bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen Donors in Organometallic Chemistry and Homogeneous Catalysis
Authors: Togni Antonio , Venanzi Luigi M.
Published: December 2003

Homogeneous catalysis has been responsible for many major recent developments in synthetic organic chemistry. The combined use of organometallic and coordination chemistry has produced a number of new and powerful synthetic methods for important classes of compounds in general and for optically active substances in particular. For this purpose, complexes with optically active ligands have been used, most of them coordinating through phosphorus. More recent developments have highlighted the use of “nitrogen‐donors”, particularly as they are easily obtained from the “chiral pool”. However, the remarkable achievements in this area have been based on an empirical approach. This article attempts to bridge the gap between the synthetic and the coordination chemist. The first section discusses the rates of formation and dissociation of complexes with nitrogen donors, their relationship to the rates of product formation, and presents the factors which induce homolytic cleavage of MC bonds. It also provides a summary of the main types of organometallic complexes formed by metal centers coordinated to nitrogen donors and their reactivity patterns. The second section highlights the most significant, homogeneously catalyzed reactions involving complexes with nitrogen ligands. Foremost among them are the asymmetric aspects of hydrogenation (particularly those involving boranes as reducing agents), hydrosilylation, cyclopropanations, Diels‐Alder reactions, aldol condensations, alkylation of aldehydes, conjugate addition reactions, Grignard cross‐coupling reactions, allylic alkylations, oxidation reactions, olefin epoxidations, and di‐hydroxylation of olefins.
Novel Carbon Compounds with “Naked” Cn Units
Authors: Lang Heinrich
Published: December 2003

1,3‐Dimetallaallenes 1 or carbyne complexes 2 are the simplest examples of compounds in which different transition metal complex fragments or units of main group elements are terminally bound to Cn bridges. Polymers such as 3 with C4 bridges which link d8 ML2 building blocks are of particular interest as materials with novel properties.
equation image
Opportunities for New Chemical Libraries: Unnatural Biopolymers and Diversomers
Authors: Liskamp Rob M. J.
Published: December 2003

The search for lead compounds may well be simplified by libraries of unnatural compounds, whose lead compounds may require less extensive modifications for the development of drug candidates than those derived from peptide and oligonucleotide libraries. An oligocarbamate library described by Cho et al. and a benzodiazepine library proposed by Hobbs DeWitt et al. should point the way to a large number of libraries.
C70 Is More Stable than C60: Experimental Determination of the Heat of Formation of C70
Authors: Beckhaus Hans‐Dieter , Verevkin Sergej , Rüchardt Christoph , Diederich François , Thilgen Carlo , ter Meer Hans‐Ulrich , Mohn Holger , Müller Wolfgang
Published: December 2003

C70, C60,…, diamond, graphite. The accurate calorimetric determination of the standard heats of formation of highly pure C60 and C70 confirms the fundamental statements concerning the stability in the series of the allotropic forms of carbon predicted from calculations. MM3 force‐field calculations provide the best prediction of the experimental values.
Molecular Catalysts for Multielectron Redox Reactions of Small Molecules: The “Cofacial Metallodiporphyrin” Approach
Authors: Collman James P. , Wagenknecht Paul S. , Hutchison James E.
Published: December 2003

The role of metalloenzymes in important biological transformations has attracted increasing attention over the past several decades. Of the many chemical transformations mediated by enzymes, few are as challenging as multielectron redox reactions. Recent studies have revealed a partial structural and mechanistic description of these redox‐active metalloenzymes, but there is much still to be learned regarding the mechanisms of substrate transformation. Due to the complexity of the metalloenzyme systems, simplified model systems are employed to mimic structural or functional features of the enzyme. In multielectron redox enzymes, several metals are probably in‐volved in both substrate binding and the subsequent redox reactions. Thus, functional mimics of multielectron redox enzymes might also need two or more metal centers to be efficacious. The roles of multiple metal centers are to (1) increase the substrate's affinity for the catalyst, (2) increase the rate of electron transfer to the bound substrate, (3) increase the reactivity of the bound substrate, and (4) inhibit deleterious side reactions. Deter‐mining the importance of each factor may help in the development of these catalysts. Cofacial metallodiporphyrins, because of the control they provide over the geometric and electronic properties of the synthetic reaction center, are ideal bimetallic model complexes. The knowledge gained from model studies will help in understanding the mechanisms of metalloenzymes and can be used to design new homogeneous catalysts to effect multielectron transformations.
Synthesis and Reactions of Optically Active Cyanohydrins
Authors: Effenberger Franz
Published: December 2003

Cyanohydrins have always held a place of importance both as technical products and as reagents in organic chemistry. It is surprising, therefore, that optically active Cyanohydrins have been extensively investigated and employed for syntheses relatively recently. This can be explained by the fact that only in the past few years have enzymatic methods made chiral Cyanohydrins readily available in high optical purity. Chiral Cyanohydrins are widespread in nature in the form of the respective glycosides and serve roughly 3000 plants and many insects as antifeedants. For the preparative organic chemist, this class of compounds offers an enormous synthetic potential for making other chiral compounds accessible. In a few instances, the pharmacological principle of a drug also incorporates a chiral cyanohydrin as constitutive structural element. In the development of novel, physiologically active compounds all possible stereo‐isomers must be synthesized and investigated with respect to their activity range and the pathway of their metabolic transformations and/or degradation. The development of simple synthetic procedures for such compounds, which also entail a high degree of stereoselectivity, therefore has prime importance. To this end chiral Cyanohydrins may serve as stereochemically pure starting materials.

