bluuebunny/crossref_metadata_2025 huggingface dataset:
Het probleem van meetinvariantie bij het vergelijken van subgroepen op basis van somscores
Authors: De Boeck Arne , Hardyns Wim , Pauwels Lieven
Published: October 2014

The problem of measurement invariance when using sum scores to make group comparisons. A case study on the measurement of avoidance behavior

Using summated scale scores to make group comparisons is only meaningful if one can assume that the scale measures attribute in the same way in each of the groups involved in the comparison. This assumption is called measurement invariance. This contribution discusses the use of modern statistical measurement models to test this assumption and to verify the consequences of a possible violation for the comparison of group means. In the empirical part of the contribution the authors illustrate their account by examining whether a scale assessing avoidance behavior – commonly used in fear of crime research – is invariant across gender and age groups.
Applying a Political Economy of Health standpoint to traditional food acquisition practices and the inequitable prevalence of obesity and diabetes amongst First Nations peoples in British Columbia
Authors: Merz Colin , Steinberg Malcolm
Published: October 2014

The inequitable population prevalence rates of obesity and diabetes being experienced by First Nations peoples in British Columbia require public health protection practitioners to deepen their inquiry into the social determinants of these chronic conditions. These attempts need to be placed within the context of food insecurity that is garnering growing attention from public health at large and, more specifically, within the emerging Indigenous consensus understanding of the relationship between the ongoing nutrition transition and the inequitable prevalence rates of these conditions. We suggest that these reflections are productively theorized from a Political Economy of Health standpoint and supported by representative findings from the First Nations Regional Longitudinal Health Survey. This theoretical perspective supports the viewpoint that the inequitable expression of these chronic conditions can be attributed to the nutrition transition that populations experienced as they were shifted from a traditional subsistence diet to a commoditized, industrialized food production system. This analysis also supports the structural recommendations of the British Columbia Food Systems Network Working Group on Indigenous Food Sovereignty that would remove barriers and threats to traditional food acquisition. These include making environmental protection and conservation of biological diversity a priority in all land use planning; setting aside adequate tracts of land for the protection, conservation, and restoration of Indigenous food systems; giving priority to traditional food and cultural values in contemporary forestry, fisheries, rangeland, and agrarian management policies and practice; and giving priority to Indigenous food and cultural harvesting over commoditized, export-oriented commercial harvesting. Public health protection practitioners will be progressively challenged to support these recommendations by the communities they serve. Although there is no guarantee that implementation of these recommendations will reverse the trend of decreasing participation rates in traditional food harvesting in British Columbia, we suggest that unless many of the systemic irrationalities, vested interests, and historically unjust rationales for maintaining the status quo with respect to Indigenous food sovereignty are interrogated and challenged, an ancient lifeway grounded in demonstrably sustainable traditional food harvesting practices will remain threatened.
Reprogramming Human Retinal Pigmented Epithelial Cells to Neurons Using Recombinant Proteins
Authors: Hu Qirui , Chen Renwei , Teesalu Tambet , Ruoslahti Erkki , Clegg Dennis O.
Published: October 2014

Somatic cells can be reprogrammed to an altered lineage by overexpressing specific transcription factors. To avoid introducing exogenous genetic material into the genome of host cells, cell-penetrating peptides can be used to deliver transcription factors into cells for reprogramming. Position-dependent C-end rule (CendR) cell- and tissue-penetrating peptides provide an alternative to the conventional cell-penetrating peptides, such as polyarginine. In this study, we used a prototypic, already active CendR peptide, RPARPAR, to deliver the transcription factor SOX2 to retinal pigmented epithelial (RPE) cells. We demonstrated that RPE cells can be directly reprogrammed to a neuronal fate by introduction of SOX2. Resulting neuronal cells expressed neuronal marker mRNAs and proteins and downregulated expression of RPE markers. Cells produced extensive neurites and developed synaptic machinery capable of dye uptake after depolarization with potassium. The RPARPAR-mediated delivery of SOX2 alone was sufficient to allow cell lineage reprogramming of both fetal and stem cell-derived RPE cells to become functional neurons.
Salient features of the dual‐frequency, dual‐polarized, Doppler radar for remote sensing of precipitation
Authors: Vega Manuel A. , Chandrasekar V. , Carswell James , Beauchamp Robert M. , Schwaller Mathew R. , Nguyen Cuong
Published: October 2014

The global precipitation measurement (GPM) mission is an international satellite mission to obtain accurate observations of precipitation on a global scale every 3 h. Its (GPM) core satellite was launched on 27 February 2014 with two science instruments: the microwave imager and the dual‐frequency precipitation radar. Ground validation is an integral part of the GPM mission where instruments are deployed to complement and correlate with spacecraft instruments. The dual‐frequency, dual‐polarization, Doppler radar (D3R) is a critical ground validation instrument that was developed for the GPM program. This paper describes the salient features of the D3R in the context of the GPM ground validation mission. The engineering and architectural overview of the radar is described, and observations from successful GPM ground validation field experiments are presented.
Multimodel Bayesian analysis of groundwater data worth
Authors: Xue Liang , Zhang Dongxiao , Guadagnini Alberto , Neuman Shlomo P.
Published: October 2014

