bluuebunny/crossref_metadata_2025 huggingface dataset:
Dehydration and rehydration of palygorskite and the influence of water on the nanopores
Authors: Kuang Wenxing , Facey Glenn A. , Detellier Christian
Published: September 2004

The dehydration and rehydration processes of the clay mineral palygorskite (PFl-1) were studied by textural analysis, thermogravimetric analysis connected with mass spectrometry (TGA-MS), and29Si and1H solid-state NMR techniques. The TGA-MS results clearly reveal weight losses at maxima of 70°C, 190°C, 430°C and 860°C. PFl-1 is characterized by a micropore area of 93 m2/g, corresponding to a micropore volume of 47 mm3/g. These values are also obtained for the sample heated up to 200°C for 20 h. Further heating at 300°C produces a collapse of the structure, as shown by the almost complete loss of microporosity.

The29Si NMR spectra of palygorskite show two main resonances at −92.0 and −97.5 ppm, attributed to one of the two pairs of equivalent Si nuclei in the basal plane. A minor resonance at −84.3 ppm is attributed to Q2(Si-OH) Si nuclei. The resonance at −92.0 ppm is assigned to the central Si position, while the resonance at −97.5 ppm is assigned to the edge Si sites. It is confirmed bysolid-state29Si and1H NMR that nearly complete rehydration is achieved by exposing palygorskite samples that have been partially dehydrated at 150°C and 300°C, to D2O or water vapor at room temperature. When the rehydration is accomplished with D2O, the atoms are disordered across all the protons sites.
Effects of γ radiation on chromate immobilization by calcined hydrotalcites
Authors: Martinez-Gallegos Sonia , Bulbulian Silvia
Published: September 2004

The ability of hydrotalcites to retain anionic wastes was studied. In particular, Cr(VI)-adsorbed hydrotalcites were heated to immobilize Cr(VI) in the solid sample. When the heating temperature increased up to 500°C, the lamellar structure of hydrotalcite was lost. At high temperatures (1200°C), the solids were recrystallized in the form of a spinel. Lixiviation with 1 N and 5 N NaCl solutions were utilized to simulate the effect of sea water and of concentrated NaCl solutions in salt mines on the immobilization of Cr. Radiation damage on the solid containing the immobilized Cr was studied by γ-irradiating with a 60Co source at 1000 and 6000 kGy. The Cr-containing samples heated at 1200°C, whether irradiated or not, safely immobilized Cr in the hydrotalcite mainly in the form of MgCr2O4 spinel. Irradiation of hydrotalcites revealed two different effects: (1) samples heated up to 1200°C evolved as a solid in which chromium was retained more firmly than in the non-irradiated material, irradiation enhancing the spinel formation; (2) the structure of samples heated at 1200°C developed a preferential crystallite orientation rather than a purely random one or new location of chromium ions, this effect did not affect Cr immobilization in the solid. Chromium lixiviation with 5 N NaCl solution was always less than the corresponding value with 1 N NaCl solution, probably due to the poor mobility of Cl− ions in the highly concentrated NaCl solution.
On-Line Gel Permeation Chromatography/Nuclear Magnetic Resonance of Complex Polymer Formulations
Authors: Robertson D. F. , Heron J. E. , Beckett M. C.
Published: September 2004

Separation of synthetic polymer mixtures by gel permeation chromatography (GPC), followed by on-line detection using a 500 MHz nuclear magnetic resonance (NMR) spectrometer, has been demonstrated using three different polymer formulations as examples. The mobile phase used in all cases was deutero-chloroform, and an inexpensive commercially available flow cell was used as a link between the separation and detection stages of the experiment. Using this technique it is possible to derive chemical information relating to specific molecular sizes of polymer mixtures, and not just the size-averaged information that would be obtained from standard NMR experiments. This provides an invaluable tool for the deformulation of complex mixtures such as those found in the surfactants and adhesives industries.
Determination of Depleted Uranium in Urine via Isotope Ratio Measurements Using Large-Bore Direct Injection High Efficiency Nebulizer—Inductively Coupled Plasma Mass Spectrometry
Authors: Westphal Craig S. , McLean John A. , Hakspiel Shelly J. , Jackson William E. , McClain David E. , Montaser Akbar
Published: September 2004

Inductively coupled plasma mass spectrometry (ICP-MS), coupled with a large-bore direct injection high efficiency nebulizer (LB-DIHEN), was utilized to determine the concentration and isotopic ratio of uranium in 11 samples of synthetic urine spiked with varying concentrations and ratios of uranium isotopes. Total U concentrations and 235U/238U isotopic ratios ranged from 0.1 to 10 μg/L and 0.0011 and 0.00725, respectively. The results are compared with data from other laboratories that used either α-spectrometry or quadrupole-based ICP-MS with a conventional nebulizer–spray chamber arrangement. Severe matrix effects due to the high total dissolved solid content of the samples resulted in a 60 to 80% loss of signal intensity, but were compensated for by using 233U as an internal standard. Accurate results were obtained with LB-DIHEN– ICP-MS, allowing for the positive identification of depleted uranium based on the 235U/238U ratio. Precision for the 235U/238U ratio is typically better than 5% and 15% for ICP-MS and α-spectrometry, respectively, determined over the concentrations and ratios investigated in this study, with the LB-DIHEN–ICP-MS system providing the most accurate results. Short-term precision (6 min) for the individual 235U and 238U isotopes in synthetic urine is better than 2% ( N = 7), compared to ∼5% for conventional nebulizer–spray chamber arrangements and >10% for α-spectrometry. The significance of these measurements is discussed for uranium exposure assessment of Persian Gulf War veterans affected by depleted uranium ammunitions.
Pulsed-Laser Crossed-Beam Thermal Lens Spectrometry for Detection in a Microchannel: Influence of the Size of the Excitation Beam Waist
Authors: Ghaleb Khalil Abbas , Georges Joseph
Published: September 2004