In the present review, the following topics will be addressed: enantioselective addition of hydrogen cyanide (HCN), catalysed by the enzymes (R)‐and (S)‐oxynitrilase, to aldehydes and Ketones yielding (R) and (S) cyanohydrins, respectivity; enantioselective addition of HCN to aldehydes catalyzed by cyclic dipeptides; enantioselective esterification of racemic ocyanohydrins and enantioselective hydrolysis of cyanohydrin esters caytalyzed by lipases and esterases, reprectively; transformation of the nitrile groups of chiral cyanohydrins to provide optically active α‐hydroxycarboxylic acids, aldehydes, and ketones, as well as 2‐amino alcohols; sulfonylation of the OH group of chiral cyanohydrins to furnish optically active α‐sulfonyloxynitriles which undergo SN2 displacement of the activated OH group yielding α‐azido‐, α‐amino, and α‐fluoronitriles with inverted configuration.
New Ionic, Isoelectronic Analogues of CO2 and CS2
Authors: Klapötke Thomas M.
Published: December 2003

The linear arrangement of the atoms in CO2 also occurs, in most cases, in its anionic analogues NBN3− and CBN4−, as well as in the ions SNS+, PCS3−, and PBP3− that are analogous to CS2. Many of the findings and structures predicted by quantum chemical calculations have since been confirmed by crystal structure analyses. This should encourage the synthesis of additional isoelectronic analogues.
Peptidomimetics—Tailored Enzyme Inhibitors
Authors: Gante Joachim
Published: December 2003

Peptides and proteins (there is no clear boundary between the two classes of compounds) are absolutely essential components of organisms in many ways. While proteins have biocatalytic functions and are important components of tissues, peptides play an important role in the organism as hormones, neurotransmitters, and neuromodulators. Peptides and their analogues have long been used in medicinal chemistry as therapeutic agents for pathological conditions generally characterized by a disruption of the interplay between messenger molecules or enzyme substrates and their targets, the receptors and enzymes. For various biochemical and biophysical reasons there is an increasing tendency towards the use of chemical “Trojan horses” known as peptidomimetics. The chances that such agents are active generally increase with the magnitude of the “deceptive effect”, in other words in proportion to the degree of conversion of a peptide into a non‐peptide. Rational design has become a catchphrase which is at present applied frequently to the development of peptidomimetics. New computer programs are invaluable tools in such design processes. However, in spite of the many advances already made, we are still far from the final goal, the de novo design of peptidomimetics. Rational design is nonetheless advancing rapidly, and it is already clear that developments in the area of peptidomimetics have given a great boost to peptide chemistry as a whole. This can be expected to continue, so that in future peptide chemistry may be characterized by a type of symbiotic alliance between peptides and non‐peptides.
Blue‐Violet Pentamethylbismuth
Authors: Neumüller Bernhard , Dehnicke Kurt
Published: December 2003

The simplest pentaalkylbismuth(V) compound, pentamethylbismuth (1), was recently prepared by Seppelt et al. (Angew. Chem. Int. Ed. Engl. 1994, 33, 976). Bismuth(V) has a very high oxidation potential, and for a long time, therefore, its compounds could only be isolated with the most electronegative bonding partners oxygen and fluorine; the only pentaorganobismuth(V) compounds known were pentaaryl derivatives. After the outstanding preparative achievement of Seppelt et al. theoreticians are challenged: The relationship between the color and the structure of penta‐organobismuth(V) compounds is not yet fully understood.
equation image
Synthesis and Characterization of the First Thiaselanes
Authors: Hahn Josef , Klünsch René
Published: December 2003

Stable as a solid at −40°C, dithiatriselane 1 was formed in the reaction of Se2Cl2 with liquid H2S in CS2, in addition to other disproportionation products such as 2 and 3. Reactions in H2S2 provided sulfur‐rich thiaselanes. The 1H and 77Se NMR spectra of the product mixtures could be interpreted unambiguously.
equation image
Recycling in the Earth's Atmosphere: The OH Radical—Its Importance for the Chemistry of the Atmosphere and the Determination of Its Concentration
Authors: Comes Franz Josef
Published: December 2003

The troposphere, the part of the earth's atmosphere which is closest to the surface, harbors important life processes. This important part of our environment contains primarily nitrogen and oxygen. In addition, it comprises a number of other substances, which are generally present in low concentrations. The primary reason for the low content of these trace components is the activity of a diatomic radical, namely the hydroxyl radical. OH is the main constituent of the oxidizing potential of the troposphere and causes the transformation of many trace components into water‐soluble forms, which can then rain out and be removed from the troposphere. OH has therefore acquired the title “detergent of the atmosphere”. The knowledge of local hydroxyl radical concentrations is therefore an important piece of information, especially with respect to model calculations for atmospheric chemistry. The OH concentration is very low and its determination represents a significant analytical challenge. It is controlled in a delicate manner by chemical formation and decomposition reactions, which interact to create a recycling process in the troposphere.
Spectroscopic Studies of Anhydroretinol, an Endogenous Mammalian and Insect retro‐Retinoid
Authors: Derguini Fadila , Nakanishi Koji , Buck Jochen , Hämmerling Ulrich , Grün Felix
Published: December 2003

