bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature-dependent residual broadening of x-ray diffraction spectra in nanocrystalline plasticity
Authors: Brandstetter S. , Budrović Ž. , Van Petegem S. , Schmitt B. , Stergar E. , Derlet P. M. , Van Swygenhoven H.
Published: November 2005

In situ x-ray diffraction peak profile analysis at room temperature has shown that peak broadening during plastic deformation is reversible upon unloading for nanocrystalline metals, demonstrating the lack of a developing permanent dislocation network. In this letter, we show that the peak broadening is not reversible when similar load-unload cycles are performed at 180 K. However, by then warming the sample to 300 K, peak broadening recovers to a great extent and all subsequent plastic deformation load∕unload cycles are characterized again by a reversible peak broadening. The temperature-dependent residual peak broadening provides explicit evidence of a thermal component in the nanocrystalline deformation mechanism.
Drastic change of electric double layer capacitance by surface functionalization of carbon nanotubes
Authors: Kim Yong-Tae , Ito Yoshiaki , Tadai Kenji , Mitani Tadaoki , Kim Un-Seok , Kim Hyung-Sun , Cho Byung-Won
Published: November 2005

In this letter we show that it is possible to drastically change electric double layer capacitance, from a large increase to complete disappearance, by introducing various surface functional groups on carbon nanotubes. The introduction of surface carboxyl groups created a 3.2 times larger capacitance due to the increased hydrophilicity of the multiwalled carbon nanotubes in an aqueous electrolyte. In contrast, the introduction of alkyl groups resulted in a marked decrease of capacitance. Notably, we unexpectedly observed the complete disappearance of capacitance for samples functionalized with longer alkyl groups than octyl, indicating the perfect block of proton access to the carbon nanotubes’ surfaces by extreme hydrophobicity.
Demonstration of a semipolar (101¯3¯) InGaN∕GaN green light emitting diode
Authors: Sharma R. , Pattison P. M. , Masui H. , Farrell R. M. , Baker T. J. , Haskell B. A. , Wu F. , DenBaars S. P. , Speck J. S. , Nakamura S.
Published: November 2005

We demonstrate the growth and fabrication of a semipolar (101¯3¯) InGaN∕GaN green (∼525nm) light emitting diode (LED). The fabricated devices demonstrated a low turn-on voltage of 3.2V and a series resistance of 14.3Ω. Electroluminescence measurements on the semipolar LED yielded a reduced blueshifting of the peak emission wavelength with increasing drive current, compared to a reference commercial c-plane LED. On-wafer measurements yielded an approximately linear increase in output power with drive current, with measured values of 19.3 and 264μW at drive currents of 20 and 250mA, respectively. The external quantum efficiency did not decrease appreciably at high currents. Polarization anisotropy was also observed in the electroluminescence from the semipolar green LED, with the strongest emission intensity parallel to the [12¯10] direction. A polarization ratio of 0.32 was obtained at a drive current of 20mA.
Ion blistering of boron-doped silicon: The critical role of defect passivation
Authors: Desrosiers N. , Giguère A. , Moutanabbir O. , Terreault B.
Published: November 2005

The microscopic mechanism of hydrogen ion blistering of silicon was investigated using Raman scattering spectroscopy and thermal desorption spectrometry. The data in B-doped Si(∼10−3∕Ωcm) are particularly worth noting, since B doping at this level strongly reduces both the ion dose and the thermal budget required for blistering. In that case the Si–H stretch mode is found to be shifted markedly towards higher frequencies characteristic of highly passivated vacancies and internal surfaces. It is deduced that the degree of defect passivation is a most critical factor for blistering.
Single-hole transistor in p-type GaAs∕AlGaAs heterostructures
Authors: Grbić Boris , Leturcq Renaud , Ensslin Klaus , Reuter Dirk , Wieck Andreas D.
Published: November 2005

A single-hole transistor is patterned in a p-type, C-doped GaAs∕AlGaAs heterostructure by scanning probe oxidation lithography. Clear Coulomb blockade resonances have been observed at Thole=300mK. A charging energy of ∼1.5meV is extracted from Coulomb diamond measurements, in agreement with the lithographic dimensions of the dot. The absence of excited states in Coulomb diamond measurements, as well as the temperature dependence of Coulomb peak heights indicate that the dot is in the multilevel transport regime. Fluctuations in peak spacings larger than the estimated mean single-particle level spacing are observed.
Properties of a CuAu phase of AgGaSe2 grown on [100] GaAs substrate
Authors: Choi I. H. , Yu P. Y.
Published: November 2005

Recently, it has been suggested theoretically [A. Janotti and S.-H. Wei, Appl. Phys. Lett. 81, 3957 (2002)] that, if AgGaSe2 with the CuAu structure can be grown epitaxially on ZnSe, it will be an excellent source for spin-polarized electrons. Here we report the growth and properties of epitaxial films of AgGaSe2 with the CuAu structure on (100) GaAs substrates and compared them with those of chalcopyrite AgGaSe2.
Marine diatoms as optical chemical sensors
Authors: De Stefano Luca , Rendina Ivo , De Stefano Mario , Bismuto Alfredo , Maddalena Pasqualino
Published: November 2005

