bluuebunny/crossref_metadata_2025 huggingface dataset:
Stiffness Evolution of Granular Materials Stabilized with Foamed Bitumen and Cement
Authors: Halles Felipe , Thenoux Guillermo , González Álvaro
Published: November 2013

From the literature, it is possible to find two trends regarding the stiffness evolution of foamed bitumen stabilized–recycled mixtures. The first trend indicates that once the foamed bitumen mix reaches a constant value because of the curing process, the stiffness decreases with time because of load cycles. The second trend indicates that stiffness remains constant after the curing process. In this research, the stiffness evolution of foamed bitumen mixes stabilized with different bitumen and cement contents was studied. The stiffness was measured by using the indirect tensile fatigue test. Results indicated that once the foamed bitumen mix reached a constant value because of the curing process, stiffness decreased or remained constant depending on the stress level applied to the foamed bitumen layer. If the stress level is lower than a specific value, the stiffness of the mix will remain constant at a value extremely close to the initial stiffness. If the stress level is greater than a specific value, the stiffness of the mix will decrease gradually. In addition, the reduction rate of the stiffness will be greater with higher stress level. The analysis of results from mixes with different bitumen and cement contents allows identification of the effect of both stabilizing agents in the long-term stiffness evolution.
Reinforcement Tensile Behavior under Cyclic Moving Wheel Loads
Authors: Tang Xiaochao , Palomino Angelica M. , Stoffels Shelley M.
Published: November 2013

Numerous studies have revealed the benefits of using geogrids in a flexible pavement, especially for reducing permanent deformation. One of the questions that remain about the effectiveness of a geogrid in reinforcing of pavement is the extent to which the geogrid is engaged and mobilized throughout its service. This paper presents results of a laboratory study on various geogrid products embedded in flexible-pavement sections. The laboratory-scale pavement sections were subjected to cyclic moving wheel loads by using reduced-scale accelerated pavement testing (APT). During the APT, strains that developed in the geogrids were measured at intervals of loading applications by strain gauges installed in pairs on the upper and lower surfaces of the geogrid ribs. Permanent deformation of the subgrade was also measured at the same intervals of loading applications. The measurements of geogrid strains throughout the construction process indicated that the construction resulted in a considerable prestressing effect on the geogrids. Measurements from the individual strain gauges in pairs showed that the gauges installed on the upper surfaces of the ribs were in compression while those on the lower surfaces were in tension; the situation suggested a significant effect on the flexural deflection of the ribs on the tensile strain measurements from the strain gauges. Furthermore, it was observed that geogrid ribs in the longitudinal direction of traffic loading were not mobilized, while considerable strains were developed in geogrid ribs in the direction transverse to traffic loading. A clear correlation was found between the reinforcing forces developed in the geogrids and the performance of the reinforced subgrade in relation to resisting permanent deformation.
Cortical Auditory-Evoked Potentials (CAEPs) in Adults in Response to Filtered Speech Stimuli
Authors: Carter Lyndal , Dillon Harvey , Seymour John , Seeto Mark , Van Dun Bram
Published: November 2013

