bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphatidylinositol 3-Kinase-γ Signaling Promotes Campylobacter jejuni–Induced Colitis through Neutrophil Recruitment in Mice
Authors: Sun Xiaolun , Liu Bo , Sartor Ryan Balfour , Jobin Christian
Published: November 2012

Crypt abscesses caused by excessive neutrophil accumulation are prominent features of human campylobacteriosis and its associated pathology. The molecular and cellular events responsible for this pathological situation are currently unknown. We investigated the contribution of PI3K-γ signaling in Campylobacter jejuni–induced neutrophil accumulation and intestinal inflammation. Germ-free and specific pathogen-free Il10−/− and germ-free Il10−/−;Rag2−/− mice were infected with C. jejuni (109 CFU/mouse). PI3K-γ signaling was manipulated using either the pharmacological PI3K-γ inhibitor AS252424 (i.p. 10 mg/kg daily) or genetically using Pi3k-γ−/− mice. After up to 14 d, inflammation was assessed histologically and by measuring levels of colonic Il1β, Cxcl2, and Il17a mRNA. Neutrophils were depleted using anti-Gr1 Ab (i.p. 0.5 mg/mouse/every 3 d). Using germ-free Il10−/−;Rag2−/− mice, we observed that innate immune cells are the main cellular compartment responsible for campylobacteriosis. Pharmacological blockade of PI3K-γ signaling diminished C. jejuni–induced intestinal inflammation, neutrophil accumulation, and NF-κB activity, which correlated with reduced Il1β (77%), Cxcl2 (73%), and Il17a (72%) mRNA accumulation. Moreover, Pi3k-γ−/− mice pretreated with anti–IL-10R were resistant to C. jejuni–induced intestinal inflammation compared with Wt mice. This improvement was accompanied by a reduction of C. jejuni translocation into the colon and extraintestinal tissues and by attenuation of neutrophil migratory capacity. Furthermore, neutrophil depletion attenuated C. jejuni–induced crypt abscesses and intestinal inflammation. Our findings indicate that C. jejuni–induced PI3K-γ signaling mediates neutrophil recruitment and intestinal inflammation in Il10−/− mice. Selective pharmacological inhibition of PI3K-γ may represent a novel means to alleviate severe cases of campylobacteriosis, especially in antibiotic-resistant strains.
AnHLA-DRB1–Coded Signal Transduction Ligand Facilitates Inflammatory Arthritis: A New Mechanism of Autoimmunity
Authors: Holoshitz Joseph , Liu Ying , Fu Jiaqi , Joseph Jeena , Ling Song , Colletta Alessandro , Sharma Prannda , Begun Dana , Goldstein Steven , Taichman Russell
Published: November 2012

Particular alleles of HLA contribute to disease susceptibility and severity in many autoimmune conditions, but the mechanisms underlying these associations are often unknown. In this study, we demonstrate that the shared epitope (SE), an HLA-DRB1–coded sequence motif that is the single most significant genetic risk factor for erosive rheumatoid arthritis, acts as a signal transduction ligand that potently activates osteoclastogenesis, both in vitro and in vivo. The SE enhanced the production of several pro-osteoclastogenic factors and facilitated osteoclast (OC) differentiation in mouse and human cells in vitro. Transgenic mice expressing a human HLA-DRB1 allele that code the SE motif demonstrated markedly higher propensity for osteoclastogenesis and enhanced bone degradation capacity ex vivo. In addition, the SE enhanced the differentiation of Th17 cells expressing the receptor activator for NF-κB ligand. When the two agents were combined, IL-17 and the SE enhanced OC differentiation synergistically. When administered in vivo to mice with collagen-induced arthritis, the SE ligand significantly increased arthritis severity, synovial tissue OC abundance, and bone erosion. Thus, the SE contributes to arthritis severity by activating an OC-mediated bone-destructive pathway. These findings suggest that besides determining the target specificity of autoimmune responses, HLA molecules may influence disease outcomes by shaping the pathogenic consequences of such responses.
TIM-3 Regulates Innate Immune Cells To Induce Fetomaternal Tolerance
Authors: Chabtini Lola , Mfarrej Bechara , Mounayar Marwan , Zhu Bing , Batal Ibrahim , Dakle Pranal J. , Smith Brian D. , Boenisch Olaf , Najafian Nader , Akiba Hisaya , Yagita Hideo , Guleria Indira
Published: November 2012

TIM-3 is constitutively expressed on subsets of macrophages and dendritic cells. Its expression on other cells of the innate immune system and its role in fetomaternal tolerance has not yet been explored. In this study, we investigate the role of TIM-3–expressing innate immune cells in the regulation of tolerance at the fetomaternal interface (FMI) using an allogeneic mouse model of pregnancy. Blockade of TIM-3 results in accumulation of inflammatory granulocytes and macrophages at the uteroplacental interface and upregulation of proinflammatory cytokines. Furthermore, TIM-3 blockade inhibits the phagocytic potential of uterine macrophages resulting in a build up of apoptotic bodies at the uteroplacental interface that elicits a local immune response. In response to inflammatory cytokines, Ly-6ChiGneg monocytic myeloid–derived suppressor cells expressing inducible NO synthase and arginase 1 are induced. However, these suppressive cells fail to downregulate the inflammatory cascade induced by inflammatory granulocytes (Ly-6CintGhi) and apoptotic cells; the increased production of IFN-γ and TNF-α by inflammatory granulocytes leads to abrogation of tolerance at the FMI and fetal rejection. These data highlight the interplay between cells of the innate immune system at the FMI and their influence on successful pregnancy in mice.
TLR9-Dependent IL-23/IL-17 Is Required for the Generation of Stachybotrys chartarum–Induced Hypersensitivity Pneumonitis
Authors: Bhan Urvashi , Newstead Michael J. , Zeng Xianying , Podsaid Amy , Goswami Moloy , Ballinger Megan N. , Kunkel Steven L. , Standiford Theodore J.
Published: November 2012

