bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Information Representation with Stable Firing Rates and Chaotic Spatiotemporal Spike Patterns in a Neural Network Model
Authors: Araki Osamu , Aihara Kazuyuki
Published: July 2002

Although various means of information representation in the cortex have been considered, the fundamental mechanism for such representation is not well understood. The relation between neural network dynamics and properties of information representation needs to be examined. We examined spatial pattern properties of mean firing rates and spatiotemporal spikes in an interconnected spiking neural network model. We found that whereas the spatiotemporal spike patterns are chaotic and unstable, the spatial patterns of mean firing rates (SPMFR) are steady and stable, reflecting the internal structure of synaptic weights. Interestingly, the chaotic instability contributes to fast stabilization of the SPMFR. Findings suggest that there are two types of network dynamics behind neuronal spiking: internally-driven dynamics and externally driven dynamics. When the internally driven dynamics dominate, spikes are relatively more chaotic and independent of external inputs; the SPMFR are steady and stable. When the externally driven dynamics dominate, the spiking patterns are relatively more dependent on the spatiotemporal structure of external inputs. These emergent properties of information representation imply that the brain may adopt a dual coding system. Recent experimental data suggest that internally driven and externally driven dynamics coexist and work together in the cortex.
Attention Modulation of Neural Tuning Through Peak and Base Rate
Authors: Nakahara Hiroyuki , Wu Si , Amari Shun-ichi
Published: July 2002

This study investigates the influence of attention modulation on neural tuning functions. It has been shown in experiments that attention modulation alters neural tuning curves. Attention has been considered at least to serve to resolve limiting capacities and to increase the sensitivity to attended stimulus, while the exact functions of attention are still under debate. Inspired by recent experimental results on attention modulation, we investigate the influence of changes in the height and base rate of the tuning curve on the encoding accuracy, using the Fisher information. Under an assumption of stimulus-conditional independence of neural responses, we derive explicit conditions that determine when the height and base rate should be increased or decreased to improve encoding accuracy. Notably, a decrease in the tuning height and base rate can improve the encoding accuracy in some cases. Our theoretical results can predict the effective size of attention modulation on the neural population with respect to encoding accuracy. We discuss how our method can be used quantitatively to evaluate different aspects of attention function.
Equivalence of a Sprouting-and-Retraction Model and Correlation-Based Plasticity Models of Neural Development
Authors: Miller Kenneth D.
Published: July 2002

A simple model of correlation-based synaptic plasticity via axonal sprouting and retraction (Elliott, Howarth, & Shadbolt, 1996a) is shown to be equivalent to the class of correlation-based models (Miller, Keller, & Stryker, 1989), although these were formulated in terms of weight modification of anatomically fixed synapses. Both models maximize the same measure of synaptic correlation, subject to certain constraints on connectivity. Thus, the analyses of the correlation-based models suffice to characterize the behavior of the sprouting-and-retraction model. More detailed models are needed for theoretical distinctions to be drawn between plasticity via sprouting and retraction, weight modification, or a combination.

The model of Elliott et al. involves stochastic search through allowed weight patterns for those that improve correlations. That of Miller et alinstead follows dynamical equations that determine continuous changes of the weights that improve correlations. The identity of these two approaches is shown to depend on the use of subtractive constraint enforcement in the models of Miller et al. More generally, to model the idea that neural development acts to maximize some measure of correlation subject to a constraint on the summed synaptic weight, the constraint must be enforced subtractively in a dynamical model.
The Canonical Form of Nonlinear Discrete-Time Models
Authors: Dreyfus Gérard , Idan Yizhak
Published: July 2002

Discrete-time models of complex nonlinear processes, whether physical, biological, or economical, are usually under the form of systems of coupled difference equations. In analyzing such systems, one of the first tasks is to find a state-space description of the process—that is, a set of state variables and the associated state equations. We present a methodology for finding a set of state variables and a canonical representation of a class of systems described by a set of recurrent discrete-time, time-invariant equations. In the field of neural networks, this is of special importance since the application of standard training algorithms requires the network to be in a canonical form. Several illustrative examples are presented.
Disambiguating Different Covariation Types
Authors: Brody Carlos D.
Published: July 2002

Covariations in neuronal latency or excitability can lead to peaks in spike train covariograms that may be very similar to those caused by spike timing synchronization (see companion article). Two quantitative methods are described here. The first is a method to estimate the excitability component of a covariogram, based on trial-by-trial estimates of excitability. Once estimated, this component may be subtracted from the covariogram, leaving only other types of contributions. The other is a method to determine whether the covariogram could potentially have been caused by latency covariations.
The Continuum of Operating Modes for a Passive Model Neuron
Authors: Kisley Michael A. , Gerstein George L.
Published: July 2002

