bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociating the Neural Mechanisms of Visual Attention in Change Detection Using Functional MRI
Authors: Huettel Scott A. , Güzeldere Güven , McCarthy Gregory
Published: July 2002

We investigated using functional magnetic resonance imaging (fMRI) the neural processes associated with performance of a change-detection task. In this task, two versions of the same picture are presented in alternation, separated by a brief mask interval. Even when the two pictures greatly differ (e.g., as when a building is in different locations), subjects report that identification of the change is difficult and often take 30 or more seconds to identify the change. This phenomenon of “change blindness” provides a powerful and novel paradigm for segregating components of visual attention using fMRI that can otherwise be confounded in short-duration tasks. By using a response-contingent event-related analysis technique, we successfully dissociated brain regions associated with different processing components of a visual change-detection task. Activation in the calcarine cortex was associated with task onset, but did not vary with the duration of visual search. In contrast, the pattern of activation in dorsal and ventral visual areas was temporally associated with the duration of visual search. As such, our results support a distinction between brain regions whose activation is modulated by attentional demands of the visual task (extrastriate cortex) and those that are not affected by it (primary visual cortex). A second network of areas including central sulcus, insular, and inferior frontal cortical areas, along with the thalamus and basal ganglia, showed phasic activation tied to the execution of responses. Finally, parietal and frontal regions showed systematic deactivations during task performance, consistent with previous reports that these regions may be associated with nontask semantic processing. We conclude that detection of change, when transient visual cues are not present, requires activation of extrastriate visual regions and frontal regions responsible for eye movements. These results suggest that studies of change blindness can inform understanding of more general attentional processing.
What Processing Is Impaired in Apperceptive Agnosia? Evidence from Normal Subjects
Authors: Vecera Shaun P. , Gilds Kendra S.
Published: July 2002

Visual agnosia is a neuropsychological syndrome characterized by a failure of object identification. Apperceptive agnosia, an object identification deficit caused by damage to early perceptual processes, has been explained by appealing to both damaged early sensory processes and to damaged preattentive grouping processes. Which of these two explanations best accounts for the behavior of these patients? We present results from two experiments designed to distinguish rival theoretical accounts of apperceptive agnosia. In our studies, we attempted to simulate apperceptive agnosia in neurologically intact subjects. Sensory-deficit accounts of the syndrome predict that degrading visual processing would make normal subjects perform like patients; grouping-deficit accounts predict that removing perceptual organization cues from visual displays would make normal subjects perform like patients. We were able to simulate the behavior of an apperceptive agnosic patient by removing perceptual organization cues, consistent with a grouping-deficit account of this syndrome. The implications for understanding both apperceptive agnosia and normal visual functioning are discussed.
Weak, Stochastic Temporal Correlation of Large-Scale Synaptic Input Is a Major Determinant of Neuronal Bandwidth
Authors: Halliday David M.
Published: July 2002

We determine the bandwidth of a model neurone to large-scale synaptic input by assessing the frequency response between the outputs of a two-cell simulation that share a percentage of the total synaptic input. For temporally uncorrelated inputs, a large percentage of common inputs are required before the output discharges of the two cells exhibit significant correlation. In contrast, a small percentage (5%) of the total synaptic input that involves stochastic spike trains that are weakly correlated over a broad range of frequencies exert a clear influence on the output discharge of both cells over this range of frequencies. Inputs that are weakly correlated at a single frequency induce correlation between the output discharges only at the frequency of correlation. The strength of temporal correlation required is sufficiently weak that analysis of a sample pair of input spike trains could fail to reveal the presence of correlated input. Weak temporal correlation between inputs is therefore a major determinant of the transmission to the output discharge of frequencies present in the spike discharges of presynaptic inputs, and therefore of neural bandwidth.
Predictions of the Spontaneous Symmetry-Breaking Theory for Visual Code Completeness and Spatial Scaling in Single-Cell Learning Rules
Authors: Webber Chris J. S.
Published: July 2002

This article shows analytically that single-cell learning rules that give rise to oriented and localized receptive fields, when their synaptic weights are randomly and independently initialized according to a plausible assumption of zero prior information, will generate visual codes that are invariant under two-dimensional translations, rotations, and scale magnifications, provided that the statistics of their training images are sufficiently invariant under these transformations. Such codes span different image locations, orientations, and size scales with equal economy. Thus, single-cell rules could account for the spatial scaling property of the cortical simple-cell code. This prediction is tested computationally by training with natural scenes; it is demonstrated that a single-cell learning rule can give rise to simple-cell receptive fields spanning the full range of orientations, image locations, and spatial frequencies (except at the extreme high and low frequencies at which the scale invariance of the statistics of digitally sampled images must ultimately break down, because of the image boundary and the finite pixel resolution). Thus, no constraint on completeness, or any other coupling between cells, is necessary to induce the visual code to span wide ranges of locations, orientations, and size scales. This prediction is made using the theory of spontaneous symmetry breaking, which we have previously shown can also explain the data-driven self-organization of a wide variety of transformation invariances in neurons' responses, such as the translation invariance of complex cell response.
Convergent Decomposition Techniques for Training RBF Neural Networks
Authors: Buzzi C. , Grippo L. , Sciandrone M.
Published: July 2002

