bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of glutamate and nitric oxide in the reproductive neuroendocrine system
Authors: Dhandapani Krishnan M , Brann Darrell W 
Published: April 2011

The preovulatory surge of gonadotropin releasing hormone (GnRH) is essential for mammalian reproduction. Recent work has implicated the neurotransmitters glutamate and nitric oxide as having a key role in this process. Large concentrations of glutamate are found in several hypothalamic nuclei known to be important for GnRH release and glutamate receptors are also located in these key hypothalamic nuclei. Administration of glutamate agonists stimulate GnRH and LH release, while glutamate receptor antagonists attenuate the steroid-induced and preovulatory LH surge. Glutamate has also been implicated in the critical processes of puberty, hormone pulsatility, and sexual behavior. Glutamate is believed to elicit many of these effects by activating the release of the gaseous neurotransmitter, nitric oxide (NO). NO potently stimulates GnRH by activating a heme containing enzyme, guanylate cyclase, which in turn leads to increased production of cGMP and GnRH release. Recent work has focused on identifying anchoring and (or) clustering proteins that target glutamate receptors to the synapse and couple the glutamate-NO neurotransmission system. The present review will discuss these new findings, as well as the role of glutamate and nitric oxide in important mammalian reproductive events, with a focus on the hypothalamic control of preovulatory GnRH release.Key words: glutamate, nitric oxide, GnRH, postsynaptic density, hypothalamus.
Improved purification protocol of the HSV-1 protease catalytic domain, using immunoaffinity
Authors: McKercher G , Bonneau P R , Lagacé L , Thibeault D , Massariol M -J , Krogsrud R , Lawetz C , McDonald P C , Cordingley M G 
Published: April 2011

The catalytic domain of herpes simplex virus protease was expressed in baculovirus-infected cells and purified in milligram quantities by ion-exchange and size-exclusion chromatography. The usefulness of this material was limited by the presence of a contaminating proteolytic activity, which caused time-dependent degradation of the protease. As a result we decided to explore an alternative approach to purification. Specific monoclonal antibodies were produced and evaluated by surface plasmon resonance as ligands for immunoaffinity chromatography. One monoclonal antibody, 6H4, was chosen for coupling to an affinity support, and the resulting column allowed us to obtain a pure and stable enzyme. Immunoaffinity chromatography of herpes simplex virus type 1 protease resulted in successful elimination of the contaminating protease activity. Moreover the immunoaffinity column permitted the isolation of stable and pure enzyme in a one-column procedure.Key words: herpes virus protease, immunoaffinity chromatography, purification.
Behaviour of water-jet mined caverns in oil sand and shale
Authors: Wong Ron CK 
Published: April 2011

Cavern of up to 10 m in diameter were mined in oil sand and shale formations at depths of 500 m in Cold Lake, Alberta. The cavens were subjected to high-pressure water jetting, pumping bitumensand slurry to the surface, cyclic water pressurization and depressurization, and gas exsolution. Roof and wall shapes were monitored by sonar logs. Numerical models are proposed to explain the roof and wall sloughing mechanisms in oil sand and shale. Key words: oil sand, shale, cavern, water jetting, collapse mechanism.
Pile response due to unsupported excavation-induced lateral soil movement
Authors: Poulos H G , Chen L T 
Published: April 2011

In this paper, a two-stage analysis involving the finite element method and the boundary element method is used to study pile response due to excavtion-induced lateral soil movements, focusing on unsupported excavations in clay layers. It is shown that the pile response in this case is different from that caused by excavations which are braced. Design charts for estimating pile bending moments and deflections are presented for free-head single piles, and these may be used in practice for assessing the behaviour of existing piles due to the excavation. However, proper account should be taken of the pile head condition, which has been found to have a major effect on the pile bending moment. The application of the charts is demonstrated via a study of a published case history. Comparisons are presented between measured pile behaviour and that predicted both from the chart solutions and the computer analyses, and reasonably good agreement is found between them. Key words: analysis, boundary element, excavation, finite element, pile, soil, movement.
Cyclobutenyl derivatives of phosphorus and sulfur
Authors: Cullen W. R. , Dawson D. S. , Dhaliwal P. S. 
Published: April 2011

