bluuebunny/crossref_metadata_2025 huggingface dataset:
The Earliest Diagnosis of Acute Myocardial Infarction
Authors: Rozenman Yoseph , Gotsman Mervyn S.
Published: July 2002

Acute myocardial infarction results from the cessation of myocardial blood flow caused by thrombotic occlusion of a coronary artery. Rapid restoration of blood flow to the ischemic myocardium minimizes cardiac damage and improves early and long-term morbidity and mortality. Chest pain is the first symptom of myocardial infarction, but in some patients with silent ischemia, the disease can be diagnosed only in retrospect. In symptomatic patients, myocardial infarction should be accurately and promptly diagnosed so that reperfusion therapy can begin immediately. Electrocardiography is the simplest diagnostic modality. Although regional ST-segment elevation is specific, it is not sensitive. In contrast, new computerized algorithms for electrocardiographic analysis and serial monitoring increase sensitivity without decreasing specificity. In the emergency room, echocardiography is used to diagnose patients with no prior history of coronary artery disease whose electrocardiograms proved nondiagnostic.

Time-consuming perfusion nuclear studies are inferior to echocardiography but may nevertheless enable physicians to diagnose myocardial infarction in the emergency room. Although the presence of excess creatine kinase is a sign of myocardial necrosis, its increase is delayed for a few hours after coronary occlusion. Doctors can diagnose myocardial infarction as early as two hours after coronary occlusion with the help of simpler automatic assays of MB-creatine kinase mass that use monoclonal antibodies. Other investigational markers of myocardial necrosis include myoglobin and troponin. Elevation of a circulating protein marker also signifies established necrosis, but physicians hope to achieve reperfusion through therapy before irreversible damage occurs.
AN URGE TO EXPLAIN THE INCOMPREHENSIBLE: Geoffrey Harris and the Discovery of the Neural Control of the Pituitary Gland
Authors: Raisman G.
Published: July 2002

▪ Abstract  Geoffrey Harris is responsible for our view that the brain controls the endocrine system by an exquisitely regulated pattern of synthesis and release of individual members of a family of peptide hormones. These hormones are carried through a portal vascular system that passes from the hypothalamus to the pituitary gland, where they selectively regulate the secretion of the six anterior pituitary hormones.

This family of hypothalamic hormones is highly conserved in all vertebrates, including humans. They are essential for all aspects of reproduction—courtship, mating, pregnancy and young rearing—and they are responsible for the seasonal regulation of breeding. The hypothalamic control mechanism for reproduction is sexually dimorphic, with a basic female pattern that becomes masculinized under the influence of specific steroid hormones acting during development. Other members of the hypothalamic hormone family specifically regulate the secretion of pituitary growth hormone and the anterior pituitary hormones controlling the functions of the thyroid and adrenal glands. The secretion of the hypothalamic hormones is itself regulated by the feedback of the target gland hormones (such as estrogen and progesterone), which concurrently act on the brain to elicit appropriate behavior patterns.

The hypothalamo-hypophysial axis plays a crucial role in the struggle for the survival of the species. By bringing the endocrine system under the control of the brain, it allows access to external environmental inputs, learned behavior patterns, and the whole of the central integrative machinery needed for the bodily functions to be sensitively and optimally adapted to the ever-changing challenges and opportunities in the outside world.
THE POTENTIAL OF FARNESYLTRANSFERASE INHIBITORS AS CANCER CHEMOTHERAPEUTICS
Authors: Gibbs Jackson B. , Oliff Allen
Published: July 2002

Mutant ras oncogenes and alterations in the mitogenic signaling pathways that they regulate are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. Of the possible approaches to inhibit Ras function, much attention has focused on a posttranslational modification, farnesylation, which is required for the subcellular localization of Ras to the plasma membrane and is critical to Ras cell-transforming activity. Inhibitors of the enzyme that catalyzes Ras farnesylation, farnesyl-protein transferase (FPTase), have been developed. These compounds inhibit the tumorigenic phenotypes of ras-transformed cells and human tumor cells in cell culture and in animal models. Moreover, FPTase inhibitors have not demonstrated toxicity to normal cells in culture or to normal tissues in mice. FPTase inhibitors are among the first small molecule compounds designed from studies of oncogenes that might serve as novel cancer chemotherapeutics.
SATELLITE TOBACCO MOSAIC VIRUS
Authors: Dodds J. Allan
Published: July 2002

▪ Abstract  Satellite tobacco mosaic virus (STMV) is a small, spherical ssRNA virus common in a natural wild plant, Nicotiana glauca or tree tobacco, in southern California and is one of the best-studied satellite viruses. It is the only satellite virus that has rod-shaped viruses (tobamoviruses) for its helper. In addition to describing the general properties of STMV, this review focuses on (a) the structural properties of the virus particle including the RNA within the particle that is partially double stranded; (b) the genetic diversity within the type strain before and after serial passage and between different field isolates; (c) the effect of experimental mutation on infectivity, replication, and symptomatology; and (d) the genetic changes that occur when the satellite virus adapts to different helper tobamoviruses.
Foucault Steals Political Science
Authors: Brass Paul R.
Published: July 2002

