bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of core-shell structure KClO4@Al/CuO Nanoenergetic material and enhancement of thermal behavior
Authors: Yang Fan , Kang Xiaoli , Luo Jiangshan , Yi Zao , Tang Yongjian
Published: June 2017

In this paper, a solvent/non-solvent synthetic approach has been utilized in preparing a new nanoenergetic material KClO4@Al/CuO by coating Al/CuO nanocomposites particles with a layer of nanoscale oxidizer KClO4. The coating process and mechanism are discussed. The composites of Al/CuO are uniformly mixed by mechanical ball milling process and CuO acts as a catalytic metallic oxide. The ternary mixtures KClO4@Al/CuO were characterized by X-ray diffraction (XRD) and the results reveal that after ball-milling and chemical synthesis process, the phase compositions haven’t changed. Scan electron microscopy (SEM) images show that these energetic nanocomposites consist of small clusters of Al/CuO that are in intimate contact with a continuous and clear-cut KClO4 layer (100–400 nm). In a Scanning transmission electron microscopy (STEM) elemental map, high K/Cl intensity on the perimeter of the nanoparticles and high Cu/Al content in the interior powerfully demonstrated the KClO4@Al/CuO core-shell nanostructure. Electrical ignition experiments and pressure cell test prove that these nanoenergetic composites are more sensitive to ignition with much higher burning rate than traditional formulations (conventional counterparts). To quantify the enhancement of thermal behavior, Thermogravimetry (TG) and Differential scanning calorimetry (DSC) were performed and the results show that the burning rate of these energetic nanocomposites nearly tripled.
Fibronectin promotes directional persistence in fibroblast migration through interactions with both its cell-binding and heparin-binding domains
Authors: Missirlis Dimitris , Haraszti Tamás , Kessler Horst , Spatz Joachim P.
Published: June 2017

The precise mechanisms through which insoluble, cell-adhesive ligands induce and regulate directional cell migration remain obscure. We recently demonstrated that elevated surface density of physically adsorbed plasma fibronectin (FN) promotes high directional persistence in fibroblast migration. While cell-FN association through integrins α5β1and αvβ3was necessary, substrates that selectively engaged these integrins did not support the phenotype. We here show that high directional persistence necessitates a combination of the cell-binding and C-terminal heparin-binding domains of FN, but does not require the engagement of syndecan-4 or integrin α4β1. FN treatment with various fixation agents indicated that associated changes in fibroblast motility were due to biochemical changes, rather than alterations in its physical state. The nature of the coating determined the ability of fibroblasts to assemble endogenous or exogenous FN, while FN fibrillogenesis played a minor, but significant, role in regulating directionality. Interestingly, knockdown of cellular FN abolished cell motility altogether, demonstrating a requirement for intracellular processes in enabling fibroblast migration on FN. Lastly, kinase inhibition experiments revealed that regulation of cell speed and directional persistence are decoupled. Hence, we have identified factors that render full-length FN a promoter of directional migration and discuss the possible, relevant mechanisms.
Structural Characterization of the SMRT Corepressor Interacting with Histone Deacetylase 7
Authors: Desravines Danielle C. , Serna Martin Itziar , Schneider Robert , Mas Philippe J. , Aleksandrova Nataliia , Jensen Malene Ringkjøbing , Blackledge Martin , Hart Darren J.
Published: June 2017

The 2525 amino acid SMRT corepressor is an intrinsically disordered hub protein responsible for binding and coordinating the activities of multiple transcription factors and chromatin modifying enzymes. Here we have studied its interaction with HDAC7, a class IIa deacetylase that interacts with the corepressor complex together with the highly active class I deacetylase HDAC3. The binding site of class IIa deacetylases was previously mapped to an approximate 500 amino acid region of SMRT, with recent implication of short glycine-serine-isoleucine (GSI) containing motifs. In order to characterize the interaction in detail, we applied a random library screening approach within this region and obtained a range of stable, soluble SMRT fragments. In agreement with an absence of predicted structural domains, these were characterized as intrinsically disordered by NMR spectroscopy. We identified one of them, comprising residues 1255–1452, as interacting with HDAC7 with micromolar affinity. The binding site was mapped in detail by NMR and confirmed by truncation and alanine mutagenesis. Complementing this with mutational analysis of HDAC7, we show that HDAC7, via its surface zinc ion binding site, binds to a 28 residue stretch in SMRT comprising a GSI motif followed by an alpha helix.
Super-resolution microscopy with very large working distance by means of distributed aperture illumination
Authors: Birk Udo , Hase Johann v. , Cremer Christoph
Published: June 2017

The limits of conventional light microscopy (“Abbe-Limit“) depend critically on the numerical aperture (NA) of the objective lens. Imaging at large working distances or a large field-of-view typically requires low NA objectives, thereby reducing the optical resolution to the multi micrometer range. Based on numerical simulations of the intensity field distribution, we present an illumination concept for a super-resolution microscope which allows a three dimensional (3D) optical resolution around 150 nm for working distances up to the centimeter regime. In principle, the system allows great flexibility, because the illumination concept can be used to approximate the point-spread-function of conventional microscope optics, with the additional benefit of a customizable pupil function. Compared with the Abbe-limit using an objective lens with such a large working distance, a volume resolution enhancement potential in the order of 104 is estimated.
Towards Printable Natural Dielectric Cloaks via Inverse Scattering Techniques
Authors: Di Donato Loreto , Isernia Tommaso , Labate Giuseppe , Matekovits Ladislau
Published: June 2017

