bluuebunny/crossref_metadata_2025 huggingface dataset:
Der Stellenwert der testpsychologischen Befunde bei der Begutachtung von Rentenantragsstellern wegen verminderter Erwerbsfähigkeit
Authors: Braungardt Tanja , Schneider Wolfgang
Published: June 2016

Zusammenfassung. Wir haben die Ergebnisse der testpsychologischen Verfahren von 100 Begutachteten, die Rentenanträge wegen verminderter Erwerbsfähigkeit gestellt haben, mit den Ergebnissen der gesunden Normstichprobe der jeweiligen Fragebogenverfahren verglichen. Es zeigte sich, dass 44 % der zu Begutachteten auf der Skala «Offenheit» des Freiburger Persönlichkeitsinventars unterdurchschnittliche Werte erreichten, d. h. diesen Fragebogen und u. U. auch die anderen Fragebögen tendenziös i.S. einer sozialen Erwünschtheit, bearbeitet haben. Die Ergebnisse zeigten weiterhin, dass die zu Begutachtenden sich v. a. körperlich als stark belastet erleben. Ihre interaktionellen Schwierigkeiten stufen sie geringer ein als die gesunde Normstichprobe. Psychotherapeutischen Behandlungsansätzen stehen sie eher ablehnend gegenüber und ihre Veränderungsmotivation ist als eher gering einzustufen.
Kompetenzentwicklung über Selbstreflexion
Authors: Kraske Marlene , Niemann Bibiane , Fehling Patrick
Published: June 2016

Zusammenfassung. Auf der Basis des empirisch begründeten Kompetenzmodells von Christa Olbrich entstand unter Bezugnahme auf das Konzept des situierten Lernens nach Holoch und dem Modell der strukturierten Reflexion nach Johns der SeRPA©, ein Instrument, das zu Aspekten der Kompetenzdiagnostik und -entwicklung in der praktischen Ausbildung in der Gesundheits- und Krankenpflegeausbildung geeignet erscheint. Dieser wurde mittels Expertenbefragung und Pretest modifiziert und validiert.
Das ABC der Selbstfürsorge für Lehrende und Lernende in den Pflegeberufen
Authors: Doppelfeld Silke
Published: June 2016

Zusammenfassung. Auszubildende zur Pflegefachkraft werden am Lernort Praxis mit den traumatischen Erlebensweisen ihrer PatientInnen konfrontiert. Das Miterleben von schwerer Krankheit, massiven körperlichen Verletzungen und Tod kann durch Übertragungsphänomene traumatisierende Wirkung auf die Lernenden entfalten. Das ABC – der Selbstfürsorge ist eine alltagstaugliche Methode, die sich sowohl für die Lernenden als auch für die Lehrenden als praktikabel erwiesen hat, um die eigene Gesundheit zu erhalten.
Western Pacific hydroclimate linked to global climate variability over the past two millennia
Authors: Griffiths Michael L. , Kimbrough Alena K. , Gagan Michael K. , Drysdale Russell N. , Cole Julia E. , Johnson Kathleen R. , Zhao Jian-Xin , Cook Benjamin I. , Hellstrom John C. , Hantoro Wahyoe S.
Published: June 2016

Interdecadal modes of tropical Pacific ocean-atmosphere circulation have a strong influence on global temperature, yet the extent to which these phenomena influence global climate on multicentury timescales is still poorly known. Here we present a 2,000-year, multiproxy reconstruction of western Pacific hydroclimate from two speleothem records for southeastern Indonesia. The composite record shows pronounced shifts in monsoon rainfall that are antiphased with precipitation records for East Asia and the central-eastern equatorial Pacific. These meridional and zonal patterns are best explained by a poleward expansion of the Australasian Intertropical Convergence Zone and weakening of the Pacific Walker circulation (PWC) between ∼1000 and 1500 CE Conversely, an equatorward contraction of the Intertropical Convergence Zone and strengthened PWC occurred between ∼1500 and 1900 CE. Our findings, together with climate model simulations, highlight the likelihood that century-scale variations in tropical Pacific climate modes can significantly modulate radiatively forced shifts in global temperature.
A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells
Authors: Zhang Ya , Huang Liang , Fu Haiqing , Smith Owen K. , Lin Chii Mei , Utani Koichi , Rao Mishal , Reinhold William C. , Redon Christophe E. , Ryan Michael , Kim RyangGuk , You Yang , Hanna Harlington , Boisclair Yves , Long Qiaoming , Aladjem Mirit I.
Published: June 2016