The subject matter of what has been traditionally considered central to political science, namely, power and government, has been stolen by Foucault while central trends in the discipline as a whole have departed markedly from serious engagement with those topics. Yet Foucault's discussions and analyses of power and government are so original, so striking in their import not only for the way we do political science, but for our lives, thought, and practices as scholars, that his work ought by now to have become a focal point for the resurrection of these topics and their restoration to centrality in the discipline.
ASSESSMENT OF OCCUPATIONAL EXPOSURES IN COMMUNITY-BASED CASE-CONTROL STUDIES
Authors: McGuire Valerie , Nelson Lorene M. , Koepsell Thomas D. , Checkoway Harvey , Longstreth W. T.
Published: July 2002

▪ Abstract  Assessing occupational exposures in community-based studies is a challenge for investigators because there are no standardized or validated approaches for collecting information regarding occupational history. The strengths and limitations of the methods available for assessing occupational exposures are reviewed. In community-based case-control studies, the prevalence of most chemical agents is low. The common sources of misclassification in these studies are addressed, as are strategies for dealing with misclassification bias. Methods to assess the presence and magnitude of differential reporting by cases and controls are outlined, together with analytic strategies to improve the classification of occupational exposures.
Importance of Monocyte Chemoattractant Protein-1 Pathway in Neointimal Hyperplasia After Periarterial Injury in Mice and Monkeys
Authors: Egashira Kensuke , Zhao Qingwei , Kataoka Chu , Ohtani Kishou , Usui Makoto , Charo Israel F. , Nishida Ken-ichi , Inoue Shujiro , Katoh Makoto , Ichiki Toshihiro , Takeshita Akira
Published: July 2002

Neointimal hyperplasia is a major cause of restenosis after coronary intervention. Because vascular injury is now recognized to involve an inflammatory response, monocyte chemoattractant protein-1 (MCP-1) might be involved in underlying mechanisms of restenosis. In the present study, we demonstrate the important role of MCP-1 in neointimal hyperplasia after cuff-induced arterial injury. In the first set of experiments, placement of a nonconstricting cuff around the femoral artery of intact mice and monkeys resulted in inflammation in the early stages and subsequent neointimal hyperplasia at the late stages. We transfected with an N-terminal deletion mutant of the human MCP-1 gene into skeletal muscles to block MCP-1 activity in vivo. This mutant MCP-1 works as a dominant-negative inhibitor of MCP-1. This strategy inhibited early vascular inflammation (monocyte infiltration, increased expression of MCP-1, and inflammatory cytokines) and late neointimal hyperplasia. In the second set of experiments, the cuff-induced neointimal hyperplasia was found to be less in CCR2-deficient mice than in control CCR2
+/+
mice. The MCP-1/CCR2 pathway plays a central role in the pathogenesis of neointimal hyperplasia in cuffed femoral artery of mice and monkeys. Therefore, the MCP-1/CCR2 pathway can be a therapeutic target for human restenosis after coronary intervention.
An Exploration of How Objectivity Is Practiced in Art
Authors: Hanrahan Siún
Published: July 2002

In the binary economy of art and science, art's subjectivity is widely perceived as undermining its contribution to knowledge. Even when invoked by those with a vested interest in art, the potential ascribed to art within this economy does not do justice to the range and critical power of art. Trans-gressing this art-science binary, the author explores how objectivity is practiced within art and argues that the relationship between art and science is not a matter of boundaries but of intertwined in-flections of understanding.
Aesthetically Evolved Virtual Pets
Authors: Ray Thomas S.
Published: July 2002

The author applies aesthetic, emotional and empathetic selection to a derivative of Karl Sims's Evolved Virtual Creatures. The resulting Creatures can be beautiful or strange and provoke strong reactions in human observers. The author posits that it may therefore be possible to evolve virtual pets to which humans can form strong emotional bonds.
Genetic Art and the Aesthetics of Biology
Authors: Tomasula Steve
Published: July 2002

The creation of Alba, the first mammal genetically engineered to be a work of art, accents the increasing number of artists who take as their medium plants, cells, genes and other biological materials. Like traditional artists, these bioartists raise traditional art issues; but since their work collapses the gap between art and science, representation and biological form, they also marry the rich tradition of manipulating nature for aesthetic reasons, the ethical complexities created by today's biotech revolution and the historical ramifications of applying aesthetic judgment to humans.
Total Reconstruction, PF Movement, and Derivational Order
Authors: Sauerland Uli , Elbourne Paul
Published: July 2002

Theories of total reconstruction have generally supposed that movement can be followed by an undoing operation like LF lowering (May 1977, 1985) or deletion of higher copies (Chomsky 1993). We argue that reconstruction effects can be derived only if the original movement is purely phonological. There are no undoing operations. We present three distinct arguments, based on an interaction between raising and wh-movement in English, facts from agreement with group terms in British English, and multiple scrambling in Japanese. The arguments imply that the T-model is correct in supposing that movement that affects both LF and PF must precede movement that affects only PF.
The Stress of English Words 1968–1998
Authors: Halle Morris
Published: July 2002

