bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacy Faculty Members' Perception of Contemporary Pharmacy Practice
Authors: Ng Karen W.K. , Rosenthal Meagen M. , Tsuyuki Ross T. 
Published: September 2011

Objective: Previous research has shown that community pharmacists describe their role mostly in product-focused rather than patient-centred terms. We wondered if pharmacy faculty members think similarly, which might influence how students, and subsequently, new pharmacists think. The objective of this study was to examine how pharmacy faculty members describe the health care role of pharmacists. Method: We telephoned 101 randomly selected Canadian pharmacy faculty members. The surveyor posed as a sociology student studying the use of language. We asked a single question: “What does a pharmacist do?,” asking respondents to answer in a few short phrases that were recorded verbatim. Responses were analyzed by content and categories were established from previous studies, coded as “patient-centred,” “product-focused (dispensing),” “research” or “business-related.” Results: Ninety-four faculty members (71% were pharmacists) provided 200 responses. Of the responses, 40% were categorized as patient-centred, 32.5% were product-focused and 5% were research- or business-related. Evaluating participants' first responses, faculty members who were pharmacists offered a patient-centred description in 59% of responses, while non-pharmacists provided a more pro duct-focused description. The most frequently used terms to describe a pharmacist's role were: patient, medication, educate, dispense, responsible, safety and ensure. Conclusions: Pharmacy faculty members' perception of the role of pharmacists may influence the culture of the profession. We found that faculty members were more idealistic about patient-centred roles for pharmacists than community or hospital pharmacists, but a large proportion (mainly nonpharmacist faculty members) still describe a product-focused role.
Pharmacokinetics of Antiretroviral Drugs in Anatomical Sanctuary Sites: The Fetal Compartment (Placenta and Amniotic Fluid)
Authors: Else Laura J , Taylor Stephen , Back David J , Khoo Saye H 
Published: September 2011

HIV resides within anatomical ‘sanctuary sites’ where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Widespread implementation of antiretroviral therapy has seen a significant decline in the incidence of mother-to-child transmission (MTCT) of HIV. In addition to suppression of maternal plasma/genital viral loads, antiretroviral agents that cross the placenta and achieve adequate concentrations in the fetal compartment may exert a greater prophylactic effect. Penetration of antiretrovirals in the fetal compartment is expressed by accumulation ratios derived from the measurement of drug concentrations in paired maternal plasma and umbilical cord samples. The nucleoside analogues and nevirapine accumulate extensively in cord blood and in the surrounding amniotic fluid, whereas the protease inhibitors (PIs) exhibit low-to-moderate placental accumulation. Early data suggest that high placental/neonatal concentrations are achieved with raltegravir, but to a lesser extent with etravirine and maraviroc (rank order of accumulation: raltegravir/nucleoside reverse transcriptase inhibitor [tenofovir > zidovudine/lamivudine/emtricitabine/stavudine/abacavir] > non-nucleoside reverse transcriptase inhibitor [nevirapine > etravirine] > PI > maraviroc/enfuvirtide). More comprehensive in vivo pharmacokinetic data are required to justify the potential use of these agents as safe and effective options during pregnancy.
Ouverture du colloque « La cour et les sciences : naissance des politiques scientifiques dans les cours européennes aux xviie et xviiie siècles »
Authors: Aillagon Jean-Jacques , Saule Béatrix 
Published: September 2011

