bluuebunny/crossref_metadata_2025 huggingface dataset:
Unthermostated Multichannel Heat Conduction Calorimeter
Authors: Wadsö L
Published: December 2004

Heat conduction calorimetry is a convenient method to detect cement-admixture incompatibility. However, such instruments tend to be used mainly in chemical laboratories. This paper presents the design of a simple unthermostated heat conduction calorimeter that can simultaneously monitor the heat production rate in 14 samples of cement paste or mortar. As it is not thermostated, its performance is governed by the ambient temperature stability and the heat capacity balance between each sample and its reference. The paper shows that the instrument can be used to detect cement-admixture incompatibility and to quantify retardation time.
Polycarboxylate Polymers and Blends in Different Cements
Authors: Mäder U , Schober I , Wombacher F , Ludirdja D
Published: December 2004

During the last few years, polycarboxylate based polymers have become very popular. They contain a polycarboxylic backbone onto which ethyleneoxide side chains have been grafted. However its dispersing and slump keeping properties vary significantly, depending on the chemical structure. The dispersing properties of two polymers having a different number of polyoxyethlene (PEO) graft chains relative to the length of the backbone were evaluated in cement paste by measuring adsorption on cement paste and flow properties in different mortar compositions. The effects of the polymers on the fluidity and the retention of flow of the cementitious systems are significantly different. While one polymer gives a very strong initial water reduction, the second one shows excellent flow retaining properties. When combined, the two polymers are well suited for the production of RMC and self-consolidating concrete mixes with different cements and in different climate zones.
Direct Simple Shear Testing for Post-Cyclic Degradation in Stiffness of Nonplastic Silt
Authors: Song BW , Yasuhara K , Murakami S
Published: December 2004

Using a sequential procedure of cyclic and postcyclic direct simple shear tests, the stiffness degradation characteristics of nonplastic silt are studied during and immediately after cyclic loading by direct simple shear (DSS) tests. The results from cyclic and postcyclic DSS tests were interpreted using methods modified from those adopted for cyclic and postcyclic triaxial tests. In particular, the effect of initial static shear stress (ISSS) on postcyclic behavior is considered for nonplastic silt. The findings obtained from the sequential DSS testing on nonplastic silt are: (i) during cyclic loading the tendency of the stiffness to decrease with increasing normalized pore pressure is different for plastic and nonplastic silts, (ii) since the relation between equivalent stiffness ratio and single amplitude shear strain for nonplastic silt does not filt the Hardin-Drnevich Model, new modified relation is needed, (iii) the larger the ISSS is, the faster the decrease in stiffness ratio becomes, and (iv) the decrease of stiffness ratio for nonplatic silt is less marked than that for plastic silt when plotted against the normalized pore pressure after cyclic load.
Measurement of Crystalline Swelling in Expansive Clay
Authors: Likos WJ
Published: December 2004

An experimental system for measuring relationships among relative humidity, moisture content, and the corresponding volume changes associated with hydration-related, or “crystalline,” swelling in expansive clay is described. The system is capable of actively controlling relative humidity between approximately 1 and 90% along either wetting or drying paths in a small environmental chamber. Axial strain and moisture content of compacted expansive clay specimens are monitored as the specimen swells or shrinks in response to imposed changes in humidity. Application of the system is demonstrated for a specimen of Wyoming Na+-smectite. Hysteresis is observed between the wetting and drying loops of the humidity-water content relationship as well as the humidity-strain relationship. Characteristic wavy patterns are noted in both relationships that are interpreted to indicate the successive adsorption and desorption of discrete molecular layers of water associated with crystalline swelling. Humidity values at which the transitions in the stable hydrate states occur compare well with previous results obtained from humidity-controlled X-ray diffraction tests. The maximum axial strain attributed to the crystalline swelling process is 16.3 %.
Design and Construction of Three Instrumented Test Piles to Examine Time Dependent Pile Capacity Gain
Authors: Paikowsky SG , Hajduk EL
Published: December 2004

Three heavily instrumented test piles were designed, constructed, and installed at a bridge reconstruction site in Newbury, Massachusetts as part of a research initiative into time dependent pile capacity gain. Pile instrumentation consisted primarily of an alternating pattern of piezometers and strain gages, allowing for correlation between pile capacity gain and excess pore pressure dissipation along discrete pile segments. Additional instrumentation within the piles included accelerometers, telltales, and radial pressure cells, allowing monitoring of total pressure at the pile wall. Standard dynamic gages (strain gages and accelerometers) were also attached to the piles during dynamic testing. A total of 86 vibrating wire, 17 electrical resistance, 17 telltales, and 4 piezo-resistive gages were installed within the test piles to record strain, displacement, pressure, and acceleration.

