bluuebunny/crossref_metadata_2025 huggingface dataset:
Capillary gel electrophoresis for the quantification and purity determination of recombinant proteins in inclusion bodies
Authors: Espinosa‐de la Garza Carlos E. , Perdomo‐Abúndez Francisco C. , Campos‐García Víctor R. , Pérez Néstor O. , Flores‐Ortiz Luis F. , Medina‐Rivero Emilio
Published: July 2013

In this work, a high‐resolution CGE method for quantification and purity determination of recombinant proteins was developed, involving a single‐component inclusion bodies (IBs) solubilization solution. Different recombinant proteins expressed as IBs were used to show method capabilities, using recombinant interferon‐β 1b as the model protein for method validation. Method linearity was verified in the range from 0.05 to 0.40 mg/mL and a determination coefficient (r2) of 0.99 was obtained. The LOQs and LODs were 0.018 and 0.006 mg/mL, respectively. RSD for protein content repeatability test was 2.29%. In addition, RSD for protein purity repeatability test was 4.24%. Method accuracy was higher than 90%. Specificity was confirmed, as the method was able to separate recombinant interferon‐β 1b monomer from other aggregates and impurities. Sample content and purity was demonstrated to be stable for up to 48 h. Overall, this method is suitable for the analysis of recombinant proteins in IBs according to the attributes established on the International Conference for Harmonization guidelines.
A novel epigenetic CREB‐miR‐373 axis mediates ZIP4‐induced pancreatic cancer growth
Authors: Zhang Yuqing , Yang Jingxuan , Cui Xiaobo , Chen Yong , Zhu Vivian F. , Hagan John P. , Wang Huamin , Yu Xianjun , Hodges Sally E. , Fang Jing , Chiao Paul J. , Logsdon Craig D. , Fisher William E. , Brunicardi F. Charles , Chen Changyi , Yao Qizhi , Fernandez‐Zapico Martin E. , Li Min
Published: July 2013

Changes in the intracellular levels of the essential micronutrient zinc have been implicated in multiple diseases including pancreatic cancer; however, the molecular mechanism is poorly understood. Here, we report a novel mechanism where increased zinc mediated by the zinc importer ZIP4 transcriptionally induces miR‐373 in pancreatic cancer to promote tumour growth. Reporter, expression and chromatin immunoprecipitation assays demonstrate that ZIP4 activates the zinc‐dependent transcription factor CREB and requires this transcription factor to increase miR‐373 expression through the regulation of its promoter. miR‐373 induction is necessary for efficient ZIP4‐dependent enhancement of cell proliferation, invasion, and tumour growth. Further analysis of miR‐373 in vivo oncogenic function reveals that it is mediated through its negative regulation of TP53INP1, LATS2 and CD44. These results define a novel ZIP4‐CREB‐miR‐373 signalling axis promoting pancreatic cancer growth, providing mechanistic insights explaining in part how a zinc transporter functions in cancer cells and may have broader implications as inappropriate regulation of intracellular zinc levels plays an important role in many other diseases.
Gabapentin‐induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain
Authors: Hooker B.A. , Tobon G. , Baker S.J. , Zhu C. , Hesterman J. , Schmidt K. , Rajagovindan R. , Chandran P. , Joshi S.K. , Bannon A.W. , Hoppin J. , Beaver J. , Fox G.B. , Day M. , Upadhyay J.
Published: July 2013

Background

The function of brain networks can be changed in a maladaptive manner in response to chronic neuropathic pain. Analgesics can reduce pain by acting on such networks via direct or indirect (peripheral or spinal) mechanisms. This investigation aimed to map gabapentin's pharmacodynamics (PD) in the rodent brain following induction of neuropathic pain in order to further understand its PD profile.

Methods

Pharmacological magnetic resonance imaging (phMRI) and a novel functional connectivity analysis procedure were performed following vehicle or gabapentin treatment in the rat spinal nerve ligation (SNL) model of neuropathic pain as well as sham animals.

Results

phMRI performed in SNL animals revealed robust gabapentin‐induced responses throughout the hippocampal formation, yet significant (p < 0.05, corrected for multiple comparisons) responses were also measured in other limbic structures and the sensorimotor system. In comparison, sham animals displayed weaker and less widespread phMRI signal changes subsequent to gabapentin treatment. Next, communities of networks possessing strong functional connectivity were elucidated in vehicle‐treated SNL and sham animals. We observed that SNL and sham animals possessed distinct functional connectivity signatures. When measuring how gabapentin altered the behaviour of the discovered networks, a decrease in functional connectivity driven by gabapentin was not only observed, but the magnitude of this PD effect was greater in SNL animals.