We explore the way in which uncertain descriptions of aquifer heterogeneity and groundwater flow impact one's ability to assess the worth of collecting additional data. We do so on the basis of Maximum Likelihood Bayesian Model Averaging (MLBMA) by accounting jointly for uncertainties in geostatistical and flow model structures and parameter (hydraulic conductivity) as well as system state (hydraulic head) estimates, given uncertain measurements of one or both variables. Previous description of our approach was limited to geostatistical models based solely on hydraulic conductivity data. Here we implement the approach on a synthetic example of steady state flow in a two‐dimensional random log hydraulic conductivity field with and without recharge by embedding an inverse stochastic moment solution of groundwater flow in MLBMA. A moment‐equations‐based geostatistical inversion method is utilized to circumvent the need for computationally expensive numerical Monte Carlo simulations. The approach is compatible with either deterministic or stochastic flow models and consistent with modern statistical methods of parameter estimation, admitting but not requiring prior information about the parameters. It allows but does not require approximating lead predictive statistical moments of system states by linearization while updating model posterior probabilities and parameter estimates on the basis of potential new data both before and after such data are actually collected.
Probabilistic collocation method for strongly nonlinear problems: 2. Transform by displacement
Authors: Liao Qinzhuo , Zhang Dongxiao
Published: October 2014

The probabilistic collocation method (PCM) is widely used for uncertainty quantification and sensitivity analysis. In paper 1 of this series, we demonstrated that the PCM may provide inaccurate results when the relation between the random input parameter and the model response is strongly nonlinear, and presented a location‐based transformed PCM (xTPCM) to address this issue, relying on the transform between response and location. However, the xTPCM is only applicable for one‐dimensional problems, and two or three‐dimensional problems in homogeneous media. In this paper, we propose a displacement‐based transformed PCM (dTPCM), which is valid in two or three‐dimensional problems in heterogeneous media. In the PCM, we first select collocation points and run model/simulator to obtain response, and then approximate the response by polynomial construction. Whereas, in the dTPCM, we apply motion analysis to transform the response to displacement. That is, the response field is now represented by the displacement field. Next, we approximate the displacement instead of the response by polynomial, since the displacement is more linear to the input parameter than the response. Finally, we randomly generate a sufficient number of displacement samples and transform them back to obtain response samples to estimate statistical properties. Through multiphase flow and solute transport examples, we demonstrate that the dTPCM provides much more accurate statistics than does the PCM, and requires considerably less computer time than does the Monte Carlo (MC) method.
Prevalence of and Factors Associated With Increased Arterial Stiffness in Patients With Primary Sjögren's Syndrome
Authors: Sabio José Mario , Sánchez‐Berná Isabel , Martinez‐Bordonado Josefina , Vargas‐Hitos José Antonio , Navarrete‐Navarrete Nuria , Expósito Ruíz Manuela , Jiménez‐Alonso Juan
Published: October 2014

Objective

To compare the presence of subclinical atherosclerosis measured by means of pulse wave velocity (PWV) in women with primary Sjögren's syndrome (SS) versus a healthy age‐ and sex‐matched control group, and to identify factors independently associated with PWV in primary SS.

Methods

Forty‐four women with primary SS and 78 age‐matched healthy women without overt cardiovascular (CV) diseases were assessed for traditional and nontraditional CV risk factors. PWV was also performed. A linear regression analysis was used to identify factors independently associated with PWV in primary SS.

Results

Women with primary SS had significantly higher PWV than controls (P = 0.030), and the frequency of increased PWV was significantly higher in this group (25% versus 8%; P = 0.013). The proportion of patients ages ≤50 years (ratio 4.6) with increased PWV was almost 2‐fold higher than those ages >50 years (ratio 2.4) with respect to controls. Positivity for anti‐SSB was more frequent in patients with normal PWV than in those with increased PWV (61% versus 18%; P = 0.034). Women with primary SS and increased PWV had lower levels of 25‐hydroxyvitamin D (25[OH]D; P = 0.047) than primary SS patients with normal PWV. In addition, 25(OH)D levels tended to correlate inversely with PWV in women with primary SS (P = 0.067), but not in controls (P = 0.97). In multivariate analysis, the Framingham Risk Score (FRS) and Sjögren's Syndrome Damage Index emerged as factors independently correlated with PWV.

Conclusion

Women with primary SS had higher PWV than controls, but a similar FRS. The FRS and chronic damage were found to be independently associated with PWV.
Quasi‐Three‐Dimensional Angle‐Tolerant Electromagnetic Illusion Using Ultrathin Metasurface Coatings
Authors: Jiang Zhi Hao , Werner Douglas H.
Published: October 2014

Low‐profile and light‐weight coatings that offer comprehensive manipulation of the electromagnetic scattering for finite‐length objects are highly desirable, but not yet achieved, for applications including camouflaging, deceptive sensing, radar cognition control, and defense security. Here, for the first time, the theory, practical design, and experimental demonstration of quasi‐three‐dimensional and angle‐tolerant electromagnetic illusion coatings are presented which have been enabled by ultrathin single‐layer functional metasurfaces. By controlling the multiple Mie scattering coefficients using the tangential and non‐vanishing radial electromagnetic responses of the metasurface, the quasi‐two‐dimensional coating transforms the electromagnetic perception of one object to mimic that of another which has been pre‐selected by the designer. The illusion coating, which is homogeneous but anisotropic, is realized using hundreds of composite electric and magnetic sub‐wavelength unit cells operating at frequencies away from their resonance. Two different prototypes of the metasurface illusion coatings were fabricated and characterized, demonstrating very good camouflaging performance for finite‐length dielectric as well as conducting objects within a field‐of‐view up to ±10° off normal. This work paves the way for practical artificially engineered material coatings with exotic and versatile scattering control capabilities that would enable a wide range of applications throughout the entire electromagnetic spectrum.
Mechanochemical Stimulation of MCF7 Cells with Rod‐Shaped Fe–Au Janus Particles Induces Cell Death Through Paradoxical Hyperactivation of ERK
Authors: Kilinc Devrim , Lesniak Anna , Rashdan Suad A. , Gandhi Dhruv , Blasiak Agata , Fannin Paul C. , von Kriegsheim Alex , Kolch Walter , Lee Gil U.
Published: October 2014