Crossed-beam thermal lens spectrometry is especially designed for the detection of very small samples in capillary tubes and more generally in microfluidic devices. In this work, the effect of the size of the excitation beam with respect to the size of the sample microchannel has been investigated. Although the signal is inversely proportional to the size of the excitation waist into the sample, the use of large waists may provide greater sensitivities when short-pulse excitation lasers are used and allows easier optimization of the optical design. On the contrary, the use of small beam waists reduces the edge effects that can arise depending on the nature and thickness of the walls of the sample holder. Moreover, small beams provide better spatial resolution and have allowed the measurement of flow velocities as low as 1 mm s−1.
Minimizing Urine Autofluorescence under Multi-Photon Excitation Conditions
Authors: Bukowski Eric J. , Bright Frank V.
Published: September 2004

We report on the effects of excitation wavelength, laser power, and phase resolution on the multi-photon-excited autofluorescence (background) from human urine. When compared to the autofluorescence under one-photon excitation conditions (λex = 260–480 nm), the urine multi-photon-excited autofluorescence (λex = 725–950 nm) can be less complicated. However, at higher laser powers, the multi-photon-excited autofluorescence spectra that are produced by excitation above ∼775 nm are more complex in comparison to the corresponding one-photon-excited autofluorescence. The origin of these more complex spectra arises from simultaneous two- and three-photon-driven excitation of intrinsic luminescent species within the urine. At lower laser powers, three-photon-driven processes are minimized and the autofluorescence spectrum is simplified. Phase resolution is used to further minimize the urine autofluorescence, but it cannot fully eliminate autofluorescence even when excitation is performed under multi-photon conditions at 950 nm. For detecting 250 nM Rhodamine 6G (a mock analyte) dissolved in urine, we find that the two-photon excitation is superior in comparison to one-photon excitation by 5- to 70-fold, depending on the excitation wavelength. Phase resolution combined with two-photon excitation leads to an additional 5- to 7-fold improvement in signal-to-background ratios in comparison to steady-state two-photon excitation.
A Non-Lensed Fiber-Optic Resonance-Enhanced Multiphoton Ionization Probe
Authors: Chinni Rosemarie C. , Gold Dave M. , Brown Steve B. , Chang John T. , Angel S. Michael , Colston Bill W.
Published: September 2004

We have developed a miniature fiber-optic probe with no focusing optics for in situ analysis of volatile organic compounds (VOCs). The probe uses an optical fiber to transmit a laser pulse to a vapor sample causing it to ionize adjacent to the fiber tip through a resonance-enhanced multiphoton ionization (REMPI) process. The distal end of the optical fiber is contained co-axially within 2-mm-inner-diameter stainless steel tubing that serves as an electrode. The electrode is biased at a high positive potential to collect electrons. The current generated is shown to be proportional over about two orders of magnitude to the concentration of the species ionized. Visible wavelength REMPI spectroscopy is used to determine probe sensitivities of 20 ppb (benzene) and 43 ppb (toluene). Designing the probe without focusing optics specifies an achromatic ionization region constant in size and position as the laser wavelength is scanned, which simplifies data collection and reduction. Focusing achromatic systems are discussed and the potential signal improvement is estimated.
Assessing Soil Respiration by Means of Near-Infrared Diode Laser Spectroscopy
Authors: Gianfrani L. , Rocco A. , Battipaglia G. , Castrillo A. , Gagliardi G. , Peressotti A. , Cotrufo M. F.
Published: September 2004

High-resolution diode laser spectroscopy in the near-infrared region is applied to the accurate measurement of soil respiration. In particular, the use of a diode-laser-based spectrometer has allowed the implementation, for the first time, of a static accumulation method capable of measuring soil respiration from continuous measurements of CO2 concentrations, with minor perturbation on soil respiration as well as on CO2 transport and emission. The system has been tested in a laboratory experiment by detection of CO2 production from sandy matrices, inoculated with active soil microbes and supplied with different amounts of decomposable plant material. Respiration rates of all samples were then retrieved using a diffusion model. The results of the laboratory tests are in agreement with those expected on the basis of sample composition. Examples of operation with real soil samples are also reported. We discuss the possible field application of the system, in conjunction with closed static soil chambers.
Noradrenaline Triggers GABAAInhibition of Bed Nucleus of the Stria Terminalis Neurons Projecting to the Ventral Tegmental Area
Authors: Dumont Éric C. , Williams John T.
Published: September 2004