This paper describes (i) the initial installation location of the test piles, (ii) the design and layout of the individual test piles, (iii) the selection and installation design of the individual instrumentation within the test piles, and (iv) assembly of the test piles. Sample measurements of the various instruments and a summary of the instrumentation performance are also presented.
The Generalized Subtraction Correction Algorithm for Measuring Duct Leakage Using a Blower Door
Authors: Katz M , Witriol NM , Erinjeri J
Published: December 2004

The Generalized Subtraction Correction Algorithm (GSCA) improves upon the Modified Subtraction method for determining duct-leakage-to-outside using only a blower door. GSCA utilizes attic pressure both to calculate a generalized Subtraction Correction Factor and to properly identify and assign the correct pressure difference between the ducts and attic responsible for the calculated duct-leakage flow. This paper also describes the normal procedures that enhance the accuracy of data collection and the subsequent tests on the resulting information for validating the applicability of GSCA to an individual home. GSCA collects associated pressure-coupling data and enhances the reliability of house-leakiness results.
Mechanical Properties of Municipal Solid Waste
Authors: Vilar OM , Carvalhod MdeF
Published: December 2004

This paper deals with the compressibility and shear strength of Municipal Solid Waste (MSW) as measured in the laboratory. The waste studied was recovered from Bandeirantes Sanitary Landfill (São Paulo, Brazil) and is about 15 years old. More than 50 % by weight of MSW is organic paste and as much as 17 % is plastic and other strip materials. Consolidation and drained and undrained triaxial compression tests were performed in reconstituted waste specimens of large dimensions and with different unit weights considering both saturated specimens and specimens tested at natural moisture content. It is shown that the MSW exhibits a pronounced secondary compression; the influence of void ratio and stress on secondary compression index is discussed and compared with available data from MSW and soft soils. Typical stress-strain curves are presented and some peculiarities are shown, as the absence of failure even at large strains, up to 30 %, implies the need of deriving shear strength envelopes based on strain. The influence of saturation and of unit weight on shear strength is also addressed as well as the shear strength mobilization that shows that the friction tends to be fully mobilized at strains of about 20 %, while the cohesion intercept starts to be mobilized at strains of 10% and even more and a limiting value could not be observed in the strain range attained in the tests. The development of pore water pressures in the undrained tests and the variation of undrained shear strength with effective confining pressure are also addressed.
An Energy-Based Crack Extension Formulation for Crack Resistance Characterization of Ductile Materials
Authors: Chaouadi R
Published: December 2004

Crack resistance behavior is an important property for reactor pressure vessel embrittlement evaluation as reactors operate in the upper shelf ductile regime. This property consists in evaluating the change of crack length with the applied loading expressed in terms of the J-integral. While J-integral formulation is available for standard geometries and it is relatively easy to determine, crack extension is either measured directly on the fracture surface of a number of specimens or estimated from one single specimen, necessitating sophisticated instrumentation. Based on a number of experimental observations, a simple procedure is presented which is based solely on the load-displacement test record and the initial and final crack length to determine the full crack resistance curve. The reliability of this new procedure for determining the crack resistance, the initiation toughness, and the tearing resistance is illustrated by several examples covering a wide range of materials and cracked specimen configurations.
Influence of Hysteretic Heating on Asphalt Fatigue Characterization
Authors: Lundström R , Ekblad J , Isacsson U
Published: December 2004

This paper presents a study focusing on the influence of hysteretic heating on asphalt samples during laboratory fatigue testing. The experimental test setup for material characterization and temperature measurements, including its effect on fatigue test results, as well as theoretical aspects on hysteretic heating, are described. The experimental part of the investigation concerns linear viscoelastic and cyclic fatigue characterization of six asphalt concrete mixtures using uniaxial testing. All the mixtures show nominally identical volumetric properties (aggregate size distribution, binder and air void content) but different binder properties. Three base bitumens and three polymer modified binders were used. The cyclic fatigue tests were carried out at 0, 10, and 20°C using controlled strain and stress modes and different excitation amplitudes. In order to acquire knowledge regarding temperature changes during fatigue testing, several experimental techniques were used. The main thermal study was performed using thermocouples attached to the midheight envelope surface of each sample. The sample surface temperature distribution and its evolution during fatigue testing were investigated using an infrared thermal camera. Furthermore, a limited study of the magnitude of difference between surface and maximum temperature inside the sample was carried out using thermocouples embedded during gyratory compaction. When compared, each method shows advantages and disadvantages regarding simplicity and reliability. In principle, the three methods provide similar results, but the type of information obtained differs among the methods. The use of thermocouples attached to the envelope surface during fatigue testing provides accurate and consistent results of global temperature that can be used to investigate the influence of heating on asphalt fatigue characteristics. By use of thermal measurements and a continuum damage model, it was possible to show a pronounced effect of heating on fatigue behavior. The influence of heating was especially obvious at high excitation amplitudes and elevated temperatures, i.e., conditions where the material produces high amounts of viscoelastic dissipated energy as well as temperature sensitive material behavior.
The Effects of Tonic Locus Ceruleus Output on Sensory-Evoked Responses of Ventral Posterior Medial Thalamic and Barrel Field Cortical Neurons in the Awake Rat
Authors: Devilbiss David M. , Waterhouse Barry D.
Published: December 2004

