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Signalling adaptor TRAF1 modulation, as a therapeutic target, to restore HCV-specific cytotoxic T cell response reactivity during chronic infection
No full textHepatitis C virus (HCV) worldwide infects around 170 million people. Two thirds of primo-infections develop a chronic disease that could lead to cirrhosis and hepatocellular carcinoma. This infection can be cured with direct acting anti-virals (DAA) but there are still difficult to treat cases relapsing after treatment, in which immunotherapy could play a role in curation. A successful immune response against HCV depends on virus-specific CD8+ T cells. During chronic infection, these cells are functionally impaired. The degree of this immune impairment could rely on the grade of co-stimulation failure over time of infection.
The analysis of this dataset shows that:
(1) Patients with short-mid lasting HCV infection had mild exhausted T cells, featured by loss of the key signal transducer (TRAF1) of the positive checkpoint 4-1BB/4-1BBL.
(2) The functionality of these cells can be restored by IL-7-induced TRAF1 up-regulation, while in long-lasting infection to block the negative-costimulatory pathway PD-1/PD-L1 was also necessary.
(3) Nevertheless, this last strategy was only useful in slow-fibrosers, suggesting an extreme T cell exhaustion or deletion in rapid fibrosers.
In sum, our work supports novel ways of restoring specific CD8+ T cell response during chronic HCV infection, shedding light on the importance of TRAF1 signalling, which could be a promising target for immunotherapy in non-responders to DAA
Experiment STAbility of liquid COlumns (STACO) on the Advanced Fluid Physics Module (FPM) aboard Spacelab-D2
No full textDuring the second German Mission of Spacelab (1993, Spacelab D-2) an experiment on the mechanical stability of liquid columns was performed. A liquid column is a liquid mass held between to solid (circular) supports. A 30 mm in diameter and 90 mm long liquid drop was stablished in the Advanced Fluid Physics Module (AFPM) and was subjected to different mechanical stimuli (rotation of the supports, oscillation of one of the supports, change in volume and in length) to check whether the resulting drop was stable or not. Results were obtained in terms of images and recorded in a video sequence. Telemetry of the different stimuli and parameter values was also recorded. Objetive: The aim of this experiment was to measure the outer shape deformation of long liquid bridges near their stability limit under microgravity, caused by g-jitters and by some controlled mechanical disturbances (change of geometry, change of volume, rotation and vibration). The liquid used was a silicone-oil 10 times more viscous than water (5 times for the last run). The working length of the liquid column was 85 mm. The two solid supports are made of aluminium, of 30 mm in diameter, with a sharp cutback (30 deg. edge) to prevent liquid spreading over the edges. This choice of geometry allows a direct comparison with other TEXUS experiments where two discs of 30 mm in diameter and 86 mm apart were used to hold a cylindrical liquid column (35 mm discs were used in SL-D1 and 40 mm discs on SL-1). A top priority was to verify the results of a previous experiment performed on SL-D1, and because an equivalent Bond number Bo=0.007 was deduced from this experiment and there was no reason to expect a different behaviour, it was planned, in a second run to make use of unequal discs of 30 mm and 28 mm in a second run to precisely counterbalance the expected deformation and better quantify this effect. Procedures: The actual procedures executed were: -- Run 1: background sensing, disc oscillation at 0.40 Hz, 0.41 Hz, 0.42 Hz and again 0.42 Hz. -- Run 2: background sensing and disc separation until breakage of the column. -- Run 3: background sensing. Results: An example of free oscillations of a liquid column (diameter 30 mm, length 85 mm, volume 60 cc), due to g-jitter, is shown in Video1, recorded during the background sensing phase of Run 2. Video2 shows the breakage of the same column caused by disc separation at constant volume. This experiment enabled to accurately measure the response of the 85 mm-long cylindrical liquid column to a forced axial vibration of one of the supporting discs, and found that it is in very good agreement with theory, and complements other measurements performed in the same flight but with shorter columns by D. Langbein. An achievement is the high accuracy reached in automatic image analysis, of the order of 30 microns in object size (0.1 pixels in the 512*512 image), which represents a great improvement in comparison to the manually digitised hard-prints of previous flights. The more puzzling question left after the experiment is the lack of reproducibility of the steady averaged deformation measurement, perhaps because it is not a characteristic of the configuration and may be dependent on details of hardware (e.g. materials used, rounding of wetted corners) that escape control of the experimenter and are different for each campaign. As usual, more experiments are needed to elucidate the unexpected results of this one, but a clear progress in the overall experiment planning is evident
Informe sobre calidad de las revistas en el área de Comunicación. Versión 2015
No full textEl objetivo de este informe es establecer un listado de las revistas más valoradas en los diferentes sistemas de evaluación de calidad, nacionales e internacionales. Se trata de comparar los grupos de revistas que obtienen las máximas puntuaciones en cada uno de ellos para establecer los títulos coincidentes. Aunque el resultado puede dejar fuera revistas importantes consideradas individualmente, el consenso refuerza la valoración positiva del grupo resultante. Este sistema entraña no obstante algunas dificultades, por lo que hay que tomarlo sólo como un análisis aproximativo que puede ayudar al investigador tanto a la hora de publicar como en el momento de la valoración en los diferentes procesos oficiales de acreditación y evaluación
Transient Stability Constrained Optimal Power Flow GAMS model generator on Python
No full textTransient Stability Constrained Optimal Power Flow (TSCOPF) is a nonlinear optimization problem used to perform economic dispatches while ensuring transient stability. This paper proposes a multi-contingency TSCOPF model that retains the dynamics of all generators and includes a transient synchronous generator dq-axis model. Program write_tscopf.py automatically reads the system data from standard PSSE raw files, builds the TSCOPF model tscopf.gms on high-level modelling system GAMS and solves it using a non-heuristic Interior Point algorithm. This approach facilitates the application of the model to a variety of systems and scenarios. Data for the New England 39 Bus System and the IEEE 118 Bus system are included
Prices and real wages in seventeenth-century Madrid
No full textDatos de investigación generados por José Ignacio Andrés Ucendo (Universidad del País Vasco) y Ramón Lanza García (Universidad Autónoma de Madrid) y utilizados en la elaboración del artículo "Prices and real wages in seventeeth-century in Madrid" que se ha publicado en la revista Economic Historic Review 67.3 (2014): 607-62