In this article we define globally convergent decomposition algorithms for supervised training of generalized radial basis function neural networks. First, we consider training algorithms based on the two-block decomposition of the network parameters into the vector of weights and the vector of centers. Then we define a decomposition algorithm in which the selection of the center locations is split into sequential minimizations with respect to each center, and we give a suitable criterion for choosing the centers that must be updated at each step. We prove the global convergence of the proposed algorithms and report the computational results obtained for a set of test problems.
Neural Processing in the Subsecond Time Range in the Temporal Cortex
Authors: Nakamura Kiyohiko
Published: July 2002

The hypothesis that cortical processing of the millisecond time range is performed by latency competition between the first spikes produced by neuronal populations is analyzed. First, theorems that describe how the mechanism of latency competition works in a model cortex are presented. The model is a sequence of cortical areas, each of which is an array of neuronal populations that laterally inhibit each other. Model neurons are integrate-and-fire neurons. Second, the model is applied to the ventral pathway of the temporal lobe, and neuronal activity of the superior temporal sulcus of the monkey is reproduced with the model pathway. It consists of seven areas: V1, V2/V3, V4, PIT, CIT, AIT, and STPa. Neural activity predicted with the model is compared with empirical data. There are four main results: (1) Neural responses of the area STPa of the model showed the same fast discrimination between stimuli that the corresponding responses of the monkey did: both were significant within 5 ms of the response onset. (2) The hypothesis requires that the response latency of cortical neurons should be shorter for stronger responses. This requirement was verified by both the model simulation and the empirical data. (3) The model reproduced fast discrimination even when spontaneous random firing of 9 Hz was introduced to all the cells. This suggests that the latency competition performed by neuronal populations is robust. (4) After the first few competitions, the mechanism of latency competition always detected the strongest of input activations with different latencies.
A Cerebellar Model of Timing and Prediction in the Control of Reaching
Authors: Barto Andrew G. , Fagg Andrew H. , Sitkoff Nathan , Houk James C.
Published: July 2002

A simplified model of the cerebellum was developed to explore its potential for adaptive, predictive control based on delayed feedback information. An abstract representation of a single Purkinje cell with multistable properties was interfaced, using a formalized premotor network, with a simulated single degree-of-freedom limb. The limb actuator was a nonlinear spring-mass system based on the nonlinear velocity dependence of the stretch reflex. By including realistic mossy fiber signals, as well as realistic conduction delays in afferent and efferent pathways, the model allowed the investigation of timing and predictive processes relevant to cerebellar involvement in the control of movement. The model regulates movement by learning to react in an anticipatory fashion to sensory feedback. Learning depends on training information generated from corrective movements and uses a temporally asymmetric form of plasticity for the parallel fiber synapses on Purkinje cells.
Gentle Fire: An Early Approach to Live Electronic Music
Authors: Davies Hugh
Published: July 2002

The author describes the circumstances of the formation and development of the live electronic music group Gentle Fire, in discussing aspects affecting elecronic music in general and those particular to the ensemble. He stresses Gentle Fire's distinctive approaches toward collaboration and technology, giving particular attention to its unique group compositions. Collaborations with contemporaries are also discussed. Finally, the author addresses the factors leading to the dissolution of the group.
Remembering How to Forget: An Artist's Exploration of Sound
Authors: Scanner
Published: July 2002

This article is an introduction to the work of electronic sound artist Scanner, which explores the place of memory, the cityscape and the relationship between the public and the private within contemporary sound art. Beginning with a historical look at his CD releases a decade ago, the article explores his move from his cellular phone works to his more collaborative digital projects in recent times. With descriptions of several significant performance works, public art commissions and film soundtrack work, the piece explores the resonances and meanings with the ever-changing digital landscape of a contemporary sound artist.
Cognitive Repositioning inside a Desktop VE: The Constraints Introduced by First-versus Third-Person Imagery and Mental Representation Richness
Authors: Amorim Michel-Ange , Trumbore Ben , Chogyen Pema L.
Published: July 2002

Cognitive repositioning is crucial for anticipating the content of the visual scene from new vantage points in virtual environments (VE). This repositioning may be performed using either a first-(immersive-like) or a third-person imagery perspective (via an imaginary avatar). A three-phase study examined the effect of mental representation richness and imagery perspective on the anticipation of new vantage points and their associated objects inside an unfamiliar but meaningfully organized VE. Results showed that the initial level of encoding affects the construction of spatial knowledge, whose exploration is then constrained mostly by the imagery perspective that has been adopted, and the spatial arrangement of the environment. A third-person perspective involves mental extrapolation of directions with the help of a scanning process whose rate of processing is faster than the process used to generate the missing 3-D representation of first-person perspectives. Finally, anticipation of a new vantage point precedes access to its associated object mainly when adopting a first-person perspective for exploring the environment. These findings may prove to be of potential interest when defining cognitively valid rules for real-time automatic camera control in VEs.
Evolutionary Algorithms for the Satisfiability Problem
Authors: Gottlieb Jens , Marchiori Elena , Rossi Claudio
Published: July 2002

