bluuebunny/crossref_metadata_2025_split huggingface dataset:
Group B Streptococci Induce Proinflammatory Responses via a Protein Kinase D1–Dependent Pathway
Authors: Upadhyay Kirtikumar , Park Jeoung-Eun , Yoon Tae Won , Halder Priyanka , Kim Young-In , Metcalfe Victoria , Talati Ajay J. , English B. Keith , Yi Ae-Kyung 
Published: May 2017

Abstract
Group B streptococci (GBS) are one of the leading causes of life-threatening illness in neonates. Proinflammatory responses to GBS mediated through host innate immune receptors play a critical role in the disease manifestation. However, the mechanisms involved in proinflammatory responses against GBS, as well as the contribution of signaling modulators involved in host immune defense, have not been fully elucidated. In the present study, we investigated the role of protein kinase D (PKD)1 in the proinflammatory responses to GBS. We found that both live and antibiotic-killed GBS induce activation of PKD1 through a pathway that is dependent on the TLR signaling adaptor MyD88 and its downstream kinase IL-1R–associated kinase 1, but independent of TNFR-associated factor 6. Our studies using pharmacological PKD inhibitors and PKD1-knockdown macrophages revealed that PKD1 is indispensable for GBS-mediated activation of MAPKs and NF-κB and subsequent expression of proinflammatory mediators. Furthermore, systemic administration of a PKD inhibitor protects d-galactosamine–sensitized mice from shock-mediated death caused by antibiotic-killed GBS. These findings imply that PKD1 plays a critical regulatory role in GBS-induced proinflammatory reactions and sepsis, and inhibition of PKD1 activation together with antibiotic treatment in GBS-infected neonates could be an effective way to control GBS diseases.
Kinase Activities of RIPK1 and RIPK3 Can Direct IFN-β Synthesis Induced by Lipopolysaccharide
Authors: Saleh Danish , Najjar Malek , Zelic Matija , Shah Saumil , Nogusa Shoko , Polykratis Apostolos , Paczosa Michelle K. , Gough Peter J. , Bertin John , Whalen Michael , Fitzgerald Katherine A. , Slavov Nikolai , Pasparakis Manolis , Balachandran Siddharth , Kelliher Michelle , Mecsas Joan , Degterev Alexei 
Published: May 2017

Abstract
The innate immune response is a central element of the initial defense against bacterial and viral pathogens. Macrophages are key innate immune cells that upon encountering pathogen-associated molecular patterns respond by producing cytokines, including IFN-β. In this study, we identify a novel role for RIPK1 and RIPK3, a pair of homologous serine/threonine kinases previously implicated in the regulation of necroptosis and pathologic tissue injury, in directing IFN-β production in macrophages. Using genetic and pharmacologic tools, we show that catalytic activity of RIPK1 directs IFN-β synthesis induced by LPS in mice. Additionally, we report that RIPK1 kinase–dependent IFN-β production may be elicited in an analogous fashion using LPS in bone marrow–derived macrophages upon inhibition of caspases. Notably, this regulation requires kinase activities of both RIPK1 and RIPK3, but not the necroptosis effector protein, MLKL. Mechanistically, we provide evidence that necrosome-like RIPK1 and RIPK3 aggregates facilitate canonical TRIF–dependent IFN-β production downstream of the LPS receptor TLR4. Intriguingly, we also show that RIPK1 and RIPK3 kinase–dependent synthesis of IFN-β is markedly induced by avirulent strains of Gram-negative bacteria, Yersinia and Klebsiella, and less so by their wild-type counterparts. Overall, these observations identify unexpected roles for RIPK1 and RIPK3 kinases in the production of IFN-β during the host inflammatory responses to bacterial infection and suggest that the axis in which these kinases operate may represent a target for bacterial virulence factors.
The Juxtamembrane Domain of Butyrophilin BTN3A1 Controls Phosphoantigen-Mediated Activation of Human Vγ9Vδ2 T Cells
Authors: Peigné Cassie-Marie , Léger Alexandra , Gesnel Marie-Claude , Konczak Fabienne , Olive Daniel , Bonneville Marc , Breathnach Richard , Scotet Emmanuel 
Published: May 2017