The synthesis of non-magnetic 2D dielectric cloaks as proper solutions of an inverse scattering problem is addressed in this paper. Adopting the relevant integral formulation governing the scattering phenomena, analytic and numerical approaches are exploited to provide new insights on how frequency and direction of arrival of the incoming wave may influence the cloaking mechanism in terms of permittivity distribution within the cover region. In quasi-static (subwavelength) regime a solution is analytically derived in terms of homogeneous artificial dielectric cover with ε < ε0, which is found to be a necessary and sufficient condition for achieving omnidirectional cloaking. On the other hand, beyond quasi-static regime, the cloaking problem is addressed as an optimization task looking for only natural dielectric coatings with ε > ε0 able to hide the object for a given number of directions of the incident field. Simulated results confirm the validity of both analytic and numerical methodologies and allow to estimate effective bandwidths both in terms of frequency range and direction of arrival of the impinging field.
Allosteric modulatory effects of SRI-20041 and SRI-30827 on cocaine and HIV-1 Tat protein binding to human dopamine transporter
Authors: Sun Wei-Lun , Quizon Pamela M. , Yuan Yaxia , Zhang Wei , Ananthan Subramaniam , Zhan Chang-Guo , Zhu Jun
Published: June 2017

Dopamine transporter (DAT) is the target of cocaine and HIV-1 transactivator of transcription (Tat) protein. Identifying allosteric modulatory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific and clinical interest. We demonstrated that tyrosine 470 and 88 act as functional recognition residues in human DAT (hDAT) for Tat-induced inhibition of DA transport and transporter conformational transitions. Here we investigated the allosteric modulatory effects of two allosteric ligands, SRI-20041 and SRI-30827 on cocaine binding on wild type (WT) hDAT, Y470 H and ﻿Y﻿88 F mutants. Effect of SRI-30827 on Tat-induced inhibition of [3H]WIN35,428 binding was also determined. Compared to a competitive DAT inhibitor indatraline, both SRI-compounds displayed a similar decrease (30%) in IC50for inhibition of [3H]DA uptake by cocaine in WT hDAT. The addition of SRI-20041 or SRI-30827 following cocaine slowed the dissociation rate of [3H]WIN35,428 binding in WT hDAT relative to cocaine alone. Moreover, Y470H and Y88F hDAT potentiate the inhibitory effect of cocaine on DA uptake and attenuate the effects of SRI-compounds on cocaine-mediated dissociation rate. SRI-30827 attenuated Tat-induced inhibition of [3H]WIN35,428 binding. These observations demonstrate that tyrosine 470 and 88 are critical for allosteric modulatory effects of SRI-compounds on the interaction of cocaine with hDAT.
Interaction of the Antimicrobial Peptide Aurein 1.2 and Charged Lipid Bilayer
Authors: Rai Durgesh K. , Qian Shuo
Published: June 2017

Aurein 1.2 is a potent antimicrobial peptide secreted by frog Litoria aurea. As a short membrane-active peptide with only 13 amino acids in sequence, it has been found to be residing on the surface of lipid bilayer and permeabilizing bacterial membranes at high concentration. However, the detail at the molecular level is largely unknown. In this study, we investigated the action of Aurein 1.2 in charged lipid bilayers composed of DMPC/DMPG. Oriented Circular Dichroism results showed that the peptide was on the surface of lipid bilayer regardless of the charged lipid ratio. Only at a very high peptide-to-lipid ratio (~1/10), the peptide became perpendicular to the bilayer, however no pore was detected by neutron in-plane scattering. To further understand how it interacted with charged lipid bilayers, we employed Small Angle Neutron Scattering to probe lipid distribution across bilayer leaflets in lipid vesicles. The results showed that Aurein 1.2 interacted strongly with negatively charged DMPG, causing strong asymmetry in lipid bilayer. At high concentration, while the vesicles were intact, we found additional structure feature on the bilayer. Our study provides a glimpse into how Aurein 1.2 disturbs anionic lipid-containing membranes without pore formation.
Dysbiosis in chronic periodontitis: Key microbial players and interactions with the human host
Authors: Deng Zhi-Luo , Szafrański Szymon P. , Jarek Michael , Bhuju Sabin , Wagner-Döbler Irene
Published: June 2017

Periodontitis is an extremely prevalent disease worldwide and is driven by complex dysbiotic microbiota. Here we analyzed the transcriptional activity of the periodontal pocket microbiota from all domains of life as well as the human host in health and chronic periodontitis. Bacteria showed strong enrichment of 18 KEGG functional modules in chronic periodontitis, including bacterial chemotaxis, flagellar assembly, type III secretion system, type III CRISPR-Cas system, and two component system proteins. Upregulation of these functions was driven by the red-complex pathogens and candidate pathogens, e.g. Filifactor alocis, Prevotella intermedia, Fretibacterium fastidiosum and Selenomonas sputigena. Nine virulence factors were strongly up-regulated, among them the arginine deiminase arcA from Porphyromonas gingivalis and Mycoplasma arginini. Viruses and archaea accounted for about 0.1% and 0.22% of total putative mRNA reads, respectively, and a protozoan, Entamoeba gingivalis, was highly enriched in periodontitis. Fourteen human transcripts were enriched in periodontitis, including a gene for a ferric iron binding protein, indicating competition with the microbiota for iron, and genes associated with cancer, namely nucleolar phosphoprotein B23, ankyrin-repeat domain 30B-like protein and beta-enolase. The data provide evidence on the level of gene expression in vivo for the potentially severe impact of the dysbiotic microbiota on human health.
3D Super-Resolution Optical Profiling Using Microsphere Enhanced Mirau Interferometry
Authors: Kassamakov Ivan , Lecler Sylvain , Nolvi Anton , Leong-Hoï Audrey , Montgomery Paul , Hæggström Edward
Published: June 2017

