bluuebunny/crossref_metadata_2025 huggingface dataset:
NONLINEAR ELECTROABSORPTION IN ASYMMETRIC TRIANGULAR QUANTUM WELI SELF-ELECTRO-OPTIC EFFECT DEVICES
Authors: PUECHNER R.A. , GERBER D.S. , DROOPAD R. , MARACAS G.N.
Published: November 2004

The electroabsorptive behavior of asymmetric triangular quantum wells (ATQW) in the active region of a p-i-n self-electro-optic effect device (SEED) structure is experimentally investigated. Excition transition energies are measured by photoluminescence and photocurrent spectroscopy at room temperature and at low temperatures. Room-temperature excitonic linewidths of 9.2 meV for a 265-Å ATQW have been obtained. The electric field modulation of excitonic absorption in ATQWs with compositional grading, both increasing and decreasing in the growth direction is presented. When compared with a similar rectangular quantum-well device, it is observed that ATQWs have intrinsically higher responsivity, comparable room temperature linewidths, and higher device on/off ratios.
THIRD-ORDER NONLINEAR OPTICAL PROPERTIES OF METALLO-PHTHALOCYANINES
Authors: SHIRK JAMES S. , LINDLE J.R. , BARTOLI F.J. , KAFAFI ZAKYA H. , SNOW ARTHUR W. , BOYLE MICHAEL E.
Published: November 2004

This paper discusses the third-order nonlinear optical (NLO) properties of metal-free, lead and transition metal phthalocyanines, as well as scandium, yttrium and lanthanide bisphthalocyanines measured by time-resolved degenerate four-wave mixing at 1064 nm. The study focuses on the structure-property relationships and explores the possible mechanisms leading to the enhanced third-order optical nonlinearity measured for this interesting class of NLO materials.
COOP: A SELF-ASSESSMENT BASED APPROACH TO COOPERATING EXPERT SYSTEMS
Authors: SHEKHAR SHASHI , RAMAMOORTHY C. V.
Published: November 2004

Conventional Expert System Shells do not help in developing AI programs for large applications like automated factories, which require multi-disciplinary knowledge and which are geographically distributed. To support these applications, a shell must provide tools for a knowledge-based system to (i) reason about the need for cooperation, (ii) understand global knowledge to locate relevant expert systems and (iii) select appropriate cooperation plans. Contemporary approaches like Blackboard [1], Contract-net [2] and Distributed problem solving [3] help in exploring alternative cooperation plans without any reasoning about the need for cooperation and understanding of global knowledge. Coop [4] support cooperation models to characterize three essential decisions in the cooperation process. It provides a computational method to decide if an expert system needs to consult with other expert systems. We provide techniques select appropriate cooperation plans.
NATURAL LANGUAGE PROCESSING WITHIN A SLOT GRAMMAR FRAMEWORK
Authors: MCCORD MICHAEL , BERNTH ARENDSE , LAPPIN SHALOM , ZADROZNY WLODEK
Published: November 2004

This paper contains brief descriptions of the latest form of Slot Grammar and four natural language processing systems developed in this framework. Slot Grammar is a lexicalist, dependency-oriented grammatical system, based on the systematic expression of linguistic rules and data in terms of slots (essentially grammatical relations) and slot frames. The exposition focuses on the kinds of analysis structures produced by the Slot Grammar parser. These structures offer convenient input to post-syntactic processing (in particular to the applications dealt with in the paper); they contain in a single structure a useful combination of surface structure and logical form. The four applications discussed are: (1) An anaphora resolution system dealing with both NP anaphora and VP anaphora (and combinations of the two). (2) A meaning postulate based inference system for natural language, in which inference is done directly with Slot Grammar analysis structures. (3) A new transfer system for the machine translation system LMT, based on a new representation for Slot Grammar analyses which allows more convenient tree exploration. (4) A parser of "constructions", viewed as an extension of the core grammar allowing one to handle some linguistic phenomena that are often labeled "extragrammatical", and to assign a semantics to them.
A SURVEY ON THE PARALLEL DISTRIBUTED PROCESSING OF PRODUCTION SYSTEMS
Authors: SOHN ANDREW , GAUDIOT JEAN-LUC
Published: November 2004

The importance of production systems in artificial intelligence (AI) has been repeatedly demonstrated by a large number of expert systems. As the number and size of expert systems grow, there has however been an emerging obstacle in such AI applications: the large processing time. The need for faster execution of production systems has spurred research in both the software and hardware domains, including connectionist architectures. This paper surveys various aspects of parallel distributed processing of production systems. Approaches taken to date to solve the problems associated with production systems are classified here into three levels: the algorithmic level, the parallel implementation level, and the connectionist level. Several pattern matchers and multiple rule firing principles are presented to demonstrate the algorithm level improvement. Several parallel implementation efforts are surveyed along with experimental results on real machines or with simulators. The presentation of three different types of connectionist production systems (local, distributed, and hierarchical representation) completes this survey. Finally, we explore some potential avenues towards the implementation of a true asynchronous parallel production system.
LEARNING FROM EXAMPLES IN UNIVERSE OF DISCOURSE DESCRIBED BY A SET OF EQUATIONS
Authors: KOUNALIS EMMANUEL
Published: November 2004

Generalization is an important operation for programs that learn. Anti-unification guarantees the existence of a term which is the most specific generalization of a collection of terms. This provides a formal basis for learning from examples. However, such generalization may be "too" general and therefore counterexamples are required to restrict them. In this case, the learner has to check whether the resulting formula provides a concept to learn, i.e. whether a formula of the form t/{t1,…,tn} is a generalization, where t is viewed as a generalization of a set of examples and t1,…,tn are counterexample. The formula t/{t1,…,tn} is often called an implicit representation. The implicit representation t/{t1,…,tn} is a generalization iff there exist ground (variable-free) instances of t which are not instances of t1,…,tn. This is a non-trivial task even when there is no background knowledge (see [15]).

