bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acylsilanes in Rhodium(III)‐Catalyzed Directed Aromatic C–H Alkenylations and Siloxycarbene Reactions with CC Double Bonds
Authors: Becker Peter , Priebbenow Daniel L. , Pirwerdjan Ramona , Bolm Carsten 
Published: November 2013

AbstractAcylsilanes are known to undergo a 1,2‐silicon‐to‐oxygen migration under thermal or photochemical conditions to form siloxycarbenes. However, there are few reports regarding the application of siloxycarbenes in organic synthesis and surprisingly, their reaction with CC double or triple bonds remains virtually unexplored. To facilitate such a study, previously inaccessible aromatic acylsilanes containing an ortho‐tethered CC double bond were identified as suitable substrates. To access these key intermediates, we developed a new synthetic method utilizing a rhodium‐catalyzed oxidative Heck‐type olefination involving the application of an acylsilane moiety as a directing group. When exposed to visible‐light irradiation, the ortho‐olefinated acylsilanes underwent a smooth intramolecular cyclization process to afford valuable indanone derivatives in quantitative yields. This result paves the way for the development of new transformations involving siloxycarbene intermediates.
Regioselective and Stereospecific Deuteration of Bioactive Aza Compounds by the Use of Ruthenium Nanoparticles
Authors: Pieters Grégory , Taglang Céline , Bonnefille Eric , Gutmann Torsten , Puente Céline , Berthet Jean‐Claude , Dugave Christophe , Chaudret Bruno , Rousseau Bernard 
Published: November 2013

AbstractAn efficient H/D exchange method allowing the deuteration of pyridines, quinolines, indoles, and alkyl amines with D2 in the presence of Ru@PVP nanoparticles is described. By a general and simple procedure involving mild reaction conditions and simple filtration to recover the labeled product, the isotopic labeling of 22 compounds proceeded in good yield with high chemo‐ and regioselectivity. The viability of this procedure was demonstrated by the labeling of eight biologically active compounds. Remarkably, enantiomeric purity was conserved in the labeled compounds, even though labeling took place in the vicinity of the stereogenic center. The level of isotopic enrichment observed is suitable for metabolomic studies in most cases. This approach is also perfectly adapted to tritium labeling because it uses a gas as an isotopic source. Besides these applications to molecules of biological interest, this study reveals a rich and underestimated chemistry on the surface of ruthenium nanoparticles.
An Antibody with a Variable‐Region Coiled‐Coil “Knob” Domain
Authors: Zhang Yong , Goswami Devrishi , Wang Danling , Wang Tsung‐Shing Andrew , Sen Shiladitya , Magliery Thomas J. , Griffin Patrick R. , Wang Feng , Schultz Peter G. 
Published: November 2013

AbstractThe X‐ray crystal structure of a bovine antibody (BLV1H12) revealed a unique structure in its ultralong heavy chain complementarity determining region 3 (CDR3H) that folds into a solvent‐exposed β‐strand “stalk” fused to a disulfide crosslinked “knob” domain. We have substituted an antiparallel heterodimeric coiled‐coil motif for the β‐strand stalk in this antibody. The resulting antibody (Ab‐coil) expresses in mammalian cells and has a stability similar to that of the parent bovine antibody. MS analysis of H–D exchange supports the coiled‐coil structure of the substituted peptides. Substitution of the knob‐domain of Ab‐coil with bovine granulocyte colony‐stimulating factor (bGCSF) results in a stably expressed chimeric antibody, which proliferates mouse NFS‐60 cells with a potency comparable to that of bGCSF. This work demonstrates the utility of this novel coiled‐coil CDR3 motif as a means for generating stable, potent antibody fusion proteins with useful pharmacological properties.
Compensation of microwave‐source heating attenuation into epoxy–glass composites: Experimental results
Authors: Douadji Lyes , Du Wei Wei , Li Cheng 
Published: November 2013

