bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bcl‐2 Antagonists Kill Plasmacytoid Dendritic Cells From Lupus‐Prone Mice and Dampen Interferon‐α Production
Authors: Zhan Yifan , Carrington Emma M. , Ko Hyun‐Ja , Vikstrom Ingela B. , Oon Shereen , Zhang Jian‐Guo , Vremec David , Brady Jamie L. , Bouillet Philippe , Wu Li , Huang David C. S. , Wicks Ian P. , Morand Eric F. , Strasser Andreas , Lew Andrew M. 
Published: November 2014

ObjectiveInterferon‐α (IFNα)–producing plasmacytoid dendritic cells (PDCs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). IFNα‐related genes are highlighted among SLE susceptibility alleles and are characteristically expressed in the blood of patients with SLE, while in mouse models of lupus, PDC numbers and IFNα production are increased. This study was undertaken to investigate the effects of inhibitors that selectively target different antiapoptotic molecules on the survival of PDCs.MethodsPDC numbers, in vitro survival, and expression of antiapoptotic molecules were evaluated in lupus‐prone (NZB × NZW)F1 (NZB/NZW) mice. The impact of Bcl‐2 antagonists and glucocorticoids on PDCs was evaluated in vitro and in vivo. IFNα production by NZB/NZW mice was evaluated before and after treatment with Bcl‐2 antagonists.ResultsPDCs, but not lymphoid tissue–resident conventional DCs, largely relied on the antiapoptotic protein Bcl‐2 for survival. The enlarged PDC compartment in NZB/NZW mice was associated with selectively prolonged survival and increased Bcl‐2 transcription. Functionally, this resulted in enhanced production of IFNα. Bcl‐2 inhibitors selectively killed mouse and human PDCs, including PDCs from SLE patients, but not conventional DCs, dampened IFNα production by PDCs, and synergized with glucocorticoids to kill activated PDCs.ConclusionEnhanced PDC survival is a likely contributing factor to enhanced IFNα production by lupus PDCs. Bcl‐2 antagonists potently and selectively kill PDCs and reduce IFNα production. Thus, we believe that they are attractive candidates for treating PDC‐associated diseases.
Malondialdehyde‐Acetaldehyde Adducts and Anti–Malondialdehyde‐Acetaldehyde Antibodies in Rheumatoid Arthritis
Authors: Thiele Geoffrey M. , Duryee Michael J. , Anderson Daniel R. , Klassen Lynell W. , Mohring Stephen M. , Young Kathleen A. , Benissan‐Messan Dathe , Sayles Harlan , Dusad Anand , Hunter Carlos D. , Sokolove Jeremy , Robinson William H. , O'Dell James R. , Nicholas Anthony P. , Tuma Dean J. , Mikuls Ted R. 
Published: November 2014

ObjectiveMalondialdehyde‐acetaldehyde (MAA) adducts are a product of oxidative stress associated with tolerance loss in several disease states. This study was undertaken to investigate the presence of MAA adducts and circulating anti‐MAA antibodies in patients with rheumatoid arthritis (RA).MethodsSynovial tissue from patients with RA and patients with osteoarthritis (OA) were examined for the presence of MAA‐modified and citrullinated proteins. Anti‐MAA antibody isotypes were measured in RA patients (n = 1,720) and healthy controls (n = 80) by enzyme‐linked immunosorbent assay. Antigen‐specific anti–citrullinated protein antibodies (ACPAs) were measured in RA patients using a multiplex antigen array. Anti‐MAA isotype concentrations were compared in a subset of RA patients (n = 80) and matched healthy controls (n = 80). Associations of anti‐MAA antibody isotypes with disease characteristics, including ACPA positivity, were examined in all RA patients.ResultsExpression of MAA adducts was increased in RA synovial tissue compared to OA synovial tissue, and colocalization with citrullinated proteins was found. Increased levels of anti‐MAA antibody isotypes were observed in RA patients compared to controls (P < 0.001). Among RA patients, anti‐MAA antibody isotypes were associated with seropositivity for ACPAs and rheumatoid factor (P < 0.001) in addition to select measures of disease activity. Higher anti‐MAA antibody concentrations were associated with a greater number of positive antigen‐specific ACPA analytes (expressed at high titer) (P < 0.001) and a higher ACPA score (P < 0.001), independent of other covariates.ConclusionMAA adduct formation is increased in RA and appears to result in robust antibody responses that are strongly associated with ACPAs. These results support speculation that MAA formation may be a cofactor that drives tolerance loss, resulting in the autoimmune responses characteristic of RA.
Acid/Base‐Triggered Switching of Circularly Polarized Luminescence and Electronic Circular Dichroism in Organic and Organometallic Helicenes
Authors: Saleh Nidal , Moore Barry , Srebro Monika , Vanthuyne Nicolas , Toupet Loïc , Williams J. A. Gareth , Roussel Christian , Deol Kirandeep K. , Muller Gilles , Autschbach Jochen , Crassous Jeanne 
Published: November 2014