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease that develops after repeated exposure to inhaled particulate Ag. Stachybotrys chartarum is a dimorphic fungus that has been implicated in a number of respiratory illnesses, including HP. In this study, we have developed a murine model of S. chartarum–induced HP that reproduces pathology observed in human HP, and we have hypothesized that TLR9-mediated IL-23 and IL-17 responses are required for the generation of granulomatous inflammation induced by inhaled S. chartarum. Mice that undergo i.p. sensitization and intratracheal challenge with 106 S. chartarum spores developed granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of T cells. S. chartarum sensitization and challenge resulted in robust pulmonary expression of IL-17 and IL-23. S. chartarum–mediated granulomatous inflammation required intact IL-23 or IL-17 responses and required TLR9, because TLR9−/− mice displayed reduced IL-17 and IL-23 expression in whole lung associated with decreased accumulation of IL-17 expressing CD4+ and γδ T cells. Compared with S. chartarum–sensitized dendritic cells (DC) isolated from WT mice, DCs isolated from TLR9−/− mice had a reduced ability to produce IL-23 in responses to S. chartarum. Moreover, shRNA knockdown of IL-23 in DCs abolished IL-17 production from splenocytes in response to Ag challenge. Finally, the intratracheal reconstitution of IL-23 in TLR9−/− mice recapitulated the immunopathology observed in WT mice. In conclusion, our studies suggest that TLR9 is critical for the development of Th17-mediated granulomatous inflammation in the lung in response to S. chartarum.
AMP-Activated Protein Kinase Restricts IFN-γ Signaling
Authors: Meares Gordon P. , Qin Hongwei , Liu Yudong , Holdbrooks Andrew T. , Benveniste Etty N.
Published: November 2012

Inflammation in the CNS contributes to neurologic disorders. Neuroinflammation involves the release of inflammatory molecules from glial cells, such as astrocytes and microglia, and can lead to neuronal damage if unabated. In multiple sclerosis, peripheral immune cells, including IFN-γ–producing Th1 cells, infiltrate the CNS and are important in shaping the inflammatory microenvironment, in part through cytokine-mediated interactions with glial cells. Recent evidence suggests that AMP-activated protein kinase (AMPK), a central regulator of energetic metabolism, can regulate inflammatory gene expression. In this study, we identified that IFN-γ induces biphasic AMPK signaling, suggestive of negative-feedback mechanisms. Activation of AMPK suppresses several IFN-γ–induced cytokines and chemokines in primary astrocytes and microglia. IFN-γ regulates gene expression through activation of STAT1, and deletion of AMPK results in a marked increase in basal expression of STAT1. Conversely, activation of AMPK blocks IFN-γ–induced STAT1 expression. Deletion of AMPK leads to increased basal and IFN-γ–induced expression of inflammatory molecules, including TNF-α, CXCL10, and CCL2. AMPK does not affect the phosphorylation of STAT1, but instead attenuates nuclear translocation of STAT1, DNA binding, and subsequent gene expression. In vivo, AMPK signaling during experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, is downregulated in the brain at onset and peak of disease. Diminution of AMPK signaling in vivo correlates with increased expression of IFN-γ and CCL2 in the CNS. Overall, these findings provide the first link between AMPK and STAT1 and may provide important clues about how bioenergetics and inflammation are linked.
Bridgeland-stable moduli spaces for $K$-trivial surfaces
Authors: Arcara Daniele , Bertram Aaron
Published: November 2012

We give a one-parameter family of Bridgeland stability conditions on the derived category of a smooth projective complex surface

S

and describe "wall-crossing behavior'' for objects with the same invariants as

\mathcal O_C(H)

when

H

generates Pic

(S)

and

C \in |H|

. If, in addition,

S

is a K3 or Abelian surface, we use this description to construct a sequence of fine moduli spaces of Bridgeland-stable objects via Mukai flops and generalized elementary modifications of the universal coherent sheaf. We also discover a natural generalization of Thaddeus' stable pairs for curves embedded in the moduli spaces.
Transcendence with Rosen continued fractions
Authors: Bugeaud Yann , Hubert Pascal , Schmidt Thomas A.
Published: November 2012

We give the first transcendence results for the Rosen continued fractions. Introduced over half a century ago, these fractions expand real numbers in terms of certain algebraic numbers.
A comprehensive proof of localization for continuous Anderson models with singular random potentials
Authors: Germinet François , Klein Abel
Published: November 2012

We study continuous Anderson Hamiltonians with non-degenerate single site probability distribution of bounded support, without any regularity condition on the single site probability distribution. We prove the existence of a strong form of localization at the bottom of the spectrum, which includes Anderson localization (pure point spectrum with exponentially decaying eigenfunctions) with finite multiplicity of eigenvalues, dynamical localization (no spreading of wave packets under the time evolution), decay of eigenfunctions correlations, and decay of the Fermi projections. We also prove log-Hölder continuity of the integrated density of states at the bottom of the spectrum.
The Witten-Reshetikhin-Turaev invariants of finite order mapping tori II
Authors: Andersen Jørgen Ellegaard , Himpel Benjamin
Published: November 2012

We identify the leading order term of the asymptotic expansion of the Witten–Reshetikhin–Turaev invariants for finite order mapping tori with classical invariants for all simple and simply-connected compact Lie groups. The square root of the Reidemeister torsion is used as a density on the moduli space of flat connections and the leading order term is identified with the integral over this moduli space of this density weighted by a certain phase for each component of the moduli space. We also identify this phase in terms of classical invariants such as Chern–Simons invariants, eta invariants, spectral flow and the