For corrigendum see DOI:10.1002/anie.199423481
Designer Proteins: On the Art of Synthesizing De Novo Metalloproteins
Authors: Kraatz Heinz‐Bernhard
Published: December 2003

Straddling the boundaries between protein chemistry and coordination chemistry, a promising new field of research has developed. The latest work in this area includes the synthesis of metal‐binding metalloproteins by M. R. Ghadiri et al. and the introduction of redox‐active centers in nonnatural proteins by W. F. DeGrado et al. One can imagine that the concepts behind these syntheses can be extended to, for example, the preparation of metalloproteins that could function as light‐harvesting analogues of the photosystem of green plants.
Bridgehead Functionalization of Non‐Enolizable Ketones: The First Preparatively Useful Methods
Authors: Spitz Urs P. , Eaton Philip E.
Published: December 2003

For corrigendum see DOI:10.1002/anie.199613481
Vitamin B12: How the Problem of Its Biosynthesis Was Solved
Authors: Blanche Francis , Cameron Beatrice , Crouzet Joel , Debussche Laurent , Thibaut Denis , Vuilhorgne Marc , Leeper Finian J. , Battersby Alan R.
Published: December 2003

Vitamin B12 is an essential vitamin for human health, and lack of it leads to pernicious anemia. This biological activity has attracted intense interest for some time; in addition, the complex architecture of the B12 molecule has fascinated chemists and biochemists since its discovery as the first natural organocobalt complex and the establishment of its structure by X‐ray analysis. The organic ligand surrounding the cobalt displays many stereogenic centers along its periphery carrying reactive functional groups. This complexity led vitamin B12 to be rightly regarded as an extreme challenge to the synthetic chemist. Yet microorganisms achieve this synthesis in vivo with complete control of regio‐ and stereochemistry. How do they do it? This review tells the full remarkable story. Success in unraveling this biosynthetic puzzle resulted from a collaborative effort by biologists and chemists using the full range of methods available from their disciplines–from genetics at one end of the spectrum to synthesis and NMR spectroscopy at the other. This work can act as a guide for future research on the biosynthesis of yet more complex natural substances.
A Cyclic Hexairon(III) Complex with an Octahedrally Coordinated Sodium Ion at the Center, an Example of the [12]Metallacrown‐6 Structure Type
Authors: Caneschi Andrea , Cornia Andrea , Lippard Stephen J.
Published: December 2003

A crown composed purely of inorganic components forms the core of complex cation 1. Interest in this polyiron ion is based on its potential relevance to intermediates in the formation of the ferritin core and the hydrolytic polymerization of FeIII salts. The crown structure is supported by the inclusion of a sodium ion within the Fe6O6 ring.
equation image
Chiral Recognition in π Complexes of Alkenes, Aldehydes, and Ketones with Transition Metal Lewis Acids; Development of a General Model for Enantioface Binding Selectivities
Authors: Gladysz J. A. , Boone Brian J.
Published: December 2003

Prochiral alkenes, aldehydes, and ketones constitute the most frequently used starting materials for enantioselective organic syntheses. Protocols often involve chiral binding agents or Lewis acids that can give two diastereomeric adducts, the ratios of which are measures of chiral recognition. With π adducts, the diastereomers differ in the enantioface of the CC or OC group bound to the Lewis acid. This review provides the first comprehensive analysis of such equilibria and related binding phenomena with chiral transition metal Lewis acids. An extensive body of data from the authors' laboratory for complexes of the pyramidal rhenium fragment [(η5−C5H5)Re(No)(PPh3)]+ (I) affords particular insight. Literature data for other complexes are also summarized. A general model for chiral recognition based upon the relative steric properties of four quadrants is presented. This enables binding selectivities to be individually and rationally optimized for different classes of ligands. Electronic effects are also identified and correlated with specific structural properties. Relationships between binding equilibria, reactivity, and product configurations are discussed.
Protein Synthesis by Chemical Ligation of Unprotected Peptides in Aqueous Solution
Authors: Walker Michael A.
Published: December 2003

Orthogonal and native chemical ligation are two terms of a novel method for synthesizing proteins. It is particularly useful where molecular biology techniques fail, for example, for the synthesis of analogs of natural proteins from unnatural building blocks. Since the innovative method proceeds without carboxyl‐group activation or side‐chain protection, it is very easy to use and will find application by the average organic chemist.
Cluster Assembly by Hydrogen Bonds: Channel Structure of Cu4L4 Cubanes
Authors: Oshio Hiroki , Saito Yuki , Ito Tasuku
Published: December 2003

A high‐spin ground state characterizes the cubane complex, which was obtained from copper(II) acetate monohydrate and the bridging ligand 2‐(4‐hyroxysalicylidenamino)ethanol. In the crystal these cubane clusters are arranged to give a channel structure (depicted on the right), which is attributed to a hydrogen‐bonding network formed between hydroxyl groups and water molecules.
Theoretical Studies of the Structure, Aromaticity, and Magnetic Properties of o‐Benzyne
Authors: Jiao Haijun , Schleyer Paul von Ragué , Warmuth Ralf , Houk Kendall N. , Beno Brett R.
Published: December 2003