Several evolutionary algorithms have been proposed for the satisfiability problem. We review the solution representations suggested in literature and choose the most promising one the bit string representation for further evaluation. An empirical comparison on commonly used benchmarks is presented for the most successful evolutionary algorithms and for WSAT, a prominent local search algorithm for the satisfi-ability problem. The key features of successful evolutionary algorithms are identified, thereby providing useful methodological guidelines for designing new heuristics. Our results indicate that evolutionary algorithms are competitive to WSAT.
The Dewatering of Economic Growth
Authors: Rock Michael T.
Published: July 2002

Recent research has found an inverted U relationship between freshwater use and income after controlling for freshwater availability, the structure of the economy, and several policy variables. This suggests that the intensity of freshwater use must be declining with income growth. This hypothesis is tested by developing a simple, informal model of the determinants of freshwater‐use intensities across countries and over time. Results suggest that water‐use intensity declines across the entire range of per capita incomes extant in the world today. They also show that the relationship between intensity of use and income is mediated by an economy's natural water endowment, the structure of the economy, and government policies. Four policies, in particular, affect the water‐use intensity of economies. Open trade policies and tough environmental regulatory policies lower water use intensities, and narrowly defined food self‐sufficiency policies and socialist development policies increase water‐use intensities. These findings suggest that those interested in water, water scarcity, and water policy need to extend beyond simple extrapolations of past consumption patterns and narrowly focused water policies (such as water pricing) if they want to improve water management practices.
Quantitative Industrial Ecology & Ecological Economics
Authors: Koenig Herman E. , Cantlon John E.
Published: July 2002

This article presents a theoretical foundation for integrating three otherwise disparate areas of human thought and understanding: technology, ecology, and economics. The article presents the mathematical foundations for quantifying the biophysical (mass, energy, and informational) aspects of economic production systems and their interaction with natural systems. These mathematical relationships are required for the on‐going ecological and economic design of technological production networks by enterprise management, thereby extending the scope and scale of quantitative engineering design from the domain of individual technologies to networks of technologies at enterprise, corporate, and industrial levels of technological organization.

The analytical framework extends the practical utility of ecology, as an applied natural science, from passive environmental monitoring and prediction to active institutional participation in an informational feedback control strategy pursuant to economically abating the ecological risks of industrial growth, development, and modernization at local, regional, and global levels of ecological organization. And it provides the applied natural‐science underpinnings and the informational feedback control institutions required to support economics as an applied social science. In this context ecological risk‐control pricing is presented as a supplement to conventional economic policies at local, regional, and national levels of economic organization.
The Politics of Cold War Culture
Authors: Shaw Tony
Published: July 2002

This article examines the relationship between politics and culture in Great Britain and the United States during the Cold War, with particular emphasis on the period from the late 1940s to the early 1960s. The article critically examines several recent books on British and American Cold War cultural activities, both domestic and external. The review covers theatrical, cinematic, literary, and broadcast propaganda and analyzes the complex network of links between governments and private groups in commerce, education, labor markets, and the mass entertainment media. It points out the fundamental differences between Western countries and the Soviet bloc and provides a warning to those inclined to view Western culture solely through a Cold War prism.
A CASE OF BENIGN IMPERIAL NEGLECT AND ITS CONSEQUENCES
Authors: Blenkinsopp Joseph
Published: July 2002

Edomites were already well established in the Judean Negev before the Babylonian conquest, and archaeological evidence suggests that they profited by the disturbances of those years (597-582 bce) to infiltrate much of the province south of Jerusalem. After the collapse of the Neo-Babylonian empire, the interest of the Persians in the region was restricted to protecting the trade routes along the Mediterranean coast and the Transjordanian plateau and the approaches to Egypt. They also had no interest in sponsoring the return of deported Judaeans to the region. Once it became clear that there would be no intervention from distant Susa, the pace of Edomite colonisation quickened, a semi-deserted Jerusalem was occupied, and a sanctuary to the supreme Edomite deity Qôs (Qaus) arose on the site of the destroyed Yahweh temple. This ruled out the possibility of repatriation, and Judaism developed as a scattering of ritually segregated enclaves in different countries in line with other religions in late antiquity.
FIGHT STRATEGIES DIFFER WITH SIZE AND ALLOMETRIC GROWTH OF CLAWS IN CRAYFISH, ORCONECTES RUSTICUS
Authors: Schroeder Lisa , Huber Robert
Published: July 2002

This study examines differences in fighting strategies between small and large male crayfish, Orconectes rusticus. Due to allometric growth of claws, fighting weapons are of disproportionate size in large crayfish compared to those in smaller individuals. Presumably, such differences in the prominence of claws are reflected in differences in the likelihood of injuries, and we thus explored fighting in size-matched pairs of small or large crayfish and assessed associated strategies in situations of conflict. Although fighting reached the highest intensities in a similar proportion of instances in small and large pairs, differences in fighting strategies were evident. Small crayfish escalated more rapidly, fights were settled more quickly, and were resolved overall at lower intensities. This may be explained by lower risks of injury compared to encounters among larger males due to proportionally smaller claws. Larger males thus appear to spend considerably more time in assessing their opponent's fighting ability before each escalation event.
Influence of temperature on the infectivity of entomopathogenic nematodes (Steinernema and Heterorhabditis spp.) to larvae and pupae of the vine weevil Otiorhynchus sulcatus (Coleoptera: Curculionidae)
Authors: Long Steve , Fenlon John , Richardson Paul
Published: July 2002