We present quantitative three dimensional images of grooves on a writable Blu-ray Disc based on a single objective Mirau type interferometric microscope, enhanced with a microsphere which is considered as a photonic nanojet source. Along the optical axis the resolution of this microsphere assisted interferometry system is a few nanometers while the lateral resolution is around 112 nm. To understand the physical phenomena involved in this kind of imaging we have modelled the interaction between the photonic jet and the complex disc surface. Agreement between simulation and experimental results is demonstrated. We underline that although the ability of the microsphere to generate a photonic nanojet does not alone explain the resolution of the interferometer, the nanojet can be used to try to understand the imaging process. To partly explain the lateral super-resolution, the potential role of coherence is illustrated. The presented modality may have a large impact on many fields from bio-medicine to nanotechnology.
Epigenetic and antitumor effects of platinum(IV)-octanoato conjugates
Authors: Novohradsky Vojtech , Zanellato Ilaria , Marzano Cristina , Pracharova Jitka , Kasparkova Jana , Gibson Dan , Gandin Valentina , Osella Domenico , Brabec Viktor
Published: June 2017

We present the anticancer properties of cis, cis, trans-[Pt(IV)(NH3)2Cl2(OA)2] [Pt(IV)diOA] (OA = octanoato), Pt(IV) derivative of cisplatin containing two OA units appended to the axial positions of a six-coordinate Pt(IV) center. Our results demonstrate that Pt(IV)diOA is a potent cytotoxic agent against many cancer cell lines (the IC50 values are approximately two orders of magnitude lower than those of clinically used cisplatin or Pt(IV) derivatives with biologically inactive axial ligands). Importantly, Pt(IV)diOA overcomes resistance to cisplatin, is significantly more potent than its branched Pt(IV) valproato isomer and exhibits promising in vivo antitumor activity. The potency of Pt(IV)diOA is a consequence of several factors including enhanced cellular accumulation correlating with enhanced DNA platination and cytotoxicity. Pt(IV)diOA induces DNA hypermethylation and reduces mitochondrial membrane potential in cancer cells at levels markedly lower than the IC50 value of free OA suggesting the synergistic action of platinum and OA moieties. Collectively, the remarkable antitumor effects of Pt(IV)diOA are a consequence of the enhanced cellular uptake which makes it possible to simultaneously accumulate high levels of both cisplatin and OA in cells. The simultaneous dual action of cisplatin and OA by different mechanisms in tumor cells may result in a markedly enhanced and unique antitumor effects of Pt(IV) prodrugs.
Fabrication of modified hydrogenated castor oil/GPTMS-ZnO composites and effect on UV resistance of leather
Authors: Ma Jianzhong , Duan Limin , Lu Juan , Lyu Bin , Gao Dangge , Wu Xionghu
Published: June 2017

Leather products are made from the natural skin collagen fibers. It is vulnerable to the environmental factor such as solar ultraviolet irradiation in the using process. Therefore anti-UV performance is a very important quality, particularly for chrome-free leather. ZnO is a well-known UV absorber commonly used in the cosmetic industry. We have investigated its potential to increase the anti-UV performance of chrome-free leather. Modified hydrogenated castor oil/GPTMS-ZnO (MHCO/ GPTMS-ZnO) composites were prepared using spherical ZnO nanoparticles, hydrogenated castor oil, maleic anhydride and sodium bisulfite. MHCO/GPTMS-ZnO composites have better anti-UV ability and stability. MHCO/GPTMS-ZnO composites were applied to the leather processing. The treated samples were exposed to artificial sunlight. Anti-yellowing tests showed that MHCO/GPTMS-ZnO composites significantly improved anti-UV performance of leather.
Metabolic and evolutionary patterns in the extremely acidophilic archaeon Ferroplasma acidiphilum YT
Authors: Golyshina Olga V. , Tran Hai , Reva Oleg N. , Lemak Sofia , Yakunin Alexander F. , Goesmann Alexander , Nechitaylo Taras Y. , LaCono Violetta , Smedile Francesco , Slesarev Alexei , Rojo David , Barbas Coral , Ferrer Manuel , Yakimov Michail M. , Golyshin Peter N.
Published: June 2017

Ferroplasmaceaerepresent ubiquitous iron-oxidising extreme acidophiles with a number of unique physiological traits. In a genome-based study ofFerroplasma acidiphilumYT, the only species of the genusFerroplasmawith a validly published name, we assessed its central metabolism and genome stability during a long-term cultivation experiment. Consistently with physiology, the genome analysis points toF. acidiphilumYThaving an obligate peptidolytic oligotrophic lifestyle alongside with anaplerotic carbon assimilation. This narrow trophic specialisation abridges the sugar uptake, although all genes for glycolysis and gluconeogenesis, including bifunctional unidirectional fructose 1,6-bisphosphate aldolase/phosphatase, have been identified. Pyruvate and 2-oxoglutarate dehydrogenases are substituted by ‘ancient’ CoA-dependent pyruvate and alpha-ketoglutarate ferredoxin oxidoreductases. In the lab culture, after ~550 generations, the strain exhibited the mutation rate of ≥1.3 × 10−8single nucleotide substitutions per site per generation, which is among the highest values recorded for unicellular organisms. All but one base substitutions were G:C to A:T, their distribution between coding and non-coding regions and synonymous-to-non-synonymous mutation ratios suggest the neutral drift being a prevalent mode in genome evolution in the lab culture. Mutations in nature seem to occur with lower frequencies, as suggested by a remarkable genomic conservation inF. acidiphilumYTvariants from geographically distant populations.
Enhanced Optical Properties of ZnO and CeO2-coated ZnO Nanostructures Achieved Via Spherical Nanoshells Growth On A Polystyrene Template
Authors: Eltayeb Asmaa , Daniels Stephen , McGlynn Enda
Published: June 2017

