bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central Nervous System Concentrations of Cyclooxygenase-2 Inhibitors in Humans
Authors: Dembo Gregory , Park Sang B. , Kharasch Evan D. 
Published: January 2005

Background
Cyclooxygenase-2 (COX-2)-selective inhibitors (coxibs) are under investigation for the potential therapy, attenuation, or prevention of neuroinflammatory and neurodegenerative disorders. Coxibs are also a significant advance in pain therapy and are traditionally considered to achieve analgesia via peripheral effects. However, in animals, central nervous system (CNS) COX-2 activity and prostanoid concentrations are increased by peripheral inflammation, central sensitization has been proposed to account for long-term pain-related phenomena, and coxibs achieve significant cerebrospinal fluid (CSF) concentrations and may cause analgesia via CNS action. Nevertheless, it remains unknown whether or which coxibs reach the CNS in humans. This investigation determined whether coxibs can reach the CNS in humans, based on CSF concentrations.

Methods
Ten healthy human volunteers simultaneously received a single oral dose of celecoxib (200 mg), rofecoxib (50 mg), and valdecoxib (40 mg). Blood and CSF were serially sampled for 10 h, and plasma total and unbound and CSF coxib concentrations were quantified by mass spectrometry.

Results
Total plasma concentrations and time to maximum plasma concentration were similar among the three coxibs. In contrast, unbound (free) plasma concentrations differed significantly. Maximum unbound plasma concentrations were 1.4 +/- 0.5, 42 +/- 17, and 6.0 +/- 2.9 ng/ml, respectively, for celecoxib, rofecoxib, and valdecoxib. COX-2 inhibitors rapidly penetrated the CNS. Maximum CSF concentrations were 2 +/- 2, 57 +/- 25, and 10 +/- 4 ng/ml, respectively, for celecoxib, rofecoxib, and valdecoxib. CSF concentrations exceeding the median inhibitory concentration for COX-2 were achieved by rofecoxib and valdecoxib but not celecoxib.

Conclusions
These results show that coxibs do reach the CNS in humans, with rapid penetration, and in concentrations apparently sufficient to inhibit COX-2 activity. There were significant differences among coxibs in CSF penetration. Unbound (free) plasma coxib concentration was the major determinant of CSF concentration. This supports the hypothesis that coxibs may act, in part, in the human CNS, provide important new information on the mechanism and treatment of pain and may guide coxib selection for therapeutic trials when CNS penetration is desirable.
Intrathecal Morphine Reduces Allodynia after Peripheral Nerve Injury in Rats via Activation of a Spinal A1 Adenosine Receptor
Authors: Zhang Yong , Conklin Dawn R. , Li Xinhui , Eisenach James C. 
Published: January 2005

Background
The degree to which intrathecally administered morphine can alleviate hypersensitivity in animals after peripheral nerve injury is controversial, and the mechanisms by which morphine works in these circumstances are uncertain. In normal animals, morphine induces adenosine release, and in vitro data suggest that this link is disrupted after peripheral nerve injury. Therefore, using a controlled, blinded study design, the authors tested intrathecal morphine efficacy in rats with peripheral nerve injury and the role of spinal A1 adenosine receptors in the action of morphine.

Methods
Male rats underwent intrathecal catheter implantation and lumbar spinal nerve ligation, resulting in hypersensitivity to tactile stimulation of the paw. Intrathecal morphine alone or with naloxone or the specific A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentyxanthine (DPCPX), was administered, and withdrawal threshold to von Frey filament application to the hind paw was determined.

Results
Intrathecal morphine (0.25-30 microg) dose-dependently reversed mechanical hypersensitivity after spinal nerve ligation, with an ED50 of 0.79 microg. The effect of morphine was blocked by intrathecal naloxone. Intrathecal DPCPX alone had no effect on withdrawal threshold after spinal nerve ligation but completely reversed the effect of morphine, with an ID50 of 5.6 microg.

