bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing Origin of Binding Difference of inhibitors to MDM2 and MDMX by Polarizable Molecular Dynamics Simulation and QM/MM-GBSA Calculation
Authors: Chen Jianzhong , Wang Jinan , Zhang Qinggang , Chen Kaixian , Zhu Weiliang 
Published: November 2015

AbstractBinding abilities of current inhibitors to MDMX are weaker than to MDM2. Polarizable molecular dynamics simulations (MD) followed by Quantum mechanics/molecular mechanics generalized Born surface area (QM//MM-GBSA) calculations were performed to investigate the binding difference of inhibitors to MDM2 and MDMX. The predicted binding free energies not only agree well with the experimental results, but also show that the decrease in van der Walls interactions of inhibitors with MDMX relative to MDM2 is a main factor of weaker bindings of inhibitors to MDMX. The analyses of dihedral angles based on MD trajectories suggest that the closed conformation formed by the residues M53 and Y99 in MDMX leads to a potential steric clash with inhibitors and prevents inhibitors from arriving in the deep of MDMX binding cleft, which reduces the van der Waals contacts of inhibitors with M53, V92, P95 and L98. The calculated results using the residue-based free energy decomposition method further prove that the interaction strength of inhibitors with M53, V92, P95 and L98 from MDMX are obviously reduced compared to MDM2. We expect that this study can provide significant theoretical guidance for designs of potent dual inhibitors to block the p53-MDM2/MDMX interactions.
Metformin suppressed the proliferation of LoVo cells and induced a time-dependent metabolic and transcriptional alteration
Authors: He Jiaojiao , Wang Ke , Zheng Ningning , Qiu Yunping , Xie Guoxiang , Su Mingming , Jia Wei , Li Houkai 
Published: November 2015

AbstractMetformin is a widely used anti-diabetic drug with potential anti-tumor activity. However, little is known about its global metabolic and transcriptional impacts on tumor cells. In current study, we performed a metabolic profiling on human-derived colon cancer LoVo cells treated by 10 mM metformin for 8, 24 and 48 h. An obvious time-dependent metabolic alteration was observed from 8 to 48 h, prior to the reduction of cell viability. A total of 47, 45 and 66 differential metabolites were identified between control and metformin-treated cells at three time points. Most of the metabolites were up-regulated at 8 h, but down-regulated at 24 and 48 h by metformin. These metabolites were mainly involved in carbohydrates, lipids, amino acids, vitamins and nucleotides metabolism pathways. Meanwhile, the transcirptomic profile revealed 134 and 3061 differentially expressed genes at 8 and 24 h by metformin. In addition to the cancer signaling pathways, expression of genes involved in cell energy metabolism pathways was significantly altered, which were further validated with genes in glucose metabolism pathway. Altogether, our current data indicate that metformin suppressed the proliferation of LoVo cells, which may be due to the modulation on cell energy metabolism at both metabolic and transcriptional levels in a time-dependent way.
A Novel Self-Assembling Al-based Composite Powder with High Hydrogen Generation Efficiency
Authors: Wang Cuiping , Liu Yuheng , Liu Hongxin , Yang Tao , Chen Xinren , Yang Shuiyuan , Liu Xingjun 
Published: November 2015

AbstractIn this study, a novel self-assembling hydrogen generation powder comprised of 80Al-10Bi-10Sn wt.% was prepared using the gas atomization method and then collected in an air environment. The morphological and hydrolysis properties of the powders were investigated. The results indicated that the powders formed unique core/shell microstructures with cracked surfaces and (Bi, Sn)-rich phases distributed on the Al grain boundaries. The powders exhibited good oxidation resistance and reacted violently with distilled water at temperatures as low as 0 °C. Furthermore, at 30 °C, the powders exhibited a hydrogen conversion yield of 91.30% within 16 minutes. The hydrogen produced by this powder could be directly used in proton exchange membrane fuel cells. The mechanisms of the hydrolysis reactions were also analyzed.
Resonances of nanoparticles with poor plasmonic metal tips
Authors: Ringe Emilie , DeSantis Christopher J. , Collins Sean M. , Duchamp Martial , Dunin-Borkowski Rafal E. , Skrabalak Sara E. , Midgley Paul A. 
Published: November 2015

