bluuebunny/crossref_metadata_2025 huggingface dataset:
Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells
Authors: Paulus A , Akhtar S , Caulfield T R , Samuel K , Yousaf H , Bashir Y , Paulus S M , Tran D , Hudec R , Cogen D , Jiang J , Edenfield B , Novak A , Ansell S M , Witzig T , Martin P , Coleman M , Roy V , Ailawadhi S , Chitta K , Linder S , Chanan-Khan A
Published: November 2016

The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics. Here we provide a comprehensive preclinical report on the anti-WM activity of VLX1570, a novel small-molecule inhibitor of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Both DUBs reside in the 19 S proteasome cap and their inhibition by VLX1570 results in rapid and tumor-specific apoptosis in bortezomib- or ibrutinib-resistant WM cells. Notably, treatment of WM cells with VLX1570 downregulated BCR-associated elements BTK, MYD88, NFATC, NF-κB and CXCR4, the latter whose dysregulated function is linked to ibrutinib resistance. VLX1570 administered to WM-xenografted mice resulted in decreased tumor burden and prolonged survival (P=0.0008) compared with vehicle-treated mice. Overall, our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant WM and carries a high potential for clinical translation.
Vital staining for cell death identifies Atg9a-dependent necrosis in developmental bone formation in mouse
Authors: Imagawa Yusuke , Saitoh Tatsuya , Tsujimoto Yoshihide
Published: November 2016

Programmed cell death has a crucial role in various biological events, including developmental morphogenesis. Recent evidence indicates that necrosis contributes to programmed cell death in addition to apoptosis, but it is unclear whether necrosis acts as a compensatory mechanism for failure of apoptosis or has an intrinsic role during development. In contrast to apoptosis, there have been no techniques for imaging physiological necrosis in vivo. Here we employ vital staining using propidium iodide to identify cells with plasma membrane disruption (necrotic cells) in mouse embryos. We discover a form of necrosis at the bone surface, which does not occur in embryos with deficiency of the autophagy-related gene Atg9a, although it is unaffected by Atg5 knockout. We also find abnormalities of the bone surface in Atg9a knockout mice, suggesting an important role of Atg9a-dependent necrosis in bone surface formation. These findings suggest that necrosis has an active role in developmental morphogenesis.
Differential Canalograms Detect Outflow Changes from Trabecular Micro-Bypass Stents and Ab Interno Trabeculectomy
Authors: Parikh Hardik A. , Loewen Ralitsa T. , Roy Pritha , Schuman Joel S. , Lathrop Kira L. , Loewen Nils A.
Published: November 2016

Recently introduced microincisional glaucoma surgeries that enhance conventional outflow offer a favorable risk profile over traditional surgeries, but can be unpredictable. Two paramount challenges are the lack of an adequate training model for angle surgeries and the absence of an intraoperative quantification of surgical success. To address both, we developed an ex vivo training system and a differential, quantitative canalography method that uses slope-adjusted fluorescence intensities of two different chromophores to avoid quenching. We assessed outflow enhancement by trabecular micro-bypass (TMB) implantation or by ab interno trabeculectomy (AIT). In this porcine model, TMB resulted in an insignificant (p > 0.05) outflow increase of 13 ± 5%, 14 ± 8%, 9 ± 3%, and 24 ± 9% in the inferonasal, superonasal, superotemporal, and inferotemporal quadrant, respectively. AIT caused a 100 ± 50% (p = 0.002), 75 ± 28% (p = 0.002), 19 ± 8%, and 40 ± 21% increase in those quadrants. The direct gonioscopy and tactile feedback provided a surgical experience that was very similar to that in human patients. Despite the more narrow and discontinuous circumferential drainage elements in the pig with potential for underperformance or partial stent obstruction, unequivocal patterns of focal outflow enhancement by TMB were seen in this training model. AIT achieved extensive access to outflow pathways beyond the surgical site itself.
Hydrogen separation through tailored dual phase membranes with nominal composition BaCe0.8Eu0.2O3-δ:Ce0.8Y0.2O2-δ at intermediate temperatures
Authors: Ivanova Mariya E. , Escolástico Sonia , Balaguer Maria , Palisaitis Justinas , Sohn Yoo Jung , Meulenberg Wilhelm A. , Guillon Olivier , Mayer Joachim , Serra Jose M.
Published: November 2016

Hydrogen permeation membranes are a key element in improving the energy conversion efficiency and decreasing the greenhouse gas emissions from energy generation. The scientific community faces the challenge of identifying and optimizing stable and effective ceramic materials for H2 separation membranes at elevated temperature (400–800 °C) for industrial separations and intensified catalytic reactors. As such, composite materials with nominal composition BaCe0.8Eu0.2O3-δ:Ce0.8Y0.2O2-δ revealed unprecedented H2 permeation levels of 0.4 to 0.61 mL·min−1·cm−2 at 700 °C measured on 500 μm-thick-specimen. A detailed structural and phase study revealed single phase perovskite and fluorite starting materials synthesized via the conventional ceramic route. Strong tendency of Eu to migrate from the perovskite to the fluorite phase was observed at sintering temperature, leading to significant Eu depletion of the proton conducing BaCe0.8Eu0.2O3-δ phase. Composite microstructure was examined prior and after a variety of functional tests, including electrical conductivity, H2-permeation and stability in CO2 containing atmospheres at elevated temperatures, revealing stable material without morphological and structural changes, with segregation-free interfaces and no further diffusive effects between the constituting phases. In this context, dual phase material based on BaCe0.8Eu0.2O3-δ:Ce0.8Y0.2O2-δ represents a very promising candidate for H2 separating membrane in energy- and environmentally-related applications.
Association of LRRK2 R1628P variant with Parkinson’s disease in Ethnic Han-Chinese and subgroup population
Authors: Zhang Pei , Wang Qingzhi , Jiao Fengjuan , Yan Jianguo , Chen Lijun , He Feng , Zhang Qian , Tian Bo
Published: November 2016