Conclusions
This study is in accord with two recent reports that support short-term efficacy of intrathecal morphine to reverse hypersensitivity to mechanical stimuli in animal models of neuropathic pain. Despite previous studies demonstrating that morphine releases less adenosine after peripheral nerve injury, the current study suggests that the antihypersensitivity effect of morphine in these conditions is totally reliant on A1 adenosine receptor activation.
Social discount rates for member countries of the European Union
Authors: Evans David J. , Sezer Haluk 
Published: January 2005

PurposeThis paper sets out to estimate discount rates for EU members, on a consistent time preference basis, for application in the appraisal of social projects. The value of the discount rate can have an important influence on the allocation of funds between short‐term and long‐term uses.Design/methodology/approachA key component of the social discount rate is the elasticity of marginal utility of consumption (e) and it is estimated from OECD data relating to marginal and average rates of income tax. A tax model based on the principle of equal absolute sacrifice of satisfaction is employed.FindingsThe estimated discount rates, based on social time preference, mostly lie in the range 3‐5.5 per cent. The main source of variation in rates is differential growth in per capita consumption. Estimates of e are reasonably consistent and for 15 of the countries they lie in the range 1.3‐1.6.Research limitations/implicationsFor more comprehensive tax information, then additional data from each country's tax authority are required. The research on estimates of e and social time preference rates can be extended to cover non‐European countries.Practical implicationsIn the interests of a consistent equitable treatment of future generations, member countries of the EU should employ the same methodology in estimating social discount rates.Originality/valueThis paper applies a practical tax‐based approach to the estimation of e for a large number of European countries. The paper will be of interest to academics specialising in welfare economics and to practitioners involved in social project appraisal.
Optimization of thermal resistance of stacked micro‐channel using genetic algorithms
Authors: Jeevan K. , Quadir G.A. , Seetharamu K.N. , Azid I.A. , Zainal Z.A. 
Published: January 2005

PurposeTo determine the optimal dimensions for a stacked micro‐channel using the genetic algorithms (GAs) under different flow constraints.Design/methodology/approachGA is used as an optimization tool for optimizing the thermal resistance of a stacked micro‐channel under different flow constraints obtained by using the one dimensional (1D) and two dimensional (2D) finite element methods (FEM) and by thermal resistance network model as well (proposed by earlier researcher). The 2D FEM is used to study the effect of two dimensional heat conduction in the micro‐channel material. Some parametric studies are carried out to determine the resulting performance of the stacked micro‐channel. Different number of layers of the stacked micro‐channel is also investigated to study its effect on the minimum thermal resistance.FindingsThe results obtained from the 1D FEM analysis compare well with those obtained from the thermal resistance network model. However, the 2D FEM analysis results in lower thermal resistance and, therefore, the importance of considering the conduction in two dimensions in the micro‐channel is highlighted.Research limitations/implicationThe analysis is valid for constant properties fluid and for steady‐state conditions. The top‐most surfaces as well as the side surfaces of the micro‐channel are considered adiabatic.Practical implicationsThe method is very useful for practical design of micro‐channel heat‐sinks.Originality/valueFEM analyses of stacked micro‐channel can be easily implemented in the optimization procedure for obtaining the dimensions of the stacked micro‐channel heat‐sinks for minimum thermal resistance.
Steady and unsteady thermal analysis of a triple stack cold plate with heat losses
Authors: Lin Beh Shiao , Ooi C.K. , Quadir G.A. , Seetharamu K.N. 
Published: January 2005