Diethylphosphine and methanethiol react with the cyclobutenes [Formula: see text](X = Cl, F) to give the compounds (C2H5)2 [Formula: see text] (Y = Cl, F) and [Formula: see text] (Y = F, Cl, C2H5). The disubstituted compound [Formula: see text] is also obtained from CH3SH and [Formula: see text].The related di(tertiary phosphine) (C6H5)2- [Formula: see text] can similarly be prepared. Methanethiol adds to [Formula: see text] to give the cyclobutane, but reacts with [Formula: see text]to give [Formula: see text]and with [Formula: see text] to give the cyclobutenone [Formula: see text]. Tetra-methyldiphosphine and [Formula: see text] yield the disubstituted compound [Formula: see text], whereas a cyclobutenone is obtained when (C6H5)2P—P(C6H5)2 reacts with [Formula: see text]. In some reactions, the phosphorane (C6H5)2PF3 is obtained, probably from (C6H5)2PF.
Structure and dynamics of azapropazone derivatives studied by crystallography and nuclear magnetic resonance
Authors: Fauconnier Theresa , Bain Alex D , Hazendonk Paul , Bell R A , Lock Colin JL 
Published: April 2011

The X-ray crystal structure of a derivative of the nonsteroidal anti-inflammatory drug, azapropazone, has been determined using a data set obtained from a charge-coupled device (CCD) area detector. Azapropazone itself, 5-(dimethylamino)-9-methyl-2-propyl-1H-pyrazolo[1,2-a][1,2,4]benzotriazine- 1,3(2H)-dione, has previously been shown to be nonplanar, probably due to steric interactions between the pyrazolidine ring and the exocyclic dimethylamino group. The derivative studied in this work, 3-dimethylamino-7-methyl-1,2,4-benzotriazine, does not have the pyrazolidine ring and is shown here to be strictly planar. There is also a significant difference in the kinetics of restricted rotation around the bond joining the dimethylamino group to the triazine ring, as measured by NMR. Both the enthalpy and entropy of activation are quite different. For the chemical exchange of the two methyl groups in azapropazone, Δ Hdouble dagger = 36 ± 0.5 kJ mol-1, and Δ Sdouble dagger = -34 ± 2 J K-1. For the derivative, Δ Hdouble dagger = 48 ± 0.4 kJ mol-1, and Δ Sdouble dagger = -12 ± 2 J K-1. This is rationalized by assuming the equilibrium state of the derivative is planar, and this defines the potential energy curve. The ground state of azapropazone is relatively destabilized, and somewhat disordered, by the steric interaction. Therefore, azapropazone has a small barrier to surmount, and the entropy of activation should be negative.Key words: NMR, chemical exchange, entropy, barriers to rotation, crystal structure.
The reactivity of the high-energy intermediates formed in the reactions of Group 13 metal atoms and aromatic alkenes
Authors: Joly Helen A , Kepes Maria , Roy Natalie , Prpic Jason 
Published: April 2011

Group 13 metal atoms were reacted with aromatic alkenes in a specialized metal atom reactor known as a "rotating cryostat." The nature of the intermediates formed was deduced from a GC-MS study of their hydrolysis and deuterolysis products. The product studies suggest that 2-phenylaluminacyclopropane, cis- and trans-3,4-diphenylaluminacyclopentane, and cis- and trans- 2,4-diphenylaluminacyclopentane are formed when Al atoms react with styrene, and 2-methyl-2-phenylaluminacyclopropane and 3,4-dimethyl- 3,4-diphenylaluminacyclopentane are formed when Al atoms react with α -methylstyrene. These findings are consistent with the radicals detected in the EPR spectroscopic studies of Al-alkene reaction mixtures prepared under similar conditions. Mechanisms for the formation of the organoaluminium intermediates are discussed. Analogous organogallium intermediates are formed when gallium atoms react with styrene. The reductive coupling of styrene did not occur when In and Tl atoms were used. Only trace quantities of phenylethane were detected in the hydrolyzed reaction mixture.Key words: Group 13 metal atoms, aluminium atoms, organoaluminium intermediates, metal atom reactions.
Thermodynamic calculations for reactions involving hydrogen halide polymers, ions, and Lewis acid adducts. 4. The temperature dependence of some reactions of HF and HCl
Authors: Rankin Kathryn N , Chandler W David , Johnson Keith E 
Published: April 2011

