bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical absorbers based on strong interference in ultra‐thin films
Authors: Kats Mikhail A. , Capasso Federico 
Published: September 2016

AbstractOptical absorbers find uses in a wide array of applications across the electromagnetic spectrum, including photovoltaic and photochemical cells, photodetectors, optical filters, stealth technology, and thermal light sources. Recent efforts have sought to reduce the footprint of optical absorbers, conventionally based on graded structures or Fabry‐Perot‐type cavities, by using emerging concepts in plasmonics, metamaterials, and metasurfaces. Unfortunately, these new absorber designs require patterning on subwavelength length scales, and are therefore impractical for many large‐scale optical and optoelectronic devices.In this article, we summarize recent progress in the development of optical absorbers based on lossy films with thicknesses significantly smaller than the incident optical wavelength. These structures have a small footprint and require no nanoscale patterning. We outline the theoretical foundation of these absorbers based on “ultra‐thin‐film interference”, including the concepts of loss‐induced phase shifts and critical coupling, and then review several applications, including ultra‐thin color coatings, decorative photovoltaics, high‐efficiency photochemical cells, and infrared scene generators.
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Tensile versus AFM testing of electrospun PVA nanofibers: Bridging the gap from Microscale to nanoscale
Authors: Neugirg Benedikt R. , Burgard Matthias , Greiner Andreas , Fery Andreas 
Published: September 2016

ABSTRACTDesign and application of mechanically extraordinary nanofibers requires their full comprehension, based on conclusive testing methods. Electrospun polymer nanofibers, for instance, show a progressive and pronounced increase in their Young's moduli when diameters decrease below the µm scale. Measurement of mechanical properties in this diameter range is challenging and in the vast majority of reports, two classes of methods are commonly used: highly sensitive tensile testing and atomic force microscopy three‐point deformation testing. Despite the methods' inherent dissimilarity, we resolve their conformity for the first time, with respect to the determination of Young's moduli. Here, we benchmark them against each other for electrospun polyvinyl‐alcohol nanofibers, a well‐defined model system. Our results provide an experimental basis for a comprehensive understanding of nanofiber structures and its implications on their mechanical properties. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 2418–2424
The intervening removable affinity tag (iRAT) production system facilitates Fv antibody fragment‐mediated crystallography
Authors: Nomura Yayoi , Sato Yumi , Suno Ryoji , Horita Shoichiro , Iwata So , Nomura Norimichi 
Published: September 2016

AbstractFv antibody fragments have been used as co‐crystallization partners in structural biology, particularly in membrane protein crystallography. However, there are inherent technical issues associated with the large‐scale production of soluble, functional Fv fragments through conventional methods in various expression systems. To circumvent these problems, we developed a new method, in which a single synthetic polyprotein consisting of a variable light (VL) domain, an intervening removable affinity tag (iRAT), and a variable heavy (VH) domain is expressed by a Gram‐positive bacterial secretion system. This method ensures stoichiometric expression of VL and VH from the monocistronic construct followed by proper folding and assembly of the two variable domains. The iRAT segment can be removed by a site‐specific protease during the purification process to yield tag‐free Fv fragments suitable for crystallization trials. In vitro refolding step is not required to obtain correctly folded Fv fragments. As a proof of concept, we tested the iRAT‐based production of multiple Fv fragments, including a crystallization chaperone for a mammalian membrane protein as well as FDA‐approved therapeutic antibodies. The resulting Fv fragments were functionally active and crystallized in complex with the target proteins. The iRAT system is a reliable, rapid and broadly applicable means of producing milligram quantities of Fv fragments for structural and biochemical studies.
Effects of ligand binding on the stability of aldo–keto reductases: Implications for stabilizer or destabilizer chaperones
Authors: Kabir Aurangazeb , Honda Ryo P. , Kamatari Yuji O. , Endo Satoshi , Fukuoka Mayuko , Kuwata Kazuo 
Published: September 2016

