bluuebunny/crossref_metadata_2025 huggingface dataset:
IMRT Treatment Planning on 4D Geometries for the Era of Dynamic MLC Tracking
Authors: Suh Yelin , Murray Walter , Keall Paul J.
Published: December 2013

The problem addressed here was to obtain optimal and deliverable dynamic multileaf collimator (MLC) leaf sequences from four-dimensional (4D) geometries for dynamic MLC tracking delivery. The envisaged scenario was where respiratory phase and position information of the target was available during treatment, from which the optimal treatment plan could be further adapted in real time. A tool for 4D treatment plan optimization was developed that integrates a commercially available treatment planning system and a general-purpose optimization system. The 4D planning method was applied to the 4D computed tomography planning scans of three lung cancer patients. The optimization variables were MLC leaf positions as a function of monitor units and respiratory phase. The objective function was the deformable dose-summed 4D treatment plan score. MLC leaf motion was constrained by the maximum leaf velocity between control points in terms of monitor units for tumor motion parallel to the leaf travel direction and between phases for tumor motion parallel to the leaf travel direction. For comparison and a starting point for the 4D optimization, three-dimensional (3D) optimization was performed on each of the phases. The output of the 4D IMRT planning process is a leaf sequence which is a function of both monitor unit and phase, which can be delivered to a patient whose breathing may vary between the imaging and treatment sessions. The 4D treatment plan score improved during 4D optimization by 34%, 4%, and 50% for Patients A, B, and C, respectively, indicating 4D optimization generated a better 4D treatment plan than the deformable sum of individually optimized phase plans. The dose-volume histograms for each phase remained similar, indicating robustness of the 4D treatment plan to respiratory variations expected during treatment delivery. In summary, 4D optimization for respiratory phase-dependent treatment planning with dynamic MLC motion tracking improved the 4D treatment plan score by 4–50% compared with 3D optimization. The 4D treatment plans had leaf sequences that varied from phase to phase to account for anatomic motion, but showed similar target dose distributions in each phase. The current method could in principle be generalized for use in offline replanning between fractions or for online 4D treatment planning based on 4D cone-beam CT images. Computation time remains a challenge.
“Age Inflation and Deflation” in Medieval China
Authors: Chen Sanping
Published: December 2013

Using the twelve-year animal cycle, this paper uncovers and examines the dual phenomena of “age inflation” and “age deflation” in medieval China. While the first part raises serious doubt on the accuracy of the conventional method for calculating birth year in premodern China, the second section examining the deflation phenomenon provides yet another proof of the omnipotent law of economic rationality.
Narratives of Tampering in the Earliest Commentaries on the Qurʾān. By Gordon Nickel
Authors: Powers David S.
Published: December 2013

Narratives of Tampering in the Earliest Commentaries on the Qurʾān. By Gordon Nickel. History of Christian-Muslim Relations, vol. 13. Leiden: Brill, 2011. Pp. xx + 244. $146.
Writing the Mughal World: Studies on Culture and Politics. Muzzafar Alam and Sanjay Subrahmanyam
Authors: Hanifi Shah Mahmoud
Published: December 2013

Writing the Mughal World: Studies on Culture and Politics. Muzzafar Alam and Sanjay Subrahmanyam. New York: Columbia University Press, 2011. Pp. xviii + 516. $89.50, £62 (cloth); $29.50, £20.50 (paper).
Appearance of Persian on Islamic Art. By Bernard O’Kane
Authors: Pancaroǧlu Oya
Published: December 2013

The Appearance of Persian on Islamic Art. By Bernard O’Kane. Biennial Ehsan Yarshater Lecture Series, vol. 4. New York: Persian Heritage Foun- dation, 2009. Pp. xiv + 208, illus. $68.
Optimizing the Water‐Energy‐Food Nexus in the Asia‐Pacific Ring of Fire
Authors: Taniguchi Makoto , Allen Diana , Gurdak Jason
Published: December 2013

Climate change and economic development are causing increased pressure on global water, energy, and food resources, presenting increased levels of trade‐offs and conflicts among these resources and stakeholders. Because these resources are interconnected, policy development and resource management require careful consideration of the complex interconnections between nature and society. A balance between risk and resilience is critical for achieving human and environmental security, particularly in Asia, a region within the “Ring of Fire,” which is experiencing drastic social change alongside the huge potential risks and benefits associated with development. The 2011 Fukushima nuclear accident and aftermath underscore the importance of developing policy and management options that maximize security and minimize risk within the water‐energy‐food (WEF) nexus.
Long‐term changes in the Coulomb failure function on inland active faults in southwest Japan due to east‐west compression and interplate earthquakes
Authors: Shikakura Yosuke , Fukahata Yukitoshi , Hirahara Kazuro
Published: December 2013

