bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical seismic fragility functions for highway and railway embankments and cuts
Authors: Argyroudis Sotiris , Kaynia Amir M.
Published: February 2015

A fundamental tool in seismic risk assessment of transportation systems is the fragility curve, which describes the probability that a structure will reach or exceed a certain damage state for a given ground motion intensity. Fragility curves are usually represented by two‐parameter (median and log‐standard deviation) cumulative lognormal distributions.

In this paper, a numerical approach, in the spirit of the IDA, is applied for the development of fragility curves for highways and railways on embankments and in cuts due to seismic shaking. The response of the geo‐construction to increasing levels of seismic intensity is evaluated using a 2D nonlinear finite element model, with an elasto‐plastic criterion to simulate the soil behavior. A calibration procedure is followed in order to account for the dependency of both the stiffness and the damping to the soil strain level. The effect of soil conditions and ground motion characteristics on the response of the embankment and cut is taken into account considering different typical soil profiles and seismic input motions. This study will provide input for the assessment of the vulnerability of the road/railway network regarding the performance of the embankments and cuts; therefore, the level of damage is described in terms of the permanent ground displacement in these structures.

The fragility curves are estimated based on the evolution of damage with increasing earthquake intensity, which is described by PGA. The proposed approach allows the evaluation of new fragility curves considering the distinctive features of the element's geometry, the input motion, and the soil properties as well as the associated uncertainties. A relationship between the computed permanent ground displacement on the surface of the embankment and the PGA in the free field is also suggested based on the results of the numerical analyses. Finally, the proposed fragility curves are compared with existing empirical data and the limitations of their applicability are outlined. Copyright © 2015 John Wiley & Sons, Ltd.
A population‐based single nucleotide polymorphism array analysis of genomic aberrations in younger adult acute lymphoblastic leukemia patients
Authors: Dirse Vaidas , Bertasiute Agne , Gineikiene Egle , Zvirblis Tadas , Dambrauskiene Ruta , Gerbutavicius Rolandas , Juozaityte Elona , Malciute Ligita , Paulsson Kajsa , Griskevicius Laimonas
Published: February 2015

Adult acute lymphoblastic leukemia (ALL) is characterized by a high frequency of abnormal karyotypes some of which are related to outcome. Single nucleotide polymorphism (SNP) array analysis provides a highly sensitive platform to detect large and small genomic aberrations. SNP array profiling data in adult ALL are limited and further systematic studies of this patient group are needed. We performed a population‐based SNP array analysis of genomic aberrations and their influence on survival in 66 Lithuanian 18–65 year old ALL patients diagnosed between 2007 and 2013. Most aberrations were detected in chromosome arm 9p, chromosome arm 6q, chromosome arm 13q, and chromosome 17. The recurrently targeted copy number abnormalities involved several leukemia‐related genes—CDKN2A/B, MLL, IKZF1, PAX5, RB1, TP53, and ETV6. We identified several new recurrent aberrations with possible new target genes: SMARCA4 in 19p13.2, RNASEL in 1q25.3, ARHGEF12 in 11q23.3, and LYL1 in 19p13.2. Aberrations in chromosome 13 and the RB1 gene as well as CDKN2A/B gene status were related to the outcome. © 2015 Wiley Periodicals, Inc.
Inhibition of wild‐type p53‐induced phosphatase 1 promotes liver regeneration in mice by direct activation of mammalian target of rapamycin
Authors: Zhang Lingling , Liu Leiming , He Zhiyong , Li Guangbing , Liu Junping , Song Zhangfa , Jin Hongchuan , Rudolph Karl Lenhard , Yang Huayu , Mao Yilei , Zhang Lianfeng , Zhang Hongbing , Xiao Zhicheng , Ju Zhenyu
Published: February 2015

The liver possesses extraordinary regenerative capacity in response to injury. However, liver regeneration (LR) is often impaired in disease conditions. Wild‐type p53‐induced phosphatase 1 (Wip1) is known as a tumor promoter and enhances cell proliferation, mainly by deactivating antioncogenes. However, in this work, we identified an unexpected role of Wip1 in LR. In contrast to its known role in promoting cell proliferation in extrahepatic tissue, we found that Wip1 suppressed hepatocyte proliferation after partial hepatectomy (PHx). Deletion of Wip1 increased the rate of LR after PHx. Enhanced LR in Wip1‐deficient mice was a result of the activation of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) pathway. Furthermore, we showed that Wip1 physically interacted with and dephosphorylated mTOR. Interestingly, inhibition of Wip1 also activated the p53 pathway during LR. Disruption of the p53 pathway further enhanced LR in Wip1‐deficient mice. Therefore, inhibition of Wip1 has a dual role in LR, i.e., promoting hepatocyte proliferation through activation of the mTORC1 pathway, meanwhile suppressing LR through activation of the p53 pathway. However, the proregenerative role of mTORC1 overwhelms the antiproliferative role of p53. Furthermore, CCT007093, a Wip1 inhibitor, enhanced LR and increased the survival rate of mice after major hepatectomy. Conclusion: mTOR is a new direct target of Wip1. Wip1 inhibition can activate the mTORC1 pathway and enhance hepatocyte proliferation after hepatectomy. These findings have clinical applications in cases where LR is critical, including acute liver failure, cirrhosis, or small‐for‐size liver transplantations. (Hepatology 2015;61:2030‐2041)
The Creativity‐Performance Relationship: How Rewarding Creativity Moderates the Expression of Creativity
Authors: Sue‐Chan Christina , Hempel Paul S.
Published: February 2015