Multifunctional nanoparticles that actively target‐specific tissues are studied for cancer diagnosis and treatment. Magnetically and optically active particles are of particular interest because they enable multiple imaging modalities and physically modulated therapies, such as magnetic hyperthermia. Fe–Au nanorods are synthesized that have a long iron segment, coated with polyethylene glycol, and a short gold tip functionalized with heregulin (HRG), a known ligand of ErbB family of receptors. HRG–nanorods preferentially target MCF7 cells relative to MDA‐MB‐231 cells, as demonstrated in a novel microfluidics device. Targeting rates of these classical breast cancer cells correlate with their differential expression of ErbB2/3 receptors. HRG–nanorod binding stimulates the extracellular signal‐regulated kinase 1/2 (ERK) phosphorylation in MCF7 cells. The increase in ERK phosphorylation is linked to “active zones,” dynamic regions in the cell periphery, which exhibit higher rates of particle binding than the rest of the cell. Periodically stretching cells using magnetic tweezers further activates ERK, which leads to cell death in cells co‐treated with B‐Raf inhibitors, through ERK hyperactivation. Although to a lesser extent, cell death is also achieved through magnetic hyperthermia. These results demonstrate nanoscale targeting and localized mechanochemical treatment of specific cancer cell lines based on their receptor expression using multifunctional nanoparticles.
Direct Assembly of Benzo[a]carbazole‐5‐carboxylates via a Diels–Alder Reaction with Arynes and 3‐Alkenylindoles
Authors: Tao Yuan , Zhang Fei , Tang Chen‐Yu , Wu Xin‐Yan , Sha Feng
Published: October 2014

A concise and direct synthetic strategy for the construction of benzo[a]carbazole‐5‐carboxylates has been disclosed via the Diels–Alder reaction of arynes and 3‐alkenylindoles. The reaction is highly selective and affords the benzo[a]carbazole‐5‐carboxylates in good‐to‐excellent yields.
Access to Fluorine‐Containing Asparagine and Glutamine Analogues via Palladium‐Catalyzed Formate Reduction
Authors: Usuki Yoshinosuke , Wakamatsu Yosuke , Yabu Minoru , Iio Hideo
Published: October 2014

A synthesis of fluorine‐containing asparagine and glutamine analogues via palladium‐catalyzed formate reduction of fluorinated carbonate esters is described. Primary amide moieties at the side‐chain of asparagine and glutamine were successfully replaced with fluoroolefins, which are proposed to be aprotic mimics for amides due to their electronic properties.
Mechanics of freely‐suspended ultrathin layered materials
Authors: Castellanos‐Gomez Andres , Singh Vibhor , van der Zant Herre S. J. , Steele Gary A.
Published: October 2014

The study of atomically thin two‐dimensional materials is a young and rapidly growing field. In the past years, a great advance in the study of the remarkable electrical and optical properties of 2D materials fabricated by exfoliation of bulk layered materials has been achieved. Due to the extraordinary mechanical properties of these atomically thin materials, they also hold a great promise for future applications such as flexible electronics. For example, this family of materials can sustain very large deformations without breaking. Due to the combination of small dimensions, high Young's modulus and high crystallinity of 2D materials, they have attracted the attention of the field of nanomechanical systems as high frequency and high quality factor resonators. In this article, we review experiments on static and dynamic response of 2D materials. We provide an overview and comparison of the mechanics of different materials, and highlight the unique properties of these thin crystalline layers. We conclude with an outlook of the mechanics of 2D materials and future research directions such as the coupling of the mechanical deformation to their electronic structure.
Mayflies (Ephemeroptera) as indicators of environmental changes in the past five decades: a case study from the Morava and Odra River Basins (Czech Republic)
Authors: Zedková Blanka , Rádková Vanda , Bojková Jindřiška , Soldán Tomáš , Zahrádková Světlana
Published: October 2014

Large‐scale and intensive human activities have caused widespread and profound changes in the diversity and structure of biological communities. Historical or long‐term data are an important tool for the quantification and understanding of temporal changes. A comparison of Ephemeroptera collected at 60 streams in the Morava and Odra river basins in two periods, 1955–1960 and 2006–2011, enabled an estimate of changes in their assemblages induced by various human pressures to be made.

The taxonomic composition of mayfly assemblages was substantially dissimilar between the two periods, although the changes were not associated with a decline in regional or local diversity. Only lowland rivers lost several of their original species, mostly habitat specialists. Species replacement, a leading driver of dissimilarity, caused shifts towards more simplified, less specialized assemblages in large rivers, and towards more pollution‐ and siltation‐tolerant assemblages in small rivers. The increase in cold‐water specialists and a stable share of generalists suggested the maintenance of a certain level of specialization in the assemblages of brooks.

The most marked change in the assemblage was associated with the impaired or bad water quality of rivers in the 1950s, which persisted or further deteriorated in the ensuing decades. Assemblages that were influenced by a slight deterioration or improvement in water quality were less altered, unless affected by other pressures (such as channel or discharge modifications).

The results indicate that the causes of changes in the assemblages are many and complex, although heavy pollution overrides other influences. Direct habitat loss or their degradation by siltation appear to be leading contributors to changes in assemblages. The results imply the need for the application of a catchment‐scale perspective for the restoration of streams and the conservation of the remaining well‐preserved stretches of lowland rivers.