Inland earthquake activity in and around the Kinki region, southwest Japan, increases in the period from several decades before to about a decade after the occurrence of great interplate earthquakes along the Nankai Trough. To quantitatively investigate this relationship, we calculated long‐term changes in the Coulomb failure function (ΔCFF) on inland active faults in this region with viscoelastic slip response functions. As sources for the change in CFF, we investigated east‐west compression within the Niigata‐Kobe Tectonic Zone (NKTZ), historical interplate earthquakes and interseismic locking along the Nankai Trough subduction zone, and historical inland earthquakes in this region. Among these sources, the NKTZ east‐west compression is the primary cause of the long‐term changes in CFF. The changes in CFF due to interplate earthquakes are mostly negative on reverse faults and positive on strike‐slip faults. This result suggests that the inland reverse faulting activity mostly increases before interplate earthquakes and decreases after the earthquakes, whereas strike‐slip activity is mostly suppressed before interplate earthquakes and increases thereafter. This suggestion is supported by spatiotemporal pattern of historical inland earthquakes if focal mechanisms of historical earthquakes correspond to fault geometries in the region. The calculated changes in CFF are usually consistent with the occurrence of historical inland earthquakes. If we use the change in shear stress instead of the change in CFF, this consistency is enhanced, which suggests low apparent coefficients of friction in this region.
Waveguide effects in very high rate GPS record of the 6 April 2009, Mw 6.1 L'Aquila, central Italy earthquake
Authors: Avallone Antonio , Rovelli Antonio , Di Giulio Giuseppe , Improta Luigi , Ben‐Zion Yehuda , Milana Giuliano , Cara Fabrizio
Published: December 2013

A 10 Hz sampling frequency GPS station was installed near L'Aquila a few days before the 6 April 2009 Mw 6.1 earthquake. It recorded displacement waveforms during the main shock and the largest Mw 5.4 aftershock of 7 April. The horizontal components of the main shock contain a high‐amplitude (43 cm peak‐to‐peak) nearly harmonic (1 Hz) wave train not evident in other nearby instrumental records. The persistency of this feature during aftershocks recorded by a temporarily colocated seismological station highlights a local site effect. Traditional models based on near‐surface velocity structure and topography variations fail to reproduce the size and frequency band of the observed amplified motion. The amplified wave train can be explained by a low‐velocity fault zone layer below the station. This model fits the delay of the large‐amplitude nearly harmonic wave train after the S wave phase and is consistent with the variation in the fault excitation efficiency between the two shocks in relation to their different source depth and location. Synthetic calculation of trapped waves in a model consisting of two quarter spaces separated by a 650 m wide low‐velocity zone with 50% velocity reduction and Q value of 20 fit well the observed anomalous record. The parameters of the model fault zone layer are consistent with geological evidence of a broad damage zone adjacent to the station and a similar site response found in this crustal zone with ambient noise. Results of shallow seismic surveys and sonic logs from deep wells provide independent constraints on the host rock velocities.
A meteorological forcing data set for global crop modeling: Development, evaluation, and intercomparison
Authors: Iizumi Toshichika , Okada Masashi , Yokozawza Masayuki
Published: December 2013

The Global Risk Assessment toward Stable Production of Food (GRASP) project uses global crop models to evaluate the impacts on global food security by changes in climate extremes, water resources, and land use. Such models require meteorological forcing data. This study presents the development of the GRASP forcing data that is a hybrid of the reanalyses (ERA‐40 and JRA‐25) and observations. The GRASP data offer daily mean, maximum, and minimum 2 m air temperatures as well as precipitation, solar radiation, vapor pressure, and 10 m wind speed over global land areas, excluding Antarctica, for the period 1961–2010 at a grid size of 1.125°. The monthly climatologies of the variables of the GRASP data were forced to be close to those of the observations for the baseline period (1961–1990 or 1983–2005) through bias corrections. The GRASP data are intercompared with other forcing data for land surface modeling (the S06, WATCH Forcing Data, and WATCH Forcing Data Methodology Applied to ERA‐Interim data). The results demonstrate that the daily minimum temperature, diurnal temperature range, vapor pressure, solar radiation, and wind speed from the GRASP data are more valuable for crop modeling than the reanalyses and other forcing data. For remaining variables, the reliability of the GRASP data is higher than that of the reanalyses and on a similar level with that of the other forcing data. The GRASP data offer accurate estimates of daily weather as the inputs for crop models, providing unique opportunities to link historical changes in climate with crop production over the last half century.
Wellbeing Begins with “We”
Authors: Kok Bethany E. , Fredrickson Barbara L.
Published: December 2013

Social closeness is a critical component of wellbeing, both mental and physical. Socially connected people appear to live longer, happier, and healthier lives, to have stronger and more resilient immune systems, and to be less prone to developing various mental illnesses including anxiety and depression. Much attention has been directed to interventions that foster social closeness in vulnerable groups such as elderly persons, mentally ill people, at‐risk youths, and those who report often feeling lonely. Less work has been done to develop social closeness interventions for non‐lonely individuals. In this chapter, we briefly review the literature linking social closeness and wellbeing, describe and compare the benefits to wellbeing of interventions that increase social closeness for lonely and non‐lonely individuals, and explore the role of individual differences and electronically mediated communication in modifying the effectiveness of social closeness interventions.
Filtered and heterogeneity‐based subgrid modifications for gas–solid drag and solid stresses in bubbling fluidized beds
Authors: Schneiderbauer Simon , Pirker Stefan
Published: December 2013