Recent studies have linked certain single nucleotide polymorphisms in the leucine-rich repeat kinase 2 (LRRK2) gene with Parkinson’s disease (PD). The R1628P variant of LRRK2 may be a specific risk factor for PD in ethnic Han-Chinese populations. This study is to elucidate the epidemiological feature of R1628P in ethnic Han-Chinese population with PD. A comprehensive meta-analysis was performed to evaluate the precise association between R1628P variant and the risk for PD in ethnic Han-Chinese and subgroups stratified by gender, onset age, or family history. The analysis assessing the role of R1628P on the risk of PD in ethnic Han-Chinese supported a significant association, and the odds ratio was 1.86. We further estimate the specific prevalence in relevant ethnic Han-Chinese subgroups. After stratifying the eligible data by gender, onset age, or family history, significant associations were found in all male, female, early-onset, late-onset, familial and sporadic subgroups, and the odds ratio were 1.90, 1.94, 2.12, 1.75, 6.71 and 1.81 respectively. In conclusion, our meta-analysis suggests that R1628P variant of LRRK2 has a significant association with the risk of PD in ethnic Han-Chinese and subgroup population.
IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner
Authors: Liu Dan , Cao Tuanping , Wang Na , Liu Chengfei , Ma Ning , Tu Ran , Min Xiaoyun
Published: November 2016

IL-25, a new member of the IL-17 cytokine family, is involved in type 2 immunity initiation and has been associated with the pathogenesis of rheumatoid arthritis (RA). However, its exact role remains unclear. Here, we aimed to analyse IL-25 expression in the serum and synovial fluid of RA patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, we investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. We further determined whether IL-25 can alleviate collagen-induced arthritis (CIA) development in mice and the underlying mechanisms using in vitro and in vivo experiments. Our results showed that IL-25 was upregulated in the serum and synovial fluid of RA patients. Increased serum IL-25 levels were associated with disease severity and inflammatory response in RA patients. Furthermore, IL-25 inhibited CD4+ T-cell activation and differentiation into Th17 cells, without affecting Th1 cells in human RA and CIA models. Administration of IL-25 could attenuate CIA development by Th17 suppression in an IL-13-dependent manner. Our findings indicate that IL-25 plays a potent immunosuppressive role in the pathogenesis of RA and CIA by downregulating Th17 cell response, and thus, may be a potential therapeutic agent for RA.
Very Short Mitochondrial DNA Fragments and Heteroplasmy in Human Plasma
Authors: Zhang Ruoyu , Nakahira Kiichi , Guo Xiaoxian , Choi Augustine M.K. , Gu Zhenglong
Published: November 2016

Cell free DNA (cfDNA) has received increasing attention and has been studied in a broad range of clinical conditions. However, few studies have focused on mitochondrial DNA (mtDNA) in the cell free form. We optimized DNA isolation and sequencing library preparation protocols to better retain short DNA fragments from plasma, and applied these optimized methods to plasma samples from patients with sepsis. Our methods can retain substantially shorter DNA, resulting in an average of 11.5 fold increase in short DNA fragments yield (DNA <100bp). We report that cf-mtDNA in plasma is highly enriched in short-size cfDNA (30~60 bp). Motivated by this unique size distribution, we size-selected short cfDNA, which further increased the mtDNA recovery rate by an average of 10.4 fold. We then detected mtDNA heteroplasmy in plasma from 3 patients. In one patient who previously received bone marrow transplantation, different minor allele frequencies were observed between plasma and leukocytes at heteroplasmic sites, consistent with mixed-tissue origin for cfDNA. For the other two patients, the heteroplasmy pattern is also different between plasma and leukocyte. Our study shed new lights into the architecture of the cfDNA, and mtDNA heteroplasmy identified in plasma provides new potential for biomarker discovery.
Membrane glycerolipidome of soybean root hairs and its response to nitrogen and phosphate availability
Authors: Wei Fang , Fanella Brian , Guo Liang , Wang Xuemin
Published: November 2016

Root hairs are tubular extensions of specific root epidermal cells important in plant nutrition and water absorption. To determine membrane glycerolipids in root hairs and roots may differ, as well as their respective response to nutrient availability, this study analyzed the membrane glycerolipid species in soybean root hairs and in roots stripped of root hairs, and their response to nitrogen (N) and phosphate (Pi) supplementation. The ratio of phospholipids to galactolipids was 1.5 fold higher in root hairs than in stripped roots. Under Pi deficiency, the ratio of phospholipids to galactolipids in stripped roots decreased with the greatest decrease found in the level of phosphatidylethanolamine (PE) in root hairs and stripped roots, and root hairs had an increased level of phosphatidic acid (PA). When seedlings were not supplied with N, the level of the N-containing lipids PE and phosphatidylserine in root hairs decreased whereas the level of non-N-containing lipids galactolipids and PA increased compared to N-supplied conditions. In stripped roots, the level of major membrane lipids was not different between N-sufficient and -deficient conditions. The results indicate that the membrane glycerolipidomes in root hairs are more responsive to nutrient availability than are the rest of roots.
In Vivo Bioluminescence Tomography for Monitoring Breast Tumor Growth and Metastatic Spreading: Comparative Study and Mathematical Modeling
Authors: Mollard Séverine , Fanciullino Raphaelle , Giacometti Sarah , Serdjebi Cindy , Benzekry Sebastien , Ciccolini Joseph
Published: November 2016

