bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Exercise on Cognitive Abilities
Authors: Gomez‐Pinilla Fernando , Hillman Charles
Published: December 2012

Scientific evidence based on neuroimaging approaches over the last decade has demonstrated the efficacy of physical activity improving cognitive health across the human lifespan. Aerobic fitness spares age‐related loss of brain tissue during aging, and enhances functional aspects of higher order regions involved in the control of cognition. More active or higher fit individuals are capable of allocating greater attentional resources toward the environment and are able to process information more quickly. These data are suggestive that aerobic fitness enhances cognitive strategies enabling to respond effectively to an imposed challenge with a better yield in task performance. In turn, animal studies have shown that exercise has a benevolent action on health and plasticity of the nervous system. New evidence indicates that exercise exerts its effects on cognition by affecting molecular events related to the management of energy metabolism and synaptic plasticity. An important instigator in the molecular machinery stimulated by exercise is brain‐derived neurotrophic factor, which acts at the interface of metabolism and plasticity. Recent studies show that exercise collaborates with other aspects of lifestyle to influence the molecular substrates of cognition. In particular, select dietary factors share similar mechanisms with exercise, and in some cases they can complement the action of exercise. Therefore, exercise and dietary management appear as a noninvasive and effective strategy to counteract neurological and cognitive disorders. © 2013 American Physiological Society.Compr Physiol3:403‐428, 2013.
Calcium Signaling in the Liver
Authors: Amaya Maria Jimena , Nathanson Michael H.
Published: December 2012

Intracellular free Ca2+([Ca2+]i) is a highly versatile second messenger that regulates a wide range of functions in every type of cell and tissue. To achieve this versatility, the Ca2+signaling system operates in a variety of ways to regulate cellular processes that function over a wide dynamic range. This is particularly well exemplified for Ca2+signals in the liver, which modulate diverse and specialized functions such as bile secretion, glucose metabolism, cell proliferation, and apoptosis. These Ca2+signals are organized to control distinct cellular processes through tight spatial and temporal coordination of [Ca2+]i signals, both within and between cells. This article will review the machinery responsible for the formation of Ca2+signals in the liver, the types of subcellular, cellular, and intercellular signals that occur, the physiological role of Ca2+signaling in the liver, and the role of Ca2+signaling in liver disease. © 2013 American Physiological Society.Compr Physiol3:515‐539, 2013.
Iron Homeostasis in the Liver
Authors: Anderson Erik R. , Shah Yatrik M.
Published: December 2012

Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver that control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary cause of iron‐related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver‐derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely, the heart and pancreas from iron‐induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. © 2013 American Physiological Society.Compr Physiol3:315‐330, 2013.
Magnetic Poly(vinylpyridine)‐Coated Carbon Nanotubes: An Efficient Supramolecular Tool for Wastewater Purification
Authors: Maggini Laura , Raquez Jean‐Marie , Marega Riccardo , Jensen Ahrens Jennifer , Pineux Florent , Meyer Franck , Dubois Philippe , Bonifazi Davide
Published: December 2012

Herein, we report the first example of a supramolecular carbon nanotube (CNT)‐based magnetic depolluting agent for divalent metal ion (M2+) removal from aqueous solutions. In particular, magnetic multi‐walled carbon nanotubes (m‐MWCNTs) coated with poly(vinylpyridine) (PVPy) self‐aggregate in aqueous solutions that contain divalent metal ions (such as Zn2+, Cu2+and Pb2+) to form tight insoluble bundles in which the M2+ions remain trapped through pyridyl–M2+–pyridyl interactions. Magnetic filtration ultimately affords the efficient separation of the depolluted solution from the precipitated M2+‐CNT agglomerates. Upon acid treatment, the supramolecular threads could be disassembled to afford the free CNT–polymer hybrid, thus allowing recycling of the depolluting agent. All materials and complexation/decomplexation steps were thoroughly characterised by using thermogravimetric analysis (TGA), X‐ray photoelectron spectroscopy (XPS), transmission and scanning electron microscopy (TEM and SEM, respectively). The quantification of the M2+residual concentrations in water was evaluated by using inductively coupled plasma optical emission spectroscopy (ICP‐OES), which showed that, depending on the metal cation, this material can remove up to 99 % of the contaminant.
A Flexible Metal‐Catalyzed Synthesis of Highly Substituted Aryl Phenanthrenyl Selenides
Authors: Lim Wontaeck , Rhee Young Ho
Published: December 2012

An efficient method for the preparation of diaryl selenides, which are important in biology and materials science, is described. Specifically, the development of highly substituted phenanthrenyl phenyl selenides 4 and 6 by metal‐catalyzed cyclization of o‐phenylarylalkynes species 1 was successfully performed. The selectivity for 9‐ and 10‐selenyl phenanthrenes was perfectly controlled by indium(III) and gold(I) catalysts, and the reactions proceed through different pathways. For the In(OTf)3 catalyst system, 6‐endo cyclization of alkyne 3 gives product 4 in which the selenium group is retained. In contrast, for the AuCl(IPr)/AgSbF6 catalyst system, transformation of metal–alkyne complex 2 into vinylidene–gold intermediate 5 gives product 6 in which the selenium group is migrated. Various substrates, even electronically poor substrates, can be converted into phenanthrenes with high selectivity in high yield under very mild conditions.
Geoarchaeological Investigations of Midden‐Formation Processes in the Early to Late Ceramic Neolithic Levels at Çatalhöyük, Turkey ca. 8550–8370 cal BP
Authors: Shillito Lisa‐Marie , Matthews Wendy
Published: December 2012