Conclusions

Using phMRI and functional connectivity analysis approaches, the PD effects of gabapentin in a preclinical neuropathic pain state were characterized. Furthermore, the current results offer insights on which brain systems gabapentin directly or indirectly acts upon.
Nanoprofiles evaluation of ZnO thin films by an evanescent light method
Authors: Mirchin Nina , Peled Aaron , Duta Liviu , Popescu Andrei C. , Dorcioman Gabriela , Mihailescu Ion N.
Published: July 2013

The extraction efficiency of evanescent light from ZnO nanolayers and their thickness profiles in the range of (1–105) nm was evaluated by a new microscopy technique, differential evanescent light intensity imaging method. It is based on capturing the evanescent light scattered by the layer of the material deposited on glass substrates. The analyzed ZnO films were obtained by pulsed laser deposition at 27°C and 100°C, using a nanosecond UV laser source. Microsc. Res. Tech., 76:992–996, 2013. © 2013 Wiley Periodicals, Inc.
Autofluorescence removal using a customized filter set
Authors: Pang Zhengyu , barash Eugene , Santamaria‐Pang Alberto , Sevinsky Christopher , Li Qing , Ginty Fiona
Published: July 2013

Quantitative fluorescence microscopy is severely hindered by intrinsic autofluorescence (AF). Endogenous fluorescent molecules in tissue and cell samples emit fluorescence that often dominates signals from specific dyes. This makes AF removal critical to the development and practice of quantitative fluorescence microscopy. In this study, we showed that AF signal could be separated from specific signal using a customized filter set. The filter set used the same excitation and beam splitter as the standard filter set, but the emission filter was red‐shifted 40–60 nm from the peak of the specific dye. This filter set configuration collected mostly AF with minimum contribution from the specific dye. A linear transformation of AF images was required to correct for the difference in exposure and filter configuration. The constants (slope and intercept) in linear transformation were obtained through a pixel to pixel comparison between AF images (no staining) obtained by the standard filter set and the customized AF filter set. After staining of specific dye, the standard filter collecting target dye spectra was used to capture both target signal and AF, whereas customized filter was used to capture only AF. AF removal was accomplished by subtracting the linear transformed AF image from the image obtained from the standard filter. To validate our approach, we examined weak staining of androgen receptor in an AF abundant prostate tissue sample. Our method revealed a similar but cleaner nuclear staining of androgen receptor in a specimen, when compared to a traditional autofluorescence removal method. Microsc. Res. Tech., 76:1007–1015, 2013. © 2013 Wiley Periodicals, Inc.
Anatomical and scanning electron microscopic characteristics of the tongue in the pampas deer (Cervidae: Ozotoceros bezoarticus, Linnaeus 1758)
Authors: Erdoğan Serkan , Pérez William
Published: July 2013

This study represents the first definitive anatomical description of the tongue and lingual papillae of the pampas deer and compares the different information on the morphology of the other ruminant species available in the literature. In this study, the tongues of four adult and one fetal deer were used. The tongue was elongated with an oval or rounded apex. The filiform papillae on the lingual apex were smaller than the ones on the dorsal and lateral surfaces of the lingual body. Two very thin secondary papillary projections were found to emerge from the bilateral sides of some filiform papillae. Spherical fungiform papillae were randomly distributed among filiform papillae on dorsal surface of the lingual body and ventral surface of the apex. More developed conical papillae were observed in the caudal half of the lingual torus, whereas the rostral half of the torus had smaller conical papillae. Each conical papilla included shallow longitudinal groove on its anterior surface and some conical papillae on the lingual torus had bifid sharp apices. On the caudal portion of the torus, we also observed a few fungiform papillae, which were larger than those located on the lingual body. There were no lenticular papillae on the lingual torus, and five to nine round or oval circumvallate papillae were situated on each caudolateral side of the lingual torus. Morphological features of the tongue in the pampas deer were more similar to wild ruminant species than they were to domestic species. Microsc. Res. Tech., 76:1025–1034, 2013. © 2013 Wiley Periodicals, Inc.
Cloud optical and microphysical properties derived from ground‐based and satellite sensors over a site in the Yangtze Delta region
Authors: Liu Jianjun , Li Zhanqing , Zheng Youfei , Chiu J. Christine , Zhao Fengsheng , Cadeddu Maria , Weng Fuzhong , Cribb Maureen
Published: July 2013

Comprehensive surface‐based retrievals of cloud optical and microphysical properties were made at Taihu, a highly polluted site in the central Yangtze Delta region, during a research campaign from May 2008 to December 2009. Cloud optical depth (COD), effective radius (Re), and liquid water path (LWP) were retrieved from measurements made with a suite of ground‐based and spaceborne instruments, including an Analytical Spectral Devices spectroradiometer, a multifilter rotating shadowband radiometer, a multichannel microwave radiometer profiler, and the Moderate Resolution Imaging Spectroradiometer (MODIS) on Terra and Aqua satellites. Retrievals from zenith radiance measurements capture better the temporal variation of cloud properties than do retrievals from hemispherical fluxes. Annual mean LWP, COD, and Re are 115.8 ± 90.8 g/m2, 28.5 ± 19.2, and 6.9 ± 4.2 µm. Over 90% of LWP values are less than 250 g/m2. Most of the COD values (>90%) fall between 5 and 60, and ~80% of Re values are less than 10 µm. Maximum (minimum) values of LWP and Re occur in summer (winter); COD is highest in winter and spring. Raining and nonraining clouds have significant differences in LWP, COD, and Re. Rainfall frequency is best correlated with LWP, followed by COD and Re. Cloud properties retrieved from multiple ground‐based instruments are also compared with those from satellite retrievals. On average, relative to surface retrievals, mean differences of satellite retrievals in cloud LWP, COD, and Re were −33.6 g/m2 (−26.4%), −5.8 (−31.4%), and 2.9 µm (29.3%) for 11 MODIS‐Terra overpasses and −43.3 g/m2 (−22.3%), −3.0 (−10.0%), and −1.3 µm (−12.0%) for 8 MODIS‐Aqua overpasses, respectively. These discrepancies indicate that MODIS cloud products still suffer from large uncertainties in this region.
Communicate, don't litigate: The Schwartz Center Connections Program
Authors: Lown Beth A. , Gareis Karen , Kormos William , Kriegel Gila , Leffler Daniel , Richter Jim , Ship Amy , Weil Eric , Manning Colleen
Published: July 2013