\rho

-invariant. As a result, we show agreement with the semiclassical approximation as predicted by the method of stationary phase.
Polynomial invariants of graphs on surfaces
Authors: Askanazi Ross , Chmutov Sergei , Estill Charles , Michel Jonathan , Stollenwerk Patrick
Published: November 2012

For a graph embedded into a surface, we relate many combinatorial parameters of the cycle matroid of the graph and the bond matroid of the dual graph with the topological parameters of the embedding. This gives an expression of the polynomial, defined by M. Las Vergnas in a combinatorial way using matroids as a specialization of the Krushkal polynomial, defined using the symplectic structure in the first homology group of the surface.
Network Topology Models for Multihop Wireless Networks
Authors: Faragó András
Published: November 2012

A typical feature of huge, random network topologies is that they are too large to allow a fully detailed description. Such enormous, complex network topologies are encountered in numerous settings and have generated many research investigations. Well-known examples are the Internet and its logical overlay networks, such as the World Wide Web as well as online social networks. At the same time, extensive and rapidly growing wireless ad hoc and sensor networks also lead to hard topology modeling questions. In the current paper, we primarily focus on large, random wireless networks but also consider Web and Internet models. We survey a number of existing models that aim at describing the network topology. We also exhibit common generalizations of various sets of models that cover a number of known constructions as special cases. We demonstrate that higher levels of abstraction, despite their very general nature, can still be meaningfully analyzed and offers quite useful and unique help in solving certain hard networking problems. We believe that this research area can and will generate further significant contributions to the analysis of very large networks.
Non‐stoichiometry in Oxide Thin Films: A Chemical Capacitance Study of the Praseodymium‐Cerium Oxide System
Authors: Chen Di , Bishop Sean R. , Tuller Harry L.
Published: November 2012

While the properties of functional oxide thin films often depend strongly on their oxygen stoichiometry, there have been few ways to extract this information reliably and in situ. In this work, the derivation of the oxygen non‐stoichiometry of dense Pr0.1Ce0.9O2−δ thin films from an analysis of chemical capacitance obtained by impedance spectroscopy is described. Measurements are performed on electrochemical cells of the form Pr0.1Ce0.9O2−δ/Y0.16Zr0.84O1.92/Pr0.1Ce0.9O2−δ over the temperature range of 450 to 800 °C and oxygen partial pressure range of 10−5 to 1 atm O2. With the aid of a defect equilibria model, approximations relate chemical capacitance directly to non‐stoichiometry, without need for fitting parameters. The calculated non‐stoichiometry allows extraction of the thermodynamic constants defining defect generation. General agreement of these constants with bulk values derived by thermogravimetric analysis is found, thereby confirming the suitability of this technique for measuring oxygen non‐stoichiometry of thin oxide films. Potential sources of error observed in earlier chemical capacitance studies on perovskite structured oxide films are also discussed.
Hierarchical Multi‐Step Folding of Polymer Bilayers
Authors: Stoychev Georgi , Turcaud Sébastien , Dunlop John W. C. , Ionov Leonid
Published: November 2012

A highly complex multi‐step folding of isotropic stimuli‐responsive polymer bilayers resulting in a variety of 2D and 3D structures is reported. Experimental observations allow determination of empirical rules, which can be used to direct the folding of polymer films in a predictable manner. In particular, it is demonstrated that these rules can be used for the design of a 3D pyramid. The understanding and know‐how attained in this study allow the very simple design of highly complex, self‐folding 3D objects and open new horizons for 3D patterning, important for the design of microfluidic devices, biomaterials, and soft electronics.
Epilepsy with cognitive deficit and autism spectrum disorders: Prospective diagnosis by array CGH
Authors: Nicholl Jillian , Waters Wendy , Suwalski Shanna , Brown Sue , Hull Yvonne , Harbord Michael G. , Entwistle John , Thompson Suzanna , Clark Damian , Pridmore Claire , Haan Eric , Barnett Christopher , McGregor Lesley , Liebelt Jan , Thompson Elizabeth M. , Friend Kathryn , Bain Sharon M. , Yu Sui , Mulley John C.
Published: November 2012

The clinical significance of chromosomal microdeletions and microduplications was predicted based on their gene content, de novo or familial inheritance and accumulated knowledge recorded on public databases. A patient group comprised of 247 cases with epilepsy and its common co‐morbidities of developmental delay, intellectual disability, autism spectrum disorders, and congenital abnormalities was reviewed prospectively in a diagnostic setting using a standardized oligo‐array CGH platform. Seventy‐three (29.6%) had copy number variations (CNVs) and of these 73 cases, 27 (37.0%) had CNVs that were likely causative. These 27 cases comprised 10.9% of the 247 cases reviewed. The range of pathogenic CNVs associated with seizures was consistent with the existence of many genetic determinants for epilepsy. © 2012 Wiley Periodicals, Inc.
(Un‐)expected nocturnal activity in “Diurnal” Lemur catta supports cathemerality as one of the key adaptations of the lemurid radiation
Authors: Donati Giuseppe , Santini Luca , Razafindramanana Josia , Boitani Luigi , Borgognini‐Tarli Silvana
Published: November 2012

