Novel Imaging-Based Techniques Reveal a Role for PD-1/PD-L1 in Tumor Immune Surveillance in the Lung

The binding of immune inhibitory receptor Programmed Death 1 (PD-1) on T cells to its ligand PD-L1 has been implicated as a major contributor to tumor induced immune suppression. Clinical trials of PD-L1 blockade have proven effective in unleashing therapeutic anti-tumor immune responses in a subset of patients with advanced melanoma, yet current response rates are low for reasons that remain unclear. Hypothesizing that the PD-1/PD-L1 pathway regulates T cell surveillance within the tumor microenvironment, we employed intravital microscopy to investigate the in vivo impact of PD-L1 blocking antibody upon tumor-associated immune cell migration. However, current analytical methods of intravital dynamic microscopy data lack the ability to identify cellular targets of T cell interactions in vivo, a crucial means for discovering which interactions are modulated by therapeutic intervention. By developing novel imaging techniques that allowed us to better analyze tumor progression and T cell dynamics in the microenvironment; we were able to explore the impact of PD-L1 blockade upon the migratory properties of tumor-associated immune cells, including T cells and antigen presenting cells, in lung tumor progression. Our results demonstrate that early changes in tumor morphology may be indicative of responsiveness to anti-PD-L1 therapy. We show that immune cells in the tumor microenvironment as well as tumors themselves express PD-L1, but immune phenotype alone is not a predictive marker of effective anti-tumor responses. Through a novel method in which we quantify T cell interactions, we show that T cells are largely engaged in interactions with dendritic cells in the tumor microenvironment. Additionally, we show that during PD-L1 blockade, non-activated T cells are recruited in greater numbers into the tumor microenvironment and engage more preferentially with dendritic cells. We further show that during PD-L1 blockade, activated T cells engage in more confined, immune synapse-like interactions with dendritic cells, as opposed to more dynamic, kinapse-like interactions with dendritic cells when PD-L1 is free to bind its receptor. By advancing the contextual analysis of anti-tumor immune surveillance in vivo, this study implicates the interaction between T cells and tumor-associated dendritic cells as a possible modulator in targeting PD-L1 for anti-tumor immunotherapy.

You Know You Are Evidence-Based If...

This issue of the Family Preservation Journal further contributes to our knowledge of what works in family preservation and family support by offering seven articles that are evidence-based.

Women’s experiences with the use of medical abortion in a legally restricted context: the case of Argentina

This article presents the findings of a qualitative study exploring the experiences of women living in Buenos Aires Metropolitan Area, Argentina, with the use of misoprostol for inducing an abortion. We asked women about the range of decisions they had to make, their emotions, the physical experience, strategies they needed to use, including seeking health care advice and in dealing with a clandestine medical abortion, and their overall evaluation of the experience. An in-depth interview schedule was used. The women had either used misoprostol and sought counselling or care at a public hospital (n=24) or had used misoprostol based on the advice of a local hotline, information from the internet or from other women (n=21). Four stages in the women’s experiences were identified: how the decision to terminate the pregnancy was taken, how the medication was obtained, how the tablets were used, and reflections on the outcome whether or not they sought medical advice. Safety and privacy were key in deciding to use medical abortion. Access to the medication was the main obstacle, requiring a prescription or a friendly drugstore. Correct information about the number of pills to use and dosage intervals was the least easy to obtain and caused concerns. The possibility of choosing a time of privacy and having the company of a close one was highlighted as a unique advantage of medical abortion. Efforts to improve abortion law, policy and service provision in Argentina in order to ensure the best possible conditions for use of medical abortion by women should be redoubled.

Satellite-based daily lake areas in the Yangtze Basin, China, 2000-2011

The Yangtze River Basin downstream of China's Three Gorges Dam (TGD) (thereafter referred to as "downstream" basin) hosts the largest cluster of freshwater lakes in East Asia. These lakes are crucial water stocks to local biophysical environments and socioeconomic development. Existing studies document that individual lakes in this region have recently experienced dramatic changes under the context of enduring meteorological drought, continuous population growth, and extensive water regulation since TGD's initial impoundment (i.e., June, 2003). However, spatial and temporal patterns of lake dynamics across the complete downstream Yangtze basin remain poorly characterized. Using daily MODIS imagery and an advanced thematic mapping scheme, this study presents a comprehensive monitoring of area dynamics in the downstream lake system at a 10-day temporal resolution during 2000-2011. The studied lakes constitute ~76% (~11,400 km**2) of the total downstream lake area, including the entire +70 major lakes larger than 20 km**2. The results reveal a decadal net decline in lake inundation area across the downstream Yangtze Basin, with a cumulative decrease of 849 km**2 or 7.4% from 2000 to 2011. Despite an excessive precipitation anomaly in the year 2010, the decreasing trend was tested significant in all seasons. The most substantial decrease in the post-TGD period appears in fall (1.1%/yr), which intriguingly coincides with the TGD water storage season. Regional lake dynamics exhibit contrasting spatial patterns, manifested as evident decrease and increase of aggregated lake areas respectively within and beyond the Yangtze Plain. This contrast suggests a marked vulnerability of lakes in the Yangtze Plain, to not only local meteorological variability but also intensified human water regulations from both the upstream Yangtze main stem (e.g., the TGD) and tributaries (e.g., lakes/reservoirs beyond the Yangtze Plain). The produced lake mapping result and derived lake area dynamics across the downstream Yangtze Basin provides a crucial monitoring basis for continuous investigations of changing mechanisms in the Yangtze lake system.

