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En 1449 se produjo en Toledo una de las rebeliones populares de mayor relevancia en la Castilla del siglo XV. Referida por todas las crónicas de la época, en ella el común de la ciudad puso en cuestión tanto la legitimidad gubernativa del rey como los mecanismos de integración en la societas christiana de los nuevos convertidos a la fe católica. Dada la trascendencia de tales hechos, el episodio siempre ha tenido un gran impacto bibliográfico, reseñándose en múltiples publicaciones. La información sobre la revuelta, aun así, suele ser iterativa, viéndose muy condicionada por una metodología con un enfoque centrado en la “cuestión conversa” y por una falta de nuevas fuentes de estudio que obstaculiza el análisis. A tenor de esto, el presente trabajo replantea el punto de vista a la hora de examinar los alborotos, insistiéndose en lo relevante de la cultura política y la opinión pública, y en su naturaleza de alzamiento en comunidad, con rasgos parecidos a los que tendría la sublevación de los comuneros. Por otro lado, se aportan informaciones inéditas que dan frescura al relato de los hechos y que permiten una aproximación más inmediata a lo ocurrido. Y, por último, se abre una vía de estudio sin explorar, la de la participación en los altercados de las villas y aldeas del entorno de Toledo, que rompe con la imagen eminentemente urbana que ha venido ofreciéndose de la sublevación y que multiplica las posibilidades de acercamiento a los disturbios, pasando de lo urbano a lo territorial. In 1449, one of the most relevant popular revolts in Castile took place in Toledo. Referred to in all chronicles, people of the city questioned both the governmental legitimacy of the king and the mechanisms for integration into societas christiana of new converts to Catholic faith. Due to the relevant transcendence of this historical episode, it has had a notorious bibliographical impact and has been described in many publications. However, information on the urban revolt tends to be iterative and it is highly conditioned by a methodology focused on the “cuestión conversa”. In addition, the lack of documentation hampers the analyses. With these problems as background, this paper reconsiders views on the Toledo riots and compares them with the comuneros´ rebellion, drawing attention to political culture and public opinion. Otherwise, unpublished documentation examined offers freshness in account of the events and allows us a more immediate approach to revolt. This paper breaks with the preponderantly urban image of conflict that historians have traditionally offered and transcends from urban to territorial. In this way, it is opened an unexplored line of research about participation in uprising of villages near Toledo that multiplies possibilities of approaching what happened in 1449. Este trabajo forma parte de los resultados del proyecto de investigación «Ciudad, economía y territorio en Castilla-La Mancha durante la Baja Edad Media», referencia SBPLY/19/180501/000187 (años 2020-2023), financiado por la Junta de Comunidades de Castilla-La Mancha.

There is evidence of synergy between radiotherapy and immunotherapy. Radiotherapy can increase liberation of tumor antigens, causing activation of antitumor T-cells. This effect can be boosted with immunotherapy. Radioimmunotherapy has potential to increase tumor control rates. Biomathematical models of response to radioimmunotherapy may help on understanding of the mechanisms affecting response, and assist clinicians on the design of optimal treatment strategies. In this work we present a biomathematical model of tumor response to radioimmunotherapy. The model uses the linear-quadratic response of tumor cells to radiation (or variation of it), and builds on previous developments to include the radiation-induced immune effect. We have focused this study on the combined effect of radiotherapy and PDL1/CTLA4 therapies. The model can fit preclinical data of volume dynamics and control obtained with different dose fractionations and PDL1/CTLA4. A biomathematical study of optimal combination strategies suggests that a good understanding of the involved biological delays, the biokinetics of the immunotherapy drug, and the interplay between them, may be of paramount importance to design optimal radioimmunotherapy schedules. Biomathematical models like the one we present can help to interpret experimental data on the synergy between radiotherapy and immunotherapy, and to assist in the design of more effective treatments.

This systematic review aims to summarize the effects of wearing different types of wetsuits and swimsuits in front crawl swimming performance and physiological- and biomechanical-related variables. The Web of Science, PubMed, Scopus and the Proceedings of the International Symposium on Biomechanics and Medicine in Swimming databases were searched from inception to 25th March 2022. From the 1398 studies initially found, 26 studies were included in the review. The quality assessment and inter-rater reliability between researchers were conducted. The full body was the most studied wetsuit, with its use allowing 3.2–12.9% velocity increments in distances ranging from 25 to 1500 m, in incremental tests, in 5 and 30 min continuous swimming and in open water events. The sleeveless long vs. the full-body wetsuit led to a 400–800 m performance enhancement. Higher stroke rate, stroke length and stroke index were observed while using three different covered body part wetsuits vs. a regular swimsuit, with a lower energy cost being observed when swimming with the full-body wetsuit compared to a swimsuit. These findings provide useful information for coaches, swimmers and triathletes about the full-body and sleeveless long/short wetsuit use, since these three wetsuits allow improving swimming performance in different distances in diverse aquatic environments.

The copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) moiety held together via linkers of variable lengths containing a 1,2,3-triazole ring and 3, 4, or 7 CH2 groups. The heterodimers were tested as inhibitors of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The enantiomeric heterodimers with the longest linkers exhibited the highest inhibition potencies for AChE (IC50 = 9.7 nM and 11 nM) and BuChE (IC50 = 8.1 nM and 9.1 nM). AChE exhibited the highest enantioselectivity (ca. 4-fold). The enantiomeric pairs of the heterodimers were found to be inactive (GI50 > 100 µM), or to have weak antiproliferative properties (GI50 = 84–97 µM) against a panel of human cancer cells.