Complex micro- and nanostructured materials for optical sensing purposes are designed and fabricated using top technologies. A completely different approach to engineering systems at the nanoscale consists in recognizing the nanostructures and morphologies that nature has optimized during life’s history on earth. We have found that the photoluminescence emission from silica skeleton of marine diatoms Thalassiosira rotula Meunier is strongly dependent on the surrounding environment. Both the optical intensity and the peaks positions are affected by gases and organic vapors. Depending on the electronegativity and polarizing ability, some substances quench the luminescence, while others effectively enhance it. These phenomena allow the discrimination between different substances. These naturally occurring organisms are thus good candidates as optical sensing materials.
Fabrication of versatile nanocomponents using single-crystalline Au nanoplates
Authors: Yun Yong Ju , Park Gwangseo , Ah Chil Seong , Park Hyung Ju , Yun Wan Soo , Ha Dong Han
Published: November 2005

We suggest an approach to the fabrication of versatile nanocomponents designed deliberately by selective Ga+ focused-ion-beam etching or Ar+ ion milling of single-crystalline Au nanoplates synthesized by the chemical reaction. The nanocomponents have various shapes like gear, wheel, dumbbell, square and letter “A” with in-plane size of about 400nm and thickness of 40–50nm. They can be picked up or moved freely one by one to be assembled into sophisticated nanodevices or micromachines. The applicability of our approach both to the fundamental research and to the applied research is discussed.
Temperature-insensitive flexible polymer wavelength filter fabricated on polymer substrates
Authors: Nam Sung-Hyun , Kang Jae-Wook , Kim Jang-Joo
Published: November 2005

Temperature-insensitive polymer wavelength filters with silicon nitride gratings were fabricated on a polymer substrate. Polymer waveguides on polymer substrates were fabricated on top of the Si wafer with a water soluble poly(vinylalcohol) (PVA) interlayer between the Si wafer and polymer waveguides. After the completion of the waveguides, the polymer waveguides are separated from the substrate by dissolving the PVA layer to form all polymer waveguides. The novel process provides a way to overcome the problem of the thermal instability of polymer substrate when the polymer waveguides are directly fabricated on polymer substrates. The polymeric wavelength filter fabricated on a polymer substrate exhibits one order of magnitude lower Bragg wavelength shift with temperature than the device on the Si-wafer in the temperature range of 25–70°C, which is consistent with theoretical prediction.
Current-voltage characteristics of p-InGaN∕n-GaN vertical conducting diodes on n+-SiC substrates
Authors: Nishikawa Atsushi , Kumakura Kazuhide , Akasaka Tetsuya , Makimoto Toshiki
Published: November 2005

p - In Ga N ∕ n - Ga N vertical conducting diodes have been grown on n+-SiC substrates by low-pressure metalorganic vapor phase epitaxy and their current-voltage characteristics have been investigated. The typical forward voltage drop was 3.8–4.0 V at a forward current density of 100A∕cm2 with an on-state resistance of ∼1.3mΩcm2. The ideality factor of the samples was ∼2, meaning that the tunneling current through defects is small enough in these devices. The breakdown voltage (VB) increased with increasing n-GaN layer thickness, while it increased with decreasing carrier concentration of the layer by substituting undoped GaN for n-GaN. When the undoped GaN layer thickness was increased to 1800 nm, the highest breakdown voltage of 305 V was obtained with a low on-state resistance (Ron) of 1.51mΩcm2, leading to the figure-of-merit, (VB)2∕Ron, of 62MW∕cm2.
Environmental and genetic control of morphogenesis in crops: towards models simulating phenotypic plasticity
Authors: Dingkuhn Michael , Luquet Delphine , Quilot Benedicte , de Reffye Philippe
Published: November 2005

As molecular biologists are realising the importance of physiology in understanding functional genomics of quantitative traits, and as physiologists are realising the formidable prospects for improving their phenotypic models with information on the underlying gene networks, researchers worldwide are working on linked physiological–genetic models. These efforts are in their early methodological stage despite, or because of, the availability of many different types of models, the problem being to bring together the different ways that scientists see the plant. This paper describes some current efforts to adapt phenotype models to the objective of simulating gene-phene processes at the plant or crop scale. Particular emphasis is given to the models’ capacity to simulate genotype × environment interaction and the resulting phenotypic plasticity, assuming that this permits the defining of model parameters that are closer to specific gene action. Three different types of approaches are presented: (1) a generic, mathematical-architectural model called GREENLAB that simulates resource-modulated morphogenesis; (2) an ecophysiological model of peach tree fruit development and filling, parameterised for a mapping population to evaluate the potential of plugging quantitative trait locus (QTL) effects into the model; and (3) the new model Ecomeristem that constructs plant architecture and its phenotypic plasticity from meristem behaviour, the principal hypothesis being that resource limitations and stresses feed back on the meristems. This latter choice is based on the fact that gene expression happens to a large extent in the meristems. The model is evaluated on the basis of preliminary studies on vegetative-stage rice. The different modelling concepts are critically discussed with respect to their ability to simulate phenotypic plasticity and to operate with parameters that approximate specific gene action, particularly in the area of morphogenesis.
Evolution in the genus Cicer - vernalisation response and low temperature pod set in chickpea (C. arietinum L.) and its annual wild relatives
Authors: Berger Jens D. , Buck Renee , Henzell Jennifer M. , Turner Neil C.
Published: November 2005

