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We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.
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Ego , Autocontrol , Teorema de Bayes , Humanos , Proyectos de InvestigaciónRESUMEN
The present study evaluated the potential use of Twitter data for providing risk indices of STIs. We developed online risk indices (ORIs) based on tweets to predict new HIV, gonorrhea, and chlamydia diagnoses, across U.S. counties and across 5 years. We analyzed over one hundred million tweets from 2009 to 2013 using open-vocabulary techniques and estimated the ORIs for a particular year by entering tweets from the same year into multiple semantic models (one for each year). The ORIs were moderately to strongly associated with the actual rates (.35 < rs < .68 for 93% of models), both nationwide and when applied to single states (California, Florida, and New York). Later models were slightly better than older ones at predicting gonorrhea and chlamydia, but not at predicting HIV. The proposed technique using free social media data provides signals of community health at a high temporal and spatial resolution.
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Macrodatos , Infecciones por Chlamydia/epidemiología , Gonorrea/epidemiología , Infecciones por VIH/epidemiología , Medios de Comunicación Sociales , California/epidemiología , Infecciones por Chlamydia/diagnóstico , Estudios Transversales , Florida/epidemiología , Gonorrea/diagnóstico , VIH , Infecciones por VIH/diagnóstico , Humanos , New York/epidemiología , Salud Pública , Medición de Riesgo , Enfermedades de Transmisión Sexual/epidemiología , Estados Unidos/epidemiologíaRESUMEN
Passive immunization against ß-amyloid (Aß) has become an increasingly desirable strategy as a therapeutic treatment for Alzheimer's disease (AD). However, traditional passive immunization approaches carry the risk of Fcγ receptor-mediated overactivation of microglial cells, which may contribute to an inappropriate proinflammatory response leading to vasogenic edema and cerebral microhemorrhage. Here, we describe the generation of a humanized anti-Aß monoclonal antibody of an IgG4 isotype, known as MABT5102A (MABT). An IgG4 subclass was selected to reduce the risk of Fcγ receptor-mediated overactivation of microglia. MABT bound with high affinity to multiple forms of Aß, protected against Aß1-42 oligomer-induced cytotoxicity, and increased uptake of neurotoxic Aß oligomers by microglia. Furthermore, MABT-mediated amyloid plaque removal was demonstrated using in vivo live imaging in hAPP((V717I))/PS1 transgenic mice. When compared with a human IgG1 wild-type subclass, containing the same antigen-binding variable domains and with equal binding to Aß, MABT showed reduced activation of stress-activated p38MAPK (p38 mitogen-activated protein kinase) in microglia and induced less release of the proinflammatory cytokine TNFα. We propose that a humanized IgG4 anti-Aß antibody that takes advantage of a unique Aß binding profile, while also possessing reduced effector function, may provide a safer therapeutic alternative for passive immunotherapy for AD. Data from a phase I clinical trial testing MABT is consistent with this hypothesis, showing no signs of vasogenic edema, even in ApoE4 carriers.
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Enfermedad de Alzheimer/terapia , Péptidos beta-Amiloides/inmunología , Inmunoglobulina G/farmacología , Microglía/efectos de los fármacos , Microglía/metabolismo , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Animales Recién Nacidos , Receptor 1 de Quimiocinas CX3C , Células Cultivadas , Corteza Cerebral/citología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta Inmunológica , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/inmunología , Proteínas Fluorescentes Verdes/genética , Hipocampo/citología , Humanos , Inmunoglobulina G/metabolismo , Masculino , Ratones , Ratones Transgénicos , Microscopía Confocal , Persona de Mediana Edad , Mutación/genética , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/metabolismo , Placa Amiloide/inmunología , Placa Amiloide/metabolismo , Placa Amiloide/patología , Presenilina-1/genética , Unión Proteica/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Quimiocina/genética , Estadísticas no Paramétricas , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Increasing evidence implicates Aß peptides self-assembly and fibril formation as crucial events in the pathogenesis of Alzheimer disease. Thus, inhibiting Aß aggregation, among others, has emerged as a potential therapeutic intervention for this disorder. Herein, we employed 3-aminopyrazole as a key fragment in our design of non-dye compounds capable of interacting with Aß42 via a donor-acceptor-donor hydrogen bond pattern complementary to that of the ß-sheet conformation of Aß42. The initial design of the compounds was based on connecting two 3-aminopyrazole moieties via a linker to identify suitable scaffold molecules. Additional aryl substitutions on the two 3-aminopyrazole moieties were also explored to enhance π-π stacking/hydrophobic interactions with amino acids of Aß42. The efficacy of these compounds on inhibiting Aß fibril formation and toxicity in vitro was assessed using a combination of biophysical techniques and viability assays. Using structure activity relationship data from the in vitro assays, we identified compounds capable of preventing pathological self-assembly of Aß42 leading to decreased cell toxicity.
