Characterizing the Humoral Response to Flavivirus Infection

Flaviviruses are positive (+) sense, single-stranded RNA viruses of the Flaviviridae family that are transmitted by mosquitoes. For our studies, we focused on Zika virus (ZIKV) and Japanese encephalitis virus (JEV). Most human infections with ZIKV historically resulted in a mild self-limiting febrile illness. However, since 2013, a worldwide spread and increase in ZIKV infections has been observed. Notably, ZIKV has been associated with autoimmune ascending paralysis (Guillain-Barré Syndrome) and ophthalmologic effects in adults and intrauterine growth restriction and microcephaly in developing fetuses. Current vaccine efforts utilize technologies implemented for related flaviviruses (yellow fever virus (YFV), Dengue virus (DENV), and JEV) including subunit-based, chemically inactivated, and live-attenuated vaccines. Furthermore, co-circulation of flaviviruses, such as DENV and ZIKV in regions of South America, make it desirable to generate a vaccine that protects against both. JEV infections are usually clinically asymptomatic or result in a mild self-limiting febrile illness. However, disseminated infection and viral penetration of the blood-brain barrier into the central nervous system results in meningitis and encephalitis, which are associated with high morbidity and mortality. Children are especially vulnerable to neuroinvasion due to lack of prior immunity and the relative immaturity of their immune responses. Although vaccination programs in endemic countries have decreased the incidence of disease, existing vaccines have limitations including multiple dose requirements and reactogenicity. Finally, a major issue in vaccine efficacy is the derivation from genotype III (GIII) strains, the concurrent diversity of JEV worldwide, and the scarcity of efficacy testing across multiple genotypes. Currently, there are five genotypes of JEV that encompass approximately 100 unique strains. In addition, the dominant genotypes vary by country and are not static over time. We are interested in understanding the immunologic restriction of flavivirus infection by characterizing the interaction between viruses and the humoral response. We identified a panel of mouse and human derived anti-ZIKV monoclonal mAbs and found that ZIKV specific mAbs strongly neutralize multiple strains of ZIKV of Asian and African lineages compared to mAbs that recognize a cross-reactive determinant. Additionally, we identified a novel conformational inter-dimer epitope that when bound, results in significant reduction in in vitro infection and in vivo protection. We tested the prophylactic and therapeutic efficacy of the strongest neutralizing mAbs in adult male mice for lethality and pregnant female mice for transplacental protection of fetuses. We also tested a panel of anti-DENV mAbs derived from naturally infected patients. We confirmed that EDE1 mAbs, which have stronger virus binding in the absence of glycosylation compared to EDE2 mAbs, are more potent neutralizers of multiple ZIKV strains. We demonstrated that viral seeding of immune privileged sites, such as testis and fetus, occurs by the second day post-infection and mAb administration after this may reduce but not eliminate viral burden and effects in the acute and persistent stages of infection. For JEV, we generated a panel of mouse and human anti-JEV mAbs. We identified a subset of domain I and domain III specific mAbs that can neutralize JEV strains representative of four different genotypes. Subsequent in vivo testing demonstrated a broad range of effective doses that protected prior to and following infection with highly virulent strains of JEV representative of multiple genotypes. We anticipate that further understanding of epitope specificity for neutralization and protection is essential for understanding the efficacy of current (for JEV) and future (for ZIKV) vaccines to multiple strains and genotypes. Moreover, this will improve our understanding of correlates of protection of flavivirus vaccines which remain poorly understood, apart from YFV

