bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple and novel method to design flexible and transparent epoxy resin with tunable mechanical properties
Authors: Huang Jinrui , Nie Xiaoan
Published: April 2016

Flexible and transparent epoxy resin is fabricated by adding modified resin (MR) into diglycidyl ether of bisphenol A (DGEBA). The MR is prepared by the ring‐opening of the epoxy functional group of the DGEBA. The mechanical properties of the epoxy resin are tuned by adjusting the weight ratio of MR to DGEBA. When the MR content is 25 wt%, the elongation at break and the tensile strength of the epoxy resin can reach 69.1% and 27.0 MPa, respectively. Cured blends of DGEBA and MR are characterized using scanning electron microscopy, dynamic mechanical analysis and thermogravimetric analysis to reveal the mechanism of improving the flexibility of the epoxy resin while maintaining excellent transparency. © 2016 Society of Chemical Industry
Positron annihilation lifetime study of atomic imperfections in nanostructurized solids: On the parameterized trapping in wet‐milled arsenic sulfides As4S4
Authors: Shpotyuk Oleh , Ingram Adam , Filipecki Jacek , Bujňáková Zdenka , Baláž Peter
Published: April 2016

The phenomenon of positron–electron annihilation in lifetime measuring mode is considered as a tool to study nanostructurization in solids possessing mixed positron and positronium (Ps) trapping. Structural inhomogeneities due to guest nanoparticles in such solids are described in terms of substitution trapping in positron‐ and Ps‐related sites within the same host matrix. The developed approach allows estimation of interfacial free‐volume voids as being responsible for positron trapping and defect‐free bulk positron lifetimes of nanoparticle‐modified solids. For the example of arsenic sulfide, As4S4 nanoparticles embedded in polyvinylpyrrolidone (PVP) environment under high‐energy ball milling, an alternative algorithm to parameterize these structural imperfections is justified. Interfacial free‐volume voids between neighboring nanoparticles filled with loosely packed As4S4 crystallites are considered as the most probable positron trapping sites. The observed variations in mixed positron–Ps trapping modes under nanostructurization are adequately defined with respect to the chemistry of guest nanoparticles. Direct evidence for this algorithm is provided as the basis of experimental three‐term decomposed positron lifetime spectra for As4S4–PVP nanocomposites parameterized with respect to different fitting protocols.
Handling incomplete correlated continuous and binary outcomes in meta‐analysis of individual participant data
Authors: Gomes Manuel , Hatfield Laura , Normand Sharon‐Lise
Published: April 2016

Meta‐analysis of individual participant data (IPD) is increasingly utilised to improve the estimation of treatment effects, particularly among different participant subgroups. An important concern in IPD meta‐analysis relates to partially or completely missing outcomes for some studies, a problem exacerbated when interest is on multiple discrete and continuous outcomes. When leveraging information from incomplete correlated outcomes across studies, the fully observed outcomes may provide important information about the incompleteness of the other outcomes. In this paper, we compare two models for handling incomplete continuous and binary outcomes in IPD meta‐analysis: a joint hierarchical model and a sequence of full conditional mixed models. We illustrate how these approaches incorporate the correlation across the multiple outcomes and the between‐study heterogeneity when addressing the missing data. Simulations characterise the performance of the methods across a range of scenarios which differ according to the proportion and type of missingness, strength of correlation between outcomes and the number of studies. The joint model provided confidence interval coverage consistently closer to nominal levels and lower mean squared error compared with the fully conditional approach across the scenarios considered. Methods are illustrated in a meta‐analysis of randomised controlled trials comparing the effectiveness of implantable cardioverter‐defibrillator devices alone to implantable cardioverter‐defibrillator combined with cardiac resynchronisation therapy for treating patients with chronic heart failure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Joint modelling of longitudinal and multi‐state processes: application to clinical progressions in prostate cancer
Authors: Ferrer Loïc , Rondeau Virginie , Dignam James , Pickles Tom , Jacqmin‐Gadda Hélène , Proust‐Lima Cécile
Published: April 2016

Joint modelling of longitudinal and survival data is increasingly used in clinical trials on cancer. In prostate cancer for example, these models permit to account for the link between longitudinal measures of prostate‐specific antigen (PSA) and time of clinical recurrence when studying the risk of relapse. In practice, multiple types of relapse may occur successively. Distinguishing these transitions between health states would allow to evaluate, for example, how PSA trajectory and classical covariates impact the risk of dying after a distant recurrence post‐radiotherapy, or to predict the risk of one specific type of clinical recurrence post‐radiotherapy, from the PSA history. In this context, we present a joint model for a longitudinal process and a multi‐state process, which is divided into two sub‐models: a linear mixed sub‐model for longitudinal data and a multi‐state sub‐model with proportional hazards for transition times, both linked by a function of shared random effects. Parameters of this joint multi‐state model are estimated within the maximum likelihood framework using an EM algorithm coupled with a quasi‐Newton algorithm in case of slow convergence. It is implemented under R, by combining and extending mstate and JM packages. The estimation program is validated by simulations and applied on pooled data from two cohorts of men with localized prostate cancer. Thanks to the classical covariates available at baseline and the repeated PSA measurements, we are able to assess the biomarker's trajectory, define the risks of transitions between health states and quantify the impact of the PSA dynamics on each transition intensity. Copyright © 2016 John Wiley & Sons, Ltd.
Study of complexes formation between transition metal ions and amylopectin in DMSO/H2O solution
Authors: Peres Gisele Louro , Leite Daiani Canabarro , da Silveira Nadya Pesce
Published: April 2016