AbstractLigands such as enzyme inhibitors stabilize the native conformation of a protein upon binding to the native state, but some compounds destabilize the native conformation upon binding to the non‐native state. The former ligands are termed “stabilizer chaperones” and the latter ones “destabilizer chaperones.” Because the stabilization effects are essential for the medical chaperone (MC) hypothesis, here we have formulated a thermodynamic system consisting of a ligand and a protein in its native‐ and non‐native state. Using the differential scanning fluorimetry and the circular dichroism varying the urea concentration and temperature, we found that when the coenzyme NADP+ was absent, inhibitors such as isolithocholic acid stabilized the aldo–keto reductase AKR1A1 upon binding, which showed actually the three‐state folding, but destabilized AKR1B10. In contrast, in the presence of NADP+, they destabilized AKR1A1 and stabilized AKR1B10. To explain these phenomena, we decomposed the free energy of stabilization (ΔΔG) into its enthalpy (ΔΔH) and entropy (ΔΔS) components. Then we found that in a relatively unstable protein showing the three‐state folding, native conformation was stabilized by the negative ΔΔH in association with the negative ΔΔS, suggesting that the stabilizer chaperon decreases the conformational fluctuation of the target protein or increase its hydration. However, in other cases, ΔΔG was essentially determined by the delicate balance between ΔΔH and ΔΔS. The proposed thermodynamic formalism is applicable to the system including multiple ligands with allosteric interactions. These findings would promote the development of screening strategies for MCs to regulate the target conformations.
Tolerability of a rapid‐escalation vinblastine‐prednisolone protocol in dogs with mast cell tumours
Authors: Serra Varela Juan Carlos , Pecceu Evi , Handel Ian , Lawrence Jessica 
Published: September 2016

AbstractOptimal chemotherapy protocols for high‐risk mast cell tumours (MCTs) are unknown. The purpose of this study was to determine the tolerability and toxicity profile of a rapidly escalating vinblastine and prednisolone protocol (VPP) in which 3.00 mg/m2was administered once 7 days apart: at day 14 and at day 21. Dogs with chemotherapy‐naïveMCTs presenting to the Oncology Service of a single institution were prospectively enrolled to receive escalating vinblastine, and haematology and a standardised quality‐of‐life questionnaire were assessed prior to each dosage. Thirty‐four dogs were included: 30 with microscopic disease treated with adequate local therapy and four with macroscopic disease. Of 220 doses of vinblastine administered, 4% were associated with grade 3 and 4 toxicity. A total of 70% of dogs tolerated 3.00 mg/m2given 7 days apart at day 14 and 21, although 29% of dogs developed dose‐limiting toxicities and 8% discontinued the protocol due to toxicity. In conclusion,VPPwas well‐tolerated overall, although prior to further dose intensity optimisation, it is important to determine if dose intensity is linked to outcome in canineMCTto avoid unwarranted toxicity.
Acute β‐Hydroxy‐β‐Methyl Butyrate Suppresses Regulators of Mitochondrial Biogenesis and Lipid Oxidation While Increasing Lipid Content in Myotubes
Authors: Schnuck Jamie K. , Johnson Michele A. , Gould Lacey M. , Gannon Nicholas P. , Vaughan Roger A. 
Published: September 2016

