bluuebunny/crossref_metadata_2025 huggingface dataset:
BEYOND THE STEADY STATE: MANAGING DISCONTINUOUS PRODUCT AND PROCESS INNOVATION
Authors: PHILLIPS WENDY , NOKE HANNAH , BESSANT JOHN , LAMMING RICHARD
Published: April 2006

Research on the innovation process and its effective management has consistently highlighted a set of themes constituting "good practice". The limitation of such "good practice" is that it relates to what might be termed "steady state" innovation — essentially innovative activity in product and process terms which is about "doing what we do, but better". The prescription works well under these conditions of (relative) stability in terms of products and markets but is not a good guide when elements of discontinuity come into the equation. Discontinuity arises from shifts along technological, market, political and other frontiers and requires new or at least significantly adapted approaches to their effective management. This paper highlights empirical findings from a selection of companies involved in a project sponsored by the U.K. Department of Trade and Industry. The results indicate a number of key routines that organisations could implement to enable discontinuous innovation.
SEASONAL CONTROL OF TUBERIZATION IN POTATO: Conserved Elements with the Flowering Response
Authors: Rodríguez-Falcón Mariana , Bou Jordi , Prat Salomé
Published: April 2006

Fluctuations in day length determine the time to flower in many plants and in potato are critical to promote differentiation of tubers. Day length is perceived in the leaves and under inductive conditions these synthesize a systemic signal that is transported to the underground stolons to induce tuber development. Flowering tobacco shoots grafted into potato stocks promote tuberization in the stocks, indicating that the floral and tuber-inducing signals might be similar. We describe recent progress in the identification of the molecular mechanisms underlying day-length recognition in potato. Evidence has been obtained for a conserved function of the potato orthologs of the CONSTANS (CO) and FLOWERING LOCUS T (FT) proteins in tuberization control under short days (SDs). These observations indicate that common regulatory pathways are involved in both flowering and tuberization photoperiodic responses in plants.
GLYCOSYLTRANSFERASES OF LIPOPHILIC SMALL MOLECULES
Authors: Bowles Dianna , Lim Eng-Kiat , Poppenberger Brigitte , Vaistij Fabián E.
Published: April 2006

Glycosyltransferases of small molecules transfer sugars to a wide range of acceptors, from hormones and secondary metabolites to biotic and abiotic chemicals and toxins in the environment. The enzymes are encoded by large multigene families and can be identified by a signature motif in their primary sequence, which classifies them as a subset of Family 1 glycosyltransferases. The transfer of a sugar onto a lipophilic acceptor changes its chemical properties, alters its bioactivity, and enables access to membrane transporter systems. In vitro studies have shown that a single gene product can glycosylate multiple substrates of diverse origins; multiple enzymes can also glycosylate the same substrate. These features suggest that in a cellular context, substrate availability is a determining factor in enzyme function, and redundancy depends on the extent of coordinate gene regulation. This review discusses the role of these glycosyltransferases in underpinning developmental and metabolic plasticity during adaptive responses.
SUGAR SENSING AND SIGNALING IN PLANTS: Conserved and Novel Mechanisms
Authors: Rolland Filip , Baena-Gonzalez Elena , Sheen Jen
Published: April 2006

Sugars not only fuel cellular carbon and energy metabolism but also play pivotal roles as signaling molecules. The experimental amenability of yeast as a unicellular model system has enabled the discovery of multiple sugar sensors and signaling pathways. In plants, different sugar signals are generated by photosynthesis and carbon metabolism in source and sink tissues to modulate growth, development, and stress responses. Genetic analyses have revealed extensive interactions between sugar and plant hormone signaling, and a central role for hexokinase (HXK) as a conserved glucose sensor. Diverse sugar signals activate multiple HXK-dependent and HXK-independent pathways and use different molecular mechanisms to control transcription, translation, protein stability and enzymatic activity. Important and complex roles for Snf1-related kinases (SnRKs), extracellular sugar sensors, and trehalose metabolism in plant sugar signaling are now also emerging.
TRANSCRIPTIONAL REGULATORY NETWORKS IN CELLULAR RESPONSES AND TOLERANCE TO DEHYDRATION AND COLD STRESSES
Authors: Yamaguchi-Shinozaki Kazuko , Shinozaki Kazuo
Published: April 2006

Plant growth and productivity are greatly affected by environmental stresses such as drought, high salinity, and low temperature. Expression of a variety of genes is induced by these stresses in various plants. The products of these genes function not only in stress tolerance but also in stress response. In the signal transduction network from perception of stress signals to stress-responsive gene expression, various transcription factors and cis-acting elements in the stress-responsive promoters function for plant adaptation to environmental stresses. Recent progress has been made in analyzing the complex cascades of gene expression in drought and cold stress responses, especially in identifying specificity and cross talk in stress signaling. In this review article, we highlight transcriptional regulation of gene expression in response to drought and cold stresses, with particular emphasis on the role of transcription factors and cis-acting elements in stress-inducible promoters.
Protein Misfolding, Functional Amyloid, and Human Disease
Authors: Chiti Fabrizio , Dobson Christopher M.
Published: April 2006

