Search

BWL acknowledges the Royal Society for a University Research Fellowship We show that the state of a flying qubit may be transferred to a chain of identical, (near) ferromagnetically polarized, but non-interacting, static spin-1/2 particles in a passive way. During this process the flying qubit is coherently polarized, emerging in the direction of the majority static spins. We conjecture that this process is reversible for any number of flying qubits injected sequentially in an arbitrary superposition state, proving this explicitly for an arbitrary state of one and two flying qubits. We also find a special case in which we are able to prove the conjecture for an arbitrary number of qubits. Our architecture thus has the potential to be exploited as a passive quantum memory to encode the flying qubits without the necessity of resetting between successive encoding operations. We also illustrate that the quantum information may be spread over many static spins in the memory chain, making the mechanism resistant to spin decoherence and other imperfections. We discuss implementing the memory system with trapped bosonic atoms, controlled by a spatial light modulator. Publisher PDF

Urea in mouse urine results from the normal breakdown and use of protein. A variation in its content may indicate a change in the way the mouse's metabolism, liver, and kidney are functioning. To demonstrate the feasibility of using FTIR–IR cards for urine urea analysis, urine samples were obtained from two control females and four pregnant mice during their pregnancy. An internal standard, potassium thiocyanate (KSCN), was added to each of the urine samples in a 3:1 ratio. Dry urea/KSCN films were obtained by spreading the urine/KSCN samples onto the polyethylene windows of the IR cards. Sample transmission spectra were obtained using a Genesis II FTIR spectrometer (Mattson). Urea content was indicated by the ratio of the peak due to urea at 3458 cm−1 to the peak due to KSCN at 2060 cm−1. The urea molarities were determined based on a FTIR analysis of a set of standard urea/KSCN solutions. Results showed that the urea content remained at a constant level for the control mice: (3.9 ± 0.2) M for c...

Opioid peptides exert their regulatory effects on both central and pheripheral nervous systems via multiple opioid receptors that are linked to seemingly identical sets of guanine nucleotide-binding regulatory proteins (G proteins). In contrast to the μ-opioid receptor, the δ-opioid receptor can efficiently stimulate phospholipase C via G16. We used a series of μ/δ-opioid receptor chimeras to examine the involvement of intracellular receptor domains in the recognition of G16. After ascertaining that the chimeras can bind opioid ligands with high affinity and elicit inhibition of adenylyl cyclase, COS-7 cells were cotransfected with cDNAs encoding Gα16 and a μ/δ-opioid receptor chimera and assayed for [d-Ala2,d-Leu5]enkephalin-induced stimulation of phospholipase C. Our results indicate that (i) the carboxy terminal tail of the δ-opioid receptor is necessary but insufficient for conferring coupling to Gα16, (ii) the third inner loop together with the carboxy terminal tail of the δ-opioid receptor can provide sufficient contact domains for Gα16, and (iii) the first inner loop of the δ-opioid receptor, in particular Leu80, as well as the fifth transmembrane domain and/or the third extracellular loop may also contribute in defining the fidelity of interaction between the δ-opioid receptor and Gα16. These results indicate that efficient coupling of the δ-opioid receptor to Gα16 requires the participation of most of the intracellular regions, including the first intracellular loop.

The neuroprotective properties of topiramate were evaluated in a rat model of stroke in which neurodegeneration was induced by temporary global ischemia. In this model, the ischemia resulted from 11 min of cardiac arrest during atraumatic chest compression. Resuscitated rats exhibit a characteristic neurological syndrome characterized by sound-induced convulsions, specific motor and behavioral deficits, and death of hippocampal CA1 pyramidal neurons. Topiramate, when administered i.v. 30 min after resuscitation, reduced the degree of motor impairment (P0.05 vs control at doses of 10 and 20 mg/kg) and seizure severity (P0.05 vs control at a dose of 10 mg/kg on the fifth recovery day). The highest dose of topiramate (20 mg/kg i.v.) eliminated nearly all histologic signs of hippocampal ischemic neuronal injury (P0.001). Phenytoin at 20 mg/kg i.v. exhibited neuroprotectant effects similar to those observed for topiramate at 20 mg/kg i.v.. In normal rats, neither topiramate nor phenytoin at 20 mg/kg i.v. induced any apparent neurological impairment; however, at 40 and 60 mg/kg i.v. both induced a mild impairment typical of most anticonvulsants. The results of this study support the concept that topiramate possesses neuroprotective properties.