Background:Previous studies have demonstrated that cortical auditory-evoked potentials (CAEPs) can be reliably elicited in response to speech stimuli in listeners wearing hearing aids. It is unclear, however, how close to the aided behavioral threshold (i.e., at what behavioral
sensation level) a sound must be before a cortical response can reliably be detected.Purpose:The purpose of this study was to systematically examine the relationship between CAEP detection and the audibility of speech sounds (as measured behaviorally), when the listener is wearing a
hearing aid fitted to prescriptive targets. A secondary aim was to investigate whether CAEP detection is affected by varying the frequency emphasis of stimuli, so as to simulate variations to the prescribed gain-frequency response of a hearing aid. The results have direct implications for
the evaluation of hearing aid fittings in nonresponsive adult clients, and indirect implications for the evaluation of hearing aid fittings in infants.Research Design:Participants wore hearing aids while listening to speech sounds presented in a sound field. Aided thresholds were measured,
and cortical responses evoked, under a range of stimulus conditions. The presence or absence of CAEPs was determined by an automated statistic.Study Sample:Participants were adults (6 females and 4 males). Participants had sensorineural hearing loss ranging from mild to severe-profound
in degree.Data Collection and Analysis:Participants' own hearing aids were replaced with a test hearing aid, with linear processing, during assessments. Pure-tone thresholds and hearing aid gain measurements were obtained, and a theoretical prediction of speech stimulus audibility for
each participant (similar to those used for audibility predictions in infant hearing aid fittings) was calculated. Three speech stimuli, (/m/, /t/, and /g/) were presented aided (monaurally, nontest ear occluded), free field, under three conditions (+4 dB/octave, −4 dB/octave, and without
filtering), at levels of 40, 50, and 60 dB SPL (measured for the unfiltered condition). Behavioral thresholds were obtained, and CAEP recordings were made using these stimuli. The interaction of hearing loss, presentation levels, and filtering conditions resulted in a range of CAEP test behavioral
sensation levels (SLs), from −25 to +40 dB.Results:Statistically significant CAEPs (p < .05) were obtained for virtually every presentation where the behavioral sensation level was >10 dB, and for only 5% of occasions when the sensation level was negative. In these
(“false-positive”) cases, the greatest (negative) sensation level at which a CAEP was judged to be present was −6 dB SL.Conclusions:CAEPs are a sensitive tool for directly evaluating the audibility of speech sounds, at least for adult listeners. CAEP evaluation was
found to be more accurate than audibility predictions, based on threshold and hearing aid response measures.
Responsiveness in Rheumatoid Arthritis. A Report from the OMERACT 11 Ultrasound Workshop
Authors: Iagnocco Annamaria , Naredo Esperanza , Wakefield Richard , Bruyn George A.W. , Collado Paz , Jousse-Joulin Sandrine , Finzel Stephanie , Ohrndorf Sarah , Delle Sedie Andrea , Backhaus Marina , Berner-Hammer Hilde , Gandjbakhch Frederique , Kaeley Gurjit , Loeuille Damien , Moller Ingrid , Terslev Lene , Aegerter Philippe , Aydin Sibel , Balint Peter V. , Filippucci Emilio , Mandl Peter , Pineda Carlos , Roth Johannes , Magni-Manzoni Silvia , Tzaribachev Niolay , Schmidt Wolfgang A. , Conaghan Philip G. , D’Agostino Maria-Antonietta
Published: November 2013

Objective.

To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Task Force on the validity of different US measures in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) presented during the OMERACT 11 Workshop.

Methods.

The Task Force is an international group aiming to iteratively improve the role of US in arthritis clinical trials. Recently a major focus of the group has been the assessment of responsiveness of a person-level US synovitis score in RA: the US Global Synovitis Score (US-GLOSS) combines synovial hypertrophy and power Doppler signal in a composite score detected at joint level. Work has also commenced examining assessment of tenosynovitis in RA and the role of US in JIA.

Results.

The US-GLOSS was tested in a large RA cohort treated with biologic therapy. It showed early signs of improvement in synovitis starting at Day 7 and increasing to Month 6, and demonstrated sensitivity to change of the proposed grading. Subsequent voting questions concerning the application of the US-GLOSS were endorsed by > 80% of OMERACT delegates. A standardized US scoring system for detecting and grading severity of RA tenosynovitis and tendon damage has been developed, and acceptable reliability data were presented from a series of exercises. A preliminary consensus definition of US synovitis in pediatric arthritis has been developed and requires further testing.

Conclusion.

At OMERACT 11, consensus was achieved on the application of the US-GLOSS for evaluating synovitis in RA; and work continues on development of RA tenosynovitis scales as well as in JIA synovitis.
Influence of barefoot, barefoot inspired and conventional shoes on tibial accelerations and loading kinetics during running in natural rearfoot strikers
Authors: Sinclair J. , Taylor P.J. , Andrews S.
Published: November 2013

Running barefoot and in footwear designed to mimic barefoot locomotion, has received considerable attention in footwear research. This study examined the differences in impact force and tibial acceleration parameters. Ten male participants completed 10 trials when running barefoot, in vibram five-fingers and in conventional footwear at three locomotion velocities: walk, jog and run (1.25, 3.5 and 5.0 m/s, respectively). Impact force and tibial acceleration parameters were synchronously obtained and contrasted between footwear and velocities using 3 (footwear) x 3 (velocity) repeated measures ANOVA's. Significant main effects were obtained for both footwear and velocity which suggest that barefoot running at higher velocities is associated with increases in impact loading magnitude. This leads to the conclusion that barefoot locomotion may be associated with increased risk of injury regardless of running velocity and that more specifically running barefoot at higher velocities should be undertaken with caution.
Evaluación de la longitud de grietas por fatiga mediante la deformación plástica en muestras compactas de tracción empleando el ruido magnético de Barkhausen
Authors: De los Reyes-Rodríguez F. , De Diego-Velasco G. , Capó-Sánchez J. , Franco-Fidalgo E.
Published: November 2013