AbstractLeucine modulates synthetic and degradative pathways in muscle, possibly providing metabolic benefits for both athletes and diseased populations. Leucine has become popular among athletes for improving performance and body composition, however little is known about the metabolic effects of the commonly consumed leucine‐derived metabolite β‐hydroxy‐β‐methyl butyrate (HMB). Our work measured the effects of HMB on metabolic protein expression, mitochondrial content and metabolism, as well as lipid content in skeletal muscle cells. Specifically, cultured C2C12 myotubes were treated with either a control or HMB ranging from 6.25 to 25 μM for 24 h and mRNA and/or protein expression, oxygen consumption, glucose uptake, and lipid content were measured. Contrary to leucine's stimulatory effect on metabolism, HMB‐treated cells exhibited significantly reduced regulators of lipid oxidation including peroxisome proliferator‐activated receptor alpha (PPARα) and PPARβ/δ, as well as downstream target carnitine palmitoyl transferase, without alterations in glucose or palmitate oxidation. Furthermore, HMB significantly inhibited activation of the master regulator of energetics, AMP‐activated protein kinase. As a result, HMB‐treated cells also displayed reduced total mitochondrial content compared with true control or cells equivocally treated with leucine. Additionally, HMB treatment amplified markers of lipid biosynthesis (PPARγ and fatty acid synthase) as well as consistently promoted elevated total lipid content versus control cells. Collectively, our results demonstrate that HMB did not improve mitochondrial metabolism or content, and may promote elevated cellular lipid content possibly through heightened PPARγ expression. These observations suggest that HMB may be most beneficial for populations interested in stimulating anabolic cellular processes.
Comparison of hemodynamic effects of biventricular versus left ventricular only pacing in patients receiving cardiac resynchronization therapy: A before–after clinical trial
Authors: Faghfourian Babak , Homayoonfar Shahram , Rezvanjoo Mahdi , Poorolajal, MD, PhD Jalal , Emam Amir Hossein 
Published: September 2016

AbstractBackgroundBiventricular (BiV) pacing is the most common mode of delivering cardiac resynchronization therapy (CRT). However, initial clinical studies have indicated that left ventricular (LV) pacing is not inferior to BiV pacing. This study was conducted to address whether LV only pacing can provide the same hemodynamic response as BiV pacing.MethodsThis before–after clinical trial was conducted at Ekbatan Hospital, from July 2012 to November 2014. Patients with a LV ejection fraction ≤35% and a QRS duration ≥0.12 s who had a standard indication for ventricular pacing were enrolled. The CRT devices of all patients had already been set for BiV pacing. Therefore, their CRT devices were set for LV only pacing for 3 months. The hemodynamic status of the patients was assessed by echocardiography before setting the CRT device to LV only pacing (as a control) and 3 months after (as an intervention).ResultsThere was no statistically significant difference between the effect of BiV pacing and LV only pacing on the hemodynamic responses including LV ejection fraction, LV end diastolic and systolic volume, and velocity time integral of the aortic valve. Moreover, no significant difference was seen between men and women either.ConclusionsLV only pacing is not inferior to BiV pacing, and the hemodynamic response was similar in the two groups. However, the LV mode has a number of advantages over the BiV mode. More evidence, based on large clinical trials, is needed to confirm our results.
Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer
Authors: Dalgleish Angus G , Stebbing Justin , Adamson Douglas JA , Arif Seema Safia , Bidoli Paolo , Chang David , Cheeseman Sue , Diaz-Beveridge Robert , Fernandez-Martos Carlos , Glynne-Jones Rob , Granetto Cristina , Massuti Bartomeu , McAdam Karen , McDermott Raymond , Martín Andrés J Muñoz , Papamichael Demetris , Pazo-Cid Roberto , Vieitez Jose M , Zaniboni Alberto , Carroll Kevin J , Wagle Shama , Gaya Andrew , Mudan Satvinder S 
Published: September 2016

Abstract

Background:
Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma.

Methods:
Patients were randomised (2 : 1) to IMM-101 (10 mg ml−l intradermally)+GEM (1000 mg m−2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected.

Results:
IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01).