The complexation ability of amylopectin (starch polymer) treated with ultrasound in DMSO/H2O solution was investigated with respect to several metal ions, with the assistance of a factorial design (experimental planning), in order to establish and optimize the best complexation conditions. Acetate, chloride, and nitrate were counter‐ions in the metal salts. The effects of temperature, time, and salt amount were evaluated during the complexation reactions using multivariate analysis, a set of mathematic methods capable of evaluating all system variables at once and, through this, temperature was found to be the most influential variable. Results for pH and conductivity provided evidence of complex formation between amylopectin and metal ions. In addition, small shifts in the vibrational frequency between the pure biopolymer and its metal complexes were detected using principal component analysis by interval (i‐PCA, a multivariate analysis method), supporting the formation of complexes. The complexes formed with CuII and CrIII ions presented the best complexation yield (40.0 and 55.4%, respectively) with the biopolymer.
Brief Report: Elastin Microfibril Interface 1 and Integrin-Linked Protein Kinase Are Novel Markers of Islet Regenerative Function in Human Multipotent Mesenchymal Stromal Cells
Authors: Lavoie Jessie R. , Creskey Marybeth M. , Muradia Gauri , Bell Gillian I. , Sherman Stephen E. , Gao Jun , Stewart Duncan J. , Cyr Terry D. , Hess David A. , Rosu-Myles Michael
Published: April 2016

Multipotent mesenchymal stromal cell (MSC) transplantation is proposed as a novel therapy for treating diabetes by promoting the regeneration of damaged islets. The clinical promise of such treatments may be hampered by a high degree of donor-related variability in MSC function and a lack of standards for comparing potency. Here, we set out to identify markers of cultured human MSCs directly associated with islet regenerative function. Stromal cultures from nine separate bone marrow donors were demonstrated to have differing capacities to reduce hyperglycemia in the NOD/SCID streptozotocin-induced diabetic model. Regenerative (R) and non-regenerative (NR) MSC cultures were directly compared using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics. A total of 1,410 proteins were quantified resulting in the identification of 612 upregulated proteins and 275 downregulated proteins by ± 1.2-fold in R-MSC cultures. Elastin microfibril interface 1 (EMILIN-1), integrin-linked protein kinase (ILK), and hepatoma-derived growth factor (HDGF) were differentially expressed in R-MSCs, and Ingenuity Pathway Analyses revealed each candidate as known regulators of integrin signaling. Western blot validation of EMILIN-1, ILK, and HDGF not only showed significantly higher abundance levels in R-MSCs, as compared with NR-MSCs, but also correlated with passage-induced loss of islet-regenerative potential. Generalized estimating equation modeling was applied to examine the association between each marker and blood glucose reduction. Both EMILIN-1 and ILK were significantly associated with blood glucose lowering function in vivo. Our study is the first to identify EMILIN-1 and ILK as prospective markers of islet regenerative function in human MSCs.
Pharmacological Modulation of Ischemic‐Reperfusion Injury during Pringle Maneuver in Hepatic Surgery. A Prospective Randomized Pilot Study
Authors: Donadon Matteo , Molinari Andrea Forastieri , Corazzi Francesco , Rocchi Laura , Zito Paola , Cimino Matteo , Costa Guido , Raimondi Ferdinando , Torzilli Guido
Published: April 2016

Background

The Pringle maneuver, which is performed during liver surgery to reduce blood loss, may result in liver ischemia/reperfusion injury resulting in metabolic, immunological, and microvascular changes, which may lead to hepatocellular damage. The aim of this study was the investigation of the effects of N‐acetylcysteine (NAC) and methylprednisolone (MET) in the modulation of liver warm ischemia during hepatic resection.

Methods

Forty‐eight patients were enrolled in a pilot double‐blind, randomized clinical trial. The patients received either NAC, MET, or placebo. The primary endpoint was the reduction in postoperative alanine aminotransferase and bilirubin. The secondary endpoint was the difference in morbidity and mortality.

Results

All the 48 patients had liver resection with no mortality. Morbidity was observed in 8 (16 %) patients equally distributed among the groups. There was a significant favorable recovery of liver function tests in patients treated with NAC or MET compared with the placebo when the Pringle maneuver exceeded 70 min.

Conclusions

The administration of NAC or MET prior to the Pringle maneuver during hepatic resection is associated with lower postoperative aberration in liver function tests compared with placebo when the Pringle maneuver exceeded 70 min. Larger studies are required to validate our findings and to investigate the specific role of NAC and MET in liver surgery.
Response to Treatment is Highly Predictable in cN0 Patients with Papillary Thyroid Carcinoma
Authors: Gorshtein Alexander , Benbassat Carlos , Robenshtok Eyal , Shimon Ilan , Hirsch Dania
Published: April 2016

Background

While involvement of macrometastatic lymph nodes is a recognized independent predictor of an adverse course in papillary thyroid cancer (PTC) patients, the clinicopathological variables associated with disease persistence/recurrence in clinically node‐negative (cN0) disease are not well defined. The indications for prophylactic central neck dissection (pCND) in this patient group remain unclear as well. We aim to investigate the risk factors associated with short‐ and long‐term persistence/recurrence of PTC in patients with cN0 disease at presentation compared to patients with PTC and cervical lymph node involvement (N1) and the response to initial treatment in these subgroups of patients.

