bluuebunny/crossref_metadata_2025 huggingface dataset:
PUFA stabilizes a conductive state of the selectivity filter in IKs channels
Authors: Golluscio Alessia , Eldstrom Jodene , Jowais Jessica J , Perez Marta Elena , Cunningham Kevin Peter , De La Cruz Alicia , Wu Xiaoan , Corradi Valentina , Tieleman D Peter , Fedida David , Larsson H Peter
Published: March 2024

In cardiomyocytes, the KCNQ1/KCNE1 channel complex mediates the slow delayed-rectifier current (IKs), pivotal during the repolarization phase of the ventricular action potential. Mutations in IKs cause long QT syndrome (LQTS), a syndrome with a prolonged QT interval on the ECG, which increases the risk of ventricular arrhythmia and sudden cardiac death. One potential therapeutical intervention for LQTS is based on targeting IKs channels to restore channel function and/or the physiological QT interval. Polyunsaturated fatty acids (PUFAs) are potent activators of KCNQ1 channels and activate IKs channels by binding to two different sites, one in the voltage sensor domain – which shifts the voltage dependence to more negative voltages – and the other in the pore domain – which increases the maximal conductance of the channels (Gmax). However, the mechanism by which PUFAs increase the Gmax of the IKs channels is still poorly understood. In addition, it is unclear why IKs channels have a very small single-channel conductance and a low open probability or whether PUFAs affect any of these properties of IKs channels. Our results suggest that the selectivity filter in KCNQ1 is normally unstable, contributing to the low open probability, and that the PUFA-induced increase in Gmax is caused by a stabilization of the selectivity filter in an open-conductive state.
Binding of PUFA stabilizes a conductive state of the selectivity filter in IKs channels
Authors: Golluscio Alessia , Eldstrom Jodene , Jowais Jessica J. , Perez-Rodriguez Marta E. , Cunningham Kevin P. , de la Cruz Alicia , Wu Xiaoan , Fedida David , Larsson H. Peter
Published: March 2024

In cardiomyocytes, the KCNQ1/KCNE1 channel complex mediates the slow delayed-rectifier current (IKs), pivotal during the repolarization phase of the ventricular action potential. Mutations in IKs cause Long QT Syndrome (LQTS), a syndrome with a prolonged QT interval on the ECG, which increases the risk of ventricular arrhythmia and sudden cardiac death. One potential therapeutical intervention for LQTS is based on targeting IKs channels to restore channel function and/or the physiological QT interval. Polyunsaturated fatty acids (PUFAs) are potent activators of KCNQ1 channels and activate IKs channels by binding to two different sites, one in the voltage sensor domain (VSD) – which shifts the voltage dependence to more negative voltages– and the other in the pore domain (PD) – which increases the maximal conductance of the channels (Gmax). However, the mechanism by which PUFAs increase the Gmax of the IKs channels is still poorly understood. In addition, it is unclear why IKs channels have a very small single channel conductance and a low open probability or whether PUFAs affect any of these properties of IKs channels. Our results suggest that the selectivity filter in KCNQ1 is normally unstable, explaining the low open probability, and that the PUFA-induced increase in Gmax is caused by a stabilization of the selectivity filter in an open-conductive state.
Benchmarking a targeted 16S ribosomal RNA gene enrichment approach to reconstruct ancient microbial communities
Authors: Eisenhofer Raphael , Wright Sterling , Weyrich Laura
Published: March 2024

The taxonomic characterization of ancient microbiomes is a key step in the rapidly growing field of paleomicrobiology. While PCR amplification of the 16S ribosomal RNA (rRNA) gene is a widely used technique in modern microbiota studies, this method has systematic biases when applied to ancient microbial DNA. Shotgun metagenomic sequencing has proven to be the most effective method in reconstructing taxonomic profiles of ancient dental calculus samples. Nevertheless, shotgun sequencing approaches come with inherent limitations that could be addressed through hybridization enrichment capture. When employed together, shotgun sequencing and hybridization capture have the potential to enhance the characterization of ancient microbial communities. Here, we develop, test, and apply a hybridization enrichment capture technique to selectively target 16S rRNA gene fragments from the libraries of ancient dental calculus samples generated with shotgun techniques. We simulated data sets generated from hybridization enrichment capture, indicating that taxonomic identification of fragmented and damaged 16S rRNA gene sequences was feasible. Applying this enrichment approach to 15 previously published ancient calculus samples, we observed a 334-fold increase of ancient 16S rRNA gene fragments in the enriched samples when compared to unenriched libraries. Our results suggest that 16S hybridization capture is less prone to the effects of background contamination than 16S rRNA amplification, yielding a higher percentage of on-target recovery. While our enrichment technique detected low abundant and rare taxa within a given sample, these assignments may not achieve the same level of specificity as those achieved by unenriched methods.
Improving Heat Efficiency of Aniline Production Process by Modifying Heat Transfer Fluid Looping System in Heating and Cooling Process
Authors: Ahdan Muhammad , Saputra Alfan Rizky , Ivan Rifqy , Panjaitan Yohanes Mangarohontua
Published: March 2024

