bluuebunny/crossref_metadata_2025 huggingface dataset:
La política exterior de Bolivia en tiempos de Evo Morales Ayma
Authors: Ceppi Natalia
Published: August 2014

El presente trabajo analiza la política exterior boliviana a partir de la llegada de Evo Morales,considerando la diplomacia desplegada en el ámbito de Naciones Unidas y las relaciones bilaterales más destacadas en el período 2006-2013. Se parte de la idea de que las transformaciones experimentadas en el ámbito doméstico —tanto en los postulados ideológicos como en materia político-económica— han repercutido en el proceso de ajuste y reestructuración que atraviesa la agenda externa del país. En este sentido, se afirma que en tiempos de Evo, la política exterior se diferencia de los gobiernos anteriores entres puntos principales: los principios y objetivos que la sustentan; la valoración otorgadaa los espacios multilaterales como foros de debate y discusión; y los vínculos de Estadoa Estado.
Estudios críticos de fronteras. Aportes de los estudios culturales
Authors: Sánchez Leandro
Published: August 2014

En este ensayo se reseñará una bibliografía interdisciplinar, pero con anclaje en las relaciones internacionales, que analiza la práctica de las fronteras en la actualidad. Este texto aunará de manera general una bibliografía heterogénea, cuya complejidad no puede ser tratada en profundidad aquí, pero esperamos sea de valor. El lector debe tener en cuenta que las generalizaciones se han hecho uniendo enfoques y opiniones plurales. El objetivo es poner en diálogo lo que estos textos sostienen, con ciertos aportes provenientes de los estudios culturales, con el propósito de dotar a los estudios internacionales de mayores herramientas analíticas.
Physical and chemical characterizations of biochars derived from different agricultural residues
Authors: Jindo K. , Mizumoto H. , Sawada Y. , Sanchez-Monedero M. A. , Sonoki T.
Published: August 2014

Abstract. Biochar has received large attention as a strategy to tackle against carbon emission. Not only carbon fixation has been carried out but also other merits for agricultural application due to unique physical and chemical character such as absorption of contaminated compounds in soil, trapping ammonia and methane emission from compost, and enhancement of fertilizer quality. In our study, different local waste feed stocks (rice husk, rice straw, wood chips of apple tree (Malus Pumila) and oak tree (Quercus serrata)), in Aomori, Japan, were utilized for creating biochar with different temperature (400–800 °C). Concerning to the biochar production, the pyrolysis of lower temperature had more biochar yield than higher temperature pyrolysis process. On the contrary, surface areas and adsorption characters have been increased as increasing temperature. The proportions of carbon content in the biochars also increased together with increased temperatures. Infrared-Fourier spectra (FT-IR) and 13C-NMR were used to understand carbon chemical compositions in our biochars, and it was observed that the numbers of the shoulders representing aromatic groups, considered as stable carbon structure appeared as the temperature came closer to 600 °C, as well as in FT-IR. In rice materials, the peak assigned to SiO2, was observed in all biochars (400–800 °C) in FT-IR. We suppose that the pyrolysis at 600 °C creates the most recalcitrant character for carbon sequestration, meanwhile the pyrolysis at 400 °C produces the superior properties as a fertilizer by retaining volatile and easily labile compounds which promotes soil microbial activities.
Effects of surface wind speed decline on modeled hydrological conditions in China
Authors: Liu X. , Zhang X.-J. , Tang Q. , Zhang X.-Z.
Published: August 2014

Abstract. Surface wind speed decline in China has been widely reported, but its effects on hydrology have not been fully evaluated to date. In this study, the effects of wind speed change on modeled hydrological conditions are investigated using the Variable Infiltration Capacity (VIC) hydrological model for China during the 1966–2011 period. Two model experiments, i.e., VIC simulations with the observed (EXP1) and detrended wind speed (EXP2), are performed over the major river basins in China. The differences between the two experiments are analyzed to assess the effects of wind speed decline. Results show that wind speed has decreased by 29% in China. The wind speed decline would have resulted in a decrease in evapotranspiration of 1–3% of mean annual evapotranspiration and an increase in runoff of 1–6% of mean annual runoff at most basins in China. The sensitivities of evapotranspiration and runoff changes to wind speed change are larger in humid areas than dry areas, while the sensitivity of soil moisture change to wind speed change is situation dependent. The wind speed decline would have offset the expansion of the drought area in China. It has contributed to reducing drought areas by 8.8% of the mean drought area (i.e., approximate 106 × 103 km2 out of 1.2 × 106 km2) over China. The reductions of soil moisture drought induced by wind speed decline are large (more than 5% of the mean drought area) in most basins, except in the Southwest and Pearl River basins.
Simulating tsunami propagation in fjords with long wave models
Authors: Løvholt F. , Glimsdal S. , Lynett P. , Pedersen G.
Published: August 2014

Abstract. Tsunamis induced by rock slides constitute a severe hazard towards coastal fjord communities. Fjords are narrow and rugged with steep slopes, and modeling the short-frequency and high-amplitude tsunamis in this environment is demanding. In the present paper, our ability (and the lack thereof) to simulate tsunami propagation and run-up in fjords for typical wave characteristics of rock slide induced waves is demonstrated. The starting point is a 1 : 500 scale model of the topography and bathymetry of Storfjorden fjord system in western Norway. Using measured wave data from the scale model as input to numerical simulations, we find that the leading wave is moderately influenced by non-linearity and dispersion. For the trailing waves, dispersion and dissipation from the alongshore inundation on the traveling wave become more important. Tsunami inundation were simulated at the two locations of Hellesylt and Geiranger, providing good match with the measurements in the former location. In Geiranger, the most demanding case of the two, discrepancies are larger, which may in part be explained by scale effects, and in part combinations of errors emerging from both wave propagation along large stretches of the fjord and the inundation model itself.
How Do Innovation Partners Differ with Respect to Innovation Type and Stage in the Innovation Journey of Farmers?
Authors: Lambrecht Evelien , Kühne Bianka , Gellynck Xavier
Published: August 2014