In this paper, ZnO, CeO2 and CeO2-coated ZnO nanostructures were synthesised by simple and efficient low temperature wet chemical methods on Si (100) and quartz substrates. The ZnO films were prepared by a drop coating deposition method. This was then combined with a thin layer of the redox active material CeO2 to form CeO2-coated ZnO films. Spherical ZnO nanoshell structures and CeO2-coated ZnO nanoshells have been prepared using polystyrene (PS) sphere monolayer templates. The structural properties and morphologies of the nanostructures were analysed by x-ray diffraction (XRD) and scanning electron microscopy (SEM). The nanostructure compositions are studied in more detail using secondary ion mass spectroscopy (SIMS). The optical properties of the nanostructures were measured using ultraviolet-visible (UV-Vis) absorption spectroscopy in order to ascertain the effects of the nanoshell structures and the whispering gallery modes associated with these structures on the optical properties of the deposits. Our data show UV and visible light absorption was very significantly enhanced due to this nanostructuring.
Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
Authors: Uranga Romina María , Millán Carola , Barahona María José , Recabal Antonia , Salgado Magdiel , Martinez Fernando , Ordenes Patricio , Elizondo-Vega Roberto , Sepúlveda Fernando , Uribe Elena , García-Robles María de los Ángeles
Published: June 2017

Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons. In this study, we developed an adenovirus expressing GK shRNA to inhibit GK expression in vivo. When injected into the 3V of rats, this adenovirus preferentially transduced tanycytes. qRT-PCR and Western blot assays confirmed GK mRNA and protein levels were lower in GK knockdown animals compared to the controls. In response to an intracerebroventricular glucose injection, the mRNA levels of anorexigenic POMC and CART and orexigenic AgRP and NPY neuropeptides were altered in GK knockdown animals. Similarly, food intake, meal duration, frequency of eating events and the cumulative eating time were increased, whereas the intervals between meals were decreased in GK knockdown rats, suggesting a decrease in satiety. Thus, GK expression in the ventricular cells appears to play an important role in feeding behavior.
Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice
Authors: Giersch Katja , Homs Maria , Volz Tassilo , Helbig Martina , Allweiss Lena , Lohse Ansgar W. , Petersen Jörg , Buti Maria , Pollicino Teresa , Sureau Camille , Dandri Maura , Lütgehetmann Marc
Published: June 2017

Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species. Peg-IFNα and peg-IFNλ reduced HDV viremia (1.4 log and 1.2 log, respectively) and serum HBsAg levels (0.9-log and 0.4-log, respectively). Intrahepatic quantification of genomic and antigenomic HDV RNAs revealed a median ratio of 22:1 in untreated mice, resembling levels determined in HBV/HDV infected patients. Both IFNs greatly reduced intrahepatic levels of genomic and antigenomic HDV RNA, increasing the amounts of HDAg- and antigenomic RNA-negative hepatocytes. ETV-mediated suppression of HBV replication (2.1-log) did not significantly affect HBsAg levels, HDV productivity and/or release. In humanized mice lacking adaptive immunity, IFNs but not ETV suppressed HDV. Viremia decrease reflected the intrahepatic reduction of all HDV markers, including the antigenomic template, suggesting that intracellular HDV clearance is achievable.
Qualifying a eukaryotic cell-free system for fluorescence based GPCR analyses
Authors: Zemella Anne , Grossmann Solveig , Sachse Rita , Sonnabend Andrei , Schaefer Michael , Kubick Stefan
Published: June 2017

Membrane proteins are key elements in cell-mediated processes. In particular, G protein-coupled receptors (GPCRs) have attracted increasing interest since they affect cellular signaling. Furthermore, mutations in GPCRs can cause acquired and inheritable diseases. Up to date, there still exist a number of GPCRs that has not been structurally and functionally analyzed due to difficulties in cell-based membrane protein production. A promising approach for membrane protein synthesis and analysis has emerged during the last years and is known as cell-free protein synthesis (CFPS). Here, we describe a simply portable method to synthesize GPCRs and analyze their ligand-binding properties without the requirement of additional supplements such as liposomes or nanodiscs. This method is based on eukaryotic cell lysates containing translocationally active endogenous endoplasmic reticulum-derived microsomes where the insertion of GPCRs into biologically active membranes is supported. In this study we present CFPS in combination with fast fluorescence-based screening methods to determine the localization, orientation and ligand-binding properties of the endothelin B (ET-B) receptor upon expression in an insect-based cell-free system. To determine the functionality of the cell-free synthesized ET-B receptor, we analyzed the binding of its ligand endothelin-1 (ET-1) in a qualitative fluorescence-based assay and in a quantitative radioligand binding assay.
A new paradigm for antiangiogenic therapy through controlled release of bevacizumab from PLGA nanoparticles
Authors: Sousa Flávia , Cruz Andrea , Fonte Pedro , Pinto Inês Mendes , Neves-Petersen Maria Teresa , Sarmento Bruno
Published: June 2017