Whether cortical neurons act as coincidence detectors or temporal integrators has implications for the way in which the cortex encodes information—by average firing rate or by precise timing of action potentials. In this study, we examine temporal coding by a simple passive-membrane model neuron responding to a full spectrum of multisynaptic input patterns, from highly coincident to temporally dispersed. The temporal precision of the model's action potentials varies continuously along the spectrum, depends very little on the number of synaptic inputs, and is shown to be tightly correlated with the mean slope of the membrane potential preceding the output spikes. These results are shown to be largely independent of the size of postsynaptic potentials, of random background synaptic activity, and of shape of the correlated multisynaptic input pattern. An experimental test involving membrane potential slope is suggested to help determine the basic operating mode of an observed cortical neuron.
Blind Separation of a Mixture of Uniformly Distributed Source Signals: A Novel Approach
Authors: Basak Jayanta , Amari Shun-ichi
Published: July 2002

A new, efficient algorithm for blind separation of uniformly distributed sources is proposed. The mixing matrix is assumed to be orthogonal by prewhitening the observed signals. The learning rule adaptively estimates the mixing matrix by conceptually rotating a unit hypercube so that all output signal components are contained within or on the hypercube. Under some ideal constraints, it has been theoretically shown that the algorithm is very similar to an ideal [Formula: see text] convergent algorithm, which is much faster than the existing [Formula: see text] convergent algorithms. The algorithm has been generalized to take care of the noisy signals by adaptively dilating the hypercube in conjunction with its rotation.
Stereo Augmented Reality in the Surgical Microscope
Authors: King A. P. , Edwards P. J. , Maurer C. R. , Cunha D. A. de , Gaston R. P. , Clarkson M. , Hill D. L. G. , Hawkes D. J. , Fenlon M. R. , Strong A. J. , Cox T. C. S. , Gleeson M. J.
Published: July 2002

This paper describes the MAGI (microscope-assisted guided interventions) augmented-reality system, which allows surgeons to view virtual features segmented from preoperative radiological images accurately overlaid in stereo in the optical path of a surgical microscope. The aim of the system is to enable the surgeon to see in the correct 3-D position the structures that are beneath the physical surface. The technical challenges involved are calibration, segmentation, registration, tracking, and visualization. This paper details our solutions to these problems. As it is difficult to make reliable quantitative assessments of the accuracy of augmented-reality systems, results are presented from a numerical simulation, and these show that the system has a theoretical overlay accuracy of better than 1 mm at the focal plane of the microscope. Implementations of the system have been tested on volunteers, phantoms, and seven patients in the operating room. Observations are consistent with this accuracy prediction.
A Study of the Simulated Evolution of the Spectral Sensitivity of Visual Agent Receptors
Authors: Liese Achim , Polani Daniel , Uthmann Thomas
Published: July 2002

In this article we study a model for the evolution of the spectral sensitivity of visual receptors for agents in a continuous virtual environment. The model uses a genetic algorithm (GA) to evolve the agent sensors along with the control of the agents by requiring the agents to solve certain tasks in the simulation environment. The properties of the evolved sensors are analyzed for different scenarios. In particular, it is shown that the GA is able to find a balance between sensor costs and agent performance in such a way that the spectral sensor sensitivity reflects the emission spectrum of the target objects and that the capability of the sensors to evolve can help the agents significantly in adapting to their task.
Price and Niche Wars in a Free-Market Economy of Software Agents
Authors: Kephart Jeffrey O. , Hanson James E. , Sairamesh Jakka
Published: July 2002

One scenario of the future of computation populates the Internet with vast numbers of software agents providing, trading, and using a rich variety of information goods and services in an open, free-market economy. An essential task in such an economy is the retailing or brokering of information: gathering it from the right producers and distributing it to the right consumers. This article investigates one crucial aspect of brokers' dynamical behavior, their price-setting mechanisms, in the context of a simple information-filtering economy.

We consider only the simplest cases in which a broker sets its price and product parameters based solely on the system's current state, without explicit prediction of the future. Analytical and numerical results show that the system's dynamical behavior in such “myopic” cases is generally an unending cycle of disastrous competitive “wars” in price/product space. These in turn are directly attributable to the existence of multiple peaks in the brokers' profitability landscapes, a feature whose generality is likely to extend far beyond our model.
On the Baldwin Effect
Authors: Bull Larry
Published: July 2002

In this article the effects of altering the rate and amount of learning on the Baldwin effect are examined. Using a version of the abstract tunable NK model, it is shown that the adaptation process is sensitive to the rate of learning, particularly as the correlation of the underlying fitness landscape varies. Typically a high learning rate proves most beneficial as landscape correlation decreases. It is also shown that the amount of learning can have a significant effect on the adaptation process, where increased amounts of learning prove beneficial under higher learning rates on uncorrelated landscapes.
The Demise of Non-Communist Parties in North Korea (1945–1960)
Authors: Lankov Andrei N.
Published: July 2002

This article, based on newly declassified material from the Russian archives, deals with the fate of non-Communist parties in North Korea in the 1950s. Like the “people's democracies” in Eastern Europe, North Korea had (and still technically has) a few non-Communist parties. The ruling Communist party included these parties within the framework of a “united front,” designed to project the facade of a multiparty state, to control domestic dissent, and to establish links with parties in South Korea. The article traces the history of these parties under Soviet and local Communist control from the mid-1940s to their gradual evisceration in the 1950s.
LIFE INTERESTS AND INTER-GENERATIONAL TRANSFER OF PROPERTY AVOIDING THE LAW OF SUCCESSION
Authors: Carroll Lucy
Published: July 2002

