Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors.

Small chemicals like drugs tend to bind to proteins via noncovalent bonds, e.g. hydrogen bonds, salt bridges or electrostatic interactions. Some chemicals interact with other molecules than the actual target ligand, representing so-called 'off-target' activities of drugs. Such interactions are a main cause of adverse side effects to drugs and are normally classified as predictable type A reactions. Detailed analysis of drug-induced immune reactions revealed that off-target activities also affect immune receptors, such as highly polymorphic human leukocyte antigens (HLA) or T cell receptors (TCR). Such drug interactions with immune receptors may lead to T cell stimulation, resulting in clinical symptoms of delayed-type hypersensitivity. They are assigned the 'pharmacological interaction with immune receptors' (p-i) concept. Analysis of p-i has revealed that drugs bind preferentially or exclusively to distinct HLA molecules (p-i HLA) or to distinct TCR (p-i TCR). P-i reactions differ from 'conventional' off-target drug reactions as the outcome is not due to the effect on the drug-modified cells themselves, but is the consequence of reactive T cells. Hence, the complex and diverse clinical manifestations of delayed-type hypersensitivity are caused by the functional heterogeneity of T cells. In the abacavir model of p-i HLA, the drug binding to HLA may result in alteration of the presenting peptides. More importantly, the drug binding to HLA generates a drug-modified HLA, which stimulates T cells directly, like an allo-HLA. In the sulfamethoxazole model of p-i TCR, responsive T cells likely require costimulation for full T cell activation. These findings may explain the similarity of delayed-type hypersensitivity reactions to graft-versus-host disease, and how systemic viral infections increase the risk of delayed-type hypersensitivity reactions.

Compilation of measurements from two interdisciplinary STAR-shaped surveys in the North Sea: The ZISCH - Dataset

The measurements were obtained during two North Sea wide STAR-shaped cruises during summer 1986 and winter 1987, which were performed to investigate the circulation induced transport and biologically induced pollutant transfer within the interdisciplinary research in the project "ZISCH - Zirkulation und Schadstoffumsatz in der Nordsee / Circulation and Contaminant Fluxes in the North Sea (1984-1989)". The inventory presents parameters measured on hydrodynamics, nutrient dynamics, ecosystem dynamics and pollutant dynamics in the pelagic and benthic realm. The research program had the objective of quantifying fluxes of major budgets, especially contaminants in the North Sea. In spring 1986, following the phytoplankton spring bloom, and in late winter 1987, at minimum primary production activity, the North Sea ecosystem was investigated on a station net covering the whole North Sea. The station net was shaped like a star. Sampling started in the centre, followed by the northwest section and moving counter clockwise around the North Sea following the residual currents. By this strategy, a time series was measured in the central North Sea and more synoptic data sets were obtained in the individual sections. Generally advection processes have to be considered when comparing the data from different stations. The entire sampling period lasted for more than six weeks in each cruise. Thus, a time-lag should be considered especially when comparing the data from the eastern and the western part of the central and northern North Sea, where samples were taken at the beginning and at the end of the campaign. The ZISCH investigations represented a qualitatively and quantitatively new approach to North Sea research in several respects. (1) The first simultaneous blanket coverage of all important biological, chemical and physical parameters in the entire North Sea ecosystem; (2) the first simultaneous measurements of major contaminants (metals and organohaline compounds) in the different ecosystem compartments; (3) simultaneous determinations of atmospheric inputs of momentum, energy and matter as important ecosystem boundary conditions; (4) performance of the complex measurement program during two seasons, namely the spring plankton bloom and the subsequent winter period of minimal biological activity; and (5) support of data analysis and interpretation by oceanographic and meteorological numerical models on the same scales.

North Atlantic IODP Site 303-U1308 Middle Pleistocene Heinrich Events record

Heinrich events are well documented for the last glaciation, but little is known about their occurrence in older glacial periods of the Pleistocene. Here we report scanning XRF and bulk carbonate d18O results from Integrated Ocean Drilling Program Site U1308 (reoccupation of Deep Sea Drilling Project Site 609) that are used to develop proxy records of ice-rafted detritus (IRD) for the last ~1.4 Ma. Ca/Sr is used as an indicator of IRD layers that are rich in detrital carbonate (i.e., Heinrich layers), whereas Si/Sr reflects layers that are poor in biogenic carbonate and relatively rich in detrital silicate minerals. A pronounced change occurred in the composition and frequency of IRD at ~640 ka during marine isotope stage (MIS) 16, coinciding with the end of the middle Pleistocene transition. At this time, "Hudson Strait" Heinrich layers suddenly appeared in the sedimentary record of Site U1308, and the dominant period of the Si/Sr proxy shifted from 41 ka prior to 640 ka to 100 ka afterward. The onset of Heinrich layers during MIS 16 represents either the initiation of surging of the Laurentide Ice Sheet (LIS) off Hudson Strait or the first time icebergs produced by this process survived the transport to Site U1308. We speculate that ice volume (i.e., thickness) and duration surpassed a critical threshold during MIS 16 and activated the dynamical processes responsible for LIS instability in the region of Hudson Strait. We also observe a strong coupling between IRD proxies and benthic d13C variation at Site U1308 throughout the Pleistocene, supporting a link between iceberg discharge and weakening of thermohaline circulation in the North Atlantic.