The locus of innovation is the network within which a farm is embedded. This paper investigates the relationships between network partners and innovation (types and stages in the process) in agriculture, which is unique in this field. In contrast to the majority of innovation studies, the authors also include marketing and organizational innovations and investigate the need for different partners along the innovation journey. The study is based on in-depth interviews with farmers. The findings provide useful research-related and managerial implications that enable farmers and network coordinators to improve the innovation capacity in agriculture via networking. The main conclusion is that, depending on the stage in the innovation journey and the type of innovation, different resources and hence different partners are needed. Therefore, farmers must be aware of the importance of partner suitability and network heterogeneity related to the type of innovation and stage in their innovation process.
SMEs Competing in the Food Sector
Authors: Conway Clifford
Published: August 2014

‘Internet Review’ provides critical commentary on entrepreneurship, small business and innovation information on the Web.
Mechanical properties of structural maritime pine sawn timber from Galicia [Spain] (Pinus pinaster Ait. ssp. atlantica)
Authors: Carballo J. , Hermoso E. , Fernández-Golfín J. I.
Published: August 2014

The use of maritime pine sawn timber in structural applications requires knowledge of its mechanical properties. Standards have changed, however, since the last research on this timber was performed. In the present study, 491 beams of maritime pine from Galicia, of structural-use size but different cross-section, were tested according to these modified standards. Each beam was visually graded according to standard UNE 56.544 and subjected to a four point bending tesThe strength classes assigned by the visual grades awarded suggest this material to have greater structural capacity than that currently assumed. The relationships between the modulus of elasticity, strength and density were also examined.
Primary results of 2-dimensional electrophoresis for protein studies of Gentiana kurroo Royle somatic embryos derived from long-term embryogenic cell suspensions
Authors: Niedziela Agnieszka , Rybczyński Jan J.
Published: August 2014

Two-dimensional gel electrophoresis was used to compare protein expression profiles between various stages of Gentiana kurroo Royle somatic embryos. Seven distinct stages (I–VII) were pointed out and measured from long-term embryogenic cell suspension. Isoelectric focusing was done in the pH intervals 3–10, and the second dimension was carried out with 13% SDS-polyacrylamide gel electrophoresis. Dependent on the stage from about 400 (stage IV) to more than 700 (stage II) protein spots were totally detected. The molecular weight of abundant proteins range from 12 to 70 kDa, however, majority of proteins were located between 20–49 kDa spots on the gels. The highest difference in the number of spots appeared in the case of globular embryo (stage I) and elongated cotyledonary stage (stage VII) with differences being about 130 spots. The relevance of embryogenic cell suspension choice for proteomic analysis as well as expediency of the increasing number of particular embryo stages is discussed.
Forward and Inverse Dynamics of the Biped PASIBOT
Authors: Corral Eduardo , Meneses Jesús , Castejón Cristina , García-Prada Juan Carlos
Published: August 2014

This article addresses the supporting foot slippage of the biped robot PASIBOT and develops its forward and inverse dynamics for simple and double support phases. To address the slippage phenomenon, we consider an additional degree of freedom at the supporting foot and also distinguish between static and kinetic friction conditions. The inverse and forward dynamics, accounting for support foot slippage, are encoded in MATLAB. The algorithm predicts the motion of the biped from the torque function given by the biped's sole motor. Thus, the algorithm becomes an indispensable tool for studying transient states of the biped (for example, the torques required for starting and braking), as well as defining the conditions that prevent or control slippage. Since the developed code is parametric, its output can greatly assist in the design, optimization and control of PASIBOT and similar biped robots. The topology, kinematics and inverse dynamics of the one-degree-of-freedom biped PASIBOT have been previously described, but without regard to slippage between the supporting foot and the ground.
Modelling and Control of the Multi-Stage Cable Pulley-Driven Flexible-Joint Robot
Authors: Pitakwatchara Phongsaen
Published: August 2014

This work is concerned with the task space impedance control of a robot driven through a multi-stage nonlinear flexible transmission system. Specifically, a two degrees-of-freedom cable pulley-driven flexible-joint robot is considered. Realistic modelling of the system is developed within the bond graph modelling framework. The model captures the nonlinear compliance behaviour of the multi-stage cable pulley transmission system, the spring effect of the augmented counterbalancing mechanism, the major loss throughout the system elements, and the typical inertial dynamics of the robot. Next, a task space impedance controller based on limited information about the angle and the current of the motors is designed. The motor current is used to infer the transmitted torque, by which the motor inertia may be modulated. The motor angle is employed to estimate the stationary distal robot link angle and the robot joint velocity. They are used in the controller to generate the desired damping force and to shape the potential energy of the flexible joint robot system to the desired configuration. Simulation and experimental results of the controlled system signify the competency of the proposed control law.
Rail-Guided Multi-Robot System for 3D Cellular Hydrogel Assembly with Coordinated Nanomanipulation
Authors: Wang Huaping , Shi Qing , Nakajima Masahiro , Takeuchi Masaru , Chen Tao , Di Pei , Huang Qiang , Fukuda Toshio
Published: August 2014

