bluuebunny/crossref_metadata_2025 huggingface dataset:
6 - Le Parlement congolais post-élection dans le processus de construction de l’espace public : mythe ou réalité ?
Authors: Tukala Célestin Tshimande
Published: November 2011

Depuis 2007, la RDC dispose d’un Parlement issu des élections libres, pluralistes, démocratiques, transparentes et crédibles. Il est à pied d’œuvre depuis ce temps et, a eu à légiférer et à débattre des nombreuses questions dont les plus importantes nous semblent être la question de la nationalité qui a été à la base de deux conflits armées que le pays a connus. Malgré l’organisation des élections, la mise en place du Parlement élu et l’existence d’une loi sur la nationalité, la problématique de la nationalité demeure toujours. La loi elle-même n’est pas respectée par les gouvernants, qui font montre de l’extranéité. Cela a suscité des remous et a contraint le parlement à lancer un moratoire qui n’a jamais été appliqué. Le parlement s’est saisi de ce problème qui a fait l’objet d’un débat mais le parlement n’a trouvé aucune solution à cette question du moratoire.
Il y a aussi la question sur les violents incidents ayant opposé la police Nationale congolaise (PNC) et le Bandu Dia Kongo (BDK) à Matadi et les territoires de Luozi, Seke Banza et Lukula, en février et mars 2008. Accusé de s’être arrogé les pouvoirs de l’Etat dans plusieurs villages où la présence de la PNC était très faible, le Gouvernement a lancé des opérations pour restaurer l’autorité de l’Etat dans l’ensemble du Bas Congo. Ces opérations ont vite pris la dimension de l’usage excessif de la force, des exécutions arbitraires, la destruction systématique des églises et des maisons du BDK, ainsi que le nombre important d’arrestations arbitraires.
D’autres question émergent notamment la question du crash de l’avion ‘Antonov’ mettant à nu l’inexistence d’une législation rigide dans le secteur de transports aussi crucial pour la sécurité de la population et celle de la convention de collaboration entre la RDC et le groupement des entreprises chinoises. Il se dégage des débats en rapport avec les questions traitées au parlement, un manque d’intérêt manifeste pour la mise en route d’une véritable démocratie politique, économique et sociale. Cet exposé veut explicitement de manière concrète et adéquate aux cas singuliers, analyser la qualité des débats au parle ent pour en savoir si elle peut concourir à la construction de l’espace public.
7 - Behind the Curtains of State Power: Religious Groups and the Struggle for Ascendancy in Nigerian Public Institutions - A Critical Appraisal
Authors: Obianyo Nkolika E.
Published: November 2011

In secular states, religion is expected to occupy a backseat in public life; but in states like Nigeria, this is not so as religion, after ethnicity, has turned out to become a major determinant of political behaviour. It serves as both a unifying and a divisive factor. It unifies Nigerians who share the same belief across ethnic lines and, at the same time, puts them in contest with others who hold different beliefs. Hence, there are several contestations along religious lines. The proliferation of these divides has also given rise to the proliferation of these contestations. Traditionally, this contest has been between the Moslem and Christian groups; but contrary to popular opinion, within the two major religious groups there are several other contestations. Today, there is the contest between Pentecostal and non- Pentecostal Christians, Roman Catholics and non-Roman Catholic Christians (especially the Anglican sect). These contests focus on the relative strength of each group or sect in the corridors of state power. Against this backdrop, this article examines the origin and dynamics of this trend with respect to the Christian religious group in Nigeria. It argues that religion, like ethnicity, serves as instrument for the acquisition of state power, public positions and resources, and consequently as an instrument of exclusion and inclusion in the quest for ascendancy among contestants for state power and public positions. The article argues that this trend cannot be divorced from the ‘rentier’ and ‘allocative’ character of the post-colonial state of Nigeria in which occupants of state power not only use the state to improve their material well-being but also that of their primordial groups from which they draw support when the competition gets stiff. The ar ticle examines the implications of this trend for development and efficiency of public institutions in Nigeria.
9 - Des cimetières lotis à Kisangani : exemple d’un débat occulte sur la gestion des espaces publics en RDC
Authors: Ndemba Roger Ekongo
Published: November 2011

Dans les principales villes de la RDC, comme dans celles de la plupart des pays africains, les cimetières sont des espaces publics gérés par les municipalités. Jadis réservés aux morts et objet de respect, d’entretien régulier et de protection tous azimuts, ces sites sont de nos jours en proie à une gestion peu responsable de la part des pouvoirs publics. Les débats publics sur la question sont quasiment occultés. A Kisangani, la transformation de bon nombre de cimetières non désaffectés en des lieux d’habitation frise la profanation des ces sites. On y voit des vivants et des morts cohabiter côte à côte. Par-delà les problèmes de santé et d’hygiène publique, cette cohabitation pose en outre le problème de la révolution des croyances et des mentalités ainsi que celui de l’inefficacité des politiques publiques en matière d’urbanisation. Un débat public sur la question, grâce notamment à une société civile forte et dynamique et des pouvoirs publics responsabilisés, permettra de mettre fin à la banalisation du « sacré » et du « mystique » ainsi qu’à une gestion peu responsable de nos espaces publics.
Sorafenib, a multikinase inhibitor, is effective in vitro against non‐hodgkin lymphoma and synergizes with the mTOR inhibitor rapamycin
Authors: Ramakrishnan Vijay , Timm Michael , Haug Jessica L. , Kimlinger Teresa K. , Halling Timothy , Wellik Linda E. , Witzig Thomas E. , Vincent Rajkumar S. , Adjei Alex A. , Kumar Shaji
Published: November 2011