Chickpea (Cicer arietinum) developed as a post-rainy season, spring-sown crop early in its evolution and spread into warm subtropical regions, in contrast to its wild relatives that have remained as winter annuals in West and Central Asia. To test whether these different life cycles selected for different phenological strategies in wild and cultivated Cicer, germplasm from a wide range of habitats was subjected to different cold treatments (vernalisation, control) at germination, and phenology evaluated at warm and cool field sites (14.8–15.1°C and 13.1°C, respectively). All wild Cicer species, except for C. yamashitae, responded positively to vernalisation and accelerated the dates of flowering, podding, and maturity. There was no vernalisation response in cultivated chickpea, whereas C. arietinum/C. echinospermum and C. arietinum/C. reticulatum interspecific hybrids were intermediate, flowering 6–16 days earlier after vernalisation. Relative podding dates differed between sites. Chickpea podded earlier than most vernalised wild species under warm conditions, but not at the cool site. Regression against post-anthesis temperature showed that the delay in podding was consistent with a lack of cold tolerance in the cultigen. The interspecific hybrids were significantly more cold tolerant than chickpea, and the wild species were almost insensitive to the temperature range recorded at the cool site.
Vernalisation responsiveness and a greater tolerance of low temperatures during the reproductive phase demonstrate that the annual wild Cicer species harbour important traits that can be used to widen adaptation in the cultigen, and may help to improve the performance of chickpea as a Mediterranean cool-season crop.
Calcium extrusion is critical for cardiac morphogenesis and rhythm in embryonic zebrafish hearts
Authors: Ebert A. M. , Hume G. L. , Warren K. S. , Cook N. P. , Burns C. G. , Mohideen M. A. , Siegal G. , Yelon D. , Fishman M. C. , Garrity D. M.
Published: November 2005

Calcium entry into myocytes drives contraction of the embryonic heart. To prepare for the next contraction, myocytes must extrude calcium from intracellular space via the Na+/Ca2+exchanger (NCX1) or sequester it into the sarcoplasmic reticulum, via the sarcoplasmic reticulum Ca2+-ATPase2 (SERCA2). In mammals, defective calcium extrusion correlates with increased intracellular calcium levels and may be relevant to heart failure and sarcoplasmic dysfunction in adults. We report here that mutation of the cardiac-specific NCX1 (NCX1h) gene causes embryonic lethal cardiac arrhythmia in zebrafishtremblor(tre) embryos. Thetreventricle is nearly silent, whereas the atrium manifests a variety of arrhythmias including fibrillation. Calcium extrusion defects intremutants correlate with severe disruptions in sarcomere assembly, whereas mutations in the L-type calcium channel that abort calcium entry do not produce this phenotype. Knockdown ofSERCA2activity by morpholino-mediated translational inhibition or pharmacological inhibition causes embryonic lethality due to defects in cardiac contractility and morphology but, in contrast totremutation, does not produce arrhythmia. Analysis of intracellular calcium levels indicates that homozygoustreembryos develop calcium overload, which may contribute to the degeneration of cardiac function in this mutant. Thus, the inhibition of NCX1h versus SERCA2 activity differentially affects the pathophysiology of rhythm in the developing heart and suggests that relative levels of NCX1 and SERCA2 function are essential for normal development.
Mutagenic specificity of endogenously generated abasic sites in
Saccharomyces cerevisiae
chromosomal DNA
Authors: Auerbach Paul , Bennett Richard A. O. , Bailey Elisabeth A. , Krokan Hans E. , Demple Bruce
Published: November 2005

Abasic [apurinic/apyrimidinic (AP)] sites are common, noncoding DNA lesions. Despite extensive investigation, the mutational pattern they provoke in eukaryotic cells remains unresolved. We constructed
Saccharomyces cerevisiae
strains in which chromosomal AP sites were generated during normal cell growth by altered human uracil-DNA glycosylases that remove undamaged cytosines or thymines. The mutation target was the
URA3
gene inserted near the
ARS309
origin to allow defined replication polarity. Expression of the altered glycosylases caused a 7- to 18-fold mutator effect in AP endonuclease-deficient (Δ
apn1
) yeast, which depended highly on the known translesion synthesis enzymes Rev1 and DNA polymerase ζ. For the C-glycosylase, GC>CG transversions were the predominant mutations, followed by GC>AT transitions. AT>CG transversions predominated for the T-glycosylase. These results support a major role for Rev1-dependent dCMP insertion across from AP sites and a lesser role for dAMP insertion. Unexpectedly, there was also a significant proportion of dTMP insertions that suggest another mutational pathway at AP sites. Although replication polarity did not strongly influence mutagenesis at AP sites, for certain mutation types, there was a surprisingly strong difference between the transcribed and non-transcribed strands of
URA3
. The basis for this strand discrimination requires further exploration.
Structure of a group A streptococcal phage-encoded virulence factor reveals a catalytically active triple-stranded β-helix
Authors: Smith Nicola L. , Taylor Edward J. , Lindsay Anna-Marie , Charnock Simon J. , Turkenburg Johan P. , Dodson Eleanor J. , Davies Gideon J. , Black Gary W.
Published: November 2005