The nitrobenzene hydrogenation process is a highly exothermic reaction which causes the product temperature will increase and then needs to be cooled down with a heat exchanger. The modification process is needed to improve the heat efficiency of the nitrobenzene hydrogenation process by utilizing the heat from reactor product. Heat transfer fluid is used as a medium of heat transfer for both heating and cooling, so that will create a looping heat transfer process. The looping system of heat transfer fluid receives heat from reactor product and then reuses the heat to reheat the recycled hydrogen and for other utilities, so additional energy for these processes is not required. The process modification was simulated using Aspen HYSYS and the comparison of heat efficiency between the basic and the modified process is calculated using the net-energy formula. The results obtained that the net-energy (NE) value for both basic and modified process is 96,714,359.832 kJ/h and 9.869 kJ/h. This shows that the modified process has better energy efficiency compared to the basic process as the net-energy value is closer to zero. Therefore, this modification increases the heat efficiency of the aniline production through nitrobenzene hydrogenation process. Copyright © 2024 by Authors, Published by Universitas Diponegoro and BCREC Publishing Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).
Reducing Energy Consumption in the Synthesis of Dimethyl Ether (DME) from Methanol Dehydration by Modifying Heat Transfer Unit Using Aspen HYSYS
Authors: Faisal Muhammad Auliya , Puspaningrum Faradiba , Novalia Fera Yeniza , Sabrilla Tian Shilfa
Published: March 2024

In the pursuit of a transport sector free from fossil fuels, the incorporation of Dimethyl ether (DME) emerges as a commendable ecological substitute. The DME is a synthetically produced serves as a viable alternative to conventional fuels such as diesel and liquified petroleum gas (LPG). The Dimethyl Ether (DME) production is carried out by catalytic dehydration of methanol over an acidic zeolite-based catalyst. The technological process for the DME synthesis was simulated using Aspen HYSYS based on the combined operating parameters of the reaction dynamic model for the methanol dehydration reaction. This paper attempts to evaluate a modification in dehydration of methanol process to reducing energy consumption by modifying heat transfer unit. The heater and cooler heat transfer units were converted into heat exchangers (HE) by utilizing the output of the process that can be used for other processes so that energy consumption is reduced. The temperature of reaction and the heat transfer unit are modified to reduce energy consumption from 11.850 MMBtu/h to 7.6291 MMBtu/h by changing one heater and one cooler with two heat exchangers. Copyright © 2024 by Authors, Published by Universitas Diponegoro and BCREC Publishing Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).
Maximizing Chlorobenzene Product Yield by Modifying The Benzene Chlorination Process
Authors: Syalom Michael Natan , Danuwijaya Fauzan Akmal , Rusully Lalu Muhammad Imam , Aradhea Muhammad Arif Tirtana
Published: March 2024

Chlorobenzene is extensively used in the manufacture of phenol, aniline, and DDT; as a solvent for paints; and as a heat transfer medium. It is also occasionally used in the dry-cleaning industry. With the many uses of chlorobenzene, its production must have high efficiency both in terms of energy and mass in order to obtain maximum profits. In this paper, we will explain how to maximize chlorobenzene product yield by modifying the benzene chlorination process. The process modification was carried out by adding one distillation column unit and one mixer unit. Meanwhile, to carry out sensitivity analysis, case study tools on chemical engineering software were used. Based on process modifications, an increase in chlorobenzene yield was obtained from 83% to 98%. The results of the case study indicate that the higher the benzene pressure entering the reactor, the lower the yield of the liquid product exiting the reactor. Meanwhile, the higher the ratio of benzene mass flow to chlorine gas mass flow, the higher the yield of the liquid product exiting the reactor. Copyright © 2024 by Authors, Published by Universitas Diponegoro and BCREC Publishing Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).
Improving Energy Efficiency with Heat Exchanger and Optimizing Operating Conditions for Sorbitol Production from Dextrose
Authors: Vernando Dio Fani , Rodifa Muhammad , Muhammad Rizdian Arsyal , Simanungkalit Raysa Yuliana Br
Published: March 2024

Sorbitol is a sugar alcohol which has a molecular formula of C6H14O6. The production of sorbitol by the hydrogenation process is carried out at high pressure so that a large amount of energy is required. The use of considerable energy in the production process supports the need for innovation for energy efficiency in the production of sorbitol from dextrose, which is expected to help increase sorbitol production so that it can meet market needs. The innovation carried out here is to change the operating conditions with the help of Ru/ASMA@AC catalyst so that the temperature required during the reaction is low. In addition, modifying the use of heat exchanger units so that the heat generated during operation is reused. These innovations were simulated using Aspen HYSYS software. The results of the simulation proved to be able to improve energy efficiency by reducing the performance of compressors and coolers used during production and saving considerable energy. Copyright © 2024 by Authors, Published by Universitas Diponegoro and BCREC Publishing Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).
Selective Immobilization of Protein Clusters on Polymeric Nanocraters
Authors: Valsesia A. , Colpo P. , Meziani T. , Bretagnol F. , Lejeune M. , Rossi F. , Bouma A. , Garcia‐Parajo M.
Published: May 2006

A method for fabricating chemically nanopatterned surfaces based on a combination of colloidal lithography and plasma‐ enhanced chemical vapor deposition (PECVD) is presented. This method can be applied for the creation of different nanopatterns, and it is in principle not limited in patterning resolution. Nanocraters of poly(acrylic acid) (carboxylic moieties) surrounded by a matrix of poly(ethylene glycol) are fabricated. Chemical force microscopy demonstrates that the process is able to produce the expected surface chemical contrast. Finally, the carboxylic groups of the craters are activated in order to induce the covalent binding of fluorescent‐labeled proteins. Fluorescence investigation using scanning confocal microscopy shows that the proteins are preferentially attached inside the functional craters.
Room‐Temperature Synthesis of Porous Nanoparticulate TiO2 Films for Flexible Dye‐Sensitized Solar Cells
Authors: Zhang D. , Yoshida T. , Oekermann T. , Furuta K. , Minoura H.
Published: May 2006

