bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferons
Authors: Ahmed Chulbul M , Johnson Howard M
Published: May 2017

Interferons are a group of proteins defined primarily by their antiviral properties. There are three major types based on gene and protein structure, as well as receptors unique to the types. Type I interferons are composed of 15 or more members, type II of only one member and type III of four members. In addition to their defining antiviral activity, the interferons are multifunctional as immune regulators, cell function modulators and antitumor agents. Tyrosine kinases called Janus kinases (JAKs) and transcription factors called signal transducers and activators of transcription (STATs) are key players in gene activation by interferons, but the specificity of such activation is best understood in the context of ligand and receptor along with JAKs and STATs at the response elements of genes specifically activated by interferons.

Key Concepts

Interferons are a crucial group of proteins defined by their broad‐spectrum antiviral properties.

In addition to their antiviral properties, interferons play a key role in positive and negative immune regulation.

Type I interferon, β, negatively regulates the immune system and is thus a therapeutic for multiple sclerosis.

Type I interferon, α, exacerbates the autoimmune disease systemic lupus erythematosus.

The JAK/STAT signal transduction system plays a key role in gene activation by interferons.

The non‐canonical pathway of interferon signalling provides insight into the specificity of genetic and epigenetic aspects of interferon signalling.

The interferon system is a prototype for other cytokines, growth factors and hormones that use the JAK/STAT system.
Hypersensitivity:
IgE
‐Mediated (Type
I
)
Authors: Delves Peter J
Published: May 2017

Hypersensitivity reactions, which are classified into 4 types (type I‐IV), are over‐zealous immune responses due to the fact that they are directed against harmless antigens, are of excessive magnitude, and/or are occurring in inappropriate body locations. Type I, or sometimes type IV, hypersensitivity reactions are responsible for the symptoms of allergy. Huge numbers of people suffer from allergic responses, which can vary in significance from being mildly inconvenient to resulting in rapid death. Allergic responses due to type I hypersensitivity are often referred to as atopic allergy and are mediated by the IgE class of antibody bound to tissue mast cells and to circulating blood basophils. Cross‐linking of the IgE by allergen results in the release of a plethora of inflammatory mediators that cause the symptoms. A variety of tests are available to assist in the diagnosis of type I hypersensitivity, and a range of therapies are used to control the diseases it causes.

Key Concepts

There are four main types of hypersensitivity reactions, which are characterised by inappropriate or exaggerated immune responses.

Type I hypersensitivity reactions involve the activation of tissue mast cells and blood basophils when IgE molecules bound to their surface become linked together by an allergen.

Substantial numbers of individuals develop allergies due to type I (IgE‐mediated) hypersensitivity, also referred to as atopic allergy.

Allergies that are caused by type I hypersensitivity include hay fever, asthma, eczema and food allergy.

The IgE antibodies are bound to the cell surface of the mast cells and basophils via a high affinity Fc receptor for IgE (FcϵR1).

Susceptibility to the development of type I hypersensitivity has been linked to polymorphisms in several different genes.

Activation of mast cells and basophils leads to the release of many different mediators of inflammation including histamine, prostaglandins and leukotrienes.

The release of inflammatory mediators by mast cells and basophils is a component of normal immune responses, but in atopic allergy the response is inappropriate because it is against a substance that would not normally pose a threat.

There are a number of different approaches to the treatment of atopic allergy, but the best strategy in individuals that have already become sensitised, and when feasible, is avoidance of re‐exposure to the allergen.
Hepatitis
A
Virus
Authors: Feng Zongdi
Published: May 2017

Hepatitis A virus (HAV) is one of the five human hepatitis viruses that replicate in and cause inflammation of the liver. HAV is transmitted through a faecal–oral route and has a unique life cycle in that it is shed as naked virions into the faeces but circulates in an enveloped form in the blood. In addition, the virus has several unique mechanisms to evade detection by the host immune system. The majority of HAV infections are self‐limited and asymptomatic, but severe forms sometimes occur, particularly in the elderly. HAV has only one serotype, and persons infected with HAV usually develop lifelong immunity. Incidence rates of HAV infections have been greatly reduced owing to improved sanitation and the use of very successful vaccines.

Key Concepts

The hepatitis A virus is transmitted via the faecal–oral route and is a major cause of acute hepatitis worldwide.

HAV only infects humans and non‐human primates, although HAV‐like viruses infect a range of animal species.

HAV infection is extraordinary ‘stealthy’, and the virus has multiple mechanisms to evade the host immune response.

HAV is shed as naked virions in the faeces but circulates as quasi‐enveloped virions in the blood.

Hepatitis A vaccine is one of the most successful vaccines ever developed, providing lifelong protection when given either pre‐exposure or post‐exposure.
Mononuclear Phagocyte System
Authors: Vegh Peter , Fletcher James , Dixon David , Haniffa Muzlifah
Published: May 2017

The mononuclear phagocyte system is part of the innate immune system and comprises dendritic cells (DCs), monocytes and macrophages, which fulfil a range of tasks essential for homeostasis and immunity. Macrophages and DCs were originally thought to be variations of monocytes, but recent evidence has defined the distinct origins of macrophages, monocytes and DCs. Mononuclear phagocytes are functionally specialised and play a critical role in all phases of the immune response. They detect and phagocytose pathogens, recruit cells, initiate adaptive immunity by presenting antigens to T cells and coordinate the resolution of inflammation and wound healing. Macrophages have additional vital functions in tissue development and homeostasis.

Key Concepts

Mononuclear phagocytes (dendritic cells, monocytes and macrophages) are a diverse group of cells with a wide range of functions essential for maintaining organism integrity.