Researchers have argued that creativity is intrinsically motivated, and that rewarding creativity can stifle creativity. Using a sample of 310 employees reporting to 50 different supervisors, we instead show that rewarding creativity influences the relationship between creativity and performance by changing the nature of expressed creativity. We do this by examining novelty and usefulness as separate dimensions. High perceived reward enhances the relationship between novelty and performance while diminishing the relationship between usefulness and performance. The moderating effect of reward for creativity on the relationship between creativity and performance was not observed when we operationalized creativity as an integrated, unidimensional construct. © 2015 Wiley Periodicals, Inc.
Competitive Counterion Binding Regulates the Aggregation Onset of Vimentin Intermediate Filaments
Authors: Dammann Christian , Herrmann Harald , Köster Sarah
Published: February 2015

Aggregation is a commonly observed phenomenon when mixing charged biopolymers and counterions. However, it remains a challenge to find a general description for the involved mechanisms. Here, we investigate vimentin intermediate filaments, which are overall highly negatively charged, as a prime example of such biological polyelectrolytes. We experimentally determine the onset cation concentration for aggregation, and set it in relation to the calculated relative cation concentrations in the vicinity of the filament surface. Our analysis shows that to achieve aggregation, about 50 % of the monovalent cations originally present have to be replaced by di‐ or multivalent cations. We are thus able to predict the bulk cation concentration, which mediates aggregation of highly negatively charged vimentin filaments.
Symmetry of Bioinspired Short Peptide Nanostructures and Their Basic Physical Properties
Authors: Handelman Amir , Shalev Gil , Rosenman Gil
Published: February 2015

Supramolecular bioinspired peptide nanostructures are considered as a new frontier in materials science and engineering. The nano‐crystalline packing of various peptide nanostructures, and especially those lacking a center of symmetry at the nanoscale, give rise to exceptional physical properties. Specifically, native aromatic diphenylalanine (FF) and aliphatic dileucine (LL) based nanotubes, which are related to hexagonal and orthorhombic non‐centrosymmetric crystalline groups respectively, exhibit fundamental physical phenomena, such as piezoelectricity and second harmonic generation (SHG). This review covers our latest findings on the physical properties of FF and LL nanostructures. We show that heat treatment at the temperature range of 140–180 °C induces irreversible phase transition in FF and LL nanotubes, wherein all their physical properties and structure at all levels (molecular, electronic, optical, space symmetry, morphology, wettability) change. Using high resolution microscopy tools, based on Kelvin probe force microscopy (KPFM), piezoresponse force microscopy (PFM), and SHG, as well as Raman spectroscopy, we demonstrate that the phase‐transition phenomena in FF and LL nanotubes leads to full reconstruction and reassembling of native open‐end nanotubes into new fiber‐like structures, followed by deep variation of non‐centrosymmetric to centrosymmetric space symmetry. As a result, the newly generated centrosymmetric phase in FF and LL nanostructures demonstrates neither piezoelectric effect nor nonlinear optical activity.
Integrated Management Tool for Water, Crop, Soil and N‐Fertilizers: The Saltmed Model
Authors: Ragab Ragab
Published: February 2015

Good management will be required to double food production by 2050. Testing management strategies is commonly carried out in the field. Such trials are costly and require quite a long time to produce consistent and reliable results. An alternative option to field trials would be the use of tested models. Models can run with ‘what‐if’ scenarios depicting different types of field management. They are a less costly and faster alternative to field trials.

In contrast to some existing models, the SALTMED 2013 model is designed for general applications that include various irrigation systems and water application strategies, water of different qualities, variety of crops and trees, different nitrogen‐based fertilizers and different soil types. The model can simulate up to 20 fields with different treatments, different crops, different irrigation systems and management as well as different N‐fertilizer applications. The SALTMED model has been tested using field experiment data from Portugal, Italy, Denmark, Morocco, Egypt, Syria, Brazil and Iran. It successfully simulated soil moisture, salinity, nitrogen content, grain yield and total dry matter.

The model provides academics, professionals and extension services with a management tool for crops, soil, water and nitrogen fertilizers. This paper describes the processes, the equations of the model and summarizes the different applications and results obtained. Copyright © 2015 John Wiley & Sons, Ltd.
How does a hydrocarbon staple affect peptide hydrophobicity?
Authors: Sim Adelene Y. L. , Verma Chandra
Published: February 2015

Water is essential for the proper folding of proteins and the assembly of protein–protein/ligand complexes. How water regulates complex formation depends on the chemical and topological details of the interface. The dynamics of water in the interdomain region between an E3 ubiquitin ligase (MDM2) and three different peptides derived from the tumor suppressor protein p53 are studied using molecular dynamics. The peptides show bimodal distributions of interdomain water densities across a range of distances. The addition of a hydrocarbon chain to rigidify the peptides (in a process known as stapling) results in an increase in average hydrophobicity of the peptide–protein interface. Additionally, the hydrophobic staple shields a network of water molecules, kinetically stabilizing a water chain hydrogen‐bonded between the peptide and MDM2. These properties could result in a decrease in the energy barrier associated with dehydrating the peptide–protein interface, thereby regulating the kinetics of peptide binding. © 2015 Wiley Periodicals, Inc.
A coarse‐grained MARTINI‐like force field for DNA unzipping in nanopores
Authors: Stachiewicz Anna , Molski Andrzej
Published: February 2015