Monoclonal antibodies have deserved a remarkable interest for more than 40 years as a vital tool for the treatment of various diseases. Still, there is a raising interest to develop advanced monoclonal antibody delivery systems able to tailor pharmacokinetics. Bevacizumab is a humanized immunoglobulin IgG1 used in antiangiogenic therapies due to its capacity to inhibit the interaction between vascular endothelial growth factor and its receptor. However, bevacizumab-based antiangiogenic therapy is not always effective due to poor treatment compliance associated to multiples administrations and drug resistance. In this work, we show a promising strategy of encapsulating bevacizumab to protect and deliver it, in a controlled manner, increasing the time between administrations and formulation shelf-life. Nanoencapsulation of bevacizumab represents a significant advance for selective antiangiogenic therapies since extracellular, cell surface and intracellular targets can be reached. The present study shows that bevacizumab-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles does not impair its native-like structure after encapsulation and fully retain the bioactivity, making this nanosystem a new paradigm for the improvement of angiogenic therapy.
The efficacy and toxicities of intensive induction chemotherapy followed by concurrent chemoradiotherapy in nasopharyngeal carcinoma patients with N3 disease
Authors: Zhang Yingying , Chen Mingqiu , Chen Cheng , Kong Lin , Lu Jiade J. , Xu Benhua
Published: June 2017

To assess the feasibility, efficacy and safety of 4 cycles of induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CRT) in nasopharyngeal carcinoma (NPC) patients with N3 disease. ICT consisting of paclitaxel (135 mg/m2) and nedaplatin (80 mg/m2) given every 3 weeks for 4 cycles followed by cisplatin-based CRT was planned. 22 patients completed 4 cycles of TP regimen ICT and the CRT according to the protocol. After 4 cycles of ICT, the ORR of the primary site was 100% (CR 22.7%, PR 77.3%), and that of the cervical lymph nodes was 95.5% (CR 27.3%, PR 68.2%). After the completion of CRT, the ORR of the primary site was 100% (CR 81.8%, PR 18.2%), and that of the cervical lymph nodes also reached 100% (CR 86.4%, PR 3.6%). The main hematological adverse events were grade 1 to 2 (G1/G2) neutropenia/anemia without febrile neutropenia. The most frequent toxicities during CRT were G1/G2 neutropenia, asthenia, oropharyngeal mucositis and skin injury. The median follow-up time was 46.5 (14 to 75) months. The 3-year PFS, DMFS, LRFS and OS were 81.8%, 81.8%, 100%, and 90.9%, respectively. The results suggest that intensive ICT followed by CRT in NPC patients with N3 disease is effective and well tolerated.
A Nationwide Study of Severe and Protracted Diarrhoea in Patients with Primary Immunodeficiency Diseases
Authors: Lee Wen-I , Chen Chien-Chang , Jaing Tang-Her , Ou Liang-Shiou , Hsueh Chuen , Huang Jing-Long
Published: June 2017

Diarrhoea lasting longer than 14 days and failing to respond to conventional management is defined as severe and protracted diarrhoea (SD). In this study, we investigated the prevalence, pathogens and prognosis of SD in primary immunodeficiency diseases (PIDs). Among 246 patients with predominantly paediatric-onset PIDs from 2003–2015, 21 [Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each)] and five [CVID (four), SCID (one)] without identified mutations had SD before prophylactic treatment. Detectable pathogens included pseudomonas, salmonella (six each), E. coli, cytomegalovirus, coxsackie virus and cryptosporidium (one each), all of whom improved after a mean 17 days of antibiotics and/or IVIG treatment. Seven (7/26; 27.0%) patients died [respiratory failure (four), lymphoma, sepsis and intracranial haemorrhage (one each)]. The patients with WAS, CGD and CD40L and SD had a higher mortality rate than those without. Another five males with mutant XIAP, STAT1, FOXP3 (one each) and STAT3 (two) had undetectable-pathogenic refractory diarrhoea (RD) that persisted >21 days despite aggressive antibiotic/steroid treatment and directly resulted in mortality. For the patients with RD without anti-inflammatory optimization, those with mutant XIAP and FOXP3 died of Crohn’s-like colitis and electrolyte exhaustion in awaiting transplantation, while transplantation cured the STAT1 patient.
Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo
Authors: Pepe Anna , Avolio Rosario , Matassa Danilo Swann , Esposito Franca , Nitsch Lucio , Zurzolo Chiara , Paladino Simona , Sarnataro Daniela
Published: June 2017

Shadoo (Sho), a member of prion protein family, has been shown to prevent embryonic lethality in Prnp0/0 mice and to be reduced in the brains of rodents with terminal prion diseases. Sho can also affect PrP structural dynamics and can increase the prion conversion into its misfolded isoform (PrPSc), which is amyloidogenic and strictly related to expression, intracellular localization and association of PrPC to lipid rafts. We reasoned that if Sho possesses a natural tendency to convert to amyloid-like forms in vitro, it should be able to exhibit “prion-like” properties, such as PK-resistance and aggregation state, also in live cells. We tested this hypothesis, by different approaches in neuronal cells, finding that Sho shows folding properties partially dependent on lipid rafts integrity whose alteration, as well as proteasomal block, regulated generation of intermediate Sho isoforms and exacerbated its misfolding. Moreover, a 18 kDa isoform of Sho, likely bearing the signal peptide, was targeted to mitochondria by interacting with the molecular chaperone TRAP1 which, in turn controlled Sho dual targeting to ER or mitochondria. Our studies contribute to understand the role of molecular chaperones and of PrP-related folding intermediates in “prion-like” conversion.
Nucleotide based covalent inhibitors of KRas can only be efficient in vivo if they bind reversibly with GTP-like affinity
Authors: Müller Matthias P. , Jeganathan Sadasivam , Heidrich Angelika , Campos Jeremy , Goody Roger S.
Published: June 2017