The 3D assembly of micro-/nano-building blocks with multi-nanomanipulator coordinated manipulation is one of the central elements of nanomanipulation. A novel rail-guided nanomanipulation system was proposed for the assembly of a cellular vascular-like hydrogel microchannel. The system was equipped with three nanomanipulators and was restricted on the rail in order to realize the arbitrary change of the end-effectors during the assembly. It was set up with hybrid motors to achieve both a large operating space and a 30 nm positional resolution. The 2D components such as the assembly units were fabricated through the encapsulation of cells in the hydrogel. The coordinated manipulation strategies among the multi-nanomanipulators were designed with vision feedback and were demonstrated through the bottom-up assembly of the vascular-like microtube. As a result, the multi-layered microchannel was assembled through the cooperation of the nanomanipulation system.
Thermodynamic Analysis of Weak Protein Interactions Using Sedimentation Equilibrium
Authors: Sergeev Yuri V. , Dolinska Monika B. , Wingfield Paul T.
Published: August 2014

Proteins self‐associate to form dimers and tetramers. Purified proteins are used to study the thermodynamics of protein interactions using the analytical ultracentrifuge. In this approach, monomer‐dimer equilibrium constants are directly measured at various temperatures. Data analysis is used to derive thermodynamic parameters, such as Gibbs free energy, enthalpy, and entropy, which can predict which major forces are involved in protein association. Curr. Protoc. Protein Sci. 77:20.13.1‐20.13.15. © 2014 by John Wiley & Sons, Inc.
Isolation and Characterization of Mouse Innate Lymphoid Cells
Authors: Halim Timotheus Y.F. , Takei Fumio
Published: August 2014

Innate lymphoid cells (ILCs) are rare populations of cytokine‐producing lymphocytes and are divided into three groups, namely ILC1, ILC2, and ILC3, based on the cytokines that they produce. They comprise less than 1% of lymphocytes in mucosal tissues and express no unique cell surface markers. Therefore, they can only be identified by combinations of multiple cell surface markers and further characterized by cytokine production in vitro. Thus, multicolor flow cytometry is the only reliable method to purify and characterize ILCs. Here we describe the methods for cell preparation, flow cytometric analysis, and purification of murine ILC2 and ILC3. Curr. Protoc. Immunol. 106:3.25.1‐3.25.13. © 2014 by John Wiley & Sons, Inc.
Measurement of Peptide Binding to MHC Class II Molecules by Fluorescence Polarization
Authors: Yin Liusong , Stern Lawrence J.
Published: August 2014

Peptide binding to major histocompatibility complex class II (MHCII) molecules is a key process in antigen presentation and CD4+ T cell epitope selection. This unit describes a fairly simple but powerful fluorescence polarization‐based binding competition assay to measure peptide binding to soluble recombinant MHCII molecules. The binding of a peptide of interest to MHCII molecules is assessed based on its ability to inhibit the binding of a fluorescence‐labeled probe peptide, with the strength of binding characterized as IC50 (concentration required for 50% inhibition of probe peptide binding). Data analysis related to this method is discussed. In addition, this unit includes a support protocol for fluorescence labeling peptide using an amine‐reactive probe. The advantage of this protocol is that it allows simple, fast, and high‐throughput measurements of binding for a large set of peptides to MHCII molecules. Curr. Protoc. Immunol. 106:5.10.1‐5.10.12. © 2014 by John Wiley & Sons, Inc.
Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease
Authors: Agosta Federica , Dalla Libera Dacia , Spinelli Edoardo Gioele , Finardi Annamaria , Canu Elisa , Bergami Alessandra , Bocchio Chiavetto Luisella , Baronio Manuela , Comi Giancarlo , Martino Gianvito , Matteoli Michela , Magnani Giuseppe , Verderio Claudia , Furlan Roberto
Published: August 2014

Objectives

We have described cerebrospinal fluid (CSF) myeloid microvesicles (MVs) as a marker of microglia activation during neuroinflammation in Alzheimer disease (AD), and characterized their ability to produce toxic amyloid β1–42 (Aβ1–42) oligomers from aggregated or soluble substrate. The aim of this study is to investigate the association of CSF myeloid MVs with neuroimaging, clinical, and paraclinical data in AD and mild cognitive impairment (MCI).

Methods

We collected CSF from 106 AD patients, 51 MCI patients, and 29 neurologically healthy controls. We examined CSF myeloid MV content and AD markers. A subgroup of 34 AD and 21 MCI patients underwent structural and diffusion tensor MRI.

Results

Higher levels of myeloid MVs were found in the CSF of AD patients and MCI patients converting within 3 years relative to controls, but also, at a lower level, in MCI patients not converting to AD. CSF myeloid MVs were associated with Tau but not with Aβ1–42 CSF levels. CSF MVs levels correlated with white matter (WM) tract damage in MCI, and with hippocampal atrophy in AD.

