bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing lifetime and photoluminescence imaging pattern recognition methodologies for predicting solar cell results based on as‐cut wafer properties
Authors: Sinton Ronald A. , Haunschild Jonas , Demant Matthias , Rein Stefan
Published: July 2012

Wafer quality is extremely important in determining yield and efficiency of solar cells. Ideally, this wafer quality should be determined for incoming wafers before solar cell fabrication based on the electronic quality of the wafers. Recent papers have discussed methodologies for doing this by using lifetime measurement and pattern recognition of photoluminescence (PL) images. This paper compares results from quasi‐steady‐state photoconductance (QSSPC) lifetime measurements with PL imaging pattern recognition of dislocations. By using a more complete analysis of the lifetime and the PL data than performed in some recent publications, a more detailed physical picture is presented here, which reconciles contradictions between previous results. In particular, the differences between PL and QSSPC lifetime measurements on as‐cut wafers are discussed. The trends in voltage prediction based on measured lifetime, doping, and PL‐determined dislocation densities are shown. Copyright © 2012 John Wiley & Sons, Ltd.
Novel antimicrobial polyethylene composites prepared by metallocenic in situ polymerization with TiO2‐based nanoparticles
Authors: Zapata Paula A. , Palza Humberto , Delgado Katherine , Rabagliati Franco M.
Published: July 2012

Polyethylene (PE) composites with titanium oxide (TiO2) nanoparticles were produced via in situ polymerization representing a novel route to obtain antimicrobial polymeric materials. The TiO2 nanoparticles synthesized by the sol–gel method were used either as‐synthesized or modified organically with hexadecyltrimethoxysilane (Mod‐TiO2). These particles were added, together with the catalytic system (formed by a metallocenic catalyst and methylaluminoxane as cocatalyst), directly to the reactor, yielding in situ PE composites with 2 and 8 wt % content of nanofiller. The catalytic polymerization activity presented a slight decrease with the incorporation of the TiO2 and Mod‐TiO2 nanoparticles compared to polymerization without filler. Regarding the properties of the composites, crystallinity increased slightly when the different nanofillers were added, and the elastic modulus increased around 15% compared to neat PE. PE/TiO2 nanocomposites containing 8 wt % of TiO2 exposed to UVA irradiations presented antimicrobial activity against Escherichia coli. The PE/Mod‐TiO2 nanocomposite with 8 wt % filler killed 99.99% of E. coli, regardless of light and time irradiation. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Revisit to the photocrosslinking behavior of PVA‐SbQ as a water‐soluble photopolymer with anomalously low contents of quaterized stilbazol side chains
Authors: Ichimura Kunihiro , Iwata Shuji , Mochizuki Shin'ya , Ohmi Mamoru , Adachi Daisaku
Published: July 2012

The photocrosslinking behavior of poly(vinyl alcohol) (PVA) substituted with 0.1, 0.3, 1.3, and 4.0 mol % of styrylpyridinium (SbQ) (PVA‐SbQs) side chains was reinvestigated. Even‐order derivative spectra of films of PVAs loaded with 0.1 and 0.3 mol % of SbQ revealed the presence of subpeaks owing to vibrational transitions, whereas PVA bearing 1.3 and 4.0 mol % of SbQ displayed a new blue‐shifted band (H‐band) at 328 nm due to H‐aggregation. Changes in derivative spectra disclosed the rapid disappearance of the H‐band of PVA‐SbQs under UV irradiation within exposure doses of 10 mJ cm−2. On the other hand, the films of the PVA‐SbQs were insolubilized upon UV irradiation at exposure doses of 2 and 3 mJ cm−2, respectively, leading to the conclusion that the high photosensitivity comes from the photodimerization of H‐aggregate as a ground‐state dimer. Fluorescence measurements implied the presence of J‐aggregate at 386 nm, but the involvement of the J‐aggregation in photocrosslinking was excluded because of its negligible fraction. A photosensitive emulsion of poly(vinyl acetate) emulsified with PVA‐SbQ exhibited similar changes in higher‐order derivative spectra in film and applied to fabricate a stencil for screen printing with aid of an LED‐emitting 375 nm light. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Synthesis and characterization of graphene‐containing thermoresponsive nanocomposite hydrogels of poly(N‐vinylcaprolactam) prepared by frontal polymerization
Authors: Sanna Roberta , Sanna Davide , Alzari Valeria , Nuvoli Daniele , Scognamillo Sergio , Piccinini Massimo , Lazzari Massimo , Gioffredi Emilia , Malucelli Giulio , Mariani Alberto
Published: July 2012

Thermoresponsive poly(N‐vinylcaprolactam) nanocomposite hydrogels containing graphene were successfully prepared by frontal polymerization. High concentration of graphene (5.0 mg/mL) was obtained by direct graphite sonication in the self‐same liquid monomer, thus avoiding any chemical manipulation and obtaining “real” graphene as nanofiller instead of one of its more or less oxidized derivative, which is what generally reported in published reports. Furthermore, the corresponding nanocomposites were obtained without using any solvent to be eventually removed. The materials were fully characterized by RAMAN, SEM, and TEM, and their swelling behavior and rheological properties were investigated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Preparation, Characterization and Optimization of Egg Albumin Nanoparticles as Low Molecular‐Weight Drug Delivery Vehicle
Authors: Taheri Elham Sadat , Jahanshahi Mohsen , Mosavian Mohammad Taghi Hamed
Published: July 2012