Two different approaches to constitutive relations for filtered two‐fluid models (TFM) of gas–solid flows are deduced. The first model (Model A) is derived using systematically filtered results obtained from a highly resolved simulation of a bubbling fluidized bed. The second model (Model B) stems from the assumption of the formation of subgrid heterogeneities inside the suspension phase of fluidized beds. These approaches for the unresolved terms appearing in the filtered TFM are, then, substantiated by the corresponding filtered data. Furthermore, the presented models are verified in the case of the bubbling fluidized bed used to generate the fine grid data. The numerical results obtained on coarse grids demonstrate that the computed bed hydrodynamics is in fairly good agreement with the highly resolved simulation. The results further show that the contribution from the unresolved frictional stresses is required to correctly predict the bubble rise velocity using coarse grids. © 2013 American Institute of Chemical Engineers AIChE J, 60: 839–854, 2014
Self‐reported skin symptoms and skin‐related quality of life among Latino immigrant poultry processing and other manual workers
Authors: Quandt Sara A. , Newman Jill C. , Pichardo‐Geisinger Rita , Mora Dana C. , Chen Haiying , Feldman Steven R. , Arcury Thomas A.
Published: December 2013

Background

Manual labor employment occurs in environments with exposures likely to impact skin‐related quality of life (SRQOL).

Objectives

The objectives of this paper are to (1) document the dimensions of SRQOL, (2) examine its association with skin symptoms, and (3) identify the predictors of SRQOL in Latino manual workers.

Methods

A population‐based survey of 733 Latino manual workers obtained Dermatology Life Quality Index (DLQI) and skin symptoms in the prior year.

Results

Two‐thirds of workers were employed in production. Skin symptoms in prior year were reported by 23%. Impaired SRQOL was reported by 23%. In multivariate analyses, reduced SRQOL was associated with age, occupation, childhood indigenous language use, and experience of skin symptoms in the prior year.

Conclusions

Despite overall high SRQOL exposures in some immigrant occupational groups produce reduce SRQOL. This rural, immigrant population faces significant obstacles to obtaining dermatological care; efforts are needed to improve their SRQOL. Am. J. Ind. Med. 57:605–614, 2014. © 2013 Wiley Periodicals, Inc.
Assessing the exposure of lion tamarins (Leontopithecusspp.) to future climate change
Authors: Meyer Andreas L.S. , Pie Marcio R. , Passos Fernando C.
Published: December 2013

Understanding how biodiversity will respond to climate change is a major challenge in conservation science. Climatic changes are likely to impose serious threats to many organisms, especially those with narrow distribution ranges, small populations and low dispersal capacity. Lion tamarins (Leontopithecusspp.) are endangered primates endemic to Brazilian Atlantic Forest (BAF), and all four living species are typical examples of these aggravating conditions. Here, we integrate ecological niche modeling and GIS‐based information about BAF remnants and protected areas to estimate the exposure (i.e., the extent of climate change predicted to be experienced by a species) of current suitable habitats to climate change for 2050 and 2080, and to evaluate the efficacy of existing reserves to protect climatically suitable areas. Niche models were built using Maxent and then projected onto seven global circulation models derived from the A1B climatic scenario. According to our projections, the occurrence area ofL. caissarawill be little exposed to climate change. Western populations ofL.chrysomelascould be potentially exposed, while climatically suitable habitats will be maintained only in part of the eastern region. Protected areas that presently harbor large populations ofL. chrysopygusandL.rosaliawill not retain climatic suitability by 2080. Monitoring trends of exposed populations and protecting areas predicted to hold suitable conditions should be prioritized. Given the potential exposure of key lion tamarin populations, we stress the importance of conducting additional studies to assess other aspects of their vulnerability (i.e., sensitivity to climate and adaptive capacity) and, therefore, to provide a more solid framework for future management decisions in the context of climate change. Am. J. Primatol. 76:551–562, 2014. © 2013 Wiley Periodicals, Inc.
Hydrodynamic investigation on gas–solid two‐phase flow character in a circulating fluidized bed
Authors: Wang Xueyao , Fan Baoguo , Lei Jing , Lei Fulin , Xiao Yunhan
Published: December 2013

Riser is the key component of circulating fluidized bed reactors, in which gas–solid or catalytic reactions occurs. The flow hydrodynamics and Geldart B type solids' concentration profiles in the riser, under higher superficial gas velocity, larger solids circulation rate, and wide ranges of operating conditions, were the focuses of this experimental study. The typical core‐annulus structure with clusters and a small amount of particles' back‐mixing phenomena near the wall of the riser was observed. The axial solids concentration distributions in the riser with an abrupt T‐shape exit were characterized by a dense region near the bottom, a dilute region toward the up‐middle zone, and a dense region near the top exit. Solids became dilute, and the back‐mixing phenomena weakened with the increase of superficial gas velocity. And the solids concentration at the same height position increased with the increment of solids circulation rate. Furthermore, the effects of two exit configurations, namely smooth C‐shape and abrupt T‐shape, on the flow characteristics were investigated. In order to compare the influence of particles' density and diameter, four single Geldart D particles and a soybean and millet two‐phase mixture are chosen as bed materials to study the bubbling bed flow character. Copyright © 2013 Curtin University of Technology and John Wiley & Sons, Ltd.
Reprocessing effects on polypropylene/silica nanocomposites
Authors: Dorigato Andrea , Pegoretti Alessandro
Published: December 2013