Methods

Data were collected retrospectively for 392 consecutive patients with PTC, 223 with cN0 disease and 169 with N1 disease, who were treated and followed at a single tertiary medical center in which pCND is not routinely performed for PTC.

Results

Compared to patients with N1 disease, patients with cN0 disease had significantly smaller tumors, lower rates of multifocality, and less extrathyroidal extension. Persistency rates at 1 year were 6.7 % in the cN0 group and 47 % in the N1 group, and at last follow‐up, 3.6 and 33.5 %, respectively (p = 0.001 for both time points). Within the cN0 group, those with persistent disease at 1 year (n = 15) had significantly larger tumors and higher stimulated thyroglobulin. Only six had structural residual disease, four of them lymph node metastases. All patients with persistent disease were initially treated with total thyroidectomy and radioiodine. Recurrence occurred in only three patients. After 8.3 ± 3.8 years of follow‐up, eight patients with cN0 had persistent disease, three of them biochemical. Higher American Joint Committee of Cancer stage and extrathyroidal extension were the only factors that predicted disease persistence at the last follow‐up in this group.

Conclusions

Patients with cN0 PTC and no distant metastases are usually disease free after thyroidectomy with/without radioactive iodine and do not need further interventions. The initial staging in these patients is a valid prognostic factor for disease outcomes.
The motion of a freely floating cylinder in the presence of a wall and the approximation of resonances
Authors: McIver P. , Porter R.
Published: April 2016

A linear theory, based on wide-spacing and high-frequency approximations, is developed to describe resonant behaviour in two-dimensional water-wave problems involving a freely floating half-immersed cylinder in the presence of a vertical rigid wall. The theory is not able to describe the lowest-frequency resonance, but otherwise yields explicit approximations for the locations of resonances in the complex plane and for their corresponding residues. Two problems are investigated in detail: the time-domain motion following a vertical displacement of the cylinder from equilibrium, and the time-harmonic motion of a cylinder that is excited by an incident plane wave.
Explicit expressions for eddy-diffusivity fields and effective large-scale advection in turbulent transport
Authors: Boi S. , Mazzino A. , Lacorata G.
Published: April 2016

Large-scale transport is investigated in terms of new explicit expressions for eddy diffusivities and effective advection obtained from asymptotic perturbative methods. The carrier flow is formed by a large-scale component plus a small-scale contribution mimicking a turbulent flow. The scalar dynamics is observed in its pre-asymptotic regimes (i.e. on scales comparable to those of the large-scale velocity). The resulting eddy diffusivity is thus a tensor field which explicitly depends on the large-scale velocity. Small-scale interactions also cause the emergence of an effective large-scale (compressible) advection field which, as a result of the present study however, turns out to be of negligible importance. Two issues are addressed by means of Lagrangian simulations: quantifying the possible deterioration of the eddy-diffusivity/effective advection description by reducing to zero the spectral gap separating the large-scale velocity component from the small-scale component; comparing the accuracy of our closure against other simple, reasonable, options. Answering these questions is important in view of possible applications of our closure to tracer dispersion in environmental flows.
Stagnation and mass loss on a Himalayan debris-covered glacier: processes, patterns and rates
Authors: THOMPSON SARAH , BENN DOUGLAS I. , MERTES JORDAN , LUCKMAN ADRIAN
Published: April 2016

The ablation areas of debris-covered glaciers typically consist of a complex mosaic of surface features with contrasting processes and rates of mass loss. This greatly complicates glacier response to climate change, and increases the uncertainty of predictive models. In this paper we present a series of high-resolution DEMs and repeat lake bathymetric surveys on Ngozumpa Glacier, Nepal, to study processes and patterns of mass loss on a Himalayan debris-covered glacier in unprecedented detail. Most mass loss occurs by melt below supraglacial debris, and melt and calving of ice cliffs (backwasting). Although ice cliffs cover only ~5% of the area of the lower tongue, they account for 40% of the ablation. The surface debris layer is subject to frequent re-distribution by slope processes, resulting in large spatial and temporal differences in debris-layer thickness, enhancing or inhibiting local ablation rates and encouraging continuous topographic inversion. A moraine-dammed lake on the lower glacier tongue (Spillway Lake) underwent a period of rapid expansion from 2001 to 2009, but later experienced a reduction of area and volume as a result of lake level lowering and sediment redistribution. Rapid lake growth will likely resume in the near future, and may eventually become up to 7 km long.
Facing Marxist Orthodoxy: Western Marxism,The Making, and the Communist Historiographies of Czechoslovakia and Poland, 1948–1990
Authors: Kučera Rudolf
Published: April 2016

Although the impact of Thompson’s work outside the UK has been recognized and pointed to many times, the ways in which Thompsonian categories and concepts, or Marxist thought from the West more broadly, was received in the countries of the former Eastern Bloc remain rather unclear. AlthoughThe Makinghas never been translated into Polish, Czech, or Slovak, the historians of East-Central European countries were not totally cut off from Western scholarship. Major academic institutes and universities throughout the communist bloc maintained basic contacts with colleagues in the West, and Thompson’s work was known among some local social historians. Marxism from the West in general and Thompson’s work in particular posed challenges that had to be dealt with. This paper traces the ways in which historians of Poland and Czechoslovakia responded to these challenges to the official position of Marxist orthodoxy. TakingThe Makingas an example, it highlights the reception (or lack thereof) of Western influences on local scholarship, and the dynamics of these encounters – whether they were affirmative or critical – in relation to the changing political landscape of East-Central European countries after World War II.
CPA Calculation Method based on AIS Position Prediction
Authors: Sang Ling-zhi , Yan Xin-ping , Wall Alan , Wang Jin , Mao Zhe
Published: April 2016