The susceptibilities of early and late instar vine weevil larvae and pupae to three species of entomopathogenic nematodes, indigenous to the UK, were tested in a series of bioassays. Steinernema kraussei (isolates L017 and L137), S. feltiae (the commercial product Nemasys®) and Heterorhabditis megidis (the commercial product Nemasys® H, reared both in vivo in Galleria mellonella larvae and in vitro), were tested at 6, 10 and 18°C for 2 weeks (early instars of O. sulcatus) or 3 weeks (late instars and pupae of O. sulcatus). Nematodes were applied to over 3800 larvae or pupae and there were over 400 untreated controls. Each insect was examined subsequently to determine mortality, and parasitised specimens were dissected to establish whether adult nematodes had developed. Differences in pathogenicity between H. megidis reared in vitro and in vivo were demonstrated. S. kraussei (L137) was consistently the most virulent nematode isolate at low temperatures. The results revealed a significant (P < 0.001) effect of temperature on small larvae of O. sulcatus, but also showed differential levels of mortality, not due to nematodes, for both small larvae and pupae. The use of Abbott's correction for control mortality is challenged and the validity of competing risks theory examined.In einer Reihe von Biotests wurde die Anfälligkeit von frühen und späten Larvenstadien sowie Puppen des Rüsselkäfers Otiorhynchus sulcatus gegenüber drei in UK einheimischen entomopathogenen Nematoden untersucht. Steinernema kraussei (isolate L017 und L137), S. feltiae (Handelsprodukt Nemasys®) und Heterorhabditis megidis (Handelsprodukt Nemasys® H, beide in vivo an Larven von Galleria mellonella und in vitro gezüchtet) wurden bei 6, 10 and 18°C für zwei Wochen (frühe Stadien von O. sulcatus) oder drei Wochen (späte Stadien und Puppen von O. sulcatus) geprüft. Über 3800 Larven oder Puppen wurden mit Nematoden behandelt, daneben gab es über 400 unbehandelte Kontrollen. Anschliessend wurde jedes Insekt untersucht, um die Mortalität zu bestimmen. Parasitierte Exemplare wurden aufpräpariert um festzustellen, ob sich adulte Nematoden entwickelt hatten. Zwischen in vitro und in vivo kultivierten H. megidis konnten Unterschiede in der Pathogenität festgestellt werden. S. kraussei (L137) war bei niedrigen Temperaturen durchgehend das virulenteste Isolat. Die Ergebnisse zeigten eine signifikante (P < 0.001) Wirkung der Temperatur auf kleine Larven von O. sulcatus. Sie zeigten für kleine Larven und Puppen aber auch unterschiedliche Mortlitätsgrade an, die nicht auf Nematoden zurückgingen. Die Anwendung von Abbott's Korrektur zur Prüfung der Mortalität wird kritisch hinterfragt, die Gültigkeit der Theorie der “competing risks” wird geprüft.
“Colonized Body,” “Oriental Machine”: Debating Race, Railroads, and the Politics of Reconstruction in Germany and East Africa, 1906–1910
Authors: Naranch Bradley D.
Published: July 2002

Theyears 1906–1910 were a period of crisis and unstable consensus in German colonial history. In contrast to the debates of the previous two decades following Chancellor Otto von Bismarck's 1884 decision to establish overseas protectorates, colonial discourse in Germany after 1905 shifted decisively away from abstract considerations of the desirability of colonies for economic and imperialist expansion to focus on the more practical matters of colonial policy and long-term developmental reform. Indeed, given the fact that by 1905 the German colonial empire covered a sprawling expanse of land six times the size of the German state, including territories in Africa, the South Pacific, and a naval base (Tsingtao) on the coast of China, the enormous challenges of managing its far-flung and costly possessions were becoming increasingly difficult to meet. For better or for worse, the Kaiserreich had become a de facto colonial power, and German society was increasingly and uncomfortably being forced to recognize the hazards and burdens of its fledgling global empire.
SCHREBER'S SOUL-VOLUPTUOUSNESS: MYSTICISM, MADNESS AND THE FEMININE IN SCHREBER'S MEMOIRS
Authors: Robbins Brent Dean
Published: July 2002