The lateral part of the ventral bed nucleus of the stria terminalis (vlBNST) is a critical site for the antiaversive effects of noradrenergic drugs during opioid withdrawal. The objective of the present study is to identify the cellular action(s) of noradrenaline in the vlBNST after withdrawal froma5d treatment with morphine. The vlBNST is a heterogeneous cell group with multiple efferent projections. Therefore, neurons projecting to the midbrain were identified by retrograde transport of fluorescent microspheres injected in the ventral tegmental area (VTA). Whole-cell voltage clamp recordings of these neurons and of those sharing physiological properties were done in brain slices. Noradrenaline activated α1-adrenergic receptors to increase GABAA-IPSC frequency. Noradrenaline produced a similar increase in GABAA-IPSCs during acute opioid withdrawal, but this increase resulted from activation ofβ-adrenergic receptors, adenylyl cyclase, and protein kinase A, as well as α1-adrenergic receptors. Given that neurons in the vlBNST send an excitatory projection to the VTA, noradrenaline may reduce excitatory drive to mesolimbic dopamine cells. This mechanism might contribute to the withdrawal-induced inhibition of dopamine neurons and explain how noradrenergic drugs microinjected into the vlBNST reduce aversive aspects of opioid withdrawal.
Evidence That Each S Cone in Macaque Fovea Drives One Narrow-Field and Several Wide-Field Blue-Yellow Ganglion Cells
Authors: Schein Stan , Sterling Peter , Ngo Ivy Tran , Huang Teresa M. , Herr Steve
Published: September 2004

A rule of retinal wiring is that many receptors converge onto fewer bipolar cells and still fewer ganglion cells. However, for each S cone in macaque fovea, there are two S-cone ON bipolar cells and two blue-yellow (BY) ganglion cells. To understand this apparent rule reversal, we reconstructed synaptic patterns of divergence and convergence and determined the basic three-tiered unit of connectivity that repeats across the retina. Each foveal S cone diverges to four S-cone ON bipolar cells but contacts them unequally, providing 1–16 ribbon synapses per cell. Next, each bipolar cell diverges to two BY ganglion cells and also contacts them unequally, providing ∼14 and ∼28 ribbon synapses per cell. Overall, each S cone diverges to approximately six BY ganglion cells, dominating one and contributing more modestly to the others. Conversely, of each pair of BY ganglion cells, one is dominated by a single S cone and one is diffusely driven by several. This repeating circuit extracts blue/yellow information on two different spatiotemporal scales and thus parallels the circuits for achromatic, spatial vision, in which each cone dominates one narrow-field ganglion cell (midget) and contributes some input to several wider-field ganglion cells (parasol). Finally, because BY ganglion cells have coextensive +S and –(L+M) receptive fields, and each S cone contributes different weights to different BY ganglion cells, the coextensive receptive fields must be already present in the synaptic terminal of the S cone. The S-cone terminal thus constitutes the first critical locus for BY color vision.
Tumor Necrosis Factor-Like Weak Inducer of Apoptosis-Induced Neurodegeneration
Authors: Potrovita Ioana , Zhang Wen , Burkly Linda , Hahm Kyungmin , Lincecum John , Wang Monica Z. , Maurer Martin H. , Rossner Moritz , Schneider Armin , Schwaninger Markus
Published: September 2004

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor (TNF) family of cytokines. It has proangiogenic and proinflammatory propertiesin vivoand induces cell death in tumor cell lines. TWEAK effects are mediated by the membrane receptor Fn14. In a systematic search for genes regulated in a murine stroke model with the tag-sequencing technique massively parallel signature sequencing, we have identified TWEAK as an induced gene. After 24 hr of focal cerebral ischemiain vivoor oxygen glucose deprivation in primary cortical neurons, both TWEAK and its receptor Fn14 were significantly upregulated. TWEAK induced cell death in primary neurons. Transfection of a nuclear factor (NF)-κB-luciferase fusion gene demonstrated that TWEAK stimulated transcriptional activity of NF-κB through Fn14 and the IκB kinase. Inhibition of NF-κB reduced TWEAK-stimulated neuronal cell death, suggesting that NF-κB mediates TWEAK-induced neurodegeneration at least in part. Intraperitoneal injection of a neutralizing anti-TWEAK antibody significantly reduced the infarct size after 48 hr of permanent cerebral ischemia. In summary, our data show that TWEAK induces neuronal cell death and is involved in neurodegenerationin vivo.
Frontal Lobe Volume, Function, and β-Amyloid Pathology in a Canine Model of Aging
Authors: Tapp P. Dwight , Siwak Christina T. , Gao Fu Qiang , Chiou Jr-Yuan , Black Sandra E. , Head Elizabeth , Muggenburg Bruce A. , Cotman Carl W. , Milgram Norton W. , Su Min-Ying
Published: September 2004

Application of magnetic resonance imaging (MRI) techniques reveals that human brain aging varies across cortical regions. One area particularly sensitive to normal aging is the frontal lobes.In vitroneuropathological studies and behavioral measures in a canine model of aging previously suggested that the frontal lobes of the dog might be sensitive to aging. In the present study, MRI scans were acquired to compare age-related changes in frontal lobe volume with changes in executive functions andβ-amyloid pathology in the frontal cortex of beagle dogs aged 3 months to 15 years. Decreases in total brain volume appeared only in senior dogs (aged 12 years and older), whereas frontal lobe atrophy developed earlier, appearing in the old dogs (aged 8-11 years). Hippocampal volume also declined with age, but not occipital lobe volume past maturity. Reduced frontal lobe volume correlated with impaired performance on measures of executive function, including inhibitory control and complex working memory, and with increased β-amyloid accumulation in the frontal cortex. Age-related hippocampal atrophy also correlated with complex working memory but not inhibitory control, whereas occipital lobe volume did not correlate with any cognitive measure. These findings are consistent with the frontal lobe theory of aging in humans, which suggests that the frontal lobes and functions subserved by this region are compromised early in aging.
Chronic Morphine Sensitizes the Brain Norepinephrine System to Corticotropin-Releasing Factor and Stress
Authors: Xu Guang-Ping , Van Bockstaele Elisabeth , Reyes Beverly , Bethea Thelma , Valentino Rita J.
Published: September 2004