We present here a method to check whether an implicit representation t/{t1,…,tn} is a generalization with respect to a finite set of equations which describes the background knowledge problem, i.e. whether there exists a ground instance of t which is not equivalent to any ground instance of t1,…,tn with respect to a set E of equations. Whereas this problem is in general undecidable since the equality is so, we show in this paper that in this case where the set E of equations is compiled into a ground convergent term rewriting system, we can discover concepts in Universe of Discourse with background knowledge described by a finite set of equations. We show how the method applies to induce concepts in theories of elementary arithmetic.
COMBINATORIAL SEARCH ALGORITHMS WITH META-CONTROL: MODELING AND IMPLEMENTATIONS
Authors: WAH BENJAMIN W. , CHU LON-CHAN
Published: November 2004

In this paper, we model search algorithms with meta-control, allowing resource constraints, approximation, and parallel processing to be incorporated easily in the search process. The basic building block of the model is a hierarchical search process (HSP) consisting of context-free and context-sensitive grammars classified according to problem-independent and problem-dependent parts. The context-sensitive components are used mainly for evaluating decision parameters and in ordering production rules in the context-free grammar. The execution of the grammars for given initial conditions may invoke other HSPs already defined in the system. We describe ISE (acronym for Integrated Search Environment), a tool that implements hierarchical searches with meta-control. By separating the problem-dependent and problem-independent components in ISE, new search methods based on a combination of existing methods can be developed easily by coding a single master control program. Further, new applications solved by searches can be developed by coding the problem-dependent parts and reusing the problem-independent parts already developed. We describe the organization of ISE and present experiments carried out on the system.
CLOSED 3–MANIFOLDS UNCHANGED BY DEHN SURGERY
Authors: MATHIEU Yves
Published: November 2004

If X is the space of the trefoil knot, we can find, for every integer e, two slopes on ∂X, ρe, γe, such that the Dehn fillings X (ρe) and X (γe) are homeomorphic 3-manifolds. The cores of the surgeries are inequivalent knots with homeomorphic complements. Analogous results are available if X is the knotspace of a 2-bridge torus knot. In an atoroidal homology sphere knots are determined by their complement if and only if hyperbolic knots are.
QUASIPOSITIVE ANNULI (CONSTRUCTIONS OF QUASIPOSITIVE KNOTS AND LINKS, IV)
Authors: RUDOLPH LEE
Published: November 2004

The modulus of quasipositivityq(K) of a knot K was introduced as a tool in the knot theory of complex plane curves, and can be applied to Legendrian knot theory in sym-plectic topology. It has also, however, a straightforward characterization in ordinary knot theory: q(K) is the supremum of the integers f such that the framed knot (K, f) embeds non-trivially on a fiber surface of a positive torus link. Geometric constructions show that −∞ < q(K), calculations with link polynomials that q(K) < ∞. The present paper aims to provide sharper lower bounds (by optimizing the geometry with positive plats) and more readily calculated upper bounds (by modifying known link polynomials), and so to compute q(K) for various classes of knots, such as positive closed braids (for which q(K) = μ(K) − 1) and most positive pretzels. As an aside, it is noted that a recent result of Kronheimer & Mrowka implies that q(K) < 0 if K is slice.
RECOGNIZING NONORIENTABLE SEIFERT BUNDLES
Authors: WHITTEN WILBUR
Published: November 2004

Roughly speaking, a compact, orientable, irreducible 3-manifold M with infinite fundamental group is a Seifert fiber space, if either 1) π1M contains a nontrivial, cyclic, normal subgroup (the so-called Seifert-fiber-space conjecture), 2) M is finitely covered by a Seifert fiber space, or 3) π1M is isomorphic to the group of a Seifert fiber space. Excluding a fake P2 × S1 where necessary, we show in this paper that similar results hold when M is nonorientable.
RIBBON KNOTS WITH TWO RIBBON TYPES
Authors: YASUDA TOMOYUKI
Published: November 2004

A ribbon n-knot Kn is constructed by attaching m bands to m + 1n-spheres in the euclidean (n + 2)-space. There are many way of attaching them; as a result, Kn has many presentations which are called ribbon presentations. But concerning the case of m = 1, it was proved in the case of n = 1 by M. Scharlemann, and n ≥ 2 by Y. Marumoto that if Kn is unknotted, its ribbon presentation is essentially unique. In this note, we will prove in the case of m = 1 and n ≥ 2 that there are infinitely many ribbon n-knots which has essentially different two ribbon presentations.
STATISTICAL ANALYSES ON AN UPDATED CATALOGUE OF VOIDS
Authors: HAQUE-COPILAH S. , BASU D.
Published: November 2004