This study aimed at evaluating the reliability and precision of Diffuse Luminescent Imaging Tomography (DLIT) for monitoring primary tumor and metastatic spreading in breast cancer mice, and to develop a biomathematical model to describe the collected data. Using orthotopic mammary fat pad model of breast cancer (MDAMB231-Luc) in mice, we monitored tumor and metastatic spreading by three-dimensional (3D) bioluminescence and cross-validated it with standard bioluminescence imaging, caliper measurement and necropsy examination. DLIT imaging proved to be reproducible and reliable throughout time. It was possible to discriminate secondary lesions from the main breast cancer, without removing the primary tumor. Preferential metastatic sites were lungs, peritoneum and lymph nodes. Necropsy examinations confirmed DLIT measurements. Marked differences in growth profiles were observed, with an overestimation of the exponential phase when using a caliper as compared with bioluminescence. Our mathematical model taking into account the balance between living and necrotic cells proved to be able to reproduce the experimental data obtained with a caliper or DLIT imaging, because it could discriminate proliferative living cells from a more composite mass consisting of tumor cells, necrotic cell, or inflammatory tissues. DLIT imaging combined with mathematical modeling could be a powerful and informative tool in experimental oncology.
Resistive Switching in All-Printed, Flexible and Hybrid MoS2-PVA Nanocomposite based Memristive Device Fabricated by Reverse Offset
Authors: Rehman Muhammad Muqeet , Siddiqui Ghayas Uddin , Gul Jahan Zeb , Kim Soo-Wan , Lim Jong Hwan , Choi Kyung Hyun
Published: November 2016

Owing to the increasing interest in the nonvolatile memory devices, resistive switching based on hybrid nanocomposite of a 2D material, molybdenum disulphide (MoS2) and polyvinyl alcohol (PVA) is explored in this work. As a proof of concept, we have demonstrated the fabrication of a memory device with the configuration of PET/Ag/MoS2-PVA/Ag via an all printed, hybrid, and state of the art fabrication approach. Bottom Ag electrodes, active layer of hybrid MoS2-PVA nanocomposite and top Ag electrode are deposited by reverse offset, electrohydrodynamic (EHD) atomization and electrohydrodynamic (EHD) patterning respectively. The fabricated device displayed characteristic bistable, nonvolatile and rewritable resistive switching behavior at a low operating voltage. A decent off/on ratio, high retention time, and large endurance of 1.28 × 102, 105 sec and 1000 voltage sweeps were recorded respectively. Double logarithmic curve satisfy the trap controlled space charge limited current (TCSCLC) model in high resistance state (HRS) and ohmic model in low resistance state (LRS). Bendability test at various bending diameters (50-2 mm) for 1500 cycles was carried out to show the mechanical robustness of fabricated device.
The mutation p.E113K in the Schiff base counterion of rhodopsin is associated with two distinct retinal phenotypes within the same family
Authors: Reiff Charlotte , Owczarek-Lipska Marta , Spital Georg , Röger Carsten , Hinz Hebke , Jüschke Christoph , Thiele Holger , Altmüller Janine , Nürnberg Peter , Da Costa Romain , Neidhardt John
Published: November 2016

The diagnoses of retinitis pigmentosa (RP) and stationary night blindness (CSNB) are two distinct clinical entities belonging to a group of clinically and genetically heterogeneous retinal diseases. The current study focused on the identification of causative mutations in the RP-affected index patient and in several members of the same family that reported a phenotype resembling CSNB. Ophthalmological examinations of the index patient confirmed a typical form of RP. In contrast, clinical characterizations and ERGs of another affected family member showed the Riggs-type CSNB lacking signs of RP. Applying whole exome sequencing we detected the non-synonymous substitution c.337G > A, p.E113 K in the rhodopsin (RHO) gene. The mutation co-segregated with the diseases. The identification of the pathogenic variant p.E113 K is the first description of a naturally-occurring mutation in the Schiff base counterion of RHO in human patients. The heterozygous mutation c.337G > A in exon 1 was confirmed in the index patient as well as in five CSNB-affected relatives. This pathogenic sequence change was excluded in a healthy family member and in 199 ethnically matched controls. Our findings suggest that a mutation in the biochemically well-characterized counterion p.E113 in RHO can be associated with RP or Riggs-type CSNB, even within the same family.
Dynamically sculpturing plasmonic vortices: from integer to fractional orbital angular momentum
Authors: Wang Yu , Zhao Peng , Feng Xue , Xu Yuntao , Liu Fang , Cui Kaiyu , Zhang Wei , Huang Yidong
Published: November 2016

As a fundamental tool for light-matter interactions, plasmonic vortex (PV) is extremely useful due to the unique near field property. However, it is a pity that, up to now, the orbital angular momentum (OAM) carried by PVs could not be dynamically and continuously tuned in practice as well as the properties of fractional PVs are still not well investigated. By comparing with two previously reported methods, it is suggested that our proposal of utilizing the propagation induced radial phase gradient of incident Laguerre-Gaussian (LG) beam is a promising candidate to sculpture PVs from integer to fractional OAM dynamically. Consequently, the preset OAM of PVs could have four composing parts: the incident spin and orbital angular momentum, the geometric contribution of chiral plasmonic structure, and the radial phase gradient dependent contribution. Moreover, an analytical expression for the fractional PV is derived as a linear superposition of infinite numbers of integer PVs described by Bessel function of the first kind. It is also shown that the actual mean OAM of a fractional PV would deviate from the preset value, which is similar with previous results for spatial fractional optical vortices.
EGFR tyrosine kinase inhibitors versus chemotherapy as first-line therapy for non-small cell lung cancer patients with the L858R point mutation
Authors: Xu Jianlin , Yang Haitang , Jin Bo , Lou Yuqing , Zhang Yanwei , Zhang Xueyan , Zhong Hua , Wang Huiming , Wu Dan , Han Baohui
Published: November 2016