Anthropogenic midden deposits are remarkably well preserved at the Neolithic settlement of Çatalhöyük and provide significant archaeological information on the types and nature of activities occurring at the site. To decipher their complex stratigraphy and to investigate formation processes, a combination of geoarchaeological techniques was used. Deposits were investigated from the early ceramic to late Neolithic levels, targeting continuous sequences to examine high resolution and broader scale changes in deposition. Thin‐section micromorphology combined with targeted phytolith and geochemical analyses indicates they are composed of a diverse range of ashes and other charred and siliceous plant materials, with inputs of decayed plants and organic matter, fecal waste, and sedimentary aggregates, each with diverse depositional pathways. Activities identified include in situ burning, with a range of different fuel types that may be associated with different activities. The complexity and heterogeneity of the midden deposits, and thus the necessity of employing an integrated microstratigraphic approach is demonstrated, as a prerequisite for cultural and palaeoenvironmental reconstructions.
The dual role of the novel Wnt receptor tyrosine kinase, ROR2, in human carcinogenesis
Authors: Ford Caroline E. , Qian Ma Sean Si , Quadir Ashfaque , Ward Robyn L.
Published: December 2012

The Wnt signaling pathway is involved in the development and progression of many human cancers, yet attempts to target the pathway therapeutically have been disappointing to date. The recent discovery that the ROR2 receptor tyrosine kinase (RTK) is a novel Wnt receptor provides the potential to target the non‐canonical Wnt pathway for cancer treatments. As a member of the RTK superfamily of surface receptors ROR2 appears to possess dual roles as a tumor suppressor or activator depending on tumor type. This review will explore the dual role of ROR2 in tumorigenesis and provide an up to date analysis of current literature in this rapidly expanding field.
Low‐dose gemcitabine depletes regulatory T cells and improves survival in the orthotopic Panc02 model of pancreatic cancer
Authors: Shevchenko Ivan , Karakhanova Svetlana , Soltek Sabine , Link Julia , Bayry Jagadeesh , Werner Jens , Umansky Viktor , Bazhin Alexandr V.
Published: December 2012

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human neoplasms with extremely poor prognosis and a low survival rate. Immunosuppressive cell populations, e.g. regulatory T cells (Treg), appear to be important in PDAC, contributing to patient's poor prognosis. Therefore, we investigated the PDAC microenvironment with a focus on conventional and regulatory T cells in view of their potential therapeutic importance. We found that tumors from the murine Panc02 orthotopic model of PDAC were infiltrated with high numbers of Treg. Remarkably, these cells exhibited the effector/memory phenotype, suggesting their enhanced suppressive activity and higher proliferation capacity. Although we observed a steady increase in transforming growth factor‐β (TGF‐β) levels in the tumors, treatment with a specific inhibitor of TGF‐β receptor I kinase failed to abrogate Treg accumulation. A CCR4 antagonist did not affect Treg percentage in the tumor either. However, intense Treg cell division in the tumor microenvironment was demonstrated, suggesting local proliferation as a major mechanism of Treg accumulation in PDAC. Notably, this accumulation was reduced by low‐dose gemcitabine administration, resulting in a modestly increased survival of PDAC mice. Our results provide an insight into mechanisms of immunosuppression in PDAC, suggesting an important role for proliferative expansion of effector/memory Treg. Low‐dose gemcitabine therapy selectively depletes Treg, providing a basis for new modalities of PDAC therapy.
Energy and Charge Transfer Dynamics in Doped Semiconductor Nanocrystals
Authors: Chen Hsiang‐Yun , Son Dong Hee
Published: December 2012

Doping semiconductor nanocrystals with transition metal ions introduces new optical, electronic, and magnetic properties to the host semiconductor nanocrystals. The energy transfer and charge transfer between exciton and dopant ions are the key photophysical processes responsible for the unique properties of doped semiconductor nanocrystals, which are distinct from their undoped counterparts. Since the energy transfer and charge transfer processes between exciton and dopant ions compete with the usual relaxation pathways of the exciton, competition among different dynamic processes ultimately determines the photophysical properties of doped nanocrystals. In this review, we discuss the dependence of the dynamics of the energy transfer and charge transfer processes in Mn‐doped II‐VI semiconductor nanocrystals on the structure of the host nanocrystal, spatial distribution of the dopant ions within the nanocrystal, and charge carrier‐trapping molecules near the surface of the nanocrystals.
A pilot study of macrophage responses to silk fibroin particles
Authors: Cui Xidong , Wen Jianchuan , Zhao Xia , Chen Xin , Shao Zhengzhong , Jiang Jack J.
Published: December 2012

Silk fibroin (SF) shows promise for tissue engineering and other biomedical applications due to its excellent biocompatibility, unique biomechanical properties, and controllable biodegradability. The particulate form of SF materials may have many potential uses, including the use as a filler for tissue defects or as a controlled‐release agent for drug delivery. However, many past in vivo and in vitro studies evaluating the biocompatibility and biodegradability of SF have involved bulk implants. It is essential to evaluate the inflammatory effects of SF particles before further use. In this study, two different sizes of SF particles were evaluated to assess their impact on the release of tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐6, in comparison with lipopolysaccharide positive control stimulation. The inflammatory processes were characterized using real‐time reverse transcription polymerase chain reaction, enzyme‐linked immunosorbent assay, and light microscopy evaluations. The results indicated that small silk fibroin particles and large silk fibroin particles, in culture with RAW 264.7 murine macrophage cells for 24 h, caused up‐regulation of mRNA coding for TNF‐α, which indicated that both size of particles have potential inflammatory effects. There was a statistically significant increase in this up‐regulation under small silk fibroin stimulation. However, the immunosorbent assay suggested that there was virtually no observed release of IL‐1β, IL‐6, or TNF‐α, relative to the control group. The results suggest that SF particles of the chosen dimensions may have good biocompatibility in culture with RAW 264.7 murine macrophages. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Influence of membrane cholesterol and substrate elasticity on endothelial cell spreading behavior
Authors: Hong Zhongkui , Ersoy Ilker , Sun Mingzhai , Bunyak Filiz , Hampel Paul , Hong Zhenling , Sun Zhe , Li Zhaohui , Levitan Irena , Meininger Gerald A. , Palaniappan Kannappan
Published: December 2012