Non‐Hodgkin lymphoma (NHL) represents a heterogenous group of neoplasias originating from lymphoid cells. Increased angiogenesis and expression of Vascular Endothelial Growth Factor (VEGF) and its receptors (VEGFR) have been found to be associated with NHL disease progression. Increase in VEGF and other cytokines stimulate signaling cascades, including the Ras/Raf/Mek/Erk pathway, resulting in increased proliferation and decreased apoptosis. Here, we report the in vitro antilymphoma activity of sorafenib, an inhibitor of VEGFR and Raf kinase. Sorafenib induced potent cytotoxicity in NHL cell lines and patient samples. This induction of cytotoxicity was associated with a corresponding increase in apoptotic cell death. Mechanism of action of sorafenib was investigated in follicular (DoHH2) and Burkitt lymphoma (Raji) cell lines. pStat3, pAkt, Mcl1, and Xiap were downregulated in both cell lines, whereas pErk decreased in Raji but not in DoHH2 cells following sorafenib treatment. IL6 was unable to prevent sorafenib induced repression of pStat3, pAkt, Mcl1, and Bcl‐Xl. Sorafenib in combination with an mTORC1 inhibitor rapamycin demonstrated synergy in inducing cytotoxicity in NHL cells. Sorafenib/rapamycin combination resulted in downregulation of pAkt, pmTOR, p‐p70S6K, p4EBP1, pGSK3β, Mcl1, and Bcl‐Xl. On the basis of our results, a clinical trial is underway using sorafenib with everolimus in NHL patients., 2012. © 2011 Wiley Periodicals, Inc.
Optochemische Genetik
Authors: Fehrentz Timm , Schönberger Matthias , Trauner Dirk
Published: November 2011

Transmembranrezeptoren ermöglichen die Kommunikation zwischen Zellen und ihrer Umgebung. Die Stimuli, die diese Rezeptoren aktivieren, treten in Form von Änderungen der Ligandenkonzentration (z. B. Hormone oder Neurotransmitter), der Temperatur, des Drucks (z. B. Schallwellen oder Berührungen), des Transmembranpotentials oder der Lichtintensität auf. Viele Transmembranrezeptoren sind heutzutage in atomarer Auflösung charakterisiert, und unser Verständnis ihrer funktionellen Eigenschaften hat sich in vergangenen Jahren deutlich verbessert. Infolgedessen können diese hochentwickelten molekularen Maschinen umprogrammiert und gegenüber unnatürlichen Reizen sensibilisiert werden. In diesem Aufsatz zeigen wir, wie spannungs‐ und ligandengesteuerte Ionenkanäle mit synthetischen Lichtschaltern ausgestattet werden können. Die daraus resultierenden künstlichen Lichtrezeptoren können genutzt werden, um neurale Aktivität mit einer außergewöhnlichen zeitlichen und räumlichen Präzision optisch zu kontrollieren. Sie sind bereits erfolgreich in lebenden Systemen eingesetzt worden und könnten in Zukunft bei der Wiederherstellung des Sehprozesses und der optischen Kontrolle anderer Sinneswahrnehmungen Anwendung finden. Die Kombination von synthetischen Photoschaltern und Rezeptorproteinen erweitert das Feld der Optogenetik. Darüber hinaus verleiht sie der chemischen Genetik eine neue Dimension, weswegen wir vorschlagen, diesen Forschungsansatz “optochemische Genetik” zu nennen.
Fluorescence enhancement of rare earth Tb(III) by Tm(III) in benzyl benzoylmethyl sulphoxide complexes
Authors: Li Wen‐Xian , Chai Wen‐Juan , Liu Yu , Li Ying‐Jie , Ren Tie , Zhang Jing , Ao Bo‐Yang
Published: November 2011

A series of rare earth complexes [(TbxTmy)L5(ClO4)2](ClO4)·3H2O (x:y = 1.000:0.000, 0.999:0.001, 0.995:0.005, 0.990:0.010, 0.950:0.050, 0.900:0.100, 0.800:0.200, 0.700:0.300; L = C6H5CH2SOCH2COC6H5) (Tb(III) luminescence ion; Tm(III) doped inert ion) were synthesized and characterized by elemental analysis, infrared spectra (IR) and 1H‐NMR. The photophysical properties of these complexes were studied in detail using ultraviolet absorption spectra, fluorescent spectra and lifetimes. The fluorescence spectra of complexes indicated that the fluorescence emission intensity was significantly enhanced by Tm(III). The complexes showed the best luminescence properties when the mole ratio Tb(III):Tm(III) was 0.990:0.010. The fluorescence intensity could be increased to 390%. Additionally, phosphorescence spectra and the luminescence mechanisms are discussed. Copyright © 2011 John Wiley & Sons, Ltd.
A rapid and sensitive determination of aucubin in rat plasma by liquid chromatography–tandem mass spectrometry and its pharmacokinetic application
Authors: Xu Wei , Deng Zhipeng , Guo Hong , Ling Peixue
Published: November 2011