A polypropylene matrix was melt compounded with a given amount (2 vol %) of both untreated (hydrophilic) and surface treated (hydrophobic) fumed silica nanoparticles with the aim to investigate the influence of the time under processing conditions on the microstructure and thermo‐mechanical properties of the resulting materials. Chain scission reactions induced by thermal processing caused a remarkable decrease of the melt viscosity, as revealed by the melt flow index values of both neat matrix and nanocomposites, but the degradative effect was significantly hindered by the presence of silica nanoparticles. It was observed that the size of nanofiller aggregates noticeably decreased as the compounding time increased, especially when hydrophobic silica nanofiller was considered. While the melting temperature seemed to be unaffected by the processing time, a remarkable embrittlement of the samples was observed for prolonged compounding times. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40242.
Structure evolution during uniaxial tensile deformation of high density polyethylene before and after irradiation by 1 MeV electrons
Authors: Rui Erming , Yang Jianqun , Li Xingji , Liu Chaoming , Tian Feng , Gao Feng , Li Xiuhong , Geng Hongbin
Published: December 2013

The structural evolution of high density polyethylene (HDPE) during uniaxial tensile deformation, before and after irradiation by 1 MeV electrons, is in situ studied by synchrotron small angle X‐ray scattering (SAXS) and wide angle X‐ray diffraction (WAXD). Both the pristine and the irradiated HDPE exhibit three regions of deformation behavior. It is shown that the deformation in the first region is in accord with the change in long period of the lamellar structure. In the following two regions, both the strain‐induced melting and strain‐induced crystallization could occur. The tensile stress decreases with strain in the second region due to the dominant melting effect. In the third region, the synergistic effect of the melting and crystallization results in stress leveling off first, and then the tensile stress increases again because the crystallization effect becomes dominant at higher strains. For the irradiated HDPE, the irradiation‐induced crosslinking network slows down the deformation process. Compared to the pristine one, all the tensile stress is rather higher at a given strain for the irradiated HDPE. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40269.
Catastrophic depletion of reef‐associated sea cucumbers: resource management/reef resilience issues for an Indonesian marine park and the wider Indo‐Pacific
Authors: Lane David J. W. , Limbong Daniel
Published: December 2013

Commercial species of shallow‐water, tropical, aspidochirotid sea cucumbers (bêche‐de‐mer) in the Indo‐West Pacific, many of them, at maturity, large and conspicuous benthic members of coral reef or seagrass/sediment environments, represent a high‐value marine resource, traditionally fished for centuries, but which currently are being heavily overfished, largely through a growing demand from mainland China and regional markets in the supply chain.

Population losses are exemplified by a study at Bunaken National Marine Park, North Sulawesi, Indonesia, where densities of commercial sea cucumber species are very low following earlier harvesting and where drop‐out of species records has occurred over a 17‐year study period.

Sea cucumber populations have not recovered from overexploitative depredations despite the designation of this area as a National Marine Park in 1991 and the commencement of protection measures.

This pattern of overexploitation, replicated across the tropical Indo‐Pacific, has detrimental implications for many coastal communities traditionally or currently dependent on this high‐value resource.

In addition there are potentially serious implications of overharvesting – reviewed here – for reef ecosystem resilience.

Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis and Antiproliferative Activity of Some Androstene Oximes and Their O‐Alkylated Derivatives
Authors: Acharya Pratap Chandra , Bansal Ranju
Published: December 2013

In order to study the structure–activity relationship with respect to the cytotoxicity of steroidal oximes, several 6E‐hydroximino‐4‐ene steroids and their O‐alkylated derivatives were synthesized. The oxime ethers were solidified and purified by preparing their corresponding oxalate salts. The new derivatives as well as some previously synthesized ones were evaluated for in vitro antineoplastic activity against a panel of 60 cancer cell lines at 10 µM. The oximes and oxime ethers were found to have moderate to good antiproliferative activity against various leukemia, colon, melanoma, and renal cancer cell lines.
Electron transfer reactions of ruthenium(II)–bipyridine complexes carrying tyrosine moiety with quinones
Authors: Mareeswaran Paulpandian Muthu , Rajkumar Eswaran , Sathish Veerasamy , Rajagopal Seenivasan
Published: December 2013

Three ruthenium(II)–bipyridine complexes carrying a tyrosine moiety were synthesized and photophysical and electron transfer studies with quinones were carried out using absorption and emission spectral techniques. The binding efficiency of quinones with ruthenium(II)–bipyridine complexes was also studied using these techniques. The binding efficiency was moderate and similar for all complexes with all quinones. The quenching modes were also similar and efficient for all complexes with all quinones. The quenching processes were diffusion controlled. The rate of electron transfer was calculated using semiclassical theory. Copyright © 2013 John Wiley & Sons, Ltd.
Newly engineered cyan fluorescent proteins with enhanced performances for live cell FRET imaging
Authors: Mérola Fabienne , Fredj Asma , Betolngar Dahdjim‐Benoît , Ziegler Cornelia , Erard Marie , Pasquier Hélène
Published: December 2013