Protein nanoparticles have been recognized as carriers to deliver low molecular‐weight drugs, anticancer drug, DNA, vaccines, oligonucleotides, peptides and etc. The purpose of this research was preparation of Egg Albumin (EA) nanoparticle with suitable size/size distribution and good surface properties for drug delivery application based on simple coacervation method along with optimization of the nanoparticles by employing Taguchi method. Several synthesis parameters were examined to characterize their impacts on nanoparticle size and topography. These variables were including temperature, EA concentration, desolvating agent volume, pH value and agitation speed. In addition, size and morphology of prepared nanoparticles were analyzed by photon correlation spectroscopy (PCS) as well as atomic force microscopy (AFM). As result of Taguchi analysis in this research, desolvating agent volume and pH were most influencing factors on particle size. The minimum size of nanoparticles (∼51 nm) were obtained at Temperature 55 °C, 30 mg/ml EA concentration, desolvating agent volume 50 ml, agitation speed of 500 rpm and pH 4. The mechanistic of optimum conditions for preparing protein nanoparticles from Egg Albumin for the first time and their characterization as delivering nano system are discussed.
Preparation and Characterization of Activated Carbon – nFe3O4, Activated Carbon – nSiO2 and Activated Carbon – nZnO Hybrid Materials
Authors: Fatoki Olalekan S. , Ayanda Olushola S. , Adekola Folahan A. , Ximba Bhekumusa J. , Opeolu Beatrice O.
Published: July 2012

The preparation and physicochemical characterization of activated carbon, nano metal oxides, and activated carbon – nFe3O4, activated carbon – nSiO2 and activated carbon – nZnO hybrid materials has been undertaken. The materials have been characterized by scanning and transmission electron microscopy, x‐ray diffraction, CNH analysis and Fourier transform infrared spectroscopy. Surface area and porosity, ash content, pH, and point of zero charge were also measured. The results showed that the surfaces of activated carbon, nSiO2, activated carbon – nFe3O4, activated carbon – nSiO2 and activated carbon – nZnO are suitable for the sorption of cationic complexes while the surfaces of nFe3O4 and nZnO are favourable to the sorption of anionic complexes of heavy metals. Results also showed that the composition of the activated carbon and nano metal oxides increased the surface and micropore areas of nano metal oxides due to the large number of micropores and crevices on the surface of the hybrid materials.
Electrophysiological and behavioural responses of Pityophthorus pubescens (Coleoptera: Scolytinae) to (E,E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(−)‐verbenone in Pinus radiata (Pinaceae) stands in northern Spain
Authors: López Sergio , Quero Carmen , Iturrondobeitia Juan Carlos , Guerrero Ángel , Goldarazena Arturo
Published: July 2012

BACKGROUND: Some twig beetles in the genus Pityophthorus (Coleoptera: Scolytinae) may vector pitch canker disease Fusarium circinatum (Niremberg & O'Donnell) of Pinus spp. (Pinaceae). Because Pityophthorus pubescens (Marsh.) has been found to be associated with F. circinatum in the Basque Country (northern Spain), various experiments were conducted to assess the beetle's behavioural responses to (E, E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(−)‐verbenone to develop a potential inhibitor to host attraction. These experiments comprise electroantennographic and double‐choice olfactometer tests, as well as field assays in Pinus radiata D. Don stands.

RESULTS: Both sexes of P. pubescens showed similar electroantennographic responses to different doses (from 1 ng to 1 µg in decadic steps) of each individual compound, with depolarisations to (S)‐(‐)‐verbenone (100 ng) being similar to those of the aggregation pheromone (+)‐trans‐pityol. In olfactometer assays, both sexes were significantly attracted to (+)‐trans‐pityol, but the attraction was reduced when increasing amounts of the chemicals were added to the pheromone. Particularly relevant was the repellent effect induced by (S)‐(−)‐verbenone at 1 ng dose and higher. In the field, (E, E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(−)‐verbenone reduced significantly the number of beetles attracted to (+)‐trans‐pityol and racemic trans‐pityol, with (S)‐(−)‐verbenone being the most effective.

CONCLUSIONS: (S)‐(−)‐Verbenone showed an interesting potential for use in the protection of P. radiata stands. A potentially effective strategy, which could be implemented in further, more in‐depth studies, could involve the use of this semiochemical as repellent and (+)‐trans‐pityol‐baited traps as attractant in a ‘push‐pull’ strategy. Copyright © 2012 Society of Chemical Industry
Calcium Channel Blocking Activity in Desmostachya bipinnata (L.) Explains its use in Gut and Airways Disorders
Authors: Abdur Rahman Hafiz Muhammad , Bashir Samra , Gilani Anwarul Hassan
Published: July 2012