Interactions between implanted materials and the surrounding host cells critically affect the fate of bioengineered materials. In this study, the biomechanical response of bovine aortic endothelial cells (BAECs) with different membrane cholesterol levels to polyacrylamide (PA) gels was investigated by measuring cell adhesion and spreading behaviors at varying PA elasticity. The elasticity of gel substrates was manipulated by cross‐linker content. Type I collagen (COL1) was coated on PA gel to provide a biologically functional environment for cell spreading. Precise quantitative characterization of changes in cell area and perimeter of cells across two treatments and three bioengineered substrates were determined using a customized software developed for computational image analysis. We found that the initial response of endothelial cells to changes in substrate elasticity was determined by membrane cholesterol levels, and that the extent of endothelial cell spreading increases with membrane cholesterol content. All of the BAECs with different cholesterol levels showed little growth on substrates with elasticity below 20 kPa, but increased spreading at higher substrate elasticity. Cholesterol‐depleted cells were consistently smaller than control and cholesterol‐enriched cells regardless of substrate elasticity. These observations indicate that membrane cholesterol plays an important role in cell spreading on soft biomimetic materials constructed with appropriate elasticity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Further insights in the ability of classical nonadditive potentials to model actinide ion–water interactions
Authors: Réal Florent , Trumm Michael , Schimmelpfennig Bernd , Masella Michel , Vallet Valérie
Published: December 2012

Pursuing our efforts on the development of accurate classical models to simulate radionuclides in complex environments (Réal et al., J. Phys. Chem. A 2010, 114, 15913; Trumm et al. J. Chem. Phys. 2012, 136, 044509), this article places a large emphasis on the discussion of the influence of models/parameters uncertainties on the computed structural, dynamical, and temporal properties. Two actinide test cases, trivalent curium and tetravalent thorium, have been studied with three different potential energy functions, which allow us to account for the polarization and charge‐transfer effects occurring in hydrated actinide ion systems. The first type of models considers only an additive energy term for modeling ion/water charge‐transfer effects, whereas the other two treat cooperative charge‐transfer interactions with two different analytical expressions. Model parameters are assigned to reproduce high‐level ab initio data concerning only hydrated ion species in gas phase. For the two types of cooperative charge‐transfer models, we define two sets of parameters allowing or not to cancel out possible errors inherent to the force field used to model water/water interactions at the ion vicinity. We define thus five different models to characterize the solvation of each ion. For both ions, our cooperative charge‐transfer models lead to close results in terms of structure in solution: the coordination number is included within 8 and 9, and the mean ion/water oxygen distances are 2.45 and 2.49 Å, respectively, for Th(IV) and Cm(III). © 2012 Wiley Periodicals, Inc.
Synthesis and Insecticidal Activities: cis‐Nitenpyram Analogs with 1,4‐Dihydropyridine Scaffold
Authors: Liu Tian‐Yan , Xue Si‐Jia , Chen Yan‐Xia , Fang Ting , Wu Ying , Wang Jing
Published: December 2012

By means of multicomponent reactions, via Michael addition, nucleophilic addition, using nitenpyram, substituted aromatic aldehydes, and cyanoacetate compounds or propanedinitrile, a new series of cis‐configuration nitenpyram analogs (1a‐1k) were synthesized by introducing the 1,4‐dihydropyridine scaffold pharmacophore, as shown in Scheme 1. The structures of all compounds were confirmed by IR, 1HNMR, 13C NMR, and elemental analysis. The preliminary bioassay showed that most of the target compounds exhibited good mortality against Aphis craccivora at 500 mg/L.
Synthesis and Antibacterial Activity of New Diaryldiamines
Authors: Samrin Farhana , Sharma Akash , Khan Inshad Ali , Puri Sadhna
Published: December 2012

Several new quinolines and quinazolines (4, 10, 13) have been synthesized from cheap and readily available chemicals through a series of simple chemical transformations. Most of the synthesized compounds have been evaluated for antibacterial activity against Gram positive and Gram negative strains. Some of the synthesized compounds displayed interesting activity but not very promising for further development.
Synthesis, Crystal Structure, and Fungicidal Activity of Novel 1,5‐Diaryl‐1H‐Pyrazol‐3‐Oxy Derivatives Containing Oxyacetic Acid or Oxy(2‐thioxothiazolidin‐3‐yl)ethanone Moieties
Authors: Liu Yuanyuan , He Guangke , Kai Chen , Li Yufeng , Zhu Hongjun
Published: December 2012

