bluuebunny/crossref_metadata_2025 huggingface dataset:
The Unsettling Location of a Settler Nation: Argentina, from Settler Economy to Failed Developing Nation
Authors: Salvatore Ricardo D.
Published: September 2008

The international location of Argentina—its “place” in the scale of “progress and civilization” designed by European industrialized nations—has been shifting since the consolidation of the nation-state in 1880. Viewed as a successful settler economy by North American travelers and businessmen at the beginning of the twentieth century (as a “land of opportunity”), Argentina came to represent all the institutional and character flaws associated with “failed development” by the second half of the century. This fall changed the nature of possible comparisons, making less credible early associations with advanced European settler colonies and facilitating an understanding of Argentina as part of Latin America. This essay examines a series of discourses about the nature and location of Argentina. Underneath the shift in comparative frameworks, it is suggested, there was a growing uneasiness about the initial relationship between race and nation. The writings of nationalists in the 1930s and the mass following of a political movement (Peronism) placed serious doubts on the fiction of Argentina as a “white nation.”
The Unsettler
Authors: Farred Grant
Published: September 2008

Working through and against the paradigmatic history of the settler, a protagonist routinely recognized as critical to colonial, anticolonial, and postcolonial thinking, this essay offers a counterpart: the unsettler. Profiling the unsettler in a critique of the political situation that obtains in the embattled Sudanese region of Darfur, the intent here is to suggest that while the unsettler's origins (and political tendencies) are not easily distinguishable from those of his settler roots, the unsettler is a very particular instantiation of (state-sponsored) political violence. The unsettler is marked by the determination to “make”—in the process of “unmaking” the national populace, dividing one constituency from another, through deracination and physical and rhetorical attacks—the postcolonial nation a deeply discriminatory, which is to say, racially specific, construct. This essay posits the Janjawid, an especially recriminatory and bloody militia mobilized by the riverine Khartoum government against the “black Darfurians,” as the postcolonial instance through which to think about the figure of the unsettler.
“How many Mexicans [is] a horse worth?” The League of United Latin American Citizens, Desegregation Cases, and Chicano Historiography
Authors: Saldaña-Portillo María Josefina
Published: September 2008

Why is Spain's role as a colonizing power in the Americas overlooked by scholars of white settler colonialism? If European ventures in such disparate places as Australia, New Zealand, South Africa, Canada, the United States, Angola, and Algeria can all be viewed through the scholarly lens of white settler colonialism, why not Latin America? In this essay, I attempt to answer these questions through an analysis of the confrontation of racial ideologies that occurred between Mexicans and Anglos in the U.S. Southwest. Legally, Mexican Americans were considered part of the “white” race after 1897, but how did Mexican Americans understand this putative whiteness, especially given their racial inscription as mestizos under Spanish colonial and Mexican postcolonial law? I examine the desegregation cases brought on behalf of Mexican American plaintiffs between 1929 and 1954, in which Mexican American litigators argued that as Mexicans were racially white, schools and juries in the Southwest violated their due process rights by segregating them or discriminating against them in jury selection. Chicano historiography has derided this generation of civil rights activists as race traitors. However, I examine the court records, letters, and speeches of these legal activists, as well as Américo Paredes's George Washington Gómez, to see how these civil rights activists challenge the very meaning of “whiteness” when they claim it in the face of racial exclusion and violence.
Where the Nation Takes Place: Proprietary Regimes, Antistatism, and U.S. Settler Colonialism
Authors: Goldstein Alyosha
Published: September 2008

This essay examines the present-day conditions of settler colonialism in the United States by focusing on the constitutive force of liberal juridical and proprietary regimes and the historical permutations of federalism. Goldstein argues that white settler colonialism in the United States is articulated with the present-day constellation of neoliberal antistatism and post–civil rights “color-blind” discourse. His argument is developed through an analysis of the U.S. vote against the UN Declaration on the Rights of Indigenous Peoples in 2007, the Supreme Court ruling on City of Sherrill v. Oneida Indian Nation of New York (2005), and contemporary antisovereignty groups organizing against American Indian self-determination. Antisovereignty activists contend that U.S. federal Indian law confers “special rights” based on race to tribes and that tribal sovereignty not only deprives Indian members of constitutional rights, but also promotes privileged “racial” separatism fundamentally hostile to the principles of U.S. democracy. Attending to the problematic formulations of the antisovereignty movement, Goldstein considers how this rhetoric is both articulated and disarticulated from the broader structures of governance and juridical authority in the United States. This essay considers the role of settler land claims historically and in the present, and studies how contemporary antisovereignty initiatives amplify the history of North American conquest and genocide in order to argue against the legitimacy of current tribal claims to land and self-determination.
Terrorism and the Novel, 1970–2001
Authors: Appelbaum Robert , Paknadel Alexis
Published: September 2008