AbstractThe catalytic and optical properties of metal nanoparticles can be combined to create platforms for light-driven chemical energy storage and enhanced in-situ reaction monitoring. However, the heavily damped plasmon resonances of many catalytically active metals (e.g. Pt, Pd) prevent this dual functionality in pure nanostructures. The addition of catalytic metals at the surface of efficient plasmonic particles thus presents a unique opportunity if the resonances can be conserved after coating. Here, nanometer resolution electron-based techniques (electron energy loss, cathodoluminescence and energy dispersive X-ray spectroscopy) are used to show that Au particles incorporating a catalytically active but heavily damped metal, Pd, sustain multiple size-dependent localized surface plasmon resonances (LSPRs) that are narrow and strongly localized at the Pd-rich tips. The resonances also couple with a dielectric substrate and other nanoparticles, establishing that the full range of plasmonic behavior is observed in these multifunctional nanostructures despite the presence of Pd.
Microenvironmental Hypoxia regulates FLT3 expression and biology in AML
Authors: Sironi Silvia , Wagner Michaela , Kuett Alexander , Drolle Heidrun , Polzer Harald , Spiekermann Karsten , Rieger Christina , Fiegl Michael 
Published: November 2015

AbstractFms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase constitutively expressed by acute myeloid leukaemia (AML) blasts. In addition, 25% of AML patients harbour a FLT3-ITD mutation, associated with inferior outcome due to increased relapse rate. Relapse might be propagated by interactions between AML blasts and the bone marrow microenvironment. Besides cellular elements of the microenvironment (e.g. mesenchymal stromal cells), bone marrow hypoxia has emerged as an additional crucial component. Hence, effects of hypoxia on FLT3 expression and biology could provide novel insight into AML biology. Here we show that 25% of AML patients down-regulate FLT3 expression on blasts in response to in vitro hypoxia (1% O2), which was independent of its mutational state. While virtually no AML cell lines regulate FLT3 in response to hypoxia, the down-regulation could be observed in Ba/F3 cells stably transfected with different FLT3 mutants. Hypoxia-mediated down-regulation was specific for FLT3, reversible and proteasome-dependent; with FLT3 half-life being significantly shorter at hypoxia. Also, PI-3K inhibition could partially abrogate down-regulation of FLT3. Hypoxia-mediated down-regulation of FLT3 conferred resistance against cytarabine in vitro. In conclusion, FLT3 expression in AML is dependent on the oxygen partial pressure, but response to hypoxia differs.
Femtosecond laser rapid fabrication of large-area rose-like micropatterns on freestanding flexible graphene films
Authors: Shi Xuesong , Li Xin , Jiang Lan , Qu Liangti , Zhao Yang , Ran Peng , Wang Qingsong , Cao Qiang , Ma Tianbao , Lu Yongfeng 
Published: November 2015

AbstractWe developed a simple, scalable and high-throughput method for fabrication of large-area three-dimensional rose-like microflowers with controlled size, shape and density on graphene films by femtosecond laser micromachining. The novel biomimetic microflower that composed of numerous turnup graphene nanoflakes can be fabricated by only a single femtosecond laser pulse, which is efficient enough for large-area patterning. The graphene films were composed of layer-by-layer graphene nanosheets separated by nanogaps (~10–50 nm) and graphene monolayers with an interlayer spacing of ~0.37 nm constituted each of the graphene nanosheets. This unique hierarchical layering structure of graphene films provides great possibilities for generation of tensile stress during femtosecond laser ablation to roll up the nanoflakes, which contributes to the formation of microflowers. By a simple scanning technique, patterned surfaces with controllable densities of flower patterns were obtained, which can exhibit adhesive superhydrophobicity. More importantly, this technique enables fabrication of the large-area patterned surfaces at centimeter scales in a simple and efficient way. This study not only presents new insights of ultrafast laser processing of novel graphene-based materials but also shows great promise of designing new materials combined with ultrafast laser surface patterning for future applications in functional coatings, sensors, actuators and microfluidics.
QUANTITY: An Isobaric Tag for Quantitative Glycomics
Authors: Yang Shuang , Wang Meiyao , Chen Lijun , Yin Bojiao , Song Guoqiang , Turko Illarion V. , Phinney Karen W. , Betenbaugh Michael J. , Zhang Hui , Li Shuwei 
Published: November 2015