A novel room‐temperature method for the preparation of porous TiO2 films with high performance in dye‐sensitized solar cells (DSSCs) has been developed. In this method a small amount of TiIV tetraisopropoxide (TTIP) is added to an ethanolic paste of TiO2 nanoparticles, where it hydrolyzes in situ and connects the TiO2 particles to form a homogenous and mechanically stable film of up to 10 μm thickness without crack formation. Residual organics originating from the TTIP were removed by UV–ozone treatment of the films, leading to a remarkable improvement of the cell efficiency. Intensity‐modulated photocurrent/voltage spectroscopy (IMPS/IMVS) showed that the main effect of the UV–ozone treatment is to suppress the recombination of photogenerated electrons, thereby extending their lifetime. The efficiency was further increased by preheating the TiO2 nanoparticles before the paste preparation to remove contaminants originating from the preparation process of the particles. Solar‐to‐electric energy conversion efficiencies of 4.00 and 3.27 % have been achieved for cells with conductive glass and plastic film substrates, respectively, under illumination with AM 1.5 (100 mW cm–2) simulated sunlight.
Organo‐metal Diodes Based on a Nanoparticulate Poly(3,4‐ethylenedioxythiophene) Composite
Authors: Zhang R. , Barnes A. , Wang Y. , Chambers B. , Wright P. V.
Published: May 2006

Diodes composed of a nanoparticulate composite of poly(3,4‐ethylenedioxythiophene) and a Cu–Cu2+ redox couple in a poly(ethylene oxide)–LiBF4 polymer‐electrolyte matrix between Ag and Zr electrodes show rectifications in excess of 50 000 at applied fields of 4 V. These large changes are considered to arise from both rectification at the Zr/ZrO2 composite interface and from the switching of the composite material between two conductivity states by the application of a low potential field. The preparation and electrochemical characterisation of these novel active devices are discussed.
Sacrificial‐Layer Atomic Layer Deposition for Fabrication of Non‐Close‐Packed Inverse‐Opal Photonic Crystals
Authors: Graugnard E. , King J. S. , Gaillot D. P. , Summers C. J.
Published: May 2006

A method is presented for predicting and precisely controlling the structure of photonic crystals fabricated using sacrificial‐layer atomic layer deposition. This technique provides a reliable method for fabrication of high‐quality non‐close‐packed inverse shell opals with large static tunability and precise structural control. By using a sacrificial layer during opal infiltration, the inverse‐opal pore size can be increased with sub‐nanometer resolution and without distorting the lattice to allow for a high degree of dielectric backfilling and increased optical tunability. For a 10 % sacrificial layer, static tunability of 80 % is predicted for the inverse opal. To illustrate this technique, SiO2 opal templates were infiltrated using atomic layer deposition of ZnS, Al2O3, and TiO2. Experimentally, a static tunability of over 600 nm, or 58 %, was achieved and is well described by both a geometrical model and a numerical‐simulation algorithm. When extended to materials of higher refractive index, this method will allow the facile fabrication of 3D photonic crystals with optimized photonic bandgaps.
Readily decomposed thermosetting resins for recovering and reusing resin‐embedded materials
Authors: Mimura K. , Ito H.
Published: May 2006

To help recover the intrinsically valuable, reusable metal parts at the end of a product's life‐cycle, we have used thermosetting (epoxy) resin that contains a small amount of thermoplastic polymer, polyethersulfone, which can be readily chemically decomposed. In a morphologically homogeneous modified thermosetting resin, the resin portion does not readily decompose when treated with an organic solvent, and chemical resistance equals the unmodified epoxy resin. A resin portion with thermoplastic polymer having continuous‐phase morphology was finely broken down by treatment with an organic solvent, and the embedded metal parts were separated and recovered. Readily decomposed thermosetting resin can thus be obtained by controlling the morphology of the thermoplastic polymer in the thermosetting resin to form a continuous phase. We also obtained a material having continuous variation in the phase morphology of a cured resin, from that with homogeneous morphology to that with continuous‐phase morphology of the thermoplastic polymer: phase structure inclination material. We were thus able to control the decomposition rate by chemical treatment in one resin. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1463–1470, 2006
Heuristic problems in defining the three‐dimensional arrangement of the ventricular myocytes
Authors: Anderson Robert H. , Ho Siew Yen , Sanchez‐Quintana Damian , Redmann Klaus , Lunkenheimer Paul P.
Published: May 2006