A series of novel 1,5‐diaryl‐1H‐pyrazol‐3‐oxy derivatives containing oxyacetic acid or oxy(2‐thioxothiazolidin‐3‐yl)ethanone moieties were prepared from methyl 3‐arylacrylates via a serial of reactions included addition‐cyclization, oxidation, substitution, hydrolysis, and condensation. Their structures were confirmed by 1H‐NMR, 13C‐NMR, IR, and elemental analysis. In addition, the crystal structure of the compound 2‐(1,5‐diphenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐thioxothiazolidin‐3‐yl)ethanone was determined by single crystal X‐ray diffraction analysis. Bioassay results indicated that the compound 2‐(5‐(4‐chlorophenyl)‐1‐phenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐thioxo‐thiazolidin‐3‐yl)ethanone exhibited moderate inhibitory activity against Gibberella zeae at the dosage of 10 μg mL−1.
Aromatization and Halogenation of 3,3a,4,5‐Tetrahydro‐3‐aryl‐2‐phenyl‐2H‐benzo[g]indazole Using I2/DMSO, CuCl2/DMSO, and N‐Bromosuccinimide
Authors: Lokhande Pradeep D. , Hasanzadeh Kamal , Khaledi Hamid , Mohd Ali Hapipah
Published: December 2012

The treatment of 3,3a,4,5‐tetrahydro‐3‐aryl‐2‐phenyl‐2H‐benzo[g]indazoles 4 with I2/DMSO led to the oxidation of the five‐member rings (5) as well as the iodination of N‐phenyl moieties along with oxidation of the five‐member rings (6). However, the reactions of 4 with CuCl2/DMSO gave only compounds 5. The reaction of N‐bromosuccinimide (NBS) with compounds 4 resulted in fully aromatization along with bromination at C‐5 of the indazole rings (7). The indazole six‐member rings in compounds 5 and 6 also underwent aromatization along with bromination by using NBS (7 and 8).
Synthesis and Evaluation of Antimicrobial Activity of Some New Hetaryl‐Azoles Derivatives Obtained from 2‐Aryl‐4‐methylthiazol‐5‐carbohydrazides and Isonicotinic Acid Hydrazide
Authors: Tiperciuc Brînduşa , Zaharia Valentin , Colosi Ioana , Moldovan Cristina , Crişan Ovidiu , Pîrnau Adrian , Vlase Laurian , Duma Mihaela , Oniga Ovidiu
Published: December 2012

A series of new 1,3,4‐oxadiazole/thiadiazole and 1,2,4‐triazole derivatives have been synthesized starting from 2‐aryl‐4‐methylthiazol‐5‐carbohydrazides and isonicotinic acid hydrazide. All the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectrometry. The synthesized compounds were screened for their antibacterial and antifungal activity, assessed as growth inhibition diameter. Some of them showed good antibacterial activity against gram positive Staphylococcus aureus, while the antibacterial activity against Listeria monocytogenes, Escherichia coli, and Salmonella typhymurium and antifungal activity against Candida albicans was modest. None of the tested compounds showed inhibitory activity against gram positive bacteria Enterococcus faecalis and Bacillus cereus and against gram negative bacteria Pseudomonas aeruginosa.
An Efficient Synthesis of Isomeric 1‐(1‐Alkyl‐1H‐pyrazolyl) Ethanones
Authors: Taydakov Ilya , Krasnoselskiy Sergey
Published: December 2012

A simple and versatile general method for the preparation of N‐substituted 3‐, 4‐, or 5‐acetylpyrazoles from corresponding acids via hydrolysis and decarboxylation of substituted diethyl [(1‐alkyl‐1H‐pyrazolyl)carbonyl]malonates was developed. Title compounds were prepared in three steps without isolation of intermediates in 48–82% overall yield.
Syntheses of Three New Pyridyl Thienopyridine Ligands via the Hurtley Reaction
Authors: Steen Robert O. , Nurkkala Lasse J. , Dunne Simon J.
Published: December 2012

The tridentate pyridyl thienopyridines 5‐phenyl‐7‐(pyridin‐2‐yl)thieno[2,3‐c]pyridine (L1), 7‐(pyridin‐2‐yl)‐5‐(thiophen‐2‐yl)‐thieno[2,3‐c]pyridine (L2) and 5,7‐di(pyridin‐2‐yl)thieno[2,3‐c]pyridine (L3) have been synthesized via the Hurtley reaction. L1 and L2 were synthesized by condensing 3‐bromothiophene‐2‐carboxylic acid with phenyl‐1,3‐butanedione and 1‐thienyl‐1,3‐butanedione respectively. L3 was synthesized by condensing 3‐bromothiophene‐2‐carboxylic acid with benzoylacetonitrile. Ring closure and a subsequent Negishi or Stille cross‐coupling afforded L1, L2, and L3 in an overall yield of 20, 3, and 6%, respectively.
Convenient Approaches towards the Synthesis of Novel Pyrano[2,3‐a]carbazoles
Authors: Prabakaran Kumaresan , Zeller Matthias , Szalay Paul S. , Rajendra Prasad Karam J.
Published: December 2012

Previously not easily accessible pyrano[2,3‐a]carbazoles were synthesized in highly convergent syntheses avoiding multistep procedures from readily available 1‐hydroxycarbazoles. Substituted pyrano[2,3‐a]carbazoles were produced by three different methods by treatment of the 1‐hydroxycarbazoles with dimethyl acetylene dicarboxylate (DMAD) and triphenylphoshine, by reaction with ethyl 2‐methylacetoacetate in the presence of ZnCl2/POCl3, and by reaction with trifluoroacetic acid followed by Wittig reaction with (carbethoxymethylene) triphenylphosphorane. The article also highlights the optimization of reaction conditions and strategies to avoid formation of byproducts for all three types of reactions.
An Efficient Synthesis of New 5‐(1‐Aryl‐1H‐pyrazole‐4‐yl)‐1H‐tetrazoles from 1‐Aryl‐1H‐pyrazole‐4‐carbonitriles via[3 + 2] Cycloaddition Reaction
Authors: dos Santos Maurício S. , Bernardino Alice M. R. , Pinheiro Luiz C. S. , Canto‐Cavalheiro Marilene M. , Leon Leonor L.
Published: December 2012