Copyright © 2014 John Wiley & Sons, Ltd.
Combined Inhibition of Tumor Necrosis Factor α and Interleukin‐17 As a Therapeutic Opportunity in Rheumatoid Arthritis: Development and Characterization of a Novel Bispecific Antibody
Authors: Fischer Jens A. A. , Hueber Axel J. , Wilson Stacy , Galm Margarete , Baum Wolfgang , Kitson Christopher , Auer Johannes , Lorenz Stefan H. , Moelleken Jörg , Bader Martin , Tissot Alain C. , Tan Seng‐Lai , Seeber Stefan , Schett Georg
Published: October 2014

Objective

Rheumatoid arthritis therapies that are based on inhibition of a single cytokine, e.g., tumor necrosis factor α (TNFα) or interleukin‐6 (IL‐6), produce clinically meaningful responses in only about half of the treated patients. This study was undertaken to investigate whether combined inhibition of TNFα and IL‐17 has additive or synergistic effects in the suppression of mesenchymal cell activation in vitro and inflammation and tissue destruction in arthritis in vivo.

Methods

Cultures of human fibroblast‐like synoviocytes (FLS) were stimulated with TNFα, IL‐17, or a combination of both. Single/combined neutralizing antibodies against TNFα and IL‐17 were used to examine in vitro cytokine responses and in vivo development of arthritis and bone and cartilage destruction in TNFα‐transgenic mice. Bispecific anti–TNFα/IL‐17 antibodies were designed, and their potential to block cytokine responses in human FLS was tested.

Results

TNFα and IL‐17 had additive/synergistic effects in promoting production of IL‐6, IL‐8, and granulocyte colony‐stimulating factor, as well as matrix metalloproteinases, in FLS. Bispecific anti–TNFα/IL‐17 antibodies showed superior efficacy in blocking cytokine and chemokine responses in vitro. Furthermore, dual versus single inhibition of both cytokines using neutralizing antibodies was more effective in inhibiting the development of inflammation and bone and cartilage destruction in arthritic mice.

Conclusion

Combined blockade of TNFα and IL‐17 was more effective than single blockade in inhibiting cytokine, chemokine, and matrix enzyme responses from human mesenchymal cells and in blocking tissue destruction associated with arthritis, and additionally showed a positive impact on rebalance of bone homeostasis. Bispecific anti–TNFα/IL‐17 antibodies may have superior efficacy in the treatment of arthritis and may overcome the limited therapeutic responses obtained with single cytokine neutralization.
Transcription Factor Snail Regulates Tumor Necrosis Factor α–Mediated Synovial Fibroblast Activation in the Rheumatoid Joint
Authors: Chen Shih‐Yao , Shiau Ai‐Li , Li Yuan‐Tsung , Lin Chi‐Chen , Jou I‐Ming , Liu Ming‐Fei , Wu Chao‐Liang , Wang Chrong‐Reen
Published: October 2014

Objective

The transcription factor Snail is involved in various biologic functions. We hypothesized that this molecule regulates tumor necrosis factor α (TNFα)–mediated synovial fibroblast activation in the rheumatoid joint. The aim of this study was to examine the role of Snail in the expression of cadherin‐11 (Cad‐11) and myofibroblast markers, interleukin‐6 (IL‐6) production, and the invasive ability of cells.

Methods

Synovium samples were obtained from patients with rheumatoid arthritis (RA) and from rats with collagen‐induced arthritis (CIA). Synovial fibroblasts were treated with TNFα or a Wnt signaling inducer, and the joints of rats with CIA were injected with a TNFα antagonist. Modulation of Snail expression in the synovial fibroblasts and joints was performed by lentiviral vector–mediated transfer of complementary DNA or short hairpin RNA.

Results

The expression of Snail and Cad‐11 was higher in synovium and synovial fibroblasts from patients with RA compared with patients with osteoarthritis and was increased in rats with CIA. TNFα stimulation or activation of Wnt signaling up‐regulated the expression of Snail, Cad‐11, and α‐smooth muscle actin (α‐SMA) in synovial fibroblasts, and anti‐TNFα therapy down‐regulated the expression of Snail, Cad‐11, and α‐SMA in the joints of rats with CIA. Although synovial fibroblast transfectants in which Snail was overexpressed showed increased expression of Cad‐11 and α‐SMA and enhanced TNFα‐mediated invasive capacity and IL‐6 production, synovial fibroblast transfectants from rats with CIA in which Snail was silenced showed decreased expression and had the opposite effect on these functions. Normal joints in which Snail was overexpressed had hyperplastic synovium, with increased expression of Cad‐11, α‐SMA, and IL‐6. Silencing Snail expression ameliorated arthritis, with reduced Cad‐11 expression and reduced levels of extracellular matrix deposition in the joints of rats with CIA, whereas overexpression of Snail exacerbated arthritis, with increased Cad‐11 expression and increased levels of extracellular matrix deposition.

Conclusion

Our results demonstrate that Snail regulates TNFα‐mediated activation of synovial fibroblasts in the rheumatoid joint. These findings may contribute to the pharmacologic development of therapeutics targeting synovial fibroblasts in patients with RA.
Amelioration of Tissue Fibrosis by Toll‐like Receptor 4 Knockout in Murine Models of Systemic Sclerosis
Authors: Takahashi Takehiro , Asano Yoshihide , Ichimura Yohei , Toyama Tetsuo , Taniguchi Takashi , Noda Shinji , Akamata Kaname , Tada Yayoi , Sugaya Makoto , Kadono Takafumi , Sato Shinichi
Published: October 2014

Objective

Bleomycin‐induced fibrosis and the tight skin (TSK/+) mouse are well‐established experimental murine models of human systemic sclerosis (SSc). Growing evidence has demonstrated the pivotal role of Toll‐like receptors (TLRs) in several autoimmune inflammatory diseases, including SSc. This study was undertaken to determine the role of TLR‐4 in the fibrotic processes in these murine models.