Macrophages are tissue resident, play a central role in homeostasis, perform tissue‐specific functions and orchestrate immune responses.

Dendritic cells are specialised antigen‐presenting cells with superior ability to initiate immune responses.

Monocytes are circulating leucocytes that can enter the tissue and have important roles in phagocytosis, inflammation and wound healing.

Mononuclear phagocytes coordinate innate and adaptive immune response.
Protein–Protein Interactions: The Structural Foundation of Life Complexity
Authors: Paola Luisa Di , Giuliani Alessandro
Published: May 2017

The amazing variety of protein functions are often covered by protein complexes, so understanding protein–protein interactions means coming deeply into the functional role of proteins in life.

In the last years, the investigation of protein–protein interactions has become central in many fields, spanning from molecular biology to pharmacology. In this article, we present a state of the art of methods for such investigation, along with perspectives of applications. We stressed the multiscale nature of approaches, longing from genome‐wide analysis to the detailed study of protein–protein interface on single residues.

The most innovative approaches, based on complex network theory, shed a very bright light on future trends for protein–protein applications on drug design and on molecular therapy for diseases where protein association plays a pivotal role (misfolding).

Key Concepts

Protein–protein interactions underlie several physiological mechanisms.

The analysis of protein–protein interfaces is crucial to quantify protein complex stability.

Hotspot residues provide the largest contribution to protein–protein binding energy.

Experimental methods point to identify hotspots and quantify binding energy.

Molecular docking allows a fine analysis of protein–protein interface.

Network‐based approaches clarify the multiscale nature of protein–protein interactions.
Spleen: Disorders
Authors: Kuchar Ernest , Karlikowska‐Skwarnik Monika
Published: May 2017

The spleen is an important peripheral immunologic organ although not essential for life. The main functions of the spleen are filtering of blood, lymphopoiesis and immunoglobulin production. The spleen is abundantly supplied with blood, which the other secondary lymphoid organs do not have, and clears particulate material, for example, opsonised bacteria from the blood. Reduced function, known as functional asplenia, is observed in many various pathological conditions, for example, when the spleen is congested with blood or when infiltrated by metastatic tumours or contains large haemangiomas. Most common causes of splenic hypofunction are coeliac disease, sprue, sickle cell disease and haematologic disorders. Individuals with removed spleen or impaired splenic function are prone to serious and often fatal bacterial infections. The vast majority of these serious infections, caused by encapsulated bacteria (pneumococci, meningococci and
Haemophilus influenzae
type b) can be effectively prevented by immunisations and antibiotic prophylaxis.

Key Concepts

Spleen is an important secondary immunologic organ located in the left epigastrium beneath the lower rib cage, responsible for blood filtration and antibodies production.

Spleen is important but not essential for life and can be removed.

Reduced spleen function, known as functional asplenia, is observed in various pathological conditions including sickle cell disease, celiac disease and haematologic disorders.

Spleen dysfunction is associated with increased risk of serious and sometimes fatal bacterial sepsis or meningitis, usually caused by pneumococci and other capsular bacteria.

The vast majority of bacterial infections in asplenic individuals can be prevented by currently available immunisations and prophylactic antibiotics.
VitaminB12: Disorders of Absorption and Metabolism
Authors: Watkins David , Rosenblatt David S
Published: May 2017

Derivatives of vitamin B12(cobalamin) are required for activity of two enzymes: methylmalonyl‐CoA mutase, which catalyses conversion of methylmalonyl‐CoA to succinyl‐CoA, and methionine synthase, which converts homocysteine to methionine. Cobalamin deficiency results in the accumulation of methylmalonic acid and homocysteine in blood and urine. Clinically, deficiency results in megaloblastic anaemia and subacute combined degeneration of the spinal cord, loss of sensation, ataxia, dementia and psychosis. Dietary cobalamin deficiency is rare in developed countries, except for individuals consuming a vegan diet. A more common cause of cobalamin deficiency is pernicious anaemia, an autoimmune disease that results in inability to absorb cobalamin from the intestine. A number of rare genetic disorders have been identified that result in either failure to absorb dietary cobalamin, to transport cobalamin from the intestine to cells that require it for metabolism or to convert intracellular cobalamin to one or both of its coenzyme derivatives, adenosylcobalamin and methylcobalamin.

Key Concepts

Cobalamin (vitamin B12) is required for activity of two enzymes, methylmalonyl‐CoA mutase and methionine synthase, in mammalian cells.

Cobalamin deficiency results in accumulation of methylmalonic acid and homocysteine in blood and urine.

Clinically, deficiency is characterised by megaloblastic anaemia and/or neurological problems.

Uptake of dietary cobalamin requires the binding protein intrinsic factor, secreted by parietal cells of the stomach, and the intestinal receptor cubam.

Autoimmune destruction of parietal cells results in pernicious anaemia.

Mutations in the genes encoding intrinsic factor or the components of cubam (cubilin and amnionless) result in heritable cobalamin malabsorption and signs of cobalamin deficiency.

Peripheral cells take up cobalamin bound to the transport protein transcobalamin by carrier‐mediated endocytosis.

Cells convert cobalamin to adenosylcobalamin, required by methylmalonyl‐CoA mutase, and methylcobalamin, required by methionine synthase.

Rare mutations affecting genes involved in cobalamin metabolism result in decreased synthesis of either or both cobalamin derivatives.