Mammalian chromosome replication starts from distinct sites; however, the principles governing initiation site selection are unclear because proteins essential for DNA replication do not exhibit sequence-specific DNA binding. Here we identify a replication-initiation determinant (RepID) protein that binds a subset of replication-initiation sites. A large fraction of RepID-binding sites share a common G-rich motif and exhibit elevated replication initiation. RepID is required for initiation of DNA replication from RepID-bound replication origins, including the origin at the human beta-globin (HBB) locus. At HBB, RepID is involved in an interaction between the replication origin (Rep-P) and the locus control region. RepID-depleted murine embryonic fibroblasts exhibit abnormal replication fork progression and fewer replication-initiation events. These observations are consistent with a model, suggesting that RepID facilitates replication initiation at a distinct group of human replication origins.
The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
Authors: Boada-Romero Emilio , Serramito-Gómez Inmaculada , Sacristán María P. , Boone David L. , Xavier Ramnik J. , Pimentel-Muiños Felipe X.
Published: June 2016

A coding polymorphism of human ATG16L1 (rs2241880; T300A) increases the risk of Crohn’s disease and it has been shown to enhance susceptibility of ATG16L1 to caspase cleavage. Here we show that T300A also alters the ability of the C-terminal WD40-repeat domain of ATG16L1 to interact with an amino acid motif that recognizes this region. Such alteration impairs the unconventional autophagic activity of TMEM59, a transmembrane protein that contains the WD40 domain-binding motif, and disrupts its normal intracellular trafficking and its ability to engage ATG16L1 in response to bacterial infection. TMEM59-induced autophagy is blunted in cells expressing the fragments generated by caspase processing of the ATG16L1-T300A risk allele, whereas canonical autophagy remains unaffected. These results suggest that the T300A polymorphism alters the function of motif-containing molecules that engage ATG16L1 through the WD40 domain, either by influencing this interaction under non-stressful conditions or by inhibiting their downstream autophagic signalling after caspase-mediated cleavage.
Truncated Variants of Gaussia Luciferase with Tyrosine Linker for Site-Specific Bioconjugate Applications
Authors: Hunt Eric A. , Moutsiopoulou Angeliki , Ioannou Stephanie , Ahern Katelyn , Woodward Kristen , Dikici Emre , Daunert Sylvia , Deo Sapna K.
Published: June 2016

Gaussia luciferase (Gluc)—with its many favorable traits such as small size, bright emission and exceptional stability—has become a prominent reporter protein for a wide range of bioluminescence-based detection applications. The ten internal cysteine residues crucial to functional structure formation, however, make expression of high quantities of soluble protein in bacterial systems difficult. In addition to this challenge, the current lack of structural data further complicates the use of Gluc for in vitro applications, such as biosensors, or cellular delivery, both of which rely heavily on robust and reproducible bioconjugation techniques. While Gluc is already appreciably small for a luciferase, a reduction in size that still retains significant bioluminescent activity, in conjunction with a more reproducible bioorthogonal method of chemical modification and facile expression in bacteria, would be very beneficial in biosensor design and cellular transport studies. We have developed truncated variants of Gluc, which maintain attractive bioluminescent features and have characterized their spectral and kinetic properties. These variants were purified in high quantities from a bacterial system. Additionally, a C-terminal linker has been incorporated into these variants that can be used for reliable, specific modification through tyrosine-based bioconjugation techniques, which leave the sensitive network of cysteine residues undisturbed.
Metagenomic discovery of novel enzymes and biosurfactants in a slaughterhouse biofilm microbial community
Authors: Thies Stephan , Rausch Sonja Christina , Kovacic Filip , Schmidt-Thaler Alexandra , Wilhelm Susanne , Rosenau Frank , Daniel Rolf , Streit Wolfgang , Pietruszka Jörg , Jaeger Karl-Erich
Published: June 2016

DNA derived from environmental samples is a rich source of novel bioactive molecules. The choice of the habitat to be sampled predefines the properties of the biomolecules to be discovered due to the physiological adaptation of the microbial community to the prevailing environmental conditions. We have constructed a metagenomic library in Escherichia coli DH10b with environmental DNA (eDNA) isolated from the microbial community of a slaughterhouse drain biofilm consisting mainly of species from the family Flavobacteriaceae. By functional screening of this library we have identified several lipases, proteases and two clones (SA343 and SA354) with biosurfactant and hemolytic activities. Sequence analysis of the respective eDNA fragments and subsequent structure homology modelling identified genes encoding putative N-acyl amino acid synthases with a unique two-domain organisation. The produced biosurfactants were identified by NMR spectroscopy as N-acyltyrosines with N-myristoyltyrosine as the predominant species. Critical micelle concentration and reduction of surface tension were similar to those of chemically synthesised N-myristoyltyrosine. Furthermore, we showed that the newly isolated N-acyltyrosines exhibit antibiotic activity against various bacteria. This is the first report describing the successful application of functional high-throughput screening assays for the identification of biosurfactant producing clones within a metagenomic library.
Wideband nonlinear spectral broadening in ultra-short ultra - silicon rich nitride waveguides
Authors: Choi Ju Won , Chen George F. R. , Ng D. K. T. , Ooi Kelvin J. A. , Tan Dawn T. H.
Published: June 2016