There is lack of consensus concerning the three‐dimensional arrangement of the myocytes within the ventricular muscle masses. Bioengineers are seeking to model the structure of the heart. Although the success of such models depends on the accuracy of the anatomic evidence, most of them have been based on concepts that are far from anatomical reality, which ignore many significant previous accounts of anatomy presented over the past 400 years. During the 19th century, Pettigrew emphasized that the heart was built on the basis of a modified blood vessel rather than in the form of skeletal muscles. This fact was reemphasized by Lev and Simkins as well as Grant in the 20th century, but the caveats listed by these authors have been ignored by proponents of two current concepts, which state either that the myocardium is arranged in the form of a “unique myocardial band,” or that the walls of the ventricles are sequestrated in uniform fashion by laminar sheets of fibrous tissue extending from epicardium to endocardium. These two concepts are themselves incompatible and are further at variance with the majority of anatomic studies, which have emphasized the regional heterogeneity to be found in the three‐dimensional packing of the myocytes within a supporting matrix of fibrous tissue. We reemphasize the significance of this three‐dimensional muscular mesh, showing how the presence of intruding aggregates of myocytes extending in oblique transmural fashion also contends against the notion that all myocytes are orientated with their long axes parallel to the epicardial and enodcardial surfaces. Anat Rec Part A 288A:579–586, 2006. © 2006 Wiley‐Liss, Inc.
Absolute Configuration of New Cytotoxic and Other Bioactive Trichothecene Macrolides
Authors: Shen Li , Jiao Rui H. , Ye Yong H. , Wang Xiao T. , Xu Chen , Song Yong C. , Zhu Hai L. , Tan Ren X.
Published: May 2006

Three new cytotoxic 10,13‐cyclotrichothecane‐derived macrolides, myrothecines A–C (1–3), were characterized from the extracts of two Myrothecium roridum strains, IFB‐E009 and IFB‐E012, isolated as endophytic fungi found on the traditional Chinese medicinal plants Trachelospermum jasminoides and Artemisia annua, respectively. The absolute configuration of myrothecines A–C was elucidated by a combination of spectral techniques (UV, IR, MS, circular dichroism (CD), 1H and 13C NMR, DEPT, 1H–1H COSY, NOESY, HMQC, and HMBC spectrascopic analyses), Mosher's ester analysis, and single‐crystal X‐ray diffraction. The absolute configuration of the reported bioactive analogue, mytoxin B was established by correlating its spectral data with that of known absolute configurational structures. Furthermore, the significance in endophytism (or symbiosis) and biocatabolism, highlighted by production of those macrolides by the endophytic strains, is discussed in brief.
The effect of acidic and basic additives on the enantioseparation of basic drugs using polysaccharide‐based chiral stationary phases
Authors: Ye Yun K. , Stringham Rodger W.
Published: May 2006

The enantioseparation of nine commercially available basic drugs was achieved on polysaccharide‐based chiral stationary phases with the acidic additive ethanesulfonic acid and the basic additive butylamine. Seven different commercially available CSPs were used for the study (AD, AS, OD, OJ, OG, OB, and OC). Mobile phase additives have been proven to be essential in obtaining satisfactory enantio‐resolution in terms of both efficiency and selectivity. Significantly improved selectivities were obtained for the basic probe drugs with the acidic additive, ethanesulfonic acid, rather than the basic additive, butylamine. This is best seen with Chiralpak AS CSP. No enantioseparation for the nine drugs was observed when butylamine was used as an additive; however, satisfactory enantioseparation for the nine drugs was achieved using ethanesulfonic acid. Higher column efficiencies were observed with the acidic additive, especially when isopropanol was used as a modifier. Higher sensitivity was also achieved with ethanesulfonic acid because of the significantly lower background at the UV detection wavelength. The acidic additive was demonstrated to be superior to the basic additive for the enantioseparation of basic drugs using seven different polysaccharide‐based CSPs. These results are counterintuitive to the common “rule of thumb” in enantioseparation that states acidic additives work best for acidic analytes and basic additives work best for basic analytes. The beneficial effects of acidic additive in enantioseparations observed in this study could significantly improve the applicability of polysaccharide‐based CSPs for the enantioseparation of basic analytes. Chirality 18:519–530, 2006. © 2006 Wiley‐Liss, Inc.
Endothelial cell fatty acid unsaturation mediates cold‐induced oxidative stress
Authors: Zieger Michael A.J. , Gupta Mahesh P. , Siddiqui Rafat A.
Published: May 2006

Ultraprofound hypothermia (< 5°C) induces changes to cell membranes such as liquid‐to‐gel lipid transitions and oxidative stress that have a negative effect on membrane function and cell survival. We hypothesized that fatty acid substitution of endothelial cell lipids and alterations in their unsaturation would modify cell survival at 0°C, a temperature commonly used during storage and transportation of isolated cells or tissues and organs used in transplantation. Confluent bovine aortic endothelial cells were treated with 18‐carbon fatty acids (C18:0, C18:1n‐9, C18:2n‐6, or C18:3n‐3), C20:5n‐3 or C22:6n‐3 (DHA), and then stored at 0°C without fatty acid supplements. Storage of control cells caused the release of lactate dehydrogenase (LDH) and a threefold increase in lipid peroxidation (LPO) when compared to control cells not exposed to cold. Pre‐treating cells with C18:0 decreased the unsaturation of cell lipids and reduced LDH release at 0°C by 50%, but all mono‐ or poly‐unsaturated fatty acids increased injury in a concentration‐dependent manner and as the extent of fatty acid unsaturation increased. DHA‐treatment increased cell fatty acid unsaturation and caused maximal injury at 0°C, which was prevented by lipophilic antioxidants BHT or vitamin E, the iron chelator deferoxamine, and to a lesser extent by vitamin C. Furthermore, the cold‐induced increase in LPO was reduced by C18:0, vitamin E, or DFO but enhanced by DHA. In conclusion, the findings implicate iron catalyzed free radicals and LPO as a predominant mechanism of endothelial cell injury at 0°C, which may be reduced by increasing lipid saturation or treating cells with antioxidants. J. Cell. Biochem. 99: 784–796, 2006. © 2006 Wiley‐Liss, Inc.
Hydrogen peroxide and endothelin‐1 are novel activators of betacellulin ectodomain shedding
Authors: Sanderson Michael P. , Abbott Catherine A. , Tada Hiroko , Seno Masaharu , Dempsey Peter J. , Dunbar Andrew J.
Published: May 2006