Little is known about effective educational approaches intended to reduce malpractice risk by improving communication with patients and among multidisciplinary teams in outpatient settings in order to prevent diagnostic delays and errors. This article discusses a prospective, controlled educational intervention that aimed to open lines of communication among teams in two disciplines: identifying how and why communication lapses occur between disciplines and with patients, and articulating strategies to avert them.
Automated, wireless, continuous, intelligent, and noninvasive systems for risk management and performance improvement in vital signs monitoring
Authors: Bauer Jeffrey C.
Published: July 2013

Few health professionals need to stay up‐to‐date on as many different problems and solutions as risk managers do. Consequently, a single solution that resolves several problems at once is really helpful for job performance, especially when it doesn't require duplicating effort in multiple areas. This article summarizes current literature about one such technology that helps risk managers address 3 of today's biggest challenges for healthcare delivery organizations: reducing costs, improving quality, and preventing harm across the continuum of clinical care; ensuring valid and reliable data for healthcare clinical and managerial decision makers; and adopting technologies that improve the medical marketplace.
Why are autopsy rates low in Japan? Views of ordinary citizens and doctors in the case of unexpected patient death and medical error
Authors: Maeda Shoichi , Kamishiraki Etsuko , Starkey Jay , Ikeda Noriaki
Published: July 2013

This article examines what could account for the low autopsy rate in Japan based on the findings from an anonymous, self‐administered, structured questionnaire that was given to a sample population of the general public and physicians in Japan. The general public and physicians indicated that autopsy may not be carried out because: (1) conducting an autopsy might result in the accusation that patient death was caused by a medical error even when there was no error (50.4% vs. 13.1%, respectively), (2) suggesting an autopsy makes the families suspicious of a medical error even when there was none (61.0% vs. 19.1%, respectively), (3) families do not want the body to be damaged by autopsy (81.6% vs. 87.3%, respectively), and (4) families do not want to make the patient suffer any more in addition to what he/she has already endured (61.8% vs. 87.1%, respectively).
Molecular epidemiology of rubella viruses involved in congenital rubella infections in São Paulo, Brazil, between 1996 and 2009
Authors: Curti Suely Pires , Figueiredo Cristina Adelaide , de Oliveira Maria Isabel , Andrade Joelma Queiroz , Zugaib Marcelo , Frugis Yu Ana Lucia , Oliveira Danielle Bruna , Durigon Edison Luiz
Published: July 2013

Rubella virus (RV) infection during the early stages of pregnancy can lead to serious birth defects, known as congenital rubella syndrome (CRS). This retrospective study was conducted between 1996 and 2009 with surveillance specimens collected from patients suspected of congenital rubella infection (CRI) and CRS. The clinical samples (nine amminiotic fluid, eight urine, eight blood, one conception product, and one placenta) were sent for viral isolation and genotyping. Twenty‐seven sequences were analysed and four genotypes (1a, 1B, 1G, and 2B) were identified in São Paulo that were involved in congenital infection. To our knowledge, this study is the first report that describes genetic diversity of the circulating rubella strains involved in CRI. J Med. Virol. 85:2034–2041, 2013. © 2013 Wiley Periodicals, Inc.
Decreased expression of microRNA‐625 is associated with tumor metastasis and poor prognosis in patients with colorectal cancer
Authors: Lou Xiaolou , Qi Xiaoliang , Zhang Yong , Long Houdong , Yang Jianjun
Published: July 2013

Background

MicroRNAs (miRNAs) play an essential role in colorectal cancer (CRC) development and progression. Aberrant miR‐625 expression has been reported in several cancers. However, the clinical significance of miR‐625 in human CRC has not been addressed.

Methods

miR‐625 expression was determined in 96 pairs of primary CRC and their corresponding adjacent nontumor tissues by quantitative reverse transcriptase‐polymerase chain reaction. Associations of miR‐625 expression with demographic and clinicopathologic features were determined. Additionally, the effects of ectopic expression of miR‐625 on cell migration and invasion were investigated in vitro and in vivo.

Results

miR‐625 was significantly downregulated in CRC tissues and cell lines. In addition, the decreased expression of miR‐625 was positively associated with advanced lymph node metastasis (P = 0.038), liver metastasis (P = 0.031), poor overall survival (P = 0.002), and an unfavorable prognosis for CRC patients, as determined through a multivariate analysis (P = 0.034). Moreover, functional assays demonstrated that ectopic miR‐625 expression inhibits the invasion and migration of HCT116 CRC cells both in vitro and in vivo.