Since 1970, terrorism has become a prominent subject for English-language novels. In an attempt to characterize the modern terrorism novel and the cultural work it has performed, the authors have devised a typology of terrorism-infiction from 1970 through 2001. Over a thousand novels were documented, including both thrillers and mainstream works. A sample of twenty-five novels from the period was then selected for careful reading, analysis, and comparison. Preliminary results establish that though there is a great deal of diversity in terrorism novels, both in what they do with terrorism and why, they are by and large focused less on politics than on sentiment and less on the perpetrators of terrorism than on its victims. But novels introduce an innovation in what has been called the “mythography of terrorism” by introducing new types of “controlling consciousnesses” through which terrorist violence is perceived.
Description, Narrative, and Explanation: Text-Type Categories and the Cognitive Foundations of Discourse Competence
Authors: Herman David
Published: September 2008

Description, narrative, and explanation can be viewed both as cognitive activities and as forms of communication, that is, text types embedded within sociocultural, institutional, and discipline-specific histories of practice. I relate these three text-type categories to research on categorization processes more generally, exploring what might constitute the “basic” level of a taxonomy of text types (i.e., the most cognitively fundamental level) and also what might be considered prototypical features of descriptions, explanations, and stories (i.e., the features found fully realized in exemplars or standard cases of these types). Building on the taxonomy outlined in the first three sections of the essay, especially my account of core features of explanation, the final section constitutes a “coda” in which I use the taxonomy to investigate how narrative relates to description and explanation in contexts of scientific inquiry in particular.
The Trouble with Cephalopoda
Authors: Bencivenga Ermanno
Published: September 2008

No other natural kind receives as much abuse in the Aristotelian corpus as the octopus, and an instructive itinerary through that corpus can be constructed by following the manifestations of such abuse. Specifically, the octopus is judged “stupid” and endowed with poor, rudimentary structure; together with fellow cephalopoda and mollusks, it is even regarded as behaving “contrary to nature.” The moral that emerges from following this path is that Aristotle may be expressing here a deep conflict between two different models equally present in his work, though they are assigned very different emphasis. Also, importantly, mollusks are said to be “mutilated,” which aligns the treatment they receive with the one Aristotle famously reserves for women.
Moving Constants—in the West
Authors: Andersen Wayne
Published: September 2008

This essay forms part of an “elegiac symposium” on “what gets lost during paradigm shifts,” and it replies to an earlier contribution to that symposium, “Regarding Change at Ise-Jingu” by Jeffrey M. Perl (14, no. 2 [2008]: 208-20; DOI 10.1215/0961754X-2007-069]). Andersen argues against or supplements Perl's contention that Japanese attitudes toward change differ radically from those that are standard in the West. Andersen expands on arguments made by Roland Barthes—an explicator and partisan of Japanese thought—to show that at least one Greek myth (that of the unchanging ship Argo) deals with change, originality, updating, fakes, and replication in a way similar to those standard in Japanese culture. Andersen then pursues his argument, as well, with respect to works by Rodin, Sade, and Leonardo da Vinci.
What Giordano Bruno Left Behind
Authors: Rowland Ingrid D.
Published: September 2008

Burned at the stake for heresy in Rome in 1600, the Italian philosopher Giordano Bruno was the first modern thinker to propose that the universe contained an infinite number of planetary systems revolving around individual stars. He announced his startling propositions at the moment when European explorers were beginning to reveal the real size and complexity of earth itself (indeed, Bruno also spoke forcefully against the violence and profiteering of Spanish colonial efforts) and when natural philosophers had begun to dispute about the very structure of the universe. It may not be a coincidence that the religious troubles of sixteenth-century Europe arose at a time when humanity's very place in the world and the cosmos no longer seemed certain. In Bruno's case, pursuit of his ideas compelled him to leave behind not only the security of his Dominican convent in Naples, but also, and more radically, the security of a traditional sense of who and where he was. His infinite universe terrified a thinker as unconventional as Johannes Kepler, and still more it terrified the Inquisition. For Bruno himself, the excitement of this infinitely expanded vision of the cosmos was usually enough to overrule any doubt, but when Kepler compared living in Bruno's universe to permanent exile, he captured an essential quality of the Italian philosopher: an intense solitude, a solitude for which his philosophy was only ever a partial cure.
Modernism's Love Child
Authors: Wong Yoke-Sum
Published: September 2008

According to Thomas Kuhn, the entrenchment of a paradigm, especially in the critical stages when facing anomalies, requires the further suppression of competing ideas. This essay addresses the unconscious entrenchment of European modernist aesthetics in the everyday, especially in the American suburbs of the 1950s, and its popular and cultural manifestations. Taking Levittown as a starting point, modernist architectural principles have since its construction radiated into the mass-housing market and materialized in housing development projects that have led to the rise of suburbia and, more recently, the New Urbanism. Despite the conventional separations of modernism from the more criticized mass-housing development, the same principles of security, shelter, community, and utopia are present in each. Presented by some architects as a postmodernist aesthetic, the central tenets of modernism are still pursued and reimagined as timeless principles in the building of new housing communities, recycled and reconstituted to meet the dreams and desires of the public—a utopia that is both avant-garde and kitsch.
Controlled Heterogeneous Collection: The Role of Occupation Numbers
Authors: Gerardi A. , Tardelli P.
Published: September 2008