The efficacy of EGFR tyrosine kinase inhibitors (TKIs) varies among different EGFR mutations. Here, we directly compared the efficacy of first-line TKIs to chemotherapy for non-small cell lung cancer (NSCLC) patients with the L858R mutation. The progression-free survival (PFS) for patients receiving TKIs as first-line therapy was longer than those who received chemotherapy (hazard ratio [HR]: 0.44, P < 0.001). Subgroup analyses showed that first-line TKI therapy resulted in longer PFS among non-smokers (HR: 0.41, P < 0.001), male (HR: 0.49, P = 0.002), female (HR: 0.39, P < 0.001), and patients with adenocarcinoma histology (HR: 0.41, P < 0.001). However, among patients with non-adenocarcinoma histology (HR: 1.11, P = 0.824) and those who used to smoke (HR: 0.55, P = 0.093), first-line TKI therapy failed to demonstrate statistically longer PFS compared to chemotherapy. Our results demonstrated that for patients with L858R mutation, first-line TKI therapy provided better survival benefits. However, among non-adenocarcinoma patients and those who used to smoke, the PFS in cohorts receiving first-line chemotherapy or TKI were not significantly different. The results of the current study will be helpful for decision-making in the treatment of patients with L858R mutation.
Mechanisms of arrhythmogenesis related to calcium-driven alternans in a model of human atrial fibrillation
Authors: Chang Kelly C. , Trayanova Natalia A.
Published: November 2016

The occurrence of atrial fibrillation (AF) is associated with progressive changes in the calcium handling system of atrial myocytes. Calcium cycling instability has been implicated as an underlying mechanism of electrical alternans observed in patients who experience AF. However, the extent to which calcium-induced alternation of electrical activity in the atria contributes to arrhythmogenesis is unknown. In this study, we investigated the effects of calcium-driven alternans (CDA) on arrhythmia susceptibility in a biophysically detailed, 3D computer model of the human atria representing electrical and structural remodeling secondary to chronic AF. We found that elevated propensity to CDA rendered the atria vulnerable to ectopy-induced arrhythmia. It also increased the complexity and persistence of arrhythmias induced by fast pacing, with unstable scroll waves meandering and frequently breaking up to produce multiple wavelets. Our results suggest that calcium-induced electrical instability may increase arrhythmia vulnerability and promote increasing disorganization of arrhythmias in the chronic AF-remodeled atria, thus playing an important role in the progression of the disease.
Understanding the Antifungal Mechanism of Ag@ZnO Core-shell Nanocomposites against Candida krusei
Authors: Das Bhaskar , Khan Md. Imran , Jayabalan R. , Behera Susanta K. , Yun Soon-Il , Tripathy Suraj K. , Mishra Amrita
Published: November 2016

In the present paper, facile synthesis of Ag@ZnO core-shell nanocomposites is reported where zinc oxide is coated on biogenic silver nanoparticles synthesized using Andrographis paniculata and Aloe vera leaf extract. Structural features of as synthesized nanocomposites are characterized by UV-visible spectroscopy, XRD, and FTIR. Morphology of the above core-shell nanocomposites is investigated by electron microscopy. As synthesized nanocomposite material has shown antimicrobial activity against Candida krusei, which is an opportunistic pathogen known to cause candidemia. The possible mode of activity of the above material has been studied by in-vitro molecular techniques. Our investigations have shown that surface coating of biogenic silver nanoparticles by zinc oxide has increased its antimicrobial efficiency against Candida krusei, while decreasing its toxicity towards A431 human epidermoid carcinoma cell lines.
Constitutive cyclic GMP accumulation in Arabidopsis thaliana compromises systemic acquired resistance induced by an avirulent pathogen by modulating local signals
Authors: Hussain Jamshaid , Chen Jian , Locato Vittoria , Sabetta Wilma , Behera Smrutisanjita , Cimini Sara , Griggio Francesca , Martínez-Jaime Silvia , Graf Alexander , Bouneb Mabrouk , Pachaiappan Raman , Fincato Paola , Blanco Emanuela , Costa Alex , De Gara Laura , Bellin Diana , de Pinto Maria Concetta , Vandelle Elodie
Published: November 2016

The infection of Arabidopsis thaliana plants with avirulent pathogens causes the accumulation of cGMP with a biphasic profile downstream of nitric oxide signalling. However, plant enzymes that modulate cGMP levels have yet to be identified, so we generated transgenic A. thaliana plants expressing the rat soluble guanylate cyclase (GC) to increase genetically the level of cGMP and to study the function of cGMP in plant defence responses. Once confirmed that cGMP levels were higher in the GC transgenic lines than in wild-type controls, the GC transgenic plants were then challenged with bacterial pathogens and their defence responses were characterized. Although local resistance was similar in the GC transgenic and wild-type lines, differences in the redox state suggested potential cross-talk between cGMP and the glutathione redox system. Furthermore, large-scale transcriptomic and proteomic analysis highlighted the significant modulation of both gene expression and protein abundance at the infection site, inhibiting the establishment of systemic acquired resistance. Our data indicate that cGMP plays a key role in local responses controlling the induction of systemic acquired resistance in plants challenged with avirulent pathogens.
Measurement of in-plane elasticity of live cell layers using a pressure sensor embedded microfluidic device
Authors: Lin Chien-Han , Wang Chien-Kai , Chen Yu-An , Peng Chien-Chung , Liao Wei-Hao , Tung Yi-Chung
Published: November 2016

