Las guerras del siglo XX

Este dosier complementa la obra ‘El lugar de las mujeres en la historia’ y ha sido elaborado por el mismo equipo investigador. Con idéntica articulación por capítulos, las propuestas de trabajo, eminentemente prácticas, se han pensado para incitar a la reflexión –tanto en las aulas como fuera de ellas– acerca de los diversos itinerarios de la historia de las mujeres. Fragmentos de obra escrita, imágenes y propuestas de actividades conforman una guía para que quien lea la obra amplíe sus saberes para obtener un conocimiento claro y provechoso, una visión más veraz y completa de nuestra historia, una historia de hombres y mujeres, de lo que fuimos y de lo que somos. Isabel Morant, Rosa Ríos y Rafael Valls, con una larga y consolidada trayectoria docente e investigadora, han dirigido y coordinado la obra, escrita por una amplia nómina de docentes de todos los niveles educativos

Estudio del impacto del estrés de combate en el tiro

Poco se ha estudiado hasta ahora sobre el estrés de combate y sus efectos. Por ello este proyecto pretende arrojar un poco de luz sobre este aspecto y, más en concreto, sobre los efectos que este tipo de estrés produce en la precisión de un soldado de infantería durante un combate a corta distancia. Para lograr este objetivo, este trabajo presenta un estudio aplicado de cómo el estrés afecta al tiro en esas circunstancias. Este ha sido realizado en las instalaciones de la Brigada de Infantería Mecanizada “Guzmán el Bueno” X y en él ha participado personal de dicha brigada. A su vez, se han tenido en cuenta las opiniones de sus cuadros de mando con experiencia en operaciones.<br /

Proteomic Identification of Potential Target Proteins of Cathepsin W for Its Development as a Drug Target for Influenza

Influenza A virus (IAV) coopts numerous host factors for efficient replication. The cysteine protease cathepsin W (CTSW) has been identified as one host factor required for IAV entry, specifically for the escape of IAVs from late endosomes. However, the substrate specificity of CTSW and the proviral mechanism are thus far unknown. Here, we show that intracellular but not secreted CTSW promotes viral entry. We reveal 79 potential direct and 31 potential indirect cellular target proteins of CTSW using the high-throughput proteomic approach terminal amine isotopic labeling of substrates (TAILS) and determine the cleavage motif shared by the substrates of CTSW. Subsequent integration with data from RNA interference (RNAi) screens for IAV host factors uncovers first insights into the proviral function of CTSW. Notably, CTSW-deficient mice display a 25% increase in survival and a delay in mortality compared to wild-type mice upon IAV infection. Altogether, these findings support the development of drugs targeting CTSW as novel host-directed antiviral therapies. IMPORTANCE Influenza viruses are respiratory pathogens and pose a constant threat to human health. Although antiviral drugs are available for influenza, the emergence and spread of drug-resistant viruses is cause for concern. Therefore, the development of new antivirals with lower chances of their target viruses acquiring resistance is urgently needed to reduce the high morbidity and mortality caused by influenza. Promising alternatives to drugs targeting viral proteins are those directed against host factors required for viral replication. The cysteine protease cathepsin W (CTSW) is an important host factor for IAV replication, and its proteolytic activity is required for fusion of viral and endosomal membranes. In this work, we identify a number of hitherto unknown CTSW substrates, providing new insights into virus-host interactions, and reveal that CTSW might also play a proviral role in an in vivo model. These results support the development of CTSW as a drug target for next-generation antivirals against influenza

Proteomic identification of potential target proteins of cathepsin W for its development as a drug target for influenza

Influenza A virus (IAV) coopts numerous host factors for efficient replication. The cysteine protease cathepsin W (CTSW) has been identified as one host factor required for IAV entry, specifically for the escape of IAVs from late endosomes. However, the substrate specificity of CTSW and the proviral mechanism are thus far unknown. Here, we show that intracellular but not secreted CTSW promotes viral entry. We reveal 79 potential direct and 31 potential indirect cellular target proteins of CTSW using the high-throughput proteomic approach terminal amine isotopic labeling of substrates (TAILS) and determine the cleavage motif shared by the substrates of CTSW. Subsequent integration with data from RNA interference (RNAi) screens for IAV host factors uncovers first insights into the proviral function of CTSW. Notably, CTSW-deficient mice display a 25% increase in survival and a delay in mortality compared to wild-type mice upon IAV infection. Altogether, these findings support the development of drugs targeting CTSW as novel host-directed antiviral therapies