Desmostachya bipinnata, despite of its popular medicinal uses, has not been widely studied for its effect in diarrhea, indigestion, and asthma. The aim of the present investigation was to provide scientific rationale for these applications. The crude aqueous‐methanolic extract of D. bipinnata (Db.Cr) was evaluated through in vivo and in vitro experiments. Db.Cr (100–500 mg/kg) protected mice against castor oil–induced diarrhea, similar to loperamide. When tested on gut preparations, Db.Cr produced an atropine‐sensitive spasmogenic effect in rabbit jejunum up to 5 mg/mL, followed by a partial relaxation at 10 mg/mL. With atropine preincubation, a verapamil‐like inhibitory effect was evident against spontaneous and high K+ (80 mM)–induced contractions. The maximum stimulant effect was comparable with the acetylcholine‐induced maximum contraction and was similarly reproducible in guinea pig ileum. Db.Cr inhibited carbachol (1 μM)‐induced contraction in rabbit trachea but caused an atropine‐sensitive accentuation of high K+–induced contraction at 0.003–0.3 mg/mL followed by inhibition at 1–5 mg/mL. On activity‐directed fractionation, inhibitory effect was concentrated on organic and stimulant effect in aqueous fraction. This study, suggesting the presence of calcium antagonist activity, possibly underlying its medicinal effect in hyperactive gut and respiratory disorders, and cholinergic activity, possibly underlying its digestive effect, provides rationale for these therapeutic uses of D. bipinnata. Copyright © 2012 John Wiley & Sons, Ltd.
Effectiveness and Safety of a Mouthwash Containing Essential Oil Ingredients
Authors: Vlachojannis Christian , Winsauer Heinz , Chrubasik Sigrun
Published: July 2012

The mouthwash, Listerine®, was compounded in 1879 from four essential oils. Later, the oils were replaced by one ingredient per oil with approximately 25% ethanol as a vehicle to keep them in solution. From then on, Listerine® was no longer a medicinal plant product. In 2003, a review by the FDA Subcommittee on Oral Health Care Drug Products for Over‐the‐Counter Human Use concluded that the product is effective and safe, and a review of studies published in the meantime showed that Listerine® fulfils the consensus criteria for an effective antigingivitis/antiplaque product. However, concerns have been raised about the long‐term safety of some of the ingredients, particularly the ethanol content, and in the light of these concerns, the evidence has been re‐examined for both the efficacy and safety of Listerine®. In summary, the studies support the claim that Listerine® shows benefit for oral health, but the concerns over its safety remain to be clarified. Until these have been addressed, high risk populations (children, alcohol addicts, patients with genetic deficiencies in ethanol metabolism) should use alcohol‐free mouthwashes for the maintenance of oral health. Copyright © 2012 John Wiley & Sons, Ltd.
Auraptene and its Effects on the Re‐emergence of Colon Cancer Stem Cells
Authors: Epifano Francesco , Genovese Salvatore , Miller Rebecca , Majumdar Adhip P. N.
Published: July 2012

Recent studies indicate that auraptene (7‐geranyloxycoumarin, AUR), a geranyloxycoumarin extracted from fruits of edible plants belonging to the Rutaceae family, may represent a novel lead compound for dietary colon cancer chemoprevention in rodents. As a continuation of studies aimed to better depict the pharmacological effects and mechanism of action of the title natural compound, the current investigation was undertaken to determine whether AUR would be able to prevent the growth and sphere (surrogate tumors) formation of FOLFOX‐resistant colon cancer cells that are highly enriched in cancer stem cells (CSCs). Our results demonstrate that AUR at a concentration of 10 μM was able to inhibit the growth and formation of colonospheres of FOLFOX‐resistant colon cancer HT‐29 cells in vitro. The corresponding parental cells were also similarly affected by AUR at the same concentration level. The reduction in the growth and colonospheres formation in FOLFOX‐resistant HT‐29 was also associated with a concomitant decrease in phospho‐epidermal growth factor receptor. These findings suggest that AUR could prevent the re‐emergence of CSCs. Copyright © 2012 John Wiley & Sons, Ltd.
Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) Extracts Inhibit the Growth of the Breast Cancer Cell Lines MDA‐MB‐231 and MCF‐7, But Not the Brain Tumour Cell Line U251 In Vitro
Authors: Özkan Muge , Mutiso Patrick B. C. , Nahar Lutfun , Liu Peng , Brown Sarah , Wang Weiguang , Sarker Satyajit D.
Published: July 2012

Zanthoxylum usambarense (Engl.) Kokwaro has traditionally been used for the treatment of malaria, upper respiratory tract infections, cough, rheumatism, tooth decay and sore gums in Kenya and other African countries. Dried ground parts of Z. usambarense were extracted by maceration using methanol (MeOH) at room temperature, extract was dried and reconstituted in 70% aq. MeOH and partitioned against n‐hexane and chloroform (CHCl3) to obtain MeOH, n‐hexane and CHCl3 extracts. All extracts were assessed for cytotoxicity against two breast cancer cell lines, MDA‐MB‐231 and MCF‐7, and the brain tumour cell line U251 by the MTT assay. The free‐radical scavenging activity of the extracts was also determined by the 2,2‐diphenyl‐1‐picryhydrazyl (DPPH) assay. In the DPPH assay, the MeOH extract was found to be the most active free‐radical scavenger with a RC50 value of 41.1 × 10−3 mg/mL. It also displayed significant cytotoxicity against the MCF‐7 cell line (IC50 42.9 µg/mL) and appeared to have induced cell death through apoptosis. None of the test extracts showed any activity against the U251 cell line at test concentrations. The present findings demonstrated that Z. usambarense could be a potential source for new cytotoxic compounds for possible anticancer drug development. Copyright © 2012 John Wiley & Sons, Ltd.
Interaction mechanisms between poly(amido‐amine) and nano‐silicon dioxide
Authors: Jin Tao , Li Xiaoyu , Sun Haiqing
Published: July 2012

To gain insight into the attachment of Si+ (SC) and SiO− (SOA) ions (regarded as guests) to the lowest generation, NH2‐terminated poly(amidoamine) (PAMAM) dendrimers (regarded as host) in the gas phase, density functional theory is used to investigate the structures and energetics of the complexes with B3LYP/6‐31+G (d) and HF/6‐31G basis sets. The initial parameters are obtained through the initial optimizations at the HF level using the most basic STO‐3G basis set. Various initial configurations of the ions bound to PAMAM are tested, and four stable conformers are found, i.e., types A to D. Types 1A and 2C are the most stable due to the chemical bond formations of SiN° and SiO, respectively. For type B, SC coordination to amide O sites occurs via electrostatic induction. For type D, SOA coordination to amide hydrogen and amine hydrogen sites occurs via hydrogen bond interaction. Spatial hindrance, electrostatic induction force, and hydrogen‐bond interaction play important roles in the complexation process. © 2013 Wiley Periodicals, Inc.