Our aim was to establish the determinants explaining the wetsuit advantages in middle-distance swimming efforts. Thirty-one triathletes and open water swimmers performed two 400 m front crawl bouts in a 25 m swimming pool with swim and wetsuits (with 48 h rest in-between). Anthropometric, kinematic and physiological variables were measured and Pearson correlation coefficients and stepwise linear regression analysis were used to determine their relationships. Associations observed in the 400 m front crawl included time improved using wetsuit with swimmers age (r=0.38; p=0.017), cross-sectional area (r=0.33; p=0.034), wetsuit upper limbs thickness (r=–0.49; p=0.010), ΔInternational Swimming Federation Points (r=–0.39;p=0.016), Δstroke rate (SR, r=0.48; p=0.003), Δstroke length (SL, r=-0.39; p=0.015), Δpropelling efficiency (r=–0.37; p=0.019) and Δblood lactate concentrations (r=0.30; p=0.048) in the total sample. In females, associations were found between the time improved and wetsuit upper and lower limbs thickness (both r=–0.78; p=0.011), and in males associations were found between time improved and age (r=0.43; p=0.030), ΔSR (r=0.56; p=0.005) and ΔSL (r=–0.44; p=0.026). Furthermore, 48% of the 400 m front crawl time improved was explained by wetsuit upper limbs thickness and SR changes (total sample), 62% explained by the wetsuit lower limbs thickness (females) and 48% of this enhancement was related to age and SR changes (males). Therefore, faster upper and lower limbs actions and wetsuit upper and lower limbs thickness are beneficial for 400 m front crawl performance improvement.

Purpose: To assess changes in swimming performance, anthropometrics, kinematics, energetics, and strength after 5-week training cessation. Methods: Twenty-one trained and highly trained swimmers (13 males: 17.4 [3.1] y; 50-m front crawl 463 [77] FINA points; 8 females: 16.7 [1.7] y; 50-m front crawl 535 [48] FINA points) performed a 50-m front-crawl all-out swim test, dryland and pool-based strength tests, and 10-, 15-, 20-, and 25-m front-crawl all-out efforts for anaerobic critical velocity assessment before and after a 5-week training cessation. Heart rate and oxygen uptake () were continuously measured before and after the 50-m swim test (off-kinetics). Results: Performance was impaired 1.9% (0.54 s) for males (P = .007, d = 0.91) and 2.9% (0.89 s) for females (P = .033, d = 0.93). Neither the anthropometrical changes (males: r2 = .516, P = .077; females: r2 = .096, P = .930) nor the physical activities that each participant performed during the off-season (males: r2 = .060, P = .900; females: r2 = .250, P = .734) attenuated performance impairments. Stroke rate and clean swimming speed decreased (P P > .05). Blood lactate concentrations remained similar (P > .05), but peak decreased in females (P = .04, d = 0.85). Both sexes showed higher heart rate before and after the 50-m swim test after 5 weeks (P P = .035, d = 0.65). Lower in-water force during tethered swimming at zero speed was observed in males (P = .033, d = 0.69). Regarding dryland strength, lower-body impairments were observed for males, while females showed upper-body impairments (P Conclusions: A 5-week training cessation yielded higher heart rate in the 50-m front crawl, anaerobic pathways, and dryland strength impairments. Coaches should find alternatives to minimize detraining effects during the off-season.

Alzheimer's disease (AD) constitutes one of the most devastating diseases, with an extraordinarily high increase expected for the next few years. Despite the numerous efforts so far, there is still no cure but just palliative treatments.The main topic covered herein has been the development of butyrylcholinesterase (BuChE) inhibitors with the aim of increasing the levels of the neurotransmitter acetylcholine (ACh). Two main groups of compounds have been considered: multitarget and non-multitarget ligands, depending on whether the structural design is focused or not on other key targets and pathogenic factors of the disease. Seventeen patents regarding multitarget-directed ligands (MTDLs), twelve for non-multitarget derivatives, and three for miscellaneous use have been covered in the period 2018-2021.BuChE is an attractive target in the treatment of AD. It is the most prevalent cholinesterase within more advanced stages of the disease, so drugs inhibiting it would be suitable for the treatment of mid- to severe Alzheimer's patients. Moreover, BuChE has been proved to be connected with some other key hallmarks of the disease, like amyloidogenesis; hybridization of a BuChE-targeting pharmacophore with other scaffolds designed for other therapeutic targets is quite a promising design for potential anti-Alzheimer's drugs.

