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We demonstrate coherent three-photon excitation of the strontium clock transition with a contrast of 51(12)% using a Bose-Einstein condensate. We follow it up with a demonstration of three-photon STIRAP-like transfer, overcoming the typical limitations of this technique to odd-level numbers. We also measure the two-body loss coefficient of ^{84}Sr clock-state atoms. Our work constitutes an essential step towards outcoupling a continuous atom laser beam and provides a fast excitation mechanism for quantum simulation using bosonic alkaline-earth-like atoms. more...

Studies have shown that the heterocyclic molecules of the 2,2-diphenyl-1,3,2-oxazaborolidin-5-one (DPOXA) type have wide and varied biological activity with herbicidal, insecticidal, fungicidal, antibacterial, and apoptotic properties. Several methods are reported for synthesizing this type of molecule, but they require strong acid conditions to release phenylboronic acid, the residues of which impact the environment. The method of synthesis proposed in this study uses montmorillonite (TAFF), microwave irradiation, and an eight α-amino acid. The transformation percentages evaluated by UHPLC-MS/MS, and generated from the optimal conditions of power (W), temperature (°C,) and the amount of TAFF (mg), reflect excellent yields ranging from 81-96 %, in a reaction time of 5 min under solvent-free conditions. Findings allow us to confirm that this methodology is adequate for synthesizing this type of molecule, which has shown significant biological activity. more...

The axolotl, known for its remarkable regenerative abilities, is an excellent model for studying regenerative therapies. Nevertheless, the precise molecular mechanisms governing its regenerative potential remain uncertain. In this study, we collected samples from axolotls of different ages, including 8-year-old individuals and 8-month-old juveniles, obtaining their blastemas 10 days after amputation. Subsequently, we conducted a transcriptomic analysis comparing our samples to a set of previously published experiments. Our analysis unveiled a distinctive transcriptional response in the blastema, characterized by differential gene expression associated with processes such as bone and tissue remodeling, transcriptional regulation, angiogenesis, and intercellular communication. To gain deeper insights, we compared these findings with those from aged axolotls that showed no signs of regeneration 10 days after amputation. We identified four genes—FSTL1, ADAMTS17, GPX7, and CTHRC1—that showed higher expression in regenerating tissue compared to aged axolotls. Further scrutiny, including structural and homology analysis, revealed that these genes are conserved across vertebrate species. Our discoveries point to a group of proteins relevant to tissue regeneration, with their conservation in vertebrates suggesting critical roles in development. These findings also propose a novel gene set involved in axolotl regeneration, laying a promising foundation for future investigations across vertebrates. more...

Los impactos expuestos en la pandemia en la estructura productiva acontecieron de manera diversa y diferencial. Ante ello nos preguntamos: ¿cómo se reconfigurarán los espacios-tiempo de las movilidades contem­poráneas a partir de la crisis del covid-19? Desde una perspectiva de la espacialidad y las prácticas sociales, ¿cómo se interpreta en forma sustantiva el turismo posvacuna? Para el abordaje de los interrogantes presen­tados, este trabajo se estructura de acuerdo con una caracterización de ese momento en términos de los cambios societales y su conexión con el fenómeno de la pandemia, luego se abordan los cambios de percepción de espacio-tiempo y la visibilización y actualización de históricas disputas aso­ciadas a la desigualdad. En diálogo con lo anterior, se reflexiona sobre los procesos de desterritorialización y reterritorialización como parte de un continuum signado por un escenario de desigualdad, conflictos y reconfiguraciones manifiestas en los territorios contempo­ráneos. Por último, el escrito indaga el turismo posvacuna desde una perspectiva de la espacialidad y las prácticas sociales. more...

We present a faster repumping scheme for strontium magneto-optical traps operating on the broad 5s^{2}^{1}S_{0}−5s5p^{1}P_{1} laser cooling transition. Contrary to existing repumping schemes, we directly address lost atoms that spontaneously decayed to the 5s4d^{1}D_{2} state, sending them back into the laser cooling cycle by optical pumping on the 5s4d^{1}D_{2}−5s8p^{1}P_{1} transition. We thus avoid the ∼100µs-slow decay path from 5s4d^{1}D_{2} to the 5s5p^{3}P_{1,2} states that is part of other repumping schemes. Using one low-cost external-cavity diode laser emitting at 448nm, we show our scheme increases the flux out of a 2D magneto-optical trap by 60% compared to without repumping. Furthermore, we perform spectroscopy on the 5s4d^{1}D_{2}−5s8p^{1}P_{1} transition and measure its frequency ν_{^{88}Sr}=(668917515.3±4.0±25)MHz. We also measure the frequency shifts between the four stable isotopes of strontium and infer the specific mass and field shift factors, δν_{SMS}^{88,86}=−267(45)MHz and δν_{FS}^{88,86}=2(42)MHz. Finally, we measure the hyperfine splitting of the 5s8p^{1}P_{1} state in fermionic strontium and deduce the magnetic dipole and electric quadrupole coupling coefficients A=−4(5)MHz and B=5(35)MHz. Our experimental demonstration shows that this simple and very fast scheme could improve the laser cooling and imaging performance of cold strontium atom devices, such as quantum computers based on strontium atoms in arrays of optical tweezers. more...