This article was published online on 5 July 2012. An error was subsequently identified. This notice is included in the online and print version to indicate that both have been corrected on 3 August 2012.
A new dynamic identity‐based authentication protocol for multi‐server environment using elliptic curve cryptography
Authors: Khan Muhammad Khurram , He Debiao
Published: July 2012

With the popularity of Internet and wireless networks, more and more network architectures are used in multi‐server environment, in which users remotely access servers through open networks. For the reliability of accessing these remote services, user must pass a verification procedure to obtain the authorization for legal resource acquisition and data exchange. Recently, several dynamic identity‐based authentication protocols for multi‐server environment have been proposed, but all of these protocols have been cryptanalyzed by other scholars. In this paper, we propose a new dynamic identity‐based authentication protocol for multi‐server environment using elliptic curve cryptography. The analysis shows that our protocol could overcome security weaknesses in the previously published protocols. Hence, our protocol is more suitable for practical applications. Copyright © 2012 John Wiley & Sons, Ltd.
Unified threat model for analyzing and evaluating software threats
Authors: Li XiaoHong , He Ke , Feng Zhiyong , Xu Guangquan
Published: July 2012

Design‐level vulnerabilities are a major source of security problems in software programs. For the purpose of improving the trustworthiness of software designs, this paper presents a unified threat model for representing, analyzing, and evaluating software threats at various design stages. Unified threat models represent software threats via tree structures with AND/OR logical relationships and evaluates software threats in a cost‐effective way based on attack paths. Mitigation measures for software threats are designed and prioritized based on the evaluation results, which make it possible to design high‐quality software security programs that resist identified software threats. A case study for an online banking system is given to systematically demonstrate the application of unified threat models in software threat analysis and evaluation. The results from the case study demonstrate that the unified threat model is superior to traditional threat trees in accurately evaluating results, designing mitigation measures, and guiding software security testing. Copyright © 2012 John Wiley & Sons, Ltd.
A simple Bayesian decision‐theoretic design for dose‐finding trials
Authors: Fan Shenghua Kelly , Lu Ying , Wang You‐Gan
Published: July 2012

A flexible and simple Bayesian decision‐theoretic design for dose‐finding trials is proposed in this paper. In order to reduce the computational burden, we adopt a working model with conjugate priors, which is flexible to fit all monotonic dose‐toxicity curves and produces analytic posterior distributions. We also discuss how to use a proper utility function to reflect the interest of the trial. Patients are allocated based on not only the utility function but also the chosen dose selection rule. The most popular dose selection rule is the one‐step‐look‐ahead (OSLA), which selects the best‐so‐far dose. A more complicated rule, such as the two‐step‐look‐ahead, is theoretically more efficient than the OSLA only when the required distributional assumptions are met, which is, however, often not the case in practice. We carried out extensive simulation studies to evaluate these two dose selection rules and found that OSLA was often more efficient than two‐step‐look‐ahead under the proposed Bayesian structure. Moreover, our simulation results show that the proposed Bayesian method's performance is superior to several popular Bayesian methods and that the negative impact of prior misspecification can be managed in the design stage. Copyright © 2012 John Wiley & Sons, Ltd.
Estimation of treatment effect under non‐proportional hazards and conditionally independent censoring
Authors: Boyd Adam P. , Kittelson John M. , Gillen Daniel L.
Published: July 2012

In clinical trials with time‐to‐event outcomes, it is common to estimate the marginal hazard ratio from the proportional hazards model, even when the proportional hazards assumption is not valid. This is unavoidable from the perspective that the estimator must be specified a priori if probability statements about treatment effect estimates are desired. Marginal hazard ratio estimates under non‐proportional hazards are still useful, as they can be considered to be average treatment effect estimates over the support of the data. However, as many have shown, under non‐proportional hazard, the ‘usual’ unweighted marginal hazard ratio estimate is a function of the censoring distribution, which is not normally considered to be scientifically relevant when describing the treatment effect. In addition, in many practical settings, the censoring distribution is only conditionally independent (e.g., differing across treatment arms), which further complicates the interpretation. In this paper, we investigate an estimator of the hazard ratio that removes the influence of censoring and propose a consistent robust variance estimator. We compare the coverage probability of the estimator to both the usual Cox model estimator and an estimator proposed by Xu and O'Quigley (2000) when censoring is independent of the covariate. The new estimator should be used for inference that does not depend on the censoring distribution. It is particularly relevant to adaptive clinical trials where, by design, censoring distributions differ across treatment arms. Copyright © 2012 John Wiley & Sons, Ltd.
Dynamic randomization and a randomization model for clinical trials data
Authors: Kaiser Lee D.
Published: July 2012