This paper presents an updated catalogue of voids which contains the Kauffmann and Fairall1 sample as a subset, and includes all reported voids in the literature to date. Our catalogue contains 182 voids. Several statistical analyses have been performed on this data and the results show that (i) voids are found to be distributed fairly homogeneously and isotropically throughout the sky, (ii) the most frequent size of the voids in the sky has a radius less than 10 Mpc, (iii) the size of the voids in terms of the volume obeys a relationship with distance (redshift) in the sense that larger voids are located at greater distances.
STRUCTURE OF INTRUDER STATES
Authors: ARENAS PERIS G. E.
Published: November 2004

Nuclear intruder states are described in terms of a weak-coupling model which permits to extract important information from experimental data. The monopole neutron–proton interaction plays a fundamental role in the energy systematics of these states and a model consistent method to obtain its matrix elements from experiment has been developed. Calculations without free parameters were performed for a large variety of excitations throughout the Nuclide Chart. The agreement with experiment is quite satisfactory.
IN-MEDIUM NEUTRON-PROTON MASS DIFFERENCE WITH NUCLEAR CHIRAL MODELS
Authors: KREIN G. , MENEZES D. P. , NIELSEN M.
Published: November 2004

The neutron-proton mass difference in nuclear matter is calculated within the context of chiral models involving nucleon and meson degrees of freedom. The interplay of chiral symmetry and charge symmetry breaking on neutron and proton self-energies are discussed in a relativistic Hartree–Fock approximation. Exchange terms are crucial to obtain different contributions for the neutron and proton self-energies. Density dependence of meson masses and coupling constants are taken into account. We find that the neutron-proton mass difference in nuclear matter increases as the density increases, contrary to the predictions of several quark models and of QCD sum rules at finite density.
A SYSTEMATIC METHOD TO ARTICULATE STRATEGIC VISION: AN ILLUSTRATION WITH A SMALL BUSINESS OWNER-MANAGER
Authors: COSSETTE PIERRE
Published: November 2004

The concept of strategic vision has attracted growing interest in recent years. However, very few methods exist to help enterprise leaders make their strategic vision more explicit. The goal of this research is to present and illustrate a new systematic method to help enterprise leaders articulate and question their strategic visions. The method is based on cognitive mapping, and can be broken down into four phases: an exploration phase, in which the leader explores his or her own ideas using a specially designed grid; a validation phase, to verify the credibility or "validity" of the cognitive map resulting from the first phase; an analysis phase, where the semantic network formed by the concepts and links of the map are analyzed using the Decision Explorer software; and a finalization phase, where the leader, after being informed of the results of validated map analysis and the researcher's interpretation of them, confirms or modifies the strategic vision. The paper contains a detailed description of the four phases together with the results obtained with the owner-manager of a small manufacturing business in Québec. Since the method described supports thinking and thus action, it is likely to be of interest to practitioners and consultants. Academics may also benefit from it, since it can be used to study strategic vision and its impact.
TRIGGERS AND BARRIERS AFFECTING ENTREPRENEURIAL INTENTIONALITY: THE CASE OF WESTERN AUSTRALIAN NASCENTE ENTREPRENEURS
Authors: VOLERY THIERRY , DOSS NOELLE , MAZZAROL TIM , THEIN VICKI
Published: November 2004

This paper sheds light on the process leading to new enterprise formation while identifying the triggers and barriers to business start-ups. A new approach was used in this study to focus on the pre-decision stage, i.e. the intention and characteristics of nascent entrepreneurs. In addition to the "usual" triggers to start-up, this study has highlighted a more intriguing one: the will to invest savings in a business venture which will provide the investor with a job and the satisfaction of being rewarded on merits. The results suggest that this trigger matches the profile of mid-career professionals who want to become self-employed. Underlying barriers include the lack of resources, compliance costs, and the hard reality of "going into business".
REORGANISATIONS TO INCREASE ENTREPRENEURIAL FLEXIBILITY
Authors: WITT PETER
Published: November 2004

A large number of corporations around the world have changed their organisational structure in the past few years. The aim is to overcome rigid structures and to increase entrepreneurial flexibility. This paper first defines entrepreneurial flexibility and then analyses the forms of flexible organisational structures to determine the essential components of entrepreneurial and flexible organisational designs. The results indicate that, although many different flexible organisational forms have been proposed and implemented, entrepreneurial flexibility requires three organisational characteristics: teamwork, intense information and knowledge transfer between organisational units, and fewer hierarchy levels. Entrepreneurial flexibility does not imply dissoluteness and a lack of structure. Hierarchy and control remain important in every organisation.
EMPLOYEE STOCK OPTION SCHEMES IN SINGAPORE
Authors: LIM BOON-CHYE , HO KWEE-CHOO , NG BEE-YEN , TAN HAI-WUN
Published: November 2004

Among the various suggestions for improving the Singapore economy, a high-level task-force known as the Economic Committee in its 1986 report has suggested that Employee Stock Option Schemes (ESOS) "should be encouraged, as this is a good way to foster greater commitment of employees to their companies' financial performance". This paper discusses the status of Employee Stock Option Schemes in Singapore. An examination of the companies listed on the Main Board of the Stock Exchange of Singapore shows that only a minority of the Singapore incorporated and listed companies have offered ESOS. The study also finds that ESOS tends to be offered by the bigger companies within each sector of the economy. The results of a recent questionnaire survey show that among the companies that offered ESOS, motivating employees is the most popular objective for offering such schemes and these schemes are judged to be satisfactory in achieving it.
NETWORKING AND ENTREPRENEURIAL SUCCESS IN A TRANSITION ECONOMY
Authors: KUZNETSOV ANDREI , MCDONALD FRANK , KUZNETSOVA OLGA
Published: November 2004