This article investigates the velocity field of a free-surface flow subjected to harmonic deformation of the channel bottom, progressing asymptotically from a flat initial state to a maximum amplitude. Assuming a uniform main flow with the primary velocity component transverse to the bed undulation, analytical solutions are obtained for the three velocity components and free surface distortion using the method of perturbations. The perturbation components of the velocity field, streamlines, and surface deformation depend on a dimensionless parameter that reflects the fluid inertia induced by bed deformation relative to viscous resistance. When viscous effects dominate, a monotonic decay of the perturbations from the bed to the free surface is observed. In contrast, when inertia dominates, the perturbations can exhibit an oscillatory behavior and introduce circulation cells in the plane normal to the main flow. The interplay between inertia and viscosity reveals scenarios where surface and bed deformations are either in or out of phase, influencing vertical velocity components. Figures illustrate these phenomena, providing insights into the complex dynamics of free-surface flows with harmonic bed deformation in the direction normal to the main flow, and amplitude growing with time. The results are limited to small deformations of the channel bottom, as imposed by the linearization of the momentum equations. Even so, to the best of the authors’ knowledge, this problem has not been addressed before. more...

En este escrito se presenta de forma general una curiosidad matemática que rápidamente llama la atención per se, la cual describe un patrón peculiar que cumplen los primeros dígitos de datos obtenidos de diversas situaciones ordinarias y de muchos procesos reales, conocida como Ley de Benford o Fenómeno de los Dígitos Significativos. Además de analizar y reproducir el cumplimiento de este singular principio matemático que siguen los dígitos significativos para algunos ejemplos típicos encontrados en la literatura, también se analiza el cumplimiento de esta ley en casos de interés particular, y se describen posibles aplicaciones potenciales. more...

Abstract High-grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy due to the lack of reliable biomarkers, effective treatment, and chemoresistance. Improving the diagnosis and the development of targeted therapies is still needed. The molecular pathomechanisms driving HGSC progression are not fully understood though crucial for effective diagnosis and identification of novel targeted therapy options. The oncogene CTCFL (BORIS), the paralog of CTCF, is a transcriptional factor highly expressed in ovarian cancer (but in rarely any other tissue in females) with cancer-specific characteristics and therapeutic potential. In this work, we seek to understand the regulatory functions of CTCFL to unravel new target genes with clinical relevance. We used in vitro models to evaluate the transcriptional changes due to the presence of CTCFL, followed by a selection of gene candidates using de novo network enrichment analysis. The resulting mechanistic candidates were further assessed regarding their prognostic potential and druggability. We show that CTCFL-driven genes are involved in cytoplasmic membrane functions; in particular, the PI3K-Akt initiators EGFR1 and VEGFA, as well as ITGB3 and ITGB6 are potential drug targets. Finally, we identified the CTCFL targets ACTBL2, MALT1 and PCDH7 as mechanistic biomarkers to predict survival in HGSC. Finally, we elucidated the value of CTCFL in combination with its targets as a prognostic marker profile for HGSC progression and as putative drug targets. more...

Acute type A dissection presenting with cerebral malperfusion has high morbidity and mortality. Given the complexity of underlying vascular involvement, it is a challenging clinical scenario. Many of these patients are not deemed surgical candidates. If surgery is considered, it often requires complex aortic arch and neck vessel reconstruction. We present a 48-year-old male with an acute type A aortic dissection that presented with paraplegia and decreased level of consciousness. A Computed Tomography showed occlusion of both common carotid arteries. He was successfully treated with a multi-site perfusion strategy and a Hybrid Frozen Elephant Trunk graft to achieve fast restoration of the cerebral circulation and minimize brain ischemia and permanent neurological damage. From this case, we learn that aggressive arch and neck vessel reconstruction supported by multi-site perfusion could help improve mortality and neurological outcomes in selected patients. more...