Cyan fluorescent proteins (CFPs) derived from Aequorea victoria green fluorescent protein are the most widely used Förster resonant energy transfer (FRET) donors in genetically encoded biosensors for live‐cell imaging and bioassays. However, the weak and complex fluorescence emission of cyan variants, such as enhanced cyan fluorescent protein (ECFP) or Cerulean, has long remained a major bottleneck in these FRET techniques. Recently, several CFPs with greatly improved performances, including mTurquoise, mTurquoise2, mCerulean3, and Aquamarine, have been engineered through a mixture of site‐directed and large‐scale random mutagenesis. This review summarizes the engineering and relative merits of these new cyan donors, which can readily replace popular CFPs in FRET imaging protocols, while reaching fluorescence quantum yields close to 90%, and unprecedented long, near‐single fluorescence lifetimes of about 4 ns. These variants display an increased general photostability and much reduced environmental sensitivity, notably towards acid pH. These new, bright, and robust CFPs now open up exciting outlooks for fluorescence lifetime imaging microscopy and advanced quantitative FRET analyses in living cells. In addition, the stepwise engineering of Aquamarine shows that only two critical mutations in ECFP, and one in Cerulean, are required to achieve these performances, which brings new insights into the structural bases of their photophysical properties.
Allosteric transitions of the maltose transporter studied by an elastic network model
Authors: Li Chun Hua , Yang Yong Xiao , Su Ji Guo , Liu Bin , Tan Jian Jun , Zhang Xiao Yi , Wang Cun Xin
Published: December 2013

The maltose transporter from Escherichia coli is one of the ATP‐binding cassette (ABC) transporters that utilize the energy from ATP hydrolysis to translocate substrates across cellular membranes. Until 2011, three crystal structures have been determined for maltose transporter at different states in the process of transportation. Here, based on these crystal structures, the allosteric pathway from the resting state (inward‐facing) to the catalytic intermediate state (outward‐facing) is studied by applying an adaptive anisotropic network model. The results suggest that the allosteric transitions proceed in a coupled way. The closing of the nucleotide‐binding domains occurs first, and subsequently this conformational change is propagated to the transmembrane domains (TMD) via the EAA and EAS loops, and then to the maltose‐binding protein, which facilitates the translocation of the maltose. It is also found that there exist nonrigid‐body and asymmetric movements in the TMD. The cytoplasmic gate may only play the role of allosteric propagation during the transition from the pretranslocation to outward‐facing states. In addition, the results show that the movment of the helical subdomain towards the RecA‐like subdomain mainly occurs in the earlier stages of the transition. These results can provide some insights into the understanding of the mechanism of ABC transporters. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 758–768, 2014.
Fast hemicellulose quantification via a simple one‐step acid hydrolysis
Authors: Gao Xiadi , Kumar Rajeev , Wyman Charles E.
Published: December 2013

As the second most common polysaccharides in nature, hemicellulose has received much attention in recent years for its importance in biomass conversion in terms of producing high yields of fermentable sugars and value‐added products, as well as its role in reducing biomass recalcitrance. Therefore, a time and labor efficient method that specifically analyzes hemicellulose content would be valuable to facilitate the screening of biomass feedstocks. In this study, a one‐step acid hydrolysis method was developed, which applied 4 wt% sulfuric acid at 121°C for 1 h to rapidly quantify XGM (xylan + galactan + mannan) contents in various types of lignocellulosic biomass and model hemicelluloses. This method gave statistically identical results in XGM contents compared to results from conventional two‐step acid hydrolysis while significantly shortening analysis time. Biotechnol. Bioeng. 2014;111: 1088–1096. © 2014 Wiley Periodicals, Inc.
Comparative pharmacokinetics studies of benzoylhypaconine, benzoylmesaconine, benzoylaconine and hypaconitine in rats by LC‐MS method after administration of Radix Aconiti Lateralis Praeparata extract and Dahuang Fuzi Decoction
Authors: Liu Xiao , Li Huan , Song Xiaoqing , Qin Kunming , Guo Hui , Wu Li , Cai Hao , Cai Baochang
Published: December 2013

A rapid and sensitive high‐performance liquid chromatography–mass spectrometric (HPLC‐MS) method was developed and validated for simultaneous determination of benzoylhypaconine (BHA), benzoylmesaconine (BMA), benzoylaconine (BAC) and hypaconitine (HA) in rat plasma for the first time. The analytes were separated on a Kromasil C18 column with a total running time of 11 min. The validation data demonstrated a sound feasibility for the newly developed method and it was then applied to the pharmacokinetic study of these analytes in rats. Pharmacokinetic behaviors of BHA, BMA, BAC and HA in rats were studied after oral administration of Radix Aconiti Lateralis Praeparata extract (FZ) and Dahuang Fuzi Decoction (DFD). The main parameters for the two groups of subjects were compared, and significant differences between Radix Aconiti Lateralis Praeparata extract group and Dahuang Fuzi Decoction group in calculated parameters, such as the area under the plasma concentration–time from zero to the last quantifiable time‐point (AUC0–t), the area under the plasma concentration–time curve from zero to infinity (AUC0–∞), peak plasma concentration (Cmax), half‐life of elimination (T1/2), mean retention time (MRT0–t), plasma clearance (CL), volume of distribution (Vd) and time to reach Cmax (Tmax), were found. After oral administration of DFD, the AUC0–t, AUC0–∞ and Cmax of BHA, BMA, BAC and HA decreased remarkably (p < 0.05) compared with those of the FZ extract group. Vd and CL values of BHA, BMA, BAC and HA increased, two of which showed significant difference (p < 0.05). T1/2 and MRT0–t values of BHA, BMA and BAC in the DFD group were significantly delayed compared with those of FZ extract group. Only the Tmax of HA, the toxic ingredient in FZ, delayed significantly in DFD group compared with the value of FZ group. All these pharmacokinetic parameters were statistically compared, and the rationality of the combination for DFD was clearly demonstrated. Copyright © 2013 John Wiley & Sons, Ltd.
A novel LC‐MS/MS method for determination of tissue distribution and excretion of timosaponin B‐II in rat biological matrices
Authors: Xu Zhongyuan , Gao Shouhong , Cai Fei , Zhang Feng , Jiang Wei , Liu Xiaowei , Chen Wansheng
Published: December 2013