PurposeTo provide some new and additional data for the design of a triple stack cold plate.Design/methodology/approachA detailed finite element formulation for the triple stack cold plate with and without heat losses from the top and bottom surfaces of the stack is presented to determine its performance under steady as well as unsteady conditions. The effects of the number of unit cells, different heat losses as well as the governing dimensionless parameter, M (involving stack dimension, properties of the stack material and the variation in the heat transfer coefficient) on the performance of the stack are investigated. The detailed formulation of the asymptotic waveform evaluation scheme is also given and applied to determine the transient performance of the stack.FindingsThe methods of analysis described are quite simple to use to determine the steady and unsteady performance of the triple stack cold plate under different operating conditions. The heat losses from the top and bottom surfaces of the stack do affect the maximum temperature of the stack and in such case, the assembled stack should be analysed.Research limitations/implicationsThe analysis is limited to an incompressible fluid. The effect of varying mass flow rate of the fluid in the stack passages is also not considered.Practical implicationsNew and additional generated data will be helpful in the design of cold plates used in the cooling of electronic components.Originality/valueThe asymptotic waveform evaluation scheme is used for the first time to determine the transient performance of the triple stack cold plate under different operating conditions. The results thus obtained are compared well with those found from the finite element analysis (FEM), but the computational effort and time required in the analysis is much small as compared to those required in the FEM analysis.
Mapping protein energy landscapes with amide hydrogen exchange and mass spectrometry: I. A generalized model for a two‐state protein and comparison with experiment
Authors: Xiao Hui , Hoerner Joshua K. , Eyles Stephen J. , Dobo Andras , Voigtman Edward , Mel'čuk Andre I. , Kaltashov Igor A. 
Published: January 2005

AbstractProtein amide hydrogen exchange (HDX) is a convoluted process, whose kinetics is determined by both dynamics of the protein and the intrinsic exchange rate of labile hydrogen atoms fully exposed to solvent. Both processes are influenced by a variety of intrinsic and extrinsic factors. A mathematical formalism initially developed to rationalize exchange kinetics of individual amide hydrogen atoms is now often used to interpret global exchange kinetics (e.g., as measured in HDX MS experiments). One particularly important advantage of HDX MS is direct visualization of various protein states by observing distinct protein ion populations with different levels of isotope labeling under conditions favoring correlated exchange (the so‐called EX1 exchange mechanism). However, mildly denaturing conditions often lead to a situation where the overall HDX kinetics cannot be clearly classified as either EX1 or EX2. The goal of this work is to develop a framework for a generalized exchange model that takes into account multiple processes leading to amide hydrogen exchange, and does not require that the exchange proceed strictly via EX1 or EX2 kinetics. To achieve this goal, we use a probabilistic approach that assigns a transition probability and a residual protection to each equilibrium state of the protein. When applied to a small protein chymotrypsin inhibitor 2, the algorithm allows complex HDX patterns observed experimentally to be modeled with remarkably good fidelity. On the basis of the model we are now in a position to begin to extract quantitative dynamic information from convoluted exchange kinetics.
Specific erythrocyte binding capacity and biological activity of Plasmodium falciparum erythrocyte binding ligand 1 (EBL‐1)‐derived peptides
Authors: Curtidor Hernando , Rodríguez Luis E. , Ocampo Marisol , López Ramses , García Javier E. , Valbuena John , Vera Ricardo , Puentes Álvaro , Vanegas Magnolia , Patarroyo Manuel E. 
Published: January 2005

AbstractErythrocyte binding ligand 1 (EBL‐1) is a member of the ebl multigene family involved in Plasmodium falciparum invasion of erythrocytes. We found that five EBL‐1 high‐activity binding peptides (HABPs) bound specifically to erythrocytes: 29895 (41HKKKSGELNNNKSGILRSTY60), 29903 (201LYECGK‐KIKEMKWICTDNQF220), 29923 (601CNAILGSYADIGDIVRGLDV620), 29924(621WRDINTNKLSEK‐FQKIFMGGY640), and 30018 (2481LEDIINLSKKKKKSINDTSFY2500). We also show that binding was saturable, not sialic acid‐dependent, and that all peptides specifically bound to a 36‐kDa protein on the erythrocyte membrane. The five HABPs inhibited in vitro merozoite invasion depending on the peptide concentration used, suggesting their possible role in the invasion process.
Physicochemical and residue conservation calculations to improve the ranking of protein–protein docking solutions
Authors: Duan Yuhua , Reddy Boojala V.B. , Kaznessis Yiannis N. 
Published: January 2005

