromic film and plastic scintillator. The depth dose calculations in water showed good agreement with the previously published measurements with the calculations being about 2.5% lower than the film measurements and about 2.5% higher than the scintillator measurements. This work then uses the verified Monte Carlo code to present a dose rate table for the intravascular beta source.
A formalism for independent checking of Gamma Knife dose calculations
Authors: Tsai Jen‐San , Engler Mark J. , Rivard Mark J. , Mahajan Anita , Borden Jonathan A. , Zheng Zhen
Published: July 2002

For stereotactic radiosurgery using the Leksell Gamma Knife system, it is important to perform a pre‐treatment verification of the maximum dose calculated with the Leksell stereotactic radiosurgery system. This verification can be incorporated as part of a routine quality assurance (QA) procedure to minimize the chance of a hazardous overdose. To implement this procedure, a formalism has been developed to calculate the dose using the following parameters: average target depth coordinates of the maximum dose location or any other dose point(s) to be verified, 3‐dimensional (3‐dim) beam profiles or off‐center‐ratios (OCR) of the four helmets, helmet size i, output factor plug factor each shot j coordinates and shot treatment time The average depth of the target was obtained either from MRI/CT images or ruler measurements of the Gamma Knife Bubble Head Frame. and were then compared to evaluate the accuracy of this independent calculation. The proposed calculation for an independent check of has been demonstrated to be accurate and reliable, and thus serves as a QA tool for Gamma Knife stereotactic radiosurgery.
An equivalent square field formula for determining head scatter factors of rectangular fields
Authors: Kim Siyong , Zhu Timothy C. , Palta Jatinder R.
Published: July 2002

A simple formula is derived for the calculation of an equivalent square field that gives the same head scatter factor as a given rectangular field. This formula is based strictly on the configuration of a medical linear accelerator treatment head. The geometric parameters used are the distances between the target and the top of each field‐defining aperture. The formula accounts for both the effect of field elongation and the collimator exchange effect. This method predicts the output to within 1% accuracy for both open and wedged fields and does not require any new measured data other than the field size dependence of head scatter for a range of square field sizes. Interestingly, the formula we derived has the same format as the formula that was empirically obtained by Vadash and Bjärngard [Med. Phys. 20, 733–734 (1993)].
Automated analysis of the American College of Radiology mammographic accreditation phantom images
Authors: Brooks Kenneth W. , Trueblood Jon H. , Kearfott Kimberlee J. , Lawton Daryl T.
Published: July 2002

A significant metric in federal mammography quality standards is the phantom image quality assessment. The present work seeks to demonstrate that automated image analyses for American College of Radiology (ACR) mammographic accreditation phantom (MAP) images may be performed by a computer with objectivity, once a human acceptance level has been established. Twelve MAP images were generated with different x‐ray techniques and digitized. Nineteen medical physicists in diagnostic roles (five of which were specially trained in mammography) viewed the original film images under similar conditions and provided individual scores for each test object (fibrils, microcalcifications, and nodules). Fourier domain template matching, used for low‐level processing, combined with derivative filters, for intermediate‐level processing, provided translation and rotation‐independent localization of the test objects in the MAP images. The visibility classification decision was modeled by a Bayesian classifer using threshold contrast. The 50% visibility contrast thresholds established by the trained observers' responses were: fibrils 1.010, microcalcifications 1.156, and nodules 1.016. Using these values as an estimate of human observer performance and given the automated localization of test objects, six images were graded with the computer algorithm. In all but one instance, the algorithm scored the images the same as the diagnostic physicists. In the case where it did not, the margin of disagreement was 10% due to the fact that the human scoring did not allow for half‐visible fibrils (agreement occurred for the other test objects). The implication from this is that an operator‐independent, machine‐based scoring of MAP images is feasible and could be used as a tool to help eliminate the effect of observer variability within the current system, given proper, consistent digitization is performed.
Improved Bayesian image estimation for digital chest radiography
Authors: Baydush Alan H. , Bowsher James E. , Laading Jacob K. , Floyd Carey E.
Published: July 2002

Purpose: Previously, we have shown that Spatially Varying Bayesian Image Estimation (SVBIE) can be used to reduce scatter and improve contrast‐to‐noise ratios (CNR) in digital chest radiographs with no degradation of image resolution. This previous algorithm used a model for scatter compensation that was derived for emission tomography. Here, we develop and evaluate a new iterative SVBIE technique that incorporates a scatter model derived for projection radiography. Materials and Methods: Portable digital radiographs of an anthropomorphic chest phantom were obtained along with quantitative scatter measurements using a calibrated photostimulable phosphor system. The new iterative SVBIE technique was applied to the phantom image to reduce scatter. Scatter fraction reduction, CNR improvement, and resolution degradation were evaluated. Results: Residual scatter fractions were reduced to less than 2% in the lungs and 30% in the mediastinum at 14 iterations. CNR was improved by approximately 50% in the lung region and 187% in the mediastinum. Resolution was not degraded. Conclusions: The new SVBIE technique can reduce scatter to levels far below those provided by an antiscatter grid and can increase CNR without loss of resolution. The new technique outperforms the previous Bayesian techniques.
Lens coupling efficiency: Derivation and application under differing geometrical assumptions
Authors: Yu Tong , Boone John M.
Published: July 2002