Ab initio MP2/6-311++G(d,p) structure optimizations and frequency calculations have been carried out on 10 polymers, (HX)n; on eight polyhalohydrogenate(1-) anions, HnXn+1-, and on four polyhalohydrogen(I) cations, Hn+1Xn+, (X = F and Cl) at a number of temperatures from 188 to 673 K, and at various total pressures. From the results, ΔG° and K values have been calculated for some reactions involving these species, and the relative amounts determined under a variety of conditions: nHX –> (HX)n (n = 2-6) HX + HnXn+1- àHn+1Xn+2- (n = 0-3) HX + Hn+1Xn+ àHn+2Xn+1+ (n = 0, 1) There are some marked differences between the fluorine and chlorine series, but generally, the relative amounts of the large molecules and ions decrease as the temperature increases. For all reactions, ln K can be expressed as function to the fourth power in 1/T indicating that ΔH° is more or less temperature dependent over a range of 400-500°.Key words: ab initio, thermodynamics, HCl, HF.
Aqueous nonelectrolyte solutions. Part XVI. Formula of deuterium sulfide D-hydrate and its dissociation thermodynamic functions
Authors: Clarke Colin W , Glew David N 
Published: April 2011

A method has been devised to approximate both the hydrate formula number n and the standard thermodynamic functions for hydrate dissociation from the temperature change of the hydrate former fugacity along a univariant three-phase (hl1g) equilibrium line. Thermodynamic equations are derived, their validity discussed, and an iterative method for their solution is described. The univariant (hl1g) equilibrium dissociation of deuterium sulfide D-hydrate (D2S·nD2O phase h) into gaseous deuterium sulfide (g) and liquid deuterium oxide (l1) has been treated to give approximate formulae and dissociation constants at 58 temperatures from 2.798 to 30.666°C. Dissociation equilibrium constants Kp(h–> l1g) have been represented as a function of temperature by a four-parameter equation which yields both values and standard errors (i) for ΔHot(h–> l1g) and ΔCpot(h–> l1g) the standard enthalpy and heat capacity changes for D-hydrate dissociation and (ii) for n = r the approximate formula number of the D-hydrate at each experimental temperature. The formula D2S·6.115D2O with standard error 0.018D2O is found for deuterium sulfide D-hydrate at lower quadruple point Q(hs1l1g) 3.392°C; an approximate formula D2S·5.840D2O with SE 0.019D2O is found at upper quadruple point Q(hs1l2g) 30.770°C. Key words: clathrate D-hydrate of deuterium sulfide, deuterium sulfide D-hyfrate, formula of deuterium sulfide D-hydrate, thermodynamics of clathrate hydrate dissociation, dissociation equilibrium constant of deuterium sulfide D-hydrate, standard enthalpy, and heat capacity changes for dissociation of deuterium sulfide D-hydrate.
Action de l'Acide Dipropylacétique Chez le Papio papio Photosensible
Authors: Patry G. , Naquet R. 
Published: April 2011

It has been recently proved that n-dipropylacetate increases the level of cerebral γ-aminobutyric acid. Intravenous injections of various doses of the former were administered to eight baboons (Papio papio) that were more or less photosensitive and exhibited convulsive seizures. The results show that n-dipropylacetate can protect (although usually only briefly) against clinical manifestations, and less effectively against EEG manifestations, induced by intermittent light stimulation. Furthermore, protection against grand-mal discharges seems to outlast protection against myoclonic discharges.
Targeting the p53 Pathway in Retinoblastoma with Subconjunctival Nutlin-3a
Authors: Brennan Rachel C. , Federico Sara , Bradley Cori , Zhang Jiakun , Flores-Otero Jacqueline , Wilson Matthew , Stewart Clinton , Zhu Fangyi , Guy Kip , Dyer Michael A. 
Published: April 2011