En este trabajo se estudia la influencia de distintos parámetros de la señal del ruido magnético de Barkhausen (RMB) en la deformación plástica (DP) y, en consecuencia, en la longitud de grieta de probetas compactas de tracción (PCT), fabricadas con aceros 12Cr1MoV y 11Cr1Mo respectivamente, los cuales son empleados principalmente en la industria termoenergética a nivel mundial. Este estudio se lleva a cabo con el objetivo de conocer, por medio de parámetros del RMB, la longitud de la grieta y el momento más próximo a su incubación, lo cual permite perfeccionar el proceso de preagrietamiento, previo el ensayo de velocidad de propagación de grietas a elevadas temperaturas. Se determina el voltaje medio cuadrado (Vrms) y el máximo voltaje de pico (MVP) de la señal del RMB, magnitudes que decrecen con el incremento de la deformación plástica para cada uno de los aceros estudiados; por otra parte, con el incremento de la deformación plástica se observa, para valores medios de la frecuencia, una correlación lógica entre esta magnitud y la densidad espectral, así como una variación de la amplitud, ancho y forma de los picos de la envolvente de la señal.
Fault Detection for Dynamic Systems based on Multirate Sampling
Authors: Qiu Aibing , Shi Junjie , Wang Shengfeng
Published: November 2013

In many complex systems such as distributed multi-sensor systems, different sensors may work with multiple sampling periods. In this paper, the problem of fault detection for this kind of systems is considered. Firstly, by mapping the multirate measurements onto fast time instants, a new measurement equation with variable dimensions is obtained. Based on this, a multirate Kalman filter based residual generator is designed to deliver residual signal at a fast rate, which is further evaluated in a dynamic window. The proposed scheme has no need to process some troublesome issues such as noise correlation and causality constrains caused by traditional lifting technique. A numerical simulation is presented to illustrate our approach.
Making accessibility analyses accessible: A tool to facilitate the public review of the effects of regional transportation plans on accessibility
Authors: Golub Aaron , Robinson Glenn , Nee Brendan
Published: November 2013

The regional transportation planning process in the United States has not been easily opened to public oversight even after strengthened requirements for public participation and civil rights considerations. In the effort to improve the public review of regional transportation plans, this paper describes the construction of a proof-of concept web-based tool designed to analyze the effects of regional transportation plans on accessibility to jobs and other essential destinations. The tool allows the user to analyze disparities in accessibility outcomes by demographic group, specifically income and race, as required by civil rights-related planning directives. The tool makes cumulative-opportunity measures of the number of essential destinations reachable within certain times by public transit and automobile. The tool is constructed to analyze the San Francisco Bay Area’s 2005 regional transportation plan. Users can choose to make measures for a particular neighborhood or for all neighborhoods in the region with certain demographic characteristics. Two example analyses are shown with an interpretation and discussion of calculator outputs.
Book Review: Triumph of the City, Edward Glaeser
Authors: Good Max , Derrible Sybil
Published: November 2013

The authors review the book Triumph of the City by Edward Glaeser, published in 2011.
From Novelty to Normal: 3DTV as Special Effect
Authors: Brown Simon
Published: November 2013

In cinemas and on television, the 3D viewing experience is marketed as being both more ‘immersive’ than 2D, and as an ‘experience’ which augments the normal 2D viewing experience. Focussing on 3D on television, this article presents an aesthetic analysis of a range of 3DTV content. In doing so it considers the extent to which the variety of 3DTV programming, coupled with its low market penetration, offers a barrier to 3DTV becoming familiar enough to move beyond being a gimmick or a special effect, and explores what 3DTV programme makers are doing to overcome this.
Building and Sustaining Community Cyber‐Infrastructure for the Hydrologic Sciences
Authors: Arrigo Jennifer , Tarboton David , Couch Alva
Published: November 2013

As part of its mission to empower scientists to discover, use, store, and share water data from multiple sources, the Consortium of Universities for the Advancement of Hydrologic Sciences, Inc. (CUAHSI) Water Data Center (http://wdc.cuahsi.org) held a conference to provide a forum for researchers working in hydroinformatics and modeling, scientists using and managing large amounts of data, and others interested in advancing standards and best practices for water data access, discovery, and sharing.
Variety Is the Spice of Fall Meeting
Authors: Finn Carol
Published: November 2013

In just a few weeks, thousands of Earth and space scientists will gather in San Francisco for AGU's 46th annual Fall Meeting, where they will present their research, participate in workshops and town hall meetings, and network until they drop. With a crowd this large, there's bound to be some variety in the types of attendees. But what makes Fall Meeting such an amazing and inspiring event are the forms that variety takes.
Conditions and threshold for magma transfer in the layered upper crust: Insights from experimental models
Authors: Ritter Malte C. , Acocella Valerio , Ruch Joel , Philipp Sonja L.
Published: November 2013