However highly eulogized as an intellectual and legal achievement, in practice many individuals consider that the Islamic law of succession would, in their particular circumstances, produce an inappropriate distribution of their estate. Several tactics have been utilized to avoid the application of the law of succession to some or all of the property. These tactics are either inconvenient to the donor (hiba) or can no longer be relied upon with confidence (South Asian hiba-bi'l-'iwad and waqf). This essay focuses on less well known transactions involving the transfer of, or the reservation of, rights in the usufruct. Hiba of the corpus combined with a reservation to the donor of rights in the usufruct permits the donor to enjoy the benefits of the property until death, while securing transfer of the property to chosen successors in a manner which completely avoids the law of succession.
Wet Nurses in Early Imperial China
Authors: Lee Jen-Der
Published: July 2002

Wet nurses in early imperial China were chosen from household slaves based on their physical and psychological conditions. A wet nurse would be asked to mind her diet and behavior, with special restrictions on sex and drinks; her duties, besides breastfeeding, often consisted of caring for, and sometimes providing preliminary instruction for, the newborn. Indolent and distrusted wet nurses could be whipped or executed, but loyal and intimate ones could bring themselves and their family material and honorary rewards. It was the honorary rewards that shattered conventional gender and status boundaries and provoked criticism from their contemporaries.
COMPARATIVISM AND SOCIOBIOLOGICAL THEORY
Authors: Martin Luther
Published: July 2002

While the "academic study of religion" is often considered to be synonymous with "comparative religion," little attention has been given by scholars of religion to theories of comparison. When scholars of religion turn to the social sciences, as they often do in matters of theory, they find the situation with respect to comparison is little better. Recent attention to such theoretical reflections on comparative methods among some social scientists have, however, reopened the question of "human universals," themes familiar to scholars of religion from the phenomenology of religions but increasingly eschewed by them as ahistorical, at best, and theologically shaped, at worst. If, however, comparative studies are to avoid metaphysical musings and ethnocentric excesses, they might best proceed on the theoretical basis of natural, species-specific characteristics of human beings and demonstrate the relationships among the biological and cognitive constraints on human beings, on the one hand, and their social and historical constructions, on the other. Whatever else "religion" may be, it is a social fact and human sociality seems to be one "universal" characteristic of human beings about which there seems to be some consensus among representatives of the various sciences. This paper looks at some of the biological and cognitive explanations proposed for human sociality, outlines a social - and parallel religious - typology based on such explanations, and suggests in a preliminary way a "test" for this typological hypothesis against ethnographic/historical data from two ancient but disparate cultures, China and Greece.
Animals in Psychology Education and Student Choice
Authors: Cunningham Paul
Published: July 2002

This article identifies some of the important issues that underlie student-teacher conflicts regarding animal experimentation and dissection in psychology education. Understanding the reasons why students object to animal laboratories, why some teachers may refuse students access to non-animal alternatives, and why other teachers support student choice is an important first step in resolving student-teacher disputes regarding the use of animals in the psychology classroom. The article discusses why establishing an openly declared student choice policy at schools that use animals in psychology education is a reasonable thing to do and describes how a student choice policy works in practice.
The reproductive cycle of Pleurodema thaul (Anura, Leptodactylidae) in central Chile
Authors: Ortiz Juan Carlos , Díaz-Páez Helen
Published: July 2002

The reproductive cycle of Pleurodema thaul is described. Males were analyzed according to their spermatogenic stage using histological sections of their testes. For females we used the size and pigmentation of the ovarian follicles. The results show a partially continuous reproductive cycle. Males produce sperm during almost all the year. Spermatogenesis is initiated in summer (February-March), when the seminiferous tubules contain abundant undifferentiated spermatozoids, which are transformed to spermatozoa as fall advances (MayJune). The first spermatozoa appeared in late May, and spermatogenesis increased from July to September, sometimes to November. Females present bimodal vitellogenic activity. The first vitellogenic phase is initiated in late February with a progressive maturation of the oocytes, reaching the post-vitellogenic stage between June and August. The breeding period is established during these months and continues until December. In September, some females can begin the vitellogenesis, with a second stage that ends in middle December, when the oocytes that were not spawned, pass massively to the atresic stage. The fat bodies show a synchronic increase with the gametogenic activity in both sexes, that coincide with the greater reproductive activity. Fat bodies are likely to be used as energetic reserve for the vitellogenic activity. Resumen. Se describe el ciclo reproductivo de Pleurodema thaul. El ciclo de los machos fue analizado según su estado espermatogénico realizando cortes histológicos de testículos. El ciclo de las hembras se analizó de acuerdo a la variación anual de los tamaños y pigmentación de los folículos ováricos. Los resultados muestran un ciclo reproductivo parcialmente continuo. Los machos producen espermatozoides durante casi todo el año. La espermatogénesis se inicia en verano (febrero-marzo), donde los túbulos seminíferos se encuentran con abundantes espermátidas indiferenciadas, que se transforman en espermatozoides a medida que avanza el otoño (mayo-junio). Los primeros espermatozoides son liberados a mediados de mayo. La espermatogénesis se incrementa de julio a septiembre y se puede extender hasta noviembre. Las hembras presentan actividad vitelogénica bimodal. Una primera onda se inicia a fines de febrero con una maduración progresiva de los oocitos, alcanzando el estado post-vitelogénico entre junio y agosto. El periodo de apareamiento se establece entre estos meses y continua hasta diciembre. En septiembre, algunas hembras parecen reiniciar la vitelogénica, con una segunda onda que concluye a mediados de diciembre, cuando los oocitos que no han sido desovados, pasan masivamente al estado atrésico. En ambos casos, los cuerpos grasos muestran un aumento en forma sincrónica con la actividad gametogénica, coincidiendo con el período de mayor actividad reproductiva, por lo que se estima su utilización como reserva energética para la actividad vitelogénica.
FEMALE CONTROL OF PATERNITY DURING COPULATION: INBREEDING AVOIDANCE IN FERAL CATS
Authors: Ishida Yasuko , Yahara Tetsukazu , Kasuya Eiiti , Yamane Akihiro
Published: July 2002