À l’occasion de l’exposition « Sciences et curiosités à la cour de Versailles » au château de Versailles (26 octobre 2010 au 3 avril 2011), le Centre de recherche du château de Versailles a organisé le colloque « La cour et les sciences : naissance des politiques scientifiques dans les cours européennes aux xviie et xviiie siècles ». Pour les sciences et pour le royaume – devrions-nous dire. En effet, la cour, siège du pouvoir et lieu de concentration des capitaux, soutenait la recherche scientifique tandis que cette dernière devait servir les intérêts généraux du pays et la gloire de son souverain. En un temps qui ignorait encore la séparation entre les deux cultures, scientifique et technique d’un côté, humaniste et artistique de l’autre, on vit cependant s’affirmer une nouvelle idée de la science. Cette modernité, la plupart du temps, ne put exister sans le concours actif des princes. La cour, comme lieu d’expérimentation, d’innovations techniques, apparaît comme un des moteurs des évolutions de la recherche, permettant notamment des applications concrètes. L’implication des souverains européens, par leur éducation, par leurs rapports privilégiés avec les savants, fut souvent à l’origine du développement des connaissances scientifiques dans de nombreux domaines. Dans ce colloque, il s’agit donc essentiellement d’étudier les politiques scientifiques volontaristes ou non des états européens sous l’Ancien Régime en s’attachant particulièrement à la recherche « fondamentale » et à la recherche « utile » (amélioration de la santé, lutte contre la famine, progrès des techniques, des constructions et des bâtiments, etc.). Volontairement comparatistes, les études englobent l’aire géographique européenne à travers trois axes : le financement des sciences et des scientifiques, la communauté scientifique face à la cour et, enfin, la diffusion et la culture scientifique à la cour.
Critical Roles of ASC Inflammasomes in Caspase-1 Activation and Host Innate Resistance to Streptococcus pneumoniae Infection
Authors: Fang Rendong , Tsuchiya Kohsuke , Kawamura Ikuo , Shen Yanna , Hara Hideki , Sakai Shunsuke , Yamamoto Takeshi , Fernandes-Alnemri Teresa , Yang Ruili , Hernandez-Cuellar Eduardo , Dewamitta Sita R. , Xu Yanting , Qu Huixin , Alnemri Emad S. , Mitsuyama Masao 
Published: September 2011

Abstract
Streptococcus pneumoniae is a Gram-positive, extracellular bacterium that is responsible for significant mortality and morbidity worldwide. Pneumolysin (PLY), a cytolysin produced by all clinical isolates of the pneumococcus, is one of the most important virulence factors of this pathogen. We have previously reported that PLY is an essential factor for activation of caspase-1 and consequent secretion of IL-1β and IL-18 in macrophages infected with S. pneumoniae. However, the host molecular factors involved in caspase-1 activation are still unclear. To further elucidate the mechanism of caspase-1 activation in macrophages infected with S. pneumoniae, we examined the involvement of inflammasomes in inducing this cellular response. Our study revealed that apoptosis-associated specklike protein containing a caspase recruitment domain (ASC), an adaptor protein for inflammasome receptors such as nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2), is essentially required for the induction of caspase-1 activation by S. pneumoniae. Caspase-1 activation was partially impaired in NLRP3−/− macrophages, whereas knockdown and knockout of AIM2 resulted in a clear decrease in caspase-1 activation in response to S. pneumoniae. These results suggest that ASC inflammasomes, including AIM2 and NLRP3, are critical for caspase-1 activation induced by S. pneumoniae. Furthermore, ASC−/− mice were more susceptible than wild-type mice to S. pneumoniae, with impaired secretion of IL-1β and IL-18 into the bronchoalveolar lavage after intranasal infection, suggesting that ASC inflammasomes contribute to the protection of host from infection with PLY-producing S. pneumoniae.
Pyridone 6, a Pan-JAK Inhibitor, Ameliorates Allergic Skin Inflammation of NC/Nga Mice via Suppression of Th2 and Enhancement of Th17
Authors: Nakagawa Ryusuke , Yoshida Hideyuki , Asakawa Mayako , Tamiya Taiga , Inoue Naoko , Morita Rimpei , Inoue Hiromasa , Nakao Atsuhito , Yoshimura Akihiko 
Published: September 2011

Abstract
Atopic dermatitis (AD) is a common pruritic inflammatory disease triggered by a defective skin barrier and immunodysregulation. AD has been considered a typical example of a Th2 response associated with allergic disease. In the early phases of the disease, symptoms include IgE hyperproduction, eosinophil accumulation, and mast cell activation; in the chronic phase, a Th1-dominant immune response is also observed at the sites of AD skin lesions. The role of IL-17–producing Th (Th17) cells in AD has not been established. In the current study, we found that pyridone 6 (P6), a pan-JAK inhibitor, delayed the onset and reduced the magnitude of skin disease in an AD-like skin-disease model of NC/Nga mice. P6 reduced IFN-γ and IL-13, whereas it enhanced IL-17 and IL-22 expression. In vitro, P6 also inhibited both Th1 and Th2 development, whereas it promoted Th17 differentiation from naive T cells when present within a certain range of concentrations. This was probably because P6 strongly inhibited STAT1, STAT5, and STAT6 phosphorylation, whereas STAT3 phosphorylation was less efficiently suppressed by P6 at the same concentration. Furthermore, IL-22 protects keratinocytes from apoptosis induced by IFN-γ, and administration of IL-17 and IL-22 partially ameliorated skin diseases in NC/Nga mice. These results suggested that the JAK inhibitor P6 is therapeutic for AD by modulating the balance of Th2 and Th17.
Hepatitis B Virus Induces a Novel Inflammation Network Involving Three Inflammatory Factors, IL-29, IL-8, and Cyclooxygenase-2
Authors: Yu Yi , Gong Rui , Mu Yongxin , Chen Yanni , Zhu Chengliang , Sun Zhichen , Chen Mingzhou , Liu Yingle , Zhu Ying , Wu Jianguo 
Published: September 2011