A series of new 5‐(1‐aryl‐1H‐pyrazole‐4‐yl)‐1H‐tetrazoles 4a‐l were synthesized via [3 + 2] cycloaddition reaction from 1‐aryl‐1H‐pyrazole‐4‐carbonitriles 3a‐l, sodium azide and ammonium chloride, using dimethylformamide (DMF) as solvent, in good yields: 64–85%. The structures of these newly synthesized compounds were determined from the IR, 1H‐ and 13C‐NMR spectroscopic data and elemental analyses.
Antiselective Three‐Component Mannich Reactions in Thiopyran‐4‐one System
Authors: Abaee M. Saeed , Mojtahedi Mohammad M. , Akbari Ali , Mehraki Ehsan , Wahid Mesbah A. , Harms Klaus
Published: December 2012

The one‐pot, three‐component Mannich reactions of thiopyran‐4‐one 1 with different aromatic aldehydes and aniline derivatives in the presence of catalytic quantities of ZrOCl2.8H2O (15 mol %) led to rapid and high yield formation of various 3‐methylamino substituted derivatives of 1 at room temperature. Spectroscopic and X‐ray analyses of the products suggested the formation of the anti stereoisomers as the major product of the reactions.
Extraction of fullerenes from environmental matrices as affected by solvent characteristics and analyte concentration
Authors: Place Benjamin J. , Kleber Markus , Field Jennifer A.
Published: December 2012

Fullerenes possess unique chemical properties that make the isolation of these compounds from heterogeneous environmental matrices difficult. For example, previous reports indicate that toluene‐based extraction techniques vary in their ability to extract C60, especially from highly carbonaceous solid matrices. Here, we examined the effects of (i) solvent type (toluene alone versus an 80:20 v/v mixture of toluene and 1‐methylnaphthalene) and (ii) analyte concentration on the extraction efficiency of an isotopically labeled surrogate compound, 13C60. The toluene/1‐methylnaphthalene mixture increased fullerene extraction efficiency from carbon lampblack by a factor of five, but was not significantly different from 100% toluene when applied to wood stove soot or montmorillonite. Recovery of the 13C60 surrogate declined with decreasing analyte concentration. The usefulness of isotopically labeled surrogate is demonstrated and the study provides a quantitative assessment regarding the dependence of fullerene extraction efficiencies on the geochemical characteristics of solid matrices.
Nanostructure Transitions and Their Relation to Mechanical Properties in Polyethylene/Polyamide 6 Microfibrillar Composites as Revealed by SAXS/Straining Studies
Authors: Dencheva Nadya , Denchev Zlatan , Stribeck Norbert , Motovilin Mladen , Zeinolebadi Ahmad , Funari Sergio S. , Botta Stephan
Published: December 2012

Microfibrillar composites (MFC) with a matrix of high‐density polyethylene (HDPE) and reinforcements of polyamide 6 (PA6) are tensile tested while collecting 2D small‐angle X‐ray scattering patterns. The scattering of the isotropic matrix is separated from that of the oriented fibrils and the chord distribution functions (CDF) are computed. The changes in CDF peaks during the stretching process are registered and related to the nanostructure evolution in the samples. It is demonstrated how compatibilization of the HDPE and PA6 components and additional reinforcement of the PA6 fibrils with nanoclays influence the nanostructure of the fibrils and the mechanical behavior of the MFCs. The structural changes in the transcrystalline HDPE are consistent with a reversible strain‐induced crystallization.
Facile Synthesis of Multicompartment Micelles Based on Biocompatible Poly(3‐hydroxyalkanoate)
Authors: Babinot Julien , Renard Estelle , Le Droumaguet Benjamin , Guigner Jean‐Michel , Mura Simona , Nicolas Julien , Couvreur Patrick , Langlois Valérie
Published: December 2012

In this paper, a straightforward method to produce poly(3‐hydroxyalkanoate)‐based multicompartment micelles (MCMs) is presented. Thiol‐ene addition is used to graft sequentially perfluorooctyl chains and poly(ethylene glycol) oligomers onto poly(3‐hydroxyoctanoate‐co‐hydroxyundecenoate) oligomers backbone. Well‐defined copolymers are obtained as shown by 1H NMR and size‐exclusion chromatography. After nanoprecipitation in water, novel PHA‐based MCMs are evidenced by cryo‐transmission electron microscopy. Moreover, the cytocompatibility of MCMs is demonstrated in vitro via cell viability assay.
Raising the Roof: The Preferential Pharmacological Stimulation of Th1 and Th2 Responses Mediated by NKT Cells
Authors: East James E. , Kennedy Andrew J. , Webb Tonya J.
Published: December 2012