Randomization models are useful in supporting the validity of linear model analyses applied to data from a clinical trial that employed randomization via permuted blocks. Here, a randomization model for clinical trials data with arbitrary randomization methodology is developed, with treatment effect estimators and standard error estimators valid from a randomization perspective. A central limit theorem for the treatment effect estimator is also derived. As with permuted‐blocks randomization, a typical linear model analysis provides results similar to the randomization model results when, roughly, unit effects display no pattern over time. A key requirement for the randomization inference is that the unconditional probability that any patient receives active treatment is constant across patients;when this probability condition is violated, the treatment effect estimator is biased from a randomization perspective. Most randomization methods for balanced, 1 to 1, treatment allocation satisfy this condition. However, many dynamic randomization methods for planned unbalanced treatment allocation, like 2 to 1, do not satisfy this constant probability condition, and these methods should be avoided. Copyright © 2012 John Wiley & Sons, Ltd.
Sample size formulas for estimating intraclass correlation coefficients with precision and assurance
Authors: Zou G. Y.
Published: July 2012

The number of subjects required to estimate the intraclass correlation coefficient in a reliability study has usually been determined on the basis of the expected width of a confidence interval. However, this approach fails to explicitly consider the probability of achieving the desired interval width and may thus provide sample sizes that are too small to have adequate chance of achieving the desired precision. In this paper, we present a method that explicitly incorporates a prespecified probability of achieving the prespecified width or lower limit of a confidence interval. The resultant closed‐form formulas are shown to be very accurate. Copyright © 2012 John Wiley & Sons, Ltd.
Rapid DNA, RNA and protein extraction protocols optimized for slow continuously growing yeast cultures
Authors: Sasidharan Kalesh , Amariei Cornelia , Tomita Masaru , Murray Douglas B.
Published: July 2012

Conventional extraction protocols for yeast have been developed for relatively rapid‐growing low cell density cultures of laboratory strains and often do not have the integrity for frequent sampling of cultures. Therefore, these protocols are usually inefficient for cultures under slow growth conditions or of non‐laboratory strains. We have developed a combined mechanical and chemical disruption procedure using vigorous bead‐beating that can consistently disrupt yeast cells (> 95%), irrespective of cell cycle and metabolic state. Using this disruption technique coupled with quenching, we have developed DNA, RNA and protein extraction protocols that are optimized for a large number of samples from slow‐growing high‐density industrial yeast cultures. Additionally, sample volume, the use of expensive reagents/enzymes, handling times and incubations were minimized. We have tested the reproducibility of our methods using triplicate/time‐series extractions and compared these with commonly used protocols or commercially available kits. Moreover, we utilized a simple flow‐cytometric approach to estimate the mitochondrial DNA copy number. Based on the results, our methods have shown higher reproducibility, yield and quality. Copyright © 2012 John Wiley & Sons, Ltd.
The Features of Interaction of Bis(4, 6‐di‐tert‐butyl‐N‐(2, 6‐diisopropylphenyl)‐o‐amidophenolato)tin(IV) with Bromine and Iodine
Authors: Ilyakina Ekaterina V. , Poddel'sky Andrey I. , Piskunov Alexandr V. , Fukin Georgii K. , Cherkasov Vladimir K. , Abakumov Gleb A.
Published: July 2012

The oxidation of tin(IV) bis‐amidophenolate (APiPr)2Sn·THF (I) by bromine and iodine leads to the formation of monoradical mixed‐ligand complexes (APiPr)(ISQiPr)SnBr·THF (II) and (APiPr)(ISQiPr)SnI·THF (III) or diradical complexes (ISQiPr)2SnBr2 (IV) and (ISQiPr)2SnI2 (V), respectively [APiPr = dianion 4, 6‐di‐tert‐butyl‐N‐(2, 6‐diisopropylphenyl)‐o‐amidophenolate; ISQiPr = radical‐anion 4, 6‐di‐tert‐butyl‐N‐(2, 6‐diisopropylphenyl)‐o‐iminobenzosemiquinone], depending on the molar ratio of reagents (2:1 or 1:1). According to EPR data for compounds II and III, the unpaired electron is delocalized between both organic ligands. The EPR spectrum of IV in toluene matrix at 130 K is typical for diradical species with S = 1 with parameters D = 530 G, E = 105 G. The mixed‐ligand complexes II and III are unstable and undergo to symmetrization leading to formation of IV or V. The molecular structures of IV and V are determined by X‐ray analysis.
Pathological and clinical impact of neoadjuvant chemoradiotherapy using full‐dose gemcitabine and concurrent radiation for resectable pancreatic cancer
Authors: Sho Masayuki , Akahori Takahiro , Tanaka Toshihiro , Kinoshita Shoichi , Tamamoto Tetsuro , Nomi Takeo , Yamato Ichiro , Hokuto Daisuke , Yasuda Satoshi , Kawaguchi Chihiro , Nishiofuku Hideyuki , Marugami Nagaaki , Enomonoto Yasunori , Kasai Takahiko , Hasegawa Masatoshi , Kichikawa Kimihiko , Nakajima Yoshiyuki
Published: July 2012

Background/purpose

The therapeutic options available as preoperative strategies for resectable pancreatic cancer have received worldwide attention. We have recently introduced neoadjuvant chemoradiotherapy (NACRT) to achieve local control and possibly complete cure. In this study, we have retrospectively evaluated its impact on pathology and the perioperative clinical course in addition to its safety.

Methods

Sixty‐one patients who received full‐dose gemcitabine (1000 mg/m2) preoperatively with concurrent radiation (50 or 54 Gy) were evaluated. Seventy‐one patients who received no preoperative therapy served as controls. Perioperative outcomes, postoperative complications, immunonutritional status, and the performance of adjuvant chemotherapy were compared.