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Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/química , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/química , Pirazoles/química , Línea Celular Tumoral , Citotoxinas/antagonistas & inhibidores , Citotoxinas/química , Humanos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Secundaria de Proteína , Relación Estructura-ActividadRESUMEN
Many people engage with a diverse array of social media platforms, raising concerns that this diversity of platforms may be linked to negative affect, hypothesized to arise from multitasking or identify diffusion. Using a large representative sample (N = 1,372) of US adults from the authoritative General Social Survey, we examine associations between social media diversity and well-being and propose a self-selection explanation for these associations. Even without accounting for selection bias, we find few and only small associations. Importantly, after using a rigorous propensity-score weighting technique to adjust for selection bias, these associations disappear. Further, we also document few negative associations between the use of specific social media platforms and well-being. Our findings suggest that (i) diverse social media use is not a major risk factor to adult well-being; (ii) negative correlations reported in the literature may be spurious; (iii) technology use research needs to take self-selection biases seriously.
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OBJECTIVES: To understand whether health insurance coverage of vaccine costs and discussing vaccination with a healthcare provider are necessary for trust in CDC (Centers for Disease Control) to increase the uptake of the vaccine. METHOD: A nationally representative sample of 2,549 adults from the United States answered questions about trust in CDC, insurance coverage, interactions with healthcare providers, and risk perceptions, and then provided longitudinal reports of actual vaccination against influenza during the course of the 2018-19 flu season. RESULTS: Trust in CDC as a source of information on vaccines was a strong precursor of vaccination. According to multilevel regressions, however, this effect was localized to respondents who had insurance coverage or whose providers discussed the vaccine with them. Further, the effect of trust was even stronger when both insurance coverage and healthcare provider discussions were present. CONCLUSIONS: Environmental factors supportive of vaccination increased the positive influence of trust in CDC on vaccine uptake by almost 50 percent. Insurance companies and healthcare providers can promote vaccination by covering the costs of vaccination and discussing vaccines in personalized conversations with patients.
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Vacunas contra la Influenza , Gripe Humana , Adulto , Humanos , Gripe Humana/prevención & control , Salud Pública , Confianza , Estados Unidos , VacunaciónRESUMEN
Driven by the growing threat of antimicrobial resistance, the design of intrinsically bactericidal surfaces has been gaining significant attention. Proposed surface topography designs are often inspired by naturally occurring nanopatterns on insect wings that mechanically damage bacteria via membrane deformation. The stability of and the absence of chemicals in such surfaces support their facile and sustainable employment in avoiding surface-born pathogen transmission. Recently, the deflection of controllably nanofabricated pillar arrays has been shown to strongly affect bactericidal activity, with the limits of mechanical effectiveness of such structures remaining largely unexplored. Here, we examine the limits of softer, commonly used polymeric materials and investigate the interplay between pillar nanostructure sizing and flexibility for effective antibacterial functionality. A facile, scalable, UV nanoimprint lithography method was used to fabricate nanopillar array topographies of variable sizes and flexibilities. It was found that bacterial death on nanopillars in the range of diameters ≤100 nm and Young's moduli ≥1.3 GPa is increased by 3.5- to 5.6-fold, while thicker or softer pillars did not reduce bacterial viability. To further support our findings, we performed a finite element analysis of pillar deformation. It revealed that differences in the amount of stress exerted on bacterial membranes, generated from the stored elastic energy in flexible pillars, contribute to the observed bactericidal performance.