In mammals, the pontine nucleus locus ceruleus (LC) is the sole source of norepinephrine (NE) projections to the forebrain. Increasing tonic discharge of LC neurons elevates extracellular levels of NE in the cortex and thalamus. Tonic LC discharge is linked to the level of wakefulness and behavioral performance, demonstrating an optimal firing rate during sustained attention tasks. Iontophoretic application of NE to target neurons in the forebrain has been shown to produce a diverse set of neuromodulatory actions, including augmentation of synaptically evoked discharge as well as suppression of spontaneous and stimulus-evoked firing patterns. Iontophoretic studies cataloged potential NE effects; however, the context in which such actions could occur in awake behaving animals remained controversial. To address this issue, the current study examined the effects of increasing tonic LC output on spontaneous and stimulus-evoked discharge of neurons within the ventroposterior medial (VPM) thalamus and barrel field (BF) somatosensory cortex of awake animals using multichannel extracellular recording strategies. The present findings indicate two primary outcomes that result from increasing frequencies of LC stimulation, either an inverted-U facilitating response profile or monotonic suppression of sensory-evoked neuronal responses. Increased tonic LC output generally decreased neuronal response latency measures for both BF cortical and VPM thalamic cells. LC-mediated effects on target VPM and BF cortical neuron sensory processing are consistent with previous demonstrations of NE modulatory actions on central neurons but indicate that such actions are cell specific. Moreover, clear differences were observed between the modulation of VPM and BF cortical cells. These data suggest that sensory signal processing is continually altered over the range of tonic LC discharge frequencies that occur in the waking animal. Such changes may account for LC-mediated shifts in sensory network performance across multiple stages of arousal and attention.
A Novel Ca2+-Independent Signaling Pathway to Extracellular Signal-Regulated Protein Kinase by Coactivation of NMDA Receptors and Metabotropic Glutamate Receptor 5 in Neurons
Authors: Yang Lu , Mao Limin , Tang Qingsong , Samdani Shazia , Liu Zhenguo , Wang John Q.
Published: December 2004

The specification and organization of glutamatergic synaptic transmission require the coordinated interaction among glutamate receptors and their synaptic adaptor proteins closely assembled in the postsynaptic density (PSD). Here we investigated the interaction between NMDA receptors and metabotropic glutamate receptor 5 (mGluR5) in the integral regulation of extracellular signal-regulated protein kinase (ERK) and gene expression in cultured rat striatal neurons. We found that coapplication of NMDA and the mGluR5 agonist (S)-3,5-dihydroxyphenylglycine synergistically increased ERK phosphorylation. Interestingly, the synergistic increase in ERK phosphorylation was dependent on the cross talk between NMDA receptor-associated synaptic adaptor protein PSD-95 and the mGluR5-linked adaptor protein Homer1b/c but not on the conventional Ca2+signaling derived from NMDA receptors (Ca2+influx) and mGluR5 (intracellular Ca2+release). This was demonstrated by the findings that the synergistic phosphorylation of ERK induced by coactivation of NMDA receptors and mGluR5 was blocked by either a Tat peptide that disrupts NMDA receptor/PSD-95 binding or small interfering RNAs that selectively reduce cellular levels of Homer1b/c. Furthermore, ERK activated through this PSD-95/Homer1b/c-dependent and Ca2+-independent pathway was able to phosphorylate the two key transcription factors Elk-1 and cAMP response element-binding protein, which further leads to facilitation of c-Fos expression. Together, we have identified a novel Ca2+-independent signaling pathway to ERK by the synergistic interaction of NMDA receptors and mGluR5 via their adaptor proteins in the PSD of neurons, which underlies a synapse-to-nucleus communication important for the transcriptional regulation.
Acid-Induced Pain and Its Modulation in Humans
Authors: Jones Nicholas G. , Slater Rebeccah , Cadiou Herve , McNaughton Peter , McMahon Stephen B.
Published: December 2004

Despite the discovery of ion channels that are activated by protons, we still know relatively little about the signaling of acid pain. We used a novel technique, iontophoresis of protons, to investigate acid-induced pain in human volunteers. We found that transdermal iontophoresis of protons consistently caused moderate pain that was dose-dependent. A marked desensitization occurred with persistent stimulation, with a time constant of ∼3 min. Recovery from desensitization occurred slowly, over many hours. Acid-induced pain was significantly augmented in skin sensitized by acute topical application of capsaicin. However, skin desensitized by repeated capsaicin application showed no significant reduction in acid-induced pain, suggesting that both capsaicin-sensitive and insensitive sensory neurons contribute to acid pain. Furthermore, topical application of non-steroidal anti-inflammatory drugs (NSAIDs) significantly attenuated acid-evoked pain but did not affect the heat pain threshold, suggesting a specific interaction between NSAIDs and peripheral acid sensors. Subcutaneous injection of amiloride (1 mm) also significantly inhibited the pain induced by iontophoresis of acid, suggesting an involvement of acid-sensing ion channel (ASIC) receptors. Conversely, iontophoresis of acid over a wide range of skin temperatures from 4 to 40°C produced only minor changes in the induced pain. Together these data suggest a prominent role for ASIC channels and only a minor role for transient receptor potential vanilloid receptor-1 as mediators of cutaneous acid-induced pain.
Direct Excitation of Inhibitory Interneurons by Extracellular ATP Mediated by P2Y1Receptors in the Hippocampal Slice
Authors: Kawamura Masahito , Gachet Christian , Inoue Kazuhide , Kato Fusao
Published: December 2004

ATP is an important cell-to-cell signaling molecule mediating the interactions between astrocytes and neurons in the CNS. In the hippocampal slices, ATP suppresses excitatory transmission mostly through activation of adenosine A1receptors, because the ectoenzyme activity for the extracellular breakdown of ATP to adenosine is high in slice preparations in contrast to culture environments. Because the hippocampus is also rich in the expression of P2 receptors activated specifically by ATP, we examined whether ATP modulates neuronal excitability in the acute slice preparations independently of adenosine receptors. Although ATP decreased the frequency of spontaneously occurring EPSCs in the CA3 pyramidal neurons through activation of adenosine A1receptors, ATP concurrently increased the frequency of IPSCs in a manner dependent on action potential generation. This effect was mediated by P2Y1receptors because (1) 2-methylthio-ATP (2meSATP) was the most potent agonist, (2) 2′-deoxy-N6-methyladenosine-3′,5′-bisphosphate diammonium (MRS2179) abolished this effect, and (3) this increase in IPSC frequency was not observed in the transgenic mice lacking P2Y1receptor proteins. Application of 2meSATP elicited MRS2179-sensitive time- and voltage-dependent inward currents in the interneurons, which depolarized the cell to firing threshold. Also, it increased [Ca2+]iin both astrocytes and interneurons, but, unlike the former effect, the latter was entirely dependent on Ca2+entry. Thus, in hippocampal slices, in addition to activating A1receptors of the excitatory terminals after being converted to adenosine, ATP activates P2Y1receptors in the interneurons, which is linked to activation of unidentified excitatory conductance, through mechanisms distinct from those in the astrocytes.
The Generation of Dopaminergic Neurons by Human Neural Stem Cells Is Enhanced by Bcl-XL, BothIn VitroandIn Vivo
Authors: Liste Isabel , García-García Elisa , Martínez-Serrano Alberto
Published: December 2004

Progress in stem cell biology research is enhancing our ability to generate specific neuron types for basic and applied studies and to design new treatments for neurodegenerative diseases. In the case of Parkinson's disease (PD), alternative human dopaminergic (DAergic) neurons other than primary fetal tissue do not yet exist. One possible source could be human neural stem cells (hNSCs), although the yield in DAergic neurons and their survival are very limited.

In this study, we found that Bcl-XLenhances (one-to-two orders of magnitude) the capacity for spontaneous dopaminergic differentiation of hNSCs, which then exceeds that of cultured human ventral mesencephalic tissue. Bcl-XLalso enhanced total neuron generation by hNSCs, but to a lower extent. Neuronal phenotypes other than DA were not affected by Bcl-XL, indicating an exquisitely specific effect on DAergic neurons.In vivo, grafts of Bcl-XL-overexpressing hNSCs do generate surviving human TH+neurons in the adult rat 6-OH-dopamine lesioned striatum, something never seen when naive hNSCs were transplanted. Most of the data obtained here in terms of the effects of Bcl-XLare consistent with an enhanced survival type of mechanism and not supportive of induction, specification, or proliferation of DAergic precursors.

From thisin vitroandin vivoevidence, we conclude that enhancing Bcl-XLexpression is important to obtain human DAergic neurons from hNSCs. These findings may facilitate the development of drug-screening and cell-replacement activities to discover new therapeutic strategies for PD.
Medial Hypothalamic 5-Hydroxytryptamine (5-HT)1AReceptors Regulate Neuroendocrine Responses to Stress and Exploratory Locomotor Activity: Application of Recombinant Adenovirus Containing 5-HT1ASequences
Authors: Li Qian , Holmes Andrew , Ma Li , Van de Kar Louis D. , Garcia Francisca , Murphy Dennis L.
Published: December 2004

Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1Areceptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1Asense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1Areceptors in the hypothalamus. The expression of the 5-HT1Agenes is controlled by the 5-HT1Apromoter, so that they are only expressed in 5-HT1Areceptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1Areceptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/-mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1Areceptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1Areceptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors.
Rho-Kinase Inhibition Enhances Axonal Plasticity and Attenuates Cold Hyperalgesia after Dorsal Rhizotomy
Authors: Ramer Leanne M. , Borisoff Jaimie F. , Ramer Matt S.
Published: December 2004

Dorsal rhizotomy results in primary deafferentation of the dorsal horn with concomitant sprouting of spared intraspinal monoaminergic axons. Because descending monoaminergic systems are thought to mitigate nociceptive transmission from the periphery and because dorsal rhizotomy can result in neuropathic pain, we sought to determine whether the rhizotomy-induced sprouting response could be further augmented. Because myelin-derived molecules mask endogenous plasticity of CNS axons and because myelin-inhibitory signaling occurs through the Rho-GTPase pathway, we inhibited Rho-pathway signaling after cervical dorsal rhizotomy in rats. An increase in the density of serotonergic- and tyrosine hydroxylase-positive fibers was seen in the dorsal horn 1 week after septuple rhizotomy, and axon density continued to increase for at least 1 month. One week after septuple rhizotomy, administration of intrathecal Y-27632, an antagonist of Rho-kinase (ROCK), increased the density of both fiber types over vehicle-treated controls. To examine behavioral effects of both cervical rhizotomy and ROCK inhibition, we examined responses to evoked pain: mechanical and thermal allodynia and cold hyperalgesia in the forepaw were examined after single, double, and quadruple rhizotomies of dorsal roots of the brachial plexus. The most notable behavioral outcome was the development of cold hyperalgesia in the affected forepaw after rhizotomies of the C7 and C8 dorsal roots. Application of Y-27632 both attenuated cold hyperalgesia and induced monoaminergic plasticity after C7/8 rhizotomy. Thus, inhibition of Rho-pathway signaling both promoted the sprouting of intact supraspinal monoaminergic fibers and alleviated pain after dorsal rhizotomy.
Mapping Netrin Receptor Binding Reveals Domains of Unc5 Regulating Its Tyrosine Phosphorylation
Authors: Kruger Robert P. , Lee Jeeyong , Li Weiquan , Guan Kun-Liang
Published: December 2004

Netrin and its receptors Unc5 and deleted in colorectal carcinoma (DCC) regulate axon guidance and cell migration. We defined domains involved in the interactions between netrin-1, DCC, and Unc5c. We show that Unc5 requires both Ig domains to interact with netrin. DCC binds through the fourth fibronectin type III domain, whereas netrin binds through multiple domains to both receptors. We examined the functional consequences of removing the netrin binding and nonbinding domains from Unc5in vitroandin vivo. In human embryonic kidney 293 cells, removal of the netrin binding second Ig domain causes an increase in basal tyrosine phosphorylation, whereas removal of the netrin nonbinding thrombospondin domains decreases tyrosine phosphorylation. Moreover, experiments inCaenorhabditis elegansindicate that both netrin binding and nonbinding domains are necessary for phenotypic rescue of anunc-5loss of function mutation.
Frequency-Dependent Modulation of Retinogeniculate Transmission by Serotonin
Authors: Seeburg Daniel P. , Liu Xiaojin , Chen Chinfei
Published: December 2004

The relay of visual information converging in the lateral geniculate nucleus (LGN) en route to the visual cortex is modulated by projections from brainstem nuclei. The release of serotonin, one mediator of these effects, has been shown to act at a presynaptic site to inhibit neurotransmitter release at the retinogeniculate synapse, the connection between retinal ganglion cells and thalamocortical relay neurons in the LGN. To understand how serotonergic inhibition of synaptic transmission influences the transfer of information at this synapse, we examined the EPSCs and firing responses of relay neurons to 5-carboxytryptamine (5-CT), a 5-HT1receptor agonist that preferentially activates the presynaptic over postsynaptic modulatory effects of serotonin. Bath application of 5-CT inhibits synaptic strength, relieves synaptic depression, and reduces the total synaptic charge transferred at the retinogeniculate synapse in mouse LGN brain slices. In contrast, 5-CT does not significantly alter the membrane potential response of relay neurons to trains of intracellular current injections. Here we show that presynaptic serotonergic modulation results in a frequency-dependent inhibition of relay neuron firing. At low-frequency stimulation, 5-CT markedly reduces charge transfer at the retinogeniculate synapse, thus inhibiting relay neuron firing. However, inhibition of firing by 5-CT is diminished during high-frequency stimulation, because relief from synaptic depression partially offsets the reduction in charge transfer. Thus, presynaptic serotonergic inhibition plays a powerful role in modulating the frequency range of visual information transmitted via the retinogeniculate synapse such that high-frequency inputs are more reliably transmitted than low-frequency inputs.
Phosphotidylinositol 4,5-Bisphosphate Signals Underlie Receptor-Specific Gq/11-Mediated Modulation of N-Type Ca2+Channels
Authors: Gamper Nikita , Reznikov Vitaliy , Yamada Yoichi , Yang Jian , Shapiro Mark S.
Published: December 2004

Modulation of voltage-gated Ca2+channels via G-protein-coupled receptors is a prime mechanism regulating neurotransmitter release and synaptic plasticity. Despite extensive studies, the molecular mechanism underlying Gq/11-mediated modulation remains unclear. We found cloned and native N-type Ca2+channels to be regulated by phosphotidylinositol 4,5-bisphosphate (PIP2). In inside-out oocyte patches, PIP2greatly attenuated or reversed the observed rundown of expressed channels. In sympathetic neurons, muscarinic M1ACh receptor suppression of the Ca2+current (ICa) was temporally correlated with PIP2hydrolysis, blunted by PIP2in whole-cell pipettes, attenuated by expression of PIP2-sequestering proteins, and became irreversible when PIP2synthesis was blocked. We also probed mechanisms of receptor specificity. Although bradykinin also induced PIP2hydrolysis, it did not inhibitICa. However, bradykinin receptors became nearly as effective as M1receptors when PIP2synthesis, IP3receptors, or the activity of neuronal Ca2+sensor-1 were blocked, suggesting that bradykinin receptor-induced intracellular Ca2+increases stimulate PIP2synthesis, compensating for PIP2hydrolysis. We suggest that differential use of PIP2signals underlies specificity of Gq/11-coupled receptor actions on the channels.
Peroxisome Proliferator-Activated Receptor γ Induces a Clearance Mechanism for the Amyloid-β Peptide
Authors: Camacho Ira Espuny , Serneels Lutgarde , Spittaels Kurt , Merchiers Pascal , Dominguez Diana , De Strooper Bart
Published: December 2004

We investigated whether peroxisome proliferator-activated receptor γ (PPARγ) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. Inducing expression or activating PPARγ using synthetic agonists of the thiazolinedione family results in a dramatic decrease in the levels of the amyloid-β (Aβ) peptide in the conditioned medium of neuronal and non-neuronal cells. PPARγ does not affect expression or activity of any of the secretases involved in the generation of the Aβ peptide but induces a fast, cell-bound clearing mechanism responsible for the removal of the Aβ peptide from the medium. Although PPARγ expression is generally low in the CNS, induction of PPARγ expression during inflammation could be beneficial for inducing Aβ clearance. We confirm that the Aβ clearance mechanism can indeed be induced by PPARγ activation in primary murine-mixed glia and cortical neuronal cultures. Our results suggest that PPARγ-controlled mechanisms should be explored further as potential drug targets for Alzheimer's disease treatment.
Prolegomena to Future Experimental Efforts on Genetic Code Engineering by Expanding Its Amino Acid Repertoire
Authors: Budisa Nediljko
Published: December 2004

Protein synthesis and its relation to the genetic code was for a long time a central issue in biology. Rapid experimental progress throughout the past decade, crowned with the recently elucidated ribosomal structures, provided an almost complete description of this process. In addition important experiments provided solid evidence that the natural protein translation machinery can be reprogrammed to encode genetically a vast number of non‐coded (i.e. noncanonical) amino acids. Indeed, in the set of 20 canonical amino acids as prescribed by the universal genetic code, many desirable functionalities, such as halogeno, keto, cyano, azido, nitroso, nitro, and silyl groups, as well as CC or CC bonds, are absent. The ability to encode genetically such chemical diversity will enable us to reprogram living cells, such as bacteria, to express tailor‐made proteins exhibiting functional diversity. Accordingly, genetic code engineering has developed into an exciting emerging research field at the interface of biology, chemistry, and physics.
Degradation and drug‐release studies of a poly(glycolide‐co‐trimethylene carbonate) copolymer (Maxon)
Authors: Noorsal K. , Mantle M. D. , Gladden L. F. , Cameron R. E.
Published: December 2004

Poly(glycolide‐co‐trimethylene carbonate) is available commercially as a monofilament suture known as Maxon. The literature has shown that Maxon sutures possess a slow degradation rate of about 7 months and exhibit relatively high mechanical strength in comparison with other absorbable sutures. However, very few articles are available on the degradation of unoriented Maxon. This study was designed to explore the chemical and physical aspects of the degradation of unoriented Maxon and its potential as a drug‐release device. Several analytical techniques were used, including mass measurements, simultaneous small‐angle X‐ray scattering and wide‐angle X‐ray scattering, and thermoporometry. Magnetic resonance imaging and drug‐release measurements were carried out with UV spectroscopy. The results suggest that unoriented suture‐based Maxon undergoes multiple stages of hydrolytic degradation, which involve hydration, and active and postactive periods. The drug‐release mechanism is controlled by diffusion in the early degradation stages and polymer erosion in the later stages of release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 475–486, 2005
Degradation of low density polyethylene during extrusion. IV. Off‐flavor compounds in extruded films of stabilized LDPE
Authors: Andersson Thorbjörn , Holmgren Max Hallin , Nielsen Tim , Wesslén Bengt
Published: December 2004

This study was aimed at finding a correlation between the experienced off‐flavor in packed foods and the presence of specific degradation products in LDPE packaging films. The possibility to trap degradation products by chemical reactions with scavengers, i.e., a zeolite additive or antioxidants, was investigated This would prevent degradation products from migrating to the polymer film surface and further into food in contact with the film. It was found that off‐flavor noted in water packed in LDPE films depended on extrusion temperature and exposure time for the melt to oxygen, that is, the parameters that influence the contents of oxidation products that are able to migrate from the polymer film. It was also found that adsorption of oxidative degradation products in a zeolite additive or protection of LDPE by using antioxidants could prevent off‐flavor in the packed product (water). However, the antioxidant should be selected with regard to extrusion temperature because thermal instability in the additive might jeopardize the intended effect. Multifunctional antioxidants seem to provide improved protection, the most effective one evaluated in this work being Irganox E201, i.e., vitamin E. Concentrations of oxidized degradation products are well correlated to the perceived off‐flavor in the packed water. The highest correlation between off‐flavor and oxidized components was found for ketones in the range of C7 to C9 and aldehydes in the range of C6 to C9. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 583–595, 2005
Variability of the division of the cortical branches of the posterior cerebral artery
Authors: Ladzinski Piotr , Maliszewski Mariusz
Published: December 2004