The information on the Closest Point of Approach (CPA) of another vessel to own ship is required in a potential collision situation as it helps determines the risk to each vessel. CPA is usually calculated based on the speed and direction of the approaching ship neglecting the Change Of Speed (COS) and the Rate Of Turn (ROT). This will make the CPA less useful. To improve the CPA calculation, Automatic Identification System (AIS) information containing the Speed Over Ground (SOG), Course Over Ground (COG), COS and ROT is used. Firstly, a model using these four factors is built to predict ship positions better. Secondly, a three-step CPA searching method is developed. The developed CPA calculation method can assist in informing the navigation decisions and reducing unnecessary manoeuvres. Through the analysis of a real collision scenario, this paper shows that the proposed method can help identify and warn of anomalous ship behaviours in a realistic time frame.
The Chp1 chromodomain binds the H3K9me tail and the nucleosome core to assemble heterochromatin
Authors: Zocco Manuel , Marasovic Mirela , Pisacane Paola , Bilokapic Silvija , Halic Mario
Published: April 2016

To maintain genome stability, cells pack large portions of their genome into silent chromatin or heterochromatin. Histone H3 lysine 9 methylation, a hallmark of heterochromatin, is recognized by conserved readers called chromodomains. But how chromodomains interact with their actual binding partner, the H3K9 methylated nucleosome, remains elusive. We have determined the structure of a nucleosome trimethylated at lysine 9 of histone H3 (H3K9me3 Nucleosome) in a complex with the chromodomain of Chp1, a protein required for RNA interference-dependent heterochromatin formation in fission yeast. The cryo-electron microscopy structure reveals that the chromodomain of Chp1 binds the histone H3 lysine 9 methylated tail and the core of the nucleosome, primarily histones H3 and H2B. Mutations in chromodomain of Chp1 loops, which interact with the nucleosome core, abolished this interaction in vitro. Moreover, fission yeast cells with Chp1 loop mutations have a defect in Chp1 recruitment and heterochromatin formation. This study reveals the structural basis for heterochromatic silencing and suggests that chromodomains could read histone code in the H3 tail and the nucleosome core, which would provide an additional layer of regulation.
Mitogen‐activated Tasmanian devil blood mononuclear cells kill devil facial tumour disease cells
Authors: Brown Gabriella K , Tovar Cesar , Cooray Anne A , Kreiss Alexandre , Darby Jocelyn , Murphy James M , Corcoran Lynn M , Bettiol Silvana S , Lyons A Bruce , Woods Gregory M
Published: April 2016

Devil facial tumour disease (DFTD) is a transmissible cancer that has brought the host species, the Tasmanian devil, to the brink of extinction. The cancer cells avoid allogeneic immune recognition by downregulating cell surface major histocompatibility complex (MHC) I expression. This should prevent CD8+ T cell, but not natural killer (NK) cell, cytotoxicity. The reason why NK cells, normally reactive to MHC‐negative cells, are not activated to kill DFTD cells has not been determined. The immune response of wild devils to DFTD, if it occurs, is uncharacterised. To investigate this, we tested 12 wild devils with DFTD, and found suggestive evidence of low levels of antibodies against DFTD cells in one devil. Eight of these devils were also analysed for cytotoxicity, however, none showed evidence for cytotoxicity against cultured DFTD cells. To establish whether mimicking activation of antitumour responses could induce cytotoxic activity against DFTD, Tasmanian devil peripheral blood mononuclear cells (PBMCs) were treated with either the mitogen Concanavalin A, the Toll‐like receptor agonist polyinosinic:polycytidylic acid or recombinant Tasmanian devil IL‐2. All induced the PBMC cells to kill cultured DFTD cells, suggesting that activation does not occur after encounter with DFTD cells in vivo, but can be induced. The identification of agents that activate cytotoxicity against DFTD target cells is critical for developing strategies to protect against DFTD. Such agents could function as adjuvants to induce functional immune responses capable of targeting DFTD cells and tumours in vivo.
Retinoic acid suppresses IL‐17 production and pathogenic activity of γδ T cells in CNS autoimmunity
Authors: Raverdeau Mathilde , Breen Conor J , Misiak Alicja , Mills Kingston HG
Published: April 2016

Retinoic acid (RA) in the steady state enhances induction of Foxp3+ regulatory T (Treg) cells and inhibits differentiation of Th1 and Th17 cells, thereby maintaining tolerance, but can in inflammatory conditions promote effector Th1 and Th17 cells that mediate inflammation. IL‐17‐producing γδ T cells have recently been shown to have a major pathogenic role in autoimmune diseases. Here, we examined the immunomodulatory effects of RA on γδ T cells. We found that RA had a dramatic suppressive effect on IL‐17A and IL‐17F production by γδ T cells stimulated with IL‐1β and IL‐23. RA suppressed RORγt, IL‐1R and IL‐23R expression in γδ T cells. Treatment of mice with RA suppressed IL‐17 production by γδ T cells in vivo. Furthermore, treatment of T cells with RA attenuated their ability to induce disease in experimental autoimmune encephalomyelitis (EAE), a murine model for multiple sclerosis. This was associated with a reduction in the number of central nervous system‐infiltrating γδ T cells, but also CD4+ T cells that produced IL‐17A, IL‐17F or GM‐CSF. Interestingly, treatment of γδ T cells with RA or removal of γδ T cells from a bulk population of T cells significantly reduced their capacity to induce EAE, demonstrating a critical role for γδ T cells in promoting pathogenic Th17 cells. Our findings demonstrate that the anti‐inflammatory properties of RA are mediated in part by suppressing STAT3‐mediated activation of cytokine production and cytokine receptor expression in γδ T cells, which suppresses their ability to activate Th17 cells.
Genomics of a phototrophic nitrite oxidizer: insights into the evolution of photosynthesis and nitrification
Authors: Hemp James , Lücker Sebastian , Schott Joachim , Pace Laura A , Johnson Jena E , Schink Bernhard , Daims Holger , Fischer Woodward W
Published: April 2016