Mutations in certain transcription regulators can affect expression of genes encoding cobalamin metabolising enzymes, resulting in altered cobalamin coenzyme synthesis.
Molecular Genetics of Galactosaemia
Authors: Timson David J
Published: May 2017

Galactosaemia is a relatively rare, genetic disease that commonly manifests with cataracts in childhood. More severe forms result in significant developmental abnormalities resulting in physical and cognitive disabilities. Three genes are affected: galactose 1‐phosphate uridylyltransferase (
GALT
; type I galactosaemia), galactokinase (
GALK1
; type II) and UDP‐galactose 4'‐epimerase (
GALE
; type III). Clinical outcomes vary widely in severity and depend on the gene affected, the precise mutation(s) present and the patient's environment. The disease can be diagnosed by altered metabolite levels, reduced enzyme activity and sequencing of the affected gene. In many cases, mutations in one of these three genes result in a protein that is unstable and/or misfolded with consequent reduction in enzymatic activity. Understanding how loss of activity of these enzymes results in the disease phenotypes is a key priority in current research.

Key Concepts

Galactosaemia is an inherited metabolic disease affecting the genes encoding enzymes of galactose metabolism.

Three types of galactosaemia are recognised depending on which gene is affected.

Type I galactosaemia is the most common and affects
GALT
that encodes galactose 1‐phosphate uridylyltransferase.

The severity of symptoms of galactosaemia is highly varied depending on the precise mutation(s) present and the patient's environment.

Our understanding of the normal regulation of these genes in humans is incomplete.

Diagnosis may be initially made by increased galactose or galactose 1‐phosphate levels.

Diagnosis is normally confirmed through measuring enzyme activities and sequencing the affected gene.

In many cases, point mutations result in proteins that are misfolded and/or unstable.

Our understanding of how mutated genes and altered biochemistry lead to the disease phenotypes is incomplete.

Bakers' yeast, fruit flies, nematode worms and mice have all been used successfully as models for galactosaemia.
Dealloying in Individual Nanoparticles and Thin Film Grains: A Bragg Coherent Diffractive Imaging Study
Authors: Cha Wonsuk , Liu Yihua , You Hoydoo , Stephenson Gregory Brian , Ulvestad Andrew
Published: May 2017

Dealloying is a process whereby selective dissolution results in a porous, strained structure often with new properties. The process is of both intrinsic and applied interest, and recently has been used to make highly active catalysts. The porosity has been studied using electron microscopy while the dealloying‐induced strain has been studied at the ensemble level using X‐ray diffraction. Despite the importance of local, for example, at the individual particle or grain level, strain in controlling the properties of the dealloyed material, it remains unresolved due to the difficulty of imaging 3D strain distributions with nanometer resolution in reactive environments. This information could play an integral role in understanding and controlling lattice strain for a variety of applications. Here, 3D strain distributions in individual nanoparticles and thin film grains in silver–gold alloys undergoing nitric acid‐induced dealloying are imaged by Bragg coherent diffractive imaging. Particles exhibit dramatic changes in their local strains due to dealloying but grains do not. The average lattice in both grains and particles contracts during dealloying. In general, the results reveal significant dealloying‐induced strain heterogeneity at the nanoscale in both isolated and extended samples, which may be utilized to develop advanced nanostructures for a variety of important applications.
Ink‐Free Reversible Optical Writing in Monolayers by Polymerization of a Trifunctional Monomer: Toward Rewritable “Molecular Paper”
Authors: Müller Vivian , Hungerland Tim , Baljozovic Milos , Jung Thomas , Spencer Nicholas D. , Eghlidi Hadi , Payamyar Payam , Schlüter A. Dieter
Published: May 2017

A Langmuir–Blodgett film consisting of a dense array of trifunctional monomers bearing three 1,8‐diazaanthracene units is polymerized at an air/water interface or after transfer on solid substrates. The transfer does not affect the excimer fluorescence of the film, indicating that the monomers' packing with their diazaanthracene units stacked face‐to‐face is retained—a prerequisite for successful polymerization. The monomer film can be polymerized in confined areas on solid substrates by UV irradiation with a confocal microscope laser. The underlying chemistry of the polymerization, a [4+4]‐cycloaddition of the diazaanthracene units, leads to disappearance of the fluorescence in the irradiated regions which enables writing into the monolayer on a µm scale—thus the term “molecular paper.” The reaction can be reversed by heating which leads to a recovery of the fluorescence and to erasing of the writing. Alternative pathways for this phenomenon are discussed and control experiments are conducted to rule them out.
Work Function Tunable Titanium Carbonitride Nanostructures for High‐Efficiency, Rechargeable Li–Iodine Batteries
Authors: Anju V. G. , Austeria Muthu P. , Sampath S.
Published: May 2017

Present study discusses the effects of parameters like work function, adsorption energy, and density of states in tuning the electrocatalytic activity of highly stable, corrosion resistant, ceramic, titanium carbonitride nanostructures. Kelvin force microscopy reveals that the work function of titanium carbonitrides can be tuned from TiN (3.8 eV) to TiC (5.3 eV), through various TiCxNy compositions. The composition, TiC0.7N0.3, possesses a value of 4.85 eV, close to the potential of the redox couple (I3−/I−, 4.9 eV) with favorable adsorption characteristics. Density functional theory calculations reveal favorable interactions between TiC0.7N0.3 and iodine/iodide couple. Nanostructures of TiC0.7N0.3 with several micron length are synthesized and the mechanism of formation is deciphered to be based on oriented growth in one dimension. The nanostructures are very effective catalysts for I3−/I− redox reaction that leads to Li–I2 batteries with superior gravimetric energy density of 447 Wh kg−1 and a high open circuit voltage of 3.3 V. The battery delivers reversible stable capacity of 254 and 160 mAh g−1 at drain currents of 2.5 and 5 mA cm−2, respectively, with a Coulombic efficiency ≥98%. The tailored battery can hold high drain currents of 10 mA cm−2, delivering stable capacity for ≈7000 cycles.
Solid Supported Chiral N‐Picolylimidazolidinones: Recyclable Catalysts for the Enantioselective, Metal‐ and Hydrogen‐Free Reduction of Imines in Batch and in Flow Mode
Authors: Porta Riccardo , Benaglia Maurizio , Annunziata Rita , Puglisi Alessandra , Celentano Giuseppe
Published: May 2017