Natural killer T (NKT) cells serve as a bridge between the innate and adaptive immune systems, and manipulating their effector functions can have therapeutic significances in the treatment of autoimmunity, transplant biology, infectious disease, and cancer. NKT cells are a subset of T cells that express cell‐surface markers characteristic of both natural killer cells and T cells. These unique immunologic cells have been demonstrated to serve as a link between the innate and adaptive immune systems through their potent cytokine production following the recognition of a range of lipid antigens, mediated through presentation of the major histocompatibility complex (MHC) class I like CD1d molecule, in addition to the NKT cell's cytotoxic capabilities upon activation. Although a number of glycolipid antigens have been shown to complex with CD1d molecules, most notably the marine sponge derived glycolipid alpha‐galactosylceramide (α‐GalCer), there has been debate as to the identity of the endogenous activating lipid presented to the T‐cell receptor (TCR) via the CD1d molecule on antigen‐presenting cells (APCs). This review aims to survey the use of pharmacological agents and subsequent structure–activity relationships (SAR) that have given insight into the binding interaction of glycolipids with both the CD1d molecules as well as the TCR and the subsequent immunologic response of NKT cells. These studies not only elucidate basic binding interactions but also pave the way for future pharmacological modulation of NKT cell responses.
Application of two‐dimensional selective‐TOCSY HMBC for structure elucidation of impurities in mixture without separation
Authors: Hwang Tsang‐Lin , Ronk Michael , Milne Jacqueline E.
Published: December 2012

In the pharmaceutical industry, regulatory expectations driven by patient safety considerations make structure elucidation of impurities at levels greater than 0.1% in the active pharmaceutical ingredient (API) of primary interest. Impurities can be generated from isomers in starting materials, or produced from different process steps toward the final API. Proton peaks belonging to different impurities could be potentially identified in the one‐dimensional 1H NMR spectrum, when evaluated in combination with two‐dimensional (2‐D) COSY and HSQC data. However, in 2‐D HMBC data, correlation responses from different impurities may overlap with those from the major component, causing uncertainty of long‐range proton to carbon correlations and quaternary carbon assignments. This observation prompts us to design the 2‐D selective‐TOCSY HMBC experiment to distinguish responses from different impurities in mixtures to obtain 2‐D NMR data for each impurity, thus eliminating the use of a chromatographic isolation step to obtain material for NMR analysis. This methodology is demonstrated for structure elucidation of impurities ranging from 8.2% in the raw material to 0.4% in the API in this study, and would be particularly useful for industrial samples in which the solubility and availability of material are not an issue. Copyright © 2012 John Wiley & Sons, Ltd.
Cycloolefin Copolymers by Early and Late Transition Metal Catalysts
Authors: Tritto Incoronata , Boggioni Laura , Ravasio Andrea , Scalcione Giulia
Published: December 2012

The complex [Pd(κ2‐P,O‐{2‐(2‐MeOC6H4)2P}C6H4SO3)Me(dmso)] (1) is investigated for the copolymerization of (E) with norbornene (N) and functionalized N derivatives affording P(E‐co‐N) in excellent yields. Copolymer molar masses are higher than those of PE and increase with N concentration. In addition, the complex [Ti(κ2‐N,O‐{2,6‐F2C6H3N = C(Me)C(H) = C(CF3)O})2Cl2] (2) is evaluated as catalyst for living E‐co‐N copolymerization upon activation with dried methylaluminoxane between 25 and 90 °C. Copolymerization at different [N]/[E] feed ratios affords stereoirregular alternating high molar mass P(E‐co‐N) with narrow molar mass distribution. P(E‐co‐N) living copolymerization is demonstrated by kinetics at 50 °C. Block copolymers are synthesized and fully characterized.

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A DFT study on the structure and radical scavenging activity of newly synthesized hydroxychalcones
Authors: Xue Yunsheng , Zhang Ling , Li Yanli , Yu Ding , Zheng Youguang , An Lin , Gong Xuedong , Liu Yi
Published: December 2012

Quantum‐chemical computations based on the density functional theory have been employed to study the relation between the structure and the radical scavenging activity of six newly synthesized hydroxychalcones. The three main working mechanisms, hydrogen atom transfer (HAT), stepwise electron‐transfer‐proton‐transfer, and sequential‐proton‐loss‐electron‐transfer (SPLET), were investigated, and the O–H bond dissociation enthalpy, ionization potential, proton dissociation enthalpy, and electron transfer energy parameters were computed in the gas phase and in solvents using PCM model. The geometry structure, radical, electron character, and the frontier molecular orbital were analyzed to explore the key factors that influence the radical scavenging activity of the hydroxychalcones. Results indicated that 3,4‐dihydroxychalcone (6) possessing the catechol functionality is expected to be more efficient hydrogen atom and proton donor than others. The theoretical results confirm the important role of the B‐ring and shed light on the role of the o‐dihydroxy (catechol) moiety in the antioxidant properties of hydroxychalcones. In addition, the calculated results are in good agreement with experimental values. It was found that HAT is the most favored mechanism for explaining the radical‐scavenger activity of hydroxychalcone in the gas phase, whereas SPLET mechanism is thermodynamically preferred pathway in aqueous solutions. Copyright © 2012 John Wiley & Sons, Ltd.
Verification of the fitted crystal‐field Hamiltonian parametrization by the crystal‐field splitting second moment
Authors: Mulak Maciej , Mulak Jacek
Published: December 2012

