bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Sarcoplasmic Reticulum (SR) Calcium Content on SR Calcium Release Elicited by Small Voltage-Clamp Depolarizations in Frog Cut Skeletal Muscle Fibers Equilibrated with 20 mM EGTA
Authors: Pape Paul C. , Carrier Nicole
Published: July 2002

Cut muscle fibers from Rana temporaria (sarcomere length, 3.5–3.9 μm; 14–16°C) were mounted in a double Vaseline-gap chamber and equilibrated with an external solution that contained tetraethyl ammonium– gluconate and an internal solution that contained Cs as the principal cation, 20 mM EGTA, and 0 Ca. Fibers were stimulated with a voltage-clamp pulse protocol that consisted of pulses to −70, −65, −60, −45, and −20 mV, each separated by 400-ms periods at −90 mV. The change in total Ca that entered into the myoplasm (Δ[CaT]) and the Ca content of the SR ([CaSR]) were estimated with the EGTA/phenol red method (Pape, P.C., D.-S. Jong, and W.K. Chandler. 1995. J. Gen. Physiol. 106:259–336). Fibers were stimulated with the pulse protocol, usually every 5 min, so that the resting value of [CaSR] decreased from its initial value of 1,700–2,300 μM to values near or below 100 μM after 18–30 stimulations. Three main findings for the voltage pulses to −70, −65, and −60 mV are: (a) the depletion-corrected rate of Ca release (release permeability) showed little change when [CaSR] decreased from its highest level (>1,700 μM) to ∼1,000 μM; (b) as [CaSR] decreased below 1,000 μM, the release permeability increased to a maximum level when [CaSR] was near 300 μM that was on average about sevenfold larger than the values observed for [CaSR] > 1,000 μM; and (c) as [CaSR] decreased from ∼300 μM to <100 μM, the release permeability decreased, reaching half its maximum value when [CaSR] was ∼110 μM on average. It was concluded that finding b was likely due to a decrease in Ca inactivation, while finding c was likely due to a decrease in Ca-induced Ca release.
Imaging Ca2+ Entering the Cytoplasm through a Single Opening of a Plasma Membrane Cation Channel
Authors: Zou Hui , Lifshitz Lawrence M. , Tuft Richard A. , Fogarty Kevin E. , Singer Joshua J.
Published: July 2002

Discrete localized fluorescence transients due to openings of a single plasma membrane Ca2+ permeable cation channel were recorded using wide-field digital imaging microscopy with fluo-3 as the Ca2+ indicator. These transients were obtained while simultaneously recording the unitary channel currents using the whole-cell current-recording configuration of the patch-clamp technique. This cation channel in smooth muscle cells is opened by caffeine (Guerrero, A., F.S. Fay, and J.J. Singer. 1994. J. Gen. Physiol. 104:375–394). The localized fluorescence transients appeared to occur at random locations on the cell membrane, with the duration of the rising phase matching the duration of the channel opening. Moreover, these transients were only observed in the presence of sufficient extracellular Ca2+, suggesting that they are due to Ca2+ influx from the bathing solution. The fluorescence transient is characterized by an initial fast rising phase when the channel opens, followed by a slower rising phase during prolonged openings. When the channel closes there is an immediate fast falling phase followed by a slower falling phase. Computer simulations of the underlying events were used to interpret the time course of the transients. The rapid phases are mainly due to the establishment or removal of Ca2+ and Ca2+-bound fluo-3 gradients near the channel when the channel opens or closes, while the slow phases are due to the diffusion of Ca2+ and Ca2+-bound fluo-3 into the cytoplasm. Transients due to short channel openings have a “Ca2+ spark-like” appearance, suggesting that the rising and early falling components of sparks (due to openings of ryanodine receptors) reflect the fast phases of the fluorescence change. The results presented here suggest methods to determine the relationship between the fluorescence transient and the underlying Ca2+ current, to study intracellular localized Ca2+ handling as might occur from single Ca2+ channel openings, and to localize Ca2+ permeable ion channels on the plasma membrane.
In Vivo Assessment of Local Phosphodiesterase Activity Using Tailored Cyclic Nucleotide–Gated Channels as Camp Sensors
Authors: Rich Thomas C. , Tse Tonia E. , Rohan Joyce G. , Schaack Jerome , Karpen Jeffrey W.
Published: July 2002