En la sentencia analizada se resuelve si, ante la ausencia de repetición en el recurso de suplicación de la reclamación de indemnización por daños morales derivados de la vulneración de derecho fundamental ya contenida en la demanda, la Sala del TSJ debe pronunciarse -pues no lo hace en este caso- sobre tal cuestión accesoria cuando estima por primera vez en sentencia de suplicación la petición principal de extinción del contrato por voluntad del trabajador al amparo del art. 50 ET, en caso de concurrir un grave incumplimiento por parte de la empresa vulnerador de la garantía de indemnidad por otras reclamaciones judiciales anteriores del trabajador. La sentencia de la Sala IV despeja la cuestión admitiendo la petición de incongruencia omisiva contenida en el recurso de casación para unificación de doctrina, de manera que, declarado como conculcado un derecho fundamental, se debe fijar el importe del daño moral por aplicación del art. 183 LRJS o, cuando menos, un pronunciamiento respecto de la misma, aun cuando no se haya reiterado tal exigencia en el recurso de suplicación. The judgment under consideration determines whether, in the absence of a repetition in the application for compensation for moral damages arising from the infringement of fundamental rights already contained in the claim, the Supreme Court of Justice must rule -since it does not do so in this case- on such an accessory question when it considers for the first time in the appeal judgment the main request for termination of the contract by will of the worker under Art. 50 ET (Statute of Workers) ,in the case of a serious breach by the company violating the guarantee of indemnity for other previous legal claims of the worker. The judgment of Chamber IV clears the matter by accepting the request for omission contained in the appeal for unification of doctrine, so that, declared as violated a fundamental right, the amount of moral damage has to be set by application of art. 183 LRJS or, at least, a ruling thereon, even if no such requirement has been reiterated in the application.

El presente estudio reúne un grupo de cuentas de collar oculadas halladas en la región suroeste de la Meseta Norte, fechadas en su mayoría a partir de mediados de la Edad del Hierro (ss. V-IV a.C.). Se trata tanto de viejas y conocidas piezas, como de nuevas e inéditas, con la intención de analizarlas en conjunto para saber cómo, cuándo y por dónde llegaron a los distintos yacimientos prehistóricos de las actuales provincias de Salamanca y Ávila. Para ello, se ha establecido una comparación con otras cuentas oculadas halladas en asentamientos de la Península Ibérica y las Islas Baleares, extrayendo algunas conclusiones sobre la importación de materiales, el intercambio entre comunidades y la herencia de la influencia mediterránea en la zona.

In the last decade, our group has been very active at developing and assaying complex libraries of scaffolds with a focus on their potential to identify bioactive drug candidates for neurodegenerative diseases, particularly Alzheimer’s disease (AD). Attention has been focused on isatin-based oxindole scaffolds, for which promising results concerning butyrylcholinesterase (BuChE) inhibitory activity have previously been obtained. Considering some published reports and detailed analysis of the pharmacophores of commercially available drugs for AD (powerful cholinesterase (ChE) inhibitors), we performed a strategic structural modification of the isatin core and generated a new family of isatin-based oxindole hybrids (27 new compounds) possessing crucial key functional units in their framework. The syntheses were accomplished using multiple approaches, including simple N-alkylation reactions, copper-catalyzed amination reactions, and click chemistry. The resulting library was evaluated on ChE and MAO enzymes, both of which are involved in the pathophysiology of neurodegeneration. IC50 values of 1.6 and 2.6 μM (BuChE assays), were achieved for the best inhibitors.

A partir de documentación de archivo en gran parte inédita, en este trabajo se reflexiona sobre la problemática existente en torno a las distintasvaloraciones del perdón del rey al gran noble, y se analizan sus cláusulas y condicionantes, partiendo del hecho de que en la Castilla bajomedieval laalta nobleza era un grupo con una idiosincrasia muy específica, dado su enorme poderío político y económico, que le permitía incluso sostener a ejércitos privados.

Extended presentation of the FEM solver, capillary model, pimo diffusion, and sensitivity analysis

There is increasing evidence that high doses of radiotherapy, like those delivered in stereotactic body radiotherapy (SBRT), trigger indirect mechanisms of cell death. Such effect seems to be two-fold. High doses may trigger an immune response and may cause vascular damage, leading to cell starvation and death. Development of mathematical response models, including indirect death, may help clinicians to design SBRT optimal schedules. Despite increasing experimental literature on indirect tumor cell death caused by vascular damage, efforts on modeling this effect have been limited. In this work, we present a biomathematical model of this effect. In our model, tumor oxygenation is obtained by solving the reaction–diffusion equation; radiotherapy kills tumor cells according to the linear–quadratic model, and also endothelial cells (EC), which can trigger loss of functionality of capillaries. Capillary death will affect tumor oxygenation, driving nearby tumor cells into severe hypoxia. Capillaries can recover functionality due to EC proliferation. Tumor cells entering a predetermined severe hypoxia status die according to a hypoxia-death model. This model fits recently published experimental data showing the effect of vascular damage on surviving fractions. It fits surviving fraction curves and qualitatively reproduces experimental values of percentages of functional capillaries 48 hours postirradiation, and hypoxic cells pre- and 48 hours postirradiation. This model is useful for exploring aspects of tumor and EC response to radiotherapy and constitutes a stepping stone toward modeling indirect tumor cell death caused by vascular damage and accounting for this effect during SBRT planning.Significance:A novel biomathematical model of indirect tumor cell death caused by vascular radiation damage could potentially help clinicians interpret experimental data and design better radiotherapy schedules.