Trade Coefficients and the Role of Elasticity in a Spatial CGE Model Based on the Armington Assumption

The Armington Assumption in the context of multi-regional CGE models is commonly interpreted as follows: Same commodities with different origins are imperfect substitutes for each other. In this paper, a static spatial CGE model that is compatible with this assumption and explicitly considers the transport sector and regional price differentials is formulated. Trade coefficients, which are derived endogenously from the optimization behaviors of firms and households, are shown to take the form of a potential function. To investigate how the elasticity of substitutions affects equilibrium solutions, a simpler version of the model that incorporates three regions and two sectors (besides the transport sector) is introduced. Results indicate: (1) if commodities produced in different regions are perfect substitutes, regional economies will be either autarkic or completely symmetric and (2) if they are imperfect substitutes, the impact of elasticity on the price equilibrium system as well as trade coefficients will be nonlinear and sometimes very sensitive.

Project Management Learning in a Collaborative Distant Learning Context - An Actual On-going Experience

The goal of this paper is to show the results of an on-going experience on teaching project management to grade students by following a development scheme of management related competencies on an individual basis. In order to achieve that goal, the students are organized in teams that must solve a problem and manage the development of a feasible solution to satisfy the needs of a client. The innovative component advocated in this paper is the formal introduction of negotiating and virtual team management aspects, as different teams from different universities at different locations and comprising students with different backgrounds must collaborate and compete amongst them. The different learning aspects are identified and the improvement levels are reflected in a rubric that has been designed ad hoc for this experience. Finally, the effort frameworks for the student and instructor have been established according to the requirements of the Bologna paradigms. This experience is developed through a software-based support system allowing blended learning for the theoretical and individual?s work aspects, blogs, wikis, etc., as well as project management tools based on WWW that allow the monitoring of not only the expected deliverables and the achievement of the goals but also the progress made on learning as established in the defined rubric

Competence Monitoring in Project Teams by using Web based portfolio management systems

This paper reports a learning experience related to the acquisition of project management competences. Students from three different universities and backgrounds, cooperate in a common project that drives the learning-teaching process. Previous related works on this initiative have already evaluated the goodness of this multidisciplinary, project-based learning approach in the context of a new educative paradigm. Yet the innovative experience has allowed the authors to define a rubric in order to measure specific competences in project management. The study shows the rubric’s main aspects as well as competence acquisition evaluation alternatives, based in the metrics defined. Key indicators and specific reports obtained from data base fields in the web tool will support this work. As a result, new competences can be assessed, such ones like teamwork, problem solving, communication and leadership. Final goal is to provide an overall competence map to the students at the same time they improve their skills.

Desing and Validation of a Light Inference System to Support Embedded Context Reasoning

Embedded context management in resource-constrained devices (e.g. mobile phones, autonomous sensors or smart objects) imposes special requirements in terms of lightness for data modelling and reasoning. In this paper, we explore the state-of-the-art on data representation and reasoning tools for embedded mobile reasoning and propose a light inference system (LIS) aiming at simplifying embedded inference processes offering a set of functionalities to avoid redundancy in context management operations. The system is part of a service-oriented mobile software framework, conceived to facilitate the creation of context-aware applications—it decouples sensor data acquisition and context processing from the application logic. LIS, composed of several modules, encapsulates existing lightweight tools for ontology data management and rule-based reasoning, and it is ready to run on Java-enabled handheld devices. Data management and reasoning processes are designed to handle a general ontology that enables communication among framework components. Both the applications running on top of the framework and the framework components themselves can configure the rule and query sets in order to retrieve the information they need from LIS. In order to test LIS features in a real application scenario, an ‘Activity Monitor’ has been designed and implemented: a personal health-persuasive application that provides feedback on the user’s lifestyle, combining data from physical and virtual sensors. In this case of use, LIS is used to timely evaluate the user’s activity level, to decide on the convenience of triggering notifications and to determine the best interface or channel to deliver these context-aware alerts.d