ABSTRACTThe final goal of this study was to manufacture an epoxy–glass leaf spring by microwave processing. The physical properties of the final part to be manufactured, in particular, the mechanical properties, were directly related at the repartition of microwave‐source heating during the treatment. The major problem in microwave processing, however, is the attenuation of the microwave source. Here, we propose a dielectric effect of attenuation inversion of the electromagnetic waves as a new method for the uniform treatment of epoxy–glass by microwave energy. This solution used the dielectric properties of the mold to control the microwave‐heat‐source attenuation into the composite to be treated. Many experiments were carried out to validate the proposed solution. The results show that the microwave‐source heating attenuation could controlled and inversed. We demonstrated the uniform treatment of epoxy–glass parts about 100 cm long by means of the compensation of microwave‐source attenuation. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2014,131, 39908.
Genome‐Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögren's Syndrome
Authors: Altorok Nezam , Coit Patrick , Hughes Travis , Koelsch Kristi A. , Stone Donald U. , Rasmussen Astrid , Radfar Lida , Scofield R. Hal , Sivils Kathy L. , Farris A. Darise , Sawalha Amr H. 
Published: November 2013

ObjectivePrimary Sjögren's syndrome (SS) is a systemic autoimmune disease with incompletely understood etiology. This study was undertaken to investigate the role of epigenetic dysregulation in the pathogenesis of primary SS.MethodsA genome‐wide DNA methylation study was performed in naive CD4+ T cells from 11 patients with primary SS compared to age‐, sex‐, and ethnicity‐matched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array, and the data were validated using bisulfite sequencing.ResultsGenome‐wide analyses identified 553 hypomethylated CpG sites and 200 hypermethylated CpG sites in naive CD4+ T cells from patients with primary SS as compared to healthy controls, representing 311 hypomethylated and 115 hypermethylated gene regions. The hypomethylated genes in patients with primary SS included LTA (encoding lymphotoxin α). Other relevant genes, such as CD247, TNFRSF25, PTPRC, GSTM1, and PDCD1, were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18, and IFITM1. A group of genes encoding members of the solute carrier proteins were differentially methylated. In addition, the transcription factor gene RUNX1 was hypermethylated in patients with primary SS, suggesting a possible connection to lymphoma predisposition. Gene ontology (GO) analysis of hypomethylated genes demonstrated enrichment of genes involved in lymphocyte activation and immune response. GO terms for hypermethylated genes included antigen processing and presentation.ConclusionThis is the first epigenome‐wide DNA methylation study in patients with primary SS. These findings highlight a role for DNA methylation in primary SS and identify disease‐associated DNA methylation changes in several genes and pathways in naive CD4+ T cells from patients with primary SS that may be involved in the pathogenesis of this disease.
Gene Expression Analysis of Murine and Human Osteoarthritis Synovium Reveals Elevation of Transforming Growth Factor β–Responsive Genes in Osteoarthritis‐Related Fibrosis
Authors: Remst D. F. G. , Blom A. B. , Vitters E. L. , Bank R. A. , van den Berg W. B. , Blaney Davidson E. N. , van der Kraan P. M. 
Published: November 2013

ObjectiveSynovial fibrosis is a major contributor to joint stiffness in osteoarthritis (OA). Transforming growth factor β (TGFβ), which is elevated in OA, plays a key role in the onset and persistence of synovial fibrosis. However, blocking of TGFβ in OA as a therapeutic intervention for fibrosis is not an option since TGFβ is crucial for cartilage maintenance and repair. Therefore, we undertook the present study to seek targets downstream of TGFβ for preventing OA‐related fibrosis without interfering with joint homeostasis.MethodsExperiments were performed to determine whether genes involved in extracellular matrix turnover were responsive to TGFβ and were elevated in OA‐related fibrosis. We analyzed gene expression in TGFβ‐stimulated human OA synovial fibroblasts and in the synovium of mice with TGFβ‐induced fibrosis, mice with experimental OA, and humans with end‐stage OA. Gene expression was determined by microarray, low‐density array, or quantitative polymerase chain reaction analysis.ResultsWe observed an increase in expression of procollagen genes and genes encoding collagen crosslinking enzymes under all of the OA‐related fibrotic conditions investigated. Comparison of gene expression in TGFβ‐stimulated human OA synovial fibroblasts, synovium from mice with experimental OA, and synovium from humans with end‐stage OA revealed that the genes PLOD2, LOX, COL1A1, COL5A1, and TIMP1 were up‐regulated in all of these conditions. Additionally, we confirmed that these genes were up‐regulated by TGFβ in vivo in mice with TGFβ‐induced synovial fibrosis.ConclusionMost of the up‐regulated genes identified in this study would be poor targets for therapy development, due to their crucial functions in the joint. However, the highly up‐regulated gene PLOD2, responsible for the formation of collagen crosslinks that make collagen less susceptible to enzymatic degradation, is an attractive and promising target for interference in OA‐related synovial fibrosis.
Pharmacologic Repression of Retinoic Acid Receptor–Related Orphan Nuclear Receptor γ Is Therapeutic in the Collagen‐Induced Arthritis Experimental Model
Authors: Chang Mi Ra , Lyda Brent , Kamenecka Theodore M. , Griffin Patrick R. 
Published: November 2013