Selecting the best resin tapping method and stimulant paste in the resin tapping process is crucial. In timber-oriented rainy Atlantic pine forests of north-west Spain, the interest in resin tapping is raising but information on the best tapping methods and pastes is still lacking. In this study, an appropriate experimental design used on five representative plots of Pinus pinaster, allowed us to explore the resin productive differences between two tapping methods (traditional Spanish method and circular groove) and three stimulant treatments (control, Ethephon and ASACIF). The use of a standardized measure of resin yield allowed to adequately compare methods differing in groove length. Results indicated that the standard resin yield was 1.43 times greater with the traditional method than with the circular groove method. The two stimulant pastes drastically increased resin yield (up to 6 fold) in all sites and for all tapping methods. The effectiveness of the paste was also influenced by the tapping method, obtaining greater increases in resin yield after the application of stimulant paste in trees with the circular groove method. Resin yield was only slightly related to the dasometric variables and varied among test sites when no pastes were used, but differences among sites disappeared when stimulant pastes were used. Our results contribute to the understanding of the factors involved in resin performance and the technological development of the sector.

Trabajadora interpone demanda contra el despido disciplinario decidido por su empleadora y solicita la nulidad de la decisión extintiva, alegando la concurrencia de discriminación por considerar que la empresa acuerda el despido tras causar baja la demandante. Subsidiariamente, se reclama la improcedencia del despido. La sentencia dictada por el Juzgado de lo Social nº 1 de Gijón, interpretando la Ley 15/2022, de 12 de julio, declara la nulidad del despido y razona que no es necesaria la anterior equiparación entre enfermedad y discapacidad, sino que la discriminación por enfermedad constituye un motivo de nulidad autónomo. A worker files a lawsuit against the disciplinary dismissal decided by her employer and requests the nullity of the decision to dismiss on the grounds of discrimination, considering that the company agrees to fire her after her medical discharge. In the alternative, the dismissal is claimed to be inadmissible. The judgment handed down by the Social Court No 1 of Gijón, interpreting Law 15/2022 of 12 July, declares the dismissal null and void and states that the previous equality between illness and disability is not necessary, but discrimination on grounds of illness is a self-standing ground of nullity.

Don Pedro Girón, maestre de la Orden de Calatrava entre 1445 y 1466, fue uno de los personajes más controvertidos de la Castilla del siglo XV, tanto por su supuesta actitud despiadada, como, sobre todo, por seguir los pasos de su hermano, el sibilino marqués de Villena, don Juan Pacheco. En este trabajo se analizan las repercusiones que tuvo una de las mandas que el maestre dejó instituidas en su testamento, en la que requería que, en su nombre, por el bien de su alma y en exoneración de su conciencia, se indemnizase a las víctimas de sus robos y sus abusos de poder. Su hijo y heredero, Juan Téllez Girón, el segundo conde de Urueña, hubo de afrontar durante décadas la obligación de resarcimiento que su padre había establecido, hasta que, definitivamente, decidió requerir la ayuda de uno de los grandes juristas al servicio del papa, Giovanni Battista Caccialupi, que le ofreció una solución legal y teológica, que, por fin, le permitiría librarse del desagravio requerido.

Competitive progressions are necessary to ensure that peak performance occurs when medals are decided. This study aimed to: i) study the coefficient of variation (CV) and performance changes (%Δ) among swimmers who participated in different rounds (i.e., heats, semi-finals and finals); ii) study the CV changes as a function of FINA-points. A total of 1447 performances were analysed in the 100 and 200 m-races during the Budapest 2021 European-Championships. Linear mixedeffects models were applied for total and split-times to obtain intraathlete CV and %Δ. The FINA-points were studied with two-way ANOVA and Pearson’s correlation assessed the relations with CV. The CV in 100 m-races was: 0.48 ± 0.21% for males and 0.50 ± 0.20% for females (Δ = −0.66%); in 200 m-races: 0.63 ± 0.36% and 0.60 ± 0.34% (Δ = −0.82%). There were differences in FINA-points between strokes and distances (p < 0.02) associated with higher CV for the 200 m-races (r = 0.37; p = 0.003), indicating changes in performance over the rounds. Swimmers’ finalists performed easier during the heats by going slower in the first 50 m-lap; however, some of them would have little chance of qualifying during major championships because some events were below FINA-points world-standards., This study was supported by grants awarded by the Ministry of Science, Innovation and Universities (Spanish Agency of Research) and the European Regional Development Fund (ERDF): [PGC2018-102116-B-I00] ‘SWIM II: Specific Water Innovative Measurements: Applied to the performance improvement’ and the Spanish Ministry of Education, Culture and Sport: FPU17/02761, FPU16/02629 and FPU19/02477 grants.

La formación docente y el uso de la tecnología en la práctica pedagógica, son una imperiosa necesidad requerida por las circunstancias que vive el mundo; la formación docente debe ser permanente, rigurosa, versátil y a tono con los cambios que la tecnología provee. El objetivo es, analizar el avance de la producción científica sobre la plataforma Moodle en la formación de docentes en servicio durante el periodo del 2011 al 2020, es una revisión sistemática y de análisis bibliométrico, se ha realizado la búsqueda de documentos en las bases de datos Scopus, ESBCOhost, Educational Resource Information Center (ERIC), SciencieDirect y Bielefeld Academic Search Engine (BASE), utilizando los operadores booleanos AND y OR, para la selección de artículos se ha usado la técnica prisma, obteniendo 26 artículos como muestra. Del análisis de los artículos se puede considerar que la formación a través de la plataforma Moodle, es un campo fértil para generar programas de formación continua a los docentes en servicio. En conclusión, se puede aseverar que el uso apropiado de la plataforma Moodle en los sistemas educativos es una alternativa a la educación presencial.

