bluuebunny/crossref_metadata_2025 huggingface dataset:
General circulation model estimates of aerosol transport and radiative forcing during the Indian Ocean Experiment
Authors: Reddy M. Shekar , Boucher O. , Venkataraman C. , Verma S. , Léon J.‐F. , Bellouin N. , Pham M.
Published: August 2004

Aerosol sources, transport, and sinks are simulated, and aerosol direct radiative effects are assessed over the Indian Ocean for the Indian Ocean Experiment (INDOEX) Intensive Field Phase during January to March 1999 using the Laboratoire de Météorologie Dynamique (LMDZT) general circulation model. The model reproduces the latitudinal gradient in aerosol mass concentration and optical depth (AOD). The model‐predicted aerosol concentrations and AODs agree reasonably well with measurements but are systematically underestimated during high‐pollution episodes, especially in the month of March. The largest aerosol loads are found over southwestern China, the Bay of Bengal, and the Indian subcontinent. Aerosol emissions from the Indian subcontinent are transported into the Indian Ocean through either the west coast or the east coast of India. Over the INDOEX region, carbonaceous aerosols are the largest contributor to the estimated AOD, followed by sulfate, dust, sea salt, and fly ash. During the northeast winter monsoon, natural and anthropogenic aerosols reduce the solar flux reaching the surface by 25 W m−2, leading to 10–15% less insolation at the surface. A doubling of black carbon (BC) emissions from Asia results in an aerosol single‐scattering albedo that is much smaller than in situ measurements, reflecting the fact that BC emissions are not underestimated in proportion to other (mostly scattering) aerosol types. South Asia is the dominant contributor to sulfate aerosols over the INDOEX region and accounts for 60–70% of the AOD by sulfate. It is also an important but not the dominant contributor to carbonaceous aerosols over the INDOEX region with a contribution of less than 40% to the AOD by this aerosol species. The presence of elevated plumes brings significant quantities of aerosols to the Indian Ocean that are generated over Africa and Southeast and east Asia.
Scattering matrices of volcanic ash particles of Mount St. Helens, Redoubt, and Mount Spurr Volcanoes
Authors: Muñoz O. , Volten H. , Hovenier J. W. , Veihelmann B. , van der Zande W. J. , Waters L. B. F. M. , Rose W. I.
Published: August 2004

We present measurements of the whole scattering matrix as a function of the scattering angle at a wavelength of 632.8 nm in the scattering angle range 3°–174° of randomly oriented particles taken from seven samples of volcanic ashes corresponding to four different volcanic eruptions: the 18 May 1980 Mount St. Helens eruption, the 1989–1990 Redoubt eruption, and the 18 August and 17 September 1992 Mount Spurr eruptions. The samples were collected at different distances from the vent. The samples studied contain large mass fractions of fine particles and were chosen to represent ash that could remain in the atmosphere for at least hours or days. They include fine ashfall samples that fell at a variety of distances from the volcano and pyroclastic flows that retained their fine fractions. Together, they represent a range of ashes likely to remain in the atmosphere in volcanic clouds following eruptions from convergent plate boundary volcanoes, Earth's most important group of explosive sources of ash. All measured scattering matrix elements are confined to rather limited domains when plotted as functions of the scattering angle following the general trends presented by irregular mineral particles. This similarity in the scattering behavior justifies the construction of an average scattering matrix for volcanic ash particles as a function of the scattering angle. To facilitate the use of the average scattering matrix for multiple‐scattering calculations with polarization included, we present a synthetic scattering matrix based on the average scattering matrix for volcanic ashes and the assumption that the diffraction forward scattering peak is the same for randomly oriented nonspherical particles and projected‐surface‐area‐equivalent spheres. This synthetic scattering matrix is normalized so that the average of its 1‐1 element over all directions equals unity. It is available in the full range from 0° to 180° and can be used, for example, for interpretation of remote‐sensing data after a volcanic eruption when the actual properties of the volcanic ash are not known. The measured results for the Mount St. Helens sample have been compared with results of Lorenz‐Mie calculations for projected‐surface‐area‐equivalent spheres with the refractive index of the Mount St. Helens particles. We find strong differences between measured and calculated values.
Soil water evaporation during the dry season in an arid zone
Authors: Agam (Ninari) Nurit , Berliner Pedro R. , Zangvil Abraham , Ben‐Dor Eyal
Published: August 2004

The objective of this study was to assess the relative magnitude of latent heat flux density over a bare loess soil in the Negev desert throughout the dry season, during which the atmospheric models usually assume the lack of latent heat flux. The measurements were carried out in the northern Negev, Israel, over a bare loess soil, during nine 24‐hour field campaigns throughout the dry season of 2002. In addition to a micrometeorological station that was set up in the research site, an improved microlysimeter was installed. The representativity of the microlysimeter was assessed by comparing its surface temperature to that of the surrounding surface using thermal images acquired on an hourly basis during several campaigns. It was found that although the water content of the uppermost soil is significantly lower than the wilting point, for which most of the commonly used meteorological models would assume no latent heat flux, the latter was ∼20% of the net‐radiation during the night and 10–15% during the day. It is therefore concluded that latent heat flux plays a major role in the dissipation of the net radiation during the dry season in the Negev desert.
Ignition threshold for impact‐generated fires
Authors: Durda Daniel D. , Kring David A.
Published: August 2004