Interpretation

Microglial MVs are neurotoxic and myelinotoxic in the presence of Aβ1–42. CSF myeloid MVs, mirroring microglia activation and MV release, are associated with WM damage in MCI and hippocampal atrophy in AD. This suggests that hippocampal microglia activation, in the presence of Aβ1–42 in excess, produces neurotoxic and oligodendrotoxic oligomers that, through WM tract damage, spread disease to neighboring and connected areas, causing local microglia activation and propagation of disease through the same sequence of events. Ann Neurol 2014;76:813–825
High‐Silica Zeolite SSZ‐61 with Dumbbell‐Shaped Extra‐Large‐Pore Channels
Authors: Smeets Stef , Xie Dan , Baerlocher Christian , McCusker Lynne B. , Wan Wei , Zou Xiaodong , Zones Stacey I.
Published: August 2014

The synthesis of the high‐silica zeolite SSZ‐61 using a particularly bulky polycyclic structure‐directing agent and the subsequent elucidation of its unusual framework structure with extra‐large dumbbell‐shaped pore openings are described. By using information derived from a variety of X‐ray powder diffraction and electron microscopy techniques, the complex framework structure, with 20 Si atoms in the asymmetric unit, could be determined and the full structure refined. The Si atoms at the waist of the dumbbell are only three‐connected and are bonded to terminal O atoms pointing into the channel. Unlike the six previously reported extra‐large‐pore zeolites, SSZ‐61 contains no heteroatoms in the framework and can be calcined easily. This, coupled with the possibility of inserting a catalytically active center in the channel between the terminal O atoms in place of H+, afford SSZ‐61 intriguing potential for catalytic applications.
Pineapple agroindustrial residues for the production of high value bacterial cellulose with different morphologies
Authors: Algar Itxaso , Fernandes Susana C. M. , Mondragon Gurutz , Castro Cristina , Garcia‐Astrain Clara , Gabilondo Nagore , Retegi Aloña , Eceiza Arantxa
Published: August 2014

Bacterial cellulose (BC) with different morphologies was biosynthesized by Gluconacetobacter medellinensis strain under static and dynamic culture conditions using sugar cane juice and pineapple residues as sources of carbon and other nutrients. Hestrin and Schramm's standard culture medium was used as reference. The fermentation condition and resulting yield, physico‐chemical properties, and morphology relationships of obtained cellulose were analyzed. Pineapple agroindustrial residues can be envisaged as an inexpensive and sustainable alternative resource for the production of different BC morphologies. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41237.
Unprecedented Sensitization of Visible and Near‐Infrared Lanthanide Luminescence by Using a Tetrathiafulvalene‐Based Chromophore
Authors: Feng Min , Pointillart Fabrice , Le Guennic Boris , Lefeuvre Bertrand , Golhen Stéphane , Cador Olivier , Maury Olivier , Ouahab Lahcène
Published: August 2014

Ligand L was synthesized and then coordinated to [Ln(hfac)3]⋅2 H2O (LnIII=Tb, Dy, Er; hfac−=1,1,1,5,5,5‐hexafluoroacetylacetonate anion) and [Ln(tta)3]⋅2 H2O (LnIII=Eu, Gd, Tb, Dy, Er, Yb; tta−=2‐thenoyltrifluoroacetonate) to give two families of dinuclear complexes [Ln2(hfac)6(L)]⋅C6H14 and [Ln2(tta)6(L)]⋅2 CH2Cl2. Irradiation of the ligand at 37 040 cm−1 and 29 410 cm−1 leads to tetrathiafulvalene‐centered and 2,6‐di(pyrazol‐1‐yl)‐4‐pyridine‐centered fluorescence, respectively. The ligand acts as an organic chromophore for the sensitization of the infrared ErIII (6535 cm−1) and YbIII (10 200 cm−1) luminescence. The energies of the singlet and triplet states of L are high enough to guarantee an efficient sensitization of the visible EuIII luminescence (17 300–14 100 cm−1). The EuIII luminescence decay can be nicely fitted by a monoexponential function that allows a lifetime estimation of (0.49±0.01) ms. Finally, the magnetic and luminescence properties of [Yb2(hfac)6(L)]⋅C6H14 were correlated, which allowed the determination of the crystal field splitting of the 2F7/2 multiplet state with MJ=±1/2 as ground states.
Sicherheit von Offshore‐Windenergieanlagen
Authors: Hansen Michael , Schmidt Boso
Published: August 2014

Die Offshore‐Windenergie ist mit dem ersten deutschen Offshore‐Windpark alpha ventus in Wassertiefen über 30 m vorgedrungen. Gelten für diese Offshore‐Windenergieanlagen (OWEA), die 60 km vor der Küste stehen, die gleichen Designprinzipien wie für landgestützte Anlagen? Wie sieht es mit dem Risiko dieser Anlagen aus und wie ist dieses definiert?

Diese und weitere Fragen führten dazu, dass seit 2009 in dem interfakultativen Verbundforschungsvorhaben Probabilistische Sicherheitsbewertung von Offshore‐Windenergieanlagen (PSB OWEA) zehn Institute aus den Fakultäten Bauingenieurwesen, Elektrotechnik und Maschinenbau der Leibniz Universität Hannover gemeinsam an wesentlichen Fragen zur Anlagensicherheit offshore forschen. Aufgrund des immensen Investitionsvolumens offshore besteht das wesentliche Ziel darin, die Zuverlässigkeit der gesamten Anlage sowie einzelner Anlagenteile und Bauteilkomponenten zu bestimmen und zu bewerten. Die Forschungsschwerpunkte wurden an den Interessen und Notwendigkeiten der Wirtschaft und Zertifizierung gespiegelt und ausgerichtet.

In diesem Beitrag werden aktuelle Sicherheitsbetrachtungen für OWEA mit Bezug zu den nationalen und internationalen Regelungen dargestellt.

Safety of Offshore Wind Turbines

The first German offshore wind farm alpha ventus was built in water depth more than 30 m. Are the design principles for these offshore wind turbines (OWT) erected about 60 km distance to the coast similar to the principles used for wind‐turbines onshore? What about the risk of these investments and how is it defined?

