bluuebunny/crossref_metadata_2025 huggingface dataset:
Optically synaptic films using spiropyran J‐aggregates
Authors: Miyata A. , Matsushima T. , Ohki H. , Unuma Y. , Higashigaki Y.
Published: May 2005

Spiropyran SP1822 J‐aggregate LB films show a non‐linear photochromic response with a threshold against the incident light intensity of a CW dye laser. Using two laser beams operating below the threshold level intensity, the logic ‘AND’ function was found to be optically stored as an overlapping region of two incident patterns. We proposed the adoption of an LB film of spiropyran J‐aggregates to store the memory matrix Tijkl as an overlapping region of learning input pattern Vij and multi‐image input pattern Vkl in order to construct an optical neural network system based on Hopfield model.
Preparation and purification of metal fluorides for crystals and glasses
Authors: Kinsman B. E. , Hanney R.
Published: May 2005

The development of low‐loss fluoride glass fibres for transoceanic telecommunications led to an increased demand for inorganic fluorides with ultrahigh purity in respect of transition metals, rare earths and oxygen. This review paper describes the Merck Ltd strategy for achieving a wide range of metallic fluorides using methods of preparation and purification selected for a combination of technical efficacy and economic practicability. General preparative methods involving aqueous and non‐aqueous routes are described, together with purification methods such as ion exchange, zone refining and vacuum sublimation. The special role of ammonium fluoride complexes is discussed. The application of these general methods to the manufacture of fluoride glass components is described, with special reference to the ZBLAN formulation. Additional glass compositions and their individual requirements are also discussed. The parallel application of high‐purity metal fluorides in the growth of optical crystals is emphasised, the history of fluoride ultrapurification having begun with the early demand for high‐quality UV and IR crystals such as CaF2 and LiF.
Characterisation of TiN films prepared by electron shower, arc ion‐plating and sputtering methods
Authors: Yumoto H. , Kaneko K. , Ishihara M. , Akasi K. , Kaneko T.
Published: May 2005

It has been found that TiN films with high wear resistance and high adhesion can be prepared by electron shower deposition and arc ion plating on glass and austenitic stainless steel (SUS 316) substrates. The high wear resistance is principally explained by the grain size and surface morphology. Fine {100}‐faceted crystals (10–150 nm) grew on the surface. The typical morphology of the crystals was triangular pyramidal. The crystallite size was changed by the bias voltage. Faceted crystals produced by arc ion plating were rounded and smoothed by a change in bias, but were unaltered in samples prepared by the electron shower process. The fine faceted surfaces had higher wear resistance than the granularly rounded ones. When TiO2 was formed at the interface of the glass substrate, the adhesion was lowered. The high‐adhesion film prepared by electron shower deposition contained a small amount of TiO2 at the interface.
Coupling monolayers for protection of microelectronic circuits
Authors: Fabianowski Wojciech , Jaccodine Ralph , Kodnani Ramesh , Pearson Raymond , Smektala Piotr
Published: May 2005

Two polymeric coatings, a silicone gel (Dow Corning 6646) and an epoxy resin (Dexter FP 4402), were glob‐top coated onto representative microelectronic circuits, AT&T Triple Track Testers (TTTs), and subjected to the Pressure Cooker Test (PCT). Coupling monolayers were self‐ assembled on the TTTs prior to encapsulation to improve the moisture protection capabilities of the coatings. Leakage current measurements were made to evaluate the effect of applied monolayers on the moisture protection capability. The moisture protection capability was assessed in short‐term and long‐term leakage current measurements. MHDA (16‐mercaptohexadecanoic acid) and APS (gamma‐aminopropyltriethoxysilane) monolayers, in combination with silicone gel and epoxy resin respectively, exhibited very good moisture protection performance.
Irregular shifts of excitonic states in reflectivity and PL spectra of ZnSe crystals under uniaxial stress
Authors: Negrii V. D. , Kulakov M. P.
Published: May 2005

Splittings and shifts of excitonic states in ZnSe crystals under uniaxial stress along [100], [111] and [110] directions were studied by spatially resolved spectroscopy of both the reflectivity and the photoluminescence (PL) at 5 K. These methods enabled us to check the local strains in different surface microareas of deformed crystals and as a result to reveal the irregular free and bound exciton state shifts related to the influence of the strain nonuniformity and to the presence of structural imperfections (twins) in the crystals. It is shown that elastic deformation of twinned crystals along directions not exactly [111] gives rise to a doublet structure for all the bound exciton lines in the PL spectra. New values of deformation potentials for ZnSe crystals were deduced. The anisotropic influence of the uniaxial stress on the free and bound exciton state splittings was determined.
Molecular image‐processing devices based on chemical reaction systrems. 3: Some operational characteristics of excitable light‐sensitive media used for image processing
Authors: Rambidi N. G. , Maximychev A. V.
Published: May 2005

Operational features of excitable Belousov–Zhabotinsky‐type light‐sensitive media that can be used to implement image‐processing operations are discussed. They embrace (i) the main primitive responses of such media to light excitation as a function of medium acidity, temperature and light exposure, (ii) the characteristics of temporal evolution of stored media and (iii) the resolution and information content inherent in images stored by excitable media. It is shown that controlling the acidity of the medium, its temperature and the duration of light exposure enables one to get reproducible results.
Molecular image‐processing devices based on chemical reaction systems. 4: Image‐processing operations performed by active media functioning in the oscillating mode
Authors: Rambidi N. G. , Maximychev A. V.
Published: May 2005

Basic primitive image‐processing operations performed by chemical dynamic media functioning in the oscillating mode are discussed. These operations have rather high computational complexity and can be considered as simulation of human vision capabilities.
MOCVD of group III chalcogenides
Authors: Barron Andrew R.
Published: May 2005