Background/Objective: Stroke knowledge is variable within and between countries. It is determined by school grade, geographical location, and language barriers. This study aims to evaluate the knowledge of stroke symptoms, risk factors, and treatment in a specific population in Mexico. Methods: We surveyed volunteer participants among the inhabitants of a medium- income condominium complex and employees of a pharmaceutical company located in Mexico City between 2016 and 2018. We collected information regarding knowledge of stroke definitions, symptoms, risk factor identification, and treatment. Results: We surveyed 499 participants at both sites, with a median age of 44 years (interquartile range 31-70) and mean years of education of 16.09 years (SD 3.67). The recognition of different definitions regarding stroke was highly heterogeneous, with “brain hemorrhage” and “stroke” being the most known. Among participants, 70% knew at least one stroke symptom. Out of four risk factors, a mean of 3 are identified when prompted, with dyslipidemia being the least acknowledged. While 70% of participants recognize stroke as treatable, only 12-25% know about intravenous thrombolysis. There was no significant difference in overall stroke knowledge between surveyed sites. Conclusions: Knowledge about stroke remains highly heterogeneous in our population. While the knowledge of the general presentation of stroke is higher than in other studies, probably due to the higher mean school education, the awareness of treatment options is low. New public education programs should consider including this information, because it may improve the proportion of cases treated promptly. more...

Chromatin maintenance and remodeling are processes that take place alongside DNA repair, replication, or transcription to ensure the survival and adaptability of a cell. The environment and the needs of the cell dictate how chromatin is remodeled; particularly where and which histones are deposited, thus changing the canonical histone array to regulate chromatin structure and gene expression. Chromatin is highly dynamic, and histone variants and their chaperones play a crucial role in maintaining the epigenetic regulation at different genomic regions. Despite the large number of histone variants reported to date, studies on their roles in physiological processes and pathologies are emerging but continue to be scarce. Here, we present recent advances in the research on histone variants and their chaperones, with a focus on their importance in molecular mechanisms such as replication, transcription, and DNA damage repair. Additionally, we discuss the emerging role they have in transposable element regulation, aging, and chromatin remodeling syndromes. Finally, we describe currently used methods and their limitations in the study of these proteins and highlight the importance of improving the experimental approaches to further understand this epigenetic machinery. more...

Abstract COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV, and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA, and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that has therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19. more...

Objectives: The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated. Methods: A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components. Results: The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C. Conclusions: The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction. more...

Este artículo propone una reconstrucción integral de la historia del Centro Piloto de París, una oficina creada en la capital francesa por la dictadura militar argentina en 1977. Su misión oficial fue difundir la propaganda del régimen para mejorar su imagen en Europa, donde crecían las denuncias de los exiliados por las violaciones a los derechos humanos en la Argentina. Sin embargo, durante una etapa de su existencia, el Centro Piloto no sólo atendió esa labor sino que, además, cobijó operaciones secretas de los represores de la Escuela de Mecánica de la Armada (ESMA) que respondían a los planes políticos del almirante Emilio Massera. A partir del uso de fuentes testimoniales y documentales, este trabajo traza una cronología detallada de la historia de la oficina creada en Francia, en la que se distinguen los momentos diferenciados de su actividad. A su vez, este despliegue en perspectiva permite observar la proyección en el Centro Piloto de tres rasgos definitorios del régimen militar: el carácter imbricado de la relación entre las dimensiones legal y clandestina del aparato represivo; la existencia de una interna política feroz en el seno de las Fuerzas Armadas que impactaba en el “frente externo” de la dictadura; y el desarrollo de una “dimensión productiva” de la represión clandestina. more...

MicroRNAs are small noncoding transcripts that posttranscriptionally regulate gene expression via base-pairing complementarity. Their role in cancer can be related to tumor suppression or oncogenic function. Moreover, they have been linked to processes recognized as hallmarks of cancer, such as apoptosis, invasion, metastasis, and proliferation. Particularly, one of the first oncomiRs found upregulated in a variety of cancers, such as gliomas, breast cancer, and colorectal cancer, was microRNA-21 (miR-21). Some of its target genes associated with cancer are PTEN (phosphatase and tensin homolog), PDCD4 (programmed cell death protein 4), RECK (reversion-inducing cysteine-rich protein with Kazal motifs), and STAT3 (signal transducer activator of transcription 3). As a result, miR-21 has been proposed as a plausible diagnostic and prognostic biomarker, as well as a therapeutic target for several types of cancer. Currently, research and clinical trials to inhibit miR-21 through anti-miR-21 oligonucleotides and ADM-21 are being conducted. As all of the evidence suggests, miR-21 is involved in carcinogenic processes; therefore, inhibiting it could have effects on more than one type of cancer. However, whether miR-21 can be used as a tissue-specific biomarker should be analyzed with caution. Consequently, the purpose of this review is to outline the available information and recent advances regarding miR-21 as a potential biomarker in the clinical setting and as a therapeutic target in cancer to highlight its importance in the era of precision medicine. more...

ABSTRACT We describe a 60-year-old woman with post-myocardial infarction (MI) ventricular septal defect (VSD) and cardiogenic shock who was successfully stabilized with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge therapy for the surgical closure of her VSD. This case highlights the role of VA-ECMO in the management of post-MI VSD to improve the results of surgical repair and patient survival. more...

