bluuebunny/crossref_metadata_2025 huggingface dataset:
When Teachers are Confronted with Ideological Aspects of Their Profession
Authors: Norlund Anita
Published: July 2014

This article falls within the research area of school development. It also takes into account neo-liberal tendencies, such as they have been approached in educational research. The article takes as its starting point a development project that began when four rural secondary schools turned to their regional university for scientific support. It seems to be a general fact that more and more schools are turning to universities for help as a result of being subjected to ranking lists — i.e. a neo-liberally oriented phenomenon. School development work has proven difficult in general terms, and current tendencies, the author argues, risk reinforcing these difficulties. The urgent practical needs of schools risk colliding with the critical interests of academia. This, the author argues, is a problem that needs further exploration. The aim of this article is to explore responses from teachers towards a specific activity that encouraged them to take an objective look at their day-to-day practices, and to relate teaching and assessment approaches theoretically to pupils' social backgrounds. Three aspects were investigated in particular: first, teachers' attitudinal responses to being provided with an understanding of diverse and conflicting interests; second, teachers' attitudinal responses to being provided with tools for encountering school rhetoric in a critical way; and, third, teachers' attitudinal responses to being guided by a specific pedagogic discourse. The data consists of 61 written responses from teachers representing four rural schools. The ‘appraisal theory’ was adopted as an analytical tool for capturing the teachers' evaluative stances. The results highlight the intricacies of confronting teachers with certain sociological and theoretical topics that reveal the fact that the school is not a neutral place. The author suggests that there should be further debate on this matter.
Between Social Tutelage and Individual Responsibility: Dilemmas of Higher Education in Eastern Europe
Authors: Peshkopia Ridvan
Published: July 2014

What explains the crisis of the Eastern European universities, and how can they overcome it? This article tries to find the causes of such a crisis in the communist tradition and the lingering communitarian systems of thought in Eastern Europe. The current state-controlled academic systems in the region continue to reproduce such a culture. Instead, this article suggests the transformation of Eastern European universities to entrepreneurial universities focused on creating entrepreneurial graduates who invest in and benefit from their careers. A university—industry—government triple helix model would have been the right model had not industry in many Eastern European countries collapsed under communist regimes. In such a case, universities should take over the task of encouraging industry creation. Also, other societal stakeholders might help.
Atmospheric Ozone and Methane in a Changing Climate
Authors: Isaksen Ivar , Berntsen Terje , Dalsøren Stig , Eleftheratos Kostas , Orsolini Yvan , Rognerud Bjørg , Stordal Frode , Søvde Ole , Zerefos Christos , Holmes Chris
Published: July 2014

Ozone and methane are chemically active climate-forcing agents affected by climate–chemistry interactions in the atmosphere. Key chemical reactions and processes affecting ozone and methane are presented. It is shown that climate-chemistry interactions have a significant impact on the two compounds. Ozone, which is a secondary compound in the atmosphere, produced and broken down mainly in the troposphere and stratosphre through chemical reactions involving atomic oxygen (O), NOx compounds (NO, NO2), CO, hydrogen radicals (OH, HO2), volatile organic compounds (VOC) and chlorine (Cl, ClO) and bromine (Br, BrO). Ozone is broken down through changes in the atmospheric distribution of the afore mentioned compounds. Methane is a primary compound emitted from different sources (wetlands, rice production, livestock, mining, oil and gas production and landfills).Methane is broken down by the hydroxyl radical (OH). OH is significantly affected by methane emissions, defined by the feedback factor, currently estimated to be in the range 1.3 to 1.5, and increasing with increasing methane emission. Ozone and methane changes are affected by NOx emissions. While ozone in general increase with increases in NOx emission, methane is reduced, due to increases in OH. Several processes where current and future changes have implications for climate-chemistry interactions are identified. It is also shown that climatic changes through dynamic processes could have significant impact on the atmospheric chemical distribution of ozone and methane, as we can see through the impact of Quasi Biennial Oscillation (QBO). Modeling studies indicate that increases in ozone could be more pronounced toward the end of this century. Thawing permafrost could lead to important positive feedbacks in the climate system. Large amounts of organic material are stored in the upper layers of the permafrost in the yedoma deposits in Siberia, where 2 to 5% of the deposits could be organic material. During thawing of permafrost, parts of the organic material that is deposited could be converted to methane. Furthermore, methane stored in deposits under shallow waters in the Arctic have the potential to be released in a future warmer climate with enhanced climate impact on methane, ozone and stratospheric water vapor. Studies performed by several groups show that the transport sectors have the potential for significant impacts on climate-chemistry interactions. There are large uncertainties connected to ozone and methane changes from the transport sector, and to methane release and climate impact during permafrost thawing.
Development of a Functionally Minimized Mutant of the R3C Ligase Ribozyme Offers Insight into the Plausibility of the RNA World Hypothesis
Authors: Kurihara Eri , Uchida Sayuri , Umehara Takuya , Tamura Koji
Published: July 2014