Peptides or proteins convert under some conditions from their soluble forms into highly ordered fibrillar aggregates. Such transitions can give rise to pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. In this review, we identify the diseases known to be associated with formation of fibrillar aggregates and the specific peptides and proteins involved in each case. We describe, in addition, that living organisms can take advantage of the inherent ability of proteins to form such structures to generate novel and diverse biological functions. We review recent advances toward the elucidation of the structures of amyloid fibrils and the mechanisms of their formation at a molecular level. Finally, we discuss the relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate and describe some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior.
The Structure and Function of Telomerase Reverse Transcriptase
Authors: Autexier Chantal , Lue Neal F.
Published: April 2006

The structure and integrity of telomeres are essential for genome stability. Telomere dysregulation can lead to cell death, cell senescence, or abnormal cell proliferation. The maintenance of telomere repeats in most eukaryotic organisms requires telomerase, which consists of a reverse transcriptase (RT) and an RNA template that dictates the synthesis of the G-rich strand of telomere terminal repeats. Structurally, telomerase reverse transcriptase (TERT) contains unique and variable N- and C-terminal extensions that flank a central RT-like domain. The enzymology of telomerase includes features that are both similar to and distinct from those characteristic of other RTs. Two distinguishing features of TERT are its stable association with the telomerase RNA and its ability to repetitively reverse transcribe the template segment of RNA. Here we discuss TERT structure and function; its regulation by RNA-DNA, TERT-DNA, TERT-RNA, TERT-TERT interactions, and TERT-associated proteins; and the relationship between telomerase enzymology and telomere maintenance.
Ribonucleotide Reductases
Authors: Nordlund Pär , Reichard Peter
Published: April 2006

Ribonucleotide reductases (RNRs) transform RNA building blocks to DNA building blocks by catalyzing the substitution of the 2′OH-group of a ribonucleotide with a hydrogen by a mechanism involving protein radicals. Three classes of RNRs employ different mechanisms for the generation of the protein radical. Recent structural studies of members from each class have led to a deeper understanding of their catalytic mechanism and allosteric regulation by nucleoside triphosphates. The main emphasis of this review is on regulation of RNR at the molecular and cellular level. Conformational transitions induced by nucleotide binding determine the regulation of substrate specificity. An intricate interplay between gene activation, enzyme inhibition, and protein degradation regulates, together with the allosteric effects, enzyme activity and provides the appropriate amount of deoxynucleotides for DNA replication and repair. In spite of large differences in the amino acid sequences, basic structural features are remarkably similar and suggest a common evolutionary origin for the three classes.
Axonal Transport and Alzheimer's Disease
Authors: Stokin Gorazd B. , Goldstein Lawrence S.B.
Published: April 2006

In contrast to most eukaryotic cells, neurons possess long, highly branched processes called axons and dendrites. In large mammals, such as humans, some axons reach lengths of over 1 m. These lengths pose a major challenge to the movement of proteins, vesicles, and organelles between presynaptic sites and cell bodies. To overcome this challenge axons and dendrites rely upon specialized transport machinery consisting of cytoskeletal motor proteins generating directed movements along cytoskeletal tracks. Not only are these transport systems crucial to maintain neuronal viability and differentiation, but considerable experimental evidence suggests that failure of axonal transport may play a role in the development or progression of neurological diseases such as Alzheimer's disease.
Domains, Motifs, and Scaffolds: The Role of Modular Interactions in the Evolution and Wiring of Cell Signaling Circuits
Authors: Bhattacharyya Roby P. , Reményi Attila , Yeh Brian J. , Lim Wendell A.
Published: April 2006

Living cells display complex signal processing behaviors, many of which are mediated by networks of proteins specialized for signal transduction. Here we focus on the question of how the remarkably diverse array of eukaryotic signaling circuits may have evolved. Many of the mechanisms that connect signaling proteins into networks are highly modular: The core catalytic activity of a signaling protein is physically and functionally separable from molecular domains or motifs that determine its linkage to both inputs and outputs. This high degree of modularity may make these systems more evolvable—in principle, novel circuits, and therefore highly innovative regulatory behaviors, can arise from relatively simple genetic events such as recombination, deletion, or insertion. In support of this hypothesis, recent studies show that such modular systems can be exploited to engineer nonnatural signaling proteins and pathways with novel behavior.
Cold-Adapted Enzymes
Authors: Siddiqui Khawar Sohail , Cavicchioli Ricardo
Published: April 2006