In 2009 researchers of the Leibniz Universität Hannover started the research project Probabilistic safety assessment of offshore wind turbines (PSA OWT) to think about these and further questions. Since then ten institutes from the faculties of civil engineering, electrical and mechanical engineering research together in the field of the safety of OWT. Regarding the immense volume of offshore investment the target objective is to determine and to evaluate the reliability of the total system as well as individual system components. The main questions were discussed with representatives of industry and certification to bring the interests and needs into line.

The current safety assessment of OWT are presented in this paper with respect to national and international regulations.
Automatic analyzer for highly polar carboxylic acids based on fluorescence derivatization–liquid chromatography
Authors: Todoroki Kenichiro , Nakano Tatsuki , Ishii Yasuhiro , Goto Kanoko , Tomita Ryoko , Fujioka Toshihiro , Min Jun Zhe , Inoue Koichi , Toyo'oka Toshimasa
Published: August 2014

A sensitive, versatile, and reproducible automatic analyzer for highly polar carboxylic acids based on a fluorescence derivatization–liquid chromatography (LC) method was developed. In this method, carboxylic acids were automatically and fluorescently derivatized with 4‐(N,N‐dimethylaminosulfonyl)‐7‐piperazino‐2,1,3‐benzoxadiazole (DBD‐PZ) in the presence of 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride by adopting a pretreatment program installed in an LC autosampler. All of the DBD‐PZ‐carboxylic acid derivatives were separated on the ODS column within 30 min by gradient elution. The peak of DBD‐PZ did not interfere with the separation and the quantification of all the acids with the exception of lactic acid. From the LC‐MS/MS analysis, we confirmed that lactic acid was converted to an oxytriazinyl derivative, which was further modified with a dimethoxy triazine group of 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMT‐MM). We detected this oxytriazinyl derivative to quantify lactic acid. The detection limits (signal‐to‐noise ratio = 3) for the examined acids ranged from 0.19 to 1.1 µm, which correspond to 95–550 fmol per injection. The intra‐ and inter‐day precisions of typical, highly polar carboxylic acids were all <9.0%. The developed method was successfully applied to the comprehensive analysis of carboxylic acids in various samples, which included fruit juices, red wine and media from cultured tumor cells. Copyright © 2014 John Wiley & Sons, Ltd.
Mutations in POLE and survival of colorectal cancer patients – link to disease stage and treatment
Authors: Stenzinger Albrecht , Pfarr Nicole , Endris Volker , Penzel Roland , Jansen Lina , Wolf Thomas , Herpel Esther , Warth Arne , Klauschen Frederick , Kloor Matthias , Roth Wilfried , Bläker Hendrik , Chang‐Claude Jenny , Brenner Hermann , Hoffmeister Michael , Weichert Wilko
Published: August 2014

Recent molecular profiling studies reported a new class of ultramutated colorectal cancers (CRCs), which are caused by exonuclease domain mutations (EDMs) in DNA polymerase ϵ (POLE). Data on the clinical implications of these findings as to whether these mutations define a unique CRC entity with distinct clinical outcome are lacking. We performed Sanger sequencing of the POLE exonuclease domain in 431 well‐characterized patients with microsatellite stable (MSS) CRCs of a population‐based patient cohort. Mutation data were analyzed for associations with major epidemiological, clinical, genetic, and pathological parameters including overall survival (OS) and disease‐specific survival (DSS). In 373 of 431 MSS CRC, all exons of the exonuclease domain were analyzable. Fifty‐four mutations were identified in 46 of these samples (12.3%). Besides already reported EDMs, we detected many new mutations in exons 13 and 14 (corresponding to amino acids 410–491) as well as in exon 9 and exon 11 (corresponding to aa 268–303 and aa 341–369). However, we did not see any significant associations of EDMs with clinicopathological parameters, including sex, age, tumor location and tumor stage, CIMP, KRAS, and BRAF mutations. While with a median follow‐up time of 5.0 years, survival analysis of the whole cohort revealed nonsignificantly different adjusted hazard ratios (HRs) of 1.35 (95% CI: 0.82–2.25) and 1.44 (0.81–2.58) for OS and DSS indicating slightly impaired survival of patients with EDMs, subgroup analysis for patients with stage III/IV disease receiving chemotherapy revealed a statistically significantly increased adjusted HR (1.87; 95%CI: 1.02–3.44). In conclusion, POLE EDMs do not appear to define an entirely new clinically distinct disease entity in CRC but may have prognostic or predictive implications in CRC subgroups, whose significance remains to be investigated in future studies.
Selective TRAIL‐induced cytotoxicity to lung cancer cells mediated by miRNA response elements
Authors: Wu Guodong , Ji Zhiyong , Li Haifeng , Lei Yu , Jin Xiaoyuan , Yu Yingqing , Sun Mingli
Published: August 2014

Lung cancer is among the most common cancers, and the current therapeutic strategies are still inefficient in most cases. Tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) is a promising biological agent for cancer treatment because of its potent pro‐apoptotic effect on cancer cells. However, TRAIL also induces apoptosis in normal cells and therefore may cause toxicity to normal tissues if clinically applied. To address this issue, we inserted microRNA response elements (MREs) of miR‐133a, miR‐137 and miR‐449a, which are all underexpressed in lung cancer cells, into an adenoviral vector to regulate TRAIL expression. This MRE‐regulated vector (Ad‐TRAIL‐MRE) was able to express TRAIL in a lung‐cancer‐specific fashion. No TRAIL expression was detected in normal cells. Consistently, Ad‐TRAIL‐MRE exerted cytotoxicity to lung cancer cells, rather than normal cells, perhaps via inducing selective apoptosis. The selective TRAIL‐mediated growth‐inhibiting effect was further confirmed in a tumour xenograft model. Also, Ad‐TRAIL‐MRE only resulted in very low hepatotoxicity when applied. Collectively, we generated a novel TRAIL‐expressing adenoviral vector that was regulated by MREs. This strategy permits TRAIL expression in a lung‐cancer‐specific manner and is worth further studying for clinical trials. Copyright © 2014 John Wiley & Sons, Ltd.
Assembly of Multiple Components in a Hybrid Microcapsule: Designing a Magnetically Separable Pd Catalyst for Selective Hydrogenation
Authors: Amali Arlin Jose , Sharma Bikash , Rana Rohit Kumar
Published: August 2014