The R3C ligase ribozyme is an artificial ligase ribozyme produced by modification of the ribozyme that lacks cytidine. Here, we attempted to modify the original R3C ribozyme (73 nucleotides) by reducing the number of nucleotides while maintaining the maximum possible catalytic efficiency. By partially deleting both the “grip” (P4 + P5) and “hammer” (P3) stem-loops, we found the critical border to retain activity comparable to that of full-length R3C. The three-way junction structure was necessary to maintain enzymatic function and the stability of the “grip” (P4 + P5) stem had a large influence on the catalytic activity of R3C. The final minimized ribozyme we obtained comprised ~50 nucleotides, comparable to the estimated length of prebiotically synthesized RNA. Our findings suggest that the autocatalytic function in ribozymes is indeed possible to obtain using sequence lengths achievable with prebiotic synthesis.
Effects of Tatariside G Isolated from Fagopyrum tataricum Roots on Apoptosis in Human Cervical Cancer HeLa Cells
Authors: Li Yuan , Wang Su-Juan , Xia Wei , Rahman Khalid , Zhang Yan , Peng Hao , Zhang Hong , Qin Lu-Ping
Published: July 2014

Cervical cancer is the second most common female carcinoma. Current therapies are often unsatisfactory, especially for advanced stage patients. The aim of this study was to explore the effects of tatariside G (TG) on apoptosis in human cervical cancer HeLa cells and the possible mechanism of action involved. An MTT assay was employed to evaluate cell viability. Hoechst 33258 staining and flow cytometry (FCM) assays were used to detect cell apoptosis. The protein expression of phosphorylated JNK, P38, ERK and Akt and cleaved caspase-3 and caspase-9 was evaluated by western blot analysis. Additionally, the mRNA expression of caspase-3 and caspase-9 was measured by fluorescent quantitative reverse transcription-PCR (FQ-RT-PCR). TG notably inhibited cell viability, enhanced the percentage of apoptotic cells, facilitated the phosphorylation of p38 MAPK and JNK proteins and caspase-3 and caspase-9 cracking, downregulated the phosphorylation level of Akt, and increased the loss of MMP and the mRNA expression of caspase-3 and caspase-9. TG-induced apoptosis is associated with activation of the mitochondrial death pathway. TG may be an effective candidate for chemotherapy against cervical cancer.
Un suceso real como argumento de comedia: la conversión de La Baltasara
Authors: García González Almudena
Published: July 2014

La Baltasara fue una célebre actriz entre finales del siglo XVI y principios del XVII, que dejó los escenarios para retirarse a vivir en una ermita hasta su muerte. Este suceso fue recuperado varios años más tarde por Luis Vélez de Guevara, Antonio Coello y Francisco de Rojas Zorrilla como argumento para una de las comedias que los tres dramaturgos escribieron en colaboración, titulada con el nombre de la actriz. A lo largo de este artículo, se presentan varios datos documentales con los que se pretende aportar información sobre la actriz y su retiro. Asimismo, se analizan los motivos y elementos dramáticos que configuran la pieza, tomados de uno de los géneros más exitosos en la época: las comedias de santos.
Almanzor: drama histórico de Blas Infante
Authors: Esquerrá Nonell Josep
Published: July 2014

La reciente publicación de una obra de teatro inédita y original de Blas Infante: Almanzor, drama histórico incompleto escrito hacia la primera mitad de los años 20 del siglo pasado, abre posibilidades de interpretación con respecto a otra obra escrita en el mismo periodo, La Dictadura Pedagógica, con una finalidad clara de superación de la España de la Restauración desde el punto de vista histórico. Almanzor es además su segunda obra de temática andalusí, junto con Motamid, último rey de Sevilla. La obra es, principalmente, una adaptación de la Historia de los musulmanes de España hasta la conquista de los almorávides de R. P. Dozy. Pertenece a la modalidad dramática que el Modernismo denominó teatro poético, pero la obra tiene una honda raíz romántica. Infante recrea, una vez más, el glorioso pasado de Al-Ándalus.
La autoría del apunte teatral El triunfo mayor de Ciro y la impresa Araspas y Pantea
Authors: González Martínez Javier J.
Published: July 2014

El corpus del dramaturgo del Siglo de Oro Luis Vélez de Guevara sigue despertando dudas. Hasta ahora el único testimonio que se conocía de la pieza El triunfo mayor de Ciro era un apunte conservado en la Biblioteca Histórica Municipal de Madrid. En este estudio se revela un testimonio anterior en más de un siglo: se trata de la comedia Araspas y Pantea, atribuida a Francisco Salgado en la Parte 36 de la colección Escogidas.
Conexiones románicas: las versiones castellanas de las Epístolas de Séneca (BNE 8852)
Authors: Martínez Romero Tomàs
Published: July 2014

El estudio del contenido del manuscrito 8852 de la Biblioteca Nacional de España permite confirmar la existencia de dos traducciones castellanas medievales diferentes de las Epistulae ad Lucilium: una dependiente de la primera versión catalana y otra, de la traducción francesa anterior. Gracias a ello, se dibuja un mapa muy complejo de la difusión del texto de Séneca en lengua romance y de su circulación por el occidente medieval.
Fortuna de un verso de Sannazaro: para una metafísica del olvido en la poesía española del Siglo de Oro
Authors: Morros Mestres Bienvenido
Published: July 2014