By far the largest proportion of the Earth's biosphere is comprised of organisms that thrive in cold environments (psychrophiles). Their ability to proliferate in the cold is predicated on a capacity to synthesize cold-adapted enzymes. These enzymes have evolved a range of structural features that confer a high level of flexibility compared to thermostable homologs. High flexibility, particularly around the active site, is translated into low-activation enthalpy, low-substrate affinity, and high specific activity at low temperatures. High flexibility is also accompanied by a trade-off in stability, resulting in heat lability and, in the few cases studied, cold lability. This review addresses the structure, function, and stability of cold-adapted enzymes, highlighting the challenges for immediate and future consideration. Because of the unique properties of cold-adapted enzymes, they are not only an important focus in extremophile biology, but also represent a valuable model for fundamental research into protein folding and catalysis.
STRESS PROTEIN EXPRESSION KINETICS
Authors: Diller Kenneth R.
Published: April 2006

In all organisms there is an elevated synthesis of a select family of “stress proteins” in response to a broad array of environmentally driven stress vectors including elevated or depressed temperature, changes in pH, treatment with many classes of chemicals, ischemia, desiccation, and UV irradiation. The presence of stress proteins, often termed heat shock proteins (HSPs), has been recognized for more than four decades, and there is an extensive literature that addresses the structure and properties of HSPs, their function in normal and injured cells and tissues, and the molecular mechanisms of HSP expression in response to stress. Owing to this substantial aggregate of research, there is a growing appreciation of the potential for manipulating the magnitude and timing of elevated HSP expression to achieve targeted therapeutic objectives. The successful realization of this potential requires an understanding of the kinetics of the HSP expression process in response to sublethal stress regimens along with the ability to model the governing events in the process to design practical protocols that could be applied in therapeutic settings. Significant progress has been made in recent years in defining and developing capabilities in these two areas.
DRUG-ELUTING BIORESORBABLE STENTS FOR VARIOUS APPLICATIONS
Authors: Zilberman Meital , Eberhart Robert C.
Published: April 2006

A stent is a medical device designed to serve as a temporary or permanent internal scaffold to maintain or increase the lumen of a body conduit. Metallic coronary stents were first introduced to prevent arterial dissections and to eliminate vessel recoil and intimal hyperplasia associated with percutaneous transluminal coronary angioplasty. The stent application range has expanded as more experience was gained, and encouraging results have been obtained in the treatment of vascular diseases. Stents are currently used for support of additional body conduits, including the urethra, trachea, and esophagus. The rationale for bioresorbable stents is the support of a body conduit only during its healing process. The stent mass and strength decrease with time, and the mechanical load is gradually transferred to the surrounding tissue. Bioresorbable stents also enable longer term delivery of drugs to the conduit wall from an internal reservoir and abolish the need for a second surgery to remove the device. The present review describes recent advances in bioresorbable stents, focusing on drug-eluting bioresorbable stents for various applications. Controlled release of an active agent from a stent can be used to enhance healing of the surrounding tissues, to increase the implant's biocompatibility, as well as to help cure certain diseases. Because a lot of research in this field has been done by us, examples for these functions are described based mainly on developments in our laboratories.
MICROVASCULAR PERSPECTIVE OF OXYGEN-CARRYING AND -NONCARRYING BLOOD SUBSTITUTES
Authors: Intaglietta Marcos , Cabrales Pedro , Tsai Amy G.
Published: April 2006

The development of an alternative to natural blood has evolved from the initial goal of replicating blood properties to the current objective of formulating a fluid that can be used to replace blood while preserving microvascular function and delivering oxygen. The properties of this fluid are counterintuitive and different from blood because it has high viscosity, oxygen affinity, and a low oxygen carrier concentration when compared with blood. The optimal oxygen carrier devised presently is poly-ethylene-conjugated human hemoglobin, a material demonstrated to be vasoinactive and void of the toxicities present in previous hemoglobin formulations. A feature of this material is that it is effective in small quantities, and therefore amplifies the equivalent supply of blood derived from blood donations.
BIOIMPEDANCE TOMOGRAPHY (ELECTRICAL IMPEDANCE TOMOGRAPHY)
Authors: Bayford R.H.
Published: April 2006

Electrical impedance tomography (EIT) is a relatively new imaging method that has evolved over the past 20 years. It has the potential to be of great value in clinical diagnosis; however, EIT is a technically difficult problem to solve in terms of developing hardware for data capture and the algorithms to reconstruct the images. This review looks at the development of EIT and how it has evolved. It focuses on its clinical applications, examining hardware for the collection of data and reconstruction algorithms to generate images. Finally, this review looks at future developments that are evolving from EIT. These new variations use mixed modalities that may produce interesting new clinical imaging tools.
MULTIMODALITY IN VIVO IMAGING SYSTEMS: Twice the Power or Double the Trouble?
Authors: Cherry Simon R.
Published: April 2006