Methods

We generated a murine model of bleomycin‐induced SSc using TLR‐4−/− mice and TLR‐4−/−;TSK/+ mice. The mechanisms by which TLR‐4 contributes to pathologic tissue fibrosis were investigated in these 2 models by histologic examination, hydroxyproline assay, enzyme‐linked immunosorbent assay, real‐time polymerase chain reaction, and flow cytometry.

Results

Dermal and lung fibrosis was attenuated in bleomycin‐treated TLR‐4−/− mice compared with their wild‐type counterparts. Inflammatory cell infiltration, expression of various inflammatory cytokines, and pathologic angiogenesis induced by bleomycin treatment were suppressed with TLR‐4 deletion. Furthermore, the increased expression of interleukin‐6 (IL‐6) in fibroblasts, endothelial cells, and immune cells in response to bleomycin in vivo and to lipopolysaccharide in vitro was notably abrogated in the absence of TLR‐4. Moreover, TLR‐4 deletion was associated with alleviated B cell activation and skew toward a Th2/Th17 response against bleomycin treatment. Importantly, in TSK/+ mice, another SSc murine model, TLR‐4 abrogation attenuated hypodermal fibrosis.

Conclusion

These results indicate the pivotal contribution of TLR‐4 to the pathologic tissue fibrosis of SSc murine models. Our results indicate the critical role of TLR‐4 signaling in the development of tissue fibrosis, suggesting that biomolecular TLR‐4 targeting might be a potential therapeutic approach to SSc.
Dual B Cell Immunotherapy Is Superior to Individual Anti‐CD20 Depletion or BAFF Blockade in Murine Models of Spontaneous or Accelerated Lupus
Authors: Lin WeiYu , Seshasayee Dhaya , Lee Wyne P. , Caplazi Patrick , McVay Sami , Suto Eric , Nguyen Allen , Lin Zhonghua , Sun Yonglian , DeForge Laura , Balazs Mercedesz , Martin Flavius , Zarrin Ali A.
Published: October 2014

Objective

To determine whether a combination of B cell depletion and BAFF blockade is more effective than monotherapy in treating models of spontaneous or accelerated systemic lupus erythematosus (SLE) in (NZB × NZW)F1 mice.

Methods

Clinical parameters such as disease progression–free survival, proteinuria, and renal injury were assessed in models of spontaneous, interferon‐α (IFNα)–accelerated, or pristane‐accelerated lupus in (NZB × NZW)F1 mice. Treatment arms included anti‐CD20 (B cell depletion), B lymphocyte stimulator receptor 3 fusion protein (BR‐3‐Fc) (BAFF blockade), the combination of anti‐CD20 and BR‐3‐Fc, isotype control, or cyclophosphamide. In models of spontaneous, IFNα‐accelerated, or pristane‐accelerated lupus, mice were treated for 24 weeks, 8 weeks, or 12 weeks, respectively. Peripheral and resident B cell subsets and various autoantibodies were examined.

Results

Compared to B cell depletion or BAFF blockade alone, combined therapy significantly improved disease manifestations in all 3 lupus models. In addition, marginal zone B cells, plasmablasts, and circulating and tissue plasma cells were decreased more effectively. Dual B cell immunotherapy also reduced multiple classes of pathogenic autoantibodies, consistent with its observed effectiveness in reducing immune complex–mediated renal injury.

Conclusion

Dual immunotherapy via B cell depletion and BAFF blockade is more efficacious than single agent immunotherapy in murine SLE models, and this combination treatment is predicted to be an effective strategy for immunotherapy in human SLE.
Effect of Axial Ligands on the Molecular Configurations, Stability, Reactivity, and Photodynamic Activities of Silicon Phthalocyanines
Authors: Luan Liqiang , Ding Lanlan , Shi Jiawei , Fang Wenjuan , Ni Yuxing , Liu Wei
Published: October 2014

To demonstrate the effect of axial ligands on the structure–activity relationship, a series of axially substituted silicon phthalocyanines (SiPcs) have been synthesized with changes to the axial ligands. The reactivity of the axial ligand upon shielding by the phthalocyanine ring current, along with their stability, photophysical, and photodynamic therapy (PDT) activities were compared and evaluated for the first time. As revealed by single‐crystal XRD analysis, rotation of the axial OMe ligands was observed in SiPc 3, which resulted in two molecular configurations coexisting synchronously in both the solid and solution states and causing a split of the phthalocyanine α protons in the 1H NMR spectra that is significantly different from all SiPcs reported so far. The remarkable photostability, good singlet oxygen quantum yield, and efficient in vitro photodynamic activity synergistically show that compound 3 is one of the most promising photosensitizers for PDT.
Suppression of CCN formation by bromine chemistry in the remote marine atmosphere
Authors: Breider Thomas James , Chipperfield Martyn P. , Mann Graham W. , Woodhouse Matthew T. , Carslaw Ken S.
Published: October 2014

Using a global model, we investigate how bromine chemistry affects cloud condensation nuclei (CCN) formation in the remote marine atmosphere. Bromine increases dimethylsulphide (DMS) oxidation but lowers SO2 yield, leading to less sulphate aerosol. The effect is largest (3–7% decrease in total CCN and 15–30% decrease in CCN from DMS) over the summertime southern ocean, a region of strong bromine release from sea‐salt. DMS and bromine emissions have a coupled feedback effect on CCN. Increased DMS enhances the release of sea‐salt bromine through increased aerosol acidity. This enhanced bromine suppresses the CCN response to increased DMS by up to 30%.
Do age‐associated DNA methylation changes increase the risk of malignant transformation?
Authors: Wagner Wolfgang , Weidner Carola I. , Lin Qiong
Published: October 2014