El presente trabajo estudia el tema del amor más allá del olvido entre los poetas del siglo de oro. Todos ellos lo trataron por influencia de un idilio atribuido a Teócrito y que en el Renacimiento fue muy conocido porque se tradujo también al latín: los primeros en plantearlo fueron Joan Roís de Corella y Jacopo Sannazaro ya en la segunda mitad del siglo XV. Por influencia del italiano los autores posteriores ya lo desarrollaron ampliamente.
Factores de riesgo y protección/resiliencia en el acoso escolar adolescente. Análisis longitudinal
Authors: Hernández de Frutos Teodoro , Del Olmo Vicén Nuria
Published: July 2014

Las teorías del riesgo, protección/resiliencia han surgido con fuerza en los últimos años porque explican satisfactoriamente, en opinión de una por parte significativa de la comunidad universitaria, porque algunos adolescentes se hunden en un medio ambiente hostil, mientras que otros sobreviven sin que parezca que les afecte, como si estuvieran inmunizados contra las adversidades que se han ido encontrando a lo largo de su vida. Estas teorías aplicadas al acoso adolescente podría explicar porque algunos jóvenes lo padecen y otros no, a pesar de compartir la misma atmósfera vital (edad, género, escuela, barrio, medios de comunicación). El presente meta análisis indaga sobre los riesgos y resiliencias procedentes del medio ambiente social en la versión de Bronfenbrenner tomando en cuenta que las resiliencias no necesariamente tienen que proceder de aspectos individuales debidos a la personalidad o a los otros significantes, como enfatizan algunas teorías, sino que pueden ser también factores ambientales los que ejerzan ese papel incrementando o reduciendo los efectos. Dado que en una parte de la literatura especializada se utiliza el concepto de manera confusa identificando acoso escolar solo con un comportamiento agresivo individual, es necesario apuntar que aquí se utiliza como un concepto mutidimensional, es decir, como una única variable que incluye la agresión individual, la agresión colectiva, la victimización individual y la victimización colectiva. De esta forma se evita el malentendido de un uso holístico y omnicomprensivo no siempre diferenciado, lo que puede provocar confusión. Tomando en cuenta además que tanto el que ejerce como el que lo padece, aunque en diferente grado, se enfrentan a riesgos, protección y resiliencia.
Numerical Simulations of Capacitive Resistivity Imaging (CRI) Measurements
Authors: Uhlemann Sebastian , Kuras Oliver
Published: July 2014

Electrical resistivity tomography (ERT) is a well‐developed geophysical technique that is used to study a variety of geoscientific problems. In recent years it has been applied to the study of permafrost processes at both field and laboratory scale. However, highly resistive surface conditions limit its applicability due to high and variable contact resistances. The use of capacitively coupled sensors is expected to overcome this problem by providing a steady contact impedance regime. Although the theory of capacitive resistivity imaging (CRI) is well understood, a point‐pole approximation of the sensors is typically used to show the similarity between CRI and ERT. Due to their nature, capacitive sensors cannot be designed as point‐poles as they require a finite extent. This paper assesses the effects the finite size of sensors has on the applicability of CRI theory and aims to provide an improved understanding of the measured data. We employ finite‐element numerical modelling to simulate CRI measurements over a homogeneous halfspace and on a finite rock sample. The results of a parameter study over a homogeneous halfspace are compared to an analytical solution. Observed discrepancies between the two solutions clearly indicate that large sensor sizes and small sensor separations violate the point‐pole assumption of the analytical solution. In terms of data interpretation, this dictates that sensor separations smaller than twice the sensor size have to be avoided in order to remain below a generic error threshold of 5%. We show that sensor elevation, halfspace resistivity, halfspace permittivity, and measurement frequency have only minor effects on the discrepancy between simulation and analytical solution. The simulation of sequential CRI measurements on a finite rock sample suggests that, in line with expectations, the measured signals lie mainly in the 4th quadrant of the complex plane. However, we can also observe data with negative geometric factors, which are related to uncommon array. A comparison between simulated and measured data showed very good agreement; it validated the simulations and explained the measured data acquired using a prototype multisensor CRI system. We show that a comparison of simulated and measured imaginary parts of the transfer impedance can be used to assess CRI measurement errors. Our work demonstrates that finite‐element numerical modelling of CRI measurements is a valuable tool with which to define limitations on array design and to assess data quality.
Calibration of frequency‐domain electromagnetic devices used in near‐surface surveying
Authors: Thiesson Julien , Kessouri Pauline , Schamper Cyril , Tabbagh Alain
Published: July 2014

For the past forty years electromagnetic prospecting instruments have played a growing role in the mapping of soil EM properties in the very low‐frequency (VLF) range for a large variety of applica tions and they are now beginning to be applied in the medium‐frequency range. Measurement interpretations, however, necessitate expressing the results in terms of physical properties. This step allows not only comparisons and joint interpretation with data generated by different electromag netic induction (EMI) instruments but also with other types of field measurements e.g., vertical electrical sounding (VES) or electrical resistivity tomography (ERT) or laboratory tests on samples.