A physically valid parametrization of the crystal‐field (CF) Hamiltonian HCF has to reproduce not only the energy of Stark sublevels but also the multipolar structure of the central ion surroundings. The square of the second moment $\sigma {}^{2} {\left( {\left| {J} \right\rangle } \right)}$ of $\left| {J} \right\rangle $ electronic state CF splitting must be a superposition of squares of the second moments of the partial splittings produced separately by the individual multipoles: $\sigma {}^{2} {\left( {\left| {J} \right\rangle } \right)} = \sum\nolimits_{k} {\sigma _{k}^{2} } {\left( {\left| {J} \right\rangle } \right)} = {\left[ {1/(2J + 1)} \right]}\sum\nolimits_{k} {A_{k}^{2} {\left( {\left| {J} \right\rangle } \right)}} S_{k}^{2} $, where $A_{k} {\left( {\left| {J} \right\rangle } \right)}$ represents the modulus of a k‐rank multipole of the central ion electronic eigenstate $\left| {J} \right\rangle $, whereas $S_{k} = {\left( {[1/(2k + 1)]\sum\nolimits_{q} {\left| {B_{kq} } \right|^{2} } } \right)}^{1/2} $ is the k‐rank CF strength. The relationship between $\sigma {}^{2} {\left( {\left| {J} \right\rangle } \right)}$ known from experiment and $S_{k}^{2} $ obtained from fitting procedure allows us to verify whether the parametrization is physically valid. It is demonstrated by several examples of CF splittings of electronic states of trivalent lanthanide ions in different crystal matrices. The approach is confined only to the states with good quantum numbers J. Nevertheless, by finding such states in any analyzed spectrum, the method can provide the actual multipole characteristics of HCF, and plays the role of a preparametrization. In general, the stepwise fitting procedure can never lead to parametrizations with a correct multipolar structure due to the limitation of the initial eigenfunctions. In consequence, the pertinent crystal‐field parameters (CFPs) are burdened with a methodical inherent fault. The loss of physical meaning of fitted CFPs, its source and consequences, constitute the main theme of the paper.
Balancing Multiple Criteria Incorporating Cost using Pareto Front Optimization for Split‐Plot Designed Experiments
Authors: Lu Lu , Anderson‐Cook Christine M.
Published: December 2012

Finding a D‐optimal design for a split‐plot experiment requires knowledge of the relative size of the whole plot (WP) and sub‐plot error variances. Since this information is typically not known a priori, we propose an optimization strategy based on balancing performance across a range of plausible variance ratios. This approach provides protection against selecting a design which could be sub‐optimal if a single initial guess is incorrect. In addition, options for incorporating experimental cost into design selection are explored. The method uses Pareto front multiple criteria optimization to balance these objectives and allows the experimenter to understand the trade‐offs between several design choices and select one that best suits the goals of the experiment. We present new algorithms for populating the Pareto front for the split‐plot situation when the number of WPs is either fixed or flexible. We illustrate the method with a case study and demonstrate how considering robustness across variance ratios offers improved performance. The Pareto approach identifies multiple promising designs, and allows the experimenter to understand trade‐offs between alternatives and examining their robustness to different ways of combining the objectives. New graphical summaries for up to four criteria are developed to help guide improved decision‐making. Copyright © 2012 John Wiley & Sons, Ltd.
Collision‐induced dissociation of synthetic polymers containing hydride groups: the case of poly(methylhydrosiloxane) homopolymers and poly(methylhydrosiloxane)‐co‐(dimethylsiloxane) copolymers
Authors: Fouquet Thierry , Chendo Christophe , Toniazzo Valérie , Ruch David , Charles Laurence
Published: December 2012

RATIONALE

When substituting one methyl moiety by a hydrogen atom in each end‐group of a trimethylsilyl‐terminated poly(dimethylsiloxane) (PDMS), dissociation reactions of oligomers adducted with ammonium were observed to proceed at a much higher rate, evidencing the high reactivity of hydride groups. Polymeric molecules containing methylhydrosiloxane (MHS) units could thus be expected to exhibit a different tandem mass spectrometric (MS/MS) behavior from PDMS.

METHODS

Trimethylsilyl‐terminated PMHS and trimethylsilyl‐terminated poly(MHS)‐co‐(DMS) were electrosprayed in the gas phase either as ammonium adducts or lithium adducts. Product ions generated upon collision‐induced dissociation (CID) were accurately mass measured in an orthogonal acceleration time‐of‐flight mass analyzer.

RESULTS

In contrast to PDMS adducted with lithium, useful structural features could be obtained from product ions generated upon CID of lithium adducts of PMHS. The presence of multiple hydride groups in PMHS induced numerous rearrangements when activating ammonium adducts of these oligomers. MS/MS reactions observed for cationic adducts of MHS‐DMS co‐oligomers were clearly a combination of major dissociation routes established for the corresponding homopolymers. However, the concerted loss of H2 and ammonia typically observed from ammonium adducts of PMHS was always shown to generate a quite abundant product ion even from co‐oligomers enriched with DMS units.

CONCLUSIONS

The high reactivity of hydride moieties, previously evidenced when these groups were at the end of PDMS chains, is also at work in PMHS, where each monomer contains a Si‐H function. The presence of these hydride groups would increase the nucleophilic character of the oxygen atoms, favoring a tight bonding of lithium, and hence allowing in‐chain cleavages to occur. In PMHS ammonium adducts, the particular reactivity of hydride moieties was illustrated by multiple hydride transfers but also by a dehydrogenation reaction systematically observed to proceed, together with the loss of ammonia, from all precursor ions. This latter reaction remained a very competitive process even from MHS/DMS co‐oligomers with a low relative number of MHS units. Copyright © 2012 John Wiley & Sons, Ltd.
Evaluation of electron ionization cross‐sections of methyl halides
Authors: Kumar Rajeev , Pal Satyendra
Published: December 2012

RATIONALE

Electron collision with methyl halides CH3X (X = F, Cl, Br) plays an important role in various atmospheric and plasma modelling processes. The gaseous methyl halides are harmful to the troposphere and the stratospheric ozone layer. Knowledge of the ionization cross sections and ionization rate coefficients of the free gaseous halides is therefore desirable in the study of these processes.