The betacellulin precursor (pro‐BTC) is a novel substrate for ADAM10‐mediated ectodomain shedding. In this report, we investigated the ability of novel physiologically relevant stimuli, including G‐protein coupled receptor (GPCR) agonists and reactive oxygen species (ROS), to stimulate pro‐BTC shedding. We found that in breast adenocarcinoma MCF7 cells overexpressing pro‐BTC, hydrogen peroxide (H2O2) was a powerful stimulator of ectodomain shedding. The stimulation of pro‐BTC shedding by H2O2 was blocked by the broad‐spectrum metalloprotease inhibitor TAPI‐0 but was still functional in ADAM17 (TACE)‐deficient stomach epithelial cells indicating the involvement of a distinct metalloprotease. H2O2‐induced pro‐BTC shedding was blocked by co‐culturing cells in the anti‐oxidant N‐acetyl‐L‐cysteine but was unaffected by culture in calcium‐deficient media. By contrast, calcium ionophore, which is a previously characterized activator of pro‐BTC shedding, was sensitive to calcium depletion but was unaffected by co‐culture with the anti‐oxidant, identifying a clear distinction between these stimuli. We found that in vascular smooth muscle cells overexpressing pro‐BTC, the GPCR agonist endothelin‐1 (ET‐1) was a strong inducer of ectodomain shedding. This was blocked by a metalloprotease inhibitor and by overexpression of catalytically inactive E385A ADAM10. However, overexpression of wild‐type ADAM10 or ADAM17 led to an increase in ET‐1‐induced pro‐BTC shedding providing evidence for an involvement of both enzymes in this process. This study identifies ROS and ET‐1 as two novel inducers of pro‐BTC shedding and lends support to the notion of activated shedding occurring under the control of physiologically relevant stimuli. J. Cell. Biochem. 99: 609–623, 2006. © 2006 Wiley‐Liss, Inc.
The electrothermal macromodel of the MA7800 monolithic positive‐voltage regulators family
Authors: Zarębski Janusz , Górecki Krzysztof
Published: May 2006

This paper presents the problem of modelling the linear three‐terminal monolithic positive‐voltage regulators belonging to the MA7800 family with self‐heating taken into account. The new electrothermal compact macromodel of the considered family of devices has been proposed by the authors. This macromodel was implemented to SPICE with the use of the ABM option. The proposed macromodel was verified experimentally for the MA7805 regulator and a good agreement between the calculation and measurement results was obtained. Copyright © 2006 John Wiley & Sons, Ltd.
Interannual variability of the tropical Atlantic independent of and associated with ENSO: Part I. The North Tropical Atlantic
Authors: Handoh Itsuki C. , Matthews Adrian J. , Bigg Grant R. , Stevens David P.
Published: May 2006

The interannual variability of the tropical Atlantic ocean–atmosphere system is examined using 50 years of sea‐surface temperature (SST) and re‐analysis data, and satellite data when available. A singular value decomposition analysis of 12‐ to 72‐month bandpass filtered SST and zonal wind stress reveals two dominant modes of interannual variability. The SST anomalies are confined to the North Tropical Atlantic (NTA) in the first mode and extend over the equatorial and South Tropical Atlantic in the second mode. No evidence is found for an Atlantic SST dipole. The structure of the first (NTA) mode is examined in detail here, while the second mode has been described in a companion paper. In particular, the relationship of the NTA mode with El Niño–Southern Oscillation (ENSO) is investigated. There are 12 NTA events (seven warm and five cold) that are associated with ENSO, and 18 NTA events (seven warm and 11 cold) that are independent of ENSO.

The ENSO‐associated NTA events appear to be a passive response to remote ENSO forcing, mainly via a Pacific‐North America (PNA)‐like wave train that induces SST anomalies over the NTA through changes in the surface wind and latent heat flux. The NTA anomalies peak four months after ENSO. There does not appear to be an atmospheric response to the NTA SST anomalies as convection over the Atlantic is suppressed by the anomalous Walker circulation due to ENSO.