19 Pág. Centro de Investigación en Sanidad Animal (CISA), Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78-0.90) and neurological controls (AUC = 0.73-0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer's disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring., We thank the HUB-ICO-IDIBELL-Biobank and the CERCA Programme of the Generalitat de Catalunya for institutional support. This study was funded by the Instituto Carlos III (Grants Number CP16/00041 and PI19/00144) to FL. This project was also funded by la Fundació La Marató de TV3 (Grants No. 201821-30, 201821-31and 201821-32 to FL, JCE and EV, respectively) and by the Fondo Europeo de Desarrollo Regional (FEDER) through the Interreg V-A España-Francia-Andorra (POCTEFA 2014–2020) programme (at 65%) to IF. AVP is supported by the Beatriu de Pinós programme (2018-BP-00129) from the Ministry of Business and nowledge of the Government of Catalonia, and cofunded by the EU Horizon 2020 programme under an MSCA grant agreement (801370). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and the UK Dementia Research Institute at UCL. KB is supported by the Swedish Research Council (#2017-00915), the Swedish State Support for Clinical Research (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and the European Union Joint Programme for Neurodegenerative Disorders (JPND2019-466-236). AL is supported by the Ministero della Salute, Italy, for the national surveillance of Creutzfeldt-Jakob disease. This research was also supported in part by the Alberta Synergies in Alzheimer’s and Related Disorders (SynAD) programme which is funded by the Alzheimer Society of Alberta and Northwest Territories through their Hope for Tomorrow programme and the University Hospital Foundation. SynAD operates in partnership with the Neuroscience and Mental Health Institute at the University of Alberta. JADR was supported by grants from the Spanish Ministry of Science, Innovation and Universities (MICINN/FEDER) (RTI2018-099773-B-I00), the CERCA Programme, and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (SGR2017-648) and CIBERNED (CMED2018-2)

espanolA pesar de la importancia que la historiografia espanola ha dado en los ultimos anos a la cultura politica vigente en la Castilla del otono el Medievo, la retorica y el lexico de la paz han quedado fuera de los analisis por diversas cuestiones que se matizan en el presente trabajo, en el cual, de la misma manera, se reflexiona sobre como se configuraba el discurso de la pacificacion, que formulas lo definian, cuales eran los motivos por los que se recurria a su uso, y, en fin, en que parametros debe concebirse la retorica de la paz, atendiendo a la dialectica desarrollada en la Castilla de los siglos XIV y XV entre los reyes, la nobleza y las ciudades, en la que las Cortes jugaron un papel definitorio. EnglishThe present article reflects on the reasons why the rhetoric and lexicon of peace have been largely neglected by Spanish historiography, despite the strong historiographical focus on the political culture of Castile in the late Middle Ages. It explains the mechanisms of the discourse of peace as well as the reasons for its use. Finally, it proposes which parameters should be employed for analysing the peacemaking rhetoric, taking into account the dialectic between kings, cities and nobility in the fourteenth and fifteenth centuries, when the Courts played a defining role.

In swimming, the beneficial effects of the in-water warm-up are often undermined by the long transition periods before competition (≥ 20 min). For that reason, studies comparing the effects of in-water warm-ups followed by dryland activities have been conducted in the swimming literature. This has brought conflicting evidence due to large combinations of supervised and unsupervised warm-up procedures used. Therefore, a scoping review was performed to discuss (1) why warm-up strategies are important for competitive swimming; to identify (2) what are the different warm-up approaches available in the literature, and; to establish (3) what are the main conclusions, considerations and gaps that should be addressed in further research to provide clearer guidance for interventions. The search was conducted on PubMed, Web of Science, Scopus, and SPORTDiscus databases. To be considered eligible, studies must have assessed acute short-term responses of warm-up procedures in swimmers by using randomized controlled trials or pre-post study designs. A total of 42 articles were included in this review. The effectiveness of warm-up responses was evaluated based on the inclusion or not of warm-up, the type of conditioning activity (in-water exercise, inwater exercise combined with dryland or dryland exercise only), its duration, and intensity. (1) Warm-up mechanisms have been mainly related to temperature changes associated to cardiovascular adaptations and short-term specific neuromuscular adaptations. Thus, maintaining muscle activity and body temperature during the transition phase immediately prior to competition could help swimmers’ performance; (2) the most common approach before a race usually included a moderate mileage of in-water warm-up (~ 1000 m) performed at an intensity of ≤ 60% of the maximal oxygen consumption, followed by dryland protocols to keep the muscle activity and body temperature raised during the transition phase. Dryland activities could only optimize performance in sprint swimming if performed after the in-water warm-up, especially if heated clothing elements are worn. Using tethered swimming and hand-paddles during warm-ups does not provide superior muscular responses to those achieved by traditional in-water warm-ups, possibly because of acute alterations in swimming technique. In contrast, semi-tethered resisted swimming may be considered as an appropriate stimulus to generate post-activation performance enhancements; (3) nothing has yet been investigated in backstroke, butterfly or individual medley, and there is a paucity of research on the effects of experimental warm-ups over distances greater than 100 m. Women are very under-represented in warm-up research, which prevents conclusions about possible sex-regulated effects on specific responses to the warm-up procedures., Agencia de Innovacion y Desarrollo de Andalucia, European Commission, SWIM FOR LIFE B-SEJ-164-UGR20, Spanish Government FPU17/02761 FPU19/02477

The United States Department of Agriculture (USDA) system has five retail cut yield (RCY) classes, whereas the former Canadian system had three total lean yield (TLY) classes. A total of 720 beef carcasses were used to develop a modified grade ruler, harmonizing the Canadian grades into five classes. Beef carcasses (n = 750) from three Canadian federally inspected facilities were graded using both USDA and Canadian (harmonized ruler) systems for external validation. Agreement between the USDA-RCY and the Canadian TLY was high (R2 = 0.80). The validation between the harmonized ruler and the USDA-RCY showed a standard deviation of the difference of 1.32 and a coefficient of concordance of 0.83.