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Nanoestructuras , Polímeros , Animales , Antibacterianos/farmacología , Bacterias , Viabilidad Microbiana , Nanoestructuras/química , Polímeros/farmacologíaRESUMEN
Migration has been proposed as one of the factors that shape cultural similarities across countries. However, studying the relationship between culture and migration has been challenging, in part because culture is difficult to quantify. The traditionally used survey questionnaires have a number of drawbacks, including that they are costly and difficult to scale to a large number of countries. To complement survey data, we propose the use of passively-collected digital traces from social media. We focus on food and drink as markers of a country's culture. We then measure similarities between countries in terms of food and drink interests using aggregated data from the Facebook Advertising Platform. Methodologically, we offer approaches to measure the similarity between countries with both symmetric and asymmetric indices. Substantively, we assess the association between migration cultural similarity between countries by comparing our measure of cultural similarity with international migration data. In most countries, larger immigrant populations are associated with more similar food and drink preferences between their country of origin and the country of destination. Our results suggest that immigrants contribute to bringing the culture of their home countries to new countries. Moreover, our study identifies considerable variability in this pattern across countries.
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Medios de Comunicación SocialesRESUMEN
Collective cellular behavior in confluent monolayers supports physiological and pathological processes of epithelial development, regeneration, and carcinogenesis. Here, the attainment of a mature and static tissue configuration or the local reactivation of cell motility involve a dynamic regulation of the junctions established between neighboring cells. Tricellular junctions (tTJs), established at vertexes where three cells meet, are ideally located to control cellular shape and coordinate multicellular movements. However, their function in epithelial tissue dynamic remains poorly defined. To investigate the role of tTJs establishment and maturation in the jamming and unjamming transitions of epithelial monolayers, a semi-automatic image-processing pipeline is developed and validated enabling the unbiased and spatially resolved determination of the tTJ maturity state based on the localization of fluorescent reporters. The software resolves the variation of tTJ maturity accompanying collective transitions during tissue maturation, wound healing, and upon the adaptation to osmolarity changes. Altogether, this work establishes junctional maturity at tricellular contacts as a novel biological descriptor of collective responses in epithelial monolayers.
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Simple, self-posed questions may modulate behavioral repetition of choices in situations that are neither fully habitual nor fully intentional. In six experiments, participants were trained to repeatedly choose their preferred door out of an array of three doors. Questions generally increased speed in the upcoming task, supporting past findings that even exposure to question-like syntax can enhance performance. More importantly, affirmatively phrased questions like Which one should I choose?, framed either as an instruction to make the choice or as material unrelated to the study, produced more choice repetition than presenting either no question at all or a control question. In contrast, negatively phrased questions like Which one should I not choose? decreased behavior repetition. These effects allowed efficient and fast responding and thus showed features of automaticity. These findings imply that self-talk questions can affect choices in various domains of interest to social, clinical, educational, and health psychology.
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This research aimed to determine the nature of social media discussions about HIV. With the goal of conducting a descriptive analysis, we collected almost 1,000 tweets posted February to September 2015. The sample of tweets included keywords related to HIV or behavioral risk factors (e.g., sex, drug use) and was coded for content (e.g., HIV), behavior change strategies, and message source. Seven percent of tweets concerned HIV/AIDS, which were often referred to as jokes or insults. The majority of tweets coded as behavior change attempts involved attitude change strategies. The majority of the tweets (80%) came from private users (vs. organizations). Different types of sources employed different types of behavior change strategies: For instance, private users, compared to experts or organizations, included more strategies to decrease detrimental attitudes (29% versus 6%, p < .001), and also more strategies to counter myths and misinformation (6% versus 1%, p = .008). In summary, tweets related to HIV/AIDS and associated risk factors frequently use the terms in jokes and insults, come largely from private users, and entail attitudinal and informational strategies. Online health campaigns with clear calls to action and corrections of misinformation may make important contributions to social media conversations about HIV/AIDS.