In nanopore force spectroscopy (NFS) a charged polymer is threaded through a channel of molecular dimensions. When an electric field is applied across the insulating membrane, the ionic current through the nanopore reports on polymer translocation, unzipping, dissociation, and so forth. We present a new model that can be applied in molecular dynamics simulations of NFS. Although simplified, it does reproduce experimental trends and all‐atom simulations. The scaled conductivities in bulk solution are consistent with experimental results for NaCl for a wide range of electrolyte concentrations and temperatures. The dependence of the ionic current through a nanopore on the applied voltage is symmetric and, in the voltage range used in experiments (up to 2 V), linear and in good agreement with experimental data. The thermal stability and geometry of DNA is well represented. The model was applied to simulations of DNA hairpin unzipping in nanopores. The results are in good agreement with all‐atom simulations: the scaled translocation times and unzipping sequence are similar. © 2015 Wiley Periodicals, Inc.
Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety
Authors: Xu Zhenhua , Davis Hugh M. , Zhou Honghui
Published: February 2015

Immune‐mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin‐associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti‐inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti‐tumor necrosis factor‐α agents (anti‐TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6‐mercaptopurine) often increases the systemic exposure of the anti‐TNFα agent and decreases the formation of antibodies to the anti‐TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long‐term combination therapy with immunomodulators and anti‐TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit‐risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti‐TNFα agents.
Considerations for clinical pharmacology studies for biologics in emerging markets
Authors: Damle Bharat , White Robert , Wang Huifen Faye
Published: February 2015

Registration of innovative biologics in Emerging Markets (EMs) poses many opportunities and challenges. The BRIC‐MT countries (Brazil, Russia, India, China, Mexico, and Turkey) that are the fastest growing markets and regulators in these countries have imposed certain requirements, including the need for local clinical studies, for registration of biologics. The regulatory landscape in these countries is rapidly evolving, which necessitates an up‐to‐date understanding of such requirements. There is growing evidence which suggests that race, after accounting for body weight differences, may not influence the pharmacokinetics of biologics to the same extent that it does for small molecules. Thus, the requirements for clinical pharmacology trials in EMs are driven mainly by regulatory needs set forth by local Ministry of Health. In addition to the clinical Phase I to III studies done in the global program that supports registration in large geographies, countries such as China require local single and multiple dose Phase I studies. Participating in global studies with clinical sites within their country may be sufficient for some markets, while other regulators may be satisfied with a Certificate of Pharmaceutical Product. This paper discusses the current requirements for registration of innovative biologics in key EMs.
Beyond peptides and mAbs—current status and future perspectives for biotherapeutics with novel constructs
Authors: AlDeghaither Dalal , Smaglo Brandon G. , Weiner Louis M.
Published: February 2015

Biotherapeutics are attractive anti‐cancer agents due to their high specificity and limited toxicity compared to conventional small molecules. Antibodies are widely used in cancer therapy, either directly or conjugated to a cytotoxic payload. Peptide therapies, though not as prevalent, have been utilized in hormonal therapy and imaging. The limitations associated with unmodified forms of both types of biotherapeutics have led to the design and development of novel structures, which incorporate key features and structures that have improved the molecules' abilities to bind to tumor targets, avoid degradation, and exhibit favorable pharmacokinetics. In this review, we highlight the current status of monoclonal antibodies and peptides, and provide a perspective on the future of biotherapeutics using novel constructs.
Clinical pharmacology of bispecific antibody constructs
Authors: Rathi Chetan , Meibohm Bernd
Published: February 2015

The confluence of rapid scientific advancements especially in protein engineering and recombinant technology, unmet medical needs, and commercial incentives have led to the development of the next generation of therapeutic proteins. Bispecific antibody constructs are one of the novel strategies that is being pursued, combining the ability to bind simultaneously to two distinct targets and the advantages of purpose‐designed and optimized antibody‐based scaffolds. Their pharmacokinetic and pharmacodynamic properties, including their immunogenic potential, are closely related to their structural features and ability to interact with disposition mechanisms of immunoglobulin molecules. Catumaxomab and blinatumomab are bispecific constructs that are approved for clinical use and have provided clinical pharmacology data for this novel class of therapeutics. This knowledgebase on the clinical behavior of bispecific therapeutic proteins is poised to rapidly evolve over the next few years with many development programs having entered the clinical development stage.
A Novel One‐Pot Method for the Synthesis of Pyrimidine Derivatives Using Ketene N,S‐Acetal with Aryl Aldehydes
Authors: Hagimori Masayori , Murakami Yuka , Mizuyama Naoko , Tominaga Yoshinori
Published: February 2015