In various physiological activities, cells experience stresses along their in-plane direction when facing substrate deformation. Capability of continuous monitoring elasticity of live cell layers during a period is highly desired to investigate cell property variation during various transformations under normal or disease states. This paper reports time-lapsed measurement of live cell layer in-plane elasticity using a pressure sensor embedded microfluidic device. The sensor converts pressure-induced deformation of a flexible membrane to electrical signals. When cells are cultured on top of the membrane, flexural rigidity of the composite membrane increases and further changes the output electrical signals. In the experiments, human embryonic lung fibroblast (MRC-5) cells are cultured and analyzed to estimate the in-plane elasticity. In addition, the cells are treated with a growth factor to simulate lung fibrosis to study the effects of cell transformation on the elasticity variation. For comparison, elasticity measurement on the cells by atomic force microscopy (AFM) is also performed. The experimental results confirm highly anisotropic configuration and material properties of cells. Furthermore, the in-plane elasticity can be monitored during the cell transformation after the growth factor stimulation. Consequently, the developed microfluidic device provides a powerful tool to study physical properties of cells for fundamental biophysics and biomedical researches.
Effect of magnetron sputtering parameters and stress state of W film precursors on WSe2 layer texture by rapid selenization
Authors: Li Hongchao , Gao Di , Xie Senlin , Zou Jianpeng
Published: November 2016

Tungsten diselenide (WSe2) film was obtained by rapid selenization of magnetron sputtered tungsten (W) film. To prevent WSe2 film peeling off from the substrate during selenization, the W film was designed with a double-layer structure. The first layer was deposited at a high sputtering-gas pressure to form a loose structure, which can act as a buffer layer to release stresses caused by WSe2 growth. The second layer was deposited naturally on the first layer to react with selenium vapour in the next step. The effect of the W film deposition parameters(such as sputtering time, sputtering-gas pressure and substrate bias voltage)on the texture and surface morphology of the WSe2 film was studied. Shortening the sputtering time, increasing the sputtering-gas pressure or decreasing the substrate bias voltage can help synthesize WSe2 films with more platelets embedded vertically in the matrix. The stress state of the W film influences the WSe2 film texture. Based on the stress state of the W film, a model for growth of the WSe2 films with different textures was proposed. The insertion direction of the van der Waals gap is a key factor for the anisotropic formation of WSe2 film.
Association of EGFR Exon 19 Deletion and EGFR-TKI Treatment Duration with Frequency of T790M Mutation in EGFR-Mutant Lung Cancer Patients
Authors: Matsuo Norikazu , Azuma Koichi , Sakai Kazuko , Hattori Satoshi , Kawahara Akihiko , Ishii Hidenobu , Tokito Takaaki , Kinoshita Takashi , Yamada Kazuhiko , Nishio Kazuto , Hoshino Tomoaki
Published: November 2016

The most common event responsible for resistance to first- and second-generation (1st and 2nd) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is acquisition of T790M mutation. We examined whether T790M is related to clinicopathologic or prognostic factors in patients with relapse of EGFR mutant non-small cell lung cancer (NSCLC) after treatment with 1st or 2nd EGFR-TKIs. We retrospectively reviewed the T790M status and clinical characteristics of 73 patients with advanced or recurrent NSCLC who had been treated with EGFR-TKIs and undergone rebiopsy at Kurume University Hospital between March 2005 and December 2015. T790M mutation was more frequent in patients with EGFR exon 19 deletion mutation (63%, 26/41) than in those with L858R mutation (38%, 12/32) (p = 0.035). The median total duration of 1st or 2nd EGFR-TKI treatment was significantly longer in patients with T790M mutation than in those without (15.3 months vs 8.1 months, p < 0.001). Multivariate analysis revealed that the type of EGFR mutation and the total duration of EGFR-TKI treatment were significantly associated with T790M prevalence. Patients with EGFR exon 19 deletion mutation who receive long-term EGFR-TKI therapy show a high prevalence of T790M mutation. The present data are potentially important for clinical decision-making in NSCLC patients with EGFR mutation.
Surface-Enhanced Impulsive Coherent Vibrational Spectroscopy
Authors: Du Juan , Harra Juha , Virkki Matti , Mäkelä Jyrki M. , Leng Yuxin , Kauranen Martti , Kobayashi Takayoshi
Published: November 2016

Surface-enhanced Raman spectroscopy (SERS) has attracted a lot of attention in molecular sensing because of the remarkable ability of plasmonic metal nanostructures to enhance the weak Raman scattering process. On the other hand, coherent vibrational spectroscopy triggered by impulsive excitation using ultrafast laser pulses provides complete information about the temporal evolution of molecular vibrations, allowing dynamical processes in molecular systems to be followed in “real time”. Here, we combine these two concepts and demonstrate surface-enhanced impulsive vibrational spectroscopy. The vibrational modes of the ground and excited states of poly[2-methoxy-5-(2-ethylhexyloxy)−1,4-phenylenevinylene] (MEH-PPV), spin-coated on a substrate covered with monodisperse silver nanoparticles, are impulsively excited with a sub-10 fs pump pulse and characterized with a delayed broad-band probe pulse. The maximum enhancement in the spectrally and temporally resolved vibrational signatures averaged over the whole sample is about 4.6, while the real-time information about the instantaneous vibrational amplitude together with the initial vibrational phase is preserved. The phase is essential to determine the vibrational contributions from the ground and excited states.
Multifunctional Optical Thin Films Fabricated by the Photopolymerization of Uniaxially Oriented Lyotropic Liquid Crystal Monomers for Electro-Optical Devices
Authors: Im Pureun , Choi Yu-Jin , Yoon Won-Jin , Kang Dong-Gue , Park Minwook , Kim Dae-Yoon , Lee Cheul-Ro , Yang Seungbin , Lee Ji-Hoon , Jeong Kwang-Un
Published: November 2016