Magma transfer, i.e., dike propagation, is partly controlled by Young's modulus (elasticity) contrasts (ratio upper layer to lower layer modulus) in the host rock. Here we try to better constrain the elasticity contrasts controlling the propagation velocity of dikes and their arrest. We simulate dike propagation in layered elastic media with different elasticity contrasts. Salted gelatin and water represent host rock and magma, respectively. For common density ratios between magma and host rock (~1.1), velocity variations are observed and a critical threshold in the elasticity contrast between layers results in the Young's modulus ratio of 2.1 ± 0.6. Naturally occurring elasticity contrasts can be much higher than this experimental threshold, suggesting that dike arrest due to heterogeneous elastic host rock properties is more frequent than expected. Examples of recently deflected or stalled dikes inside volcanoes and the common presence of high‐velocity bodies below volcanoes suggest that better defining elasticity contrasts below volcanoes helps in forecasting eruptions.
High‐Performance Hybrid Solar Cell Made from CdSe/CdTe Nanocrystals Supported on Reduced Graphene Oxide and PCDTBT
Authors: Tong Shi Wun , Mishra Nimai , Su Chen Liang , Nalla Venkatram , Wu Wenya , Ji Wei , Zhang Jie , Chan Yinthai , Loh Kian Ping
Published: November 2013

Core/shell tetrapods synthesized from CdSe and CdTe exhibit a type II band offset that induces separation of charge upon photoexcitation and localizes carriers to different regions of the tetrahedral geometry. CdSe/CdTe nanocrystals immobilized on oleylamine‐functionalized reduced graphene oxide (rGO) sheets can be homogeneously mixed with an organic dye (PCDTBT) to form donor–acceptor dispersed heterojunctions and exhibit a high power conversion efficiency of ∼3.3% in solar cell devices. The near‐IR light absorbing type II nanocrystals complement the absorption spectrum of the visible light‐absorbing organics. The high efficiency is attributed to the amine‐functionalized rGO sheets, which allow intimate contact with the nanocrystals and efficient dispersal in the organic matrix, contributing to highly efficient charge separation and transfer at the nanocrystal, rGO, and polymer interfaces.
Genetic services and attitudes in primary care pediatrics
Authors: Rinke Michael L. , Mikat‐Stevens Natalie , Saul Robert , Driscoll Amy , Healy Jill , Tarini Beth A.
Published: November 2013

Given the integral role primary care pediatricians (PCPs) play in caring for children with genetic conditions, we aimed to identify current practices of PCPs regarding genetic patients, their attitudes toward genetic medical care and their choices regarding family history taking. We conducted an on‐line survey of a national convenience sample of PCPs associated with the American Academy of Pediatrics' Quality Improvement Innovation Networks. Eighty‐eight respondents (29% response rate) were included in the analysis. Seventy‐four (86%) reported ordering genetic based tests three or less times annually. Eleven (13%) strongly agreed that they discuss with patients the potential risks, benefits, and limitations of genetic tests. Forty‐three (49%) agreed or strongly agreed that they feel competent in providing healthcare to patients related to genetics and genomics. Perceived competence was not associated with more recent training (P = 0.29), number of genetic tests ordered annually (P = 0.84) or mean number of weekly patient encounters (P = 0.15). 100% of participants stated that taking a family history is important. 27 (31%) agreed or strongly agreed that they gather a minimum of a three‐generation family history. Forty‐one of the 63 participants with an electronic health record (65%) reported their system was fair or poor in its ability to easily capture a three‐generation family history. PCPs interested in quality improvement reported variation in care practices for children with genetic diseases and a majority did not feel competent to provide genetic related healthcare. Research should focus on improving the care and diagnosis of children with genetic disorders and enhanced integration of genetic medicine into routine primary preventative care. © 2013 Wiley Periodicals, Inc.
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

Acylsilanes 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

An 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

The 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

The 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

Objective

Primary 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.

Methods

A 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.

Results

Genome‐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.

Conclusion

This 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

Objective

Synovial 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.

Methods

Experiments 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.

Results

We 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.

Conclusion

Most 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

Objective

The 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).

Methods

Collagen 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.

Results

Treatment 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.

