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El presente artículo busca analizar la tirantez producida entre el desarrollo del derecho constitucional a la protesta social –reunión pacífica, articulo 37 de la Constitución Política (1991) – y los derechos de las personas que no participan en ella. El artículo describe y analiza la línea jurisprudencial existente sobre la materia y presenta algunos comentarios guiados por el análisis económico del derecho y los métodos de interpretación constitucional.

The inherent poor sampling of fragment ions in time-of-flight mass analyzers was recently improved for data-dependent acquisition (DDA) by considering their drift times in traveling wave ion mobility spectrometry (TWIMS). Here, we extend this TWIMS-DDA approach to the data-independent acquisition (DIA) mode MS

El rol de la Corte Suprema en el sistema jurisdiccional de libre competencia ha tenido una creciente trascendencia en los últimos años, principalmente por medio del conocimiento del recurso de reclamación. En virtud de esto, este trabajo busca analizar algunas facetas clave para un efectivo diseño jurídico-institucional en la materia, planteando ciertas preguntas: ¿cuál es la naturaleza jurídica del recurso de reclamación?, ¿cómo diseñamos un sistema que balancee las potestades del Tribunal de Defensa de la Libre Competencia con las de la Corte Suprema? Finalmente, se hace una propuesta de lege ferenda que diferencia el recurso si se trata de un procedimiento contencioso o no contencioso.

Mas-related G protein-coupled receptor X1 (MRGPRX1) is a human sensory neuron-specific receptor and potential target for the treatment of pain. Positive allosteric modulators (PAMs) of MRGPRX1 have the potential to preferentially activate the receptors at the central terminals of primary sensory neurons and minimize itch side effects caused by peripheral activation. Using a high-throughput screening (HTS) hit, a series of thieno[2,3-d]pyrimidine-based molecules were synthesized and evaluated as human MRGPRX1 PAMs in HEK293 cells stably transfected with human MrgprX1 gene. An iterative process to improve potency and metabolic stability led to the discovery of orally available 6-(tert-butyl)-5-(3,4-dichlorophenyl)-4-(2-(trifluoromethoxy)phenoxy)thieno[2,3-d]pyrimidine (1t), which can be distributed to the spinal cord, the presumed site of action, following oral administration. In a neuropathic pain model induced by sciatic nerve chronic constriction injury (CCI), compound 1t (100 mg/kg, po) reduced behavioral heat hypersensitivity in humanized MRGPRX1 mice, demonstrating the therapeutic potential of MRGPRX1 PAMs in treating neuropathic pain.

Cognitive impairment is a common aspect of multiple sclerosis (MS) for which there are no treatments. Reduced brain N-acetylaspartylglutamate (NAAG) levels are linked to impaired cognition in various neurological diseases, including MS. NAAG levels are regulated by glutamate carboxypeptidase II (GCPII), which hydrolyzes the neuropeptide to N-acetyl-aspartate and glutamate. GCPII activity is upregulated multifold in microglia following neuroinflammation. Although several GCPII inhibitors, such as 2-PMPA, elevate brain NAAG levels and restore cognitive function in preclinical studies when given at high systemic doses or via direct brain injection, none are clinically available due to poor bioavailability and limited brain penetration. Hydroxyl-dendrimers have been successfully used to selectively deliver drugs to activated glia. Methods: We attached 2-PMPA to hydroxyl polyamidoamine (PAMAM) dendrimers (D-2PMPA) using a click chemistry approach. Cy5-labelled-D-2PMPA was used to visualize selective glial uptake in vitro and in vivo. D-2PMPA was evaluated for anti-inflammatory effects in LPS-treated glial cultures. In experimental autoimmune encephalomyelitis (EAE)-immunized mice, D-2PMPA was dosed biweekly starting at disease onset and cognition was assessed using the Barnes maze, and GCPII activity was measured in CD11b+ hippocampal cells. Results: D-2PMPA showed preferential uptake into microglia and robust anti-inflammatory activity, including elevations in NAAG, TGFβ, and mGluR3 in glial cultures. D-2PMPA significantly improved cognition in EAE mice, even though physical severity was unaffected. GCPII activity increased >20-fold in CD11b+ cells from EAE mice, which was significantly mitigated by D-2PMPA treatment. Conclusions: Hydroxyl dendrimers facilitate targeted drug delivery to activated microglia. These data support further development of D-2PMPA to attenuate elevated microglial GCPII activity and treat cognitive impairment in MS.

Introducción: En los últimos años, el sector construcción en Colombia, se ha ubicado en cuarto lugar entre los sectores económicos con mayor accidentalidad en el país, las cifras indican que de los 1.233 accidentes laborales en Colombia, 156 pertenecen al sector construcción. La capacitación en seguridad y salud en el trabajo juega un papel fundamental para reducir índices de accidentalidad. Se hace necesario implementar estrategias con herramientas de capacitación modernos e innovadores que logren persuadir y motivar a los trabajadores, promoviendo comportamientos seguros de trabajo. Objetivo: Mencionar algunas estrategias y herramientas digitales actualizadas para la capacitación en Seguridad y Salud en el Trabajo, en el sector construcción. Método: Revisión teórico descriptiva de tipo documental. Algunas bases de datos consultadas fueron, Medline, ScienceDirect, Scopus, SciELO, Proquest y Pubmed. Como criterio de selección, se incluyeron artículos en inglés y español a partir del año 2015 y algunos anteriores como referentes históricos. Se consideró un período de publicación mayor al 90% que cumpliera la publicación a partir del año 2015. De más de 80 trabajos consultados, 53 cumplieron los criterios de inclusión, además, se validó cada Descriptor en Ciencias de la Salud (Decs). Conclusiones: Existen diferentes estrategias y herramientas que podrían ser usadas para la capacitación en riesgos laborales, que van desde las actividades lúdicas, herramientas digitales y estrategias de participación activa del trabajador que permitan una mayor concientización y apropiación del conocimiento en materia de seguridad, incentivando la aplicación de prácticas seguras teniendo en cuenta su contexto crítico de accidentalidad.