A controlled heterogeneous collection of identical items is presented. According to their level of wear and tear, they are divided into a finite number of classes and the partition of the collection is allowed to change over time. A suitable exchangeability assumption is made to preserve the property that the items be identical. The role of the occupation numbers is investigated and a filtering problem is set up, where the observation is the cardinality of a particular class. A control on the dynamics of the items is introduced, and the existence of an optimal control is proved. A discrete-time approximation for the separated problem, which is a finite-dimensional one, is performed. As a consequence, an approximation for the value function is given.
Random Walk Delayed on Percolation Clusters
Authors: Comets Francis , Simenhaus François
Published: September 2008

We study a continuous-time random walk on the d-dimensional lattice, subject to a drift and an attraction to large clusters of a subcritical Bernoulli site percolation. We find two distinct regimes: a ballistic one, and a subballistic one taking place when the attraction is strong enough. We identify the speed in the former case, and the algebraic rate of escape in the latter case. Finally, we discuss the diffusive behavior in the case of zero drift and weak attraction.
Average-Case Analysis of Cousins in m-ary Tries
Authors: Mahmoud Hosam M. , Ward Mark Daniel
Published: September 2008

We investigate the average similarity of random strings as captured by the average number of ‘cousins’ in the underlying tree structures. Analytical techniques including poissonization and the Mellin transform are used for accurate calculation of the mean. The string alphabets we consider are m-ary, and the corresponding trees are m-ary trees. Certain analytic issues arise in the m-ary case that do not have an analog in the binary case.
Development and evaluation of new control algorithms for a mechanical golf swing device
Authors: Harper T , Roberts J R , Jones R , Carrott A J
Published: September 2008

Golf swing machines have become fundamental tools in the development of new equipment because they provide more consistent swing motions than golfers. Golf robots perform a simplification of the complex sequence of motions that compose a golf swing; however, traditional devices are typically capable of performing only a single swing profile at variable speeds. Significant differences exist between individual golfers' swing motions, especially for golfers of different ability, experience, and physical stature, which suggests a requirement for swing profile variability in mechanical simulators. This investigation has found that the swing motion of a traditional golf robot provides a poor representation of golfers' swings and, as a result, a bespoke control system has been developed for a commercially available golf robot to enable performance of variable swing profiles with positional feedback. Robot swing command files are generated by fitting a curve to a number of discrete data points that are equally spaced in time, and which define angles representative of individual golfers' swings. The swing profiles of a professional golfer and a traditional golf robot were repeated accurately using this golf robot with a modified motion control system. The capability for individual golfers' swings to be accurately replicated using a mechanical device was demonstrated using feedback data. All manufacturers recognize the importance of tailoring equipment to the unique characteristics of a particular golfer's swing, and this increased robot functionality will provide considerable benefits in the development of customized equipment.
Biological computation of optimal task arrangement for a flexible machining cell
Authors: Bakar R A , Watada J
Published: September 2008

A flexible manufacturing system (FMS) plays an important and central role in today's advanced manufacturing. It replaces human tasks (especially those that are highly dangerous ones), efficiently performed tasks, or crucially precise tasks. Considering the NP-hard nature of such computation when the numbers of parameters, robots, or/and tasks are increasing. The objective of this paper is to propose a super parallel computation method optimally to rearrange tasks of an FMS in a production line. A biological computing approach is presented to minimize the waiting time of machines and workstations, and maximize the usage of robots. Biological computing with powerful massive parallelism enables the generation of all feasible solutions at one time, as opposed to the limitation of conventional computing in reaching an optimal solution. The proposed method is illustrated using two different examples of single and multiple robots. Finally, solving an FMS problem is explained from a biological computing point of view.
Anti-windup adaptive control of concatenated closed-link hyper-redundant manipulators
Authors: Koganezawa K , Stoten D P
Published: September 2008

This paper addresses the problem of controlling serial link hyper-redundant manipulators (HRM). Due to the large number of degrees of freedom (DOF) in such devices, the associated dynamics are relatively complicated, non-linear, and subject to a high level of parameter uncertainty. This makes the control problem particularly difficult to solve. An adaptive control scheme based on the minimum control synthesis (MCS) algorithm has therefore been proposed that has been successfully used for controlling similarly complex machines and devices across a number of diverse fields.

