bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon-α and Interleukin-12 Are Induced Differentially by Toll-like Receptor 7 Ligands in Human Blood Dendritic Cell Subsets
Authors: Ito Tomoki , Amakawa Ryuichi , Kaisho Tsuneyasu , Hemmi Hiroaki , Tajima Kenichirou , Uehira Kazutaka , Ozaki Yoshio , Tomizawa Hideyuki , Akira Shizuo , Fukuhara Shirou
Published: July 2002

Dendritic cells (DCs) play a crucial role in the immune responses against infections by sensing microbial invasion through toll-like receptors (TLRs). In humans, two distinct DC subsets, CD11c− plasmacytoid DCs (PDCs) and CD11c+ myeloid DCs (MDCs), have been identified and can respond to different TLR ligands, depending on the differential expression of cognate TLRs. In this study, we have examined the effect of TLR-7 ligands on human DC subsets. Both subsets expressed TLR-7 and could respond to TLR-7 ligands, which enhanced the survival of the subsets and upregulated the surface expression of costimulatory molecules such as CD40, CD80, and CD86. However, the cytokine induction pattern was distinct in that PDCs and MDCs produced interferon (IFN)-α and interleukin (IL)-12, respectively. In response to TLR-7 ligands, the Th1 cell supporting ability of both DC subsets was enhanced, depending on the cytokines the respective subsets produced. This study demonstrates that TLR-7 exerts its biological effect in a DC subset-specific manner.
Permeation Properties of Inward-Rectifier Potassium Channels and Their Molecular Determinants
Authors: Choe Han , Sackin Henry , Palmer Lawrence G.
Published: July 2002

The structural domains contributing to ion permeation and selectivity in K channels were examined in inward-rectifier K+ channels ROMK2 (Kir1.1b), IRK1 (Kir2.1), and their chimeras using heterologous expression in Xenopus oocytes. Patch-clamp recordings of single channels were obtained in the cell-attached mode with different permeant cations in the pipette. For inward K+ conduction, replacing the extracellular loop of ROMK2 with that of IRK1 increased single-channel conductance by 25 pS (from 39 to 63 pS), whereas replacing the COOH terminus of ROMK2 with that of IRK1 decreased conductance by 16 pS (from 39 to 22 pS). These effects were additive and independent of the origin of the NH2 terminus or transmembrane domains, suggesting that the two domains form two resistors in series. The larger conductance of the extracellular loop of IRK1 was attributable to a single amino acid difference (Thr versus Val) at the 3P position, three residues in front of the GYG motif. Permeability sequences for the conducted ions were similar for the two channels: Tl+ > K+ > Rb+ > NH4+. The ion selectivity sequence for ROMK2 based on conductance ratios was NH4+ (1.6) > K+ (1) > Tl+ (0.5) > Rb+ (0.4). For IRK1, the sequence was K+ (1) > Tl+ (0.8) > NH4+ (0.6) >> Rb+ (0.1). The difference in the NH4+/ K+ conductance (1.6) and permeability (0.09) ratios can be explained if NH4+ binds with lower affinity than K+ to sites within the pore. The relatively low conductances of NH4+ and Rb+ through IRK1 were again attributable to the 3P position within the P region. Site-directed mutagenesis showed that the IRK1 selectivity pattern required either Thr or Ser at this position. In contrast, the COOH-terminal domain conferred the relatively high Tl+ conductance in IRK1. We propose that the P-region and the COOH terminus contribute independently to the conductance and selectivity properties of the pore.
Tea+-Sensitive Kcnq1 Constructs Reveal Pore-Independent Access to Kcne1 in Assembled IKs Channels
Authors: Kurokawa J. , Motoike H.K. , Kass R.S.
Published: July 2002

I Ks, a slowly activating delayed rectifier K+ current through channels formed by the assembly of two subunits KCNQ1 (KvLQT1) and KCNE1 (minK), contributes to the control of the cardiac action potential duration. Coassembly of the two subunits is essential in producing the characteristic and physiologically critical kinetics of assembled channels, but it is not yet clear where or how these subunits interact. Previous investigations of external access to the KCNE1 protein in assembled IKs channels relied on occlusion of the pore by extracellular application of TEA+, despite the very low TEA+ sensitivity (estimated EC50 > 100 mM) of channels encoded by coassembly of wild-type KCNQ1 with the wild type (WT) or a series of cysteine-mutated KCNE1 constructs. We have engineered a high affinity TEA+ binding site into the h-KCNQ1 channel by either a single (V319Y) or double (K318I, V319Y) mutation, and retested it for pore-delimited access to specific sites on coassembled KCNE1 subunits. Coexpression of either KCNQ1 construct with WT KCNE1 in Chinese hamster ovary cells does not alter the TEA+ sensitivity of the homomeric channels (IC50 ≈ 0.4 mM [TEA+]out), providing evidence that KCNE1 coassembly does not markedly alter the structure of the outer pore of the KCNQ1 channel. Coexpression of a cysteine-substituted KCNE1 (F54C) with V319Y significantly increases the sensitivity of channels to external Cd2+, but neither the extent of nor the kinetics of the onset of (or the recovery from) Cd2+ block was affected by [TEA+]o at 10× the IC50 for channel block. These data strongly suggest that access of Cd2+ to the cysteine-mutated site on KCNE1 is independent of pore occlusion caused by TEA+ binding to the outer region of the KCNE1/V319Y pore, and that KCNE1 does not reside within the pore region of the assembled channels.
K+ Occupancy of the N-Methyl-d-Aspartate Receptor Channel Probed by Mg2+ Block
Authors: Zhu Yongling , Auerbach Anthony
Published: July 2002