Ordenamiento territorial con evaluación multicriterio

The project studied the best alternative of three scenarios of possible land use in the department of Huiliches, province of Neuquén. Ecological economy tools were combined to incorporate environmental and cultural values ​​as well as economic ones, with tools in geographic information systems. These tools generated a current productive scenario, a future scenario that followed the current development strategies, and another alternative scenario where activities that seek to transform the ideological bases of development were modified and incorporated. The ultimate goal of this project is to propose new management practices and new activities that, in addition to generating monetary gains, respect natural cycles and diverse cultural values. This information is intended to be a fundamental tool to address strategies of transition towards another style of development more harmonious with nature and, therefore, with society.El proyecto estudió la mejor alternativa de tres escenarios de posibles de uso del suelo en el departamento de Huiliches, provincia de Neuquén. Se combinaron herramientas de la economía ecológica para incorporar valores ambientales y culturales además de los económicos, con herramientas en sistemas de información geográfica. Con dichas herramientas se generó un escenario productivo actual, un escenario futuro que siguió las estrategias de desarrollo actuales, y otro escenario alternativo donde se modificaron e incorporaron actividades que buscan transformar las propias bases ideológicas del desarrollo. El fin último de este proyecto es proponer nuevas prácticas de manejo y nuevas actividades que, además de generar ganancias monetarias, respeten los ciclos naturales y los diversos valores culturales. Esta información pretende ser una herramienta fundamental para abordar estrategias de transición hacia otro estilo de desarrollo más armónico con la naturaleza y, por lo tanto, con la sociedad

El método de lectoescritura phonics en el desarrollo de las competencias del idioma inglés

La presente investigación tiene como objetivo determinar cómo el método Phonics mejora el desarrollo de las competencias del idioma inglés en los docentes de una I.E. de Trujillo, 2021. La investigación es de tipo aplicada, pues se ha tomado en cuenta el método Phonics para mejorar las competencias en el idioma inglés en los docentes de una I.E. de Trujillo, así mismo es pre experimental, debido a que se realizará un pretest y postest al momento de realizar el programa de Método Phonics. La investigación tiene como población 18 docentes de la I.E. Montessori International College de Trujillo. La técnica utilizada fue la encuesta, y su instrumento el cuestionario, mediante la rúbrica, que permitió la recolección de la información. Como resultados se obtuvo que los docentes presentaban un nivel medio para las dimensiones speaking y listening con 50 y 39% respectivamente y luego de la aplicación del programa se obtuvieron valores del 100% en nivel alto para cada dimensión. Y finalmente, como conclusión principal se confirmó la hipótesis general donde el método de lectoescritura Phonics influye en la mejora del desarrollo de las competencias de lecto-escritura del idioma inglés en los profesores del colegio Montessori International College de Trujillo, 2021

HELPING QUIET AND REMOTE PARTICIPANTS CONTRIBUTE MORE EFFECTIVELY TO TELECONFERENCES

Quiet and remote participants often have trouble contributing on conference calls when there is a dominant speaker. Meetings can be more effective when they include the perspectives of all attendees. Presented herein are techniques to combine visual analysis with monitoring of unmute/mute activities in order to notify meeting participants when a quiet or remote meeting participant wants to speak in a conference that is dominated by an active speaker

SPEECH AND SENTIMENT ANALYSIS TO PROVIDE SPOKEN LANGUAGE FEEDBACK TO SECOND-LANGUAGE LEARNERS AND SPEECH THERAPY PATIENTS

Language instruction and speech therapy are challenging endeavors. The different challenges that are associated with such endeavors have been exacerbated by the impact of coronavirus disease 2019 (COVID-19), where, for example, language instruction and speech therapy are increasingly taking place through teleconferences. To address the types of challenges that were described above, techniques are presented herein that encompass the combination of a phonetic understanding of a speaker\u27s utterance (as understood by, for example, a speech transcription engine coupled with knowledge of a speaker\u27s native language) with a sentiment analysis of a native and/or non-native speaker (obtained by, for example, performing facial recognition) to identify when a sound production problem is material. Such sentiment analysis can provide for the automated delivery of real-time feedback to language learners and speech therapy patients to help them effectively target the sounds that they are trying to produce. Aspects of the presented techniques may include displaying notifications (e.g., textual hints, pictures, video clips, etc.) to session participants to provide real-time feedback within collaboration systems