This paper is devoted to solve the steady monoenergetic Fokker-Planck equation in the 1D slab when the incoming fluxes and the source term are allowed to depend on the azimuth θ. The problem is spl...

By far, the standard implementation of finite difference schemes for forward–backward partial differential equations consists in employing an iterative method. This paper collects a series of numerical results which demonstrate that a direct implementation can reduce the computing time. An effective way of choosing the seed for the iterative method naturally arises.

Este trabajo ha obtenido un accésit del Premio «Estudios Financieros» 2020 en la modalidad de Contabilidad y Administración de Empresas. El objetivo del presente trabajo es analizar la política de dotación de provisiones legales de la banca europea durante el periodo 2008-2017. Dichas provisiones constituyen una herramienta para mejorar la transparencia de la empresa, pero pueden obedecer también a motivaciones discrecionales. Utilizando una muestra de 92 bancos sistémicos de 18 países supervisados por el Mecanismo Único de Supervisión del Banco Central Europeo, nuestra investigación propone tres resultados principales. En primer lugar, encontramos una relación negativa entre la discrecionalidad directiva y las provisiones legales, lo que sugiere una renuencia por parte de los directivos al reconocimiento del riesgo. Un segundo resultado es el efecto moderador de la independencia del consejo de administración, que se erige en instrumento que favorece la dotación de las correspondientes provisiones legales cuando la discrecionalidad directiva así lo aconseja. En tercer lugar, nuestros resultados avalan la eficacia de un entorno institucional adecuado (en términos de calidad legal y protección de los inversores), que constituye una condición necesaria para que el consejo de administración desarrolle su tarea.

Purpose To develop multi-compartment mechanistic models of dynamics of stem and functional cell populations in epithelium after irradiation. Methods and materials: We present two models, with three (3C) and four (4C) compartments respectively. We use delay differential equations, and include accelerated proliferation, loss of division asymmetry, progressive death of abortive stem cells, and turnover of functional cells. The models are used to fit experimental data on the variations of the number of cells in mice mucosa after irradiation with 13 Gy and 20 Gy. Akaike information criteria (AIC) was used to evaluate the performance of each model. Results Both 3C and 4C models provide good fits to experimental data for 13 Gy. Fits for 20 Gy are slightly poorer and may be affected by larger uncertainties and fluctuations of experimental data. Best fits are obtained by imposing constraints on the fitting parameters, so to have values that are within experimental ranges. There is some degeneration in the fits, as different sets of parameters provide similarly good fits. Conclusions The models provide good fits to experimental data. Mechanistic approaches like this can facilitate the development of mucositis response models to nonstandard schedules/treatment combinations not covered by datasets to which phenomenological models have been fitted. Studying the dynamics of cell populations in multifraction treatments, and finding links with induced toxicity, is the next step of this work.

Introduction: Parkinson's disease (PD) is a chronic neurological disorder whose pathogenesis involves the loss of dopaminergic neurons and dopamine terminals, formation of Lewy bodies, and microgli...

Este trabajo se enmarca dentro del acondicionamiento ambiental de viviendas en clima calido-humedo, y en la obtencion de condiciones de confort termico por medios predominantemente pasivos. El analisis se centra en una vivienda representativa de las tipologias constructivas de La Habana (Cuba), como ejemplo caracteristico del clima calido-humedo. Se analiza mediante un software de simulacion dinamica la evolucion de la temperatura interior de la vivienda para diferentes situaciones de ventilacion natural y de las estrategias de sombreamiento en combinacion con aquellas. Al comparar las temperaturas interiores de la vivienda, resultantes de la simulacion efectuada, con las exteriores hora a hora y dia a dia proporcionadas por el modelo, se cuantifican las amortiguaciones y amplitudes de la onda termica en condiciones de invierno y de verano, en funcion de las diferentes estrategias adoptadas, y se valoran las situaciones termicas obtenidas en orden a una mejor habitabilidad de la vivienda.