Affinity labels have proven to be useful tools in opioid research. We review experiments carried out with the mu opioid receptor affinity label, beta-funaltrexamine (2), that support the concept of different recognition sites for mu opioid agonists and antagonists. The data are interpreted in the context of a dimeric receptor that contains two allosterically coupled binding sites: one that binds endogenous agonist, and the second that functions as an inhibitory modulator of agonism. It is proposed that exogenous antagonists bind selectively to the second site. The first of a new class of affinity labels, PGNA (5), that contains the phthaldehyde moiety attached to an opioid antagonist pharmacophore, is described. This class of ligands has been named 'reporter affinity labels' because covalent association leads to the formation of a fluorescent isoindole that is diagnostic for cross-linking of lysine and cysteine residues. PGNA binds opioid receptors covalently, as suggested by (a) irreversible binding to cloned opioid receptors, (b) irreversible opioid antagonism in the guinea pig ileum preparation, and (c) ultra-long opioid antagonism in mice. Since flow cytometry experiments revealed specific enhancement of fluorescence in cloned mu receptors after a 1 min exposure to 5, it is concluded that covalent binding has occurred via the formation of an isoindole, presumably by cross-linking neighboring lysine and cysteine residues in the vicinity of the receptor recognition site.

The ability of the body to respond to changes in oxygen (O 2 ) is an integral part of both fetal development and adaptation to environmental hypoxia. Oxygen sensing is mediated by the homeostatic oxygen sensing system, which includes structures such as the resistance pulmonary arteries (PA), ductus arteriosus, carotid bodies and neuroepithelial bodies that function together to improve oxygen uptake and delivery. Within the PA, hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion to ventilation, whereas systemic arteries dilate during hypoxia. It is hypothesized that subunit(s) of the mitochondrial electron transport chain (ETC) serve as a redox-sensitive O 2 sensor, and modulate vascular tone via release of reactive oxygen species (ROS). However, the identity of the specific subunits within the megacomplexes that accounts for O 2 sensing remains elusive. Hence, the ETC composition and function of mitochondria from rat pulmonary and renal artery (RA) smooth muscle cells (SMC) were compared. Relative to RASMC, PASMC exhibit increased Complex I activity under both normoxic and hypoxic conditions. Mass spectrometry analysis and gene expression array have identified seven candidate proteins/subunits within the mitochondrion and electron transport chain that are differentially expressed between PASMC and RASMC, including iron-sulfur subunits of Complexes I and III, and uncoupling proteins UCP2 and UCP3. We also measured hydrogen peroxide (H 2 O 2 ) flux in PASMC during the acute hypoxic response using a pH-sensitive, H 2 O 2 -specific vector under flow conditions, with increased intracellular calcium as a marker of vasoconstriction. Upon exposure to hypoxia, H 2 O 2 levels decrease immediately prior to the increase in intracellular calcium, supporting the theory that a decrease in mitochondrial ROS, and specifically H 2 O 2 , during hypoxia is the cellular signal mediating HPV. Further experiments aim to confirm the identity of the mitochondrial oxygen sensor using gene knockdown/silencing of candidate proteins. Identification of specific components of the oxygen sensing system may identify therapeutic targets for diseases in which oxygen-sensing is disordered, such as pulmonary arterial hypertension, chronic altitude sickness and chronic obstructive pulmonary disease.