MCS has a number of attractive features: e.g. no a priori knowledge of the robot structure is required, there is no need for parameter identification, no precise adjustment of control parameters is necessary, and stability proofs have been well established. After a brief summary of the basic MCS algorithm, an improved algorithm is introduced, which provides a more robust environment in terms of adaptive gain windup protection. A proof of stability, based upon the passivity criterion, is also provided. Simulation results are included, which demonstrate the control effectiveness of the new adaptive algorithm when applied to a manipulator consisting of serially connected, closed-link units.
Model predictive control of low Earth-orbiting satellites using magnetic actuation
Authors: Wood M , Chen W H
Published: September 2008

This paper presents a model predictive control approach for regulating the attitude of magnetically actuated satellites. Unlike other contributions in this area, a predictive control approach is developed which guarantees closed-loop stability of satellite configurations with unstable open-loop pitch dynamics. With the pitch axis being unstable, two magnetic dipoles are used exclusively for regulation of this axis. This allows the dynamics to be treated as a linear time-invariant system, and a simple proportional—derivative (PD) scheme is implemented. A model predictive controller is designed to regulate the lateral dynamics, with a Lyapunov function derived to guarantee asymptotic stability of the closed-loop system. The regulation of the lateral dynamics is achieved with a singe dipole moment, with a novel reformulation of the lateral dynamics also providing an explicit link between the two controllers. Simulations demonstrate the effectiveness and stability of the proposed algorithm when applied to the European Space Agency's GOCE satellite.
Statistical algorithm for the adaptation of detection thresholds
Authors: Stotsky A A
Published: September 2008

Many event detection mechanisms in spark ignition automotive engines are based on the comparison of the engine signals to the detection threshold values. Different signal qualities for new and aged engines necessitate the development of an adaptation algorithm for the detection thresholds. An adaptation algorithm for the detection threshold is developed with the confidence interval method used as the basis for adaptation. The detection threshold is presented using a confidence interval with a given significance level. The adaptation is performed for an aged engine such that the significance level remains constant regardless of engine age and changing detection threshold values. This, in turn, guarantees the same event detection performance for new and aged engines/sensors. Adaptation of the engine knock detection threshold is given as an example.
Stability of discrete-time uncertain systems with a time-varying state delay
Authors: Chen K-F , Fong I-K
Published: September 2008

The stability analysis problem for unforced discrete-time systems with a time-varying state delay is considered. Stability criteria for nominal and uncertain system models are derived such that the upper and lower bounds on the delay time can be determined to ensure asymptotic stability. There is no need to assume that the system is stable when the delay vanishes. Adopting the linear matrix inequality approach enables the computations to be implemented conveniently. Compared with existing results in the literature, the proposed method is less conservative for many cases.
Design, identification, and control of piezoactuated positioning mechanism based on adaptive inverse method
Authors: Ru C , Shao B , Chen L , Rong W , Sun L
Published: September 2008

Precision positioning mechanisms using piezoelectric stack actuators have a very wide range of applications. However, loss of tracking positioning precision in piezoelectric actuators occurs as a result of hysteresis during long-range applications and creep effects. This paper proposes two models that can simultaneously describe the hysteresis and creep phenomena of a piezoelectric actuator. Based on the hysteresis model and creep model, an adaptive inverse control approach is presented for improving the tracking performance of piezo-nanopositioning. The inverse controller is identified by using least mean square algorithm. The realization of the adaptive inverse controller for the linearization of a piezoelectric actuator is formulated. Finally, a tracking control experiment of piezoelectric actuators for a desired trajectory is performed according to the proposed method. The experimental results demonstrate that the positioning precision is noticeably improved in open-loop operation compared with the conventional open-loop control without any compensation.
Development and experimental validation of real-time executable models of primary fly-by-wire actuators
Authors: Di Rito G , Denti E , Galatolo R
Published: September 2008

The availability of practical real-time models of primary flight actuators is a key aspect for performing hardware-in-the-loop simulations of fly-by-wire flight control systems. The solution could be offered by empirical models tuned on experimental data, but this approach would imply that hardware-in-the-loop simulations could be performed only after the actuators have been designed, constructed, and tested. The alternative approach, to which this work refers, is to develop high-fidelity actuator models based on the component physics and to reduce their complexity by trying to obtain a compromise between accuracy of results and real-time execution requirements. In the paper, real-time models of a servo-hydraulic actuator for primary flight controls are developed, taking into account the basic features of the fly-by-wire implementation (the non-linear direct-drive servovalve dynamics, the structural compliance, the oil compressibility, the saturation of commands, and the digital controls) as well as other physical phenomena, which are often disregarded in hydraulic actuator modelling (the hinge play, the flow forces on the servovalve spool, and the laminar servovalve flow). The simulation results of models characterized by different levels of complexity are compared with experimental data obtained by testing the aileron actuator of a modern fly-by-wire aircraft, and the relative importance of the model characteristics is highlighted and discussed, providing useful guidelines about actuator model reduction for real-time applications.
Exponential stability of competitive neural networks with time-varying and distributed delays
Authors: Nie X , Cao J
Published: September 2008

In this paper, time-varying and distributed delays are introduced into competitive neural networks and the global exponential stability for the neural networks is investigated. By using this analysis method, inequality techniques, and the properties of an M-matrix, several novel delay-independent sufficient conditions ensuring the existence, uniqueness, and global exponential stability of the equilibrium point are derived. The obtained results are different from and less restrictive than those given in the existing literature, and the boundedness and differentiability of the activation functions and the differentiability of the time-varying delays are removed. Two examples with their simulations are given to show their good agreement with the theoretical results.
Automated behaviour recognition in mobile robots using symbolic dynamic filtering
Authors: Mallapragada G , Chattopadhyay I , Ray A
Published: September 2008