The single-channel kinetics of extracellular Mg2+ block was used to probe K+ binding sites in the permeation pathway of rat recombinant NR1/NR2B NMDA receptor channels. K+ binds to three sites: two that are external and one that is internal to the site of Mg2+ block. The internal site is ∼0.84 through the electric field from the extracellular surface. The equilibrium dissociation constant for this site for K+ is 304 mM at 0 mV and with Mg2+ in the pore. The occupancy of any one of the three sites by K+ effectively prevents the association of extracellular Mg2+. Occupancy of the internal site also prevents Mg2+ permeation and increases (by approximately sevenfold) the rate constant for Mg2+ dissociation back to the extracellular solution. Under physiological intracellular ionic conditions and at −60 mV, there is ∼1,400-fold apparent decrease in the affinity of the channel for extracellular Mg2+ and ∼2-fold enhancement of the apparent voltage dependence of Mg2+ block caused by the voltage dependence of K+ occupancy of the external and internal sites.
Probability measures in 𝑊*𝐽-algebras in Hilbert spaces with conjugation
Authors: Matvejchuk Marjan
Published: July 2002

Let

M

\mathcal {M}

be a real

W

∗

W^{*}

-algebra of

J
J

-real bounded operators containing no central summand of type

I

2

I_{2}

in a complex Hilbert space

H
H

with conjugation

J
J

. Denote by

P
P

the quantum logic of all

J
J

-orthogonal projections in the von Neumann algebra

N

=

M

+
i

M

{\mathcal {N}}={\mathcal {M}}+ i{\mathcal {M}}

. Let

μ
:
P
→
[
0
,
1
]

\mu :P\rightarrow [0,1]

be a probability measure. It is shown that

N

\mathcal {N}

contains a finite central summand and there exists a normal finite trace

τ
\tau

on

N

\mathcal {N}

such that

μ
(
p
)
=
τ
(
p
)

\mu (p)=\tau (p)

,

∀
p
∈
P

\forall p\in P

.
Exact iterative reconstruction algorithm for multivariate irregularly sampled functions in spline-like spaces: The 𝐿^{𝑝}-theory
Authors: Aldroubi Akram , Feichtinger Hans
Published: July 2002

We prove that the exact reconstruction of a function

s
s

from its samples

s
(

x
i

)

s (x_i)

on any “sufficiently dense" sampling set

{

x
i

}

i
∈
Λ

\{x_i\}_{i\in \Lambda }

can be obtained, as long as

s
s

is known to belong to a large class of spline-like spaces in

L
p

(

R

n

)

L^p (\mathcal {R}^n)

. Moreover, the reconstruction can be implemented using fast algorithms. Since a limiting case is the space of bandlimited functions, our result generalizes the classical Shannon-Whittaker sampling theorem on regular sampling and the Paley-Wiener theorem on non-uniform sampling.
Periodic points of holomorphic maps via Lefschetz numbers
Authors: Fagella Núria , Llibre Jaume
Published: July 2002

In this paper we study the set of periods of holomorphic maps on compact manifolds, using the periodic Lefschetz numbers introduced by Dold and Llibre, which can be computed from the homology class of the map. We show that these numbers contain information about the existence of periodic points of a given period; and, if we assume the map to be transversal, then they give us the exact number of such periodic orbits. We apply this result to the complex projective space of dimension

n
n

and to some special type of Hopf surfaces, partially characterizing their set of periods. In the first case we also show that any holomorphic map of

C

P

(
n
)

{\mathbb CP}(n)

of degree greater than one has infinitely many distinct periodic orbits, hence generalizing a theorem of Fornaess and Sibony. We then characterize the set of periods of a holomorphic map on the Riemann sphere, hence giving an alternative proof of Baker’s theorem.
Embedded singular continuous spectrum for one-dimensional Schrödinger operators
Authors: Remling Christian
Published: July 2002

We investigate one-dimensional Schrödinger operators with sparse potentials (i.e. the potential consists of a sequence of bumps with rapidly growing barrier separations). These examples illuminate various phenomena related to embedded singular continuous spectrum.
ISWI Remodeling Complexes inXenopusEgg Extracts: Identification as Major Chromosomal Components that Are Regulated by INCENP-aurora B
Authors: MacCallum David E. , Losada Ana , Kobayashi Ryuji , Hirano Tatsuya
Published: July 2002

We previously characterized major components of mitotic chromosomes assembled in Xenopus laevis egg extracts and collectively referred to them as Xenopuschromosome–associated polypeptides (XCAPs). They included five subunits of the condensin complex essential for chromosome condensation. In an effort to identify novel proteins involved in this process, we have isolated XCAP-F and found it to be theXenopus ortholog of ISWI, a chromatin remodeling ATPase. ISWI exists in two major complexes in Xenopus egg extracts. The first complex contains ACF1 and two low-molecular-weight subunits, most likely corresponding to Xenopus CHRAC. The second complex is a novel one that contains theXenopus ortholog of the human Williams syndrome transcription factor (WSTF). In the absence of the ISWI complexes, the deposition of histones onto DNA is apparently normal, but the spacing of nucleosomes is greatly disturbed. Despite the poor spacing of nucleosomes, ISWI depletion has little effect on DNA replication, chromosome condensation or sister chromatid cohesion in the cell-free extracts. The association of ISWI with chromatin is cell cycle regulated and is under the control of the INCENP-aurora B kinase complex that phosphorylates histone H3 during mitosis. Apparently contradictory to the generally accepted model, we find that neither chromosome condensation nor chromosomal targeting of condensin is compromised when H3 phosphorylation is drastically reduced by depletion of INCENP-aurora B.
Docking of hydrophobic ligands with interaction-based matching algorithms.
Authors: Rarey M , Kramer B , Lengauer T
Published: July 2002

