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DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelates that give only a single isomer in solution when complexed with lanthanide (Ln(3+)) ions is of value for studying protein dynamics and interactions via NMR. Herein, we have investigated the geometries, energetics, and electrostatic potentials of Lu complexed with DOTA (1), ring methylated M4DOTA (2), and arm methylated R-DOTMA (3) and S-DOTMA (4), as well as, both ring and arm methylated 4S-4S-M4DOTMA (5) and 4S-4R-M4DOTMA (6) at the level of M06-L/6–31+G(d)-SDD, to elucidate the origin of the isomer stability. These analyses indicate that the electrostatic repulsion between the arm methyl and the neighboring carboxylate significantly destabilizes the square antiprism (SAP) isomer of Lu-5 and the twisted square antiprism (TSAP) isomer of Lu-6, while the steric repulsion between the ring and arm methyl groups attenuates the stability of both TSAP of Lu-5 and SAP of Lu-6. To rationalize the variable temperature proton NMR spectra, the energy barriers for the inter-conversion in Lu-5 and Lu-6 via arm rotation were also calculated. The modulation of the stability and rigidity of Ln complexes via a modification of DOTA is also discussed. Our investigation will aid to design better chelates for the Ln(3+) ions for its use in molecular medicine.

Understanding the functions of graphicons such as emojis, images, memes, videos, GIFs, emoticons, and stickers has become increasingly relevant as they have become extensively integrated into textual messages on Facebook, especially in group chats. This study aimed to investigate the forms and functions of graphicons used by young Filipino users (ages 18-31) on Facebook group chats. The datasets were extracted from the corpora, ten Facebook group chats, each lasting for three months, and analyzed using or computer-mediated discourse analysis or language-focused content analysis. According to the findings of this study, emoji was the most widely used graphicon by young Filipino users on Facebook, while sticker was the least. Adopting Herring and Dainas’ six functions of graphicons (2017), the researcher discovered additional five functions on Facebook group chats. These functions are identified as mention, reaction, riff, tone modification, action, narrative sequence, response, sharing, replacement, complement, and attention. It was also discovered that a graphicon could serve more than one function in a conversation. Tone modification was the most commonly used function, while the narrative sequence was the least. It was found out that in both emojis and emoticons, ‘tone modification’ was the most used function while ‘sharing’ in both images and videos. Meanwhile, ‘action’ was the most used function in GIFs, ‘attention’ in memes, and ‘mention’ in stickers. Because of the significantly increased use of online communication, this study may provide insight on how people may use these graphicons in their everyday conversations.

Objetivo. Analizar las tendencias investigativas en relación con el costeo de proyectos de la economía creativa. Métodos. Se desarrolló un análisis bibliométrico a partir de la base de datos Scopus, aplicando una ecuación de búsqueda y calculando indicadores de tipo bibliométricos como cantilidad, calidad e identificación de temas emergentes a partir de los documentos publicados entre 1970 y 2020. Resultados. Las industrias creativas ha sido un tema de interés de los investigadores desde el año 1997; sin embargo, se logra observar un crecimiento continuo a partir del año 2001, fecha que coincide con las primeras publicaciones realizadas por el profesor John Howkins, de igual forma se identifica que desde las ciencias sociales demuestran un mayor interés por la temática Conclusiones. Se evidencia un impacto y crecimiento del área de estudio, lo que valida la conveniencia de los proyectos de investigación orientados a las metodologías de costeo de proyectos de la industria creativa.

PURPOSE: PSMA overexpression has been associated with aggressive prostate cancer (PCa). However, PSMA PET imaging has revealed highly variable changes in PSMA expression in response to ADT treatment ranging from increases to moderate decreases. To better understand these PSMA responses and potential relationship to progressive PCa, the PET imaging agent, [(18)F]DCFPyL, was used to assess changes in PSMA expression in response to ADT using genomically characterized LuCaP patient-derived xenograft mouse models (LuCaP-PDXs) which were found to be sensitive to ADT (LuCaP73 and LuCaP136;CS) or resistant (LuCaP167;CR). METHODS: [(18)F]DCFPyL (2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) was used to assess PSMA in vitro (saturation assays) in LuCaP tumor membrane homogenates and in vivo (imaging/biodistribution) in LuCaP-PDXs. Control and ADT-treated LuCaPs were imaged before ADT (0 days) and 2-, 7-, 14-, and 21-days post-ADT from which tumor:muscle ratios (T:Ms) were determined and concurrently tumor volumes were measured (caliper). After the 21-day imaging, biodistributions and histologic/genomic (PSMA, AR) analysis were done. RESULTS: [(18)F]DCFPyL exhibited high affinity for PSMA and distinguished different levels of PSMA in LuCaP tumors. Post-ADT CS LuCaP73 and LuCaP136 tumor volumes significantly decreased at day 7 or 14 respectively vs controls, whereas the CR LuCaP167 tumor volumes were minimally changed. [(18)F]DCFPyL imaging T:Ms were increased 3–5-fold in treated LuCaP73 tumors vs controls, while treated LuCaP136 T:Ms remained unchanged which was confirmed by day 21 biodistribution results. For treated LuCaP167, T:Ms were decreased (~ 45 %) vs controls but due to low T:M values (