A review is presented of recent advances in the metal organic chemical vapour deposition (MOCVD) of thin films of group III chalcogenides, including their application for the passivation of GaAs surfaces. The majority of studies involve the deposition of thermodynamic phases of composition ME and M2E3 (MGa, In; ES, Se, Te), however, MOCVD allows for the growth of either high‐pressure (tetragonal InS) or non‐thermodynamic phases (metastable cubic phases of GaS and InSe). Based on the results to date, a series of goals for molecular control over the structure of deposited films is discussed.
Direct observation of the stacked structure in substituted copper phthalocyanine LB films with STM
Authors: Zlatkin A. , Yudin S. , Simon J. , Hanack M. , Lehman H.
Published: May 2005

The in‐plane molecular structures of octa‐alkyl substituted copper phthalocyanine LB films deposited on graphite have been resolved with a scanning tunnelling microscope (STM). The face‐to‐face stacking of Pc macrocycles has been observed in the topographies of R8PcCu monolayers. The stacking period was found to be 3.8–4 Å and the molecular rows were separated by 19 Å and 16 A for (C6H13)PcCu and (C5H11)PcCu respectively.
Effect of nitrogen addition on optical properties of fluorozirconate glasses
Authors: Samek L. , Miniewicz A.
Published: May 2005

The linear and non‐linear optical properties of fluorozirconate glasses with and without nitrogen, namely ZrF4BaF2LaF3AIF3 and ZrF4BaF2LaF3AIF3AIN, have been studied. The glass containing nitrogen exhibits a 5 nm shift of the transmittance edge in the UV region towards longer wavelength, whereas there is no change in the IR transmittance. Measurements show a small increase in the linear index of refraction in the visible region and a small decrease in the non‐linear (intensity‐dependent) refractive index coefficient n2. Longitudinal and transverse sound velocities estimated from Brillouin‐scattering experiments for both glasses amount to 6311 and 4514 ms−1, respectively.
Implanted polymer junctions obtained with electrogenerated polythiophene films
Authors: Lucas B. , Rodriguez J. , Otero T. F. , Guille B. , Moliton A
Published: May 2005

Using polythiophene films (∼5 μm thick) electrogenerated by trapezoidal waves of potential, then partially reduced, we realised metal‐polythiophene contacts on the one hand. The electrical characteristics of a steel/polythiophene/gold sandwich structure are presented. We consider that the rectifying contact takes place between steel and p‐type polythiophene. On the other hand, we showed that p‐type polythiophene could be compensated after an implantation of alkali ions (Cs+ or Na+) in order to lead to the realisation of PN junctions. We particularly prove that the use of Na+ ions results in junctions yielding currents which are higher than with Cs+ ions. Current‐voltage and capacitance‐voltage characteristics have been presented so as to show that the junction effect is due to the efficiency of the doping by ionic implantation. These electrical measurements seem to be stable after several weeks in air.
Laser‐Assisted etching and metallisation of via‐holes in polyethylene terephthalate
Authors: Lyalin A. A. , Nunuparov M. S. , Simakin A. V. , Shafeev G. A.
Published: May 2005

Experimental results are presented on via‐hole etching in a thick (100 μm) film of polyethylene terephthalate (PET) with the help of a copper vapour laser (wavelength γ=510 nm, pulse duration 10 ns, repetition rate 8 kHz). The rate of via‐hole formation is as high as 100 μms−1. The effective coupling of the polymer film to the laser radiation is due to the formation of highly absorbing graphitised regions in the bulk of the film, which is initially transparent at the laser wavelength. The side walls of the hole can be metallised by simultaneous decomposition of a Pd(acac)2 spun‐on layer as a precursor for subsequent electroless Ni deposition. The activation of the inner surface of the hole is achieved as a result of the precursor vapour entering the hole during laser etching. The metallised via‐hole provides a good electrical interconnection of the two sides of the PET film.
Organic molecular rectifiers
Authors: Geddes N. J. , Sambles J. R. , Martin A. S.
Published: May 2005

In the field of molecular scale electronics the drive is towards the fabrication of self‐assembled, organic, nanoscale architectures which will have an active role to play in novel electronic devices. As a formative step towards this goal the creation of an organic analogue to the p–n junction was proposed by Aviram and Ratner in the 1970s. In their proposal a monomolecular layer of a charge transfer species controls current flow between a pair of metal electrodes, allowing easy flow for only one polarity of the applied voltage. Such metal/molecular layer/metal structures have now been fabricated, utilising the self‐ordering properties of Langmuir–Blodgett films to form the organic layer, with one dimension of the device being reduced to the molecular scale. The fabrication techniques involved in the generation of these M/LB/M junctions are now described along with the present understanding of conduction mechanisms through such nanoscale thickness junctions. These structures clearly show that the organic molecular layers can control current passage in electronic devices emulating some of the characteristics of an inorganic semiconducting p–n junction.
Photoreflectance characterisation of GaAs and GaAs/GaAIAs structures grown by MOCVD
Authors: Misiewicz J. , Jezierski K. , Sitarek P. , Markiewicz P. , Korbutowicz R. , Panek M. , Ściana B. , Tłaczała M.
Published: May 2005

Epitaxial undoped and doped (Si and Zn) GaAs and GaAIAs layers as well as heterostructures of GaAs/GaAIAs have been grown in an atmospheric pressure, vertical MOCVD system. Room temperature photoreflectance (PR) has been applied to characterise the layers and heterostructures as well as multiple quantum wells. The surface‐ and interface‐related PR has been studied by application of Kramers–Kronig analysis. A decomposition of the PR spectrum into spectra connected with the surface region and with the interface has been proposed.
Gene transfer of glutamic acid decarboxylase reduces neuropathic pain
Authors: Hao Shuanglin , Mata Marina , Wolfe Darren , Glorioso Joseph C. , Fink David J.
Published: May 2005

We tested whether transfer of the gene coding for glutamic acid decarboxylase to dorsal root ganglion using a herpes simplex virus vector to achieve release of GABA in dorsal horn would attenuate nociception in this condition. Subcutaneous inoculation of a replication‐defective herpes simplex virus vector expressing glutamic acid decarboxylase (vector QHGAD67) 7 days after selective L5 spinal nerve ligation reversed mechanical allodynia and thermal hyperalgesia; the antiallodynic effect lasted 6 weeks and was reestablished by reinoculation. QHGAD67 inoculation also suppressed induction of c‐Fos and phosphorylated extracellular signal–regulated kinase 1 and 2 in the spinal cord. Ann Neurol 2005;57:914–918
The nervous system as ectopic germinal center: CXCL13 and IgG in lyme neuroborreliosis
Authors: Narayan Kavitha , Dail Donna , Li Libin , Cadavid Diego , Amrute Sheela , Fitzgerald‐Bocarsly Patricia , Pachner Andrew R.
Published: May 2005

Lyme neuroborreliosis (LNB) is a chronic infection in which B‐cell activation, plasma cell infiltration, and enhanced Ig production in infected tissue are prominent feature. However, little is known about how B cells and plasma cells invade and persist in target organs. To assess this issue, we developed real‐time PCR measurements of IgG and CXCL13 production. We used these RNA assays and specific enzyme‐linked immunosorbent assays for protein and demonstrated that human peripheral blood mononuclear cells (PBMCs), stimulated by Borrelia burgdorferi sonicate, produced CXCL13 and IgG. Magnetic separation of PBMC populations and flow cytometry showed that CXCL13 is produced by dendritic cells. We then measure the expression of CXCL13 and IgG in tissues and correlated the expression of these host genes with spirochetal load. We also measured expression of dbpA and BBK32, two spirochetal genes important in chronic infection. There was a strong correlation between host immune response gene expression (CXCL13 and IgG) and spirochetal load. Immunohistochemistry of infected nonhuman primates tissue confirmed that CXCL13 is expressed in the nervous system. We conclude that persistent production of CXCL13 and IgG within infected tissue, two characteristics of ectopic germinal centers, are definitive features of LNB. Ann Neurol 2005;57:813–823
Cerebrospinal fluid neprilysin is reduced in prodromal Alzheimer's disease
Authors: Maruyama Masahiro , Higuchi Makoto , Takaki Yoshie , Matsuba Yukio , Tanji Haruko , Nemoto Miyako , Tomita Naoki , Matsui Toshifumi , Iwata Nobuhisa , Mizukami Hiroaki , Muramatsu Shin‐Ichi , Ozawa Keiya , Saido Takaomi C. , Arai Hiroyuki , Sasaki Hidetada
Published: May 2005

Amyloid β peptide (Aβ) has been implicated in Alzheimer's disease (AD) as an initiator of the pathological cascades. Several lines of compelling evidence have supported major roles of Aβ‐degrading enzyme neprilysin in the pathogenesis of sporadic AD. Here, we have shown a substantial reduction of cerebrospinal fluid (CSF) neprilysin activity (CSF‐NEP) in patients with AD‐converted mild cognitive impairment and early AD as compared with age‐matched control subjects. The altered CSF‐NEP likely reflects changes in neuronal neprilysin, since transfer of neprilysin from brain tissue into CSF was demonstrated by injecting neprilysin‐carrying viral vector into the brains of neprilysin‐deficient mice. Interestingly, CSF‐NEP showed an elevation with the progression of AD. Along with a close association of CSF‐NEP with CSF tau proteins, this finding suggests that presynaptically located neprilysin can be released into CSF as a consequence of synaptic disruption. The impact of neuronal damages on CSF‐NEP was further demonstrated by a prominent increase of CSF‐NEP in rats exhibiting kainate‐induced neurodegeneration. Our results unequivocally indicate significance of CSF‐NEP as a biochemical indicator to pursue a pathological process that involves decreased neprilysin activity and Aβ‐induced synaptic toxicity, and the support the potential benefits of neprilysin up‐regulation in ameliorating neuropathology in prodromal and early AD. Ann Neurol 2005;57:832–842
NOA‐03 trial of high‐dose methotrexate in primary central nervous system lymphoma: Final report
Authors: Herrlinger Ulrich , Küker Wilhelm , Uhl Martin , Blaicher Hans‐Peter , Karnath Hans‐Otto , Kanz Lothar , Bamberg Michael , Weller Michael
Published: May 2005

The NOA‐03 trial explored high‐dose methotrexate alone in 37 patients with primary central nervous system lymphoma. The overall median survival was 25 months. After 4 years, the rate of leukoencephalopathy in patients surviving more than 12 months was 58% with and 10% without whole‐brain radiotherapy given at relapse (p = 0.11). Attention deficits were found in all six tested patients, and memory deficits in four patients. Two patients had normal, three had moderately restricted, and one had markedly restricted quality of life. Thus, high‐dose methotrexate with deferred radiotherapy had only moderate efficacy and was associated with significant neurotoxicity in long‐term surviving patients. Ann Neurol 2005;57:843–847
Molecular pathology and clinical characteristics of oligodendroglial neoplasms
Authors: Walker Carol , Du Plessis Daniel G. , Joyce Kathy A. , Fildes Diane , Gee Abigail , Haylock Brian , Husband David , Smith Trevor , Broome John , Warnke Peter C.
Published: May 2005

To evaluate the role of molecular genetics in the routine clinic, we investigated allelic imbalance at 1p36, 19q13, 17p13, 10p12‐15, and 10q22‐26 and p53 mutation in 100 oligodendroglial neoplasms diagnosed at a single treatment center between 2000 and 2003. The ‐1p/‐19q genotype, seen in 64, 34, 77, and 30% of OII, OAII, OIII, and OAIII respectively, was inversely related to p53 mutation and 17p13 loss. Genotype was unrelated to tumor location and could not distinguish high‐grade tumors that presented de novo from those that progressed from a previous lower grade malignancy. Presentation with seizures was more common in cases with the ‐1p/‐19q genotype, and these remained stable for longer before treatment. In longitudinal samples, 74% retained their initial histological differentiation, whereas 29% showed new genetic alterations, the ‐1p/‐19q genotype being acquired in three cases. Loss of 1p36 and 19q13, 17p13, chromosome 10, and p53 mutation were significantly associated with survival from presentation in Kaplan–Meier analysis (p < 0.01), and loss of 1p36 and 19q13 and loss of 17p13 retained significance in multivariate analysis. In this recently diagnosed unselected series, clinical differences in tumors with and without the ‐1p/‐19q genotype support a genetic approach to aid diagnosis and prognostication for oligodendroglial neoplasms. Ann Neurol 2005;57:855–865
Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging
Authors: Coutts Shelagh B. , Simon Jessica E. , Eliasziw Michael , Sohn Chul‐Ho , Hill Michael D. , Barber Philip A. , Palumbo Vanessa , Kennedy James , Roy Jayanta , Gagnon Alexis , Scott James N. , Buchan Alastair M. , Demchuk Andrew M.
Published: May 2005

We examined whether the presence of diffusion‐weighted imaging (DWI) lesions and vessel occlusion on acute brain magnetic resonance images of minor stroke and transient ischemic attack patients predicted the occurrence of subsequent stroke and functional outcome. 120 transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale ≤ 3) patients were prospectively enrolled. All were examined within 12 hours and had a magnetic resonance scan within 24 hours. Overall, the 90‐day risk for recurrent stroke was 11.7%. Patients with a DWI lesion were at greater risk for having a subsequent stroke than patients without and risk was greatest in the presence of vessel occlusion and a DWI lesion. The 90‐day risk rates, adjusted for baseline characteristics, were 4.3% (no DWI lesion), 10.8% (DWI lesion but no vessel occlusion), and 32.6% (DWI lesion and vessel occlusion) (p = 0.02). The percentages of patients who were functionally dependent at 90 days in the three groups were 1.9%, 6.2%, and 21.0%, respectively (p = 0.04). The presence of a DWI lesion and a vessel occlusion on a magnetic resonance image among patients presenting acutely with a transient ischemic attack or minor stroke is predictive of an increased risk for future stroke and functional dependence. Ann Neurol 2005;57:848–854
POLG mutations and Alpers syndrome
Authors: Davidzon Guido , Mancuso Michelangelo , Ferraris Silvio , Quinzii Catarina , Hirano Michio , Peters Heidi L. , Kirby Denise , Thorburn David R. , DiMauro Salvatore
Published: May 2005

Alpers–Huttenlocher syndrome (AHS) an autosomal recessive hepatocerebral syndrome of early onset, has been associated with mitochondrial DNA (mtDNA) depletion and mutations in polymerase gamma gene (POLG). We have identified POLG mutations in four patients with hepatocerebral syndrome and mtDNA depletion in liver, who fulfilled criteria for AHS. All were compound heterozygous for the G848S and W748S mutations, previously reported in patients with progressive external ophtalmoplegia or ataxia. We conclude that AHS should be included in the clinical spectrum of mtDNA depletion and is often associated with POLG mutations, which can cause either multiple mtDNA deletions or mtDNA depletion. Ann Neurol 2005;57:921–924
Genetic dissection of photosensitivity and its relation to idiopathic generalized epilepsy
Authors: Tauer Ulrike , Lorenz Susanne , Lenzen Kirsten P. , Heils Armin , Muhle Hiltrud , Gresch Meike , Neubauer Bernd A. , Waltz Stephan , Rudolf Gabrielle , Mattheisen Manuel , Strauch Konstantin , Nürnberg Peter , Schmitz Bettina , Stephani Ulrich , Sander Thomas
Published: May 2005

Photosensitivity or photoparoxysmal response (PPR) is a common and highly heritable electroencephalographic trait characterized by an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. PPR occurs frequently associated with idiopathic generalized epilepsies (IGEs). The present genomewide linkage scan was designed to map susceptibility loci for PPR and to explore their genetic relationship with IGE. The study included 60 families with at least two siblings displaying PPR. To dissect PPR‐specific and IGE‐related susceptibility loci, we defined two distinct family subgroups, comprising 19 families with predominantly pure PPR and photosensitive seizures (PPR‐families) and 25 families, in which PPR was strongly associated with IGE (PPR/IGE‐families). MOD score analyses provided significant evidence for linkage to the region 6p21.2 in the PPR‐families (empirical p = 0.00004) and suggestive evidence for linkage to the region 13q31.3 in the PPR/IGE families (p = 0.00015), both with a best‐fitting recessive mode of inheritance. In the PPR/IGE‐families, linkage evidence was even stronger (p = 0.00003) when the trait definition was broadened by IGE traits. Our study shows two PPR‐related susceptibility loci, depending on the familial background of IGE. The locus on 6p21.2 seems to predispose to PPR itself, whereas the locus on 13q31.3 also confers susceptibility to IGE. Ann Neurol 2005;57:866–873
Autologous mesenchymal stem cell transplantation in stroke patients
Authors: Bang Oh Young , Lee Jin Soo , Lee Phil Hyu , Lee Gwang
Published: May 2005

Mesenchymal stem cell (MSC) transplantation improves recovery from ischemic stroke in animals. We examined the feasibility, efficacy, and safety of cell therapy using culture‐expanded autologous MSCs in patients with ischemic stroke. We prospectively and randomly allocated 30 patients with cerebral infarcts within the middle cerebral arterial territory and with severe neurological deficits into one of two treatment groups: the MSC group (n = 5) received intravenous infusion of 1 × 108 autologous MSCs, whereas the control group (n = 25) did not receive MSCs. Changes in neurological deficits and improvements in function were compared between the groups for 1 year after symptom onset. Neuroimaging was performed serially in five patients from each group. Outcomes improved in MSC‐treated patients compared with the control patients: the Barthel index (p = 0.011, 0.017, and 0.115 at 3, 6, and 12 months, respectively) and modified Rankin score (p = 0.076, 0.171, and 0.286 at 3, 6, and 12 months, respectively) of the MSC group improved consistently during the follow‐up period. Serial evaluations showed no adverse cell‐related, serological, or imaging‐defined effects. In patients with severe cerebral infarcts, the intravenous infusion of autologous MSCs appears to be a feasible and safe therapy that may improve functional recovery. Ann Neurol 2005;57:874–882
RON‐regulated innate immunity is protective in an animal model of multiple sclerosis
Authors: Tsutsui Shigeki , Noorbakhsh Farshid , Sullivan Andrea , Henderson Andrew J. , Warren Kenneth , Toney‐Earley Kenya , Waltz Susan E. , Power Christopher
Published: May 2005

The tyrosine kinase receptor RON and its ligand, macrophage stimulating protein (MSP), exert inhibitory effects on systemic innate immunity, but their CNS expression and impact on human neuroinflammatory diseases are unknown were RON and MSP present in human brain perivascular macrophages and microglia, but RON mRNA and protein abundance in the CNS were diminished in both MS patients and the MS animal model, experimental autoimmune encephalomyelitis (EAE). Treatment of differentiated human monocytoid cells with MSP resulted in significant reduction of interleukin (IL)–1β, tumor necrosis factor (TNF)–α and MMP‐9 mRNA levels, whereas minimal effects were observed in human astrocytes. After induction of EAE, RON knockout and heterozygote animals exhibited significantly increased CNS proinflammatory gene (TNF‐α, MMP‐12) expression compared with wild‐type littermate controls, although IL‐4 levels were suppressed in both RON‐deficient groups. Neurological disease in RON‐deficient animals showed a more rapid onset with overall worsened severity, together with exacerbated demyelination, axonal injury, and neuroinflammation after EAE induction. The proto‐oncogene, c‐Cbl, which modulates ubiquitylation of RON, was increased in glia in both MS brains and EAE spinal cords. Thus, the MSP‐RON pathway represents a novel regulatory mechanism within the CNS by which innate immunity and its pathogenic effects could be targeted for future therapeutic interventions. Ann Neurol 2005;57:883–895
Correlates of hippocampal neuron number in Alzheimer's disease and ischemic vascular dementia
Authors: Zarow Chris , Vinters Harry V. , Ellis William G. , Weiner Michael W. , Mungas Dan , White Lon , Chui Helena C.
Published: May 2005

The cornu ammonis 1 region of the hippocampus (CA1) sector of hippocampus is vulnerable to both Alzheimer's disease (AD)‐type neurofibrillary degeneration and anoxia–ischemia. The objective of this article is to compare number and size of neurons in CA1 in AD versus ischemic vascular dementia. Unbiased stereological methods were used to estimate the number and volume of neurons in 28 autopsy‐derived brain samples. For each case, the entire hippocampus from one cerebral hemisphere was sliced into 5mm slabs (5–7 slabs/case), cut into 50μm sections, and stained with gallocyanine. Using the optical dissector, we systematically sampled the number and size of neurons throughout the extent of CA1 and CA2. The total number of neurons was significantly less in AD compared with ischemic vascular dementia (p < 0.02), but there was no significant difference in neuron size. The greatest loss of neurons was observed in two cases with combined AD and hippocampal sclerosis. Regardless of causative diagnosis, the number of CA1 neurons correlates with magnetic resonance imaging–derived hippocampal volume (r = 0.72; p < 0.001) and memory score (r = 0.62; p < 0.01). We conclude that although CA1 neuron loss is more consistently observed in AD than ischemic vascular dementia, severity of loss shows the expected correlation with structure and function across causative subtype. Reductions in magnetic resonance imaging–derived hippocampal volume reflect loss, rather than shrinkage, of CA1 neurons. Ann Neurol 2005;57:896–903
Sparse multifocal stimuli for the detection of multiple sclerosis
Authors: Ruseckaite Rasa , Maddess Teddy , Danta Gytis , Lueck Christian J. , James Andrew C.
Published: May 2005

We compared the diagnostic capabilities of contrast reversal and sparse pattern pulse stimulation for dichoptic multifocal visual evoked potentials (mfVEPs) measured in normal subjects and multiple sclerosis (MS) patients. Multifocal responses were obtained from 27 normal subjects and 50 relapsing‐remitting patients, 26 of whom had experienced optic neuritis (ON+). The patient groups were matched for length of disease and number of clinical attacks. Compared with the responses of normal subjects those of MS patients had significantly smaller response amplitudes, lower signal‐to‐noise ratios, more complex response waveforms, and longer response delays. The effects were larger for sparser stimuli. Sensitivities and specificities for the different stimulus types were estimated from receiver operator characteristic (ROC) plots. Bootstrap estimates of the accuracies of the ROCs for the most promising measure, the template delays, indicated the sparsest stimulus would deliver 92% sensitivity at a false‐positive rate of 0%. In contrast, at 92% sensitivity the conventional mfVEP stimulus misdiagnosed more than 20% of the normal population. The results were similar for patients with no history of ON (ON−). In performing well in patients with no history of ON, the sparse mfVEPs seem to measure progressive damage associated with axon and gray matter losses rather than damage associated with a history of serious inflammation. Ann Neurol 2005;57:904–913
Deep brain stimulation to relieve drug‐resistant SUNCT
Authors: Leone Massimo , Franzini Angelo , D'Andrea Giovanni , Broggi Giovanni , Casucci Gerardo , Bussone Gennaro
Published: May 2005