Streptococcus pyogenes
(group A Streptococcus) causes severe invasive infections including scarlet fever, pharyngitis (streptococcal sore throat), skin infections, necrotizing fasciitis (flesh-eating disease), septicemia, erysipelas, cellulitis, acute rheumatic fever, and toxic shock. The conversion from nonpathogenic to toxigenic strains of
S. pyogenes
is frequently mediated by bacteriophage infection. One of the key bacteriophage-encoded virulence factors is a putative “hyaluronidase,” HylP1, a phage tail-fiber protein responsible for the digestion of the
S. pyogenes
hyaluronan capsule during phage infection. Here we demonstrate that HylP1 is a hyaluronate lyase. The 3D structure, at 1.8-Å resolution, reveals an unusual triple-stranded β-helical structure and provides insight into the structural basis for phage tail assembly and the role of phage tail proteins in virulence. Unlike the triple-stranded β-helix assemblies of the bacteriophage T4 injection machinery and the tailspike endosialidase of the
Escherichia coli
K1 bacteriophage K1F, HylP1 possesses three copies of the active center on the triple-helical fiber itself without the need for an accessory catalytic domain. The triple-stranded β-helix is not simply a structural scaffold, as previously envisaged; it is harnessed to provide a 200-Å-long substrate-binding groove for the optimal reduction in hyaluronan viscosity to aid phage penetration of the capsule.
The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase
Authors: Kim Myung Hee , Choi Won-Chan , Kang Hye Ok , Lee Jong Suk , Kang Beom Sik , Kim Kyung-Jin , Derewenda Zygmunt S. , Oh Tae-Kwang , Lee Choong Hwan , Lee Jung-Kee
Published: November 2005

In many Gram-negative bacteria, including a number of pathogens such asPseudomonas aeruginosaandErwinia carotovora, virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusibleN-acyl-l-homoserine lactones (AHLs) as intercellular messenger molecules. A number of organisms also contain genes coding for lactonases that hydrolyze AHLs into inactive products, thereby blocking the quorum-sensing systems. Consequently, these enzymes attract intense interest for the development of antiinfection therapies. However, the catalytic mechanism of AHL-lactonase is poorly understood and subject to controversy. We here report a 2.0-Å resolution structure of the AHL-lactonase fromBacillus thuringiensisand a 1.7-Å crystal structure of its complex withl-homoserine lactone. Despite limited sequence similarity, the enzyme shows remarkable structural similarities to glyoxalase II and RNase Z proteins, members of the metallo-β-lactamase superfamily. We present experimental evidence that AHL-lactonase is a metalloenzyme containing two zinc ions involved in catalysis, and we propose a catalytic mechanism for bacterial metallo-AHL-lactonases.
The relationship between FRQ-protein stability and temperature compensation in theNeurosporacircadian clock
Authors: Ruoff Peter , Loros Jennifer J. , Dunlap Jay C.
Published: November 2005

Temperature compensation is an important property of all biological clocks. InNeurospora crassa, negative-feedback regulation on thefrequency(frq) gene's transcription by the FRQ protein plays a central role in the organism's circadian pacemaker. Earlier model calculations predicted that the stability of FRQ should determine the period length ofNeurospora's circadian rhythm as well as the rhythm's temperature compensation. Here, we report experimental FRQ protein stabilities infrqmutants at 20°C and 25°C, and estimates of overall activation energies for mutant FRQ protein degradation. The results are consistent with earlier model predictions, i.e., temperature compensation ofNeurospora's circadian rhythm is a highly regulated process where the stability of FRQ is an important factor in determiningNeurospora's circadian period as well as the clock's temperature compensation. The partial loss of temperature compensation infrq7andfrqS513Imutants can be described by a simple negative-feedback model (the Goodwin oscillator) when the experimentally obtained activation energies of FRQ degradation for theses mutants are incorporated into the model.
Assessing the spatiotemporal evolution of neuronal activation with single-trial event-related potentials and functional MRI
Authors: Eichele Tom , Specht Karsten , Moosmann Matthias , Jongsma Marijtje L. A. , Quiroga Rodrigo Quian , Nordby Helge , Hugdahl Kenneth
Published: November 2005

The brain acts as an integrated information processing system, which methods in cognitive neuroscience have so far depicted in a fragmented fashion. Here, we propose a simple and robust way to integrate functional MRI (fMRI) with single trial event-related potentials (ERP) to provide a more complete spatiotemporal characterization of evoked responses in the human brain. The idea behind the approach is to find brain regions whose fMRI responses can be predicted by paradigm-induced amplitude modulations of simultaneously acquired single trial ERPs. The method was used to study a variant of a two-stimulus auditory target detection (odd-ball) paradigm that manipulated predictability through alternations of stimulus sequences with random or regular target-to-target intervals. In addition to electrophysiologic and hemodynamic evoked responses to auditory targets
per se
, single-trial modulations were expressed during the latencies of the P2 (170-ms), N2 (200-ms), and P3 (320-ms) components and predicted spatially separated fMRI activation patterns. These spatiotemporal matches, i.e., the prediction of hemodynamic activation by time-variant information from single trial ERPs, permit inferences about regional responses using fMRI with the temporal resolution provided by electrophysiology.
Breaking the diffraction barrier in fluorescence microscopy at low light intensities by using reversibly photoswitchable proteins
Authors: Hofmann Michael , Eggeling Christian , Jakobs Stefan , Hell Stefan W.
Published: November 2005