The ENSO‐independent NTA events also appear to be induced by an extratropical wave train from the Pacific sector (but one that is independent of Pacific SST), and forcing by the North Atlantic Oscillation (NAO) also contributes. As the event matures, the atmosphere does respond to the NTA SST anomalies, with enhanced convection over the Caribbean and a wave train that propagates northeastward to Europe. Copyright © 2006 Royal Meteorological Society
Isolation and minimization of head motion‐induced signal variations in fMRI data using independent component analysis
Authors: Liao Rui , McKeown Martin J. , Krolik Jeffrey L.
Published: May 2006

Task‐related head movement during acquisition of fMRI data represents a serious confound for both motion correction and estimates of task‐related activation. Cost functions implemented in most conventional motion‐correction algorithms compare two volumes for similarity but fail to account for signal variability that is not due to motion (e.g., brain activation). We therefore recently proposed the theoretical basis for a novel method for fMRI motion correction, termed motion‐corrected independent component analysis (MCICA), that allows for brain activation present in an fMRI time‐series to be implicitly modeled and mitigates motion‐induced signal changes without having to directly estimate the motion parameters (Liao et al., IEEE Transactions on Medical Imaging 2005;25:29–44). To explore the effects of non‐movement‐related signal changes on registration error, we performed several previously proposed test simulations (Freire et al., IEEE Transactions on Medical Imaging 2002;21:470–484) to evaluate the performance of MCICA and compare it with the conventional square‐of‐difference‐based measures such as LS‐SPM and LS‐AIR. We demonstrate that for both simulated data and real fMRI images, the proposed MCICA method performs favorably. Specifically, in simulations MCICA was more robust to the addition of simulated activation, and did not lead to the detection of false activations after correction for simulated task‐correlated motion. With actual data from a motor fMRI experiment, the time course of the derived continually task‐related ICA component became more correlated with the underlying behavioral task after preprocessing with MCICA compared to other methods, and the associated activation map was more clustered in the primary motor and supplementary motor cortices without spurious activation at the brain edge. We conclude that assessing the statistical properties of a motion‐corrupted volume in relation to other volumes in the series, as is done with MCICA, is an accurate means of differentiating between motion‐induced signal changes and other sources of variability in fMRI data. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Increased productivity in quantitative bioanalysis using a monolithic column coupled with high‐flow direct‐injection liquid chromatography/tandem mass spectrometry
Authors: Huang Mike‐Qingtao , Mao Yan , Jemal Mohammed , Arnold Mark
Published: May 2006

The feasibility of using a monolithic column as the analytical column in conjunction with high‐flow direct‐injection liquid chromatography/tandem mass spectrometry (LC/MS/MS) to increase productivity for quantitative bioanalysis has been investigated using plasma samples containing a drug and its epimer metabolite. Since the chosen drug and its epimer metabolite have the same selected reaction monitoring (SRM) transitions, chromatographic baseline separation of these two compounds was required. The results obtained from this monolithic column system were directly compared with the results obtained from a previously validated assay using a conventional C18 column as the analytical column. Both systems have the same sample preparation, mobile phases and MS conditions. The eluting flow rate for the monolithic column system was 3.2 mL/min (with 4:1 splitting) and for the C18 column system was 1.2 mL/min (with 3:1 splitting). The monolithic column system had a run time of 5 min and the conventional C18 column system had a run time of 10 min. The methods on the two systems were found to be equivalent in terms of accuracy, precision, sensitivity and chromatographic separation. Without sacrificing the chromatographic separation, sensitivity, accuracy and precision of the method, the reduced run time of the monolithic column method increased the sample throughput by a factor of two. Copyright © 2006 John Wiley & Sons, Ltd.
Separation of a BMS drug candidate and acyl glucuronide from seven glucuronide positional isomers in rat plasma via high‐performance liquid chromatography with tandem mass spectrometric detection
Authors: Xue Y.‐J. , Simmons Neal J. , Liu Jane , Unger Steve E. , Anderson Danielle F. , Jenkins Rand G.
Published: May 2006

A high‐performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed and validated for the determination of a BMS drug candidate and its acyl glucuronide (1‐O‐β glucuronide) in rat plasma. A 50‐µL aliquot of each plasma sample was fortified with acetonitrile containing the internal standard to precipitate proteins and extract the analytes of interest. After mixing and centrifugation, the supernatant from each sample was transferred to a 96‐well plate and injected into an LC/MS/MS system. Chromatographic separation was achieved isocratically on a Phenomenex Luna C18, 3 mm × 150 mm, 3 µm column. The mobile phase contained 0.075% formic acid in 70:30 (v/v) acetonitrile/water. Under the optimized chromatographic conditions, the BMS drug candidate and its acyl glucuronide were separated from its seven glucuronide positional isomers within 10 min. Resolution of the parent from all glucuronides and acyl glucuronide from its positional isomers was critical to avoid their interference with quantitation of parent or acyl glucuronide. Detection was by positive ion electrospray MS/MS on a Sciex API 4000. The standard curve, which ranged from 5 to 5000 ng/mL, was fitted to a 1/x2 weighted quadratic regression model for both the BMS drug candidate and its acyl glucuronide. Whole blood and plasma stability experiments were conducted to establish the sample collection, storage, and processing conditions. The validation results demonstrated that this method was rugged and repeatable. The same methodology has also been used in mouse and human plasma for the determination of the BMS drug candidate and its acyl glucuronide. Copyright © 2006 John Wiley & Sons, Ltd.
Study of the phase I and phase II metabolism of nephrotoxin aristolochic acid by liquid chromatography/tandem mass spectrometry
Authors: Chan Wan , Cui Liang , Xu Guowang , Cai Zongwei
Published: May 2006