Results

Fifty‐nine patients (97 %) completed NACRT. Toxicity was acceptable and the regimen was feasible as outpatient treatment. The perioperative outcomes were closely comparable to control. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group. The rate of lymph node metastasis and stage was lower in the NACRT group. Furthermore, R0 resection could be achieved in 92 % of patients treated with NACRT. Nutritional status decreased after NACRT and further deteriorated during adjuvant chemotherapy. The initiation of postoperative chemotherapy was delayed in the NACRT group.

Conclusions

Our current protocol of neoadjuvant chemoradiotherapy is feasible and substantially improves the pathology. However, it has some detrimental effects on postoperative nutritional status and performance of adjuvant chemotherapy. Furthermore, it should be noted that there is a possibility of arterial complications.
Human neuronal coenzyme Q10 deficiency results in global loss of mitochondrial respiratory chain activity, increased mitochondrial oxidative stress and reversal of ATP synthase activity: implications for pathogenesis and treatment
Authors: Duberley Kate E. C. , Abramov Andrey Y. , Chalasani Annapurna , Heales Simon J. , Rahman Shamima , Hargreaves Iain P.
Published: July 2012

Disorders of coenzyme Q10 (CoQ10) biosynthesis represent the most treatable subgroup of mitochondrial diseases. Neurological involvement is frequently observed in CoQ10 deficiency, typically presenting as cerebellar ataxia and/or seizures. The aetiology of the neurological presentation of CoQ10 deficiency has yet to be fully elucidated and therefore in order to investigate these phenomena we have established a neuronal cell model of CoQ10 deficiency by treatment of neuronal SH‐SY5Y cell line with para‐aminobenzoic acid (PABA). PABA is a competitive inhibitor of the CoQ10 biosynthetic pathway enzyme, COQ2. PABA treatment (1 mM) resulted in a 54 % decrease (46 % residual CoQ10) decrease in neuronal CoQ10 status (p < 0.01). Reduction of neuronal CoQ10 status was accompanied by a progressive decrease in mitochondrial respiratory chain enzyme activities, with a 67.5 % decrease in cellular ATP production at 46 % residual CoQ10. Mitochondrial oxidative stress increased four‐fold at 77 % and 46 % residual CoQ10. A 40 % increase in mitochondrial membrane potential was detected at 46 % residual CoQ10 with depolarisation following oligomycin treatment suggesting a reversal of complex V activity. This neuronal cell model provides insights into the effects of CoQ10 deficiency on neuronal mitochondrial function and oxidative stress, and will be an important tool to evaluate candidate therapies for neurological conditions associated with CoQ10 deficiency.
Phase I study of enzastaurin and bevacizumab in patients with advanced cancer: safety, efficacy and pharmacokinetics
Authors: Nwankwo Nwabundo , Zhang Zhe , Wang Ting , Collins Connie , Resta Lee , Ermisch Sabine , Day Jeannette , Decker Rodney , Kornberg Lori , Nicol Steven , Thornton Donald , Armstrong Deborah K. , Carducci Michael A.
Published: July 2012

Purpose Given distinct mechanism of actions of enzastaurin and bevacizumab, preclinical studies suggest enhanced antitumor activity in combination. This phase I study assessed the combination’s safety and efficacy. Patients and methods Six advanced cancer patients could be enrolled in each of 11 cohorts. Patients received an enzastaurin loading dose. Oral enzastaurin (500 mg once daily [QD], 250 mg twice daily [BID], 375 mg BID, 500 mg BID, and 750 mg BID) was escalated in each cohort in combination with bevacizumab dosed at 5 mg/kg every 2 weeks, 10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks until a dose-limiting toxicity (DLT) occurred in 2 of 6 patients in any cohort. Results Sixty-seven patients (31, ovarian cancer [ovcar]) were evaluable for safety and efficacy. Six treatment-related DLTs occurred: grade 3 fatigue (n = 4), grade 4 cerebral hemorrhage, and grade 3 elevated aspartate transaminase. Common drug-related toxicities included change in color of urine and stool, fatigue, pain, diarrhea, and nausea. The maximum tolerated dose of enzastaurin was 750 mg BID in combination with any tested bevacizumab dose/schedule. Overall response rate was 19.4 % (32.3 % ovcar). Median time to progression was 3.7 months (95 % confidence interval [CI], 2.7–5.5), with 8.3 months (95 % CI, 3.7–11.1) in ovcar. Overall, 35.9 % (50.4 % ovcar) of patients remained without disease progression after 6 months. Conclusion The recommended phase II doses of enzastaurin were 500 mg QD up to 500 mg BID with any tested dose/schedule of bevacizumab. This combination demonstrated encouraging clinical activity, particularly in ovcar.
Congenital constriction ring in children: Sine plasty combined with removal of fibrous groove and fasciotomy
Authors: Hung Nguyen Ngoc
Published: July 2012

Objective

To evaluate the clinical and functional results of a technical procedure used in the surgical treatment of congenital constriction ring (CCR) in children.

Materials and methods

This was a retrospective study undertaken to evaluate the results of surgical techniques performed from January 1995 to December 2005 on 95 patients with 134 congenital constriction bands. Due to the drop-out of nine patients during follow-up, data on 86 patients (121 congenital constriction rings; average age at surgery 1 year 2 months) were analyzed. The extent of the constrictions was classified by according to the Patterson criteria. All patients were treated by two-stage sine plasty combined with removal of the fibrous groove and fasciotomy, with one-half of the ring removed during the first stage and the other half removed 1 week later during the second state. The surgical outcomes were assess according to the Moses criteria.