AbstractElectronic circular dichroism and circularly polarized luminescence acid/base switching activity has been demonstrated in helicene‐bipyridine proligand 1 a and in its “rollover” cycloplatinated derivative 2 a. Whereas proligand 1 a displays a strong bathochromic shift (>160 nm) of the nonpolarized and circularly polarized luminescence upon protonation, complex 2 a displays slightly stronger emission. This strikingly different behavior between singlet emission in the organic helicene and triplet emission in the organometallic derivative has been rationalized by using quantum‐chemical calculations. The very large bathochromic shift of the emission observed upon protonation of azahelicene‐bipyridine 1 a has been attributed to the decrease in aromaticity (promoting a charge‐transfer‐type transition rather than a π–π* transition) as well as an increase in the HOMO–LUMO character of the transition and stabilization of the LUMO level upon protonation.
The Rate and Shape of Change in Binge Eating Episodes and Weight: An Effectiveness Trial of Emotionally Focused Group Therapy for Binge‐Eating Disorder
Authors: Compare Angelo , Tasca Giorgio A. 
Published: November 2014

ObjectiveThis study investigated the phases of change and the relationship between binge eating (BE) episodes and weight across 20 weeks of emotionally focused group therapy (EFGT) and combined therapy (CT) of EFGT plus dietary counselling for BE disorder.MethodsWe used a non‐randomized observational study design that included 118 obese adult patients with BE disorder who were treated by manualized therapy protocols. Participants were assigned to treatment condition (EFGT or CT) based on consensus among clinicians. Participants were assessed weekly during the 20 weeks of therapy for weight and BE episodes and at pre‐treatment and 6 months post‐treatment.ResultsBinge eating episodes and weight significantly declined during EFGT and CT. Compared with EFGT, CT resulted in more rapid weight loss across weeks of therapy. BE episodes and weight significantly covaried, and their positive association increased as sessions progressed. Change in BE episodes and weight during treatment was best modelled by a cubic growth curve showing a slow rate of change in early sessions, a faster rate of change in middle sessions and a slower rate of change in late sessions. This cubic modelling of change was associated with better outcomes 6 months post‐treatment.ConclusionCubic modelling of change supported a three‐stage model of EFGT and CT, and the cubic trajectory was associated with better outcomes at follow‐up. The addition of dietary counselling to EFGT resulted in earlier response to treatment in terms of BE episodes and weight among those in the CT condition. Copyright © 2014 John Wiley & Sons, Ltd.Key Practitioner Message

Decline in binge eating (BE) episodes is related to decline in weight, and this relationship was greater towards the end of treatment.
Emotionally focused group therapy plus dietary counselling that targets both affect regulation and nutritional problems resulted in faster rate of response early in treatment both in terms of BE episodes and weight.
Combined emotionally focused group therapy and dietary counselling may provide clinicians with an additional approach to treating BE disorder.
Study on cognitive DF relaying cooperation with the mutual interference between primary and secondary users over Nakagami‐m fading channels
Authors: Jia Xiangdong , Deng Pengfei , Yang Longxiang , Zhu Hongbo 
Published: November 2014