Abstract
Retinoblastoma is a rare childhood cancer of the retina that begins in utero and is diagnosed in the first years of life. The goals of retinoblastoma treatment are ocular salvage, vision preservation, and reduction of short- and long-term side effects without risking mortality because of tumor dissemination. To identify better chemotherapeutic combinations for the treatment of retinoblastoma, several groups have developed genetic mouse models and orthotopic xenograft models of human retinoblastoma for preclinical testing. Previous studies have implicated the MDMX protein in the suppression of the p53 pathway in retinoblastoma and shown that the MDM2/MDMX antagonist, Nutlin-3a, can efficiently induce p53-mediated cell death in retinoblastoma cell lines. However, Nutlin-3a cannot be administered systemically to treat retinoblastoma, because it has poor penetration across the blood–ocular barrier. Therefore, we developed an ocular formulation of Nutlin-3a, Nutlin-3aOC, and tested the pharmacokinetics and efficacy of this new formulation in genetic and human retinoblastoma orthotopic xenograft models of retinoblastoma. Here, we show that Nutlin-3aOC specifically and efficiently targets the p53 pathway and that the combination of Nutlin-3aOC with systemic topotecan is a significantly better treatment for retinoblastoma than currently used chemotherapy in human orthotopic xenografts. Our studies provide a new standardized approach to evaluate and prioritize novel agents for incorporation into future clinical trials for retinoblastoma. Cancer Res; 71(12); 4205–13. ©2011 AACR.
Cost Effectiveness of Warfarin Versus Aspirin in Patients Older Than 75 Years With Atrial Fibrillation
Authors: Jowett Sue , Bryan Stirling , Mant Jonathan , Fletcher Kate , Roalfe Andrea , Fitzmaurice David , Lip Gregory Y.H. , Hobbs F.D. Richard 
Published: April 2011

Background and Purpose—
Oral anticoagulants are effective at reducing stroke compared with aspirin in atrial fibrillation patients older than 75 years. Although the benefits of reduced stroke risk outweigh the risks of bleeding, the cost effectiveness of warfarin in this patient population has not yet been established.

Methods—
An economic evaluation was conducted alongside a randomized, controlled trial; 973 patients ≥75 years of age with atrial fibrillation were recruited from primary care and randomly assigned to either take warfarin or aspirin. Follow-up was for a mean of 2.7 years. Costs of thrombotic and hemorrhagic events, anticoagulation clinic visits, and primary care utilization were determined. Clinical benefits were expressed in terms of a primary event avoided: fatal/nonfatal disabling stroke, intracranial hemorrhage, or systemic embolism. A cost-utility analysis was performed using quality-adjusted life years as the benefit measure.

Results—
Total costs over 4 years were lower in the warfarin group (difference, −£165; 95% CI, −£452–£89), primarily driven by the difference in primary event costs. The primary event rate over 4 years was lower in the warfarin group (0.049 versus 0.099), and the quality-adjusted life years score was higher (difference, 0.02; 95% CI, −0.07–0.11). With lower costs and a higher quality-adjusted life years score, warfarin is the dominant treatment, but the differences in both costs and effects are small.

Conclusions—
Warfarin is cost-effective compared with aspirin in atrial fibrillation patients age ≥75 years. These data support the anticoagulant therapy option in this high-risk patient population. However, the small differences in costs and effects indicate the importance of exploring patient preferences.
A Topographic Study of the Evolution of the MR DWI/PWI Mismatch Pattern and Its Clinical Impact
Authors: Ogata Toshiyasu , Nagakane Yoshinari , Christensen Soren , Ma Henry , Campbell Bruce C.V. , Churilov Leonid , Olivot Jean-Marc , Desmond Patricia M. , Albers Gregory W. , Davis Stephen M. , Donnan Geoffrey A. 
Published: April 2011

Background and Purpose—
The ischemic penumbra may be classical, with complete annular configuration around the infarct core, or nonclassical with a more fragmented pattern. We tested the hypotheses that these penumbral patterns may: be associated with specific predictive factors, influence infarct growth and clinical outcome, and influence the effect of tissue plasminogen activator (t-PA).