In analogy to the role of long‐chain polyamines in biosilicification, poly‐L‐lysine facilitates the assembly of nanocomponents to design multifunctional microcapsule structures. The method is demonstrated by the fabrication of a magnetically separable catalyst that accommodates Pd nanoparticles (NPs) as active catalyst, Fe3O4 NPs as magnetic component for easy recovery of the catalyst, and silica NPs to impart stability and selectivity to the catalyst. In addition, polyamines embedded inside the microcapsule prevent the agglomeration of Pd NPs and thus result in efficient catalytic activity in hydrogenation reactions, and the hydrophilic silica surface results in selectivity in reactions depending on the polarity of substrates.
Synthesis of Site‐Specifically Phosphate‐Caged siRNAs and Evaluation of Their RNAi Activity and Stability
Authors: Wu Li , Pei Fen , Zhang Jinhao , Wu Junzhou , Feng Mengke , Wang Yuan , Jin Hongwei , Zhang Liangren , Tang Xinjing
Published: August 2014

A complete set of new photolabile nucleoside phosphoramidites were synthesized, then site‐specifically incorporated into sense or antisense strands of siRNA for phosphate caging. Single caging modification was made along siRNA strands and their photomodulation of gene silencing were examined by using the firefly luciferase reporter gene. Several key phosphate positions were then identified. Furthermore, multiple caging modifications at these key positions led to significantly enhanced photomodulation of gene silencing activity, suggesting a synergistic effect. The caging group on both the terminally phosphate‐caged siRNA and the single‐stranded caged RNA has comparatively high stability, whereas hydrolysis of the caged group from the internally caged siRNA was observed, irrespective of the presence of Mg2+. Molecular dynamic simulations demonstrated that enhanced hydrolysis of the caging group on internally phosphate‐caged siRNAs was due to easy fragmentation of the caging group upon formation of the pentavalent intermediate of the phosphotriester with attack by water. The caging group in the terminally phosphate‐caged siRNA or single‐stranded caged RNA prefers to form π–π stacks with nearby nucleobases. In addition to providing explanations for previous observations, this study sheds further light on the design of caged oligonucleotides and indicates the direction of future development of nucleic acid drugs with phosphate modifications.
α‐Keto Phenylamides as P1′‐Extended Proteasome Inhibitors
Authors: Voss Constantin , Scholz Christoph , Knorr Sabine , Beck Philipp , Stein Martin L. , Zall Andrea , Kuckelkorn Ulrike , Kloetzel Peter‐Michael , Groll Michael , Hamacher Kay , Schmidt Boris
Published: August 2014

The major challenge for proteasome inhibitor design lies in achieving high selectivity for, and activity against, the target, which requires specific interactions with the active site. Novel ligands aim to overcome off‐target‐related side effects such as peripheral neuropathy, which is frequently observed in cancer patients treated with the FDA‐approved proteasome inhibitors bortezomib (1) or carfilzomib (2). A systematic comparison of electrophilic headgroups recently identified the class of α‐keto amides as promising for next generation drug development. On the basis of crystallographic knowledge, we were able to develop a structure–activity relationship (SAR)‐based approach for rational ligand design using an electronic parameter (Hammett’s σ) and in silico molecular modeling. This resulted in the tripeptidic α‐keto phenylamide BSc4999 [(S)‐3‐(benzyloxycarbonyl‐(S)‐leucyl‐(S)‐leucylamino)‐5‐methyl‐2‐oxo‐N‐(2,4‐dimethylphenyl)hexanamide, 6 a], a highly potent (IC50=38 nM), cell‐permeable, and slowly reversible covalent inhibitor which targets both the primed and non‐primed sites of the proteasome’s substrate binding channel as a special criterion for selectivity. The improved inhibition potency and selectivity of this new α‐keto phenylamide makes it a promising candidate for targeting a wider range of tumor subtypes than commercially available proteasome inhibitors and presents a new candidate for future studies.
Human treg cells are characterized by low/negative CD6 expression
Authors: Garcia Santana Carlos A. , Tung James W. , Gulnik Sergei
Published: August 2014