SummaryIn this paper, the cognitive relay cooperation (CRC) wireless communication systems are investigated over Nakagami‐m fading channels. The decode‐and‐forward (DF) relay is employed to assist the communications between cognitive source and destination. Especially, to achieve full diversity order, we consider the case in which there is a direct path between cognitive source and destination. Besides the interference at primary users (PUs) created by secondary users (SUs), the interference at SUs created by PUs is also considered. For the interested CRC systems, we first achieve the exact expression for the CDF of the equivalent end‐to‐end signal‐to‐interference ratio (SIR) of CRC systems. Then, with the exact CDF, the exact average symbol error ratio (SER) and outage performance of CRC systems are achieved. The derivation is of significance, by which we can obtain a detailed knowledge about CRC systems. Though a single integral included in the derivation, it can be calculated numerically by employing some mathematical tools such as Matlab. At the same time, to obtain the insight and highlight the effect of system parameters on the considered CRC systems, by using the high SIR approximation, we obtain the asymptotic closed‐form expression of CDF as well as the ones of average SER and outage probability. From the asymptotic results, we can find the main factors that dominate the performance of CRC systems. The presented simulation results for outage probability and average SER show the derivations and simulations are in agreement. Moreover, in high SIR the achieved asymptotic results match well the exact ones. As a result, in high SIR we can employ the asymptotic closed‐form solutions to evaluate the exact performance of CRC systems. This can reduce greatly the implementation complexity. Besides this, the simulations also show that the diversity order is dominated by the fading severities of the secondary systems, i.e. the diversity order be proportional to the summation of the minimum fading severity between the two hops and that of the direct link. In contrast, the parameters of the primary systems only affect the coding gain, not the diversity gain. Copyright © 2014 John Wiley & Sons, Ltd.
Bis(trimethylsilyl)selenide in the Selective Synthesis of β‐Hydroxy, β‐Mercapto, and β‐Amino Diorganyl Diselenides and Selenides Through Ring Opening of Strained Heterocycles
Authors: Tanini Damiano , Degl'Innocenti Alessandro , Capperucci Antonella 
Published: November 2014

AbstractA novel approach to the synthesis of β‐substituted dialkyl diselenides and selenides is described through reaction of bis(trimethylsilyl)selenide with epoxides, thiiranes, and aziridines catalyzed by tetrabutylammonium fluoride. Selective formation of a wide variety of β‐hydroxy, β‐mercapto, and β‐amino diselenides and selenides is achieved by controlling the reaction conditions in the regioselective attack of the silyl selenide onto the ring‐strained heterocycles. All reactions occur in a highly regioselective and enantioconservative manner, affording the title compounds with good to high yields. Selenium‐77 NMR chemical shifts were measured to verify the selective formation of the β‐substituted diselenides and selenides.
Synthesis and Cytotoxic Activity of Self‐Assembling Squalene Conjugates of 3‐[(Pyrrol‐2‐yl)methylidene]‐2,3‐dihydro‐1H‐indol‐2‐one Anticancer Agents
Authors: Buchy Eric , Valetti Sabrina , Mura Simona , Mougin Julie , Troufflard Claire , Couvreur Patrick , Desmaële Didier 
Published: November 2014

AbstractSqualenoyl conjugates of semaxanib and sunitinib, two potent antiangiogenic (pyrrolyl)methylidenyl‐substituted oxindole multitarget tyrosine kinase inhibitors, were synthesized with a hemiaminal‐based pH‐sensitive linker. The prodrugs were prepared according to a three‐step sequence involving (i) N‐alkylation with chloromethoxy‐triisopropylsilane; (ii) desilylation; and (iii) acylation with trisnorsqualenic acid. These squalenoyl prodrugs were found to self‐assemble into nanoassemblies in aqueous media without the need for any surfactant. The nanosized aggregates were characterized by dynamic light scattering and transmission electron microscopy, and appeared to be stable in water for several days, as determined by particle‐size measurement. In vitro biological studies showed that squalenoyl sunitinib nanoassemblies are notably cytotoxic against the human umbilical vein endothelial cell line (HUVEC), which is involved in the tumor vessel formation.
A Synthetic Route to 3‐(Heteroaryl)‐7‐hydroxycoumarins Designed for Biosensing Applications
Authors: Roubinet Benoît , Chevalier Arnaud , Renard Pierre‐Yves , Romieu Anthony 
Published: November 2014