A very simple and facile one‐pot method for the synthesis of pyrimidine derivatives is presented. In this method, 2‐aryl‐pyrimidine derivatives were prepared by the reaction of ketene N,S‐acetal 1 with commercially available aryl aldehydes by heating under solvent and catalyst‐free conditions. The synthesized pyrimidine derivatives showed blue‐green fluorescence in solid state.
Synthesis and Antitumor Activity Evaluation of Some Novel‐Fused and Spiro Heterocycles Derived from a 2(3H)‐Furanone Derivative
Authors: Abou‐Elmagd Wael S. I. , Hashem Ahmed I.
Published: February 2015

2(3H)‐furanone 1 was fused with methyl‐4‐aminobenzoate followed by hydrazinolysis to give the acid hydrazide derivative 3. Treatment of 3 with carbon disulfide gave 4‐amino‐5‐mercapto‐3‐substituted triazole derivative 5. The presence of mercapto and amino groups adjacent to each other in compound 5 made it valuable key precursor for the formation of fused and spiro heterocycles. Ring transformation of 5 into triazolothiadiazole and triazolothiadiazine derivatives is investigated. The antitumor and antimicrobial activities of the synthesized compounds were evaluated. Some of the tested compounds showed promising activities.
An Empirical Study of the Impact of IT on Performance in Indian Service Industries
Authors: Kumar Behera Ajay , Nayak Narayan Chandra , Das Harish Chandra , Mohapatra Rabindra Narayan
Published: February 2015

An analysis of the relationship between information technology (IT) adoption and usage in Indian banking and software firms reveals the impact of IT in terms of efficiency, effectiveness, and productivity. The findings of a study of 125 service firms suggest that IT usage has a positive linear relationship with organizational performance, and that organizational performance has a positive correlation with such factors as staff attitude toward IT usage. In addition, tenure of IT adoption and utility of IT contributes significantly toward enhanced service performance. ©2015 Wiley Periodicals, Inc.
On the Statistical Calibration of Physical Models
Authors: Sargsyan K. , Najm H. N. , Ghanem R.
Published: February 2015

We introduce a novel statistical calibration framework for physical models, relying on probabilistic embedding of model discrepancy error within the model. For clarity of illustration, we take the measurement errors out of consideration, calibrating a chemical model of interest with respect to a more detailed model, considered as “truth” for the present purpose. We employ Bayesian statistical methods for such model‐to‐model calibration and demonstrate their capabilities on simple synthetic models, leading to a well‐defined parameter estimation problem that employs approximate Bayesian computation. The method is then demonstrated on two case studies for calibration of kinetic rate parameters for methane air chemistry, where ignition time information from a detailed elementary‐step kinetic model is used to estimate rate coefficients of a simple chemical mechanism. We show that the calibrated model predictions fit the data and that uncertainty in these predictions is consistent in a mean‐square sense with the discrepancy from the detailed model data.
Nitrate drawdown and its unexpected isotope effect in the Danube estuarine transition zone
Authors: Möbius Jürgen , Dähnke Kirstin
Published: February 2015

The northwestern Black Sea Shelf region suffered from severe eutrophication in recent decades, mainly due to the Danube River's increased nutrient loads, as well as nutrient remineralization in sediments. During two cruises (spring 2012 and summer 2013) in the Danube River Delta–Black Sea transition zone, we analyzed dissolved nutrients, dual isotope signatures of nitrate, and δ15N of suspended particulate matter across the salinity gradient, and two pore water nutrient profiles (only 2013) in the outer river plume. We aimed to investigate nitrogen turnover and nutrient dynamics in the present Black Sea Shelf region in order to elucidate the contemporary role of nitrogen inputs of the River Danube in the light of the past, severely eutrophic, situation in the Delta region. Data indicate intense drawdown of river‐borne nitrate, phosphate, and dissolved silica in the river plume. Isotopic patterns of nitrate and suspended N illustrate exceptionally clearly the dominance of nitrate assimilation over the entire salinity gradient. An unusual 1.9 : 1 enrichment of δ18ONO3 to δ15NNO3 questions the usually uniform enrichment that is attributed to phytoplankton. Accordingly, we investigated the potential effects of nitrate regeneration and uptake by heterotrophic plankton on the isotopic composition of nitrate in the Delta. Overall, our data suggest that today, the nitrogen input from the Danube River is taken up within the salinity gradient in large quantities, and its immediate effects on the eutrophication status of the Black Sea shelf are relatively limited.
Controlled Remodeling of Hydrogel Networks and Subsequent Crosslinking: A Strategy for Preparation of Alginate Hydrogels with Ultrahigh Density and Enhanced Mechanical Properties
Authors: Shin Bom Yi , Kim Jaeyun
Published: February 2015

Spherical alginate hydrogels—microbeads—are usually prepared via ionic crosslinking by dripping the alginate solution into a solution of divalent cations. However, the applicable concentration of alginate solution in current fabrication methods is limited to a maximum of 2–2.5 wt% due to the high viscosity of alginate in an aqueous solution. In this work, we propose a simple strategy, a remodeling of polymer networks and subsequent crosslinking process (RsC process), to prepare uniform alginate microbeads with ultrahigh alginate density, up to ≈38 wt%, via size reduction to 34% of the initial size. The uniform, ionically crosslinked alginate microbeads are shrunk via solvent exchange using an organic solvent while maintaining the spherical morphology. The shrunken state of alginate microbeads is fixed via secondary crosslinking of the alginate. Alginate hydrogels prepared via the RsC process show enhanced, controllable mechanical properties. This simple approach may be applied to any type of alginate‐based hydrogel of various size, shape, and structure to prepare hydrogels with high alginate density with tailored mechanical properties.