Examining Topoisomers of a Snake-Venom-Derived Peptide for Improved Antimicrobial and Antitumoral Properties

Ctn[15-34], the C-terminal section of crotalicidin (Ctn), a cathelicidin from a South American pit viper, is an antimicrobial and antitumoral peptide with remarkably longer stability in human serum than the parent Ctn. In this work, a set of topoisomers of both Ctn and Ctn[15-34], including the retro, enantio, and retroenantio versions, were synthesized and tested to investigate the structural requirements for activity. All topoisomers were as active as the cognate sequences against Gram-negative bacteria and tumor cells while slightly more toxic towards normal cells. More importantly, the enhanced serum stability of the D-amino-acid-containing versions suggests that such topoisomers must be preferentially considered as future antimicrobial and anticancer peptide leads

Control of DC/DC Buck–Parallel Converter Implemented in FPGA

[ES] El presente artículo documenta el diseño e implementación de un controlador robusto para el convertidor CD/CD Reductor–Paralelo, bajo la perspectiva de la planitud diferencial y la técnica del control por rechazo activo de perturbaciones basado en un observador GPI. Los objetivos principales del controlador propuesto son: regular la tensión de salida y equilibrar las corrientes de los convertidores en paralelo. Para el modelado de la arquitectura hardware de este controlador se utiliza una herramienta con alto nivel de abstracción de hardware y se implementa en un FPGA Artix–7 de la compañía Xilinx. Finalmente, se muestran resultados experimentales del desempeño del controlador, cuando se somete al convertidor a diversas perturbaciones externas, desconocidas y variantes con el tiempo, y a cambios en los parámetros del mismo.[EN] This paper documents the design and implementation of a controller for DC/DC Buck–Parallel Converter under the perspective of differential flatness and active disturbance rejection control approach based on GPI extended state observer. The main objectives of the proposed controller are to regulate the output voltage and a balance of currents for parallel converters. The hardware architecture of this controller was modelled using tools with a high level of hardware abstraction and implemented in a FPGA Artix-7 of the Xilinx Company. Finally, the performance of the proposed controller is shown through a series of experiments that consisted of subjecting the converter to various external, unknown and variant over time disturbances, and changes in system parameters.Guerrero Ramírez, EO.; Martínez Barbosa, A.; Guzmán Ramírez, E.; Linares Flores, J.; Sira Ramírez, H. (2018). Control del Convertidor CD/CD Reductor–Paralelo Implementado en FPGA. Revista Iberoamericana de Automática e Informática industrial. 15(3):309-316. https://doi.org/10.4995/riai.2018.8925OJS309316153Alvarez, J., Lago, A., Nogueiras, A., Martínez, P., Marcos, J., Doval, J. y López, O. 2006, FPGA implementation of a fuzzy controller for automobile DC-DC converters. IEEE International Conference, 237-240.Cid-Pastor, A., Martìnez-Salamero, L., Alonso, C., Leyva, R., Singer S., 2007, Paralleling DC-DC switching converters by means of power gyrators, IEEE transactions on power electronics, no. 6, vol. 22, 2444-2453.Jaber, A., Qahouq, A., y Huang, L., 2008, N-phase sensorless current sharing digital controller, Power Electronics Specialist Conference, 1257-1262.Kailath, T., 1980, Linear Systems, Prentice-Hall Information.Lévine, J., Analysis and Control of Nonlinear Systems: A Flatness-based Approach, Springer Science & Business Media.Li, S., Yang, J., Chen, W.-H., Chen, X., 2014, Disturbance Observer-Based Control: Methods and Applications, CRC Press Taylor Francis.Linares-Flores, J., Barahona-Avalos, J.L., Sira-Ramírez, H. y Contreras-Ordaz, M.A., 2012, Robust Passivity-Based Control of a Buck-Boost-Converter/DC-Motor System: An Active Disturbance Rejection Approach, IEEE Transactions on Industry Applications, no. 6, vol. 48, 2362-2371.Qiao, L. y Jie, W., 2005, Implementation of a New Nonlinear Controller for DC-DC Converter Using Matlab and DSPACE DSP, IEEE ISIE, Dubrovnik, Croacia, 621-626.Sarvi, M., Derakhshan, M., Sedighizadeh, M., 2014, A new intelligent controller for parallel DC/DC converters, International Journal of Engineering, no. 1, vol. 27, 131-142.Shrud, M. A., Kharaz, A. H., Ashur, A. S. y Benamar, M., 2010, Analysis and simulation of automotive interleaved buck converter, World Academy of Science, Engineering and Technology, no. 3, vol. 4, 10-17.Shui-Chun, L. y Chin-Chin, T., 2004, Adaptive voltage regulation and equal current distribution of parallel-buck DC-DC converters using backstepping sliding mode control, 30th IEEE IECON, 1018-1023.Sira-Ramírez, H. y Agrawal, S. K., 2004, Diferentially Flat Systems, Marcel Dekker Inc.Sira-Ramírez, H., Linares-Flores, J., Luviano-Juárez, A. y Cortés-Romero, J., 2015, Ultramodelos Globales y el Control por Rechazo Activo de Perturbaciones en Sistemas No Lineales Diferencialmente Planos, RIAI, no. 2, vol. 12, 133-144.Sira-Ramírez, H., Luviano-Juárez, A. y Cortés-Romero, J., 2011, Control lineal robusto de sistemas no lineales diferencialmente planos, RIAI, no. 1, vol. 8, 14-28.Sira-Ramírez, H., Luviano-Juárez, A., Ramírez-Neria, M. y Zurita-Bustamante E. W., 2017, Active DisturbanceRejection Control of Dinamic Systems: A Flatness-Based Approach, Butterworth-Heinemann publications.Sira-Ramírez, H. y Rosales-Díaz, D., 2014, Decentralized Active Disturbance Rejection Control of Power Converters Serving a Time Varying Load, Proceedings of the 33rd Chinese Control Conference, Nanling, China, 4348-4353.Slotine, J.J.E., Li, W., 1991, Applied Nonlinear Control, Prentice-Hall.Ramos, R., Biel, D. y Fossas, E., 2011, Control en modo deslizante para un convertidor reductor multifase en entrelazado con ecualización de corriente, XVIII Seminario Anual de Automática, Electrónica Industrial e Instrumentación, 161-166