A sensitive, accurate, rapid and robust LC‐MS‐MS method for the quantification of aucubin, a major bioactive constituent of Aucuba japonica, Eucommia ulmoides and Plantago asiatica, was established and validated in rat plasma. Plasma samples were simply precipitated by adding methanol and the supernatant was chromatographed by a Diamonsil® C18(2) column with the mobile phase comprising a mixture of 10 mm ammonium acetate in methanol and that in water with the ratio of 50:50 (v/v). Quantification of aucubin was performed by mass spectrometry in the multiple‐reaction monitoring mode with positive atmospheric ionization at m/z 364 → 149 for aucubin, and m/z 380 → 165 for catalpol (IS), respectively. The retention time was 2.47 and 2.44 min for aucubin and the IS, respectively. The calibration curve (10.0–30,000 ng/mL) was linear (r2 > 0.99) and the lower limit of quantification was 10.0 ng/mL in the rat plasma sample. The method showed satisfactory results such as sensitivity, specificity, precision, accuracy, recovery, freeze–thaw and long‐term stability. This simple LC‐MS method was successfully applied in a pharmacokinetic study carried out in Sprague–Dawley rats after oral administration of aucubin at a single dose of 50 mg/kg. Herein the pharmacokinetic study of aucubin is reported for the first time. Copyright © 2011 John Wiley & Sons, Ltd.
Development of a rapid and sensitive SPE‐LC‐MS/MS method for the simultaneous estimation of fluoxetine and olanzapine in human plasma
Authors: Gopinath Shanmugam , Kumar Ramadass Satiesh , Alexander Sekar , Danabal Palanisamy
Published: November 2011

A high‐performance liquid chromatographic assay with tandem mass spectrometric detection was developed to simultaneously quantify fluoxetine and olanzapine in human plasma. The analytes and the internal standard (IS) duloxetine were extracted from 500 μL aliquots of human plasma through solid‐phase extraction. Chromatographic separation was achieved in a run time of 4.0 min on a Hypersil Gold C18 column (50 × 4.6 mm, 5 µm) using isocratic mobile phase consisting of acetonitrile–water containing 2% formic acid (70:30, v/v), at a flow‐rate of 0.5 mL/min. Detection of analytes and internal standard was performed by electrospray ionization tandem mass spectrometry, operating in positive‐ion and multiple reaction monitoring acquisition mode. The protonated precursor to product ion transitions monitored for fluoxetine, olanzapine and IS were m/z 310.01 → 147.69, 313.15 → 256.14 and 298.1 → 153.97, respectively. The method was validated over the concentration range of 1.00–150.20 ng/mL for fluoxetine and 0.12–25.03 ng/mL for olanzapine in human plasma. The intra‐batch and inter‐batch precision (%CV) across four quality control levels was ≤6.28% for both the analytes. In conclusion, a simple and sensitive analytical method was developed and validated in human plasma. This method is suitable for measuring accurate plasma concentration in bioequivalence study and therapeutic drug monitoring as well, following combined administration. Copyright © 2011 John Wiley & Sons, Ltd.
Stable Analogues of OSB‐AMP: Potent Inhibitors of MenE, the o‐Succinylbenzoate‐CoA Synthetase from Bacterial Menaquinone Biosynthesis
Authors: Lu Xuequan , Zhou Rong , Sharma Indrajeet , Li Xiaokai , Kumar Gyanendra , Swaminathan Subramanyam , Tonge Peter J. , Tan Derek S.
Published: November 2011

MenE, the o‐succinylbenzoate (OSB)‐CoA synthetase from bacterial menaquinone biosynthesis, is a promising new antibacterial target. Sulfonyladenosine analogues of the cognate reaction intermediate, OSB‐AMP, have been developed as inhibitors of the MenE enzymes from Mycobacterium tuberculosis (mtMenE), Staphylococcus aureus (saMenE) and Escherichia coli (ecMenE). Both a free carboxylate and a ketone moiety on the OSB side chain are required for potent inhibitory activity. OSB‐AMS (4) is a competitive inhibitor of mtMenE with respect to ATP (Ki=5.4±0.1 nM) and a noncompetitive inhibitor with respect to OSB (Ki=11.2±0.9 nM). These data are consistent with a Bi Uni Uni Bi Ping‐Pong kinetic mechanism for these enzymes. In addition, OSB‐AMS inhibits saMenE with ${K{{{\rm app}\hfill \atop {\rm i}\hfill}}}$=22±8 nM and ecMenE with ${K{{{\rm OSB}\hfill \atop {\rm i}\hfill}}}$=128±5 nM. Putative active‐site residues, Arg222, which may interact with the OSB aromatic carboxylate, and Ser302, which may bind the OSB ketone oxygen, have been identified through computational docking of OSB‐AMP with the unliganded crystal structure of saMenE. A pH‐dependent interconversion of the free keto acid and lactol forms of the inhibitors is also described, along with implications for inhibitor design.
Iron‐Mediated and ‐Catalyzed Metalative Cyclization of Electron‐Withdrawing‐Group‐Substituted Alkynes and Alkenes with Grignard Reagents
Authors: Hata Takeshi , Sujaku Shiro , Hirone Naoki , Nakano Kirihiro , Imoto Junsuke , Imade Haduki , Urabe Hirokazu
Published: November 2011