Background: Platelet-rich plasma (PRP) is a biological intra-articular therapy that has shown good clinical outcomes in patients with knee osteoarthritis (OA) and has been widely studied from in vitro to pre-clinical animal models. We aimed to synthesize non-clinical evidence regarding the different effects related to PRP. Methods: A systematic literature review was conducted in the MEDLINE, EMBASE, and Google Scholar databases in December 2020. Studies were included if they were non-clinical basic science publications describing the effect of PRP treatment, studies focused on knee OA, and articles reporting the use of PRP or a similar platelet-derived product. Included articles were assessed and categorized based on the effect or the mechanism of the action described. The main findings of each study were obtained and analyzed. Results: A total of 41 articles were included to review the outcomes of interest. The most frequently reported mechanism was the modulation of genes involved in synthesizing and degrading the cartilage extracellular matrix (ECM), followed by ECM morphological analysis, inflammation, and cell proliferation. PRP preparations with low and high content of leukocytes were equally reported. Conclusions: The studies reviewed provide evidence for several ways in which PRP can act once it is present in the intra-articular environment. The vast majority of data support a beneficial effect of PRP therapy, especially for leukocyte-poor PRP formulations. The evidence collected gives us a clue as to what the mechanism of action could be. However, the great heterogeneity in the study formulations and models implies further investigation. more...

Este trabajo tiene por objetivo defender la incorporación de la perspectiva de género como una estrategia que favorece el logro de la tutela judicial efectiva para mujeres y personas LGBTIQ+. Afirmamos que el acceso a la justicia debe ser comprendido como un derecho humano indispensable en un Estado democrático, debiendo cuidar la remoción de los obstáculos que afectan especialmente a estas categorías de personas, como lo han indicado estándares internacionales de derechos humanos. En ese contexto, a partir del caso chileno, sostenemos que la perspectiva de género es una herramienta que, llevada al ejercicio de la función jurisdiccional, contribuye a hacer efectiva la tutela judicial. more...

Este artículo propone un cruce, a través del exilio, entre dos campos que hasta la actualidad no han dialogado en profundidad: el de las investigaciones sobre las organizaciones armadas y el de los estudios sobre el movimiento de denuncia de las violaciones a los derechos humanos de la última dictadura argentina. Por eso, profundiza en los vínculos que se establecieron entre la organización armada Montoneros y la Comisión Argentina de Derechos Humanos (CADHU) desde el comienzo de su “exilio orgánico”, entre fines de 1976 y principios de 1977, hasta la realización del “testimonio de París” y la última disidencia montonera, entre fines de 1979 y principios de 1980. A través de un mosaico de fuentes que incluye documentos partidarios, entrevistas a los protagonistas e informes desclasificados de la inteligencia militar, el trabajo aborda el rol desempeñado por las organizaciones armadas en la constitución de las redes que motorizaron inicialmente la denuncia transnacional de las violaciones a los derechos humanos cometidas por la dictadura en la Argentina. more...

En este artículo se ejemplifica una búsqueda de estado de la cuestión en relación a los conceptos fake news, posverdad y desinformación, en la base de datos Web of Science. La idea de la confección de un estado de la cuestión, a pesar de ser una actividad de rutina en los procesos de investigación, implica dar cuenta de las diferencias singulares cuando se abordan temas emergentes (tales como los conceptos aquí tratados) y, particularmente, en los últimos 15 años, a partir de herramientas hemerográficas, a su vez, basadas en herramientas hemerométricas. Mediante un rastreo hemerográfico con los recursos que provee Web of Science, se lleva a cabo una sistematización para ofrecer una muestra de las posibilidades de esa base para elaborar un estado de la cuestión. Se encontró que esta herramienta -si bien de acceso restringido- es muy útil para la elaboración de los primeros mapas temáticos en la búsqueda de tópicos emergentes y la identificación de núcleos de investigación por áreas disciplinares, autores y diferendos conceptuales. more...

In this study, freeze-drying microencapsulation was proposed as a technology for the production of powdered hop extracts with high stability intended as additives/ingredients in innovative formulated food products. The effects of different carriers (maltodextrin, Arabic gum, and their mixture in 1:1 w/w ratio) on the physical and techno-functional properties, bitter acids content, yield and polyphenols encapsulation efficiency of the powders were assessed. Additionally, the powders’ stability was evaluated for 35 days at different temperatures and compared with that of non-encapsulated extract. Coating materials influenced the moisture content, water activity, colour, flowability, microstructure, and water sorption behaviour of the microencapsulates, but not their solubility. Among the different carriers, maltodextrin showed the lowest polyphenol load yield and bitter acid content after processing but the highest encapsulation efficiency and protection of hop extracts’ antioxidant compounds during storage. Irrespective of the encapsulating agent, microencapsulation did not hinder the loss of bitter acids during storage. The results of this study demonstrate the feasibility of freeze-drying encapsulation in the development of functional ingredients, offering new perspectives for hop applications in the food and non-food sectors. more...