This paper introduces a dynamic data-driven method for signature detection in mobile robots. The core concept of the paper is built upon the principles of symbolic dynamic filtering (SDF) that can be used to extract relevant information in complex dynamical systems. The objective here is to identify the robot behaviour in real time as accurately as possible. The proposed method is validated by experimentation on a networked robotics test bed to detect and identify the type and motion profile of the robots under consideration.
Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo
Authors: Kaiser Constanze , Dobrikova Elena Y. , Bradrick Shelton S. , Shveygert Mayya , Herbert James T. , Gromeier Matthias
Published: September 2008

Protein synthesis is tightly controlled by assembly of an intricate ribonucleoprotein complex at the m7GTP-cap on eukaryotic mRNAs. Ensuing linear scanning of the 5′ untranslated region (UTR) is believed to transfer the preinitiation complex to the initiation codon. Eukaryotic mRNAs are characterized by significant 5′ UTR heterogeneity, raising the possibility of differential control of translation initiation rate at individual mRNAs. Curiously, many mRNAs with unconventional, highly structured 5′ UTRs encode proteins with central biological roles in growth control, metabolism, or stress response. The 5′ UTRs of such mRNAs may influence protein synthesis rate in multiple ways, but most significantly they have been implicated in mediating alternative means of translation initiation. Cap-independent initiation bypasses strict control over the formation of initiation intermediates at the m7GTP cap. However, the molecular mechanisms that favor alternative means of ribosome recruitment are not understood. Here we provide evidence that eukaryotic initiation factor (eIF) 4G controls cap-independent translation initiation at the c-myc and vascular endothelial growth factor (VEGF) 5′ UTRs in vivo. Cap-independent translation was investigated in tetracycline-inducible cell lines expressing either full-length eIF4G or a C-terminal fragment (Ct) lacking interaction with eIF4E and poly(A) binding protein. Expression of Ct, but not intact eIF4G, potently stimulated cap-independent initiation at the c-myc/VEGF 5′ UTRs. In vitro RNA-binding assays suggest that stimulation of cap-independent translation initiation by Ct is due to direct association with the c-myc/VEGF 5′ UTR, enabling 43S preinitiation complex recruitment. Our work demonstrates that variant translation initiation factors enable unconventional translation initiation at mRNA subsets with distinct structural features.
Severe Sepsis Caused by Arcanobacterium haemolyticum: A Case Report and Review of the Literature
Authors: Therriault Bridgette L , Daniels Lindsay Mayer , Carter Yvonne L , Raasch Ralph H
Published: September 2008

Objective:

To describe a case of severe sepsis, cavitary pneumonia, and pyomyositis caused by Arcanobacterium haemolyticum.

Case Summary:

An 18-year-old male with a medical history significant for mild asthma presented to the emergency department complaining of a 7-day history of fever, diffuse myalgias, nausea, vomiting, diarrhea, and pain in his right upper quadrant, right shoulder, and left thigh. Cultures of blood, bronchoalveolar fluid, and suríace and surgical swabs from the patient's left lower extremity grew A haemolyticum. The patient was successfully treated with intravenous penicillin G 4 million units every 4 hours and azithromycin 500 mg onca daily for 14 days. Within 36 hours after initiation of focused therapy, he became afebrile, pain decreased, and pulmonary symptoms abated. Oral azithromycin 500 mg/day for an additional 3 weeks was prescribed on discharge, and the patient showed no relapse at 2-month follow-up.

Discussion:

A. haemolyticum Is a weakly acid-fast, branching gram-positive bacillus most commonly implicated in pharyngitis in healthy adolescents and skin and soft-tissue infections in older, immunocompromised patients. Systemic infections are rarely reported in the literature. This organism remains susceptible to most classes of antimicrobials, Including penicillins, cephalosporins, carba-penems, macrolides, tetracyclines, clindamycin, and vancomycin. Routine resistance has been reported only with trimethoprim/sulfamethoxazole.

Conclusions:

To our knowledge, there are no published case reports of severe sepsis caused by A. haemolyticum. While treatment options are numerous, we recommend (he use of intravenous penicillin or a cephalosporin as first-line pharmacologic management of deep-seated infections caused by this rare organism.
Pharmacokinetic Interaction Between Everolimus and Antifungal Triazoles in a Liver Transplant Patient
Authors: Pea Federico , Baccarani Umberto , Tavio Marcello , Cojutti Piergiorgio , Adani Gian Luigi , Londero Angela , Baraldo Massimo , Franceschi Loretta , Furlanut Mario , Viale Pierluigi
Published: September 2008

Objective:

TO describe the management of a pharmacokinetic interaction between azole antifungals (fluconazole and voriconazole) and everolimus in a patient who underwent an orthotopic liver transplant.