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A Novel Near‐IR Effective Pyrene‐Based Donor–Acceptor Electrochrome
Authors: Sefer Emre , Hacioglu Serife O. , Tonga Murat , Toppare Levent , Cirpan Ali , Koyuncu Sermet
Published: February 2015

In this work, a novel donor–acceptor electrochromic monomer (3HTP), containing a pyrene subunit connected to a quinoxaline acceptor bridge, is synthesized. The corresponding polymer, poly‐(3HTP), is directly deposited onto an indium tin oxide (ITO)/glass surface via an electrochemical process. Atomic force microscopy (AFM) images reveal that the electrochemically deposited poly‐(3HTP) has a smooth surface due to self‐assembly of the planar pyrene subunit. Electrochemical and optical properties are investigated via cyclic voltammetry and UV–vis absorption measurements. The polymer film shows a multielectrochromic feature at both anodic and cathodic regimes. Poly‐(3HTP) exhibits a strong near‐infrared (NIR) absorption at the oxidized state with an optical contrast of 88% (at 1800 nm), a very fast response time of 0.5 s and fast switching times, and long‐term stability. Density functional theory calculations reveal that the molecule has a high planarity, and the NIR absorption arises from a strong intramolecular charge transfer from the polymer backbone to the planar pyrene subunit.

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Modeling of Branching Distributions in Butyl Acrylate Polymerization Applying Monte Carlo Methods
Authors: Drache Marco , Hosemann Benjamin , Laba Tetyana , Beuermann Sabine
Published: February 2015

Monte Carlo (MC) methods were applied to the complex kinetic model of butyl acrylate polymerizations. The MC simulator mcPolymer developed in house allows for handling chain‐length‐dependent termination kinetics. The simulations provide detailed information on the microstructure of each individual polymer chain. For example, the number of short chain branches (SCBs) on each polymer chain and the length of the monomer sequence between two short chain branches are captured. It is shown that the maximum of the branching density distribution is shifted to shorter chain lengths with reaction time. Variation of initiator concentration does not lead to significant changes in the sequence length distributions and branching distributions as long as the same monomer conversion is reached.
On finite volume method implementation of poro‐elasto‐plasticity soil model
Authors: Tang Tian , Hededal Ole , Cardiff Philip
Published: February 2015

Accurate prediction of the interactions between the nonlinear soil skeleton and the pore fluid under loading plays a vital role in many geotechnical applications. It is therefore important to develop a numerical method that can effectively capture this nonlinear soil‐pore fluid coupling effect. This paper presents the implementation of a new finite volume method code of poro‐elasto‐plasticity soil model. The model is formulated on the basis of Biot's consolidation theory and combined with a perfect plasticity Mohr‐Coulomb constitutive relation. The governing equation system is discretized in a segregated manner, namely, those conventional linear and uncoupled terms are treated implicitly, while those nonlinear and coupled terms are treated explicitly by using any available values from previous time or iteration step. The implicit–explicit discretization leads to a linearized and decoupled algebraic system, which is solved using the fixed‐point iteration method. Upon the convergence of the iterative method, fully nonlinear coupled solutions are obtained. Also explored in this paper is the special way of treating traction boundary in finite volume method compared with FEM. Finally, three numerical test cases are simulated to verify the implementation procedure. It is shown in the simulation results that the implemented solver is capable of and efficient at predicting reasonable soil responses with pore pressure coupling under different loading situations. Copyright © 2015 John Wiley & Sons, Ltd.
Solvolytic reactivity of pyridinium ions
Authors: Jurić Sandra , Kronja Olga
Published: February 2015

The leaving group abilities of pyridine, 4‐methylpyridine, and 4‐chloropyridine in SN1 solvolytic reactions have been determined by analyzing the rate constants of X,Y‐substituted benzhydrylpyridinium salts obtained in various solvents. By applying the linear free energy relationship equation, log k = sf (Ef + Nf), the nucleofuge specific parameters of 4‐substituted pyridine have been extracted. Because of solvation in the reactant ground state, the reactivity (nucleofugality, Nf) of a given pyridine decreases as the polarity of the solvent increases. High slope parameters (sf > 1) may be due to the spread of the energy levels of the benzhydrylium ion/pyridine pair intermediates in comparison to benzhydrylium ion/chloride pairs (sf ≈ 1). Because of slow heterolysis step of pyridinium salts in various solvents, some are stable under normal conditions. Copyright © 2015 John Wiley & Sons, Ltd.
Substituent effects in the Diels–Alder reactions of butadienes, cyclopentadienes, furans and pyroles with maleic anhydride
Authors: Qiu Yongge
Published: February 2015