Abstract
Vγ9Vδ2 T lymphocytes are the major human peripheral γδ T cell subset, with broad reactivity against stressed human cells, including tumor cells. Vγ9Vδ2 T cells are specifically activated by small phosphorylated metabolites called phosphoantigens (PAg). Stress-induced changes in target cell PAg levels are specifically detected by butyrophilin (BTN)3A1, using its intracellular B30.2 domain. This leads to the activation of Vγ9Vδ2 T cells. In this study, we show that changes in the juxtamembrane domain of BTN3A1, but not its transmembrane domain, induce a markedly enhanced or reduced γδ T cell reactivity. There is thus a specific requirement for BTN3A1’s juxtamembrane domain for correct γδ T cell–related function. This work identified, as being of particular importance, a juxtamembrane domain region of BTN3A molecules identified as a possible dimerization interface and that is located close to the start of the B30.2 domain.
Genetic and Small Molecule Disruption of the AID/RAD51 Axis Similarly Protects Nonobese Diabetic Mice from Type 1 Diabetes through Expansion of Regulatory B Lymphocytes
Authors: Ratiu Jeremy J. , Racine Jeremy J. , Hasham Muneer G. , Wang Qiming , Branca Jane A. , Chapman Harold D. , Zhu Jing , Donghia Nina , Philip Vivek , Schott William H. , Wasserfall Clive , Atkinson Mark A. , Mills Kevin D. , Leeth Caroline M. , Serreze David V. 
Published: May 2017

Abstract
B lymphocytes play a key role in type 1 diabetes (T1D) development by serving as a subset of APCs preferentially supporting the expansion of autoreactive pathogenic T cells. As a result of their pathogenic importance, B lymphocyte–targeted therapies have received considerable interest as potential T1D interventions. Unfortunately, the B lymphocyte–directed T1D interventions tested to date failed to halt β cell demise. IgG autoantibodies marking humans at future risk for T1D indicate that B lymphocytes producing them have undergone the affinity-maturation processes of class switch recombination and, possibly, somatic hypermutation. This study found that CRISPR/Cas9-mediated ablation of the activation-induced cytidine deaminase gene required for class switch recombination/somatic hypermutation induction inhibits T1D development in the NOD mouse model. The activation-induced cytidine deaminase protein induces genome-wide DNA breaks that, if not repaired through RAD51-mediated homologous recombination, result in B lymphocyte death. Treatment with the RAD51 inhibitor 4,4′-diisothiocyanatostilbene-2, 2′-disulfonic acid also strongly inhibited T1D development in NOD mice. The genetic and small molecule–targeting approaches expanded CD73+ B lymphocytes that exert regulatory activity suppressing diabetogenic T cell responses. Hence, an initial CRISPR/Cas9-mediated genetic modification approach has identified the AID/RAD51 axis as a target for a potentially clinically translatable pharmacological approach that can block T1D development by converting B lymphocytes to a disease-inhibitory CD73+ regulatory state.
An Inverse Source Non-local Problem for a Mixed Type Equation with a Caputo Fractional Differential Operator
Authors: Karimov E. , Al-Salti N. , Kerbal S. 
Published: May 2017

AbstractWe consider the unique solvability of an inverse-source problem with integral transmitting condition for a time-fractional mixed type equation in rectangular domain where the unknown source term depends only on the space variable. The solution is based on a series expansion using a bi-orthogonal basis in space, corresponding to a non-self-adjoint boundary value problem. Under certain regularity conditions on the given data, we prove the uniqueness and existence of the solution for the given problem. The influence of the transmitting condition on the solvability of the problem is also demonstrated. Two different transmitting conditions are considered — viz. a full integral form and a special case. In order to simplify the bulky expressions appearing in the proof of our main result, we establish a new property of the recently introduced Mittag-Leffler type function in two variables.
Modulus-based Synchronous Multisplitting Iteration Methods for an Implicit Complementarity Problem
Authors: Li Chen-Liang , Hong Jun-Tao 
Published: May 2017

AbstractWe construct modulus-based synchronous multisplitting iteration methods to solve a large implicit complementarity problem on parallel multiprocessor systems, and prove their convergence. Numerical results confirm our theoretical analysis and show that these new methods are efficient.
Summertime observations of elevated levels of ultrafine particles in the high Arctic marine boundary layer
Authors: Burkart Julia , Willis Megan D. , Bozem Heiko , Thomas Jennie L. , Law Kathy , Hoor Peter , Aliabadi Amir A. , Köllner Franziska , Schneider Johannes , Herber Andreas , Abbatt Jonathan P. D. , Leaitch W. Richard 
Published: May 2017