Canavan disease (CD) is a progressive, fatal neurological disorder that begins in infancy resulting from a mutation in aspartoacyclase (ASPA), an enzyme that catalyzes the deacetylation of N-acetyl aspartate (NAA) into acetate and aspartate. Increased NAA levels in the brains of affected children are one of the hallmarks of CD. Interestingly, genetic deletion of N-acetyltransferase-8-like (NAT8L), which encodes aspartate N-aceyltransferase (ANAT), an enzyme responsible for the synthesis of NAA from l-aspartate and acetyl-CoA, leads to normalization of NAA levels and improvement of symptoms in several genetically engineered mouse models of CD. Therefore, pharmacological inhibition of ANAT presents a promising therapeutic strategy for treating CD. Currently, however, there are no clinically viable ANAT inhibitors. Herein we describe the development of fluorescence-based high throughput screening (HTS) and radioactive-based orthogonal assays using recombinant human ANAT expressed in E. coli. In the fluorescence-based assay, ANAT activity was linear with respect to time of incubation up to 30 min and protein concentration up to 97.5 ng/μL with Km values for l-aspartate and acetyl-CoA of 237 μM and 11 μM, respectively. Using this optimized assay, we conducted a pilot screening of a 10 000-compound library. Hits from the fluorescence-based assay were subjected to an orthogonal radioactive-based assay using L-[U-14C] aspartate as a substrate. Two compounds were confirmed to have dose-dependent inhibition in both assays. Inhibitory kinetics studies of the most potent compound revealed an uncompetitive inhibitory mechanism with respect to l-aspartate and a noncompetitive inhibitory mechanism against acetyl-CoA. The screening cascade developed herein will enable large-scale compound library screening to identify novel ANAT inhibitors as leads for further medicinal chemistry optimization.

Con el presente estudio de investigación, se pretendió obtener información relevante acerca del comportamiento de los consumidores de la empresa CASA LUKER en la zona sur de la ciudad de Bogotá, una vez de identificó una disminución significativa en la demanda de Chocolate Quesada durante dos periodos consecutivos. En ese sentido se propuso un estudio que permitió analizar las causas de la disminución de las ventas del chocolate Quesada en la zona sur de Bogotá, específicamente las localidades de Bosa y Tunjuelito. Se presenta un estudio mixto y transversal de estudio de caso, definido sobre la demanda de Chocolate Quesada en dos tiendas de la zona sur de Bogotá. Este trabajo de campo se realizó en dos fases. Por último, se realizó un análisis de las encuestas realizadas en los dos sectores cuya población tiene el mismo estrato socioeconómico y características similares, generando así las posibles soluciones que permita una mayor rotación del chocolate Quesada. Cabe resaltar el hecho de que la mayoría de personas encuestadas fue de sexo femenino, con un 71%, el estrato 2 fue el que más encuestados tuvo con un 70% seguido del estrato 1 con un 17%, así mismo el rango de edad al que se le realizaron la mayor cantidad de encuestas fue de 20 - 39 años. El 83% de la población encuestada afirmó reconocer el chocolate Quesada y, de estos, solo a un 32% manifestó no gustarle la nueva presentación. En general el comportamiento de estos estratos está encaminado a una relación de un precio medio con un buen sabor de chocolate y con un consumo un poco bajo, en donde sale a relucir el estrato 1, siendo este el único que tiene como presencia el precio más alto del mercado y sin ningún encuestado que prefiera el precio más bajo, a esto se adiciona el hecho de que su consumo sea un poco mayor al de los otros estratos analizados, concluyendo así que la mayoría de personas prefieren un consumo moderado y un precio medio para el chocolate.

Hand-to-Face transmission has been estimated to be a minority, yet non-negligible, vector of COVID-19 transmission and a major vector for multiple other pathogens. At the same time, as it cannot be effectively addressed with mainstream protection measures, such as wearing masks or tracing contacts, it remains largely untackled. To help address this issue, we have developed Saving Face - an app that alerts users when they are about to touch their faces, by analyzing the distortion patterns in the ultrasound signal emitted by their earphones. The system only relies on pre-existing hardware (a smartphone with generic earphones), which allows it to be rapidly scalable to billions of smartphone users worldwide. This paper describes the design, implementation and evaluation of the system, as well as the results of a user study testing the solution's accuracy, robustness, and user experience during various day-to-day activities (93.7% Sensitivity and 91.5% Precision, N=10). While this paper focuses on the system's application to detecting hand-to-face gestures, the technique can also be applicable to other types of gestures and gesture-based applications.