MOTIVATION: Matching of chemical interacting groups is a common concept for docking and fragment placement algorithms in computer-aided drug design. These algorithms have been proven to be reliable and fast if at least a certain number of hydrogen bonds or salt bridges occur. However, the algorithms typically run into problems if hydrophobic fragments or ligands should be placed. In order to dock hydrophobic fragments without significant loss of computational efficiency, we have extended the interaction model and placement algorithms in our docking tool FlexX. The concept of multi-level interactions is introduced into the algorithms for automatic selection and placement of base fragments. RESULTS: With the multi-level interaction model and the corresponding algorithmic extensions, we were able to improve the overall performance of FlexX significantly. We tested the approach with a set of 200 protein-ligand complexes taken from the Brookhaven Protein Data Bank (PDB). The number of test cases which can be docked within 1.5 A RMSD from the crystal structure can be increased from 58 to 64%. The performance gain is paid for by an increase in computation time from 73 to 91 s on average per protein-ligand complex. AVAILABILITY: The FlexX molecular docking software is available for UNIX platforms IRIX, Solaris and Linux. See http://cartan.gmd.de/FlexX for additional information.
EMBL-Align: a new public nucleotide and amino acid multiple sequence alignment database
Authors: Lombard V. , Camon E. B. , Parkinson H. E. , Hingamp P. , Stoesser G. , Redaschi N.
Published: July 2002

Summary: The submission of multiple sequence alignment data to EMBL has grown 30-fold in the past 10 years, creating a problem of archiving them. The EBI has developed a new public database of multiple sequence alignments called EMBL-Align. It has a dedicated web-based submission tool, Webin-Align. Together they represent a comprehensive data management solution for alignment data. Webin-Align accepts all the common alignment formats and can display data in CLUSTALW format as well as a new standard EMBL-Align flat file format. The alignments are stored in the EMBL-Align database and can be queried from the EBI SRS (Sequence Retrieval System) server.

Availability: Webin-Align: http://www.ebi.ac.uk/embl/Submission/align_top.html, EMBL-Align: ftp://ftp.ebi.ac.uk/pub/databases/embl/align, http://srs.ebi.ac.uk/

Contact: align@ebi.ac.uk

* To whom correspondence should be addressed.
Jab1 antagonizes TGF‐β signaling by inducing Smad4 degradation
Authors: Wan Mei , Cao Xuesong , Wu Yalei , Bai Shuting , Wu Liyu , Shi Xingming , Wang Ning , Cao Xu
Published: July 2002

Tumor suppressor Smad4 is the common signaling effector in the transforming growth factor β (TGF‐β) superfamily. Phosphorylated regulatory Smads (R‐Smads) interact with Smad4, and the complex translocates into the nucleus to regulate gene transcription. Proper TGF‐β signaling requires precise control of Smad functions. Smurfs have been shown to mediate the degradation of R‐Smads but not the common‐partner Smad4. We report a novel mechanism of Smad4 degradation. Jab1 interacts directly with Smad4 and induces its ubiquitylation for degradation. Jab1 was initially identified as a co‐activator of c‐Jun, and it also induces degradation of cell cycle inhibitor p27 and tumor suppressor p53. Ectopic expression of Jab1 decreased endogenous Smad4 steady‐state levels. The 26S proteasome inhibitors lactacystin and MG132 reduced the degradation rate of Smad4 protein. Examination of the effects of JAB1‐induced Smad4 degradation indicates that Jab1 inhibited TGF‐β‐induced gene transcription. Our data suggest that Jab1 antagonizes TGF‐β function by inducing degradation of Smad4 through a distinct degradation pathway.
Boundary‐independent polar nonsense‐mediated decay
Authors: Wang Jun , Gudikote Jayanthi P , Olivas O Renee , Wilkinson Miles F
Published: July 2002

Nonsense‐mediated decay (NMD) is an RNA surveillance mechanism that degrades mRNAs containing premature termination (nonsense) codons. The second signal for this pathway in mammalian cells is an intron that must be at least ∼55 nucleotides downstream of the nonsense codon. Although the functional significance of this ‘−55 boundary rule’ is not known, it is widely thought to reflect the important role of an exon junction protein complex deposited just upstream of exon–exon junctions after RNA splicing. Here we report that a T‐cell receptor (TCR)‐β gene did not conform to this rule. Rather than a definitive boundary position, nonsense codons had a polar effect, such that nonsense codons distant from the terminal downstream intron triggered robust NMD and proximal nonsense codons caused modest NMD. We identified a region of the TCR‐β gene that conferred this boundary‐independent polar expression pattern on a heterologous gene. Collectively, our results suggest that TCR‐β transcripts contain one or more sequence elements that elicit an unusual NMD response triggered by a novel second signal that ultimately causes boundary‐independent polar regulation. TCR genes may have evolved this unique NMD response because they frequently acquire nonsense codons during normal development.
The in-vitro activity of moxifloxacin against Legionella species and the effects of medium on susceptibility test results
Authors: Ruckdeschel G. , Dalhoff A.
Published: July 2002