Fluorescence microscopy is indispensable in many areas of science, but until recently, diffraction has limited the resolution of its lens-based variant. The diffraction barrier has been broken by a saturated depletion of the marker's fluorescent state by stimulated emission, but this approach requires picosecond laser pulses of GW/cm
2
intensity. Here, we demonstrate the surpassing of the diffraction barrier in fluorescence microscopy with illumination intensities that are eight orders of magnitude smaller. The subdiffraction resolution results from reversible photoswitching of a marker protein between a fluorescence-activated and a nonactivated state, whereby one of the transitions is accomplished by means of a spatial intensity distribution featuring a zero. After characterizing the switching kinetics of the used marker protein asFP595, we demonstrate the current capability of this RESOLFT (reversible saturable optical fluorescence transitions) type of concept to resolve 50–100 nm in the focal plane. The observed resolution is limited only by the photokinetics of the protein and the perfection of the zero. Our results underscore the potential to finally achieve molecular resolution in fluorescence microscopy by technical optimization.
Identification of a high-affinity binding site involved in the transport of endocannabinoids
Authors: Moore S. A. , Nomikos G. G. , Dickason-Chesterfield A. K. , Schober D. A. , Schaus J. M. , Ying B.-P. , Xu Y.-C. , Phebus L. , Simmons R. M. A. , Li D. , Iyengar S. , Felder C. C.
Published: November 2005

Phytocannabinoids, such as the principal bioactive component of marijuana, Δ9-tetrahydrocannabinol, have been used for thousands of years for medical and recreational purposes. Δ9-Tetrahydrocannabinol and endogenous cannabinoids (e.g., anandamide) initiate their agonist properties by stimulating the cannabinoid family of G protein-coupled receptors (CB1and CB2). The biosynthesis and physiology of anandamide is well understood, but its mechanism of uptake (resulting in signal termination by fatty acid amide hydrolase) has been elusive. Mounting evidence points to the existence of a specific anandamide transport protein; however, no direct evidence for this protein has been provided. Here, we use a potent, competitive small molecule inhibitor of anandamide uptake (LY2318912, IC507.27 ± 0.510 nM) to identify a high-affinity, saturable anandamide transporter binding site (LY2318912;Kd= 7.62 ± 1.18 nM,Bmax= 31.6 ± 1.80 fmol/mg protein) that is distinct from fatty acid amide hydrolase. Systemic administration of the inhibitor into rodents elevates anandamide levels 5-fold in the brain and demonstrates efficacy in the formalin paw-licking model of persistent pain with no obvious adverse effects on motor function. Identification of the anandamide transporter binding site resolves a missing mechanistic link in endocannabinoid signaling, andin vivoresults suggest that endocannabinoid transporter antagonists may provide a strategy for positive modulation of cannabinoid receptors.
Cytochrome
c
conformations resolved by the photon counting histogram: Watching the alkaline transition with single-molecule sensitivity
Authors: Perroud Thomas D. , Bokoch Michael P. , Zare Richard N.
Published: November 2005

We apply the photon counting histogram (PCH) model, a fluorescence technique with single-molecule sensitivity, to study pH-induced conformational changes of cytochrome
c
. PCH is able to distinguish different protein conformations based on the brightness of a fluorophore sensitive to its local environment. We label cytochrome
c
through its single free cysteine with tetramethylrhodamine-5-maleimide (TMR), a fluorophore with specific brightnesses that we associate with specific protein conformations. Ensemble measurements demonstrate two different fluorescence responses with increasing pH: (
i
) a decrease in fluorescence intensity caused by the alkaline transition of cytochrome
c
(pH 7.0–9.5), and (
ii
) an increase in intensity when the protein unfolds (pH 9.5–10.8). The magnitudes of these two responses depend strongly on the molar ratio of TMR used to label cytochrome
c
. Using PCH we determine that this effect arises from the proportion of a nonfunctional conformation in the sample, which can be differentiated from the functional conformation. We further determine the causes of each ensemble fluorescence response: (
i
) during the alkaline transition, the fluorophore enters a dark state and discrete conformations are observed, and (
ii
) as cytochrome
c
unfolds, the fluorophore incrementally brightens, but discrete conformations are no longer resolved. Moreover, we also show that functional TMR-cytochrome
c
undergoes a response of identical magnitude regardless of the proportion of nonfunctional protein in the sample. As expected for a technique with single-molecule sensitivity, we demonstrate that PCH can directly observe the most relevant conformation, unlike ensemble fluorometry.
Altered differentiation of neural stem cells in fragile X syndrome
Authors: Castrén Maija , Tervonen Topi , Kärkkäinen Virve , Heinonen Seppo , Castrén Eero , Larsson Kim , Bakker Cathy E. , Oostra Ben A. , Åkerman Karl
Published: November 2005

Fragile X syndrome, a common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP) due to a mutation in the
FMR1
gene. We investigated the differentiation of neural stem cells generated from the brains of
fmr1-
knockout (KO) mice and from postmortem tissue of a fragile X fetus. Mouse and human FMRP-deficient neurospheres generated more TuJ1-positive cells (3-fold and 5-fold, respectively) than the control neurospheres generated from normal mouse and human brains, and these cells showed morphological alterations with fewer and shorter neurites and a smaller cell body volume. The number of cells expressing glial fibrillary acidic protein and generated by these neurospheres was reduced because of increased apoptotic cell death. Furthermore, there was an increase in a population of cells with intense oscillatory Ca
2+
responses to neurotransmitters in differentiated cells lacking FMRP. In addition, the number of cells in a cohort of bromodeoxyuridine-labeled newborn cells was increased in the subventricular zone of the telencephalon of the
fmr1
-KO mouse
in vivo
. These results demonstrate substantial alterations in the early maturation of FMRP-deficient neural stem cells in fragile X syndrome and in the
fmr1
-KO mice.
Zfp312 is required for subcortical axonal projections and dendritic morphology of deep-layer pyramidal neurons of the cerebral cortex
Authors: Chen Jie-Guang , Rašin Mladen-Roko , Kwan Kenneth Y. , Šestan Nenad
Published: November 2005