Los estudios sobre la influencia de los caminos heurísticos y sesgos cognitivos en el desarrollo de las funciones públicas, específicamente en el desarrollo del control y vigilancia fiscal, son de desarrollo ínfimo en Colombia. En consecuencia, el objetivo del presente artículo es realizar un análisis descriptivo sobre los principales hallazgos que marcan el estudio sobre la arquitectura de las decisiones humanas, en el marco del control y vigilancia fiscal en Colombia. Para este objetivo, se realizará especial énfasis en decantar la estructura del control y vigilancia fiscal y algunos resultados de su gestión que permitan detectar los efectos invisibles de algunos caminos heurísticos y sesgos sobre el proceso de adopción de decisiones en desarrollo del control fiscal. Studies on the influence of heuristic pathways and cognitive biases in the development of public functions, specifically in the development of fiscal control and surveillance are underdeveloped in Colombia. Consequently, the objective of this article is to carry out a descriptive analysis on the main findings that mark the study on the architecture of human decisions, demarcating them within the framework of fiscal control. For this objective, special emphasis will be placed on settling the structure of fiscal control and surveillance and some results. This analysis will detect the invisible effects of some heuristic paths and biases on the decision-making process in development of fiscal control.

Desde el siglo XVII, los sermones de António Vieira —considerado por Fernando Pessoa como el «Emperador de la lengua portuguesa»— se hicieron famosos en distintos territorios del orbe católico, al ser publicados tanto en portugués como en otras lenguas. Su obra ha sido objeto de admiración y de análisis académicos. En el mundo hispánico, su prestigio como predicador motivó diversas ediciones de sus sermones en español hasta mediados del siglo xviii, pero una edición crítica contemporánea era una labor aún por emprender. En este volumen se presentan cinco sermones de Vieira —uno de ellos traducido al español por primera vez— que muestran de manera clara los diferentes periodos de su vida y su postura frente a algunas de las problemáticas más importantes de la época: la función del predicador en la propagación de la fe católica, las discusiones dogmáticas que aún en el siglo xvii se estaban definiendo y la identidad política de un sujeto de la modernidad temprana. Adicionalmente, este volumen contiene tres artículos que analizan los sermones vieirianos, permitiéndole al lector contemporáneo tener un acercamiento crítico a la obra de un autor clave del barroco iberoamericano.

SYNGAP1is a major genetic risk factor for global developmental delay, autism spectrum disorder, and epileptic encephalopathy.De novoloss-of-function variants in this gene cause a neurodevelopmental disorder defined by cognitive impairment, social-communication disorder, and early-onset seizures. Cell biological studies in mouse and rat neurons have shown thatSyngap1regulates developing excitatory synapse structure and function, with loss-of-function variants driving formation of larger dendritic spines and stronger glutamatergic transmission. However, studies to date have been limited to mouse and rat neurons. Therefore, it remains unknown howSYNGAP1loss of function impacts the development and function of human neurons. To address this, we used CRISPR/Cas9 technology to ablateSYNGAP1protein expression in neurons derived from a commercially available induced pluripotent stem cell line (hiPSC) obtained from a human female donor. Reducing SynGAP protein expression in developing hiPSC-derived neurons enhanced dendritic morphogenesis, leading to larger neurons compared with those derived from isogenic controls. Consistent with larger dendritic fields, we also observed a greater number of morphologically defined excitatory synapses in cultures containing these neurons. Moreover, neurons with reduced SynGAP protein had stronger excitatory synapses and expressed synaptic activity earlier in development. Finally, distributed network spiking activity appeared earlier, was substantially elevated, and exhibited greater bursting behavior inSYNGAP1null neurons. We conclude thatSYNGAP1regulates the postmitotic maturation of human neurons made from hiPSCs, which influences how activity develops within nascent neural networks. Alterations to this fundamental neurodevelopmental process may contribute to the etiology ofSYNGAP1-related disorders.SIGNIFICANCE STATEMENTSYNGAP1is a major genetic risk factor for global developmental delay, autism spectrum disorder, and epileptic encephalopathy. While this gene is well studied in rodent neurons, its function in human neurons remains unknown. We used CRISPR/Cas9 technology to disruptSYNGAP1protein expression in neurons derived from an induced pluripotent stem cell line. We found that induced neurons lacking SynGAP expression exhibited accelerated dendritic morphogenesis, increased accumulation of postsynaptic markers, early expression of synapse activity, enhanced excitatory synaptic strength, and early onset of neural network activity. We conclude thatSYNGAP1regulates the postmitotic differentiation rate of developing human neurons and disrupting this process impacts the function of nascent neural networks. These altered developmental processes may contribute to the etiology ofSYNGAP1disorders.

Neutral sphingomyelinase 2 (nSMase2) catalyzes the cleavage of sphingomyelin to phosphorylcholine and ceramide, an essential step in the formation and release of exosomes from cells that is critical for intracellular communication. Chronic increase of brain nSMase2 activity and related exosome release have been implicated in various pathological processes, including the progression of Alzheimer’s disease (AD), making nSMase2 a viable therapeutic target. Recently, we identified phenyl (R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)-pyrrolidin-3-yl)carbamate 1 (PDDC), the first nSMase2 inhibitor that possesses both favorable pharmacodynamics and pharmacokinetic (PK) parameters, including substantial oral bioavailability, brain penetration, and significant inhibition of exosome release from the brain in vivo. Herein we demonstrate the efficacy of 1 (PDDC) in a mouse model of AD and detail extensive structure–activity relationship (SAR) studies with 70 analogues, unveiling several that exert similar or higher activity against nSMase2 with favorable pharmacokinetic properties.