Los museos mineralógicos de las Escuelas de Minas españolas

Se trata de ver el estado actual de los museos mineralógicos en las Escuelas de Minas.

Hacia una metodología en la enseñanza de las rocas y de los minerales industriales

El mercado de las rocas industriales desde el punto de vista económico se ha desarrollado de manera espectacular en los últimos tiempos. Eso es especialmente cierto en lo que se refiere a las rocas ornamentales, si bien los materiales pétreos utilizados en la construcción han experimentado también un importante ascenso.

Homography-based ground plane detection using a single on-board camera

This study presents a robust method for ground plane detection in vision-based systems with a non-stationary camera. The proposed method is based on the reliable estimation of the homography between ground planes in successive images. This homography is computed using a feature matching approach, which in contrast to classical approaches to on-board motion estimation does not require explicit ego-motion calculation. As opposed to it, a novel homography calculation method based on a linear estimation framework is presented. This framework provides predictions of the ground plane transformation matrix that are dynamically updated with new measurements. The method is specially suited for challenging environments, in particular traffic scenarios, in which the information is scarce and the homography computed from the images is usually inaccurate or erroneous. The proposed estimation framework is able to remove erroneous measurements and to correct those that are inaccurate, hence producing a reliable homography estimate at each instant. It is based on the evaluation of the difference between the predicted and the observed transformations, measured according to the spectral norm of the associated matrix of differences. Moreover, an example is provided on how to use the information extracted from ground plane estimation to achieve object detection and tracking. The method has been successfully demonstrated for the detection of moving vehicles in traffic environments.

Learning an L1-regularized Gaussian Bayesian Network in the Equivalence Class Space

Learning the structure of a graphical model from data is a common task in a wide range of practical applications. In this paper, we focus on Gaussian Bayesian networks, i.e., on continuous data and directed acyclic graphs with a joint probability density of all variables given by a Gaussian. We propose to work in an equivalence class search space, specifically using the k-greedy equivalence search algorithm. This, combined with regularization techniques to guide the structure search, can learn sparse networks close to the one that generated the data. We provide results on some synthetic networks and on modeling the gene network of the two biological pathways regulating the biosynthesis of isoprenoids for the Arabidopsis thaliana plant

Performance of Scheduling Policies in Adversarial Networks with Non-synchronized Clocks

In this paper we generalize the Continuous Adversarial Queuing Theory (CAQT) model (Blesa et al. in MFCS, Lecture Notes in Computer Science, vol. 3618, pp. 144–155, 2005) by considering the possibility that the router clocks in the network are not synchronized. We name the new model Non Synchronized CAQT (NSCAQT). Clearly, this new extension to the model only affects those scheduling policies that use some form of timing. In a first approach we consider the case in which although not synchronized, all clocks run at the same speed, maintaining constant differences. In this case we show that all universally stable policies in CAQT that use the injection time and the remaining path to schedule packets remain universally stable. These policies include, for instance, Shortest in System (SIS) and Longest in System (LIS). Then, we study the case in which clock differences can vary over time, but the maximum difference is bounded. In this model we show the universal stability of two families of policies related to SIS and LIS respectively (the priority of a packet in these policies depends on the arrival time and a function of the path traversed). The bounds we obtain in this case depend on the maximum difference between clocks. This is a necessary requirement, since we also show that LIS is not universally stable in systems without bounded clock difference. We then present a new policy that we call Longest in Queues (LIQ), which gives priority to the packet that has been waiting the longest in edge queues. This policy is universally stable and, if clocks maintain constant differences, the bounds we prove do not depend on them. To finish, we provide with simulation results that compare the behavior of some of these policies in a network with stochastic injection of packets.

Dimensional synthesis of a spherical parallel manipulator based on the evaluation of global performance indexes

In this work, the dimensional synthesis of a spherical Parallel Manipulator (PM) with a -1S kinematic chain is presented. The goal of the synthesis is to find a set of parameters that defines the PM with the best performance in terms of workspace capabilities, dexterity and isotropy. The PM is parametrized in terms of a reference element, and a non-directed search of these parameters is carried out. First, the inverse kinematics and instantaneous kinematics of the mechanism are presented. The latter is found using the screw theory formulation. An algorithm that explores a bounded set of parameters and determines the corresponding value of global indexes is presented. The concepts of a novel global performance index and a compound index are introduced. Simulation results are shown and discussed. The best PMs found in terms of each performance index evaluated are locally analyzed in terms of its workspace and local dexterity. The relationship between the performance of the PM and its parameters is discussed, and a prototype with the best performance in terms of the compound index is presented and analyzed.