Cellular and humoral immunity protect against vaginal Zika virus infection in mice

ABSTRACT Zika virus (ZIKV), which can cause devastating disease in fetuses of infected pregnant women, can be transmitted by mosquito inoculation and sexual routes. Little is known about immune protection against sexually transmitted ZIKV. In this study, we show that previous infection through intravaginal or subcutaneous routes with a contemporary Brazilian strain of ZIKV can protect against subsequent intravaginal challenge with a homologous strain. Both routes of inoculation induced high titers of ZIKV-specific and neutralizing antibody in serum and the vaginal lumen. Virus-specific T cells were recruited to and retained in the female reproductive tract after intravaginal and subcutaneous ZIKV infection. Studies in mice with genetic or acquired deficiencies in B and/or T cells demonstrated that both lymphocyte populations redundantly protect against intravaginal challenge in ZIKV-immune animals. Passive transfer of ZIKV-immune IgG or T cells significantly limited intravaginal infection of naive mice, although antibody more effectively prevented dissemination throughout the reproductive tract. Collectively, our experiments begin to establish the immune correlates of protection against intravaginal ZIKV infection, which should inform vaccination strategies in nonpregnant and pregnant women. IMPORTANCE The recent ZIKV epidemic resulted in devastating outcomes in fetuses and may affect reproductive health. Unlike other flaviviruses, ZIKV can be spread by sexual contact as well as a mosquito vector. While previous studies have identified correlates of protection for mosquito-mediated infection, few have focused on immunity against sexual transmission. As exposure to ZIKV via mosquito bite has likely occurred to many living in areas where ZIKV is endemic, our study addresses whether this route of infection can protect against subsequent sexual exposure. We demonstrate that subcutaneous ZIKV infection can protect against subsequent vaginal infection by generating both local antiviral T cell and antibody responses. Our research begins to define the immune correlates of protection for ZIKV infection in the vagina and provides a foundation for testing ZIKV vaccines against sexual transmission. </jats:p

A Three-Dimensional Dynamic Supramolecular "Sticky Fingers" Organic Framework.

Engineering high-recognition host-guest materials is a burgeoning area in basic and applied research. The challenge of exploring novel porous materials with advanced functionalities prompted us to develop dynamic crystalline structures promoted by soft interactions. The first example of a pure molecular dynamic crystalline framework is demonstrated, which is held together by means of weak "sticky fingers" van der Waals interactions. The presented organic-fullerene-based material exhibits a non-porous dynamic crystalline structure capable of undergoing single-crystal-to-single-crystal reactions. Exposure to hydrazine vapors induces structural and chemical changes that manifest as toposelective hydrogenation of alternating rings on the surface of the [60]fullerene. Control experiments confirm that the same reaction does not occur when performed in solution. Easy-to-detect changes in the macroscopic properties of the sample suggest utility as molecular sensors or energy-storage materials

Patterns of brain atrophy in dysexecutive amnestic mild cognitive impairment raise confidence about prodromal AD dementia

Background: Prediction models aimed at detecting risk of progression from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) dementia increase their accuracy when impaired executive functions enter the analysis. This suggests that impaired executive functions in MCI are likely linked to the prodromal stages of AD dementia. Neuroimaging assessment of such patients would allow exploring if they show AD related patterns of brain atrophy. We hypothesized that AD sensitive brain regions would show discrimination between dysexecutive amnestic MCI (maMIC) and healthy controls. Method: We analysed 32 healthy controls and 23 MCI patients. Patients were divided in single domain amnestic MCI, multidomain amnestic MCI (i.e., with the dysexecutive component), and non-amnestic MCI. Brain volume data entered regression models to analyse which brain regions predict group membership (control vs maMCI). Stepwise lineal regression model was then conducted to identify the brain regions with better prediction power. Results: Four variables were able to predict group membership in simple lineal regression models: entorhinal cortex, lingual gyrus and parahippocampal gyrus in the left hemisphere and fusiform gyrus in the right hemisphere. The entorhinal cortex provided the most accurate model (F(1, 42) = 14.19, p=0.001, R2=0.24). Linear regression models were run with performance on executive function tasks including tests of switching, planning, verbal fluency and working memory. The most accurate model returned Letters and Numbers and categories fluency (F(2, 44) = 21.35, p=0.000, R2=0.48) suggesting that working memory and category generation are the functions contributing to the dysexecutive profiles observed in maMCI patients. Conclusion: Dysexecutive profiles in multidomain amnestic MCI together with neuroimaging volumetric analysis increase the probability of identifying the prodromal stages of AD dementia