This article presents a method of analysis of variation in the cortical branching of the posterior cerebral artery (PCA). The method takes account of previous observations and reflects various symptoms of such variation. Of 100 cerebral hemispheres into whose vessels a contrast medium was injected, 94 hemispheres have been qualified for further examination. In six hemispheres, there were anomalies of the PCA, which are not included in the present analysis of division. A general model of the division of the artery has been developed. On the basis of this model, principles of the analysis of the variation have been discussed. The model comprises of three elements. The first is the main trunk. The second is intermediate trunks. The third element may appear in two forms: proper cortical arteries and cortical arterial groups. The main trunk was defined as the vessels arising from the final division of the basilar artery with its end in the place of branching of the most peripheral proper cortical artery, that is, parieto‐occipital artery. Intermediate trunks are these parts of the PCA that extend between the main trunk and proper cortical arteries or cortical arterial groups. The identification criterion for the intermediate trunks is its length, which is to be equal to or exceed the sum of the radius of the two vessels, which the intermediate trunk gives off. There have been distinguished primary and secondary intermediate trunks. Proper cortical arteries or cortical arterial groups are parts of the PCA by means of which blood is supplied directly to the cortex. Cortical branches of the PCA of a relatively constant topography and vascularization were termed proper cortical arteries. In some cases, cortical branches are accompanied by small vessels of varying number and size. They were named accessory cortical arteries. Proper cortical arteries together with accompanying accessory cortical arteries have been named cortical arterial groups. The number of the proper cortical arteries is considered to be constant and is six. The theory of combinations has been applied to establish all possible branching variants. There are 16 such variants. Eleven of them (68%) were represented in the analyzed material. In seven hemispheres (7.4%), intermediate trunks were not observed. In 87 hemispheres (92.6%), there were present primary intermediate trunks. In four hemispheres (4.2%), there were found primary and secondary intermediate trunks. Both proper cortical arteries and cortical arterial groups reached the first five cortical areas of the PCA. The last cortical area was reached by a cortical arterial group only. © 2004 Wiley‐Liss, Inc.
Epididymis of viscacha (Lagostomus maximus maximus): Morphological changes during the annual reproductive cycle
Authors: Aguilera‐Merlo Claudia , Muñoz Estela , Dominguez Susana , Scardapane Luis , Piezzi Ramón
Published: December 2004

Little is known about morphological changes in the epididymis in relation to the natural photoperiod or their influence on sperm maturation. The viscacha is a seasonal rodent living in the Southern Hemisphere. The adult males exhibit an annual reproductive cycle with periods of maximum gonadal activity and gonadal regression. In this work, we studied seasonal variations in the morphology and cellular population of the epididymis during both periods, and we compared these results with those recorded at the testicular level. Epididymides were removed and studied by light microscopy. Measurements of luminal diameter, epithelial height, thickness of the lamina propria, and relative cellular distribution were performed. Analysis of variance (ANOVA) or nonparametric ANOVA was used to compare the results. Striking quantitative and qualitative changes were observed. Epididymides in periods of gonadal regression showed a significant decrease in luminal diameter and epithelial height in cauda, while the thickness of the lamina propria increased. In the epididymal corpus, the number of clear cells increased, and the cytoplasm of principal cells showed numerous giant vacuoles. During the active period, the number of halo cells increased and the cytoplasm of these cells was filled with dense bodies. In conclusion, the epididymis of the viscacha exhibits important seasonal morphological changes throughout annual reproductive cycle. The epididymal corpus and cauda segments appeared to be the segments most sensitive to seasonal cyclical variations of the external environment. We therefore postulate that the epididymal morphology of the viscacha probably could be regulated by the natural photoperiod. © 2004 Wiley‐Liss, Inc.
T‐Shaped Nets of Antimony Atoms in the Binary Antimonide Hf5Sb9.
Authors: Assoud Abdeljalil , Kleinke Katja M. , Soheilnia Navid , Kleinke Holger
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Electric‐Field‐Induced Conductance Switching in FeCo Prussian Blue Analogues.
Authors: Sato Osamu , Kawakami Tomoko , Kimura Masanobu , Hishiya Shoko , Kubo Shoichi , Einaga Yasuaki
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis and Electrochemistry of the Monolacunary Dawson‐Type Tungstoarsenate [H4AsW17O61]11‐ and Some First‐Row Transition‐Metal Ion Derivatives.
Authors: Mbomekalle Israel‐Martyr , Keita Bineta , Lu Yu Wei , Nadjo Louis , Contant Roland , Belai Nebebech , Pope Michael T.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Evaluation of (+)‐Sparteine‐Like Diamines for Asymmetric Synthesis.
Authors: Dearden Michael J. , McGrath Matthew J. , O'Brien Peter
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Double Stereodifferentiation in the “Acetate‐Type” Aldol Reaction with Garner′s Aldehyde. Stereocontrolled Synthesis of Polyhydroxylated γ‐Amino Carbonyl Compounds.
Authors: Vicario Jose L. , Rodriguez Monica , Badia Dolores , Carrillo Luisa , Reyes Efraim
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Condensation of 1‐Amino‐4‐azafluorene with α‐Diketones and α,β‐Unsaturated Ketones.
Authors: Varlamov A. V. , Levov A. N. , Toze F. , Chernyshev A. I.
Published: December 2004

For Abstract see ChemInform Abstract in Full Text.
Potassium Fluoride Assisted Selective Acetylation of Alcohols with Acetic Acid.
Authors: Bosco J. W. John , Raju B. Rama , Saikia Anil K.
Published: December 2004

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Efficient and Selective Synthesis of 6,7‐Dehydrostipiamide via Zr‐Catalyzed Asymmetric Carboalumination and Pd‐Catalyzed Cross‐Coupling of Organozincs
Authors: Zeng Xingzhong , Zeng Fanxing , Negishi Ei‐ichi
Published: December 2004