Baculoviridae is a large family of arthropod-infective viruses. Recombinant baculoviruses have many applications, the best known is as a system for large scale protein production in combination with insect cell cultures. More recently recombinant baculoviruses have been utilized for the display of proteins of interest with applications in medicine. In the present review we analyze the different strategies for the display of proteins and peptides on the surface of recombinant baculoviruses and provide some examples of the different proteins displayed. We analyze briefly the commercially available systems for recombinant baculovirus production and display and discuss the future of this emerging and powerful technology. more...

Este estudio exploratorio tiene como finalidad identificar las principales percepciones de docentes de educación pública básica en la ciudad de Guadalajara, México, en torno al proceso de migración a modalidades no presenciales durante el inicio de la pandemia por la COVID-19. La meta general tras el diseño del trabajo empírico fue crear un corte sincrónico sobre la presencia de estas percepciones para poder comparar, en estudios posteriores y a mediano plazo, las posibles oscilaciones en las percepciones entre los mismos docentes y, probablemente, entre otro tipo de actores. more...

La convocatoria para la recepción de artículos de los volúmenes 13 de la revista Jurídicas versa sobre la “Constitucionalización del derecho”; para tal efecto se buscaron trabajos que abordaran el tema desde un espectro amplio proveniente tanto de las diferentes áreas jurídicas como de las ciencias sociales y las humanidades con los resultados correlativos a categorías, aproximaciones y contextos diversos. more...

La convocatoria de la Revista Jurídicas sobre la constitucionalización del derecho, convocó múltiples voces y análisis sobre este fenómeno que ha tenido también diferentes expresiones en las tradiciones jurídicas anglosajona y continental. Revisar las formas como emerge este fenómeno en las diferentes áreas e instituciones del derecho, refleja la riqueza de la discusión e investigación que hay sobre el tema; a la vez que confirma su importancia para los investigadores debido a que sus desarrollos han impactado e impactarán el futuro y la transformación del derecho no solo en Colombia, sino en el mundo. more...

El concepto de supremacía de la Constitución es hoy el elemento esencial del constitucionalismo contemporáneo, el cual es resultado de importantes evoluciones en el tiempo y se ha visto reforzado en muchos países con la creación del control de constitucionalidad. Sin embargo, esta noción tiene contenidos variables en función de cada tradición y de cada sistema jurídico, de manera que no es una cuestión resuelta. Un análisis desde el derecho comparado permite abarcar la supremacía de la Constitución desde ópticas diversas y estudiar sus diferentes elementos para darle un contorno más certero a esta. Específicamente, este artículo hace un análisis jurisprudencial que permite establecer las aracterísticas propias de este concepto en diferentes sistemas jurídicos y mostrar su actualidad e importancia. more...

Este artículo plantea un abordaje histórico de la producción testimonial que realizaron desde el exilio los sobrevivientes de los centros clandestinos de detención (CCD) de la última dictadura argentina. En este marco, se reconstruyen los principales ámbitos de circulación pública de sus relatos sobre el cautiverio y se ofrece un análisis de su evolución a lo largo del período 1976-1983. El trabajo se propone no sólo recuperar su aporte específico a la lucha contra el régimen militar, sino también tensionar la construcción de sentidos que postula el silenciamiento público de los sobrevivientes a causa de las acusaciones de “traición”. Finalmente, se exploran las modulaciones específicas que asumieron, en la producción testimonial de los sobrevivientes, una serie de fenómenos que atravesaron al movimiento antidictatorial exilar en su conjunto: la elaboración de saberes tempranos sobre el dispositivo represivo clandestino para su difusión en el extranjero, la relación entre las lógicas políticas revolucionaria y humanitaria en el ejercicio de la denuncia, la naturaleza transnacional de las redes de activismo antidictatorial y la construcción de diferentes categorías de víctimas de la violencia represiva. more...

Gene mutations are strongly associated with tumor progression and are well known in cancer development. However, recently discovered epigenetic alterations have shown the potential to greatly influence tumoral response to therapy regimens. Such epigenetic alterations have proven to be dynamic, and thus could be restored. Due to their reversible nature, the promising opportunity to improve chemotherapy response using epigenetic therapy has arisen. Beyond helping to understand the biology of the disease, the use of modern clinical epigenetics is being incorporated into the management of the cancer patient. Potential epidrug candidates can be found through a process known as drug repositioning or repurposing, a promising strategy for the discovery of novel potential targets in already approved drugs. At present, novel epidrug candidates have been identified in preclinical studies and some others are currently being tested in clinical trials, ready to be repositioned. This epidrug repurposing could circumvent the classic paradigm where the main focus is the development of agents with one indication only, while giving patients lower cost therapies and a novel precision medical approach to optimize treatment efficacy and reduce toxicity. This review focuses on the main approved epidrugs, and their druggable targets, that are currently being used in cancer therapy. Also, we highlight the importance of epidrug repurposing by the rediscovery of known chemical entities that may enhance epigenetic therapy in cancer, contributing to the development of precision medicine in oncology. more...