Simple reversible competitive inhibition of nucleotide binding of GTP to Ras family GTPases has long been recognized as an unlikely approach to manipulating the activity of such proteins for experimental or therapeutic purposes. This is due to the high affinity of GTP to GTPases coupled with high cellular GTP concentrations, but also to problems of specificity for the highly conserved binding sites in GTPases. A recent approach suggested that these problems might be overcome by using GDP derivatives that can undergo a covalent reaction with disease specific mutants, in particular addressing inhibition of KRasG12C using GDP equipped with an electrophilic group at the β-phosphate. We show here that a major drawback to this approach is a loss of reversible affinity of such β-modified derivatives for Ras of at least 104 compared to GTP and GDP. With the help of a thorough kinetic characterization, we show that this leads to covalent reaction times that are too slow to make the compounds attractive for intracellular use, but that generation of a hypothetical reactive GDP derivative that retains the high reversible affinity of GDP/GTP to Ras might be a viable alternative.
Recovery of the first full-length genome sequence of a parapoxvirus directly from a clinical sample
Authors: Günther Thomas , Haas Ludwig , Alawi Malik , Wohlsein Peter , Marks Jerzy , Grundhoff Adam , Becher Paul , Fischer Nicole
Published: June 2017

We recovered the first full-length poxvirus genome, including the terminal hairpin region, directly from complex clinical material using a combination of second generation short read and third generation nanopore sequencing technologies. The complete viral genome sequence was directly recovered from a skin lesion of a grey seal thereby preventing sequence changes due to in vitro passaging of the virus. Subsequent analysis of the proteins encoded by this virus identified genes specific for skin adaptation and pathogenesis of parapoxviruses. These data warrant the classification of seal parapoxvirus, tentatively designated SePPV, as a new species within the genus Parapoxvirus.
Distribution and kinetics of the Kv1.3-blocking peptide HsTX1[R14A] in experimental rats
Authors: Bergmann Ralf , Kubeil Manja , Zarschler Kristof , Chhabra Sandeep , Tajhya Rajeev B. , Beeton Christine , Pennington Michael W. , Bachmann Michael , Norton Raymond S. , Stephan Holger
Published: June 2017

The peptide HsTX1[R14A] is a potent and selective blocker of the voltage-gated potassium channel Kv1.3, which is a highly promising target for the treatment of autoimmune diseases and other conditions. In order to assess the biodistribution of this peptide, it was conjugated with NOTA and radiolabelled with copper-64. [64Cu]Cu-NOTA-HsTX1[R14A] was synthesised in high radiochemical purity and yield. The radiotracer was evaluated in vitro and in vivo. The biodistribution and PET studies after intravenous and subcutaneous injections showed similar patterns and kinetics. The hydrophilic peptide was rapidly distributed, showed low accumulation in most of the organs and tissues, and demonstrated high molecular stability in vitro and in vivo. The most prominent accumulation occurred in the epiphyseal plates of trabecular bones. The high stability and bioavailability, low normal-tissue uptake of [64Cu]Cu-NOTA-HsTX1[R14A], and accumulation in regions of up-regulated Kv channels both in vitro and in vivo demonstrate that HsTX1[R14A] represents a valuable lead for conditions treatable by blockade of the voltage-gated potassium channel Kv1.3. The pharmacokinetics shows that both intravenous and subcutaneous applications are viable routes for the delivery of this potent peptide.
High-resolution imaging of a cell-attached nanointerface using a gold-nanoparticle two-dimensional sheet
Authors: Masuda Shihomi , Yanase Yuhki , Usukura Eiji , Ryuzaki Sou , Wang Pangpang , Okamoto Koichi , Kuboki Thasaneeya , Kidoaki Satoru , Tamada Kaoru
Published: June 2017

This paper proposes a simple, effective, non-scanning method for the visualization of a cell-attached nanointerface. The method uses localized surface plasmon resonance (LSPR) excited homogeneously on a two-dimensional (2D) self-assembled gold-nanoparticle sheet. The LSPR of the gold-nanoparticle sheet provides high-contrast interfacial images due to the confined light within a region a few tens of nanometers from the particles and the enhancement of fluorescence. Test experiments on rat basophilic leukemia (RBL-2H3) cells with fluorescence-labeled actin filaments revealed high axial and lateral resolution even under a regular epifluorescence microscope, which produced higher quality images than those captured under a total internal reflection fluorescence (TIRF) microscope. This non-scanning-type, high-resolution imaging method will be an effective tool for monitoring interfacial phenomena that exhibit relatively rapid reaction kinetics in various cellular and molecular dynamics.
Design of Non-Deterministic Quasi-random Nanophotonic Structures Using Fourier Space Representations
Authors: Yu Shuangcheng , Wang Chen , Zhang Yichi , Dong Biqin , Jiang Zhen , Chen Xiangfan , Chen Wei , Sun Cheng
Published: June 2017

Despite their seemingly random appearances in the real space, quasi-random nanophotonic structures exhibit distinct structural correlations and have been widely utilized for effective photon management. However, current design approaches mainly rely on the deterministic representations consisting two-dimensional (2D) discretized patterns in the real space. They fail to capture the inherent non-deterministic characteristic of the quasi-random structures and inevitably result in a large design dimensionality. Here, we report a new design approach that employs the one-dimensional (1D) spectral density function (SDF) as the unique representation of non-deterministic quasi-random structures in the Fourier space with greatly reduced design dimensionality. One 1D SDF representation can be used to generate infinite sets of real space structures in 2D with equally optimized performance, which was further validated experimentally using light-trapping structures in a thin film absorber as a model system. The optimized non-deterministic quasi-random nanostructures improve the broadband absorption by 225% over the unpatterned cell.
Targeting the duality of cancer
Authors: Arbiser Jack L. , Bonner Michael Y. , Gilbert Linda C.
Published: June 2017