This chapter examines how institutional imperialism technically shapes and politically frames national development in the dynamic relations between the world order and regions. The investigation focuses on the political economy of Colombia’s incorporation into the Organization of Economic Cooperation and Development (OECD) between 2010 and 2018. Departing from a critical global political economy (GPE) approach, the investigation critically explores the role assumed by the OECD as neutral and purely technical, analyzing the dynamics of power in the intersections of domestic-international economics. It shows how the OECD technically shapes and politically frames national development in key areas that define the international insertion of the country into the world economy, with domestic laws based on the Washington Consensus and post-Consensus. Three major conclusions are reached. The first is that international organizations can determine domestic policies of development with the aim of inserting peripheral countries within an imperialist economy so as to facilitate the transfer of value, as is shown to be the case with Colombia. The second contribution is how multilateral recommendations become central conditionalities that define the relationship between the international organization and the state but are presented as neutral and technical standards. Finally, the chapter describes how this dynamic of imperialist economic integration took form in several domestic policies in Colombia, presenting them as ‘better policies for development’.

SummaryLoss-of-function variants in SYNAGP1 cause a developmental encephalopathy defined by cognitive impairment, autistic features, and epilepsy. SYNGAP1 splicing leads to expression of distinct functional protein isoforms. Splicing imparts multiple cellular functions of SynGAP proteins through coding of distinct C-terminal motifs. However, it remains unknown how these different splice sequences function in vivo to regulate neuronal function and behavior. Reduced expression of SynGAP-α1/2 C-terminal splice variants in mice caused severe phenotypes, including reduced survival, impaired learning, and reduced seizure latency. In contrast, upregulation of α1/2 expression improved learning and increased seizure latency. Mice expressing α1-specific mutations, which disrupted SynGAP cellular functions without altering protein expression, promoted seizure, disrupted synapse plasticity, and impaired learning. These findings demonstrate that endogenous SynGAP isoforms with α1/2 spliced sequences promote cognitive function and impart seizure protection. Regulation of SynGAP-α expression or function may be a viable therapeutic strategy to broadly improve cognitive function and mitigate seizure.

Loss-of-function variants in

Con este trabajo se obtuvo una bebida funcional y natural en polvo a base de ingredientes naturales con alto contenido proteico mediante el proceso de secado por aspersión. Se evaluaron sensorialmente dos formulaciones de una bebida funcional, seleccionando solo una de ellas, la cual se sometió a las siguientes condiciones de operación: velocidad del disco atomizador (30,000 RPM), temperatura de entrada del aire (145 °C) y temperatura de salida del aire (80 °C). Aunado a lo anterior se realizó el análisis fisicoquímico y bromatológico tanto al alimento funcional en estado líquido como al obtenido en polvo con el fin de comparar su calidad nutricional. Las características fisicoquímicas y nutricionales, en particular el contenido proteico del producto funcional en polvo se conservó y una vez reconstituido en agua tuvo una buena aceptación sensorial.

Research shows that in unidirectional composites, fiber breaks and clusters of fiber breaks play a role in the failure onset of the composites [1]. So far, we know no attempts to the date have been made to analyze the fiber break development in short-aligned fiber composites, specifically using E-glass HYBON 2026. O[1]ur challenge is to determine whether there is a similar behavior in aligned short composites and its relationship with the microstructural parameter of fiber orientation distribution. This is important as it is measurable parameter to add value to recycled fiber composites. The more aligned the composite the higher mechanical properties and the higher the added value for recycling. We focused on using synchrotron x-ray computed tomography while performing hold-at-displacement scans to evaluate the fiber microstructure. We found the fiber breaks do not have the same orientation distribution as the non-broken fibers.

Canavan disease (CD) is a progressive, fatal neurological disorder that begins in infancy resulting from a mutation in aspartoacyclase (ASPA), an enzyme that catalyzes the deacetylation of

This article details an eclectic bibliometric method to study brand personality, identifying theoretical buildings and possible emerging research topics across marketing science fields. A mix of diverse bibliometric software and multiple correspondence analyses related to the topic supports considerations of four methodological phases, in particular: (1) research overview, (2) authors, (3) semantics, and (4) models. The bibliometric findings offer a catalog of BP research approaches. A comparison of research trends associated with renowned marketing science organizations and the current analyses suggest emerging research topics. Continued research should adopt and improve bibliometric methods and multiple correspondence analyses, despite to their heterogeneity.

El presente artículo de investigación es el resultado de la reflexión personal del autor acerca de los factores económicos y jurídicos que impulsaron al Gobierno de Colombia –Ministerio de Comercio, Industria y Turismo– a expedir un serie de normativas encaminadas a la creación de un mercado electrónico de facturas. El presente estudio descriptivo y explicativo se desarrolla bajo el análisis de la normativa expedida sobre el particular y sobre las condiciones de mercado existentes, haciéndose evidente un bajo nivel de inclusión financiera, así como el problema generalizado en la obtención de financiamiento externo por parte de las pequeñas y medianas empresas en Colombia, lo que impulsó una política pública de intervención en los mercados a fin de corregir las fallas expuestas, buscando generar fuentes alternativas de financiamiento para el segmento de pequeñas y medianas empresas en Colombia. This research article is the result of the author’s personal reflection on the economic and legal factors that led the Government of Colombia –Ministry of Commerce, Industry and Tourism– to issue a series of regulations aimed at the creation of an electronic market invoices. The present descriptive and explanatory study is developed under the analysis of the regulations issued and on the existing market conditions, this analysis evidenced a low level of financial inclusion, as well as the generalized problem in the obtaining of external financing by the Small and medium-sized enterprises in Colombia, the above allowed the issuance of a public policy of intervention in the markets in order to correct the market failures, seeking to generate alternative sources of financing for the referred segment of companies.