This article describes an on-campus celebration program for National Chemistry Week (NCW) at the University of Pittsburgh at Titusville (UPT). The program, consisting of a chemistry magic show, hands-on chemistry fun, and a poster display session, was presented free of charge to the public on the Saturday of NCW. Presenting the program on campus avoided the transportation of the necessary materials, allowed the incorporation of many interesting demonstrations, and provided an opportunity for the school to showcase its state-of-the-art facilities. The program reached the public through different media, such as flyers, newspapes, and TV and radio. Over 100 people of all ages from the local community participated in the program. One of the most successful characteristics of the program was the substantial involvement of college students taking chemistry classes. Directly doing or seeing various reactions that involved changes in color or production of sound, heat, or light was stimulating and memorable. Many student participants became chemistry club members right after the events and were excited about more opportunities to explore the world of chemistry. This article also described activities highlighting the theme of NCW 1999, “Celebrating Polymers.”

Affinity chromatography using immobilized S-protein was used for the screening of affinity peptide ligands from two soluble peptide libraries. Peptide library I consisted of octamers with glycine (G) at both termini of each peptide, i.e. GXXXXXXG. The six center positions were constructed using random sequences of six L-amino acids (Y, N, F, E, V, and L). Peptide library II also consisted of octamers but with glycine and valine (V) at both termini of each peptide (GVZZZZVG). The four variable center positions of peptide library II were random sequences of 18 L-amino acids. Peptides that were retained specifically on the immobilized S-protein column were eluted by 2% acetic acid. The peptides in the acid eluate were further separated using reversed-phase HPLC. Each separated peptide fraction was collected and the peptide sequences deconvoluted by mass spectrometry (MS/MS). The screenings of peptide libraries I and II resulted in 12 and 7 affinity peptides, respectively. Eight out of the twelve peptides from peptide library I contained the clear consensus sequence NFEV. Peptide library II resulted in affinity peptides with the sequences GVNFEVVG, GVNFTVVG and GVFFEL(I)VG. The advantages and limitations of affinity chromatography in peptide library screening are discussed.

Chronic exposure of mu-and delta-opioid receptors to their agonists leads to different rates in receptor down-regulation. In order to analyze the role of the carboxyl terminus of mu-and delta-opioid receptors in the difference in the rate of down-regulation, two chimeras of these receptors were generated by swapping the carboxyl termini; MORTAGDT and DORTAGMT. These chimeras were tagged at the N-terminus with hemagglutinin (HA) epitope (YPYDVPDYA), which can be recognized by the monoclonal antibody 12CA5, and then stably expressed in Neuro 2A (N2A) cells. The swapping of the carboxyl termini did not alter the ligand selectivity of these receptor chimeras. However, they did exhibit a reduction in agonist potency to inhibit forskolin-stimulated adenylyl cyclase activity for all agonists tested except etorphine which had a potency comparable to that of wild type receptors. Treatment of the N2A cells expressing MORTAGDT with 50 nM etorphine produced a faster rate of receptor down-regulation when compared to the wild type mu-opioid receptor. Immunofluorescence microscopy of the MORTAGDT chimera using a monoclonal antibody against HA confirmed internalization of the receptors after treatment with etorphine for 1 and 6h. There was a reduction in the HA-immunoreactivity at the cell surface of the MORTAGDT chimera concurrent with more noticeable HA-immunoreactivity inside the cell compared to the wild type receptor. On the other hand, the rate of down-regulation of DORTAGMT receptors was seen to be the same as the wild type delta-opioid receptor after etorphine treatment. Immunofluorescence studies showed more reduction in cell surface staining of the DORTAGMT chimera compared to the wild type receptor. These data suggest the involvement of the carboxyl terminus in agonist-induced down-regulation and internalization of the nu-opioid receptor. However, different mechanisms that are unrelated to the carboxyl terminus may operate in the down-regulation of delta-opioid receptor.