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by an abnormal activation of lung epithelium and fibroblasts, as well as an excessive accumulation of extracellular matrix. Pirfenidone was introduced as a therapeutic option for IPF and chronic hypersensitive pneumonitis (cHP), a related disease. However, high plasma concentrations, which can be achieved even at recommended doses, are frequently associated with adverse events. Hence, an extended release formulation (XP), yielding lower peak plasma concentrations, has been developed. The aim of this study was to compare the pharmacokinetic properties of XP with those of the immediate (IR) formulation in patients with IPF or cHP. Data were analyzed using two pharmacokinetic approaches, conventional non compartmental analysis and a population analysis using the nonlinear mixed effects model technique. Results observed with both approaches were consistent. Drug exposure was similar with both formulations. However, XP exhibited less concentration fluctuations and a longer mean resident time. These results suggest that XP could be a feasible option to reduce adverse events associated to pirfenidone elevated concentrations. Nevertheless, efficacy studies are required to fully document the therapeutic potential of XP. more...

Abstract: This article is focused on the ill studied topic of the Colombian Constitutional Court’s ancillary powers, and especially on its decisions regarding a person’s refusal to attend hearings related to Congress’ control functions. Thus, the text begins with the origins of this power discussed at the constituent assembly, then analyzing it in Comparative Constitutional Law. Also taking into account both theoretical and practical elements — such as doctrine, norms and case law—, it does propose two hypotheses concerning its character and effects, concluding that entails an exercise of judicial power with res iudicata force and that it comprises a especial type of judicial review more...

Conventional heating and solvothermal synthetic methods (with or without microwave activation) have been used to study the reaction of o-, m- and p-methoxybenzoic acid with [Ru2Cl(μ-O2CMe)4]. The tetrasubstituted series [Ru2Cl(µ-O2CC6H4-R)4], with R = o-OMe, m-OMe and p-OMe, has been prepared by the three procedures. Depending on the synthetic method and the experimental conditions, three compounds have been isolated (1a, 1b, 1c) with the o-methoxybenzoate ligand. However, with the m- and p-methoxybenzoate ligands, only the complexes 2 and 3 have been obtained, respectively. Compound 1a, with stoichiometry [Ru2Cl(µ-O2CC6H4-o-OMe)4]n, shows a polymeric structure with the chloride ions bridging the diruthenium units to form linear chains. Compounds 2 and 3, with the same stoichiometry, predictably form zig-zag chains in accordance with their insolubility and their magnetic measurements. Compound 1b, [Ru2Cl(µ-O2CC6H4-o-OMe)4(EtOH)], is a discrete molecular species with a chloride ion and one ethanol molecule occupying the axial positions of the dimetallic unit. Compound 1c is a cation-anion complex, [Ru2(µ-O2CC6H4-o-OMe)4(MeOH)2][Ru2Cl2(µ-O2CC6H4-o-OMe)4]. The cationic complex has two solvent molecules at the axial positions whereas the anionic complex has two chloride ligands at these positions. Complexes have been characterized by elemental analyses, mass spectrometry and IR and UV-vis-NIR spectroscopies. A magnetic study of complexes 1a, 1b, 2 and 3 have also been carried out. The crystal structure of compounds 1b and 1c have been solved by single X-ray crystal methods. more...

The morphological characteristics of ZnO nanostructures were systematically studied from dense rods to flower-like shapes. The ZnO flower-like samples were prepared by direct decomposition of a Zn(OH)42– precursor and by the sequential nucleation and growth method consisted of a multistep synthesis of complex nanostructured films. Condition-dependent experiments systematically were compared as to reveal the formation and detailed growth process of ZnO nanosized crystallites and aggregates. X-ray diffraction, transmission and scanning electron microscopy indicated that the precursor, solution basicity, reaction temperature and pressure as well as reaction time, were responsible for the variations of the morphologies. ZnO flower-like and large nanorods of exceptional uniformity, orientation alignment, and optical properties have been produced in this work. Several synthesis steps are needed to produce oriented nanostructures that are more complex than simple nanorod architectures. These structures have potential applications in building functional electronics devices and optoelectronic properties. more...

