bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of sputtering parameters on (AlCrMnMoNiZr)N films
Authors: Ren B. , Lv S-J. , Zhao R-F. , Liu Z-X. , Guan S-K.
Published: January 2014

To optimise the performance of high entropy alloy nitride films, (AlCrMnMoNiZr)N films were deposited through reactive radio frequency magnetron sputtering at a certain N2/Ar flow ratios of 0·5. The effects of sputtering power and substrate temperature on the structure and properties of the films were investigated. Results showed that sputtering power had strong effects on the phase transformation from amorphous to face centred cubic solid solution structure with (200) preferred orientation. The films with coarsened grains had a higher hardness at high substrate temperature because of the inverse Hall–Petch effect. When the sputtering parameters were set at 250 W and 600 K, high hardness of 15–18 GPa and low friction coefficient of 0·12∼0·15 can be obtained. Therefore, the optimised parameters are 250 W and 600 K.
Optimisation of experimental conditions for pulse electrodeposition of nanostructured platinum
Authors: Nasiri Vatan H. , Mohammad Shafiee M. , Khanfekr A. , Laleh M. , Kaffashan H. , Jafarzadeh K.
Published: January 2014

Square wave cathodic current modulation was used to electrodeposit nanostructured platinum on niobium. The crystallite size, surface morphology and active surface area of deposits were strongly dependent on the process parameters such as pulse duty cycle, peak current density and pulse frequency. Microstructure, surface morphology and grain size of the deposits were studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Cyclic voltammetry was also used to determine the deposit's effective surface area. The best quality platinum coated electrode was obtained from the pulse plating condition of 15 Hz frequency, 9 mA cm−2 peak current density and 30% duty cycle. Moreover, AFM observations demonstrated that the best quality Pt/Nb electrode has the highest active surface area fr of 281 cm2 with the finest grain size of 52 nm. This means that the structure of the coating can be controlled by the electrodeposition parameters resulting in an increased electrochemical surface area.
Influence of magnetic fields on cobalt electrodeposition
Authors: Yu Y. D. , Song Z. L. , Ge H. L. , Wei G. Y.
Published: January 2014

Magnetic fields parallel to electrodes were introduced during plating process to prepare cobalt films from baths without additives. Effects of magnetic intensities on the nucleation process, electrochemical mechanism and surface morphology were investigated. It was found that limiting current and deposition mass increased gradually with the rise in magnetic intensities. Magnetohydrodynamic phenomenon (magnetic fields can induce currents in a moving conductive fluid, which in turn creates forces on the fluid and also changes the magnetic field itself) caused by Lorentz forces could agitate to decrease thickness of diffusion layers, which contribute to the increase in deposition rate. Reduction of cobalt on copper substrates without magnetic fields showed instantaneous nucleation process. However, cobalt reduction with 1 T magnetic intensity deviated from instantaneous nucleation process as a result of micromagnetohydrodynamic (micro-MHD) flows. Films of smaller grain size and compact surface could be obtained under 1 T magnetic intensity as a result of MHD effects.
Enhancement of microhardness and wear resistance of Ni–CeO2 nanocomposite coatings
Authors: Qu N. S. , Hu X. Y. , Qian W. H. , Zhu Z. W.
Published: January 2014

The improvement of the incorporated nanoparticle content in nanocomposite coatings is a key factor in composite electrodeposition. This paper describes a modified sediment co-deposition (SCD) technique which has been developed to produce Ni–CeO2 nanocomposite coatings, with the aim of enhancing the embedded CeO2 nanoparticle content. The maximum content of CeO2 particles in the nanocomposite coatings created using this modified SCD technique is 7·09 wt-%, which is the highest reported. A maximum microhardness of 630 HV is obtained, which is significantly greater than that observed in nanocomposite coatings fabricated using the conventional electrodeposition technique. As the wear resistance of the nanocomposite coatings increases with increasing incorporated CeO2 nanoparticle content, so this nanocomposite coating with an incorporated CeO2 nanoparticle content of 7·09 wt-% exhibits maximum wear resistance.
Microstructure and mechanical properties of surface layer of M50NiL steel plasma nitrided
Authors: Wang X. A. , Yan M. F. , Zhang C. S. , Zhang Y. X.
Published: January 2014

The quenched M50NiL steel specimens have been plasma nitrided at temperatures from 460 to 590°C for 4 h under a constant mixture gaseous supply of 0·05N2–0·4H2 L min−1. The effects of the treatment temperature on the microstructure, microhardness and wear resistance of the surface nitrided layers are studied. The results show that the plasma nitrided layer includes only the diffusion layer without conventional compound layer. The surface hardness is significantly enhanced. α′-Fe and γ′-Fe4N phases in surface layer are formed at relatively low nitriding temperatures (460–560°C), while a low nitrogen phase FeN0·076 forms when the nitriding temperature exceeds 575°C. With the increase in nitriding temperature, the nitrided layer thickness increases, whereas both the surface and core microhardness of the nitrided specimens decreases. The wear resistance of specimens can also be improved significantly by plasma nitriding.
Surface modification through self-assembled microrod networks
Authors: Kim Sunhyung , Park Sangwoo , Lee Sang-Yup
Published: January 2014

Surface modification by the construction and surface polymerisation of microrod networks is demonstrated here. The hydrophobic microrod networks are produced through the self-assembly of a novel organic molecule, N’1,N’6-bis(3-(1-pyrrolyl)propanoyl) hexanedihydrazide (DPH). The microrods generated grow to create a network structure that enhances hydrophobicity by providing roughness on a surface, leading to a ∼20° increase in the water contact angle. The hydrophobic surface was modified to become a hydrophilic surface by treatment with a chemical oxidant that induced polymerisation of the pyrrole rings on the surface of the micronetwork. In addition to the hydrophilic conversion of the surface functional groups, surface roughness was also reduced by the polymerisation. This study demonstrates that the self-assembly of the DPH molecule can be exploited to customise surfaces that require facile hydrophobic/hydrophilic surface modification.
Studies on thermal shock resistance of TiN and TiAlN coatings under pulsed laser irradiation
Authors: Deng J. , Li S. , Xing Y. , Li Y.
Published: January 2014