Phosphodiesterases (PDEs) catalyze the hydrolysis of the second messengers cAMP and cGMP. However, little is known about how PDE activity regulates cyclic nucleotide signals in vivo because, outside of specialized cells, there are few methods with the appropriate spatial and temporal resolution to measure cyclic nucleotide concentrations. We have previously demonstrated that adenovirus-expressed, olfactory cyclic nucleotide–gated channels provide real-time sensors for cAMP produced in subcellular compartments of restricted diffusion near the plasma membrane (Rich, T.C., K.A. Fagan, H. Nakata, J. Schaack, D.M.F. Cooper, and J.W. Karpen. 2000. J. Gen. Physiol. 116:147–161). To increase the utility of this method, we have modified the channel, increasing both its cAMP sensitivity and specificity, as well as removing regulation by Ca2+-calmodulin. We verified the increased sensitivity of these constructs in excised membrane patches, and in vivo by monitoring cAMP-induced Ca2+ influx through the channels in cell populations. The improved cAMP sensors were used to monitor changes in local cAMP concentration induced by adenylyl cyclase activators in the presence and absence of PDE inhibitors. This approach allowed us to identify localized PDE types in both nonexcitable HEK-293 and excitable GH4C1 cells. We have also developed a quantitative framework for estimating the KI of PDE inhibitors in vivo. The results indicate that PDE type IV regulates local cAMP levels in HEK-293 cells. In GH4C1 cells, inhibitors specific to PDE types I and IV increased local cAMP levels. The results suggest that in these cells PDE type IV has a high Km for cAMP, whereas PDE type I has a low Km for cAMP. Furthermore, in GH4C1 cells, basal adenylyl cyclase activity was readily observable after application of PDE type I inhibitors, indicating that there is a constant synthesis and hydrolysis of cAMP in subcellular compartments near the plasma membrane. Modulation of constitutively active adenylyl cyclase and PDE would allow for rapid control of cAMP-regulated processes such as cellular excitability.
Attitudes toward science among the European public: a methodological analysis
Authors: Pardo Rafael , Calvo Félix
Published: July 2002

Over the past decade, several influential papers examining the relationship between scientific knowledge and attitudes toward science have been published. The 1992 Eurobarometer has been the preferred source of data for analysis, and a number of suggestive conclusions regarding the extent and nature of the links between knowledge and attitudes have been proposed. Summated scales were built through principal component analysis of the attitudinal items and reliability analysis, but little attention has been paid to the content of the attitudinal items and to the metric and conceptual weaknesses of the scales. A more parsimonious revision of the data, carried out here, shows that the measures used are fuzzy and, as a consequence, the empirical support for some published results is very limited. We suggest that more theoretical effort should be devoted to the design of questionnaires and to the combined use of statistical exploratory techniques and qualitative analysis in the interpretation of the data.
Cyclic torsion of elliptic curves
Authors: Nakamura Tetsuo
Published: July 2002

LetEEbe an elliptic curve over a number fieldkksuch thatEndk⁡E\operatorname {End}_{k}E=Z= {\mathbf Z}and letw(k)w(k)denote the number of roots of unity inkk. Ross proposed a question: IsEEisogenous overkkto an elliptic curveE′/kE’/ksuch thatE′(k)torsE’(k)_{tors}is cyclic of order dividingw(k)w(k)? A counter-example of this question is given. We show thatEEis isogenous toE′/kE’/ksuch thatE′(k)tors⊂Z/w(k)2ZE’(k)_{tors}\,\subset {\mathbf Z}/w(k)^2{\mathbf Z}. In caseEEhas complex multiplication andEndk⁡E=Z\operatorname {End}_kE={\mathbf Z}, we obtain certain criteria whether or notEEis isogenous toE′/kE’/ksuch thatE′(k)tors⊂Z/2ZE’(k)_{tors}\,\subset {\mathbf Z}/2{\mathbf Z}.
On exact quadrature formulas for harmonic functions on polyhedra
Authors: Gustafsson Björn , Putinar Mihai
Published: July 2002

A classical quadrature result for analytic functions of a complex variable due to Motzkin and Schoenberg is extended to higher dimensions. A general scheme for integrating on polyhedra solutions of partial differential equations is discussed.
Computation of Nielsen numbers for maps of closed surfaces
Authors: Davey O. , Hart E. , Trapp K.
Published: July 2002

LetXXbe a closed surface, and letf:X→Xf: X \rightarrow Xbe a map. We would like to determineMin(f):=min{|Fixg|:g≃f}.\text {Min}(f):= \mathrm {min} \{ | \mathrm {Fix}g| : g \simeq f\}.Nielsen fixed point theory provides a lower boundN(f)N(f)forMin(f)\text {Min}(f), called the Nielsen number, which is easy to define geometrically and is difficult to compute. We improve upon an algebraic method of calculatingN(f)N(f)developed by Fadell and Husseini, so that the method becomes algorithmic for orientable closed surfaces up to the distinguishing of Reidemeister orbits. Our improvement makes tractable calculations of Nielsen numbers for many maps on surfaces of negative Euler characteristic. We apply the improved method to self-maps on the connected sum of two tori including classes of examples for which no other method is known. We also include the application of this algebraic method to maps on the Klein bottleKK. Nielsen numbers for maps onKKwere first calculated (geometrically) by Halpern. We include a sketch of Halpern’s never published proof thatN(f)=Min(f)N(f)= \text {Min}(f)for all mapsffonKK.
Complete solutions of a family of quartic Thue and index form equations
Authors: Mignotte Maurice , Pethö Attila , Roth Ralf
Published: July 2002

Continuing the recent work of the second author, we prove that the diophantine equation\[fa(x,y)=x4−ax3y−x2y2+axy3+y4=1f_a(x,y)=x^4-ax^3 y-x^2 y^2+axy^3+y^4=1\]for|a|≥3|a|\ge 3has exactly 12 solutions except when|a|=4|a|=4, when it has 16 solutions. Ifα=α(a)\alpha =\alpha (a)denotes one of the zeros offa(x,1)f_a(x,1), then for|a|≥4|a|\ge 4we also find allγ∈Z[α]\gamma \in \Bbb Z[\alpha ]withZ[γ]=Z[α]\Bbb Z[\gamma ]=\Bbb Z[\alpha ].
Some extensions of the Lanczos-Ortiz theory of canonical polynomials in the Tau Method
Authors: Bunchaft M.
Published: July 2002