The in-vitro activities of moxifloxacin, ciprofloxacin, erythromycin and rifampicin against 49 Legionella spp. isolates were determined by an agar dilution method with buffered charcoal yeast extract agar containing α-ketoglutarate. Because the inhibitory effects of charcoal in the test media were pronounced (92% for quinolones, 90.5% for rifampicin and 92.5% for erythromycin), the MICs were corrected for the charcoal-bound fraction of the antibiotics. The corrected geometric mean MICs were 0.018 mg/L for moxifloxacin, 0.02 mg/L for ciprofloxacin, 0.27 mg/L for erythromycin and 0.005 mg/L for rifampicin.
The fluid physics of signal perception by mate-tracking copepods
Authors: Yen Jeannette , Weissburg Marc J. , Doall Michael H.
Published: July 2002

Within laboratory–induced swarms of the marine copepodTemora longicornis, the male exhibits chemically mediated trail–following behaviour, concluding with fluid mechanical provocation of the mate–capture response. The location and structure of the invisible trail were determined by examining the specific behaviour of the female copepods creating the signal, the response of the male to her signal, and the fluid physics of signal persistence. Using the distance of the mate–tracking male from the ageing trail of the female, we estimated that the molecular diffusion coefficient of the putative pheromonal stimulant was 2.7 times–5cm2s–1, or 1000 times slower than the diffusion of momentum. Estimates of signal strength levels, using calculations of diffusive properties of odour trails and attenuation rates of fluid mechanical signals, were compared to the physiological and behavioural threshold detection levels. Males find trails because of strong across–plume chemical gradients; males sometimes go the wrong way because of weak along–plume gradients; males lose the trail when the female hops because of signal dilution; and mate–capture behaviour is elicited by suprathreshold flow signals. The male is stimulated by the female odour to accelerate along the trail to catch up with her, and the boundary layer separating the signal from the chemosensitive receptors along the copepod antennule thins. Diffusion times, and hence reaction times, shorten and behavioural orientation responses can proceed more quickly. While ‘perceptive’ distance to the odour signal in the trail or the fluid mechanical signal from the female remains within 1 to 2 body lengths (< 5 mm), the ‘reactive’ distance between males and females was an order of magnitude larger. Therefore, when nearest–neighbour distances are 5 cm or less, as in swarms of 104copepods m–3, mating events are facilitated. The strong similarity in the structure of mating trails and vortex tubes (isotropic, millimetre—centimetre scale, 10:1 aspect ratio, 10 s persistence), indicates that these trails are constrained by the same physical forces that influence water motion in a low Reynolds number fluid regime, where viscosity limits forces to the molecular scale. The exploratory reaches of mating trails appear inscribed within Kolmogorov eddies and may represent a measure of eddy size. Biologically formed mating trails, however, are distinct in their flow velocity and chemical composition from common small–scale turbulent features; and mechanoreceptive and chemoreceptive copepods use their senses to discriminate these differences. Zooplankton are not aimless wanderers in a featureless environment. Their ambit is replete with clues that guide them in their efforts for survival in the ocean.
The genetic epidemiology of multiple sclerosis
Authors: Compston Alastair
Published: July 2002

Epidemiological studies have implicated an interplay between genetic and environmental factors in the aetiology of multiple sclerosis (MS). There is a familial recurrence rate of approximately 15%. Meta–analysis of the recurrence risk shows that the rate is highest overall for siblings, then parents and children, with lower rates in second– and third–degree relatives. Recurrence is highest for monozygotic twins. Conversely, the frequency in adoptees is similar to the population lifetime risk. The age–adjusted risk for half siblings is also less than for full siblings. Recurrence is higher in the children of conjugal pairs with MS than the offspring of single affecteds. These classical genetic observations suggest that MS is a complex trait in which susceptibility is determined by several genes acting independently or epistatically. Comparisons between co–affected sibling pairs provide no evidence for correlation with age or year at onset and mode of presentation or disability. Thus far, the identification of susceptibility genes has proved elusive but genetic strategies are now in place which should illuminate the problem. The main dividend will be an improved understanding of the pathogenesis. To date, population studies have demonstrated an association between the class II major histocompatibility complex (MHC) alleles DR15 and DQ6 and their corresponding genotypes. An association with DR4, with or without the primary DR15 link, is seen in some Mediterranean populations. Candidate gene approaches have otherwise proved unrewarding. Four groups of investigators have undertaken a systematic search of the genome. In common with most other complex traits, no major susceptibility gene has been identified but regions of interest have been provisionally identified. These genetic analyses are predicated on the assumption that MS is one disease. Genotypic and phenotypic analyses are beginning to question this assumption. A major part of future studies in the genetics of MS will be to resolve the question of disease heterogeneity.
Genomic imprinting, sibling solidarity and the logic of collective action
Authors: Haig David , Wilkins Jon F.
Published: July 2002