This study was supported by the Ministry of Economy, Industry and Competitiveness (Spanish Agency of Research) and the European Regional Development Fund (ERDF); PGC2018-102116-B-I00 ‘SWIM II: Specific Water Innovative Measurements: Applied to the performance improvement’ and the Spanish Ministry of Education, Culture and Sport: FPU17/02761, FPU16/02629, and FPU19/02477 grant. This article is a part of an international thesis belonging to the Program of PhD in Biomedicine (B11.56.1), from the University of Granada, Granada (Spain), The level of expertise must be defined for the sample studied when report research in sport. Concretely in swimming, apart from the participants’ background, the competitive status is based on the level that swimmers participate. Thus, the International Swimming Federation (FINA) points are added to improve the sample level characterization. The aim of this study was two-fold: 1) to assess whether national and regional swimmers from different countries differ in their performance level (based on FINA points), and 2) to propose a model that allows standardizing the research results in swimming. The FINA points of 5876 participants (males = 2962 and females = 2914) in 100 m butterfly, backstroke, breaststroke, and freestyle were retrieved from nationals (n = 21) and regionals (n = 44) swimming competitions. One-way analysis of variance was conducted to test the difference in FINA points between swimmers of different countries. Significant disparities (100 to 350 FINA points; p, Spanish Ministry of Education, Culture and Sport: FPU17/02761, FPU16/02629, and FPU19/02477, Ministry of Economy, Industry and Competitiveness (Spanish Agency of Research) and the European Regional Development Fund (ERDF); PGC2018-102116-B-I00 ‘SWIM II: Specific Water Innovative Measurements: Applied to the performance improvement

Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1 and N-4 and the nature of the chalcogen atom (S, Se). These compounds were evaluated towards

The authors gratefully acknowledge funding support from the Spanish Ministry of Science, Innovation and Universities (PGC2018-102052-B-C21 and PID2020-116460RB-I00) and the Junta de Andaluci ' a (FQM-394 and FQM-134). The authors gratefully acknowledge the funding support of FEDER/Junta de Andaluci ' a Consejeri ' a de Economi ' a y Conocimiento, Grant B-AGR-193-UGR18. O. L. and J. G. F. B. also thank Grant PID2020-116460RB-I00 funded by MCIN/AEI/10.13039/50110 0011033. S. R. acknowledge the Juan de la Cierva Fellowship (IJC2019-038894-I). Mari ' a D. Navarro-Hortal and Jose M. Romero-Ma ' rquez are FPU fellows from the Spanish Ministry of Educacio ' n y Formacio ' n Profesional., A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)(2)] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units formed by a Pd2+ ion coordinated to two molecules of the glz ligand, in which palladium ions exhibit a distorted plane-square coordination sphere. This novel material behaves like a good and selective inhibitor of butyrylcholinesterase, one of the most relevant therapeutic targets against Alzheimer's disease. Analysis of the enzyme kinetics showed a mixed mode of inhibition, the title compound being capable of interacting with both the free enzyme and the enzyme-substrate complex. Finally, the palladium compound shows promising protective activity against A beta-induced toxicity in the Caenorhabditis elegans model, which has never been reported., Spanish Government PGC2018-102052-B-C21 PID2020-116460RB-I00, Junta de Andalucia FQM-394 FQM-134, FEDER/Junta de Andaluci'a Consejeri'a de Economi'a y Conocimiento B-AGR-193-UGR18, MCIN/AEI/ PID2020-116460RB-I00, Juan de la Cierva Fellowship IJC2019-038894-I

The chromane ring system is widely distributed in nature and has proven to be a highly potent pharmacophore in medicinal chemistry, which includes the area of Alzheimer's and Parkinson's diseases. We report on the development of a gem-dimethylchroman-4-ol family that was shown to give good inhibition of equine serum butyrylcholinesterase (eqBuChE) (in the range 2.9 - 7.3 μM) and in the same range of currently used drugs. We also synthesized a small library of gem-dimethylchroman-4-amine compounds, via a simple reductive amination of the corresponding chromanone precursor, that were also selective for eqBuChE presenting inhibitions in the range 7.6 - 67 μM. Kinetic studies revealed that they were mixed inhibitors. Insights into their mechanism of action were obtained through molecular docking and STD-NMR experiments, and the most active examples showed excellent drug-likeness and pharmacological properties predicted using Swiss-ADME. We also prepared a set of propargyl gem-dimethylchromanamines, for monoamine oxidase (MAO) inhibition but they were only moderately active (the best being 28% inhibition at 1 µM on MAO-B). Overall, our compounds were found to be best suited as inhibitors for BuChE.

Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1 and N-4 and the nature of the chalcogen atom (S, Se). These compounds were evaluated towards Trypanosoma cruzi and Trichomonas vaginalis. Thiosemicarbazide 31 showed the best trypanocidal profile (epimastigotes), similar to benznidazole (BZ): IC50 (31)=28.72 μM (CL-B5 strain) and 33.65 μM (Y strain), IC50 (BZ)=25.31 μM (CL-B5) and 22.73 μM (Y); it lacked toxicity over mammalian cells (CC50 > 256 µM). Thiosemicarbazones 49, 51 and 63 showed remarkable trichomonacidal effects (IC50 =16.39, 14.84 and 14.89 µM) and no unspecific cytotoxicity towards Vero cells (CC50 ≥ 275 µM). Selenoisosters 74 and 75 presented a slightly enhanced activity (IC50=11.10 and 11.02 µM, respectively). Hydrogenosome membrane potential and structural changes were analysed to get more insight into the trichomonacidal mechanism.