Prolonged exposure to aristolochic acid (AA) was shown to pose rapid progressive renal fibrosis in Belgian women in a slimming regime in the early 1990s. AA was also demonstrated to be strong carcinogen in rats. The carcinogenicity of AA is generally believed to be related to the nitro‐reduction of AA, in which the aristolactam‐nitriumion ion with a delocalized positive charge is the ultimate carcinogen. In this study, the phase I and phase II metabolism of AA was investigated by using an in vitro system with rat liver S9 and an in vivo animal study with Sprague‐Dawley rats. AA was found to have been undergone hydroxylation, lactam formation, and desnitro and desmethyl transformations. Three conjugated metabolites of AA, namely the N‐ and O‐glucuronides of aristolactams, were detected directly in pre‐concentrated urine sample, with no acid hydrolysis or enzymatic digestion. Structural elucidation of the metabolites was performed by using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The results indicated that N‐glucuronidation was the major phase II metabolic pathway for the aristolactams formed by AA after their nitro‐reduction. Copyright © 2006 John Wiley & Sons, Ltd.
Comparison of flow injection analysis electrospray mass spectrometry and tandem mass spectrometry and electrospray high‐field asymmetric waveform ion mobility mass spectrometry and tandem mass spectrometry for the determination of underivatized amino acids
Authors: McCooeye Margaret , Mester Zoltán
Published: May 2006

Twenty proteinogenic amino acids (AAs) were determined without derivatization using flow injection analysis followed by electrospray ionization mass spectrometry and tandem mass spectrometry (ESI‐MS and ESI‐MS/MS) and electrospray ionization high‐field asymmetric waveform ion mobility mass spectrometry and tandem mass spectrometry (ESI‐FAIMS‐MS and ESI‐FAIMS‐MS/MS), in positive and negative ionization modes. Three separate sets of ESI‐FAIMS conditions were used for the separation and detection of the 20 AAs. Typically ESI‐FAIMS‐MS showed somewhat improved sensitivity and significantly better signal‐to‐noise ratios than ESI‐MS mainly due to the elimination of background noise. However, the difference between ESI‐FAIMS‐MS and ESI‐MS/MS was significantly less. ESI‐FAIMS was able to partially or completely resolve all the isobaric amino acid overlaps such as leucine, isoleucine and hydroxyproline or lysine and glutamine. Detection limits for the amino acids in ESI‐FAIMS‐MS mode ranged from 2 ng/mL for proline to 200 ng/mL for aspartic acid. Overall, ESI‐FAIMS‐MS is the preferred method for the quantitative analysis of AAs in a hydrolyzed yeast matrix. Copyright © 2006 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
An experimental study of oscillatory convection in liquid gallium
Authors: Braunsfurth Manfred G. , Mullin T.
Published: May 2006

Results are presented of an experimental study of the onset of time-dependent flows in a sample of liquid gallium subjected to a horizontal temperature gradient. The primary control parameter is the Grashof number which is set by the temperature difference. However, we have also taken the novel approach of varying the Prandtl number in a systematic way using the applied mean temperature. This has uncovered some surprising new dynamical states. Furthermore, the interaction between competing oscillatory flows has produced interesting dynamical behaviour including secondary Hopf bifurcations where both the frequency and amplitude grow from zero as the critical point is passed.
C2_4_4 microheterogeneity and HLA Class I
Authors: Wenda S. , Dauber E.M. , Stadlbacher S. , Glock B. , Fischer M. , Körmöczi G.F. , Mayr W.R.
Published: May 2006

Abstract:  The microheterogeneity of the tetranucleotide repeat locus C2_4_4 situated in the HLA class I region (6p21.3) was investigated by sequencing 50 alleles in an Austrian population sample of 240 unrelated Caucasoid individuals. Several different sequences were found in alleles of the same length. Analysis of the associations between the sequenced C2_4_4 alleles and HLA class I showed a strong linkage disequilibrium between the C2_4_4*9 sequence variants and two different HLA class I haplotypes, as well as between the most common *17 sequence and one HLA‐ABC haplotype. No clear cut association could be observed in C2_4_4*16 and *18. The results of this study demonstrate that the exclusive use of microsatellite polymorphisms for the definition of HLA haplotypes is generally not possible.
Maximizing optimal hematopoietic stem cell donor selection from registries of unrelated adult volunteers
Authors: Hurley C.K. , Vina M. Fernandez , Setterholm M.
Published: May 2006

Abstract: Today, more than 50 registries of HLA‐typed potential adult hematopoietic stem cell donors have been established in 40 countries and include more than 7.5 million volunteers. HLA testing of new volunteers includes HLA‐A, ‐B and often ‐DR typing at low to intermediate resolution. Searching patients are tested for these same loci, preferably at a higher level of resolution. Over 95,000 patient searches are received by registries annually resulting in approximately 4660 unrelated transplants. In 2001, nearly one‐third of transplants involved a patient in one country receiving stem cells from a donor in another. The diversity of the HLA system complicates the search process, requiring sophisticated registry algorithms for matching, and expertise in allele and haplotype frequencies and associations to design search strategies. Within registries, HLA frequency data have been used to evaluate optimal registry size and composition.
Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression
Authors: Carrier Erica J. , Auchampach John A. , Hillard Cecilia J.
Published: May 2006