Treatment of ethyl (E)‐5,5‐bis[(benzyloxy)methyl]‐8‐(N,N‐diethylcarbamoyl)‐2‐octen‐7‐ynoate with an iron reagent generated from FeCl2 and tBuMgCl in a ratio of 1:4 (abbreviated as FeCl2/4 tBuMgCl) afforded ethyl [4,4‐bis[(benzyloxy)methyl]‐2‐[(E)‐(N,N‐diethylcarbamoyl)methylene]cyclopent‐1‐yl]acetate in good yield. Deuteriolysis of an identical reaction mixture afforded the bis‐deuterated product ethyl [4,4‐bis[(benzyloxy)methyl]‐2‐[(E)‐(N,N‐diethylcarbamoyl)deuteriomethylene]cyclopent‐1‐yl]deuterioacetate, thus confirming the existence of the corresponding dimetalated intermediate. The latter intermediate can react with halogens or aldehydes to facilitate further synthetic transformations. The amount of FeCl2 was reduced to catalytic levels (10 mol % relative to enyne), and catalytic cyclizations of this sort proceeded with yields comparable to those of the aforementioned stoichiometric reactions. The cyclization of diethyl (E,E)‐2,7‐nonadienedioate with a stoichiometric amount of FeCl2/4 tBuMgCl, followed by the addition of sBuOH as a proton source, afforded a mixture of 2‐(ethoxycarbonyl)‐3‐bicyclo[3.3.0]octanone and its enol form in good yield. The use of aldehyde or ketone in place of sBuOH afforded 2‐(ethoxycarbonyl)‐3‐bicyclo[3.3.0]octanone, which has an additional hydroxyalkyl side chain. Additionally, the metalation of a carbon–carbon unsaturated bond in N,N‐diethyl‐5,5‐bis[(benzyloxy)methyl]‐7,8‐epoxy‐2‐octynamide or (E)‐3,3‐dimethyl‐6‐(N,N‐diethylcarbamoyl)‐5‐hexenyl p‐toluenesulfonate with FeCl2/4 tBuMgCl or FeCl2/4 PhMgBr was followed by an intramolecular alkylation with an epoxide or alkyl p‐toluenesulfonate to afford 5,5‐bis[(benzyloxy)methyl]‐3‐[(E)‐(N,N‐diethylcarbamoyl)methylene]‐1‐cyclohexanol or N,N‐diethyl(3,3‐dimethylcyclopentyl)acetamide after hydrolysis. In both cases, the remaining metalated portion α to the amide group was confirmed by deuteriolysis and could be utilized for an alkylation with methyl iodide.
Well‐Organized Zeolite Nanocrystal Aggregates with Interconnected Hierarchically Micro–Meso–Macropore Systems Showing Enhanced Catalytic Performance
Authors: Yang Xiao‐Yu , Tian Ge , Chen Li‐Hua , Li Yu , Rooke Joanna C. , Wei Ying‐Xu , Liu Zhong‐Min , Deng Zhao , Van Tendeloo Gustaaf , Su Bao‐Lian
Published: November 2011

Preparation and characterization of well‐organized zeolitic nanocrystal aggregates with an interconnected hierarchically micro–meso–macro porous system are described. Amorphous nanoparticles in bimodal aluminosilicates were directly transformed into highly crystalline nanosized zeolites, as well as acting as scaffold template. All pores on three length scales incorporated in one solid body are interconnected with each other. These zeolitic nanocrystal aggregates with hierarchically micro–meso–macroporous structure were thoroughly characterized. TEM images and 29Si NMR spectra showed that the amorphous phase of the initial material had been completely replaced by nanocrystals to give a micro–meso–macroporous crystalline zeolitic structure. Catalytic testing demonstrated their superiority due to the highly active sites and the presence of interconnected micro–meso–macroporosity in the cracking of bulky 1,3,5‐triisopropylbenzene (TIPB) compared to traditional zeolite catalysts. This synthesis strategy was extended to prepare various zeolitic nanocrystal aggregates (ZSM‐5, Beta, TS‐1, etc.) with well‐organized hierarchical micro–meso–macroporous structures.
Evidences for the Key Role of Hydrogen Bonds in Nucleophilic Aromatic Substitution Reactions
Authors: Chéron Nicolas , El Kaïm Laurent , Grimaud Laurence , Fleurat‐Lessard Paul
Published: November 2011

The effect of hydrogen bonds on the fate of nucleophilic aromatic substitutions (SNAr) has been studied in silico using a density functional theory approach in the condensed phase. The importance of these hydrogen bonds can explain the “built‐in solvation” model of Bunnett concerning intermolecular processes between halogenonitrobenzenes and amines. It is also demonstrated that it can explain experimental results for a multicomponent reaction (the Ugi–Smiles coupling), involving an intramolecular SNAr (the Smiles rearrangement) as the key step of the process. Modeling reveals that when an intramolecular hydrogen bond is present, it lowers the activation barrier of this step and enables the multicomponent reaction to proceed.
Rotational Spectrum and Internal Dynamics of Tetrahydrofuran–Krypton
Authors: Gou Qian , Feng Gang , Evangelisti Luca , Maris Assimo , Marchini Marianna , Velino Biagio , Caminati Walther
Published: November 2011

The rotational spectrum of the tetrahydrofuran–krypton van der Waals complex has been investigated by pulsed‐jet Fourier transform microwave spectroscopy. The spectra of the 84Kr and 86Kr isotopologues have been assigned and the krypton atom is located nearly over the oxygen atom, almost perpendicular to the COC plane. Each rotational transition is split into two component lines due to, according to the observed Coriolis coupling term between the tunneling states, the residual pseudorotational effects of the ring in the complex. The splitting between the two vibrational sublevels is 87.462(2) and 87.062(2) MHz for the 84Kr and 86Kr isotopologues, respectively. These splittings have been used to determine the barrier to inversion, B2=67 cm−1. The dissociation energy has been estimated to be 3.7 kJ mol−1 from centrifugal distortion effects.
Biomarkers: improving the cost‐effectiveness of biological drugs for autoimmune disorders
Authors: Gurwitz David
Published: November 2011