Oxygenic photosynthesis evolved from anoxygenic ancestors before the rise of oxygen ~2.32 billion years ago; however, little is known about this transition. A high redox potential reaction center is a prerequisite for the evolution of the water-oxidizing complex of photosystem II. Therefore, it is likely that high-potential phototrophy originally evolved to oxidize alternative electron donors that utilized simpler redox chemistry, such as nitrite or Mn. To determine whether nitrite could have had a role in the transition to high-potential phototrophy, we sequenced and analyzed the genome of Thiocapsa KS1, a Gammaproteobacteria capable of anoxygenic phototrophic nitrite oxidation. The genome revealed a high metabolic flexibility, which likely allows Thiocapsa KS1 to colonize a great variety of habitats and to persist under fluctuating environmental conditions. We demonstrate that Thiocapsa KS1 does not utilize a high-potential reaction center for phototrophic nitrite oxidation, which suggests that this type of phototrophic nitrite oxidation did not drive the evolution of high-potential phototrophy. In addition, phylogenetic and biochemical analyses of the nitrite oxidoreductase (NXR) from Thiocapsa KS1 illuminate a complex evolutionary history of nitrite oxidation. Our results indicate that the NXR in Thiocapsa originates from a different nitrate reductase clade than the NXRs in chemolithotrophic nitrite oxidizers, suggesting that multiple evolutionary trajectories led to modern nitrite-oxidizing bacteria.
Cumulative early life adversity predicts longevity in wild baboons
Authors: Tung Jenny , Archie Elizabeth A. , Altmann Jeanne , Alberts Susan C.
Published: April 2016

In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations.
Super-complexes of adhesion GPCRs and neural guidance receptors
Authors: Jackson Verity A. , Mehmood Shahid , Chavent Matthieu , Roversi Pietro , Carrasquero Maria , del Toro Daniel , Seyit-Bremer Goenuel , Ranaivoson Fanomezana M. , Comoletti Davide , Sansom Mark S. P. , Robinson Carol V. , Klein Rüdiger , Seiradake Elena
Published: April 2016

Latrophilin adhesion-GPCRs (Lphn1–3 or ADGRL1–3) and Unc5 cell guidance receptors (Unc5A–D) interact with FLRT proteins (FLRT1–3), thereby promoting cell adhesion and repulsion, respectively. How the three proteins interact and function simultaneously is poorly understood. We show that Unc5D interacts with FLRT2 in cis, controlling cell adhesion in response to externally presented Lphn3. The ectodomains of the three proteins bind cooperatively. Crystal structures of the ternary complex formed by the extracellular domains reveal that Lphn3 dimerizes when bound to FLRT2:Unc5, resulting in a stoichiometry of 1:1:2 (FLRT2:Unc5D:Lphn3). This 1:1:2 complex further dimerizes to form a larger ‘super-complex’ (2:2:4), using a previously undescribed binding motif in the Unc5D TSP1 domain. Molecular dynamics simulations, point-directed mutagenesis and mass spectrometry demonstrate the stability and molecular properties of these complexes. Our data exemplify how receptors increase their functional repertoire by forming different context-dependent higher-order complexes.
Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans
Authors: Broecker Felix , Hanske Jonas , Martin Christopher E. , Baek Ju Yuel , Wahlbrink Annette , Wojcik Felix , Hartmann Laura , Rademacher Christoph , Anish Chakkumkal , Seeberger Peter H.
Published: April 2016

Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development. Based on molecular-level glycan–antibody interaction analyses, we here demonstrate that the C. difficile surface polysaccharide-I (PS-I) can be resembled by multivalent display of minimal disaccharide epitopes on a synthetic scaffold that does not participate in binding. We show that antibody avidity as a measure of antigenicity increases by about five orders of magnitude when disaccharides are compared with constructs containing five disaccharides. The synthetic, pentavalent vaccine candidate containing a peptide T-cell epitope elicits weak but highly specific antibody responses to larger PS-I glycans in mice. This study highlights the potential of multivalently displaying small oligosaccharides to achieve antigenicity characteristic of larger glycans. The approach may result in more cost-efficient carbohydrate vaccines with reduced synthetic effort.
Genetically encoded photocrosslinkers locate the high-affinity binding site of antidepressant drugs in the human serotonin transporter
Authors: Rannversson Hafsteinn , Andersen Jacob , Sørensen Lena , Bang-Andersen Benny , Park Minyoung , Huber Thomas , Sakmar Thomas P. , Strømgaard Kristian
Published: April 2016