Widespread fires can be generated after large impact events by atmospheric heating caused by the reaccretion of high‐energy, vapor‐rich plume material. We examine the threshold irradiance levels necessary for spontaneous and pilot ignition of various types of vegetation and define three specific cases for investigation: (1) 51 kW/m2 for a period of at least 2 min to spontaneously ignite wood; (2) 20 kW/m2 for a period of at least 20 min to ignite wood in the presence of an ignition source; and (3) 28 kW/m2 for a period of at least 1 min to ignite foliage, rotten wood, and forest litter. The threshold ejected plume mass for continent‐wide spontaneous ignition of wood is ∼2 to 6 × 1015 kg, independent of impact location but dependent on the details of the ejecta speed distribution. The threshold ejected plume mass for global spontaneous ignition of wood is in the range ∼1 to 2 × 1016 kg. The threshold plume masses for continent‐wide and global fires are very nearly the same for piloted ignition of wood, while the threshold plume masses for continent‐wide and global ignition of leaves and forest litter are significantly lower, by a factor of ∼2 to 3. Impact craters of at least 85 km diameter are needed to produce continental‐scale fires, and craters of ∼135 km diameter are needed for global‐scale fires.
On neoclassical effects in the theory of magnetic islands
Authors: Smolyakov A. I. , Lazzaro E.
Published: August 2004

Neoclassical viscosity affects the stability of magnetic islands by providing additional source of the transverve electric current contributing to the net longitudinal current in the magnetic island. One component of such neoclassical longitudinal current has a structure similar to the ion polarization current with enhanced plasma inertia and was investigated previosly. We show that in addition to the neoclassical inertia term, there is additional neoclassical current associated with variations of plasma pressure within the perturbed magnetic surfaces. Such variations can be caused by the ion polarization drift across the magnetic surface and finite heat conductivity in the parallel direction. A contribution of the neoclassical current due to plasma pressure variations is of the same order or larger than the standard ion polarization and bootstrap current terms. New terms will affect overall stability of magnetic islands and may provide a new threshold mechanism for the neoclassical tearing modes.
Contour dynamics method for solving the Grad–Shafranov equation with applications to high beta equilibria
Authors: Gourdain P.-A. , Leboeuf J.-N.
Published: August 2004

Numerous methods exist to solve the Grad–Shafranov equation, describing the equilibrium of a plasma confined by an axisymmetric magnetic field. Nevertheless, they are limited to low beta or small plasma pressure. Combining a nonconservative variational principle with a contour dynamics approach, the approach presented in this paper converges for extreme high beta configurations. By reducing the dimension of the problem from two to one, a compact and efficient numerical algorithm can be developed, and a wide range of boundary shapes can be utilized. Furthermore, the iterative nature of this technique greatly facilitates convergence at high beta while minimizing computation times.
Dispersion characteristics and field structure of surface waves in a warm inhomogeneous plasma column
Authors: Cho Suwon
Published: August 2004

The electron temperature and the radial inhomogeneity of the plasma density are considered in studying the characteristics of the surface electromagnetic wave in a plasma column. The Maxwell equations are combined with the fluid momentum equation to obtain the governing wave equations. For a uniform plasma the wave equations are analytically solved yielding the dispersion relation in a closed form and they are solved by the finite difference method after being converted to an operator eigenvalue equation for a nonuniform plasma. It is shown that the influence of the thermal electron motion is closely related to the density profile and the plasma column radius in addition to the electron temperature and collision frequency. Finally, the electric field structure is found to be quite different from the one obtained from the cold plasma theory.
Waves in two-dimensional hexagonal crystal
Authors: Duan Wen-shan , Wan Gui-xin , Wang Xiao-yun , Lin Mai-mai
Published: August 2004

Two-dimensional hexagonal crystal is investigated in this paper. The dispersion relations for both compressional and transverse waves in different directions are studied as well. The analytical results are in agreement with the experimental ones reported previously. The small amplitude but finite long wavelength nonlinear waves propagating in the hexagonal crystal are also investigated. This investigation indicates that the solitary waves propagating in the directions of either n or m are stable.
Protein patterns at lipid bilayer junctions
Authors: Parthasarathy Raghuveer , Groves Jay T.
Published: August 2004

We introduce a simple intermembrane junction system in which to explore pattern and structure formation by membrane-bound proteins. The junction consists of a planar lipid bilayer to which one species of protein (an IgG antibody) is bound, forming a 2D, compressible fluid. Upon the adhesion of a second lipid bilayer, the formerly uniformly distributed proteins rapidly reorganize into patterns of dense and sparse zones. Using a combination of complementary imaging techniques (fluorescence microscopy, fluorescence interference contrast microscopy, and fluorescence resonance energy transfer), we reconstruct the 3D structure of these intermembrane patterns with nanometer-scale topographic resolution, revealing the orientation of the proteins. The patterns form as the rapid bilayer-bilayer adhesion, often radiating outward from an initial, circular contact site, pushes aside the antibodies, sweeping them into areas of high density and clearing low-density regions. Coarsening of these local features is energetically costly and therefore kinetically trapped; the patterns do not change over tens of minutes. These studies demonstrate that membrane mechanical forces alone, i.e., in the absence of specific biochemical interactions, can drive μm-scale organization of membrane proteins.
RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca
2+
release (SOICR)
Authors: Jiang Dawei , Xiao Bailong , Yang Dongmei , Wang Ruiwu , Choi Philip , Zhang Lin , Cheng Heping , Chen S. R. Wayne
Published: August 2004