The calibration process here proposed is based on comparisons between the instrument respons es and: (1) an exact 1D multi‐layer analytical modelling that takes the three EM properties into account, i.e., the electrical conductivity, the complex magnetic susceptibility and the complex die lectric permittivity when the instrument is elevated above a layered ground; (2) the response to purely conductive metallic spheres, which only depends on the diameter of the spheres. It is applied to two instrument prototypes: one in the VLF frequency range and the other in the medium‐frequency (MF) range.
Mechanics Analysis of Long Jump by Means of the Theory of Artificial Neural Networks
Authors: Wang Qun Long
Published: July 2014

Takeoff is extremely important to long jump. The paper analyzes the mechanics characteristics of takeoff for long jump by means of the theory of neural network. It firstly discusses some importantly influencing factors for long jump in theory. On the basis of description of the theory of Artificial Neural Network, the back propagation network is applied to model the long jump. The results show that an excellent performance of long jump is depend on a rapid run-up speed and the rhythm of the final two steps.
Aerodynamic Performance Evaluation with a New Method for Darrieus Wind Turbine
Authors: Mei Yi , Qu Jian Jun
Published: July 2014

The operation condition for darrieus wind turbine is usually complex in urban sites. One of characteristics is unsteady tip speed ratios during the rotor operating, which makes the widely used aerodynamic performance indicator, maximum power coefficient, not so suitable for evaluating vertical axis rotor performance. In this paper, a new method based on the power coefficient values under variable tip speed ratios was developed and the mathematical expression derived by numerical integration measure was presented. Furthermore, a novel wind turbine power performance indicator, average effective wind energy utilization coefficient, has been defined for the rotor performance assessment. A wind tunnel case of darrieus wind turbine with different blade cord length was selected for analyzing. Results demonstrate the proposed method is correct and practical.
Design and Implementation of an Integrated Wireless Communication, Localization and Monitoring System for Coal Mines
Authors: Li Xiao Dong , Rong Guo Guang , Zhu Yong Xin
Published: July 2014

As major areas in the world have been protected with surveillance information with the development of wireless communication technologies, underground mines are still hit by frequent accidents due to insufficient monitoring and sensing, which would be improved with implementation of Internet of Things (IOT). However, a low-power, high reliability wireless communication equipment integrated with personnel localization, underground gas monitoring and IOT functions has not been implemented to enable underground IOT. Having explored wireless technologies and underground communication technologies, we propose in the paper the design of a communication system incorporating wireless call, gas monitoring, personnel localization functions through the integration of ZigBee (IEEE802.15.4) and Ethernet. This system has been realized and tested under laboratory conditions. The system was accepted by China coal mines in principle for application in their coal mine production line.
Experimental Research on Mechanical Properties of SPS Composite Plate
Authors: Zou Guang Ping , Wu Ye
Published: July 2014

This paper briefly describes the preparation process of SPS composite plate. The compress, buckling and three-point bending tests of SPS composite steel plates are studied. Each test gives the failure mode and stress-strain curve. The results may provide a reference for further research and engineering applications of SPS composite plate.
Research on Electronic Measuring Technology with Development of Total Station Coordinate Traverse Adjustment Program
Authors: Liu Dong Wen , Chen Ya Kai , Qiao Zhi Yong , Jiang Shu , Zhang Juan Juan , Wang Ting Ting
Published: July 2014

This paper presents a method for measuring total station coordinate traverse, and the method of using indirect adjustment and rigorous indirect adjustment with restrictions Based on Visual Studio 2010 programming environment ,use C # programming language,GDI + graphics processing and software engineering technology to research related program design.The Program is designed to achieve the automation, intelligence and high precision of outcome traverse adjustment.
Information Technology in an Improved Supervised Locally Linear Embedding for Recognizing Speech Emotion
Authors: Huang Ri Sheng
Published: July 2014

To improve effectively the performance on speech emotion recognition, it is needed to perform nonlinear dimensionality reduction for speech feature data lying on a nonlinear manifold embedded in high-dimensional acoustic space. This paper proposes an improved SLLE algorithm, which enhances the discriminating power of low-dimensional embedded data and possesses the optimal generalization ability. The proposed algorithm is used to conduct nonlinear dimensionality reduction for 48-dimensional speech emotional feature data including prosody so as to recognize three emotions including anger, joy and neutral. Experimental results on the natural speech emotional database demonstrate that the proposed algorithm obtains the highest accuracy of 90.97% with only less 9 embedded features, making 11.64% improvement over SLLE algorithm.
Research on Applied Technology in Storing and Transmitting Medical Image Based on DICOM
Authors: Miao Yu , Yang Hua Min , Shi Wei Li , Cao Yan Ni , Zhang Li Yuan
Published: July 2014

DICOM is the international standard for the digital imaging communication in medicine. This paper introduces the development of DICOM and analyzes the communication process based on DICOM protocol. Besides, the communication between store SCP and store SCU was designed and implemented.
Applied Technology in an Adaptive Particle Filter Based on Interval Estimation and KLD-Resampling
Authors: Zhang Jian , Shen Ling
Published: July 2014