Timosaponin B‐II (TB‐II) is a natural bioactive steroid glycoside extracted from the Chinese medicinal herb Anemarrhena asphodeloides Bge. (Fam. Liliaceae). It has been demonstrated to have a good anti‐inflammatory effect and a low bioavailability (1.1%). Clinical research has focused on developing it into a completely new medicine. In this study, a rapid and sensitive analytical method based on LC‐MS/MS has been developed for the determination of TB‐II in rat biological matrices (tissues, bile, urine and feces samples). The analytes and internal standard were isolated from 100 μL samples by solid‐phase extraction and then separated using a DIKMA Inertsil ODS‐3 column (5 µm, 2.1 × 150 mm) with an isocratic mobile phase consisting of acetonitrile–0.05% formic acid (35:65) at a flow rate of 0.25 mL/min. Calibration curves (1/χ2‐weighted) offered satisfactory linearity (r2 ≥ 0.990) within the test range. The accuracy, precision, recoveries and matrix effects were satisfactory in all the biological matrices examined. The assay was successfully applied to a tissue distribution and excretion study in rats. The preclinical data are useful for the design of clinical trials of TB‐II. Copyright © 2013 John Wiley & Sons, Ltd.
Assessing the survival ofMycobacterium tuberculosisin unembalmed and embalmed human remains
Authors: Correia J.C. , Steyl J.L. , De Villiers H.C.
Published: December 2013

Anatomy and mortuary technical staff faces an ever existing risk of contracting an infectious disease, such asMycobacterium tuberculosis(MTB), when exposed to human remains. The transfer and handling of a corpse expels air from the lungs of the diseased and this aerosolizes the bacilli. It is for this reason that personal protective equipment and work space precautions such as ultraviolet germicidal irradiation is a necessity. In this study, the authors explore the viability of MTB before and after embalming. Briefly, lung tissue samples, both apical and hilar, were obtained from 20 cadavers whose death certificate indicated MTB as cause of death. The first sample was taken before embalming and second set 3 weeks after embalming. Tissue was deposited into sterile specimen containers and transported for analysis which includedMycobacteriumgrowth indicator tube cultures and polymerase chain reaction. Results demonstrated that both the apical and the perihilar sample tested positive prior to embalming, 36 days after death. After three weeks post‐embalming none tested positive. The results demonstrated that MTB can remain viable after death for up to 36 days. This viability extends beyond the documented cases and highlights the need for precautionary measures and standard operating procedures in accordance with occupational health and safety guidelines. Clin. Anat. 27:304–307, 2014. © 2013 Wiley Periodicals, Inc.
Automated resolution of overlapping peaks in chromatographic data
Authors: Johnsen Lea G. , Amigo José Manuel , Skov Thomas , Bro Rasmus
Published: December 2013

Parallel factor analysis 2 (PARAFAC2) has been shown to be a powerful tool for resolution of complex overlapping peaks in chromatographic analyses. It is particularly useful because of its ability to handle shifts in the elution time mode and peak shape changes. Like all curve resolution techniques, PARAFAC2 will only find chemically meaningful parameters (elution time profiles and mass spectra) if the correct number of factors are determined. So far, the primary way to determine an appropriate number of factors, when using PARAFAC2, is to calculate models with different number of factors and then inspect the models manually. This approach is time consuming, and the result may be biased because of the manual assessment of the model quality, making PARAFAC2 inaccessible for analytical chemists in general. Here, we develop a method that can determine an appropriate number of factors in an automated way. The automation is based on a number of model diagnostics (quality criteria) collected from models with different numbers of factors. Combining these diagnostics, it is possible to assess what the appropriate number of components is. In this work, only gas chromatography–mass spectrometry data are considered. However, it will most likely be fairly straightforward to expand the work to also cover liquid chromatography data (with a multivariate detector). Automating the model quality evaluation of the PARAFAC2 model enables both the inexperienced and trained user to perform comprehensive and advanced analysis of chromatographic data with a minimum of manual work. © 2013 The Authors. Journal of Chemometrics Published by John Wiley & Sons Ltd.
Simultaneous LC–MS/MS Determination of Imidazolinone Herbicides Together with Other Multiclass Pesticide Residues in Soil
Authors: Martins Gisele L. , Friggi Caroline A. , Prestes Osmar D. , Vicari Michele C. , Friggi Daniela A. , Adaime Martha B. , Zanella Renato
Published: December 2013