Esta investigación tuvo el objectivo de caracterizar las discusiones sobre VIH en los medios sociales. Con el objetivo de realizar un análisis descriptivo, recogimos alrededor de mil tweets entre febrero y septiembre del 2015. Estos tweets fueron seleccionados si incluían palabras claves relacionadas con el VIH o con factores de riesgo conductual tales como sexo o uso de drogas. Cuatro codificadores clasificaron los tweets en función del contenido (e.g., el VIH como enfermedad, referido a un product o servicio), la estrategia de cambio conductual (cambio conductual, llamada a la acción, o corrección de mitos), y la fuente del mensaje (e.g., usuarios privados, expertos, empresas comerciales). La mayoría de los tweets (80%) provenía de usuarios privados en lugar de institucionales. El 7% de los tweets se refería estrictamente al VIH u otras infecciones de transmisión sexual, frecuentemente utilizando esos términos como bromas o insultos, tales como escribir que una experiencia displacentera "me dio SIDA". La mayoría de los intentos de cambio conductual incluía estrategias de reducción de actitudes negativas. Fuentes de distintos tipos empleaban estrategias de cambio conductual de distintos tipos. Por ejemplo, usuarios privados (comparados con expertos, organizaciones comerciales, y otras organizaciones, tal como periódicos y ONGs), publicaban más mesajes clasificados como estrategias de promoción de actitudes negativas (29% versus 6%, p < .001), y tenían más correcciones de mitos (6% versus 1%, p = .008). En resumen, los tweets que mencionan el VIH o factores de riesgo de VIH utilizan los términos en bromas e insultos con gran frecuencia, provienen mayormente de usuarios privados, e incluyen estrategias de cambio de actitud. Las campañas de Internet con llamadas claras a la acción y con correcciones de mitos pueden hacer contribuciones importantes a las conversaciones sobre VIH en los medios sociales.
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OBJECTIVES: Social media messages have been increasingly used in health campaigns about prevention, testing, and treatment of HIV. We identified factors leading to the retransmission of messages from expert social media accounts to create data-driven recommendations for online HIV messaging. DESIGN AND METHODS: We sampled 20â201 HIV-related tweets (posted between 2010 and 2017) from 37 HIV experts. Potential predictors of retransmission were identified based on prior literature and machine learning methods, and were subsequently analyzed using multilevel negative binomial models. RESULTS: Fear-related language, longer messages, and including images (e.g. photos, gif, or videos) were the strongest predictors of retweet counts. These findings were similar for messages authored by HIV experts, and also messages retransmitted by experts, but created by nonexperts (e.g. celebrities or politicians). CONCLUSIONS: Fear appeals affect how much HIV messages spread on Twitter, as do structural characteristics, like the length of the tweet and inclusion of images. A set of five data-driven recommendations for increasing message spread is derived and discussed in the context of current centers for disease control and prevention social media guidelines.
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Terapia Conductista/métodos , Transmisión de Enfermedad Infecciosa/prevención & control , Infecciones por VIH/prevención & control , Educación en Salud/métodos , Medios de Comunicación Sociales , Infecciones por VIH/diagnóstico , HumanosRESUMEN
Dynamic combinatorial chemistry (DCC) is a recently introduced supramolecular approach to generate libraries of chemical compounds based on reversible exchange processes. The building elements are spontaneously and reversibly assembled to virtually encompass all possible combinations, allowing for simple one-step generation of complex libraries. The method has been applied to a variety of combinatorial systems, ranging from synthetic models to materials science and drug discovery, and enables the establishment of adaptive processes due to the dynamic interchange of the library constituents and its evolution toward the best fit to the target. In particular, it has the potential to become a useful tool in the direct screening of ligands to a chosen receptor without extensive prior knowledge of the site structure, and several biological systems have been targeted. In the vast field of glycoscience, the concept may find special perspective in response to the highly complex nature of carbohydrate-protein interactions. This chapter summarises studies that have been performed using DCC in biological systems, with special emphasis on glycoscience.