Despite the well-established role of the human serotonin transporter (hSERT) in the treatment of depression, the molecular details of antidepressant drug binding are still not fully understood. Here we utilize amber codon suppression in a membrane-bound transporter protein to encode photocrosslinking unnatural amino acids (UAAs) into 75 different positions in hSERT. UAAs are incorporated with high specificity, and functionally active transporters have similar transport properties and pharmacological profiles compared with wild-type transporters. We employ ultraviolet-induced crosslinking with p-azido-L-phenylalanine (azF) at selected positions in hSERT to map the binding site of imipramine, a prototypical tricyclic antidepressant, and vortioxetine, a novel multimodal antidepressant. We find that the two antidepressants crosslink with azF incorporated at different positions within the central substrate-binding site of hSERT, while no crosslinking is observed at the vestibular-binding site. Taken together, our data provide direct evidence for defining the high-affinity antidepressant binding site in hSERT.
Integrated multi-omics analysis of oligodendroglial tumours identifies three subgroups of 1p/19q co-deleted gliomas
Authors: Kamoun Aurélie , Idbaih Ahmed , Dehais Caroline , Elarouci Nabila , Carpentier Catherine , Letouzé Eric , Colin Carole , Mokhtari Karima , Jouvet Anne , Uro-Coste Emmanuelle , Martin-Duverneuil Nadine , Sanson Marc , Delattre Jean-Yves , Figarella-Branger Dominique , de Reyniès Aurélien , Ducray François ,   POLA network, Adam Clovis , Andraud Marie , Aubriot-Lorton Marie-Hélène , Bauchet Luc , Beauchesne Patrick , Bielle Franck , Blechet Claire , Campone Mario , Carpentier Antoine F. , Carpiuc Ioana , Cazals-Hatem Dominique , Chenard Marie-Pierre , Chiforeanu Danchristian , Chinot Olivier , Cohen-Moyal Elisabeth , Colin Philippe , Dam-Hieu Phong , Desenclos Christine , Desse Nicolas , Dhermain Frederic , Diebold Marie-Danièle , Eimer Sandrine , Faillot Thierry , Fesneau Mélanie , Fontaine Denys , Gaillard Stéphane , Gauchotte Guillaume , Gaultier Claude , Ghiringhelli François , Godard Joel , Gueye Edouard Marcel , Guillamo Jean Sebastien , Hamdi-Elouadhani Selma , Honnorat Jerome , Kemeny Jean Louis , Khallil Toufik , Labrousse François , Langlois Olivier , Laquerriere Annie , Larrieu-Ciron Delphine , Lechapt-Zalcman Emmanuelle , Guérinel Caroline Le , Levillain Pierre-Marie , Loiseau Hugues , Loussouarn Delphine , Maurage Claude-Alain , Menei Philippe , Motsuo Fotso Marie Janette , Noel Georges , Parker Fabrice , Peoc'h Michel , Polivka Marc , Quintin-Roué Isabelle , Ramirez Carole , Ricard Damien , Richard Pomone , Rigau Valérie , Rousseau Audrey , Runavot Gwenaelle , Sevestre Henri , Tortel Marie Christine , Vandenbos Fanny , Vauleon Elodie , Viennet Gabriel , Villa Chiara
Published: April 2016

Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished on the basis of the IDH mutation and 1p/19q co-deletion. Here we present an integrated analysis of the transcriptome, genome and methylome of 156 OT. Not only does our multi-omics classification match the current classification but also reveals three subgroups within 1p/19q co-deleted tumours, associated with specific expression patterns of nervous system cell types: oligodendrocyte, oligodendrocyte precursor cell (OPC) and neuronal lineage. We confirm the validity of these three subgroups using public datasets. Importantly, the OPC-like group is associated with more aggressive clinical and molecular patterns, including MYC activation. We show that the MYC activation occurs through various alterations, including MYC genomic gain, MAX genomic loss, MYC hypomethylation and microRNA-34b/c down-regulation. In the lower grade glioma TCGA dataset, the OPC-like group is associated with a poorer outcome independently of histological grade. Our study reveals previously unrecognized heterogeneity among 1p/19q co-deleted tumours.
Structural control of mixed ionic and electronic transport in conducting polymers
Authors: Rivnay Jonathan , Inal Sahika , Collins Brian A. , Sessolo Michele , Stavrinidou Eleni , Strakosas Xenofon , Tassone Christopher , Delongchamp Dean M. , Malliaras George G.
Published: April 2016

Poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate), PEDOT:PSS, has been utilized for over two decades as a stable, solution-processable hole conductor. While its hole transport properties have been the subject of intense investigation, recent work has turned to PEDOT:PSS as a mixed ionic/electronic conductor in applications including bioelectronics, energy storage and management, and soft robotics. Conducting polymers can efficiently transport both holes and ions when sufficiently hydrated, however, little is known about the role of morphology on mixed conduction. Here, we show that bulk ionic and electronic mobilities are simultaneously affected by processing-induced changes in nano- and meso-scale structure in PEDOT:PSS films. We quantify domain composition, and find that domain purification on addition of dispersion co-solvents limits ion mobility, even while electronic conductivity improves. We show that an optimal morphology allows for the balanced ionic and electronic transport that is critical for prototypical mixed conductor devices. These findings may pave the way for the rational design of polymeric materials and processing routes to enhance devices reliant on mixed conduction.
NETosis and lack of DNase activity are key factors in Echis carinatus venom-induced tissue destruction
Authors: Katkar Gajanan D. , Sundaram Mahalingam S. , NaveenKumar Somanathapura K. , Swethakumar Basavarajaiah , Sharma Rachana D. , Paul Manoj , Vishalakshi Gopalapura J. , Devaraja Sannaningaiah , Girish Kesturu S. , Kemparaju Kempaiah
Published: April 2016