Chronic opiate use produces persistent changes in brain neurons that are expressed as adverse effects, including physical dependence and compulsive drug-seeking behavior. Dysregulation of the hypothalamic-pituitary-adrenal response to stress also occurs with chronic opiate administration and has been implicated as a contributing factor to continued substance abuse. This study provides the first evidence for dysregulation of the central noradrenergic response to stress by chronic opiates. Chronic morphine selectively sensitized locus ceruleus (LC)-norepinephrine (NE) neurons to corticotropin-releasing factor (CRF), an integral mediator of the stress response. CRF doses that were inactive in vehicle-treated rats produced a near-maximal activation of LC neurons of rats chronically administered morphine. LC sensitization to CRF was not solely a pharmacological phenomenon but was expressed as hyperresponsivity to physiological stress. Finally, opiate-induced LC sensitization translated to a change in the behavioral repertoire in response to environmental stress (swim stress) such that NE-mediated hyperactive behaviors predominated. The opiate-induced sensitization of the central NE response to stress predicts that chronic opiate administration increases vulnerability to certain stress-related symptoms (e.g., hyperarousal, attentional dysfunction), and this may contribute to the maintenance of opiate-seeking behavior.
Longitudinal Mapping of Cortical Thickness and Brain Growth in Normal Children
Authors: Sowell Elizabeth R. , Thompson Paul M. , Leonard Christiana M. , Welcome Suzanne E. , Kan Eric , Toga Arthur W.
Published: September 2004

Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of ∼0.4-1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Broca's area) and bilateral posterior perisylvian (Wernicke's area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.
Evidence for Differential Cortical Input to Direct Pathway versus Indirect Pathway Striatal Projection Neurons in Rats
Authors: Lei Wanlong , Jiao Yun , Del Mar Nobel , Reiner Anton
Published: September 2004

The two main types of corticostriatal neurons are those that project only intratelencephalically (IT-type), the intrastriatal terminals of which are 0.41 μm in mean diameter, and those that send their main axon into pyramidal tract and have a collateral projection to striatum (PT-type), the intrastriatal terminals of which are 0.82 μm in mean diameter. We used three approaches to examine whether the two striatal projection neuron types (striatonigral direct pathway vs striatopallidal indirect pathway) differ in their input from IT-type and PT-type neurons. First, we retrogradely labeled one striatal projection neuron type or the other with biotinylated dextran amine (BDA)-3000 molecular weight. We found that terminals making asymmetric axospinous contact with striatonigral neurons were 0.43 μm in mean diameter, whereas those making asymmetric axospinous contact with striatopallidal neurons were 0.69 μm. Second, we preferentially immunolabeled striatonigral neurons for D1dopamine receptors or striatopallidal neurons for D2dopamine receptors and found that axospinous terminals had a smaller mean size (0.45 μm) on D1+ spines than on D2+ spines (0.61 μm). Finally, we combined selective BDA labeling of IT-type or PT-type terminals with immunolabeling for D1or D2, and found that IT-type terminals were twice as common as PT-type on D1+ spines, whereas PT-type terminals were four times as common as IT-type on D2+ spines. These various results suggest that striatonigral neurons preferentially receive input from IT-type cortical neurons, whereas striatopallidal neurons receive greater input from PT-type cortical neurons. This differential cortical connectivity may further the roles of the direct and indirect pathways in promoting desired movements and suppressing unwanted movements, respectively.
Low Ethanol Concentrations Selectively Augment the Tonic Inhibition Mediated by δ Subunit-Containing GABAAReceptors in Hippocampal Neurons
Authors: Wei Weizheng , Faria Leonardo Coutinho , Mody Istvan
Published: September 2004

In central neurons, a tonic conductance is activated by ambient levels of the inhibitory transmitter GABA. Here, we show that in dentate gyrus granule cells, where tonic inhibition is mediated by δ subunit-containing GABAAreceptors, this conductance is augmented by low concentrations (30 mm) of ethanol. In contrast, the tonic inhibition mediated by α5 subunit-containing receptors of CA1 pyramidal cells is not affected. The effect of ethanol on tonic inhibition specifically reduces the excitability of the dentate gyrus and identifies the δ subunit-dependent tonic inhibition as a likely site of ethanol action in the brain.
Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation
Authors: López-Moreno José Antonio , González-Cuevas Gustavo , de Fonseca Fernando Rodríguez , Navarro Miguel
Published: September 2004