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Structure—Activity Relationships of Epolactaene Derivatives: Structural Requirements for Inhibition of Hsp60 Chaperone Activity.
Authors: Nagumo Yoko , Kakeya Hideaki , Yamaguchi Junichiro , Uno Takao , Shoji Mitsuru , Hayashi Yujiro , Osada Hiroyuki
Published: December 2004

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New Approach for Two Chromene Carboxylic Acids Having a Fully Substituted Benzene Ring.
Authors: Yamaguchi Seiji , Maekawa Mikiko , Murayama Yohei , Miyazawa Masahiro , Hirai Yoshiro
Published: December 2004

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Ligand Conformation Has a Definitive Effect on 5‐HT1A and Serotonin Reuptake Affinity.
Authors: Boy Kenneth M. , Dee Michael , Yevich Joseph , Torrente John , Gao Qi , Iben Lawrence , Stark Arlene , Mattson Ronald J.
Published: December 2004

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Interaction of Methyl 5,6‐Dialkyl‐2‐amino‐3‐cyanopyridine‐4‐carboxylates with Primary Amines.
Authors: Vasiliev A. N. , Lyshchikov A. N. , Nasakin O. E. , Kayukov Ya. S.
Published: December 2004

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Preparation of α‐Ketophosphonates by Oxidation of α‐Hydroxyphosphonates with Pyridinium Chlorochromate (PCC)
Authors: Firouzabadi Habib , Iranpoor Nasser , Sobhani Sara
Published: December 2004

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Stereoselective Synthesis and Preliminary Evaluation of New D‐3‐Heteroarylcarbonylalanines as Ligands of the NMDA Receptor.
Authors: Lima Paulo G. , Caruso Rodrigo R. B. , Alves Simone O. , Pessoa Renata F. , Mendonca‐Silva Dayde L. , Nunes Ricardo J. , Noel Francois , Castro Newton G. , Costa Paulo R. R.
Published: December 2004

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Identification of a Potent and Rapidly Reversible Inhibitor of the 20S‐Proteasome.
Authors: Purandare Ashok V. , Wan Honghe , Laing Naomi , Benbatoul Khalid , Vaccaro Wayne , Poss Michael A.
Published: December 2004

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The Absolute Configuration of Peroxisomicines A1 and A2
Authors: Perez Alejandro , Ramirez‐Duron Rosalba , Pineyro‐Lopez Alfredo , Waksman Noemi , Reichert Matthias , Bringmann Gerhard
Published: December 2004

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Thermodynamically Controlled Self‐Assembly of Two‐Dimensional Oxide Nanostructures.
Authors: Schoiswohl Johannes , Surnev Svetlozar , Sock Michael , Ramsey Michael G. , Kresse Georg , Netzer Falko P.
Published: December 2004

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Synthetic Studies on N‐Methylwelwitindolinone C Isothiocyanate (Welwistatin) and Related Substructures
Authors: Avendano Carmen , Menendez J. Carlos
Published: December 2004

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Synthesis of Cell Adhesion Inhibitors via Crystallization‐driven Dynamic Transformations
Authors: Eriksson Magnus , Farina Vittorio , Kapadia Suresh , Napolitano Elio , Yee Nathan K.
Published: December 2004

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Synthesis of Five‐ and Six‐Membered Heterocycles Through Palladium‐Catalyzed Reactions
Authors: Kirsch G. , Hesse S. , Comel A.
Published: December 2004

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Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy
Authors: Schuetze Scott M. , Rubin Brian P. , Vernon Cheryl , Hawkins Douglas S. , Bruckner James D. , Conrad Ernest U. , Eary Janet F.
Published: December 2004

BACKGROUND

Patients with high‐grade soft tissue sarcomas are at high risk of developing local disease recurrence and metastatic disease. [F‐18]‐fluorodeoxy‐D‐glucose (FDG) positron emission tomography (PET) scans are hypothesized to detect histopathologic response to therapy and to predict risk of tumor progression in patients with various malignancies. Serial FDG‐PET scans were taken to determine the correlation between FDG uptake and patient outcomes in patients receiving multimodality treatment of extremity sarcomas.

METHODS

Forty‐six patients with high‐grade localized sarcomas were studied. The maximum standardized uptake values (SUVmax) of tumors were measured before receipt of neoadjuvant chemotherapy and again before surgery. Resected specimens were examined for residual viable tumor. Patients were followed up at least annually for evidence of local and distant recurrence of disease and survival.

RESULTS

Patients with a baseline tumor SUVmax ≥ 6 and < 40% decrease in FDG uptake were at high risk of systemic disease recurrence estimated to be 90% at 4 years from the time of initial diagnosis. Patients whose tumors had a ≥ 40% decline in the SUVmax in response to chemotherapy were at a significantly lower risk of recurrent disease and death after complete resection and adjuvant radiotherapy.

CONCLUSIONS

The FDG‐PET scan was found to be a useful method with which to predict the outcomes of patients with high‐grade extremity soft tissue sarcomas treated with chemotherapy. The pretreatment tumor SUVmax and change in SUVmax after neoadjuvant chemotherapy independently identified patients at high risk of tumor recurrence. The FDG‐PET scan showed promise as a tool to identify the patients with sarcoma who are most likely to benefit from chemotherapy. Cancer 2005. © 2004 American Cancer Society.