In this study, activation energies in the Diels–Alder reactions of a series of substituted butadienes, cyclopentadienes, furans and pyroles with maleic anhydride were calculated by the M06‐2X/6‐31G(d) method. The substituent effects on the reactivity and the endo–exo selectivity have been examined. The strength of reactivity effect has an order of pyroles > furans > cyclopentadienes > butadienes, which is highly correlated with the lowest unoccupied molecular orbital energy, the electronic chemical potential and the electrophilicity of parent diene but relatively less correlated with the highest occupied molecular orbital energy and chemical hardness. The trend that an increase of necleophilicity caused by an electron‐donating group on the diene favors the endo TS is effective with C2 substitution. With C1 substitution, the trend is ambiguous or even opposite. Copyright © 2015 John Wiley & Sons, Ltd.
Drug delivery and release systems for targeted tumor therapy
Authors: Böhme David , Beck‐Sickinger Annette G.
Published: February 2015

Most toxic agents currently used for chemotherapy show a narrow therapeutic window, because of their inability to distinguish between healthy and cancer cells. Targeted drug delivery offers the possibility to overcome this issue by selectively addressing structures on the surface of cancer cells, therefore reducing undesired side effects. In this broad field, peptide–drug conjugates linked by intracellular cleavable structures have evolved as highly promising agents. They can specifically deliver toxophores to tumor cells by targeting distinct receptors overexpressed in cancer. In this review, we focus on these compounds and describe important factors to develop a highly efficient peptide–drug conjugate. The necessary properties of tumor‐targeting peptides are described, and the different options for cleavable linkers used to connect toxic agents and peptides are discussed, and synthetic considerations for the introduction of these structures are reported. Furthermore, recent examples and current developments of peptide–drug conjugates are critically evaluated with a special focus on the applied linker structures and their future use in cancer therapy. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
Morphology and size effects on the reduction of silver oxide by hydrogen
Authors: Schimo Gabriela , Kreuzer Andreas Michael , Hassel Achim Walter
Published: February 2015

The dependence of reactivity towards hydrogen on size and morphology was studied for silver oxide Ag2O microparticles. Morphological tuning of the microparticles, which appeared in a size range from 340 to 1400 nm, was achieved in a wet‐chemical synthesis approach. Thermogravimetric measurements allowed the determination of onset temperatures and reaction rates for reduction with gaseous hydrogen as reducing agent. The results reveal the high complexity of the Ag2O reduction process, on which both the surface to volume ratio as well as the facet dependent activity of the morphologies have great influence. Differential scanning calorimetry was employed to study reduction by hydrogen, desorbing from a hydrogen‐loaded palladium foil, showing great effect of contact area size on the reactivity.
Chemical depth profiling and 3D reconstruction of III–V heterostructures selectively grown on non‐planar Si substrates by MOCVD
Authors: Gorbenko V. , Veillerot M. , Grenier A. , Audoit G. , Hourani W. , Martinez E. , Cipro R. , Martin M. , David S. , Bao X. , Bassani F. , Baron T. , Barnes J.‐P.
Published: February 2015

The chemical characterization of novel 3D architectures with nanometre‐scale dimensions is extremely challenging. The chemical composition of InGaAs/AlAs quantum wells selectively grown in SiO2 trenches, 100–300 nm wide, is studied. Combining high lateral resolution 3D ToF‐SIMS analysis and Auger measurements, the chemical composition of individual trenches was obtained confirming the uniformity of these III–V heterostructures. These results correlate well with an average approach using SIMS depth profiling. The effects of ion beam orientation on the surface topography of confined structures were highlighted. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Carbon footprint of robotically‐assisted laparoscopy, laparoscopy and laparotomy: a comparison
Authors: Woods Demetrius L. , McAndrew Thomas , Nevadunsky Nicole , Hou June Y. , Goldberg Gary , Yi‐Shin Kuo Dennis , Isani Sara
Published: February 2015

Background

To date there have been no comprehensive, comparative assessments of the environmental impact of surgical modalities. Our study seeks to quantify and compare the total greenhouse gas emissions, or 'carbon footprint', attributable to three surgical modalities.

Methods

A review of 150 staging procedures, employing laparotomy (LAP), conventional laparoscopy (LSC) or robotically‐assisted laparoscopy (RA‐LSC), was performed. The solid waste generated (kg) and energy consumed (kWh) during each case were quantified and converted into their equivalent mass of carbon dioxide (kg CO2e) release into the environment. The carbon footprint is the sum of the waste production and energy consumption during each surgery (kg CO2e).

Results

The total carbon footprint of a RA‐LSC procedure is 40.3 kg CO2e/patient (p < 0.01). This represents a 38% increase over that of LSC (29.2 kg CO2e/patient; p < 0.01) and a 77% increase over LAP (22.7 kg CO2e/patient; p < 0.01).

Conclusions

Our results provide clinicians, administrators and policy‐makers with knowledge of the environmental impact of their decisions to facilitate adoption of sustainable practices. Copyright © 2015 John Wiley & Sons, Ltd.
Accounting for informatively missing data in logistic regression by means of reassessment sampling
Authors: Lin Ji , Lyles Robert H.
Published: February 2015

We explore the ‘reassessment’ design in a logistic regression setting, where a second wave of sampling is applied to recover a portion of the missing data on a binary exposure and/or outcome variable. We construct a joint likelihood function based on the original model of interest and a model for the missing data mechanism, with emphasis on non‐ignorable missingness. The estimation is carried out by numerical maximization of the joint likelihood function with close approximation of the accompanying Hessian matrix, using sharable programs that take advantage of general optimization routines in standard software. We show how likelihood ratio tests can be used for model selection and how they facilitate direct hypothesis testing for whether missingness is at random. Examples and simulations are presented to demonstrate the performance of the proposed method. Copyright © 2015 John Wiley & Sons, Ltd.
Spanifold: spanning tree flattening onto lower dimension
Authors: Chenouri Shoja'eddin , Kobelevskiy Petr , Small Christopher G.
Published: February 2015