Cancer is the second leading cause of death in the United States, and is an increasing cause of death in the developing world. While there is great heterogeneity in the anatomic site and mutations involved in human cancer, there are common features, including immortal growth, angiogenesis, apoptosis evasion, and other features, that are common to most if not all cancers. However, new features of human cancers have been found as a result of clinical use of novel “targeted therapies,” angiogenesis inhibitors, and immunotherapies, including checkpoint inhibitors. These findings indicate that cancer is a moving target, which can change signaling and metabolic features based upon the therapies offered. It is well-known that there is significant heterogeneity within a tumor and it is possible that treatment might reduce the heterogeneity as a tumor adapts to therapy and, thus, a tumor might be synchronized, even if there is no major clinical response. Understanding this concept is important, as concurrent and sequential therapies might lead to improved tumor responses and cures. We posit that the repertoire of tumor responses is both predictable and limited, thus giving hope that eventually we can be more effective against solid tumors. Currently, among solid tumors, we observe a response of 1/3 of tumors to immunotherapy, perhaps less to angiogenesis inhibition, a varied response to targeted therapies, with relapse and resistance being the rule, and a large fraction being insensitive to all of these therapies, thus requiring the older therapies of chemotherapy, surgery, and radiation. Tumor phenotypes can be seen as a continuum between binary extremes, which will be discussed further. The biology of cancer is undoubtedly more complex than duality, but thinking of cancer as a duality may help scientists and oncologists discover optimal treatments that can be given either simultaneously or sequentially.
Upconversion fluorescence imaging of HeLa cells using ROS generating SiO2-coated lanthanide-doped NaYF4 nanoconstructs
Authors: Kowalik Przemysław , Elbaum Danek , Mikulski Jakub , Fronc Krzysztof , Kamińska Izabela , Morais Paulo C. , Eduardo de Souza Paulo , Nunes Rodrigo Barbosa , Veiga-Souza Fabiane Hiratsuka , Gruzeł Grzegorz , Minikayev Roman , Wojciechowski Tomasz , Mosiniewicz-Szablewska Ewa , Szewczyk Maciej , Pawlyta Mirosława , Sienkiewicz Andrzej , Łapiński Mariusz , Zajdel Karolina , Stępień Piotr , Szczepkowski Jacek , Jastrzębski Włodzimierz , Frontczak-Baniewicz Małgorzata , Paszkowicz Wojciech , Sikora Bożena
Published: June 2017

Multicolor upconversion of SiO2-coated nanoparticles using for cells imaging and reactive oxygen species generation.
Efficient energy-level modification of novel pyran-annulated perylene diimides for photocatalytic water splitting
Authors: Wang Ran , Li Gang , Zhang Andong , Wang Wen , Cui Guanwei , Zhao Jianfeng , Shi Zhiqiang , Tang Bo
Published: June 2017

This work reports a facile method to prepare pyran-annulated perylene diimides, which are used as photocatalysts in photocatalytic water splitting.
Intermix of metal nanoparticles–single wall carbon nanotubes
Authors: Xu Feng , Lu Qin , Ye Lin , Tsang S. C. Edman
Published: June 2017

Separated metal islands with no inter-atomic mixing on single walled carbon nanotubes exhibit electrocatalytic properties comparable to corresponding nanoalloy structures.
Salt-induced cluster formation of gold nanoparticles followed by stopped-flow SAXS, DLS and extinction spectroscopy
Authors: Carl Nico , Prévost Sylvain , Fitzgerald Joseph P. S. , Karg Matthias
Published: June 2017

The salt-induced cluster formation of negatively charged gold nanoparticles was studied by time-resolved DLS, stopped-flow SAXS and in-situ extinction spectroscopy.
The electronic transport properties of zigzag phosphorene-like MX (M = Ge/Sn, X = S/Se) nanostructures
Authors: Zhang Mengjun , An Yipeng , Sun Yongqiang , Wu Dapeng , Chen Xuenian , Wang Tianxing , Xu Guoliang , Wang Kun
Published: June 2017

Zigzag phosphorene-like MXene (M = Ge/Sn, X = S/Se) nanoribbons present various electronic transport properties.
Methanol–methanol and methanol–water systems: the intermolecular interactions controlling the transition from small clusters to the liquid phase
Authors: Albertí Margarita , Amat Anna , Aguilar Antonio , Pirani Fernando
Published: June 2017

The present paper focuses on the characterization of the properties of methanol and water molecules in gas and liquid enviroments.
Photoprotection: extending lessons learned from studying natural sunscreens to the design of artificial sunscreen constituents
Authors: Baker Lewis A. , Marchetti Barbara , Karsili Tolga N. V. , Stavros Vasilios G. , Ashfold Michael N. R.
Published: June 2017

Ultrafast pump–probe spectroscopies and computational chemistry unravel the excited state photophysics responsible for the photostability of molecules in natural and commercial sunscreens.
Noble metal-free catalytic decarboxylation of oleic acid to n-heptadecane on nickel-based metal–organic frameworks (MOFs)
Authors: Yang L. , McNichols B. W. , Davidson M. , Schweitzer B. , Gómez-Gualdrón D. A. , Trewyn B. G. , Sellinger A. , Carreon M. A.
Published: June 2017

Herein we demonstrate novel noble metal-free catalytic systems based on Ni MOFs that can effectively convert oleic acid into heptadecane.
Polymer [Pd(CH2SO2C6H4Me)2]n, a precursor to remarkably stable Pd organometallics
Authors: Pérez-Briso Celeste , Gallego Ana M. , Martín-Alvarez Jose M. , Martínez-Ilarduya Jesús M. , Espinet Pablo
Published: June 2017