Although among feral cats, Felis catus, females copulate with multiple males, they do not accept all mounting or copulation attempts by males during their oestrous period. We observed eight female cats over their oestrous periods to examine whether or not female cats control paternity of their offspring in the field. The females were courted by between nine and 19 males, but copulated with only three to nine of them. Firstly, we compared female receptivity to male attempts among the eight females and tested how female traits affect their receptivity. Female receptivity to male attempts varied among the females both at mounting and at copulation. Females were more choosy at the time of copulation than at mounting. Females with a shorter oestrous duration and a lighter body weight tended to accept mounts more frequently than the females with a longer oestrous duration and a higher body weight. Older and lighter females tended to accept copulation more frequently than younger and heavier females. Females courted by fewer males per day also tended to accept copulations more frequently. Secondly, combining behavioural observations and determined kinship, we assessed whether females avoided copulating with their kin. The results showed that female cats avoid inbreeding with their close kin during copulation but not with distant relatives. Copulation attempts by kin males were less frequently accepted than those by nonkin males. Thirdly, we tested whether male age and body weight affect their mating success, but we failed to find any such correlation. These results support the hypothesis that female cats control paternity of their offspring during copulation.
AUDITORY EXPERIENCE DOES NOT SHAPE SEXUAL PREFERENCES FOR SONGS IN FEMALE NORTHERN CARDINALS
Authors: Yamaguchi Ayako
Published: July 2002

Bird song is typically used by males to attract females. As a consequence of the vocal learning process, the acoustic morphology of male songs shows marked geographic variation. Whether females use variation in male songs to choose mates has been controversial (reviewed by Catchpole & Slater, 1995). In some species, the song types that females produce when treated hormonally have been considered to be the song types they prefer in the context of mate choice. To examine this notion, I investigated the song type preferences of female northern cardinals (Cardinalis cardinalis) using a more direct measure, copulation solicitation display. Unlike females of many other species of songbirds in the Temperate zone, female cardinals naturally develop songs by imitating adults just as males do, allowing direct identification of when and what song types are memorized by females for vocal production. I sought to determine if the memory trace formed for vocal performance is identical with the memory trace that guides song type preference in a sexual context, and whether females truly form any song type preference based on auditory experience during the first year of their lives. To address these questions, audio-video playback experiments were carried out on captive-raised adult cardinals whose complete auditory history was known. The results showed that female cardinals did not come to prefer any song type based on experience; they responded equally to all conspecific song types. Thus, memory formed for vocal production in females is not equal to song type preferred in sexual context. The results suggest that variation in song types is not important for mate choice in cardinals.
Heterodera glycines Ichinohe, 1952 (Nematoda: Tylenchida) from Argentina. 1. Morphological and morphometrical characterisation of second-stage juveniles
Authors: Doucet Marcelo , Lax Paola
Published: July 2002

Second-stage juveniles from two populations of Heterodera glycines races 1 and 3 from different areas in Argentina were characterised on the basis of an analysis of morphological and morphometrical characters. Some of the morphological characters assessed were found to be subject to intra- and inter-population variability. It was not possible to detect clear differences between the populations of the two races under consideration. Most of the morphometrical characters showed ranges different from those known for other populations of the species and reduced variability. The analysis of variance revealed significant statistical differences for most of the morphometrical characters studied.
Some observations on the morphology and protein profiles of the slug-parasitic nematodes Phasmarhabditis hermaphrodita and P. neopapillosa (Nematoda: Rhabditidae)
Authors: Hooper David , Wilson Michael , Rowe Janet , Glen David
Published: July 2002