A successful Russian entrepreneur was selected as a case study in order to find out if this person required any specific qualities different from those routinely attributed by academic literature to his counterpart in the West. Results reported here provide early evidence of great similarities in the typology of successful entrepreneurs in transition and market economies. Yet if the qualities required are ranged according to their importance there is a clear bias towards the ability to create or join networks and the advantage of sharing common values arising from the importance of personal contacts to obtain resources in Russia.
LOCAL CULTURE MEETS SINGLE EUROPEAN MARKET - AN ASSESSMENT OF INTERNATIONALIZATION CHALLENGES AND OPPORTUNITIES FOR INDEPENDENT ENTREPRENEURS IN THE FRENCH BOOK RETAIL SECTOR
Authors: PIOCH ELKE , SCHMIDT RUTH A.
Published: November 2004

The introduction of the Single European Market (SEM) acted as a catalyst to internationalization activities throughout the European Union (EU). Set against the backdrop of a wider study of retail change within the SEM this industry case study examines the changing role of the independent sector within French book retailing in the face of a growing trend towards cross-border activity. The interplay between consumer culture and the dynamics of the changing structural components of the market is discussed against the backdrop of a wider EU context. Barriers and challenges as well as opportunities for international activities are examined and the respective positioning of the different types of retail capital considered. Conclusions highlight the importance of entrepreneurial style rather than the size of the firm as a driver of international activity and present a discussion of likely future trends in this market.
Skeletal muscle myofibrillar protein metabolism in heart failure: relationship to immune activation and functional capacity
Authors: Toth Michael J. , Matthews Dwight E. , Ades Philp A. , Tischler Marc D. , Van Buren Peter , Previs Michael , LeWinter Martin M.
Published: November 2004

Chronic heart failure is characterized by changes in skeletal muscle that contribute to physical disability. Most studies to date have investigated defects in skeletal muscle oxidative capacity. In contrast, less is known about how heart failure affects myofibrillar protein metabolism. Thus we examined the effect of heart failure on skeletal muscle myofibrillar protein metabolism, with a specific emphasis on changes in myosin heavy chain (MHC) protein content, synthesis, and isoform distribution in 10 patients with heart failure (63 ± 3 yr) and 11 controls (70 ± 3 yr). In addition, we examined the relationship of MHC protein metabolism to inflammatory markers and physical function. Although MHC and actin protein content did not differ between groups, MHC protein content decreased with increasing disease severity in heart failure patients ( r = −0.748, P < 0.02), whereas actin protein content was not related to disease severity. No difference in MHC protein synthesis was found between groups, and MHC protein synthesis rates were not related to disease severity. There were, however, relationships between C-reactive protein and both MHC protein synthesis ( r = −0.442, P = 0.05) and the ratio of MHC to mixed muscle protein synthesis ( r = −0.493, P < 0.03). Heart failure patients showed reduced relative amounts of MHC I ( P < 0.05) and a trend toward increased MHC IIx ( P = 0.06). In regression analyses, decreased MHC protein content was related to decreased exercise capacity and muscle strength in heart failure patients. Our results demonstrate that heart failure affects both the quantity and isoform distribution of skeletal muscle MHC protein. The fact that MHC protein content was related to both exercise capacity and muscle strength further suggests that quantitative alterations in MHC protein may have functional significance.
Assessment of heat production, heat loss, and core temperature during nitrous oxide exposure: a new paradigm for studying drug effects and opponent responses
Authors: Kaiyala Karl J. , Ramsay Douglas S.
Published: November 2004

Studies using core temperature (Tc) have contributed greatly to theoretical explanations of drug tolerance and its relationship to key features of addiction, including dependence, withdrawal, and relapse. Many theoretical accounts of tolerance propose that a given drug-induced psychobiological disturbance elicits opponent responses that contribute to tolerance development. This proposal and its theoretical extensions (e.g., conditioning as a mechanism of chronic tolerance) have been inferred from dependent variables, such as Tc, which represent the summation of multiple underlying determinants. Direct measurements of determinants could increase the understanding of opponent processes in tolerance, dependence, and withdrawal. The proximal determinants of Tc are metabolic heat production (HP) and heat loss (HL). We developed a novel system for simultaneously quantifying HP (indirect calorimetry), HL (direct gradient layer calorimetry), and Tc (telemetry) during steady-state administrations of nitrous oxide (N2O), an inhalant with abuse potential that has been previously used to study acute and chronic tolerance development to its hypothermia-inducing property. Rats were administered 60% N2O ( n = 18) or placebo gas ( n = 16) for 5 h after a 2-h placebo baseline exposure. On average, N2O rapidly but transiently lowered HP and increased HL, each by ∼16% ( P < 0.001). On average, rats reestablished and maintained thermal equilibrium (HP = HL) at a hypothermic Tc (−1.6°C). However, some rats entered positive heat balance (HP > HL) after becoming hypothermic such that acute tolerance developed, i.e., Tc rose despite continued drug administration. This work is the first to directly quantify the thermal determinants of Tc during administration of a drug of abuse and establishes a new paradigm for studying opponent processes involved in acute and chronic hypothermic tolerance development.
Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney
Authors: Adin Christopher A. , Croker Byron P. , Agarwal Anupam
Published: November 2004