AbstractGlycan is an important class of macromolecules that play numerous biological functions. Quantitative glycomics - analysis of glycans at global level - however, is far behind genomics and proteomics owing to technical challenges associated with their chemical properties and structural complexity. As a result, technologies that can facilitate global glycan analysis are highly sought after. Here, we present QUANTITY (Quaternary Amine Containing Isobaric Tag for Glycan), a quantitative approach that can not only enhance detection of glycans by mass spectrometry, but also allow high-throughput glycomic analysis from multiple biological samples. This robust tool enabled us to accomplish glycomic survey of bioengineered Chinese Hamster Ovary (CHO) cells with knock-in/out enzymes involved in protein glycosylation. Our results demonstrated QUANTITY is an invaluable technique for glycan analysis and bioengineering.
The Dimensionality of Spanish in Young Spanish–English Dual-Language Learners
Authors:   Language and Reading Research Consortium (LARRC)
Published: November 2015

Purpose
This study examined the latent dimensionality of Spanish in young Spanish–English dual-language learners (DLLs).

Method
Two hundred eighty-six children participated. In their prekindergarten year, children completed norm-referenced and experimental language measures in Spanish requiring different levels of cognitive processing in both receptive and expressive language modalities.

Results

The best-fitting model suggested a bifactor solution with a single general language factor
L
plus two additional factors
word knowledge
and
integrative language knowledge
. The general trait
L
reflects the proportion of common item variance for all of the items, and the group traits of word knowledge and integrative language knowledge explain additional domain-specific variance for those item subsets.

Conclusion

Results suggest that the Spanish language in preschool-age Spanish–English DLLs is not separable into content, form, and use, nor is it separable by higher- and lower-level language domains or processing demands. Instead it appears that a general language factor underlies oral language in Spanish in DLL preschoolers and that other factors account for additional variance over and above
L
. Findings are discussed in relation to a companion study of monolingual English-speaking prekindergarteners.

Supplemental Material

https://doi.org/10.23641/asha.6170303
Performance evaluation of broken gap Esaki tunnel diodes on Si and GaSb substrates
Authors: Thomas P.M. , Filmer M.J. , Gaur A. , Rommel S.L. , Bhatnagar K. , Droopad R. 
Published: November 2015

n‐InAs/p‐GaSb Esaki diodes with 3 nm GaSb i‐layers are fabricated on Si and GaSb substrates. The on Si sample devices exhibit lower peak to valley ratios and peak current density than their on GaSb counterparts at 3.27 against 4.45 and 119 against 336 kA/cm2, respectively. The findings are similar to other reports of integrating III–V Esaki diodes onto Si.
Bandwidth enhancement of compact monopole antenna with triple band rejections
Authors: Li Tong , Zhu Cheng , Cao Xiangyu , Gao Jun 
Published: November 2015

A compact monopole antenna with enhanced bandwidth and triple band rejections for ultra‐wideband applications is presented. The base of the proposed antenna is a semicircular patch which is fed by a modified tapered coplanar waveguide line. By using the trident‐shaped feed line, much wider impedance bandwidth is obtained. To avoid potential interferences, two trapezoid stubs and a C‐shaped stub are printed on the back surface of the substrate and are connected to the antenna through three vias. The proposed antenna is practically fabricated with a compact size of 20 × 24 mm2. Good agreement is achieved between the simulation and measurement, which shows that the proposed antenna offers a very wide bandwidth from 3.02 to 20.8 GHz (149%) with triple band rejections covering the 3.5 GHz WiMAX and 5.2/5.8 GHz WLAN bands.
High dynamic range single channel sampling of wideband RF signals using ultra‐fast nanoscale photoconductive switching
Authors: Tripon‐Canseliet C. , Zegaoui M. , Jestin G. , Coinon C. , Berger P. , Baili G. , Descamps‐Mandine A. , Maksimovic I. , Decoster D. , Hodé J.M. , Dolfi D. , Chazelas J. 
Published: November 2015

This Letter reports on new experimental high dynamic range sub‐sampling performances obtained from nanoscale microwave photoconductive switches operating under a 0.8 µm wavelength pulsed illumination. Experimental results have been performed on different samples benefiting of a low temperature grown Gallium Arsenide absorbing layer on GaAs substrate, coplanar microwave electrode profile optimisation, and the use of an ultra‐low noise jitter optical source delivering optical pulses of 1 to10 ps pulse width at a 2 GHz repetition frequency at 0.8 µm optical wavelength. Thanks to carrier lifetime tunability achievement from 1 to 20 ps, in association with a carrier mobility of 3900 cm²/V.s, experimental demonstrations of 54 and 45 dB signal‐to‐noise ratio microwave signal sampling for signals at 5,76 and 20 GHz frequency bandwidth respectively confirms submicron devices functionality as a new class of single channel photonic analogue to digital converters.
Very large bandwidth continuous time analogue equaliser in InP DHBT for beyond‐100 GBd optical communication applications
Authors: Mettetal R. , Dupuy J.‐Y. , Jorge F. , Riet M. , Nodjiadjim V. , Konczykowska A. , Ouslimani A. 
Published: November 2015