Conclusions

Our results suggest that miR‐625 may serve as an efficient clinical biomarker and a therapeutic tool for the inhibition of metastasis in CRC. J. Surg. Oncol. 2013 108:230–235. © 2013 Wiley Periodicals, Inc.
Calcium‐Mediated Secondary Cross‐Linking of Bisphosphonated Oligo(poly(ethylene glycol) Fumarate) Hydrogels
Authors: Nejadnik M. Reza , Yang Xia , Mimura Tokio , Birgani Zeinab Tahmasebi , Habibovic Pamela , Itatani Kiyoshi , Jansen John A. , Hilborn Jons , Ossipov Dmitri , Mikos Antonios G. , Leeuwenburgh Sander C. G.
Published: July 2013

This study demonstrates, for the first time, that synthetic PEG‐based hydrogels can be cross‐linked reversibly by calcium upon functionalization of the polymer backbone with bisphosphonate groups (BPs) that allow for the formation of strong coordination bonds with divalent metal ions such as Mg2+ and Ca2+. More specifically, it is shown that BP‐functionalized hydrogels can be shaped by providing calcium ions as reversible physical cross‐linkers.
Classes of convolution type operators on unions of bounded intervals
Authors: Bastos M. A. , Lopes P. A.
Published: July 2013

An invertibility theory for classes of convolution type operators on a union of bounded intervals whose kernels have Fourier transforms which are related to solutions of corona problems is established and the corresponding formulas for the inverse operators are given. A generalization of the portuguese transformation for matrix functions is obtained and is used to establish the invertibility theory for one of the above mentioned classes of operators. The same transformation allows, also, to establish the equivalence between convolution type operators on an union of disjoint intervals and convolution type operators on a bounded interval.
Facile One‐Step Synthesis of Monodisperse Micron‐Sized Latex Particles with Highly Carboxylated Surfaces
Authors: Appel Jeroen , Akerboom Sabine , Fokkink Remco G. , Sprakel Joris
Published: July 2013

A facile method for the aqueous synthesis of monodisperse and micronmeter‐sized colloids with highly carboxylated surfaces is presented. The method is applied to three different monomers, styrene, methyl methacrylate, and 2,2,2‐trifluoroethyl methacrylate, and illustrate tuning of the size and monodispersity in the reactions. High surface density of carboxylic acids of up to 10 COOH nm−2 from potentiometric titrations, is achieved through copolymerization with itaconic acid. The versatility of this system is highlighted by creating highly fluorescent and monodisperse particles that can be index matched in aqueous solution and through surface modification via the carboxylic acid groups using standard amidation chemistry.

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Lidamycin inhibits tumor initiating cells of hepatocellular carcinoma Huh7 through GSK3β/β‐catenin pathway
Authors: Chen Yi , Yu Dongke , Zhang Caixia , Shang Boyang , He Hongwei , Chen Jinjing , Zhang Hao , Zhao Wuli , Wang Zhen , Xu Xiaoyu , Zhen Yongsu , Shao Rong‐guang
Published: July 2013

Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating cells of hepatocellular carcinoma Huh7 and identified the potential mechanism. Flow cytometry analysis and sorting assay, surface marker assay, sphere formation assay, and aldefluor assay were used to evaluate the effect of lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential mechanism, the activity of GSK3β/β‐catenin pathway was detected by Western blot and T cell factors transcriptional activity assay. Subcutaneous tumor model in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells. Lidamycin decreased the proportion of EpCAM+ cells and the expression of EpCAM protein. Lidamycin inhibited sphere formation of sorted EpCAM+ cells in 7 d, and of parental cells in three serial passages. The population of aldehyde dehydrogenase‐positive cells was reduced by lidamycin. In addition, lidamycin restrained tumor volume and incidence in vivo. Lidamycin activated GSK3β, and degraded the activity of β‐catenin. Consequently, transcriptional activity of β‐catenin/T cell factors was decreased. In brief, these results suggest that lidamycin suppressed Huh7 tumor initiating cells via GSK3β/β‐catenin pathway. These findings reveal the potential mechanism of lidamycin on tumor initiating cells and the benefit for further clinical evaluation. © 2013 Wiley Periodicals, Inc.
Sensorimotor adaptation of speech in Parkinson's disease
Authors: Mollaei Fatemeh , Shiller Douglas M. , Gracco Vincent L.
Published: July 2013

The basal ganglia are involved in establishing motor plans for a wide range of behaviors. Parkinson's disease (PD) is a manifestation of basal ganglia dysfunction associated with a deficit in sensorimotor integration and difficulty in acquiring new motor sequences, thereby affecting motor learning. Previous studies of sensorimotor integration and sensorimotor adaptation in PD have focused on limb movements using visual and force‐field alterations. Here, we report the results from a sensorimotor adaptation experiment investigating the ability of PD patients to make speech motor adjustments to a constant and predictable auditory feedback manipulation. Participants produced speech while their auditory feedback was altered and maintained in a manner consistent with a change in tongue position. The degree of adaptation was associated with the severity of motor symptoms. The patients with PD exhibited adaptation to the induced sensory error; however, the degree of adaptation was reduced compared with healthy, age‐matched control participants. The reduced capacity to adapt to a change in auditory feedback is consistent with reduced gain in the sensorimotor system for speech and with previous studies demonstrating limitations in the adaptation of limb movements after changes in visual feedback among patients with PD. © 2013 International Parkinson and Movement Disorder Society
Development of a Hetero‐Bimetallic Phillips‐Type Catalyst for Ethylene Polymerization
Authors: Zeng Yanning , Matta Akanksha , Dwivedi Sumant , Taniike Toshiaki , Terano Minoru
Published: July 2013