The slug parasitic nematodes Phasmarhabditis hermaphrodita and P. neopapillosa are described and figured including observations with the scanning electron microscope. P. hermaphrodita is a protandrous hermaphrodite and males were not found in most of the cultures derived from slugs. Populations in which males were common were identified as P. neopapillosa. Apart from their mode of reproduction, these two species are morphologically identical. Protein electrophoresis using the Pharmacia PhastSystem or a cellulose acetate system stained for phosphoglucose isomerase resulted in very different patterns for the two species, indicating that their different specific identities are warranted. Quelques observations sur la morphologie et les profils proteiniques des nematodes parasites de limaces Phasmarhabditis hermaphrodita et P. neopapillosa (Nematoda: Rhabditida) - Les nematodes parasites de limaces Phasmarhabditis hermaphrodita et P. neopapillosa sont decrits et illustres notamment en microscopie electronique a balayage. L'electrophorese des proteines a l'aide du Pharmacia PhastSystem ou d'une procedure utilisant un systeme a l'acetate de cellulose colorant la phosphoglucose isomerase definit des profils tres differents chez les deux especes, confirmant ainsi a chacune leur statut d'espece valide.
Effects of chemical composition and temperature of heating on the infrared spectra of Li-saturated dioctahedral smectites. (I) Mid-infrared region
Authors: Madejová J. , Bujdák J. , Petit S. , Komadel P.
Published: July 2002

Infrared spectroscopy in the mid-IR region was used to follow the structural changes occurring in five Li-saturated dioctahedral smectites upon heating. The smectites included three montmorillonites, an Fe-beidellite and a ferruginous smectite. Fixation of Li+ ions in the structure even upon heating at 120°C caused the appearance of an AlMgLiOH-stretching band near 3670 cm–1 in the spectra of all three montmorillonites. This band confirmed the presence of Li(I) in the previously vacant octahedral positions in montmorillonites. No similar band was observed in the spectra of ferruginous heated smectites with prevailing tetrahedral charge. A gradual upward frequency shift and decrease in intensity of the AlAlOH-bending band showed that Li(I) present in the hexagonal cavities causes pronouncedperturbation of this OH-bending mode. The Li(I) present in the octahedral sheets causes small perturbations of the OH-bending mode near 850 cm–1 and activation of a new OH-bending mode near 803 cm–1. Reversible changes in the positions of the stretching Si–O and bending OH bands in the spectra of Fe-beidellite and a ferruginous smectite proved that Li was present in these minerals primarily in the hexagonal holes of the tetrahedral sheets.
Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia
Authors: Aprikyan Andrew A. G. , Liles W. Conrad , Rodger Elin , Jonas Mechthild , Chi Emil Y. , Dale David C.
Published: July 2002

Cyclic neutropenia (CN) is a congenital hematopoietic disorder characterized by remarkably regular oscillations of blood neutrophils from near normal to extremely low levels at 21-day intervals. Recurring episodes of severe neutropenia lead to repetitive and sometimes life-threatening infections. To investigate the cellular mechanism of CN, the ultrastructure and the proliferative and survival characteristics of bone marrow–derived CD34+ early progenitors, CD33+/CD34− myeloid progenitors, and CD15+ neutrophil precursors from CN patients and healthy volunteers were studied. The ultrastructural studies showed profound apoptotic features in bone marrow progenitor cells in CN. Colony-forming assays demonstrated a 75% decrease in the number of early myeloid-committed colonies compared with controls. Long-term culture-initiating cell assays demonstrated a 6-fold increase in production of primitive progenitor cells in CN. To determine whether accelerated apoptosis might account for the underproduction of myeloid progenitors, the hematopoietic subpopulations were labeled with fluorescein isothiocyanate–annexin V and analyzed by flow cytometry. Short-term culture of CN cells resulted in apoptosis of approximately 65% of CD34+ cells, 80% of CD33+/CD34− cells, and more than 70% of CD15+ cells, as compared with 20%, 7%, and 15% apoptosis in respective control subpopulations. Evidence of accelerated apoptosis of bone marrow progenitor cells was observed in all 8 patients participating in the study, regardless of the stage in the CN cycle in which bone marrow aspirations were obtained. Granulocyte colony-stimulating factor therapy of CN patients significantly improved survival of bone marrow progenitor cells. These data indicate that ineffective production of neutrophils is due to accelerated apoptosis of bone marrow myeloid progenitor cells in CN.
ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture
Authors: Hershko Chaim , Konijn Abraham M. , Nick Hans Peter , Breuer William , Cabantchik Zvi Ioav , Link Gabriela
Published: July 2002

ICL670A (formerly CGP 72 670) or 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]- benzoic acid is a tridentate iron-selective synthetic chelator of the bis-hydroxyphenyl-triazole class of compounds. The present studies used selective radioiron probes of hepatocellular and reticuloendothelial (RE) iron stores in hypertransfused rats and iron-loaded heart cells to define the source of iron chelated in vivo by ICL670A and its mode of excretion, to examine its ability to remove iron directly from iron-loaded myocardial cells, and to examine its ability to interact with other chelators through a possible additive or synergistic effect. Results indicate that ICL670A given orally is 4 to 5 times more effective than parenteral deferoxamine (DFO) in promoting the excretion of chelatable iron from hepatocellular iron stores. The pattern of iron excretion produced by ICL670A is quite different from that of DFO and all iron excretion is restricted to the bile regardless of whether it is derived from RE or hepatocellular iron stores. Studies in heart cell cultures have shown a favorable interaction between DFO and ICL670A manifested in improved chelating efficiency of ICL670A, which is most probably explained by an exchange of chelated iron between ICL670A and DFO. These unique chelating properties of ICL670A may have practical implications for current efforts to design better therapeutic strategies for the management of transfusional iron overload.
Telomere length in leukocyte subpopulations of patients with aplastic anemia
Authors: Brümmendorf Tim H. , Maciejewski Jaroslaw P. , Mak Jennifer , Young Neal S. , Lansdorp Peter M.
Published: July 2002