The cardiac ryanodine receptor (RyR2) governs the release of Ca
2+
from the sarcoplasmic reticulum, which initiates muscle contraction. Mutations in RyR2 have been linked to ventricular tachycardia (VT) and sudden death, but the precise molecular mechanism is unclear. It is known that when the sarcoplasmic reticulum store Ca
2+
content reaches a critical level, spontaneous Ca
2+
release occurs, a process we refer to as store-overload-induced Ca
2+
release (SOICR). In view of the well documented arrhythmogenic nature of SOICR, we characterized the effects of disease-causing RyR2 mutations on SOICR in human embryonic kidney (HEK)293 cells and found that, at elevated extracellular Ca
2+
levels, HEK293 cells expressing RyR2 displayed SOICR in a manner virtually identical to that observed in cardiac cells. Using this cell model, we demonstrated that the RyR2 mutations linked to VT and sudden death, N4104K, R4496C, and N4895D, markedly increased the occurrence of SOICR. At the molecular level, we showed that these RyR2 mutations increased the sensitivity of single RyR2 channels to activation by luminal Ca
2+
and enhanced the basal level of [
3
H]ryanodine binding. We conclude that disease-causing RyR2 mutations, by enhancing RyR2 luminal Ca
2+
activation, reduce the threshold for SOICR, which in turn increases the propensity for triggered arrhythmia. Abnormal RyR2 luminal Ca
2+
activation likely contributes to the enhanced SOICR commonly observed in various cardiac conditions, including heart failure, and may represent a unifying mechanism for Ca
2+
overload-associated VT.
Asynchronous replication timing of telomeres at opposite arms of mammalian chromosomes
Authors: Zou Ying , Gryaznov Sergei M. , Shay Jerry W. , Wright Woodring E. , Cornforth Michael N.
Published: August 2004

Telomeres are defining structural elements of all linear chromosomes, yet information concerning the timing of their replication in higher eukaryotes is surprisingly limited. We developed an approach that allowed a study of telomere replication patterns of specific mammalian chromosomes. In the Indian muntjac (
Muntiacus muntjac
), replication timing between respective telomeres of homologous chromosomes was highly coordinated, but no such synchrony was evident for p- and q-arm telomeres of the same chromosome. This finding contrasts with the coordinated timing of both ends of each chromosome in yeast. Also in contrast to yeast, where replication of all telomeres is confined to late S phase, we found specific telomeres in Indian muntjac chromosomes that replicated early in S and other telomeres that replicated later. Finally, replication timing of some but not all telomeres was influenced by telomere length. Knowledge of telomere replication timing represents a first step toward understanding the relationship between telomere replication and telomerase action. The approach, which we call replicative detargeting fluorescence
in situ
hybridization, is widely applicable to different species and genetic loci.
An enzymatic molten globule: Efficient coupling of folding and catalysis
Authors: Vamvaca Katherina , Vögeli Beat , Kast Peter , Pervushin Konstantin , Hilvert Donald
Published: August 2004

A highly active, monomeric chorismate mutase, obtained by topological redesign of a dimeric helical bundle enzyme from
Methanococcus jannaschii
, was investigated by NMR and various other biochemical techniques, including H/D exchange. Although structural disorder is generally considered to be incompatible with efficient catalysis, the monomer, unlike its natural counterpart, unexpectedly possesses all of the characteristics of a molten globule. Global conformational ordering, observed upon binding of a transition state analog, indicates that folding can be coupled to catalysis with minimal energetic penalty. These results support the suggestion that many modern enzymes might have evolved from molten globule precursors. Insofar as their structural plasticity confers relaxed substrate specificity and/or catalytic promiscuity, molten globules may also be attractive starting points for the evolution of new catalysts in the laboratory.
Aging reduces neural specialization in ventral visual cortex
Authors: Park Denise C. , Polk Thad A. , Park Rob , Minear Meredith , Savage Anna , Smith Mason R.
Published: August 2004

The present study investigated whether neural structures become less functionally differentiated and specialized with age. We studied ventral visual cortex, an area of the brain that responds selectively to visual categories (faces, places, and words) in young adults, and that shows little atrophy with age. Functional MRI was used to estimate neural activity in this cortical area, while young and old adults viewed faces, houses, pseudowords, and chairs. The results demonstrated significantly less neural specialization for these stimulus categories in older adults across a range of analyses.
Drosophila
lifespan enhancement by exogenous bacteria
Authors: Brummel Ted , Ching Alisa , Seroude Laurent , Simon Anne F. , Benzer Seymour
Published: August 2004

We researched the lifespan of
Drosophila
under axenic conditions compared with customary procedure. The experiments revealed that the presence of bacteria during the first week of adult life can enhance lifespan, despite unchanged food intake. Later in life, the presence of bacteria can reduce lifespan. Certain long-lived mutants react in different ways, indicating an interplay between bacteria and longevity-enhancing genes.
Therapeutic vaccination using CD4+CD25+antigen-specific regulatory T cells
Authors: Bluestone Jeffrey A. , Tang Qizhi
Published: August 2004