Freud's 1911 case study based on Schreber's (1903) Memoirs of My Nervous Illness provides the investigator with the opportunity to reexamine Freud's interpretation through a return to the original data Freud used. This study reveals both the insights and limitations of Freud's theory of paranoia. An alternative interpretation of the case is overed from an existential-phenomenological perspective which aims both to expand upon and transform Freud's study without negating its value. Freud draws on the mythologies of the sun to argue for his hypothesis that the "father-complex" lies behind Schreber's God. By following some of the many other mythological themes in Schreber's memoirs, Freud's interpretation is opened to a larger, socially and historically situated context. An examination of cross-cultural and historical studies of mystical experience shows how Schreber's psychosis is simultaneously a form of madness and spiritual breakthrough. Schreber's is viewed as a narcissistic experience of the infant-child in which the imaginal has been exiled from rational, modern adulthood and is inaccessible to Cartesian language. Instead of recognizing the soul-full world of "miracles," Schreber envisions the absorption of the entire world into himself and he thus becomes an inflated caricature of the "heroic ego" at its extreme .
Correlation between crystallochemical parameters of phyllosilicates and mineral facies in very low-grade metasediments of the Betic Cordilleras, Spain: a synthesis
Authors: Ruiz Cruz M. D. , Rodríguez Jiménez P.
Published: July 2002

Clay mineral evolution in diagenetic and very low-grade metamorphic sedimentary rocks from the Maláguide Complex was studied using the following parameters: illite and chlorite crystallinity, b cell dimension of illite, chemistry of chlorite, and the occurrence and distribution of the following phyllosilicates: I-S mixed-layer minerals, kaolin polytypes, chlorite-bearing mixedlayer minerals (tosudite and mica-chlorite interstratifications), vermiculite-like minerals, paragonite and biotite. The distribution of IC values permits the subdivision of the study area into three zones: diagenetic, anchizone and epizone. On the contrary, the distribution of CC values cannot be used in the study of the metamorphic zonation. The mineralogy and b dimension of illite indicate that the Maláguide samples display a low to low-medium pressure metamorphism, also characterized by steep temperature gradients.

The correlation between IC data and distribution of other significant minerals has permitted the establishment of a zonation within the chlorite zone, which is confirmed by the appearance of some index minerals, such as paragonite, biotite, chloritoid and andalusite.
Raman study of high-pressure phase transitions in dehydrated analcime
Authors: Miroshnichenko Yu. M. , Goryainov S. V.
Published: July 2002

The high-pressure behaviour (up to 30 kbar) of dehydrated analcime, Na[AlSi2O6), has been studied in detail using polarized microscopy and Raman micro-spectroscopy. Samples were compressed using a diamond anvil cell in a quasi-hydrostatic medium (glycerol or water-ice). Two transitions at 3.7 and 11 kbar were observed.

At the first transition, phase II is observed under cross polarized light as a contrasting black zone, moving from the edge to the centre of the sample. At this transition the strong Raman doublet at ∼480 and 500 cm−1 transforms discontinuously to a singlet, which is similar to that of quasi-cubic natural analcime. This transition, with an increase of effective symmetry, seems unusual on increasing pressure.

The analcime framework may be thought of as an array of four-, six-, or eight-membered interconnected rings. Phase transitions in the analcime group are considered in the literature in terms of deformations of the six-membered rings. However, the present work shows that these phase transitions should be associated with deformations of the four-membered rings (as the minimum size secondary building units) by rotation of rigid TO4 units. The strongest Raman band frequency is correlated with the mean T-O-T angle inside the four-membered ring: a rate of 4.5 cm−1/degree was found for analcimes and leucites. Using this correlation, one can estimate from Raman data the possible deformation of four-membered rings at the phase transitions.
Equation of state of phase E
Authors: Crichton W. A. , Ross N. L.
Published: July 2002

The isothermal equation of state (EoS) of phase E, Mg1.96(7)Fe0.072(5)Si1.04(5)H3.7(8)O6, has been determined using high-pressure single-crystal X-ray diffraction. A third-order Birch Murnaghan EoS fit to pressue-volume data collected from room pressure and temperature to 6.7 GPa reveals that phase E has the lowest bulk modulus, KT = 92.9(7) GPa, and highest pressure derivative of the bulk modulus, K' = 7.3(2), for any dense hydrous magnesium silicate (DHMS) yet measured. A parameterized third-order Birch-Murnaghan EoS was also fit to the unit-cell parameters which display significant curvature with increasing pressure. This analysis shows that the c-axis (Kc = 89.1(10) GPa) is 6% more compressible than the a-axis (Ka = 94.8(6) GPa), with little of the anisotropy commonly observed in other layered structures. The high K' is indicative of the similarity to layers of the brucite structure. The introduction of interlayer cation polyhedra to the structure serves to reduce both the anisotropy, by reducing the compressibility perpendicular to the sheets, and the ability to shear, by increasing the coherence between layers.
Phase transitions in perovskites near the tricritical point: an experimental study of KMn1–xCaxF3 and SrTiO3
Authors: Gallardo M. C. , Romero F. J. , Hayward S. A. , Salje E. K. H. , del Cerro J.
Published: July 2002

We present experimental data for the Pm3m-I4/mcm phase transitions in the perovskite crystals KMn1-xCaxF3 and SrTiO3. Comparison of calorimetric data (latent heat and specific heat) with order parameter data (measured with X-ray rocking methods) indicates that these transitions follow mean-field behaviour, and may be described using Landau potentials where the free energy expansion includes terms up to Q6. This potential is characteristic of transitions close to the tricritical point. Comparison of the behaviour of SrTiO3 and KMnF3 indicates that KMnF3 is closer to the tricritical point; a small amount of substitution of Ca for Mn causes the transition to cross the tricritical point from first order to second order behaviour.
Unavailability of CD147 leads to selective erythrocyte trapping in the spleen
Authors: Coste Isabelle , Gauchat Jean-François , Wilson Anne , Izui Shozo , Jeannin Pascale , Delneste Yves , MacDonald H. Robson , Bonnefoy Jean-Yves , Renno Toufic
Published: July 2002