Aquacultivated sea cucumbers often suffer from SKin Ulceration Diseases (SKUDs). SKUDs have been observed in six holothuroid species from nine countries. All SKUDs present a similar symptom—the skin ulceration—and can be induced by bacteria, viruses, or abiotic factors. We here provide an update on SKUDs in holothuroids and analyse the case of the SKUD observed in Holothuria scabra in Madagascar. Field observations revealed a seasonality of the disease (i.e. wintertime maximum peak). Morphological analyses of integument ulcers showed that sea cucumbers react by forming a collagen fibre plug. Metagenomic analyses revealed a higher proportion of Vibrionaceae (Gammaproteobacteria) in ulcers in comparison to the healthy integument of the same individuals. Experimental infection assays were performed with ulcer crude extracts and bacteria isolated from these extracts (e.g. Vibrio parahaemolyticus) but did not significantly induce skin ulceration. Our results suggest that the disease is not induced by a pathogen or, at the very least, that the pathogen is not found within the ulcers as the disease is not transmissible by contact. An initial cause of the SKUD in Madagascar might be the repeated and prolonged exposures to cold temperatures. Opportunistic bacteria could settle in the dermis of ulcerated individuals and promote the ulcer extension. We propose a general nomenclature for SKUDs based on the acronym of the disease, the affected sea cucumber species (e.g. Hs for Holothuria scabra), the concerned region using an ISO code 3166-2 (e.g. MG for Madagascar), the description date (e.g. 20 for the year 2020), and, when known, the inducing agent (first letter of the general taxon, b for bacteria, v for virus in currently known cases; a a if it is an abiotic inducing parameter; nothing if the inducing cause has not been precisely identified). The disease described in this work will be designated under the name SKUD Hs-MG-20.

The autonomous vehicle is both an exciting yet complex field to dig in these past few years. Many have ventured out to develop Level 4 Autonomous Vehicle but up to this point, many issues were still arising about its safety, perception and sensing capabilities, tracking, and localization. This paper aims to address the struggles of developing an acceptable model for object detection in real-time. Object detection is one of the challenging areas of autonomous vehicles due to the limitations of the camera, lidar, radar, and other sensors, especially during night-time. There were various datasets and models available, but the number of samples, the labels, the occlusions, and other factors may affect the performance of the dataset. To address the mentioned problem, this study has undergone a rigorous process of scene selection and imitation to deal with the imbalance dataset, applied the state-of-the-art YOLO architecture for the model development. After the development process, the model was deployed in a multi-GPU architecture that lessens the computational load on a single GPU structure and was tested on a 12-meter fully electric autonomous bus. This study will lead to the development of a usable and safe autonomous bus that will lead the future of public transportation.