Many different types of radiation have been exploited to provide images of the structure and function of tissues inside a living subject. Each imaging modality is characterized by differing resolutions on the spatial and temporal scales, and by a different sensitivity for measuring properties related to morphology or function. Combinations of imaging modalities that integrate the strengths of two modalities, and at the same time eliminate one or more weaknesses of an individual modality, thus offer the prospect of improved diagnostics, therapeutic monitoring, and preclinical research using imaging approaches. This review discusses the advantages and challenges in developing multimodality imaging systems for in vivo use, highlights some successful combinations that are now routinely used in the clinic and in research, and discusses recent advances in multimodality instrumentation that may offer new opportunities for imaging.
RECENT APPROACHES TO INTRACELLULAR DELIVERY OF DRUGS AND DNA AND ORGANELLE TARGETING
Authors: Torchilin Vladimir P.
Published: April 2006

Intracellular delivery of various drugs, including DNA, and drug carriers can sharply increase the efficiency of various treatment protocols. However, the receptor-mediated endocytosis of drugs, drug carriers, and DNA results in their lysosomal delivery and significant degradation. The problem can be solved and therapy efficacy still further increased if the approaches for direct intracytoplasmic delivery that bypass the endocytic pathway are developed. This is especially important for many anticancer drugs (proapoptotic drugs whose primary action site is the mitochondrial membrane) and gene therapy (nuclear or mitochondrial genomes should be targeted). This review considers several current approaches for intracellular drug delivery: the use of pH-sensitive liposomes, the use of cell-penetrating proteins and peptides, and the use of immunoliposomes targeting intracellular antigens. Among intracellular targets, nuclei (gene therapy), mitochondria (proapoptotic cancer therapy and targeting of the mitochondrial genome), and lysosomes (lysosomal targeting of enzymes for the therapy of the lysosomal storage diseases) are considered. Examples of successful intracellular and organelle-specific delivery of biologically active molecules, including DNA, are presented; unanswered questions, challenges, and future trends are also discussed.
LAB ON A CD
Authors: Madou Marc , Zoval Jim , Jia Guangyao , Kido Horacio , Kim Jitae , Kim Nahui
Published: April 2006

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.
MATHEMATICAL MODELING OF TUMOR-INDUCED ANGIOGENESIS
Authors: Chaplain M.A.J. , McDougall S.R. , Anderson A.R.A.
Published: April 2006

Angiogenesis, the growth of a network of blood vessels, is a crucial component of solid tumor growth, linking the relatively harmless avascular and the potentially fatal vascular growth phases of the tumor. As a process, angiogenesis is a well-orchestrated sequence of events involving endothelial cell migration and proliferation; degradation of tissue; new capillary vessel formation; loop formation (anastomosis) and, crucially, blood flow through the network. Once there is flow associated with the nascent network, subsequent growth evolves both temporally and spatially in response to the combined effects of angiogenic factors, migratory cues via the extracellular matrix, and perfusion-related hemodynamic forces in a manner that may be described as both adaptive and dynamic. In this article, we first present a review of previous theoretical and computational models of angiogenesis and then indicate how recent developments in flow models are providing insight into antiangiogenic and chemotherapeutic drug treatment of solid tumors.
RUNNING INTERFERENCE: Prospects and Obstacles to Using Small Interfering RNAs as Small Molecule Drugs
Authors: Dykxhoorn Derek M. , Lieberman Judy
Published: April 2006

RNA interference (RNAi) is a well-conserved, ubiquitous, endogenous mechanism that uses small noncoding RNAs to silence gene expression. The endogenous small RNAs, called microRNAs, are processed from hairpin precursors and regulate important genes involved in cell death, differentiation, and development. RNAi also protects the genome from invading genetic elements, encoded by transposons and viruses. When small double-stranded RNAs, called small interfering (si)RNAs, are introduced into cells, they bind to the endogenous RNAi machinery to disrupt the expression of mRNAs containing complementary sequences with high specificity. Any disease-causing gene and any cell type or tissue can potentially be targeted. This technique has been rapidly utilized for gene-function analysis and drug-target discovery and validation. Harnessing RNAi also holds great promise for therapy, although introducing siRNAs into cells in vivo remains an important obstacle. Pilot siRNA clinical studies began just three years after the discovery that RNAi works in mammalian cells. This review discusses recent progress and obstacles to using siRNAs as small molecule drugs.
SPINACH ON THE CEILING: A Theoretical Chemist's Return to Biology
Authors: Karplus Martin
Published: April 2006