Adhesive interactions with stromal cells and the extracellular matrix are essential for the differentiation and migration of hematopoietic progenitors. In the erythrocytic lineage, a number of adhesion molecules are expressed in the developing erythrocytes and are thought to play a role in the homing and maturation of erythrocytic progenitors. However, many of these molecules are lost during the final developmental stages leading to mature erythrocytes. One of the adhesion molecules that remains expressed in mature, circulating erythrocytes is CD147. This study shows that blockade of this molecule on the cell surface by treatment with F(ab′)2 fragments of anti-CD147 monoclonal antibody disrupts the circulation of erythrocytes, leading to their selective trapping in the spleen. Consequently, mice develop an anemia, and de novo, erythropoietin-mediated erythropoiesis in the spleen. In contrast, these changes were not seen in mice similarly treated with another antierythrocyte monoclonal antibody with a different specificity. These results suggest that the CD147 expressed on erythrocytes likely plays a critical role in the recirculation of mature erythrocytes from the spleen into the general circulation.
Second generation knockout sickle mice: the effect of HbF
Authors: Fabry Mary E. , Suzuka Sandra M. , Weinberg Rona S. , Lawrence Christine , Factor Stephen M. , Gilman John G. , Costantini Frank , Nagel Ronald L.
Published: July 2002

Sickle transgenic mice expressing exclusively human globins are desirable for studying pathophysiology and testing gene therapy strategies, but they must have significant pathology and show evidence of amelioration by antisickling hemoglobins. Mice were generated that expressed exclusively human sickle hemoglobin with 3 levels of HbF using their previously described sickle constructs (cointegrated human miniLCRα2 and miniLCRβS [PNAS 89:12150, 1992]), mouse α- and β-globin-knockouts, and 3 different human γ-transgenes. It was found that, at all 3 levels of HbF expression, these mice have balanced chain synthesis, nearly normal mean corpuscular hemoglobin, and, in some cases, F cells. Mice with the least adult HbF expression were the most severe. Progressive increase in HbF from less than 3% to 20% to 40% correlated with progressive increase in hematocrit (22% to 34% to 40%) and progressive decrease in reticulocyte count (from 60% to 30% to 13%). Urine concentrating ability was normalized at high HbF, and tissue damage detected by histopathology and organ weight were ameliorated by increased HbF. The γ-transgene that produces intermediate levels of HbF was introduced into knockout sickle mice described by Pàszty and coworkers that express the miniLCRα1GγAγδβStransgene and have fetal but not adult expression of HbF. It was found that the level of HbF required to ameliorate low hematocrit and normalize urine concentrating defect was different for the miniLCRα2βS and miniLCRα1GγAγδβS mice. We conclude that knockout mice with the miniLCRα2βS transgene and postnatal expression of HbF have sufficiently faithful sickle pathology to serve as a platform for testing antisickling interventions.
Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma–associated herpesvirus
Authors: Zoeteweij J. Paul , Moses Ashlee V. , Rinderknecht Andrea S. , Davis David A. , Overwijk Willem W. , Yarchoan Robert , Orenstein Jan M. , Blauvelt Andrew
Published: July 2002

Kaposi sarcoma–associated herpesvirus (KSHV) is associated with KS, primary effusion lymphoma (PEL), and multicentric Castleman disease. Reactivation of KSHV in latently infected cells and subsequent plasma viremia occur before the development of KS. Intracellular signaling pathways involved in KSHV reactivation were studied. In latently infected PEL cells (BCBL-1), KSHV reactivation in single cells was determined by quantitative flow cytometry. Viral particle production was determined by electron microscope analyses and detection of minor capsid protein in culture supernatants. Agents that mobilized intracellular calcium (ionomycin, thapsigargin) induced expression of KSHV lytic cycle-associated proteins and led to increased virus production. Calcium-mediated virus reactivation was blocked by specific inhibitors of calcineurin-dependent signal transduction (cyclosporine, FK506). Similarly, calcium-mediated virus reactivation in KSHV-infected dermal microvascular endothelial cells was blocked by cyclosporine. Furthermore, retroviral transduction with plasmid DNA encoding VIVIT, a peptide specifically blocking calcineurin-NFAT interactions, inhibited calcium-dependent KSHV reactivation. By contrast, chemical induction of lytic-phase infection by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate was blocked by protein kinase C inhibitors, but not by calcineurin inhibitors. In summary, calcineurin-dependent signal transduction, an important signaling cascade in vivo, induces calcium-dependent KSHV replication, providing a possible target for the design of antiherpesvirus strategies in KSHV-infected patients.
Lack of neighborhood effects from a transcriptionally active phosphoglycerate kinase–neo cassette located between the murine β-major and β-minor globin genes
Authors: Kaufman Richard M. , Lu Zhi Hong , Behl Rajesh , Holt Jo M. , Ackers Gary K. , Ley Timothy J.
Published: July 2002