Current Incidence and risk factors of fecal incontinence after acute stroke affecting functionally independent people

Background: Previously published retrospective series show a high prevalence of fecal incontinence (FI) in stroke patients. We aimed to analyze in a prospective series the current incidence of FI in acute stroke in functionally independent patients and its evolution over time and the patient characteristics associated with the appearance of FI in acute stroke. Methods: We included consecutive patients with acute stroke admitted in our stroke unit who fulfilled the following inclusion criteria: a first episode of stroke, aged >18 years, with no previous functional dependency [modified Rankin Scale (mRS) = 2] and without previous known FI. FI was assessed by a multidisciplinary trained team using dedicated questionnaires at 72 ± 24 h (acute phase) and at 90 ± 15 days (chronic phase). Demographic, medical history, clinical and stroke features, mortality, and mRS at 7 days were collected. Results: Three hundred fifty-nine (48.3%) of 749 patients (mean age 65.9 ± 10, 64% male, 84.1% ischemic) fulfilled the inclusion criteria and were prospectively included during a 20-month period. FI was identified in 23 patients (6.4%) at 72 ± 24 h and in 7 (1.9%) at 90 days ± 15 days after stroke onset. FI was more frequent in hemorrhagic strokes (18 vs. 5%, p 0.007) and in more severe strokes [median National Institute of Health Stroke Scale (NIHSS) 18 (14–22) vs. 5 (3–13), p < 0.0001]. No differences were found regarding age, sex, vascular risk factors, or other comorbidities, or affected hemisphere. Patients with NIHSS =12 (AUC 0.81, 95% CI 0.71 to 0.89) had a 17-fold increase for the risk of FI (OR 16.9, IC 95% 4.7–60.1) adjusted for covariates.Peer ReviewedPostprint (published version