Natural regulatory T cells (nTreg) can suppress different immune‐cell responses and maintain the balance between tolerance and immunity in the individual. These cells are defined by CD4+, CD25hi, and FOXP3+ expression, although a variety of other nTreg‐associated markers have been reported to be expressed at different levels (e.g., HLA‐DR, CTLA‐4, GARP, Helios, CD39, etc.), presumably reflecting different functional stages of the heterogeneous nTreg population. Several markers show low/negative expression (i.e., CD127, CD49d, and CD26), but none of these markers are specific to nTreg. CD25hi expression has been a useful surface marker to identify/isolate nTreg; however, CD25 is also expressed on “adaptive” or “induced” Treg, as well as in activated conventional T cells. In addition, the fact that FOXP3 is also found in CD25 low/negative CD4+ T cells, and in a subset of CD8+ T cells, further complicates the definition of a specific nTreg marker. Although CD4+, CD25hi, and CD127low/negative markers characterize the majority of nTreg, it is still imperative to find additional surface‐marker combinations that improve the identification/isolation of nTreg and their subsets. Herein, we present evidence that CD4+CD25hi CD6lo/− nTreg have high expression of FOXP3and exhibit in vitro suppressive activity on CD8+ T‐cell proliferation. Dot‐plot analyses of CD4+ cells, with CD6, CD127, CD49d, or CD26 reveal that a higher enrichment yield of CD25hiFOXP3+ cells can be achieved in the combined CD6lo/−CD127lo/− population. We conclude that FOXP3+ nTreg cells are characterized by CD6lo/− expression, providing a new tool for the identification of nTreg cells without recourse to intracellular staining, and for the purification of these cells by negative selection. © 2014 International Society for Advancement of Cytometry
Metal–Insulator Interplays Rendered by Lattice Transformations and Structural Disorder in DOEO Salts
Authors: Bardin Andrey A. , Kotov Alexander I. , Buravov Lev I. , Khasanov Salavat S. , Shibaeva Rimma P.
Published: August 2014

Three salts, β‐DOEO2NO3(H2O) (I), β″‐DOEO2NO3(H2O) (II), and β″‐DOEO2HSO4(H2O) (III), have been synthesized and characterized by means of four‐probe conductivity measurements from room temperature down to 4.2 K and X‐ray single crystal analysis at room temperature and 100 K. Salt I shows dielectric properties below room temperature, and salts II and III are stable metals. The DOEO molecules in I–III are packed into organic (conductive) layers expanding along the ab plane. The layer packing in II and III is the same in the projection along the long molecular axis and is of the β″ type, but differs noticeably in the perpendicular direction. Salts I and II are not isostructural, but their structures are very similar. However, the electronic structures of II and III are very similar, which leads to quantitatively comparable conductivities for II and III. The upper bands of II and III are 1/4‐filled, whereas strong dimerization and band splitting leads to effective 1/2‐filling of the upper band in I, which predetermines stable metallic properties for the former and renders strong electronic correlations in the latter. A superstructure of I is formed at room temperature. The Fermi surface obtained by means of extended Hückel tight‐binding (EHTB) calculations is essentially altered by the superstructure: Two parallel 1D chains instead of a set of 1D chains and closed 2D pockets visible on the substructure are realized. The Fermi surface of I consists of flattened sections that could be a source of nesting instability. In contrast, the appearance of a superstructure of II at 100 K does not alter the Fermi surface that significantly, leaving the 2D conduction system intact and the Fermi surface with enough curvature to be stable against nesting effects. The DOEO terminal ethylene groups are strongly disordered in I with position occupancies (PO) of 0.6/0.4, less disordered in III (PO: 0.8/0.2), and fully ordered in II at room temperature. All these factors together with the very large value of the dimensionless ratio U/W = 1.66, where U is an on‐site Coulomb repulsion and W is a bandwidth, indicate that I most likely is a Mott insulator.
Thiacrown Ethers with Oxygen and Sulfur for Coordination: Formation of the Pd and Pt Complexes and Pseudorotaxane with Dialkylammonium
Authors: Nagai Hiroyuki , Suzaki Yuji , Osakada Kohtaro
Published: August 2014

Mono‐, di‐ tri‐, and tetrathiadibenzo[24]crown‐8‐ethers with eight oxygen or sulfur atoms within the 24‐menbered ring have been synthesized by using 1,2‐benzenedithiol and 2‐hydroxythiophenol as the starting materials. The thia[24]crown ethers form [2]pseudorotaxanes with dibenzylammonium salts, the association constants of which vary depending on the numbers and positions of the sulfur and oxygen atoms. The [2]pseudorotaxane of 1,4‐dithiadibenzo[24]crown‐8‐ether (1,4‐DTC) was converted into its Pd complex [PdCl2(1,4‐DTC)] by the addition of [PdCl2(cod)] (cod = 1,5‐cyclooctadiene), accompanied by the liberation of dibenzylammonium. Subsequent addition of PPh3 to the mixture led to regeneration of the [2]pseudorotaxane. A [2]pseudorotaxane composed of 1,4‐DTC and dialkylammonium with two vinyl groups at both ends of the axis component underwent a cross‐metathesis reaction with an acrylate ester to form the corresponding [2]rotaxane with an interlocked structure.
Immunosuppressive Diterpenes from Phomopsis sp. S12
Authors: Wei Wei , Gao Jian , Shen Yan , Chu Yan L. , Xu Qiang , Tan Ren X.
Published: August 2014

New immunosuppressants are needed to assist therapeutic efforts to manage immunological diseases. Along with known compounds 1–4, new diterpenes myrocin E (5), libertellenone J (6) and libertellenone K (7) were isolated from the culture of Phomopsis sp. S12, from the apparently normal seed of Illigera rhodantha (Hernandiaceae). The structures were elucidated by a combination of spectroscopic and computational approaches, in conjunction with the low‐temperature (100 K) single‐crystal X‐ray diffraction with copper Kα radiation. Libertellenone J (6) was shown to reduce significantly the production of NO, IL‐1β, IL‐6 and TNF‐α with an IC50 range of 2.2–10.2 μM, and to decrease the levels of iNOS, IL‐1β, IL‐6 and TNF‐α mRNA expression in lipopolysaccharide‐activated macrophages with IC50 values of 3.5–15.2 μM. These significant results may inspire the development of new immunosuppressive agents.
Ring‐Expanding Metathesis Oligomerization of Cyclic Nitrones
Authors: Imada Yasushi , Okita Chiaki , Maeda Hiroki , Kishimoto Masayuki , Sugano Yoshinori , Kaneshiro Hiroyuki , Nishida Yuri , Kawamorita Soichiro , Komiya Naruyoshi , Naota Takeshi
Published: August 2014