Biological drugs are gradually becoming the treatment of choice for chronic autoimmune diseases. However, their high costs are a key healthcare concern limiting their attractiveness for payers. This can, in part, be offset by implementing drug response biomarkers so that payers will only cover the drugs for patients who are most likely to benefit from them. Identifying such biomarkers in turn depends on the availability of well‐characterized clinical samples. Research collaboration between the pharmaceutical industry, clinicians, and academia is paramount for achieving this goal. Drug Dev Res 72:549–552, 2011. © 2011 Wiley Periodicals, Inc.
Emergence of small‐molecule CXCR4 antagonists as novel immune and hematopoietic system regulatory agents
Authors: Wilson Lawrence J. , Liotta Dennis C.
Published: November 2011

The chemokine CXCR4 receptor is a G‐protein‐coupled receptor that has multiple functions in normal physiologies involving the hematopoietic and immune systems. Although the CXCR4 receptor was initially discovered as one of the co‐receptors involved in human immune deficiency virus (HIV) cell entry, it has also been linked to many central immune system functions through the direct regulation of cell trafficking and adhesion, and is present in many cell types within the body. The receptor ligand combination of CXCL12 (SDF‐1) and CXCR4 underlies pathologies such as HIV infection, cancer metastasis and drug resistance, leukemia progression, rheumatoid arthritis, and lupus. This alternative and widespread functionality has allowed researchers to discover new potential uses for substances that are CXCR4 antagonists. This has resulted in approval of the first CXCR4 antagonist, plerixafor injection (AMD3100), for hematopoietic stem cell mobilization. Newer agents are under clinical evaluation for HIV, cancer, and stem cell mobilization. As these agents are further investigated, new uses and therapeutic interventions for CXCR4 antagonists will be discovered. Drug Dev Res 72:598–602, 2011. © 2011 Wiley Periodicals, Inc.
Anti‐tumor necrosis factor‐α therapies for immune‐mediated and inflammatory skin diseases
Authors: Dessinioti Clio , Stratigos Alexander J. , Katsambas Andreas , Antoniou Christina
Published: November 2011

Anti‐tumor necrosis factor‐α (TNF‐α) therapies, also called biologic therapies or immunotherapies, are being used increasingly in dermatology, rheumatology, and gastroenterology in the context of established and emerging indications. Anti‐TNF agents target TNF‐α and include infliximab (a chimeric IgG1 monoclonal antibody), adalimumab (a fully human recombinant IgG1 monoclonal antibody), and etanercept (a dimeric fusion protein of TNFR1 linked to the Fc portion of IgG1). Among skin diseases, only plaque psoriasis represents an approved indication for the use of anti‐TNF‐α agents; however, anti‐TNF therapies have been used as off‐label treatments in a plethora of immune‐mediated or inflammatory cutaneous disorders, such as hidradenitis suppurativa, alopecia areata, pyoderma gangrenosum, and pemphigus vulgaris. In this short review we present accumulating evidence regarding the dual effect of these therapies in inflammatory skin diseases, either resulting in improvement or acting as a paradoxical trigger for their development. The proposed mechanism of action of anti‐TNF treatments on pathogenic key points of these skin conditions is also discussed. Drug Dev Res 72:615–622, 2011. © 2011 Wiley Periodicals, Inc.
Belimumab therapy for systemic lupus erythematosus and potential treatment of rheumatoid arthritis
Authors: Ding Changhai , Li Ran , Xu Jianhua , Cicuttini Flavia , Jones Graeme
Published: November 2011

B‐lymphocyte stimulator (BLyS) maintains the survival of B cells, and is elevated in serum or locally in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Belimumab (LymphoStat‐B) is a fully human IgG1λ monoclonal antibody that binds to soluble human BLyS and inhibits its biological activity. It has been developed for therapy for SLE and the potential treatment of other autoimmune diseases. Belimumab was well tolerated in the treatment of SLE for more than 5 years and of RA for more than 24 weeks. In the pooled analyses of two Phase III trials including 1,684 seropositive SLE patients, a statistically significant improvement was observed for the SLE responder index at week 52 for belimumab 1 mg/kg and 10 mg/kg as compared with placebo (46% vs 39%, P = 0.006; 51% vs 39%, P<0.0001, respectively). It modestly reduced the signs and symptoms of RA, most notably in subgroups such as patients with high disease activity, positive rheumatoid factor, and no prior anti‐tumor necrosis factor (TNF) treatment. Belimumab has been approved by the US Food and Drug Administration for the treatment of adult patients with active and seropositive SLE who are receiving standard therapy, but its place in the treatment of RA and other autoimmune diseases remains uncertain. Drug Dev Res 72:623–633, 2011. © 2011 Wiley Periodicals, Inc.
Current management of Behçet's syndrome
Authors: Nowatzky Johannes , Yazici Yusuf
Published: November 2011

Behçet's syndrome (BS), or Behçet's disease (BD), is a multisystem inflammatory disorder that mainly affects population clusters along the Old Silk Road; however, it has been reported worldwide. The disease is currently classified as a vasculitis, characterized by sporadic outbreaks. The hallmarks of BS are recurrent, painful oral ulcers. Skin, eyes, central nervous system (CNS), gastrointestinal tract (GI) tract, and other organs may also be involved. CNS, GI, and major vascular involvement can be life‐threatening, and uveitis may lead to blindness. Immunosuppressive and immunomodulatory treatment is the mainstay of therapy for this inflammatory disease. Whereas the most frequently used agents for the treatment of BS have been corticosteroids, colchicine, and azathioprine, the introduction of anti‐tumor necrosis factor (TNF) agents and interferon‐α (IFN‐α) has begun to revolutionize the treatment of Behçet's eye disease and the management of other major organ manifestations. Data from randomized controlled trials (RCTs) showing beneficial effects for some of its disease manifestations are available for azathioprine, colchicine, cyclosporine, etanercept, IFN‐α depot‐methylprednisolone, and others. Currently, an evidence‐based approach to the management of BS is possible only for eye, mucocutaneous, and joint involvement, whereas recommendations for the treatment of gastrointestinal, neurological, and vascular disease remain based on expert opinion. Drug Dev Res 72:647–656, 2011. © 2011 Wiley Periodicals, Inc.
Electrocatalytic Oxidation of Estrogenic Phenolic Compounds at a Nickel‐Modified Glassy Carbon Electrode
Authors: Muna Grace W. , Kaylor Adam , Jaskowski Bonnie , Sirhan Lama R. , Kelley Craig T.
Published: November 2011