Heme oxygenase-1 (HO-1) is induced as an adaptive and protective response to tissue injury. HO-1 degrades heme into carbon monoxide (CO) and biliverdin; the latter is then converted to bilirubin. These reaction products have powerful antiapoptotic and antioxidant effects. Manipulation of the HO-1 system by administration of micromolar doses of exogenous CO or bilirubin has been performed in several organ systems, but the dose-related effects of these reaction products have not been investigated in the kidney. The purpose of this study was to evaluate the efficacy and dose-related protective effects of 1 or 10 μM bilirubin flush before a 20-min period of warm ischemia. In an effort to minimize interactions with other chemical messengers or organ systems, we elected to use an isolated, perfused rat kidney model with an acellular, oxygenated perfusate. Using this model, we demonstrated that bilirubin treatment resulted in significant improvements in renal vascular resistance, urine output, glomerular filtration rate, tubular function, and mitochondrial integrity after ischemia-reperfusion injury (IRI). Beneficial effects on organ viability were achieved most consistently with a dose of 10 μM bilirubin. We conclude that the protective effects of HO-1 activity during IRI in the kidney are mediated, at least in part, by bilirubin and that pretreatment with micromolar doses of bilirubin may offer a simple and inexpensive method to improve renal function after IRI.
Encoding of Amplitude and Rate of Tooth Loads by Human Periodontal Afferents From Premolar and Molar Teeth
Authors: Johnsen Skjalg E. , Trulsson Mats
Published: November 2004

Microneurographic recordings were obtained from 20 periodontal mechanoreceptive afferents in the inferior alveolar nerve while force profiles of different amplitudes and rates were applied to a premolar or the first molar in the most sensitive direction. The majority of afferents (17/20) showed a hyperbolic relationship between the steady-state discharge rate and the amplitude of the stimulating force, featuring a pronounced saturation tendency. These afferents were also characterized by a similar decline in dynamic sensitivity with increasing amplitude of background force. However, a few afferents (3/20) showed nearly linear stimulus-response relationships and a small decline in dynamic sensitivity with increasing tooth load. Quantitative models developed for all afferents successfully predicted the afferent discharge rates for novel force stimulations. Application of the transfer function to chewing forces predicted that the discharge rates of periodontal afferents rapidly increased at initial tooth contact and continued to discharge as long as the tooth was loaded. However, due to the marked saturation tendencies at higher forces, most periodontal afferents poorly encoded the magnitude of the strong chewing forces. In addition, the discharge rates of a minority of afferents continued to reflect the force profile during high chewing forces. The results revealed that periodontal afferents of posterior teeth were less sensitive at low tooth loads compared with afferents of anterior teeth. During each chewing cycle, periodontal afferents may provide information about the mechanical properties of food shortly after tooth contact that can be used to scale the muscle commands of the upcoming power phase.
Propofol-Block of SK Channels in Reticular Thalamic Neurons Enhances GABAergic Inhibition in Relay Neurons
Authors: Ying Shui-Wang , Goldstein Peter A.
Published: November 2004

The GABAergic reticular thalamic nucleus (RTN) is a major source of inhibition for thalamocortical neurons in the ventrobasal complex (VB). Thalamic circuits are thought to be an important anatomic target for general anesthetics. We investigated presynaptic actions of the intravenous anesthetic propofol in RTN neurons, using RTN-retained and RTN-removed brain slices. In RTN-retained slices, focal and bath application of propofol increased intrinsic excitability, temporal summation, and spike firing rate in RTN neurons. Propofol-induced activation was associated with suppression of medium afterhyperpolarization potentials. This activation was mimicked and completely occluded by the small conductance calcium-activated potassium (SK) channel blocker apamin, indicating that propofol could enhance RTN excitability by blocking SK channels. Propofol increased GABAergic transmission at RTN-VB synapses, consistent with excitation of presynaptic RTN neurons. Stimulation of RTN resulted in synaptic inhibition in postsynaptic neurons in VB, and this inhibition was potentiated by propofol in a concentration-dependent manner. Removal of RTN resulted in a dramatic reduction of both spontaneous postsynaptic inhibitory current frequency and propofol-mediated inhibition of VB neurons. Thus the existence and activation of RTN input were essential for propofol to elicit thalamocortical suppression; such suppression resulted from shunting through the postsynaptic GABAA receptor-mediated chloride conductance. The results indicate that propofol enhancement of RTN-mediated inhibitory input via blockade of SK channels may play a critical role in “gating” spike firing in thalamocortical relay neurons.
Pulsatile Luteinizing Hormone and Follicle-Stimulating Hormone Secretion and Gonadotropin Subunit mRNA Levels in the Ovariectomized GPR-4 Transgenic Rat
Authors: El Majdoubi Mohammed , Paruthiyil Sreenivasan , Weiner Richard I.
Published: November 2004