Previous proton NMR and electronic spectroscopy studies have demonstrated that the square-planar complex of Ni(II) and 1,4,8,11-tetraazacyclotetradecane (cyclam) exists in two stable isomeric conformations, namely the R,S,R,S form or trans-I isomer and the R,R,S,S form or trans-III isomer. Electrochemical analysis of the trans-I isomer of Ni(II)-cyclam has demonstrated rapid conversion to the trans-III cyclam conformation following oxidation to Ni(III). The mechanism and kinetics for this oxidatively-induced isomerization were studied by the technique of cyclic voltammetry (CV) with simulation of CV traces by finite-difference computations. The most crucial mechanistic indicator was found to be the transient trans-I-Ni(III) species. This intermediate was detected by CV over a pH range 2-4 and was found to have an apparent half-life of ca. 400 ms at room temperature. Remarkably, this life-time was approximately a billionfold shorter than the corresponding trans-I-Ni(II) species. Measurements made at varied solution temperature and pH demonstrated that the oxidatively induced isomerization followed an apparent square-scheme, where the trans-I/III isomerization process of Ni(III) was independent of pH. This finding precluded a base-catalyzed isomerization process that has been previously identified for the Ni(II) system. Arrhenius plots of the forward isomerization rate constant allowed the extraction of activation parameters for the Ni(III) process. These parameters are discussed with respect to possible rate-determining steps.

Addition of a range of nucleophiles to arene-manganese tricarbonyl complexes, carrying a chiral non-racemic 2,5-dimethylpyrrolidine substituent, results in diastereomeric excesses of up to 94%. Dependence of the level of asymmetric induction on reactivity and steric bulk of the nucleophile is observed, revealing a rather complex set of controlling factors for the reaction.

The coming occultation observational program in Purple Mountain Observatory will be introduced.

Topiramate, a structurally novel anticonvulsant, and phenytoin were evaluated in a rat model of ischemia-induced epilepsy. In this model a transient global cerebral ischemia is induced by cardiac compression. By precisely controlling the experimental conditions the procedure causes reproducible neurological deficits that include audiogenic epileptic seizures. The seizures can be broadly separated into three types reflecting the degree of severity: wild running, clonic seizures, and tonic extension seizures of the forelimbs and hindlimbs. Topiramate and phenytoin blocked all three types of seizures. Calculated ED50 values for topiramate 1 hr after oral administration were 8.2, 13.0 and 36.1 mg/kg for blockade of tonic extension seizures, clonic seizures and wild running, respectively. Corresponding ED50 values for phenytoin were 5.0, 10.8 and 20.7 mg/kg. These results support the concept that the anticonvulsant activity of these drugs is due primarily to an ability to block the spread of seizures.

Peptide libraries can be used to identify ligands that bind specifically to a desired protein. These peptides may have significant advantages as specific ligands for affinity chromatography separations. This article describes the use of one of such peptide, Try-Asn-Phe-Glu-Val-Leu, as a ligand for the purification of S-protein using affinity chromatography. General strategies for peptide immobilization are discussed and the conditions for peptide immobilization to Emphazetrade mark gel are optimized. The effects of peptide orientation and peptide densities on protein binding are studied. Results indicate that the peptide affinity is not affected by the orientation of the peptide during immobilization, but association constants can be reduced by one order of magnitude when compared with the values in solution.With increased peptide density, the protein binding capacity of the gel increases, but both the percentage of peptide utilization and apparent binding constant between immobilized peptide and S-protein decrease. S-protein is separated from a mixture with BSA via affinity chromatography using specific elution with the peptide in solution.Finally, direct purification of S-protein from an enzymatic digestion mixture of ribonuclease A is demonstrated.(c) 1995 John WileySons, Inc.