For the treatment of β-globin gene defects, a homologous recombination-mediated gene correction approach would provide advantages over random integration-based gene therapy strategies. However, “neighborhood effects” from retained selectable marker genes in the targeted locus are among the key issues that must be taken into consideration for any attempt to use this strategy for gene correction. An Ala-to-Ile mutation was created in the β6 position of the mouse β-major globin gene (β6I) as a step toward the development of a murine model system that could serve as a platform for therapeutic gene correction studies. The marked β-major gene can be tracked at the level of DNA, RNA, and protein, allowing investigation of the impact of a retained phosphoglycerate kinase (PGK)-neo cassette located between the mutant β-major and β-minor globin genes on expression of these 2 neighboring genes. Although the PGK-neo cassette was expressed at high levels in adult erythroid cells, the abundance of the β6I mRNA was indistinguishable from that of the wild-type counterpart in bone marrow cells. Similarly, the output from the β-minor globin gene was also normal. Therefore, in this specific location, the retained, transcriptionally active PGK-neo cassette does not disrupt the regulated expression of the adult β-globin genes.
Erythropoietin (Epo) and EpoR expression and 2 waves of erythropoiesis
Authors: Lee Robert , Kertesz Nathalie , Joseph Sean B. , Jegalian Armin , Wu Hong
Published: July 2002

Erythropoiesis occurs in 2 distinct waves during embryogenesis: the primitive wave in the extra-embryonic yolk sac (YS) followed by the definitive wave in the fetal liver and spleen. Even though progenitors for both cell types are present in the YS blood islands, only primitive cells are formed in the YS during early embryogenesis. In this study, it is proposed that erythropoietin (Epo) expression and the resultant EpoR activation regulate the timing of the definitive wave. First, it was demonstrated that Epo and EpoR gene expressions are temporally and spatially segregated: though EpoR is expressed early (embryonic days 8.0-9.5) in the yolk sac blood islands, no Epo expression can be detected in this extra-embryonic tissue. Only at a later stage can Epo expression be detected intra-embryonically, and the onset of Epo expression correlates with the initiation of definitive erythropoiesis. It was further demonstrated that the activation of the EpoR signaling pathway by knocking-in a constitutively active form of EpoR (R129C EpoR) can lead to earlier onset of definitive erythropoiesis in the YS. Thus, these results provide the first in vivo mechanism as to how 2 erythroid progenitor populations can coexist concurrently in the YS yet always differentiate successively during embryogenesis.
Rabaptin-5 is a novel fusion partner to platelet-derived growth factor β receptor in chronic myelomonocytic leukemia
Authors: Magnusson Magnus K. , Meade Kristin E. , Brown Kevin E. , Arthur Diane C. , Krueger Lisa A. , Barrett A. John , Dunbar Cynthia E.
Published: July 2002

Chromosomal translocations involving the platelet-derived growth factor β receptor (PDGFβR) gene have been reported in some patients with chronic myelomonocytic leukemia (CMML). The resultant fusion proteins have constitutive PDGFβR tyrosine kinase activity, but the partner genes previously reported(tel, Huntingtin interacting protein 1[HIP-1], H4/D10S170) have poorly understood roles in the oncogenic activity of the fusion proteins. A novel PDGFβR fusion protein has been characterized in a patient with CMML and an acquired t(5;17)(q33;p13). Southern blot analysis on patient leukemia cells demonstrated involvement of the PDGFβR gene. Using 5′ rapid amplification of complementary DNA ends–polymerase chain reaction (RACE-PCR) on patient RNA, rabaptin-5 was identified as a novel partner fused in-frame to thePDGFβR gene. The new fusion protein includes more than 85% of the native Rabaptin-5 fused to the transmembrane and intracellular tyrosine kinase domains of the PDGFβR. Transduction with a retroviral vector expressing rabaptin-5/PDGFβRtransformed the hematopoietic cell line Ba/F3 to growth factor independence and caused a fatal myeloproliferative disease in mice. Rabaptin-5 is a well-studied protein shown to be an essential and rate-limiting component of early endosomal fusion through interaction with the Ras family GTPases Rab5 and Rab4. The fusion protein includes 3 of 4 coiled-coil domains (involved in homodimerization of native rabaptin-5), 2 caspase-3 cleavage sites, and a binding site for the tumor suppressor gene tuberin (tuberous sclerosis complex-2). Early endosomal transport is critical in regulation of various growth factor receptors, through ligand-induced clathrin-mediated endocytosis, and thus this new fusion protein links together 2 important pathways of growth regulation.
TT virus contaminates first-generation recombinant factor VIII concentrates
Authors: Azzi Alberta , De Santis Riccardo , Morfini Massimo , Zakrzewska Krystyna , Musso Roberto , Santagostino Elena , Castaman Giancarlo
Published: July 2002