ObjectiveThe nuclear receptor retinoic acid receptor–related orphan nuclear receptor γ (RORγ; T cell–specific isoform RORγt) is a key regulator of Th17 cell differentiation, controlling the production of the inflammatory cytokine interleukin‐17 (IL‐17). Lipopolysaccharide (LPS) stimulation of monocytes leads to the induction of RORγ. We previously showed that the potent and selective inverse agonist of RORγ, SR2211, was effective at suppressing IL‐17 production in EL4 cells. The aim of this study was to examine the effects of SR2211 treatment on proinflammatory cytokine expression in LPS‐stimulated RAW 264.7 cells as well as on joint inflammation in vivo in mice with collagen‐induced arthritis (CIA).MethodsCollagen was injected into the tail of DBA mice, followed by a booster inoculation 21 days later. Three days prior to the booster inoculation, SR2211 was administered twice daily for 15 days. Thymus, spleen, and draining lymph nodes (DLNs) were then harvested, and Th17 cell differentiation and DLN stimulation were performed.ResultsTreatment of Th17 cells with SR2211 suppressed the expression and production of inflammatory cytokines. Likewise, SR2211 reduced inflammatory cytokine production in LPS‐stimulated RAW 264.7 cells. Mice with CIA that received SR2211 twice daily for 15 days exhibited a statistically significant reduction in joint inflammation as compared to mice that received only vehicle. Interestingly, systemic Th1 cell activation was detected in SR2211‐treated mice with CIA, as indicated by an increase in interferon‐γ levels.ConclusionThe findings of this study support the idea of targeting RORγ to therapeutically repress inflammatory T cell function and macrophage activation in humans with rheumatoid arthritis. Compounds such as SR2211 have potential utility for the treatment of inflammatory disease.
Immunohistochemical characterization of novel murine monoclonal antibodies against human placenta‐specific 1
Authors: Ghods Roya , Ghahremani Mohammad Hossein , Darzi Maryam , Mahmoudi Ahmad‐Reza , Yeganeh Omid , Bayat Ali Ahmad , Pasalar Parvin , Jeddi‐Tehrani Mahmood , Zarnani Amir‐Hassan 
Published: November 2013

AbstractHuman PLAC1 (placenta‐specific 1) is a new member of cancer–testis antigens with 212 amino acids, and its expression is restricted to placenta and at much lower levels to testis. Recently, ectopic expression of the PLAC1 transcript has been demonstrated in a wide range of human tumors and cancer cell lines with a proposed function in tumor cell growth. No monoclonal anti‐PLAC1 antibody applicable to immunohis‐tochemical staining is available so far. To better understand the PLAC1 expression and localization, we aimed to produce monoclonal antibodies (mAbs) against the extracellular region of PLAC1. Mice were immunized with a synthetic peptide corresponding to the C‐terminal 11 amino acids of PLAC1 conjugated with a carrier protein. Hybridomas were produced by standard protocol and screened for positive reactivity by enzyme‐linked immunosorbent assay. Reactivity of final two clones was then assessed by Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). Both clones showed a specific immunostaining pattern in human term placenta as the positive control. Reactivity was mostly localized to the cytoplasm of syncytiotrophoblasts. One of the clones showed an excellent staining signal in breast, ovary, and prostate cancer cell lines. Importantly, no reactivity was observed with human lymph node cells or prostate. None of the mAbs were able to detect PLAC1 in Western blot. Based on the present results, these mAbs can be used for detection of PLAC1 in IHC and ICC techniques.
Prenatal diagnosis of femoral–facial syndrome: Report of two cases
Authors: Silvas Emil , Rypens Françoise , Jovanovic Mubina , Delezoide Anne‐Lise , Patey Natalie 
Published: November 2013