TiN and TiAlN nitride coatings were deposited on WC/Co cemented carbide by cathode arc evaporation technique. The microstructural and fundamental properties of these nitride coatings were examined. Thermal shock tests were carried out on these nitride coatings by laser irradiation, and thermal shock behaviours were examined by scanning electron microscopy. Results showed that the major factors causing failure of these nitride coatings after laser irradiation were thermal stress and oxidation. The formation of cracks on the irradiated coating surface is attributed to the shrinkage and relaxation of thermal stresses during laser irradiation. The critical power density at which the coating is fractured is 20×108 W m−2 for the TiN coating and 45×108 W m−2 for the TiAlN coating. The coatings with Al (TiAlN) exhibited higher thermal shock resistance over the one without Al (TiN). Analysis of the repeated laser irradiated coating surfaces demonstrated that the TiN coating was composed mainly of crack networks, spallation and bulges, whereas the TiAlN coating experienced less damage than the TiN coating and showed a lot of cavities on the coating surface.
Scratch resistance enhancement of 3-glycidyloxypropyltrimethoxysilane coating incorporated with silver nanoparticles
Authors: Vengadaesvaran B. , Arun N. , Chanthiriga R. , Bushroa A. R. , Ramis Rau S. , Ramesh K. , Vikneswaran R. , Alshabeeb G. H. E. , Ramesh S. , Arof A. K.
Published: January 2014

An effective method to enhance scratch resistance was developed using a 3-glycidyloxyproplytrimethoxysilane as a base on the formation of a transparent coating on glass substrate. The addition of silver nanoparticles improves further the scratch hardness of the thin film coating. The critical load obtained from the microscratch test increases from 2931 to 3319 mN upon the addition of silver nanoparticles. The size of silver nanoparticle was analysed using transmission electron microscope (TEM) and was found to be in the range of 20–40 nm. Addition of silver nanoparticles also increases the surface energy; hence the result enhances the hydrophobicity compared to substrate with only GLYMO coated on it.
Bone marrow stroma CD40 expression correlates with inflammatory mast cell infiltration and disease progression in splenic marginal zone lymphoma
Authors: Franco Giovanni , Guarnotta Carla , Frossi Barbara , Piccaluga Pier Paolo , Boveri Emanuela , Gulino Alessandro , Fuligni Fabio , Rigoni Alice , Porcasi Rossana , Buffa Salvatore , Betto Elena , Florena Ada Maria , Franco Vito , Iannitto Emilio , Arcaini Luca , Pileri Stefano Aldo , Pucillo Carlo , Colombo Mario Paolo , Sangaletti Sabina , Tripodo Claudio
Published: January 2014

Key Points

In SMZL, the quality of BM stromal microenvironment predicts disease progression. CD40-CD40L-mediated interactions between mast cells and BM mesenchymal cells engender proinflammatory conditions within SMZL infiltrates.
Impact of mutational status on outcomes in myelofibrosis patients treated with ruxolitinib in the COMFORT-II study
Authors: Guglielmelli Paola , Biamonte Flavia , Rotunno Giada , Artusi Valentina , Artuso Lucia , Bernardis Isabella , Tenedini Elena , Pieri Lisa , Paoli Chiara , Mannarelli Carmela , Fjerza Rajmonda , Rumi Elisa , Stalbovskaya Viktoriya , Squires Matthew , Cazzola Mario , Manfredini Rossella , Harrison Claire , Tagliafico Enrico , Vannucchi Alessandro M.
Published: January 2014

Key Points

Improvements in splenomegaly and symptoms in patients receiving ruxolitinib occurred regardless of the mutations that were present. Ruxolitinib relieved the negative impact of prognostically detrimental mutations in myelofibrosis patients from the COMFORT-II study.
A modular computational framework for automated peak extraction from ion mobility spectra
Authors: D’Addario Marianna , Kopczynski Dominik , Baumbach Jörg Ingo , Rahmann Sven
Published: January 2014

Background

An ion mobility (IM) spectrometer coupled with a multi-capillary column (MCC) measures volatile organic compounds (VOCs) in the air or in exhaled breath. This technique is utilized in several biotechnological and medical applications. Each peak in an MCC/IM measurement represents a certain compound, which may be known or unknown. For clustering and classification of measurements, the raw data matrix must be reduced to a set of peaks. Each peak is described by its coordinates (retention time in the MCC and reduced inverse ion mobility) and shape (signal intensity, further shape parameters). This fundamental step is referred to aspeak extraction. It is the basis for identifying discriminating peaks, and hence putative biomarkers, between two classes of measurements, such as a healthy control group and a group of patients with a confirmed disease. Current state-of-the-art peak extraction methods require human interaction, such as hand-picking approximate peak locations, assisted by a visualization of the data matrix. In a high-throughput context, however, it is preferable to have robust methods for fully automated peak extraction.

Results

We introduce PEAX, a modular framework for automated peak extraction. The framework consists of several steps in a pipeline architecture. Each step performs a specific sub-task and can be instantiated by different methods implemented as modules. We provide open-source software for the framework and several modules for each step. Additionally, an interface that allows easy extension by a new module is provided. Combining the modules in all reasonable ways leads to a large number of peak extraction methods. We evaluate all combinations using intrinsic error measures and by comparing the resulting peak sets with an expert-picked one.