Dimensionality reduction and manifold learning techniques attempt to recover a lower‐dimensional submanifold from the data as encoded in high dimensions. Many techniques, linear or non‐linear, have been introduced in the literature. Standard methods, such as Isomap and local linear embedding, map the high‐dimensional data points into a low dimension so as to globally minimize a so‐called energy function, which measures the mismatch between the precise geometry in high dimensions and the approximate geometry in low dimensions. However, the local effects of such minimizations are often unpredictable, because the energy minimization algorithms are global in nature. In contrast to these methods, the Spanifold algorithm of this paper constructs a tree on the manifold and flattens the manifold in such a way as to approximately preserve pairwise distance relationships within the tree. The vertices of this tree are the data points, and the edges of the tree form a subset of the edges of the nearest‐neighbour graph on the data. In addition, the pairwise distances between data points close to the root of the tree undergo minimal distortion as the data are flattened. This allows the user to design the flattening algorithm so as to approximately preserve neighbour relationships in any chosen local region of the data. Copyright © 2015 John Wiley & Sons, Ltd.
Treatments with organic acids and pullulanase differently affect resistant starch and fiber composition in flour of various barley genotypes (Hordeum vulgare L.)
Authors: Harder Hauke , Khol‐Parisini Annabella , Zebeli Qendrim
Published: February 2015

An enrichment of foodstuffs with RS and dietary fiber is meaningful for a healthier diet. Main goal of this research was to evaluate the effects of treating barley with citric acid (CA), lactic acid (LA), separately or together, and with the enzyme pullulanase (PUL) on RS and the contents of main nutrients of four barley genotypes. Treatment with PUL increased the RS content from 0.26 (control) to 1.29%. Enhancement of RS was also observed with 5% LA as well as with 5% CA, but these effects were barley genotype‐dependent. Treatment with CA increased the organic residue, a fraction that includes (1 → 3,1 → 4)‐β‐glucan, from 10.2 to 14.0%. Ash contents decreased from 2.42 to 1.98% by LA treatment and neutral detergent fiber decreased from 14.1 to 8.4% by CA treatment, depending on the used barley genotype. In conclusion, data indicated that treating barley with organic acids or PUL may have the potential to enhance the RS and beneficially modulate nutrient composition of barley. Further research is warranted to understand the mechanisms behind the effects observed herein and their nutritional implications in the diet.
Probabilistic stability and ‘tall’ wind profiles: theory and method for use in wind resource assessment
Authors: Kelly Mark , Troen Ib
Published: February 2015

A model has been derived for calculating the aggregate effects of stability and the finite height of the planetary boundary layer upon the long‐term mean wind profile. A practical implementation of this probabilistic extended similarity‐theory model is made, including its incorporation within the European Wind Atlas (EWA) methodology for site‐to‐site application. Theoretical and practical implications of the EWA methodology are also derived and described, including unprecedented documentation of the theoretical framework encompassing vertical extrapolation, as well as some improvement to the methodology. Results of the modeling are shown for a number of sites, with discussion of the models' efficacy and the relative improvement shown by the new model, for situations where a user lacks local heat flux information, as well as performance of the new model using measured flux statistics. Further, the uncertainty in vertical extrapolation is characterized for the EWA model contained in standard (i.e., WAsP) wind resource assessment, as well as for the new model. Copyright © 2015 John Wiley & Sons, Ltd.
Anti‐PEG immunity: emergence, characteristics, and unaddressed questions
Authors: Yang Qi , Lai Samuel K.
Published: February 2015

The modification of protein and nanoparticle therapeutics with polyethylene glycol (PEG), a flexible, uncharged, and highly hydrophilic polymer, is a widely adopted approach to reduce RES clearance, extend circulation time, and improve drug efficacy. Nevertheless, an emerging body of literature, generated by numerous research groups, demonstrates that the immune system can produce antibodies that specifically bind PEG, which can lead to the ‘accelerated blood clearance’ of PEGylated therapeutics. In animals, anti‐PEG immunity is typically robust but short‐lived and consists of a predominantly anti‐PEG IgM response. Rodent studies suggest that the induction of anti‐PEG antibodies (α‐PEG Abs) primarily occurs through a type 2 T‐cell independent mechanism. Although anti‐PEG immunity is less well‐studied in humans, the presence of α‐PEG Abs has been correlated with reduced efficacy of PEGylated therapeutics in clinical trials. The prevalence of anti‐PEG IgG and reports of memory immune responses, as well as the existence of α‐PEG Abs in healthy untreated individuals, suggests that the mechanism(s) and features of human anti‐PEG immune responses may differ from those of animal models. Many questions, including the incidence rate of pre‐existing α‐PEG Abs and immunological mechanism(s) of α‐PEG Ab formation in humans, must be answered in order to fully address the potential complications of anti‐PEG immunity. WIREs Nanomed Nanobiotechnol 2015, 7:655–677. doi: 10.1002/wnan.1339