Theoretical computations give new insights into the energetic, geometric, and magnetic properties of highly reactive o‐benzyne. Comparisons with experimental NMR data for the species trapped in a hemicarcerand agree best for the geometry optimized at the Becke3LYP/6‐311 + G** density functional level, which has more acetylenic (cyclohexa‐3,5‐dienyne) than cumulenic character.
Can behavioral evolution be measured on a staircase? a commentary
Authors: Moore Celia L.
Published: December 2003

The serious, comparative study of behavioral complexity that Greenberg et al. advocate is a progressive direction for the field, but their proposal to separate comparative psychology from its roots in evolutionary biology seems regressive. Modern evolutionary theory has been broadened within biology to include development and paleontology alongside natural selection, making closer integration with that discipline particularly timely. Such an integrated evolutionary approach in psychology would offer a useful alternative to the adaptationism popularized by evolutionary psychology. Although the differences between comparative psychologists and biologists may be blurred in the process, the behavioral sciences will be better served by a rich biological approach to evolution than by a uniquely psychological approach. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 44: 16–20, 2004.
Neonatal novelty exposure, dynamics of brain asymmetry, and social recognition memory
Authors: Tang Akaysha C. , Reeb Bethany C.
Published: December 2003

Brief and transient early‐life stimulation via neonatal handling and neonatal novelty exposure can lead to differential changes within the right and left brains. In rats, these lateralized changes have been demonstrated behaviorally, neuroanatomically, and neurophysiologically. Recently, we found that neonatal novelty exposure can prolong the duration of social recognition memory from less than 2 hr to at least 24 hr among male rats reared in social isolation and that this enhancement is associated with an initial right‐turn preference in a novel testing cage. In contrast to stable forms of asymmetry, such as handedness, we show that this turning asymmetry is dynamic—decreasing as the animal adjusts to the novel testing environment over a 2‐day period. This change in turning asymmetry was found only among animals that experienced neonatal novelty exposure during the first 3 weeks of their lives. Furthermore, individual differences in short‐term social recognition memory for a conspecific can be predicted by this change in functional asymmetry. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 44: 84–93, 2004.
Prevention of gliotic scar formation by NeuroGel™ allows partial endogenous repair of transected cat spinal cord
Authors: Woerly Stéphane , Doan Van Diep , Sosa Norma , de Vellis Jean , Espinosa‐Jeffrey Araceli
Published: December 2003

Spinal cords of adult cats were transected and subsequently reconnected with the biocompatible porous poly (N‐[2‐hydroxypropyl] methacrylamide) hydrogel, NeuroGel™. Tissue repair was examined at various time points from 6–21 months postreconstructive surgery. We examined two typical phenomena, astrogliosis and scar formation, in spines reconstructed with the gel and compared them to those from transected non‐reconstructed spines. Confocal examination with double immunostaining for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) showed that the interface formed between the hydrogel and the spine stumps did prevent scar formation and only a moderate gliosis was observed. The gel implant provided an adequate environment for growth of myelinated fibers and we saw angiogenesis within the gel. Electron microscopy showed that regenerating axons were myelinated by Schwann cells rather than oligodendrocytes. Moreover, the presence of the gel implant lead to a considerable reduction in damage to distal caudal portions of the spine as assessed by the presence of more intact myelinated fibers and a reduction of myelin degradation. Neurologic assessments of hindlimb movement at various times confirmed that spinal cord reconstruction was not only structural but also functional. We conclude that NeuroGel lead to functional recovery by providing a favorable substrate for regeneration of transected spinal cord, reducing glial scar formation and allowing angiogenesis. © 2003 Wiley‐Liss, Inc.
High‐level expression of Dok‐1 in neurons of the primate prefrontal cortex and hippocampus
Authors: Smith A. , Wang J. , Cheng C.M. , Zhou J. , Weickert C.S. , Bondy C.A.
Published: December 2003

The docking protein p62Dok‐1 (Dok‐1) has a central role in cell signaling mediated by a wide range of protein tyrosine kinases, including intrinsic membrane kinases, such as the insulin‐like growth factor‐1 (IGF‐1) receptor. To elucidate potential IGF signaling mechanisms, we used DNA array technology to investigate novel kinase targets expressed in the primate dorsolateral prefrontal cortex (DLPFC). Dok‐1 transcripts were among the most abundant found in this structure. Because Dok‐1 expression has not been characterized in brain, we evaluated its expression pattern using immunoblotting, in situ hybridization, and immunohistochemistry in the rhesus monkey prefrontal cortex and hippocampal formation. Dok‐1 antibodies identified a 62‐kDa band in lysates from the DLPFC, consistent with the known size for Dok‐1. In situ hybridization showed that Dok‐1 mRNA was expressed in all layers of the DLPFC and in all neuronal subregions of the hippocampal formation. Immunohistochemical analysis showed Dok‐1 immunoreactivity concentrated in pyramidal neurons of cortical layers IV–V and throughout Ammon's horn and in granule neurons of the dentate gyrus. Dok‐1 expression was also identified in endothelial cells of cerebral blood vessels. These expression patterns are very similar to those of the IGF‐1 receptor and suggest that Dok‐1 could be among the downstream targets of IGF signaling in areas of the primate brain involved in learning and memory. Published 2003 Wiley‐Liss, Inc.
Differential effects of zinc on glutamatergic and GABAergic neurotransmitter systems in the hippocampus
Authors: Takeda Atsushi , Minami Akira , Seki Yumiko , Oku Naoto
Published: December 2003