Neutral sphingomyelinase 2 (nSMase2), a key enzyme in ceramide biosynthesis, is a new therapeutic target for the treatment of neurological disorders and cancer. Using 2,6-dimethoxy-4-[4-phenyl-5-(2-thienyl)-1H-imidazol-2-yl]phenol (DPTIP), our initial hit compound (IC50 = 30 nM) from nSMase2 screening efforts, as a molecular template, a series of 4-(1H-imidazol-2-yl)-2,6-dialkoxyphenol derivatives were designed, synthesized, and evaluated. Systematic examination of various regions of DPTIP identified the key pharmacophore required for potent nSMase2 inhibition as well as a number of compounds with the 4-(1H-imidazol-2-yl)-2,6-dialkoxyphenol scaffold with similar or higher inhibitory potency against nSMase2 as compared to DPTIP. Among them, 4-(4,5-diisopropyl-1H-imidazol-2-yl)-2,6-dimethoxyphenol (25b) was found to be metabolically stable against P450 metabolism in liver microsomes and displayed higher plasma exposure following oral administration as compared to DPTIP. Analysis of plasma samples identified an O-glucuronide as the major metabolite. Blockade of the phase II metabolism should further facilitate our efforts to identify potent nSMase2 inhibitors with desirable ADME properties.

Bioorganic & medicinal chemistry 27(2), 255 - 264 (2019). doi:10.1016/j.bmc.2018.11.022, A series of carbamate-based inhibitors of glutamate carboxypeptidase II (GCPII) were designed and synthesizedusing ZJ-43, N-[[[(1S)-1-carboxy-3-methylbutyl]amino]carbonyl]-L-glutamic acid, as a molecular template inorder to better understand the impact of replacing one of the two nitrogen atoms in the urea-based GCPIIinhibitor with an oxygen atom. Compound 7 containing a C-terminal 2-oxypentanedioic acid was more potentthan compound 5 containing a C-terminal glutamic acid (2-aminopentanedioic acid) despite GCPII’s preferencefor peptides containing an N-terminal glutamate as substrates. Subsequent crystallographic analysis revealedthat ZJ-43 and its two carbamate analogs 5 and 7 with the same (S,S)-stereochemical configuration adopt anearly identical binding mode while (R,S)-carbamate analog 8 containing a D-leucine forms a less extensivehydrogen bonding network. QM and QM/MM calculations have identified no specific interactions in the GCPIIactive site that would distinguish ZJ-43 from compounds 5 and 7 and attributed the higher potency of ZJ-43 andcompound 7 to the free energy changes associated with the transfer of the ligand from bulk solvent to the proteinactive site as a result of the lower ligand strain energy and solvation/desolvation energy. Our findings underscorea broader range of factors that need to be taken into account in predicting ligand-protein binding affinity.These insights should be of particular importance in future efforts to design and develop GCPII inhibitors foroptimal inhibitory potency., Published by Elsevier, Amsterdam [u.a.]

Objetivo. Realizar una búsqueda de Hantavirus y Arenavirus en pequeños roedores y establecer su distribución espacial en diferentes ecosistemas del municipio de Villavicencio, departamento del Meta, Colombia. Materiales y método. Se realizó un estudio descriptivo de corte transversal, entre octubre de 2018 octubre de 2019 en zonas periurbanas y rurales del municipio de Villavicencio. Se capturaron roedores empleando trampas tipo Sherman. La detección molecular de Hantavirus se llevó a cabo usando cebadores forward SAHN-S y reverse SAHN-C y para Arenavirus cebadores forward GP878+ y reverse GP1126. Resultados. Un total de 50 roedores fueron capturados, el éxito de captura fue del 1.7%. Los roedores capturados pertenecían a 3 familias y 6 especies, las familias más frecuentes fueron Muridae (76%) Cricetidae (22%) y Echimydae (2%). Todas las muestras resultaron negativas para Hantavirus y Arenavirus. Conclusión. El estudio de pequeños roedores contribuye con la vigilancia de enfermedades transmitidas por estos mamíferos que actúan como reservorios.

Background Delirium is a frequent event in severely ill patients; its incidence and prevalence varies depending on several factors; Covid has been associated to high incidence of delirium leading to speculation of specific mechanisms of neurotoxicity by the SARS-CoV-2. We present the analysis of risk factors for delirium incidence and the impact of delirium in the functional outcomes. Methods We included patients admitted to a referral center in Cali, Colombia between April and August 2020. Patients were evaluated for demographics, severity of disease, comorbidities, clinical outcomes, delirium and survival at discharge. We evaluated the association of patient characteristics and disease factors with delirium incidence by multivariate analysis (Hosmer and Lemeshow) and the associations of delirium with functional outcome at discharge Results Among 333 patients, 58 (17.42%. 95% CI: 13.62–21.77%) presented delirium 16 (IQR: 11 − 20) days after symptom onset. Patients with delirium were older, reported muscular weakness more often, had a higher NEWS2 score at admission, and had more comorbidities (mainly Diabetes Mellitus II). Multivariate analysis of hospitalization events and treatments found mechanical ventilation as the only significant covariate. The association between need for mechanical ventilation and delirium development was estimated at OR = 11.72, (95%CI = 4.16–34.23). Patients who developed delirium had a higher frequency of functional impairment: mRs > 2 (70.7% vs 24.7%, p