This paper demonstrates for the first time, successful electrocatalytic oxidation of electroactive estrogenic phenolic compounds (EPCs) at a nickel‐modified glassy carbon electrode (Ni‐GCE). The electrode was evaluated in terms of electrocatalytic activity, sensitivity, linear dynamic range, limit of detection, and response stability. In comparison to bare glassy carbon electrode, current amplification was observed for EPCs at Ni‐GCE, for example, for a 40 µM estrone at Ni‐GCE was amplified by a factor of 1224. The Ni‐GCE gave good figures of merit with no evidence of electrode fouling. As an example, the limit of detection (S/N=3) for 17β‐estradiol was 100 nM and the response precision (n=5) was 3.4 %.
On the distributed Lagrange multiplier/fictitious domain method for rigid‐particle‐laden flows: a proposition for an alternative formulation of the Lagrange multipliers
Authors: Yiantsios S.G.
Published: November 2011

The distributed Lagrange multiplier/fictitious domain method proposed for the direct numerical simulation of particle‐laden flows is considered in this work. First, it is demonstrated that improved accuracy is obtained with a coupled numerical scheme, whereby the pressure and the Lagrange multiplier fields enforcing incompressibility and rigid body motion, respectively, are calculated and applied together. However, the convergence characteristics of the iterative solution of the coupled scheme are poor because symmetric but indefinite and poorly conditioned matrices are produced. An analysis is then presented, which suggests that the cause for the matrix pathologies lies in the interaction of the respective matrix operators enforcing incompressibility and rigid body motion. On the basis of this analysis, an alternative formulation is developed for the Lagrange multipliers, being now composed of a set of forces distributed only on the particle boundary together with a set of couples distributed within the particle core. The new formulation is tested with several types of flows with stationary or moving particles under creeping or finite Reynolds number conditions and it is demonstrated that it produces correct results and better conditioned matrices, thus enabling faster and more reliable convergence of the conjugate gradient method. The analysis and tests, therefore, support the expectation that the proposed formulation is promising and worthy of further study and improvement. Copyright © 2011 John Wiley & Sons, Ltd.
Electric field calculations in brain stimulation based on finite elements: An optimized processing pipeline for the generation and usage of accurate individual head models
Authors: Windhoff Mirko , Opitz Alexander , Thielscher Axel
Published: November 2011

The need for realistic electric field calculations in human noninvasive brain stimulation is undisputed to more accurately determine the affected brain areas. However, using numerical techniques such as the finite element method (FEM) is methodologically complex, starting with the creation of accurate head models to the integration of the models in the numerical calculations. These problems substantially limit a more widespread application of numerical methods in brain stimulation up to now. We introduce an optimized processing pipeline allowing for the automatic generation of individualized high‐quality head models from magnetic resonance images and their usage in subsequent field calculations based on the FEM. The pipeline starts by extracting the borders between skin, skull, cerebrospinal fluid, gray and white matter. The quality of the resulting surfaces is subsequently improved, allowing for the creation of tetrahedral volume head meshes that can finally be used in the numerical calculations. The pipeline integrates and extends established (and mainly free) software for neuroimaging, computer graphics, and FEM calculations into one easy‐to‐use solution. We demonstrate the successful usage of the pipeline in six subjects, including field calculations for transcranial magnetic stimulation and transcranial direct current stimulation. The quality of the head volume meshes is validated both in terms of capturing the underlying anatomy and of the well‐shapedness of the mesh elements. The latter is crucial to guarantee the numerical robustness of the FEM calculations. The pipeline will be released as open‐source, allowing for the first time to perform realistic field calculations at an acceptable methodological complexity and moderate costs. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Quantitative effect of the neonatal fontanel on synthetic near infrared spectroscopy measurements
Authors: Dehaes Mathieu , Kazemi Kamran , Pélégrini‐Issac Mélanie , Grebe Reinhard , Benali Habib , Wallois Fabrice
Published: November 2011

Near infrared spectroscopy (NIRS) is a functional imaging technique allowing measurement of local cerebral oxygenation. This modality is particularly adapted to critically ill neonates, as it can be used at the bedside and is a suitable and noninvasive tool for carrying out longitudinal studies. However, NIRS is sensitive to the imaged medium and consequently to the optical properties of biological tissues in which photons propagate. In this study, the effect of the neonatal fontanel was investigated by predicting photon propagation using a probabilistic Monte Carlo approach. Two anatomical newborn head models were created from computed tomography and magnetic resonance images: (1) a realistic model including the fontanel tissue and (2) a model in which the fontanel was replaced by skull tissue. Quantitative change in absorption due to simulated activation was compared for the two models for specific regions of activation and optical arrays simulated in the temporal area. A correction factor was computed to quantify the effect of the fontanel and defined by the ratio between the true and recovered change. The results show that recovered changes in absorption were more precise when determined with the anatomical model including the fontanel. The results suggest that the fontanel should be taken into account in quantification of NIRS responses to avoid misinterpretation in experiments involving temporal areas, such as language or auditory studies. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
The microenvironment in hepatocyte regeneration and function in rats with advanced cirrhosis
Authors: Liu Liping , Yannam Govardhana Rao , Nishikawa Taichiro , Yamamoto Toshiyuki , Basma Hesham , Ito Ryotaro , Nagaya Masaki , Dutta-Moscato Joyeeta , Stolz Donna B. , Duan Fenghai , Kaestner Klaus H. , Vodovotz Yoram , Soto-Gutierrez Alejandro , Fox Ira J.
Published: November 2011