Improving Speech Interaction in Vehicles Using Context-Aware Information through A SCXML Framework

Speech Technologies can provide important benefits for the development of more usable and safe in-vehicle human-machine interactive systems (HMIs). However mainly due robustness issues, the use of spoken interaction can entail important distractions to the driver. In this challenging scenario, while speech technologies are evolving, further research is necessary to explore how they can be complemented with both other modalities (multimodality) and information from the increasing number of available sensors (context-awareness). The perceived quality of speech technologies can significantly be increased by implementing such policies, which simply try to make the best use of all the available resources; and the in vehicle scenario is an excellent test-bed for this kind of initiatives. In this contribution we propose an event-based HMI design framework which combines context modelling and multimodal interaction using a W3C XML language known as SCXML. SCXML provides a general process control mechanism that is being considered by W3C to improve both voice interaction (VoiceXML) and multimodal interaction (MMI). In our approach we try to anticipate and extend these initiatives presenting a flexible SCXML-based approach for the design of a wide range of multimodal context-aware HMI in-vehicle interfaces. The proposed framework for HMI design and specification has been implemented in an automotive OSGi service platform, and it is being used and tested in the Spanish research project MARTA for the development of several in-vehicle interactive applications.

Ultra Low Power FPGA-Based Architecture for Wake-up Radio in Wireless Sensor Networks

In this paper the capabilities of ultra low power FPGAs to implement Wake-up Radios (WuR) for ultra low energy Wireless Sensor Networks (WSNs) are analyzed. The main goal is to evaluate the utilization of very low power configurable devices to take advantage of their speed, flexibility and low power consumption instead of the more common approaches based on ASICs or microcontrollers. In this context, energy efficiency is a key aspect, considering that usually the instant power consumption is considered a figure of merit, more than the total energy consumed by the application.

Explicitly Context-Aware Publish/Subscribe with Context-Invariant Subscriptions

Although context could be exploited to improve the performance, elasticity and adaptation in most distributed systems that adopt the publish/subscribe (P/S) model of communication, only very few works have explored domains with highly dynamic context, whereas most adopted models are context agnostic. In this paper, we present the key design principles underlying a novel context-aware content-based P/S (CA-CBPS) model of communication, where the context is explicitly managed, focusing on the minimization of network overhead in domains with recurrent context changes thanks to contextual scoping. We highlight how we dealt with the main shortcomings of most of the current approaches. Our research is some of the first to study the problem of explicitly introducing context-awareness into the P/S model to capitalize on contextual information. The envisioned CA-CBPS middleware enables the cloud ecosystem of services to communicate very efficiently, in a decoupled, but contextually scoped fashion.

Games based learning for Exploring Cultural Conflict

In this paper we discuss the early stage design of MIXER, a technology enhance educational application focused at supporting children in learning about cultural conflict, achieved through the use of a game with an effective embodied AI agent. MIXER is being developed re-using existing technology applied to a different context and purpose with the aim of creating an educational and enjoyable experience for 9-11 year olds. This paper outlines MIXER’s underpinning technology and theory. It presents early stage design and development, highlighting current research directions.

X-parameters based analytical design of non-linear microwave circuits Application to oscillator design