A new class of solid supported chiral imidazolidinone organocatalysts for the catalytic reduction of imines with trichlorosilane has been developed. Polystyrene proved to be a more effective support than silica in terms of both chemical and stereochemical efficiency. Even with a loading as low as 1 mol% the best performing supported catalyst showed a remarkable activity and stereocontrol ability, promoting the reduction with stereoselectivities reaching 98% ee and in most cases ranging between 90–95% ee The general scope of the methodology and the good recyclability of the immobilized catalyst were demonstrated. The polystyrene‐anchored chiral catalyst was also used to prepare packed bed reactors for the continuous flow synthesis of chiral amines, that were obtained in excellent yields and enantioselectivities. By exploiting the chiral organocatalytic reactor, the in‐flow stereoselective synthesis of a common, immediate precursor of rivastigmine, of the calciomimetic (R)‐NPS 568 and of Acrylamide (S)‐A, currently under study for the treatment of neuropathic pain, was successfully accomplished.

magnified image
Ultrathin Graphene–Protein Supercapacitors for Miniaturized Bioelectronics
Authors: Mosa Islam M. , Pattammattel Ajith , Kadimisetty Karteek , Pande Paritosh , El‐Kady Maher F. , Bishop Gregory W. , Novak Marc , Kaner Richard B. , Basu Ashis K. , Kumar Challa V. , Rusling James F.
Published: May 2017

Nearly all implantable bioelectronics are powered by bulky batteries which limit device miniaturization and lifespan. Moreover, batteries contain toxic materials and electrolytes that can be dangerous if leakage occurs. Herein, an approach to fabricate implantable protein‐based bioelectrochemical capacitors (bECs) employing new nanocomposite heterostructures in which 2D reduced graphene oxide sheets are interlayered with chemically modified mammalian proteins, while utilizing biological fluids as electrolytes is described. This protein‐modified reduced graphene oxide nanocomposite material shows no toxicity to mouse embryo fibroblasts and COS‐7 cell cultures at a high concentration of 1600 µg mL−1 which is 160 times higher than those used in bECs, unlike the unmodified graphene oxide which caused toxic cell damage even at low doses of 10 µg mL−1. The bEC devices are 1 µm thick, fully flexible, and have high energy density comparable to that of lithium thin film batteries. COS‐7 cell culture is not affected by long‐term exposure to encapsulated bECs over 4 d of continuous charge/discharge cycles. These bECs are unique, protein‐based devices, use serum as electrolyte, and have the potential to power a new generation of long‐life, miniaturized implantable devices.
Nonpublication of trial results for new neurological drugs: A systematic review
Authors: Hakala Amanda K , Fergusson Dean , Kimmelman Jonathan
Published: May 2017

Objective

To evaluate nonpublication rates among trials of new successful and unsuccessful neurological drugs.

Methods

“Licensed” drugs consisted of all novel agents receiving US Food and Drug Administration (FDA) licensure 2005–2012 inclusive in seven neurological disorders. “Stalled” drugs included all experimental agents tested in the same domains that had at least one completed phase III trial in the same time frame, but failed to receive FDA approval. Trials of these drugs were included in our sample if their primary outcome collection occurred before October 1, 2010. We determined the publication status of eligible trials using searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, sponsor websites, and direct electronic query of trial contacts and sponsors. The primary outcome was time to journal publication (or results reporting in other media) after study completion.

Results

The adjusted hazard ratio for publication was 1.79 (95% confidence interval, 1.20–2.67) in favor of licensed drugs. Based on the criteria for nonpublication in this report, 14,092 and 33,882 volunteers participated in unpublished trials of licensed and stalled neurological drugs, respectively. Result data were not publicly available in any form for 10% (16 of 163) and 46% (94 of 203) of trials of licensed and stalled drugs, respectively.

Interpretation

Results of trials for stalled drugs are heavily under‐reported. This deprives research and care communities of evidence about pathophysiology, drug class effects, and the value of surrogate endpoints in trials. Ann Neurol 2017;81:782–789
Reversible Stabilisierung von Vesikeln: redox‐responsive Polymer‐Nanocontainer für den Transport in das Zellinnere
Authors: de Vries Wilke C. , Grill David , Tesch Matthias , Ricker Andrea , Nüsse Harald , Klingauf Jürgen , Studer Armido , Gerke Volker , Ravoo Bart Jan
Published: May 2017