AbstractA straightforward method to synthesize 3‐(2‐benzimidazolyl)‐7‐hydroxycoumarins, based on the condensation reaction of 7‐acetoxy‐3‐formylcoumarin with various C‐ and/or N‐substituted ortho‐phenylenediamine derivatives is presented. This unusual approach proved particularly effective for introducing different hydrophilic groups (carboxylic or sulfonic acids or trimethylalkylammonium moieties) onto the heteroaryl scaffold, leading to cyan‐green emitting coumarins that were both water‐soluble and strongly fluorescent under physiological conditions. The further extension of this condensation reaction to bis(2‐aminophenyl)diselenide enabled the first synthesis of 3‐(2‐benzoselenazolyl)‐7‐hydroxycoumarin. The potential utility of these new 7‐hydroxycoumarins was demonstrated through the synthesis and spectroscopic and analyte‐responsive behavior of fluorogenic probes suitable for sensing biologically relevant thiols and urokinase, a protease that plays a key role in cancer invasion and metastasis.
Direct Arylation of Imidazo[1,5‐a]azines Through Ruthenium and Palladium Catalysis
Authors: Sustac Roman Daniela , Poiret Valentin , Pelletier Guillaume , Charette André B. 
Published: November 2014

AbstractThe regioselective RuII‐catalyzed direct ortho‐arylation of C‐3 aryl‐substituted imidazo[1,5‐a]azines with (hetero)aryl halides was investigated. The employment of RuII and PdII catalysts in the same flask resulted in two sequential and distinct C–H bond arylations, which allowed the rapid synthesis of highly conjugated compounds.
Determination of Ultratrace Thallium(I) by Anodic Stripping Voltammetry at Bismuth Film Electrodes Following Double Deposition and Stripping Steps
Authors: Rutyna Iwona , Korolczuk Mieczyslaw 
Published: November 2014

AbstractThe double deposition and stripping steps were proposed to increase the sensitivity in anodic stripping voltammetry of thallium(I). Two in situ plated bismuth film electrodes with drastically different surface areas were exploited for the measurements. Thallium was at first deposited at the electrode with a large surface area. As the deposition step at the large electrode was finished, the electrode was moved at a short distance to the small one. The thallium stripped from the large electrode was then accumulated at the second electrode. Taking into account the small volume of space between the electrodes, the concentration of Tl(I) between the electrodes was drastically higher than that in the bulk solution. The deposition step at the second electrode was performed from solution with a higher concentration of Tl(I) therefore the detection limit was lowered. The calibration graph was linear from 5×10−11 to 5×10−9 mol L−1 following deposition time of 300 s at the first and the second electrode.
Innocent Fun or “Microslavery”?
Authors: Harvey Hayden , Havard Molly , Magnus David , Cho Mildred K. , Riedel‐Kruse Ingmar H. 
Published: November 2014

AbstractIn 2011, Ingmar Riedel‐Kruse's bioengineering laboratory at Stanford University publicized an application that uses paramecia for what the researchers termed “biotic games.” These games make use of living organisms, computer programs, and lab equipment to implement games like Pong, Pac‐man, and soccer. Gamesand related activities are often considered nonserious or trivial, whereas life, biological systems, and science are treated very seriously in moral analysis and public perception. The manipulation of living matter frequently engenders at least some controversy in the marketplace of ideas, and using living things in games is no exception. Some of the objections lodged against biotic games have appeared in the ethics literature on similar topics; however, the addition of an entertainment element introduces some objections distinct from those about similar cases, as the online comments vividly illustrate. We aim to explore and address the objections in this paper, using the comments to organize and launch the discussion. In scientific work, there is typically a presumption of some prospect of translation and application of generated knowledge for public benefit. In the case of biotic games, these applications are not self‐evident. Because of this, a serious analysis of the justifications, limitations, and features of biotic games is warranted. To this end, we outline key ethical limits that ought to be placed on these activities as well as the obligations that these activities generate for researchers, other professionals, and lay people who design, implement, use, and play them.
The Ethics of Synthetic Biology: Next Steps and Prior Questions
Authors: Kaebnick Gregory E. , Gusmano Michael K. , Murray Thomas H. 
Published: November 2014