Alcoholism is characterized by successive relapses. Recent data have shown a cross-talk between the cannabinoid system and ethanol. In this study, male Wistar rats with a limited (30 min sessions), intermittent, and extended background of alcohol operant self-administration were used. The relapse to alcohol after 1 week of alcohol deprivation was evaluated. Two weeks later, the animals were treated with the cannabinoid agonist WIN 55,212-2 (R-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate) (0, 0.4, 2.0, and 10.0 mg/kg, s.c.) during a similar alcohol deprivation period, and alcohol relapse during 2 weeks was assessed. A conditioned place preference (CPP) paradigm was used to study the rewarding properties of the cannabinoid agonist. Locomotor activity was also recorded. All doses of WIN 55,212-2 produced aversion in the CPP paradigm. The doses of 2.0 and 10.0 mg/kg resulted in an important suppression of spontaneous locomotor activity and a progressive weight loss during the next 2 weeks. The single alcohol deprivation was followed by a transient increase in their responding for alcohol from a range of 20-24 lever presses at baseline to a range of 38-48 responses in the first and second days (alcohol deprivation effect). However, the administration of WIN 55,212-2 during ethanol deprivation produced similar increased responses for alcohol but in a long-term way (at least over 2 weeks). These findings suggest that noncontingent chronic exposure to cannabinoids during alcohol deprivation can potentiate the relapse into alcohol use, indicating that functional changes in the cannabinoid brain receptor may play a key role in ethanol relapse.
Molecular Organization of the Olfactory Septal Organ
Authors: Tian Huikai , Ma Minghong
Published: September 2004

The septal organ in the mammalian nose is a distinct chemosensory organ sitting in the air path. To gain insights into its organization and function, we analyzed the chemoreceptors expressed in this area. By combining cDNA cloning, Affymetrix (Santa Clara, CA) genechips covering all the mouse olfactory receptor genes, andin situhybridization, we achieved a relatively complete expression profile of the olfactory receptor genes in the septal organ. The majority of the septal neurons express only a few receptor genes in varying patterns, with the top one in ∼50% of the cells and the top eight together in ∼93% of the cells. We demonstrated that a single neuron expresses only one receptor by a thorough combination of all the major septal receptor genes in double-labeling studies. These septal receptor genes do not form a single subfamily. Instead, these genes are distributed on a few major branches of the phylogenetic tree covering all the mouse olfactory receptors. Most of these genes are also concentrated in certain areas within the most ventral zone of the main olfactory epithelium, although their expression patterns do not match those in the septal organ. In contrary to the previous view of random distribution, our results indicate that certain olfactory receptors form “hot spots” in the nose.
Ionotropic and Metabotropic Receptors, Protein Kinase A, Protein Kinase C, and Src Contribute to C-Fiber-Induced ERK Activation and cAMP Response Element-Binding Protein Phosphorylation in Dorsal Horn Neurons, Leading to Central Sensitization
Authors: Kawasaki Yasuhiko , Kohno Tatsuro , Zhuang Zhi-Ye , Brenner Gary J. , Wang Haibin , Van Der Meer Catrien , Befort Katia , Woolf Clifford J. , Ji Ru-Rong
Published: September 2004

Molecular mechanisms underlying C-fiber stimulation-induced ERK (extracellular signal-regulated kinase) activation in dorsal horn neurons and its contribution to central sensitization have been investigated. In adult rat spinal slice preparations, activation of C-fiber primary afferents by a brief exposure of capsaicin produces an eightfold to 10-fold increase in ERK phosphorylation (pERK) in superficial dorsal horn neurons. The pERK induction is reduced by blockade of NMDA, AMPA/kainate, group I metabotropic glutamate receptor, neurokinin-1, and tyrosine receptor kinase receptors. The ERK activation produced by capsaicin is totally suppressed by inhibition of either protein kinase A (PKA) or PKC. PKA or PKC activators either alone or more effectively together induce pERK in superficial dorsal horn neurons. Inhibition of calcium calmodulin-dependent kinase (CaMK) has no effect, but pERK is reduced by inhibition of the tyrosine kinase Src. The induction of cAMP response element binding protein phosphorylation (pCREB) in spinal cord slices in response to C-fiber stimulation is suppressed by preventing ERK activation with the MAP kinase kinase inhibitor 2-(2-diamino-3-methoxyphenyl-4H-1-benzopyran-4-one (PD98059) and by PKA, PKC, and CaMK inhibitors. Similar signaling contributes to pERK induction after electrical stimulation of dorsal root C-fibers. Intraplantar injection of capsaicin in an intact animal increases expression of pCREB, c-Fos, and prodynorphin in the superficial dorsal horn, changes that are prevented by intrathecal injection of PD98059. Intrathecal PD98059 also attenuates capsaicin-induced secondary mechanical allodynia, a pain behavior reflecting hypersensitivity of dorsal horn neurons (central sensitization). We postulate that activation of ionotropic and metabotropic receptors by C-fiber nociceptor afferents activates ERK via both PKA and PKC, and that this contributes to central sensitization through post-translational and CREB-mediated transcriptional regulation in dorsal horn neurons.
Theta-Modulated Place-by-Direction Cells in the Hippocampal Formation in the Rat
Authors: Cacucci Francesca , Lever Colin , Wills Thomas J. , Burgess Neil , O'Keefe John
Published: September 2004