Abstract The nucleoplasmin family of histone chaperones is identified by a pentamer-forming domain and multiple acidic tracts that mediate histone binding and chaperone activity. Within this family, a novel domain organization was recently discovered that consists of an N-terminal nucleoplasmin-like (NPL) domain and a C-terminal FKBP peptidyl-proline isomerase domain. Saccharomyces cerevisiae Fpr4 is one such protein. Here we report that in addition to its known histone prolyl isomerase activities, the Fpr4 FKBP domain binds to nucleosomes and nucleosome arrays in vitro. This ability is mediated by a collection of basic patches that enable the enzyme to stably associate with linker DNA. The interaction of the Fpr4 FKBP with recombinant chromatin complexes condenses nucleosome arrays independently of its catalytic activity. Based on phylogenetic comparisons we propose that the chromatin binding ability of ‘basic’ FKBPs is shared amongst related orthologues present in fungi, plants, and insects. Thus, a subclass of FKBP prolyl isomerase enzymes is recruited to linker regions of chromatin. more...

During midbrain development, dopamine neuron differentiation occurs before birth. Epigenetic processes such as DNA methylation and demethylation as well as post-translational modification of histones occur during neurogenesis. Here, we administered histamine (HA) into the brain of E12 embryos in vivo and observed significant lower immunoreactivity of Lmx1a+ and Tyrosine Hydroxylase (TH)+ cells, with parallel decreases in the expression of early (Lmx1a, Msx1) and late (Th) midbrain dopaminergic (mDA) genes. With MeDIP assays we found that HA decreases the percentage of 5-methylcytosine of Pitx3 and Th, without changes in 5-hydroxymethylcytosine. Additionally, HA treatment caused a significant increase in the repressive epigenetic modifications H3K9me3 in Pitx3 and Th, and also more H3K27me3 marks in Th. Furthermore, HA has a long-term effect on the formation of the nigrostriatal and mesolimbic/mesocortical pathways, since it causes a significant decrease in midbrain TH immunoreactivity, as well as alterations in dopaminergic neuronal fibers, and significant lower TH-positive area in the forebrain in whole-mount stainings. These findings suggest that HA diminishes dopaminergic gene transcription by altering several epigenetic components related to DNA and histone modifications, which affects mDA neuron progression during development. more...

Social policies have been recognised as guiding narratives that promote and legitimise certain models of ageing. This finding, however, has been achieved by studies focussed on the reality of developed countries. Furthermore, little is known about how social policies promote age norms for later life in the context of developing countries. This research addresses this knowledge gap and focusses on the Chilean case, paying particular attention to what age norms are promoted by the two national ageing policies implemented by this country in 1996 and 2012. A critical discourse analysis method was used to identify the ways in which each policy conceptualises ageing as a social problem and the prescriptive behaviours and expectations that each policy promotes regarding old age. Results indicate that a rhetorical evolution can be observed in the analysed period, as each policy promotes different later life depictions and social norms. more...

A steady-state magneto-optical trap (MOT) of fermionic strontium atoms operating on the 7.5-kHz-wide ^{1}S_{0}-^{3}P_{1} transition is demonstrated. This MOT contains 8.4×10^{7}atoms, a loading rate of 1.3×10^{7}atoms/s, and an average temperature of 12μK. These parameters make it well suited to serve as a source of atoms for continuous-wave superradiant lasers operating on strontium's mHz-wide clock transition. Such lasers have only been demonstrated using pulsed Sr sources, limiting their range of applications. Our MOT makes an important step toward continuous operation of these devices, paving the way for continuous active optical clocks. more...

Resumen: Se propone la utilización de un controlador difuso sobre un modelo de estados mínimos con el fin de alcanzar un control de infusión de insulina continuo y eficiente en pacientes con T1DM. El sistema se apoya con un Filtro Extendido de Kalman para suplir las deficiencias de los dispositivos físicos actuales y estimar insulina remanente en el organismo con el fin de predecir su comportamiento futuro. El controlador sintonizado logra una respuesta restringida entre [80, 140] mgdl, con una media de 117, 6 mgdl y desviación estándar de 11, 3 mgdl sobre un conjunto de 365 realizaciones de 24 horas de control con 4 ingestas diarias. Estos resultados muestran que es posible diseñar controladores de baja complejidad que son fácilmente sintonizables por usuarios experimentados o médicos, con un nuevo enfoque de revisión en lazo cerrado. Además, la combinación de técnicas heurísticas con aquellas basadas en modelos permite sintentizar un controlador robusto frente al contexto real de aplicación y, también, administrar en forma eficiente el gasto de insulina. Aún así, la aplicacioón de un sistema completamente automatizado en un ser humano requerirá modelos de mayor dimensión para ajustarse a diferentes situaciones, un controlador de alta robustez y amplia adaptabilidad al organismo de cada paciente y su rutina de ingestas. Abstract: A fuzzy controller for a minimal states model is proposed to achieve a continuous and effcient insulin infusion in patients with Type 1 Diabetes. An Extended Kalman Filter is also applied to supply the deficiencies of the current glucose sensor technologies and estimate residual insulin in the system to predict future behavior. The controller is tuned manually and iteratively, and achieves closed-loop responses of glycemia constrained between [80,140] (mgdl), with a mean of 117, 6 (mgdl) and a standard deviation of 11, 3 (mgdl) over a whole year ensemble of 24-hour system responses with 4 meal intakes per day. These results show that is possible to design low complexity controllers that are easily tunable by experienced users or physicians focusing on a closed-loop system response analysis. Also, the combination of heuristic and model-based techniques allows to synthesize robust controllers for real application situations and, furthermore, effciently manage the insulin usage. Nevertheless, the actual application of a closed-loop system on a human being should require higher dimension models to fit different situations, a proven robust controller and wide adaptability to different patients and their meal intake routine. Palabras clave: Control biomédico, Control difuso, Filtros Extendidos de Kalman, Sistemas médicos, Sistemas no lineales, Keywords: Biomedical control, Extended Kalman Filters, Fuzzy control, Medical systems, Nonlinear systems more...