I was born in Vienna and came to the United States as a refugee in October 1938. This experience played an important role in my view of the world and my approach to science: It contributed to my realization that it was safe to stop working in fields that I felt I understood and to focus on different areas of research by asking questions that would teach me and others something new. I describe my experiences that led me from chemistry and physics back to my first love, biology, and outline some of the contributions I have made as part of my ongoing learning experience.
CRYO-ELECTRON MICROSCOPY OF SPLICEOSOMAL COMPONENTS
Authors: Stark Holger , Lührmann Reinhard
Published: April 2006

Splicing is an essential step of gene expression in which introns are removed from pre-mRNA to generate mature mRNA that can be translated by the ribosome. This reaction is catalyzed by a large and dynamic macromolecular RNP complex called the spliceosome. The spliceosome is formed by the stepwise integration of five snRNPs composed of U1, U2, U4, U5, and U6 snRNAs and more than 150 proteins binding sequentially to pre-mRNA. To study the structure of this particularly dynamic RNP machine that undergoes many changes in composition and conformation, single-particle cryo-electron microscopy (cryo-EM) is currently the method of choice. In this review, we present the results of these cryo-EM studies along with some new perspectives on structural and functional aspects of splicing, and we outline the perspectives and limitations of the cryo-EM technique in obtaining structural information about macromolecular complexes, such as the spliceosome, involved in splicing.
MECHANOTRANSDUCTION INVOLVING MULTIMODULAR PROTEINS: Converting Force into Biochemical Signals
Authors: Vogel Viola
Published: April 2006

Cells can sense and transduce a broad range of mechanical forces into distinct sets of biochemical signals that ultimately regulate cellular processes, including adhesion, proliferation, differentiation, and apoptosis. Deciphering at the nanoscale the design principles by which sensory elements are integrated into structural protein motifs whose conformations can be switched mechanically is crucial to understand the process of transduction of force into biochemical signals that are then integrated to regulate mechanoresponsive pathways. While the major focus in the search for mechanosensory units has been on membrane proteins such as ion channels, integrins, and associated cytoplasmic complexes, a multimodular design of tandem repeats of various structural motifs is ubiquitously found among extracellular matrix proteins, as well as cell adhesion molecules, and among many intracellular players that physically link transmembrane proteins to the contractile cytoskeleton. Single-molecule studies have revealed an unexpected richness of mechanosensory motifs, including force-regulated conformational changes of loop-exposed molecular recognition sites, intermediate states in the unraveling pathway that might either expose cryptic binding or phosphorylation sites, or regions that display enzymatic activity only when unmasked by force. Insights into mechanochemical signal conversion principles will also affect various technological fields, from biotechnology to tissue engineering and drug development.
NMR TECHNIQUES FOR VERY LARGE PROTEINS AND RNAS IN SOLUTION
Authors: Tzakos Andreas G. , Grace Christy R. R. , Lukavsky Peter J. , Riek Roland
Published: April 2006

Three-dimensional structure determination of small proteins and oligonucleotides by solution NMR is established. With the development of novel NMR and labeling techniques, structure determination is now feasible for proteins with a molecular mass of up to ∼100 kDa and RNAs of up to 35 kDa. Beyond these molecular masses special techniques and approaches are required for applying NMR as a multiprobe method for structural investigations of proteins and RNAs. It is the aim of this review to summarize the NMR techniques and approaches available to advance the molecular mass limit of NMR both for proteins (up to 1 MDa) and RNAs (up to 100 kDa). Physical pictures of the novel techniques, their experimental applications, as well as labeling and assignment strategies are discussed and accompanied by future perspectives.
NANOFIBROUS MATERIALS AND THEIR APPLICATIONS
Authors: Burger Christian , Hsiao Benjamin S. , Chu Benjamin
Published: April 2006

▪ Abstract  Nanostructured fibrous materials have been made more readily available in large part owing to recent advances in electrospinning and related technologies, including the use of electrostatic or gas-blowing forces as well as a combination of both forces. The nonwoven structure has unique features, including interconnected pores and a very large surface-to-volume ratio, which enable such nanofibrous scaffolds to have many biomedical and industrial applications. The chemical composition of electrospun membranes can be adjusted through the use of different polymers, polymer blends, or nanocomposites made of organic or inorganic materials. In addition to the control of material composition, the processing flexibility in maneuvering physical parameters and structures, such as fiber diameter, mesh size, porosity, texture, and pattern formation, offers the capability to design electrospun scaffolds that can meet the demands of numerous practical applications. This review provides a selective description of the fabrication of nanofibrous membranes and applications with specific examples in anti-adhesion in surgery and ultrafiltration in water treatment.
PROGRESS IN CERAMIC LASERS
Authors: Ikesue Akio , Aung Yan Lin , Taira Takunori , Kamimura Tomosumi , Yoshida Kunio , Messing Gary L.
Published: April 2006