The rare primary headache short‐lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is characterized by 3 to 200 attacks per day of severe unilateral orbital pain. Functional magnetic resonance imaging shows increased blood flow in the ipsilateral posterior inferior hypothalamus during attacks, indicating activation. We report the first patient with SUNCT in whom severe intractable pain (70 per day) was well controlled by electrode implant to and continuous stimulation of the posterior inferior hypothalamus. Ann Neurol 2005;57:925–927
Methylenetetrahydrofolate reductase C677T genotype and PD
Authors: de Lau Lonneke M. L. , Koudstaal Peter J. , van Meurs Joyce B. J. , Uitterlinden André G. , Hofman Albert , Breteler Monique M. B.
Published: May 2005

In a prospective, population‐based cohort study among 5,920 participants aged 55 years or older, we observed that the TT variant of the methylenetetrahydrofolate reductase C677T polymorphism is associated with an increased risk for Parkinson's disease in smokers. Both smoking and the TT genotype are known to induce hyperhomocystinemia, and synergistic effects on homocysteine levels have been reported. Increased plasma levels of homocysteine through direct neurotoxic effects might accelerate the selective dopaminergic cell death underlying Parkinson's disease. Our findings support the hypothesis that homocysteine plays a role in the pathogenesis of Parkinson's disease. Ann Neurol 2005;57:927–930
Erythromelalgia: A hereditary pain syndrome enters the molecular era
Authors: Waxman Stephen G. , Dib‐Hajj Sulayman D.
Published: May 2005

In contrast with acquired pain syndromes, molecular substrates for hereditary pain disorders have been poorly understood. Familial erythromelalgia (Weir Mitchell's disease), also known as primary erythermalgia, is an autosomal dominant disorder characterized by burning pain in the extremities in response to warm stimuli or moderate exercise. The cause of this disorder has been enigmatic, and treatment has been empirical and not very effective. Recent studies, however, have shown that familial erythromelalgia is a channelopathy caused by mutations in the gene encoding the Nav1.7 sodium channel which lead to altered channel function. Selective expression of Nav1.7 within dorsal root ganglion neurons including nociceptors (in which this channel is targeted to sensory terminals, close to impulse trigger zones) and within sympathetic ganglion neurons explains why patients experience pain but do not suffer from seizures or other manifestations of altered excitability within central nervous system neurons. Erythromelalgia is the first human disorder in which it has been possible to associate an ion channel mutation with chronic neuropathic pain. Identification of mutations within a peripheral neuron‐specific sodium channel suggests the possibility of rational therapies that target the affected channel. Moreover, because some other pain syndromes, including acquired disorders, involve altered sodium channel function, erythromelalgia may emerge as a model disease that holds more general lessons about the molecular neurobiology of chronic pain. Ann Neurol 2005;57:785–788
Cover Picture: Metal Ions as Cofactors for the Binding of Inhibitors to Methionine Aminopeptidase: A Critical View of the Relevance of In Vitro Metalloenzyme Assays (Angew. Chem. Int. Ed. 23/2005)
Authors: Schiffmann Rolf , Heine Andreas , Klebe Gerhard , Klein Christian D. P.
Published: May 2005

Metalloenzymes are often studied in the presence of unphysiologically high concentrations of metal ions. This situation may lead to artifacts in assays if the binding of an inhibitor is made possible through additional metal ions; such compounds would appear highly potent in vitro, but may not possess activity in vivo. In their Communication on page 3620 ff., C. D. P. Klein and co‐workers describe this effect with the enzyme methionine aminopeptidase as an example. (Mouse image provided by the U.S. National Park Service.)
Different Environments for a Realistic Simulation of GPCRs‐Application to the M2 Muscarinic Receptor
Authors: Jöhren Kirstin , Höltje Hans‐Dieter
Published: May 2005

A model of the human M2 muscarinic receptor was taken as an example for a class A G‐protein coupled receptor to explore the influence of different environments in a molecular dynamics simulation (MDS) on the protein structure. The most commonly used environment is the vacuum, although it is very unnatural for a transmembrane protein. As an alternative a membrane‐like system, consisting of a lipophilic central layer and two aqueous flanking layers, was tested. The most realistic system that can be applied is a phospholipid bilayer with a surrounding physiological sodium chloride solution. From all systems good protein structures were received, nevertheless clear differences between the systems were detected in the structural comparison of the models. Subsequently it was analyzed whether the observed structural differences influence ligand binding. For this purpose the antagonist (S)‐scopolamine was docked into the binding cavity, which is well known by many reported single and multiple point mutations. As expected from the observed structural variations triggered by the type of environment employed in MDS, also differences in the binding mode of (S)‐scopolamine were detected, all contacts, however, which are known to be important were found.
Pharmacokinetics of the diastereomers of arteether, a potent antimalarial drug, in rats
Authors: Sabarinath S. , Madhusudanan K. P. , Gupta R. C.
Published: May 2005

The pharmacokinetics of α‐ and β‐ diastereomers of arteether, a potent erythrocytic schizontocidal agent, and their active metabolite dihydroartemisinin were studied in male Sprague‐Dawley rats after oral, intramuscular and intravenous administrations. Oral and intramuscular studies were carried out at three dose levels at 9, 17.5 and 30 mg kg−1. The ratio of α‐ and β‐isomers was maintained at 30:70% w/w in the formulations used for the study. The average oral bioavailabilities of α‐and β‐isomers, relative to intramuscular administration, were 9.6% and 3.8%, respectively, and the average in vivo α‐ to β‐ ratio was 2.5. Following intravenous and intramuscular administrations the in vivo α‐ to β‐ ratios were 0.7 and 0.9, respectively. The β‐isomer of arteether was characterized by a longer elimination half‐life and a relatively larger volume of distribution than the α‐isomer, suggesting that β‐arteether may be responsible for the prolonged in vivo schizontocidal activity. The α‐isomer was absorbed rapidly after oral and intramuscular administrations and showed higher peak plasma concentrations but possessed a relatively shorter half‐life. There was an apparent lack of linearity observed in terms of dose and AUCs for both α‐ and β‐arteether after oral and intramuscular administrations, suggesting nonlinear dose dependent pharmacokinetics at the dose levels studied. The rate and extent of conversion of arteether isomers to dihydroartemisinin was highest with oral and intravenous administration and least with intramuscular indicating that the intramuscular route of administration of the isomeric mixture may be more beneficial for malarial chemotherapy. Copyright © 2005 John Wiley & Sons, Ltd.
Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous DA‐8159, a new erectogenic, in rats
Authors: Kim Yu C. , Shim Hyun J. , Lee Joo H. , Kim Soon H. , Kwon Jong W. , Kim Won B. , Lee Myung G.
Published: May 2005