A multifunctional optical thin film (MOTF) is fabricated by coating the newly synthesized perylene-based reactive mesogen (PBRM) and stabilized by the subsequent photopolymerization. Based on the spectroscopic results combined with morphological observations, it is found that nematic liquid crystal (NLC) is aligned parallel to the molecular long axis of PBRM not only due to the long-range physical anchoring effect but also due to the short-range molecular physical interactions between alignment layer and NLC molecules. From the electro-optical properties of LC test cells fabricated with the PBRM MOTF, it is clearly demonstrated that the PBRM MOTF can work as the planar LC alignment layer as well as the in-cell coatable polarizer. The coatable PBRM MOTF from lyotropic chromonic reactive mesogens can pave a new way for the flexible optoelectronic devices.
Eliciting maize defense pathways aboveground attracts belowground biocontrol agents
Authors: Filgueiras Camila Cramer , Willett Denis S. , Pereira Ramom Vasconcelos , Moino Junior Alcides , Pareja Martin , Duncan Larry W.
Published: November 2016

Plant defense pathways mediate multitrophic interactions above and belowground. Understanding the effects of these pathways on pests and natural enemies above and belowground holds great potential for designing effective control strategies. Here we investigate the effects of aboveground stimulation of plant defense pathways on the interactions between corn, the aboveground herbivore adultDiabrotica speciosa, the belowground herbivore larvalD. speciosa, and the subterranean ento-mopathogenic nematode natural enemyHeterorhabditis amazonensis. We show that adultD. speciosarecruit to aboveground herbivory and methyl salicylate treatment, that larvalD. speciosaare relatively indiscriminate, and thatH. amazonensisen-tomopathogenic nematodes recruit to corn fed upon by adultD. speciosa. These results suggest that entomopathogenicnematodes belowground can be highly attuned to changes in the aboveground parts of plants and that biological control can be enhanced with induced plant defense in this and similar systems.
Fluorimetric Mercury Test Strips with Suppressed “Coffee Stains” by a Bio-inspired Fabrication Strategy
Authors: Qiao Yuchun , Shang Jizhen , Li Shuying , Feng Luping , Jiang Yao , Duan Zhiqiang , Lv Xiaoxia , Zhang Chunxian , Yao Tiantian , Dong Zhichao , Zhang Yu , Wang Hua
Published: November 2016

A fluorimetric Hg2+ test strip has been developed using a lotus-inspired fabrication method for suppressing the “coffee stains” toward the uniform distribution of probe materials through creating a hydrophobic drying pattern for fast solvent evaporation. The test strips were first loaded with the model probes of fluorescent gold-silver nanoclusters and then dried in vacuum on the hydrophobic pattern. On the one hand, here, the hydrophobic constraining forces from the lotus surface-like pattern could control the exterior transport of dispersed nanoclusters on strips leading to the minimized “coffee stains”. On the other hand, the vacuum-aided fast solvent evaporation could boost the interior Marangoni flow of probe materials on strips to expect the further improved probe distribution on strips. High aqueous stability and enhanced fluorescence of probes on test strips were realized by the hydrophilic treatment with amine-derivatized silicane. A test strips-based fluorimetry has thereby been developed for probing Hg2+ ions in wastewater, showing the detection performances comparable to the classic instrumental analysis ones. Such a facile and efficient fabrication route for the bio-inspired suppression of “coffee stains” on test strips may expand the scope of applications of test strips-based “point-of-care” analysis methods or detection devices in the biomedical and environmental fields.
Disentangling gross N2O production and consumption in soil
Authors: Wen Yuan , Chen Zhe , Dannenmann Michael , Carminati Andrea , Willibald Georg , Kiese Ralf , Wolf Benjamin , Veldkamp Edzo , Butterbach-Bahl Klaus , Corre Marife D.
Published: November 2016

The difficulty of measuring gross N2O production and consumption in soil impedes our ability to predict N2O dynamics across the soil-atmosphere interface. Our study aimed to disentangle these processes by comparing measurements from gas-flow soil core (GFSC) and 15N2O pool dilution (15N2OPD) methods. GFSC directly measures soil N2O and N2 fluxes, with their sum as the gross N2O production, whereas 15N2OPD involves addition of 15N2O into a chamber headspace and measuring its isotopic dilution over time. Measurements were conducted on intact soil cores from grassland, cropland, beech and pine forests. Across sites, gross N2O production and consumption measured by 15N2OPD were only 10% and 6%, respectively, of those measured by GFSC. However, 15N2OPD remains the only method that can be used under field conditions to measure atmospheric N2O uptake in soil. We propose to use different terminologies for the gross N2O fluxes that these two methods quantified. For 15N2OPD, we suggest using ‘gross N2O emission and uptake’, which encompass gas exchange within the 15N2O-labelled, soil air-filled pores. For GFSC, ‘gross N2O production and consumption’ can be used, which includes both N2O emitted into the soil air-filled pores and N2O directly consumed, forming N2, in soil anaerobic microsites.
Self-assembly of keratin peptides: Its implication on the performance of electrospun PVA nanofibers
Authors: Kadirvelu Kavitha , Fathima Nishter Nishad
Published: November 2016