In advanced cirrhosis, impaired function is caused by intrinsic damage to the native liver cells and from the abnormal microenvironment in which the cells reside. The extent to which each plays a role in liver failure and regeneration is unknown. To examine this issue, hepatocytes from cirrhotic and age-matched control rats were isolated, characterized, and transplanted into the livers of noncirrhotic hosts whose livers permit extensive repopulation with donor cells. Primary hepatocytes derived from livers with advanced cirrhosis and compensated function maintained metabolic activity and the ability to secrete liver-specific proteins, whereas hepatocytes derived from cirrhotic livers with decompensated function failed to maintain metabolic or secretory activity. Telomere studies and transcriptomic analysis of hepatocytes recovered from progressively worsening cirrhotic livers suggest that hepatocytes from irreversibly failing livers show signs of replicative senescence and express genes that simultaneously drive both proliferation and apoptosis, with a later effect on metabolism, all under the control of a central cluster of regulatory genes, including nuclear factor κB and hepatocyte nuclear factor 4α. Cells from cirrhotic and control livers engrafted equally well, but those from animals with cirrhosis and failing livers showed little initial evidence of proliferative capacity or function. Both, however, recovered more than 2 months after transplantation, indicating that either mature hepatocytes or a subpopulation of adult stem cells are capable of full recovery in severe cirrhosis.

Conclusion :

Transplantation studies indicate that the state of the host microenvironment is critical to the regenerative potential of hepatocytes, and that a change in the extracellular matrix can lead to regeneration and restoration of function by cells derived from livers with end-stage organ failure. (Hepatology 2011)
Peer interaction in mergers: Evidence of collective rumination
Authors: Marmenout Katty
Published: November 2011

Following abundant anecdotal evidence of low morale in mergers and its important detrimental effect on postmerger performance, the purpose of this multimethod experimental study was to find out how employee reactions to a merger evolve over time following peer interaction (i.e., discussion with colleagues). Using a scenario study, initial reactions to a merger announcement were compared with socially influenced reactions. As anticipated, an overall strong detrimental effect of peer interaction on employee reactions was observed. Next, findings indicate that deal characteristics (culture clash potential, announced degree of integration, and position in deal structure) play a moderating role. Indeed, how peer interaction affects outcomes depends on the position in the deal structure. Qualitative data analysis of the group discussions sheds light on how employee reactions become more detrimental. This process is conceptualized as “collective rumination,” defined as repetitively and passively discussing organizational problems and their negative consequences with a group of peers. The study concludes with implications for practice and identifies three powerful levers (active involvement, distraction, and positive leadership) to influence the way in which employees react to the event. © 2011 Wiley Periodicals, Inc.
Previous fractures at multiple sites increase the risk for subsequent fractures: The global longitudinal study of osteoporosis in women
Authors: Gehlbach Stephen , Saag Kenneth G , Adachi Jonathan D , Hooven Fred H , Flahive Julie , Boonen Steven , Chapurlat Roland D , Compston Juliet E , Cooper Cyrus , Díez-Perez Adolfo , Greenspan Susan L , LaCroix Andrea Z , Netelenbos J Coen , Pfeilschifter Johannes , Rossini Maurizio , Roux Christian , Sambrook Philip N , Silverman Stuart , Siris Ethel S , Watts Nelson B , Lindsay Robert
Published: November 2011

Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women aged ≥55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures, respectively, since age 45 years. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no previous fractures, women with 1, 2, or ≥3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio [HR] = 7.3) and hip (HR = 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, and previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture. Women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development. © 2012 American Society for Bone and Mineral Research
Esophageal and gastric cancer incidence and mortality in alendronate users
Authors: Abrahamsen Bo , Pazianas Michael , Eiken Pia , Russell R Graham G , Eastell Richard
Published: November 2011

Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer deaths or endoscopy rates, which could be higher in bisphosphonate users and lead to more cancers being diagnosed at a stage when their esophageal or gastric location could be accurately distinguished. We conducted a register-based, open cohort study using national healthcare data for Denmark. Upper endoscopy frequency, cancer incidence and mortality was examined in 30,606 alendronate users (female, age 50+) and 122,424 matched controls. Primary outcomes were esophageal cancer incidence and death because of esophageal cancer. The analysis showed that alendronate users were more likely to have undergone recent upper endoscopy (4.1 versus 1.7%, p < 0.001). Alendronate users had a lower risk of incident gastric cancer [odds ratio (OR) 0.61; 95% confidence interval (CI): 0.39–0.97) and no increased risk of esophageal cancer (OR 0.71; 95% CI: 0.43–1.19). Risk reductions were greater in users with 10+ prescriptions. The risk of dying of esophageal cancer was significantly reduced in alendronate users after 3 years OR 0.45 (95% CI: 0.22–0.92) but not after 9 years (OR 1.01; 95% CI: 0.52–1.95). An additional comparison with etidronate users revealed no statistically significant difference in outcomes. In conclusion, we found no excess in esophageal cancer deaths or incidence. The early decrease in esophageal cancer rates may relate to the greater use of endoscopy before starting alendronate. Longer term observations also indicated no excess risk of esophageal cancer death and a significantly decreased risk of gastric cancer death. © 2012 American Society for Bone and Mineral Research
Variability of the paracrine‐induced osteoclastogenesis by human breast cancer cell lines
Authors: Costa‐Rodrigues João , Moniz Karen A. , Teixeira Manuel R. , Fernandes Maria H.
Published: November 2011