In order to find what types of hepatic microsomal cytochrome P450 (CYP) isozymes are involved in the metabolism of DA‐8159 and in the formation of DA‐8164 in rats, enzyme inducers, such as dexamethasone, phenobarbital, 3‐methylcholanthrene and isoniazid, and enzyme inhibitors, such as troleandomycin and quinine, were pretreated in rats. After a 1 min intravenous administration of DA‐8159 at a dose of 30 mg/kg to rats pretreated with dexamethasone (a main inducer of CYP3A1/2 in rats), the total areas under the plasma concentration‐time curve from time zero to time infinity (AUC) values of DA‐8159 (283 versus 349 µg min/ml) and DA‐8164 (98.0 versus 79.8 µg min/ml) were significantly smaller and greater, respectively, than those in control rats. However, the AUC values of DA‐8159 were not significantly different after pretreatment with phenobarbital, isoniazid and 3‐methylcholanthrene (main inducers of CYP2B1/2, 2E1 and 1A1/2, respectively, in rats). In rats pretreated with troleandomycin (a main inhibitor of CYP3A1/2 in rats), the AUC values of DA‐8159 (435 versus 370 µg min/ml) and DA‐8164 (34.8 versus 76.5 µg min/ml) were significantly greater and smaller, respectively. However, in rats pretreated with quinine (a main inhibitor of CYP2D1 in rats), the AUC of DA‐8159 was comparable to that in control rats. The above data indicate that DA‐8159 was metabolized and DA‐8164 was formed mainly via CYP3A1/2 in rats. Copyright © 2005 John Wiley & Sons, Ltd.
Die Ermüdungstragfähigkeit von Dübeln unter Querlast
Authors: Block Klaus , Dreier Friedrich , Bigalke Detlef
Published: May 2005

Zur Bestimmung des Einflusses der Betoneigenschaften auf die Ermüdungstragfähigkeit von Dübeln unter Querlast wurden Versuche an Verbundankern in der Größe M12 durchgeführt. Zu den untersuchten Betoneigenschaften gehören die Druckfestigkeit des Betons und ein Riß von 0, 3 mm Breite im Vergleich zum ungerissenen Beton. Die gewonnenen Ergebnisse ergaben für alle vier Versuchsreihen jeweils eine Wöhlerlinie. Darüber hinaus wurde sowohl für den gerissenen als auch für den ungerissenen Beton eine Funktion aufgestellt, mit der sich die Dauerermüdungstragfähigkeit der Verbundanker in einer beliebigen Betonfestigkeit abschätzen läßt. In bisherigen Zulassungen sind nur die ungünstigsten Werte der Ermüdungstragfähigkeit angegeben. Weiterhin konnten an den Bruchstellen und den aufgezeichneten Kenngrößen mehrere Merkmale erkannt werden, die auf die Versagensart schließen lassen. Eine bessere Planung der folgenden Versuche wird so erleichtert.
Tragverhalten einbetonierter Scherbolzen
Authors: Randl Norbert
Published: May 2005

Zur Übertragung der Querkräfte bei Bewegungsfugen wie auch zur Herstellung querkraftschlüssiger Verbindungen etwa im Betonfertigteilbau werden häufig stabförmige Stahldorne eingesetzt, die beidseitig in die anschließenden Stahlbetonbauteile eingespannt sind. Im vorliegenden Beitrag wird ein Überblick über den aktuellen Stand der Technik gegeben. Versuche aus jüngerer Zeit an beidseitig einbetonierten, randfernen Schubdornen aus Bewehrungsstahl werden vorgestellt und analysiert. Auf Basis eines modifizierten Bettungsziffernverfahrens wird unter Berücksichtigung der Plastizierung des Betons eine Bemessungsformel zur Ermittlung der Quertragfähigkeit einbetonierter Scherbolzen abgeleitet und mit bestehenden theoretischen Ansätzen und experimentellen Ergebnissen verglichen.
Betonverbinder für eine Hochgeschwindigkeits‐Bahnstrecke
Authors: Kunz Jakob
Published: May 2005

Bei einem der derzeit größten europäischen Bahninfrastrukturprojekte, der Hochgeschwindigkeitsstrecke zwischen Amsterdam und Brüssel, wird auf einer Länge von 65 km das Feste Fahrbahn System RHEDA 2000® verwendet, wobei Unter‐ und Oberbau als flache Betonplatten ausgebildet sind, welche durch Befestigungselemente verbunden werden müssen. Im Beitrag wird erläutert, wie diese Elemente auf die Anforderungen des Projektes hin entwickelt wurden. Mit umfangreichen Versuchen mußte nachgewiesen werden, daß die vorgeschlagenen Elemente alle Spezifikationen bezüglich Tragfähigkeit, Gebrauchstauglichkeit und Ermüdung erfüllen. Zur Ermittlung der Ermüdungsfestigkeit wurde die Wöhlerkurve ermittelt.
Langzeithaftfestigkeit zwischen Alt‐ und Aufbeton bei unterschiedlichen Klimabedingungen
Authors: Beushausen Hans‐Dieter , Dehn Frank , Alexander Mark
Published: May 2005