Pyramidal neurons of the cerebral cortex display marked layer- and subtype-specific differences in their axonal projections and dendritic morphologies. Here we show that transcription factor
Zfp312
is selectively expressed by layer V and VI subcortical projection pyramidal neurons and their progenitor cells. Knocking down
Zfp312
with small interfering RNAs dramatically reduced the number of subcortical axonal projections from deep-layer pyramidal neurons and altered their dendritic morphology. In contrast, misexpression of
Zfp312
in cortically projecting pyramidal neurons of layers II and III induced the expression of Tbr1, a transcription factor enriched in deep-layer neurons, and the formation of ectopic subcortical axonal projections. Thus, our results indicate that transcription factor Zfp312 plays a critical role in layer- and neuronal subtype-specific patterning of cortical axonal projections and dendritic morphologies.
Reconstructing the pathways of a cellular system from genome-scale signals by using matrix and tensor computations
Authors: Alter Orly , Golub Gene H.
Published: November 2005

We describe the use of the matrix eigenvalue decomposition (EVD) and pseudoinverse projection and a tensor higher-order EVD (HOEVD) in reconstructing the pathways that compose a cellular system from genome-scale nondirectional networks of correlations among the genes of the system. The EVD formulates a genes × genes network as a linear superposition of genes × genes decorrelated and decoupled rank-1 subnetworks, which can be associated with functionally independent pathways. The integrative pseudoinverse projection of a network computed from a “data” signal onto a designated “basis” signal approximates the network as a linear superposition of only the subnetworks that are common to both signals and simulates observation of only the pathways that are manifest in both experiments. We define a comparative HOEVD that formulates a series of networks as linear superpositions of decorrelated rank-1 subnetworks and the rank-2 couplings among these subnetworks, which can be associated with independent pathways and the transitions among them common to all networks in the series or exclusive to a subset of the networks. Boolean functions of the discretized subnetworks and couplings highlight differential, i.e., pathway-dependent, relations among genes. We illustrate the EVD, pseudoinverse projection, and HOEVD of genome-scale networks with analyses of yeast DNA microarray data.
The Internet, Organisational Change and Community Engagement: The Case of Birmingham City Council
1
Authors: Goodwin Ian
Published: November 2005

This article examines the extent to which the implementation of Internet technology by Birmingham City Council (BCC) is facilitating new forms of engagement with the communities it serves. The case study presented reveals BCC to be an organisation in complex, conflict‐ridden transition. Networked uses of Internet technologies have resulted in shifts being made towards a new form of ‘citizen‐facing’ organisation. However older, more traditional forms of hierarchical command and control persist. These are being sustained, in part, by adaptive uses of the same technologies that facilitate networking. Ultimately, this situation limits the extent to which new forms of community engagement have been achieved.
An Ethno‐linguistic Approach to the Role of Services in Knowledge Transfer: The Case of the Innovation Relay Centre of Southern Italy
1
Authors: Quatraro Francesco
Published: November 2005

Given the recent resurgence of interest in the economics of language, this paper develops an original model addressing the issue of services role in knowledge transfer by merging economic literature regarding services and technology transfer with linguistic and semiotic theories. The heuristic virtues of the model are then tested by analyzing the case of the Innovation Relay Centre (IRC) of the Apulian region in Southern Italy. This choice was due both to the strong presence in the region of small and medium sized enterprises, and to the well known lack of social capital among local firms. The model has proved to be effective in explaining IRC activity. Moreover it has allowed for the identification of strengths and weaknesses which could be useful for the elaboration of future innovation policies.
Alteration of prolactin serum levels during alcohol withdrawal correlates with craving in female patients
Authors: Hillemacher Thomas , Bayerlein Kristina , Wilhelm Julia , Reulbach Udo , Frieling Helge , Bönsch Dominikus , Kornhuber Johannes , Bleich Stefan
Published: November 2005

Dopaminergic transmission has been suggested to be a main mechanism mediating reinforcement, withdrawal and craving in alcohol dependency. Dopamine is associated with prolactin secretion, acting as a prolactin inhibitor. The aim of the present study was to investigate whether there is an association between altered prolactin levels and craving during early and late alcohol withdrawal. Therefore, we examined 145 patients suffering from alcohol dependency after admission to the detoxification unit, assessing craving with the Obsessive Compulsive Drinking Scale (OCDS) and measuring prolactin serum levels during early withdrawal (‐EW: day 0 or day 1) and late withdrawal (‐LW: day 7–day 10). We observed a significant influence of the alteration of prolactin during withdrawal on craving in female patients (Spearman's rho, OCDS‐EW: r =−0.607, p =0.001; OCDS‐LW: r =−0.730, p2 =0.530; OCDS‐LW: F =17.091, p2 =0.535). In male patients we did not find any significant results. Our findings support the previously described role of the hypothalamic–pituitary–adrenal (HPA) axis in the neurobiology of alcohol craving and show evidence of an association between increased prolactin serum levels and lower craving during alcohol withdrawal in female patients.
Dextromethorphan psychosis, dependence and physical withdrawal
Authors: Miller Shannon
Published: November 2005