CMOS-compatible nonlinear optics platforms with high Kerr nonlinearity facilitate the generation of broadband spectra based on self-phase modulation. Our ultra – silicon rich nitride (USRN) platform is designed to have a large nonlinear refractive index and low nonlinear losses at 1.55 μm for the facilitation of wideband spectral broadening. We investigate the ultrafast spectral characteristics of USRN waveguides with 1-mm-length, which have high nonlinear parameters (γ ∼ 550 W−1/m) and anomalous dispersion at 1.55 μm wavelength of input light. USRN add-drop ring resonators broaden output spectra by a factor of 2 compared with the bandwidth of input fs laser with the highest quality factors of 11000 and 15000. Two – fold self phase modulation induced spectral broadening is observed using waveguides only 430 μm in length, whereas a quadrupling of the output bandwidth is observed with USRN waveguides with a 1-mm-length. A broadening factor of around 3 per 1 mm length is achieved in the USRN waveguides, a value which is comparatively larger than many other CMOS-compatible platforms.
Acousto-microfluidics for screening of ssDNA aptamer
Authors: Park Jee-Woong , Lee Su Jin , Ren Shuo , Lee Sangwook , Kim Soyoun , Laurell Thomas
Published: June 2016

We demonstrate a new screening method for obtaining a prostate-specific antigen (PSA) binding aptamer based on an acoustofluidic separation (acoustophoreis) technique. Since acoustophoresis provides simultaneous washing and separation in a continuous flow mode, we efficiently obtained a PSA binding aptamer that shows high affinity without any additional washing step, which is necessary in other screening methods. In addition, next-generation sequencing (NGS) was applied to accelerate the identification of the screened ssDNA pool, improving the selecting process of the aptamer candidate based on the frequency ranking of the sequences. After the 8th round of the acoustophoretic systematic evolution of ligands by exponential enrichment (SELEX) and following sequence analysis with NGS, 7 PSA binding ssDNA aptamer-candidates were obtained and characterized with surface plasmon resonance (SPR) for affinity and specificity. As a result of the new SELEX method with PSA as the model target protein, the best PSA binding aptamer showed specific binding to PSA with a dissociation constant (Kd) of 0.7 nM.
Cell Deformation by Single-beam Acoustic Trapping: A Promising Tool for Measurements of Cell Mechanics
Authors: Hwang Jae Youn , Kim Jihun , Park Jin Man , Lee Changyang , Jung Hayong , Lee Jungwoo , Shung K. Kirk
Published: June 2016

We demonstrate a noncontact single-beam acoustic trapping method for the quantification of the mechanical properties of a single suspended cell with label-free. Experimentally results show that the single-beam acoustic trapping force results in morphological deformation of a trapped cell. While a cancer cell was trapped in an acoustic beam focus, the morphological changes of the immobilized cell were monitored using bright-field imaging. The cell deformability was then compared with that of a trapped polystyrene microbead as a function of the applied acoustic pressure for a better understanding of the relationship between the pressure and degree of cell deformation. Cell deformation was found to become more pronounced as higher pressure levels were applied. Furthermore, to determine if this acoustic trapping method can be exploited in quantifying the cell mechanics in a suspension and in a non-contact manner, the deformability levels of breast cancer cells with different degrees of invasiveness due to acoustic trapping were compared. It was found that highly-invasive breast cancer cells exhibited greater deformability than weakly-invasive breast cancer cells. These results clearly demonstrate that the single-beam acoustic trapping technique is a promising tool for non-contact quantitative assessments of the mechanical properties of single cells in suspensions with label-free.
Towards the Better: Intrinsic Property Amelioration in Bulk Metallic Glasses
Authors: Sarac Baran , Zhang Long , Kosiba Konrad , Pauly Simon , Stoica Mihai , Eckert Jürgen
Published: June 2016

Tailoring the intrinsic length-scale effects in bulk metallic glasses (BMGs) via post-heat treatment necessitates a systematic analyzing strategy. Although various achievements were made in the past years to structurally enhance the properties of different BMG alloys, the influence of short-term sub-glass transition annealing on the relaxation kinetics is still not fully covered. Here, we aim for unraveling the connection between the physical, (thermo)mechanical and structural changes as a function of selected pre-annealing temperatures and time scales with an in-house developed Cu46Zr44Al8Hf2 based BMG alloy. The controlled formation of nanocrystals below 50 nm with homogenous distribution inside the matrix phase via thermal treatment increase the material’s resistance to strain softening by almost an order of magnitude. The present work determines the design aspects of metallic glasses with enhanced mechanical properties via nanostructural modifications, while postulating a counter-argument to the intrinsic property degradation accounted for long-term annealing.
Dissolved oxygen content prediction in crab culture using a hybrid intelligent method
Authors: Yu Huihui , Chen Yingyi , Hassan ShahbazGul , Li Daoliang
Published: June 2016