Autoimmune disease results from the dysregulation of basic tolerogenic processes designed to control self/non-self-discrimination. Approaches to treat autoimmunity have focused historically on potent immunosuppressives that block the activation and expansion of antigen-specific T cells before they differentiate into pathogenic T cell responses. These therapies are very efficient in reducing clonal expansion and altering early signaling pathways. However, once the pathogenic responses are established (i.e., autoimmunity), the interventions are less effective on activated and differentiated T cell subsets (including memory T cells) or acting in the presence of an inflammatory milieu to abort immune responses at the target tissue and systemically. Moreover, the current immunotherapies require continuous use because they do not redirect the immune system to a state of tolerance. The continuous treatment leads to long-term toxicities and can profoundly suppress protective immune responses targeted at viruses, bacteria, and other pathogens. Over the past decade, there have been tremendous advances in our understanding of the basic processes that control immune tolerance. Among the most exciting has been the identification of a professional regulatory T cell subset that has shown enormous potential in suppressing pathologic immune responses in autoimmune diseases, transplantation, and graft vs. host disease. In this review, we summarize current efforts to induce and maintain tolerance in the autoimmune diabetes setting by using therapeutic vaccination with CD4+CD25+regulatory T cells. Emphasis will be placed on approaches to exploit regulatory T cells either directly or through the use of anti-CD3 immunotherapy.
Hepatocyte Proliferation is the Possible Mechanism for the Transient Decrease in Liver Injury During Steatosis Stage of Alcoholic Liver Disease
Authors: Apte Udayan M. , Mcree Rachel , Ramaiah Shashi K.
Published: August 2004

Steatosis is a frequent pathologic stage in alcoholic liver disease (ALD). Although the mechanisms for increased susceptibility of steatotic liver to injury have been postulated, the ability of these hepatocytes to proliferate and withstand injury is unknown. There are conflicting reports on the status of hepatocyte regeneration following chronic alcohol ingestion. Hence, the objective of this study was to investigate the temporal dynamics between the pattern of liver injury and hepatocyte proliferation during the steatosis stage of ALD. Alcoholic steatosis was induced in male Sprague—Dawley rats by feeding an ethanol (EtOH)-containing Lieber-DeCarli liquid diet for a period of 5 weeks. Microvesicular steatosis was evident in H&E sections by three weeks in the EtOH-treated rats, which further developed into panlobular macrovesicular steatosis by 5 weeks. Plasma transaminase activities indicated progressive increase in liver injury peaking at 3 weeks with significant but mild decrease at 4 and 5 weeks. CYP2E1 protein and activity was significantly increased in EtOH-fed rats as measured by Western blot and pNP hydroxylation assay. PCNA analysis of liver sections indicated that EtOH-treated rats had a significantly higher number of cells in S phase of cell division at weeks 1 (3.20 ± 0.19), 2 (7.03 ± 0.92), and 3 (4.23 ± 1.41) when compared to controls (1.5 ± 0.22). NF- κB DNA binding and Cyclin D1 proteins increased significantly in the EtOH-treated rats corresponding with enhanced hepatic proliferation. These data suggest the transient decline in liver injury during alcoholic steatosis is due to enhanced NF- κB-dependent hepatocyte proliferation.
Regional Variations of Contractile Activity in Isolated Rat Lymphatics
Authors: GASHEV ANATOLIY A. , DAVIS MICHAEL J. , DELP MICHAEL D. , ZAWIEJA DAVID C.
Published: August 2004

Objective: To evaluate lymphatic contractile activity in different regions of the lymphatic system in a single animal model (the rat thoracic duct, mesenteric, cervical, and femoral lymphatics) in response to changes in lymph pressure and flow.

Methods: The systolic and diastolic diameters of isolated, cannulated, and pressurized lymphatic vessels were measured. Contraction frequency, ejection fraction, and fractional pump flow were determined. The influences of incrementally increased transmural pressure (from 1 to 9 cm H2O) and imposed flow (from 1 to 5 cm H2O transaxial pressure gradient) were investigated.

Results: The authors determined regional differences in lymphatic contractility in response to pressure and imposed flow. They found the highest pumping (at the optimal pressure levels) in mesenteric lymphatics and lowest pumping in thoracic duct. All lymphatics had their optimal pumping conditions at low levels of transmural pressure. Different degrees of the flow‐induced inhibition of the pump were observed in the different types of lymphatics. During high flow, the active lymph pumps in thoracic duct and cervical lymphatics were almost completely abolished, whereas mesenteric and femoral lymphatics still exhibited significant active pumping.

Conclusions: The active lymph pumps in different regions of the rat body express variable relative strengths and sensitivities that are predetermined by different hydrodynamic factors and regional outflow resistances in their respective locations.
A method for estimating stochastic noise in large genetic regulatory networks
Authors: Orrell David , Ramsey Stephen , de Atauri Pedro , Bolouri Hamid
Published: August 2004

Motivation: Genetic regulatory networks are often affected by stochastic noise, due to the low number of molecules taking part in certain reactions. The networks can be simulated using stochastic techniques that model each reaction as a stochastic event. As models become increasingly large and sophisticated, however, the solution time can become excessive; particularly if one wishes to determine the effect on noise of changes to a series of parameters, or the model structure. Methods are therefore required to rapidly estimate stochastic noise.

Results: This paper presents an algorithm, based on error growth techniques from non-linear dynamics, to rapidly estimate the noise characteristics of genetic networks of arbitrary size. The method can also be used to determine analytical solutions for simple sub-systems. It is demonstrated on a number of cases, including a prototype model of the galactose regulatory pathway in yeast.

Availability: A software tool which incorporates the algorithm is available for use as part of the stochastic simulation package Dizzy. It is available for download at http://labs.systemsbiology.net/bolouri/software/Dizzy/

Contact:  dorrell@systemsbiology.org

Supplementary information: A conceptual model of the regulatory part of the galactose utilization pathway in yeast, used as an example in the paper, is available at http://labs.systemsbiology.net/bolouri/models/galconcept.dizzy
Financial Variables and the Simulated Out‐of‐Sample Forecastability of U.S. Output Growth Since 1985: An Encompassing Approach
Authors: Rapach David E. , Weber Christian E.
Published: August 2004

We reconsider the out‐of‐sample forecasting ability of a large number of financial variables with respect to real output growth over the 1985:1–1999:4 period. We show that models including financial variables display almost no forecasting ability relative to an autoregressive benchmark model over this period according to a mean squared forecast error metric. However, tests based on forecast encompassing indicate that many financial variables do, in fact, contain information that is useful for forecasting real output growth over the 1985:1–1999:4 out‐of‐sample period. Our results suggest that the extant literature exaggerates the demise of the forecasting power of financial variables with respect to real activity since the mid‐1980s.
International and Intersectoral R&D Spillovers in the OECD and East Asian Economies
Authors: Park Jungsoo
Published: August 2004

This study empirically explores international and intersectoral R&D spillover effects on the total factor productivity growth of manufacturing and nonmanufacturing sectors based on a pooled time‐series data set of 14 OECD economies and 3 East Asian economies—Korea, Singapore, and Taiwan. The study finds that foreign manufacturing R&D has strong influence on domestic productivity growths of both sectors and that domestic manufacturing R&D has a substantial intersectoral R&D spillover effect on domestic nonmanufacturing productivity growth. The social rates of return to manufacturing R&D are estimated to be two to six times greater than the private rates of return.
A Bayesian Change Point Model for Historical Time Series Analysis
Authors: Western Bruce , Kleykamp Meredith
Published: August 2004

Political relationships often vary over time, but standard models ignore temporal variation in regression relationships. We describe a Bayesian model that treats the change point in a time series as a parameter to be estimated. In this model, inference for the regression coefficients reflects prior uncertainty about the location of the change point. Inferences about regression coefficients, unconditional on the change-point location, can be obtained by simulation methods. The model is illustrated in an analysis of real wage growth in 18 OECD countries from 1965–1992.
What Do We Learn from Graduate Admissions Committees? A Multiple Rater, Latent Variable Model, with Incomplete Discrete and Continuous Indicators
Authors: Jackman Simon
Published: August 2004

What do we really know about applicants to graduate school? How much information is in an applicant's file? What do we learn by having graduate admissions committees read and score applicant files? In this article, I develop a statistical model for measuring applicant quality, combining the information in the committee members' ordinal ratings with the information in applicants' GRE scores. The model produces estimates of applicant quality purged of the influence of committee members' preferences over ostensibly extraneous applicant characteristics, such as gender and intended field of study. An explicitly Bayesian approach is adopted for estimation and inference, making it straightforward to obtain confidence intervals not only on latent applicant quality but over rank orderings of applicants and the probability of belonging in a set of likely admittees. Using data from applications to a highly ranked political science graduate program, I show that there is considerable uncertainty in estimates of applicant quality, making it impossible to make authoritative distinctions as to quality among large portions of the applicant pool. The multiple rater model I develop here is extremely flexible and has applications in fields as diverse as judicial politics, legislative politics, international relations, and public opinion.
Dynamic Tempered Transitions for Exploring Multimodal Posterior Distributions
Authors: Gill Jeff , Casella George
Published: August 2004

Multimodal, high-dimension posterior distributions are well known to cause mixing problems for standard Markov chain Monte Carlo (MCMC) procedures; unfortunately such functional forms readily occur in empirical political science. This is a particularly important problem in applied Bayesian work because inferences are made from finite intervals of the Markov chain path. To address this issue, we develop and apply a new MCMC algorithm based on tempered transitions of simulated annealing, adding a dynamic element that allows the chain to self-tune its annealing schedule in response to current posterior features. This important feature prevents the Markov chain from getting trapped in minor modal areas for long periods of time. The algorithm is applied to a probabilistic spatial model of voting in which the objective function of interest is the candidate's expected return. We first show that such models can lead to complex target forms and then demonstrate that the dynamic algorithm easily handles even large problems of this kind.
Human Septic Myopathy: Induction of Cyclooxygenase, Heme Oxygenase and Activation of the Ubiquitin Proteolytic Pathway
Authors: Rabuel Christophe , Renaud Estelle , Brealey David , Ratajczak Philippe , Damy Thibaut , Alves Arnaud , Habib Aïda , Singer Mervyn , Payen Didier , Mebazaa Alexandre
Published: August 2004

Background

Skeletal muscle failure and wasting are manifestations of sepsis in humans that leads to serious and prolonged complications. The authors investigated the role of the major proinflammatory and antiinflammatory pathways, namely the inducible isoforms cyclooxygenase (COX-2) and heme oxygenase (HO-1), and the ubiquitin proteolytic pathway in skeletal muscle of septic patients.