METHODS

The partial single and double differential cross‐sections with the integral ionization cross‐sections of the gaseous halides by electron collision were calculated using a modified Jain‐Khare semi‐empirical approach. The ionization rate coefficients corresponding to partial ionization cross‐sections were calculated by the Maxwell‐Boltzmann distribution of energy.

RESULTS

The Jain‐Khare formalism has different approaches for the evaluation of single differential, double differential and integral ionization cross‐sections. The partial single differential cross‐sections as a function of energy loss (sum of ionization threshold and the secondary electron energy) suffered by the incident electron were calculated at incident electron energies of 100 and 200 eV. The double differential cross‐sections were computed at the same electron energies and scattering angles of 30° and 60°. The behavior of double differential cross‐sections with scattering angles from 0° to 180° at constant secondary electron energies of 10 and 20 eV and fixed primary electron energies 100 and 200 eV was also calculated. The partial and total (sum of all partial cross‐sections) integral ionization cross‐sections were evaluated from the ionization threshold to 1000 eV.

CONCLUSIONS

The applied formalism is useful for the calculation of partial and total integral/or differential cross‐sections at low energies. The integral ionization cross‐sections showed good agreement with available experimental/or theoretical data. The data obtained for these compounds were not previously available, so the results will be of value to the experimental and theoretical community concerned with plasma and atmospheric processes. Copyright © 2012 John Wiley & Sons, Ltd.
Analysis of the biochemical role of Lys‐11 in polyubiquitin chain formation using quantitative mass spectrometry
Authors: Jung Jin Woo , Bae Sung Jun , Kang Gum‐Yong , Kim Kyun‐Hwan , Yeo Woon‐Seok , Park Sang‐Hyun , Seol Jae Hong , Yi Eugene C. , Kim Kwang Pyo
Published: December 2012

RATIONALE

Protein ubiquitination plays a critical role in regulating many cellular events, such as protein localization and stability, cellular signal transduction and DNA repair. Recent studies have shown that polyubiquitin (polyUb) chains elongate through heterogeneous isopeptide linkages to K11, K29, K48 and K63. In this study we have investigated the usage of isopeptide linkages of polyUb chains in different molecular weight regions by using quantitative mass spectrometry.

METHODS

Recombinant Chfr protein was autoubiquitinated by E1 enzyme, E2 enzyme UbcH5 and ubiquitin (WT Ub, K11R Ub, K48R Ub and K63R Ub) in vitro, and different molecular weight regions of ubiquitinated Chfr were then subjected to liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) following sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS‐PAGE) and in‐gel digestion.

RESULTS

Absolute QUantitative Analysis (AQUA) of polyUb chain formation with wild‐type (WT) and point mutants of ubiquitin was performed, and the results suggested that the K11 polyUb chain was most frequently used in the high ubiquitin conjugates of WT Ub. Furthermore, the extent of polyUb chain formation with K11R Ub was decreased about 10‐fold compared to polyUb chain formation with WT Ub through the entire molecular weight region. The present study suggests that the linkage through K11 plays crucial roles in polyUb chain formation.

CONCLUSIONS

Topologies of polyUb chains in the low and high Ub conjugates were studied using mass spectrometry. K48 and K63 were the primary ubiquitination sites of the low molecular weight Ub conjugates, whereas K11 was the critical site of polyUb chain formation in high molecular weight Ub conjugates. Copyright © 2012 John Wiley & Sons, Ltd.
Semi‐quantitative analysis of contaminants in soils by direct analysis in real time (DART) mass spectrometry
Authors: Grange Andrew H.
Published: December 2012

RATIONALE

Cleaning up contaminated sites is a goal of the U.S. Environmental Protection Agency (EPA). A simple, high‐throughput, inexpensive, selective, and specific screening method for semi‐volatile, polar organic contaminants would provide high spatial resolution for monitoring remediation and for documenting successful clean ups in numerous Superfund, Brownfield, and other contaminated sites.

METHODS

An autosampler/Direct Analysis in Real Time (DART)/time‐of‐flight (TOF) mass spectrometer, with or without a Vapur® evacuated flange, was used to analyze 0.01–33% levels of aspirin, diphenylamine, and pentachlorophenol mixed with soil. Triplicate water‐soaked swabs were manually rotated in wet analyte:soil mixtures, air dried for 2–3 h, and analyzed directly. To minimize carryover, insensitive and sensitive instrumental conditions were used to analyze high and low analyte levels, respectively. Simulated two‐dimensional (2D) mapping and remediation threshold experiments were performed to test the utility of DART‐TOFMS for possible sampling strategies.

RESULTS

Analyte levels differing by factors of 10 were discernible. Data were acquired for 30 swabs in 0.9 min and 3 min with helium stream temperatures of 150 °C and 250 °C and swab transport velocities of 1.45 cm/s and 0.5 cm/s, respectively. With the Vapur flange attached, the average relative standard deviations (RSDs) (n = 3) were between 16% and 40% for different analytes and analyte levels. Carryover was greatly reduced by removing the Vapur flange, but higher RSDs and occasional plugging of the cone orifice were observed.

CONCLUSIONS

A rapid, simple, rugged, and relatively inexpensive, but selective and sufficiently sensitive, semi‐quantitative screening method for semi‐volatile, polar, organic compounds in soil was demonstrated. The technique would provide the high spatial resolution necessary to find localized areas of high contamination within contaminated sites that might pose a risk to human and ecological health. Published 2012. This article is a US Government work and is in the public domain in the USA.