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Are they fresco paintings? Technical and material study of Casas Pintadas of Vasco da Gama house in Évora (Southern Portugal)
Authors: Gil Milene , Rosado Tania , Ribeiro Isabel , Pestana José A. , Caldeira Ana Teresa , Carvalho Maria Luisa , Dias Luis , Mirão José , Candeias António
Published: February 2015

The present paper describes the characterization and comparative study carried out on the 16th century murals of Casas Pintadas of the so‐called Vasco da Gama House in the town of Évora, Southern Portugal. Even today, the two existing paintings in the porch vaulted cloister raise many questions about the pictorial techniques and materials that were used. The most adopted theory is that the upper register inspired in medieval bestiary was made with a secco technique, while the lower grotteschi frieze was achieved with a fresco technique. A multianalytical research was carried out in situ and in laboratory in order to attest this hypothesis and to characterize the paintings materials. Surface examination was made with normal and racking light complemented with in situ spectrophotometry in the visible, with stratigraphic and analytical study of microsamples by optical microscopy (OM) and scanning electron microscopy coupled with energy dispersive X‐ray spectrometry (SEM‐EDS). The results show similarities in the structure and elemental composition of both paintings mortars and pigments. The mortars' inner layers (the intonaci) were made with siliceous sands mixed with a dolomitic lime‐based plaster (CaMg(CO3)2). On top of it, one to three thin layers of lime wash were applied. In SEM‐EDS elemental maps, all the pigments at the cross‐sections are embedded in a calcium carbonate matrice, and several nails marks are visible in situ with racking light in both paintings indicating a fresco technique. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis and Crystal Structures of Rb4Al2S5 and Cs4In2S5
Authors: Winkler Verena , Schlosser Marc , Pfitzner Arno
Published: February 2015

Two new alkali metal thiotrielates with the general composition M4T2S5 (M = Rb, Cs; T = Al, In) were obtained via the azide route and their crystal structures were determined from single‐crystal X‐ray diffraction data. Highly air sensitive Rb4Al2S5 crystallizes in pale red rods in the space group Pna21 (no. 33) with lattice constants a = 11.4450(5) Å, b = 11.4605(6) Å, c = 9.5727(4) Å, and a cell volume of V = 1255.6(1) Å3 with Z = 4. To the best of our knowledge, Rb4Al2S5 represents the first rubidium thioaluminate and a new structure type in the field of ternary alkali metal chalkogenometallates. Cs4In2S5 crystallizes isotypic to Rb4In2S5 in the space group P$\bar{1}$ (no. 2) with lattice constants a = 9.6871(3) Å, b = 11.1549(4) Å, c = 7.7879(3) Å, α = 110.731(3)°, β = 95.760(3)°, γ = 102.766(2)°, and a cell volume of V = 752.75(4) Å3 with Z = 2. The crystal structures of both solids consist of edge‐linked [T2S6]6– double tetrahedra, which build up one‐dimensional, polymeric 1∞[T2S54–] strands by trans‐corner sharing. The anionic chains are separated by rubidium and cesium cations, respectively. Aluminum as well as indium has a slightly distorted tetrahedral surrounding by sulfur, and the four independent rubidium atoms in Rb4Al2S5 feature distorted trigonal prismatic and distorted octahedral coordination spheres, respectively. In Cs4In2S5 the four different cesium positions show coordination numbers of six and seven. Cs4In2S5 was also characterized by Raman spectroscopy. The frequencies of In–S stretching modes are found in the range from 342 cm–1 to 292 cm–1.
Construction and Properties of Two MOFs Based on 2‐p‐Bromophenyl Imidazole Dicarboxylate
Authors: Zhu Yong‐Chao , Ren Xue , Wang Jing , Li Gang
Published: February 2015

To further explore the coordination ability of an multi‐functional ligand 2‐(p‐bromophenyl)‐1H‐imidazole‐4,5‐dicarboxylic acid (p‐BrPhH3IDC), two metal‐organic frameworks [Mn(μ2‐p‐BrPhH2IDC)2]n (I) and {[Pb(μ2‐p‐BrPhH2IDC)2]·H2O}n (II) were synthesized under hydro(solvo)thermal conditions and structurally characterized by elemental analyses, IR spectroscsopy, and single‐crystal X‐ray diffraction. Polymer I shows a 2D sheet structure. In polymer II, 1D octagonal channels are connected by the organic ligands to form a 3D architecture. Furthermore, the thermal characteristics of the two polymers and the coordination features of p‐BrPhH3IDC were investigated.
On the inverse problem of the two‐velocity tree‐like graph
Authors: Avdonin Sergei , Rivero Abdon Choque , Leugering Günter , Mikhaylov Victor
Published: February 2015

In this article the authors continue the discussion in about inverse problems for second order elliptic and hyperbolic equations on metric trees from boundary measurements. In the present paper we prove the identifiability of varying densities of a planar tree‐like network of strings along with the complete information on the graph, i.e. the lengths of the edges, the edge degrees and the angles between neighbouring edges. The results are achieved using the Titchmarch‐Weyl function for the spectral problem and the Steklov‐Poincaré operator for the dynamic wave equation on the tree. The general result is obtained by a peeling argument which reduces the inverse problem layer‐by‐layer from the leaves to the clamped root of the tree.