We report the spatial and temporal properties of a class of cells termed theta-modulated place-by-direction (TPD) cells recorded from the presubicular and parasubicular cortices of the rat. The firing characteristics of TPD cells in open-field enclosures were compared with those of the following two other well characterized cell classes in the hippocampal formation: place and head-direction cells. Unlike place cells, which code only for the animal's location, or head-direction cells, which code only for the animal's directional heading, TPD cells code for both the location and the head direction of the animal. Their firing is also strongly theta modulated, firing primarily at the negative-to-positive phase of the locally recorded theta wave. TPD theta modulation is significantly stronger than that of place cells. In contrast, the firing of head-direction cells is not modulated by theta at all. In repeated exposures to the same environment, the locational and directional signals of TPD cells are stable. When recorded in different environments, TPD locational and directional fields can uncouple, with the locational field shifting unpredictably (“remapping”), whereas the directional preference remains similar across environments.
Electrophysiological Properties of Mutant Nav1.7 Sodium Channels in a Painful Inherited Neuropathy
Authors: Cummins Theodore R. , Dib-Hajj Sulayman D. , Waxman Stephen G.
Published: September 2004

Although the physiological basis of erythermalgia, an autosomal dominant painful neuropathy characterized by redness of the skin and intermittent burning sensation of extremities, is not known, two mutations of Nav1.7, a sodium channel that produces a tetrodotoxin-sensitive, fast-inactivating current that is preferentially expressed in dorsal root ganglia (DRG) and sympathetic ganglia neurons, have recently been identified in patients with primary erythermalgia. Nav1.7 is preferentially expressed in small-diameter DRG neurons, most of which are nociceptors, and is characterized by slow recovery from inactivation and by slow closed-state inactivation that results in relatively large responses to small, subthreshold depolarizations. Here we show that these mutations in Nav1.7 produce a hyperpolarizing shift in activation and slow deactivation. We also show that these mutations cause an increase in amplitude of the current produced by Nav1.7 in response to slow, small depolarizations. These observations provide the first demonstration of altered sodium channel function associated with an inherited painful neuropathy and suggest that these physiological changes, which confer hyperexcitability on peripheral sensory and sympathetic neurons, contribute to symptom production in hereditary erythermalgia.
Phosphatidylinositol 3-Kinase Activates ERK in Primary Sensory Neurons and Mediates Inflammatory Heat Hyperalgesia through TRPV1 Sensitization
Authors: Zhuang Zhi-Ye , Xu Haoxing , Clapham David E. , Ji Ru-Rong
Published: September 2004

Although the PI3K (phosphatidylinositol 3-kinase) pathway typically regulates cell growth and survival, increasing evidence indicates the involvement of this pathway in neural plasticity. It is unknown whether the PI3K pathway can mediate pain hypersensitivity. Intradermal injection of capsaicin and NGF produce heat hyperalgesia by activating their respective TRPV1 (transient receptor potential vanilloid receptor-1) and TrkA receptors on nociceptor sensory nerve terminals. We examined the activation of PI3K in primary sensory DRG neurons by these inflammatory agents and the contribution of PI3K activation to inflammatory pain. We further investigated the correlation between the PI3K and the ERK (extracellular signal-regulated protein kinase) pathway. Capsaicin and NGF induce phosphorylation of the PI3K downstream target AKT (protein kinase B), which is blocked by the PI3K inhibitors LY294002 and wortmannin, indicative of the activation of PI3K by both agents. ERK activation by capsaicin and NGF was also blocked by PI3K inhibitors. Similarly, intradermal capsaicin in rats activated PI3K and ERK in C-fiber DRG neurons and epidermal nerve fibers. Injection of PI3K or MEK (ERK kinase) inhibitors into the hindpaw attenuated capsaicin- and NGF-evoked heat hyperalgesia but did not change basal heat sensitivity. Furthermore, PI3K, but not ERK, inhibition blocked early induction of hyperalgesia. In acutely dissociated DRG neurons, the capsaicin-induced TRPV1 current was strikingly potentiated by NGF, and this potentiation was completely blocked by PI3K inhibitors and primarily suppressed by MEK inhibitors. Therefore, PI3K induces heat hyperalgesia, possibly by regulating TRPV1 activity, in an ERK-dependent manner. The PI3K pathway also appears to play a role that is distinct from ERK by regulating the early onset of inflammatory pain.
Organic Crystal Structure Analysis and Prediction
Authors: Gavezzotti Angelo , Price Sarah L.
Published: September 2004

Organic crystals are central to the pharmaceutical, energetic, and specialty chemicals industries, and so a computational approach to predicting organic crystal structures and their properties has the potential for playing a major role in the design of new organic materials. In recent years, considerable progress has been made toward this end, moving from studies on rigid hydrocarbons to molecules with an increasing range of polar functional groups, as models for the intermolecular forces have become more realistic. Conformational flexibility produces additional challenges, as do the small energy differences between different observed crystal structures. Nevertheless, the path to more accurate thermodynamic and static property predictions is established, and the main fundamental barrier to organic crystal structure prediction is in the kinetic factors that control crystallization.
Natural Transition Orbitals
Authors: Batista Enrique R. , Martin Richard L.
Published: September 2004

The result of a calculation of excited states, be it via configuration interaction methods or density functional response theory, is a set of coefficients describing the contribution that individual orbital excitations make to the total transition. Often times, there is no dominant amplitude describing the transition, making its qualitative description difficult. Natural transition orbitals dramatically simplify the situation by providing a compact representation of the transition density matrix. This is accomplished using the corresponding orbital transformation of Amos and Hall, which renders the transition density matrix diagonal and provides a unique correspondence between the excited ‘particle’ and empty ‘hole’.
MCSTEP‐ A Multiconfigurational‐based Spin Adapted Electron Propagator Approach for Ionization Potentials and Electron Affinities
Authors: Yeager Danny L.
Published: September 2004

With electron propagator (also known assingle particle Green's function) techniques, electron removal and attachment energies are calculated directly. This avoids the sometimes inaccurate process of separately determining the total electronic energies of the neutral and ionic state and subtracting one large number from another to obtain a relatively small value, that is, the ionization potential (IP) or electron affinity (EA) of a molecule. Traditionally, these electron propagator methods used a single determinant wave function as the ‘zero order’ initial state, which was improved with Møller–Plesset perturbation theory. Although these usual perturbative electron propagator methods have been very successful, they are limited in applicability. Usual perturbative approaches usually cannot handle reliably (or at all) systems with initial states that are open shell and/or highly correlated (nondynamical correlation) for either IPs or EAs.