A precise predictive model is needed to obtain a clear understanding of the changing dissolved oxygen content in outdoor crab ponds, to assess how to reduce risk and to optimize water quality management. The uncertainties in the data from multiple sensors are a significant factor when building a dissolved oxygen content prediction model. To increase prediction accuracy, a new hybrid dissolved oxygen content forecasting model based on the radial basis function neural networks (RBFNN) data fusion method and a least squares support vector machine (LSSVM) with an optimal improved particle swarm optimization(IPSO) is developed. In the modelling process, the RBFNN data fusion method is used to improve information accuracy and provide more trustworthy training samples for the IPSO-LSSVM prediction model. The LSSVM is a powerful tool for achieving nonlinear dissolved oxygen content forecasting. In addition, an improved particle swarm optimization algorithm is developed to determine the optimal parameters for the LSSVM with high accuracy and generalizability. In this study, the comparison of the prediction results of different traditional models validates the effectiveness and accuracy of the proposed hybrid RBFNN-IPSO-LSSVM model for dissolved oxygen content prediction in outdoor crab ponds.
Nitrogen Chemistry and Coke Transformation of FCC Coked Catalyst during the Regeneration Process
Authors: Shi Junjun , Guan Jianyu , Guo Dawei , Zhang Jiushun , France Liam John , Wang Lefu , Li Xuehui
Published: June 2016

Regeneration of the coked catalyst is an important process of fluid catalytic cracking (FCC) in petroleum refining, however, this process will emit environmentally harmful gases such as nitrogen and carbon oxides. Transformation of N and C containing compounds in industrial FCC coke under thermal decomposition was investigated via TPD and TPO to examine the evolved gaseous species and TGA, NMR and XPS to analyse the residual coke fraction. Two distinct regions of gas evolution are observed during TPD for the first time and they arise from decomposition of aliphatic carbons and aromatic carbons. Three types of N species, pyrrolic N, pyridinic N and quaternary N are identified in the FCC coke, the former one is unstable and tends to be decomposed into pyridinic and quaternary N. Mechanisms of NO, CO and CO2 evolution during TPD are proposed and lattice oxygen is suggested to be an important oxygen resource. Regeneration process indicates that coke-C tends to preferentially oxidise compared with coke-N. Hence, new technology for promoting nitrogen-containing compounds conversion will benefit the in-situ reduction of NO by CO during FCC regeneration.
Inhibition of inflammatory reactions in 2,4-Dinitrochlorobenzene induced Nc/Nga atopic dermatitis mice by non-thermal plasma
Authors: Choi Jeong-Hae , Song Yeon-Suk , Lee Hae-June , Hong Jin-Woo , Kim Gyoo-Cheon
Published: June 2016

Non-thermal plasma (NTP) has recently been introduced and reported as a novel tool with a range of medicinal and biological roles. Although many studies using NTP have been performed, none has investigated the direct relationship between NTP and immune responses yet. Especially, the effects of NTP on atopic dermatitis (AD) were not been explored. Here, NTP was tested whether it controls immune reactions of AD. NTP treatment was administered to pro-inflammatory cytokine-stimulated keratinocytes and DNCB (2,4-Dinitrochlorobenzene)-induced atopic dermatitis mice, then the immune reactions of cells and skin tissues were monitored. Cells treated with NTP showed decreased expression levels of CCL11, CCL13, and CCL17 along with down-regulation of NF-κB activity. Repeated administration of NTP to AD-induced mice reduced the numbers of mast cells and eosinophils, IgE, CCL17, IFNγ levels, and inhibited NF-κB activity in the skin lesion. Furthermore, combined treatment with NTP and 1% hydrocortisone cream significantly decreased the immune responses of AD than that with either of these two treatments individually. Overall, this study revealed that NTP significantly inhibits several immune reactions of AD by regulating NF-κB activity. Therefore, NTP could be useful to suppress the exaggerated immune reactions in severe skin inflammatory diseases such as AD.
Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng
Authors: An Ya-Nan , Zhang Xue , Zhang Tian-Yuan , Zhang Meng-Yue , Qian-Zhang  , Deng Xiao-Yu , Zhao Feng , Zhu Ling-Juan , Wang Guan , Zhang Jie , Zhang Yi-Xuan , Liu Bo , Yao Xin-Sheng
Published: June 2016

Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1–5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6) and six known biogenetically related derivatives (7–12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher’s method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2–4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2-hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2–4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS.
Structural, electronic and kinetic properties of the phase-change material Ge2Sb2Te5 in the liquid state
Authors: Schumacher Mathias , Weber Hans , Jóvári Pál , Tsuchiya Yoshimi , Youngs Tristan G. A. , Kaban Ivan , Mazzarello Riccardo
Published: June 2016