In order to improve the ethylene polymerization activity and branching ability of Phillips catalysts, various bimetallic catalysts were synthesized on the basis of co‐impregnation of chromium and second metal salts. The activity and branching ability of the catalysts were enhanced by the introduction of zirconium, zinc, and vanadium, while deteriorated by the introduction of molybdenum and tungsten. On the other hand, the structure of metal salt precursors did not greatly affect the catalytic performances. X‐ray photoelectron spectroscopy (XPS) clarified a tendency that second metal with lower electronegativity decreased the electron density on chromium species, resulting in higher polymerization activity of the bimetallic catalysts plausibly due to enhanced ethylene activation. On the other hand, the branching ability of the catalyst improved as the catalyst activity increased due to more facile formation of α‐olefin co‐monomer.
Validation of a population‐based method to assess drug‐induced alterations in the QT interval: a self‐controlled crossover study
Authors: Iribarren Carlos , Round Alfred D. , Peng Jonathan A. , Lu Meng , Zaroff Jonathan G. , Holve Taylor J. , Prasad Amit , Stang Paul
Published: July 2013

Purpose

The purpose of this study was to ascertain, in the context of an integrated health care delivery system, the association between a comprehensive list of drugs known to have potential QT liability and QT prolongation or shortening.

Methods

By using a self‐controlled crossover study with 59 467 subjects, we ascertained intra‐individual change in log‐linear regression‐corrected QT (QTcreg) during the period between 1995 and mid‐2008 for 90 drugs while adjusting for age, gender, race/ethnicity, comorbid conditions, number of electrocardiograms (ECGs), and time between pre‐ECG and post‐ECG. The proportion of users of each drug‐developing incident long QT was also estimated.

Results

Two drugs (nicardipine and levalbuterol) had no statistically significant intra‐individual QTcreg shortening effects, 10 drugs had no statistically significant prolonging effect, and 78 (87%) of the drugs had statistically significant intra‐individual mean QTcreg lengthening effects, ranging from 7.6 ms for aripiprazole to 25.2 ms for amiodarone. Three drugs were associated with mean QTcreg prolongation of 20 ms or greater: amiodarone (antiarrhythmic), terfenadine (antihistaminic), and quinidine (antiarrhythmic); whereas 11 drugs were associated with mean QTcreg prolongation of 15 ms or greater but less than 20 ms: trimipramine (tricyclic antidepressant), clomipramine (tricyclic antidepressant), disopyramide (antiarrhythmic), chlorpromazine (antipsychotic), sotalol (beta blocker), itraconazole (antifungal), phenylpropanolamine (decongestant/anorectic), fenfluramine (appetite suppressant), midodrine (antihypotensive), digoxin (cardiac glycoside/antiarrhythmic), and procainamide (antiarrhythmic).

Conclusions

QT prolonging effects were common and varied in strength. Our results lend support to past Food and Drug Administration regulatory actions and support the role for ongoing surveillance of drug‐induced QT prolongation. Copyright © 2013 John Wiley & Sons, Ltd.
Late diagnosis of double aortic arch: Consequences on long‐term follow‐up
Authors: Ullmann Nicola , Menchini Laura , Salerno Teresa , Tomà Paolo , Cutrera Renato
Published: July 2013

Double aortic arch is the most common congenital anomaly of the aortic arch system, in which the trachea and esophagus are completely encircled by vascular segments of the aortic arch and its branches, often resulting in variable airway compression. One case of late diagnosis of this congenital malformation and long‐term consequences of late surgical treatment with persistent tracheo‐broncomalacia and dynamic airway obstruction is reported. This report emphasizes the importance of an early diagnosis to minimise the progressive airways damage and subsequent respiratory symptoms, that need an accurate medical follow‐up. Pediatr Pulmonol. 2014; 49:E75–E77. © 2013 Wiley Periodicals, Inc.
Design, synthesis and bioactivity evaluation of novel benzophenone hydrazone derivatives
Authors: Li Wen‐Qun , Zhang Zhi‐Jun , Nan Xiang , Liu Ying‐Qian , Hu Guan‐Fang , Yu Hai‐Tao , Zhao Xiao‐Bo , Wu Dan , Yan Li‐Ting
Published: July 2013

BACKGROUND

Benzophenone hydrazone derivatives are among the most important classes of synthetic insecticides. In an effort to discover new molecules with good insecticidal/acaricidal activities, a series of novel benzophenone hydrazone N‐acylated thiourea and urea derivatives was synthesized and bioassayed.

RESULTS

All of these compounds exhibited excellent bioactivities against T. cinnabarinus and B. brassicae, especially towards T. cinnabarinus with LC50 values ranging from 0.305 to 2.036 mmol L‐1. Moreover, the acaricidal activities against T. cinnabarinus of compounds 8a–i, 12b–f and 12h were 2.5–5.5‐fold that of parent molecule 3 based on the LC50 value.

CONCLUSION

Based on the observed bioactivities, the structure–activity relationship of these analogs was also discussed. Structure–activity relationships provided information that could direct further investigation on structure modification. Our studies indicated that benzophenone hydrazone N‐acylated thiourea and urea derivatives could be used as potential lead compounds for developing novel acaricides and insecticides. © 2013 Society of Chemical Industry
Acaricidal activities of β‐caryophyllene oxide and structural analogues derived from Psidium cattleianum oil against house dust mites
Authors: Oh Min‐Seok , Yang Ji‐Yeon , Kim Min‐Gi , Lee Hoi‐Seon
Published: July 2013

BACKGROUND

This study was to evaluate the acaricidal activities of an active compound isolated from Psidium cattleianum and structural analogues against Dermatophagoides farinae and D. pteronyssinus. β‐Caryophyllene oxide was isolated using chromatographic techniques.