Polymethylated lanthanide 4S4R-M4DOTMA complexes bearing the ring methyl groups oriented in the SSSS position and the arm methyl groups in the RRRR configuration, exists exclusively as the SAP [Λ(δδδδ)] isomer in solution throughout the lanthanide series. This observation is in contrast to Ln-8S-M4DOTMA, which was recently reported to adopt the SAP [Λ(δδδδ)] isomer in the early lanthanides, while the late lanthanides adopt the TSAP [Δ(δδδδ)] isomer.(1) The methyl groups on the ring and the arm are both oriented in the SSSS configuration for Ln-8S-M4DOTMA.(1) Quantum chemical calculations for Pr- and Yb-4S4R-M4DOTMA indicate that the SAP isomer is significantly more stable. The luminescence profiles of Eu-8S-M4DOTMA and Eu-4S4R-M4DOTMA showed similar profiles signifying identical coordination environments. The hydration state, q, of the Eu(III) complexes showed q = 0.91–0.95, while the Tb-8S-M4DOTMA had q = 0.86. A much lower q value was obtained for Tb-4S4R-M4DOTMA (q = 0.67), which indicates an elongation of the Ln-Ow bond. At 400 MHz, the relaxivity of Gd-8S-M4DOTMA is 5.1 ± 0.1 mM(−1)s(−1) and 3.9 ± 0.1 mM(−1)s(−1) at 25 °C and 37 °C, respectively, whereas the relaxivity of Gd-4S4R-M4DOTMA is 4.6 ± 0.1 mM(−1)s(−1) at 25 °C and 3.6 ± 0.1 mM(−1)s(−1) at 37 °C. At 45 MHz, the relaxivity of Gd-8S-M4DOTMA is 5.4 ± 0.1 mM(−1)s(−1) and the relaxivity of Gd-4S4R-M4DOTMA is 4.5 ± 0.1 mM(−1)s(−1) at 25 °C. The temperature dependence of the (17)O NMR transverse relaxation rate of Gd-4S4R-M4DOTMA and Gd-8S-M4DOTMA revealed a 7- fold difference in the rate of water exchange (1/k(ex) = τ(M) = 9.0 ± 0.5 ns and 1/k(ex) = τ(M) = 60 ± 3 ns). The Pr(III) complex of 8S-M4DOTMA crystallized as TSAP isomer with an apical water. The presence of the apical water for the TSAP of Pr-8S-M4DOTMA was further confirmed with the observation that the fluoride ion replaces the bound water from the TSAP isomer of Pr-8S-M4DOTMA. This was shown by the disappearance of the TSAP peaks and appearance of a new set of less shifted resonances, which exchange with the SAP isomer as confirmed by NMR exchange spectroscopy (EXSY).

Drastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized 13C probes, which can effectively interrogate crucial metabolic activities, remains one of the major bottlenecks in this growing field. Here, we demonstrate [1-13C] N-acetyl cysteine (NAC) as a novel probe for hyperpolarized 13C MRI to monitor glutathione redox chemistry, which plays a central part of metabolic chemistry and strongly influences various therapies. NAC forms a disulfide bond in the presence of reduced glutathione, which generates a spectroscopically detectable product that is separated from the main peak by a 1.5 ppm shift. In vivo hyperpolarized MRI in mice revealed that NAC was broadly distributed throughout the body including the brain. Its biochemical transformation in two human pancreatic tumor cells in vitro and as xenografts differed depending on the individual cellular biochemical profile and microenvironment in vivo. Hyperpolarized NAC can be a promising non-invasive biomarker to monitor in vivo redox status and can be potentially translatable to clinical diagnosis.

RESUMEN. Introducción: La información acerca de lesiones en piel y sus factores asociados, en trabajadores informales en América Latina y el Caribe aun es escasa. Objetivo: Determinar la relación existente entre las condiciones sociodemográficas, ambientales, laborales y la prevalencia de afecciones en la piel auto-reportada por trabajadores informales “venteros” del centro de Medellín. Material y Métodos: Estudio transversal con intención analítica y fuente primaria de información. Se incluyeron 686 trabajadores. Se aplicó encuesta asistida, previa realización de prueba piloto y estandarización de los encuestadores. Variable dependiente; prevalencia de afecciones en piel. Variables independientes; condiciones laborales, sociodemográficas y ambientales. Se realizó control de errores con análisis estadísticos y sesgos de selección e información. Se realizaron análisis univariado, bivariado y multivariado. Resultados: Trabajadores fundamentalmente hombres (57.6%), edades entre 45-59 años, 60,0% procedente de zona rural. Trabajaban > 8 horas/día (80,6%), toda la semana, con > 20 años (50,7%) en su labor. El 72,2% no utilizaba mecanismos de protección personal. 61,5% consideraba que la contaminación ambiental afectaba su labor y su salud. 19,83% presentó afectaciones cutáneas, como; alergias (12,0%), prurito y sarpullido. Menor prevalencia de alergias en hombres (24,0%) y ≥ 60 años. Mayores prevalencias en quienes laboraban >8 horas/día (94,0%), toda la semana (43,0%), con exposición a sustancias químicas (RP=1,88.IC=1,11;3,20), vendedores de mercancía y cacharro (RP =2,06.IC: 1,08;3,91). Conclusión: Explican mayor prevalencia de alergias proceder de la zona urbana, vender mercancía y cacharro, trabajar >8 horas/día, toda la semana, exponerse a sustancias químicas, considerar que la calidad del aire afecta su labor, y presentar comorbilidades.

El presente informe tiene como objetivo dar a conocer uno de los temas más relevantes en la edad contemporánea como lo es la maternidad subrogada o gestación por sustitución como lo mencionan algunos autores, desde diversos puntos de vista tanto científicas, jurídicas, económicas y religiosas, con el fin de evidenciar los pros y contras de este tema tan polémico por las implicaciones éticas, idealistas, normativas y culturales que tiene.