Genetic targeting of the cAMP-specific phosphodiesterase 4D1 (PDE4D1) to gonadotropin-releasing hormone (GnRH) neurons in the GPR-4 transgenic rat resulted in decreased luteinizing hormone (LH) pulse frequency in castrated female and male rats. A similar decrease in the intrinsic GnRH pulse frequency was observed in GT1 GnRH cells expressing the PDE4D1 phosphodiesterase. We have extended these findings in ovariectomized (OVX) GPR-4 rats by asking what effect transgene expression had on pulsatile LH and follicle-stimulating hormone (FSH) secretion, plasma and pituitary levels of LH and FSH, and levels of the α-glycoprotein hormone subunit (α-GSU), LH-β and FSH-β subunit mRNAs. In OVX GPR-4 rats the LH pulse frequency but not pulse amplitude was decreased by 50% compared to wild-type littermate controls. Assaying the same samples for FSH, the FSH pulse frequency and amplitude were unchanged. The plasma and anterior pituitary levels of LH in the GPR-4 rats were significantly decreased by approximately 45%, while the plasma but not anterior pituitary level of FSH was significantly decreased by 25%. As measured by real-time RT-PCR, the mRNA levels for the α-GSU in the GPR-4 rats were significantly decreased by 41%, the LH-β subunit by 38% and the FSH-β subunit by 28%. We conclude that in the castrated female GPR-4 rats the decreased GnRH pulse frequency results in decreased levels of LH and FSH and in the α- and β-subunit mRNA levels.
Infrared and Raman spectra of ZrSiO4 experimentally shocked at high pressures
Authors: Gucsik A. , Zhang M. , Koeberl C. , Salje E. K. H. , Redfern S. A. T. , Pruneda J. M.
Published: November 2004

Zircon- and reidite-type ZrSiO4 produced by shock recovery experiments at different pressures have been studied using infrared (IR) and Raman spectroscopy. The v3 vibration of the SiO4 group in shocked natural zircon shows a spectral change similar to that seen in radiation-damaged zircon: a decrease in frequency and increase in linewidth. The observation could imply a possible similar defective crystal structure between the damaged and shocked zircon. The shock-pressure-induced structural phase transition from zircon (I41/amd) to reidite (I41/a) is proven by the occurrence of additional IR and Raman bands. Although the SiO4 groups in both zircon- and reidite-ZrSiO4 are isolated, the more condensed scheelite gives rise to Si–O stretching bands at lower frequencies, suggesting a weakening of the bond strength. Low-temperature IR data of the reidite-type ZrSiO4 show an insignificant effect of cooling on the phonon modes, suggesting that the structural response of reidite to cooling-induced compression is weak and its thermal expansion is very small.
Quantum mechanical study of Al/Si disorder in leucite and bicchulite
Authors: Winkler B. , Milman V. , Pickard C. J.
Published: November 2004

We have studied the structures of Al/Si disordered leucite and bicchulite with a quantum mechanical version of the virtual crystal approximation, VCA. In leucite, the average tetrahedron has a composition of (AlSi2)O4, while bicchulite represents an extreme case with (Al2Si)O4tetrahedra. Both structures are well described with the VCA. In conjunction with an earlier study, where we have shown that the (AlSi)O4tetrahedra in gehlenite and Al,Si-disordered octahedra are also well reproduced, we have now established that the VCA gives a reliable description of the averaged structure of disordered aluminosilicates over the whole compositional range. The current calculations confirm that Al/Si ordering is not driving the cubic to tetragonal phase transformation in leucite. In bicchulite, the model calculations are consistent with hydrogen on Wyckoff position 8c, in agreement with the result of a single crystal X-ray diffraction study, but in variance with results based on a neutron powder diffraction study.
Roles of vascular endothelial growth factor receptor 3 signaling in differentiation of mouse embryonic stem cell–derived vascular progenitor cells into endothelial cells
Authors: Suzuki Hiroyuki , Watabe Tetsuro , Kato Mitsuyasu , Miyazawa Keiji , Miyazono Kohei
Published: November 2004

Vascular endothelial growth factor receptor 2 (VEGFR2/Flk-1)–positive cells derived from embryonic stem (ES) cells serve as vascular progenitors, which differentiate into endothelial cells (ECs) in the presence of VEGF-A. VEGFR3/Flt-4 (fms-like tyrosine kinase 4) signaling is known to be important for the development of lymphatic endothelial cells (LECs). To elucidate the roles of VEGFR3 signaling in the differentiation of vascular progenitor cells into ECs, we introduced various types of VEGFR3 cDNAs into mouse ES cells. VEGF-C, a ligand for VEGFR2 and VEGFR3, stimulated the endothelial differentiation of the VEGFR2+ cells transfected with the VEGFR3 cDNA but not those transfected with kinasenegative mutants of VEGFR3. The VEGFR3-transfected ECs exhibited high expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), one of the markers of LECs, and showed efficient binding of hyaluronan. VEGF-C(C152S), which is able to activate VEGFR3 but not VEGFR2, failed to induce the endothelial differentiation of mock- and VEGFR3-transfected VEGFR2+ cells, suggesting the essential role of VEGFR2 signaling for endothelial differentiation. Furthermore, kinase-negative mutants of VEGFR3 prevented the VEGF-C–mediated endothelial differentiation of the vascular progenitor cells. Thus, VEGFR2 signaling is required for the endothelial differentiation of mouse ES cells induced by VEGF-C, and VEGFR3 signaling may confer lymphatic endothelial-like phenotypes to ECs.
Thechiantizebrafish mutant provides a model for erythroid-specific disruption oftransferrin receptor 1
Authors: Wingert Rebecca A. , Brownlie Alison , Galloway Jenna L. , Dooley Kimberly , Fraenkel Paula , Axe Jennifer L. , Davidson Alan J. , Barut Bruce , Noriega Laura , Sheng Xiaoming , Zhou Yi , Zon Leonard I.
Published: November 2004