Conclusions

Our software PEAX is able to automatically extract peaks from MCC/IM measurements within a few seconds. The automatically obtained results keep up with the results provided by current state-of-the-art peak extraction methods. This opens a high-throughput context for the MCC/IM application field. Our software is available athttp://www.rahmannlab.de/research/ims.
Inhibition of human lung cancer cell proliferation and survival by wine
Authors: Barron Carly C , Moore Jessy , Tsakiridis Theodoros , Pickering Gary , Tsiani Evangelia
Published: January 2014

Background

Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events.

Methods

Human NSCLC adenocarcinoma A549 and H1299 cells were used. Cell proliferation was assessed by thymidine incorporation. Clonogenic assays were used to assess cell survival. Immunoblotting was used to examine total and phosphorylated levels of Akt, Erk and p53.

Results

In A549 cells red wine inhibited cell proliferation and reduced clonogenic survival at doses as low as 0.02%. Red wine significantly reduced basal and EGF-stimulated Akt and Erk phosphorylation while it increased the levels of total and phosphorylated p53 (Ser15). Control experiments indicated that the anti-proliferative effects of wine were not mediated by the associated contents of ethanol or the polyphenol resveratrol and were independent of glucose transport into cancer cells. White wine also inhibited clonogenic survival, albeit at a higher doses (0.5-2%), and reduced Akt phosphorylation. The effects of both red and white wine on Akt phosphorylation were also verified in H1299 cells.

Conclusions

Red wine inhibits proliferation of lung cancer cells and blocks clonogenic survival at low concentrations. This is associated with inhibition of basal and EGF-stimulated Akt and Erk signals and enhancement of total and phosphorylated levels of p53. White wine mediates similar effects albeit at higher concentrations. Our data suggest that wine may have considerable anti-tumour and chemoprevention properties in lung cancer and deserves further systematic investigation in animal models of lung cancer.
Nitazoxanide inhibits the replication of Japanese encephalitis virus in cultured cells and in a mouse model
Authors: Shi Zixue , Wei Jianchao , Deng Xufang , Li Shuqing , Qiu Yafeng , Shao Donghua , Li Beibei , Zhang Keyu , Xue Feiqun , Wang Xiaodu , Ma Zhiyong
Published: January 2014

Background

Japanese encephalitis virus (JEV) has a significant impact on public health. An estimated three billion people in 'at-risk’ regions remain unvaccinated and the number of unvaccinated individuals in certain Asian countries is increasing. Consequently, there is an urgent need for the development of novel therapeutic agents against Japanese encephalitis. Nitazoxanide (NTZ) is a thiazolide anti-infective licensed for the treatment of parasitic gastroenteritis. Recently, NTZ has been demonstrated to have antiviral properties. In this study, the anti-JEV activity of NTZ was evaluated in cultured cells and in a mouse model.

Methods

JEV-infected cells were treated with NTZ at different concentrations. The replication of JEV in the mock- and NTZ-treated cells was examined by virus titration. NTZ was administered at different time points of JEV infection to determine the stage at which NTZ affected JEV replication. Mice were infected with a lethal dose of JEV and intragastrically administered with NTZ from 1 day post-infection. The protective effect of NTZ on the JEV-infected mice was evaluated.

Findings

NTZ significantly inhibited the replication of JEV in cultured cells in a dose dependent manner with 50% effective concentration value of 0.12 ± 0.04 μg/ml, a non-toxic concentration in cultured cells (50% cytotoxic concentration = 18.59 ± 0.31 μg/ml). The chemotherapeutic index calculated was 154.92. The viral yields of the NTZ-treated cells were significantly reduced at 12, 24, 36 and 48 h post-infection compared with the mock-treated cells. NTZ was found to exert its anti-JEV effect at the early-mid stage of viral infection. The anti-JEV effect of NTZ was also demonstrated in vivo, where 90% of mice that were treated by daily intragastric administration of 100 mg/kg/day of NTZ were protected from a lethal challenge dose of JEV.

Conclusions

Both in vitro and in vivo data indicated that NTZ has anti-JEV activity, suggesting the potential application of NTZ in the treatment of Japanese encephalitis.
Anoctamin 1 Contributes to Inflammatory and Nerve-Injury Induced Hypersensitivity
Authors: Lee Byeongjun , Cho Hawon , Jung Jooyoung , Yang Young Duk , Yang Dong-Jin , Oh Uhtaek
Published: January 2014

Background:

Various pathological conditions such as inflammation or injury can evoke pain hypersensitivity. That represents the response to innocuous stimuli or exaggerated response to noxious stimuli. The molecular mechanism based on the pain hypersensitivity is associated with changes in many of ion channels in dorsal-root ganglion (DRG) neurons. Anoctamin 1 (ANO1/TMEM16A), a Ca2+ activated chloride channel is highly visible in small DRG neurons and responds to heat. Mice with an abolished function of ANO1 in DRG neurons demonstrated attenuated pain-like behaviors when exposed to noxious heat, suggesting a role in acute thermal nociception. In this study, we further examined the function of ANO1 in mediating inflammation- or injury-induced hyperalgesia or allodynia.

Results:

Using Advillin/Ano1fl/fl ( Adv/Ano1fl/fl) mice that have a functional ablation of Ano1 mainly in DRG neurons, we were able to determine its role in mediating thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury. The thermal hyperalgesia and mechanical allodynia induced by carrageenan injection and spared-nerve injury were significantly reduced in Adv/Ano1fl/fl mice. In addition, flinching or licking behavior after bradykinin or formalin injection was also significantly reduced in Adv/Ano1fl/fl mice. Since pathological conditions augment nociceptive behaviors, we expected ANO1's contribution to the excitability of DRG neurons. Indeed, the application of inflammatory mediators reduced the threshold for action potential (rheobase) or time for induction of the first action potential in DRG neurons isolated from control ( Ano1fl/fl) mice. These parameters for neuronal excitability induced by inflammatory mediators were not changed in Adv/Ano1fl/fl mice, suggesting an active contribution of ANO1 in augmenting the neuronal excitability.