AbstractA majority opinion seems to have emerged in scholarly analysis of the assortment of technologies that have been given the label “synthetic biology.” According to this view, society should allow the technology to proceed and even provide it some financial support, while monitor­ing its progress and attempting to ensure that the development leads to good outcomes. The near‐consensus is captured by the U.S. Presidential Commission for the Study of Bioethical Issues in its report New Directions: The Ethics of Synthetic Biology and Emerging Technologies, which arguably marked the end of a preliminary round of analysis about the ethical and policy questions raised by synthetic bi­ology. Like a number of other, earlier documents issued by various groups around the world, the re­port called attention to questions about how the technology will be used; whether it might be mis­used; what sorts of accidents might happen along the way; the economic, environmental, and social impacts of the eventual applications; whether the very idea of “synthetic biology” should be trou­bling; and how the debate over all of these ques­tions will be conducted. Also like most similar documents, however, while it called for careful monitoring and oversight of technology, it did not recommend any significant new constraints on its development and use. The commission's stance was that it would be “imprudent either to declare a moratorium on synthetic biology until all risks can be determined and mitigated, or to simply ‘let science rip,’ regardless of the likely risks.”In this report, we will take stock of the current consensus, comment on some of the major points of disagreement, and identify the next steps for the debate. In part I, we offer a brief overview of the research and applications commonly grouped together under the heading of synthetic biology, partly in order to set the stage for the rest of the discussion and partly because we want to highlight some conceptual problems that attend the very la­bel given this field. In parts II, III, and IV, we take up, respectively, three broad classes of concerns that arise in the context of synthetic biology: con­cerns about the intrinsic or inherent value of do­ing synthetic biology, concerns about the concrete harms and benefits of doing synthetic biology, and concerns about justice. Addressing these concerns requires a method for bringing the public's values to bear on policy‐making concerning emerging biotechnologies; in part V, we discuss the chal­lenges in developing such a method.
The Precautionary Attitude: Asking Preliminary Questions
Authors: Wolff Jonathan 
Published: November 2014

AbstractInnovation in basic science is often a cause for won­der and excitement. Those associated with a new development are quick to point out the anticipated benefits: a cure for cancer or dementia, an end to unsafe water or hunger. These advocates are slower to draw at­tention to the possible costs, which may become known only much later. It is always hard to have an accurate overview, as it is almost impossible to predict the total effects of the widespread adoption of any new technology and, especially, its longer‐term or cumulative effects, as as­bestos and CFCs demonstrate. For this reason, some policy‐makers or members of the public hope that we can apply “the precautionary principle” to innovation. Unfortunately, if one is looking for a principle that can guide action, then, strictly speaking, there is no pre­cautionary principle. One might better speak of a “pre­cautionary approach,” although even this needs to be unpacked.
Governing in the Context of Uncertainty
Authors: Calvert Jane 
Published: November 2014

AbstractKaebnick, Gusmano, and Murray tackle some important issues raised by the emerging field of synthetic biology. Many of these issues arise pre­cisely because synthetic biology is still emerging, making it hard, if not impossible, to predict how the technology will pan out. In the context of this uncertainty, Kaebnick, Gusmano, and Murray imply, we may have to change our familiar patterns of thinking and governing. It is this point that I elaborate on here. I argue that if we embrace the distinctive characteris­tics of emerging biotechnologies, we can shift away from attempts to analyze the risks and benefits of technologi­cal developments and toward discussions of the moti­vations and purposes that drive them in the first place. This perspective gives us a solid rationale for public and stakeholder engagement (or “democratic deliberation,” as Kaebnick et al. call it) and helps us address some of the concerns Kaebnick and colleagues raise about how this engagement should be organized.
The Existing Guidance for “Dual‐Use” Research
Authors: Gronvall Gigi Kwik 
Published: November 2014

AbstractIn considering how to weigh the risks and benefits of synthetic biology, Kaebnick, Gusmano, and Murray pose the question of whether there is scientific re­search that should not be funded or performed, or if there are potentially dangerous results that should not be wide­ly disseminated. Such questions, they propose, require a new set of rules and norms for knowledge generation—an “ethics of knowledge.” They identify two examples of research that might fall into a nonpermissible category, including “research that is aimed at producing and dis­seminating knowledge of . . . how to produce more dan­gerous forms of H5N1 and smallpox.” There are already rules and norms to guide the funding and generation of scientific knowledge, however, including research on in­fluenza and smallpox. Even if more rules and guidance were added to the practice of science, potentially prob­lematic, “dual‐use” research would still occur, and as a practical matter, it is unlikely that results from those stud­ies can be contained, particularly if the research is of wide interest.