Stable (arylsulfonyl)alkylpalladium complexes obtained from the polymer [Pd(CH2SO2C6H4Me)2]n undergo cis-to-trans isomerization in order to produce systems with stronger hydrogen bonds.
Alkali and alkaline earth metal salts of tetrazolone: structurally interesting and excellently thermostable
Authors: He Piao , Wu Le , Wu Jin-Ting , Yin Xin , Gozin Michael , Zhang Jian-Guo
Published: June 2017

Alkali and alkaline earth metal salts of tetrazolone were first reported and may be promising potential candidates of new green insensitive energetic materials.
Optimising the relaxivities of Mn2+ complexes by targeting human serum albumin (HSA)
Authors: Forgács Attila , Tei Lorenzo , Baranyai Zsolt , Esteban-Gómez David , Platas-Iglesias Carlos , Botta Mauro
Published: June 2017

The Mn2+ complexes of two differently benzyl-substituted 1,4-DO2AM ligands show a strong increase in relaxivity upon human serum albumin binding.
Addition of conductive particles to improve the performance of activated carbon air-cathodes in microbial fuel cells
Authors: Zhang Xiaoyuan , Wang Qiuying , Xia Xue , He Weihua , Huang Xia , Logan Bruce E.
Published: June 2017

Inexpensive carbon black combined with heat-treatment produced the most effective activated carbon catalyst for improving microbial fuel cell cathode performance.
The formation of p-toluic acid from coumalic acid: a reaction network analysis
Authors: Pfennig Toni , Johnson Robert L. , Shanks Brent H.
Published: June 2017

Diels–Alder cycloaddition of biomass-derived 2-pyrone coumalic acid (CMA) with propylene provides an alternative pathway to produce toluic acid (TA), a precursor to terephthalic acid (TPA) which is a key component in the manufacture of polyethylene terephthalate (PET).
Size-tunable microvortex capture of rare cells
Authors: Khojah Reem , Stoutamore Ryan , Di Carlo Dino
Published: June 2017

A wide distribution of cell sizes can be selectively captured by tuning the flow rate in a micro-vortex flow.
Xanthine sensor development based on ZnO–CNT, ZnO–CB, ZnO–GO and ZnO nanoparticles: an electrochemical approach
Authors: Rahman Mohammed M. , Marwani Hadi M. , Algethami Faisal K. , Asiri Abdullah M.
Published: June 2017

The wet-chemical method was used to prepare the various ZnO–CNT, ZnO–CB, ZnO–GO nanocomposites, and ZnO nanoparticles in higher pH medium, which were finally utilized with 5% nafion to produce a thin film of NCs/Nafion/GCE sensor that has a faster response towards selected xanthine with higher sensitivity, lower detection limit, and large linear dynamic range by electrochemical approach.
A luminescent layered hybrid Ag–Ru/LDH as a photocatalytic antibacterial agent
Authors: Xiao Fangnan , Liu Xiaolin , Xiao Yue , Chen Fangman , Wu Yunkun
Published: June 2017

We report a novel Ag–Ru/LDH hybrid that could be used as a highly effective photocatalytic antibacterial agent.
PEGylated molybdenum dichalcogenide (PEG-MoS2) nanosheets with enhanced peroxidase-like activity for the colorimetric detection of H2O2
Authors: Zhao Huimin , Li Yaxi , Tan Bing , Zhang Yaobin , Chen Xiaochi , Quan Xie
Published: June 2017

Colorimetric detection of H2O2using biocompatible and dispersible PEG-MoS2nanosheets with enhanced peroxidase-like catalytic activity.
Static pressure-induced neural differentiation of mesenchymal stem cells
Authors: Mou Xiaoning , Wang Shu , Liu Xiaowang , Guo Weibo , Li Jianhua , Qiu Jichuan , Yu Xin , Wang Zhong Lin , Liu Xiaogang , Geng Zhaoxin , Liu Hong
Published: June 2017

Growing experimental evidence suggests that physical cues play an important role in regulating the fate of stem cells and stimulating their differentiation behavior.
Tailoring degree of esterification and branching of poly(glycerol sebacate) by energy efficient microwave irradiation
Authors: Lau Chi Ching , Bayazit Mustafa Kemal , Knowles Jonathan Campbell , Tang Junwang
Published: June 2017

A branched poly(glycerol sebacate) prepolymer has been successfully synthesised via single mode microwave irradiation with an improved reaction rate and controllable properties.
Correction: Thermoresponsive gels directly obtained via visible light-mediated polymerization-induced self-assembly with oxygen tolerance
Authors: Ren Kaixuan , Perez-Mercader Juan
Published: June 2017

Correction for ‘Thermoresponsive gels directly obtained via visible light-mediated polymerization-induced self-assembly with oxygen tolerance’ by Kaixuan Ren et al., Polym. Chem., 2017, DOI: 10.1039/c7py00558j.
N-Methylcarbamoyl azide: spectroscopy, X-ray structure and decomposition via methylcarbamoyl nitrene
Authors: Wan Huabin , Li Hongmin , Xu Jian , Wu Zhuang , Liu Qifan , Chu Xianxu , Abe Manabu , Bégué Didier , Zeng Xiaoqing
Published: June 2017

N-Methylcarbamoyl azide has been characterized and the nitrene intermediate in its Curtius-rearrangement has been observed in two conformations by matrix-isolation IR and EPR spectroscopy.
A benzothiadiazole-based fluorescent sensor for selective detection of oxalyl chloride and phosgene
Authors: Zhang Wen-Qiang , Cheng Ke , Yang Xinyu , Li Qiu-Yan , Zhang He , Ma Zheng , Lu Han , Wu Hui , Wang Xiao-Jun
Published: June 2017

A turn-on fluorescent sensor based on benzothiadiazole was constructed for simultaneous selective and visual detection of oxalyl chloride and phosgene.