Conclusions:
IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.
JUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma
Authors: Titz Bjoern , Lomova Anastasia , Le Allison , Hugo Willy , Kong Xiangju , ten Hoeve Johanna , Friedman Michael , Shi Hubing , Moriceau Gatien , Song Chunying , Hong Aayoung , Atefi Mohammad , Li Richard , Komisopoulou Evangelia , Ribas Antoni , Lo Roger S , Graeber Thomas G 
Published: September 2016

AbstractA prominent mechanism of acquired resistance to BRAF inhibitors in BRAFV600-mutant melanoma is associated with the upregulation of receptor tyrosine kinases. Evidences suggested that this resistance mechanism is part of a more complex cellular adaptation process. Using an integrative strategy, we found this mechanism to invoke extensive transcriptomic, (phospho-) proteomic and phenotypic alterations that accompany a cellular transition to a de-differentiated, mesenchymal and invasive state. Even short-term BRAF-inhibitor exposure leads to an early adaptive, differentiation state change—characterized by a slow-cycling, persistent state. The early persistent state is distinct from the late proliferative, resistant state. However, both differentiation states share common signaling alterations including JUN upregulation. Motivated by the similarities, we found that co-targeting of BRAF and JUN is synergistic in killing fully resistant cells; and when used up-front, co-targeting substantially impairs the formation of the persistent subpopulation. We confirmed that JUN upregulation is a common response to BRAF inhibitor treatment in clinically treated patient tumors. Our findings demonstrate that events shared between early- and late-adaptation states provide candidate up-front co-treatment targets.
Emerging magnetism and anomalous Hall effect in iridate–manganite heterostructures
Authors: Nichols John , Gao Xiang , Lee Shinbuhm , Meyer Tricia L. , Freeland John W. , Lauter Valeria , Yi Di , Liu Jian , Haskel Daniel , Petrie Jonathan R. , Guo Er-Jia , Herklotz Andreas , Lee Dongkyu , Ward Thomas Z. , Eres Gyula , Fitzsimmons Michael R. , Lee Ho Nyung 
Published: September 2016

AbstractStrong Coulomb repulsion and spin–orbit coupling are known to give rise to exotic physical phenomena in transition metal oxides. Initial attempts to investigate systems, where both of these fundamental interactions are comparably strong, such as 3d and 5d complex oxide superlattices, have revealed properties that only slightly differ from the bulk ones of the constituent materials. Here we observe that the interfacial coupling between the 3d antiferromagnetic insulator SrMnO3 and the 5d paramagnetic metal SrIrO3 is enormously strong, yielding an anomalous Hall response as the result of charge transfer driven interfacial ferromagnetism. These findings show that low dimensional spin–orbit entangled 3d–5d interfaces provide an avenue to uncover technologically relevant physical phenomena unattainable in bulk materials.
Multiple novel gene-by-environment interactions modify the effect of FTO variants on body mass index
Authors: Young Alexander I. , Wauthier Fabian , Donnelly Peter 
Published: September 2016

AbstractGenetic studies have shown that obesity risk is heritable and that, of the many common variants now associated with body mass index, those in an intron of the fat mass and obesity-associated (FTO) gene have the largest effect. The size of the UK Biobank, and its joint measurement of genetic, anthropometric and lifestyle variables, offers an unprecedented opportunity to assess gene-by-environment interactions in a way that accounts for the dependence between different factors. We jointly examine the evidence for interactions between FTO (rs1421085) and various lifestyle and environmental factors. We report interactions between the FTO variant and each of: frequency of alcohol consumption (P=3.0 × 10−4); deviations from mean sleep duration (P=8.0 × 10−4); overall diet (P=5.0 × 10−6), including added salt (P=1.2 × 10−3); and physical activity (P=3.1 × 10−4).
MiR-21-5p Links Epithelial-Mesenchymal Transition Phenotype with Stem-Like Cell Signatures via AKT Signaling in Keloid Keratinocytes
Authors: Yan Li , Cao Rui , Liu YuanBo , Wang LianZhao , Pan Bo , Lv XiaoYan , Jiao Hu , Zhuang Qiang , Sun XueJian , Xiao Ran 
Published: September 2016