Approximately 10% of total zinc in the brain exists in synaptic vesicles of glutamatergic neurons; however, the function of vesicular zinc is poorly understood. The presynaptic action of zinc against excitatory and inhibitory neurotransmission was studied in rat hippocampus using in vivo microdialysis. When the hippocampal CA3 region was perfused with 10–300 μM ZnCl2, the level of glutamate in the perfusate was decreased, whereas the level of γ‐aminobutyric acid (GABA) was increased. Chelation of endogenous zinc with CaEDTA increased the glutamate level in the perfusate but decreased the GABA level, suggesting that zinc released into the synaptic cleft acts differentially on glutamatergic and GABAergic neurons in the CA3 region. The increase of GABA level by zinc was antagonized by 2,3‐dioxo‐6‐nitro‐1,2.3,4‐tetrahydrobenzo(f)quinoxaline‐7‐sulphonamide (NBQX), an antagonist of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)/kainate receptors, but not affected by MK801, an antagonist of N‐methyl‐D‐aspartate (NMDA) receptors, and verapamil, a blocker of voltage‐dependent calcium channels. The present study suggests that zinc enhances GABA release via potentiation of AMPA/kainate receptors in the CA3 region, followed by a decrease in presynaptic glutamate release in the same region. Zinc seems to be an inhibitory neuromodulator of glutamate release. © 2003 Wiley‐Liss, Inc.
Axonal defects in mouse models of motoneuron disease
Authors: Jablonka Sibylle , Wiese Stefan , Sendtner Michael
Published: December 2003

Human motoneuron disease is characterized by loss of motor endplates, axonal degeneration, and cell death of motoneurons. The identification of the underlying gene defects for familial ALS, spinal muscular atrophy (SMA), and spinal muscular atrophy with respiratory distress (SMARD) has pointed to distinct pathophysiological mechanisms that are responsible for the various forms of the disease. Accumulating evidence from mouse models suggests that enhanced vulnerability and sensitivity to proapoptotic stimuli is only responsible for some but not all forms of motoneuron disease. Mechanisms that modulate microtubule assembly and the axonal transport machinery are defective in several spontaneous and ENU (ethylnitrososurea) mutagenized mouse models but also in patients with mutations in the p150 subunit of dynactin. Recent evidence suggests that axonal growth defects contribute significantly to the pathophysiology of spinal muscular atrophy. Reduced levels of the survival motoneuron protein that are responsible for SMA lead to disturbed RNA processing in motoneurons. This could also affect axonal transport of mRNAs for β‐actin and other proteins that play an essential role in axon growth and synaptic function. The local translation of specific proteins might be affected, because developing motoneurons contain ribosome‐like structures in distal axons and growth cones. Altogether, the evidence from these mouse models and the new genetic data from patients suggest that axon growth and maintenance involves a variety of mechanisms, including microtubule assembly and axonal transport of proteins and ribonucleoproteins (RNPs). Thus, defects in axon maintenance could play a leading role in the development of several forms of human motoneuron disease. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 272–286, 2004
What is the importance of multivesicular bodies in retrograde axonal transport in vivo?
Authors: Weible M. W. , Hendry I. A.
Published: December 2003

Neurons with long axons have a unique problem in generating signaling cascades that are able to reach the nucleus after receptor activation by neurotrophins at the nerve terminal. The straightforward concept of receptor binding and local generation of 2nd second messenger cascades is too simplistic. In this review we will outline a mechanism that would enable the complex signals generated at the nerve terminal to be conveyed intact to the cell body. There are three different sites in the neuron where 2nd messenger proteins can interact with the signaling complex and be activated. Signaling cascades are initiated both at the nerve terminal and at the cell body when 2nd messengers are recruited to the plasma membrane by activated receptors. After receptor‐mediated endocytosis, 2nd messenger molecules continue to be recruited to the internalized vesicle; however, the mix of proteins differs in the nerve terminal and in the cell body. At the nerve terminal the activated pathways result in the formation of the neurotrophin signaling endosome, which includes molecules to be retrogradely transported to the cell body. When the retrograde neurotrophin signaling endosome reaches the cell body, it can recruit additional 2nd messenger molecules to finally generate the unique signal derived from the nerve terminal. We propose that the multivesicular body observed in vivo functions as an endosome carrier vehicle or retrosome. This retrosome enables the mix of signaling molecules recruited at the terminal to be transported intact to the cell body. This will allow the cell body to receive a snapshot of the events occurring at the nerve terminal at the time the retrosome is formed. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 230–243, 2004
Nondestructive testing and damage assessment of masonry structures
Authors: Schuller Michael P.
Published: December 2003