The article begins with reflections on the theory of Chomsky and Halle 1968, which constituted a new departure in phonology. The indebtedness of the theory to Chomsky 1951 is noted, and certain inadequacies in the theory are discussed as well as the ways these were overcome in subsequent work, including Idsardi 1992. The revised theory is illustrated with an improved account of English word stress that includes a new treatment of the “Rhythm Rule,” in particular, of contrasts such as ánecdòte vs. eléctròde; vowel shortening in poststress position (e.g., sálivàte (cf. salíva), ínfamous (cf. faámous)); and “weak” syllable effects (Burzio 1994) (e.g., Loómbardy but Lombárdi).
Hierarchical Organization of the Human Auditory Cortex Revealed by Functional Magnetic Resonance Imaging
Authors: Wessinger C. M. , VanMeter J. , Tian B. , Van Lare J. , Pekar J. , Rauschecker J. P.
Published: July 2002

The concept of hierarchical processing—that the sensory world is broken down into basic features later integrated into more complex stimulus preferences—originated from investigations of the visual cortex. Recent studies of the auditory cortex in nonhuman primates revealed a comparable architecture, in which core areas, receiving direct input from the thalamus, in turn, provide input to a surrounding belt. Here functional magnetic resonance imaging (fMRI) shows that the human auditory cortex displays a similar hierarchical organization: pure tones (PTs) activate primarily the core, whereas belt areas prefer complex sounds, such as narrow-band noise bursts.
Rate Limitations of Unitary Event Analysis
Authors: Roy A. , Steinmetz P. N. , Niebur E.
Published: July 2002

Unitary event analysis is a new method for detecting episodes of synchronized neural activity (Riehle, Grüun, Diesmann, & Aertsen, 1997). It detects time intervals that contain coincident firing at higher rates than would be expected if the neurons fired as independent inhomogeneous Poisson processes; all coincidences in such intervals are called unitary events (UEs). Changes in the frequency of UEs that are correlated with behavioral states may indicate synchronization of neural firing that mediates or represents the behavioral state.

We show that UE analysis is subject to severe limitations due to the underlying discrete statistics of the number of coincident events. These limitations are particularly stringent for low (0–10 spikes/s) firing rates. Under these conditions, the frequency of UEs is a random variable with a large variation relative to its mean. The relative variation decreases with increasing firing rate, and we compute the lowest firing rate, at which the 95% confidence interval around the mean frequency of UEs excludes zero.

This random variation in UE frequency makes interpretation of changes in UEs problematic for neurons with low firing rates. As a typical example, when analyzing 150 trials of an experiment using an averaging window 100 ms wide and a 5ms coincidence window, firing rates should be greater than 7 spikes per second.
λ-Opt Neural Approaches to Quadratic Assignment Problems
Authors: Ishii Shin , Niitsuma Hirotaka
Published: July 2002

In this article, we propose new analog neural approaches to combinatorial optimization problems, in particular, quadratic assignment problems (QAPs). Our proposed methods are based on an analog version of the λ-opt heuristics, which simultaneously changes assignments for λ elements in a permutation. Since we can take a relatively large λ value, our new methods can achieve a middle-range search over possible solutions, and this helps the system neglect shallow local minima and escape from local minima. In experiments, we have applied our methods to relatively large-scale (N = 80–150) QAPs. Results have shown that our new methods are comparable to the present champion algorithms; for two benchmark problems, they are obtain better solutions than the previous champion algorithms.
Discriminant Component Pruning: Regularization and Interpretation of Multilayered Backpropagation Networks
Authors: Koene Randal A. , Takane Yoshio
Published: July 2002

Neural networks are often employed as tools in classification tasks. The use of large networks increases the likelihood of the task's being learned, although it may also lead to increased complexity. Pruning is an effective way of reducing the complexity of large networks. We present discriminant components pruning (DCP), a method of pruning matrices of summed contributions between layers of a neural network. Attempting to interpret the underlying functions learned by the network can be aided by pruning the network. Generalization performance should be maintained at its optimal level following pruning. We demonstrate DCP's effectiveness at maintaining generalization performance, applicability to a wider range of problems, and the usefulness of such pruning for network interpretation. Possible enhancements are discussed for the identification of the optimal reduced rank and inclusion of nonlinear neural activation functions in the pruning algorithm.
The New English Keyboard School: A Second “Golden Age”
Authors: Walker Sarah E.
Published: July 2002

The author discusses the musical trajectories of several avant-garde English composers, in particular their increasing attention to works for piano. She analyzes the historical roots of this new movement and its relation to the experimental tradition from which it developed, finding continuities perhaps not often recognized or understood.
A Simple Model of Unbounded Evolutionary Versatility as a Largest-Scale Trend in Organismal Evolution
Authors: Turney Peter D.
Published: July 2002

The idea that there are any large-scale trends in the evolution of biological organisms is highly controversial. It is commonly believed, for example, that there is a large-scale trend in evolution towards increasing complexity, but empirical and theoretical arguments undermine this belief. Natural selection results in organisms that are well adapted to their local environments, but it is not clear how local adaptation can produce a global trend. In this paper, I present a simple computational model, in which local adaptation to a randomly changing environment results in a global trend towards increasing evolutionary versatility. In this model, for evolutionary versatility to increase without bound, the environment must be highly dynamic. The model also shows that unbounded evolutionary versatility implies an accelerating evolutionary pace. I believe that unbounded increase in evolutionary versatility is a large-scale trend in evolution. I discuss some of the testable predictions about organismal evolution that are suggested by the model.
Evolving Control Metabolisms for a Robot
Authors: Ziegler Jens , Banzhaf Wolfgang
Published: July 2002

This article demonstrates a new method of programming artificial chemistries. It uses the emerging capabilities of the system's dynamics for information-processing purposes. By evolution of metabolisms that act as control programs for a small robot one achieves the adaptation of the internal metabolic pathways as well as the selection of the most relevant available exteroceptors. The underlying artificial chemistry evolves efficient information-processing pathways with most benefit for the desired task, robot navigation. The results show certain relations to such biological systems as motile bacteria.
Evolution and Development of a Central Pattern Generator for the Swimming of a Lamprey
Authors: Ijspeert Auke Jan , Kodjabachian Jérôme
Published: July 2002

This article describes the design of neural control architectures for locomotion using an evolutionary approach. Inspired by the central pattern generators found in animals, we develop neural controllers that can produce the patterns of oscillations necessary for the swimming of a simulated lamprey.