The ability to operate during the day and at night (i.e., cathemerality) is common among mammals but has rarely been identified in primates. Adaptive hypotheses assume that cathemerality represents a stable adaptation in primates, while nonadaptive hypotheses propose that it is the result of an evolutionary disequilibrium arising from human impacts on natural habitats. Madagascar offers a unique opportunity to study the evolution of activity patterns as there we find a monophyletic primate radiation that shows nocturnal, diurnal, and cathemeral patterns. However, when and why cathemeral activity evolved in lemurs is the subject of intense debate. Thus far, this activity pattern has been regularly observed in only three lemurid genera but the actual number of lemur species exhibiting this activity is as yet unknown. Here we show that the ring‐tailed lemur, Lemur catta, a species previously considered to be diurnal, can in fact be cathemeral in the wild. In neighboring but distinct forest areas these lemurs exhibited either mainly diurnal or cathemeral activity. We found that, as in other cathemeral lemurs, activity was entrained by photoperiod and masked by nocturnal luminosity. Our results confirm the relationship between transitional eye anatomy and physiology and 24‐h activity, thus supporting the adaptive scenario. Also, on the basis of the most recent strepsirrhine phylogenetic reconstruction, using parsimony criterion, our findings suggest pushing back the emergence of cathemerality to stem lemurids. Flexible activity over 24‐h could thus have been one of the key adaptations of the early lemurid radiation possibly driven by Madagascar's island ecology. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc.
Adoptive regulatory T‐cell therapy protects against cerebral ischemia
Authors: Li Peiying , Gan Yu , Sun Bao‐Liang , Zhang Feng , Lu Binfeng , Gao Yanqin , Liang Weimin , Thomson Angus W. , Chen Jun , Hu Xiaoming
Published: November 2012

Objective

Recent evidence suggests that functional deficiency in regulatory T cells (Tregs), an innate immunomodulator, exacerbates brain damage after cerebral ischemia. We therefore evaluated the effect of Treg transfer in rodent models of ischemic stroke and further investigated the mechanism underlying Treg‐afforded neuroprotection.

Methods

We examined the therapeutic potential of Tregs and the mechanisms of neuroprotection in vivo in 2 rodent models of ischemic stroke and in vitro in Treg–neutrophil cocultures using a combined approach including cell‐specific depletion, gene knockout mice, and bone marrow chimeras.

Results

Systemic administration of purified Tregs at 2, 6, or even 24 hours after middle cerebral artery occlusion resulted in a marked reduction of brain infarct and prolonged improvement of neurological functions lasting out to 4 weeks. Treg‐afforded neuroprotection was accompanied by attenuated blood–brain barrier (BBB) disruption during early stages of ischemia, decreased cerebral inflammation, and reduced infiltration of peripheral inflammatory cells into the lesioned brain. Surprisingly, Tregs exerted early neuroprotection without penetrating into the brain parenchyma or inhibiting the activation of residential microglia. Rather, both in vivo and in vitro studies demonstrated that Tregs suppressed peripheral neutrophil‐derived matrix metallopeptidase‐9 production, thus preventing proteolytic damage of the BBB. In addition to its potent central neuroprotection, Treg treatment was shown to ameliorate poststroke lymphopenia, suggesting a beneficial effect on immune status.

Interpretation

Our study suggests that Treg adoptive therapy is a novel and potent cell‐based therapy targeting poststroke inflammatory dysregulation and neurovascular disruption. Ann Neurol 2013;74:458–471
LTBP4 genotype predicts age of ambulatory loss in duchenne muscular dystrophy
Authors: Flanigan Kevin M. , Ceco Ermelinda , Lamar Kay‐Marie , Kaminoh Yuuki , Dunn Diane M. , Mendell Jerry R. , King Wendy M. , Pestronk Alan , Florence Julaine M. , Mathews Katherine D. , Finkel Richard S. , Swoboda Kathryn J. , Gappmaier Eduard , Howard Michael T. , Day John W. , McDonald Craig , McNally Elizabeth M. , Weiss Robert B.
Published: November 2012

Objective

Duchenne muscular dystrophy (DMD) displays a clinical range that is not fully explained by the primary DMD mutations. Ltbp4, encoding latent transforming growth factor‐β binding protein 4, was previously discovered in a genome‐wide scan as a modifier of murine muscular dystrophy. We sought to determine whether LTBP4 genotype influenced DMD severity in a large patient cohort.

Methods

We analyzed nonsynonymous single nucleotide polymorphisms (SNPs) from human LTBP4 in 254 nonambulatory subjects with known DMD mutations. These SNPs, V194I, T787A, T820A, and T1140M, form the VTTT and IAAM LTBP4 haplotypes.

Results

Individuals homozygous for the IAAM LTBP4 haplotype remained ambulatory significantly longer than those heterozygous or homozygous for the VTTT haplotype. Glucocorticoid‐treated patients who were IAAM homozygotes lost ambulation at 12.5 ± 3.3 years compared to 10.7 ± 2.1 years for treated VTTT heterozygotes or homozygotes. IAAM fibroblasts exposed to transforming growth factor (TGF) β displayed reduced phospho‐SMAD signaling compared to VTTT fibroblasts, consistent with LTBP4' role as a regulator of TGFβ.

Interpretation

LTBP4 haplotype influences age at loss of ambulation, and should be considered in the management of DMD patients. ANN NEUROL 2013;73:481–488
Poly(vinylidene fluoride)/silica nanocomposite membranes by electrospinning
Authors: Xiong Xi , Li Qiang , Zhang Xu‐Cheng , Wang Li , Guo Zhao‐Xia , Yu Jian
Published: November 2012

Poly(vinylidene fluoride) (PVDF)/silica nanocomposite membranes containing up to 30% silica were prepared by electrospinning using colloidal silica as the source of silica and dimethyl formamide as the solvent. The fiber morphology was observed by field emission scanning electron microscopy. The average fiber diameter is about 0.3 μm for PVDF/silica composite fibers having 10–30% silica. Silica nanoparticles were observed on all fiber surfaces with fairly good dispersion and distribution. Fourier transform infrared spectroscopy and differential scanning calorimeter were used to investigate the crystallization behavior of PVDF and showed that a mixture of α‐, β‐, and γ‐phase crystals was obtained with little content of α phase and all the PVDF/silica composite membranes have similar degree of crystallinity. Static water contact angle measurements were performed to investigate the surface wettability of the membranes. The mechanical properties were evaluated by tensile tests, showing strong reinforcement effect. The tensile modulus and tensile strength increase significantly when silica is present. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Curing behaviors and thermal properties of benzoxazine and N, N′‐(2, 2, 4‐trimethylhexane‐1, 6‐diyl) dimaleimide blend
Authors: Wang Zhi , Ran Qichao , Zhu Rongqi , Gu Yi
Published: November 2012

A blend of bisphenol‐A based benzoxazine (BA‐a)/N, N′‐(2, 2, 4‐Trimethylhexane‐1, 6‐diyl) dimaleimide (TBMI) with the ratio of 1:1 was prepared and its curing behaviors were studied by differential scanning calorimetry (DSC), Fourier Transform Infrared (FTIR). The curing mechanism was proposed based on the semiquantitative analysis from FTIR spectra. The model compound was used to study the catalysis effect of BA‐a on the curing reaction of TBMI. It was found the curing reactions of BA‐a and TBMI not only proceeded simultaneously, but their coreactions also occurred. The research further indicated that negative oxygen ions from ring opening of benzoxazine mainly promoted the polymerization of maleimide groups, even though the amine group of benzoxazine had a positive effect on the reaction of maleimide groups. Besides, BA‐a and TBMI blends showed improved thermal properties based on the results from DMA and TGA. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Eco‐friendly grafting of natural biopolymer chitosan onto acylated wool fabrics using ultrasonic and study its properties
Authors: Ranjbar‐Mohammadi Marziyeh , Hajir Bahrami S. , Arami M.
Published: November 2012

The use of ultrasonic for accelerating the chemical and physical processes of wool has gained high importance. This study aims to develop a method for reducing the energy and material consumption and decreasing fiber damage. Ultrasonic equipment (20 kHz) was used for grafting chitosan to wool fabric. Experiments were carried out under different times and chitosan concentration. The results showed using this technique decreases the time required for grafting chitosan onto wool which is less than the other procedures. Differential scanning calorimetry, Fourier transform infra‐red, and weight gain analyses provided evidence that chitosan was grafted onto the acylated wool through the formation of new covalent bonds in a short time. Scanning electron microscope was used to study the morphology of wool samples before and after modification. The dyeing of the chitosan grafted‐acylated wool fabrics indicates higher dye ability and lower shrinkage compared to the acylated and raw wool samples. The findings of this study support the potential of using ultrasonic as a friendly environment method for grafting chitosan onto wool with enhanced dye ability and reduced shrinkage properties. The grafted samples showed good antibacterial properties against Staphylococcus aureus as gram‐positive and Pseudomonas aeruginosa as gram negative bacteria. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Electropolymerization of sulfonated phenol by cyclic voltammetry
Authors: Hou Hongying , Vacandio Florence , Vona Maria Luisa Di , Knauth Philippe
Published: November 2012

In this work, electropolymerization of sulfonated phenol were performed by cyclic voltammetry (CV) on planar or nano‐architecture substrates. The corresponding CV curves were analyzed and compared. The obtained polymer was characterized by SEM, EDX, and FTIR. The results suggested that it was feasible to electropolymerize sulfonated phenol on different substrates. The facility of electropolymerization on different substrates was as follows: graphite carbon > stainless steel plate > ZrO2 nanotube. The peak current density of CV curve on stainless steel kept constant from the second cycle possibly attributed to the promoting effects of sulfonic acid groups: improving the ionic conductivity, changing the packing mode of polymer chains, and enhancing the permeability of the film to monomers. This work offered some insights into electrochemical synthesis of proton‐conducting membrane for varied special applications, such as micro‐sized fuel cell, sensor, battery, and other solid‐state ionic devices. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Mesenchymal stem cells for systemic therapy: Shotgun approach or magic bullets?
Authors: Millard Susan M. , Fisk Nicholas M.
Published: November 2012

Given their heterogeneity and lack of defining markers, it is surprising that multipotent mesenchymal stem/stromal cells (MSCs) have attracted so much translational attention, especially as increasing evidence points to their predominant effect being not by donor differentiation but via paracrine mediators and exosomes. Achieving long‐term MSC donor chimerism for treatment of chronic disease remains a challenge, requiring enhanced MSC homing/engraftment properties and manipulation of niches to direct MSC behaviour. Meanwhile advances in nanoparticle technology are furthering the development of MSCs as vehicles for targeted drug delivery. For treatment of acute injuries, systemic cell‐free exosome delivery may ultimately displace current emphasis on empiric donor‐cell transplantation for anti‐inflammatory, immunomodulatory and repair‐promoting effects. Exploration of potential clinical sources of MSCs has led to increased utilisation of perinatal MSCs in allogeneic clinical trials, reflecting their ease of collection and developmentally advantageous properties.
Identification and quantitation of vesivirus 2117 particles in bioreactor fluids from infected Chinese hamster ovary cell cultures
Authors: Qiu Yongchang , Jones Nathan , Busch Michelle , Pan Peng , Keegan Jesse , Zhou Weichang , Plavsic Mark , Hayes Michael , McPherson John M. , Edmunds Tim , Zhang Kate , Mattaliano Robert J.
Published: November 2012