Abstract
Chronic inflammation induced by hepatitis B virus (HBV) is a major causative factor associated with the development of cirrhosis and hepatocellular carcinoma. In this study, we investigated the roles of three inflammatory factors, IL-8, IL-29 (or IFN-λ1), and cyclooxygenase-2 (COX-2), in HBV infection. We showed that the expression of IL-29, IL-8, and COX-2 genes was enhanced in HBV-infected patients or in HBV-expressing cells. In HBV-transfected human lymphocytes and hepatocytes, IL-29 activates the production of IL-8, which in turn enhances the expression of COX-2. In addition, COX-2 decreases the production of IL-8, which in turn attenuates the expression of IL-29. Thus, we proposed that HBV infection induces a novel inflammation cytokine network involving three inflammatory factors that regulate each other in the order IL-29/IL-8/COX-2, which involves positive regulation and negative feedback. In addition, we also demonstrated that COX-2 expression activated by IL-8 was mediated through CREB and C/EBP, which maintains the inflammatory environment associated with HBV infection. Finally, we showed that the ERK and the JNK signaling pathways were cooperatively involved in the regulation of COX-2. We also demonstrated that IL-29 inhibits HBV replication and that IL-8 attenuates the expression of IL-10R2 and the anti-HBV activity of IL-29, which favors the establishment of persistent viral infection. These new findings provide insights for our understanding of the mechanism by which inflammatory factors regulate each other in response to HBV infection.
DHX9 Pairs with IPS-1 To Sense Double-Stranded RNA in Myeloid Dendritic Cells
Authors: Zhang Zhiqiang , Yuan Bin , Lu Ning , Facchinetti Valeria , Liu Yong-Jun 
Published: September 2011

Abstract
The innate immune system is equipped with many molecular sensors for microbial DNA/RNA to quickly mount antimicrobial host immune responses. In this paper, we identified DHX9, a DExDc helicase family member, as an important viral dsRNA sensor in myeloid dendritic cells (mDCs). Knockdown of DHX9 expression by small heteroduplex RNA dramatically blocked the ability of mDCs to produce IFN-α/β and proinflammatory cytokines in response to polyinosine-polycytidylic acid, influenza A, and reovirus. DHX9 could specifically bind polyinosine-polycytidylic acid via its double-strand RNA binding motifs. DHX9 interacted with IPS-1 via the HelicC-HA2-DUF and CARD domains of DHX9 and IPS-1, respectively. Knockdown of DHX9 expression in mDCs blocked the activation of NF-κB and IFN regulatory factor 3 by dsRNA. Collectively, these results suggest that DHX9 is an important RNA sensor that is dependent on IPS-1 to sense pathogenic RNA.
Mycobacterial Secretion Systems ESX-1 and ESX-5 Play Distinct Roles in Host Cell Death and Inflammasome Activation
Authors: Abdallah Abdallah M. , Bestebroer Jovanka , Savage Nigel D. L. , de Punder Karin , van Zon Maaike , Wilson Louis , Korbee Cees J. , van der Sar Astrid M. , Ottenhoff Tom H. M. , van der Wel Nicole N. , Bitter Wilbert , Peters Peter J. 
Published: September 2011

Abstract
During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5—two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators—during the macrophage infection cycle. Using wild-type, ESX-1– and ESX-5–deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1β activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread.
Mechanism for Pre-B Cell Loss in VH-Mutant Rabbits
Authors: Robbins Gregory R. , Knight Katherine L. 
Published: September 2011