This work is inspired by Ekeberg's neuronal and mechanical model of a lamprey [11] and follows experiments in which swimming controllers were evolved using a simple encoding scheme [25, 26]. Here, controllers are developed using an evolutionary algorithm based on the SGOCE encoding [31, 32] in which a genetic programming approach is used to evolve developmental programs that encode the growing of a dynamical neural network. The developmental programs determine how neurons located on a two-dimensional substrate produce new cells through cellular division and how they form efferent or afferent interconnections. Swimming controllers are generated when the growing networks eventually create connections to the muscles located on both sides of the rectangular substrate. These muscles are part of a two-dimensional mechanical simulation of the body of the lamprey in interaction with water.

The motivation of this article is to develop a method for the design of control mechanisms for animal-like locomotion. Such a locomotion is characterized by a large number of actuators, a rhythmic activity, and the fact that efficient motion is only obtained when the actuators are well coordinated. The task of the control mechanism is therefore to transform commands concerning the speed and direction of motion into the signals sent to the multiple actuators. We define a fitness function, based on several simulations of the controller with different commands settings, that rewards the capacity of modulating the speed and the direction of swimming in response to simple, varying input signals. Central pattern generators are thus evolved capable of producing the relatively complex patterns of oscillations necessary for swimming. The best solutions generate traveling waves of neural activity, and propagate, similarly to the swimming of a real lamprey, undulations of the body from head to tail propelling the lamprey forward through water. By simply varying the amplitude of two input signals, the speed and the direction of swimming can be modulated.
MASTERS, THEIR FREED SLAVES, AND THE WAQF IN EGYPT (EIGHTEENTH-TWENTIETH CENTURIES)
Authors: Shaham Ron
Published: July 2002

The study seeks to clarify - on the basis of shari'a court decisions - the exact forms in which freed slaves benefited from waqfs founded by their former masters. The essay also analyses the ways in which gender and color of the freed slave affected his or her entitlement, and the ways in which freed slaves functioned as administrators of waqfs established by their former masters. The main finding of the study is that most of the founders, who were members of the Ottoman-Egyptian elite, were childless. For most of the founders, therefore, there was no real dilemma in deciding how to divide the usufruct of their waqfs among their children and their freed slaves. It was clear to them that, subsequent to their death, their freed slaves would be the sole beneficiaries of their waqfs.
Cosmic Distances
Authors: Mansfeld Jaap
Published: July 2002

In the Doxographi Graeci the preferred short heading of Aët. 2.31 (Greek text below, p. 28) is 'On Distances', though ps.Plutarch has a long heading. This chapter is about the distances of the sun and moon from each other and from the earth (lemmas 1 to 3, in both ps.Plutarch and Stobaeus), and of the real or apparent shape of the heaven relative to its distance from the earth (lemmas 4 and 5, Stobaeus only). Parallels from Ioann. Lydus and Theodoret for what is in ps.Plutarch are given by Diels in apparatu. To the best of my knowledge it has not been noticed that a version of ps.Plutarch's text is preserved in a scholium on the Almagest, which constitutes our earliest evidence for the text. The correctness of Diels' reconstruction is questionable. Though certainty, naturally, is beyond our reach it is quite possible that these two sets of lemmas represent two distinct Aëtian (or proto-Aëtian) chapters. These may have been coalesced by Stobaeus (or Aëtius), while ps.Plutarch abridged the second (or the two nal lemmas) away. These considerations necessitate an inquiry into the parallels that are available, including material from an introduction to Aratus. The vexing question of short versus long(er) chapter headings is also relevant in this context. Furthermore, the contrasting views regarding cosmic distances are not only a feature of the Placita literature with a distant origin in Aristotle, but also, apparently, of the commentary literature on Plato's Timaeus. Arguably in a passage in Plutarch's De facie these two traditions intersect. Finally, a case can be made out for Eudemus not Theophrastus as an intermediary source of Presocratic astronomical data in the Placita.
HAGAR AND ISHMAEL AS LITERARY FIGURES: AN INTERTEXTUAL STUDY
Authors:   Nikaido
Published: July 2002