The study, design and measurement of a continuous time analogue equaliser based on a differential cascode amplifier cell, using indium phosphide double heterojunction bipolar transistors (DHBTs) reaching an fT/fmax of 370/340 GHz are reported. A bandwidth of more than 110 GHz is achieved and a peaking of 18 dB at 95 GHz is reached. Simulations demonstrated an equalisation at 205 Gbit/s. This is believed to be the highest frequency peaking reported to date.
Temporal development of coastal ecosystems in the Baltic Sea over the past two decades
Authors: Olsson Jens , Tomczak Maciej T. , Ojaveer Henn , Gårdmark Anna , Põllumäe Arno , Müller-Karulis Bärbel , Ustups Didzis , Dinesen Grete E. , Peltonen Heikki , Putnis Ivars , Szymanek Lena , Simm Mart , Heikinheimo Outi , Gasyukov Pavel , Axe Philip , Bergström Lena 
Published: November 2015

Abstract
Coastal areas are among the most biologically productive aquatic systems worldwide, but face strong and variable anthropogenic pressures. Few studies have, however, addressed the temporal development of coastal ecosystems in an integrated context. This study represents an assessment of the development over time in 13 coastal ecosystems in the Baltic Sea region during the past two decades. The study covers between two to six trophic levels per system and time-series dating back to the early 1990s. We applied multivariate analyses to assess the temporal development of biological ecosystem components and relate these to potential driving variables associated with changes in climate, hydrology, nutrient status, and fishing pressure. Our results show that structural change often occurred with similar timing in the assessed coastal systems. Moreover, in 10 of the 13 systems, a directional development of the ecosystem components was observed. The variables representing key ecosystem components generally differed across systems, due to natural differences and limitation to available data. As a result of this, the correlation between the temporal development of the biological components in each area and the driving variables assessed was to some extent area-specific. However, change in nutrient status was a common denominator of the variables most often associated with changes in the assessed systems. Our results, additionally, indicate existing strengths as well as future challenges in the capacity of currently available monitoring data to support integrated assessments and the implementation of an integrated ecosystem-based approach to the management of the Baltic Sea coastal ecosystems.
CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas
Authors: Butcher Matthew J. , Wu Chih-I , Waseem Tayab , Galkina Elena V. 
Published: November 2015

Abstract
The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A+ cells play a role in this disease. Although elevated number of CD4+ IL-17A+ (Th17) and IL-17A+TCRγδ+ T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL-17A+ T-cell migration to atherosclerotic lesions are unclear. The chemokine receptor CXCR6 is expressed on several T-cell subsets and plays a pro-atherogenic role in atherosclerosis. Here, we used CXCR6-deficient (Cxcr6GFP/GFP) apolipoprotein E-deficient (Apoe−/−) mice to investigate the involvement of CXCR6 in the recruitment IL-17A+ T cells to atherosclerotic aortas. Flow cytometric analyses revealed reductions in Th17 and IL-17A+TCRγδ+ T cells within aged Cxcr6GFP/GFPApoe−/− aortas, in comparison with age-matched Cxcr6GFP/+Apoe−/− aortas. Although CXCR6-sufficient IL-17A+ T cells efficiently migrated toward CXCL16, the migration of CXCR6-deficient IL-17A+ T cells was abolished in transwell assays. Importantly, the recruitment of Cxcr6GFP/GFPApoe−/− IL-17A+ T cells into the aortas of Apoe−/− recipients was markedly reduced in short-term adoptive transfer experiments. Altogether these results demonstrate an important role of CXCR6 in the regulation of pathological Th17 and IL-17A+TCRγδ+ T-cell recruitment into atherosclerotic lesions.
Two Independent and Highly Efficient Open Source TKF91 Implementations
Authors: Baudis Nikolai , Barbera Pierre , Graf Sebastian , Lutteropp Sarah , Opitz Daniel , Flouri Tomáš , Stamatakis Alexandros 
Published: November 2015