Optimizing three-phase planar transformer construction

A three-phase transformer with flat conductor layers is proposed in this article. This arrangement is used for high current density transformers. Cost effectiveness in planar magnetic are related with the optimization in the number of layers in each winding. This fact takes more relevance for the medium and high power three-phase transformers where the number of parallels to achieve the required DCR is increased. The proposed method allows the use of off-the-shell core shapes that are used for single phase transformers. Cost impact is significant and design implications become more flexible. The proposed solution has been validated and compared using the conventional and the proposed methodologies to design a high power (20 kW) transformer.

Kinematic analysis of a novel 2-d.o.f. orientation device

This paper presents the development of a new parallel robot designed for helping with bone milling surgeries. The robot is a small modular wrist with 2 active degrees of freedom, and it is proposed to be used as an orientation device located at the end of a robotic arm designed for bone milling processes. A generic kinematic geometry is proposed for this device. This first article shows the developments on the workspace optimization and the analysis of the force field required to complete a reconstruction of the inferior jawbone. The singularities of the mechanism are analyzed, and the actuator selection is justified with the torque requirements and the study of the force space. The results obtained by the simulations allow building a first prototype using linear motors. Bone milling experiment video is shown as additional material.

A dual-band priority assignment algorithm for dynamic QoS resource management

Future high-quality consumer electronics will contain a number of applications running in a highly dynamic environment, and their execution will need to be efficiently arbitrated by the underlying platform software. The multimedia applications that currently execute in such similar contexts face frequent run-time variations in their resource demands, originated by the greedy nature of the multimedia processing itself. Changes in resource demands are triggered by numerous reasons (e.g. a switch in the input media compression format). Such situations require real-time adaptation mechanisms to adjust the system operation to the new requirements, and this must be done seamlessly to satisfy the user experience. One solution for efficiently managing application execution is to apply quality of service resource management techniques, based on assigning and enforcing resource contracts to applications. Most resource management solutions provide temporal isolation by enforcing resource assignments and avoiding any resource overruns. However, this has a clear limitation over the cost-effective resource usage. This paper presents a simple priority assignment scheme based on uniform priority bands to allow that greedy multimedia tasks incur in safe overruns that increase resource usage and do not threaten the timely execution of non-overrunning tasks. Experimental results show that the proposed priority assignment scheme in combination with a resource accounting mechanism preserves timely multimedia execution and delivery, achieves a higher cost-effective processor usage, and guarantees the execution isolation of non-overrunning tasks.

Design and modeling of the multi-agent robotic system: SMART

This article presents the design, kinematic model and communication architecture for the multi-agent robotic system called SMART. The philosophy behind this kind of system requires the communication architecture to contemplate the concurrence of the whole system. The proposed architecture combines different communication technologies (TCP/IP and Bluetooth) under one protocol designed for the cooperation among agents and other elements of the system such as IP-Cameras, image processing library, path planner, user Interface, control block and data block. The high level control is modeled by Work-Flow Petri nets and implemented in C++ and C♯♯. Experimental results show the performance of the designed architecture.

Metodología de ecoinnovación PDCA, aplicada al prototipo de fachada vegetal aljibe Naturpanel en el Proyecto SOS-Natura

Este artículo expone la metodología de trabajo desarrollada en las investigaciones del Departamento de Construcción y Tecnología Arquitectónicas de la UPM, basada en el concepto de ecoinnovación, y en la normativa AENOR de Ecodiseño (UNE-EN ISO 14006), en normativas relacionadas como la UNE-EN ISO 9001 y 14001, entre otras. Dicha metodología considera los aspectos medioambientales desde las primeras fases de la investigación, para aumentar la ecoeficiencia de las propuestas producidas, de manera que satisfagan las necesidades humanas y proporcionen una mejor calidad de vida, a la vez que reduzcan progresivamente los impactos ambientales y la intensidad de consumo de recursos a lo largo de su ciclo de vida, hasta un nivel, al menos, en línea con la capacidad de asimilación de la Tierra. El objetivo de esta comunicación es explicar y dar a conocer, mediante ejemplos concretos, dicha metodología; los beneficios de la misma y cómo influye su utilización en el diseño arquitectónico de fachadas vegetales.

Time and space partition platform for safe and secure flight software.

There are a number of research and development activities that are exploring Time and Space Partition (TSP) to implement safe and secure flight software. This approach allows to execute different real-time applications with different levels of criticality in the same computer board. In order to do that, flight applications must be isolated from each other in the temporal and spatial domains. This paper presents the first results of a partitioning platform based on the Open Ravenscar Kernel (ORK+) and the XtratuM hypervisor. ORK+ is a small, reliable real-time kernel supporting the Ada Ravenscar Computational model that is central to the ASSERT development process. XtratuM supports multiple virtual machines, i.e. partitions, on a single computer and is being used in the Integrated Modular Avionics for Space study. ORK+ executes in an XtratuM partition enabling Ada applications to share the computer board with other applications.