Design and Analysis of Conformal Antenna for Future Public Safety Communications: Enabling Future Public Safety Communication Infrastructure

Future 4G wireless communication systems include, in their capabilities portfolio, emergency-specific needs, such as data support, broadband communication, and extremely high reliability. An emergency situation can be addressed with undoubtedly more chances of success if augmented information is enabled within the public safety communication novel capabilities. In this article, for a fully augmented information provision based on broadband transmission, a user-end (UE) communication-capabilities enhancement is addressed by deploying multiple antennas without compromising the portability and light weight of first-responder equipment. With this aim, we propose the design of a 4.9-GHz conformal antenna array at the rescuer side (integrated in a helmet) and evaluate its performance in terms of relative data rate gain. The conformal array design is based on traditional patch antennas that consider the need for deployment over an ellipsoidal surface. The antenna array is simulated and then built, and several parameter characterizations (bandwidth, radiation pattern, reflection coefficient, and MC) and measurements are undertaken to ensure the suitability of the design. Furthermore, an analysis of the specific absorption rate (SAR) is performed to guarantee that the exposure to electromagnetic fields is below the standardized levels.The authors would like to thank Prof. Eva Rajo-Iglesias from Universidad Carlos III de Madrid. This work has been partly funded by the Spanish Government through projects CIES (RTC-2015-4213-7), MIMOTEX (TEC2014-61776-EXP) and TERESAADA (TEC2017-90093-C3-2-R) (MINECO/AEI/FEDER, UE

Manejo clínico de la infección viral del herpes simple y Candidiasis oral: Reporte de un caso clínico

La infección por herpes simple tipo I es una de las enfermedades más frecuentes que afecta a la cavidad bucal, se manifiesta en forma de vesículas que tienden a remitir después de 10 a 12 días y es altamente recidivante. El siguiente trabajo tiene como finalidad presentar el caso clínico de un paciente con herpes simple recidivante intrabucal, acompañado de dolor intenso, con síntomas y signos clínicos persistentes por un largo periodo de tiempo, que no remitía con el tratamiento. Se detectó infección de Cándida Albicans acompañando al cuadro. Se realizaron análisis de laboratorio, incluyendo el test de Elisa para confirmar presencia de HIV resultando negativo, PCR para detección de VHS tipo 1 y cultivo de Cándida Albicans. Se trató la virosis con Aciclovir en altas dosis, la infección sobreagregada con nistatina y se indicó polivitamínicos para reforzar el huésped. El paciente fue tratado multidisciplinariamente y derivado al psicólogo por presentar un cuadro de estrés, lo que permitió disminuir la ansiedad del mismo ejerciendo un rol importante en el tratamiento.Fil: Gonzalez, Maria Mercedes. Universidad Nacional del Nordeste. Facultad de Odontologia; ArgentinaFil: Rosende, Roque O.. Universidad Nacional del Nordeste. Facultad de Odontologia; ArgentinaFil: Krupp, Sebastian. Universidad Nacional del Nordeste. Facultad de Odontologia; ArgentinaFil: Rosales, Carlos A.. Universidad Nacional del Nordeste. Facultad de Odontologia; ArgentinaFil: Fernandez, Estefania Raquel. Universidad Nacional del Nordeste. Facultad de Odontologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin