bluuebunny/crossref_metadata_2025 huggingface dataset:
Layer‐By‐Layer‐Assembled Capsules and Films for Therapeutic Delivery
Authors: Becker Alisa L. , Johnston Angus P. R. , Caruso Frank
Published: August 2010

Polymeric materials formed via layer‐by‐layer (LbL) assembly have promise for use as drug delivery vehicles. These multilayered materials, both as capsules and thin films, can encapsulate a high payload of toxic or sensitive drugs, and can be readily engineered and functionalized with specific properties. This review highlights important and recent studies that advance the use of LbL‐assembled materials as therapeutic devices. It also seeks to identify areas that require additional investigation for future development of the field. A variety of drug‐loading methods and delivery routes are discussed. The biological barriers to successful delivery are identified, and possible solutions to these problems are discussed. Finally, state‐of‐the‐art degradation and cargo release mechanisms are also presented.
Hybrid RANS/LES applied to complex terrain
Authors: Bechmann A. , Sørensen N. N.
Published: August 2010

Large Eddy Simulation (LES) of the wind in complex terrain is limited by computational cost. The number of computational grid points required to resolve the near‐ground turbulent structures (eddies) are very high. The traditional solution to the problem has been to apply a wall function that accounts for the whole near‐wall region. Recently, a hybrid method was proposed in which the eddies close to the ground were modelled in a Reynolds‐averaged sense (RANS) and the eddies above this region were simulated using LES. The advantage of the approach is the ability to use shallow cells of high aspect ratio in the RANS layer and thereby resolve the mean near‐wall velocity profile. The method is applicable to complex terrain and the benefits of traditional LES are kept intact.

Using the hybrid method, simulations of the wind over a natural complex terrain near Wellington in New Zealand are demonstrated. Under certain conditions, unsteady flow features have been measured at the site—flow features that could lead to high structural loads on a planned wind farm. These transient flow phenomena are reproduced with the new method. Additionally, the results from the hybrid method are compared with RANS results. Copyright © 2010 John Wiley & Sons, Ltd.
Atmospheric turbulence and its influence on the alternating loads on wind turbines
Authors: Mücke Tanja , Kleinhans David , Peinke Joachim
Published: August 2010

Analysis of measurements on atmospheric turbulence with respect to the statistics of velocity increments reveals that the statistics are not Gaussian but highly intermittent. Here, we demonstrate that the higher quantity of extreme events in atmospheric wind fields transfers to alternating loads on the airfoil and on the main shaft in the form of torque fluctuations. For this purpose, alternating loads are discussed with respect to their increment statistics. Our conjecture is that the anomalous wind statistics are responsible for load changes, which may potentially contribute to additional loads and may cause additional fatigue. Our analysis is performed on three different wind field data sets: measured fields, data generated by a standard wind field model and data generated by an alternative model based on continuous time random walks, which grasps the intermittent structure of atmospheric turbulence in a better way. Our findings suggest that fluctuations in the loads might not be reflected properly by the standard wind field models. Copyright © 2010 John Wiley & Sons, Ltd.
Syntheses, Crystal Structures, and Thermal Stabilities of Polymorphs of Cr(thd)3
Authors: Ahmed Mohammed A. K. , Fjellvåg Helmer , Kjekshus Arne , Birkedal Renie K. , Norby Poul , Wragg David S. , Gupta Nalinava Sen
Published: August 2010

The syntheses, crystal structures, and thermal stabilities of six polymorphs of Cr(thd)3 [(thd)– = anion of H(thd) = C11H20O2 = 2,2,6,6‐tetramethylheptane‐3,5‐dione] were studied using X‐ray diffraction and differential scanning calorimetry. Compound 1 is thermodynamically stable below ca. 110 °C and forms plate‐shaped crystals [a = 9.927(5), b = 18.010(5), c = 21.427(5) Å, and β = 95.461(5)° at 295 K; space group C2/c]. Its crystal structure is isotypic with Mn(thd)3. Polymorph 4 is metastable to 1, and the only way to prepare 4 appears to be by precipitation from solution. Crystals of 4 are needle shaped [a = 28.54(3), b = 19.14(2), c = 21.92(2) Å, and β = 97.31(2)° at 295 K; space group C2/c] and this structure is isotypic with monoclinic Co(thd)3. Modifications 2, 2*, and 5 also appear as needle‐shaped crystals [orthorhombic: a = 18.97(7), b = 18.69(7), and c = 10.62(5) Å for 2 and tetragonal: a = b = 18.93(5) and c = 10.57(4) Å for 5, both at 110 K]. Crystals of 2 and 5 have limited lifetime, which depends on storage temperature and exposure to X‐rays. The conversion sequence is: 5 → 2 → 1, where the first step takes 3 to 4 h and the second some 20 h. Attempts to establish detailed accounts of the orthorhombic Co(thd)3‐type structure of 2 and 2* by SXD were unsuccessful due to disorder. The structural distinction between 2 and 2* appears to be associated with rotational disorder among the Cr(thd)3 molecules. 2* and 3 are high‐temperature modifications with stability range ca. 155–200 and ca. 200–235 °C, respectively [Cr(thd)3 melts at ca. 235 °C]. Quenched 2* can be retained as metastable at room temp. for some weeks, whereas 3 is not quenchable. High‐temperature PXD data show that 3 is cubic [a = 13.357(4) Å at 225 °C; with strong rotational disorder of the molecules]. There are only minor variations in bond lengths and angles between 1 and 4 or from 100 to 295 K, and disorder is limited.
Perioperative Management of Patients with Connective Tissue Disease
Authors: Goodman Susan M. , Figgie Mark P. , MacKenzie C. Ronald
Published: August 2010

Diseases of the connective tissue are a varied group of disorders with major musculoskeletal manifestations such as joint pain and loss of function. As a consequence of the accompanying inflammatory joint disease, such patients often require surgery. Due to the protean organ-related consequences of these conditions, patients who suffer from chronic connective tissue disease are a highly challenging population in the perioperative context. This paper reviews the management of such patients in this clinical setting.
Lipid Profiling Reveals Tissue‐Specific Differences for Ethanolamide Lipids in Mice Lacking Fatty Acid Amide Hydrolase
Authors: Kilaru Aruna , Isaac Giorgis , Tamura Pamela , Baxter David , Duncan Scott R. , Venables Barney J. , Welti Ruth , Koulen Peter , Chapman Kent D.
Published: August 2010

N‐Acylethanolamines (NAE) are fatty acid derivatives, some of which function as endocannabinoids in mammals. NAE metabolism involves common (phosphatidylethanolamines, PEs) and uncommon (N‐acylphosphatidylethanolamines, NAPEs) membrane phospholipids. Here we have identified and quantified more than a hundred metabolites in the NAE/endocannabinoid pathway in mouse brain and heart tissues, including many previously unreported molecular species of NAPE. We found that brain tissue of mice lacking fatty acid amide hydrolase (FAAH−/−) had elevated PE and NAPE molecular species in addition to elevated NAEs, suggesting that FAAH activity participates in the overall regulation of this pathway. This perturbation of the NAE pathway in brain was not observed in heart tissue of FAAH−/− mice, indicating that metabolic regulation of the NAE pathway differs in these two organs and the metabolic enzymes that catabolize NAEs are most likely differentially distributed and/or regulated. Targeted lipidomics analysis, like that presented here, will continue to provide important insights into cellular lipid signaling networks.
Post‐ischemic administration of nimodipine following focal cerebral ischemic‐reperfusion injury in rats alleviated excitotoxicity, neurobehavioural alterations and partially the bioenergetics
Authors: Babu Chidambaram Saravana , Ramanathan Muthiah
Published: August 2010

The present study focuses on the temporal calcium significance in middle cerebral artery occluded (2 h ischemia)–reperfused (70 h reperfusion) rats treated with nimodipine (NM) through concurrent measurements of excitotoxicity, bioenergetics and neurobehavioural paradigms. Further, the suitable therapeutic time window of calcium channel antagonism in stroke was also ascertained. NM (5 mg/kg, i.p.) was administered at pre (30 min before the induction of ischemia), during (1 h following occlusion of MCA) and post‐ischemic (3 h after begin of reperfusion) states. The magnitude of neuroprotection in terms of excitotoxicity (glutamate, glutamine synthetase, Na+K+ATPase), bioenergetics (ATP, NAD+) and neurobehavioural paradigms (neurological score and open field exploratory behaviour) were measured and compared to ensure the therapeutic time‐window of NM in stroke. Middle cerebral artery occlusion‐reperfusion (MCAO/R) was found to elevate glutamate, glutamine synthetase levels and deplete Na+K+ATPase activity in the vehicle treated group (IR group). Significant decrease in bioenergetics such as ATP and NAD+ levels was also observed. Further, IR group demonstrated grievous oxidative stress (increase in lipid peroxidation, protein carbonyl content, nitrite/nitrate levels and decrease in superoxide dismutase and glutathione levels) along with anxiogenic behaviour, neurological deficits and neuronal damage and decreased nuclear to cytoplasm ratio in CA1 hippocampal region. Post‐ischemic NM administration reversed the excitotoxicity, neurobehavioural and histopathological alterations significantly, but it restored bioenergetics level in MCAO/R rats only partially.

These findings were further confirmed with the combination treatment (CT) of post‐ischemic NM and pre‐ischemic memantine (MN) administration, since MN showed protective effect in the pre‐ischemic administration (Babu and Ramanathan, 2009). The failure of NM to forefend the neurodegeneration on pre‐ and during‐ischemic administration suggests that the initial phase damages in ischemic‐reperfusion (IR) might be mediated through other mechanism(s) such as glutamergic overstimulation or reverse operation of glutamate transporters. From the present study, it is concluded that calcium plays a crucial role in post‐ischemic status and the suitable therapeutic time window of calcium antagonism is the post‐ischemic state.
“One does not live by bread alone”: Rural Reform and Village Political Strategies after the Peasants' War
Authors: Close Christopher W.
Published: August 2010

On July 17, 1539, the evangelical preachers in the free imperial city Augsburg petitioned the town council to thoroughly evangelize the surrounding countryside. The clerics bemoaned the treatment of “the poor peasantry, which has been lamentably misled and left to flounder without the word of God. The peasants are very confused, for they recognize papal teachings as deceptive yet are robbed of the Gospel's healthy teaching.” It was unnatural that “so many subjects in the countryside are separated, divided, and alienated from their divinely established magistracy in matters of faith.” To remedy the situation, the pastors exhorted Augsburg's councilors to provide the villagers “with fatherly care” through “the preaching of the Gospel.” They followed this injunction with a warning. If it took no action, “then truly the honorable council will have to answer before God, since the council collects tithes and taxes (zins und gult) from the poor people as its subjects, but it does not supply them with the food of souls.”
Blood, Power, and Hypocrisy: The Murder of Robert Imbrie and American Relations with Pehlavi Iran, 1924
Authors: Zirinsky Michael P.
Published: August 2010

On Friday, July 18, 1924, Robert W. Imbrie, United States Consul in Tehran— and personal friend and special agent of Allen W. Dulles, Chief of the State Department's Near Eastern Affairs Division—was brutally killed. Imbrie was beaten to death by a mob led by members of the Muslim clergy and including many members of the Iranian Army. In the weeks preceding July 18, there had been several outbreaks of anti-Bahai violence. Imbrie and Melvin Seymour had gone that morning to investigate a miraculous watering place in central Tehran that figured in the anti-Bahai excitement. According to contemporary accounts, a Bahai had been struck blind after drinking from the source when he refused to make an offering in the name of the Shi'i saints; his sight miraculously had been restored after he had repented and made the donation.
Synoptic velocity and pressure fields at the water–sediment interface of streambeds
Authors: DETERT M. , NIKORA V. , JIRKA G. H.
Published: August 2010

This paper presents a comprehensive study of the near-bed hydrodynamics at non-moving streambeds based on laboratory experiments in open-channel flows. Pressure and velocity measurements were made with an array of up to 15 miniaturized piezo-resistive pressure sensors within the bed and slightly above it, and a two-dimensional particle-image-velocimetry (PIV) system measuring in streamwise vertical or horizontal planes. Three different types of bed materials were studied covering typical natural streambed conditions. The range of the global Reynolds number covered in the experiments was from 20000 to 200000. This study provides new insights into the flow structure over gravel beds based on the PIV measurements in both streamwise vertical and horizontal planes. In a streamwise vertical plane, large-scale wedge-like flow structures were observed where a zone of faster fluid over-rolled a zone with slower fluid. The resulting shear layer was inclined along the flow at an angle of 10°–25° to the bed, and was populated with clockwise rotating eddies. This mechanism occurred with sufficient frequency and shape to leave an ‘imprint’ in the velocity statistics. Typically, the described flow pattern is formed near the bed and is approximately scaled with the height of the logarithmic layer, although the biggest structures extended over the whole flow depth. In a horizontal near-bed plane, turbulent structures formed a patched ‘chessboard’ pattern with regions of lower and higher velocities that were elongated in the streamwise direction. Their lateral extension was typically two to four times the equivalent sand roughness with lengths up to several water depths. The dimensions of the regions were increasing linearly with the distance from the bed. These findings are consistent with conceptual models originally developed for smooth-wall flows. They also support observations made in rough-bed flume experiments, numerical simulations and natural rivers. Spatial fields of bed-pressure fluctuations were reconstructed by applying Taylor's frozen turbulence hypothesis on time data obtained with an array of pressure sensors. Based on the conditional sampling of velocity patterns associated with pressure-drop events a distinct bed-destabilizing flow-pressure pattern was identified. If a high-speed fluid in the wake of a large-scale wedge-like flow structure reaches the vicinity of the bed, a phenomenon akin to a Bernoulli effect leads to a distinctive low-pressure pattern. The resulting force may exceed the particles' submerged weight and is assumed to be able to give an initial lift to the particle. As a result, the exposed area of a particle is amplified and its angle of repose is reduced, increasing the probability for entrainment.
Streamwise vortices in shear flows: harbingers of transition and the skeleton of coherent structures
Authors: HALL PHILIP , SHERWIN SPENCER
Published: August 2010

The relationship between asymptotic descriptions of vortex–wave interactions and more recent work on ‘exact coherent structures’ is investigated. In recent years immense interest has been focused on so-called self-sustained processes in turbulent shear flows where the importance of waves interacting with streamwise vortex flows has been elucidated in a number of papers. In this paper, it is shown that the so-called ‘lower branch’ state which has been shown to play a crucial role in these self-sustained processes is a finite Reynolds number analogue of a Rayleigh vortex–wave interaction with scales appropriately modified from those for external flows to Couette flow, the flow of interest here. Remarkable agreement between the asymptotic theory and numerical solutions of the Navier–Stokes equations is found even down to relatively small Reynolds numbers, thereby suggesting the possible importance of vortex–wave interaction theory in turbulent shear flows. The relevance of the work to more general shear flows is also discussed.
On the wake-induced vibration of tandem circular cylinders: the vortex interaction excitation mechanism
Authors: ASSI G. R. S. , BEARMAN P. W. , MENEGHINI J. R.
Published: August 2010

The mechanism of wake-induced vibrations (WIV) of a pair of cylinders in a tandem arrangement is investigated by experiments. A typical WIV response is characterized by a build-up of amplitude persisting to high reduced velocities; this is different from a typical vortex-induced vibration (VIV) response, which occurs in a limited resonance range. We suggest that WIV of the downstream cylinder is excited by the unsteady vortex–structure interactions between the body and the upstream wake. Coherent vortices interfering with the downstream cylinder induce fluctuations in the fluid force that are not synchronized with the motion. A favourable phase lag between the displacement and the fluid force guarantees that a positive energy transfer from the flow to the structure sustains the oscillations. If the unsteady vortices are removed from the wake of the upstream body then WIV will not be excited. An experiment performed in a steady shear flow turned out to be central to the understanding of the origin of the fluid forces acting on the downstream cylinder.
The relationship between controlled joint torque and end-effector force in underactuated robotic systems
Authors: Park Jaeheung
Published: August 2010

The generalized Jacobian matrix was introduced for dealing with end-effector control in space robots. One of the applications of this Jacobian is to be used in Jacobian transpose control to generate joint torques given end-effector position error. It would be misleading, however, to consider the transpose of this Jacobian as a mapping from end-effector force/moment to controlled joint torques for underactuated systems or floating base robots. This paper explains why it does not represent the mapping and provides a simple example. Later, the correct mapping is provided using the dynamically consistent Jacobian inverse and then a method to compute the actuated-joint torques is explained given the desired end-effector force. Finally, the effect of using the generalized Jacobian in the Jacobian transpose control is analyzed.
The origin of the vertebrate skeleton
Authors: Pivar Stuart
Published: August 2010

The anatomy of the human and other vertebrates has been well described since the days of Leonardo da Vinci and Vesalius. The causative origin of the configuration of the bones and of their shapes and forms has been addressed over the ensuing centuries by such outstanding investigators as Goethe, Von Baer, Gegenbauer, Wilhelm His and D'Arcy Thompson, who sought to apply mechanical principles to morphogenesis. However, no coherent causative model of morphogenesis has ever been presented.

This paper presents a causative model for the origin of the vertebrate skeleton, based on the premise that the body is a mosaic enlargement of self-organized patterns engrained in the membrane of the egg cell. Drawings illustrate the proposed hypothetical origin of membrane patterning and the changes in the hydrostatic equilibrium of the cytoplasm that cause topographical deformations resulting in the vertebrate body form.
Constraints on the evolution of social institutions and their implications for information flow
Authors: DUNBAR R. I. M.
Published: August 2010

Human communities and ego-centric social networks have a distinct size that reflects a generic relationship between relative neocortex volume and social group size that is characteristic of primates in general (the ‘social brain hypothesis’). Human networks are structured into layers that reflect both differences in the frequency of contact and levels of emotional closeness. The rate of decay in the frequency of contact across network layers is very steep, and we might expect this to have a very significant effect on the likelihood of Ego finding out some novel fact when information flow is limited to face-to-face interaction. I use an analytical model parameterized by these contact frequencies to show that there may be little advantage in having a network larger than ~150 for the purposes of information exchange. I then present a Monte Carlo simulation model to show that structure significantly impedes the rate of information flow in structured communities.
POSITIVE FRAGMENTS OF RELEVANCE LOGIC AND ALGEBRAS OF BINARY RELATIONS
Authors: HIRSCH ROBIN , MIKULÁS SZABOLCS
Published: August 2010

We prove that algebras of binary relations whose similarity type includes intersection, union, and one of the residuals of relation composition form a nonfinitely axiomatizable quasivariety and that the equational theory is not finitely based. We apply this result to the problem of the completeness of the positive fragment of relevance logic with respect to binary relations.
A synopsis of urban violence in South Africa
Authors: Abrahams David
Published: August 2010

On 27 April 1994, all South Africans were permitted to vote for the first time, signalling the birth of a democratic state built on a constitutional democracy. Yet the wrath of gang-related activities in townships and other urban areas was clearly visible, as was the xenophobic violence that shocked the world. Very often the vast majority of victims have been innocent civilians, and especially women and children. This article gives an overview of the various forms of violence in South Africa and also briefly considers the state's responses to them within the various legal frameworks.
Analysis of the Indian summer monsoon system in the regional climate model COSMO‐CLM
Authors: Dobler A. , Ahrens B.
Published: August 2010

The Indian summer monsoon (ISM) influences daily lives and economies in many countries in the South Asian region. This study analyzes the representation of the ISM system in the regional climate model COSMO‐CLM. Simulations driven by ERA‐40 reanalysis and present‐day (1960–2000) data from the global climate model ECHAM5 are investigated. The ability of COSMO‐CLM to reproduce the ISM better than the coarser‐grid driving models is tested using a set of well‐established, complementary monsoon indices: the all‐India monsoon rainfall, vertical wind shear indices, and an outgoing longwave radiation (OLR) index. The results show that regarding these large‐scale indices the COSMO‐CLM simulations are not more accurate than the driving models. Considering the spatial distribution of rainfall, the ERA‐40–driven COSMO‐CLM simulations show major overestimations (about 100%) for the west coast of India and underestimations (about 50%) for the Himalayan foothills. Large biases occur in the OLR data over the Arabian Sea and the Bay of Bengal where COSMO‐CLM shows high convective activity (OLR < 180 W m−2) at about 3 times as many days as observed in the monsoon season. In the ECHAM5‐driven simulation, underestimations of rainfall also appear at the Himalayan foothills. Nevertheless, the application of COSMO‐CLM to ECHAM5 improves the temporal correlations of the modeled ISM indices, and the spatial patterns are better simulated in COSMO‐CLM with 0.44° horizontal grid spacing than in the large‐scale ECHAM5 data.
InSAR measurements of surface deformation over permafrost on the North Slope of Alaska
Authors: Liu Lin , Zhang Tingjun , Wahr John
Published: August 2010

Ground‐based measurements of active layer thickness provide useful data for validating/calibrating remote sensing and modeling results. However, these in situ measurements are usually site‐specific with limited spatial coverage. Here we apply interferometric synthetic aperture radar (InSAR) to measure surface deformation over permafrost on the North Slope of Alaska during the 1992–2000 thawing seasons. We find significantly systematic differences in surface deformation between floodplain areas and the tundra‐covered areas away from the rivers. Using floodplain areas as the reference for InSAR's relative deformation measurements, we find seasonally varying vertical displacements of 1–4 cm with subsidence occurring during the thawing season and a secular subsidence of 1–4 cm/decade. We hypothesize that the seasonal subsidence is caused by thaw settlement of the active layer and that the secular subsidence is probably due to thawing of ice‐rich permafrost near the permafrost table. These mechanisms could explain why in situ measurements on Alaskan North Slope reveal negligible trends in active layer thickness during the 1990s, despite the fact that atmospheric and permafrost temperatures in this region increased during that time. This study demonstrates that surface deformation measurements from InSAR are complementary to more traditional in situ measurements of active layer thickness, and can provide new insights into the dynamics of permafrost systems and changes in permafrost conditions.
Bayesian data fusion for water table interpolation: Incorporating a hydrogeological conceptual model in kriging
Authors: Peeters Luk , Fasbender Dominique , Batelaan Okke , Dassargues Alain
Published: August 2010

The creation of a contour map of the water table in an unconfined aquifer based on head measurements is often the first step in any hydrogeological study. Geostatistical interpolation methods (e.g., kriging) may provide exact interpolated groundwater levels at the measurement locations but often fail to represent the hydrogeological flow system. A physically based, numerical groundwater model with spatially variable parameters and inputs is more adequate in representing a flow system. Because of the difficulty in parameterization and solving the inverse problem, however, a considerable difference between calculated and observed heads will often remain. In this study the water‐table interpolation methodology presented by Fasbender et al. (2008), in which the results of a kriging interpolation are combined with information from a drainage network and a digital elevation model (DEM), using the Bayesian data fusion framework, is extended to incorporate information from a tuned analytic element groundwater model. The resulting interpolation is exact at the measurement locations whereas the shape of the head contours is in accordance with the conceptual information incorporated in the groundwater‐flow model. The Bayesian data fusion methodology is applied to a regional, unconfined aquifer in central Belgium. A cross‐validation procedure shows that the predictive capability of the interpolation at unmeasured locations benefits from the Bayesian data fusion of the three data sources (kriging, DEM, and groundwater model), compared to the individual data sources or any combination of two data sources.
Aged black carbon identified in marine dissolved organic carbon
Authors: Ziolkowski L. A. , Druffel E. R. M.
Published: August 2010

Produced on land by incomplete combustion of organic matter, black carbon (BC) enters the ocean by aerosol and river deposition. It has been postulated that BC resides in the marine dissolved organic carbon (DOC) pool before sedimentary deposition and may attribute to its great 14C age (1500–6500 14C years). Here we report the first radiocarbon measurements of BC in high molecular weight DOC (UDOM). BC exported from rivers is highly aromatic and <500 14C years old, while open ocean samples contain less aromatic BC and have an age of 18,000 ± 3,000 14C years. The low abundance of BC in UDOM (0.5–3.5%) suggests that it is more labile than presently believed and/or the low molecular weight DOC contains a larger proportion of aged BC.
Emissions of volatile organic compounds during the decomposition of plant litter
Authors: Gray Christopher M. , Monson Russell K. , Fierer Noah
Published: August 2010

Volatile organic compounds (VOCs) are emitted during plant litter decomposition, and such VOCs can have wide‐ranging impacts on atmospheric chemistry, terrestrial biogeochemistry, and soil ecology. However, we currently have a limited understanding of the relative importance of biotic versus abiotic sources of these VOCs and whether distinct types of litter emit different types and quantities of VOCs during decomposition. We analyzed VOCs emitted by microbes or by abiotic mechanisms during the decomposition of litter from 12 plant species in a laboratory experiment using proton transfer reaction mass spectrometry (PTR‐MS). Net emissions from litter with active microbial populations (non‐sterile litters) were between 0 and 11 times higher than emissions from sterile controls over a 20‐d incubation period, suggesting that abiotic sources of VOCs are generally less important than biotic sources. In all cases, the sterile and non‐sterile litter treatments emitted different types of VOCs, with methanol being the dominant VOC emitted from litters during microbial decomposition, accounting for 78 to 99% of the net emissions. We also found that the types of VOCs released during biotic decomposition differed in a predictable manner among litter types with VOC profiles also changing as decomposition progressed over time. These results show the importance of incorporating both the biotic decomposition of litter and the species‐dependent differences in terrestrial vegetation into global VOC emission models.
Computational Approaches to Ionotropic Glutamate Receptors
Authors: Vijayan Ranjit , Iorga Bogdan , Biggin Philip C.
Published: August 2010

Ionotropic glutamate receptors (iGluRs) mediate the majority of fast neurotransmission in the brain. They are tetrameric proteins that upon the binding of glutamate allow the passage of cations into or out of the cell. This flow of ions changes the transmembrane potential in that region of the cell membrane and is the physical basis for signal propagation in neurons. The iGluRs are large multi-domain proteins embedded within the membrane, a fact that has made the structural characterization rather difficult. However, the past decade has seen large increases in our understanding of the structure to function relationship in these receptors due to two key factors i) the development of a water-soluble construct of the ligand-binding domain making its structure amenable to biophysical studies including X-ray crystallography and nuclear magnetic resonance (NMR) and ii) the fact that the other domains show homology to related proteins whose structures have been recently solved enabling homology models to be developed. This structural information has formed the basis for much computational effort in recent years with particular application to the study of conformational change and compound specificity in these receptors. These computational studies have helped to formulate and reformulate working hypotheses that can be tested in the laboratory. Here we review recent computational work on the iGluRs and outline some areas for future work.
Molecular Mechanisms of Active Transport Across the Cellular Membrane
Authors: Wen Po-Chao , Huang Zhijian , Enkavi Giray , Tajkhorshid Emad
Published: August 2010

Active transport across the cellular membrane constitutes one of the most fundamental processes of life. Taking advantage of various sources of energy in a cell, e.g., ionic and pH gradients, electrical membrane potential, and ATP hydrolysis, specialized molecular machines known as membrane transporters translocate specific molecular species across the cellular membrane, often against their electrochemical gradients. Elucidation of the molecular mechanisms of these complex machines has long been hampered by lack of sufficient structural information, compounded by the complexity of their mechanisms and the lack of the temporal and spatial resolutions required to study in detail their mechanisms experimentally. Recent advances in structural determination of membrane proteins have resulted in solution of a number of high-resolution structures of membrane transporters setting the stage for simulation studies to investigate various aspects of transport at an atomic level. In this chapter, we report the results of a representative collection of our recent simulation studies performed on a number of membrane transporters for which structures became available recently. The studied transporters are structurally diverse, and, more importantly, function using different mechanisms of energy coupling and structural changes involved in the transport cycle. The studied systems reported in this chapter are: 1) the maltose transporter, representing the superfamily of ABC transporters; 2) the glutamate transporter, a member of the secondary membrane transporter family; 3) glycerol phosphate transporter, representing the major facilitator superfamily; 4) ADP/ATP carrier, a mitochondrial carrier; and, 5) the vitamin B12 transporter, representing outer membrane transporters.
MADIT‐I and MADIT‐II
Authors: MOSS ARTHUR J.
Published: August 2010

The MADIT‐I study was a proof‐of‐principle study, and this randomized trial showed that the implantable cardioverter defibrillator (ICD) saves lives in high‐risk patients with coronary heart disease. The MADIT‐II study showed that prophylactic ICD therapy was associated with significantly improved survival in patients with ischemic cardiomyopathy, as defined by documented coronary heart disease and advanced left ventricular dysfunction, without requiring screening for ventricular arrhythmias or inducibility by electrophysiologic testing. Taken together, these two trials, as well as the results from several other randomized ICD trials, indicate that ICD therapy is indicated in coronary patients who meet MADIT‐I or MADIT‐II eligibility criteria and are not excluded by major noncardiac comorbidity. (J Cardiovasc Electrophysiol, Vol. 14, pp. S96‐S98, September 2003, Suppl.)
Randomized Clinical Trials of Neurally Mediated Syncope
Authors: BRIGNOLE MICHELE
Published: August 2010

Evidence for therapy of neurally mediated syncope is generally weak. Many drugs have been used for the treatment of vasovagal syncope (beta‐blockers, disopyramide, scopolamine, clonidine, theophylline, fludrocortisone, ephedrine, dihydroergotamine, etilefrine, midodrine, clonidine, serotonin reuptake inhibitors, enalapril). In general, although the results have been satisfactory in uncontrolled trials or short‐term controlled trials, the majority of long‐term placebo‐controlled prospective trials have not been able to show a benefit of the active drug over placebo. Only two well‐designed double‐blind placebo‐controlled randomized trials have been performed—one for etilefrine and the other for atenolol—and both were unable to show a superiority of the active drug versus placebo. Four randomized clinical trials of pacing therapy—three positive and one negative—have been performed in patients affected by vasovagal syncope. The relationship between carotid sinus hypersensitivity and spontaneous, otherwise unexplained, syncope has been demonstrated. Cardiac pacing appears to be beneficial in carotid sinus syndrome; its efficacy has been demonstrated by two randomized controlled trials and confirmed by several pre‐post comparative studies, one controlled trial, and one prospective observational study. There is evidence and general agreement that cardiac pacing is useful in patients with cardioinhibitory or mixed carotid sinus syndrome. Usefulness of the treatment is less well established and divergence of opinion exists with regard to cardiac pacing in patients with cardioinhibitory vasovagal syncope. The evidence fails to support the efficacy of beta‐blocking drugs. As yet there are insufficient data to support the use of any other pharmacologic therapy for vasovagal syncope.(J Cardiovasc Electrophysiol, Vol. 14, pp. S64‐S69, September 2003, Suppl.)
Pulmonary Vein Stenosis by Ostial Irrigated‐Tip Ablation:
Authors: PÜRERFELLNER HELMUT , CIHAL RUDOLF , AICHINGER JOSEF , MARTINEK MARTIN , NESSER HANS JOACHIM
Published: August 2010

Monitoring and Prediction of PV Stenosis.
Introduction: The incidence of pulmonary vein (PV) stenosis and its time course for ostial trigger elimination in paroxysmal atrial fibrillation (PAF) is uncertain. In addition, the clinical value of serial computed tomographic (CT) scanning of the PV ostia and the predictive value of energy requirements for radiofrequency ablation have yet to be established.

Methods and Results: We performed irrigated‐tip ablation in 37 patients with drug‐resistant PAF. Serial spiral CT scans were taken prospectively in 34 patients the day before the procedure, at prehospital discharge, and at 3‐ and 6‐month follow‐up. Using a clock model, energy requirements were analyzed for every segment of the PV circumference. One hundred fifteen PVs were targeted in 57 procedures. Compared to baseline, 7 (6.08%) of 115 PV showed minor (<50%) PV stenosis. Two severe (>90%) PV stenoses (1.73%) were detected with a mean follow‐up of 275 ± 100 days. Luminal narrowing occurred most frequently in the left inferior PV (6/9 stenosed PV). Minor stenosed PVs showed their maximal luminal regression within the 3‐month follow‐up. Two of two PVs with narrowing >50% at 3 months progressed to high‐grade stenosis. Analysis of delivered energy showed no significant correlation with the degree of stenosis. However, for the left inferior PV, more energy was applied in the superior segment of a stenotic PV (6697 ± 930 J vs 3555 ± 380 J, P = 0.005).

Conclusion: Assessment of PV diameter by serial spiral CT scanning shows a low incidence of severe stenosis. The left inferior PV is at higher risk. Minor stenosed PV showed no progression after 3 months. Occurrence of stenosis tended to be related to the amount of energy delivered. (J Cardiovasc Electrophysiol, Vol. 14, pp. 158‐164, February 2003)
New Cryotechnology for Electrical Isolation of the Pulmonary Veins
Authors: AVITALL BOAZ , URBONIENE DALIA , ROZMUS GRZEGORZ , LAFONTAINE DAN , HELMS RAY , URBONAS ARVYDAS
Published: August 2010

Introduction: Creation of radiofrequency lesions to isolate the pulmonary veins (PV) and ablate atrial fibrillation (AF) has been complicated by stenosis of the PVs. We tested a cryoballoon technology that can create electrical isolation of the PVs, with the hypothesis that cryoenergy will not result in PV stenosis.

Methods and Results: Lesions were created in 9 dogs (weight 31–37 kg). Cryoenergy was applied to the PV‐left atrial (LA) interface. Data collected before and after ablation included PV orifice size, arrhythmia inducibility, electrogram activity, and pacing threshold in the PVs. Tissue examination was performed immediately after ablation in 3 dogs and after 3 months (4.8 ± 1.0) in 6 dogs. After ablation there was no localized P wave activity in the ablation zone and no LA‐PV conduction. Before ablation, the pacing threshold was

1.9 ± 1.1 mA

in each PV. After ablation, the pacing threshold increased significantly to

7.2 ± 1.8 mA

, or capture was not possible. Burst pacing did not induce any sustained arrhythmias. Most dogs had hemoptysis during the first 24 to 48 hours. Acute tissue examination revealed hemorrhagic injury of the atrial‐PV junction that extended into the lung parenchyma. After recovery, the lesions were circumferential and soft with no PV stenosis. Histologic examination revealed fibrous tissue with no PV‐LA interface thickening.

Conclusion: This new cryoballoon technology effectively isolates the PVs from LA tissue. No PV stenosis was noted. Acute tissue hemorrhage and hemoptysis are short‐term complications of this procedure. After 3 months of recovery, cryoablated tissue exhibits no collagen or cartilage formation.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 281‐286, March 2003)
5‐Hydroxytryptamine and Atrial Fibrillation:
Authors: YUSUF SHAMIL , Al‐SAADY NAAB , CAMM A. JOHN
Published: August 2010

Serotonin and Atrial Fibrillation.5‐Hydroxytryptamine, a recent addition to the list of hormonal triggers for atrial fibrillation (AF), may play a pivotal role in the induction of AF related not only to cardiac surgery but also to acute coronary syndromes, valvular heart disease, cardiomyopathies, alcoholism, aging, and conducting tissue disease. This review examines the supporting laboratory and clinical evidence and provides a comprehensive insight into the basic underlying mechanisms involved. It also delves into the potential benefits and limitations of 5‐HT4antagonists in the prevention and management of this arrhythmia.(J Cardiovasc Electrophysiol, Vol. 14, pp. 209‐214, February 2003)
Irregular Atrial Activation During Atrioventricular Nodal Reentrant Tachycardia:
Authors: GUO HONGSHENG M. , NERHEIM PAMELA , OLSHANSKY BRIAN
Published: August 2010

Controversy continues regarding the precise nature of the reentrant circuit of AV nodal reentrant tachycardia, especially the existence of an upper common pathway. In this case report, we show that marked variation and irregularity in atrial activation (maximum AA interval variation of 80 msec) can exist with fixed and constant activation of the His bundle and ventricles during AV nodal reentrant tachycardia in a 45‐year‐old female patient. We propose that irregular atrial activation is due to variable and inconsistent conduction from the AV node to the atria through the perinodal transitional cell envelope extrinsic to the reentrant circuit. Our observations support the concept of an upper common pathway, at least in some patients with AV nodal reentrant tachycardia.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 309‐313, March 2003)
Anatomy of the Pulmonary Veins in Patients with Atrial Fibrillation and Effects of Segmental Ostial Ablation Analyzed by Computed Tomography
Authors: SCHARF CHRISTOPH , SNEIDER MICHAEL , CASE IAN , CHUGH AMAN , LAI STEVE W.K. , PELOSI FRANK , KNIGHT BRADLEY P. , KAZEROONI ELLA , MORADY FRED , ORAL HAKAN
Published: August 2010

Pulmonary Vein Anatomy.
Introduction: The anatomic arrangement of pulmonary veins (PVs) is variable. No prior studies have quantitatively analyzed the effects of segmental ostial ablation on the PVs. The aim of this study was to determine the effect of segmental ostial radiofrequency ablation on PV anatomy in patients with atrial fibrillation (AF).

Methods and Results: Three‐dimensional models of the PVs were constructed from computed tomographic (CT) scans in 58 patients with AF undergoing segmental ostial ablation to isolate the PVs and in 10 control subjects without a history of AF. CT scans were repeated approximately 4 months later. PV and left atrial dimensions were measured with digital calipers. Four separate PV ostia were present in 47 subjects; 3 ostia were present in 2 subjects; and 5 ostia were present in 9 subjects. The superior PVs had a larger ostium than the inferior PVs. Patients with AF had a larger left atrial area between the PV ostia and larger ostial diameters than the controls. Segmental ostial ablation resulted in a 1.5 ± 3.2 mm narrowing of the ostial diameter. A 28% to 61% focal stenosis was present 7.6 ± 2.2 mm from the ostium in 3% of 128 isolated PVs. There were no instances of symptomatic PV stenosis during a mean follow‐up of 245 ± 105 days.

Conclusion: CT of the PVs allows identification of anatomic variants prior to catheter ablation procedures. Segmental ostial ablation results in a significant but small reduction in ostial diameter. Focal stenosis occurs infrequently and is attributable to delivery of radiofrequency energy within the PV. (J Cardiovasc Electrophysiol, Vol. 14, pp. 150‐155, February 2003)
Detection of Proarrhythmia in the Female Rabbit Heart:
Authors: HONDEGHEM LUC M. , LU HUA RONG , ROSSEM KOEN van , De CLERCK FRED
Published: August 2010

Introduction:Reliable detection of drug‐induced proarrhythmia, especially the potential for polymorphic ventricular tachycardia, is of great importance in the development of new compounds that are safe for the heart and was evaluated in a blinded study.

Methods and Results:In 142 female rabbits, the monophasic action potential was used to determine intraventricular conduction, action potential duration (APD), triangulation (APD30to APD90), reverse use‐dependence, instability and presence of chaotic behavior, early afterdepolarizations, torsades de pointes (TdP), and ventricular fibrillation. In addition, 31 coded drugs were tested in a blinded fashion in another 150 hearts. Prototype cardiovascular agents [quinidine (IA), lidocaine (IB), flecainide (IC), propranolol (II), sotalol (IIIB), amiodarone (IIIAB) and verapamil (IV)] were correctly characterized in terms of their effects upon conduction and APD. Agents documented in clinical practice to have proarrhythmic potential (droperidol, sotalol, mibefradil, bepridil, lidoflazine, ketanserin, sertindole, terfenadine, haloperidol, astemizole, cisapride, ziprasidone, lubeluzole, dofetilide, quinidine, ibutilide) were identified as such. Pimozide is reported to rarely produce TdP and was also found to elicit Class III action with few adverse effects. Equally important, agents believed not to be proarrhythmic (two solvents, atenolol, propranolol, fenoximone, cetirizine, verapamil, sildenafil, lidocaine, diltiazem) were identified as having no proarrhythmic activity.

Conclusion:The SCREENIT method properly characterized and quantified prototype cardiovascular drugs and correctly identified proarrhythmic noncardiovascular agents of various mechanisms, but it did not produce false‐positive results.(J Cardiovasc Electrophysiol, Vol. 14, pp. 287‐294, March 2003)
A Multicenter Experience with Novel Implantable Cardioverter Defibrillator Configurations in the Pediatric and Congenital Heart Disease Population
Authors: STEPHENSON ELIZABETH A. , BATRA ANJAN S. , KNILANS TIMOTHY K. , GOW ROBERT M. , GRADAUS RAINER , BALAJI SESHADRI , DUBIN ANNE M. , RHEE EDWARD K. , RO PAMELA S. , THØGERSEN ANNA M. , CECCHIN FRANK , TRIEDMAN John K. , WALSH EDWARD P. , BERUL CHARLES I.
Published: August 2010

Introduction: In pediatric and congenital heart disease patients, transvenous ICD implantation may be limited secondary to patient size, venous, or cardiac anatomy. Epicardial patches require a thoracotomy, and may lead to a restrictive pericardial process. Because of these issues, we have explored novel ICD configurations.

Methods: Retrospective review at 10 centers implanting ICDs without a transvenous shocking coil or epicardial patches.

Results: Twenty‐two patients underwent implant at a mean age of 8.9 years (range: 0.3–43.5), with a mean weight of 25.5 kg (range: 5.2–70). Diagnoses included complex CHD, intracardiac tumors, cardiomyopathy, idiopathic VT, LV noncompaction, and long QT syndrome. Three configurations were used: subcutaneous array, a transvenous design ICD lead placed on the epicardium, or a transvenous design ICD lead placed subcutaneously. Difficulties were found at implant in 8 patients: 4 had difficulty inducing VT/VF, and 4 had high DFTs. Over a mean follow‐up of 2.2 years (range: 0.2–10.5), 7 patients had appropriate shocks. Inappropriate shocks occurred in 4 patients. System revisions were required in 7 patients: 2 generator changes (in 1 patient), 3 pace‐sense lead replacement, 1 additional subcutaneous coil placement due to increased DFT, 1 upgrade to a transvenous system, and 1 revision to epicardial patch system.

Conclusions: ICD implantation can be performed without epicardial patches or transvenous high‐energy leads in this population, using individualized techniques. This will allow ICD use in patients who have intracardiac shunting or are deemed too small for transvenous ICD leads. The long‐term outcome and possible complications are as yet unknown in this population, and they should be monitored closely with follow‐up DFTs.