The prevention of adventitious agent contamination is a top priority throughout the entire biopharmaceutical production process. For example, although viral contamination of cell banks or cell cultures is rare, it can result in serious consequences (e.g., shutdown and decontamination of manufacturing facilities). To ensure virus free production, numerous in vivo and in vitro adventitious agent assays and biophysical characterizations such as electron microscopy are conducted on cell banks, raw materials, process materials, and drug substances throughout the manufacturing process. Molecular assays such as PCR and other nucleotide‐based techniques are also routinely used for screening and identification of any viral agents. However, modern techniques in protein identification of complex protein mixtures have not yet been effectively integrated throughout the industry into current viral testing strategies. Here, we report the identification and quantitation of Vesivirus 2117 particles in bioreactor fluid from infected Chinese hamster ovary cell cultures by global protein sequencing using mass spectrometry in combination with multi‐dimensional liquid‐chromatography. Following mass spectrometric data acquisition and rigorous data analysis, six virus specific peptides were identified. These peptides were fragments of two structural proteins, capsid protein pre‐cursor (four unique peptides) and small structural protein (two unique peptides), from the same species: Vesivirus 2117. Using stable heavy isotope‐labeled peptides as internal standards, we also determined the absolute concentration of Vesivirus particles in the bioreactor fluid and the ratio of two capsid proteins (VP1:VP2) in the particles as approximately 9:1. The positive identification of Vesivirus 2117 was subsequently confirmed by RT‐PCR. Biotechnol. Bioeng. 2013; 110: 1342–1353. © 2012 Wiley Periodicals, Inc.
A yeast‐based rapid prototype platform for gene control elements in mammalian cells
Authors: Wei Kathy Y. , Chen Yvonne Y. , Smolke Christina D.
Published: November 2012

Programming genetic circuits in mammalian cells requires flexible, tunable, and user‐tailored gene‐control systems. However, most existing control systems are either mechanistically specific for microbial organisms or must be laboriously re‐engineered to function in mammalian cells. Here, we demonstrate a ribozyme‐based device platform that can be directly transported from yeast to mammalian cells in a “plug‐and‐play” manner. Ribozyme switches previously prototyped in yeast are shown to regulate gene expression in a predictable, ligand‐responsive manner in human HEK 293, HeLa, and U2OS cell lines without any change to device sequence nor further optimization. The ribozyme‐based devices, which exhibit activation ratios comparable to the best RNA‐based regulatory devices demonstrated in mammalian cells to‐date, retain their prescribed functions (ON or OFF switch), tunability of regulatory stringency, and responsiveness to different small‐molecule inputs in mammalian hosts. Furthermore, we observe strong correlations of device performance between yeast and all mammalian cell lines tested (R2 = 0.63–0.97). Our unique device architecture can therefore act as a rapid prototyping platform (RPP) based on a yeast chassis, providing a well‐developed and genetically tractable system that supports rapid and high‐throughput screens for generating gene‐controllers with a broad range of functions in mammalian cells. This platform will accelerate development of mammalian gene‐controllers for diverse applications, including cell‐based therapeutics and cell‐fate reprogramming. Biotechnol. Bioeng. 2013; 110: 1201–1210. © 2012 Wiley Periodicals, Inc.
GM‐CSF enhances tumor invasion by elevated MMP‐2, ‐9, and ‐26 expression
Authors: Gutschalk Claudia M. , Yanamandra Archana K. , Linde Nina , Meides Alice , Depner Sofia , Mueller Margareta M.
Published: November 2012

Granulocyte–macrophage colony‐stimulating factor (GM‐CSF) promotes tumor progression in different tumor models in an autocrine and paracrine manner. However, at the same time GM‐CSF is used in cancer therapies to ameliorate neutropenia. We have previously shown in GM‐CSF and G‐CSF expressing or negative skin or head and neck squamous cell carcinoma that GM‐CSF expression is associated with a highly angiogenic and invasive tumor phenotype. To determine the functional contribution of GM‐CSF to tumor invasion, we stably transfected a GM‐CSF negative colon adenocarcinoma cell line HT‐29 with GM‐CSF or treated the same cell line with exogenous GM‐CSF. While GM‐CSF overexpression and treatment reduced tumor cell proliferation and tumor growth in vitro and in vivo, respectively, it contributed to tumor progression. Together with an enhanced migratory capacity in vitro, we observed a striking increase in tumor cell invasion into the surrounding tissue concomitant with the induction of an activated tumor stroma in GM‐CSF overexpressing or GM‐CSF treated tumors. In a complex 3D in vitro model, enhanced GM‐CSF expression was associated with a discontinued basement membrane deposition that might be mediated by the increased expression and activation of MMP‐2, ‐9, and ‐26. Treatment with GM‐CSF blocking antibodies reversed this effect. The increased presence and activity of these tumor cell derived proteases was confirmed in vivo. Here, expression of MMP‐26 protein was predominantly located in pre‐ and early‐invasive areas suggesting MMP‐26 expression as an early event in promoting GM‐CSF dependent tumor invasion.
Overexpression of DRAM enhances p53‐dependent apoptosis
Authors: Takahashi Masahiro , Kakudo Yuichi , Takahashi Shin , Sakamoto Yasuhiro , Kato Shunsuke , Ishioka Chikashi
Published: November 2012