In most human cells, the average length of telomere repeats at the ends of chromosomes provides indirect information about their mitotic history. To study the turnover of stem cells in patients with bone marrow failure syndromes, the telomere length in peripheral blood granulocytes and lymphocytes from patients with aplastic anemia (AA, n = 56) and hemolytic paroxysmal nocturnal hemoglobinuria (n = 6) was analyzed relative to age-matched controls by means of fluorescence in situ hybridization and flow cytometry. The telomere lengths in granulocytes from patients with AA were found to be significantly shorter than those in age-adjusted controls (P = .001). However, surprisingly, telomere length in granulocytes from AA patients who had recovered after immunosuppressive therapy did not differ significantly from controls, whereas untreated patients and nonresponders with persistent severe pancytopenia showed marked and significant telomere shortening. These results support extensive proliferation of hematopoietic stem cells in subgroups of AA patients. Because normal individuals show significant variation in telomere length, individual measurements in blood cells from AA patients may be of limited value. Whether sequential telomere length measurements can be used as a prognostic tool in this group of disorders remains to be clarified.
Molecular basis of biomaterial-mediated foreign body reactions
Authors: Hu Wen-Jing , Eaton John W. , Ugarova Tatiana P. , Tang Liping
Published: July 2002

Despite being inert and nontoxic, implanted biomaterials often trigger adverse foreign body reactions such as inflammation, fibrosis, infection, and thrombosis. With regard to the inflammatory responses to biomaterial implants, it was previously found that a crucial precedent event was the spontaneous adsorption and denaturation of fibrinogen on implant surfaces. It was further found that interactions between the phagocyte integrin Mac-1 (CD11b/CD18) and one short sequence within the fibrinogen D domain (γ190-202; P1) at least partially explained phagocyte accumulation on implant surfaces. However, the reason that adsorbed fibrinogen is proinflammatory—while soluble fibrinogen clearly is not—remained obscure. In this study, therefore, the question of how fibrinogen is converted to a proinflammatory state when adsorbed to biomaterial surfaces is investigated. In soluble fibrinogen, the 13 amino acid P1 sequence was found to be hidden. However, the adsorption and denaturation of fibrinogen on the surfaces of commonly used biomaterials lead to the exposure of P1 and a second neo-epitope, γ377-395 (P2), which also interacts with Mac-1 and is similarly occult in the soluble protein. The extent of biomaterial-mediated P1 and P2 exposure appears directly related to the severity of inflammatory responses to a test panel of biomaterials. Finally, thrombin-mediated conversion of fibrinogen to fibrin also exposes both P1 and P2 epitopes. These observations may help explain both the inflammation caused by many types of implanted biomaterials and that which occurs naturally following thrombotic events.
Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro
Authors: Mow Benjamin M. F. , Chandra Joya , Svingen Phyllis A. , Hallgren Christopher G. , Weisberg Ellen , Kottke Timothy J. , Narayanan Ven L. , Litzow Mark R. , Griffin James D. , Sausville Edward A. , Tefferi Ayalew , Kaufmann Scott H.
Published: July 2002

The adenosine triphosphate binding-site–directed agent STI571 and the tyrphostin adaphostin are undergoing evaluation as bcr/abl kinase inhibitors. The current study compared the effects of these agents on the survival of K562 cells, bcr/abl-transduced FDC-P1 cells, and myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared with healthy donors. Treatment of K562 cells with 10 μM adaphostin resulted in decreased p210bcr/ablpolypeptide levels in the first 6 hours, followed by caspase activation and accumulation of apoptotic cells in less than 12 hours. By 24 hours, 90% of the cells were apoptotic and unable to form colonies. In contrast, 20 μM STI571 caused rapid inhibition of bcr/abl autophosphorylation without p210bcr/abl degradation. Although this was followed by the inhibition of Stat5 phosphorylation and the down-regulation of Bcl-xL and Mcl-1, only 7% ± 3% and 25% ± 9% of cells were apoptotic at 16 and 24 hours, respectively. Instead, the cytotoxic effects of STI571 became more pronounced with prolonged exposure, with IC90values greater than 20 μM and 1.0 ± 0.6 μM after 24 and 48 hours, respectively. Consistent with these results, 24-hour adaphostin exposure inhibited CML granulocyte colony-forming units (CFU-G) (median IC50, 12 μM) but not normal CFU-G (median IC50, greater than 20 μM), whereas 24-hour STI571 treatment had no effect on CML or normal CFU-G. Additional experiments revealed that STI571-resistant K562 cells remained sensitive to adaphostin. Moreover, the combination of STI571 + adaphostin induced more cytotoxicity in K562 cells and in CML CFU-G than either agent alone did. Collectively, these results identify adaphostin as a mechanistically distinct CML-selective agent that retains activity in STI571-resistant cell lines.
Pre- and postnatal parental smoking and wheeze in infancy: cross cultural differences
Authors: Henderson A.J. , Sherriff A. , Northstone K. , Kukla L. , Hruba D. ,   Avon Study of Parents and Children (ALSPAC) Study Team,   European Longitudinal Study of Pregnancy and Childhood (ELSPAC) Co-ordinating Centre
Published: July 2002

In longitudinal cohort studies, the relationships between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses were compared in two geographically defined populations in Avon, UK and Brno and Znojmo in the South Moravian Region of the Czech Republic.