Die Selbstorganisation redox‐responsiver Polymer‐Nanocontainer aus einem Cyclodextrinvesikelkern und einer reduktiv spaltbaren Polymerhülle, die über Wirt‐Gast‐Erkennung auf der Vesikeloberfläche verankert ist, wird beschrieben. Die Nanocontainer weisen eine einheitliche Größe sowie eine hohe Stabilität auf und reagieren selektiv auf milde reduktive Bedingungen, was durch dynamische Lichtstreuung, Transmissionselektronenmikroskopie, Rasterkraftmikroskopie, einen quantitativen Thiolnachweis sowie Fluoreszenzspektroskopie nachgewiesen wird. Lebendzell‐Bildgebung zeigt eine spezifische redox‐responsive Freisetzung hydrophiler Frachten wie der pH‐Sonde Pyranin oder des Pilztoxins Phalloidin in Zellen. Die Ergebnisse belegen das hohe Potenzial dieser responsiven Nanocontainer für anspruchsvolle zellbiologische Anwendungen, die einen kontrollierten Transport in die Zelle erfordern.
Formation of Double‐Shelled Zinc–Cobalt Sulfide Dodecahedral Cages from Bimetallic Zeolitic Imidazolate Frameworks for Hybrid Supercapacitors
Authors: Zhang Peng , Guan Bu Yuan , Yu Le , Lou Xiong Wen (David)
Published: May 2017

Complex metal–organic frameworks used as precursors allow design and construction of various nanostructured functional materials which might not be accessible by other methods. Here, we develop a sequential chemical etching and sulfurization strategy to prepare well‐defined double‐shelled zinc–cobalt sulfide (Zn‐Co‐S) rhombic dodecahedral cages (RDCs). Yolk‐shelled zinc/cobalt‐based zeolitic imidazolate framework (Zn/Co‐ZIF) RDCs are first synthesized by a controlled chemical etching process, followed by a hydrothermal sulfurization reaction to prepare double‐shelled Zn‐Co‐S RDCs. Moreover, the strategy reported in this work enables easy control of the Zn/Co molar ratio in the obtained double‐shelled Zn‐Co‐S RDCs. Owing to the structural and compositional benefits, the obtained double‐shelled Zn‐Co‐S RDCs exhibit enhanced performance with high specific capacitance (1266 F g−1 at 1 A g−1), good rate capability and long‐term cycling stability (91 % retention over 10,000 cycles) as a battery‐type electrode material for hybrid supercapacitors.
Stable Subporphyrin meso‐Aminyl Radicals without Resonance Stabilization by a Neighboring Heteroatom
Authors: Shimizu Daiki , Furukawa Ko , Osuka Atsuhiro
Published: May 2017

Most aminyl radicals studied so far are resonance‐stabilized by neighboring heteroatoms, and those without such stabilization are usually short‐lived. We report herein that subporphyrin meso‐2,4,6‐trichlorophenylaminyl radicals and a bis(5‐subporphyrinyl)aminyl radical are fairly stable under ambient conditions without such stabilization. The subporphyrin meso‐2,4,6‐trichlorophenylaminyl radical crystal structure displays a characteristically short Cmeso−N bond and a perpendicular arrangement of the meso‐arylamino group. The stabilities of these radicals have been ascribed to extensive spin delocalization over the subporphyrin π‐electronic network as well as steric protection around the aminyl radical center.
Synthesis of a Fluorescent Analogue of Paclitaxel That Selectively Binds Microtubules and Sensitively Detects Efflux by P‐Glycoprotein
Authors: Lee Molly M. , Gao Zhe , Peterson Blake R.
Published: May 2017

The anticancer drug paclitaxel (Taxol) exhibits paradoxical and poorly understood effects against slow‐growing tumors. To investigate its biological activity, fluorophores such as Oregon Green have been linked to this drug. However, this modification increases its polarity by approximately 1000‐fold and reduces the toxicity of Taxol towards cancer cell lines by over 200‐fold. To construct more drug‐like fluorescent probes suitable for imaging by confocal microscopy and analysis by flow cytometry, we synthesized derivatives of Taxol linked to the drug‐like fluorophore Pacific Blue (PB). We found that PB‐Gly‐Taxol bound the target protein β‐tubulin with both high affinity in vitro and high specificity in living cells, exhibited substantial cytotoxicity towards HeLa cells, and was a highly sensitive substrate of the multidrug resistance transporter P‐glycoprotein (P‐gp).
Comparative study of EMI shielding effectiveness for carbon fiber pultruded polypropylene/poly(lactic acid)/multiwall CNT composites prepared by injection molding versus screw extrusion
Authors: Lee Seung Hwan , Lee Yeongbeom , Jang Myung Geun , Han Chonghun , Kim Woo Nyon
Published: May 2017

The electrical conductivity and electromagnetic interference (EMI) shielding effectiveness of the composites of polypropylene/poly(lactic acid) (PP/PLA) (70/30, wt %) with single filler of multiwall carbon nanotube (CNT) or hybrid fillers of nickel‐coated carbon fiber (CF) and CNT were investigated. For the single filler composite, higher electrical conductivity was observed when the PP‐g‐maleic anhydride was added as a compatibilizer between the PP and PLA. For the composite of the PP/PLA (70/30)/CF (20 phr)/CNT (5 phr), the composite prepared by injection molding observed a higher EMI shielding effectiveness of 50.5 dB than the composite prepared by screw extrusion (32.3 dB), demonstrating an EMI shielding effectiveness increase of 49.8%. The higher values in EMI shielding effectiveness and electrical conductivity of the PP/PLA/CF (20 phr)/CNT (5 phr) composite seemed mainly because of the increased CF length when the composites were prepared using injection molding machine, compared with the composites prepared by screw extrusion. This result suggests that the fiber length of the conductive filler is an important factor in obtaining higher values of electrical conductivity and EMI shielding effectiveness of the PP/PLA/CF/CNT composites. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45222.
A Tunable Cyclic Container: Guest‐Induced Conformational Switching, Efficient Guest Exchange, and Selective Isolation of C70 from a Fullerene Mixture
Authors: Mondal Pritam , Rath Sankar Prasad
Published: May 2017