Case Summary:

A 65-year-old male who received an orthotopic liver transplant experienced an iatrogenic retroperitoneal duodenal perforation on postoperative day 55. His condition was subsequently complicated by severe sepsis and acute renal failure. Intravenous fluconazole 400 mg, followed by 100 mg every 24 hours according to impaired renal function, was immediately started; to avoid further nephrotoxicity, immunosuppressant therapy was switched from cyclosporine plus mycophenolate mofetil to oral everolimus 0.75 mg every 12 hours. Satisfactory steady-state minimum concentration (Cmin) of everolimus was achieved (∼5 ng/mL). On day 72 posttransplant, because of invasive aspergillosis, antifungal therapy was switched to intravenous voriconazole 400 mg every 12 hours on the first day, followed by 200 mg every 12 hours; to prevent drug toxicity, the everolimus dosage was promptly lowered to 0.25 mg every 24 hours. At that time, the everolimus Cmin averaged approximately 3 ng/mL. The concentration/dose ratio of everolimus (ie, Cmin reached at steady-state for each milligram per kilogram of drug administered) was markedly lower during fluconazole versus voriconazole cotreatment (mean ± SD, 3.49 ± 0.29 vs 11.05 ± 0.81 ng/mL per mg/kg/daily; p < 0.001). Despite intensive care, the patient's condition continued to deteriorate and he died on day 84 posttransplant

Discussion:

Both azole antifungals were considered probable causative agents of an interaction with everolimus according to the Drug Interaction Probability Scale. The Interaction is due to the inhibition of CYP3A4–mediated everolimus clearance. Of note, prompt reduction of the everolimus dosage since the first azole coadministration, coupled with intensive therapeutic drug monitoring, represented a useful strategy to prevent drug overexposure.

Conclusions:

Our data suggest that during everolimus-azole cotreatment, a dose reduction of everolimus is needed to avoid overexposure. According to the different inhibitory potency of CYP3A4 activity, the reduction should be lower during fluconazole than during voriconazole cotreatment.
Tripartite Mechanism of Extinction Suggested by Dopamine Neuron Activity and Temporal Difference Model
Authors: Pan Wei-Xing , Schmidt Robert , Wickens Jeffery R. , Hyland Brian I.
Published: September 2008

Extinction of behavior enables adaptation to a changing world and is crucial for recovery from disorders such as phobias and drug addiction. However, the brain mechanisms underlying behavioral extinction remain poorly understood. Midbrain dopamine (DA) neurons appear to play a central role in most acquisition processes of appetitive conditioning. Here, we show that the responses of putative DA neurons to conditioned reward predicting cues also dynamically encode two classical features of extinction: decrement in amplitude of previously learned excitatory responses and rebound of responding on subsequent retesting (spontaneous recovery). Crucially, this encoding involves development of inhibitory responses in the DA neurons, reflecting new, extinction-specific learning in the brain. We explored the implications of this finding by adding such inhibitory inputs to a standard temporal difference model of DA cell activity. We found that combining extinction-triggered plasticity of these inputs with a time-dependent spontaneous decay of weights, equivalent to a forgetting process as described in classical behavioral extinction literature, enabled the model to simulate several classical features of extinction. A key requirement to achieving spontaneous recovery was differential rates of spontaneous decay for weights representing original conditioning and for subsequent extinction learning. A testable prediction of the model is thus that differential decay properties exist within the wider circuits regulating DA cell activity. These findings are consistent with the hypothesis that extinction processes at both cellular and behavioral levels involve a dynamic interaction between new (inhibitory) learning, forgetting, and unlearning.
Experience-Dependent Plasticity from Eye Opening Enables Lasting, Visual Cortex-Dependent Enhancement of Motion Vision
Authors: Prusky Glen T. , Silver Byron D. , Tschetter Wayne W. , Alam Nazia M. , Douglas Robert M.
Published: September 2008

Developmentally regulated plasticity of vision has generally been associated with “sensitive” or “critical” periods in juvenile life, wherein visual deprivation leads to loss of visual function. Here we report an enabling form of visual plasticity that commences in infant rats from eye opening, in which daily threshold testing of optokinetic tracking, amid otherwise normal visual experience, stimulates enduring, visual cortex-dependent enhancement (>60%) of the spatial frequency threshold for tracking. The perceptual ability to use spatial frequency in discriminating between moving visual stimuli is also improved by the testing experience. The capacity for inducing enhancement is transitory and effectively limited to infancy; however, enhanced responses are not consolidated and maintained unless in-kind testing experience continues uninterrupted into juvenile life. The data show that selective visual experience from infancy can alone enable visual function. They also indicate that plasticity associated with visual deprivation may not be the only cause of developmental visual dysfunction, because we found that experientially inducing enhancement in late infancy, without subsequent reinforcement of the experience in early juvenile life, can lead to enduring loss of function.
Precise and Fuzzy Coding by Olfactory Sensory Neurons
Authors: Hoare Derek J. , McCrohan Catherine R. , Cobb Matthew
Published: September 2008