In this study, the intertextuality of the Hagar narratives (Gen. xvi and xxi 8-21) is explored by way of comparison with three other biblical stories: Abraham's ordeal on Mt. Moriah (the Aqedah), Hannah's story, and Joseph's expulsion from Potiphar's house. The purpose is to demonstrate how the many linguistic, literary, and even redactional links between these texts point to a rationale for the prominence of Hagar and Ishmael as literary figures in Genesis, despite their role as the antagonists of Sarah and Isaac. Like Abraham, Hagar receives a promise of a child but must undergo the ordeal of almost losing that child; and like Hannah, she is persecuted by a rival wife but finds hope when visited by God's messenger. Ishmael in like manner can be compared to Joseph's character in that both are unjustly expelled from their advantageous positions because of their masters' wives, yet prosper in exile. Consequently, despite Hagar and Ishmael's negative status as Sarah's rivals, they are portrayed with literary attributes and motifs which set them apart as heroic figures, no less than the Israelite patriarchs and heroes.
Heterodera glycines Ichinohe, 1952 (Nematoda: Tylenchida) from Argentina. 2. Morphological and morphometrical characterisation of males
Authors: Doucet Marcelo , Lax Paola
Published: July 2002

Males of Heterodera glycines races 1 and 3, collected from two localities in Argentina, were morphologically and morphometrically analysed. Certain morphological characters showed inter- and intrapopulation variability. There were no characters that clearly differentiated the populations studied. Most of the morphometrical characters differed from those known for other populations of the species and showed a reduced variability. No significant differences were observed between the mean values of the two races for most of the morphometrical characters considered.
Damage potential and reproduction of Heterodera avenae on wheat and barley under Saudi field conditions
Authors: Ibrahim Ahmed , Al-Hazmi Ahmad , Al-Yahya Fahad , Alderfasi Ali
Published: July 2002

This study was conducted to determine the effect of H. avenae initial
population densities (Pi) on the yield of wheat (two growing seasons) and
barley (one season) and on nematode reproduction, under Saudi field
conditions. At increasing Pi, H. avenae suppressed (P lessequal 0.05) the
number of spikes, weight of spikes, weight of 1000 kernels, grain yield and
straw yield of wheat and barley. Grain yields were reduced by 40 to 92% for
wheat (during the two seasons) and 17 to 77% for barley. Straw yields were
also reduced, by 50 to 85 for wheat and 30 to 77% for barley. As Pi
increased, final populations of H. avenae increased (P lessequal 0.05) on
both hosts, but the nematode reproduction factor (Rf) decreased. Significant
negative linear regressions were obtained between H. avenae Pi and grain
yield of wheat and barley. Final populations (Pf) were positively correlated
with Pi on wheat and on barley. Rf was negatively correlated with Pi on
wheat and barley. Schadigungspotential und Vermehrung von Heterodera avenae
an Weizen und Gerste unter Freilandbedingungen in Saudiarabien - Die
vorliegende Untersuchung wurde durchgefuhrt, um die Wirkung
unterschiedlicher Ausgangspopulationen (Pi) von Heterodera avenae auf den
Ertrag von Weizen (zwei Vegetationsperioden) und Gerste (eine
Vegetationsperiode) sowie auf die Vermehrung der Nematoden unter
saudiarabishen Freilandbedingungen zu ermitteln. Bei steigender Pi
verminderte (P lessequal 0.05) H. avenae die Anzahl der Ahren, das
Ahrengewicht, das Tausendkorngewicht, den Korn- und den Strohertrag von
Weizen und Gerste. Die Kornertrage wurden bei Weizen (zwei
Vegetationsperioden) um 40-92% vermindert, bei Gerste um 17-77%. Auch die
Strohertrage gingen zuruck, bei Weizen um 50-85% und bei Gerste um 30-77%.
Mit zunehmender Pi stiegen die Endpopulationsdichten von H. avenae bei
beiden Wirtspflanzen an (P lessequal 0.05), doch nahm der Vermehrungsfaktor
(Rf) der Nematoden ab. Zwischen Pi von H. avenae und dem Kornertrag von
Weizen und Gerste wurden signifikante negative Regressionen erhalten. Die
Endpopulationen (Pf) waren an Weizen und Gerste positiv korreliert mit Pi.
Rf war an Weizen und Gerste negativ korreliert mit Pi.
Theories and Methods for a Social History of Historical Events — A Reply to Hermann Rebel
Authors: Suter Andreas
Published: July 2002

My study of the Swiss Peasants' War of 1653 has received four reviews in the United States. I am grateful to Hermann Rebel for supplying another, most unusual review toCentral European History. It is unusual not only in length but also in judgment. Where the other reviews wrote positively about the book, Rebel rejects it completely.

If I read Rebel correctly, his criticism covers four main points. First, he criticizes the book's theoretical point of view, alleging that the call for a “return to historical events in social history” means a return to “histoire événementielle” and would lead to “high antiquarianism.” Second, Rebel criticizes my methodological inferences from this theoretical point: systematic attention to the cultural dimension of human action; the expansion of social history's traditional methods of analysis and perspectives on time (longue durée, temps sociale) to include cultural and anthropological insights (from, i.e., Victor Turner, Mary Douglas, and Clifford Geertz); and the introduction of a “slow-motion” perspective.
Mean thickness and thickness distribution of smectite crystallites
Authors: Mystkowski K. , Środoń J . , Elsass F.
Published: July 2002