Aging of the organism is associated with highly reproducible DNA methylation (DNAm) changes, which facilitate estimation of donor age. Cancer is also associated with DNAm changes, which may contribute to disease development. Here, we speculate that age‐associated DNAm changes may increase the risk of tumor initiation. Notably, when using epigenetic signatures for age‐estimations tumor cells are often predicted to be much older than the chronological age of the patient. We demonstrate that aberrant hypermethylation within the gene DNA methyltransferase 3A (DNMT3A) – which may contribute to initiation of acute myeloid leukemia (AML) – is particularly observed in AML samples that reveal significantly more age‐associated DNAm changes. The functional relevance of age‐associated DNAm changes remains to be elucidated, but they occur genome wide, in a highly reproducible manner, and most likely influence chromatin organization – and hence may favor acquisition of aberrant DNAm patterns contributing to cancer in the elderly.
Peptide and peptide nucleic acid syntheses using a DNA/RNA synthesizer
Authors: Pokharel Durga , Fueangfung Suntara , Zhang Mingcui , Fang Shiyue
Published: October 2014

The use of an ABI 394 DNA/RNA synthesizer for peptide and peptide nucleic acid (PNA) syntheses is described. No additional physical part or software is needed for the application. A commercially available large DNA synthesis column was used, and only about half of its volume was filled with resin when the resin was fully swollen. With additional space in the top portion of the column, agitation of reaction mixture was achieved by bubbling argon from the bottom without losing solution. Removing solutions from column was achieved by flushing argon from top to bottom. Two peptide and two PNA sequences were synthesized. Good yields were obtained in all the cases. The method is easy to follow by researchers who are familiar with DNA/RNA synthesizer. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 487–493, 2014.
Development and validation of a simple and isocratic reversed‐phase HPLC method for the determination of rilpivirine from tablets, nanoparticles and HeLa cell lysates
Authors: Date Abhijit A. , Shibata Annemarie , Bruck Patrick , Destache Christopher J.
Published: October 2014

In the present investigation, a simple and isocratic HPLC‐UV method was developed and validated for determination of rilpivirine (RPV) from dosage forms (tablets and nanoparticles) and biological matrices like HeLa cell lysates. The separation and analysis of RPV was carried out under isocratic conditions using (a) a Gemini reversed‐phase C18 column (5 µm; 4.6 × 150 mm) maintained at 35°C, (b) a mobile phase consisting of a mixture of acetonitrile and 25 m m potassium dihydrogen phosphate (in the ratio 50:50 v/v) at a flow rate of 0.6 mL/min and (c) atazanavir as an internal standard. The total run time was 17 min and the analysis of RPV and internal standard was carried out at 290 nm. The method was found to be linear (r2 value > 0.998), specific, accurate and precise over the concentration range of 0.025–2 µg/mL. The lower limit of quantification was 0.025 µg/mL, the limit of detection was 0.008 µg/mL and the recovery of RPV was >90%. The stability of the RPV analytical method was confirmed at various conditions such as room temperature (24 h), −20°C (7 days), three freeze−thaw cycles and storage in an autosampler (4°C for 48 h). The method was successfully applied for the determination of RPV from conventional dosage forms like tablets, from polymeric nanoparticles and from biological matrices like HeLa cell lysates. Copyright © 2014 John Wiley & Sons, Ltd.
Stability‐indicating HPLC assay for lysine–proline–valine (KPV) in aqueous solutions and skin homogenates
Authors: Pawar Kasturi R. , Mulabagal Vanisree , Smith Forrest , Kolli Chandra S. , Rangari Vijaya K. , Babu R. Jayachandra
Published: October 2014

A simple, sensitive and stability‐indicating high‐performance liquid chromatographic (HPLC) assay method was developed and validated for a bioactive peptide, lysine–proline–valine (KPV) in aqueous solutions and skin homogenates. Chromatographic separation was achieved on a reversed phase Phenomenex C18 column (4.6 × 250 mm, packed with 5 µm silica particles) with a gradient mobile phase consisting of 0.1% trifluoroacetic acid (TFA) in water (A) and 0.1% TFA in acetonitrile (B). The proposed HPLC method was validated with respect to accuracy, precision, linearity, repeatability, limit of detection (LOD) and limit of quantitation (LOQ). The calibration curve was linear with a correlation coefficient (r) of 0.9999. Relative standard deviation values of accuracy and precision experiments were <2. The LOD and LOQ of KPV were 0.01 and 0.25 µg/mL, respectively. Under stress conditions (acid, alkali and hydrogen peroxide) KPV yielded lys–pro–diketopiperazine as major degradation product, which was identified by flow injection MS analysis. The developed HPLC method was found to be efficient in separating the active peptide from its degradation products generated under various stress conditions. Also, the validated method was able to separate KPV from other peaks arising from endogenous components of the skin homogenate. Copyright © 2014 John Wiley & Sons, Ltd.
Simultaneous determination of erlotinib and its isomeric major metabolites in human plasma using isocratic liquid chromatography–tandem mass spectrometry and its clinical application
Authors: Ishida Takuya , Naito Takafumi , Kawakami Junichi
Published: October 2014