Lanczos and Ortiz placed the canonical polynomials (c.p.’s) in a central position in the Tau Method. In addition, Ortiz devised a recursive process for determining c.p.’s consisting of a generating formula and a complementary algorithm coupled to the formula. In this paper a) We extend the theory so as to include in the formalism also the ordinary linear differential operators with polynomial coefficientsDDwith negative heighth=maxn∈N{mn−n}>0,\begin{equation*}h=\underset {{n\in N}}{\max } \{m_{n}-n\}>0, \end{equation*}wheremnm_{n}denotes the degree ofDxnDx^{n}. b) We establish a basic classification of the c.p.’sQm(x)Q_{m}(x)and their ordersm∈Mm\in M, asprimaryorderived, depending, respectively, on whether∃n∈N:mn=m\exists n\in \mathbf {N}\colon m_{n}=mor suchnndoes not exist; and we state a classification of the indicesn∈Nn\in \mathbf {N}, asgeneric(mn=n+h)(m_{n}=n+h),singular(mn>n+h)(m_{n}>n+h), andindefinite(Dxn≡0)(Dx^{n}\equiv 0). Then a formula which gives the set of primary orders is proved. c) In the rather frequent case in which all c.p.’s are primary, we establish, for differential operatorsDDwith any heighthh, a recurrency formula which generates bases of the polynomial space and their multiple c.p.’s arising from distinctxnx^{n},n∈Nn\in N, so that no complementary algorithmic construction is needed; the (primary) c.p.’s so produced are classified asgenericorsingular, depending on the indexnn. d) We establish the general properties of the multiplicity relations of the primary c.p.’s and of their associated indices. It becomes clear that Ortiz’s formula generates, forh≥0h\ge 0, the generic c.p.’s in terms of the singular and derived c.p.’s, while singular and derived c.p.’s and the multiples of distinct indices are constructed by the algorithm.
Factorization of the tenth Fermat number
Authors: Brent Richard
Published: July 2002

We describe the complete factorization of the tenth Fermat numberF10F_{10}by the elliptic curve method (ECM).F10F_{10}is a product of four prime factors with 8, 10, 40 and 252 decimal digits. The 40-digit factor was found after about 140 Mflop-years of computation. We also discuss the complete factorization of other Fermat numbers by ECM, and summarize the factorizations ofF5,…,F11F_5, \dots , F_{11}.
On the extraction technique in boundary integral equations
Authors: Schwab C. , Wendland W.
Published: July 2002

In this paper we develop and analyze a bootstrapping algorithm for the extraction of potentials and arbitrary derivatives of the Cauchy data of regular three–dimensional second order elliptic boundary value problems in connection with corresponding boundary integral equations. The method rests on the derivatives of the generalized Green’s representation formula, which are expressed in terms of singular boundary integrals as Hadamard’s finite parts. Their regularization, together with asymptotic pseudohomogeneous kernel expansions, yields a constructive method for obtaining generalized jump relations. These expansions are obtained via composition of Taylor expansions of the local surface representation, the density functions, differential operators and the fundamental solution of the original problem, together with the use of local polar coordinates in the parameter domain. For boundary integral equations obtained by the direct method, this method allows the recursive numerical extraction of potentials and their derivatives near and up to the boundary surface.
A comparison of a posteriori error estimators for mixed finite element discretizations by Raviart-Thomas elements
Authors: Wohlmuth Barbara , Hoppe Ronald
Published: July 2002

We consider mixed finite element discretizations of linear second order elliptic boundary value problems with respect to an adaptively generated hierarchy of possibly highly nonuniform simplicial triangulations. In particular, we present and analyze four different kinds of error estimators: a residual based estimator, a hierarchical one, error estimators relying on the solution of local subproblems and on a superconvergence result, respectively. Finally, we examine the relationship between the presented error estimators and compare their local components.
Double Bruhat cells and total positivity
Authors: Fomin Sergey , Zelevinsky Andrei
Published: July 2002

We study the totally nonnegative varietyG≥0G_{\ge 0}in a semisimple algebraic groupGG. These varieties were introduced by G. Lusztig, and include as a special case the variety of unimodular matrices of a given order whose all minors are nonnegative. The geometric framework for our study is provided by intersectingG≥0G_{\ge 0}with double Bruhat cells (intersections of cells of the two Bruhat decompositions ofGGwith respect to opposite Borel subgroups).
Involutions in Weyl groups
Authors: Kottwitz Robert
Published: July 2002

LetGGbe a split real group with Weyl groupWW. LetEEbe an irreducible representation ofWW. LetVVbe the stable Lie algebra version of the coherent continuation representation ofWW. The main result of this paper is a formula for the multiplicity ofEEinVV. The formula involves the position ofEEin Lusztig’s set∐M(G)\coprod \mathcal M(\mathcal {G}). The paper treats all quasi-split groupsGGas well.
Metric and geometric quasiconformality in Ahlfors regular Loewner spaces
Authors: Tyson Jeremy
Published: July 2002

Recent developments in geometry have highlighted the need for abstract formulations of the classical theory of quasiconformal mappings. We modify Pansu’s generalized modulus to study quasiconformal geometry in spaces with metric and measure-theoretic properties sufficiently similar to Euclidean space. Our basic objects of study are locally compact metric spaces equipped with a Borel measure which is Ahlfors-David regular of dimensionQ>1Q>1, and satisfies the Loewner condition of Heinonen-Koskela. For homeomorphisms between open sets in two such spaces, we prove the equivalence of three conditions: a version of metric quasiconformality, local quasisymmetry and geometric quasiconformality.