The calculation of lens coupling efficiency is often performed in the design of lens coupled digital radiographic systems, now currently under development. With these systems, an electronic camera is focused onto a planar scintillator such as a conventional intensifying screen. Historically, this calculation has relied on certain assumptions concerning the emission properties of the scintillator, and primarily this assumption is that the scintillator is either a Lambertian emitter (light is emitted over all angles equally) or a point radiator. Because there now exists new classes of scintillators such as scintillating fiber optic screens and pixelated intensifying screens, it is sometimes necessary to perform lens coupling calculations in the absence of the Lambertian and point source assumptions. In this paper we describe the necessary equations to accurately calculate lens coupling efficiency in the most general of cases. Graphical examples demonstrate the lens coupling efficiency for hypothetical Lambertian scintillating sources, for a rare earth intensifying screen, and for a scintillating fiber optical screen.
Determination of the energy fluence of diagnostic x‐ray beams from field measurements of attenuation curves
Authors: Delgado Vı́ctor , Ortiz Pedro
Published: July 2002

The use of field measurements of attenuation curves of low‐energy x‐ray beams as a functional description of the beams is presented in this work. The energy fluence carried by diagnostic x‐ray beams has been determined from Al attenuation measurements made with a quality control ionization chamber for diagnostic x‐ray equipment and with a low‐volume ionization chamber. The obtained values are compared with those obtained from a catalog of spectral data for diagnostic x rays.
Aspects of ultrasonic velocity measurement in trabecular bone
Authors: Strelitzki Roland
Published: July 2002

Osteoporosis is a major health problem in modern society. Different techniques are used to discriminate people at risk of this disease. One of them, ultrasound, has advantages compared to the more established densitometric methods. Two parameters, the velocity and the Broadband Ultrasonic Attenutation (BUA) are most often assessed on the oscalcis. The thesis examines the errors in measurement of velocity and attenuation. To confirm and demonstrate this, measurements of BUA on several commercial devices were carried out using bone phantom materials and these showed significant (up to 33 dB MHz‐1) variations. The errors in velocity measurements include those due to frequency dependence of attenuation and velocity and these factors are evaluated separately. Time and frequency domain methods are used as well as theoretical modeling. It is shown that phase velocity is more resilient and accurate than commonly used methods and provides an opportunity to measure dispersion which may be an additional and useful parameter. The use of low frequency methods, utilizing bar wave propagation is also examined. It is concluded that the way is now clear to develop alternative clinical equipment based largely on velocity measurements, which should give a closer estimate of bone strength than existing ultrasonic techniques.
Microprocessor controlled limitation system for a stand‐alone freely movable treatment couch
Authors: Van de Vondel Iwein , Coppens Luc , Verellen Dirk , Bel Arjan , Linthout Nadine , De Beukeleer Marc , Van den Berge Dirk , Storme Guy
Published: July 2002

Because of the capability of free movement in the treatment room, we recently introduced a Hercules treatment couch on one of our linear accelerators. One of the advantages of this couch is that it allows for a more flexible way of patient setup and that it can be moved entirely out of the way to enable treatment with a hospital bed. A disadvantage, however, is that the couch can hit a wall or a cover of the accelerator accidentally. A limitation system has been developed to protect both the table and the accelerator against such collisions.
Multiple scattering theory for total skin electron beam design
Authors: Antolak John A. , Hogstrom Kenneth R.
Published: July 2002

The purpose of this manuscript is to describe a method for designing a broad beam of electrons suitable for total skin electron irradiation (TSEI). A theoretical model of a TSEI beam from a linear accelerator with a dual scattering system has been developed. The model uses Fermi–Eyges theory to predict the planar fluence of the electron beam after it has passed through various materials between the source and the treatment plane, which includes scattering foils, monitor chamber, air, and a plastic diffusing plate. Unique to this model is its accounting for removal of the tails of the electron beam profile as it passes through the primary x‐ray jaws. A method for calculating the planar fluence profile for an obliquely incident beam is also described. Off‐axis beam profiles and percentage depth doses are measured with ion chambers, film, and thermoluminescent dosimeters (TLD). The measured data show that the theoretical model can accurately predict beam energy and planar fluence of the electron beam at normal and oblique incidence. The agreement at oblique angles is not quite as good but is sufficiently accurate to be of predictive value when deciding on the optimal angles for the clinical TSEI beams. The advantage of our calculational approach for designing a TSEI beam is that many different beam configurations can be tested without having to perform time‐consuming measurements. Suboptimal configurations can be quickly dismissed, and the predicted optimal solution should be very close to satisfying the clinical specifications.