New 1-aryl-3-substituted propanol derivatives as antimalarial agents

This paper describes the synthesis and in vitro antimalarial activity against a P. falciparum 3D7 strain of some new 1-aryl-3-substituted propanol derivatives. Twelve of the tested compounds showed an IC50 lower than 1 μM. These compounds were also tested for cytotoxicity in murine J774 macrophages. The most active compounds were evaluated for in vivo activity against P. berghei in a 4-day suppressive test. Compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. In addition, an FBIT test was performed to measure the ability to inhibit ferriprotoporphyrin biocrystallization. This data indicates that 1-aryl-3-substituted propanol derivatives hold promise as a new therapeutic option for the treatment of malaria

Broad-Spectrum Antiviral Therapeutics

Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.National Institute of Allergy and Infectious Diseases (U.S.) (grant AI057159)New England Regional Center of Excellence for Biodefense and Emerging Infectious DiseasesUnited States. Dept. of Defense (Director of Defense Research & Engineering)United States. Defense Threat Reduction AgencyUnited States. Defense Advanced Research Projects Agenc

Estudio de la Absorción Óptica en Silicio Poroso Tipos n y p Elaborados MedianteAtaque Electroquímico: Efecto de los Parámetros de Crecimiento (Tiempo de Ataquey Valores I-V)

En este trabajo se busca optimizar mediante los parámetros de crecimiento, las características de absorción óptica de muestras de silicio poroso n y p en la región visible del espectro electromagnético y evaluar sus posibles aplicaciones como material fototérmico en la conversión de energía solar en térmica. La elaboración de las muestras se llevará a cabo mediante la técnica de ataque electroquímico, variando el tiempo de ataque y los valores de corriente y voltaje. Este proyecto tiene como objetivo, estudiar las propiedades de absorción óptica del silicio poroso en función de los parámetros de elaboración de las muestras, además del estudio de su microestructura y propiedades térmicas y analizar su posible aplicación como material fototérmico.Articulo en extenso de memoria de SimposioInstituto Politecnico Nacional y Conacy

Simulation-based mathematical learning for higher education students from heterogeneous backgrounds

This is an Accepted Manuscript of an article published by Taylor & Francis in "Journal of Simulation" on the 2nd of February, available online: http://www.tandfonline.com/10.1080/17477778.2024.2314716[EN] This paper explores the use of simulation-based training for mathematical learning in undergraduate and graduate mathematics, science, and engineering courses. Simulation-based training offers the advantages of active learning and inquiry-based learning techniques. Furthermore, it provides extensive flexibility, ranging from user-level usage of simulations to the modification or creation of new possibilities by the student, thus engaging different cognitive levels to achieve the learning objectives. This is particularly interesting in groups consisting of students from diverse backgrounds and levels, due to factors such as their international origin or varying prior education, especially in interdisciplinary Master's degree programmes. Additionally, in online or blended environments (which have become widespread during the last years), simulation-based learning has the advantage of granting students a certain degree of autonomy, which can, to some extent, compensate for the absence of the instructor's physical presence.Campos, N.; Corlu, CG.; Nogal, M.; Juan, AA.; Caliz, C. (2024). Simulation-based mathematical learning for higher education students from heterogeneous backgrounds. Journal of Simulation. https://doi.org/10.1080/17477778.2024.231471

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

Characterization of the African swine fever virus decapping enzyme during infection

African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this phenomenon is still unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting that inhibition of cellular proteins is due to an active mRNA degradation process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping protein (ASFV-DP) which has a Nudix hydrolase motif and decapping activity in vitro. Here we show that ASFV-DP was expressed from early times and accumulated throughout the infection with a subcellular localization typical of the endoplasmic reticulum, co-localizing with the cap structure and interacting with the ribosomal protein L23a. ASFV-DP was capable of interaction with poly(A) RNA in cultured cells, primarily mediated by the N-terminal region of the protein. ASFV-DP also interacted with viral and cellular RNA in the context of infection, and its overexpression in infected cells resulted in decreased levels of both types of transcripts. This study points to ASFV-DP as a viral decapping enzyme involved in both the degradation of cellular mRNA and the regulation of viral transcripts