Die Haftung und Verträglichkeit zwischen Alt‐ und Aufbeton ist häufig das entscheidende Kriterium für die Dauerhaftigkeit und somit den Erfolg einer Sanierungsmaßnahme. In der Regel wird eine hohe Kurzeithaftfestigkeit erreicht, währenddessen zu einem späteren Zeitpunkt häufig eine Ablösung des Aufbetons vom Untergrund zu beobachten ist. Die Gründe hierfür liegen neben der falschen Bauausführung in unzureichenden Bemessungsgrundlagen in Hinblick auf die Verträglichkeit zusammengesetzter Systeme unter verschiedenen, vor allem wechselnden Umweltbedingungen. Zur Erfassung unterschiedlicher klimatischer Bedingungen wurde in einem gemeinsamen Forschungsvorhaben zwischen den Universitäten Kapstadt und Leipzig überprüft, inwieweit die Langzeithaftfestigkeit und die Verträglichkeit zwischen Altbeton und verschiedenen Aufbetonen unter wechselnden Umwelteinflüssen gewährleistet werden kann.
Philosophie des neuen DBV/BDZ‐Merkblattes “Sichtbeton”
Authors: Litzner Hans‐Ulrich , Goldammer Klaus‐Reiner
Published: May 2005

Im August 2004 hatten der Deutschen Beton‐ und Bautechnik‐Verein E.V. (DBV) und der Bundesverband der Deutschen Zementindustrie e.V. (BDZ) nach 1977 und 1997 die dritte Auflage des Merkblattes “Sichtbeton” herausgegeben. Es definiert erstmalig vier Sichtbetonklassen SB 1 bis SB 4, die sich durch Anforderungen an die Textur, die Porigkeit, an die Farbtongleichmäßigkeit, die Ebenheit sowie an die Qualität von Arbeits‐ und Schalhautfugen unterscheiden. Weitere Anforderungen betreffen Erprobungsflächen und die Qualität der Schalhaut.

Im Hauptteil des Merkblattes werden Hinweise zur Planung und Ausschreibung von Sichtbetonflächen sowie zu deren Ausführung gegeben. Sie basieren auf Erfahrungen, die in letzter Zeit an markanten Sichtbetonbauwerken gesammelt wurden. Ein abschließendes Kapitel beinhaltet die Beurteilung von Sichtbetonflächen nach deren Herstellung. Hier gilt der Grundsatz, daß der Gesamteindruck das primäre und maßgebende Kriterium ist.
Arbeitsfugen in Bauteilen aus Selbstverdichtendem Beton (SVB)
Authors: Fingerloos Frank
Published: May 2005

Für die Bemessung von Bauteilen aus Selbstverdichtendem Beton kann die DIN 1045‐1 [1] mit wenigen Änderungen und Ergänzungen verwendet werden. Diese Anpassungen werden in der DAfStb‐Richtlinie Selbstverdichtender Beton (SVB‐Richtlinie), Ausgabe November 2003 [3], geregelt.

Für die Schubkraftübertragung in Fugen wird in [3] ergänzt, daß die unbehandelte Oberfläche des SVB generell als sehr glatt anzusehen ist. Diese verschärfende, konservative Festlegung hat für die Bemessung und Ausführung von Arbeitsfugen in SVB gravierende Konsequenzen.
Zur Bemessung von Konsolen mit Stabwerkmodellen: Eine Stellungnahme zum Beitrag von Roeser und Hegger von Heft 5, S. 434–439: Zur Bemessung von Konsolen gemäß DIN 1045‐1 und DAfStb Heft 525
Authors: Reineck Karl‐Heinz , Fitik Birol
Published: May 2005

Unstrittig ist, daß die Bemessung von Konsolen mit Stabwerkmodellen erfolgen sollte und somit Abschn. 10.6.3 der DIN 1045‐1 zur Anwendung kommt. Die im Beitrag von Roeser und Hegger als Beleg für bei diesem Vorgehen auftretenden Unsicherheiten angeführten Versuche werden untersucht und die Versagensursachen nach den Versuchsberichten angegeben. Es zeigt sich, daß der Anordnung und Menge der senkrechten Bügel eine entscheidende Bedeutung zukommt und mit Stabwerkmodellen erklärt werden kann, warum bei einigen Versuchen nicht die volle Tragfähigkeit erreicht wurde. Diese Versuche liefern keinen Beleg gegen eine konsequente Bemessung von Konsolen mit Stabwerkmodellen.
Durchbiegungsberechnung an Stahlbetonträgern oder Schlankheitsnachweis? Richtigstellung und Ergänzung
Authors: Steiner Josef , Fricke Karl‐Ludwig
Published: May 2005

Zuschrift zu Fricke, K.‐L.: Durchbiegungsberechnung an Stahlbetonträgern oder Schlankheitsnachweis? Beton‐ und Stahlbetonbau 99 (2004), Heft 1, S. 52‐55, und Erwiderung.
Carbohydrates in peptide and protein design
Authors: Jensen Knud J. , Brask Jesper
Published: May 2005

Monosaccharides and amino acids are fundamental building blocks in the assembly of nature's polymers. They have different structural aspects and, to a significant extent, different functional groups. Oligomerization gives rise to oligosaccharides and peptides, respectively. While carbohydrates and peptides can be found conjoined in nature, e.g., in glycopeptides, the aim of this review is the radical redesign of peptide structures using carbohydrates, particularly monosaccharides and cyclic oligosaccharides, to produce novel peptides, peptidomimetics, and abiotic proteins. These hybrid molecules, chimeras, have properties arising largely from the combination of structural characteristics of carbohydrates with the functional group diversity of peptides. This field includes de novo designed synthetic glycopeptides, sugar (carbohydrate) amino acids, carbohydrate scaffolds for nonpeptidal peptidomimetics of cyclic peptides, cyclodextrin functionalized peptides, and carboproteins, i.e., carbohydrate‐based proteinmimetics. These successful applications demonstrate the general utility of carbohydrates in peptide and protein architecture. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 80: 747–761, 2005

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com