Pregnant females living in defined regions and with expected dates of delivery between defined dates were recruited. Females completed self-report questionnaires during pregnancy and when their infant was 6 months old. For this analysis, responses to questions about smoking during pregnancy, environmental tobacco smoke (ETS) exposure and reported wheezing illnesses of infants at 6 months after birth were used. Odds ratios for wheeze in relation to the smoking variables were calculated with adjustment for potential confounding effects.

The prevalence of smoking during pregnancy was higher in Avon (17.5%) than the Czech Republic (7.1%). Exposure of infants to ETS during the first 6 months after birth was also reported to be higher in Avon (35.5%) than the Czech Republic (9.7%). The prevalence of reported wheezing by 6 months of age was 21.4% in Avon and 10.3% in Brno and Znojmo. In Avon, there was a significant relationship between infant wheeze and maternal smoking during pregnancy (odds ratio (95% confidence interval) 1.30 (1.09–1.56), p=0.004) but not with environmental exposure after birth (1.11 (0.98–1.25)). In contrast, in Brno and Znojmo in the Czech Republic, there was a significant relationship between infant wheeze and ETS exposure (1.66 (1.17–2.36), p=0.04) but not with maternal smoking during pregnancy (0.99 (0.64–1.55)).

This study demonstrated an apparent difference in the associations between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses in two populations with different smoking prevalence. The relationships were independent of a number of potential confounding variables that have been associated with infant wheezing. Possible explanations of these observations include dose-related effects of prenatal and postnatal tobacco smoke exposure of infants.
Symptoms of asthma, bronchial responsiveness and atopy in immigrants and emigrants in Europe
Authors: Tobias A. , Soriano J.B. , Chinn S. , Anto J.M. , Sunyer J. , Burney P.
Published: July 2002

Migration studies on asthma may provide information on its environmental causes. The European Community Respiratory Health Survey has potential advantages due to the number of countries involved, standardized collection of information, assessment of directionality of migration, and availability of physiological data on bronchial responsiveness and atopy.

Prevalence rates of symptoms associated with asthma were compared for immigrants, emigrants and nonmigrants living in centres mostly in western Europe. Similar analyses were carried out for bronchial responsiveness (provocative concentration causing a 20% fall in forced expiratory volume in one second and slope) and atopy. Medication and use of health services were also explored.

Overall, 1,678 (8.6%) of 19,516 participants were immigrants in the 18 countries participating in the study, of whom 581 were emigrants from one of the participating countries. Rates of asthma symptoms were higher in immigrants (odds ratio (OR): 1.21, 95% confidence interval (CI): 1.00–1.51) and emigrants (OR: 1.31, 95% CI: 0.96–1.51) compared to nonmigrants after controlling for area, sex, age and smoking status. However, bronchial responsiveness and atopy were equally distributed between immigrants, emigrants and nonmigrants. Use of health services was observed to be similar in migrants and nonmigrants with asthma.

In the European Community Respiratory Health Survey, migrants reported more asthma symptoms, but had similar bronchial responsiveness, atopy, and use of health services when compared with the nonmigrant population.
Inspiratory flow limitation during sleep in pre-eclampsia: comparison with normal pregnant and nonpregnant women
Authors: Connolly G. , Razak A.R.A. , Hayanga A. , Russell A. , McKenna P. , McNicholas W.T.
Published: July 2002

Self-reported snoring is common in pregnancy, particularly in females with pre-eclampsia. The prevalence of inspiratory flow limitation during sleep in pre-eclamptic females was objectively assessed and compared with normal pregnant and nonpregnant females.

Fifteen females with pre-eclampsia were compared to 15 females from each of the three trimesters of pregnancy, as well as to 15 matched nonpregnant control females (total study population, 75 subjects). All subjects had overnight monitoring of respiration, oxygen saturation, and blood pressure (BP).

No group had evidence of a clinically significant sleep apnoea syndrome, but patients with pre-eclampsia spent substantially more time (31±8.4% of sleep period time, mean±sd) with evidence of inspiratory flow limitation compared to 15.5±2.3% in third trimester subjects and <5% in the other three groups (p=0.001). In the majority of pre-eclamptics, the pattern of flow limitation was of prolonged episodes lasting several minutes without associated oxygen desaturation. As expected, systolic and diastolic BPs were significantly higher in the pre-eclamptic group (p<0.001), but all groups showed a significant fall (p≤0.05) in BP during sleep.