Recent advances in nondestructive testing technology have led to mainstream use of several methods for evaluating masonry construction. Nondestructive approaches such as rebound hardness, stress wave transmission, impact‐echo, surface penetrating radar, tomographic imaging, and infrared thermography are useful for qualitative condition surveys as well as identification of internal features such as voids or areas of distress.In situtest methods are also available for determination of engineering properties. Flatjack methods are used to measure the state of compressive stress and compression response, masonry bed joint shear stress may be evaluated by anin situshear test, and mortar unit bond strength is tested by an adaptation of the bond wrench approach. Standardized methods exist for many of the evaluation approaches and related efforts are ongoing within ASTM and RILEM.
Helping students revise disruptive experientially supported ideas about thermodynamics: Computer visualizations and tactile models
Authors: Clark Douglas , Jorde Doris
Published: December 2003

This study analyzes the impact of an integrated sensory model within a thermal equilibrium visualization. We hypothesized that this intervention would not only help students revise their disruptive experientially supported ideas about why objects feel hot or cold, but also increase their understanding of thermal equilibrium. The analysis synthesizes test data and interviews to measure the impact of this strategy. Results show that students in the experimental tactile group significantly outperform their control group counterparts on posttests and delayed posttests, not only on tactile explanations, but also on thermal equilibrium explanations. Interview transcripts of experimental and control group students corroborate these findings. Discussion addresses improving the tactile model as well as application of the strategy to other science topics. The discussion also considers possible incorporation of actual kinetic or thermal haptic feedback to reinforce the current audio and visual feedback of the visualization. This research builds on the conceptual change literature about the nature and role of students' experientially supported ideas as well as our understanding of curriculum and visualization design to support students in learning about thermodynamics, a science topic on which students perform poorly as shown by the National Assessment of Educational Progress (NAEP) and Third International Mathematics and Science Study (TIMSS) studies. © 2003 Wiley Periodicals, Inc. J Res Sci Teach 41: 1–23, 2004
Violence exposure in real‐life, video games, television, movies, and the internet: is there desensitization?
Authors: Funk Jeanne B , Baldacci Heidi Bechtoldt , Pasold Tracie , Baumgardner Jennifer
Published: December 2003

It is believed that repeated exposure to real‐life and to entertainment violence may alter cognitive, affective, and behavioral processes, possibly leading to desensitization. The goal of the present study was to determine if there are relationships between real‐life and media violence exposure and desensitization as reflected in related characteristics. One hundred fifty fourth and fifth graders completed measures of real‐life violence exposure, media violence exposure, empathy, and attitudes towards violence. Regression analyses indicated that only exposure to video game violence was associated with (lower) empathy. Both video game and movie violence exposure were associated with stronger proviolence attitudes. The active nature of playing video games, intense engagement, and the tendency to be translated into fantasy play may explain negative impact, though causality was not investigated in the present design. The samples’ relatively low exposure to real‐life violence may have limited the identification of relationships. Although difficult to quantify, desensitization to violence should be further studied using related characteristics as in the present study. Individual differences and causal relationships should also be examined.
Creatine increases IGF‐I and myogenic regulatory factor mRNA in C2C12 cells
Authors: Louis Magali , Van Beneden Ronald , Dehoux Mischaël , Thissen Jean Paul , Francaux Marc
Published: December 2003

Addition of creatine to the differentiation medium of C2C12 cells leads to hypertrophy of the myotubes. To investigate the implication of insulin‐like growth factor I (IGF‐I) and myogenic regulatory factors (MRFs) in this hypertrophy, their mRNA levels were assessed during the first 72 h of differentiation. Creatine significantly increased the IGF‐I mRNA level over the whole investigated period of time, whereas the MRF mRNA levels were only augmented at precise moments, suggesting a general activation mechanism for IGF‐I and a specifically regulated mechanism for MRF transcription. Our results suggest therefore that creatine‐induced hypertrophy of C2C12 cells is at least partially mediated by overexpression of IGF‐I and MRFs.
Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: A case-control study
Authors: Poonawala Asma , Nair Satheesh P. , Thuluvath Paul J.
Published: December 2003

It has recently been suggested that nonalcoholic steatohepatitis (NASH) is an under-recognized cause of cryptogenic cirrhosis (CC) on the basis of higher prevalence of obesity and type II diabetes among these patients. To test this hypothesis, we studied 65 consecutive patients with advanced cirrhosis (Child-Pugh Score ≥ 7) of undetermined etiology (CC) from our active waiting list for liver transplantation in January 1993, 1996, and 1999. For each patient, we selected 2 age- and sex-matched controls from the corresponding lists. The prevalence of obesity (defined as body mass index [BMI] ≥ 30) and diabetes were compared between the groups. Sixteen patients (and their 32 controls) with CC were excluded as further review of records suggested other possible etiologies. Thus, the final analysis included 49 patients and 98 controls. The etiology of cirrhosis in the control group was alcohol in 16.3%, chronic viral hepatitis in 30.6%, autoimmune hepatitis in 8.2%, and primary biliary cirrhosis (PBC) or primary sclerosing cholangitis in 35.7%. The prevalence of obesity (55% vs. 24%) and type II diabetes (47% vs. 22%) was significantly higher in patients with CC compared with controls. Twenty-three percent of patients with CC had both obesity and diabetes compared with 5% among controls (P= .002). There was no difference in the prevalence of hypercholesterolemia (serum cholesterol > 200 mg/dL) between the groups. In conclusion, patients with advanced CC are more likely to be obese and diabetic compared with age- and sex-matched patients with advanced cirrhosis. This supports the hypothesis that NASH may be an etiological factor in some of the patients with CC.
Oscillatory Marangoni convection in binary mixtures in square and nearly square containers
Authors: Bergeon A. , Knobloch E.
Published: December 2003