Resumen El diseño clásico de circuitos de microondas se basa fundamentalmente en el uso de los parámetros s, debido a su capacidad para caracterizar de forma exitosa el comportamiento de cualquier circuito lineal. La relación existente entre los parámetros s con los sistemas de medida actuales y con las herramientas de simulación lineal han facilitado su éxito y su uso extensivo tanto en el diseño como en la caracterización de circuitos y subsistemas de microondas. Sin embargo, a pesar de la gran aceptación de los parámetros s en la comunidad de microondas, el principal inconveniente de esta formulación reside en su limitación para predecir el comportamiento de sistemas no lineales reales. En la actualidad, uno de los principales retos de los diseñadores de microondas es el desarrollo de un contexto análogo que permita integrar tanto el modelado no lineal, como los sistemas de medidas de gran señal y los entornos de simulación no lineal, con el objetivo de extender las capacidades de los parámetros s a regímenes de operación en gran señal y por tanto, obtener una infraestructura que permita tanto la caracterización como el diseño de circuitos no lineales de forma fiable y eficiente. De acuerdo a esta filosofía, en los últimos años se han desarrollado diferentes propuestas como los parámetros X, de Agilent Technologies, o el modelo de Cardiff que tratan de proporcionar esta plataforma común en el ámbito de gran señal. Dentro de este contexto, uno de los objetivos de la presente Tesis es el análisis de la viabilidad del uso de los parámetros X en el diseño y simulación de osciladores para transceptores de microondas. Otro aspecto relevante en el análisis y diseño de circuitos lineales de microondas es la disposición de métodos analíticos sencillos, basados en los parámetros s del transistor, que permitan la obtención directa y rápida de las impedancias de carga y fuente necesarias para cumplir las especificaciones de diseño requeridas en cuanto a ganancia, potencia de salida, eficiencia o adaptación de entrada y salida, así como la determinación analítica de parámetros de diseño clave como el factor de estabilidad o los contornos de ganancia de potencia. Por lo tanto, el desarrollo de una formulación de diseño analítico, basada en los parámetros X y similar a la existente en pequeña señal, permitiría su uso en aplicaciones no lineales y supone un nuevo reto que se va a afrontar en este trabajo. Por tanto, el principal objetivo de la presente Tesis consistiría en la elaboración de una metodología analítica basada en el uso de los parámetros X para el diseño de circuitos no lineales que jugaría un papel similar al que juegan los parámetros s en el diseño de circuitos lineales de microondas. Dichos métodos de diseño analíticos permitirían una mejora significativa en los actuales procedimientos de diseño disponibles en gran señal, así como una reducción considerable en el tiempo de diseño, lo que permitiría la obtención de técnicas mucho más eficientes. Abstract In linear world, classical microwave circuit design relies on the s-parameters due to its capability to successfully characterize the behavior of any linear circuit. Thus the direct use of s-parameters in measurement systems and in linear simulation analysis tools, has facilitated its extensive use and success in the design and characterization of microwave circuits and subsystems. Nevertheless, despite the great success of s-parameters in the microwave community, the main drawback of this formulation is its limitation in the behavior prediction of real non-linear systems. Nowadays, the challenge of microwave designers is the development of an analogue framework that allows to integrate non-linear modeling, large-signal measurement hardware and non-linear simulation environment in order to extend s-parameters capabilities to non-linear regimen and thus, provide the infrastructure for non-linear design and test in a reliable and efficient way. Recently, different attempts with the aim to provide this common platform have been introduced, as the Cardiff approach and the Agilent X-parameters. Hence, this Thesis aims to demonstrate the X-parameter capability to provide this non-linear design and test framework in CAD-based oscillator context. Furthermore, the classical analysis and design of linear microwave transistorbased circuits is based on the development of simple analytical approaches, involving the transistor s-parameters, that are able to quickly provide an analytical solution for the input/output transistor loading conditions as well as analytically determine fundamental parameters as the stability factor, the power gain contours or the input/ output match. Hence, the development of similar analytical design tools that are able to extend s-parameters capabilities in small-signal design to non-linear ap- v plications means a new challenge that is going to be faced in the present work. Therefore, the development of an analytical design framework, based on loadindependent X-parameters, constitutes the core of this Thesis. These analytical nonlinear design approaches would enable to significantly improve current large-signal design processes as well as dramatically decrease the required design time and thus, obtain more efficient approaches.

Using SCXML to integrate semantic sensor information into context-aware user interfaces

This paper describes a novel architecture to introduce automatic annotation and processing of semantic sensor data within context-aware applications. Based on the well-known state-charts technologies, and represented using W3C SCXML language combined with Semantic Web technologies, our architecture is able to provide enriched higher-level semantic representations of user’s context. This capability to detect and model relevant user situations allows a seamless modeling of the actual interaction situation, which can be integrated during the design of multimodal user interfaces (also based on SCXML) for them to be adequately adapted. Therefore, the final result of this contribution can be described as a flexible context-aware SCXML-based architecture, suitable for both designing a wide range of multimodal context-aware user interfaces, and implementing the automatic enrichment of sensor data, making it available to the entire Semantic Sensor Web

Knowledge pipeline in freight pipeline industry: competence- based model for open innovation

There is growing concern over the challenges for innovation in Freight Pipeline industry. Since the early works of Chesbrough a decade ago, we have learned a lot about the content, context and process of open innovation. However, much more research is needed in Freight Pipeline Industry. The reality is that few corporations have institutionalized open innovation practices in ways that have enabled substantial growth or industry leadership. Based on this, we pursue the following question: How does a firm’s integration into knowledge networks depend on its ability to manage knowledge? A competence-based model for freight pipeline organizations is analysed, this model should be understood by any organization in order to be successful in motivating professionals who carry out innovations and play a main role in collaborative knowledge creation processes. This paper aims to explain how can open innovation achieve its potential in most Freight Pipeline Industries.