Phase-change materials exhibit fast and reversible transitions between an amorphous and a crystalline state at high temperature. The two states display resistivity contrast, which is exploited in phase-change memory devices. The technologically most important family of phase-change materials consists of Ge-Sb-Te alloys. In this work, we investigate the structural, electronic and kinetic properties of liquid Ge2Sb2Te5 as a function of temperature by a combined experimental and computational approach. Understanding the properties of this phase is important to clarify the amorphization and crystallization processes. We show that the structural properties of the models obtained from ab initio and reverse Monte Carlo simulations are in good agreement with neutron and X-ray diffraction experiments. We extract the kinetic coefficients from the molecular dynamics trajectories and determine the activation energy for viscosity. The obtained value is shown to be fully compatible with our viscosity measurements.
Pupal diapause termination in Bactrocera minax: an insight on 20-hydroxyecdysone induced phenotypic and genotypic expressions
Authors: Chen Zhenzhong , Dong Yongcheng , Wang Yaohui , Andongma Awawing A. , Rashid Muhammad A. , Krutmuang Patcharin , Niu Changying
Published: June 2016

The Chinese citrus fruit fly,Bactrocera minax, is an economically important pest of citrus. It exhibits pupal diapause from November to May to combat harsh environmental conditions. Such a long pupal diapause is a barrier for laboratory rearing and development of control strategies against this pest. In the present study, 20-hydroxyecdysone (20E) was used to break pupal diapause ofB. minaxby topical application. After diapause termination by 20E treated, the pupal ontogenetic processes were observed along the temporal trajectory. The pupal response time to 20E was estimated by detecting the relative expression of 20E responsive genes at different times after 20E-treatment. Results revealed that 20E could effectively terminate the pupal diapause in a dose-dependent manner and significantly shorten the time for 50% adult emergence (Et50). 20E response genes, includingecr,broadandfoxo, were up-regulated within 72h, indicating these genes are involved in pupal metamorphosis and diapause termination processes. Morphological changes showed the pupal metamorphosis began ~7 days after 20E-treatment at 22 °C. This study does not only pave the way for artificial rearing in the laboratory through manipulating of pupal diapause termination, but also deepens our understanding of the underlying pupal diapause termination mechanism ofB. minax.
Joint Effect of Early Microvascular Damage in the Eye & Kidney on Risk of Cardiovascular Events
Authors: Yip Wanfen , Sabanayagam Charumathi , Ong Peng Guan , Patel Uptal D , Chow Khuan Yew , Tai E Shyong , Ling Lieng H , Wong Tien Yin , Cheung Carol Yim-lui
Published: June 2016

Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD), but not all individuals require treatment. Retinal microvascular abnormalities and microalbuminuria reflect early systemic microvascular changes. We examined the joint effect of retinal abnormalities and microalbuminuria on CVD risk in an Asian cohort. We conducted a prospective, population-based study. Retinal abnormalities were defined as presence of retinopathy and/or retinal venular widening. Microalbuminuria was defined as urinary albumin: creatinine ratio between 30–300 mg/g. Incident CVD was defined as newly diagnosed clinical stroke, acute myocardial infarction or CVD death. Cox regression models were performed to determine the associations between retinal abnormalities and microalbuminuria with risk of CVD, while controlling for established risk factors. 3,496 participants (aged ≥ 40) were free of prevalent CVD. During the follow-up (5.8 years), 126 (3.60%) participants developed CVD. Persons presenting with both retinal abnormalities and microalbuminuria were 6.71 times (95% CI, 2.68, 16.79) as likely to have incident CVD compared with those without either abnormalities. There was a significant interaction effect between retinal abnormalities and microalbuminuria on incident CVD. Assessment of retinal abnormalities in patients with microalbuminuria may provide additional value in identifying persons at risk of developing CVD.
DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose
Authors: Liu Zhi , Chen Tian , Sun Wenhua , Yuan Zongyi , Yu Mei , Chen Guoqing , Guo Weihua , Xiao Jingang , Tian Weidong
Published: June 2016

Diabetes mellitus, characterized by abnormally high blood glucose levels, gives rise to impaired bone remodeling. In response to high glucose (HG), the attenuated osteogenic differentiation capacity of human periodontal ligament stem cells (hPDLSCs) is associated with the loss of alveolar bone. Recently, DNA methylation was reported to affect osteogenic differentiation of stem cells in pathological states. However, the intrinsic mechanism linking DNA methylation to osteogenic differentiation ability in the presence of HG is still unclear. In this study, we found that diabetic rats with increased DNA methylation levels in periodontal ligaments exhibited reduced bone mass and density.In vitroapplication of 5-aza-2′-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, to decrease DNA methylation levels in hPDLSCs, rescued the osteogenic differentiation capacity of hPDLSCs under HG conditions. Moreover, we demonstrated that the canonical Wnt signaling pathway was activated during this process and, under HG circumstances, the 5-aza-dC-rescued osteogenic differentiation capacity was blocked by Dickkopf-1, an effective antagonist of the canonical Wnt signaling pathway. Taken together, these results demonstrate for the first time that suppression of DNA methylation is able to facilitate the osteogenic differentiation capacity of hPDLSCs exposed to HG, through activation of the canonical Wnt signaling pathway.
CRAF R391W is a melanoma driver oncogene
Authors: Atefi Mohammad , Titz Bjoern , Tsoi Jennifer , Avramis Earl , Le Allison , Ng Charles , Lomova Anastasia , Lassen Amanda , Friedman Michael , Chmielowski Bartosz , Ribas Antoni , Graeber Thomas G.
Published: June 2016