Inspiratory flow limitation is common during sleep in patients with pre-eclampsia, which may have implications for the pathophysiology and treatment of this disorder.
Treatment of obstructive sleep apnoea with nasal continuous positive airway pressure in stroke
Authors: Wessendorf T.E. , Wang Y-;M. , Thilmann A.F. , Sorgenfrei U. , Konietzko N. , Teschler H.
Published: July 2002

The prevalence of obstructive sleep apnoea (OSA) following stroke is high and OSA is associated with increased morbidity, mortality and poor functional outcome. Nasal continuous positive airway pressure (nCPAP) is the treatment of choice for OSA, but its effects in stroke patients are unknown.

The effectiveness and acceptance of treatment with nCPAP in 105 stroke patients with OSA, admitted to rehabilitation was prospectively investigated. Subjective wellbeing was measured with a visual analogue scale in 41 patients and 24-;h blood pressure was determined in 16 patients before and after 10 days of treatment. Differences were compared between patients who did and did not accept treatment.

There was an 80% reduction of respiratory events with concomitant increase in oxygen saturation and improvement in sleep architecture. No serious side-effects were noticed. Seventy-four patients (70.5%) continued treatment at home. Nonacceptance was associated with a lower functional status, as measured by the Barthel Index, and the presence of aphasia. Ten days after initiation of nCPAP, compliant users showed a clear improvement in wellbeing (differences in visual analogue scale (ΔVAS) mean±sd 26±26 mm)versusnoncompliant patients (ΔVAS 2±25 mm, p=0.021). Only the compliant group had a reduction in mean nocturnal blood pressure (ΔBP; −8±7.3 mmHgversus0.8±8.4 mmHg, p=0.037).

Stroke patients with obstructive sleep apnoea can be treated effectively with nasal continuous positive airway pressure and show a similar improvement and primary acceptance to obstructive sleep apnoea patients without stroke. Continuous positive airway pressure acceptance is associated with improved wellbeing and decreased nocturnal blood pressure.
Increasing prevalence of bronchial hyperresponsiveness in three selected areas in East Germany
Authors: Frye C. , Heinrich J. , Wjst M. , Wichmann H-E.
Published: July 2002

The prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergic rhinitis in children was lower in East Germany compared to West Germany. The reasons for this difference are still not understood. This study tested the hypothesis that prevalence of BHR increased in East German children after reunification.

Two consecutive cross-sectional surveys of schoolchildren aged 8–14 yrs from three communities in East Germany were carried out in 1992–1993 and 1995–1996. A subsample of 530 and 790 children with complete lung function and cold air challenge data was analysed.

The prevalence of BHR increased from 6.4% in 1992–1993 to 11.6% in 1995–1996 (odds ratio (OR): 2.0, 95% confidence interval (CI): 1.3–3.0, adjusted for age, sex, season, community and parental education). No changes were found for asthma, allergic rhinitis or allergic sensitization. In contrast, physician diagnosed bronchitis, pneumonia and frequent colds decreased significantly. The observed increase in the prevalence of BHR was reduced (OR: 1.5, 95% CI: 0.95–2.3) after adjustment for several indoor factors.

In conclusion, while the prevalence of nonallergic respiratory diseases seems to decrease, the prevalence of bronchial hyperresponsiveness might be a first indicator of the suspected increase of asthma prevalence in East Germany. The present results give indirect evidence, that less respiratory infections may be associated with higher bronchial hyperresponsiveness.
Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF
Authors: Navarro J. , Rainisio M. , Harms H.K. , Hodson M.E. , Koch C. , Mastella G. , Strandvik B. , McKenzie S.G.
Published: July 2002

The European Epidemiologic Registry of Cystic Fibrosis began collecting longitudinal data on European cystic fibrosis patients in 1994. A cross-sectional analysis was performed to identify the factors associated with low values of % predicted forced expiratory volume in one second (FEV1) upon patient enrolment.

Data from 7,010 patients aged ≥6 yrs were included. Clinical conditions, microbiological isolates and medications reported at enrolment or within the following 180 days were analysed for age-specific associations.

Factors associated with FEV1that were lower by >10% of pred values were: lower weight for age percentiles, haemoptysis, pneumothorax, pulmonary symptoms at presentation,Pseudomonas aeruginosa,Burkholderia cepacia, oral corticosteroids, nonsteroid anti-inflammatory drugs, dornase alfa, oxygen and assisted ventilation and, in patients >12 yrs old only, use of airway clearance techniques, inhaled bronchodilators, oral nutritional supplements, pancreatic enzymes and insulin or oral hypoglycaemics. Slightly impaired lung function (5–10%) was associated with: diabetes (≥18-yrs-old), gastro-oesophageal reflux, allergic bronchopulmonary aspergillosis, asthma-like symptoms, portal hypertension,Aspergillusspp. andCandidaspp. Sex,Haemophilus influenzaeandStaphylococcus aureuswere not associated with impaired pulmonary status. Regular exercise (especially in older patients) and nasal polyposis were associated with slightly better FEV1.

The results confirm those of previous studies and suggest selective prescribing in sicker patients.