Conclusions:

In addition to ANO1's role in mediating acute thermal pain as a heat sensor, ANO1 is also capable of augmenting the excitability of DRG neurons under inflammatory or neuropathic conditions and thereby aggravates inflammation- or tissue injury-induced pathological pain.
Evaluation of the accuracy of shoe fitting in older people using three‐dimensional foot scanning
Authors: Menz Hylton B , Auhl Maria , Ristevski Sonja , Frescos Nicoletta , Munteanu Shannon E
Published: January 2014

Background

Ill‐fitting footwear is a common problem in older people. The objective of this study was to determine the accuracy of shoe fitting in older people by comparing the dimensions of allocated shoes to foot dimensions obtained with a three‐dimensional (3D) scanner.

Methods

The shoe sizes of 56 older people were determined with the Brannock device®, and weightbearing foot scans were obtained with the FotoScan 3D scanner (Precision 3D Ltd, Weston‐super‐mare, UK). Participants were provided with a pair of shoes (Dr Comfort®, Vista, CA, USA), available in three width fittings (medium, wide and extra wide). The dimensions (length, ball width and ball girth) of the allocated shoes were documented according to the last measurements provided by the manufacturer. Mean differences between last dimensions and foot dimensions obtained with the 3D scanner were calculated to provide an indication of shoe fitting accuracy. Participants were also asked to report their perception of shoe fit and comfort, using 100 mm visual analogue scales (VAS).

Results

Shoe size ranged from US size 7 to 14 for men and 5.5 to 11 for women. The allocated shoes were significantly longer than the foot (mean 23.6 mm, 95% confidence interval [CI] 22.1 to 25.2; t55 = 30.3, p < 0.001), however there were no significant differences in relation to ball width (mean 1.4 mm, 95% CI −0.1 to 2.9 mm; t55 = 1.9, p = 0.066) or ball girth (mean −0.7 mm, 95% CI −6.1 to 4.8 mm; t55 = −0.2, p = 0.810). Participants reported favourable perceptions of shoe fit (mean VAS = 90.7 mm, 95% CI 88.4 to 93.1 mm) and comfort (mean VAS = 88.4 mm, 95% CI 85.0 to 91.8 mm).

Conclusion

Shoe size selection using the Brannock device® resulted in the allocation of shoes with last dimensions that were well matched to the dimensions of the foot. Participants also considered the shoes to be well fitted and comfortable. Older people with disabling foot pain can therefore be dispensed with appropriately‐fitted shoes using this technique, provided that the style and materials used are suitable and extra width fittings are available.
Elevated signal transducers and activators of transcription 1 correlates with increased C-C motif chemokine ligand 2 and C-X-C motif chemokine 10 levels in peripheral blood of patients with systemic lupus erythematosus
Authors: Dominguez-Gutierrez Paul R , Ceribelli Angela , Satoh Minoru , Sobel Eric S , Reeves Westley H , Chan Edward KL
Published: January 2014

Introduction

The present study examines the levels of recently reported biomarkers, adenosine deaminase acting on RNA (ADAR), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine 10 (CXCL10), signal transducers and activators of transcription 1 (STAT1), and miR-146a in systemic lupus erythematosus (SLE) patients over multiple visits.

Methods

Peripheral blood leukocytes were collected from 65 healthy donors and 103 SLE patients, 60 of whom had samples from 2 or more visits. Total RNA was isolated and analyzed for the expression of mRNA and microRNA using Taqman real time PCR assays. Relative expression of I-IFN signature genes, chemokines, and miR-146a were determined by the ΔΔCT method. Results were correlated with clinical data and analyzed by Wilcoxon/Kruskal-Wallis test and Fisher’s exact test.

Results

Levels of ADAR, CCL2, CXCL10, and STAT1 in SLE were significantly elevated compared with the healthy controls (P <0.0001). ADAR, CCL2, and CXCL10 showed significant correlation with IFN score in both healthy donors (P <0.0033) and SLE patients (P <0.0001). In SLE patients, miR-146a level was not significantly different from healthy controls nor correlated to the IFN score. Two STAT1 populations were identified: a low STAT1 and a high STAT1 group. High STAT1 patient visits displayed higher (P ≤0.0020) levels of CCL2 and CXCL10 than the low STAT1 patient visits. STAT1 levels correlated with IFN score in low STAT1 group but not in high STAT1 group. More importantly, high STAT1 levels appeared as an enhancer of CCL2 and CXCL10 as indicated by the significantly stronger correlation of CCL2 and CXCL10 with IFN score in high STAT1 patient visits relative to low STAT1 patient visits.

Conclusion

Our data indicate a novel role for STAT1 in the pathogenesis of SLE as an expression enhancer of CCL2 and CXCL10 in SLE patients with high levels of STAT1. Future study is needed to examine the exact role of STAT1 in the etiology of SLE.
Inducible and coupled expression of the polyomavirus middle T antigen and Cre recombinase in transgenic mice: an in vivo model for synthetic viability in mammary tumour progression
Authors: Rao Trisha , Ranger Jill J , Smith Harvey W , Lam Sonya H , Chodosh Lewis , Muller William J
Published: January 2014

Introduction

Effective in vivo models of breast cancer are crucial for studying the development and progression of the disease in humans. We sought to engineer a novel mouse model of polyomavirus middle T antigen (PyV mT)-mediated mammary tumourigenesis in which inducible expression of this well-characterized viral oncoprotein is coupled to Cre recombinase (TetO-PyV mT-IRES-Cre recombinase or MIC).