A series of smectites was investigated to reveal the thickness distribution of crystallites. The Fourier decomposition technique of Bertaut-Warren-Averbach (MudMaster program) was applied to XRD reflections of <0.2 μm, glycolated Na-clays. It was shown that the thickness distribution is lognormal and the mean thickness ranges from 5.7 to 12.3 nm (3.4 – 7.3 layers). At higher humidities, characteristic of TEM sample preparation, the mean thicknesses decrease, but the differences in mean thickness between samples are preserved. Beidellites have the thickest crystallites. The relationships between the mean thickness, volume-weighted mean thickness and the parameters of the lognormal distribution were established. Calculation of these parameters is possible, using the area and the maximum intensity of the 001 reflection. The influence of the fluctuations of d-spacing on the peak width was shown. Smectite crystallites, dispersed into individual layers during infinite osmotic swelling and rebuilt through coagulation, recover their original mean thickness and thickness distribution.
Copper-doped alumina-pillared montmorillonites as catalysts for oxidation of toluene and xylenes with hydrogen peroxide
Authors: Bahranowski K. , Gąsior M. , Kielski A. , Podobiński J. , Serwicka E. M. , Vartikian L. A. , Wodnicka K.
Published: July 2002

Catalytic properties of Cu-doped alumina-pillared montmorillonite samples have been tested in the liquid phase oxidation of toluene, o-, m-, and p-xylene with hydrogen peroxide. The results show that the clay samples possess significant activity for both the oxidation of methyl groups and hydroxylation of the aromatic ring. Physicochemical characterization of the catalysts using XRD, BET, ESR and ICP-AES techniques show that they are porous materials with Cu species located in the interlayer, present either as isolated Cu2+ ions anchored at alumina pillars or as patches of amorphous CuO. The dependence of the overall yields on the amount of Cu dopant is discussed and explained in terms of the catalyst structural properties.
Petrogenetic implications of Ba-sanidine in the Lionato Tuff (Colli Albani Volcanic District, Central Italy)
Authors: Gaeta Mario
Published: July 2002

A vitric fiamme containing BaO-bearing sanidine (BaO = 11 wt.%) was sampled (via di Fioranello, Rome) in the pyroclastic products of the Lower Flow Unit (LFU) belonging to the Villa Senni Eruption Unit in the Colli Albani Volcanic District (Roman Comagmatic Province, Central Italy). The fiamme of the LFU is essentially made up of glass, in which scarce phenocrysts of BaO-bearing sanidine, leucite and Al2O3-bearing Ca-clinopyroxene occur. In this paper the various parameters controlling barium partitioning between alkali feldspar and LFU liquid, are discussed.
Zr- and LREE-rich titanite from Tre Croci, Vico Volcanic complex
(Latium, Italy)
Authors: Della Ventura G. , Bellatreccia F. , Williams C. T.
Published: July 2002

Titanite occurs in the groundmass of a holocrystalline volcanic ejectum
collected in the pyroclastic rocks of the Vico Volcanic complex at Tre Croci, near
Viterbo, Italy. The host rock is composed of abundant K-feldspar and minor
plagioclase, biotite, clinopyroxene and a feldspathoid (sodalite). Titanite is
typically associated with zirconolite, biotite and Fe-oxides. It has a medium Al
content (Al2O3 +
Fe2O3 = 4–6 wt.%) and contains
significant amounts of Zr and LREE, with a chondrite-
normalised REE pattern similar to those of titanites
from other alkaline rocks. Titanite has been corroded by fluids probably rich in
dissolved F and P during a late alteration stage, with evidence for some
remobilization and redistribution of the REE and
actinide elements.
Posttranslational modifications of recombinant myotube-synthesized human factor IX
Authors: Arruda Valder R. , Hagstrom James N. , Deitch Jeffrey , Heiman-Patterson Terry , Camire Rodney M. , Chu Kirk , Fields Paul A. , Herzog Roland W. , Couto Linda B. , Larson Peter J. , High Katherine A.
Published: July 2002

Recent data demonstrate that the introduction into skeletal muscle of an adeno-associated viral (AAV) vector expressing blood coagulation factor IX (F.IX) can result in long-term expression of the transgene product and amelioration of the bleeding diathesis in animals with hemophilia B. These data suggest that biologically active F.IX can be synthesized in skeletal muscle. Factor IX undergoes extensive posttranslational modifications in the liver, the normal site of synthesis. In addition to affecting specific activity, these posttranslational modifications can also affect recovery, half-life in the circulation, and the immunogenicity of the protein. Before initiating a human trial of an AAV-mediated, muscle-directed approach for treating hemophilia B, a detailed biochemical analysis of F.IX synthesized in skeletal muscle was carried out. As a model system, human myotubes transduced with an AAV vector expressing F.IX was used. F.IX was purified from conditioned medium using a novel strategy designed to purify material representative of all species of rF.IX in the medium. Purified F.IX was analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), N-terminal sequence analysis, chemical γ-carboxyglutamyl analysis, carbohydrate analysis, assays for tyrosine sulfation, and serine phosphorylation, and for specific activity. Results show that myotube-synthesized F.IX has specific activity similar to that of liver-synthesized F.IX. Posttranslational modifications critical for specific activity, including removal of the signal sequence and propeptide, and γ-carboxylation of the N-terminal glutamic acid residues, are also similar, but carbohydrate analysis and assessment of tyrosine sulfation and serine phosphorylation disclose differences. In vivo experiments in mice showed that these differences affect recovery but not half-life of muscle-synthesized F.IX.
Rapid and efficient homing of human CD34+CD38−/lowCXCR4+stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2mnull mice
Authors: Kollet Orit , Spiegel Asaf , Peled Amnon , Petit Isabelle , Byk Tamara , Hershkoviz Rami , Guetta Esther , Barkai Gad , Nagler Arnon , Lapidot Tsvee
Published: July 2002