The cloning of receptors for neuropeptides made possible studies that identified the neurons that utilize these receptors. In situ hybridization can detect transcripts that encode receptors and thereby identify the cells responsible for their expression, whereas immunocytochemistry enables one to determine the region of the plasma membrane where the receptor is located. We produced antibodies to portions of the predicted amino acid sequences of delta, mu, and kappa opioid receptors and used them in combination with antibodies to a variety of neurotransmitters in multicolor immunofluorescence studies visualized by confocal microscopy. Several findings are notable: First, the cloned delta opioid receptor appears to be distributed primarily in axons, and therefore most likely functions in a presynaptic manner. Second, the cloned mu and kappa opioid receptors are found associated with neuronal plasma membranes of dendrites and cell bodies and therefore most likely function in a postsynaptic manner. However, in certain, discrete populations of neurons, mu and kappa opioid receptors appear to be distributed in axons. Third, enkephalin-containing terminals are often found in close proximity (although not necessarily synaptically linked) to membranes containing either the delta or mu opioid receptors, whereas dynorphin-containing terminals are often found in proximity to kappa opioid receptors. Finally, a substantial mismatch between opioid receptors and their endogenous ligands was observed in some brain regions. However, this mismatch was characterized by complementary zones of receptor and ligand, suggesting underlying principles of organization that underlie long-distance, nonsynaptic neurotransmission.

We have recently developed antisera which recognize epitopes of the cloned delta-opioid receptor (DOR; Dado et al., 1993). In the present report we have further characterized these antisera, and raised additional antisera in rats. We used these antisera to determine the distribution of DOR-like immunoreactivity (-Ll) in rat spinal cord and brainstem in relation to serotoninergic, noradrenergic, and enkephalinergic neurons. We found DOR-Ll in fibers and varicosities distributed throughout the spinal cord gray matter, with highest densities in the superficial dorsal horn, in autonomic regions, around the central canal as well as in the ventral horn motor nuclei. In the brainstem a dense innervation of DOR-immunoreactive (-IR) fibers was found in several nuclei such as spinal trigeminal nuclei, midline raphe nuclei, parabrachial nuclei, periaqueductal gray matter (PAG), interpeduncular nucleus, ans substantia nigra. A group of DOR-positive cells was seen in the laterodorsal tegmental nucleus. In addition, a few DOR-IR cell bodies were demonstrated in the parabrachial nuclei, interpeduncular nucleus, PAG, and superior and inferior colliculi as well as around the central canal in the spinal cord. All DOR-positive cells showed a punctuate staining pattern within the cytoplasm of the cell body and in primary dendrites. No plasma membrane staining of cells or dendrites could be demonstrated using the DOR antisera. Double- labeling experiments for DOR and 5-hydroxytryptamine (5HT, serotonin) revealed that some 5HT-IR neurons in the raphe complex were surrounded by DOR-IR fibers. In the spinal cord a high degree of coexistence was found between DOR and 5HT in nerve fibers and varicosities in the neuropil around the motoneurons and in lamina V of the dorsal horn. In autonomic regions of the spinal cord, a low degree of colocalization was seen between DOR and 5HT; in the superficial dorsal horn no coexistence was found. Tyrosine hydroxylase (TH)-positive neurons in the brainstem (in the A5 area, locus coeruleus, and A7 area) were apposed by DOR-positive fibers. However, no coexistence could be seen between DOR and TH in any part of the spinal cord. A close relation, but no coexistence, was observed between DOR- and enkephalin (ENK)-IR fibers in the spinal cord ventral horn; in the intermediolateral nucleus a low degree of colocalization was observed. Thus, a delta- opioid receptor may affect the activity of descending serotoninergic and noradrenergic neurons by means of modulating the release of neurotransmitters from afferents to these neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Background RNA interference targeting RelB can significantly attenuate ischemia/reperfusion (I/R)-induced renal dysfunction, but its roles in liver I/R injury remain to be defined. We have investigated whether siRNA targeting of RelB in liver could also elicit protection against I/R injury. Materials and methods A RelB miRNA RNAi expression plasmid, a scrambled plasmid, or phosphate-buffered saline (50 μg of the plasmid diluted in phosphate-buffered saline, 8% wt/vol) were rapidly injected, within 6–8 s, into mouse tail veins 24 h before liver I/R. Mice were subjected to 30 min of 70% hepatic ischemia or to a sham operation. Six h after reperfusion, blood and liver tissue samples were collected for subsequent assays. Results The expression level of RelB was reduced in the RelB RNAi group compared with the control group, while it was increased in the I/R group. In the sham group, malondialdehyde, myeloperoxidase (MPO), and superoxide dismutase serum levels were almost the same, but the alanine aminotransferase level in the untreated group was 20- to 25-fold lower than in the other groups. In I/R-treated mice, although alanine aminotransferase, malondialdehyde, and MPO serum levels in the RelB RNAi group were lower than in other groups, all were higher than in the sham group. Silencing RelB could inhibit the decrease of superoxide dismutase activity and the upregulation of MPO and tumor necrosis factor α induced by I/R injury. Conclusions Silencing RelB can protect the liver against I/R-induced damage. Therefore, it is a promising therapeutic target for protection against I/R injury in the liver.