▪ Abstract  Yttrium aluminum garnet (YAG) (Y3Al5O12) single crystals doped with active species such as Nd and Yb have been used as laser media in solid-state lasers requiring high energy and excellent beam quality. This is because single crystals have extremely high thermal mechanical properties and optical qualities and because they enable high-efficiency laser oscillation. In 1995 the authors, using polycrystalline Nd:YAG, demonstrated a high-efficiency laser that was comparable to a single-crystal laser. Subsequently, single-longitudinal-mode oscillation, green and blue laser oscillation, and ultrashort-pulse laser oscillation were reported. Using the ceramic powder approach, the authors developed a composite laser element with a complicated structure that could not be produced by crystal growth techniques. This review discusses problems of conventional single-crystal growth, the fabrication and characteristics of ceramic lasers, laser oscillation properties (continuous-wave and pulse operation), light-scattering sources in ceramics, and typical applications of ceramic lasers.
AMORPHOUS POROUS MIXED OXIDES: Sol-Gel Ways to a Highly Versatile Class of Materials and Catalysts
Authors: Frenzer Gerald , Maier Wilhelm F.
Published: April 2006

▪ Abstract  This review discusses the preparation, characterization, and application of amorphous porous mixed oxides, a rapidly growing class of materials with wide applications and a huge potential for the tailoring of chemical composition, microstructure, porosity, and surface properties. In contrast to crystalline materials, these amorphous mixed oxides are prepared under mild reaction conditions in ambient atmosphere. An ever-increasing variety of precursors, additives, modifiers, solvents, catalysts, and posttreatment conditions provide ample fine-tuning options. These materials often display properties commonly associated with well-defined crystalline phases. The functional properties of such solids are largely unexplored and provide a tremendous opportunity for the development of new or alternative materials (solids with a function). Here, emphasis is paid to micro- and mesoporous mixed oxides and their catalytic properties. Easy access to these materials is offset by their much more problematic characterization. Microstructure, chemical structure, morphology, and pore sizes often show broad distributions, and materials description cannot compare with the precise data associated with crystalline phases. The facile preparation and accessibility of these materials make them ideally suited for the application of high-throughput technologies (HTT), which dramatically accelerate searches for new materials as well as fine tuning and optimization. HTT also allow investigators for the first time to access and optimize multinary mixed oxides on a realistic timescale.
HYDROGEN IN METALS: Microstructural Aspects
Authors: Pundt A. , Kirchheim R.
Published: April 2006

▪ Abstract  Metal-hydrogen (M-H) systems are interesting from both a theoretical and a practical point of view. M-H systems are utilized for energy-storage systems, in sensor applications, and in catalysis. These systems are often exploited as models for studying basic material properties, especially when the size of these systems is small and nonbulk-like contributions become dominant. Surfaces, nanocrystals, vacancy- and dislocation-rich materials, thin films, multilayers, and clusters as systems of major interest are addressed in this review. We show that the hydrogen solubility of M-H systems is strongly affected by the morphology and microstructure of and the stress between regions of different hydrogen concentration. For small-sized systems, surface- or interface-related sites become important and change the overall solubility as well as the phase boundaries of M-H systems. In thin films deposited on stiff substrates, compressive stresses evolve during hydrogen loading because the films are effectively clamped to substrates. These stresses are in the GPa range and strongly depend on microstructure. Nanoparticles even change their crystallographic structure, which results in completely new phases.
ADAPTIVE ROLES OF PROGRAMMED CELL DEATH DURING NERVOUS SYSTEM DEVELOPMENT
Authors: Buss Robert R. , Sun Woong , Oppenheim Ronald W.
Published: April 2006

The programmed cell death (PCD) of developing cells is considered an essential adaptive process that evolved to serve diverse roles. We review the putative adaptive functions of PCD in the animal kingdom with a major focus on PCD in the developing nervous system. Considerable evidence is consistent with the role of PCD in events ranging from neurulation and synaptogenesis to the elimination of adult-generated CNS cells. The remarkable recent progress in our understanding of the genetic regulation of PCD has made it possible to perturb (inhibit) PCD and determine the possible repercussions for nervous system development and function. Although still in their infancy, these studies have so far revealed few striking behavioral or functional phenotypes.

“Death opens unknown doors.”