Indian Echis carinatus bite causes sustained tissue destruction at the bite site. Neutrophils, the major leukocytes in the early defence process, accumulate at the bite site. Here we show that E. carinatus venom induces neutrophil extracellular trap (NET) formation. The NETs block the blood vessels and entrap the venom toxins at the injection site, promoting tissue destruction. The stability of NETs is attributed to the lack of NETs-degrading DNase activity in E. carinatus venom. In a mouse tail model, mice co-injected with venom and DNase 1, and neutropenic mice injected with the venom, do not develop NETs, venom accumulation and tissue destruction at the injected site. Strikingly, venom-induced mice tail tissue destruction is also prevented by the subsequent injection of DNase 1. Thus, our study suggests that DNase 1 treatment may have a therapeutic potential for preventing the tissue destruction caused by snake venom.
Nanoparticle chemisorption printing technique for conductive silver patterning with submicron resolution
Authors: Yamada Toshikazu , Fukuhara Katsuo , Matsuoka Ken , Minemawari Hiromi , Tsutsumi Jun’ya , Fukuda Nobuko , Aoshima Keisuke , Arai Shunto , Makita Yuichi , Kubo Hitoshi , Enomoto Takao , Togashi Takanari , Kurihara Masato , Hasegawa Tatsuo
Published: April 2016

Silver nanocolloid, a dense suspension of ligand-encapsulated silver nanoparticles, is an important material for printing-based device production technologies. However, printed conductive patterns of sufficiently high quality and resolution for industrial products have not yet been achieved, as the use of conventional printing techniques is severely limiting. Here we report a printing technique to manufacture ultrafine conductive patterns utilizing the exclusive chemisorption phenomenon of weakly encapsulated silver nanoparticles on a photoactivated surface. The process includes masked irradiation of vacuum ultraviolet light on an amorphous perfluorinated polymer layer to photoactivate the surface with pendant carboxylate groups, and subsequent coating of alkylamine-encapsulated silver nanocolloids, which causes amine–carboxylate conversion to trigger the spontaneous formation of a self-fused solid silver layer. The technique can produce silver patterns of submicron fineness adhered strongly to substrates, thus enabling manufacture of flexible transparent conductive sheets. This printing technique could replace conventional vacuum- and photolithography-based device processing.
Use of the lichen Xanthoria mandschurica in monitoring atmospheric elemental deposition in the Taihang Mountains, Hebei, China
Authors: Liu Hua-Jie , Zhao Liang-Cheng , Fang Shi-Bo , Liu Si-Wa , Hu Jian-Sen , Wang Lei , Liu Xiao-Di , Wu Qing-Feng
Published: April 2016

Air pollution is a major concern in China. Lichens are a useful biomonitor for atmospheric elemental deposition but have rarely been used in North China. The aim of this study was to investigate the atmospheric depositions of 30 trace elements (Al, Ba, Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, K, La, Mg, Mn, Mo, Na, Ni, P, Pb, Rb, Sb, Sc, Sm, Sr, Tb, Th, Ti, Tl, V and Zn) in a region of the Taihang Mountains, Hebei Province, China using lichens as biomonitors. Epilithic foliose lichen Xanthoria mandschurica was sampled from 21 sites and analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The results show that 1) eight elements (Cd, Cr, Cu, Mo, P, Pb, Sb and Zn) are of atmospheric origin and are highly influenced by the atmospheric transportation from the North China Plain, as well as local mining activities, while 2) the remaining 22 elements are primarily of crustal origin, the concentration of which has been enhanced by local mining and quarrying activities. These results clearly validate the applicability of lichens in biomonitoring of atmospheric elemental deposition and demonstrate the spatial pattern for air pollution in the region.
Design and development of novel MRI compatible zirconium- ruthenium alloys with ultralow magnetic susceptibility
Authors: Li H.F. , Zhou F.Y. , Li L. , Zheng Y.F.
Published: April 2016

In the present study, novel MRI compatible zirconium-ruthenium alloys with ultralow magnetic susceptibility were developed for biomedical and therapeutic devices under MRI diagnostics environments. The results demonstrated that alloying with ruthenium into pure zirconium would significantly increase the strength and hardness properties. The corrosion resistance of zirconium-ruthenium alloys increased significantly. High cell viability could be found and healthy cell morphology observed when culturing MG 63 osteoblast-like cells and L-929 fibroblast cells with zirconium-ruthenium alloys, whereas the hemolysis rates of zirconium-ruthenium alloys are <1%, much lower than 5%, the safe value for biomaterials according to ISO 10993-4 standard. Compared with conventional biomedical 316L stainless steel, Co–Cr alloys and Ti-based alloys, the magnetic susceptibilities of the zirconium-ruthenium alloys (1.25 × 10−6cm3·g−1–1.29 × 10−6cm3·g−1for zirconium-ruthenium alloys) are ultralow, about one-third that of Ti-based alloys (Ti–6Al–4V, ~3.5 × 10−6cm3·g−1, CP Ti and Ti–6Al–7Nb, ~3.0 × 10−6cm3·g−1) and one-sixth that of Co–Cr alloys (Co–Cr–Mo, ~7.7 × 10−6cm3·g−1). Among the Zr–Ru alloy series, Zr–1Ru demonstrates enhanced mechanical properties, excellent corrosion resistance and cell viability with lowest magnetic susceptibility and thus is the optimal Zr–Ru alloy system as therapeutic devices under MRI diagnostics environments.
Solution-Processed Donor-Acceptor Polymer Nanowire Network Semiconductors For High-Performance Field-Effect Transistors
Authors: Lei Yanlian , Deng Ping , Li Jun , Lin Ming , Zhu Furong , Ng Tsz-Wai , Lee Chun-Sing , Ong Beng S.
Published: April 2016