Particle filter as a sequential Monte Carlo method is widely applied in stochastic sampling for state estimation in a recursive Bayesian filtering framework. The efficiency and accuracy of the particle filter depends on the number of particles and the relocating method. The automatic selection of sample size for a given task is therefore essential for reducing unnecessary computation and for optimal performance, especially when the posterior distribution greatly varies overtime. This paper presents an adaptive resampling method (IE_KLD_PF) based on interval estimation, and after interval estimating the expectation of the system states, the new algorithm adopts Kullback-Leibler distance (KLD) to determine the number of particles to resample from the interval and update the filter results by current observation information. Simulations are performed to show that the proposed filter can reduce the average number of samples significantly compared to the fixed sample size particle filter.
Grey Relation Analysis Method for Material Selection Problem with Interval Numbers
Authors: Yang Lian Wu
Published: July 2014

Material selection is an important step in the product design process. Material selection problem contains many influence factors, and thus it is actually a multi-attribute decision making problem. In some situations, measure values cannot or unsuitable to be depicted by crisp numbers. Interval number is a suitable selection in these situations, and for the material selection problem with interval numbers, a new decision making method is developed based on grey relation analysis method. The attribute weights will be determined by the coefficient of variation method. Finally, a practical example is used to illustrate the effectiveness and feasibility of the proposed method.
Specific Increase in Potency via Structure-Based Design of a TCR
Authors: Malecek Karolina , Grigoryan Arsen , Zhong Shi , Gu Wei Jun , Johnson Laura A. , Rosenberg Steven A. , Cardozo Timothy , Krogsgaard Michelle
Published: July 2014

Adoptive immunotherapy with Ag-specific T lymphocytes is a powerful strategy for cancer treatment. However, most tumor Ags are nonreactive “self” proteins, which presents an immunotherapy design challenge. Recent studies have shown that tumor-specific TCRs can be transduced into normal PBLs, which persist after transfer in ∼30% of patients and effectively destroy tumor cells in vivo. Although encouraging, the limited clinical responses underscore the need for enrichment of T cells with desirable antitumor capabilities prior to patient transfer. In this study, we used structure-based design to predict point mutations of a TCR (DMF5) that enhance its binding affinity for an agonist tumor Ag–MHC (peptide–MHC [pMHC]), Mart-1 (27L)-HLA-A2, which elicits full T cell activation to trigger immune responses. We analyzed the effects of selected TCR point mutations on T cell activation potency and analyzed cross-reactivity with related Ags. Our results showed that the mutated TCRs had improved T cell activation potency while retaining a high degree of specificity. Such affinity-optimized TCRs have demonstrated to be very specific for Mart-1 (27L), the epitope for which they were structurally designed. Although of somewhat limited clinical relevance, these studies open the possibility for future structural-based studies that could potentially be used in adoptive immunotherapy to treat melanoma while avoiding adverse autoimmunity-derived effects.
CaMKIV-Dependent Preservation of mTOR Expression Is Required for Autophagy during Lipopolysaccharide-Induced Inflammation and Acute Kidney Injury
Authors: Zhang Xianghong , Howell Gina M. , Guo Lanping , Collage Richard D. , Loughran Patricia A. , Zuckerbraun Brian S. , Rosengart Matthew R.
Published: July 2014

Autophagy, an evolutionarily conserved homeostasis process regulating biomass quantity and quality, plays a critical role in the host response to sepsis. Recent studies show its calcium dependence, but the calcium-sensitive regulatory cascades have not been defined. In this study, we describe a novel mechanism in which calcium/calmodulin-dependent protein kinase IV (CaMKIV), through inhibitory serine phosphorylation of GSK-3β and inhibition of FBXW7 recruitment, prevents ubiquitin proteosomal degradation of mammalian target of rapamycin (mTOR) and thereby augments autophagy in both the macrophage and the kidney. Under the conditions of sepsis studied, mTOR expression and activity were requisite for autophagy, a paradigm countering the current perspective that prototypically, mTOR inhibition induces autophagy. CaMKIV–mTOR-dependent autophagy was fundamentally important for IL-6 production in vitro and in vivo. Similar mechanisms were operant in the kidney during endotoxemia and served a cytoprotective role in mitigating acute kidney injury. Thus, CaMKIV–mTOR-dependent autophagy is conserved in both immune and nonimmune/parenchymal cells and is fundamental for the respective functional and adaptive responses to septic insult.
Intrahepatic Activation of Naive CD4+ T Cells by Liver-Resident Phagocytic Cells
Authors: Tay Szun S. , Wong Yik Chun , Roediger Ben , Sierro Frederic , Lu Bo , McDonald David M. , McGuffog Claire M. , Meyer Nicholas J. , Alexander Ian E. , Parish Ian A. , Heath William R. , Weninger Wolfgang , Bishop G. Alex , Gamble Jennifer R. , McCaughan Geoffrey W. , Bertolino Patrick , Bowen David G.
Published: July 2014