RESULTS

Based on the 50% lethal concentration (LD50) values against D. farinae using the fumigant method, β‐caryophyllene oxide (1.36 µg cm−2) was ∼ 7.52 times more toxic than benzyl benzoate (10.23 µg cm−2), followed by α‐caryophyllene (1.75 µg cm−2) and β‐caryophyllene (3.13 µg cm−2). Against D. pteronyssinus, β‐caryophyllene oxide (1.38 µg cm−2) was ∼ 7.22 times more toxic than benzyl benzoate (9.96 µg cm−2), followed by α‐caryophyllene (1.71 µg cm−2) and β‐caryophyllene (3.58 µg cm−2). In the contact toxicity method against D. farinae, β‐caryophyllene oxide (0.44 µg cm−2) was ∼ 17.27 times more active than benzyl benzoate (7.60 µg cm−2), followed by α‐caryophyllene (0.67 µg cm−2) and β‐caryophyllene (0.91 µg cm−2). Against D. pteronyssinus, β‐caryophyllene oxide (0.47 µg cm−2) was ∼ 13.06 times more effective than benzyl benzoate (6.14 µg cm−2), followed by α‐caryophyllene (1.71 µg cm−2) and β‐caryophyllene (3.58 µg cm−2).

CONCLUSION

β‐Caryophyllene oxide and structural analogues have potential for development as preventive agents for the control of house dust mites. © 2013 Society of Chemical Industry
Curcumin I Mediates Neuroprotective Effect Through Attenuation of Quinoprotein Formation, p‐p38 MAPK Expression, and Caspase‐3 Activation in 6‐Hydroxydopamine Treated SH‐SY5Y Cells
Authors: Meesarapee Benjawan , Thampithak Anusorn , Jaisin Yamaratee , Sanvarinda Pimtip , Suksamrarn Apichart , Tuchinda Patoomratana , Morales Noppawan Phumala , Sanvarinda Yupin
Published: July 2013

6‐Hydroxydopamine (6‐OHDA) selectively enters dopaminergic neurons and undergoes auto‐oxidation resulting in the generation of reactive oxygen species and dopamine quinones, subsequently leading to apoptosis. This mechanism mimics the pathogenesis of Parkinson's disease and has been used to induce experimental Parkinsonism in both in vitro and in vivo systems. In this study, we investigated the effects of curcumin I (diferuloylmethane) purified from Curcuma longa on quinoprotein production, phosphorylation of p38 MAPK (p‐p38), and caspase‐3 activation in 6‐OHDA‐treated SH‐SY5Y dopaminergic cells. Pretreatment of SH‐SY5Y with curcumin I at concentrations of 1, 5, 10, and 20 μM, significantly decreased the formation of quinoprotein and reduced the levels of p‐p38 and cleaved caspase‐3 in a dose‐dependent manner. Moreover, the levels of the dopaminergic neuron marker, phospho‐tyrosine hydroxylase (p‐TH), were also dose‐dependently increased upon treatment with curcumin I. Our results clearly demonstrated that curcumin I protects neurons against oxidative damage, as shown by attenuation of p‐p38 expression, caspase‐3‐activation, and toxic quinoprotein formation, together with the restoration of p‐TH levels. This study provides evidence for the therapeutic potential of curcumin I in the chemoprevention of oxidative stress‐related neurodegeneration. Copyright © 2013 John Wiley & Sons, Ltd.
Measurement of multiply substituted isotopologues ('clumped isotopes') of CO2 using a 5 kV compact isotope ratio mass spectrometer: Performance, reference frame, and carbonate paleothermometry
Authors: Rosenheim Brad E. , Tang Jianwu , Fernandez Alvaro
Published: July 2013

RATIONALE

The burgeoning field of 'clumped isotope' paleothermometry, which has broad applications in geosciences, depends almost entirely on measurements made on two types of mass spectrometer with the same ion source design. Demonstration that these measurements can be carried out on a retrofitted mass spectrometer with a different type of ion source is important to the growing community of geoscientists considering employing this technique.

METHODS

We summarize the sample preparation techniques, mass spectrometry, and data processing involved in establishing an absolute reference frame for the measurement of Δ47 in CO2 from carbonate minerals using a prototype 5 kV mass spectrometer. The prototype differs from previously marketed mass spectrometers only in the presence of six extra Faraday cups designed specifically to measure ion beams of masses 44–49. We employ pressure baseline corrections on the small mass 47 signal.

RESULTS

The system was fully capable of establishing absolute reference frames for clumped isotope carbonate paleothermometry, despite alternative use of the system for other types of measurements (carbonate δ18O and δ13C values, water δ18O and δ2H values via equilibration, and δ13C and δ15N values of sedimentary organic material) in different reference frames. Repeated measurements of CO2 from carbonate standards yielded external precisions comparable with those from other laboratories and adequate for paleothermometry to a precision of near or below ±5 °C. The accuracy was demonstrated by reasonable temperatures being obtained for different types of repeatedly measured carbonates. Measurements of the pressure baseline with every sample increased analysis times by 20 min, but decreased the stabilization time of the reference frame by days to weeks, while improving precision.