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy

Background: Lately, major advances in crucial aspects of magnetic hyperthermia (MH) therapy have been made (nanoparticle synthesis, biosafety, etc.). However, there is one key point still lacking improvement: the magnetic field-frequency product (H × f = 4.85 × 108 Am−1s−1) proposed by Atkinson–Brezovich as a limit for MH therapies. Herein, we analyze both local and systemic physiological effects of overpassing this limit. Methods: Different combinations of field frequency and intensity exceeding the Atkinson–Brezovich limit (591–920 kHz, and 10.3–18 kA/m) have been applied for 21 min to WAG/RijHsd male rats, randomly distributed to groups of 12 animals; half of them were sacrificed after 12 h, and the others 10 days later. Biochemical serum analyses were performed to assess the general, hepatic, renal and/or pancreatic function. Results: MH raised liver temperature to 42.8 ± 0.4 °C. Although in five of the groups the exposure was relatively well tolerated, in the two of highest frequency (928 kHz) and intensity (18 kA/m), more than 50% of the animals died. A striking elevation in liver and systemic markers was observed after 12 h in the surviving animals, independently of the frequency and intensity used. Ten days later, liver markers were almost recovered in all of the animals. However, in those groups exposed to 591 kHz and 16 kA/m, and 700 kHz and 13.7 kA/m systemic markers remained altered. Conclusions: Exceeding the Atkinson–Brezovich limit up to 9.59 × 109 Am−1s−1 seems to be safe, though further research is needed to understand the impact of intensity and/or frequency on physiological conditions following MH.This research was funded by Basque Country Government (grant number IT-1005-16)

Small Cell Carcinoma of the Vagina : First Systematic Review of Case Reports and Proposal of a Management Algorithm

Literature search in PubMed and Scopus was performed using the terms "small cell carcinoma" and "vagina." English-language case reports of primary SmCCV up to January 2022 were included. Twenty-nine articles describing 44 cases met our inclusion criteria. We report a new case of our hospital. The global median overall survival (mOS) was 12.00 months (95% CI = 9.31-14.69). The mOS was not reached for stage I, and it was 12.00, 12.00, 9.00, and 8.00 months for stages II, III, IVA, and IVB, respectively (statistically significant differences between stage I and stages II, III, or IVA [log rank p =.003-.017]). Thirty-five cases received local treatments (77.8%). The mOS of patients treated with surgery ± complementary chemotherapy, radiotherapy ± complementary chemotherapy, chemoradiation ± complementary chemotherapy, and surgery + radiotherapy ± complementary chemotherapy were 11.00, 12.00, 17.00, and 29.00 months, respectively. The use of adjuvant or neoadjuvant chemotherapy (64.5%, mostly platinum + etoposide) showed longer mOS (77.00 vs 15.00 months). Four of 5 tested cases presented human papillomavirus infection, 3 of them presenting type 18. Small cell carcinoma of the vagina shows dismal prognosis. Multimodal local management plus complementary chemotherapy seems to achieve better outcomes. Human papillomavirus could be related to the development of SmCCV. A diagnostic-therapeutic algorithm is proposed

IFITM3 incorporation sensitizes influenza A virus to antibody-mediated neutralization

The disease severity of influenza is highly variable in humans, and one genetic determinant behind these differences is the IFITM3 gene. As an effector of the interferon response, IFITM3 potently blocks cytosolic entry of influenza A virus (IAV). Here, we reveal a novel level of inhibition by IFITM3 in vivo: We show that incorporation of IFITM3 into IAV particles competes with incorporation of viral hemagglutinin (HA). Decreased virion HA levels did not reduce infectivity, suggesting that high HA density on IAV virions may be an antagonistic strategy used by the virus to prevent direct inhibition. However, we found that IFITM3-mediated reduction in HA content sensitizes IAV to antibody-mediated neutralization. Mathematical modeling predicted that this effect decreases and delays peak IAV titers, and we show that, indeed, IFITM3-mediated sensitization of IAV to antibody-mediated neutralization impacts infection outcome in an in vivo mouse model. Overall, our data describe a previously unappreciated interplay between the innate effector IFITM3 and the adaptive immune response