– John Masefield, 1910
ORGANELLES AND TRAFFICKING MACHINERY FOR POSTSYNAPTIC PLASTICITY
Authors: Kennedy Matthew J. , Ehlers Michael D.
Published: April 2006

Neurons are among the largest and most complex cells in the body. Their immense size and intricate geometry pose many unique cell-biological problems. How is dendritic architecture established and maintained? How do neurons traffic newly synthesized integral membrane proteins over such long distances to synapses? Functionally, protein trafficking to and from the postsynaptic membrane has emerged as a key mechanism underlying various forms of synaptic plasticity. Which organelles are involved in postsynaptic trafficking, and how do they integrate and respond to activity at individual synapses? Here we review what is currently known about long-range trafficking of newly synthesized postsynaptic proteins as well as the local rules that govern postsynaptic trafficking at individual synapses.
BRAIN WORK AND BRAIN IMAGING
Authors: Raichle Marcus E. , Mintun Mark A.
Published: April 2006

Functional brain imaging with positron emission tomography and magnetic resonance imaging has been used extensively to map regional changes in brain activity. The signal used by both techniques is based on changes in local circulation and metabolism (brain work). Our understanding of the cell biology of these changes has progressed greatly in the past decade. New insights have emerged on the role of astrocytes in signal transduction as has an appreciation of the unique contribution of aerobic glycolysis to brain energy metabolism. Likewise our understanding of the neurophysiologic processes responsible for imaging signals has progressed from an assumption that spiking activity (output) of neurons is most relevant to one focused on their input. Finally, neuroimaging, with its unique metabolic perspective, has alerted us to the ongoing and costly intrinsic activity within brain systems that most likely represents the largest fraction of the brain's functional activity.
DEEP BRAIN STIMULATION
Authors: Perlmutter Joel S. , Mink Jonathan W.
Published: April 2006

Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting to extend this mode of treatment to other conditions. Yet, the precise mechanism of action of DBS remains uncertain. Such studies have importance that extends beyond clinical therapeutics. Investigations of the mechanisms of action of DBS have the potential to clarify fundamental issues such as the functional anatomy of selected brain circuits and the relationship between activity in those circuits and behavior. Although we review relevant clinical issues, we emphasize the importance of current and future investigations on these topics.
THE HEDGEHOG PATHWAY AND NEUROLOGICAL DISORDERS
Authors: Dellovade Tammy , Romer Justyna T. , Curran Tom , Rubin Lee L.
Published: April 2006

The hedgehog pathway is a major regulator of embryonic development, and mutations that decrease its activity are known to be associated with severe defects in nervous system development. Recent evidence suggests hedgehog continues to function in adult tissue, normal as well as diseased, by regulating both cell proliferation and the production of growth and angiogenic factors. In the adult nervous system, this dual ability is especially important in regulating the behavior of neural stem and progenitor cells. This review summarizes information connecting hedgehog signaling and neural diseases, including neurodegenerative disorders and brain tumors, particularly medulloblastoma. We also describe the discovery and utility of small molecule agonists and antagonists of this pathway and their potential as novel types of therapeutics.
IMAGING VALUATION MODELS IN HUMAN CHOICE
Authors: Montague P. Read , King-Casas Brooks , Cohen Jonathan D.
Published: April 2006

To make a decision, a system must assign value to each of its available choices. In the human brain, one approach to studying valuation has used rewarding stimuli to map out brain responses by varying the dimension or importance of the rewards. However, theoretical models have taught us that value computations are complex, and so reward probes alone can give only partial information about neural responses related to valuation. In recent years, computationally principled models of value learning have been used in conjunction with noninvasive neuroimaging to tease out neural valuation responses related to reward-learning and decision-making. We restrict our review to the role of these models in a new generation of experiments that seeks to build on a now-large body of diverse reward-related brain responses. We show that the models and the measurements based on them point the way forward in two important directions: the valuation of time and the valuation of fictive experience.
LOCOMOTOR CIRCUITS IN THE MAMMALIAN SPINAL CORD
Authors: Kiehn Ole
Published: April 2006

Intrinsic spinal networks, known as central pattern generators (CPGs), control the timing and pattern of the muscle activity underlying locomotion in mammals. This review discusses new advances in understanding the mammalian CPGs with a focus on experiments that address the overall network structure as well as the identification of CPG neurons. I address the identification of excitatory CPG neurons and their role in rhythm generation, the organization of flexor-extensor networks, and the diverse role of commissural interneurons in coordinating left-right movements. Molecular and genetic approaches that have the potential to elucidate the function of populations of CPG interneurons are also discussed.
NONCANONICAL WNT SIGNALING AND NEURAL POLARITY
Authors: Montcouquiol Mireille , Crenshaw E. Bryan , Kelley Matthew W.
Published: April 2006