Methods

Protein expression was detected by Western blot techniques. Muscle biopsies were taken from two muscle groups, rectus abdominis and vastus lateralis, of septic and control patients.

Results

The study showed an increase in COX-2 and HO-1 proteins expression and an activation of the proteolytic ubiquitin pathway with a parallel increase in free ubiquitin and ubiquitinated proteins in skeletal muscle of septic but not of control patients. In addition, those patients who would die from septic shock expressed more COX-2 and HO-1 proteins in muscle biopsies than did those patients who would survive.

Conclusions

This study showed a marked involvement of local proinflammatory and antiinflammatory pathways and, more importantly, demonstrated the existence of an active ubiquitin proteolytic pathway in skeletal muscle of septic patients. Activation of ubiquitin pathway could be involved in sepsis-related muscle catabolism and wasting.
Accuracy of Pharmacokinetic Models for Predicting Plasma Fentanyl Concentrations in Lean and Obese Surgical Patients
Authors: Shibutani Kinichi , Inchiosa Mario A. , Sawada Keisuke , Bairamian Mosses
Published: August 2004

Background

The currently available pharmacokinetic models for fentanyl were derived from normal weight patients and were not scaled to body weight. Their application to obese patients may cause overprediction of the plasma concentration of fentanyl. This study examined the influence of body weight on the predictive accuracy of two models (Anesthesiology 1990; 73:1091-102 and J Pharmacol Exp Ther 1987; 240:159-66). Further, we attempted to derive suggested dosing mass weights for fentanyl that improved predicted accuracy.

Method

Seventy patients undergoing major elective surgery with total body weight (TBW) <85 kg and body mass index <30 (Group L) and 39 patients with TBW >/=85 kg and body mass index >30 (Group O) were studied. In Group L and Group O, the mean TBW was 69 kg, and 125 kg, respectively and the mean body mass index in Group L and Group O was 24 and 44, respectively. Fentanyl infusion was used during surgery and postoperatively for analgesia. Plasma fentanyl concentrations were measured and predicted concentrations were obtained by computer simulation; 465 pairs of measured and predicted values were obtained.

Results

The influence of TBW on the performance errors of the original two models was examined with nonlinear regression analysis. Shafer error versus TBW showed a highly significant negative relationship (R squared = 0.689, P < 0.001); i.e., the Shafer model systematically overestimated fentanyl concentration as weight increased. The Scott and Stanski model showed greater variation (R squared = 0.303). We used the exponential equation for Shafer performance error versus TBW to derive suggested dosing weights ("pharmacokinetic mass") for obese patients. The pharmacokinetic mass versus TBW curve was essentially linear below 100 kg (with slope of 0.65) and approached a plateau above 140 kg. For patients weighing 140 to 200 kg, dosing weights of 100-108 kg are projected. Total body clearance (ml/min) showed a strong linear correlation with pharmacokinetic mass (r = 0.793; P < 0.001), whereas the relationship with TBW was nonlinear.

Conclusion

Actual body weight overestimates fentanyl dose requirements in obese patients. Dosing weight (pharmacokinetic mass) derived from the nonlinear relationship between prediction error and TBW proved to have a linear relationship with clearance.
Influence of Hemorrhagic Shock Followed by Crystalloid Resuscitation on Propofol
Authors: Johnson Ken B. , Egan Talmage D. , Kern Steven E. , McJames Scott W. , Cluff Mark L. , Pace Nathan L.
Published: August 2004

Background

Previous work has demonstrated that ongoing hemorrhagic shock dramatically alters the distribution, clearance, and potency of propofol. Whether volume resuscitation after hemorrhagic shock restores drug behavior to baseline pharmacokinetics and pharmacodynamics remains unclear. This is particularly relevant because patients suffering from hemorrhagic shock are typically resuscitated before surgery. To investigate this, the authors studied the influence of an isobaric bleed followed by crystalloid resuscitation on the pharmacokinetics and pharmacodynamics of propofol in a swine model. The hypothesis was that hemorrhagic shock followed by resuscitation would not significantly alter the pharmacokinetics but would influence the pharmacodynamics of propofol.

Methods

After approval from the Animal Care Committee, 16 swine were randomly assigned to control and shock-resuscitation groups. Swine randomized to the shock-resuscitation group were bled to a mean arterial blood pressure of 40 mm Hg over a 20-min period and held there by further blood removal until 42 ml/kg of blood had been removed. Subsequently, animals were resuscitated with lactated Ringer's solution to maintain a mean arterial blood pressure of 70 mm Hg for 60 min. After resuscitation, propofol (750 microg x kg(-1) x min(-1)) was infused for 10 min. The control group underwent a sham hemorrhage and resuscitation and received propofol at the same dose and approximate time as the shock-resuscitation group. Arterial samples (20 from each animal) were collected at frequent intervals until 180 min after the infusion began and were analyzed to determine drug concentrations. Pharmacokinetic parameters for each group were estimated using a three-compartment model. The electroencephalogram Bispectral Index Scale was used as a measure of drug effect. Pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model.