Abstract
Pre-BCR signaling is a critical checkpoint in B cell development in which B-lineage cells expressing functional IgH μ-chain are selectively expanded. B cell development is delayed in mutant ali/ali rabbits because the a-allotype encoding VH1 gene, which is normally used in VDJ gene rearrangements in wt rabbits, is deleted, and instead, most B-lineage cells use the a-allotype encoding VH4 gene [VH4(a)], which results in a severe developmental block at the pre-B cell stage. We found that VH4(a)-utilizing pre-B cells exhibit reduced pre-BCR signaling and do not undergo normal expansion in vitro. Transduction of murine 38B9 pre-B cells with chimeric rabbit-VDJ mouse-Cμ encoding retroviruses showed VH4(a)-encoded μ-chains do not readily form signal-competent pre-BCR, thereby explaining the reduction in pre-BCR signaling and pre-B cell expansion. Development of VH4(a)-utilizing B cells can be rescued in vivo by the expression of an Igκ transgene, indicating that VH4(a)-μ chains are not defective for conventional BCR formation and signaling. The ali/ali rabbit model system is unique because VH4(a)-μ chains have the capacity to pair with a variety of conventional IgL chains and yet lack the capacity to form a signal-competent pre-BCR. This system could allow for identification of critical structural parameters that govern pre-BCR formation/signaling.
HIV-1N-Glycan Composition Governs a Balance between Dendritic Cell-Mediated Viral Transmission and Antigen Presentation
Authors: van Montfort Thijs , Eggink Dirk , Boot Maikel , Tuen Michael , Hioe Catarina E. , Berkhout Ben , Sanders Rogier W. 
Published: September 2011

AbstractThe natural function of dendritic cells (DCs) is to capture and degrade pathogens for Ag presentation. However, HIV-1 can evade viral degradation by DCs and hijack DCs for migration to susceptible CD4+ T lymphocytes. It is unknown what factors decide whether a virus is degraded or transmitted to T cells. The interaction of DCs with HIV-1 involves C-type lectin receptors, such as DC-specific ICAM-3–grabbing nonintegrin, which bind to the envelope glycoprotein complex (Env), which is decorated heavily with N-linked glycans. We hypothesized that the saccharide composition of the Env N-glycans is involved in avoiding viral degradation and Ag presentation, as well as preserving infectious virus for the transmission to target cells. Therefore, we studied the fate of normally glycosylated virus versus oligomannose-enriched virus in DCs. Changing the heterogeneous N-linked glycan composition of Env to uniform oligomannose N-glycans increased the affinity of HIV-1 for DC-specific ICAM-3–grabbing nonintegrin and enhanced the capture of HIV-1 by immature DCs; however, it decreased the subsequent transmission to target cells. Oligomannose-enriched HIV-1 was directed more efficiently into the endocytic pathway, resulting in enhanced viral degradation and reduced virus transfer to target cells. Furthermore, Env containing exclusively oligomannose N-glycans was presented to Env-specific CD4+ T cells more efficiently. Taken together, our results showed that the HIV-1 N-glycan composition plays a crucial role in the balance between DC-mediated Ag degradation and presentation and DC-mediated virus transmission to target cells. This finding may have implications for the early events in HIV-1 transmission and the induction of antiviral immune responses.
Systems of Weakly Coupled Hamilton-Jacobi Equations with Implicit Obstacles
Authors: Gomes Diogo , Serra António 
Published: September 2011

Abstract In this paper we study systems of weakly coupled Hamilton-Jacobi equations with implicit obstacles that arise in optimal switching problems. Inspired by methods from the theory of viscosity solutions and weak KAM theory, we extend the notion of Aubry set for these systems. This enables us to prove a new result on existence and uniqueness of solutions for the Dirichlet problem, answering a question of F. Camilli, P. Loreti, and N. Yamada.
3D Crack‐tip Microscopy: Illuminating Micro‐Scale Effects on Crack‐Tip Behavior
Authors: Withers Philip J. 
Published: September 2011