AbstractMany protein–protein docking algorithms generate numerous possible complex structures with only a few of them resembling the native structure. The major challenge is choosing the near‐native structures from the generated set. Recently it has been observed that the density of conserved residue positions is higher at the interface regions of interacting protein surfaces, except for antibody–antigen complexes, where a very low number of conserved positions is observed at the interface regions. In the present study we have used this observation to identify putative interacting regions on the surface of interacting partners. We studied 59 protein complexes, used previously as a benchmark data set for docking investigations. We computed conservation indices of residue positions on the surfaces of interacting proteins using available homologous sequences and used this information to filter out from 56% to 86% of generated docked models, retaining near‐native structures for further evaluation. We used a reverse filter of conservation score to filter out the majority of nonnative antigen–antibody complex structures. For each docked model in the filtered subsets, we relaxed the conformation of the side chains by minimizing the energy with CHARMM, and then calculated the binding free energy using a generalized Born method and solvent‐accessible surface area calculations. Using the free energy along with conservation information and other descriptors used in the literature for ranking docking solutions, such as shape complementarity and pair potentials, we developed a global ranking procedure that significantly improves the docking results by giving top ranks to near‐native complex structures.
Stability of HAMLET—A kinetically trapped α‐lactalbumin oleic acid complex
Authors: Fast Jonas , Mossberg Ann‐Kristin , Svanborg Catharina , Linse Sara 
Published: January 2005

AbstractThe stability toward thermal and urea denaturation was measured for HAMLET (human α‐lactalbumin made lethal to tumor cells) and α‐lactalbumin, using circular dichroism and fluorescence spectroscopy as well as differential scanning calorimetry. Under all conditions examined, HAMLET appears to have the same or lower stability than α‐lactalbumin. The largest difference is seen for thermal denaturation of the calcium free (apo) forms, where the temperature at the transition midpoint is 15°C lower for apo HAMLET than for apo α‐lactalbumin. The difference becomes progressively smaller as the calcium concentration increases. Denaturation of HAMLET was found to be irreversible. Samples of HAMLET that have been renatured after denaturation have lost the specific biological activity toward tumor cells. Three lines of evidence indicate that HAMLET is a kinetic trap: (1) It has lower stability than α‐lactalbumin, although it is a complex of α‐lactalbumin and oleic acid; (2) its denaturation is irreversible and HAMLET is lost after denaturation; (3) formation of HAMLET requires a specific conversion protocol.
Expression of andic properties in soils from Galicia (NW Spain) under forest and agricultural use
Authors: Verde J. R. , Camps Arbestain M. , Macías F. 
Published: January 2005

SummaryThe organic matter (OM) of soils with andic properties has long been considered highly stable because of the presence of Al–humus complexes and sorption of organic ligands onto amorphous compounds. In this study, we characterized soils under different land use regimes located within an amphibolitic massif close to Santiago de Compostela (Spain), where soils with andic properties are present. Slash and burn agriculture was a common practice in the area until the second half of the 20th century. Thereafter, modern agriculture was progressively introduced into the area (AGR soils), and the rest of the land was either reforested or abandoned (FOR soils). We found that the mean organic C content of AGR soils (48.7 g kg−1) was ∼ 50% that of FOR soils (94.2 g kg−1). Mean soil pH was significantly greater (P < 0.05) in the AGR than in the FOR soils (4.95 compared with 4.63), which is attributed to liming and Ca‐phosphate fertilization of the former. Mean concentrations of the Al forms studied (extractable with CuCl2, sodium pyrophosphate, ammonium oxalate, or NaOH) were significantly smaller (P < 0.01) in AGR (1.4, 4.9, 9.3, 11.0 g kg−1, respectively) than in FOR soils (3.9, 10.2, 16.5, 17.9 g kg−1, respectively). The results show the vulnerability of the OM and Al–humus complexes in these soils to modern agricultural practices, which has led to the attenuation – and in some cases even the disappearance – of andic soil properties in a relatively short time (< 30 years) following changes in land use/management. We propose the inclusion of the formative element ‘andic’ in the criteria for the definition of Umbrisol subunits; this would avoid the abrupt discontinuity observed in the current World Reference Base classification.
Soil organic carbon and its sorptive preservation in central Germany
Authors: Wiseman C. L. S. , Püttmann W. 
Published: January 2005