This study developed a method for the simultaneous determination of erlotinib and its isomeric major metabolites, OSI‐413 and OSI‐420, in human plasma using an isocratic liquid chromatography–tandem mass spectrometry. Plasma specimens deproteinized with acetonitrile were separated using a 3‐µm particle size octadecylsilyl column. The m/z values of the precursor and product ions for the analytes were as follows: erlotinib, 394.2/278.2; and OSI‐413 and OSI‐420, 380.2/278.2. The total run time was 21 min and no peaks interfering with the analytes and internal standard (d6‐erlotinib) in human plasma were observed. The calibration curves of erlotinib, OSI‐413 and OSI‐420 were linear over the concentration ranges of 10–3000, 2–500 and 2–100 ng/mL, respectively. The pretreatment recovery ratios were >86.1%. The intra‐ and inter‐assay precisions and accuracies were <12.7 and 89.0–108.9% for all analytes. This validated method was applied to the determination of plasma samples in lung cancer patients receiving 150 mg of oral erlotinib. The plasma concentration ranges of erlotinib, OSI‐413 and OSI‐420 were 373–2354, 15.7–379 and 2.5–43.6 ng/mL, respectively. In conclusion, the present method can be helpful for evaluating the plasma exposures of erlotinib and its major isomeric metabolites in clinical settings. Copyright © 2014 John Wiley & Sons, Ltd.
Collective Action and Social Change: Examining the Role of Representation in the Communication between Protesters and Third‐party Members
Authors: Batel Susana , Castro Paula
Published: October 2014

Within social psychology, it has been proposed that to understand how collective action creates social change, it is relevant to examine the role that other members of society can have on it. However, few studies have empirically examined that. We argue that for that task, it is useful, first, and as some authors have already argued, to go beyond the sole analysis of the two‐sided inter‐group relations creating collective action; and second, to articulate this with contributions from social representations theory, which recognises that to understand social change, we need to examine communicative practices, or how communication is used between collective action's actors and other actors to re‐present identities. We analyse the protests by a movement of residents from a Lisbon neighbourhood that protested against the transformation of a neighbourhood's convent. Besides discussing this transformation with local authorities and failing to achieve its aims through that, the protesters also discussed it with other citizens. The analysis of this debate shows that the arguments and actions they used change throughout time, from local to global, as the latter were the ones more endorsed by other citizens and thus those that could help the protesters to achieve their goals. Copyright © 2014 John Wiley & Sons, Ltd.
Integrated pharmacophore and docking‐based designing of dual inhibitors of aldose reductase (ALR2) and protein tyrosine phosphatase 1B (PTP1B) as novel therapeutics for insulin‐resistant diabetes and its complications
Authors: Vyas Bhawna , Silakari Om , Kaur Maninder , Singh Baldev
Published: October 2014

The dual inhibitors against aldose reductase (ALR2) and protein tyrosine phosphatase 1B (PTP1B) may present an anti‐diabetic potency in insulin resistance without risks of serious diabetic complications. Therefore, in the present study, we constructed two separate pharmacophore mapping‐based 3D quantitative structure–activity relationship models for ALR2 (AADRR.11093 with standard deviation 0.663, 0.719, F 22.3, root‐mean‐square error 0.705, 0.647, Pearson‐r 0.802) and PTP1B (AARR.155 with standard deviation 0.146, 0.945, F 82.70, root‐mean‐square error 0.351, 0.621, Pearson‐r 0.831) employing the dataset of 54 flavonoids as ALR2 inhibitors and 46 naphthoquinones as PTP1B inhibitors to identify structural features necessary for the inhibition of both enzymes. These models were subsequently used as 3D query search for hierarchical virtual screening‐based designing using the PHASE database of 1.5 million compounds. Designed dual inhibitors were further subjected to GLIDE XP docking analysis using high‐resolution 3D structures of ALR2 (1US0, at resolution of 0.66 Å) and PTP1B (2F71 at resolution of 1.55 Å) available in the Protein Data Bank to authenticate identified structural features with important binding interactions necessary for dual inhibition. Copyright © 2014 John Wiley & Sons, Ltd.
Scanning SQUID Microscopy of Local Superconductivity in Inhomogeneous Combinatorial Ceramics
Authors: Iranmanesh Mitra , Stir Manuela , Kirtley John R. , Hulliger Jürg
Published: October 2014

Although combinatorial solid‐state chemistry promises to be an efficient way to search for new superconducting compounds, the problem of determining which compositions are strongly diamagnetic in a mixed‐phase sample is challenging. By means of reactions in a system of randomly mixed starting components (Ca, Sr, Ba, La, Y, Pb, Bi, Tl, and Cu oxides), samples were produced that showed an onset of diamagnetic response above 115 K in bulk measurements. Imaging of this diamagnetic response in ceramic samples by scanning SQUID microscopy (SSM) revealed local superconducting areas with sizes down to as small as the spatial resolution of a few micrometers. In addition, locally formed superconducting matter was extracted from mixed‐phase samples by magnetic separation. The analysis of single grains (d<80 μm) by X‐ray diffraction, elemental analysis, and bulk SQUID measurements allowed Tl2Ca3Ba2Cu4O12, TlCaBaSrCu2O7−δ, BaPb0.5Bi0.25Tl0.25O3−δ, TlBa2Ca2Cu3O9, Tl2Ba2CaCu2O8, and YBa2Cu3O7 phases to be identified. SSM, in combination with other diagnostic techniques, is therefore shown to be a useful instrument to analyze inhomogeneous reaction products in the solid‐state chemistry of materials showing magnetic properties.
Fast Epitope Mapping for the Anti‐MUC1 Monoclonal Antibody by Combining a One‐Bead‐One‐Glycopeptide Library and a Microarray Platform
Authors: Garcia‐Martin Fayna , Matsushita Takahiko , Hinou Hiroshi , Nishimura Shin‐Ichiro
Published: October 2014