As part of a synthesis of evidence regarding the abuse and addiction liability of dextromethorphan (DM), an over‐the‐counter cough medicine available in over 140 preparations, an uncommonly published case of dextromethorphan dependence (addiction) is described, with specific, rarely published complications. The individual was interviewed and several medical databases were also reviewed (Medline, 1966–present; PubMed) for all content relating to the Keywords: dextromethorphan, abuse, dependence, cough medicine, addiction, withdrawal, psychosis. The patient evidenced history suggesting substance dependence, substance‐induced psychosis and substance withdrawal in relation to DM. A literature review revealed that DM has specific serotonergic and sigma‐1 opioidergic properties. Dextrorphan (DOR), the active metabolite of DM, has similar properties; however, DOR is a weaker sigma opioid receptor agonist, and a stronger NMDA receptor antagonist. DM and DOR display specific biological features of addiction, and are capable of inducing specific psychiatric sequelae. A specific, reproducible toxidrome with significant psychiatric effects occurred, when DM was abused at greater than indicated doses, with more profound and potentially life‐threatening effects at even higher doses. DM withdrawal appears evident. DM's active metabolite, DOR, has pharmacodynamic properties and intoxication effects similar to dissociatives, and may be more responsible for the dissociative effect that this DM abuser sought. However, it is this same metabolite that may be fraught with the potentially life‐threatening psychoses and dissociative‐induced accidents, as well as addiction. While DM has been hypothesized as the most commonly abused dissociative, health‐care providers seem largely unaware of its toxidrome and addiction liability.
Concentration changes of methanol in blood samples during an experimentally induced alcohol hangover state
Authors: Woo Young‐Sup , Yoon Su‐Jung , Lee Hae‐Kook , Lee Chang‐Uk , Chae Jeong‐Ho , Lee Chung , Kim Dai‐Jin
Published: November 2005

A hangover is characterized by the unpleasant physical and mental symptoms that occur between 8 and 16 hours after drinking alcohol. After inducing experimental hangover in normal individuals, we measured the methanol concentration prior to and after alcohol consumption and we assessed the association between the hangover condition and the blood methanol level. A total of 18 normal adult males participated in this study. They did not have any previous histories of psychiatric or medical disorders. The blood ethanol concentration prior to the alcohol intake (2.26?2.08) was not significantly different from that 13 hours after the alcohol consumption (3.12?2.38). However, the difference of methanol concentration between the day of experiment (prior to the alcohol intake) and the next day (13 hours after the alcohol intake) was significant (2.62?1.33/l vs. 3.88?2.10/l, respectively). A significant positive correlation was observed between the changes of blood methanol concentration and hangover subjective scale score increment when covarying for the changes of blood ethanol level (r =0.498, p
Protective effect of cyclooxygenase‐2 (COX‐2) inhibitors but not non‐selective cyclooxygenase (COX)‐inhibitors on ethanol withdrawal‐induced behavioural changes
Authors: Dhir Ashish , Naidu Pattipati , Kulkarni Shrinivas
Published: November 2005

Cyclooxygenase (COX) is reported to play a significant role in neurodegeneration. Recent studies have shown that chronic ethanol administration up‐regulates cyclooxygenase expression. In the present study we examined the effect of nimesulide (a preferential COX‐2 inhibitor), rofecoxib (a highly selective COX‐2 inhibitor) or naproxen (a non‐selective COX‐inhibitor displaying high affinity towards the COX‐1 isoenzyme) on alcohol‐induced withdrawal symptoms. Mice were made physically dependent on alcohol by the chronic administration of ethanol (2g/kg of 10% v/v), intragastrically, twice on day 1 and then once‐daily on successive days for a total of 7 days. Nimesulide [2.5mg/kg, intraperitoneally (i.p.)], rofecoxib (2mg/kg, i.p.) or naproxen (7mg/kg, i.p.) were administered daily for 7 days before administering alcohol intragastrically. After 24 hours of the last alcohol administration, the treatments were reversed and the mice were tested for withdrawal, so that the animals that had received COX‐inhibitors followed 30 minutes later by ethanol on days 1–7 were challenged with saline. Similarly, the animals which received saline followed 30 minutes later by ethanol received only saline. Behavioural analysis revealed hyperlocomotor activity, increased anxious response and increased hyperalgesia in mice. Also, alcohol withdrawal decreased the threshold for Pentylenetetrazole‐(PTZ)‐induced convulsions. Pretreatment with COX‐inhibitors rofecoxib (2mg/kg, i.p.) or nimesulide (2.5mg/kg, i.p.) displayed significant protection against ethanol‐induced withdrawal symptoms, while naproxen (7mg/kg, i.p.) was not effective in reversing alcohol‐induced withdrawal symptoms. The results of the present study suggest strongly the possible role of cyclooxygenases, particularly COX‐2 inhibitors, on ethanol‐induced withdrawal symptoms and the potential use of COX‐2 inhibitors in their prevention and treatment.
Khat (Catha edulis)—an updated review
Authors: Al‐Hebshi Nezar , Skaug Nils
Published: November 2005