With the rapid development of electromagnetic launch technology, the performance requirements for the charging power supply are increasing. To control the charging rate accurately and get the steady load voltage, a phase-shift control system was designed. This system adopted the control method which regulates the phase angles of the driving pulses by calculating the relationship of the voltage feedback and the preset charging time. According to the topology and application requirements of high-voltage high-frequency charging power supply (HVHFCPS), the simulation platform based on the PSIM software was set up. A prototype of HVHFCPS based on voltage feedback and phase-shift control was developed. The experimental results shown that the load voltage can be controlled accurately.

A rat brain cDNA library was screened for clones homologous to the recently cloned mouse delta-opioid receptor (DOR-1). Among the clones isolated was Hyp 8-1, a clone with a unique nucleotide sequence capable of encoding a putative protein which is 57-58% identical to the amino acid sequences of the cloned delta, mu and kappa opioid receptors, indicating a close relationship of Hyp 8-1 with the opioid receptor family. Several cDNAs representing possible splice variants of Hyp 8-1 were also isolated. Binding studies of COS-7 cells transfected with clone Hyp 8-1 failed to demonstrate specific binding with several 3H-opioid ligands. In situ hybridization studies indicate that the mRNA for Hyp 8-1 is distributed discretely throughout the rat brain, in an overall pattern which is different from that of several other G-protein-coupled seven transmembrane receptors. Thus, it is likely that the Hyp 8-1 cDNA encodes a novel peptide receptor.

Free radical injury to cremater muscle and pial venules was studied by intravital videomicroscopy. Insult was induced by photoactivation (mercury light, 25 lm/cm 2 at 570 nm) of intravascular rose bengal. The protective effects of flunarizine (25, 100 and 400 μ g/kg, i.v.) vs. its cyclodextrine solvent (100 mg/kg) and isovolemic saline (control) were assessed. Observations at 30 min postinsult showed that the flunarizine-treated groups had higher cremaster venular patency rates than the control group ( P μ g/kg flunarizine-treated group had a significantly higher ( P P μ g/kg, i.v.) pretreatment than without. This study characterizes the nature and time-course of free-radical-induced microvascular damage and demonstrates the protective action of flunarizine.