Three-dimensional simulations of oscillatory convection in binary mixtures driven by the Marangoni effect have been performed. The upper surface of the fluid is heated by a constant heat flux while the bottom is maintained at a constant temperature. Surface deflection is ignored. Oscillations are the result of concentration-induced changes in the surface tension due to the presence of an anomalous Soret effect. In domains with a square horizontal cross section and aspect ratio Γ=1.5 these take the form of either a standing wave with left–right reflection symmetry or a discrete rotating wave, depending on the separation ratio and the Schmidt number. Standing oscillations with reflection symmetry in a diagonal are unstable. When the cross section is slightly rectangular only the former bifurcate from the conduction state, and the transition to stable rotating waves with increasing Marangoni number proceeds via a sequence of secondary local and global bifurcations. The results are interpreted in terms of predictions from equivariant bifurcation theory.
What does measure the scaling exponent of the correlation sum in the case of human heart rate?
Authors: Säkki M. , Kalda J. , Vainu M. , Laan M.
Published: December 2003

It is shown that in the case of human heart rate, the scaling behavior of the correlation sum (calculated by the Grassberger–Procaccia algorithm) is a result of the interplay of various factors: finite resolution of the apparatus (finite-size effects), a wide dynamic range of mean heart rate, the amplitude of short-time variability being a decreasing function of the mean heart rate. This is done via constructing a simple model of heart rhythm: a signal with functionally modulated Gaussian noise. This model reproduces the scaling behavior of the correlation sum of real medical data. The value of the scaling exponent depends on all the above-mentioned factors, and is a certain measure of short-time variability of the signal.
In vitro and in vivo assessment of functional capacity of flow cytometrically sorted ram spermatozoa after freezing and thawing
Authors: Hollinshead F. K. , Gillan L. , O'Brien J. K. , Evans G. , Maxwell W. M. C.
Published: December 2003

The effect of sex sorting and freeze–thawing on the viability and fertility of ram spermatozoa was investigated in the present study. Non-sorted (control) frozen–thawed spermatozoa had a higher motility and forwards progressive motility (FPM) than sorted frozen–thawed spermatozoa (60.9 ± 2.9% v. 57.0 ± 3.3% and 4.0 ± 0.1 v. 3.5 ± 0.1 FPM, respectively; P < 0.001) after incubation (6 h at 37°C). Sorted and non-sorted (control) frozen–thawed spermatozoa had similar acrosome integrity (73.7 ± 1.8% v. 75.2 ± 2.1%, respectively) after thawing and incubation. A greater proportion of sorted spermatozoa displayed chlortetracycline staining patterns that were characteristic of capacitation (22.0 ± 2.8%; P < 0.05) than non-sorted (control) spermatozoa (15.4 ± 2.6% B pattern) before freezing. Overall, more sorted frozen–thawed spermatozoa showed patterns characteristic of being acrosome reacted (12.8 ± 0.7%; P < 0.01) and less were uncapacitated (35.5 ± 0.6%; P < 0.05) than non-sorted (control) frozen–thawed spermatozoa (7.7 ± 0.8% and 38.6 ± 0.6% for AR and F pattern, respectively). Similar numbers of non-sorted (control) and sorted frozen–thawed spermatozoa migrated through artificial cervical mucus after 1 h (76.4 ± 11.9 v. 73.9 ± 11.9 spermatozoa, respectively). The distance travelled by the vanguard spermatozoon was also similar (56.9 ± 7.8 v. 38.6 ± 5.8 mm for control and sorted spermatozoa, respectively). Sorted and control frozen–thawed spermatozoa displayed a similar pattern of binding to, and release from, an oviduct epithelial cell monolayer (OECM), but sorted frozen–thawed spermatozoa were released more rapidly (P < 0.05) than non-sorted (control) frozen–thawed spermatozoa. The pregnancy rate was higher for ewes inseminated with 100 × 106 (commercial control) frozen–thawed spermatozoa (59%) than for 5, 10, 20 and 40 × 106 total sorted frozen–thawed spermatozoa (41% overall; P < 0.001). Insemination of 16 × 106 resulted in a higher pregnancy rate (31%) than 106 (17%; P < 0.05), but was similar to ewes that received 4 × 106 sorted frozen–thawed spermatozoa (24%). Time of insemination (54, 58 and 62 h after sponge removal) had no effect on pregnancy rate. Pregnancy in gonadotrophin-releasing hormone-treated ewes was affected by insemination dose (P < 0.05) but not sperm type (sorted and non-sorted) or ram. Pregnancy was higher after insemination of 40 × 106 than 5 or 20 × 106 non-sorted (control) or sorted frozen–thawed spermatozoa (70%, 33% and 35%, respectively; P < 0.05). Sorted frozen–thawed spermatozoa may have a shorter viability within the female tract than non-sorted frozen–thawed spermatozoa.
How to Combine Chance and Determinism: Thinking about the Future in an Everett Universe
Authors: Ismael Jenann
Published: December 2003

I propose, in the context of Everett interpretations of quantum mechanics, a way of understanding how there can be genuine uncertainty about the future notwithstanding that the universe is governed by known, deterministic dynamical laws, and notwithstanding that there is no ignorance about initial conditions, nor anything in the universe whose evolution is not itself governed by the known dynamical laws. The proposal allows us to draw some lessons about the relationship between chance and determinism, and to dispel one source of the tendency among Everettians to introduce consciousness as a primitive element into physical description.
Management of Neck Metastasis with Carotid Artery Involvement
Authors: Freeman Stephen B. , Hamaker Ronald C. , Borrowdale Richard B. , Huntley Tod C.
Published: December 2003

Objectives To demonstrate aggressive management of neck metastasis adherent to the internal or common carotid artery using sound oncologic principles while minimizing the significant risk of complications.