CONCLUSIONS

Simple modifications to existing instrumentation will allow more laboratories to perform clumped isotope measurements. The prototype mass spectrometer used herein provides precision comparable with all published data. We show that, where negatively charged species are associated with large ion beams, making pressure baseline corrections with every measurement is increasingly important no matter what instrument is used. Copyright © 2013 John Wiley & Sons, Ltd.
Formation of odd‐electron product ions in collision‐induced fragmentation of electrospray‐generated protonated cathinone derivatives: aryl α‐primary amino ketones
Authors: Fornal Emilia
Published: July 2013

RATIONALE

Modification of the even‐electron rule for fragmentation reactions of protonated molecules (even electron ions) may be necessary to interpret the liquid chromatography/mass spectrometry (LC/MS) spectra of aryl α‐primary amino ketones as new designer drugs.

METHODS

Collision‐induced fragmentation of 38 protonated cathinone derivatives generated by electrospray ionisation (ESI) was examined by hybrid quadrupole time‐of‐flight mass spectrometry (Q‐TOF MS).

RESULTS

Q‐TOF MS revealed that odd‐electron product ions are often formed by collision‐induced dissociation (CID) of protonated aryl α‐primary amino ketones, contradicting the even‐electron rule. Radical cations were among the most characteristic and most abundant ions in the CID‐MS/MS product spectra, and were usually represented by basic peaks in the spectra.

CONCLUSIONS

To help elucidate the correct structures of new aryl α‐primary amino ketone drugs by LC/MS/MS, it is essential to include odd‐electron product ions in the data interpretation rules. Even and odd numbers of valence electrons in the product ions should be allowed in data interpretation. Copyright © 2013 John Wiley & Sons, Ltd.
Addressing the need for biomarker liquid chromatography/mass spectrometry assays: A protocol for effective method development for the bioanalysis of endogenous compounds in cerebrospinal fluid
Authors: Benitex Yulia , McNaney Colleen A. , Luchetti David , Schaeffer Eric , Olah Timothy V. , Morgan Daniel G. , Drexler Dieter M.
Published: July 2013

RATIONALE

Research on disorders of the central nervous system (CNS) has shown that an imbalance in the levels of specific endogenous neurotransmitters may underlie certain CNS diseases. These alterations in neurotransmitter levels may provide insight into pathophysiology, but can also serve as disease and pharmacodynamic biomarkers. To measure these potential biomarkers in vivo, the relevant sample matrix is cerebrospinal fluid (CSF), which is in equilibrium with the brain's interstitial fluid and circulates through the ventricular system of the brain and spinal cord. Accurate analysis of these potential biomarkers can be challenging due to low CSF sample volume, low analyte levels, and potential interferences from other endogenous compounds.

METHODS

A protocol has been established for effective method development of bioanalytical assays for endogenous compounds in CSF. Database searches and standard‐addition experiments are employed to qualify sample preparation and specificity of the detection thus evaluating accuracy and precision.

RESULTS

This protocol was applied to the study of the histaminergic neurotransmitter system and the analysis of histamine and its metabolite 1‐methylhistamine in rat CSF.

CONCLUSIONS

The protocol resulted in a specific and sensitive novel method utilizing pre‐column derivatization ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS), which is also capable of separating an endogenous interfering compound, identified as taurine, from the analytes of interest. Copyright © 2013 John Wiley & Sons, Ltd.
Non‐parametric linear time‐invariant extensions of non‐invertible and backlash plant
Authors: Shenton Andrew Thomas , Abass Ahmed
Published: July 2013

A rigorous validation for the use of a set of linear time‐invariant models as a surrogate in the design of controllers for uncertain nonlinear systems, which are invertible as one‐to‐one operators, such as used in the nonlinear quantitative feedback theory (NLQFT) design methodology has been given by Baños and Bailey. This paper presents a similar validation but weakens the requirement on the invertibility of the nonlinear plant by application of Kakutani's fixed‐point theorem and an incremental gain constraint on the plant within its operational envelope. The set of linear time‐invariant models to be used for design is shown to be an extension (termed here the linear time‐invariant extension—LTIE) of the nonlinear plant restricted to the desired output operating space. A new non‐parametric approach to the modelling of the LTIE is proposed which is based on Fourier transforms of the plant I/O data and which accordingly may be based solely on experimental testing without the need for an explicit parametric plant model. This new approach thus extends the application of robust linear controller design methods (including those of NLQFT) to nonlinear plants with set‐valued (multi‐valued) inverses such as those containing backlash and also to plants for which explicit parametric models are difficult to obtain. The method is illustrated by application of the non‐parametric approach to an NLQFT tracking controller design for a mechanical backlashed servomechanism problem. Copyright © 2013 John Wiley & Sons, Ltd.
LMI stability conditions for uncertain rational nonlinear systems
Authors: Trofino A. , Dezuo T.J.M.
Published: July 2013