Towards the Creation of Synthetic Bridge Digital Twins What-If Scenarios: Study Case and Calibration

Downloa

Circulating Levels of the Short-Chain Fatty Acid Acetate Mediate the Effect of the Gut Microbiome on Visceral Fat

Background: Acetate is a short-chain fatty acid (SCFA) produced by gut bacteria, which has been implicated in cardio-metabolic health. Here we examine the relationships of circulating acetate levels with gut microbiome composition and diversity and with visceral fat in a large population-based cohort. Results: Microbiome alpha-diversity was positively correlated with circulating acetate levels (Shannon, Beta [95%CI] = 0.12 [0.06, 0.18], P = 0.002) after adjustment for covariates. Six serum acetate-associated bacterial genera were also identified, including positive correlations with Coprococcus, Barnesiella, Ruminococcus, and Ruminococcaceae NK4A21 and negative correlations were observed with Lachnoclostridium and Bacteroides. We also identified a correlation between visceral fat and serum acetate levels (Beta [95%CI] = -0.07 [-0.11, -0.04], P = 2.8 x 10(-4)) and between visceral fat and Lachnoclostridium (Beta [95%CI] = 0.076 [0.042, 0.11], P = 1.44 x 10(-5)). Formal mediation analysis revealed that acetate mediates similar to 10% of the total effect of Lachnoclostridium on visceral fat. The taxonomic diversity showed that Lachnoclostridium and Coprococcus comprise at least 18 and 9 species, respectively, including novel bacterial species. By predicting the functional capabilities, we found that Coprococcus spp. present pathways involved in acetate production and metabolism of vitamins B, whereas we identified pathways related to the biosynthesis of trimethylamine (TMA) and CDP-diacylglycerol in Lachnoclostridium spp. Conclusions: Our data indicates that gut microbiota composition and diversity may influence circulating acetate levels and that acetate might exert benefits on certain cardio-metabolic disease risk by decreasing visceral fat. Coprococcus may play an important role in host health by its production of vitamins B and SCFAs, whereas Lachnoclostridium might have an opposing effect by influencing negatively the circulating levels of acetate and being involved in the biosynthesis of detrimental lipid compounds

Tree vigour influences secondary growth but not responsiveness to climatic variability in Holm oak

Many tree species from Mediterranean regions have started to show increased rates of crown defoliation, reduced groth, and dieback associated with the increase in temperatures and changes in the frequency and intensity of drought events experienced during the last decades. In this regard, Quercus ilex L. subsp. ballota (Desf.) (Holm oak), despite being a drought-tolerant species widely distributed in the Mediterranean basin, it has recently started to show acute signs of decline, extended areas from Spain being affected. However, few studies have assessed the role of climatic variability (i.e., temperature, precipitation, and drought) on the decline and resilience of Holm oak. Here, we measured secondary growth of seventy Holm oaks from a coppice stand located in central Spain. Sampled trees had different stages of decline, so they were classified into four vigour groups considering their crown foliar lost: healthy (0%), low defoliated (25%), highly defoliated (25 70%), and dying (70 100%). Our results showed that during the study period (1980 2009) the highly defoliated and dying Holm oaks grew significantly less than their healthy and low defoliated neighbours, suggesting permanent growth reduction in the less vigorous individuals. Despite these differences, all four vigour groups showed similar responses to climatic variations, especially during winter and late spring early summer seasons, and similar resilience after severe drought events, managing to significantly recover to pre-drought growth rates after only two years. Our findings, hence, illustrate that tree vigour influences secondary growth but not responsiveness to climatic variability in Holm oak. Still, as reduced growth rates are frequently associated with the process of tree mortality, we conclude that the less vigorous Holm oaks might not be able to cope with future water stress conditions, leading to increased mortality rates among this emblematic Mediterranean specie