Stem cell homing into the bone microenvironment is the first step in the initiation of marrow-derived blood cells. It is reported that human severe combined immunodeficient (SCID) repopulating cells home and accumulate rapidly, within a few hours, in the bone marrow and spleen of immunodeficient mice previously conditioned with total body irradiation. Primitive CD34+CD38−/lowCXCR4+ cells capable of engrafting primary and secondary recipient mice selectively homed to the bone marrow and spleen, whereas CD34−CD38−/lowLin− cells were not detected. Moreover, whereas freshly isolated CD34+CD38+/high cells did not home, in vivo stimulation with granulocyte colony-stimulating factor as part of the mobilization process, or in vitro stem cell factor stimulation for 2 to 4 days, potentiated the homing capabilities of cytokine-stimulated CD34+CD38+ cells. Homing of enriched human CD34+ cells was inhibited by pretreatment with anti-CXCR4 antibodies. Moreover, primitive CD34+CD38−/lowCXCR4+cells also homed in response to a gradient of human stromal cell-derived factor 1 (SDF-1), directly injected into the bone marrow or spleen of nonirradiated NOD/SCID mice. Homing was also inhibited by pretreatment of CD34+ cells with antibodies for the major integrins VLA-4, VLA-5, and LFA-1. Pertussis toxin, an inhibitor of signals mediated by Gαiproteins, inhibited SDF-1–mediated in vitro transwell migration but not adhesion or in vivo homing of CD34+ cells. Homing of human CD34+ cells was also blocked by chelerythrine chloride, a broad-range protein kinase C inhibitor. This study reveals rapid and efficient homing to the murine bone marrow by primitive human CD34+CD38−/lowCXCR4+cells that is integrin mediated and depends on activation of the protein kinase C signal transduction pathway by SDF-1.
Circulating factor VIII immune complexes in patients with type 2 acquired hemophilia A and protection from activated protein C–mediated proteolysis
Authors: Nogami Keiji , Shima Midori , Giddings John C. , Hosokawa Kazuya , Nagata Masanori , Kamisue Seiki , Suzuki Hiroshi , Shibata Masaru , Saenko Evgueni L. , Tanaka Ichiro , Yoshioka Akira
Published: July 2002

Factor VIII (FVIII) inhibitor antibodies are classified into 2 groups according to the kinetic pattern of FVIII inactivation. Type 2 antibodies are more commonly observed in patients with acquired hemophilia A and do not completely inhibit FVIII activity; in most cases, substantial levels of circulating FVIII are detected. Three type 2 autoantibodies from patients who had normal levels of FVIII antigen despite having low levels of FVIII activity were studied. The antibodies reacted exclusively with the light chain of FVIII but not with the C2 domain, and their epitopes were therefore ascribed to the regions in the A3-C1 domains. Heavy and light chains of FVIII were detected in plasma-derived immune complexes extracted by using protein G Sepharose. Direct binding assays using anhydro-activated protein C (anhydro-APC), a catalytically inactive derivative of activated protein C (APC) in which the active-site serine is converted to dehydroalanine, were used to examine the relation between immune complexes and APC. The intact FVIII, 80-kd light chain, and 72-kd light chain bound in a dose-dependent manner to anhydro-APC, with Kdvalues of 580, 540, and 310 nM, respectively, whereas no appreciable binding was detected for the heavy chain. The 3 autoantibodies blocked FVIII binding to anhydro-APC by approximately 80% and consequently inhibited APC-induced FVIII proteolytic inactivation. These antibodies also bound to a synthetic peptide, His2009-Val2018, which contains the APC binding site. The findings suggest that binding of type 2 autoantibodies, recognizing residues His2009 to Val2018, protects FVIII from APC-mediated proteolysis and might contribute to the presence of FVIII immune complexes in the circulation.
Lack of dominant-negative effects of a truncated γc on retroviral-mediated gene correction of immunodeficient mice
Authors: Otsu Makoto , Sugamura Kazuo , Candotti Fabio
Published: July 2002

A recent clinical trial of gene therapy for X-linked severe combined immunodeficiency (XSCID) has shown that retroviral-mediated gene correction of bone marrow stem cells can lead to the development of normal immune function. These exciting results have been preceded by successful immune reconstitution in several XSCID mouse models, all carrying null mutations of the common gamma chain (γc). One question not formally addressed by these previous studies is that of possible dominant-negative effects of the endogenous mutant γc protein on the activity of the wild-type transferred gene product. The present work was therefore undertaken to study whether corrective gene transfer was applicable to an XSCID murine model with preserved expression of a truncated γc molecule (Δγc+-XSCID). Gene correction of Δγc+-XSCID mice resulted in the reconstitution of lymphoid development, and preferential repopulation of lymphoid organs by gene-corrected cells demonstrated the selective advantage of γc-expressing cells in vivo. Newly developed B cells showed normalization of lipopolysaccharide-mediated proliferation and interleukin-4 (IL-4)–induced immunoglobulin G1 isotype switching. Splenic T cells and thymocytes of treated animals proliferated normally to mitogens and responded to the addition of IL-2, IL-4, and IL-7, indicating functional reconstitution of γc-sharing receptors. Repopulated thymi showed a clear increase of CD4−/CD8− and CD8+fractions, both dramatically reduced in untreated Δγc+-XSCID mice. These improvements were associated with the restoration of Bcl-2 expression levels and enhanced cell survival. These data indicate that residual expression of the endogenous truncated γc did not lead to dominant-negative effects in this murine model and suggest that patient selection may not be strictly necessary for gene therapy of XSCID.
UVB-induced apoptosis of human dendritic cells: contribution by caspase-dependent and caspase-independent pathways
Authors: Nicolò Chiara , Tomassini Barbara , Rippo Maria Rita , Testi Roberto
Published: July 2002