This paper presents LMI conditions for local, regional, and global robust asymptotic stability of rational uncertain nonlinear systems. The uncertainties are modeled as real time varying parameters with magnitude and rate of variation bounded by given polytopes and the system vector field is a rational function of the states and uncertain parameters. Sufficient LMI conditions for asymptotic stability of the origin are given through a rational Lyapunov function of the states and uncertain parameters. The case where the time derivative of the Lyapunov function is negative semidefinite is also considered and connections with the well known LaSalle's invariance conditions are established. In regional stability problems, an algorithm to maximize the estimate of the region of attraction is proposed. The algorithm consists of maximizing the estimate for a given target region of initial states. The size and shape of the target region are recursively modified in the directions where the estimate can be enlarged. The target region can be taken as a polytope (convex set) or union of polytopes (non‐convex set). The estimates of the region of attraction are robust with respect to the uncertain parameters and their rate of change. The case of global and orthant stability problems are also considered. Connections with some results found in sum of squares based methods and other related methods found in the literature are established. The LMIs in this paper are obtained by using the Finsler's Lemma and the notion of annihilators. The LMIs are characterized by affine functions of the state and uncertain parameters, and they are tested at the vertices of a polytopic region. It is also shown that, with some additional conservatism, the use of the vertices can be avoided by modifying the LMIs with the S‐Procedure. Several numerical examples found in the literature are used to compare the results and illustrate the advantages of the proposed method. Copyright © 2013 John Wiley & Sons, Ltd.
A conceptual and methodological framework for investigating etiologic heterogeneity
Authors: Begg Colin B. , Zabor Emily C. , Bernstein Jonine L. , Bernstein Leslie , Press Michael F. , Seshan Venkatraman E.
Published: July 2013

Cancer has traditionally been studied using the disease site of origin as the organizing framework. However, recent advances in molecular genetics have begun to challenge this taxonomy, as detailed molecular profiling of tumors has led to discoveries of subsets of tumors that have profiles that possess distinct clinical and biological characteristics. This is increasingly leading to research that seeks to investigate whether these subtypes of tumors have distinct etiologies. However, research in this field has been opportunistic and anecdotal, typically involving the comparison of distributions of individual risk factors between tumors classified on the basis of candidate tumor characteristics. The purpose of this article is to place this area of investigation within a more general conceptual and analytic framework, with a view to providing more efficient and practical strategies for designing and analyzing epidemiologic studies to investigate etiologic heterogeneity. We propose a formal definition of etiologic heterogeneity and show how classifications of tumor subtypes with larger etiologic heterogeneities inevitably possess greater disease risk predictability overall. We outline analytic strategies for estimating the degree of etiologic heterogeneity among a set of subtypes and for choosing subtypes that optimize the heterogeneity, and we discuss technical challenges that require further methodologic research. We illustrate the ideas by using a pooled case‐control study of breast cancer classified by expression patterns of genes known to define distinct tumor subtypes. Copyright © 2013 John Wiley & Sons, Ltd.
Numerical Simulation of Liquid Iron Flow and Heat Transfer in the Hearth of COREX Melter Gasifier during Tapping Process
Authors: Du Kaiping , Wu Shengli , Kou Mingyin , Shen Wei , Zhang Zhekai
Published: July 2013

The service life of COREX melter gasifier mainly depends on the hearth refractory erosion which is strongly affected by the liquid iron flow and the heat transfer. In the present work, a three‐dimensional mathematical model at steady state which takes fluid buoyancy force and turbulence model into consideration is introduced to describe the flow and temperature distribution in the hearth in detail. The accuracy of the model is evaluated using plant operational data. The results show that the position of serious mechanical erosion gradually shifts from the hearth pool bottom to the sidewall, as the coke bed position changes from “floating” on the liquid iron to “sitting” on the hearth pool bottom during one tapping cycle under the condition of stable tapping. The second peak of liquid iron flow, which is a noticeable feature of COREX melter gasifier in comparison with blast furnace, could result in more serious mechanical erosion of sidewall and severer thermal erosion of refractory on hearth pool bottom. The effective countermeasures of the second peak of liquid iron flow are proposed in this work. In addition, the effects of porosity of fine coke region and refractory erosion are further discussed. The results can be used to predict the inner profile of hearth and to provide guidance for protecting the hearth refractory.
Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer
Authors: Shaykhiev Renat , Wang Rui , Zwick Rachel K. , Hackett Neil R. , Leung Roland , Moore Malcolm A. S. , Sima Camelia S. , Chao Ion Wa , Downey Robert J. , Strulovici-Barel Yael , Salit Jacqueline , Crystal Ronald G.
Published: July 2013

Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans.
Force‐based disturbance observer for dynamic force control and a position/force hybrid controller
Authors: Sakaino Sho , Sato Tomoya , Ohnishi Kouhei
Published: July 2013

In this paper, a force‐based disturbance observer (DOB) and a force control system using the DOB are proposed to obtain dynamic force control under disturbances. A DOB can reduce the effect of disturbances and modeling errors on robots. In a conventional DOB, an acceleration response is fed back to a reference, enabling highly precise position control. In other words, the effect of disturbances is decreased by emphasizing the effect of inertial forces. When a force controller is implemented, however, inertial forces are regarded as disturbances respect to a force response. Because inertial forces increase according to the acceleration, conventional DOBs are not suitable for dynamic force control. In the proposed DOB, a force response is fed back instead of an acceleration response. The effect of inertial forces is thus eliminated, thereby improving the tracking performance of force controllers. The proposed method's validity is verified analytically and experimentally. A position/force hybrid controller and a DOB for the controller are proposed as an extension of the proposed DOB. A bilateral controller is given as an example of the proposed hybrid controller, and its tracking performance is demonstrated experimentally. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.