Although there has been marked progress in the chemistry of five‐ and six‐membered cyclic nitrones, medium‐ and large‐sized cyclic nitrones have remained untouched despite their potential as functional materials. Herein, we report that medium‐sized cyclic nitrones undergo ring‐expanding dimerization/oligomerization in the presence of organic or inorganic acids, and we have successfully characterized a series of novel macrocyclic polynitrones up to a 50‐membered ring size. An unprecedented ring‐size‐dependent specificity was observed for this reaction, in which cyclic nitrones with odd‐number‐membered rings are converted into dimers with high selectivity, whereas even‐number‐membered rings undergo consecutive ring‐expansion reactions to afford macrocyclic polynitrones.
Construction of a snow retention basin in an Alpine sagging mass / Errichtung eines Beschneiungsteiches in einer alpinen Sackungsmasse
Authors: Marte Roman , Moyschewitz Gerhard , Harml Josef
Published: August 2014

This contribution deals with the construction of a snow retention basin (for manufacturing snow) in the ski region Shuttleberg Flachauwinkl‐Kleinarl/Salzburg in a sagging mass movement. In the design stage it was not known whether deformations of the mass movement have to be expected and if so to what amount. Therefore probable scenarios of deformation rates of the mass movement were considered in the design and measurement equipment have been installed in order to observe the behaviour of the construction. First results of the observational system will be presented and discussed after a life time of about two years of the construction.

Im vorliegenden Beitrag wird über die Errichtung eines Beschneiungsteiches im Skigebiet Shuttleberg Flachauwinkl‐Kleinarl im Bundesland Salzburg berichtet, der in einer großräumigen aktiven Sackungsmasse errichtet wurde. Da im Zuge der Planung/Bauausführung noch nicht bekannt war, ob und in welcher Größenordnung die Sackungsmasse tatsächlich noch Bewegungen aufweist, wurde die Projektierung auf Basis realitätsnaher Szenarien hinsichtlich möglicher Hangbewegungen durchgeführt und entsprechende (messtechnische) Überwachungsmaßnahmen vorgesehen. Nach einer mittlerweile ca. zweijährigen Beobachtungszeit werden erste Ergebnisse der messtechnischen Beobachtung präsentiert und diskutiert.
Validation of a novel constitutive model for shotcrete using data from an executed tunnel / Validierung eines neuen Stoffgesetzes für Spritzbeton mittels Ergebnissen eines ausgeführten Tunnelprojekts
Authors: Saurer Erich , Marcher Thomas , Schädlich Bert , Schweiger Helmut
Published: August 2014

This paper presents the validation of a novel constitutive model for shotcrete in a tunnelling project. The shotcrete model is based on elastoplastic strain hardening/softening plasticity and can account for time dependent strength and stiffness, creep and shrinkage. The validation of the model considers the deformation behaviour of both the primary lining and the surface as well as the time dependent stress strain behaviour of the shotcrete. The calibrated model has been used to simulate the behaviour of the tunnel structure during the excavation process numerically. Furthermore different approaches to model the shotcrete lining for design are applied and briefly discussed.

Dieser Artikel befasst sich mit der Validierung eines neuen Stoffgesetzes für Spritzbeton mithilfe von Daten aus einem ausgeführten Tunnelprojekt. Das Stoffgesetz basiert auf elastoplastischer Ver‐ und Entfestigung und berücksichtigt zeitabhängige Festigkeit, Steifigkeit sowie Kriechen und Schwinden. Das kalibrierte Modell wurde verwendet, um das Verhalten des Tunnels während des Ausbruchvorgangs numerisch zu simulieren. Zudem werden verschiedene Ansätze für die Bemessung von Spritzbetonschalen angewandt und diskutiert.
Combining Family‐ and Population‐Based Imputation Data for Association Analysis of Rare and Common Variants in Large Pedigrees
Authors: Saad Mohamad , Wijsman Ellen M.
Published: August 2014

In the last two decades, complex traits have become the main focus of genetic studies. The hypothesis that both rare and common variants are associated with complex traits is increasingly being discussed. Family‐based association studies using relatively large pedigrees are suitable for both rare and common variant identification. Because of the high cost of sequencing technologies, imputation methods are important for increasing the amount of information at low cost. A recent family‐based imputation method, Genotype Imputation Given Inheritance (GIGI), is able to handle large pedigrees and accurately impute rare variants, but does less well for common variants where population‐based methods perform better. Here, we propose a flexible approach to combine imputation data from both family‐ and population‐based methods. We also extend the Sequence Kernel Association Test for Rare and Common variants (SKAT‐RC), originally proposed for data from unrelated subjects, to family data in order to make use of such imputed data. We call this extension “famSKAT‐RC.” We compare the performance of famSKAT‐RC and several other existing burden and kernel association tests. In simulated pedigree sequence data, our results show an increase of imputation accuracy from use of our combining approach. Also, they show an increase of power of the association tests with this approach over the use of either family‐ or population‐based imputation methods alone, in the context of rare and common variants. Moreover, our results show better performance of famSKAT‐RC compared to the other considered tests, in most scenarios investigated here.