BACKGROUNDFemoral–facial syndrome (FFS), also known as femoral hypoplasia–unusual facial syndrome (FHUFS) is a rare disorder, which has been more frequently described in females. Only a few cases diagnosed prenatally have been reported so far in the literature. FFS is characterized by femoral hypoplasia and various facial abnormalities, which can be associated with a variety of other malformationsCASESIn this report, we present two male fetuses which were diagnosed with FFS after detection of short femora, micrognathia, and other anomalies by ultrasonography at the age of 14 and 16 weeks, respectively. The sonographic findings were confirmed at autopsy. The differential diagnosis of FFS with other disorders characterized by hypoplastic femora is discussedCONCLUSIONFFS represents a severe condition; hence, the importance of an early prenatal diagnosis, especially in light of offering counseling for affected parents. Birth Defects Research (Part A), 97:770–773, 2013. © 2013 Wiley Periodicals, Inc.
A Platinum(II) Phenylphenanthroimidazole with an Extended Side‐Chain Exhibits Slow Dissociation from a c‐Kit G‐Quadruplex Motif
Authors: Castor Katherine J. , Liu Zhaomin , Fakhoury Johans , Hancock Mark A. , Mittermaier Anthony , Moitessier Nicolas , Sleiman Hanadi F. 
Published: November 2013

AbstractA series of three platinum(II) phenanthroimidazoles each containing a protonable side‐chain appended from the phenyl moiety through copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) were evaluated for their capacities to bind to human telomere, c‐Myc, and c‐Kit derived G‐quadruplexes. The side‐chain has been optimized to enable a multivalent binding mode to G‐quadruplex motifs, which would potentially result in selective targeting. Molecular modeling, high‐throughput fluorescence intercalator displacement (HT‐FID) assays, and surface plasmon resonance (SPR) studies demonstrate that complex 2 exhibits significantly slower dissociation rates compared to platinum phenanthroimidazoles without side‐chains and other reported G‐quadruplex binders. Complex 2 showed little cytotoxicity in HeLa and A172 cancer cell lines, consistent with the fact that it does not follow a telomere‐targeting pathway. Preliminary mRNA analysis shows that 2 specifically interacts with the ckit promoter region. Overall, this study validates 2 as a useful molecular probe for c‐Kit related cancer pathways.
[6,6]‐Open and [6,6]‐Closed Isomers of C70(CF2): Synthesis, Electrochemical and Quantum Chemical Investigation
Authors: Samoylova Nataliya A. , Belov Nikita M. , Brotsman Victor A. , Ioffe Ilya N. , Lukonina Natalia S. , Markov Vitaliy Yu. , Ruff Adrian , Rybalchenko Alexey V. , Schuler Paul , Semivrazhskaya Olesya O. , Speiser Bernd , Troyanov Sergey I. , Magdesieva Tatiana V. , Goryunkov Alexey A. 
Published: November 2013

AbstractNovel difluoromethylenated [70]fullerene derivatives, C70(CF2)n (n=1–3), were obtained by the reaction of C70 with sodium difluorochloroacetate. Two major products, isomeric C70(CF2) mono‐adducts with [6,6]‐open and [6,6]‐closed configurations, were isolated and their homofullerene and methanofullerene structures were reliably determined by a variety of methods that included X‐ray analysis and high‐level spectroscopic techniques. The [6,6]‐open isomer of C70(CF2) constitutes the first homofullerene example of a non‐hetero [70]fullerene derivative in which functionalisation involves the most reactive bond in the polar region of the cage. Voltammetric estimation of the electron affinity of the C70(CF2) isomers showed that it is substantially higher for the [6,6]‐open isomer (the 70‐electron π‐conjugated system is retained) than the [6,6]‐closed form, the latter being similar to the electron affinity of pristine C70. In situ ESR spectroelectrochemical investigation of the C70(CF2) radical anions and DFT calculations of the hyperfine coupling constants provide evidence for the first example of an inter‐conversion between the [6,6]‐closed and [6,6]‐open forms of a cage‐modified fullerene driven by an electrochemical one‐electron transfer. Thus, [6,6]‐closed C70(CF2) constitutes an interesting example of a redox‐switchable fullerene derivative.
Untutored discrimination training on paired cell images influences visual learning in cytopathology
Authors: Evered Andrew , Walker Darren , Watt Andrew A. , Perham Nick 
Published: November 2013