An effective method based on a modified quick, easy, cheap, effective, rugged, and safe sample preparation step and determination by LC with MS/MS has been developed and validated for the simultaneous determination of pesticides with different characteristics in soil samples. Several parameters that affect the extraction and analysis were studied and the proposed method was validated using spiked blank soil samples. Recoveries for the herbicides clomazone, imazapic and imazethapyr, the insecticides fipronil and thiamethoxam, and the fungicides propiconazole and trifloxystrobin from blank samples spiked at levels between 2 and 100 µg kg−1 were in the acceptable range of 72.5–119.3% with relative standard deviation below 18.2%. Method limit of detection ranged between 0.12 and 0.6 µg kg−1. The method was successfully applied to the analysis of soil samples from rice paddies were thiamethoxam (103.4–770.8 µg kg−1), imazethapyr (2.4–293.5 µg kg−1), and fipronil (2.1–170.0 µg kg−1) were found in all samples. Imazapic, clomazone, trifloxystrobin presented low concentrations and propiconazole was not detected. The main advantages of the method lie in the fact that is simple and quick to perform, demand small amount of solvent and permit the analysis of multiclass pesticides at trace levels in soil samples with good trueness and precision.
Postsynaptic distribution of IRSp53 in spiny excitatory and inhibitory neurons
Authors: Burette Alain C. , Park Haram , Weinberg Richard J.
Published: December 2013

The 53 kDa insulin receptor substrate protein (IRSp53) is highly enriched in the brain. Despite evidence that links mutations of IRSp53 with autism and other neuropsychiatric problems, the functional significance of this protein remains unclear. We used light and electron microscopic immunohistochemistry to demonstrate that IRSp53 is expressed throughout the adult rat brain. Labeling concentrated selectively in dendritic spines, where it was associated with the postsynaptic density (PSD). Surprisingly, its organization within the PSD of spiny excitatory neurons of neocortex and hippocampus differed from that within spiny inhibitory neurons of neostriatum and cerebellar cortex. The present data support previous suggestions that IRSp53 is involved in postsynaptic signaling, while hinting that its signaling role may differ in different types of neurons. J. Comp. Neurol. 522:2164–2178, 2014. © 2013 Wiley Periodicals, Inc.
Hemodynamics in two tandem aneurysms treated with flow diverters
Authors: Mut Fernando , Scrivano Esteban , Bleise Carlos , Lylyk Pedro , Cebral Juan
Published: December 2013

The purpose of this study was to investigate whether the occlusion time of cerebral aneurysms treated with flow diverters depends on the hemodynamic conditions created immediately after treatment. A case study of a pair of tandem intracranial aneurysms that were treated with flow‐diverting devices and occluded at different times was carried out. A patient‐specific computational fluid dynamics model was constructed from 3D rotational angiography images. Blood flow simulations were carried out under pulsatile physiologic conditions, and hemodynamic variables before and after deployment of the flow‐diverting devices were quantified and compared. The flow‐diverting devices reduced aneurysm inflow rates, intra‐aneurysmal flow velocities, shear rates, and wall shear stresses. The flow patterns after flow modulation by the flow diverters were smoother and with less swirling. The reductions in hemodynamic quantities depended on the aneurysm and parent artery and were larger in the aneurysm that occluded faster. The results of this case study suggest that the larger the reduction in the hemodynamic variables considered, the shorter the time it takes for the aneurysm to thrombose. This result can help us better define the goal of these interventions. Copyright © 2013 John Wiley & Sons, Ltd.
Safety, pharmacokinetics, pharmacodynamics, and bioavailability of GSK2018682, a sphingosine‐1‐phosphate receptor modulator, in healthy volunteers
Authors: Xu Jianfeng , Gray Frank , Henderson Alex , Hicks Kirsty , Yang Jiansong , Thompson Paul , Oliver Johann
Published: December 2013

The tolerability, pharmacokinetics, and pharmacodynamics of single (SD) and repeat (RD) doses of GSK2018682, a selective S1P1 receptor modulator, were evaluated in healthy volunteers. The bioavailability (BA) of different formulations and effects of food were also evaluated. SD of up to 24 mg and RD of up to 6 mg/day for 28 days were reasonably tolerated, despite higher incidences of gastrointestinal and cardiovascular adverse events compared to placebo. There was a linear relationship between dose and systemic exposure with a dose‐independent half‐life (t1/2) between 44.9 and 63.3 hours. GSK2018682 induced acute, transient and non‐symptomatic decreases in heart rate and blood pressure. Dose‐dependent reduction in absolute lymphocyte count (ALC), and all tested subsets, was observed to various degrees, up to a nadir of over 70% reduction from baseline. There was no difference in major pharmacokinetic parameters among three formulations of GSK2018682 and between fasted and fed subjects. However, there was a reduction in the extent of bradycardia following dosing in the fed state. Additionally, exercise induced robust increase in heart rate in subjects who had bradycardia following RD of GSK2018682 up to 6 mg, suggesting possible physiological methods of reducing the extent of S1P mediated bradycardia and subsequent AV‐block.
Labeling of the pathogenic bacterium Staphylococcus aureus with gold or ferric oxide‐core nanoparticles highlights new capabilities for investigation of host–pathogen interactions
Authors: Depke Maren , Surmann Kristin , Hildebrandt Petra , Jehmlich Nico , Michalik Stephan , Stanca Sarmiza E. , Fritzsche Wolfgang , Völker Uwe , Schmidt Frank
Published: December 2013