Organic field-effect transistors (OFETs) represent a low-cost transistor technology for creating next-generation large-area, flexible and ultra-low-cost electronics. Conjugated electron donor-acceptor (D-A) polymers have surfaced as ideal channel semiconductor candidates for OFETs. However, high-molecular weight (MW) D-A polymer semiconductors, which offer high field-effect mobility, generally suffer from processing complications due to limited solubility. Conversely, the readily soluble, low-MW D-A polymers give low mobility. We report herein a facile solution process which transformed a lower-MW, low-mobility diketopyrrolopyrrole-dithienylthieno[3,2-b]thiophene (I) into a high crystalline order and high-mobility semiconductor for OFETs applications. The process involved solution fabrication of a channel semiconductor film from a lower-MW (I) and polystyrene blends. With the help of cooperative shifting motion of polystyrene chain segments, (I) readily self-assembled and crystallized out in the polystyrene matrix as an interpenetrating, nanowire semiconductor network, providing significantly enhanced mobility (over 8 cm2V−1s−1), on/off ratio (107), and other desirable field-effect properties that meet impactful OFET application requirements.
Detection and characterization of two co-infection variant strains of avian orthoreovirus (ARV) in young layer chickens using next-generation sequencing (NGS)
Authors: Tang Yi , Lin Lin , Sebastian Aswathy , Lu Huaguang
Published: April 2016

Using next-generation sequencing (NGS) for full genomic characterization studies of the newly emerging avian orthoreovirus (ARV) field strains isolated in Pennsylvania poultry, we identified two co-infection ARV variant strains from one ARV isolate obtained from ARV-affected young layer chickens. The de novo assembly of the ARV reads generated 19 contigs of two different ARV variant strains according to 10 genome segments of each ARV strain. The two variants had the same M2 segment. The complete genomes of each of the two variant strains were 23,493 bp in length and 10 dsRNA segments ranged from 1192 bp (S4) to 3958 bp (L1), encoding 12 viral proteins. Sequence comparison of nucleotide (nt) and amino acid (aa) sequences of all 10 genome segments revealed 58.1–100% and 51.4–100% aa identity between the two variant strains and 54.3–89.4% and 49.5–98.1% aa identity between the two variants and classic vaccine strains. Phylogenetic analysis revealed a moderate to significant nt sequence divergence between the two variant and ARV reference strains. These findings have demonstrated the first naturally occurring co-infection of two ARV variants in commercial young layer chickens, providing scientific evidence that multiple ARV strains can be simultaneously present in one host species of chickens.
Orbital Reconstruction Enhanced Exchange Bias in La0.6Sr0.4MnO3/Orthorhombic YMnO3 Heterostructures
Authors: Zheng Dongxing , Jin Chao , Li Peng , Wang Liyan , Feng Liefeng , Mi Wenbo , Bai Haili
Published: April 2016

The exchange bias in ferromagnetic/multiferroic heterostructures is usually considered to originate from interfacial coupling. In this work, an orbital reconstruction enhanced exchange bias was discovered. As La0.6Sr0.4MnO3 (LSMO) grown on YMnO3 (YMO) suffers a tensile strain (a > c), the doubly degenerate eg orbital splits into high energy 3z2 − r2 and low energy x2 − y2 orbitals, which makes electrons occupy the localized x2 − y2 orbital and leads to the formation of antiferromagnetic phase in LSMO. The orbital reconstruction induced antiferromagnetic phase enhances the exchange bias in the LSMO/YMO heterostructures, lightening an effective way for electric-field modulated magnetic moments in multiferroic magnetoelectric devices.
Intrinsic beam emittance of laser-accelerated electrons measured by x-ray spectroscopic imaging
Authors: Golovin G. , Banerjee S. , Liu C. , Chen S. , Zhang J. , Zhao B. , Zhang P. , Veale M. , Wilson M. , Seller P. , Umstadter D.
Published: April 2016

The recent combination of ultra-intense lasers and laser-accelerated electron beams is enabling the development of a new generation of compact x-ray light sources, the coherence of which depends directly on electron beam emittance. Although the emittance of accelerated electron beams can be low, it can grow due to the effects of space charge during free-space propagation. Direct experimental measurement of this important property is complicated by micron-scale beam sizes and the presence of intense fields at the location where space charge acts. Reported here is a novel, non-destructive, single-shot method that overcame this problem. It employed an intense laser probe pulse and spectroscopic imaging of the inverse-Compton scattered x-rays, allowing measurement of an ultra-low value for the normalized transverse emittance, 0.15 (±0.06) π mm mrad, as well as study of its subsequent growth upon exiting the accelerator. The technique and results are critical for designing multi-stage laser-wakefield accelerators and generating high-brightness, spatially coherent x-rays.