bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symmetry of Bioinspired Short Peptide Nanostructures and Their Basic Physical Properties
Authors: Handelman Amir , Shalev Gil , Rosenman Gil 
Published: February 2015

AbstractSupramolecular 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

AbstractGood 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.
Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety
Authors: Xu Zhenhua , Davis Hugh M. , Zhou Honghui 
Published: February 2015

AbstractImmune‐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

AbstractRegistration 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

AbstractBiotherapeutics 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

AbstractThe 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.
On the Statistical Calibration of Physical Models
Authors: Sargsyan K. , Najm H. N. , Ghanem R. 
Published: February 2015

ABSTRACTWe 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

AbstractThe 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.image
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.image
On finite volume method implementation of poro‐elasto‐plasticity soil model
Authors: Tang Tian , Hededal Ole , Cardiff Philip 
Published: February 2015

SummaryAccurate 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.
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

AbstractBackgroundTo 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.MethodsA 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).ResultsThe 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).ConclusionsOur 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.
Probabilistic stability and ‘tall’ wind profiles: theory and method for use in wind resource assessment
Authors: Kelly Mark , Troen Ib 
Published: February 2015

AbstractA 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.1339This 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
Synthesis and Crystal Structures of Rb4Al2S5 and Cs4In2S5
Authors: Winkler Verena , Schlosser Marc , Pfitzner Arno 
Published: February 2015

AbstractTwo 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

AbstractTo 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.