An adaptable cyclic porphyrin dimer with highly flexible linkers has been used as an artificial molecular container that can efficiently encapsulate various aromatic guests (TCNQ/C60/C70) through strong π–π interactions by adjusting its cavity size and conformation. The planar aromatic guest (TCNQ) can be easily and selectively exchanged with larger aromatic guests (C60/C70). During the guest‐exchange process, the two porphyrin rings switch their relative orientation according to the size and shape of the guests. This behavior of the cyclic container has been thoroughly investigated by using UV/Vis spectroscopy, NMR spectroscopy, and X‐ray crystal structure determination of the host–guest assemblies. The electrochemical and photophysical studies demonstrated the occurrence of photoinduced electron transfer from bisporphyrin to TCNQ/C60/C70 in the respective host–guest assemblies. The cyclic host can form complexes with C60 and C70 with association constants of (2.8±0.2)×105 and (1.9±0.3)×108 m−1, respectively; the latter value represents the highest binding affinity for C70 reported so far for zinc(II) bisporphyrinic receptors. This high selectivity for the binding of C70 versus C60 allows the easy extraction and efficient isolation of C70 from a C60/C70 fullerene mixture. Experimental evidence was substantiated by DFT calculations.
Environmental assessment of bio‐based chemicals in early‐stage development: a review of methods and indicators
Authors: Broeren Martijn L.M. , Zijp Michiel C. , Waaijers‐van der Loop Susanne L. , Heugens Evelyn H.W. , Posthuma Leo , Worrell Ernst , Shen Li
Published: May 2017

Climate change and fossil resource depletion are driving a transition to a bio‐based economy, for which novel bio‐based chemical processes need to be developed. The environmental performance of the novel bio‐based chemicals should be assessed during their development, when the production process can still be adapted, although data availability is limited. Many environmental assessment methods applicable during product development (‘early‐stage methods’) exist in the literature. The aim of this study is to provide an overview of these early‐stage methods and to evaluate to what extent they are suitable for assessing bio‐based chemicals in their early‐stage development. The paper first describes the characteristics of early‐stage chemical design and the environmental impacts of bio‐based products based on published life cycle assessments. Low data requirements, the inclusion of climate change and energy indicators, and the inclusion of environmental impacts from biomass feedstock production are identified as three good‐practice principles for early‐stage assessment of bio‐based chemicals. In the second step, 27 early‐stage assessment methods are reviewed and categorized based on their scope and environmental indicators used. Finally, the reviewed methods are evaluated using the good‐practice principles. A perfect early‐stage method does not exist. However, choosing the most suitable method(s) based on the goal of an assessment and using complementary indicators leads to the most effective assessment for novel bio‐based chemicals in development. © 2017 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Chemical Industry and John Wiley & Sons, Ltd.
Schneidenlagerung von Eisenbahnbrücken
Authors: Troger Manuel , Menge Moritz , Nguyen Viet Tue , Nguyen Duc Tung , Petraschek Thomas
Published: May 2017

Baumaßnahmen von Bahninfrastrukturbetreibern konzentrieren sich heutzutage im Wesentlichen auf die Erneuerung und Instandsetzung bestehender Anlagen. Insbesondere Brückenbauten werden heute immer häufiger als Ersatzneubau im Zuge einer bestehenden Strecke geplant. Die Errichtung bzw. Erneuerung von Eisenbahnüberführungen im bestehenden Netz stellt meist einen größeren Eingriff in den betrieblichen Ablauf des Bahnverkehrs dar, was vor allem gesamtwirtschaftlich hohe Folgekosten mit sich bringen kann. Folglich ist eine immer wiederkehrende Herausforderung bei der Planung und Umsetzung solcher Ersatzneubauten, den Bahnbetrieb möglichst kurz einzuschränken bzw. zu unterbrechen.

Mit Unterstützung der ÖBB Infrastruktur AG wurde eine in diesem Einsatzgebiet alternative Herangehensweise von Schimetta Consult ZT GmbH in Zusammenarbeit mit dem Institut für Betonbau an der TU Graz untersucht. Es handelt sich dabei um Stahlbetonüberbauten, die auf Spundwandunterbauten gelagert sind. Die Untersuchungen beschränken sich auf die Machbarkeitsstudie für kurze Eisenbahnbrücken, die mittels Schneidenlagerung auf Spundwänden gelagert sind.
Expansion strategies for human mesenchymal stromal cells culture under xeno‐free conditions
Authors: Tozetti Patrícia Aparecida , Caruso Samia Rigotto , Mizukami Amanda , Fernandes Taisa Risque , da Silva Fernanda Borges , Traina Fabiola , Covas Dimas Tadeu , Orellana Maristela Delgado , Swiech Kamilla
Published: May 2017

Choosing the culture system and culture medium used to produce cells are key steps toward a safe, scalable, and cost‐effective expansion bioprocess for cell therapy purposes. The use of AB human serum (AB HS) as an alternative xeno‐free supplement for mesenchymal stromal cells (MSC) cultivation has increasingly gained relevance due to safety and efficiency aspects. Here we have evaluated different scalable culture systems to produce a meaningful number of umbilical cord matrix‐derived MSC (UCM MSC) using AB HS for culture medium supplementation during expansion and cryopreservation to enable a xeno‐free bioprocess. UCM MSC were cultured in a scalable planar (compact 10‐layer flasks and roller bottles) and 3‐D microcarrier‐based culture systems (spinner flasks and stirred tank bioreactor). Ten layer flasks and roller bottles enabled the production of 2.6 ± 0.6 × 104 and 1.4 ± 0.3 × 104 cells/cm2. UCM MSC‐based microcarrier expansion in the stirred conditions has enabled the production of higher cell densities (5.5–23.0 × 104 cells/cm2) when compared to planar systems. Nevertheless, due to the moderate harvesting efficiency attained, (80% for spinner flasks and 46.6% for bioreactor) the total cell number recovered was lower than expected. Cells maintained the functional properties after expansion in all the culture systems evaluated. The cryopreservation of cells (using AB HS) was also successfully carried out. Establishing scalable xeno‐free expansion processes represents an important step toward a GMP compliant large‐scale production platform for MSC‐based clinical applications. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1358–1367, 2017
1,2,4‐Triazine‐Modified 2′‐Deoxyuridine Triphosphate for Efficient Bioorthogonal Fluorescent Labeling of DNA
Authors: Peewasan Krisana , Wagenknecht Hans‐Achim
Published: May 2017