Abstract. Motivated by increasing levels of open ocean in the Arctic summer and the lack of prior altitude-resolved studies, extensive aerosol measurements were made during 11 flights of the NETCARE July 2014 airborne campaign from Resolute Bay, Nunavut. Flights included vertical profiles (60 to 3000 m above ground level) over open ocean, fast ice, and boundary layer clouds and fogs. A general conclusion, from observations of particle numbers between 5 and 20 nm in diameter (N5 − 20), is that ultrafine particle formation occurs readily in the Canadian high Arctic marine boundary layer, especially just above ocean and clouds, reaching values of a few thousand particles cm−3. By contrast, ultrafine particle concentrations are much lower in the free troposphere. Elevated levels of larger particles (for example, from 20 to 40 nm in size, N20 − 40) are sometimes associated with high N5 − 20, especially over low clouds, suggestive of aerosol growth. The number densities of particles greater than 40 nm in diameter (N >  40) are relatively depleted at the lowest altitudes, indicative of depositional processes that will lower the condensation sink and promote new particle formation. The number of cloud condensation nuclei (CCN; measured at 0.6 % supersaturation) are positively correlated with the numbers of small particles (down to roughly 30 nm), indicating that some fraction of these newly formed particles are capable of being involved in cloud activation. Given that the summertime marine Arctic is a biologically active region, it is important to better establish the links between emissions from the ocean and the formation and growth of ultrafine particles within this rapidly changing environment.
Variation of soil hydraulic properties with alpine grassland degradation in the eastern Tibetan Plateau
Authors: Pan Tao , Hou Shuai , Wu Shaohong , Liu Yujie , Liu Yanhua , Zou Xintong , Herzberger Anna , Liu Jianguo 
Published: May 2017

Abstract. Ecosystems in alpine mountainous regions are vulnerable and easily disturbed by global environmental change. Alpine swamp meadow, a unique grassland type in the eastern Tibetan Plateau that provides important ecosystem services to the upstream and downstream regions of international rivers of Asia and other parts of the world, is undergoing severe degradation, which can dramatically alter soil hydraulic properties and water cycling processes. However, the effects of alpine swamp meadow degradation on soil hydraulic properties and the corresponding influencing mechanisms are still poorly understood. In this study, soil moisture content (SMC), field capacity (FC) and saturated hydraulic conductivity (Ks) together with several basic soil properties under lightly degraded (LD), moderately degraded (MD) and severely degraded (SD) alpine swamp meadow were investigated; the variations in SMC, FC and Ks with alpine swamp meadow degradation and their dominant influencing factors were analysed. The results showed that SMC and FC decreased consistently from LD to SD, while Ks decreased from LD to MD and then increased from MD to SD, following the order of LD  >  SD  >  MD. Significant differences in soil hydraulic properties between degradation degrees were found in the upper soil layers (0–20 cm), indicating that the influences of degradation were most pronounced in the topsoils. FC was positively correlated with capillary porosity, water-stable aggregates, soil organic carbon, and silt and clay content; Ks was positively correlated with non-capillary porosity (NCP). Relative to other soil properties, soil porosity is the dominant factor influencing FC and Ks. Capillary porosity explained 91.1 % of total variance in FC, and NCP explained 97.3 % of total variance in Ks. The combined effect of disappearing root activities and increasing sand content was responsible for the inconsistent patterns of NCP and Ks. Our findings suggest that alpine swamp meadow degradation would inevitably lead to reduced water holding capacity and rainfall infiltration. This study provides a more comprehensive understanding of the soil hydrological effects of vegetation degradation. Further hydrological modelling studies in the Tibetan Plateau and similar regions are recommended to understand the effects of degraded alpine swamp meadows on soil hydraulic properties.
HORIZONS FOR DESIGN OF FILLED RUBBER INFORMED BY MOLECULAR DYNAMICS SIMULATION
Authors: Smith Scott M. , Simmons David S. 
Published: May 2017