The plant-derived cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both have immunosuppressive effects; although some effects of THC are mediated by the CB2receptor, CB2binds CBD weakly. In examining the effects of THC and CBD on microglial proliferation, we found that these compounds potently inhibit [3H]thymidine incorporation into a murine microglial cell line with no effect on cell cycle. Treatment with THC and CBD decreased [3H]thymidine uptake into microglia, with IC50values that match inhibition of [3H]thymidine incorporation into DNA. CBD and, less potently, THC decreased uptake of [3H]adenosine to a similar extent as [3H]thymidine in both murine microglia and RAW264.7 macrophages. Binding studies confirm that CBD binds to the equilibrative nucleoside transporter 1 with aKi< 250 nM. Because adenosine agonists have antiinflammatory effects, and because uptake of adenosine is a primary mechanism of terminating adenosine signaling, we tested the hypothesis that CBD is immunosuppressive because it enhances endogenous adenosine signaling.In vivotreatment with a low dose of CBD decreases TNFα production in lipopolysaccharide-treated mice; this effect is reversed with an A2Aadenosine receptor antagonist and abolished in A2Areceptor knockout mice. These studies demonstrate that CBD has the ability to enhance adenosine signaling through inhibition of uptake and provide a non-cannabinoid receptor mechanism by which CBD can decrease inflammation.
CytLEK1 Is a Regulator of Plasma Membrane Recycling through Its Interaction with SNAP-25
Authors: Pooley Ryan D. , Reddy Samyukta , Soukoulis Victor , Roland Joseph T. , Goldenring James R. , Bader David M.
Published: May 2006

SNAP-25 is a component of the SNARE complex that is involved in membrane docking and fusion. Using a yeast two-hybrid screen, we identify a novel interaction between SNAP-25 and cytoplasmic Lek1 (cytLEK1), a protein previously demonstrated to associate with the microtubule network. The binding domains within each protein were defined by yeast two-hybrid, coimmunoprecipitation, and colocalization studies. Confocal analyses reveal a high degree of colocalization between the proteins. In addition, the endogenous proteins can be isolated as a complex by immunoprecipitation. Further analyses demonstrate that cytLEK1 and SNAP-25 colocalize and coprecipitate with Rab11a, myosin Vb, VAMP2, and syntaxin 4, components of the plasma membrane recycling pathway. Overexpression of the SNAP-25–binding domain of cytLEK1, and depletion of endogenous Lek1 alters transferrin trafficking, consistent with a function in vesicle recycling. Taken together, our studies indicate that cytLEK1 is a link between recycling vesicles and the microtubule network through its association with SNAP-25. This interaction may play a key role in the regulation of the recycling endosome pathway.
Contribution of the mu loop to the structure and function of rat glutathione transferase M1‐1
Authors: Hearne Jennifer L. , Colman Roberta F.
Published: May 2006

The “mu loop,” an 11‐residue loop spanning amino acid residues 33–43, is a characteristic structural feature of the mu class of glutathione transferases. To assess the contribution of the mu loop to the structure and function of rat GST M1‐1, amino acid residues 35–44 (35GDAPDYDRSQ44) were excised by deletion mutagenesis, resulting in the “Deletion Enzyme.” Kinetic studies reveal that the Km values of the Deletion Enzyme are markedly increased compared with those of the wild‐type enzyme: 32‐fold for 1‐chloro‐2,4‐dinitrobenzene, 99‐fold for glutathione, and 880‐fold for monobromobimane, while the Vmax value for each substrate is increased only modestly. Results from experiments probing the structure of the Deletion Enzyme, in comparison with that of the wild‐type enzyme, suggest that the secondary and quaternary structures have not been appreciably perturbed. Thermostability studies indicate that the Deletion Enzyme is as stable as the wild‐type enzyme at 4°C and 10°C, but it rapidly loses activity at 25°C, unlike the wild‐type enzyme. In the temperature range of 4°C through 25°C, the loss of activity of the Deletion Enzyme is not the result of a change in its structure, as determined by circular dichroism spectroscopy and sedimentation equilibrium centrifugation. Collectively, these results indicate that the mu loop is not essential for GST M1‐1 to maintain its structure nor is it required for the enzyme to retain some catalytic activity. However, it is an important determinant of the enzyme's affinity for its substrates.
Crystal structure of hypothetical protein TTHB192 from Thermus thermophilus HB8 reveals a new protein family with an RNA recognition motif‐like domain
Authors: Ebihara Akio , Yao Min , Masui Ryoji , Tanaka Isao , Yokoyama Shigeyuki , Kuramitsu Seiki
Published: May 2006

We have determined the crystal structure of hypothetical protein TTHB192 from Thermus thermophilus HB8 at 1.9 Å resolution. This protein is a member of the Escherichia coli ygcH sequence family, which contains ∼15 sequence homologs of bacterial origin. These homologs have a high isoelectric point. The crystal structure reveals that TTHB192 consists of two independently folded domains, and that each domain exhibits a ferredoxin‐like fold with a four‐stranded antiparallel β‐sheet packed on one side by α‐helices. These two tandem domains face each other to generate a β‐sheet platform. TTHB192 displays overall structural similarity to Sex‐lethal protein and poly(A)‐binding protein fragments. These proteins have RNA binding activity which is supported by a β‐sheet platform formed by two tandem repeats of an RNA recognition motif domain with signature sequence motifs on the β‐sheet surface. Although TTHB192 does not have the same signature sequence motif as the RNA recognition motif domain, the presence of an evolutionarily conserved basic patch on the β‐sheet platform could be functionally relevant for nucleic acid‐binding. This report shows that TTHB192 and its sequence homologs adopt an RNA recognition motif‐like domain and provides the first testable functional hypothesis for this protein family.