Genomic imprinting has been proposed to evolve when a gene's expression has fitness consequences for individuals with different coefficients of matrilineal and patrilineal relatedness, especially in the context of competition between offspring for maternal resources. Previous models have focused on pre–emptive hierarchies, where conflict arises with respect to resource allocation between present and future offspring. Here we present a model in which imprinting arises from scramble competition within litters. The model predicts paternal–specific expression of a gene that increases an offspring's fractional share of resources but reduces the size of the resource pool, and maternal–specific expression of a gene with opposite effects. These predictions parallel the observation in economic models that individuals tend to underprovide public goods, and that the magnitude of this shortfall increases with the number of individuals in the group. Maternally derived alleles are more willing than their paternally derived counterparts to contribute to public goods because they have a smaller effective group size.
The role of peripheral T–cell deletion in transplantation tolerance
Authors: Wells Andrew D. , Li Xian–Chang , Strom Terry B. , Turka Laurence A.
Published: July 2002

The apoptotic deletion of thymocytes that express self–reactive antigen receptors is the basis of central (thymic) self–tolerance. However, it is clear that some autoreactive T cells escape deletion in the thymus and exist as mature lymphocytes in the periphery. Therefore, peripheral mechanisms of tolerance are also crucial, and failure of these peripheral mechanisms leads to autoimmunity. Clonal deletion, clonal anergy and immunoregulation and/or suppression have been suggested as mechanisms by which ‘inappropriate’ T–lymphocyte responses may be controlled in the periphery. Peripheral clonal deletion, which involves the apoptotic elimination of lymphocytes, is critical for T–cell homeostasis during normal immune responses, and is recognized as an important process by which self–tolerance is maintained. Transplantation of foreign tissue into an adult host represents a special case of ‘inappropriate’ T–cell reactivity that is subject to the same central and peripheral tolerance mechanisms that control reactivity against self. In this case, the unusually high frequency of naive T cells able to recognize and respond against non–self–allogeneic major histocompatibility complex (MHC) antigens leads to an exceptionally large pool of pathogenic effector lymphocytes that must be controlled if graft rejection is to be avoided. A great deal of effort has been directed toward understanding the role of clonal anergy and/or active immunoregulation in the induction of peripheral transplantation tolerance but, until recently, relatively little progress had been made towards defining the potential contribution of clonal deletion. Here, we outline recent data that define a clear requirement for deletion in the induction of peripheral transplantation tolerance across MHC barriers, and discuss the potential implications of these results in the context of current treatment modalities used in the clinical transplantation setting.
Drosophila Separase is required for sister chromatid separation and binds to PIM and THR
Authors: Jäger Hubert , Herzig Alf , Lehner Christian F. , Heidmann Stefan
Published: July 2002

Drosophila PIM and THR are required for sister chromatid separation in mitosis and associate in vivo. Neither of these two proteins shares significant sequence similarity with known proteins. However, PIM has functional similarities with securin proteins. Like securin, PIM is degraded at the metaphase-to-anaphase transition and this degradation is required for sister chromatid separation. Securin binds and inhibits separase, a conserved cysteine endoprotease. Proteolysis of securin at the metaphase-to-anaphase transition activates separase, which degrades a conserved cohesin subunit, thereby allowing sister chromatid separation. To address whether PIM regulates separase activity or functions with THR in a distinct pathway, we have characterized a Drosophila separase homolog (SSE). SSE is an unusual member of the separase family. SSE is only about one-third the size of other separases and has a diverged endoprotease domain. However, our genetic analyses show that SSE is essential and required for sister chromatid separation during mitosis. Moreover, we show that SSE associates with both PIM and THR. Although our work shows that separase is required for sister chromatid separation in higher eukaryotes, in addition, it also indicates that the regulatory proteins have diverged to a surprising degree, particularly in Drosophila.
Virtual micro‐intensity modulated radiation therapy
Authors: Siochi R. Alfredo C.
Published: July 2002

Virtual micro‐intensity modulated radiation therapy (VMIMRT) combines a intensity map with a intensity map, delivered at orthogonal collimator settings. The superposition of these component maps (CM) yields a virtual micro‐intensity map (VMIM) that can be delivered with a 1 cm leaf width MLC. A pair of CMs with optimal delivery efficiency and quality must be chosen, since a given VMIM can be delivered using several different pairs. This is possible since, for each group of four VMIM cells that can be covered by an MLC leaf in either collimator orientation, the minimum intensity can be delivered from either collimator setting. By varying the proportions of the minimum values that go into each CM, one can simultaneously minimize the number of potential junction effects and the number of segments required to deliver the VMIM. The minimization is achieved by reducing high leaf direction gradients in the CMs. Several pseudo‐clinical and random VMIMs were studied to determine the applicability of this new technique. A nine level boost map was also studied to investigate dosimetric and spatial resolution issues. Finally, clinical issues for this technique are discussed.
Phototimer setup for CR imaging
Authors: Christodoulou Emmanuel G. , Goodsitt Mitchell M. , Chan Heang‐Ping , Hepburn Thomas W.
Published: July 2002