Iron is a crucial metal for normal development, being required for the production of heme, which is incorporated into cytochromes and hemoglobin. The zebrafish chianti (cia) mutant manifests a hypochromic,microcytic anemia after the onset of embryonic circulation, indicative of a perturbation in red blood cell hemoglobin production. We show that cia encodes tfr1a, which is specifically expressed in the developing blood and requisite only for iron uptake in erythroid precursors. In the process of isolating zebrafish tfr1, we discovered two tfr1-like genes (tfr1a and tfr1b) and a single tfr2 ortholog. Abrogation of tfr1b function using antisense morpholinos revealed that this paralog was dispensable for hemoglobin production in red cells. tfr1b morphants exhibited growth retardation and brain necrosis, similar to the central nervous system defects observed in the Tfr1 null mouse, indicating that tfr1b is probably used by non-erythroid tissues for iron acquisition. Overexpression of mouse Tfr1, mouse Tfr2, and zebrafish tfr1b partially rescued hypochromia in cia embryos, establishing that each of these transferrin receptors are capable of supporting iron uptake for hemoglobin production in vivo. Taken together, these data show that zebrafish tfr1a and tfr1b share biochemical function but have restricted domains of tissue expression, and establish a genetic model to study the specific function of Tfr1 in erythroid cells.
FRS2-dependent SRC activation is required for fibroblast growth factor receptor-induced phosphorylation of Sprouty and suppression of ERK activity
Authors: Li Xuan , Brunton Valerie G. , Burgar Helen R. , Wheldon Lee M. , Heath John K.
Published: November 2004

Activation of signalling by fibroblast growth factor receptor leads to phosphorylation of the signalling attenuator human Sprouty 2 (hSpry2) on residue Y55. This event requires the presence of the signalling adaptor fibroblast growth factor receptor substrate 2 (FRS2). The phosphorylation of hSpry2 is therefore mediated by an intermediate kinase. Using a SRC family kinase-specific inhibitor and mutant cells, we show that hSpry2 is a direct substrate for SRC family kinases, including SRC itself. Activation of SRC via fibroblast growth factor signalling is dependent upon FRS2 and fibroblast growth factor receptor kinase activity. SRC forms a complex with hSpry2 and this interaction is enhanced by hSpry2 phosphorylation. Phosphorylation of hSpry2 is required for hSpry2 to inhibit activation of the extracellular signal-regulated kinase pathway. These results show that recruitment of SRC to FRS2 leads to activation of signal attenuation pathways.
Fad24, a mammalian homolog of Noc3p, is a positive regulator in adipocyte differentiation
Authors: Tominaga Kei , Johmura Yoshikazu , Nishizuka Makoto , Imagawa Masayoshi
Published: November 2004

Adipocyte differentiation is controlled by complex actions involving gene expression and signal transduction. From metaphase to anaphase, peroxisome proliferator-activated receptor γ, the CCAAT/enhancer-binding protein family and sterol regulatory element-binding protein-1 are known to function as master regulators. However, the mechanism underlying the earliest step, which triggers the initiation of differentiation, remains unknown. In previous reports, we have isolated a number of genes, whose expression increases in the early stage of differentiation in the mouse 3T3-L1 preadipocyte cell line. Here we report the cloning of the full-length cDNA and characterization of an unknown gene isolated previously and named fad24 (factor for adipocyte differentiation 24). Fad24 encodes a protein consisting of 807 amino acids. The deduced amino acid sequence was shown to have a basic leucine zipper motif and a NOC domain. Expression of fad24 was rapidly induced after stimulation with inducers. Furthermore, overexpression of fad24 in NIH-3T3 cells promoted adipogenesis in the presence of a ligand for peroxisome proliferator-activated receptor γ. FAD24 localizes in the nucleus, especially within nuclear speckles. As the nuclear speckle functions as a nascent transcription and pre-mRNA splicing machinery, there is a possibility that FAD24 functions as one of the components for transcription and/or pre-mRNA splicing and positively regulates adipocyte differentiation.
TruncatingAPCmutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability
Authors: Tighe Anthony , Johnson Victoria L. , Taylor Stephen S.
Published: November 2004

The majority of human tumour cells are aneuploid owing to an underlying chromosome instability phenotype. While the genetic lesions that cause chromosome instability remain undefined, mouse ES cells harbouring homozygous adenomatous polyposis coli (APC) mutations are frequently tetraploid. In addition, colon cancer cells with APC mutations have weakened kinetochore-microtubule interactions. Furthermore, mitotic spindles assembled in APC-depleted Xenopus egg extracts are aberrant. Therefore, to determine whether APC mutations can initiate chromosome instability in human cells, we expressed N-terminal APC fragments in HCT-116 cells, a near diploid colon cancer cell line with two wild-type APC alleles. We show that cells expressing N-APC mutants exit mitosis prematurely in the presence of spindle toxins, consistent with a spindle checkpoint defect. In addition, N-APC cells show enhanced survival following prolonged spindle damage. In contrast to controls, the N-APC survivors frequently contain dicentric chromosomes and then go on to become highly aneuploid. These observations suggest that truncating APC mutations can exert dominant effects which in turn can initiate chromosome instability. As such, APC mutation not only compromises tumour suppressor function but may also have oncogenic properties. We suggest therefore that the initial APC mutation acts as a `double whammy', destabilising the genome and setting the stage for deregulated proliferation upon loss of the second APC allele.
AP-1 subunits: quarrel and harmony among siblings
Authors: Hess Jochen , Angel Peter , Schorpp-Kistner Marina
Published: November 2004