Study Design Our 13 year experience of treating patients with recurrent or residual neck metastasis adherent to the internal or common carotid artery was retrospectively reviewed.

Methods Angiography was used in patients who demonstrated fixation of the carotid artery on examination or imaging, followed by balloon test occlusion and single photon emission computer tomography (SPECT) scanning. The majority of carotid resections were reconstructed with a vein graft, especially if there was insufficient collateral cerebral circulation. Radical resection of the soft tissue including the carotid artery was performed followed by 15 to 20 Gray of electron beam delivered directly to the deep tissue. More recently, the carotid has been permanently occluded preoperatively, if possible. The assessment of the cerebral circulation and management of the carotid artery were analyzed as was survival, site of recurrence, and complications.

Results Fifty‐eight charts were reviewed. The majority of patients (41) had their carotid artery reconstructed at time of resection, and the remaining had either the artery ligated or permanently occluded preoperatively. Strokes occurred in 11 patients. The median disease‐specific survival was 12 months, with 24% of patients dying from distant metastasis.

Conclusions The high risk of complications, loss of life's quality, and mortality must be balanced against the natural history of the disease if left untreated. The decision is a heavy burden for the patient, family, and head and neck surgeon.
Time Scale for Periosteal Readhesion After Brow Lift
Authors: Kim Jenny C. , Downs J. Crawford , Azuola Maria E. , Graham H. Devon
Published: December 2003

Objectives/HypothesisThe objective was to determine the time interval after brow lift required to achieve periosteal repeat adhesion to the skull with preoperative strength.

Study DesignRandomized prospective analysis of variance with repeated measures.

MethodsTwenty‐one New Zealand white rabbits, each serving as its own control, underwent subperiosteal elevation on one side of the skull. The elevated periosteum was lifted and fixed to a resorbable screw, and the contralateral periosteum was left untouched. Adhesion characteristics were subsequently examined at postoperative days 5, 6, 7, 8, 10, 12, and 17. Seven subjects were assessed histologically to determine attachment of periosteum to underlying bone. Fourteen subjects underwent biomechanical analysis of the bone‐periosteum interface using the following three measures of periosteal repeat adhesion strength: ultimate shear strength, shear stiffness, and shear energy.

ResultsBlinded histological analysis showed a qualitative increase in the number of markers of periosteal healing on days 8 to 12 for the operated sides. Analysis of ultimate shear strength and shear stiffness demonstrated a significant relationship to postoperative day (P< .001). The ultimate shear strength and shear stiffness of the operated side approached that of the nonoperated side by postoperative days 12 and 8, respectively. Shear energy was significantly lower for all time points on the operated side as compared with the control (P< .02).

ConclusionPeriosteal readhesion after surgical elevation approaches preoperative strength by the twelfth postoperative day.
Electrophysiologic Effects of Placing Cochlear Implant Electrodes in a Perimodiolar Position in Young Children
Authors: Wackym Phillip A. , Firszt Jill B. , Gaggl Wolfgang , Runge‐Samuelson Christina L. , Reeder Ruth M. , Raulie Jennifer C.
Published: December 2003

Objective The purpose of this study was to intraoperatively record the electrically evoked auditory brainstem response (EABR) before and after placement of the electrode positioning system (EPS) (CII Bionic Ear with HiFocus I cochlear implant electrode array) as well as before and after stylet removal (Nucleus Contour cochlear implant electrode array). It was hypothesized that physiologic changes would occur after perimodiolar positioning of the electrode array and these changes would be evident from the EABR recordings.

Study Design Consecutive young (11–36 month old) pediatric cochlear implant recipients (n = 17) had intraoperative EABRs recorded from three intracochlear electrodes that represented apical, medial, and basal locations. Wave V amplitudes and thresholds were studied relative to electrode location and pre‐ versus postperimodiolar positioning. These evoked potential measures were analyzed for statistical significance.

Setting Tertiary referral children's hospital/medical college.

Results Wave V thresholds of the EABR were lower, and amplitudes were larger after perimodiolar positioning, although the changes were dependent on electrode location and implant design. Statistically significant decreases in EABR wave V threshold and increases in suprathreshold wave V amplitude were found for the basal electrode for the CII Bionic Ear HiFocus I and for the apical electrode for the Nucleus Contour.

Conclusions Placement of either the CII Bionic Ear HiFocus I or Nucleus Contour cochlear implant electrode array in the perimodiolar position in young children resulted in less electrical current necessary to stimulate the auditory system. Changes in electrophysiologic thresholds and amplitudes, measured with EABR, indicate that the electrode array is placed closer to the modiolus with both electrode designs.