Drawing inspiration from the field of designer self-assembling materials, this work is aimed to focus on the self-assembling nature of extracted peptides. Hair keratin, a proteinacious reject in tanning industry has been chosen since they have been extracted and used for wide range of applications. Keratin source was subjected to five hydrolysis treatments (viz., sulphitolysis, β-mercaptoethanol, ionic liquid, thioglycolic acid and alkali) and assayed for functional groups. This was followed by the prediction of secondary structure using circular dichroism, determining the microstructural level to which the extracted peptide has self-assembled. Sulphitolysis and thioglycolic acid based hydrolysates exist in monomeric conformation, whereas β-mercaptoethanol based hydrolysate exhibited dimeric conformation. The subsequent part of the study is to incorporate these peptides into the nanofibers to study the structural implication of keratin peptides on its characteristics. Accordingly, the peptides were electrospun with PVA and subjected to morphological, mechanical, thermal and biological characterizations. Monomeric nanofiber mat has high tensile strength of around 5.5 MPa and offered lower mass transport resistance, whereas dimeric mat has high Tmof around 290 °C and was more biocompatible. These results help in understanding the extraction-structure-function aspect of the hydrolysates stressing the role of extraction methods on the choice of application.
Effects of NDRG1 family proteins on photoreceptor outer segment morphology in zebrafish
Authors: Takita Shimpei , Wada Yasutaka , Kawamura Satoru
Published: November 2016

Rods and cones are functionally and morphologically distinct. We previously identified N-myc downstream-regulated gene 1b (ndrg1b) in carp as a cone-specific gene. Here, we show that NDRG1b and its paralog, NDRG1a-1, contribute to photoreceptor outer segment (OS) formation in zebrafish. In adult zebrafish photoreceptors, NDRG1a-1 was localized in the entire cone plasma membranes, and also in rod plasma membranes except its OS. NDRG1b was expressed specifically in cones in the entire plasma membranes. In a developing retina, NDRG1a-1 was expressed in the photoreceptor layer, and NDRG1b in the photoreceptor layer plus inner nuclear layer. Based on our primary knockdown study suggesting that both proteins are involved in normal rod and cone OS development, NDRG1a-1 was overexpressed or NDRG1b was ectopically expressed in rods. These forced-expression studies in the transgenic fish confirmed the effect of these proteins on the OS morphology: rod OS morphology changed from cylindrical to tapered shape. These taper-shaped rod OSs were not stained with N,N’-didansyl cystine that effectively labels infolded membrane structure of cone OS. The result shows that rod OS membrane structure is preserved in these taper-shaped OSs and therefore, suggests that tapered OS morphology is not related to the infolded membrane structure in cone OS.
Dural arteriovenous fistula masquerading as pulsatile tinnitus: radiologic assessment and clinical implications
Authors: An Yong-Hwi , Han Sungjun , Lee Minhyung , Rhee Jihye , Kwon O-Ki , Hwang Gyojun , Jung Cheolkyu , Bae Yun Jung , An Gwang Seok , Lee Kyogu , Koo Ja-Won , Song Jae-Jin
Published: November 2016

Pulsatile tinnitus (PT) is often an initial presenting symptom of dural arteriovenous fistula (dAVF), but it may be overlooked or diagnosed late if not suspected on initial diagnostic work-up. Here, we assess anatomical features, treatment outcomes, and clinical implications of patients with PT due to dAVF. Of 220 patients who were diagnosed with dAVF between 2003 and 2014, 30 (13.6%) presented with only PT as their initial symptom. The transverse-sigmoid sinus (70.0%) was the most common site, followed by the hypoglossal canal (10.0%) and the middle cranial fossa (6.7%) on radiologic evaluation. Regarding venous drainage patterns, sinus or meningeal venous drainage pattern was the most common type (73.3%), followed by sinus drainage with a cortical venous reflux (26.7%). PT disappeared completely in 21 (80.8%) of 26 patients who underwent therapeutic intervention with transarterial embolization of the fistula, improved markedly in 3 (11.5%), and remained the same in 2 (7.7%). In conclusion, considering that PT may be the only initial symptom in more than 10% of dAVF, not only otolaryngologists but also neurologists and neurosurgeons should meticulously evaluate patients with PT. In most cases, PT originating from dAVF can be cured with transarterial embolization regardless of location and venous drainage pattern.
A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic
Authors: Zhong Ting , Yao Xin , Zhang Shuang , Guo Yang , Duan Xiao-Chuan , Ren Wei , Dan Huang  , Yin Yi-Fan , Zhang Xuan
Published: November 2016