Methods—
Using the EPITHET/DEFUSE data set, in which patients received alteplase or placebo 3 to 6 hours poststroke, perfusion-weighted imaging and diffusion-weighted imaging images were analyzed. These mismatch patterns were defined as “classical” or “nonclassical.” Multivariate analysis was used to identify variables associated with mismatch patterns, the effect of t-PA, as well as the relationship between mismatch patterns, infarct growth, and clinical outcomes.

Results—

We included 158 patients (median age, 74 years; median National Institute of Health Stroke Scale score, 12). Multivariate analysis indicated that the factors associated with classical mismatch pattern type were large mismatch volume (
P
<0.001) and cortical infarct location (
P
=0.036). Infarct growth, clinical outcome, and the efficacy of t-PA were not statistically different between patterns.

Conclusions—
Coregistered mismatch volume and cortical location of infarction were the important factors associated with presence of the classical mismatch pattern. The lack of effect of the type of mismatch patterns on infarct growth, clinical outcomes, or the benefit of t-PA would suggest that mismatch topography is less important during the hyperacute phase of ischemic stroke than during subacute phase.
Effects of Continuous Hypertonic Saline Infusion on Perihemorrhagic Edema Evolution
Authors: Wagner Ingrid , Hauer Eva-Maria , Staykov Dimitre , Volbers Bastian , Dörfler Arnd , Schwab Stefan , Bardutzky Jürgen 
Published: April 2011

Background and Purpose—
Mass effect of hematoma and the associated perihematomal edema are commonly responsible for neurological deterioration after intracerebral hemorrhage. Efficacy of surgical and medical therapy is limited. We studied the effect of early continuous hypertonic saline infusion on development of perihematomal edema after severe spontaneous supratentorial hemorrhage.

Methods—
Patients with spontaneous lobar and basal ganglia/thalamic bleeding >30 mL (n=26) were treated with early (<72 hours) continuous hypertonic saline infusion (3%) to achieve sodium of 145 to 155 mmol/L and osmolality of 310 to 320 mOsmol/kg. Evolution of absolute edema volume and relative edema volume (ratio absolute edema volume/initial hematoma volume) was assessed on repeated cranial CT and compared to historical patients (n=64) identified on database with hematoma >30 mL.

Results—

In the treatment group, absolute edema volume was significant smaller between day 8 and day 14 (
P
absolute edema volume
= 0.04) and relative edema volume was significant smaller between day 2 and day 14 (
P
relative edema volume
=0.02). Intracranial pressure crisis (>20 mm Hg for >20 minutes or new anisocoria) occurred less frequently in the treatment group (12 versus 56;
P
=0.048). In-hospital mortality was 3 (11.5%) in the hypertonic saline group and 16 (25%) in the control group (
P
=0.078). Side effects theoretically associated with hypertonic saline including cardiac arrhythmia and acute heart and renal failure occurred in both groups to a similar extent.

Conclusions—
Early and continuous infusion of hypertonic saline in patients with severe spontaneous intracerebral hemorrhage was feasible and safe. The beneficial effect of this treatment regimen on edema evolution and outcome has to be demonstrated in a controlled trial.
MCP1 haplotypes associated with protection from pulmonary tuberculosis
Authors: Intemann Christopher D , Thye Thorsten , Förster Birgit , Owusu-Dabo Ellis , Gyapong John , Horstmann Rolf D , Meyer Christian G 
Published: April 2011

AbstractBackgroundThe monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of theMCP1-362C and theMCP1-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate theMCP1gene in order to determine causal variants or haplotypes genetically and functionally.ResultsA 14 base-pair deletion in the firstMCP1intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, Pcorrected= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, Pnominal= 0.00002; adjusted Pglobal= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying theMCP1mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.ConclusionsIn addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does theMCP1-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.