The exact nature of the olfactory signals that arrive in the brain from the periphery, and their reproducibility, remain essentially unknown. In most organisms, the sheer number of olfactory sensory neurons (OSNs) makes it impossible to measure the individual responses of the entire population. We measured the individualin situelectrophysiological activity of OSNs inDrosophilalarvae, in response to stimulation with 10 aliphatic odors (alcohols and esters). We studied control larvae (a total of 296 OSNs) and larvae with a single functional OSN, created using the Gal4-upstream activator sequence system. Most OSNs showed consistent, precise responses (either excitation or inhibition) in response to a given odor. Some OSNs also showed qualitatively variable responses (“fuzzy coding”). This robust variability was an intrinsic property of these neurons: it was not attributable to odor type, concentration, stimulus duration, genotype, or interindividual differences, and was seen in control larvae and in larvae with one and two functional OSNs. We conclude that inDrosophilalarvae the peripheral code combines precise coding with fuzzy, stochastic responses in which neurons show qualitative variability in their responses to a given odor. We hypothesize that fuzzy coding occurs in other organisms, is translated into differing degrees of activation of the glomeruli, and forms a key component of response variability in the first stages of olfactory processing.
Region-Specific Changes in the Subcellular Distribution of AMPA Receptor GluR1 Subunit in the Rat Ventral Tegmental Area after Acute or Chronic Morphine Administration
Authors: Lane Diane A. , Lessard Andree A. , Chan June , Colago Eric E. O. , Zhou Yan , Schlussman Stefan D. , Kreek Mary Jeanne , Pickel Virginia M.
Published: September 2008

Opiate addiction is characterized by progressive increases in drug intake over time suggesting maladaptive changes in motivational and reward systems. These behaviors are mediated by dopaminergic neurons originating from the ventral tegmental area (VTA), and long-term changes of these dopaminergic neurons are attributed to increased postsynaptic glutamatergic activation. Indeed, chronic morphine administration is known to increase AMPA receptor glutamate receptor 1 (GluR1) subunit in the VTA. However, there is no ultrastructural evidence that morphine affects the expression or surface availability of GluR1 subunits in VTA neurons of defined distribution or transmitter phenotype. Therefore, we examined electron microscopic immunolabeling of GluR1 and tyrosine hydroxylase (TH) in two VTA regions of rats perfused 1 h after a single injection of morphine, or chronic morphine in intermittent-escalating doses for 14 d, and appropriate saline controls. Acute morphine administration produced a significant increase in GluR1 immunogold particles at the plasma membrane and postsynaptic densities in both TH- and non-TH-containing dendrites in the parabrachial VTA, a region that contains mainly prefrontal-cortical-projecting dopaminergic neurons involved in motivation and drug-seeking behavior. Chronic morphine administration maintained the increased synaptic GluR1 labeling in the parabrachial VTA, but also increased the number of GluR1-labeled synapses and TH immunoreactivity in dendrites of the paranigral VTA where substantially more dopaminergic neurons project to limbic structures implicated in locomotor activation and reward. These results demonstrate a region- and dose-dependent redistribution of GluR1-containing AMPA receptors, which is consistent with acute morphine activation of cortical-projecting VTA neurons and chronic morphine activation of limbic-projecting VTA neurons.
Cortical Plasticity Induced by Short-Term Unimodal and Multimodal Musical Training
Authors: Lappe Claudia , Herholz Sibylle C. , Trainor Laurel J. , Pantev Christo
Published: September 2008

Learning to play a musical instrument requires complex multimodal skills involving simultaneous perception of several sensory modalities: auditory, visual, somatosensory, as well as the motor system. Therefore, musical training provides a good and adequate neuroscientific model to study multimodal brain plasticity effects in humans. Here, we investigated the impact of short-term unimodal and multimodal musical training on brain plasticity. Two groups of nonmusicians were musically trained over the course of 2 weeks. One group [sensorimotor-auditory (SA)] learned to play a musical sequence on the piano, whereas the other group [auditory (A)] listened to and made judgments about the music that had been played by participants of the sensorimotor-auditory group. Training-induced cortical plasticity was assessed by recording the musically elicited mismatch negativity (MMNm) from magnetoencephalographic measurements before and after training. SA and A groups showed significantly different cortical responses after training. Specifically, the SA group showed significant enlargement of MMNm after training compared with the A group, reflecting greater enhancement of musical representations in auditory cortex after sensorimotor-auditory training compared with after mere auditory training. Thus, we have experimentally demonstrated that not only are sensorimotor and auditory systems connected, but also that sensorimotor-auditory training causes plastic reorganizational changes in the auditory cortex over and above changes introduced by auditory training alone.
Developmental Regulation of Neuromodulator Function in the Stomatogastric Ganglion of the Lobster,Homarus americanus
Authors: Rehm Kristina J. , Deeg Katherine E. , Marder Eve
Published: September 2008