Naive T cell activation is normally restricted to the lymphoid organs, in part because of their limited ability to migrate into the parenchyma of peripheral tissues. The liver vasculature is unique, however, and circulating leukocytes within the hepatic sinusoids have direct access to liver-resident cells, which include an abundant population of Kupffer cells. It is well accepted that recognition of cognate Ag within the liver leads to naive CD8+ T cell activation in situ, but it is unclear whether the liver also supports naive CD4+ T cell activation. In this study, we show that naive CD4+ T cells can be activated to proliferate in the liver when cognate Ag expression is induced in hepatocytes by recombinant adeno-associated viral vectors. Ag-specific retention and activation of naive CD4+ T cells within the liver are independent of lymphoid tissues but dependent on a clodronate liposome–sensitive population of liver-resident phagocytic cells. To our knowledge, this study provides the first unequivocal evidence that naive CD4+ T cells can be activated in a nonlymphoid organ. It also gives critical insight into how CD4+ T cells specific for Ag expressed in the liver are recruited to participate in protective or pathological responses during hepatotropic infections and autoimmune liver disease.
Independent of Plasmacytoid Dendritic Cell (pDC) infection, pDC Triggered by Virus-Infected Cells Mount Enhanced Type I IFN Responses of Different Composition as Opposed to pDC Stimulated with Free Virus
Authors: Frenz Theresa , Graalmann Lukas , Detje Claudia N. , Döring Marius , Grabski Elena , Scheu Stefanie , Kalinke Ulrich
Published: July 2014

Upon treatment with vesicular stomatitis virus (VSV) particles, plasmacytoid dendritic cells (pDC) are triggered to mount substantial type I IFN responses, whereas myeloid DC (mDC) are only minor producers. Interestingly, bone marrow–derived (BM-)mDC were more vulnerable to infection with enhanced GFP (eGFP)–expressing VSV (VSVeGFP) than BM-pDC. BM-pDC stimulated with wild-type VSV mounted TLR-dependent IFN responses that were independent of RIG-I–like helicase (RLH) signaling. In contrast, in BM-pDC the VSV variant M2 induced particularly high IFN responses triggered in a TLR- and RLH-dependent manner, whereas BM-mDC stimulation was solely RLH-dependent. Importantly, VSVeGFP treatment of BM-pDC derived from IFN-β yellow fluorescent protein (YFP) reporter mice (messenger of IFN-β) resulted in YFP+ and eGFP+ single-positive cells, whereas among messenger of IFN-β–BM-mDC most YFP+ cells were also eGFP+. This observation indicated that unlike mDC, direct virus infection was not required to trigger IFN responses of pDC. VSV-infected BM-mDC triggered BM-pDC to mount significantly higher IFN responses than free virus particles. Stimulation with infected cells enhanced the percentages of pDC subsets expressing either IFN-β+ or IFN-α6+ plus IFN-β+. Irrespective of whether stimulated with free virus or infected cells, IFN induction was dependent on autophagy of pDC, whereas autophagy of the infected mDC was dispensable. Collectively, these results indicated that productive VSV infection was needed to trigger IFN responses of mDC, but not of pDC, and that IFN responses were primarily induced by virus-infected cells that stimulated pDC in a TLR-dependent manner.
JNK2 Regulates the Functional Plasticity of Naturally Occurring T Regulatory Cells and the Enhancement of Lung Allergic Responses
Authors: Joetham Anthony , Schedel Michaela , Takeda Katsuyuki , Jia Yi , Ashino Shigeru , Dakhama Azzeddine , Lluis Anna , Okamoto Masakazu , Gelfand Erwin W.
Published: July 2014

Glucocorticoid-induced TNFR family–related protein (GITR)–mediated activation of JNK was shown to regulate the suppressive activity of CD4+CD25+ naturally occurring T regulatory cells (nTregs) in wild-type (WT) hosts. In this study, CD4+CD25+ T cells were shown to be capable of becoming pathogenic effector cells in sensitized and challenged CD8−/− recipient mice. Only GITR-expressing CD4+CD25+ T cells, but neither GITR knocked-in CD4+CD25− T cells nor GITR-silenced CD4+CD25+ T cells, enhanced development of lung allergic responses. Inhibition of JNK in WT nTregs or nTregs from GITR−/−and JNK2−/− mice failed to enhance lung allergic responses in sensitized and challenged CD8−/− recipient mice. The failure to enhance responses was associated with increased bronchoalveolar lavage fluid levels of IL-10 and TGF-β and decreased levels of IL-5, IL-6, and IL-13. In contrast, nTregs from JNK1−/− mice, similar to WT nTregs, were fully effective in enhancing responses. Thus, GITR stimulation of nTregs and signaling through JNK2, but not JNK1, triggered the loss of regulatory function while concomitantly gaining pathogenic CD4+ T effector cell function responsible for exacerbating asthma-like immunopathology.
Inhibition of Two Temporal Phases of HIV-1 Transfer from Primary Langerhans Cells to T Cells: The Role of Langerin
Authors: Nasr Najla , Lai Joey , Botting Rachel A. , Mercier Sarah K. , Harman Andrew N. , Kim Min , Turville Stuart , Center Rob J. , Domagala Teresa , Gorry Paul R. , Olbourne Norman , Cunningham Anthony L.
Published: July 2014