Methods

MIC mice were crossed to the mouse mammary tumour virus (MMTV)-reverse tetracycline transactivator (rtTA) strain to generate cohorts of virgin females carrying one or both transgenes. Experimental (rtTA/MIC) and control (rtTA or MIC) animals were administered 2 mg/mL doxycycline beginning as early as eight weeks of age and monitored for mammary tumour formation, in parallel with un-induced controls of the same genotypes.

Results

Of the rtTA/MIC virgin females studied, 90% developed mammary tumour with complete penetrance to all glands in response to doxycycline and a T50 of seven days post-induction, while induced or un-induced controls remained tumour-free after one year of induction. Histological analyses of rtTA/MIC mammary glands and tumour revealed that lesions followed the canonical stepwise progression of PyV mT tumourigenesis, from hyperplasia to mammary intraepithelial neoplasia/adenoma, carcinoma, and invasive carcinoma that metastasizes to the lung; at each of these stages expression of PyV mT and Cre recombinase transgenes was confirmed. Withdrawal of doxycycline from rtTA/MIC mice with end-stage mammary tumours led to rapid regression, yet animals eventually developed PyV mT-expressing and -non-expressing recurrent masses with varied tumour histopathologies.

Conclusions

We have successfully created a temporally regulated mouse model of PyV mT-mediated mammary tumourigenesis that can be used to study Cre recombinase-mediated genetic changes simultaneously. While maintaining all of the hallmark features of the well-established constitutive MMTV-PyV mT model, the utility of this strain derives from the linking of PyV mT and Cre recombinase transgenes; mammary epithelial cells are thereby forced to couple PyV mT expression with conditional ablation of a given gene. This transgenic mouse model will be an important research tool for identifying synthetic viable genetic events that enable PyV mT tumours to evolve in the absence of a key signaling pathway.
Impact of dual mTORC1/2 mTOR kinase inhibitor AZD8055 on acquired endocrine resistance in breast cancer in vitro
Authors: Jordan Nicola J , Dutkowski Carol M , Barrow Denise , Mottram Huw J , Hutcheson Iain R , Nicholson Robert I , Guichard Sylvie M , Gee Julia MW
Published: January 2014

Introduction

Upregulation of PI3K/Akt/mTOR signalling in endocrine-resistant breast cancer (BC) has identified mTOR as an attractive target alongside anti-hormones to control resistance. RAD001 (everolimus/Afinitor®), an allosteric mTOR inhibitor, is proving valuable in this setting; however, some patients are inherently refractory or relapse during treatment requiring alternative strategies. Here we evaluate the potential for novel dual mTORC1/2 mTOR kinase inhibitors, exemplified by AZD8055, by comparison with RAD001 in ER + endocrine resistant BC cells.

Methods

In vitro models of tamoxifen (TamR) or oestrogen deprivation resistance (MCF7-X) were treated with RAD001 or AZD8055 alone or combined with anti-hormone fulvestrant. Endpoints included growth, cell proliferation (Ki67), viability and migration, with PI3K/AKT/mTOR signalling impact monitored by Western blotting. Potential ER cross-talk was investigated by immunocytochemistry and RT-PCR.

Results

RAD001 was a poor growth inhibitor of MCF7-derived TamR and MCF7-X cells (IC50 ≥1 μM), rapidly inhibiting mTORC1 but not mTORC2/AKT signalling. In contrast AZD8055, which rapidly inhibited both mTORC1 and mTORC2/AKT activity, was a highly effective (P <0.001) growth inhibitor of TamR (IC50 18 nM) and MCF7-X (IC50 24 nM), and of a further T47D-derived tamoxifen resistant model T47D-tamR (IC50 19 nM). AZD8055 significantly (P <0.05) inhibited resistant cell proliferation, increased cell death and reduced migration. Furthermore, dual treatment of TamR or MCF7-X cells with AZD8055 plus fulvestrant provided superior control of resistant growth versus either agent alone (P <0.05). Co-treating with AZD8055 alongside tamoxifen (P <0.01) or oestrogen deprivation (P <0.05) also effectively inhibited endocrine responsive MCF-7 cells. Although AZD8055 inhibited oestrogen receptor (ER) ser167 phosphorylation in TamR and MCF7-X, it had no effect on ER ser118 activity or expression of several ER-regulated genes, suggesting the mTOR kinase inhibitor impact was largely ER-independent. The capacity of AZD8055 for ER-independent activity was further evidenced by growth inhibition (IC5018 and 20 nM) of two acquired fulvestrant resistant models lacking ER.

Conclusions

This is the first report demonstrating dual mTORC1/2 mTOR kinase inhibitors have potential to control acquired endocrine resistant BC, even under conditions where everolimus fails. Such inhibitors may prove of particular benefit when used alongside anti-hormonal treatment as second-line therapy in endocrine resistant disease, and also potentially alongside anti-hormones during the earlier endocrine responsive phase to hinder development of resistance.
Lung protection during non-invasive synchronized assist versus volume control in rabbits
Authors: Mirabella Lucia , Grasselli Giacomo , Haitsma Jack J , Zhang Haibo , Slutsky Arthur S , Sinderby Christer , Beck Jennifer
Published: January 2014

Introduction

Experimental work provides insight into potential lung protective strategies. The objective of this study was to evaluate markers of ventilator-induced lung injury after two different ventilation approaches: (1) a “conventional” lung-protective strategy (volume control (VC) with low tidal volume, positive end-expiratory pressure (PEEP) and paralysis), (2) a physiological approach with spontaneous breathing, permitting synchrony, variability and a liberated airway. For this, we used non-invasive Neurally Adjusted Ventilatory Assist (NIV-NAVA), with the hypothesis that liberation of upper airways and the ventilator’s integration with lung protective reflexes would be equally lung protective.