Approximately 75% of melanomas have known driver oncogenic mutations in BRAF, NRAS, GNA11 or GNAQ, while the mutations providing constitutive oncogenic signaling in the remaining melanomas are not known. We established a melanoma cell line from a tumor with none of the common driver mutations. This cell line demonstrated a signaling profile similar to BRAF-mutants, but lacked sensitivity to the BRAF inhibitor vemurafenib. RNA-seq mutation data implicated CRAF R391W as the alternative driver mutation of this melanoma. CRAF R391W was homozygous and over expressed. These melanoma cells were highly sensitive to CRAF, but not BRAF knockdown. In reconstitution experiments, CRAF R391W, but not CRAF WT, transformed NIH3T3 cells in soft-agar colony formation assays, increased kinase activity in vitro, induced MAP kinase signaling and conferred vemurafenib resistance. MAP kinase inducing activity was dependent on CRAF dimerization. Thus, CRAF is a bona fide alternative oncogene for BRAF/NRAS/GNAQ/GNA11 wild type melanomas.
Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy
Authors: Ang Wei Xia , Zhao Ying , Kwang Timothy , Wu Chunxiao , Chen Can , Toh Han Chong , Mahendran Ratha , Esuvaranathan Kesavan , Wang Shu
Published: June 2016

Intravesical instillation of Bacillus Calmette-Guérin is currently used as adjuvant therapy for superficial, non-muscle invasive bladder cancer (NMIBC). However, nearly 40% of patients with NMIBC will fail Bacillus Calmette-Guérin therapy. In an attempt to investigate the feasibility of using insect baculovirus-based vectors for bladder cancer therapy, we observed that intravesical instillation of baculoviruses without transgene up-regulated a set of Th1-type of cytokines and increased the survival rate of mice bearing established orthotopic bladder tumors. When baculoviral vectors were used to co-deliver the mouse CD40 ligand and IL-15 genes through intravesical instillation, the immunogene therapy triggered significantly increased bladder infiltrations of inflammatory monocytes, CD4+, CD8+ and γδ T lymphocytes. All treated animals survived beyond 12 months whereas control animals died around 2 months after tumor inoculation. We conclude that direct intravesical instillation of baculoviral gene transfer vectors holds the potential to be a novel therapeutic modality for NMIBC.
Advanced and flexible multi-carrier receiver architecture for high-count multi-core fiber based space division multiplexed applications
Authors: Asif Rameez
Published: June 2016

Space division multiplexing (SDM), incorporating multi-core fibers (MCFs), has been demonstrated for effectively maximizing the data capacity in an impending capacity crunch. To achieve high spectral-density through multi-carrier encoding while simultaneously maintaining transmission reach, benefits from inter-core crosstalk (XT) and non-linear compensation must be utilized. In this report, we propose a proof-of-concept unified receiver architecture that jointly compensates optical Kerr effects, intra- and inter-core XT in MCFs. The architecture is analysed in multi-channel 512 Gbit/s dual-carrier DP-16QAM system over 800 km 19-core MCF to validate the digital compensation of inter-core XT. Through this architecture: (a) we efficiently compensates the inter-core XT improving Q-factor by 4.82 dB and (b) achieve a momentous gain in transmission reach, increasing the maximum achievable distance from 480 km to 1208 km, via analytical analysis. Simulation results confirm that inter-core XT distortions are more relentless for cores fabricated around the central axis of cladding. Predominantly, XT induced Q-penalty can be suppressed to be less than 1 dB up-to −11.56 dB of inter-core XT over 800 km MCF, offering flexibility to fabricate dense core structures with same cladding diameter. Moreover, this report outlines the relationship between core pitch and forward-error correction (FEC).
Reassortment compatibility between PB1, PB2, and HA genes of the two influenza B virus lineages in mammalian cells
Authors: Kim Jin Il , Lee Ilseob , Park Sehee , Bae Joon-Yong , Yoo Kirim , Lemey Philippe , Park Mee Sook , Song Jin-Won , Kee Sun-Ho , Song Ki-Joon , Park Man-Seong
Published: June 2016

In addition to influenza A subtypes, two distinct lineages of influenza B virus also cause seasonal epidemics to humans. Recently, Dudas et al. have done evolutionary analyses of reassortment patterns of the virus and suggested genetic lineage relationship between PB1, PB2, and HA genes. Using genetic plasmids and reassortant viruses, we here demonstrate that a homologous lineage PB1-PB2 pair exhibits better compatibility than a heterologous one and that the lineage relationship between PB1 and HA is more important for viral replication than that between PB2 and HA. However, co-adaptation of PB1-PB2-HA genes appears to be affected by complete gene constellation.
Numerical research on the anisotropic transport of thermal neutron in heterogeneous porous media with micron X-ray computed tomography
Authors: Wang Yong , Yue Wenzheng , Zhang Mo
Published: June 2016