In order to establish the Diels–Alder reaction with inverse electron demand for postsynthetic DNA modification, a 1,2,4‐triazine‐modified 2′‐deoxyuridine triphosphate was synthesized. The bioorthogonally reactive 1,2,4‐triazine group was attached at the 5‐position of 2′‐deoxyuridine by a flexible alkyl linker to facilitate its acceptance by DNA polymerases. The screening of four DNA polymerases showed successful primer extensions, using a mixture of dATP, dGTP, dCTP, and the modified 2′‐deoxyuridine triphosphate, by using KOD XL or Vent polymerase. The triazine moiety was stable under the conditions of primer extension, which was evidenced by labeling with a BCN‐modified rhodamine at room temperature in yields of up to 82 %. Two or three modified bases could be incorporated in quantitative yields when the modification sites were separated by three base pairs. These results establish the 1,2,4‐triazene group as a bioorthogonally reactive moiety in DNA, thereby replacing the problematic 1,2,4,5‐tetrazine for postsynthetic labeling by the Diels–Alder reaction with inverse electron demand.
3D Ordered Macroporous Carbon Encapsulated ZnO Nanoparticles as a High‐Performance Anode for Lithium‐Ion Batteries
Authors: Zhang Chengwei , Zhang Zheng , Yin Fuxing , Zhang Yongguang , Mentbayeva Almagul , Babaa Moulay‐Rachid , Molkenova Anara , Bakenov Zhumabay
Published: May 2017

A one‐step template‐based technique for the fabrication of three dimensionally ordered macroporous carbon (3DOMC) was developed. 3DOMC, prepared using silica crystal as a template and soluble resol as a carbon source, possesses ordered macropores with mesoporous walls. ZnO nanoparticles were deposited on as‐prepared 3DOMC via a simple in situ growth process to form a ZnO/3DOMC anode material for lithium‐ion batteries. In the composite, the ZnO nanoparticles (≈3.9 nm) were well‐dispersed on the walls of 3DOMC. The ZnO/3DOMC anode exhibited an enhanced performance in a lithium battery delivering a specific capacity of 673 mAh g−1 at a current density of 0.1 C (0.1 C=97.8 mA g−1) after 300 cycles. This superior performance was ascribed to the ordered interconnected macropores of 3DOMC which could provide rapid diffusion paths for lithium‐ion diffusion and the electrolyte penetration, and buffer the volume changes of the ZnO nanoparticles upon cycling. Furthermore, the mesoporous structure of the 3DOMC walls could enhance the wettability of the ZnO‐based electrode, further improving its electrochemical performance.
Proteasome as a New Target for Bio‐Inspired Benzo[k,l]xanthene Lignans
Authors: Capolupo Angela , Tosco Alessandra , Mozzicafreddo Matteo , Tringali Corrado , Cardullo Nunzio , Monti Maria Chiara , Casapullo Agostino
Published: May 2017

Mass spectrometry‐based chemical proteomics is a powerful tool for the target discovery of small molecules. Here, the application of this approach is presented to define the target profile of bio‐inspired synthetic benzo[k,l]xanthene lignans endowed with interesting biological properties. Proteasome has been identified as a new main interactor for this class of compounds. A combination of molecular docking with in vitro and in cell fluorescence assays gave insights on the molecular mechanism of the interaction, highlighting the tendency of these lignans to inhibit the proteasome.
Understanding the Reactivity of Ion‐Encapsulated Fullerenes
Authors: García‐Rodeja Yago , Solà Miquel , Bickelhaupt F. Matthias , Fernández Israel
Published: May 2017

The influence of the encapsulation of an ion inside the C60 fullerene cage on its exohedral reactivity was explored by means of DFT calculations. To this end, the Diels–Alder reaction between 1,3‐cyclohexadiene and M@C60 (M=Li+, Na+, K+, Be2+, Mg2+, Al3+, and Cl−) was studied and compared to the analogous process involving the parent C60 fullerene. A significant enhancement of the Diels–Alder reactivity is found for systems having an endohedral cation, whereas a clear decrease in reactivity is observed when an anion is encapsulated in the C60 cage. The origins of this reactivity trend were quantitatively analyzed in detail by using the activation strain model of reactivity in combination with energy decomposition analysis.
Investigation of the Heat Transfer in an Inductively‐Heated Fluidized Bed with Heterogeneous Composition
Authors: Idakiev Vesselin V. , Graner Sebastian , Bück Andreas , Tsotsas Evangelos , Mörl Lothar
Published: May 2017