Methods

In this controlled and randomized in vivo laboratory study, 25 adult White New Zealand rabbits were studied, including five non-ventilated control animals. The twenty animals with aspiration-induced lung injury were randomized to ventilation with either VC (6 mL/kg, PEEP 5 cm H2O, and paralysis) or NIV-NAVA for six hours (PEEP = zero because of leaks). Markers of lung function, lung injury, vital signs and ventilator parameters were assessed.

Results

At the end of six hours of ventilation (n = 20), there were no significant differences between VC and NIV-NAVA for vital signs, PaO2/FiO2 ratio, lung wet-to-dry ratio and broncho-alveolar Interleukin 8 (Il-8). Plasma IL-8 was higher in VC (P <0.05). Lung injury score was lower for NIV-NAVA (P = 0.03). Dynamic lung compliance recovered after six hours in NIV-NAVA but not in VC (P <0.05). During VC, peak pressures increased from 9.2 ± 2.4 cm H2O (hour 1) to 12.3 ± 12.3 cm H2O (hour 6) (P <0.05). During NIV-NAVA, the tracheal end-expiratory pressure was similar to the end-expiratory pressure during VC. Two animals regurgitated during NIV-NAVA, without clinical consequences, and survived the protocol.

Conclusions

In experimental acute lung injury, NIV-NAVA is as lung-protective as VC 6 ml/kg with PEEP.
Activation of Immobilized Glucose Oxidase Enzyme by Acoustic Wave Resonance Oscillation
Authors: Nishiyama Hiroshi , Kazui Masayuki , Inoue Yasunobu
Published: January 2014

Glucose oxidase enzyme was immobilized on ferroelectric LiNbO3 single crystals that were able to generate acoustic wave resonance oscillations by radio frequency electric power. The generation of the 3.6–14.7 MHz acoustic waves with lattice distortion vertical to the surface caused increases in the enzyme activity for glucose oxidation by decreasing the activation energy of reaction. A mechanism is proposed in which the acoustic waves enhance the interactions between the glucose substrate and the enzyme.
Gold Approaches to Polycyclic Indole Alkaloids
Authors: Barbour P Michael , Marholz Laura J , Chang Le , Xu Wenqing , Wang Xiang
Published: January 2014

Indole alkaloids are a highly diverse and ubiquitous family of natural products often identified in plants that have been used as traditional medicine for millennia. Because of their complex molecular architecture and relevance as potent pharmaceuticals, efficient methods for constructing these polycyclic skeletons are essential for their synthesis. Herein, we review recent developments in gold catalysis as a means toward the synthesis of many biologically important polycyclic indole alkaloids.
Cladonia lichens on extensive green roofs: evapotranspiration, substrate temperature, and albedo
Authors: Heim Amy , Lundholm Jeremy
Published: January 2014

Green roofs are constructed ecosystems that provide ecosystem services in urban environments. Shallow substrate green roofs subject the vegetation layer to desiccation and other environmental extremes, so researchers have evaluated a variety of stress-tolerant vegetation types for green roof applications. Lichens can be found in most terrestrial habitats.  They are able to survive extremely harsh conditions, including frequent cycles of desiccation and rehydration, nutrient-poor soil, fluctuating temperatures, and high UV intensities. Extensive green roofs (substrate depth <20cm) exhibit these harsh conditions, making lichens possible candidates for incorporation into the vegetation layer on extensive green roofs.  In a modular green roof system, we tested the effect ofCladonialichens on substrate temperature, water loss, and albedo compared to a substrate-only control. Overall, theCladoniamodules had significantly cooler substrate temperatures during the summer and significantly warmer temperatures during the fall.  Additionally, theCladoniamodules lost significantly less water than the substrate-only control. This implies that they may be able to benefit neighboring vascular plant species by reducing water loss and maintaining favorable substrate temperatures.
Problems Related to Creation of Scientific Schools in Pedagogy
Authors: Артемьева  , Artemyeva Svetlana
Published: January 2014

The author examines the concept of «scientific school» in the past and at present, describes the experience of formation of the Research School «Monitoring of Education Quality» at the Department of «Pedagogy and Psychology» in «Moscow State University of Technology and Management of K. Razumovsky»
The Russian Cossacks’ Deeds on the State and Military-and-Patriotic Service In The Continuous Education Context
Authors: Шафажинская  , Shafazhinskaya Natalya
Published: January 2014

The Cossacks’ heroic deeds during the hardest periods of the

Russian history are the embodiment of the archetypal to this country’s

culture image of the brave warrior and defender. Examples of how the

Cossacks proved themselves in terms of military expertise and patriotism

on the public service should be incorporated in the system of continuous

education and general liberal education of Cossack youth.
Methodological Basis For Arranging Problems of Pedagogical Practice
Authors: Афанасьев  , Afanasev Vladimir , Афанасьева  , Afanaseva I.
Published: January 2014

The detailed descriptions of the objective, subjective, systematic, information and technological approaches are presented, with the «methodological stuff» for each approach in the form of «circuit» and systematic methods for problem solving in the field of pedagogical practice.
Special Pedagogic Aspects Of Designing Educational Process With Regard To Students’ Psychological Traits
Authors: Савенкова  , Savenkova A.
Published: January 2014