We derive from these results several corollaries. First, we show that the Loewner condition is a quasisymmetric invariant in locally compact Ahlfors regular spaces. Next, we show that a properQQ-regular Loewner space,Q>1Q>1, is not quasiconformally equivalent to any subdomain. (In the Euclidean case, this result is due to Loewner.) Finally, we characterize products of snowflake curves up to quasisymmetric/bi-Lipschitz equivalence: two such products are bi-Lipschitz equivalent if and only if they are isometric and are quasisymmetrically equivalent if and only if they are conformally equivalent.
Cointegration and Structural Change: An Application to the U.S. Demand for Money
Authors: Oh Wankeun
Published: July 2002

I perform the cointegration tests for the trivariate model of real monetary aggregates, real personal income, and short‐term interest rate. I find the existence of a long‐run relationship among these three variables. To check the stability of a long‐run money demand relationship, I implement a rank constancy test and CUSUM test. The test results show that real M1 is relatively more stable than other aggregates, but structural change occurred during the 1970s and early 1980s. This is consistent with prior research on money demand.
State Enterprise and Italy's ‘Economic Miracle’: The Ente Nazionale Idrocarburi, 1945-1962
Authors: Carnevali Francesca
Published: July 2002

The Ente Nazionale Idrocarburi (Eni) was one of Italy’s most important state-owned enterprises, a key actor in the country’s transformation from a primarily agrarian to an essentially industrial nation after the Second World War. This article focuses on the history of Eni from its inception in 1953 to the death of its founder, Enrico Mattei, in 1962; it details how, in the context of Italy’s ‘economic miracle’, Eni played an important role both as an agent of economic growth, through the supply of an inexpensive source of energy, and as one of the tools used by the party in power, the Democrazia Cristiana (Christian Democrats), to generate and maintain consensus.
Estimating Dynamic Panel Data Models in Political Science
Authors: Wawro Gregory
Published: July 2002

Panel data are a very valuable resource for finding empirical solutions to political science puzzles. Yet numerous published studies in political science that use panel data to estimate models with dynamics have failed to take into account important estimation issues, which calls into question the inferences we can make from these analyses. The failure to account explicitly for unobserved individual effects in dynamic panel data induces bias and inconsistency in cross-sectional estimators. The purpose of this paper is to review dynamic panel data estimators that eliminate these problems. I first show how the problems with cross-sectional estimators arise in dynamic models for panel data. I then show how to correct for these problems using generalized method of moments estimators. Finally, I demonstrate the usefulness of these methods with replications of analyses in the debate over the dynamics of party identification.
Revealing the factors that promote speciation
Authors: Barraclough Timothy G. , Vogler Alfried P. , Harvey Paul H.
Published: July 2002

What biological attributes of organisms promote speciation, and ultimately, species diversity? This question has a long history of interest, with proposed diversity promoters including attributes such as sexual selection, ecological specialism and dispersability. However, such ideas are difficult to test because the time–scale of processes involved is too great for direct human observation and experimentation. An increasingly powerful solution is to investigate diversity patterns among extant groups to infer the nature of processes operating during the evolution of those groups. This approach relies on the use of robust, phylogenetically based null models to overcome some of the problems inherent in observational inference. We illustrate this area by (i) discussing recent advances in identifying correlates of diversity among higher taxa, and (ii) proposing new methods for analysing patterns in species–level phylogenies, drawing examples from a wide range of organisms.
The foregut of the Mysida (Crustacea, Peracarida) and its phylogenetic relevance
Authors: Kobusch Wulf
Published: July 2002

The foreguts of the mysidsAntarctomysis maxima,A. ohlinii,Hansenomysis antarctica,Heteromysis formosa,Mesopodopsis slabberi,Neomysis integer,Paramysis kessleri,Praunus flexuosus, andSiriella jaltensiswere examined by maceration methods, histological techniques, and scanning electron microscopy. Their morphology, their connection with the midgut glands, and probable function are described and summarized. Previous stomach investigations on mysids and the results of the present study are tabulated; a list of foregut characters, common to all Mysida, is presented. The phylogenetic relevance of these characters within the Malacostraca, especially within the Peracarida, is discussed. Most features are inherited from the ground pattern of the Malacostraca or Eumalacostraca. The bulbous cardia with its dorsal fold, the armature of the lateralia, and the construction of the funnel region are apomorphies for the Mysida. The results suggest that characters of mysidan and other peracaridan foreguts might also be useful in the elucidation of the phylogeny of the Mysida and Peracarida, respectively.
A cladistic phylogeny of the family Patellidae (Mollusca: Gastropoda)
Authors: Ridgway S. A. , Reid D. G. , Taylor J. D. , Branch G. M. , Hodgson A. N.
Published: July 2002