Agile hardware design strategies have shown a fast adoption in academia and industry by bringing ideas from the software development side. However, adopted design methodologies exhibit traditional verification scenarios based on handmade testbenches. Here we describe a verification methodology for RISC-V-based processors with human-independent testbenches creation, employing high-effort verification methods throughout all processor design cycle. We demonstrated the methodology by performing verification tests in a single-issue in-order (SIIO) 32-bit RISC-V ISA based processor described in Chisel. In contrast to standard verification methods, the proposed methodology can detect bugs hard to isolate even after final FPGA implementations in-field. The generated test programs show higher coverage metrics, and χ 30 fewer instructions compared to official RISC-V torture unit tests.

© 2020 Owner/Author. Enhancing the empathy of our human interactions has been the object of intensive psychological studies for decades. The emergence of affective computing has opened the door towards technologically-enabled solutions. Yet, existing techniques struggle to attain their desired impact, often being difficult and expensive to deliver, and disconnected from daily life. Project Us' goal is to help overcome these challenges through a pair of wearable devices (in this case wristbands) that aim to trigger an empathy-enhancing effect, when being worn by two people during day-to-day conversations. The small-sized, wireless devices sense each person's electrodermal activity, associated with their level of emotional arousal, and share it to the other partner (when a threshold is exceeded) through a discreet, haptic nudge, creating a real-time feedback loop. The user study performed with 18 participants (nine romantically engaged couples) revealed that most of them found the wristbands to increase their level of awareness of the partner's emotional experience. Their interaction was analyzed based on interviews (qualitatively), and natural language processing techniques (quantitatively).

BACKGROUND: The National Examination of Knowledge in Medicine establishes the knowledge profile (PdC) a physician must possess to practice public medicine in Chile. However, no study has evaluated the perception of dermatology training regarding the acquisition of the minimum competencies required. This study described and compared the impressions of the dermatology training received by the University of Chile (UCh) graduates with graduates from other national and international faculties of medicine. MATERIALS AND METHODS: This was a cross-sectional study, based on a single survey model, applied via E-mail to registered physicians in an online database, with emphasis on UCh medicine graduates, from the generations 2012 to 2016. The data were collected anonymously, tabulated, and analyzed in MINITAB. RESULTS: From 908 UCh graduates, 141 surveys were answered (15.5%). Nine of 10 physicians considered “important” to obtain knowledge in dermatology. About 68.8% found the information they received was adequate. When comparing UCh graduates with other Chilean universities, UCh graduates had a slightly better impression of their training. When comparing Chilean versus foreign graduates, the latter presented a better perception of their preparation in cutaneous pathology. CONCLUSION: UCh graduates were satisfied with their dermatological training at the undergraduate level and felt better prepared than colleagues from other Chilean universities when facing cutaneous pathologies.

Reported work on minimum-energy (ME) computing for low-power applications has focused entirely on tracking solely the microprocessor ME voltage supply. However, the use of low-power systems requires accounting for regulator losses, voltage monitors, biasing, peripheral, clock sources, and start-up energies to adapt the correct ME supply to different operation modes. Here we demonstrate a 32-bit RISC-V IMAC based microcontroller (MCU) in 180nm CMOS technology featuring a low-energy always-on (AON) subsystem extending on ME adaption by including peripherals. AON peripherals enable the MCU for low-duty-cycle sensor node applications. Low-energy clock sources and voltage monitors enable 32.768kHz to 55MHz operation and power-gate the MCU into three power states adjusted to work at the ME supply operation. Measured start-up energies using integrated RC-based oscillators show restarting energies down to 6pJ, which is 1000X less than the energy required in MCUs that apply crystal oscillators.