Results

Three types of CCR (Patterson criteria) were identified among the 86 patients (121 constriction rings): types I (5 patients, 4.1 %), II (107, 88.5 %), III (9, 7.4 %). Of the 121 constriction rings, good results were attained in 73.6 % and fair results in 26.4 %. Sensory deficits were seen in six patients immediately after the surgery but all six had improved to a normal condition at the final follow-up examination. There were no skin necrosis or wound healing problems.

Conclusion

The combined sine plasty/removal of fibrous groove and fasciotomy method reported here is a simple and safe surgical technique for treating CCR in children.
Predictors of adolescent successful development after an exchange: The importance of activity qualities and youth input
Authors: Lawford Heather L. , Ramey Heather L. , Rose‐Krasnor Linda , Proctor Andrea S.
Published: July 2012

The purpose of this study is to examine the factors involved in predicting successful development after an intensive exchange experience in adolescence. Specifically, we considered the eight positive features, as conceptualized by Eccles and Gootman (2002), as well as the amount of input youth had into their exchange experience as predictors of successful development after the exchange. In this short‐term longitudinal study, 242 young, middle, and older adolescents, who participated in a national short‐term exchanges program, completed surveys before and after completion of the program. Overall, we found that both the eight positive features and personal input were significantly related to overall successful development after an exchange, controlling for initial reports of successful development. This research contributes to an understanding of the importance of different qualities of activity experiences in overall youth development.
Structural insights into small RNA sorting and mRNA target binding by Arabidopsis Argonaute Mid domains
Authors: Zha Xingfu , Xia Qingyou , Adam Yuan Y.
Published: July 2012

The RISC‐associated Argonaute (Ago) proteins play the catalytic role for RISC‐mediated gene regulation by selecting small RNAs and subsequent targeting and cleavage of complementary mRNAs. Ago Mid domains are proposed to play essential roles in small RNA sorting. Here, we report the crystal structures of Arabidopsis Ago1 Mid domain and its chimera mutant with part of Ago1 replaced by Ago4. The structures demonstrate that a single amino insertion in the nucleotide specificity loop of AtAgo1 will change the nucleotide binding preference of AtAgo1 from “5′‐U” to “5′‐A”. Moreover, we identify a long positively charged groove located along the “5′‐end‐nucleotide specificity loop” and occupied by several sulfate ions with the distance of 9–11 Å distance, indicating a putative mRNA target binding groove.
Involvement of hepatitis B virus X gene (HBx) integration in hepatocarcinogenesis via a recombination of HBx/Alu core sequence/subtelomeric DNA
Authors: Zhang Xuan , You Xiaona , Li Nan , Zhang Weiying , Gagos Sarantis , Wang Qi , Banos Aggelos , Cai Na , Zhang Huakun , Zhang Hang , Zhang Xuezhi , Shan Changliang , Qiu Liyan , Zhang Shuai , Lv Na , Chen Minshan , Du Yumei , Xia Jianchuan , Ye Lihong , Zhang Xiaodong
Published: July 2012

The significance of hepatitis B virus (HBV) DNA‐based integration in hepatocarcinogenesis is poorly understood. In the present study, we investigated whether the integration of HBV X gene (HBx) is involved in the event. Our finding showed that the integration of HBx fragment (316–462 bp/262–462 bp) was able to transform human immortalized normal liver LO2 cells using a cell model of HBx‐integration. We identified that the recombination, HBx/Alu core sequence/subtelomeric DNA, was required for the transformation, which could be detected in 5 out of 44 clinical HBx‐positive hepatocellular carcinoma tissues. Thus, we conclude that HBx integration is involved in the hepatocarcinogenesis.
Methamphetamine binds to α‐synuclein and causes a conformational change which can be detected by nanopore analysis
Authors: Tavassoly Omid , Lee Jeremy S.
Published: July 2012

α‐Synuclein is an intrinsically disordered protein of 140 amino acids which is abundant in dopaminergic neurons. Misfolding and aggregation of α‐synuclein leads to the formation of Lewy bodies inside the neurons which is the hallmark of Parkinson's disease and related dementias. Here we show by nanopore analysis that the recreational drug, methamphetamine, binds to the N‐terminus of α‐synuclein and causes a conformational change which cannot be detected by circular dichroism spectroscopy. The results suggest a mechanism for the psychoactivity of methamphetamine as well as an increased incidence of Parkinson's disease amongst users of the drug.
Acetylation regulates subcellular localization of eukaryotic translation initiation factor 5A (eIF5A)
Authors: Ishfaq Muhammad , Maeta Kazuhiro , Maeda Satoko , Natsume Toru , Ito Akihiro , Yoshida Minoru
Published: July 2012

Eukaryotic translation initiation factor 5A (eIF5A) is a protein subject to hypusination, which is essential for its function. eIF5A is also acetylated, but the role of that modification is unknown. Here, we report that acetylation regulates the subcellular localization of eIF5A. We identified PCAF as the major cellular acetyltransferase of eIF5A, and HDAC6 and SIRT2 as its major deacetylases. Inhibition of the deacetylases or impaired hypusination increased acetylation of eIF5A, leading to nuclear accumulation. As eIF5A is constitutively hypusinated under physiological conditions, we suggest that reversible acetylation plays a major role in controlling the subcellular localization of eIF5A.
Electronic microscopy evidence for mitochondria as targets for Cd/Se/Te‐based quantum dot 705 toxicity in vivo
Authors: Lin Chia‐Hua , Chang Louis W. , Wei Yau‐Huei , Wu Shi‐Bei , Yang Chung‐Shi , Chang Wan‐Hsuan , Chen Yu‐Ching , Lin Pin‐Pin
Published: July 2012