AbstractIn the context of a master level programming practical at the computer science department of the Karlsruhe Institute of Technology, we developed and make available two independent and highly optimized open-source implementations for the pair-wise statistical alignment model, also known as TKF91, that was developed by Thorne, Kishino, and Felsenstein in 1991. This paper has two parts. In the educational part, we cover teaching issues regarding the setup of the course and the practical and summarize student and teacher experiences. In the scientific part, the two student teams (Team I: Nikolai, Sebastian, Daniel; Team II: Sarah, Pierre) present their solutions for implementing efficient and numerically stable implementations of the TKF91 algorithm. The two teams worked independently on implementing the same algorithm. Hence, since the implementations yield identical results —with slight numerical deviations— we are confident that the implementations are correct. We describe the optimizations applied and make them available as open-source codes in the hope that our findings and software will be useful to the community as well as for similar programming practicals at other universities.
Stimulation of neuronal cells by culture supernatant of T lymphocytes triggered by anti‐CD3 mAb followed by propagation in the presence of interleukin‐2
Authors: Ishiguro Masae , Okada Alan , Asai Kiyofumi , Kojima Kiyohide , Okada Hidechika 
Published: November 2015

ABSTRACTPerformance status (PS) frequently improves occurs in cancer patients who have been infused with their own lymphokine‐activated killer T cells (LAK‐T). In the present study, a culture supernatant of LAK‐T (LAK‐T sup) administered to 8‐week‐old rats caused neurogenesis as evidenced by increased 5‐ethynyl‐2′‐deoxyuridine staining of brain tissues. Intravenous injection of granulocyte‐macrophage colony stimulating factor (GM‐CSF), a major cytokine in LAK‐T sup, had a similar effect. Furthermore, LAK‐T sup induced Ca++ increase in rat hippocampal brain slices that was detected in neuronal cells by emission of Fluo‐8 NW at 520 nm. The same effect was observed with an rGM‐CSF solution. GM‐CSF may activate neuronal cells by stimulating the glial cells that surround and attach to them. If so, GM‐CSF and LAK‐T sup may improve the motor neurons of patients with amyotrophic lateral sclerosis. The neurogenerative effect of GM‐CSF in LAK‐T sup may also help improve brain function in aged adults including those with dementia such as Alzheimer's disease.
Selective extinction drives taxonomic and functional alpha and beta diversities in island bird assemblages
Authors: Si Xingfeng , Baselga Andrés , Leprieur Fabien , Song Xiao , Ding Ping 
Published: November 2015

Summary

Taxonomic diversity considers all species being equally different from each other and thus disregards species’ different ecological functions. Exploring taxonomic and functional aspects of biodiversity simultaneously can better understand the processes of community assembly.

We analysed taxonomic and functional alpha and beta diversities of breeding bird assemblages on land‐bridge islands in the Thousand Island Lake, China. Given the high dispersal ability of most birds at this spatial scale (several kilometres), we predicted (i) selective extinction driving alpha and beta diversities after the creation of land‐bridge islands of varying area and (ii) low taxonomic and functional beta diversities that were not correlated to spatial distance.

Breeding birds were surveyed on 37 islands annually from 2007 to 2014. We decomposed beta diversity of breeding birds into spatial turnover and nestedness‐resultant components, and related taxonomic and functional diversities to island area and isolation using power regression models (for alpha diversity) and multiple regression models on distance matrices (for beta diversity). We then ran simulations to assess the strength of the correlations between taxonomic and functional diversities.

Results revealed that both taxonomic and functional alpha diversities increased with island area. The taxonomic nestedness‐resultant and turnover components increased and decreased with difference in area, respectively, but functional counterparts did not. Isolation played a minor role in explaining alpha‐ and beta‐diversity patterns. By partitioning beta diversity, we found low levels of overall taxonomic and functional beta diversities. The functional nestedness‐resultant component dominated overall functional beta diversity, whereas taxonomic turnover was the dominant component for taxonomic beta diversity. The simulation showed that functional alpha and beta diversities were significantly correlated with taxonomic diversities, and the observed values of correlations were significantly different from null expectations of random extinction.

Our assessment of island bird assemblages validated the predictions of no distance effects and low beta diversity due to pervasive dispersal events among islands and also suggested that selective extinction drives taxonomic and functional alpha and beta diversities. The contrasting turnover and nestedness‐resultant components of taxonomic and functional beta diversities demonstrate the importance of considering the multifaceted nature of biodiversity when examining community assembly.