En un contexto en el que la investigación artísitica en música («artistic research») se abre camino cada vez más rápido en el panorama educativo y en el que los estudiantes demenadan nuevas propuestas centradas en la investigación en las artes musicales, este artículo explora la oferta educativa a nivel de doctorado que, en la actualidad, está vigente en universidades y conservatorios superiores de música en Europa. Con un objetivo fundamentalmente práctico, se ofrece un estado de la cuestión que reflexiona sobre los parámetros fundamentales que todo estudiante que desee adentrarse en esta vía de investigación artísitica debe considerar. Asimismo, se recoge en una tabla adjunta la diversidad de títulos que contemplan este enfoque y se desglosan diversos parámetros que abarcan desde requisitos de admisión, hasta idiomas en los que se imparten estos estudios, créditos, duración, instituciones colaboradoras, formato de presencialidad, mecanismos de seguimiento, cuestiones relacionadas con la defensa de la tesis, áreas de estudio, precios y modalidades de financiación, entre otros aspectos. De esta manera, quienes se acerquen a este trabajo podrán seleccionar el centro que mejor se adecúe a sus necesidades, al mismo tiempo que obtendrán una visión global en torno al programa seleccionado. En suma, este artículo ofrece respuestas a la demanda actual de los músicos en la búsqueda de programas doctorales que unifiquen tanto la vía interpretativa/compositiva como la de investigación, y que se alejen de los enfoques tradicionales que, a veces únicos hace poco tiempo, ofertaban los centros de enseñanza superior. No dudamos que, con el tiempo, tanto esta tabla como el artículo se ampliarán, en paralelo a la difusión y adaptación que los centros hagan con este nuevo enfoque de estudios que se abre paso de forma lenta pero segura., In a context in which artisitic research in music is making its way more and more rapidly into the educational landscape and in which students are demanding new educational options focused on research in musical arts, this article explores the educational offer at the doctoral level that is currently presented by universities and conservatories of music in Europe. With a practical aim, this article offers a state of the art that reflects on the fundamental parameters that every student who wishes to enter this path of artistic research must consider. Likewise, the diversity of degrees that contemplate this approach is collected in an attached table where various parameters are presented, from admission requirements, to languages in which these studies are taught, credits, duration, collaborating institutions, attendance, mechanisms of monitoring the work, issues related to the viva, study areas, prices and financing modalities, among other aspects. In this way, those who approach this work will not only be able to select the center that best suits their needs, but will also obtain a global vision of selected program. In conclusion, this article offers answers to the current demand of musicians in search of doctoral programs that unifiy the interpretative/compositional path with that of research; programs whose approaches are far from the traditional ones that, sometimes unique until recently, were offered by higher education centers. We do not doubt that over time, both this table and the article will expand, in parallel with the dissemination and adaptation that this institutions will make of this new approach to research studies, which is slowly but surely gaining prominence.

Made available in DSpace on 2022-04-29T08:36:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Sucrose methacrylate (SM) is a key monomer for synthesizing biocompatible polymers with a carbohydrate core. However, controlled SM synthesis is challenging due to the possible formation of regio-isomers. This study describes SM synthesis that involves ultrasound irradiation of a homogeneous basic medium. The selectivity for mono-substituted SM was 86% within 30 min of reaction. The newly developed methodology is faster and more selective than that of mono-substituted SM synthesis already described in the literature. Universidad Santiago de Cali (USC) Facultad de Ciencias Básicas – Campus Pampalinda Sao Paulo State University (UNESP-IBILCE) Department of Chemistry and Environmental Sciences, Sao Jose Do Rio Preto Sao Paulo State University (UNESP-IBILCE) Department of Chemistry and Environmental Sciences, Sao Jose Do Rio Preto CAPES: 1760327 FAPESP: 2013/23886–4 FAPESP: 2017/13230–5 FAPESP: 2020/02471-4

Este trabajo consiste en recorrer la historia y estructura del sistema fiscal colombiano, bajo una perspectiva jurídica y económica, con miras a desentrañar su evolución y sus efectos en la realidad económica colombiana. This work consists of traversing the history and structure of the Colombian tax system, from a juridical and economic perspective, with a view to unraveling its evolution and its effects on the Colombian economic reality.

A series of thiophene-2-carboxylic acids and thiophene-3-carboxylic acids were identified as a new class of DAO inhibitors. Structure-activity relationship (SAR) studies revealed that small substituents are well-tolerated on the thiophene ring of both the 2-carboxylic acid and 3-carboxylic acid scaffolds. Crystal structures of human DAO in complex with potent thiophene carboxylic acids revealed that Tyr224 was tightly stacked with the thiophene ring of the inhibitors, resulting in the disappearance of the secondary pocket observed with other DAO inhibitors. Molecular dynamics simulations of the complex revealed that Tyr224 preferred the stacked conformation irrespective of whether Tyr224 was stacked or not in the initial state of the simulations. MM/GBSA indicated a substantial hydrophobic interaction between Tyr244 and the thiophene-based inhibitor. In addition, the active site was tightly closed with an extensive network of hydrogen bonds including those from Tyr224 in the stacked conformation. The introduction of a large branched side chain to the thiophene ring markedly decreased potency. These results are in marked contrast to other DAO inhibitors that can gain potency with a branched side chain extending to the secondary pocket due to Tyr224 repositioning. These insights should be of particular importance in future efforts to optimize DAO inhibitors with novel scaffolds.

Sor Francisca Josefa de la Concepcion fue una monja clarisa de la ciudad de Tunja que por orden de sus confesores jesuitas escribio una autobiografia titulada Vida , en la cual describe sus visiones misticas y suenos. El articulo expone que, debido a la relacion con sus confesores, su descripcion de dichas visiones sigue la tecnica de la compositio loci ensenada en los Ejercicios espirituales por Ignacio de Loyola. Al reconstruir su formacion intelectual, caracterizar su obra como parte de la escritura conventual femenina y ejemplificarla dentro de la retorica ignaciana, este articulo constituye un estudio de caso que muestra nuevas posibilidades de analizar la cultura visual colonial en la escritura y la oralidad, trascendiendo las fronteras de lo pictorico.