Background Ischemic postconditioning (IPO) has been demonstrated to attenuate ischemia/reperfusion (I/R) injury in the heart and brain, its roles to liver remain to be defined. The study was undertaken to determine if IPO would attenuate liver warm I/R injury and its protective mechanism. Methods Mice were divided into sham, I/R, IPO+I/R (occlusing the porta hepatis for 60 min, then treated for three cycles of 10 sec brief reperfusion consecutively, followed by a persistent reperfusion); L-NAME+ sham (L-NAME, 16 mg/kg, i.v., 5 min before repefusion); L-NAME+I/R; and L-NAME+ IPO. Blood flow of caudate and left lobe of the liver was blocked. Functional and morphologic changes of livers were evaluated. Contents of nitric oxide, eNOS and iNOS in serum were assayed. Concentration of eNOS, iNOS, malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in hepatic tissue were also measured. Expressions of Akt, p-Akt and HIF-1α protein were determined by western blot. Expressions of TNF-α and ICAM-1 were measured by immunohistochemistry and RT-PCR. Results IPO attenuated the dramatically functional and morphological injuries. The levels of ALT was significantly reduced in IPO+I/R group (p < 0.05). Contents of nitric oxide and eNOS in serum were increased in the IPO+I/R group (p < 0.05). IPO also up-regulated the concentration of eNOS, activity of SOD in hepatic tissue (p < 0.05), while reduced the concentration of MDA (p < 0.05). Moreover, protein expressions of HIF-1α and p-Akt were markedly enhanced in IPO+I/R group. Protein and mRNA expression of TNF-α and ICAM-1 were markedly suppressed by IPO (p < 0.05). These protective effects of IPO could be abolished by L-NAME. Conclusions We found that IPO increased the content of NO and attenuated the overproduction of ROS and I/R-induced inflammation. Increased NO contents may contribute to increasing HIF-1α level, and HIF-1α and NO would simultaneously protect liver from I/R injury. These findings suggested IPO may have the therapeutic potential through Akt-eNOS-NO-HIF pathway for the better management of liver I/R injury.

A team of University of Alberta researchers, in collaboration with an international team of investigators, has spearheaded an experiment to study the generation and transport of MeV electrons produced by ultra-high intensity second harmonic Nd:Glass laser pulses. Intensities of up to 5 x I O’ 9 W cm2 have been used to irradiate a variety of targets to investigate the conversion efficiency into MeV energy electrons, as well as the energy spectrum and angular divergence of such electrons. Their transport through a cone tip simulating the generation of an energetic electron beam for the fast ignition of a laser-compressed fuel core was also measured. The experiments were carried out at the Titan high intensity 1aser facility located at the Lawrence Livermore National Laboratory. The experiment is the first step towards evaluating the potential effectiveness of using prepulse-free shorter wavelength second harmonic laser pulses as ignition sources for Fast Ignition Fusion Energy.

Affinity labels have proven to be useful tools in opioid research. We review experiments carried out with the mu opioid receptor affinity label, beta-funaltrexamine (2), that support the concept of different recognition sites for mu opioid agonists and antagonists. The data are interpreted in the context of a dimeric receptor that contains two allosterically coupled binding sites: one that binds endogenous agonist, and the second that functions as an inhibitory modulator of agonism. It is proposed that exogenous antagonists bind selectively to the second site. The first of a new class of affinity labels, PGNA (5), that contains the phthaldehyde moiety attached to an opioid antagonist pharmacophore, is described. This class of ligands has been named 'reporter affinity labels' because covalent association leads to the formation of a fluorescent isoindole that is diagnostic for cross-linking of lysine and cysteine residues. PGNA binds opioid receptors covalently, as suggested by (a) irreversible binding to cloned opioid receptors, (b) irreversible opioid antagonism in the guinea pig ileum preparation, and (c) ultra-long opioid antagonism in mice. Since flow cytometry experiments revealed specific enhancement of fluorescence in cloned mu receptors after a 1 min exposure to 5, it is concluded that covalent binding has occurred via the formation of an isoindole, presumably by cross-linking neighboring lysine and cysteine residues in the vicinity of the receptor recognition site.

The G protein-coupled delta opioid receptor (DOR) plays a critical role in pain control. Emerging evidence shows that DOR also plays a role in neuronal differentiation and survival. Nerve growth factor (NGF) is known to be critical for the development and maintenance of the central and peripheral nervous systems. Our previous studies have shown that sustained activation of NGF/PI3K/Akt/NF-kappaB signaling is essential for NGF-induced dor gene expression during neuronal differentiation and that the epigenetic modifications at histone 3 lysine 9 temporally correlate with the dor gene transcription. In this study, we cloned the rat dor gene promoter and identified an NGF-responsive region similar to that from the mouse dor gene promoter. We further identified p300, a known NF-kappaB binding partner with intrinsic histone acetyltransferase activity, to be dynamically associated with the dor gene. We also found that assembling of RNA polymerase II (Pol II) at the promoter took place before NGF stimulation, indicating that p300 could only interact with preassembled Pol II at the promoter after NGF stimulation. Taken together, these results implicate that preassembly of the Pol II preinitiation complex, sustained activation of PI3K/Akt/NF-kappaB signaling, and dynamic p300 association at the promoters sequentially is one of the mechanisms of induction of the late phase genes during NGF-induced neuronal differentiation.