Results

The raw data demonstrated minimal differences in the mean plasma propofol concentrations between groups. The compartment analysis revealed some subtle differences between groups in the central and slow equilibrating volumes, but the differences were not significant. Hemorrhagic shock followed by resuscitation shifted the concentration effect relationship to the left, demonstrating a 1.5-fold decrease in the effect-site concentration required to achieve 50% of the maximal effect in the Bispectral Index Scale.

Conclusions

Hemorrhagic shock followed by resuscitation with lactated Ringer's solution did not alter the pharmacokinetics but did increase the potency of propofol. These results demonstrate that alterations in propofol pharmacokinetics observed in moderate to severe blood loss can be reversed with resuscitation. These results suggest that a modest reduction in propofol is prudent to achieve a desired drug effect after resuscitation from severe hemorrhagic shock.
Elimination Rate Constant Describing Clearance of Infused Fluid from Plasma Is Independent of Large Infusion Volumes of 0.9% Saline in Sheep
Authors: Svensén Christer H. , Brauer Kirk P. , Hahn Robert G. , Uchida Tatsuo , Traber Lillian D. , Traber Daniel L. , Prough Donald S.
Published: August 2004

Background

The purpose of this study was to determine the influence of varying large crystalloid infusion volumes, ranging from a volume that has been safely administered to volunteers to a volume that greatly exceeds a practical volume for studies in normovolemic humans, of rapidly infused 0.9% saline on the elimination rate constant in sheep.

Methods

Six sheep underwent three randomly ordered, 20 min, intravenous infusions of 0.9% saline in volumes of 25 ml/kg, 50 ml/kg and 100 ml/kg. Repeated measurements of arterial plasma dilution were analyzed using the volume kinetic approach to determine the apparent volumes of the central (V1) and peripheral (V2) body fluid spaces, the elimination rate constant (kr) describing clearance from the central fluid space and the rate constant (kt) for the diffusion of fluid between the central and the peripheral fluid spaces. The latter constant was split in to two constants, one describing flow out from the central fluid space and one describing flow into the central fluid space. Urinary output was measured in all sheep.

Results

kr was comparable at each infused volume (38.3 +/- 4.5, 32.2 +/- 4.2, and 36.7 +/- 7.0 ml/min, respectively, in the 25 ml/kg, 50 ml/kg, and 100 ml/kg protocols). However, for the largest infusion, other kinetic parameters were influenced by the magnitude of the infusion. V2 was significantly increased (P < 0.05) and the area under the dilution-time curve divided by the infused volume was 20% lower for the largest infusion (P < 0.03). Although urinary output increased as the infusion volume increased, only 59% of the administered volume had been excreted at 180 min after the 100 ml/kg infusion as compared with approximately 90% after the other two infusions (P < 0.01).

Conclusions

Elimination from the central fluid space of large, rapidly infused volumes of saline solution is independent of infused volume. Larger volumes are apparently cleared from the central fluid space (V1) by expansion of a peripheral volume (V2) as renal excretion fails to increase in proportion to the volume of infused fluid.
Effects of Peak Inspiratory Flow on Development of Ventilator-induced Lung Injury in Rabbits
Authors: Maeda Yoshiko , Fujino Yuji , Uchiyama Akinori , Matsuura Nariaki , Mashimo Takashi , Nishimura Masaji
Published: August 2004

Background

A lung-protecting strategy is essential when ventilating acute lung injury/acute respiratory distress syndrome patients. Current emphasis is on limiting inspiratory pressure and volume. This study was designed to investigate the effect of peak inspiratory flow on lung injury.

Methods

Twenty-four rabbits were anesthetized, tracheostomized, ventilated with a Siemens Servo 300, and randomly assigned to three groups as follows: 1) the pressure regulated volume control group received pressure-regulated volume control mode with inspiratory time set at 20% of total cycle time, 2) the volume control with 20% inspiratory time group received volume-control mode with inspiratory time of 20% of total cycle time, and 3) the volume control with 50% inspiratory time group received volume-control mode with inspiratory time of 50% of total cycle time. Tidal volume was 30 ml/kg, respiratory rate was 20 breaths/min, and positive end-expiratory pressure was 0 cm H2O. After 6 h mechanical ventilation, the lungs were removed for histologic examination.

Results

When mechanical ventilation started, peak inspiratory flow was 28.8 +/- 1.4 l/min in the pressure regulated volume control group, 7.5 +/- 0.5 l/min in the volume control with 20% inspiratory time group, and 2.6 +/- 0.3 l/min in the volume control with 50% inspiratory time group. Plateau pressure did not differ significantly among the groups. Gradually during 6 h, Pao2 in the pressure regulated volume control group decreased from 688 +/- 39 to a significantly lower 304 +/- 199 mm Hg (P < 0.05) (mean +/- SD). The static compliance of the respiratory system for the pressure regulated volume control group also ended significantly lower after 6 h (P < 0.05). Wet to dry ratio for the pressure regulated volume control group was larger than for other groups (P < 0.05). Macroscopically and histologically, the lungs of the pressure regulated volume control group showed more injury than the other groups.