SYNGAP1 loss-of-function variants are causally associated with intellectual disability, severe epilepsy, autism spectrum disorder and schizophrenia. While there are hundreds of genetic risk factors for neurodevelopmental disorders (NDDs), this gene is somewhat unique because of the frequency and penetrance of loss-of-function variants found in patients combined with the range of brain disorders associated with SYNGAP1 pathogenicity. These clinical findings indicate that SYNGAP1 regulates fundamental neurodevelopmental processes that are necessary for brain development. Here, we describe four phenotypic domains that are controlled by Syngap1 expression across vertebrate species. Two domains, the maturation of cognitive functions and maintenance of excitatory-inhibitory balance, are defined exclusively through a review of the current literature. Two additional domains are defined by integrating the current literature with new data indicating that SYNGAP1/Syngap1 regulates innate survival behaviors and brain structure. These four phenotypic domains are commonly disrupted in NDDs, suggesting that a deeper understanding of developmental Syngap1 functions will be generalizable to other NDDs of known or unknown etiology. Therefore, we discuss the known molecular and cellular functions of Syngap1 and consider how these functions may contribute to the emergence of disease-relevant phenotypes. Finally, we identify major unexplored areas of Syngap1 neurobiology and discuss how a deeper understanding of this gene may uncover general principles of NDD pathobiology.

There are a number of clinically effective treatments for stress-associated psychiatric diseases, including major depressive disorder (MDD). Nonetheless, many patients exhibit resistance to first-line interventions calling for novel interventions based on pathological mechanisms. Accumulating evidence implicates altered glutamate signaling in MDD pathophysiology, suggesting that modulation of glutamate signaling cascades may offer novel therapeutic potential. Here we report that JHU-083, our recently developed prodrug of the glutaminase inhibitor 6-diazo-5-oxo-l-norleucine (DON) ameliorates social avoidance and anhedonia-like behaviors in mice subjected to chronic social defeat stress (CSDS). JHU-083 normalized CSDS-induced increases in glutaminase activity specifically in microglia-enriched CD11b+ cells isolated from the prefrontal cortex and hippocampus. JHU-083 treatment also reverses the CSDS-induced inflammatory activation of CD11b+ cells. These results support the importance of altered glutamate signaling in the behavioral abnormalities observed in the CSDS model, and identify glutaminase in microglia-enriched CD11b+ cells as a pharmacotherapeutic target implicated in the pathophysiology of stress-associated psychiatric conditions such as MDD.

Este trabajo consiste en delimitar el concepto de equidad a la luz de la Constitución de 1991. Al efecto, se analizan la principal jurisprudencia colombiana sobre el objeto de la investigación y algunas aportaciones desde la Economía que fungieron para estructurar los conceptos de equidad económica presentes en la anotada Constitución colombiana. This paper defines the concept of equity under the Constitution of 1991. For this porpuse it will be analyzed the main colombian jurisprudence related to this matter and some contributions from the economy who has served as a basis for structuring the concepts of equity in the colombian Constitution.

[(11)C]-PK11195 (PK11195) has been widely used with positron emission tomography (PET) to assess levels of the translocator protein 18 kDa (TSPO) as a marker of neuroinflammation. Recent ligands, such as [(11)C]-PBR28 and [(11)C]-DPA713, have improved signal-to-noise ratio and specificity for TSPO over PK11195. However, these second generation radiotracers exhibit binding differences due to a single polymorphism (rs6971) that leads to three genotypes: C/C, C/T and T/T associated with high, mixed and low binding affinities, respectively. Here we report that [(3)H]-DPA-713 in the presence of cholesterol or PK11195 has an accelerated dissociation rate from TSPO in platelets isolated from individuals with the T/T genotype. This allosteric interaction was not observed in platelets isolated from individuals with the C/C or C/T genotype. The results provide a molecular rationale for low binding affinity of T/T TSPO and further support the exclusion of these subjects from PET imaging studies using second generation TSPO ligands.

Myiasis is an infestation of tissues and organs of humans and animals by Diptera larvae (flies, horseflies, mosquitoes). They are located at different body sites, and classified clinically as cutaneous, visceral and cavitary. We report a 26-year-old woman with a history of seborrheic dermatitis and recent trip to Brazil. She presented with a seven days history of suppurating wounds in the parieto-occipital area of the scalp. At physical examination we found three ulcers of approximately 1.5 cm each, with multiple mobile larvae inside. The obtained larvae were analyzed, identifying Cochliomyia hominivorax larvae at L2 and L3 stages. The patient was managed successfully with oral antimicrobials and local cleansing. The screwworm Cochliomyia hominivorax in our country is rare. Known risk factors are wounds, poor personal hygiene, extreme ages, psychiatric disorders, presence of specific dermatosis such as psoriasis and seborrheic dermatitis, among others.

There is a pressing need to improve approaches for drug discovery related to neuropsychiatric disorders (NSDs). Therapeutic discovery in neuropsychiatric disorders would benefit from screening assays that can measure changes in complex phenotypes linked to disease mechanisms. However, traditional assays that track complex neuronal phenotypes, such as neuronal connectivity, exhibit poor scalability and are not compatible with high-throughput screening (HTS) procedures. Therefore, we created a neuronal phenotypic assay platform that focused on improving the scalability and affordability of neuron-based assays capable of tracking disease-relevant phenotypes. First, using inexpensive laboratory-level automation, we industrialized primary neuronal culture production, which enabled the creation of scalable assays within functioning neural networks. We then developed a panel of phenotypic assays based on culturing of primary neurons from genetically modified mice expressing HTS-compatible reporters that capture disease-relevant phenotypes. We demonstrated that a library of 1,280 compounds was quickly screened against both assays using only a few litters of mice in a typical academic laboratory setting. Finally, we implemented one assay in a fully automated high-throughput academic screening facility, illustrating the scalability of assays designed using this platform. These methodological improvements simplify the creation of highly scalable neuron-based phenotypic assays designed to improve drug discovery in CNS disorders.