The Wnt signaling pathway regulates multiple events in development and disease in both vertebrates and invertebrates. Recently, the noncanonical Wnt signaling cascades, those that do not signal through β-catenin, have gained prominence for their role in the regulation of cellular polarity. It is not surprising that cellular polarization influences a number of different developmental events within the nervous system, including neurulation and neural tube closure, cellular migration, and uniform orientation of cells within an epithelial plane (planar cell polarity). In this review, we describe the differences between the canonical and noncanonical pathways, summarize recent data illustrating the roles of the noncanonical Wnt pathway in different polarizing events during neural development, and discuss the potential molecular mechanisms that underlie the generation of cellular asymmetry and polarity.
COMPLETE FUNCTIONAL CHARACTERIZATION OF SENSORY NEURONS BY SYSTEM IDENTIFICATION
Authors: Wu Michael C.-K. , David Stephen V. , Gallant Jack L.
Published: April 2006

System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm provides an objective method for evaluating and comparing computational models. In this chapter we review many of the system identification algorithms that have been used in sensory neurophysiology, and we show how they can be viewed as variants of a single statistical inference problem. We then review many of the practical issues that arise when applying these methods to neurophysiological experiments: stimulus selection, behavioral control, model visualization, and validation. Finally we discuss several problems to which system identification has been applied recently, including one important long-term goal of sensory neuroscience: developing models of sensory systems that accurately predict neuronal responses under completely natural conditions.
Maternal Obesity, Metabolism, and Pregnancy Outcomes
Authors: King Janet C.
Published: April 2006

▪ Abstract  About one third of all pregnant women in the United States are obese. Maternal obesity at conception alters gestational metabolic adjustments and affects placental, embryonic, and fetal growth and development. Neural tube defects and other developmental anomalies are more common in infants born to obese women; these defects have been linked to poor glycemic control. Preeclampsia, a gestational disorder occurring more frequently in obese women, appears to be due to a subclinical inflammatory state that impairs early placentation and development of its blood supply. Fetal growth and development during the last half of pregnancy depends on maternal metabolic adjustments dictated by placental hormones and the subsequent oxygen and nutrient supply. Maternal obesity affects these metabolic adjustments as well. Basal metabolic rates are significantly higher in obese women, and maternal fat gain is lower, possibly in response to altered leptin function. The usual increase in insulin resistance seen in late pregnancy is enhanced in obese mothers, causing marked postprandial increases in glucose, lipids, and amino acids and excessive fetal exposure to fuel sources, which in turn increases fetal size, fat stores, and risk for disease postnatally. Impaired glucose tolerance, gestational diabetes, and hyperlipidemia are more common among obese mothers. To date, little attention has been given to the role of diet among obese women in preventing these problems. However, studies of women with impaired glucose tolerance show that replacing refined carbohydrates and saturated fat with complex, low-glycemic carbohydrates and polyunsaturated fatty acids improves metabolic homeostasis and pregnancy outcomes. Thus, current dietary guidelines regarding the amount and type of carbohydrates and fat for nonpregnant women seem appropriate for pregnant women as well.
Control of Energy Homeostasis: Role of Enzymes and Intermediates of Fatty Acid Metabolism in the Central Nervous System
Authors: Wolfgang Michael J. , Lane M. Daniel
Published: April 2006

▪ Abstract  The regulation of energy homeostasis is critical for normal physiology and survival. Energy flux must be rigorously monitored and adjusted to ensure that fuel intake and expenditure remain within acceptable limits. The central nervous system (CNS) is, in large part, responsible for conducting this energy-monitoring function and for integrating the numerous inputs. It has become evident that neurons of the CNS monitor and respond to levels of metabolic intermediates that reflect peripheral energy status. Intermediates in the fatty acid biosynthetic pathway have been implicated as hypothalamic signaling mediators that sense and respond to changes in circulating fuels. Genetic and pharmacologic manipulation of the enzymes of fatty acid metabolism have led to the hypothesis that neuronal metabolic intermediates affect neural outputs that modify both feeding behavior and energy expenditure. This review focuses on the regulatory roles of these enzymes and intermediates in the regulation of food intake and energy balance.
Innovative Dietary Sources of N-3 Fatty Acids
Authors: Whelan Jay , Rust Cheryl
Published: April 2006

▪ Abstract  It is now established that dietary n-3 polyunsaturated fatty acids (PUFAs) are involved in health promotion and disease prevention, particularly those traditionally derived from marine sources (e.g., eicosapentaenoic acid and docosahexaenoic acid). A number of organizations have made specific recommendations for the general population to increase their intakes of these nutrients. In response to and along with these recommendations, n-3 PUFAs are being incorporated into nontraditional food sources because of advances in the technology to safely enrich/fortify our food supply. Fatty acid compositions of traditional oils (e.g., canola and soybean) are being genetically modified to deliver more highly concentrated sources of n-3 PUFA. The advent of algal sources of docosahexaenoic acid provides one of the few terrestrial sources of this fatty acid in a concentrated form. All of this is possible because of newer technologies (microencapsulation) and improved processing techniques that ensure stability and preserve the integrity of these unstable fatty acids.