ABSTRACT
Fillers such as carbon black provide a long-standing and essential strategy for the mechanical reinforcement of rubber in tires and other load-bearing applications. Despite their technological importance, however, the microscopic mechanism of this reinforcement remains a matter of considerable debate. A predictive understanding of filler-based reinforcement could catalyze the design of new rubber-filler composites with enhanced performance. Molecular dynamics simulations of rubber mechanical response in the presence of structured fillers offer a new strategy for resolving the origins of filler-based reinforcement and guiding filler design. Results of for ideal rubber-filler dispersions over a range of filler structures suggest that neither hydrodynamic effects nor non-deformable “bound rubber domains” are necessary to achieve high reinforcement. Moreover, simulations show that particle surface area is a poor predictor of reinforcement. Instead, simulated reinforcement correlates strongly with filler structure, with more rarified filler structure predicting much greater reinforcement at fixed loading. Simulation results are consistent with a scenario in which reinforcement at industrially relevant loadings is dominated by formation of a jammed network of filler particles, suggesting that reinforced rubber can be understood as a superposition of two materials: a rubbery solid, and a jammed granular solid. This perspective points to an opportunity to improve filler-reinforced rubber design by leveraging concepts and expertise developed over many decades in the fields of jamming and granular media.
EFFECT OF STEREOCHEMISTRY IN ANIONIC POLYMERIZATION MODIFIERS
Authors: Hogan Terrence E. , Kiridena Waruna , Kocsis Laura 
Published: May 2017

ABSTRACT
The influence of stereochemistry of polar modifiers on the microstructure of polybutadiene and poly(styrene-co-butadiene) was evaluated for 2,2′-ditetrahydrofurylpropane (DTHFP). The meso and d,l diastereomers were isolated from commercial 50/50 mixtures through column chromatography and characterized by 1H-NMR and gas chromatography/mass spectrometry. The meso-DTHFP was found to be more active than d,l-DTHFP in incorporation of vinyl during anionic polymerization. To form a polymer with approximately 55% vinyl, twice the amount of d,l-DTHFP was required compared with using pure meso-DTHFP. The mechanism for this effect will be discussed.
A EXPERIÊNCIA DA CONSTRUÇÃO DE UM PLANO OPERATIVO PARA O SETOR DE DEMANDA JUDICIAL NA SECRETARIA DE SAÚDE DO ESTADO DO PARANÁ
Authors: IMAZU P. , OLIVEIRA F. W. , CZEPULA A. , STRAPASSON G. C. 
Published: May 2017

Com o aumento da demanda judicial para fornecimento de medicamentos na Secretaria de Estado de Saúde do Paraná, a gestão do setor responsável tem se apresentado cada vez mais complexa. A ausência de legislação que regulamente parte da Assistência Farmacêutica (AF) dificulta mais a sua organização. Para enfrentamento dessas dificuldades foi elaborado um planejamento estratégico situacional (PES), conforme os fundamentos de Carlos Matus, seu idealizador. Este artigo relata uma experiência de elaboração de um plano operativo com quatro momentos, a saber: explicativo, normativo, estratégico e tático-operacional. No momento explicativo foi possível identificar os problemas com maior magnitude, transcendência, vulnerabilidade, urgência e factibilidade. Assim obteve-se por pontuação o problema a ser priorizado e estudado. As ações a serem realizadas para sua superação foram elencadas no momento normativo. No momento estratégico foi analisada a viabilidade e factibilidade de cada ação e atribuída atividade estratégica para aquelas que possuíam déficit. No momento tático-operacional foi elaborado o protocolo de avaliação, com indicadores e fontes de verificação para os resultados das ações. Por meio desse trabalho foi possível observar que o método de Carlos Matus é bem trabalhoso e exige bastante tempo para sua elaboração. Destacam-se como aspectos favoráveis: o foco a ser definido, o qual deve ser estudado antes do inicio do projeto, considerando o seu centralizador e o impacto que se almeja nas ações a serem realizadas; e a participação de atores internos e externos, que possibilitam o envolvimento direto de todos com o problema.
Uma escola permanentemente provisória ou provisoriamente permanente? Avaliações das escolas isoladas paulistas em documentos oficiais (1907-1944)
Authors: Oriani Angélica Pall 
Published: May 2017