A study was performed to investigate the feasibility of using the standard deviation (σ) of the pixel values in a computed radiography (CR) image and a measure of the median incident exposure on the imaging plate (IP) as parameters for setting up phototimers in a CR system. Slabs of Lucite™ 4‐, 6‐, and 8‐in.‐thick were imaged with a CR system at 70, 90, and 125 kVp at various mA s values both with grid and without grid. Incident IP exposures were measured with an ionization chamber. Images were analyzed on a workstation. The σ's in the “flat field” images were found to be approximately related to the mean incident exposure E by the relationship: indicating the quantum‐noise‐limited operation of the system. Derived relationships between the reading sensitivity of the (IP) reader (S number) and σ can be used to obtain images with a specific noise level. At our institution, where a 400 speed screen–film system is used for general radiography and 200 speed for chest radiography, radiologists generally find CR image quality acceptable when for general radiography (50–90 kVp), and for chest radiography (125 kVp). However, factors other than the amount of x‐ray quanta that form the useful image, such as the image processing mode and the amount of collimation, may affect both the sensitivity value and the image quality.
Evaluation of a model‐based treatment planning system for dose computations in the kilovoltage energy range
Authors: Alaei Parham , Gerbi Bruce J. , Geise Richard A.
Published: July 2002

The ability to determine dose distribution and calculate organ doses from diagnostic x rays has become increasingly important in recent years because of relatively high doses in interventional radiology and cardiology procedures. In an attempt to determine the dose from both diagnostic and orthovoltage x rays, we have used a commercial treatment planning system (Pinnacle, ADAC Laboratories, Milpitas, CA) to calculate the doses in phantoms from kilovoltage x rays. The planning system's capabilities for dose computation have been extended to lower energies by the addition of energy deposition kernels in the 20–110 keV range and modeling of the 60, 80, 100, and 120 kVp beams using the system. We compared the dose calculated by the system with that measured using thermoluminescent dosimeters (TLDs) placed in various positions within several phantoms. The phantoms consisted of a cubical solid water phantom, the solid water phantom with added lung and bone inhomogeneities, and the Rando anthropomorphic phantom. Using Pinnacle, a treatment plan was generated using CT scans of each of these phantoms and point doses at the positions of TLD chips were calculated. Comparisons of measured and computed values show an average difference of less than 2% within materials of atomic number less than and equal to that of water. The algorithm, however, does not produce accurate results in and around bone inhomogeneities and underestimates attenuation of x rays by bone by an average of 145%. A modification to the CT number‐to‐density conversion table used by the system resulted in significant improvements in the dose calculated to points beyond bone.
Selection of an optimal neural network architecture for computer‐aided detection of microcalcifications—Comparison of automated optimization techniques
Authors: Gurcan Metin N. , Sahiner Berkman , Chan Heang‐Ping , Hadjiiski Lubomir , Petrick Nicholas
Published: July 2002

Many computer‐aided diagnosis (CAD) systems use neural networks (NNs) for either detection or classification of abnormalities. Currently, most NNs are “optimized” by manual search in a very limited parameter space. In this work, we evaluated the use of automated optimization methods for selecting an optimal convolution neural network (CNN) architecture. Three automated methods, the steepest descent (SD), the simulated annealing (SA), and the genetic algorithm (GA), were compared. We used as an example the CNN that classifies true and false microcalcifications detected on digitized mammograms by a prescreening algorithm. Four parameters of the CNN architecture were considered for optimization, the numbers of node groups and the filter kernel sizes in the first and second hidden layers, resulting in a search space of 432 possible architectures. The area under the receiver operating characteristic (ROC) curve was used to design a cost function. The SA experiments were conducted with four different annealing schedules. Three different parent selection methods were compared for the GA experiments. An available data set was split into two groups with approximately equal number of samples. By using the two groups alternately for training and testing, two different cost surfaces were evaluated. For the first cost surface, the SD method was trapped in a local minimum 91% (392/432) of the time. The SA using the Boltzman schedule selected the best architecture after evaluating, on average, 167 architectures. The GA achieved its best performance with linearly scaled roulette‐wheel parent selection; however, it evaluated 391 different architectures, on average, to find the best one. The second cost surface contained no local minimum. For this surface, a simple SD algorithm could quickly find the global minimum, but the SA with the very fast reannealing schedule was still the most efficient. The same SA scheme, however, was trapped in a local minimum on the first cost surface. Our CNN study demonstrated that, if optimization is to be performed on a cost surface whose characteristics are not known a priori, it is advisable that a moderately fast algorithm such as a SA using a Boltzman cooling schedule be used to conduct an efficient and thorough search, which may offer a better chance of reaching the global minimum.
An experimental comparison of detector performance for computed radiography systems
Authors: Samei Ehsan , Flynn Michael J.
Published: July 2002