In this article we analyze the role of trust in the construction of social reality, arguing that it constitutes one of its essential components; namely, one that allows the creation, maintenance and collective recognition of institutions as well as their iteration and organization in subsystems. more...

Maar volcanoes are monogenetic landforms whose craters cut below the pre-eruptive surface and are surrounded by a tephra ring. Both the maar crater and the surrounding tephra rim deposits are typically formed due to magma–water explosive interactions. Northern Chile is located in the Central Volcanic Zone of the Andes where, in literature, 14 maars have been recognized as parasite (6) and individual (8) volcanoes. Amongst these individual maars, 3 of them, namely the Tilocálar Sur, Cerro Tujle, and Cerro Overo volcanoes, are not related to calderas and were emplaced more...

Social support and face-to-face learning may enhance outcomes for students who face barriers in accessing Massive Open Online Courses (MOOCs). In this study, we investigated how self-identified volunteer leaders guide and foster interactions among small groups of students who face technical and conceptual barriers in accessing MOOC content. Several months prior to the start of the MOOC (Environmental Education: Trans-disciplinary Approaches to Addressing Wicked Problems), we asked for volunteers among the registered students to lead groups for participants whose primary language was other than English and where limited Internet access, culture, or other barriers curtailed access to and understanding of course materials and pedagogy. Based on a survey and open-ended interviews (n=10), we found that group leaders were instrumental in overcoming barriers related to language, content, cultural ways of learning, access, and time. They also fostered cooperative learning strategies, which helped students acquire course content, and encouraged collaborative group projects leading to their groups adopting some features of online knowledge communities. We propose the term social learning MOOC (slMOOC) to capture a growing trend of incorporating collaborative learning strategies in xMOOCs. more...

El retorno de la democracia en la Argentina se caracterizó por el debate sobre los modos de enjuiciar a los responsables de la violencia del pasado inmediato y por la difusión masiva de los crímenes de la dictadura en el espacio público local. En este contexto, se produjo la aparición pública de un actor central del activismo en derechos humanos, cuyo papel fue fundamental en la visibilización de los crímenes del período 1976-1983: los sobrevivientes de los centros clandestinos de detención. Este artículo aborda la experiencia de esta porción de las víctimas de la represión durante los dos primeros años de democracia a partir de los sobrevivientes de “El Vesubio”, un lugar de detención ilegal ubicado en la provincia de Buenos Aires. A través del análisis de las acciones de denuncia realizadas por este grupo de sobrevivientes y del examen de las representaciones mediáticas de su figura, este trabajo pretende echar luz sobre el proceso histórico que condujo a la formación de una primera imagen pública de este segmento de las víctimas de la represión, asociada a la figura del testigo. more...

Background: Hepatitis C virus (HCV) contains a (+) ssRNA genome with highly conserved structural, functional RNA domains, many of them with unknown roles for the consecution of the viral cycle. Such genomic domains are candidate therapeutic targets. This study reports the functional characterization of a set of aptamers targeting the cis-acting replication element (CRE) of the HCV genome, an essential partner for viral replication and also involved in the regulation of protein synthesis. Methods: Forty-four aptamers were tested for their ability to interfere with viral RNA synthesis in a subgenomic replicon system. Some of the most efficient inhibitors were further evaluated for their potential to affect the recruitment of the HCV RNA-dependent RNA polymerase (NS5B) and the viral translation in cell culture. Results: Four aptamers emerged as potent inhibitors of HCV replication by direct interaction with functional RNA domains of the CRE, yielding a decrease in the HCV RNA levels higher than 90%. Concomitantly, one of them also induced a significant increase in viral translation (>50%). The three remaining aptamers efficiently competed with the binding of the NS5B protein to the CRE. Conclusions: Present findings confirm the potential of the CRE as an anti-HCV target and support the use of aptamers as molecular tools for investigating the functionality of RNA domains in viral genomes. more...