Der induktive Energieeintrag stellt eine vielversprechende Methode zur Beheizung von Wirbelschichten dar. Jedoch ist eine direkte Messung der Partikeltemperatur aufgrund der Beeinflussung der Messtechnik durch die elektromagnetische Strahlung nicht möglich. Deshalb wird zur genaueren Beschreibung der Zustände im Reaktionsraum auf ein mathematisches Modell zurückgegriffen. Ziel dieser Arbeit ist es, ein neues Wärmeübergangsmodell vorzustellen, das erstmals sowohl die Berechnung der Gas‐ und Wandtemperatur als auch die Berechnung der Temperatur von leitenden und nichtleitenden Partikeln ermöglicht.
Experimental Study on the Formation of Drops in Continuously Operated Rotor‐Stator‐Machinery
Authors: Clemens Philipp , Piesche Manfred
Published: May 2017

Rotor‐Stator‐Maschinen zeichnen sich im kontinuierlichen Betrieb durch einen homogenen Leistungseintrag und ein definiertes Verweilzeitspektrum aus. Der Einfluss der Maschinengestalt und die Prozessauslegung im laminaren Strömungsregime wurden bisher wenig betrachtet. Zur Schließung dieser Wissenslücke wurde das Prozessverhalten der genannten Maschinenklasse bei axialer Stromführung in dieser Arbeit systematisch experimentell untersucht, sowie eine energetische Optimierung der Maschinengestalt durchgeführt.
Genetic landscape of clear cell endometrial cancer and the era of precision medicine
Authors: Huang Gloria S. , Santin Alessandro D.
Published: May 2017

The increased understanding of the genetic landscape of clear cell endometrial cancer should guide the development of precision medicine strategies to improve survival.

See also pages 3261‐8.
Rare NOX3 Variants Confer Susceptibility to Agranulocytosis During Thyrostatic Treatment of Graves' Disease
Authors: Plantinga TS , Arts P , Knarren GH , Mulder AH , Wakelkamp IM , Hermus AR , Joosten LA , Netea MG , Bisschop PH , de Herder WW , Beijers HJ , de Bruin IJ , Gilissen C , Veltman JA , Hoischen A , Smit JW , Netea‐Maier RT
Published: May 2017

Agranulocytosis is a rare and serious adverse effect of antithyroid drugs, with unknown etiology. The present study aimed to uncover genetic susceptibility and underlying mechanisms of antithyroid drug‐induced agranulocytosis (ATDAC). We studied two independent families with familial Graves' disease, of which several members developed ATDAC. In addition, six sporadic ATDAC patients with Graves' disease were investigated. Whole exome sequencing analysis of affected and unaffected family members was performed to identify genetic susceptibility variants for ATDAC, followed by functional characterization of primary granulocytes from patients and unrelated healthy controls. Whole exome sequencing, cosegregation analysis, and stringent selection criteria of candidate gene variants identified NOX3 as a genetic factor related to ATDAC. Functional studies revealed increased apoptosis of methimazole‐treated granulocytes from patients carrying NOX3 variants. In conclusion, genetic variants in NOX3 may confer susceptibility to antithyroid drug‐induced apoptosis of granulocytes. These findings contribute to the understanding of the mechanisms underlying ATDAC.
Resource allocation in underlay cognitive radio networks with full‐duplex cognitive base station
Authors: Xu Ding , Li Qun
Published: May 2017

This paper considers an underlay cognitive radio network with a full‐duplex cognitive base station and sets of half‐duplex downlink and uplink secondary users, sharing multiple channels with the primary user. The resource allocation problem to maximize the sum rate of all the secondary users is investigated subject to the transmit power constraints and the interference power constraint. The optimization problem is highly nonconvex, and we jointly use the dual optimization method and the successive convex approximation method to derive resource allocation algorithms to solve the problem. Extensive simulations are shown to verify the performance of the resource allocation algorithms. It is shown that the proposed algorithms achieve much higher sum rate than that of the optimal half‐duplex algorithms and the reference full‐duplex algorithms.
Effect of GLP‐1 and GIP on C‐peptide secretion after glucagon or mixed meal tests: Significance in assessing B‐cell function in diabetes
Authors: Guglielmi C. , Del Toro R. , Lauria A. , Maurizi A.R. , Fallucca S. , Cappelli A. , Angeletti S. , Lachin J.M. , Pozzilli P.
Published: May 2017

Background

The aim of the study was to investigate the different B‐cell responses after a glucagon stimulation test (GST) versus mixed meal tolerance test (MMTT).

Methods

We conducted GST and MMTT in 10 healthy people (aged 25‐40 years) and measured C‐peptide, gastric inhibitory peptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) at different time points after the administration of 1 mg i.v. glucagon for GST or a liquid mixed meal for MMTT.

Results

The GST stimulated C‐peptide showed a mean increase of 147.1%, whereas the mean increase of MMTT stimulated C‐peptide was 99.82% (Δincrease = 47.2%). Maximum C‐peptide level reached with the MMTT was greater than that obtained with the GST (C‐pept max MMTT = 2.35 nmol/L vs C‐pep max GST = 1.9 nmol/L). A positive and linear correlation was found between the GST incremental area under the curve C‐peptide and the MMTT incremental area under the curve C‐peptide (r = 0.618, P = .05). After GST, there was no increment of GIP and glucagon like peptide‐1 levels compared to baseline levels. A positive and linear correlation between GIP and C‐peptide levels was observed only for the MMTT (r = 0.922, P = .008) indicating that in the GST, the C‐peptide response is independent of the incretin axis response.

Conclusions

Although the 2 stimulation tests may elicit a similar response in C‐peptide secretion, B‐cell response to MMTT depends on a functionally normal incretin axis. These results may have implications when investigating the B‐cell response in people with diabetes and for studies in which stimulated C‐peptide secretion is used as primary or secondary outcome for response to therapy.