The intrinsic resolution, noise, and signal‐to‐noise transfer characteristics of five commercial digital computed radiography (CR) systems were compared using identical experimental methods. The reader/screen combinations evaluated were Agfa ADC‐Compact/MD‐10, Agfa ADC‐Compact/MD‐30, Agfa ADC‐Solo/MD‐10, Agfa ADC‐Solo/MD‐30, Lumisys CR‐2000/MD‐10, Fuji FCR‐9501(HQ)/ST‐Va, Kodak CR‐400/GP‐25, and Kodak CR‐400/HR. Measurements were made at 70 and 115 kVp with 19 mm added aluminum filtration. The presampled modulation transfer functions (MTFs) of the systems were measured using an edge method. The noise power spectra (NPS) were determined by 2D Fourier analysis of uniformly exposed radiographs. The frequency‐dependent detective quantum efficiencies (DQEs) were computed from the MTF, NPS, exposure measurements, and computational estimates of the ideal signal‐to‐noise ratios. Using 70 kVp and 0.1–0.12 mm pixel sizes, spatial frequencies of 2.1, 2.0, 2.2, 1.9, 2.0, 2.0, 2.3, 2.3, and 3.5 cycles/mm were measured at 0.2 MTF for the eight reader/screen combinations, respectively. Using 70 kVp, (0.3 mR), and 0.1–0.12 mm pixel sizes, DQE(0.15) values of 20.3%, 22.9%, 24.6%, 28.6%, 22.2%, 30.0%, 29.5%, and 17.3% were obtained for the eight combinations, respectively. The corresponding values at 115 kVp were 15.9%, 18.5%, 21.5%, 21.8%, 15.3%, 23.1%, 22.3%, and 13.8%, respectively. The findings of the study demonstrate the pixel size, orientation, beam quality, screen, and reader dependencies of image quality in CR systems. The physical performance of the systems having standard‐resolution screens demonstrated similar resolution performance but more notable variations in DQE. The one high‐resolution screen tested had reduced DQE and increased MTF at high frequencies.
Dosimetric parameters for three low‐energy brachytherapy sources using the Monte Carlo N‐Particle code
Authors: DeMarco John J. , Hugo Geoff , Solberg Timothy D.
Published: July 2002

Monte Carlo calculations have been performed for the purpose of characterizing the dosimetric properties of three brachytherapy sources. The three sources are manufactured by Syncor Pharmaceuticals Inc. and consist of two seeds (BT‐125‐1 and BT‐125‐2) and one seed (BT‐103‐3). The BT‐125‐1 and BT‐125‐2 seed consists of a solid palladium and silver core, respectively. A thin layer (0.5 μm) of is adsorbed onto the solid core for each seed and encased within a titanium housing. The BT‐103‐3 seed consists of a central gold marker and four resin balls encased within a titanium housing. A thin layer of is bonded onto each resin ball. The dosimetric properties, including the dose rate constant, radial dose function, and anisotropy were calculated in water according to the TG‐43 protocol using the Monte Carlo N‐Particle code. The dose rate constant was calculated to be and for the BT‐125‐1 and BT‐125‐2 seeds, respectively. A dose rate constant of was calculated for the BT‐103‐3 seed. Radial dose function, calculated to a distance of 10 cm, and an isotropy function, calculated for radii from 0.5 to 7.0 cm, were found to be in close agreement with previously published data.
Acceleration of intensity‐modulated radiotherapy dose calculation by importance sampling of the calculation matrices
Authors: Thieke Christian , Nill Simeon , Oelfke Uwe , Bortfeld Thomas
Published: July 2002

In inverse planning for intensity‐modulated radiotherapy, the dose calculation is a crucial element limiting both the maximum achievable plan quality and the speed of the optimization process. One way to integrate accurate dose calculation algorithms into inverse planning is to precalculate the dose contribution of each beam element to each voxel for unit fluence. These precalculated values are stored in a big dose calculation matrix. Then the dose calculation during the iterative optimization process consists merely of matrix look‐up and multiplication with the actual fluence values. However, because the dose calculation matrix can become very large, this ansatz requires a lot of computer memory and is still very time consuming, making it not practical for clinical routine without further modifications. In this work we present a new method to significantly reduce the number of entries in the dose calculation matrix. The method utilizes the fact that a photon pencil beam has a rapid radial dose falloff, and has very small dose values for the most part. In this low‐dose part of the pencil beam, the dose contribution to a voxel is only integrated into the dose calculation matrix with a certain probability. Normalization with the reciprocal of this probability preserves the total energy, even though many matrix elements are omitted. Three probability distributions were tested to find the most accurate one for a given memory size. The sampling method is compared with the use of a fully filled matrix and with the well‐known method of just cutting off the pencil beam at a certain lateral distance. A clinical example of a head and neck case is presented. It turns out that a sampled dose calculation matrix with only 1/3 of the entries of the fully filled matrix does not sacrifice the quality of the resulting plans, whereby the cutoff method results in a suboptimal treatment plan.
Incorporating multi‐leaf collimator leaf sequencing into iterative IMRT optimization
Authors: Siebers Jeffrey V. , Lauterbach Marc , Keall Paul J. , Mohan Radhe
Published: July 2002

Intensity modulated radiation therapy (IMRT) treatment planning typically considers beam optimization and beam delivery as separate tasks. Following optimization, a multi‐leaf collimator (MLC) or other beam delivery device is used to generate fluence patterns for patient treatment delivery. Due to limitations and characteristics of the MLC, the deliverable intensity distributions often differ from those produced by the optimizer, leading to differences between the delivered and the optimized doses. Objective function parameters are then adjusted empirically, and the plan is reoptimized to achieve a desired deliverable dose distribution. The resulting plan, though usually acceptable, may not be the best achievable. A method has been developed to incorporate the MLC restrictions into the optimization process. Our in‐house IMRT system has been modified to include the calculation of the deliverable intensity into the optimizer. In this process, prior to dose calculation, the MLC leaf sequencer is used to convert intensities to dynamic MLC sequences, from which the deliverable intensities are then determined. All other optimization steps remain the same. To evaluate the effectiveness of deliverable‐based optimization, 17 patient cases have been studied. Compared with standard optimization plus conversion to deliverable beams, deliverable‐based optimization results show improved isodose coverage and a reduced dose to critical structures. Deliverable‐based optimization results are close to the original nondeliverable optimization results, suggesting that IMRT can overcome the MLC limitations by adjusting individual beamlets. The use of deliverable‐based optimization may reduce the need for empirical adjustment of objective function parameters and reoptimization of a plan to achieve desired results.
Comparison of characteristics of photon and electron beams generated by Philips/Elekta and Varian linear accelerators
Authors: Song Haijun , Xiao Ying , Galvin James M.
Published: July 2002