Anti‐MUC1 monoclonal antibodies (mAbs) are powerful tools that can be used to recognize cancer‐related MUC1 molecules, the O‐glycosylation status of which is believed to affect binding affinity. We demonstrate the feasibility of using a rapid screening methodology to elucidate those effects. The approach involves i) “one‐bead‐one‐compound”‐based preparation of bilayer resins carrying glycopeptides on the shell and mass‐tag tripeptides coding O‐glycan patterns in the core, ii) on‐resin screening with an anti‐MUC1 mAb, iii) separating positive resins by utilizing secondary antibody conjugation with magnetic beads, and (iv) decoding the mass‐tag that is detached from the positive resins pool by using mass spectrometric analysis. We tested a small library consisting of 27 MUC1 glycopeptides with different O‐glycosylations against anti‐MUC1 mAb clone VU‐3C6. Qualitative mass‐tag analysis showed that increasing the number of glycans leads to an increase in the binding affinity. Six glycopeptides selected from the library were validated by using a microarray‐based assay. Our screening provides valuable information on O‐glycosylations of epitopes leading to high affinity with mAb.
Heteroaromatic Belts through Fold‐in Synthesis: Mechanistic Insights into a Macrocycle‐Templated Friedel–Crafts Alkylation
Authors: Kondratowicz Mateusz , Myśliwiec Damian , Lis Tadeusz , Stępień Marcin
Published: October 2014

Direct alkylation of 9,9′,9′′‐triethyl[2.2.2](2,7)carbazolophane with dimethoxymethane or paraformaldehyde affords a belt‐like heteroaromatic structure, which forms as a kinetic product in acid‐catalyzed condensations. In a competing, thermodynamically favored process, polymeric structures are formed by a largely regioselective condensation of stereochemically rigid “semi‐belts”. The relationship between these reactivity routes is rationalized in terms of strain release and differential reversibility of consecutive condensation steps.
Ratiometric Detection of Adenosine Triphosphate (ATP) in Water and Real‐Time Monitoring of Apyrase Activity with a Tripodal Zinc Complex
Authors: Butler Stephen J.
Published: October 2014

Two tripodal fluorescent probes Zn⋅L1,2 have been synthesised, and their anion‐binding capabilities were examined by using fluorescence spectroscopy. Probe Zn⋅L1 allows the selective and ratiometric detection of adenosine triphosphate (ATP) at physiological pH, even in the presence of several competing anions, such as ADP, phosphate and bicarbonate. The probe was applied to the real‐time monitoring of the apyrase‐catalysed hydrolysis of ATP, in a medium that mimics an extracellular fluid.
Pd‐ and Cu‐Catalyzed Stereo‐ and Regiocontrolled Decarboxylative/CH Fluoroalkenylation of Heteroarenes
Authors: Rousée Kevin , Schneider Cédric , Couve‐Bonnaire Samuel , Pannecoucke Xavier , Levacher Vincent , Hoarau Christophe
Published: October 2014

Pd/Cu‐catalyzed decarboxylative/direct CH alkenylations of heteroarenes with α‐fluoroacrylic acid is reported. This method offers step‐economical and stereocontrolled access to valuable heteroarylated monofluoroalkenes as both Z and E isomers, which are known to be useful in the synthesis of fluorinated biomolecules.
Chiral Separation of G‐type Chemical Warfare Nerve Agents via Analytical Supercritical Fluid Chromatography
Authors: Kasten Shane A. , Zulli Steven , Jones Jonathan L. , Dephillipo Thomas , Cerasoli Douglas M.
Published: October 2014

Chemical warfare nerve agents (CWNAs) are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Undirected synthesis of G‐type CWNAs produces stereoisomers of tabun, sarin, soman, and cyclosarin (GA, GB, GD, and GF, respectively). Analytical‐scale methods were developed using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer for the separation, quantitation, and isolation of individual stereoisomers of GA, GB, GD, and GF. Screening various chiral stationary phases (CSPs) for the capacity to provide full baseline separation of the CWNAs revealed that a Regis WhelkO1 (SS) column was capable of separating the enantiomers of GA, GB, and GF, with elution of the P(+) enantiomer preceding elution of the corresponding P(–) enantiomer; two WhelkO1 (SS) columns had to be connected in series to achieve complete baseline resolution. The four diastereomers of GD were also resolved using two tandem WhelkO1 (SS) columns, with complete baseline separation of the two P(+) epimers. A single WhelkO1 (RR) column with inverse stereochemistry resulted in baseline separation of the GD P(–) epimers. The analytical methods described can be scaled to allow isolation of individual stereoisomers to assist in screening and development of countermeasures to organophosphorus nerve agents. Chirality 26:817–824, 2014. © 2014 The Authors. Chirality published by John Wiley Periodicals, Inc.
Investigation of Coking During Dry Reforming of Methane by Means of Thermogravimetry
Authors: Tarasov Andrey , Düdder Hendrik , Mette Katharina , Kühl Stefanie , Kähler Kevin , Schlögl Robert , Muhler Martin , Behrens Malte
Published: October 2014

Coking dynamics of Ni‐based and Ni‐free catalysts were studied in a magnetic suspension thermobalance under methane dry reforming conditions. Ni‐rich catalysts undergo strong coking featured with a surface saturation point where the coking rate is drastically reduced. Catalyst resistance towards coking may be enhanced by using noble‐metal‐based Ni‐free precursors or decreasing the Ni content in the catalytic system. The post reaction performed temperature‐programmed oxidation experiment of the coked catalyst is diffusion‐limited due to large amounts of formed carbon.