Breast cancer frequently metastasizes to the bone, often leading to the formation of osteolytic lesions. This work compares the paracrine‐induced osteoclastogenesis mediated by four human breast cancer cell lines, the estrogen‐receptor positive T47D and MCF‐7 and the estrogen‐negative SK‐BR‐3 and Hs‐578T cell lines. Human osteoclast precursor cells were cultured in the presence of conditioned media from the breast cancer cell lines (10% and 20%), collected at different culture periods (48 h, 7 days, and 14 days). Cultures performed in the absence or the presence of M‐CSF and RANKL served as negative and positive control, respectively. Results showed that the cell lines differentially expressed several osteoclastogenic genes. All cell lines exhibited a significant osteoclastogenic potential, evidenced by a high TRAP activity and number of osteoclastic cells, expression of several osteoclast‐related genes, and, particularly, a high calcium phosphate resorption activity. Differences among the osteoclastogenic potential of the cell lines were noted. T47D and MCF‐7 cell lines displayed the highest and the lowest osteoclastogenic response, respectively. Despite the variability observed, MEK and NF‐κB signaling pathways, and, at a lesser extent, PGE2 production, seemed to have a central role on the observed osteoclastogenic response. In conclusion, the tested breast cancer cell lines exhibited a high osteoclastogenic potential, although with some variability on the cell response profile, a factor to be considered in the development of new therapeutic approaches for breast cancer‐induced bone metastasis. J. Cell. Biochem. 113: 1069–1079, 2012. © 2011 Wiley Periodicals, Inc.
Helicobacter pylori CagA inhibits the expression of Runx3 via Src/MEK/ERK and p38 MAPK pathways in gastric epithelial cell
Authors: Liu Zhifang , Xu Xia , Chen Long , Li Wenjuan , Sun Yundong , Zeng Jiping , Yu Han , Chen Chunyan , Jia Jihui
Published: November 2011

Infection with CagA‐positive Helicobacter pylori is the strongest risk factor for gastric carcinoma. Upon delivery into gastric epithelial cells, CagA disturbs cellular functions by physically interacting with and deregulating intracellular signaling molecules via both tyrosine phosphorylation‐dependent and ‐independent mechanisms. Runx3 was suggested to be a tumor suppressor and closely associated with tumorigenesis and progression of gastric cancer. The aim of our study is to verify the effect of H. pylori virulence factor CagA on Runx3 expression level and investigate the corresponding molecular mechanisms and signaling pathways influencing Runx3 expression. Human gastric epithelial immortalized GES‐1 cells were transfected with CagA‐expression vector or control vector with FuGENE HD transfection reagent. Runx3 expression levels were determined by QRT‐PCR and immunoblotting. Then we constructed a 1,150 bp Runx3 promoter luciferase reporter plasmid, pGL3‐1150 bp, which was co‐transfected into GES‐1 cell with CagA‐expression vector or control vector. Luciferase reporter assay was used to determine the effects of CagA on the 1,150 bp promoter activity of Runx3. Signal inhibitors were used to detect the signal pathway(s) through which CagA affects Runx3. Our results showed that CagA can reduce the expression level of Runx3 at both mRNA and protein levels significantly. Importantly, the 1,150 bp Runx3 promoter activity was decreased in cells transfected with CagA‐expression vector comparing with cells transfected with control vector. And this inhibition is dependent on the phosphorylation of CagA. Signal pathways Src/MEK/ERK and p38 MAPK are involved in this regulation. Our findings provide new insights for understanding the mechanism of H. pylori carcinogenesis. J. Cell. Biochem. 113: 1080–1086, 2012. © 2011 Wiley Periodicals, Inc.
Ins and outs of Mycobacterium tuberculosis PPE family in pathogenesis and implications for novel measures against tuberculosis
Authors: Deng Wanyan , Xie Jianping
Published: November 2011

Mycobacterium tuberculosis is the most successful pathogen with multiple mechanisms to subvert host immune response, resulting in insidious disease. A unique Mycobacterium antigen family termed PPE (Pro‐Pro‐Glu) has long been widely speculated as “molecular mantra” to escape host immunity. Members of this family are characterized by a conserved N terminal and a variable C terminal. This family associated closely with ESAT‐6(ESX) secretion system and largely located in cell wall or cell membrane. The expression of PPE protein is temporally regulated, and highly expressed during M. tuberculosis persistence. Importantly, the distribution of PPE family is so far limited to Mycobacterium genus, prevalent among pathogenic Mycobacterium species. It is tempting to explore this family due to its potential in the latency and reactivation of M. tuberculosis. The evolution, structure, and functions of most PPE proteins remain elusive. The understanding of these questions will deepen our appreciation of the pathogenesis of M. tuberculosis and accelerate novel anti‐TB measures discovery. J. Cell. Biochem. 113: 1087–1095, 2012. © 2011 Wiley Periodicals, Inc.