Conclusion

The 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.
Technological information inequality as an incessantly moving target: The redistribution of information and communication capacities between 1986 and 2010
Authors: Hilbert Martin
Published: November 2013

This article provides first‐time empirical evidence that the digital age has first increased and then (only very recently) decreased global, international, and national inequalities of information and communication capacities among and within societies. Previous studies on the digital divide were unable to capture the detected trends appropriately, because they worked with proxies, such as the number of subscriptions or related investments, without considering the vast heterogeneity in informational performance among technological devices. We created a comprehensive data set (based on over 1,100 sources) that allows measuring information capacity directly, in bits per second, bits, and instructions per second. The newly proposed indicators provide insights into inequalities in access to, usage of, and impact of digitized information flows. It shows that the digital divide has gone into a second stage, which is based on a relative universalization of technological devices and a continuously evolving divide in terms of communication capacity.
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

Human 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

BACKGROUND

Femoral–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 malformations

CASES

In 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 discussed

CONCLUSION

FFS 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

A 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

Novel 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

BACKGROUND

Cytologists 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.

METHODS

The 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.

RESULTS

Diagnostic 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).

CONCLUSIONS

Training 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.
Structural complexity of hexagonal prismatic crystal specimens of fluorapatite‐gelatine nanocomposites: A case study in biomimetic crystal research
Authors: Kniep Rüdiger , Simon Paul , Rosseeva Elena
Published: November 2013

Hexagonal prismatic crystal‐like entities of fluorapatite‐gelatine nanocomposites were grown by double‐diffusion in gelatine gels. The Bragg pattern of the specimens (containing 2.3(3) wt.‐% gelatine) is consistent with fluorapatite. TEM images together with atomistic computer simulations reveal the material to be best described as a mosaic‐dominated nanocomposite superstructure. Intrinsic electric dipole fields (detected by electron holography), generated by a non‐classical crystallization process of composite nanoboards (elongated platelets), cause the integration of a meso/macroscopic pattern (symmetry: 6/m) of gelatine microfibrils into the superstructure matrix.
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

Multivalent 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.
Synthesis of Hybrid Ferrocene‐Proline Amides as Active Catalysts for Asymmetric Aldol Reactions in Water
Authors: Patti Angela , Pedotti Sonia
Published: November 2013

Ferrocenyl substituents were employed as lipophilic moieties and introduced into a prolinamide scaffold to afford new catalysts that were suitable for use in “on water” conditions. Five proline amides that contain a ferrocene unit were synthesized from easily accessible ferrocenylamines and evaluated as catalysts in the asymmetric direct aldol condensation of cyclohexanone with aldehydes in an aqueous medium. Optimal substrate conversion and stereoselectivity were achieved in brine and in the presence of benzoic acid as an additive. All the examined catalysts displayed good activity with a catalyst loading of 5 mol‐%, and the best results in terms of enantioselectivity were obtained by using a ferrocenyl‐prolineamide with an additional (S) chiral center. In the presence of this catalyst, a variety of aromatic aldehydes underwent a reaction in a reasonable amount time with just 2 equiv. of the cyclic ketone to give the expected aldol products in high yields (65–98 %) and with high stereoselectivities (up to 94 % ee, dr up to 93:7).
Copper‐Catalyzed Vinylsilane Allylation
Authors: Cornelissen Loïc , Vercruysse Sébastien , Sanhadji Ayoub , Riant Olivier
Published: November 2013

Soft reaction conditions, particularly important in total synthesis, have dragged many researchers into the field of silylated organic compounds. Hereby, we describe a new copper‐catalyzed vinylsilane transformation. Various vinylsilanes were allylated by using a copper(I) salt, and this led to the formation of polysubstituted 1,4‐dienes bearing sensitive moieties such as halogens, ketones, and aldehydes.
Synthesis of a Series of Enantiopure Polyhydroxylated Bicyclic N‐Heterocycles from an L‐Erythrose‐Derived Nitrone and Alkoxyallenes
Authors: Jasiński Marcin , Moreno‐Clavijo Elena , Reissig Hans‐Ulrich
Published: November 2013

Two different lithiated alkoxyallenes and the enantiopure L‐erythrose‐derived cyclic nitrone (+)‐3 were used as precursors for the preparation of novel bicyclic 2H‐1,2‐oxazine derivatives, which were formed as single diastereomers. A highly stereoselective hydroboration/oxidation sequence provided key substrates that were suitable for the synthesis of a series of polyhydroxylated bicyclic N‐heterocycles, including unique 5‐oxaindolizidines such as 8 and 12. Depending on the protecting groups installed, a straightforward ring‐opening/recyclization protocol allowed the preparation of the corresponding pyrrolizidines bearing two, three or four free hydroxy groups. By inversion of the order of reaction steps, the synthesis of novel isomeric azabicyclo[3.2.0]heptane derivatives that are the lower homologues of pyrrolizidines and indolizidines were achieved. The prepared novel polyhydroxylated compounds were examined for their property as glycosidase inhibitors, but none of the compounds showed noteworthy activity.