Conclusion

When an injurious tidal volume is delivered, the deterioration in gas exchange and respiratory mechanics, and lung injury appear to be marked at a high peak inspiratory flow.
Comparative Analgesic and Mental Effects of Increasing Plasma Concentrations of Dexmedetomidine and Alfentanil in Humans
Authors: Angst Martin S. , Ramaswamy Bhamini , Davies M Frances , Maze Mervyn
Published: August 2004

Background

In animals, systemic and intrathecal administration of the alpha2 -adrenergic receptor agonist dexmedetomidine results in robust antinociceptive effects in models of heat pain. In humans, systemically administered dexmedetomidine is approved for sedating patients in the intensive care unit. However, whether systemic administration of dexmedetomidine in humans produces significant analgesia at doses causing sedation but not unconsciousness remains controversial.

Methods

This study in human volunteers used a placebo-controlled, double-blind, and randomized design to examine whether dexmedetomidine at doses causing mild to severe sedation produces analgesia in experimental models of heat and electrical pain. Results were compared to the effects of the mu-opioid receptor agonist alfentanil. A computer-controlled infusion provided four median step-up plasma concentrations of dexmedetomidine (0.09, 0.24, 0.54, and 1.23 ng/ml) and alfentanil (13.4, 33.8, 67.8, and 126.1 ng/ml).

Results

Sedative and cognitive effects of dexmedetomidine were dose-dependent, resulting in a median sedation score of 95 of 100 and slowing of cognitive speed (reaction time, trail-making test) by a factor of about two at the highest plasma concentration. Dexmedetomidine did not attenuate heat or electrical pain. Alfentanil caused severe sedation (median sedation score 88 of 100) and slowed cognitive speed by a factor of approximately 1.4 at the highest plasma concentration. Alfentanil attenuated heat and electrical pain dose dependently.

Conclusion

This study documents that systemic dexmedetomidine lacks analgesic efficacy for heat and electrical pain at doses causing mild to severe sedation. These results provide further evidence suggesting that systemic administration of dexmedetomidine lacks broad analgesic activity in models of acute pain at doses not rendering humans unconscious.
Intrathecal Gabapentin Enhances the Analgesic Effects of Subtherapeutic Dose Morphine in a Rat Experimental Pancreatitis Model
Authors: Smiley Matthew M. , Lu Ying , Vera-Portocarrero Louis P. , Zidan Amr , Westlund Karin N.
Published: August 2004

Background

Morphine sulfate has long been used for analgesia, but clinical applications can be limited by side effects, tolerance, and potential for addiction at therapeutic doses. An agent that produces therapeutic analgesia when coadministered with low-dose morphine could have important clinical uses. The anticonvulsant agent gabapentin has been identified as having antihyperalgesic properties acting on the alpha2delta1 subunit of N-type voltage-activated calcium channels on dorsal root ganglia neurons. In this study, intrathecal gabapentin, which by itself is ineffective when administered spinally, was combined with low-dose morphine and tested in an acute bradykinin-induced pancreatitis model in rats.

Methods

An intrathecal catheter was surgically inserted into the subarachnoid space of male Sprague-Dawley rats. A laparotomy was performed for ligation and cannulation of the bile-pancreatic duct. Rats were pretreated intrathecally with artificial cerebrospinal fluid, gabapentin, morphine, or combined gabapentin and morphine 30 min before bradykinin injection into the bile-pancreatic duct. Spontaneous behavioral activity (cage crossing, rearing, and hind limb extension) was monitored before drug injection (baseline) and after bradykinin injection into the bile-pancreatic duct to assess visceral pain.

Results

Spinal pretreatment with up to 300 microg gabapentin alone was not effective in reducing hind limb extension in this model, but did restore some cage crossing and rearing behaviors. Spinal treatment with low-dose morphine reduced hind limb extension only. Spinal pretreatment with combined gabapentin and subtherapeutic doses of morphine sulfate resulted in restoration of all spontaneous behaviors to surgical baseline levels including elimination of hind limb extension.

Conclusion

Combined spinal administration of gabapentin and low doses of morphine significantly reduces pain-related behaviors in this acute rat pancreatitis model, whereas these agents were ineffective when used alone in this dose range. These data suggest that the alpha2delta1 subunit of the N-type voltage-activated Ca2+ channels is involved in transmission of this visceral pain, likely through effects on primary afferent endings in the spinal cord. Thus, gabapentin may be an effective adjuvant to initial low dose spinal opioid therapy for clinical management of visceral pain.
Subdural Empyema in Africans in Rhodesia
Authors: Glasauer Franz E. , Coots Diana , Levy Laurence F. , Auchterlonie William C.
Published: August 2004

Subdural empyema was encountered in 44 African patients in Rhodesia during the period from 1970 to 1974. Subdural empyema seems to be a relatively frequent occurrence in Africans. Sixty-eight per cent of the patients were below the age of 20 years, and males predominated. More than half of the patients had either a history or evidence of an infectious process outside the central nervous system, and about 60% demonstrated focal neurological signs. The diagnosis was confirmed by either surgery or postmortem examination. Cultures of available specimens were positive in 50%. The predominant organisms identified were Streptococcus, followed by Staphylococcus. Surgical treatment consisted mainly of multiple burr holes, drainage of the empyema, and irrigation. The mortality rate in this study was 59%, and some recognizable contributing factors are elaborated. In the discussion the authors compare these observations with pertinent reviews from the literature. Some of these findings correlate well with other reports, whereas other observations are attributed to factors partly inherent in the socio-economic structure of the African population in Rhodesia.