Reactions of [cyclopentadienyl)(1,3-dichlorobenzene)M] + PF 6 - complexes (M= Fe, Ru) with phenoxide nucleophiles were found to proceed with excellent selectivity under mild conditions to give products of monosubstitution. Using aminophenoxides, a preference for O-arylation was observed, while amino alcohols such as prolinol react selectively on nitrogen. Methodology for sequential selective displacement of both chlorides by different nucleophiles is reported

A systematic method is described for the optimization of a mobile phase for the simultaneous determination of 24 neurochemicals consisting of catecholamine, serotonin, their precursors and metabolites and related materials. This mobile phase contained sodium acetate (0.04 M), citric acid (0.01 M), sodium chloride (0.0126 M), sodium octyl sulfate (91 mg/l), tetrasodium EDTA (50 mg/l) and 10% (v/v) methanol. When this optimum mobile phase was applied to the analysis of brain tissues of the Swiss male mouse, twelve neurochemicals were quantified in the free state: tyrosine, L-beta-3,4-dihydroxyphenylanine, dopamine, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylacetic acid, norepinephrine, 3-methoxy-4-hydroxyphenylglycol, DL-3,4-dihydroxymandelic acid, DL-4-hydroxy-3-methoxymandelic acid, serotonin, L-tryptophan, 5-hydroxyindole-3-acetic acid and DL-synephrine and normetanephrine, appearing as a fused peak. This fused peak was present on the chromatogram tracings of all the mouse brain tissues. The separable neurochemicals not found by this procedure in the Swiss male mouse tissues were DL-3,4-dihydroxyphenylglycol,5-hydroxytryptophan, epinephrine, DL-octopamine, metanephrine, deoxyepinephrine, homovanillyl alcohol, N-acetylserotonin, tyramine and 3-methyltyramine.

International audience; no abstract

OBJECTIVE. The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy.METHODS. A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings, assigned randomly to head cooling for 72 hours, starting within 6 hours after birth (with the rectal temperature maintained at 34.5 ± 0.5°C), or conventional care, were studied. Death or severe disability at 18 months of age was assessed in a multicenter, randomized, controlled study (the CoolCap trial).RESULTS. Treatment, lower encephalopathy grade, lower birth weight, greater amplitude-integrated electroencephalographic amplitude, absence of seizures, and higher Apgar score, but not gender or gestational age, were associated significantly with better outcomes. In a multivariate analysis, each of the individually predictive factors except for Apgar score remained predictive. There was a significant interaction between treatment and birth weight, categorized as ≥25th or CONCLUSIONS. Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy. The protective effect of hypothermia was greater in larger infants.

Adaptive optical-coherence-domain reflectometry (OCDR) is performed by use of an adaptive interferometer and homodyne detection. The adaptive element of the interferometer is a photorefractive quantum-well device in a two-wave mixing geometry. The mixing self-adaptively maintains constant relative phase between the signal and reference waves and dynamically compensates gross movements of the sample or optical components as well as image speckle. The application described here is used for laser ranging into and through turbid media. Adaptive OCDR is a bridge between conventional optical coherence tomography and adaptive holographic optical coherence imaging. The insertion loss for the adaptive performance is -15 dB, but adaptive OCDR has potential applications for coherence tomography under conditions of large target motion and low background. We also demonstrate its potential application for optoacoustics and laser-based ultrasound detection. (C) 2004 Optical Society of America.