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Carbohidratos/química , Técnicas Químicas Combinatorias , Proteínas/química , Anhidrasas Carbónicas/química , Disulfuros/química , Iminas/química , Biología Molecular , Neuraminidasa/química , Biblioteca de Péptidos , beta-Galactosidasa/químicaRESUMEN
Abstract: This research aimed to determine the nature of social media discussions about HIV. With the goal of conducting a descriptive analysis, we collected almost 1,000 tweets posted February to September 2015. The sample of tweets included keywords related to HIV or behavioral risk factors (e.g., sex, drug use) and was coded for content (e.g., HIV), behavior change strategies, and message source. Seven percent of tweets concerned HIV/AIDS, which were often referred to as jokes or insults. The majority of tweets coded as behavior change attempts involved attitude change strategies. The majority of the tweets (80%) came from private users (vs. organizations). Different types of sources employed different types of behavior change strategies: For instance, private users, compared to experts or organizations, included more strategies to decrease detrimental attitudes (29% versus 6%, p < .001), and also more strategies to counter myths and misinformation (6% versus 1%, p = .008). In summary, tweets related to HIV/AIDS and associated risk factors frequently use the terms in jokes and insults, come largely from private users, and entail attitudinal and informational strategies. Online health campaigns with clear calls to action and corrections of misinformation may make important contributions to social media conversations about HIV/AIDS.
Resumen: Esta investigación tuvo el objetivo de caracterizar las discusiones sobre VIH en los medios sociales. Con el objetivo de realizar un análisis descriptivo, recogimos alrededor de mil tweets entre febrero y septiembre del 2015. Estos tweets fueron seleccionados si incluían palabras claves relacionadas con el VIH o con factores de riesgo conductual tales como sexo o uso de drogas. Cuatro codificadores clasificaron los tweets en función del contenido (e.g., el VIH como enfermedad, referido a un producto o servicio), la estrategia de cambio conductual (cambio conductual, llamada a la acción, o corrección de mitos), y la fuente del mensaje (e.g., usuarios privados, expertos, empresas comerciales). La mayoría de los tweets (80%) provenía de usuarios privados en lugar de institucionales. El 7% de los tweets se refería estrictamente al VIH u otras infecciones de transmisión sexual, frecuentemente utilizando esos términos como bromas o insultos, tales como escribir que una experiencia displacentera "me dio SIDA". La mayoría de los intentos de cambio conductual incluía estrategias de reducción de actitudes negativas. Fuentes de distintos tipos empleaban estrategias de cambio conductual de distintos tipos. Por ejemplo, usuarios privados (comparados con expertos, organizaciones comerciales, y otras organizaciones, tal como periódicos y ONGs), publicaban más mensajes clasificados como estrategias de promoción de actitudes negativas (29% versus 6%, p < .001), y tenían más correcciones de mitos (6% versus 1%, p = .008). En resumen, los tweets que mencionan el VIH o factores de riesgo de VIH utilizan los términos en bromas e insultos con gran frecuencia, provienen mayormente de usuarios privados, e incluyen estrategias de cambio de actitud. Las campañas de Internet con llamadas claras a la acción y con correcciones de mitos pueden hacer contribuciones importantes a las conversaciones sobre VIH en los medios sociales.
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Dynamic combinatorial chemistry (DCC) has emerged as an efficient approach to receptor/ligand identification based on the generation of combinatorial libraries by reversible interconversion of the library constituents. In this study, the implementation of such libraries on carbohydrate-lectin interactions was examined with the plant lectin Concanavalin A as a target species. Dynamic carbohydrate libraries were generated from a pool of carbohydrate aldehydes and hydrazide linker/scaffold components through reversible acylhydrazone exchange, resulting in libraries containing up to 474 constituents. Dynamic deconvolution allowed the efficient identification of the structural features required for binding to Concanavalin A and the selection of a strong binder, a tritopic mannoside, showing an IC(50)-value of 22 microM.