We specifically designed the multiconfigurational spin tensor electron propagator method (MCSTEP) and its predecessor the multiconfigurational electron propagator (MCEP) method to provide accurate IPs and EAs for systems that cannot be accurately handled by usual perturbational approaches to single particle Green's function methods, namely, when the initial state is open shell and/or has nondynamical correlation that must be accounted for. In addition, of course, the goal is to also be able to provide accurate IPs and EAs for systems with closed shell initial states without nondynamical correlation, that is, those systems that could be handled as well by usual perturbational electron propagator methods.

In this article, I will first review the theory behind the multiconfigurational spin tensor electron propagator method. Since the introduction of MCSTEP over 15 years ago, several accurate MCSTEP atomic and molecular IPs and EAs have been determined. I will summarize several of the more significant calculations to date.

An electron propagator method using a multiconfigurational second‐order perturbation theory wave function as the initial state in the fermion operator block (block 1) in the MCSTEP matrix equations was initially developed by Heryadi and Yeager. In the other blocks, an MCSCF wave function is the initial state. This new method is called EPCASPT2 and should be viewed as an extension of MCSTEP. In this article, we will review the theory behind EPCASPT2 and some of the recent calculations done using a CASPT2 wave function as the initial state in the electron propagator. We compare our results with the results of the calculations using multiconfigurational spin tensor electron propagator, full configuration interaction, and for the molecules, the multireference configuration interaction method with the same geometries and basis sets.
Aza‐Baylis–Hillman Reaction of β‐Substituted Activated Olefins with N‐Tosyl Imines
Authors: Shi Yong‐Ling , Xu Yong‐Mei , Shi Min
Published: September 2004

Aza‐Baylis–Hillman reactions of β‐substituted activated olefins such as crotonaldehyde, (E)‐propenyl phenyl ketone, hex‐2‐enal or pent‐3‐en‐2‐one with N‐tosyl imines can be carried out for the first time in the presence of tertiary phosphine Lewis bases such as PPh2Me or PPhMe2 to give the corresponding Baylis–Hillman adducts in moderate to good yields under mild reaction conditions.
Scale‐Up Studies for the Asymmetric Juliá–Colonna Epoxidation Reaction
Authors: Gerlach Arne , Geller Thomas
Published: September 2004

The asymmetric Juliá–Colonna epoxidation reaction under triphasic/PTC conditions has been successfully scaled‐up to a one‐hundred gram substrate level providing the corresponding epoxy ketone with high optical purity (up to 97% ee) and in good yield (75–78%). The amount of polyamino acid catalyst could be reduced leading to a simplified reaction work‐up. In order to minimise the overall reaction time baffled reactors with pitched‐blade impellers have been employed.
Polystyrene‐Anchored Cinchona Ammonium Salts: Easily Recoverable Phase‐Transfer Catalysts for the Asymmetric Synthesis of α‐Amino Acids
Authors: Chinchilla Rafael , Mazón Patricia , Nájera Carmen
Published: September 2004

Cinchonidine, epicinchonidine, cinchonine or quinine have been N‐anchored to cross‐linked polystyrene (Merrifield resin) or grafted polystyrene (SynPhaseTM Lanterns) affording polymer‐supported chiral ammonium salts which are employed as phase‐transfer catalysts in the asymmetric alkylation of N‐(diphenylmethylene)glycine esters. These new polymeric catalysts can be easily recovered after the reaction by simple filtration and reused.
anti‐Selective Asymmetric Synthesis of β‐Hydroxy‐α‐amino Acid Esters by the in situ Generated Chiral Quaternary Ammonium Fluoride‐Catalyzed Mukaiyama‐Type Aldol Reaction
Authors: Ooi Takashi , Taniguchi Mika , Doda Kanae , Maruoka Keiji
Published: September 2004

The aldol coupling of ketene silyl acetal 2 derived from the glycinate Schiff base with aldehydes can be efficiently catalyzed by an in situ generated, chiral quaternary ammonium fluoride of type 1 under mild, neutral conditions, affording the corresponding anti‐β‐hydroxy‐α‐amino esters predominantly with excellent enantioselectivities.
Highly Enantio‐ and Diastereoselective Organocatalytic Domino Michael‐Aldol Reactions of β‐Diketone and β‐Ketosulfone Nucleophiles with α,β‐Unsaturated Ketones
Authors: Pulkkinen Juha , Aburel Pompiliu S. , Halland Nis , Jørgensen Karl Anker
Published: September 2004