A phylogenetic hypothesis for the patellid limpets is reconstructed by cladistic analysis of morphological characters from 37 species, representing all but one of the living members of the family. Characters included in the analysis are derived from shell shape and microstructure, headfoot and pallial complex, radula and sperm. The species fall into four clades, providing the basis for a new phylogenetic classification into four monophyletic genera:Helcion(four species; southern Africa),Cymbula(eight species; southern Africa, eastern Atlantic, southern Indian Ocean),Scutellastra(17 species; southern and southwestern Africa, Australia, Indo–West Pacific, Eastern Pacific) andPatella(nine species; northeastern Atlantic and Mediterranean). The analysis suggests sister–group relationships betweenHelcionandCymbula, and betweenScutellastraandPatella. In combination with present–day patterns of geographical distribution, this phylogenetic hypothesis is used to discuss the historical biogeography of the Patellidae.Scutellastramay have originated in southern Africa and dispersed across the Pacific, or alternatively may be a primitively Tethyan group. BothHelcionandCymbulaappear to have originated in southern Africa, but threeCymbulaspecies have dispersed respectively to northwest Africa, St Helena and the southern Indian Ocean. The patellids of the northeastern Atlantic form a single clade,Patella(includingP. pellucida), which may have arrived by northward dispersal of an ancestor from southern Africa, or possibly by vicariance of a widespread ancestral Tethyan distribution. The known fossil record of patellids is too fragmentary to permit choice between these alternatives.
Ployandry versus polygyny versus parasites
Authors: Schmid-Hempel Paul , Crozier Ross H.
Published: July 2002

Although social insect colonies are most easily conceptualized as consisting of a single, once–mated queen and her worker progeny, the number of queens per colony and the number of times queens mate varies broadly in ants and other social insects. Various hypotheses have been suggested for the resulting range of breeding systems and social organizations, respectively; one set of hypotheses relating to both queen number and mate number at the same time is a need for genetic variation, especially in relation to disease resistance. We here carry out a comparative analysis using phylogenetic information and, contrary to one non–phylogenetic previous study, we find that polyandry and polygyny are not significantly associated. However, the level of relatedness within colonies, a quantity affected by both polyandry and polygyny, is significantly associated with parasite loads: species with colonies with low relatedness levels have lower parasite loads. Given that, under the variance–reduction principle, selection on queens for mating frequency ought to continue even in polygynous colonies, we suggest that while parasite loads indeed seem to correlate with intra–colony genetic variability, the relationship to polyandry and polygyny may be complex and requires considerably more experimental investigation.
Reconstructing the eyes of Urbilateria
Authors: Arendt Detlev , Wittbrodt Joachim
Published: July 2002

The shared roles ofPax6andSixhomologues in the eye development of various bilaterians suggest that Urbilateria, the common ancestors of all Bilateria, already possessed some simple form of eyes. Here, we re–address the homology of bilaterian cerebral eyes at the level of eye anatomy, of eye–constituting cell types and of phototransductory molecules. The most widespread eye type found in Bilateria are the larval pigment–cup eyes located to the left and right of the apical organ in primary, ciliary larvae of Protostomia and Deuterostomia. They can be as simple as comprising a single pigment cell and a single photoreceptor cell in inverse orientation. Another more elaborate type of cerebral pigment–cup eyes with an everse arrangement of photoreceptor cells is found in adult Protostomia. Both inverse larval and everse adult eyes employ rhabdomeric photoreceptor cells and thus differ from the chordate cerebral eyes with ciliary photoreceptors. This is highly significant because on the molecular level we find that for phototransduction rhabdomeric versus ciliary photoreceptor cells employ divergent rhodopsins and non–orthologous G–proteins, rhodopsin kinases and arrestins. Our comparison supports homology of cerebral eyes in Protostomia; it challenges, however, homology of chordate and non–chordate cerebral eyes that employ photoreceptor cells with non–orthologous phototransductory cascades.
In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone
Authors: Clément Karine , Viguerie Nathalie , Diehn Maximilian , Alizadeh Ash , Barbe Pierre , Thalamas Claire , Storey John D. , Brown Patrick O. , Barsh Greg S. , Langin Dominique
Published: July 2002

Thyroid hormones are key regulators of metabolism that modulate transcription via nuclear receptors. Hyperthyroidism is associated with increased metabolic rate, protein breakdown, and weight loss. Although the molecular actions of thyroid hormones have been studied thoroughly, their pleiotropic effects are mediated by complex changes in expression of an unknown number of target genes. Here, we measured patterns of skeletal muscle gene expression in five healthy men treated for 14 days with 75 μg of triiodothyronine, using 24,000 cDNA element microarrays. To analyze the data, we used a new statistical method that identifies significant changes in expression and estimates the false discovery rate. The 381 up-regulated genes were involved in a wide range of cellular functions including transcriptional control, mRNA maturation, protein turnover, signal transduction, cellular trafficking, and energy metabolism. Only two genes were down-regulated. Most of the genes are novel targets of thyroid hormone. Cluster analysis of triiodothyronine-regulated gene expression among 19 different human tissues or cell lines revealed sets of coregulated genes that serve similar biologic functions. These results define molecular signatures that help to understand the physiology and pathophysiology of thyroid hormone action.