Dendritic cells (DCs) play a central role in the initiation and regulation of the immune response. The modalities by which DCs are committed to undergo apoptosis are poorly defined. Here it is shown that, unlike death receptor ligands, UVB radiation triggers apoptosis of human DCs very efficiently. UVB exposure is followed by the activation of caspases 8, 9, and 3, by the loss of mitochondrial transmembrane potential (ΔΨm), and by cellular and nuclear fragmentation. Caspase inhibitors substantially prevented the occurrence of cellular and nuclear fragmentation but had no effect on UVB-induced ΔΨm dissipation. Importantly, mature DCs (MDCs) displayed relative resistance to UVB; UVB-induced caspase activation and apoptosis were substantially delayed compared to immature DCs (IDCs). Resistance correlated with the strong up-regulation of cellular FLIP and bcl2 observed in MDCs compared to IDCs.
Activation of multiple cryptic donor splice sites by the common congenital afibrinogenemia mutation, FGA IVS4 + 1 G→T
Authors: Attanasio Catia , de Moerloose Philippe , Antonarakis Stylianos E. , Morris Michael A. , Neerman-Arbez Marguerite
Published: July 2002

Our recent studies on the molecular basis of the autosomal recessive disorder congenital afibrinogenemia showed that the most common mutation is a donor splice mutation in FGA intron 4, IVS4 + 1 G→T, accounting for approximately half of disease alleles. The effect of this mutation on messenger RNA (mRNA) splicing, however, remained unproven. COS-7 cells transfected with a normal plasmid construct produced 100% mRNA molecules with correct splicing, whereas cells transfected with a mutant construct produced multiple aberrant mRNAs, due to utilization of cryptic donor splice sites situated in exon 4 and intron 4. One particular site situated 4 base pairs (bp) downstream of the normal site was used in 85% of transcripts causing afibrinogenemia by a 4-bp insertion-frameshift, leading to premature alpha-chain truncation. Our results confirm the utility of transfecting COS-7 cells to study mRNA splice-site mutations and demonstrate that the common FGA IVS4 variant is a null mutation leading to afibrinogenemia.
Long-term remission of Kaposi sarcoma–associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy
Authors: Corbellino Mario , Bestetti Giovanna , Scalamogna Chiara , Calattini Sara , Galazzi Morena , Meroni Luca , Manganaro Daniele , Fasan Marco , Moroni Mauro , Galli Massimo , Parravicini Carlo
Published: July 2002

Kaposi sarcoma–associated herpesvirus (KSHV)–related multicentric Castleman disease (MCD) is potentially lethal. Growing evidence indicates that, as in Epstein-Barr virus–driven lymphoproliferative disorders after transplantation, KSHV DNA burden in peripheral blood mononuclear cells (PBMCs) may represent the most accurate marker of disease activity. This report describes a patient with human immunodeficiency virus who was followed up clinically and by quantitative polymerase chain reaction for KSHV DNA sequences in PBMCs for more than 3 years following the diagnosis of KSHV-related MCD. Therapy with the antiherpesvirus agent cidofovir, antihuman interleukin-6 antibody BE-8, antiblastic chemotherapy, and combination antiretroviral agents did not achieve durable clinical or virologic remission of the disease. By contrast, administration of the anti-CD20 monoclonal antibody rituximab was well tolerated and allowed a 14-month remission of clinical symptoms and KSHV viremia. Rituximab should be added to the therapeutic armamentarium for KSHV-related MCD.
Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome
Authors: Kang Elizabeth M. , de Witte Moniek , Malech Harry , Morgan Richard A. , Phang Sheila , Carter Charles , Leitman Susan F. , Childs Richard , Barrett A. John , Little Richard , Tisdale John F.
Published: July 2002

To assess the safety and efficacy of nonmyeloablative allogeneic transplantation in patients with HIV infection, a clinical protocol was initiated in patients with refractory hematologic malignancies and concomitant HIV infection. The results from the first 2 patients are reported. The indications for transplantation were treatment-related acute myelogenous leukemia and primary refractory Hodgkin disease in patients 1 and 2, respectively. Only patient 1 received genetically modified cells. Both patients tolerated the procedure well with minimal toxicity, and complete remissions were achieved in both patients, but patient 2 died of relapsed Hodgkin disease 12 months after transplantation. Patient 1 continues in complete remission with undetectable HIV levels and rising CD4 counts, and with both the therapeutic and control gene transfer vectors remaining detectable at low levels more than 2 years after transplantation. These results suggest that nonmyeloablative allogeneic transplantation in the context of highly active antiretroviral therapy is feasible in patients with treatment-sensitive HIV infection.