Commissioning data of the common energy of 6 MV photon beams are analyzed for seven Philips/Elekta linacs of five different models: SL 75/5, SL 15, SL 25, SLi Precise, and SLi. The observed beam quality of 67.7%±0.3 agrees with the manufacturer's specification of 67.5%±2% but with a much smaller variation, suggesting the possibility of a more accurate beam quality guideline for acceptance commissioning of these linac models. Field size factors are less uniform, especially for the biggest field size of 40×40 but all agree within 1.1% between the five models. These 6 MV photon beams are also shown to be 0.4 MV harder than the Varian 2100C model. For commissioning electron beams generated by the Philips/Elekta models SL 15, SLi Precise and SLi, guidelines can be found from this work for the following parameters: actual field size at 100 SSD (up to ±0.6%) (different from manufacturer specified values at 95 SSD), and virtual source distance (up to ±0.7%). Significant differences are seen for (up to 3.7 mm), sigma–theta–x, effective source distance, and cone size factor. However, except for where Varian 2100C datasets are not available for comparison, the differences between the different Philips/Elekta models are comparable to those between the same Varian 2100C model linacs\smeasured by us and Watts.
Measuring dose distributions for enhanced dynamic wedges using a multichamber detector array
Authors: Liu H. Helen , Lief Eugene P. , McCullough Edwin C.
Published: July 2002

This paper investigates measuring dose distributions for enhanced dynamic wedges (EDWs) using a commercial multichamber detector array. The technical aspects of using the chamber array, including chamber calibration, selection of measurement parameters, and use of the reference chamber, have been fully investigated. The measurement results from the chamber array were also confirmed by those from the single chamber and radiographic film measurements. The results reported here showed that proper operation of the chamber array is essential to measure dose accurately for the EDW fields; the chamber detector array can be used more efficiently than a single chamber without compromising the dose measurement accuracy.
A filtration method for improving film dosimetry in photon radiation therapy
Authors: Yeo Inhwan J. , Wang C‐K Chris , Burch Sandra E.
Published: July 2002

Successful radiotherapy requires accurate dosimetry for treatment verification. Existing dosimeters such as ion chambers, TLD, and diodes have drawbacks such as relatively long measurement time and poor spatial resolution. These disadvantages become serious problems for dynamic‐wedged beams. Thus the clinical use of dynamic wedges requires an improved dosimetry method. X‐ray film may serve this purpose. However, x‐ray film is not clinically accepted as a dosimeter for photon beams, because it overresponds to photons with energies below about 400 keV. This paper presents and develops a method which was initially proposed by Burch to improve the dose response of x‐ray film in a phantom. The method is based on placing high‐atomic number foils next to the film. The foils are used as filters to preferentially remove low‐energy photons. The optimal film and filter configuration in a phantom was determined using a mathematical scheme derived in this study and a Monte Carlo technique (ITS code). The optimal configuration thus determined is as follows: the filter‐to‐film distance of 6 mm and the filter thickness of 0.15 mm for percent depth‐dose measurement; the distance of 1 cm and the thickness of 0.25 mm for off‐axis (dose) ratio measurement. The configuration was then tested with photon beams from a 4 MV linac. The test result indicates that the in‐phantom dose distribution based on the optimal configuration agrees well with those measured by ion chambers.
The linear no‐threshold response: Why not linearity?
Authors: Sinclair Warren K.
Published: July 2002

ICRP and NCRP recommend risk coefficients for use in radiation protection that are based on a linear quadratic response in the low dose region. This is a derivative of the linear no threshold (LNT) hypothesis with allowance for low dose and dose rate effects. The risk coefficients are derived from the Lifespan Study of the A‐bomb survivors but are supported by many other epidemiological studies some, such as occupational, at low doses. Nevertheless, the risk coefficients are uncertain and range (90% confidence intervals) over a factor of 2–3 above and below the nominal values. Various possible dose responses in the low dose region are considered including those that may result from adaptive responses. Laboratory studies show linearity in some systems to doses as low as 2.5 mGy. Epidemiological studies include several with significant excess risks at 100 mGy or less with at least one at 10 mGy. The linear quadratic response seems, therefore, the most likely response in the very low dose region. Adopting the linear quadratic response in the low dose region does not prevent common sense judgements about dismissing small radiation risks. NCRP defined first a negligible individual risk (1987) and then an individual dose (1993) to encourage common sense judgements in the low dose region. More consideration might be given to dismissing minor risks in common sense applications in radiation protection.
Panoramic radiology quality assessment
Authors: Goldstein Albert
Published: July 2002

A procedure is proposed for performing noninvasive x‐ray quality assessment tests on panoramic radiology equipment. A simple cardboard tube jig eliminates relative motion between the measurement system and the narrow, collimated x‐ray beam. Accurate measurements of beam HVL, x‐ray exposure coefficient of variation and mA linearity may be obtained. Use of the tube jig permits easy and routine monitoring of these important x‐ray parameters as well as consistency checks of tube output. Film/screen contact also should be routinely checked in the clinic.