[The list of transcripts corresponding to up-regulated and down-regulated genes is available as a web supplement athttp://www.genome.org.]
Monte Carlo models for dosimetry in photon beam radiotherapy
Authors: Fix Michael K.
Published: July 2002

On the basis of phase space (PS) data Monte Carlo (MC) beam models for a 6 and 15 MV photon beam have been developed. This PS information was used to develop simple point source beam models. Since these models are lacking in flexibility and show limitations in modeling the beam outside the geometric radiation field a multiple source model (MSM) was developed. Original PS data and those reproduced by the MSM are then compared in terms of fluences and mean energies, which all agree within 1%. MC‐calculated primary photon energy spectra are verified by energy spectra derived from transmission measurements. Comparisons of MC‐calculated depth doses and profiles, using original and reproduced PS data, agree within 1% and 1 mm. Deviations from measured doses are within 1.5% and 1 mm. Additionally, the MSM was supplemented with a model of an 80‐leaf MLC. Using this supplemented MSM, dose distributions are calculated in water phantoms. Two test fields for the step‐and‐shoot technique and two realistic fields delivered with dynamic MLC are investigated. MC‐calculated dose profiles are in excellent agreement with measured data from film dosimetry. To assess spectral changes caused by the MLC, energy spectra in portal planes are calculated for moving slits of different widths. The investigation shows an increase in mean photon energy of up to 16% for the 0.25 cm slit compared to the open beam for 6 MV and of up to 6% for 15 MV, respectively. The supplemented MSM has proven to be a powerful tool for investigational and benchmarking purposes and for IMRT treatment planning.
Dose optimization via index‐dose gradient minimization
Authors: Chang Sha X. , Cullip Timothy J. , Rosenman Julian G. , Halvorsen Per H. , Tepper Joel E.
Published: July 2002

This paper presents an iterative optimization algorithm based on gradient minimization of index dose, defined as the product of physical dose and a numerical index. Acting as a template the index distribution is designed to represent the dosimetry that meets the dose volume histogram‐based optimization objectives. The treatment dosimetry is optimized when the uniformity of the index‐dose distribution is maximized. Prior to optimization the user can select all or only some of the beams to be intensity modulated. The remaining unmodulated beams can be either open or wedged photon beams, electron beams, or beams of previous treatments. The optimization result and treatment delivery efficiency can often be enhanced by including not only the IM photon beams but also all suitable fixed‐beams available on the linac in the treatment plan. In addition, the doses from previous treatments can also be considered in the optimization of current treatment. Five clinical examples with different complexities in optimization objective are presented. The effects of two nonoptimization variables, beam setup and initial beam weights, on the quality of the dose optimization are also presented. The results are analyzed in terms of isodose distribution, dose volume histograms, and a dose optimization quality factor. The optimization algorithm, implemented in our in‐house TPS PLanUNC, has been used in clinical application since 1996. The primary advantages of our optimization algorithm include computational efficiency, intensity modulation selection choice, and performance reliability for a wide range of clinical beam setups and optimization objectives.
Optimization of multiple overlapping thin slab acquisition (MOTSA) MRA
Authors: Chen Dongjun
Published: July 2002

This optimization treats 2D and 3D single‐slab Time‐Of‐Flight (TOF) as opposite limiting cases of MOTSA. It was approached from a general theoretical analysis through imaging parameters such as flow velocity, T1 of blood and surrounding tissue, and size of the region of interest. The potential CNR improvement from using magnetization transfer contrast (MTC) in conjunction with the MOTSA sequence was also examined. A mathematical model was built and tested to describe evolution of hydrogen magnetization under radio frequency pulses, and the computer simulations in turn were used to determine an optimized combination of flip angle, repetition time (TR) and slab thickness. A flat slab‐selection profile was used, under the constraints of fixed anatomical coverage, total acquisition time and resolution. Results of phantom and volunteer studies agree with the computer simulation. Conclusions of this study are (1) the flow model used is adequate for imaging the human anterior cerebral arteries, a representative of intracranial arteries; (2) combination of MTC (using a binomial pulse) with MOTSA does not improve CNR; (3) the optimum MOTSA technique has the shortest TR possible, a slab thickness in which flowing blood receives approximately two flips, and a flip angle chosen to yield the maximum vessel‐to‐background CNR for that particular TR and slab thickness.
Evaluation of pre‐ and post‐reconstruction count‐dependent Metz filters for brain PET studies
Authors: Varga J. , Bettinardi V. , Gilardi M. C. , Riddell C. , Castiglioni I. , Rizzo G. , Fazio F.
Published: July 2002

In this study we evaluated pre‐ (PR‐R) and post‐reconstruction (PO‐R) count‐dependent Metz filters for PET brain studies in order to increase signal‐to‐noise ratio. A set of studies using a 3D Hoffman brain phantom was performed at various count levels, and a reference image set was created from extremely high count images. Several combinations of PR‐R and PO‐R filtering were considered to find the optimal means of processing, including: Hann filter alone; PR‐R Metz filter without or with a PO‐R low pass filter; and PO‐R Metz filter without or with a PR‐R low pass filter. A formula was established to correlate the optimal PO‐R Metz filter order with the net counts. Resolution [full width at half‐maximum (FWHM) and full width at tenth maximum (FWTM)], normalized residual mean square differences (NRMSD) between the ideal and the processed images, noise reduction and contrast were used as parameters for the evaluation of the different filter combinations. Resolution is decreased by all filter combinations that can effectively control noise; however, FWTM increases less than FWHM. NRMSD indicates that the use of Hann and (optimal) PO‐R Metz filter is the most powerful combination from among those tested. A close correlation was found between the net counts and the optimal order of the PO‐R Metz filter. At the count levels of clinical studies the PO‐R Metz filter was found to control noise much more effectively and enhance the contrast when compared to the routinely used Hann filter alone, and produced images of better quality.
Beta‐ray imaging surgical scintillation detector with visible light photon counter readout
Authors: MacDonald Lawrence R.
Published: July 2002