The anisotropic transport of thermal neutron in heterogeneous porous media is of great research interests in many fields. In this paper, it is the first time that a new model based on micron X-ray computed tomography (CT) has been proposed to simultaneously consider both the separation of matrix and pore and the distribution of mineral components. We apply the Monte Carlo method to simulate thermal neutrons transporting through the model along different directions, and meanwhile detect those unreacted thermal neutrons by an array detector on the other side of the model. Therefore, the anisotropy of pore structure can be imaged by the amount of received thermal neutrons, due to the difference of rock matrix and pore-filling fluids in the macroscopic reaction cross section (MRCS). The new model has been verified by the consistent between the simulated data and the pore distribution from X-ray CT. The results show that the evaluation of porosity can be affected by the anisotropy of media. Based on the research, a new formula is developed to describe the correlation between the resolution of array detectors and the quality of imaging. The formula can be further used to analyze the critical resolution and the suitable number of thermal neutrons emitted in each simulation. Unconventionally, we find that a higher resolution cannot always lead to a better image.
Dynamical control on helicity of electromagnetic waves by tunable metasurfaces
Authors: Xu He-Xiu , Sun Shulin , Tang Shiwei , Ma Shaojie , He Qiong , Wang Guang-Ming , Cai Tong , Li Hai-Peng , Zhou Lei
Published: June 2016

Manipulating the polarization states of electromagnetic (EM) waves, a fundamental issue in optics, attracted intensive attention recently. However, most of the devices realized so far are either too bulky in size, and/or are passive with only specific functionalities. Here we combine theory and experiment to demonstrate that, a tunable metasurface incorporating diodes as active elements can dynamically control the reflection phase of EM waves, and thus exhibits unprecedented capabilities to manipulate the helicity of incident circular-polarized (CP) EM wave. By controlling the bias voltages imparted on the embedded diodes, we demonstrate that the device can work in two distinct states. Whereas in the “On” state, the metasurface functions as a helicity convertor and a helicity hybridizer within two separate frequency bands, it behaves as a helicity keeper within an ultra-wide frequency band in the “Off” state. Our findings pave the way to realize functionality-switchable devices related to phase control, such as frequency-tunable subwavelength cavities, anomalous reflectors and even holograms.
Low palaeoelevation of the northern Lhasa terrane during late Eocene: Fossil foraminifera and stable isotope evidence from the Gerze Basin
Authors: Wei Yi , Zhang Kexin , Garzione Carmala N. , Xu Yadong , Song Bowen , Ji Junliang
Published: June 2016

The Lhasa terrane is a key region for understanding the paleoelevation of the southern Tibetan Plateau after India-Asia collision. The Gerze Basin, located in the northern part of the Lhasa terrane, is a shortening-related basin. We discovered Lagena laevis (Bandy) fossils in upper Eocene strata of the Gerze Basin. This type of foraminifera is associated with lagoon and estuarine environments, indicating that the northern part of the Lhasa terrane was near sea level during the late Eocene. We speculate that these foraminifera were transported inland by storm surges to low elevation freshwater lakes during times of marine transgressions. This inference is consistent with the relatively positive δ18O values in carbonate from the same deposits that indicate low palaeoelevations close to sea level. Considering the palaeoelevation results from the nearby Oligocene basins at a similar latitude and the volcanic history of the Lhasa terrane, we infer that large-magnitude surface uplift of the northern Lhasa terrane occurred between late Eocene and late Oligocene time.
Histone acetyltransferase HAT4 modulates navigation across G2/M and re-entry into G1 in Leishmania donovani
Authors: Yadav Aarti , Chandra Udita , Saha Swati
Published: June 2016

Histone acetyltransferases impact multiple processes. This study investigates the role of histone acetyltransferase HAT4 in Leishmania donovani. Though HAT4 was dispensable for survival, its elimination decreased cell viability and caused cell cycle defects, with HAT4-nulls experiencing an unusually long G2/M. Survival of HAT4-nulls in macrophages was also substantially compromised. DNA microarray analysis revealed that HAT4 modestly regulated the expression of only a select number of genes, thus not being a major modulator of global gene expression. Significantly, cdc20 was among the downregulated genes. To ascertain if decreased expression of cdc20 was responsible for HAT4-null growth and cell cycle defects we expressed LdCdc20 ectopically in HAT4-nulls. We found this to alleviate the aberrant growth and cell cycle progression patterns displayed by HAT4-nulls, with cells navigating G2/M phase and re-entering G1 phase smoothly. HAT4-nulls expressing LdCdc20 ectopically showed survival rates comparable to wild type within macrophages, suggesting that G2/M defects were responsible for poor survival of HAT4-nulls within host cells also. These are the first data analyzing the in vivo functional role of HAT4 in any trypanosomatid. Our results directly demonstrate for the first time a role for Cdc20 in regulating trypanosomatid G2/M events, opening avenues for further research in this area.
Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity
Authors: Baba Shiro , Onga Kazuko , Kakizawa Sho , Ohyama Kyoji , Yasuda Kunihiko , Otsubo Hiroshi , Scott Brian W. , Burnham W. McIntyre , Matsuo Takayuki , Nagata Izumi , Mori Nozomu
Published: June 2016

BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N-Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy.
Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury
Authors: Markó Lajos , Szijártó István A. , Filipovic Milos R. , Kaßmann Mario , Balogh András , Park Joon-Keun , Przybyl Lukasz , N’diaye Gabriele , Krämer Stephanie , Anders Juliane , Ishii Isao , Müller Dominik N. , Gollasch Maik
Published: June 2016

Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth−/−) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth−/− and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth−/− mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth−/− mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection.
Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma
Authors: Madeira Maria H. , Ortin-Martinez Arturo , Nadal-Nícolas Francisco , Ambrósio António F. , Vidal-Sanz Manuel , Agudo-Barriuso Marta , Santiago Ana Raquel
Published: June 2016

Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma.
A microscopic landscape of the invasive breast cancer genome
Authors: Ping Zheng , Xia Yuchao , Shen Tiansheng , Parekh Vishwas , Siegal Gene P. , Eltoum Isam-Eldin , He Jianbo , Chen Dongquan , Deng Minghua , Xi Ruibin , Shen Dejun
Published: June 2016

Histologic grade is one of the most important microscopic features used to predict the prognosis of invasive breast cancer and may serve as a marker for studying cancer driving genomic abnormalities in vivo. We analyzed whole genome sequencing data from 680 cases of TCGA invasive ductal carcinomas of the breast and correlated them to corresponding pathology information. Ten genetic abnormalities were found to be statistically associated with histologic grade, including three most prevalent cancer driver events, TP53 and PIK3CA mutations and MYC amplification. A distinct genetic interaction among these genomic abnormalities was revealed as measured by the histologic grading score. While TP53 mutation and MYC amplification were synergistic in promoting tumor progression, PIK3CA mutation was found to have alleviated the oncogenic effect of either the TP53 mutation or MYC amplification, and was associated with a significant reduction in mitotic activity in TP53 mutated and/or MYC amplified breast cancer. Furthermore, we discovered that different types of genetic abnormalities (mutation versus amplification) within the same cancer driver gene (PIK3CA or GATA3) were associated with opposite histologic changes in invasive breast cancer. In conclusion, our study suggests that histologic grade may serve as a biomarker to define cancer driving genetic events in vivo.
M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation
Authors: Okubo Makiko , Kioi Mitomu , Nakashima Hideyuki , Sugiura Kei , Mitsudo Kenji , Aoki Ichiro , Taniguchi Hideki , Tohnai Iwai
Published: June 2016

Despite the fact that radiation is one of the standard therapies in the treatment of patients with oral cancer, tumours can recur even in the early stages of the disease, negatively impacting prognosis and quality of life. We previously found that CD11b+ bone marrow-derived cells (BMDCs) were recruited into human glioblastoma multiforme (GBM), leading to re-organization of the vasculature and tumour regrowth. However, it is not yet known how these cells contribute to tumour vascularization. In the present study, we investigated the role of infiltrating CD11b+ myeloid cells in the vascularization and recurrence of oral squamous cell carcinoma (OSCC). In a xenograft mouse model, local irradiation caused vascular damage and hypoxia in the tumour and increased infiltration of CD11b+ myeloid cells. These infiltrating cells showed characteristics of M2 macrophages (M2Mφs) and are associated with the promotion of vascularization. M2Mφs promoted tumour progression in recurrence after irradiation compared to non-irradiated tumours. In addition, we found that CD11b+ myeloid cells, as well as CD206+ M2Mφs, are increased during recurrence after radiotherapy in human OSCC specimens. Our findings may lead to the development of potential clinical biomarkers or treatment targets in irradiated OSCC patients.
Realization of Plasmonic Microcavity with Full Transverse and Longitudinal Mode Selection
Authors: Liu Ju , Chen Yue-Gang , Gan Lin , Xiao Ting-Hui , Li Zhi-Yuan
Published: June 2016

Surface plasmon polaritons (SPPs) manipulation is of vital importance to construct ultracompact integrated micro/nano-optical devices and systems. Here we report the design, fabrication and characterization of a SPP microcavity with full transverse and longitudinal mode selection and control on the surface of gold film. The designed microcavity supports the fundamental and first-order transverse modes of Gaussian mode beam with controllable longitudinal modes, respectively. The transverse mode is determined by two holographic mirrors made from deliberately designed groove patterns via the surface electromagnetic wave holography methodology, while the longitudinal mode is determined by the length of cavity. Both numerical simulations and leaky-wave SPP mode observations confirm the realization of full mode selection in the fabricated cavity. Our work opens up a powerful way to fully explore longitudinal and transverse mode control in SPP microcavities, which will be beneficial for light-matter interaction enhancement, construction of novel SPP nanolaser and microlaser, optical sensing and optical information processing.