The habit of chewing fresh leaves and twigs of khat (Catha edulis) for their stimulating amphetamine‐like effects is highly prevalent in East Africa and southwest on the Arabic peninsula. There is an extensive literature on khat providing information about its history, botany, production, geographical distribution, chemistry and pharmacology, and exploring the social, economic, medical, psychological and oral aspects related to its use. Some of this literature dates as early as the 11th century; however, most of it appeared after the first scientific description of khat by Peter Forskal in 1775. This review provides a panorama of khat and the various aspects of its use. A non‐technical description of the plant chemistry and pharmacology is included. The medical, psychological and oral aspects are emphasized, and the current knowledge about the microbiological effects of khat is also presented.
Roundtable: Discussions on How Partnerships Can Help Address Access to Sterile Syringes as an Upstream Social Marketing Challenge
Authors: Williams Meredith
Published: November 2005

The transmission of HIV and viral hepatitis (hepatitis B, hepatitis C) through injection drug use is a significant public health problem in the United States. In the early fight against HIV, freestanding needle exchange programs were the focus of attempts to increase injection drug users' (IDUs‘) access to sterile syringes. At present, needle exchange programs exist in some areas, but providing access to sterile syringes for IDUs is riddled with legislative, environmental, and social barriers. These include prohibited federal funding, state and local laws prohibiting possession of syringes, and moral interference by pharmacists for issuing syringes. This roundtable session introduced the current environmental, political, and social landscape of access to sterile syringes in the United States and was supplemented with breakout work groups to determine social marketing and partnership strategies to administer public health change in the “upstream” arena. The results of the discussion groups provided innovative thinking on partnership development to stimulate effective public health change to increase IDU access to sterile syringes.
Roundtable: Exploring Downstream Partnerships to Market Zinc Supplementation to Oral Rehydration Solution (ORS) in Developing Countries
Authors: Sowers William
Published: November 2005

To explore downstream partnerships at the 2005 Innovations in Social Marketing Conference, participants formed roundtable discussion groups, assuming roles of stakeholders marketing zinc supplementation to oral rehydration solution (ORS) in a hypothetical developing country. Recent developments, including reformulation of ORS and results of clinical trials on zinc, have in effect created a new approach to diarrheal treatment, reflected in new WHO guidelines. Using ORS during diarrhea and taking zinc for 10–14 days reduces the duration and severity of episodes and helps prevent new episodes of diarrhea, a significant child health problem in developing countries.
Self-organization of an acentrosomal microtubule network at the basal cortex of polarized epithelial cells
Authors: Reilein Amy , Yamada Soichiro , Nelson W. James
Published: November 2005

Mechanisms underlying the organization of centrosome-derived microtubule arrays are well understood, but less is known about how acentrosomal microtubule networks are formed. The basal cortex of polarized epithelial cells contains a microtubule network of mixed polarity. We examined how this network is organized by imaging microtubule dynamics in acentrosomal basal cytoplasts derived from these cells. We show that the steady-state microtubule network appears to form by a combination of microtubule–microtubule and microtubule–cortex interactions, both of which increase microtubule stability. We used computational modeling to determine whether these microtubule parameters are sufficient to generate a steady-state acentrosomal microtubule network. Microtubules undergoing dynamic instability without any stabilization points continuously remodel their organization without reaching a steady-state network. However, the addition of increased microtubule stabilization at microtubule–microtubule and microtubule–cortex interactions results in the rapid assembly of a steady-state microtubule network in silico that is remarkably similar to networks formed in situ. These results define minimal parameters for the self-organization of an acentrosomal microtubule network.
Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts
Authors: Schneider Ian C. , Haugh Jason M.
Published: November 2005

Migration of eukaryotic cells toward a chemoattractant often relies on their ability to distinguish receptor-mediated signaling at different subcellular locations, a phenomenon known as spatial sensing. A prominent example that is seen during wound healing is fibroblast migration in platelet-derived growth factor (PDGF) gradients. As in the well-characterized chemotactic cells Dictyostelium discoideum and neutrophils, signaling to the cytoskeleton via the phosphoinositide 3-kinase pathway in fibroblasts is spatially polarized by a PDGF gradient; however, the sensitivity of this process and how it is regulated are unknown. Through a quantitative analysis of mathematical models and live cell total internal reflection fluorescence microscopy experiments, we demonstrate that PDGF detection is governed by mechanisms that are fundamentally different from those in D. discoideum and neutrophils. Robust PDGF sensing requires steeper gradients and a much narrower range of absolute chemoattractant concentration, which is consistent with a simpler system lacking the feedback loops that yield signal amplification and adaptation in amoeboid cells.
Terminating Wnt signals
Authors: Thorne Meghan E. , Gottardi Cara J.
Published: November 2005

Nuclear targeting of β-catenin is an obligatory step in Wnt signal transduction, but the factors that control import and export remain to be clarified. In this issue, Hendriksen et al. (p. 785) show that the RanBP3 export factor antagonizes β-catenin/T cell factor (TCF) transcription by targeting the signaling-competent form of β-catenin. We speculate that cells may use multiple export mechanisms to inhibit β-catenin signaling in different ways.