Advances in medical imaging and microneurosurgery over the last 20 years have greatly increased the prospect of locating and removing the prominent mass of a brain tumor, yet delineating the tumor boundary on the millimeter scale during surgery remains ambiguous. This thesis presents the development of a scintillation detector that images distributions of beta‐ray radiation concentrated in tumor tissue via an appropriate radiopharmaceutical. A modular design allows detector heads of various sizes to couple to photodetectors via fiber optics. The detectors are hand‐held, maneuverable, and resolve beta‐ray distributions from under 1 mm in extent. Intended use is following the removal of the main neoplasm, and the injection of a tumor specific, beta‐ray labeled radiopharmaceutical such as used in PET. The short beta‐ray range means the detector is sensitive only to surface activity. The aim is to guide a surgeon when removing residual malignant tissue. Images formed with this device allow rapid assay of the tissue bed, and distinction between concentrations of high activity and high background rates. The detector design uses a novel solid‐state photomultiplier, the visible light photon counter (VLPC). The VLPC is an impurity band‐gap avalanche photodiode with high gain (∼25 000) and high quantum efficiency (∼70%) capable of detecting single photons.
The accuracy and reproducibility of a global method to correct for geometric image distortion in the x‐ray imaging chain
Authors: Gronenschild Ed
Published: July 2002

A method to correct for geometric image distortion in the x‐ray imaging chain, so‐called dewarping, has been developed. A global two‐dimensional polynomial model of which the degree is optimized is used. The performance of the method has been tested in a number of experiments using images of a plate with a 1 cm spaced wire grid put against the input screen of the x‐ray image intensifier (14/17/27 cm). Both offline cine film and online video images were analyzed. The accuracy of the dewarp method was derived from the acquired images and from computer‐simulated distorted images. The robustness and reproducibility of the dewarp method was evaluated by means of imaging the grid in various random orientations. Three parameters describing the behavior of the algorithm were considered. One is the reproducibility of the location of a dewarped position. The second parameter is the reproducibility of the distance between two adjacent dewarped positions as a measure of the reproducibility of the size of an object under investigation. The third parameter is the reproducibility of the pixel size in the plane of the calibration plate. The major results are: the reproducibility of the location of a dewarped position was 0.01–0.04 mm for cine film and 0.04–0.07 mm for video images. The coefficient of variation of the distance between two dewarped positions was 0.04%–0.11% for cine film and 0.15%–0.18% for video images. The dewarp algorithm turned out to be fast and accurate and the distortion was removed over the whole image field down to a low random residual level. It was found that a random orientation of the grid did not affect the assessment of the distortion nor its correction. The dewarp method proved to be intrinsically robust and highly reliable. Time instability of the imaging chain was the main source of variability in the dewarp results.
Diagnostic x‐ray spectra: A comparison of spectra generated by different computational methods with a measured spectrum
Authors: Bhat Madhava , Pattison John , Bibbo Giovanni , Caon Martin
Published: July 2002

A number of computer codes, developed using semi‐empirical models, are available to compute x‐ray spectra from a tungsten target for different tube parameters. In this study x‐ray spectra measured with a high‐purity germanium detector are compared with those computed using the empirical models and previously published measured data. The computer codes used to generate the spectra are based on models proposed by Birch et al. and Tucker et al. The measured x‐ray spectra agreed well with the computed x‐ray spectra using the model of Tucker et al. whereas the model of Birch et al. produced a “harder” x‐ray spectrum compared to the measured spectra. Our measured x‐ray spectra compared well with the previously published measured spectral data of Fewell et al.
Specific absorption rate ratio patterns of cylindrical ultrasound transducers for breast tumors
Authors: Lin Win‐Li , Yen Jia‐Yush , Chen Yung‐Yaw , Cheng Kung‐Shan , Shieh Ming‐Jium
Published: July 2002

The purpose of this paper is to examine the optimal driving frequency and to configure the ultrasound energy deposition schema for a various size and location of breast tissues when a portion or the entire cylindrical ultrasound transducer is employed for breast hyperthermia treatments. This work employs a computer simulation program based on an ideal ultrasound power deposition from a cylindrical transducer. The ultrasound power within the breast is assumed to be exponentially attenuated according to the penetration depth of the ultrasound beam and a uniform absorption for the entire breast is also assumed. The distribution of the specific absorption rate (SAR) ratio is employed to determine the heating pattern of a set of given parameters. The control parameters considered are the ultrasound frequency in the breast tissue, the active portion of cylindrical transducer, and the shifting distance between the central axes of the breast and the transducer. The effect of the breast size on the SAR ratio is also considered. Simulation results demonstrate that the breast size, the ultrasound frequency in breast tissue, the shifting distance, and the active portion of the cylindrical transducer are the potential parameters for influencing the distribution of the SAR ratio. High frequencies should be used for the superficial heating treatments and the active portion of the transducer can be changed to obtain a region with an appropriate SAR ratio to cover the treatment region. Low frequencies are used for deep heating treatments and the region of the high SAR ratio can be moved by shifting the transducer and its pattern is varied with the transducer's active portion. The distribution of the SAR ratio indicates the domain of treatable tumor size and tumor depth for a given set of parameters (driving frequency, shifting distance and active portion of the transducer, as well as breast diameter). Findings of this study can be used to know whether or not the tumor is treatable as well as to select the optimal driving frequency and the appropriate active portion of the cylindrical transducer for a treatment, and hopefully to design an appropriate cylindrical ultrasound heating system for breast tumors.
Investigations on intensity‐modulated treatment techniques in conformal radiotherapy
Authors: Stein Jörg
Published: July 2002