Epidermal Langerhans cells (eLCs) uniquely express the C-type lectin receptor langerin in addition to the HIV entry receptors CD4 and CCR5. They are among the first target cells to encounter HIV in the anogenital stratified squamous mucosa during sexual transmission. Previous reports on the mechanism of HIV transfer to T cells and the role of langerin have been contradictory. In this study, we examined HIV replication and langerin-mediated viral transfer by authentic immature eLCs and model Mutz-3 LCs. eLCs were productively infected with HIV, whereas Mutz-3 LCs were not susceptible because of a lack of CCR5 expression. Two successive phases of HIV viral transfer to T cells via cave/vesicular trafficking and de novo replication were observed with eLCs as previously described in monocyte-derived or blood dendritic cells, but only first phase transfer was observed with Mutz-3 LCs. Langerin was expressed as trimers after cross-linking on the cell surface of Mutz-3 LCs and in this form preferentially bound HIV envelope protein gp140 and whole HIV particles via the carbohydrate recognition domain (CRD). Both phases of HIV transfer from eLCs to T cells were inhibited when eLCs were pretreated with a mAb to langerin CRD or when HIV was pretreated with a soluble langerin trimeric extracellular domain or by a CRD homolog. However, the langerin homolog did not inhibit direct HIV infection of T cells. These two novel soluble langerin inhibitors could be developed to prevent HIV uptake, infection, and subsequent transfer to T cells during early stages of infection.
Current Approaches and Emerging Directions in HER2-resistant Breast Cancer
Authors: Brufsky Adam M.
Published: July 2014

Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2-resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer.
Measured and modelled cloud condensation nuclei (CCN) concentration in São Paulo, Brazil: the importance of aerosol size-resolved chemical composition on CCN concentration prediction
Authors: Almeida G. P. , Brito J. , Morales C. A. , Andrade M. F. , Artaxo P.
Published: July 2014

Abstract. Measurements of cloud condensation nuclei (CCN), aerosol size distribution and non-refractory chemical composition were performed from 16 to 31 October 2012 in the São Paulo Metropolitan Area (SPMA), Brazil. CCN measurements were performed at 0.23, 0.45, 0.68, 0.90 and 1.13% water supersaturation and were subsequently compared with the Köhler theory, considering the chemical composition. Real-time chemical composition has been obtained by deploying, for the first time in the SPMA, an aerosol chemical ionization monitor (ACSM). CCN closure analyses were performed considering internal mixtures. Average aerosol composition during the studied period yielded (arithmetic mean~± standard deviation) 4.81 ± 3.05, 3.26 ± 2.10, 0.30 ± 0.27, 0.52 ± 0.32, 0.37 ± 0.21 and 0.04 ± 0.04 μg m−3 for organics, BC, NH4, SO4, NO3 and Cl, respectively. Particle number concentration was 12 813 ± 5350 cm−3, with a dominant nucleation mode. CCN concentrations were on average 1090 ± 328 and 3570 ± 1695 cm−3 at SS = 0.23% and SS = 1.13%, respectively. Results show an increase in aerosol hygroscopicity in the afternoon as a result of aerosol photochemical processing, leading to an enhancement of both organic and inorganic secondary aerosols in the atmosphere, as well as an increase in aerosol average diameter. Considering the bulk composition alone, observed CCN concentrations were substantially overpredicted when compared with the Köhler theory (44.1 ± 47.9% at 0.23% supersaturation and 91.4 ± 40.3% at 1.13% supersaturation). Overall, the impact of composition on the calculated CCN concentration (NCCN) decreases with decreasing supersaturation, partially because using bulk composition introduces less bias for large diameters and lower critical supersaturations, defined as the supersaturation at which the cloud droplet activation will take place. Results suggest that the consideration of only inorganic fraction improves the calculated NCCN. Introducing a size-dependent chemical composition based on filter measurements from previous campaigns has considerably improved simulated values for NCCN (average overprediction error 14.8 ± 38.6% at 0.23% supersaturation and 3.6 ± 21.6% at 1.13% supersaturation). This study provides the first insight on aerosol real-time composition and hygroscopicity at a site strongly impacted by emissions of a unique vehicular fleet due to the extensive biofuel usage.
Size-dependent wet removal of black carbon in Canadian biomass burning plumes
Authors: Taylor J. W. , Allan J. D. , Allen G. , Coe H. , Williams P. I. , Flynn M. J. , Le Breton M. , Muller J. B. A. , Percival C. J. , Oram D. , Forster G. , Lee J. D. , Rickard A. R. , Palmer P. I.
Published: July 2014

Abstract. Wet deposition is the dominant mechanism for removing black carbon (BC) from the atmosphere, and is key in determining its atmospheric lifetime, vertical gradient and global transport. Despite the importance of BC in the climate system, especially in terms of its ability to modulate the radiative energy budget, there are few quantitative case studies of wet removal in ambient environments. We present a case study of BC wet removal by examining aerosol size distributions and BC coating properties sampled in three Canadian boreal biomass burning plumes, one of which passed through a precipitating cloud. In this plume, the largest and most coated BC particles were found to be preferentially removed, suggesting that nucleation scavenging was the likely dominant mechanism. Calculated mass absorption coefficient (MAC) in the plumes showed no significant variation, as the shifts to smaller BC cores and thinner coatings had opposing effects. Similarly, calculated single-scatter albedo (SSA) showed little variation, as a large number of non-BC particles were also present in the precipitation-affected plume. The remaining BC cores were smaller than those observed in previous studies of BC in post-precipitation outflow over Asia, possibly due to the thick coatings associated with the biomass burning particles. This study provides important constraints to model parameterisations of BC wet removal in biomass burning regions, which will help to reduce uncertainty in radiative forcing calculations.
CHAMP climate data based on inversion of monthly average bending angles
Authors: Danzer J. , Gleisner H. , Healy S. B.
Published: July 2014