The safety of quantum dots (QDs) 705 was evaluated in this study. Mice were treated with QD705 (intravenous) at a single dose of (40 pmol) for 4, 12, 16, and 24 weeks. Effects of QD705 on kidneys were examined. While there was a lack of histopathology, reduction in renal functions was detected at 16 weeks. Electron microscopic examination revealed alterations in proximal convoluted tubule (PCT) cell mitochondria at even much earlier time, including disorientation and reduction of mitochondrial number (early change), mitochondrial swelling, and later compensatory mitochondrial hypertrophy (enlargement mitochondria: giant mitochondria with hyperplastic inner cristae) as well as mitochondrial hyperplasia (increase in mitochondrial biogenesis and numbers) were observed. Such changes probably represent compensatory attempts of the mitochondria for functional loss or reduction of mitochondria in QD705 treated animals. Moreover, degeneration of mitochondria (myelin‐figure and cytoplasmic membranous body formation) and degradation of cytoplasmic materials (isolated cytoplasmic pockets of degenerated materials and focal cytoplasmic degradation) also occurred in later time points (16–24 weeks). Such mitochondrial changes were not identical with those induced by pure cadmium. Taken together, we suggest that mitochondria appeared to be the target of QD705 toxicity and specific mitochondrial markers may be useful parameters for toxicity assessments of QDs or other metal‐based nanomaterials.
Acceptance and commitment therapy for fibromyalgia: A randomized controlled trial
Authors: Olsson G.L. , Kemani M. , Jensen K. , Kosek E. , Kadetoff D. , Sorjonen K. , Ingvar M. , Wicksell R.
Published: July 2012

Background

Recent developments within cognitive behavior therapy (CBT) have emphasized the utility of acceptance and mindfulness strategies, contrasting interventions focused on reduction or control of symptoms. A study of fMRI changes after CBT in females with fibromyalgia (FM) has been performed and results are presented elsewhere (under review). The aim of the present study was evaluate the effectiveness of Acceptance and Commitment Therapy (ACT)-based intervention for patient diagnosed with FM in comparison with a wait-list control

Method

Female patients aged 18–55 years, fulfilling the American College of Rheumatology classification criteria for FM, and with a weekly self-reported average pain intensity of >40 (VAS 0–100) were considered eligible for inclusion. Participants completed a set of questionnaires prior to treatment, immediately following the treatment and at follow 3–4 months post treatment. Primaryoutcome variable was pain disability (PDI). FIQ, SF36, SES, STAI, pain intensity, BDI, PIPS (psychological inflexibility in pain scale) were also used. The ACT-intervention consisted of twelve weekly group sessions, ten with psychologist and two with pain physician. Treatment was evaluated and mediation analyses were performed.

Results

Primary outcome measure (PDI): A significant improvement in pain disability for ACT in relation to the control condition, p < 0.001. Secondary outcome measures: ACT showed significant improvement in mental health quality of life, self-efficacy, depression, and anxiety. Consistent with hypotheses, ACT did not result in significant changes in either physical quality of life or pain intensity. Mediation analyses: A decrease in psychological inflexibility from pre to post assessments significantly mediated the improvement in pain disability.

Conclusion

The present study supports the utility of using a relatively brief ACT intervention in a group format for women diagnosed with fibromyalgia, and data suggests a mediating function on improvements in psychological flexibility.
Sortilins in neuropathic pain
Authors: Richner M. , Bjerrum O.J. , Koninck Y. De , Nykjaer A. , Vaegter C.B.
Published: July 2012

Background/aims

The molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition. We have previously described how the receptor sortilin modulates neurotrophin signaling by facilitating anterograde transport of Trk receptors. Unpublished data further link SorCS2, another member of the Sortilins family of sorting receptors (sortilin, SorLA and SorCS1–3) to BDNF signaling by regulating presynaptic TrkB trafficking. The purpose of this study is to explore the involvement of Sortilins in neuropathic pain.

Methods

We subjected wild-type (wt), sortilin knockout (Sort1
-/-) and SorCS2 knockout (SorCS2
-/-) mice to the Spared Nerve Injury (SNI) model of peripheral nerve injury. Mechanical allodynia was measured by von Frey filaments using the up-down-up method and a 3-out-of-5 thresshold.

Results

As previously described by several groups, wt mice developed significant mechanical allodynia following SNI. Interestingly however, mice lacking sortilin or SorCS2 were fully protected from development of allodynia and did not display KCC2 down-regulation following injury. In addition, a single intrathecal injection of antibodies against sortilin or SorCS2 could delay or rescue mechanical allodynia in wt SNI mice for 2-3 days. Finally, neither sortilin nor SorCS2 deficient mice responded to intrathecal injection of BDNF, in contrast to wt mice which developed transient mechanical allodynia.

Conclusion

We hypothesize that sortilin and SorCS2 are involved in neuropathic pain development by regulating TrkB signaling. Alternatively, Sortilins may directly influence the regulation of KCC2 membrane levels following injury. Both hypotheses are currently being investigated by our group.