The quality of treatment plans and delivery times of different intensity‐modulated treatment techniques were studied (tomotherapy, intensity‐modulated arc therapy, compensators and multileaf‐modulation). Multileaf‐modulation (MLM), i.e., the unidirectional sweep of leaves of a multileaf collimator (MLC), is the best compromise between plan quality and treatment time and is therefore developed further in this work. Several new methods to account for technical limitations of available MLCs were developed, implemented, and verified dosimetrically. These methods include: (1) a technique to describe transmission through different parts of the leaves; (2) synchronization of leaf trajectories to avoid mechanical collisions (adjacent opposing leaves are not generally allowed to pass each other) and underdosages caused by the tongue and groove design; (3) a method to correct for the finite source size and head scatter; (4) a generalized formalism to calculate leaf trajectories for dynamic and “step and shoot” type MLM. Furthermore, design requirements for MLCs were derived. In summary, MLM is the method of choice to deliver intensity‐modulated treatments, which provide dose distributions highly superior to conventional conformal treatments especially in very complex cases. The methods developed in this work allow an accurate and efficient generation of intensity‐modulated beams by MLM for large‐scale clinical applications.
Helical CT reconstruction with longitudinal filtration
Authors: Hu H. , Shen Y.
Published: July 2002

Each of the currently used helical reconstruction algorithms represents one tradeoff selection of the image noise or mA requirement and resultant artifacts versus the width of the section profile. For many applications, the performance tradeoffs different from those existed are desired. In this paper, we present a general framework of incorporating the longitudinal (z) filtration in helical CT reconstruction, which leads to a new class of helical reconstruction algorithms with tunable performance characteristics to suit various applications. The z‐filtering algorithm enables us to derive the performance curve of image noise or mA requirement versus the width of the section profile, whereas the existing helical reconstruction algorithms only represent limited discrete samples of the curve. We demonstrate that using a new helical reconstruction algorithm derived from this general framework, a substantial reduction in image noise or mA requirement can be achieved with a slight increase of FWHM of the section profile. Thus for many applications requiring both compact section profile and low image noise or mA requirement, the new algorithm represents a better tradeoff than both the 180° and 360° interpolation algorithms. The new algorithm also offers the following potential clinical benefits: (1) longer x‐ray tube life; (2) longer scan duration with less x‐ray tube cooling delays—longer volume coverage and/or longer thin‐slice scan; (3) less radiation to patient; (4) less image noise; and (5) less helical artifacts. Initial clinical results are also presented.
Digital x‐ray imaging using amorphous selenium: Reduction of aliasing
Authors: Ji W. G. , Zhao W. , Rowlands J. A.
Published: July 2002

Alias reduction is analyzed with the concept of an equivalent presampling filter, and a mathematical approach is established to find the equivalent presampling filter corresponding to specific digital image processing algorithms. The effects of different sampling period T and sampling aperture τ on aliasing artifacts and on the resultant detective quantum efficiency (DQE) for a self‐scanned, flat‐panel, amorphous selenium detector are obtained. Different effective apertures can be obtained from the same detector by averaging signals over adjacent pixels. It is shown that adding outputs from M adjacent pixels is equivalent to introducing an equivalent presampling filter with special properties. Appropriate selection of the averaging parameters (M and weights) is shown to reduce the aliasing artifact in the resultant image. The effect of incomplete charge collection due to geometrical effects (fill factor) is examined. It is shown that a large fill factor is desirable for aliasing reduction. The relationship between a digital filter applied to the sampled signal and its equivalent presampling analog filter is also established. Analytical formulas for the sampled spectrum of white signal and for the sampled power spectrum of white noise are obtained for aperture functions with a spatially uniform response. These formulas take into accounts aliasing artifacts, signal correlation and aperture function response, and demonstrate the dependence of sampled spectra on T and τ. With these formulas the detective quantum efficiency DQE is derived. It is shown that the resultant DQE depends only on the fill factor and the size of readout electrode but is completely independent of the degree or type of pixel averaging. That is, even though the pixel averaging method reduces aliasing it leaves DQE(ω) unchanged. When significant amplifier noise is present the DQE obtained with the pixel averaging method can be better than those obtained with an analog presampling filter. Finally, it is pointed out that the requirement of reducing aliasing artifacts conflicts with other requirements for a detector such as maximizing modulation transfer function (MTF). A careful and practical compromise has to be made by a detector designer in choosing the extent to which the aliasing artifacts are eliminated.