A chiral imidazolidine catalyst was shown to catalyze the highly enantio‐ and diastereoselective domino Michael‐aldol reaction of β‐diketone and β‐ketosulfone derivatives with α,β‐unsaturated ketones to form optically active cyclohexanones having three or four contiguous chiral centers. The Michael‐aldol adducts were formed as single diastereomers in up 99% ee.
The Development of the Asymmetric Morita—Baylis—Hillman Reaction Catalyzed by Chiral Brønsted Acids
Authors: McDougal Nolan T. , Trevellini Whitney L. , Rodgen Stacy A. , Kliman Laura T. , Schaus Scott E.
Published: September 2004

This report describes the development of a chiral Brønsted acid‐catalyzed asymmetric Morita–BaylisHillman (MBH) reaction of cyclohexenone with aldehydes. During the course of our studies on chiral Lewis acid‐promoted MBH reactions, we discovered that chiral binaphthol‐derived Brønsted acids serve as promoters of the asymmetric MBH reaction. We propose that the phosphonium enolate of cyclohexenone is stabilized via hydrogen‐bonding with the binaphthol‐derived Brønsted acid, creating a chiral nucleophile. A practical and efficient set of conditions was developed using stoichiometric PEt3 as the nucleophilic promoter and catalytic amounts of a binaphthol‐derived Brønsted acid to effect the reaction of cyclohexenone with various aliphatic and aromatic aldehydes in good yields and enantiomeric excesses (up to 96% ee).
Proline‐Derived N‐Sulfonylcarboxamides: Readily Available, Highly Enantioselective and Versatile Catalysts for Direct Aldol Reactions
Authors: Berkessel Albrecht , Koch Burkhard , Lex Johann
Published: September 2004

Proline catalysis of the asymmetric direct aldol reaction involves both the secondary amine function and the carboxyl group of the amino acid. N‐Sulfonylcarboxamides are known to be of similar acidity as carboxylic acids, and three N‐arylsulfonyl derivatives of L‐proline amide were synthesized as functionalized and versatile derivatives of L‐Pro. Their catalytic performance was evaluated in the direct aldol addition of acetone to 4‐nitrobenzaldehyde. Significantly improved reactivities and enantioselectivities were achieved in various solvents at low catalyst loadings (5–10 mol %) and at room temperature, with ees ranging up to 98%, whereas L‐proline itself afforded a maximum ee of 80% (in DMSO). Thus, N‐arylsulfonyl derivatives of proline amide represent a novel class of highly enantioselective catalysts for direct aldol reactions. Furthermore, the N‐arylsulfonyl substituent suggests possibilities for incorporation into larger catalyst assemblies (including immobilization) without affecting the catalytically active functional groups.
Catalysis of the Hajos—Parrish—Eder—Sauer—Wiechert Reaction by cis‐ and trans‐4,5‐Methanoprolines: Sensitivity of Proline Catalysis to Pyrrolidine Ring Conformation
Authors: Cheong Paul Ha‐Yeon , Houk K. N. , Warrier Jayakumar S. , Hanessian Stephen
Published: September 2004

Methanoprolines are found to be catalysts for the Hajos–Parrish–Eder–Sauer–Wiechert reaction.[1] cis‐4,5‐Methanoproline exhibits catalytic ability similar to proline (86% yield, 93% ee), whereas the trans‐4,5‐methanoproline is less selective (67% yield, 83% ee) and shows less acceleration. The reaction was also studied with hybrid density functional theory (B3LYP). The nearly planar cis‐4,5‐methanoproline amine better reflects the planar iminium of the transition states than the pyramidalized trans‐4,5‐methanoproline. This difference in conformation is responsible for the observed higher enantioselectivity and enhanced catalytic behavior of the cis‐4,5‐methanoproline.
A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10
Authors: Shimizu Satoko , Krafchak Charles , Fuse Nobuo , Epstein Michael P. , Schteingart Miriam T. , Sugar Alan , Eibschitz‐Tsimhoni Maya , Downs Catherine A. , Rozsa Frank , Trager Edward H. , Reed David M. , Boehnke Michael , Moroi Sayoko E. , Richards Julia E.
Published: September 2004

Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant disorder characterized by corneal endothelial abnormalities, which can lead to blindness due to loss of corneal transparency and sometimes glaucoma. We mapped a new locus responsible for PPCD in a family in which we excluded the previously reported PPCD locus on 20q11, and the region containing COL8A2 on chromosome 1. Results of a 317‐marker genome scan provided significant evidence of linkage of PPCD to markers on chromosome 10, with single‐point LOD scores of 2.63, 1.63, and 3.19 for markers D10S208 (at $\hat \theta = 0.03$), D10S1780 (at $\hat \theta = 0.00$), and D10S578 (at $\hat \theta = 0.06$). A maximum multi‐point LOD score of 4.35 was found at marker D10S1780. Affected family members shared a haplotype in an 8.55 cM critical interval that was bounded by markers D10S213 and D10S578. Our finding of another PPCD locus, PPCD3, on chromosome 10 indicates that PPCD is genetically heterogeneous. Guttae, a common corneal finding sometimes observed along with PPCD, were found among both affected and unaffected members of the proband's sib ship, but were absent in the younger generations of the family. Evaluation of phenotypic differences between family members sharing the same affected haplotype raises questions about whether differences in disease severity, including differences in response to surgical interventions, could be due to genetic background or other factors independent of the PPCD3 locus. © 2004 Wiley‐Liss, Inc.