BACKGROUNDCytologists must learn how to discriminate cells that might be visually very similar but have different neoplastic potential. The mechanism by which trainees learn this task is poorly researched and is the focus of the current investigation. Cognitive science offers a theoretical platform from which to design meaningful experiments that could lead to novel training strategies.METHODSThe interpretation of a cell image is a category‐discrimination task, and the process by which discrimination improves with practice is called perceptual learning. The study authors operationalized this concept by training 150 naive observers on paired cell images without providing explicit tuition, employing cervical cytology as a model system. Six strategies were tested, which differed according to the diagnostic category and level of interpretive difficulty of each image. Participants were tested before and after training to determine the extent to which visual learning had occurred.RESULTSDiagnostic accuracy improved for participants who were trained on normal/abnormal image pairs in which at least one member of the pair was “easy” to interpret (P < .05). Training was not effective when image pairs were drawn from the same diagnostic category or when both members of the pair were “difficult” to interpret (P > .05).CONCLUSIONSTraining on paired cell images without explicit tuition can be an efficient and effective means of visual learning in cytopathology, but only if care is taken to avoid image pairs from category boundaries. Training on same‐category image pairs is ineffective. This study is a step toward the development of perceptual learning modules for cytopathology. Cancer (Cancer Cytopathol) 2014;122:200–210. © 2013 American Cancer Society.
Production of sophorolipids synthesized on castor oil with glucose and glycerol by using Starmerella bombicola (ATCC 22214)
Authors: Bhangale Akash , Wadekar Sushant , Kale Sandip , Bhowmick Diptinarayan , Pratap Amit 
Published: November 2013

Biosurfactants such as sophorolipids are natural and eco‐friendly surfactants that are used in cosmetics and health care products. In addition to surfactant properties, sophorolipids also possess antimicrobial and skin healing properties. In the present work, castor oil (10%) was used as a non‐conventional carbon source in combination with glucose (10%) or with glycerol (15%) for fermentative production of novel sophorolipids by using Starmerella bombicola (ATCC 22214). The yields of sophorolipids are 6.1 g/L on castor oil with glucose as a carbon source and 2.7 g/L on castor oil with glycerol as a carbon source analyzed by anthrone method and HPLC. The structures of sophorolipids synthesized on castor oil were elucidated by liquid chromatography–mass spectrometry and 1H NMR of the purified compounds. The results indicated the incorporation of ricinoleic acid into sophorolipids without omega‐1 oxygenation step that is required for incorporation of oleic acid into sophorolipids. It resulted in the production of novel sophorolipids that can find various applications as cosmetic ingredients and antimicrobial agents.Practical applications: Castor oil, widely produced in India, contains palmitic acid (1–2%), strearic acid (1–2%), oleic acid (6–8%), linoleic acid (0.5–1%), and mainly ricinoleic acid (80–90%). The presence of hydroxyl fatty acid as ricinoleic acid makes castor oil different from other vegetable oils. Therefore, castor oil is being used as a valuable raw material in various chemicals industries. The present work proved that castor oil can be used as a new substrate for the production of sophorolipids with a novel structure having hydroxyl group on the moiety. The end product can be used for enhancement of surfactant properties in combination with a chemically synthesized surfactant.
Arranging Fullerenes through Hydrogen Bonding
Authors: Kraft Andreas , Gsänger Marcel , Beuerle Florian 
Published: November 2013

AbstractMultivalent organic molecules possessing spherically well‐arranged functionalities are promising building blocks for extended molecular networks. [60]Fullerene hexakisadducts are intriguing candidates allowing the organization of up to 12 functional groups within one molecule with high geometric precision. We have synthesized a hexakisadduct bearing 12 glycolic acid side‐chains in good yield and with high regioisomeric purity and elucidated its solid‐state structure from single crystals grown by the slow diffusion of dichloromethane into a methanol solution. Individual fullerene moieties are arranged in cubic close‐packing mode and form an extended network by means of multiple supramolecular interactions. Each molecule forms 24 hydrogen bonds and is connected to six neighbouring fullerene derivatives. The crystal structure showcases the first example of a 3D arrangement of fullerene derivatives by directed hydrogen bonding in the solid state. These findings indicate the high potential of six‐fold substituted fullerene derivatives as building blocks for crystalline frameworks.