Abstract. GNSS Radio Occultation (RO) refractivity climatologies for the stratosphere can be obtained from the Abel inversion of monthly average bending-angle profiles. The averaging of large numbers of profiles suppresses random noise and this, in combination with simple exponential extrapolation above an altitude of 80 km, circumvents the need for a "statistical optimization" step in the processing. Using data from the US-Taiwanese COSMIC mission, which provides ~ 1500–2000 occultations per day, it has been shown that this Average-Profile Inversion (API) technique provides a robust method for generating stratospheric refractivity climatologies. Prior to the launch of COSMIC in mid-2006, the data records rely on data from the CHAMP mission. In order to exploit the full range of available RO data, the usage of CHAMP data is also required. CHAMP only provided ~ 200 profiles per day, and the measurements were noisier than COSMIC. As a consequence, the main research question in this study was to see if the average bending angle approach is also applicable to CHAMP data. Different methods for suppression of random noise – statistical and through data quality pre-screening – were tested. The API retrievals were compared with the more conventional approach of averaging individual refractivity profiles, produced with the implementation of statistical optimization used in the EUMETSAT Radio Occultation Meteorology Satellite Application Facility (ROM SAF) operational processing. In this study it is demonstrated that the API retrieval technique works well for CHAMP data, enabling the generation of long-term stratospheric RO climate data records from August 2001 and onward. The resulting CHAMP refractivity climatologies are found to be practically identical to the standard retrieval at the DMI below altitudes of 35 km. Between 35 km to 50 km the differences between the two retrieval methods started to increase, showing largest differences at high latitudes and high altitudes. Furthermore, in the winter hemisphere high latitude region, the biases relative to ECMWF were generally smaller for the new approach than for the standard retrieval.
Riparian and in-stream controls on nutrient concentrations along a headwater forested stream
Authors: Bernal S. , Lupon A. , Ribot M. , Sabater F. , Martí E.
Published: July 2014

Abstract. Headwater streams have a strong capacity to transform and retain nutrients, and thus, a longitudinal decrease in stream nutrient concentrations would be expected from in-stream nutrient removal alone. Yet, a number of other factors within the catchment, including biogeochemical processing within the riparian zone and export to streams, can contribute to stream nutrient concentration, which may overcome the effect of in-stream biogeochemical processing. To explore this idea, we analyzed the longitudinal patterns of stream and riparian groundwater concentrations for chloride (Cl−), nitrate (NO3−), ammonium (NH4+), and phosphate (PO43−) along a 3.7 km reach at an annual scale. The reach showed a gradual increase in stream and riparian width, riparian tree basal area, and abundance of riparian N2-fixing tree species. Concentrations of Cl− indicated a~strong hydrological connection at the riparian-stream edge. However, stream and riparian groundwater nutrient concentrations showed a moderate to null correlation, suggesting high biogeochemical processing at the riparian-stream edge and within the stream. A mass balance approach along the reach indicated that, on average, in-stream net nutrient uptake prevailed over release for NH4+ and PO43−, but not for NO3−. On an annual basis, in-stream processes contributed to change stream input fluxes by 11%, 26%, and 29% for NO3−, NH4+, and PO43−, respectively. Yet, longitudinal trends in concentration were not consistent with the prevailing in-stream biogeochem ical processes. During the riparian dormant period, stream concentration decreased along the reach for NO3−, but increased for NH4+ and PO43−. During the riparian vegetative period, NO3− and PO43− increased along the reach while NH4+ showed no clear pattern. These longitudinal trends were partially related to riparian forest features and groundwater inputs, especially for NO3− and PO43−. Our study suggests that even though in-stream biogeochemical processing was substantial, the riparian zone can modulate the longitudinal variation in stream nutrient chemistry in this headwater stream.
I/Ca ratios in benthic foraminifera from the Peruvian oxygen minimum zone: analytical methodology and evaluation as proxy for redox conditions
Authors: Glock N. , Liebetrau V. , Eisenhauer A.
Published: July 2014

Abstract. In this study we explore the correlation of I/Ca ratios in three calcitic and one aragonitic foraminiferal species. I/Ca ratios are evaluated as possible proxies for changes in ambient redox conditions across the Peruvian oxygen minimum zone to the ambient oxygen concentrations in the habitat of the foraminiferal species studied. We test cleaning and measurement methods to determine I/Ca ratios in benthic foraminifera from the Peruvian oxygen minimum zone. All species show a positive trend in their I/Ca ratios as a function of higher oxygen concentrations and these trends are all statistically significant except for the aragonitic species Hoeglundina elegans. The most promising species appears to be Uvigerina striata which shows a highly statistically significant correlation between I/Ca ratios and bottom water (BW) oxygenation (I/Ca = 0.032(± 0.004)[O2]BW + 0.29(± 0.03), R2 = 0.61, F = 75, P < 0.0001). Although I/Ca ratios in benthic foraminifera might prove to be a valuable proxy for changing redox-conditions the iodine volatility in acidic solutions, the species dependency ofI/Ca–[O2]BW correlations, and the individual variability of single tests severely interfere with the observed I/Ca–[O2]BW relationship.