Tumor suppressor p53‐dependent apoptosis is thought to be one of the most important tumor‐suppressive mechanisms in human tumorigenesis. Till date, “super p53” mutants exhibiting more potent ability to induce apoptosis than wild‐type p53 have been reported. These super p53s may provide a clue for development of novel therapeutic targets. However, the major mechanism underlying the super p53‐dependent apoptosis remains unclear. To identify critical gene(s) in this mechanism, we performed a comprehensive and comparative expression analysis in p53‐null Saos‐2 cells with conditional expression of wild‐type p53 and S121F, which was previously reported as a super p53 mutant. We identified damage‐regulated autophagy modulator (DRAM) as one of the genes that were more upregulated by S121F than wild‐type p53. Although knockdown of DRAM was not sufficient for reducing the ability of S121F to induce apoptosis, DRAM overexpression enhanced the ability in a wild‐type p53‐dependent manner. Here, we show that DRAM is an important gene for the enhancement of p53‐dependent apoptosis. Additional analysis of the mechanism of super p53‐dependent apoptosis may lead to the identification of novel drug targets for cancer therapy.
Does elevatedpCO2affect reef octocorals?
Authors: Gabay Yasmin , Benayahu Yehuda , Fine Maoz
Published: November 2012

Increasing anthropogenicpCO2alters seawater chemistry, with potentially severe consequences for coral reef growth and health. Octocorals are the second most important faunistic component in many reefs, often occupying 50% or more of the available substrate. Three species of octocorals from two families were studied inEilat (Gulf ofAqaba), comprising the zooxanthellateOvabunda macrospiculataandHeteroxenia fuscescens(familyXeniidae), andSarcophytonsp. (familyAlcyoniidae). They were maintained under normal (8.2) and reduced (7.6 and 7.3)pHconditions for up to 5 months. Their biolological features, including protein concentration, polyp weight, density of zooxanthellae, and their chlorophyll concentration per cell, as well as polyp pulsation rate, were examined under conditions more acidic than normal, in order to test the hypothesis that risingpCO2would affect octocorals. The results indicate no statistically significant difference between the octocorals exposed to reducedpHvalues compared to the control. It is therefore suggested that the octocorals' tissue may act as a protective barrier against adversepHconditions, thus maintaining them unharmed at high levels ofpCO2.
The hydrologic implications of old field succession: depression storage and leaf litter
Authors: Richards Paul L. , Norris Mark D. , Lin Brenda B.
Published: November 2012

Previous studies have noted the importance of vegetation in controlling run‐off in terrestrial landscapes. Here, we hypothesize that ecologic succession from mowed grassland to old field to forest will impact run‐off characteristics due to changing vegetation characteristics that affect soil surface processes. We test this idea by measuring depression storage and leaf litter water retention rates in 13 sites across this successional gradient. Sites of similar slope and soil type were also evaluated against one another to isolate the effect of vegetation diversity and management on depression storage. Results showed that average ideal depression storage increased with greater vegetation diversity and structure. Effective depression storage of unmanaged systems was significantly higher than mowed systems, implying that management activities retard the natural development of microtopography. Results of leaf litter water retention varied among land covers but contributed less than depression storage for water capture. These results demonstrate the tight linkages between vegetation succession and run‐off. Understanding these characteristics is necessary for developing effective hydrologic models. Copyright © 2012 John Wiley & Sons, Ltd.
Accurate and efficient RTL power estimation based on power contour model
Authors: Kawauchi Hirofumi , Taniguchi Ittetsu , Tomiyama Hiroyuki , Fukui Masahiro
Published: November 2012

This paper proposes a new RTL power estimation method based on a power contour model. The model achieves accurate and efficient power estimation. The experimental results show that the maximum error is reduced by 56.19% and the RMS error is also reduced by 3.41% compared to the conventional table‐based RTL power estimation. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 182(3): 48–56, 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.22340
Influence of injection of concentrated NOx into diesel engine intake on exhaust gas components and fuel consumption
Authors: Yoshida Keiichiro , Kuwahara Takuya , Kuroki Tomoyuki , Okubo Masaaki
Published: November 2012

The effect of injecting NO (major content of NOx in diesel exhaust gas) into a diesel engine intake, on the reduction of NOx generation at the combustion chamber was investigated. The results demonstrate that 20 to 30% of the injected NO [0.225 to 0.72 slm (slm: standard liter per minute)] is reduced. A discussion of the NOx reduction based on the extended Zeldovich mechanism suggests that the reduction is mainly attributable to the region where the equivalence ratio ranges from 1.1 to 1.5 and that the reaction between NO and hydrocarbon species contributes slightly to the NO reduction. Further experimental data show that the injection of NO slightly improves the specific fuel consumption; for example, a 0.4% reduction is achieved when NO is injected at 0.72 slm for an intake airflow of 285 slm. The experimentally determined change in fuel consumption is highly consistent with the calculations based on the reaction enthalpy of NO reduction and CO oxidation. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 182(3): 39–47, 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.22341
Syntheses and Coordination Studies of 2‐(Phosphanylmethyl)pyridine Dioxide toward Silver (I)
Authors: Padron Daniel A. , Klausmeyer Kevin K.
Published: November 2012

The coordination properties of the 2‐[(diphenylphosphanyl)methyl]pyridine N,P‐dioxide ligand towards three different silver(I) salts are described. The molecular structures of the coordination complexes obtained showed a strong dependence on the 2‐[(diphenylphosphanyl)methyl]pyridine N,P‐dioxide ligand and the binding ability of the counterion. The strongly binding trifluoroacetate ion yielded a unique planar silver cluster complex, whereas the less strongly binding triflate and BF4– complexes yielded polymeric structures. The synthesized complexes were fully characterized by elemental analysis and multinuclear NMR spectroscopy techniques. The crystal structures were determined by single‐crystal X‐ray crystallography.
Tripodal MIII Complexes on Au(111) Surfaces: Towards Molecular “Lunar Modules”
Authors: Schramm Alexandrina , Stroh Christophe , Dössel Kerrin , Lukas Maya , Fischer Matthias , Schramm Frank , Fuhr Olaf , Löhneysen Hilbert v. , Mayor Marcel
Published: November 2012