O artigo analisa as avaliações das escolas isoladas contidas nos Annuários do ensino do estado de São Paulo (1907-1937) e nos Relatórios das delegacias regionais de ensino (1933-1944) para compreender a representação dessas instituições de ensino ao longo das décadas iniciais do século XX. Esses documentos continham os resultados das inspeções de diretores e delegados de ensino a respeito da criação, da manutenção e da atuação dos professores das escolas isoladas. A função desses documentos é perscrutada como um procedimento adotado concomitantemente à construção do sistema de ensino modelar paulista nas primeiras décadas republicanas, com o que é possível identificá-los como legitimadores, propagadores e defensores de um modelo de escola vinculado aos grupos escolares do qual as escolas isoladas se afastavam em razão de suas condições precárias. Com isso, considera-se que nos processos de avaliação e de atribuição de sentidos às instituições de ensino primário, que evidenciavam as conquistas dos grupos escolares e a provisoriedade das escolas isoladas, propagou-se a imagem destas instituições como um constante "vir a ser".A permanently provisional or provisionally permanent school? Evaluations of isolated schools of São Paulo in official documents (1907-1944). The article analyzes the evaluations of isolated schools in the Annuários do ensino do estado de São Paulo (1907-1937) and in the Relatórios das delegacias regionais de ensino (1933-1944) to understand the representation of these educational institutions throughout the first decades of the 20th century. These documents contained the results of inspections developed by school superintendents regarding the creation, maintenance and performance of teachers in isolated schools. The function of these documents is analyzed as a procedure that occurred simultaneously with the construction of the modeling teaching system of São Paulo in the first republican decades, which identify them as legitimators and advocates of a school model linked to the school groups from which isolated schools were far from due to their conditions. Therefore, it is considered that in the processes of evaluation and attribution of senses to primary education institutions, which evidenced the achievements of the school groups and the provision of isolated schools, the image of these institutions was propagated as a constant "become". Keywords: Isolated schools; São Paulo education; School groups; History of education.
Frei Betto em experiências de viagens: o cristão no socialismo real
Authors: Lobo Rhaissa Marques Botelho 
Published: May 2017

Analisam-se aqui as incursões e trabalhos pastorais nos países do socialismo real especialmente Cuba, Nicarágua, União Soviética e as reflexões que ele faz entre convergências e divergências da teoria marxista e a religião cristã.Frei Betto in travel experiences: the christian in real socialism. This paper examines the incursions and pastoral work in the countries of real socialism, especially Cuba, Nicaragua, Soviet Union, and the reflections he makes between the convergences and divergences of Marxist theory and the christian religion. Keywords: Travel; Frei Betto; Liberation Theology; Intellectual; Socialism.
Música da terra dos faraós: aprendizagens de Anttonieta de Souza numa viagem ao Egito
Authors: Monti Ednardo Monteiro Gonzaga do 
Published: May 2017

O presente estudo tem como horizonte as aprendizagens da professora Anttonieta de Souza na viagem que realizou ao Egito na década de 1950. Com base na série de artigos intitulada “Minhas impressões sobre o Egito”, as perguntas que norteiam o texto são: quais tradições e culturas musicais egípcias a artista apresentou aos leitores da Revista do Conservatório Brasileiro de Música? O que aprendeu com os estudos arqueológicos e históricos sobre a música e os músicos da terra dos faraós? Os escritos da cantora dos palcos de concerto do Rio de Janeiro, publicados no periódico oficial da instituição de ensino superior de música que ela dirigia, permitem interpretar que as bases da tradição musical daquele povo eram os rituais religiosos, os mitos, as festas populares, as canções de trabalho, as fanfarras militares e as lendas. E que os estudos musicológicos sobre a antiguidade, com os quais Anttonieta teve contato na viagem, ressaltam que os instrumentos achados nos sítios arqueológicos possibilitaram repercutir timbres que há milhares de anos não soavam; e também conhecer as vestimentas e adornos feitos com flores de lótus que cantores e instrumentistas utilizavam; e ainda, adquirir informações sobre as grandes famílias de músicos que funcionavam como espécies de dinastias artísticas.Music from the pharaoh's land: learning of Antoinetta de Souza on a trip to Egypt. This study focuses on the learnings of Professor Anttonieta de Souza during her trip to Egypt in the 1950s. Based on the series of articles entitled “Minhas impressões sobre o Egito” (My impressions about Egypt), the questions guiding the study are as follows: What Egyptian traditions and musical culture did the artist present to the readers of the Revista do Conservatório Brasileiro de Música (Brazilian Conservatory of Music’s Magazine)? What did she learn from archaeological and historical studies about music and musicians of the Pharaohs’s Land? The writings of the singer who graced the stages of Rio de Janeiro, published in the official journal of the Conservatório Brasileiro de Música that she directed herself, allow for the impression that the nucleus of the Egyptian musical culture were the religious rituals, myths, the popular parties, Work songs, military fanfare and legends. What’s more, her work that focuses on the antique music culture of Egypt emphasizes that instruments found on archaeological sites made the reverberation of timbres possible that for thousands of years did not sound; investigates the garments and accessories made from lotus flowers that singers and instrumentalists used; and considers the large families of musicians who functioned as if they were, to some extent, artistic dynasties. Keywords: Travel; Music education; Egyptian culture.