AbstractKeloid is the abnormal wound healing puzzled by the aggressive growth and high recurrence rate due to its unrevealed key pathogenic mechanism. MicroRNAs contribute to a series of biological processes including epithelial-mesenchymal transition (EMT) and cells stemness involved in fibrotic disease. Here, using microRNAs microarray analysis we found mir-21-5p was significantly up-regulated in keloid epidermis. To investigate the role of miR-21-5p in keloid pathogenesis, we transfected miR-21-5p mimic or inhibitor in keloid keratinocytes and examined the abilities of cell proliferation, apoptosis, migration and invasion, the expressions of EMT-related markers vimentin and E-cadherin and stem-like cells-associated markers CD44 and ALDH1, and the involvement of PTEN and the signaling of AKT and ERK. Our results demonstrated that up-regulation or knockdown of miR-21-5p significantly increased or decreased the migration, invasion and sphere-forming abilities of keloid keratinocytes, and the phenotype of EMT and cells stemness were enhanced or reduced as well. Furthermore, PTEN and p-AKT were shown to participate in the regulation of miR-21-5p on EMT phenotypes and stemness signatures of keloid keratinocytes, which might account for the invasion and recurrence of keloids. This molecular mechanism of miR-21-5p on keloid keratinocytes linked EMT with cells stemness and implicated novel therapeutic targets for keloids.
Endophytic fungus Phomopsis liquidambari and different doses of N-fertilizer alter microbial community structure and function in rhizosphere of rice
Authors: Siddikee Md. Ashaduzzaman , Zereen Mst Israt , Li Cai-Feng , Dai Chuan-Chao 
Published: September 2016

AbstractMicrobial community structure and functions of rhizosphere soil of rice were investigated after applying low and high doses of nitrogenous fertilizer and Phomopsis liquidambari. Average well color development, substrate richness, catabolic diversity and soil enzymes activities varied after applying N-fertilizer and P. liquidambari and were greater in P. liquidambari treated soil than only N-fertilization. Multivariate analysis distinctly separated the catabolic and enzymes activity profile which statistically proved alteration of microbial functional diversity. Nitrogen fertilizer altered microbial community structure revealed by the increased content of total PLFAs, specific subgroup marker PLFAs except fungal PLFAs and by the decreased ratio of G+/G−, sat/monunsat, iso/anteiso, F/B except trans/cis while P. liquidambari inoculation enhanced N-fertilization effect except increased fungal PLFA and decreased trans/cis. PCA using identified marker PLFAs revealed definite discrimination among the treatments which further statistically confirmed structural changed of microbial community. Nitrogenase activity representative of N-fixing community decreased in N-fertilizer treatment while P. liquidambari inoculation increased. In short, application of P. liquidambari with low doses of N-fertilizer improved rice growth and reduced N-fertilizer requirement by increasing enzymes activities involved in C, N and P cycling, structural and functional diversity of microbes, nitrogenase activity involved in N2 fixation and accumulation of total-N.
Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine
Authors: Zhang Wenjuan , Tao Qin , Guo Zihu , Fu Yingxue , Chen Xuetong , Shar Piar Ali , Shahen Mohamed , Zhu Jinglin , Xue Jun , Bai Yaofei , Wu Ziyin , Wang Zhenzhong , Xiao Wei , Wang Yonghua 
Published: September 2016

AbstractThough cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases.
3D passive stabilization of n = 0 MHD modes in EAST tokamak
Authors: Chen S. L. , Villone F. , Xiao B. J. , Barbato L. , Luo Z. P. , Liu L. , Mastrostefano S. , Xing Z. 
Published: September 2016

AbstractEvidence is shown of the capability of non-axisymmetrical conducting structures in the Experimental Advanced Superconducting Tokamak (EAST) to guarantee the passive stabilization of the n = 0 MHD unstable mode. Suitable numerical modeling of the experiments allows a clear interpretation of the phenomenon. This demonstration and the availability of computational tools able to describe the effect of 3D conductors will have a huge impact on the design of future fusion devices, in which the conducting structures closest to plasma will be highly segmented.