A series of tripodal MIII complexes (M = Ga, Mn, Fe) functionalized with three methylsulfanyl end‐groups for deposition on Au(111) were synthesized. The structures were designed to build rigid three‐dimensional molecular structures that stand on their own with multiple attachments on the metallic surface. The coordination compounds are based on a trensal [(tris(2,2′,2"‐salicylideneimino)triethylamine)] Schiff base ligand which provides stable metal complexes. The molecular structures of GaIII, FeIII, and MnIII complexes were determined by single‐crystal X‐ray diffraction crystallography. Magnetic properties depend on the coordinated metal ion and vary from a diamagnetic GaIII complex to paramagnetic high‐spin FeIII and MnIII complexes. A submonolayer of the GaIII complex deposited on Au(111) was studied in a preliminary ultra‐high‐vacuum scanning tunneling microscopy (UHV‐STM) investigation.
Continuing Issues with Lead: Recent Advances in Detection
Authors: Deibler Kristine , Basu Partha
Published: November 2012

In the past, Pb2+ was used in many industries, including gasoline, piping, toys, paints, and more. The use of lead has led to a natural increase in lead concentrations in the environment, especially in air and water. According to the U.S. Center for Disease Control “no level of lead in blood is considered safe.” Exposure to very low levels of lead can cause several health complications including developmental and neurological disorders. Over the past several years an emphasis has been placed on developing systems that can detect lead at very low concentrations. A great deal of work has been accomplished in the development of Pb2+ sensors that can not only detect but also quantify, and in some cases in the presence of other metal ions, the amount present. Herein, we describe current regulations, modes of exposure, and recent developments in sensing techniques.
Trivalent Cerium and Praseodymium Aromatic Ketone Adducts
Authors: Crozier Alan R. , Törnroos Karl W. , Maichle‐Mössmer Cäcilia , Anwander Reiner
Published: November 2012

The reactions of the aromatic ketones benzophenone and 9‐fluorenone with trivalent [LnL3] complexes [Ln = Ce, Pr; L = N(SiMe3)2, C5H5 (Cp)] produce highly colored solutions in toluene. Characterization of these complexes by X‐ray diffraction revealed them to be monoadducts of the form [LnL3(ketone)]. The crystallographically determined C–O bonds of these complexes are longer than those of the free ketones. Significant ligand‐to‐metal charge transfer is also indicated by the ν(C=O) vibration of the coordinated ketone, which appears at lower wavelength. Solution‐based 1H NMR spectroscopy showed paramagnetic spectra of complexes Ln[N(SiMe3)2]3(ketone) and Ln(C5H5)3(ketone), which further supports this finding.
Dihydropyridazine Derivatives with Cyclopenta‐, Benzo‐, Furo‐, Thiopyrano‐ and Pyrido‐Annulation
Authors: Penning Miriam , Christoffers Jens
Published: November 2012

Regioisomeric [c]annulated pyridazines were prepared from arylhydrazines and carbocyclic or heterocyclic β‐oxo esters with an α‐phenacetyl moiety. With AcOH/EtOH, the hydrazones were preferentially formed at the endocyclic ketone, which are further cyclized with trifluoroacetic acid (TFA)/CH2Cl2 to give 2,4a‐dihydropyridazines. Use of TFA/CH2Cl2 led hydrazones at the exocyclic benzoyl group, which reacted further to give 1,4‐dihydro‐4aH‐pyridazines. In this investigation, examples of the rare or unknown heterocyclic systems furo[3,4‐c]‐, thiopyrano[4,3‐c]‐ and pyrido[4,3‐c]pyridazine were prepared.
Thermal Rearrangement of Azido Ketones into Oxazoles via Azirines: One‐Pot, Metal‐Free Heteroannulation to Functionalized 1,3‐Oxazoles
Authors: Shah Shailesh R. , Navathe Sudhanva S. , Dikundwar Amol G. , Guru Row Tayur N. , Vasella Andrea T.
Published: November 2012

α‐Azidoacetophenones were converted into 2‐aryl‐1,3‐oxazole‐4‐carbaldehydes through rearrangement of the carbon framework upon exposure to DMF/POCl3. The unprecedented rearrangement occurs via alkenyl azides and 2H‐azirines. A mechanism for this unusual reaction was proposed and evidenced.
Chemoenzymatic Total Synthesis of a Naturally Occurring (5‐5′)/(8′‐O‐4″) Dehydrotrimer of Ferulic Acid
Authors: Mouterde Louis M. M. , Flourat Amandine L. , Cannet Molly M. M. , Ducrot Paul‐Henri , Allais Florent
Published: November 2012

The cross‐linking of plant cell walls by ferulate dehydrodimerization reactions is well established. Recently, a (5‐5′)/(8′‐O‐4″) dehydrotrimer of ferulic acid (A) was isolated from alkali extracts of maize bran. Its structure was elucidated on the basis of an extensive structural analysis (UV, MS, 1D and 2D NMR). This first identified ferulic acid dehydrotrimer has revealed that parietal polysaccharide chains can be more extensively cross‐linked than has been previously recognized. To produce the (5‐5′)/(8′‐O‐4″) dehydrotrimer (A) in sufficient high‐purity quantities and allow the development of analytical methodologies (e.g., LC/GC, immunohistochemistry) to identify and quantify this peculiar trimer in plant extracts or samples, its first total convergent synthesis has been achieved in 10 steps and in 18 % yield starting from commercially available vanillin by horseradish peroxidase mediated enzymatic aryl–aryl coupling, aldolization/crotonization, and Wittig olefination reactions as the key steps.