Recombinant factor VIII and factor IX concentrates, human-plasma–derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein–free) concentrates were negative for the virus. In 59% of patients treated with either first- or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin.
Interleukin-7 and interleukin-15 regulate the expression of thebcl-2 and c-myb genes in cutaneous T-cell lymphoma cells
Authors: Qin Jian-Zhong , Zhang Chun-Lei , Kamarashev Jivko , Dummer Reinhard , Burg Günter , Döbbeling Udo
Published: July 2002

Interleukin-7 (IL-7) and IL-15 have been recently identified as growth factors for cutaneous T-cell lymphoma (CTCL) cells, and they protect these cells from cell death. Using the CTCL cell line SeAx as a test system now shows that IL-7 and IL-15 are indeed necessary to maintain high levels of bcl-2. The up-regulation of bcl-2 was paralleled by increased DNA-binding activities of the transcription factors STAT2, STAT5, STAT6, and c-Myb to bcl-2gene promoter–enhancer elements. Because STAT5 and c-Myb positively regulate bcl-2, IL-7 and IL-15 may mediate some of their effects on cell death survival gene expression through these 2 factors. Constitutive activities of the 3 STAT factors and c-Myb were found in the IL-7– and IL-15–independent CTCL cell lines HUT78 and MyLa 2059. The c-Myb protein was also present in CTCL cells of the skin lesions of all investigated patients. These results indicate that IL-7 and IL-15 may increase bcl-2 expression in CTCL cells by the activation of c-myb and STAT factors.
Hypertonic Sodium Bicarbonate for Taxus media‐induced Cardiac Toxicity in Swine
Authors: Graeme Kimberlie A. , Ruha Anne‐Michelle , Tanen David A. , Curry Steven C. , Miller Mary Beth , Gerkin Richard , Reagan Christine G. , Brandon Tedd A.
Published: July 2002

Objective: To determine whether intravenous (IV) hypertonic sodium bicarbonate is effective in the reversal of QRS widening associated with severe Taxus intoxication. Methods: Seventeen anesthetized and instrumented swine were poisoned with an IV extract of Taxus media until doubling of the QRS interval on electrocardiography was achieved. After poisoning (time zero), the animals received either 4 mL/kg IV 8.4% sodium bicarbonate (experimental group; 6 animals), a similar volume of 0.7% NaCl in 10% mannitol (mannitol group; 6 animals), or nothing (control group; 5 animals). The main outcome parameter was QRS duration. Secondary outcome parameters were mean arterial pressure (MAP), heart rate (HR), and cardiac index (CI = cardiac output/kg). Additionally, arterial pH, partial pressure of carbon dioxide (pCO2), and plasma‐ionized calcium, sodium, and potassium were monitored. Results: Taxus toxicity, defined as a 100% increase in QRS duration, was produced in all animals. The animals were similar in regard to baseline and time 0 physiologic parameters as well as amount of Taxus media extract administered. From times 5 through 30 minutes, following assigned treatment, significant increases in QRS duration were detected in the experimental and mannitol groups compared with the control group. A significant lowering of MAP was found in the experimental group compared with the control group. No significant difference between groups was noted in HR or CI. The swine treated with hypertonic sodium bicarbonate had a statistically significant increase in pH, plasma sodium concentration, and base excess compared with the other groups. Conclusions: Hypertonic sodium bicarbonate was ineffective in reversing the widening of QRS interval associated with Taxus poisoning in this swine model.
Calcium‐ and phospholipid‐dependent phosphorylation of ribulose‐1,5‐bisphosphate carboxylase/oxygenase small subunit by a chloroplast envelope‐bound protein kinase in situ
Authors: Muto Shoshi , Shimogawara Kousuke
Published: July 2002

Phosphorylation of the ribulose‐1,5‐bisphosphate carboxylase/oxygenase small subunit and other polypeptides by a protein kinase bound to the chloroplast envelope in situ was inhibited by EGTA, but not by calmodulin antagonists. When the envelope membrane was extracted with 90% () cold acetone, the protein kinase activity was completely lost. The activity was restored by adding a lipid fraction extracted from the chloroplast envelope, or phospholipids such as phosphatidylserine and phosphatidylcholine. Treatment of the envelope with phospholipases decreased the protein kinase activity. This was restored by the addition of phospholipids. These results strongly suggest that the envelope‐bound protein kinase is a Ca2+‐and phospholipid‐dependent enzyme.
Fluorescence molecular relaxation studies of protein dynamics
Authors: Demchenko Alexander P.
Published: July 2002

Protein dynamics
Melittin
Fluorescence probe
Time‐resolved spectroscopy
Edge‐excitation fluorescence shift
Brain spectrin fragments and crosslinks actin filaments
Authors: Strömqvist Mats
Published: July 2002

The effect of brain spectrin (fodrin) on actin has been studied using viscometry and fluorimetry. Brain spectrin resembles erythrocyte spectrin tetramer in its action on actin. Both proteins crosslink actin filaments giving rise to a large increase in the viscosity but fluorimetry shows that neither affects actin polymerization significantly. In addition, brain spectrin as well as erythrocyte spectrin fragments preformed actin filaments. Actin filaments incubated in the presence of either of the two proteins incorporate actin monomers at a much higher rate showing that more filament ends are generated.