SummarySoils are increasingly viewed as a potential sink for atmospheric carbon. However, their use to meet CO2 emission reductions is problematic for there are knowledge gaps regarding the mechanisms involved in the sequestration of organic carbon (OC). There is evidence which suggests that OC concentrations are controlled by the mineralogy and related specific surface area (SSA) of a given soil. The goal of this study was to examine the importance of sorptive mechanisms on OC stabilization. The objectives were (i) to determine the SSA, clay mineralogy and dithionite‐ and oxalate‐extractable Fe and Al concentrations of several soils, and (ii) to analyse how these variables are related to OC concentrations. Five soils were sampled and analysed: two Umbrisols, a Stagnic Acrisol, an Anthrosol/Vertisol/Gleysol‐Chernozem and a Gleysol (FAO terminology), all located in Hesse, Germany. Oxalate‐extractable Fe and Al were found to be the best predictors of OC concentrations in the soils examined. Specific surface area correlated significantly with the OC content of the B and C horizons of one Umbrisol and the entire profile of the Anthrosol/Vertisol/Gleysol‐Chernozem. The relationship between SSA and OC concentrations is likely to be restricted to certain soils and might be a product of the sorptive capacity of Fe and Al oxides. We can assume that the available mineral surface area on oxides is a limiting factor in terms of a soil's capacity to sequester organic carbon. As such, attention should be paid to soil mineralogy and how this might limit the use of soils as a sink for atmospheric CO2.
Short‐term effects of management on the soil structure in a deep tilled hardened volcanic‐ash soil (cangahua) in Ecuador
Authors: Podwojewski P. , Germain N. 
Published: January 2005

SummaryIn the Ecuadorian Cordillera, the hardened volcanic ashes (cangahuas) account for 15% of the cultivated area. The soil resulting from the fragmentation of these materials, generally by heavy machinery, shows an apparent stable millimetric structure. However, this new structure is highly susceptible to disintegration under rain, because it contains no organic matter and little clay, and the material itself is readily eroded in consequence.We studied the evolution of soil aggregate stability in two factorial experiments during five cultivation cycles with two kinds of soil preparation and five fertilization treatments. The aggregate stability was not influenced by either kind of soil preparation, nor by large additions of cattle manure (80 t ha−1) or green manure (10 t ha−1), nor by growing a perennial grass. The variation in the aggregate stability seemed to depend on the components inherited from the original volcanic material: in the plots with larger clay content, and with swelling clay minerals, the aggregates were less stable than those composed of isometric fine silt particles.
Risk factors for chronic insomnia following hospitalization
Authors: Griffiths Maree F. , Peerson Anita 
Published: January 2005

Aim.  This paper reports a study whose purpose was to determine whether there is an increase in the incidence of chronic insomnia following hospitalization and, if so, to identify patients at risk.Background.  The consequences of difficulty sleeping in hospital have received scant attention from clinicians or researchers. Implicit in this lack of interest is the assumption that difficulty in sleeping is a transient reaction to hospitalization that will resolve on discharge, an assumption not empirically supported. It has been argued that in susceptible people this type of temporary disruption to sleep can be the catalyst for the development of chronic insomnia.Method.  Established sleep and depression rating instruments were used to monitor the sleep of 57 cardiac and 29 orthopaedic patients after elective surgery (n = 86), recruited through a hospital preadmission clinic.Results.  Preadmission chronic insomnia of 10% was consistent with general population prevalence estimates of 6–12%. Three months after discharge the incidence had almost doubled to 19%. Sixty‐one per cent of this variance could be explained by hyperarousal, sleep hygiene issues, and dysfunctional cognitions about sleep. Depression was found to be a salient predictor but not an independent risk factor. Age, sex, and hospital‐related data, such as score for difficulty sleeping in hospital, proved to be statistically insignificant.Conclusions.  The results support the role of hyperarousal and dysfunctional sleep attitudes and behaviours as stronger predictors of chronic insomnia than patient demographics or environmental issues. Given that most of the patients were ambivalent about how they slept in hospital, with high satisfaction (71%) in the presence of significant disruption (63%), preadmission sleep education given to these patients prior to admission potentially contributed to the development of more realistic expectations of the quality of in‐hospital sleep.