It is discussed how to take into consideration the individual/

psychological features of students when designing the educational

process. Based on the findings of the Russian researchers, the author

identifies masculine and feminine characteristics of boys and girls, and

points out specific aspects to be considered when designing educational

processes for different gender groups.
Education Quality Management: A Review Of Methodological Concepts
Authors: Ахриева  , Akhrieva Anna
Published: January 2014

The issues related to the definition of «quality of education»

concept and several approaches developed in the area of education

quality management are outlined. The analytical review of academic

pedagogical literature is given. The concepts presented are treated

with respect to their practical applicability within the existing educational

systems. The ways to arrange potential problems are suggested.
Competitive Environment of Current Vocational Education
Authors: Ковалев  , Kovalev Dmitriy
Published: January 2014

The characteristic features of competitive environment in the

sphere of vocational education are discussed. The author extrapolates the

main trends specific to the training of competitive specialists on vocational

education.
The development of rural tourism and the formation of a training system
Authors: Павлов  , Pavlov O. , Павлова  , Pavlova E.
Published: January 2014

Great changes in socio-cultural, political and economic fields

require new understanding of professional education system in rural

development. Development of professional education system in rural

tourism is happened to be social demand of community: nowadays total

requirements for graduates are been changing. There is a need in new

understanding of professional education for rural tourism which can

combine both requirement in versatility on high education level and its

adequacy in order to satisfy needs of rural community.
Posttransplantation Bone Marrow Assessment by Quantifying Hematopoietic Cell–Derived mRNAs in Plasma Exosomes/Microvesicles
Authors: Aoki Jun , Ohashi Kazuteru , Mitsuhashi Masato , Murakami Taku , Oakes Melanie , Kobayashi Takeshi , Doki Noriko , Kakihana Kazuhiko , Sakamaki Hisashi
Published: January 2014

BACKGROUND

Bone marrow (BM) aspiration often can be a painful medical procedure. It is unavoidable, however, because hematopoietic precursor cells (HPC) exist only in BM and few escape to peripheral blood (PB). We hypothesized that HPCs might release exosomes and microvesicles (EMV) in BM, and the resulting EMV would penetrate into PB. Such BM-derived EMV might be identified in PB by measuring specific mRNAs produced by HPC.

METHODS

Human plasma was applied to an EMV-capture filter plate. After centrifugation, captured EMV were lysed on the filter plate. Resulting lysates were transferred to an oligo(dT)-immobilized microplate for mRNA isolation followed by reverse transcription PCR (RT-PCR). Using this system, myeloid-, erythroid-, and megakaryocyte-lineage–specific poly(A)+ mRNAs were quantified in plasma obtained from 18 patients who had undergone hematopoietic stem cell transplantation (HSCT).

RESULTS

When fluorescent liposomes were applied to the filter plate, more than 95% of applied liposomes were absorbed. When human plasma was applied, a scanning electron microscope showed EMV-like particles on the membrane of the filter plate. After RT-PCR, various HPC-specific mRNAs were detected, and the results were equivalent to those derived from the standard ultracentrifugation method. The levels of these mRNAs were undetectable after HSCT and became detectable 1–2 weeks after HSCT, a substantially earlier time point than with traditional hematological analysis. The recovery of EMV mRNA at day 15 corresponded to the final clinical outcome at day 180.

CONCLUSIONS

HPC-derived mRNAs in plasma EMV may represent new biomarkers for the assessment of BM condition and could reduce the necessity for frequent BM aspiration.
Da violência à civilização hércules, o super‑homem da antiguidade
Authors: Silva Maria De Fátima
Published: January 2014

Hércules, o herói de uma antiguidade insondável, situou‑se no mundo grego comoum símbolo pan‑helénico. Como figura transversal na cultura e na literatura grega ao longo dos séculos, o filho de Zeus e de Alcmena sofreu um processo de ajustamento a uma mentalidade em constante evolução. Assim, de vencedor brutal e violento, evoluiu para o protector de fracos e símbolo de um processo civilizacional, que ajudou a construir.
As aulas e os problemas de filosofia natural do P. Francisco Mendoça SJ
Authors: Urbano Carlota Miranda
Published: January 2014

A autora propõe-se apresentar o De floribus Philosophiae do célebre jesuítaFrancisco Mendoça (†1626), que foi professor de Filosofia e reitor no Colégiodas Artes em Coimbra nos primeiros anos do séc. XVII. A obra em causa vempublicada num grosso volume que o mesmo Colégio editou depois da sua mortee que teve por título: Viridarium Sacrae et profanae eruditionis ou Jardim deerudição sagrada e profana, um verdadeiro monumento do saber enciclopédico.No De floribus Philosophiae, reúnem-se 47 problemas ou questões que hojediriam respeito a domínios do saber tão distintos como a geografia e a anatomia, a física e a psicologia, ou a astronomia e a antropologia. A compreensão de um texto desta natureza carece, por isso, de uma abordagem multidisciplinar que não cabe num estudo desta dimensão. No entanto, apresentado na perspectiva do humanista, o texto do P. Mendoça pode oferecer ao cientista matéria para o estudo da história das ciências. É o que nos propomos fazer, seleccionando para o nosso trabalho alguns passos. São de assinalar, entre outros aspectos, o rigor na citação e a variedade de autores citados, desde os antigos clássicos e pagãos aos mais recentes e contemporâneos do mestre que viriam a ser reconhecidos como reputados físicos, astrónomos e matemáticos.
A Helena de Seferis, um grito contra a guerra
Authors: Pociña Andrés
Published: January 2014