The AP-1 transcription factor is mainly composed of Jun, Fos and ATF protein dimers. It mediates gene regulation in response to a plethora of physiological and pathological stimuli, including cytokines, growth factors, stress signals, bacterial and viral infections, as well as oncogenic stimuli. Studies in genetically modified mice and cells have highlighted a crucial role for AP-1 in a variety of cellular events involved in normal development or neoplastic transformation causing cancer. However, emerging evidence indicates that the contribution of AP-1 to determination of cell fates critically depends on the relative abundance of AP-1 subunits, the composition of AP-1 dimers, the quality of stimulus, the cell type and the cellular environment. Therefore, AP-1-mediated regulation of processes such as proliferation, differentiation, apoptosis and transformation should be considered within the context of a complex dynamic network of signalling pathways and other nuclear factors that respond simultaneously.
Long-range Ordering in Water–Halide Ion Interactions: A Database Study
Authors: Prabakaran Ponraj , Singarayan Maria G
Published: November 2004

A detailed analysis of water–halide ion interactions using the Cambridge Structural Database reveals predominant cyclic hydrogen-bonded (H2O·X−)2 clusters and isostructural tapes of 4,5,6-membered rings leading to channel hydrates.
Multiple Complications and Withdrawal Syndrome Associated with Quetiapine/Venlafaxine Intoxication
Authors: Précourt Andréanne , Dunewicz Magdalena , Grégoire Geneviève , Williamson David R
Published: November 2004

OBJECTIVE:

To report a case of quetiapine/venlafaxine intoxication associated with multiple complications and to review their possible relationship with these 2 drugs.

CASE SUMMARY:

A 53-year-old white man was admitted to the hospital for loss of consciousness secondary to voluntary intoxication with venlafaxine and quetiapine. Several complications were attributable to this intoxication including seizures, prolonged coma, respiratory depression, neuroleptic malignant syndrome, prolonged QRS and QTc intervals, and a possible venlafaxine withdrawal syndrome.

DISCUSSION:

Quetiapine could be responsible for the neuroleptic malignant syndrome presented in this case. Moreover, venlafaxine intoxication, fever, autonomic instability, and myoclonus presented serotonin syndrome as a differential diagnosis. Potential causes of seizures and prolongation of the QRS and QTc intervals are reviewed. Finally, prolonged coma and late venlafaxine withdrawal are discussed with regard to the pharmacodynamics and pharmacokinetics of drug elimination in the context of intoxication.

CONCLUSIONS:

Clinicians should be aware of possible complications following intoxication with atypical antipsychotics and antidepressants, including protracted altered mental status.
Clinical Chemistry through Clinical Chemistry: A Journal Timeline
Authors: Rej Robert
Published: November 2004

The establishment of the modern discipline of clinical chemistry was concurrent with the foundation of the journal Clinical Chemistry and that of the American Association for Clinical Chemistry in the late 1940s and early 1950s. To mark the 50th volume of this Journal, I chronicle and highlight scientific milestones, and those within the discipline, as documented in the pages of Clinical Chemistry. Amazing progress has been made in the field of laboratory diagnostics over these five decades, in many cases paralleling—as well as being bolstered by—the rapid pace in the development of computer technologies. Specific areas of laboratory medicine particularly well represented in Clinical Chemistry include lipids, endocrinology, protein markers, quality of laboratory measurements, molecular diagnostics, and general advances in methodology and instrumentation.
Visual Experience Regulates Transient Expression and Dendritic Localization of Fragile X Mental Retardation Protein
Authors: Gabel Lisa A. , Won Sandra , Kawai Hideki , McKinney Margaret , Tartakoff Alan M. , Fallon Justin R.
Published: November 2004

Fragile X syndrome is the most common form of inherited mental retardation and is caused by the loss of function of the Fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein thought to play a key role in protein synthesis-dependent synaptic plasticity. The regulation of FMRP expression itself is also likely to be an important control point in this process. Here we used dark-reared/light-exposed rats to determine the role of experience in regulating FMRP levels in the visual cortex. We find that FMRP levels increase in the cell bodies and dendrites of visual cortical neurons after as little as 15 min of light exposure. Remarkably, FMRP expression in these neurons returns to baseline levels by 30 min of light exposure. These changes were post-transcriptional because the FMR1 mRNA levels remained constant over this time period. A transient increase in FMRP levels was also observed in synaptic fractions prepared from visual cortices of light-exposed animals. In contrast, α-calcium/calmodulin-dependent kinase II expression showed a sustained upregulation under these conditions. Finally, the increase in FMRP expression was inhibited by blockade of NMDA receptors. This tight temporal-spatial regulation suggests that FMRP plays a dynamic role in a distinct epoch of experience-dependent synaptic plasticity.