AbstractTraditionally the driving force for crack growth is described in terms of global parameters which, for continua, nevertheless reflect the local conditions at the crack‐tip. Mimicking nature, materials microstructures are now being designed at the microscale, or even the nanoscale, employing interfaces and heterogeneities to shield the propagating crack for improved resistance to sub‐critical crack growth. In such cases global approaches simply will not do. Information is needed about intrinsic damage occurring ahead, and extrinsic shielding mechanisms behind, the crack. Here, high resolution X‐ray imaging and diffraction modes analogous to those in 2D electron microscopy are combined to form a 3D “crack‐tip microscope”. In this way one can quantify the effect of microstructural scale events on the crack‐tip environment. The technique is applied to study overload phenomena under fatigue, to characterize the bridging ligaments under stress corrosion cracking and fiber bridging during fatigue of a metal matrix composite. Besides identifying shielding mechanisms, it provides three methods for calculating the effective stress intensity at the crack tip; namely from the near tip stress field, from crack face tractions and from crack opening displacements. The wider opportunities opened up by this approach to study self‐healing, transformation toughening and other microstructural toughening mechanisms are also discussed.
Atomic Switch: Atom/Ion Movement Controlled Devices for Beyond Von‐Neumann Computers
Authors: Hasegawa Tsuyoshi , Terabe Kazuya , Tsuruoka Tohru , Aono Masakazu 
Published: September 2011

AbstractAn atomic switch is a nanoionic device that controls the diffusion of metal ions/atoms and their reduction/oxidation processes in the switching operation to form/annihilate a conductive path. Since metal atoms can provide a highly conductive channel even if their cluster size is in the nanometer scale, atomic switches may enable downscaling to smaller than the 11 nm technology node, which is a great challenge for semiconductor devices. Atomic switches also possess novel characteristics, such as high on/off ratios, very low power consumption and non‐volatility. The unique operating mechanisms of these devices have enabled the development of various types of atomic switch, such as gap‐type and gapless‐type two‐terminal atomic switches and three‐terminal atomic switches. Novel functions, such as selective volatile/nonvolatile, synaptic, memristive, and photo‐assisted operations have been demonstrated. Such atomic switch characteristics can not only improve the performance of present‐day electronic systems, but also enable development of new types of electronic systems, such as beyond von‐ Neumann computers.
Brønsted Acid‐Promoted Sequential Hydroarylation– Hydroamidation of Arene‐Tethered 1‐(2‐Alkynylphenyl)ureas: Direct Access to 4,4‐Spiro‐3,4‐dihydro‐2‐(1H)‐quinazolinones
Authors: Wang Honggen , Zhao Jiaji , Zhang Jiancun , Zhu Qiang 
Published: September 2011

AbstractA Brønsted acid‐promoted approach to 4,4‐sipro‐3,4‐dihydro‐2‐(1H)‐quinazolinones from arene‐tethered 1‐(2‐alkynylphenyl)ureas has been developed. The reaction is initiated by intramolecular hydroarylation followed by hydroamidation, assisted by intramolecular proton transfer from the protonated urea moiety. A variety of tethering atoms, including carbon, oxygen, sulfur, and protected nitrogen are compatible with the reaction conditions.
Konjugierte Makrocyclen: Konzepte und Anwendungen
Authors: Iyoda Masahiko , Yamakawa Jun , Rahman M. Jalilur 
Published: September 2011

AbstractEines der wichtigsten Ziele in den Materialwissenschaften, der Chemie und der Physik ist die Herstellung von großen konjugierten Makrocyclen genau definierter Form, da solche Moleküle nicht nur theoretisch und experimentell interessant sind, sondern auch potenzielle Anwendungen in der Nanotechnologie haben. Vollständig ungesättigte Makrocyclen werden als Modelle für vollständig konjugierte π‐Systeme mit Hohlräumen herangezogen. Solche konjugierten π‐Systeme zeigen aufgrund ihrer cyclischen Konjugation ein ungewöhnliches optisches und magnetisches Verhalten. Makrocyclen haben nach innen und nach außen gerichtete Bindungsstellen, und eine positionsspezifische Substitution an beiden oder nur einer der beiden Bindungsstellen kann attraktive Strukturen zugänglich machen. Von besonderer Bedeutung sind ein‐, zwei‐ und dreidimensionale supramolekulare Nanostrukturen. Um die Bildung dieser Strukturen kontrollieren zu können, bietet sich die Bottom‐Up‐Synthese ausgehend von π‐expandierten Makrocyclen an. Zahlreiche formstabile π‐konjugierte Makrocyclen wurden synthetisiert, davon aber nur eine begrenzte Zahl an nanoskaligen Vertretern. In diesem Aufsatz konzentrieren wir uns auf nanometergroße π‐konjugierte Makrocyclen (>1 nm Durchmesser) sowie Riesenmakrocyclen (>2 nm Durchmesser) und fassen deren Synthesen und Eigenschaften zusammen.