Aproximación y comentario del poema “Helena” (1953) del eximio poeta griego Yorgos Seferis, premio Nobel de Literatura en 1963; después de su traducción al portugués, el autor estudia las curiosas circunstancias de su publicación, su relación con los antecedentes clásicos, su significado en la obra y en la vida de Seferis y en la Grecia de 1955, y, por último, su sentido universal como poema antibélico y pacifista en una Grecia y una Europa sumidas en la persistente destrucción física y política que marcó buena parte del siglo XX, cuyas consecuenicas se viven tan trágicamente todavía en nuestros días en Grecia y otros países del Mediterráneo.
La Antígona de Fenicias o la larga sombra de la Antígona de Sófocles
Authors: Talens Carmen Morenilla
Published: January 2014

La sombra de la Antígona de Sófocles ha mediatizado la transmisión e interpretación de las Fenicias de Eurípides. Tres pasajes de Fenicias proyectan en conjunto la imagen de una Antígona muy humana y de una gran entereza de ánimo, próxima al personaje de Sófocles. El primero, la teichoscopía del prólogo; el segundo, una escena central, vv. 1264‑1283, preludio del último estásimo. En el tercero, formado por dos escenas, vv. 1480‑1539 y 1540‑1580, el protagonismo de Antígona es notable y revelador de su carácter. La ausencia del primero, cuya autenticidad ha sido cuestionada, privaría a la Antígona de Fenicias de unos rasgos de carácter que en conjunto hacen de ella un personaje muy humano.
Las citas de Platón en las Cuestiones homericas de Porfirio
Authors: Guillén Lucía Rodríguez‑Noriega
Published: January 2014

Este trabajo estudia las citas de Platón contenidas en las Cuestiones Homéricasde Porfirio, ocupándose de su tipología (cita literal, alusión, paráfrasis, etc.), si setrata o no de citas de primera mano, su función en la obra y sus posibles paralelosen otros autores.
El discurso de Agripa en la Guerra de los judíos de Flavio Josefo: apuntes para un análisis estilístico
Authors: Horrillo Miguel Ángel Rodríguez
Published: January 2014

Se analiza el discurso de Agripa en el libro segundo de la Guerra de los judíos desde un punto de vista estilístico. El discurso constituye un ejemplo de μελετή literaria en el que Josefo emplea los recursos de imitación y de estilo para generar interacciones culturales entre la Grecia clásica y el presente.
Preconceito e ciência: o ataque de Pietro Andrea Mattioli a Amato Lusitano
Authors: Pinto Antônio Guimarães
Published: January 2014

Neste artigo, que decorre da tradução, que acabámos há pouco, do livro que o médico e botânico italiano Pietro Andrea Mattioli escreveu em latim contra o também médico Amato Lusitano, procurámos mostrar como o preconceito religioso e racial, de par com a soberba académica, podem distorcer o rigor e isenção nas ciências mais aparentemente isentas de motivações ideológicas ou nacionais. Numa perspectiva de análise sobretudo literária e histórico‑cultural, tentámos provar a falta de probidade científica e seriedade moral com que o conceituado sábio de Siena atacou e procurou destruir a carreira científica, e quem sabe até a própria existência física, do seu colega hebreu‑português.
Consideraciones sobre la crisis de los años 68-69
Authors: Rabanal Alonso Manuel Abilio
Published: January 2014

El año que va desde la muerte de Nerón al comienzo del imperio de Vespasiano representa una encrucijada militar y socioeconómica. Sus protagonistas merecen el calificativo de triunfadores coyunturales. Cuando llegar al poder depende de la mejor oferta económica o de la donación de puestos administrativos, nada puede haber políticamente consistente. Esta es una de las razones fundamentales de la crisis del año conocido como «de los cuatro emperadores».
Quantum Grothendieck rings and derived Hall algebras
Authors: Hernandez David , Leclerc Bernard
Published: January 2014

Let 𝔤 = 𝔫 ⊕ 𝔥 ⊕ 𝔫- be a simple Lie algebra over ℂ of type A, D, E, and let
Uq
(L𝔤) be the associated quantum loop algebra.
Following Nakajima [Ann. of Math. (2) 160 (2004), 1057–1097], Varagnolo–Vasserot [Studies in memory of Issai Schur, Birkhäuser-Verlag, Basel (2002), 345–365], and the
first author [Adv. Math. 187 (2004), 1–52],
we study a t-deformation 𝒦
t
of the Grothendieck ring of
a tensor category 𝒞ℤ of finite-dimensional Uq
(L𝔤)-modules.
We obtain a presentation of 𝒦
t
by generators and relations.

Let Q be a Dynkin quiver of the same type as 𝔤.
Let DH(Q) be the derived Hall algebra of the bounded derived category
Db
(mod(F
Q)) over a finite field F,
introduced by Toën [Duke Math. J. 135 (2006), 587–615]. Our presentation shows that
the specialization of 𝒦
t
at t = |F|1/2 is isomorphic to
DH(Q). Under this isomorphism, the classes of fundamental Uq
(L𝔤)-modules
are mapped to scalar multiples of the classes of indecomposable objects in DH(Q).

Our presentation of 𝒦
t
is deduced from the preliminary study of a tensor subcategory 𝒞
Q
of 𝒞ℤ analogous to the heart mod(F
Q) of the
triangulated category Db
(mod(F
Q)). We show that the t-deformed
Grothendieck ring 𝒦
t,Q
of 𝒞
Q
is isomorphic to the positive
part of the quantum enveloping algebra of 𝔤, and that the basis
of classes of simple objects of 𝒦
t,Q
corresponds to the dual of
Lusztig's canonical basis. The proof relies on the algebraic characterizations
of these bases, but we also give a geometric approach in the last section.

It follows that for every orientation Q of the Dynkin diagram,
the category 𝒞
Q
gives a new categorification of the
coordinate ring ℂ[N] of a unipotent group N
with Lie algebra 𝔫,
together with its dual canonical basis.