Neuromodulatory substances have profound effects on the two motor patterns generated by the adult crustacean stomatogastric ganglion (STG), the gastric mill rhythm and the pyloric rhythm. Developmentally regulated changes in the modulatory functions of neuromodulators could therefore play an important role in the maturation of the output from the developing STG. We compared the effects of neuromodulators on isolated embryonic and adult STG of the lobster,Homarus americanus. Bath application of Val1-SIFamide, a peptide whose expression is different in embryos and adults, activated different neuron classes in embryos and adults.Cancer borealistachykinin-related peptide 1a, a peptide that does not appear in the terminals of modulatory neurons in the STG until after embryonic development, also produced different motor patterns in embryos and adults. In contrast, red pigment concentrating hormone, a peptide with a similar distribution in the STNS across development, produced similar motor patterns in embryonic and adult STG. Proctolin, serotonin, and allatostatin were also physiologically active on the isolated embryonic STG. Together, these results demonstrate that receptors to many neuromodulators are present and functional on STG neurons before the motor patterns of the stomatogastric nervous system are mature. Moreover, neuromodulator responses change during development, perhaps contributing to the maturation of the output from the stomatogastric nervous system.
Identification of Transmembrane Domain 5 as a Critical Molecular Determinant of Menthol Sensitivity in Mammalian TRPA1 Channels
Authors: Xiao Bailong , Dubin Adrienne E. , Bursulaya Badry , Viswanath Veena , Jegla Timothy J. , Patapoutian Ardem
Published: September 2008

TRPA1 is a member of the transient receptor potential (TRP) family of ion channels and is expressed in a subset of nociceptive neurons. An increasing body of evidence suggests that TRPA1 functions as a chemical nocisensor for a variety of reactive chemicals, such as pungent natural compounds and environmental irritants. Activation of TRPA1 by reactive compounds has been demonstrated to be mediated through covalent modification of cytoplasmic cysteines located in the N terminus of the channel, rather than classical lock-and-key binding. TRPA1 activity is also modulated by numerous nonreactive chemicals, but the underlying mechanism is unknown. Menthol, a natural nonreactive cooling compound, is best known as an activator of TRPM8, a related TRP ion channel required for cool thermosensationin vivo. More recently, menthol has been shown to be an activator of mouse TRPA1 at low concentrations, and a blocker, at high concentrations. Here, we show that human TRPA1 is only activated by menthol, whereas TRPA1 from nonmammalian species are insensitive to menthol. Mouse-human TRPA1 chimeras reveal the pore region [including transmembrane domain 5 (TM5) and TM6] as the critical domain determining whether menthol can act as an inhibitor. Furthermore, chimeras betweenDrosophila melanogasterand mammalian TRPA1 highlight specific residues within TM5 critical for menthol responsiveness. Interestingly, this TM5 region also determines the sensitivity of TRPA1 to other chemical modulators. These data suggest separable structural requirements for modulation of TRPA1 by covalent and nonreactive molecules. Whether this region is involved in binding or gating of TRPA1 channels is discussed.
Induction of Proneurotrophins and Activation of p75NTR-Mediated Apoptosis via Neurotrophin Receptor-Interacting Factor in Hippocampal Neurons after Seizures
Authors: Volosin Marta , Trotter Christy , Cragnolini Andrea , Kenchappa Rajappa S. , Light Matthew , Hempstead Barbara L. , Carter Bruce D. , Friedman Wilma J.
Published: September 2008

Seizure-induced damage elicits a loss of hippocampal neurons mediated to a great extent by the p75 neurotrophin receptor (NTR). Proneurotrophins, which are potent apoptosis-inducing ligands for p75NTR, were increased in the hippocampus, particularly in astrocytes, by pilocarpine-induced seizures; and infusion of anti-pro-NGF dramatically attenuated neuronal loss after seizures. The p75NTRis expressed in many different cell types in the nervous system, and can mediate a variety of different cellular functions by recruiting specific intracellular binding proteins to activate distinct signaling pathways. In this study, we demonstrate that neurotrophin receptor-interacting factor (NRIF) mediates apoptotic signaling via p75NTRin hippocampal neuronsin vitroandin vivo. After seizure-induced injury,NRIF−/−mice showed an increase in p75NTRexpression in the hippocampus; however, these neurons failed to undergo apoptosis in contrast to wild-type mice. Treatment of cultured hippocampal neurons with proneurotrophins induced association of NRIF with p75NTRand subsequent translocation of NRIF to the nucleus, which was dependent on cleavage of the receptor. Neurons lacking NRIF were resistant to p75NTR-mediated apoptosisin vitroandin vivo. In addition, we demonstrate some mechanistic differences in p75NTRsignaling in hippocampal neurons compared with other cell types. Overall, these studies demonstrate the requirement for NRIF to signal p75NTR-mediated apoptosis of hippocampal neurons and that blocking pro-NGF can inhibit neuronal loss after seizures.