Throughout the world, infections caused by bacteria such as Staphylococcus aureus are a major cause of morbidity and mortality. In order to gain some understanding of the complicated physiological link between host and pathogen, modern techniques such as confocal microscopy and sophisticated OMICs technologies are suitable. However, labeling of pathogens such as S. aureus with green fluorescent protein, for example, or the generation of a reliable antibody, which are prerequisites for the application of reproducible isolation techniques, does not always succeed. Here, we present a universal approach for monitoring pathogen traffic after internalization into host cells by fluorescence microscopy and for isolation of bacteria from host–pathogen interaction assays using gold or ferric oxide‐core, poly(vinyl alcohol) coated, and fluorescence‐labeled nanoparticles (NP). The incubation of S. aureus HG001 with those NP had only minor effects on the bacterial growth in vitro. Quantitative proteome analysis after 24 h of NP incubation revealed that presence of NP provoked only marginal changes in the proteome pattern. The method presented enabled us to investigate the behavior of S. aureus HG001 during infection of S9 human epithelial cells by means of fluorescence microscopy and proteomics using magnetic separation or cell sorting. © 2013 International Society for Advancement of Cytometry
Juvenile play experience does not affect nicotine sensitization and voluntary consumption of nicotine in adult rats
Authors: Himmler B.T. , Nakahashi A. , Snow E. , McMickle A. , Muhammad A. , Biondolillo K.D. , Pellis S.M. , Kolb B.
Published: December 2013

Juvenile play experiences promote behavioral flexibility in rats. If other early positive experiences, such as tactile stimulation, are given prior to exposure to psychostimulants, the behavioral response to the drug is attenuated. The objective of the present study was to determine if the experience of juvenile play behavior would attenuate the response to nicotine. Two experiments were conducted: (1) behavioral sensitization to nicotine exposure, and (2) voluntary consumption of nicotine. For both experiments, rats were reared either with three same‐sex peers (play group) or one adult (no play group) during their juvenile period. Then, as adults, half of each group was exposed to repeated injections of nicotine and the other half to saline. Prior play experience had no effect on behavioral sensitization or on voluntary consumption of nicotine. It remains to be determined whether juvenile experience with play influences the rewarding properties of nicotine in social contexts as adults. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 1052–1060, 2014.
Lamotrigine use in patients with binge eating and purging, significant affect dysregulation, and poor impulse control
Authors: Trunko Mary Ellen , Schwartz Terry A. , Marzola Enrica , Klein Angela S. , Kaye Walter H.
Published: December 2013

Objective

Some patients with symptoms of binge eating and purging are successfully treated with specific serotonin reuptake inhibitors (SSRIs), but others experience only partial or no benefit. Significant affect dysregulation and poor impulse control may be characteristics that limit responsiveness.

Method

We report on the treatment of five patients with bulimia nervosa (BN), anorexia nervosa—binge/purge type (AN‐B/P) or eating disorder not otherwise specified (EDNOS), using the anticonvulsant lamotrigine after inadequate response to SSRIs.

Results

Following addition of lamotrigine to an antidepressant in four cases, and switch from an antidepressant to lamotrigine in one case, patients experienced substantial improvement in mood reactivity and instability, impulsive drives and behaviors, and eating‐disordered symptoms.

Discussion

These findings raise the possibility that lamotrigine, either as monotherapy or as an augmenting agent to antidepressants, may be useful in patients who binge eat and purge, and have significant affect dysregulation with poor impulse control. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:329–334)
Air‐Stable and Volatile Bis(pyridylalkenolato)germanium(II), ‐tin(II), and ‐lead(II) Complexes
Authors: Heidemann Tim , Mathur Sanjay
Published: December 2013

Homoleptic germanium(II), tin(II), and lead(II) complexes of the general formula M(2‐PyCHCOCF3)2 (M = Ge, Sn, Pb; Py = pyridine) were synthesized by treating the corresponding silyl amides [M{N(SiMe3)2}2] with two equivalents of a 3,3,3‐trifluoro‐1‐(2‐pyridyl)prop‐1‐en‐2‐ol (2‐PyCHCOHCF3) ligand. Single‐crystal X‐ray diffraction revealed the bidentate chelation of 2‐PyCHCOHCF3, which imposes a distorted trigonal bipyramidal geometry for all three molecular structures; this distortion is highest for the lead compound, probably as a result of the high s character of the lone pair of electrons present on the metal centers. The monomeric nature of the compounds in solution was confirmed by multinuclear NMR spectroscopy, whereas a polymeric structure is observed for the lead complex in the solid state.
Tris(pyrazolyl)phosphine Oxide and Tris(triazolyl)phosphine Oxide Scorpion Ligands
Authors: Tazelaar Cornelis G. J. , Lyaskovskyy Volodymyr , van Doorn Ilana M. , Schaapkens Xander , Lutz Martin , Ehlers Andreas W. , Slootweg J. Chris , Lammertsma Koop
Published: December 2013

DFT calculations were performed on copper(I) complexes of neutral scorpion ligands based on either pyrazolyl (Pz) or triazolyl (Tz) rings with both methane and phosphine oxide apexes, that is, HC(Pz)3, OP(Pz)3, HC(Tz)3, and OP(Tz)3. The analyses reveal that all four ligands have similar donor properties and that their differences are easily compensated by the proper choice of substituents. This computational study strongly suggests that the readily synthesizable neutral phosphine oxide capped scorpion ligands should have broad applicability. Experimentally, the two OP‐capped ligands act differently on copper(I) complexation. With OP(Tz)3, a crystallographically characterized dimeric tris(triazolyl)phosphine oxide based copper(I) complex was obtained, whereas instead a monomer was reported for OP(Pz)3.