The main objective of this study was to demonstrate the proof-of-principle for the hypothesis that conjugated linoleic acid-paclitaxel conjugate (CLA-PTX), a novel fatty acid modified anti-cancer drug conjugate, could self-assemble forming nanoparticles. The results indicated that a novel self-assembling nanomedicine, CLA-PTX@PEG NPs (about 105 nm), with Cremophor EL (CrEL)-free and organic solvent-free characteristics, was prepared by a simple precipitation method. Being the ratio of CLA-PTX:DSPE-PEG was only 1:0.1 (w/w), the higher drug loading CLA-PTX@PEG NPs (about 90%) possessed carrier-free characteristic. The stability results indicated that CLA-PTX@PEG NPs could be stored for at least 9 months. The safety of CLA-PTX@PEG NPs was demonstrated by the MTD results. The anti-tumor activity and cellular uptake were also confirmed in thein vitroexperiments. The lower crystallinity, polarity and solubility of CLA-PTX compared with that of paclitaxel (PTX) might be the possible reason for CLA-PTX self-assembling forming nanoparticles, indicating a relationship between PTX modification and nanoparticles self-assembly. Overall, the data presented here confirm that this drug self-delivery strategy based on self-assembly of a CLA-PTX conjugate may offer a new way to prepare nanomedicine products for cancer therapy involving the relationship between anticancer drug modification and self-assembly into nanoparticles.
Highly efficient dual-wavelength mid-infrared CW Laser in diode end-pumped Er:SrF2 single crystals
Authors: Ma Weiwei , Qian Xiaobo , Wang Jingya , Liu Jingjing , Fan Xiuwei , Liu Jie , Su Liangbi , Xu Jun
Published: November 2016

The spectral properties and laser performance of Er:SrF2 single crystals were investigated and compared with Er:CaF2. Er:SrF2 crystals have larger absorption cross-sections at the pumping wavelength, larger mid-infrared stimulated emission cross-sections and much longer fluorescence lifetimes of the upper laser level (Er3+:4I11/2 level) than those of Er:CaF2 crystals. Dual-wavelength continuous-wave (CW) lasers around 2.8 μm were demonstrated in both 4at.% and 10at.% Er:SrF2 single crystals under 972 nm laser diode (LD) end pumping. The laser wavelengths are 2789.3 nm and 2791.8 nm in the former, and 2786.4 nm and 2790.7 nm in the latter, respectively. The best laser performance has been demonstrated in lightly doped 4at.% Er:SrF2 with a low threshold of 0.100 W, a high slope efficiency of 22.0%, an maximum output power of 0.483 W.
Smart Nanocomposites of Cu-Hemin Metal-Organic Frameworks for Electrochemical Glucose Biosensing
Authors: He Juan , Yang Han , Zhang Yayun , Yu Jie , Miao Longfei , Song Yonghai , Wang Li
Published: November 2016

Herein, a smart porous material, Cu-hemin metal-organic-frameworks (Cu-hemin MOFs), was synthesized via assembling of Cu2+ with hemin to load glucose oxidase (GOD) for electrochemical glucose biosensing for the first time. The formation of the Cu-hemin MOFs was verified by scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, N2 adsorption/desorption isotherms, UV-vis absorption spectroscopy, fluorescence spectroscopy, thermal analysis and electrochemical techniques. The results indicated that the Cu-hemin MOFs showed a ball-flower-like hollow cage structure with a large specific surface area and a large number of mesopores. A large number of GOD molecules could be successfully loaded in the pores of Cu-hemin MOFs to keep their bioactivity just like in a solution. The GOD/Cu-hemin MOFs exhibited both good performance toward oxygen reduction reaction via Cu-hemin MOFs and catalytic oxidation of glucose via GOD, superior to other GOD/MOFs and GOD/nanomaterials. Accordingly, the performance of GOD/Cu-hemin MOFs-based electrochemical glucose sensor was enhanced greatly, showing a wide linear range from 9.10 μM to 36.0 mM and a low detection limit of 2.73 μM. Moreover, the sensor showed satisfactory results in detection of glucose in human serum. This work provides a practical design of new electrochemical sensing platform based on MOFs and biomolecules.
Biodistribution of cisplatin revealed by imaging mass cytometry identifies extensive collagen binding in tumor and normal tissues
Authors: Chang Qing , Ornatsky Olga I. , Siddiqui Iram , Straus Rita , Baranov Vladimir I. , Hedley David W.
Published: November 2016

Imaging mass cytometry was used for direct visualization of platinum localization in tissue sections from tumor and normal tissues of cisplatin-treated mice bearing pancreas cancer patient-derived xenografts. This recently-developed technology enabled simultaneous detection of multiple markers to define cell lineage, DNA damage response, cell proliferation and functional state, providing a highly detailed view of drug incorporation in tumor and normal tissues at the cellular level. A striking and unanticipated finding was the extensive binding of platinum to collagen fibers in both tumor and normal mouse tissues. Time course experiments indicated the slow release of stroma-bound platinum, although it is currently unclear if released platinum retains biological activity. Imaging mass cytometry offers a unique window into the in vivo effects of platinum compounds, and it is likely that this can be extended into the clinic in order to optimize the use of this important class of agent.
Varying structural motifs in the salen based metal complexes of Co(ii), Ni(ii) and Cu(ii): synthesis, crystal structures, molecular dynamics and biological activities
Authors: Saini Anoop Kumar , Kumari Pratibha , Sharma Vinay , Mathur Pradeep , Mobin Shaikh M.
Published: November 2016

Four new metal complexes which demonstrates varying structural motifs from monomeric to dimeric to tetrameric complexes by slightly altering the reaction conditions and their biological applications.
Handheld XRF and Raman equipment for the in situ investigation of Roman finds in the Villa dei Quintili (Rome, Italy)
Authors: Alberti R. , Crupi V. , Frontoni R. , Galli G. , La Russa M. F. , Licchelli M. , Majolino D. , Malagodi M. , Rossi B. , Ruffolo S. A. , Venuti V.
Published: November 2016

A variety of fragments of frescoes coming from the Villa dei Quintili in Rome and dating back to the II century A.D. were subjected to, first of all, an X-ray fluorescence (XRF) analysis by optimizing a portable spectrometer for non-destructive investigation in the field of cultural heritage.