Concerned by the urgent need to explore new approaches for the treatment of Alzheimer's disease, we herein describe the synthesis and evaluation of new multitarget molecules. In particular, we have focused our attention on modulating the activity of cholinesterases (AChE, BuChE) in order to restore the levels of the neurotransmitter acetylcholine, and of O-GlcNAcase (OGA), which is associated with hyperphosphorylation of tau protein, in turn related to the formation of neurofibrillary tangles in the brain. Specifically, we considered the possibility of using carbohydrate-fused 1,3-selenazolines, decorated with a 2-alkylamino or 2-alkoxy moieties. On the one hand, the presence of a selenium atom might be useful in modulating the intrinsic oxidative stress in AD. On the other hand, such bicyclic structure might behave as a transition state analogue of OGA hydrolysis. Moreover, upon protonation, it could mimic the ammonium cation of acetylcholine. The lead compound, bearing a propylamino moiety on C-2 position of the selenazoline motif, proved to be a good candidate against AD; it turned out to be a strong inhibitor of BuChE (IC

La Revolución cubana constituye probablemente el hecho más influyente en la historia contemporánea de América Latina por su alcance y significado. Todavía hoy, los ecos de aquel acontecimiento se proyectan sobremanera en el presente y los numerosos interrogantes que sigue generando lo convierten en un terreno extraordinariamente fértil para su estudio. En el presente artículo queremos explorar las potencialidades que ofrece la historia oral para tal fin. Para ello, nos servimos de las historias de vida de algunos sujetos que tuvieron experiencia directa o participaron del acontecer político y social de Cuba desde la década de los cincuenta hasta el presente en distintos escenarios. El rescate de sus voces nos permite acercarnos a la experiencia vivida de la Revolución y nos ayuda a comprender el significado mismo de ese proceso histórico. The Cuban Revolution constitute probably the most influential event in the contemporary history of Latin America due to its scope and significance. Even today, the echoes of that historical event are projected greatly in the present and the numerous of unanswered questions that still generate turn into extraordinary field to this study. In the present article we want to explore the potentialities what the oral history can offer us to reach that objective. In order to dive into this issue we shall focus in the life stories of some person who had direct experience or taken part in political and social happen in Cuba, from fifties decade to the present in a different scenes. The rescue of their voices allows us to approach the “lived experience” of the Revolution and helps us to know the very meaning of that historical process.

Cancer, one of the most devastating degenerative diseases nowadays, is one of the main targets in Medicinal Chemistry and Pharmaceutical industry. Due to the significant increase in the incidence of cancer within world population, together with the complexity of such disease, featured with a multifactorial nature, access to new drugs targeting different biological targets connected to cancer is highly necessary.:Among the vast arsenal of compounds exhibiting antitumor activities, this review will cover the use of carbohydrate derivatives as privileged scaffolds. Their hydrophilic nature, together with their capacity of establishing selective interactions with biological receptors located on cell surface, involved in cell-to-cell communication processes, has allowed the development of an ample number of new templates useful in cancer treatment.:Their intrinsic water solubility has allowed their use as of pro-drug carriers for accessing more efficiently the pharmaceutical targets. The preparation of glycoconjugates in which the carbohydrate is tethered to a pharmacophore has also allowed a better permeation of the drug through cellular membranes, in which selective interactions with the carbohydrate motifs are involved. In this context, the design of multivalent structures (e.g. gold nanoparticles) has been demonstrated to enhance crucial interactions with biological receptors like lectins, glycoproteins that can be involved in cancer progression.:Moreover, the modification of the carbohydrate structural motif, by incorporation of metal complexes, or by replacing their endocyclic oxygen, or carbon atoms with heteroatoms has led to new antitumor agents.:Such diversity of sugar-based templates with relevant antitumor activity will be covered in this review.

espanolEl presente trabajo analiza el fenomeno de la concesion de licencias de armas por parte de la monarquia castellana durante los ultimos anos del siglo xv, atendiendo a las motivaciones esgrimidas por los solicitantes, a las condiciones que se consideraban para su obtencion y a su vinculo con la conformacion de grupos armados y con el papel del sistema judicial. En virtud de ello, las 345 licencias de armas concedidas por el Consejo Real de Castilla que son objeto de estudio permiten aproximarnos a problematicas como la de la criminalidad y el uso de las armas, los mecanismos establecidos de regulacion de los conflictos sociales y los limites de la justicia. Los salvoconductos para transitar con cascos, broqueles, punales o espadas nos situan en un escenario social apasionante, en el que convivian las presiones vecinales –la necesidad de mantener la fama; la honra en el ejercicio del derecho a la venganza–, las ansias de riqueza y la desesperacion por sobrevivir. EnglishThis paper analyses the granting of arms licenses by the Castilian monarchy in the last years of the fifteenth century. It refers to issues such as motivations given by the applicants, conditions considered for obtaining them, their relations with development of armed groups and the role of the judicial system. 345 weapons licenses granted by the Royal Council studied allow us to approach problem of violence and use of weapons, regulation mechanisms of social conflict and limits of the royal justice in the Castilian Middle Ages. Documents for walking with helmets, broaches, daggers or swords put us in an exciting social setting, where coexisted desperation to survive with neighbourhood pressures –honour in the exercise of revenge– and desire for wealth –that led to forgive a death in exchange for a good bag of money–.

The fatty acid composition of retail lamb backfat commonly available in Western Canada was analyzed, including 16 lambs collected from a slaughter plant in central Alberta, and backfat collected from racks and chops imported from Australia (n = 8) and New Zealand (n = 8). Lamb fat from New Zealand was the richest source of vaccenic and rumenic acids. Both New Zealand and Australian lamb were the richest source of n-3 fatty acids. North American lamb was richer in t10-18:1, but a subset had fatty acid compositions similar to New Zealand lamb.