Using Priming to Study Social Categorization

Do people spontaneously categorize stereotypically masculine and stereotypically feminine trait and job labels according to gender? The present experiment provided a methodologically stringent test of automatic gender-based categorization using a modification of a semantic priming methodology. Subjects processing goals were manipulated by asking questions about primes that either did or did not require semantic processing. Results provide support for a spontaneous gender-based categorization of trait labels regardless of the processing goals. However, semantic processing goals appear to be necessary for a spontaneous gender-based categorization of job labels

Convergent communication, sensing and localization in 6g systems: An overview of technologies, opportunities and challenges

Herein, we focus on convergent 6G communication, localization and sensing systems by identifying key technology enablers, discussing their underlying challenges, implementation issues, and recommending potential solutions. Moreover, we discuss exciting new opportunities for integrated localization and sensing applications, which will disrupt traditional design principles and revolutionize the way we live, interact with our environment, and do business. Regarding potential enabling technologies, 6G will continue to develop towards even higher frequency ranges, wider bandwidths, and massive antenna arrays. In turn, this will enable sensing solutions with very fine range, Doppler, and angular resolutions, as well as localization to cm-level degree of accuracy. Besides, new materials, device types, and reconfigurable surfaces will allow network operators to reshape and control the electromagnetic response of the environment. At the same time, machine learning and artificial intelligence will leverage the unprecedented availability of data and computing resources to tackle the biggest and hardest problems in wireless communication systems. As a result, 6G will be truly intelligent wireless systems that will provide not only ubiquitous communication but also empower high accuracy localization and high-resolution sensing services. They will become the catalyst for this revolution by bringing about a unique new set of features and service capabilities, where localization and sensing will coexist with communication, continuously sharing the available resources in time, frequency, and space. This work concludes by highlighting foundational research challenges, as well as implications and opportunities related to privacy, security, and trust

Reversed-phase liquid chromatography coupled on-line to estrogen receptor bioaffinity detection based on fluorescence polarization

We describe the development and validation of a high-resolution screening (HRS) platform which couples gradient reversed-phase high-performance liquid chromatography (RP-HPLC) on-line to estrogen receptor α (ERα) affinity detection using fluorescence polarization (FP). FP, which allows detection at high wavelengths, limits the occurrence of interference from the autofluorescence of test compounds in the bioassay. A fluorescein-labeled estradiol derivative (E2-F) was synthesized and a binding assay was optimized in platereader format. After subsequent optimization in flow-injection analysis (FIA) mode, the optimized parameters were translated to the on-line HRS bioassay. Proof of principle was demonstrated by separating a mixture of five compounds known to be estrogenic (17β-estradiol, 17α-ethinylestradiol and the phytoestrogens coumestrol, coumarol and zearalenone), followed by post-column bioaffinity screening of the individual affinities for ERα. Using the HRS-based FP setup, we were able to screen affinities of off-line-generated metabolites of zearalenone for ERα. It is concluded that the on-line FP-based bioassay can be used to screen for the affinity of compounds without the disturbing occurrence of autofluorescence

Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1-driven acute lymphoblastic leukemia

The cellular receptor Notch1 is a central regulator of T-cell development, and as a consequence, Notch1 pathway appears upregulated in > 65% of the cases of T-cell acute lymphoblastic leukemia (T-ALL). However, strategies targeting Notch1 signaling render only modest results in the clinic due to treatment resistance and severe side effects. While many investigations reported the different aspects of tumor cell growth and leukemia progression controlled by Notch1, less is known regarding the modifications of cellular metabolism induced by Notch1 upregulation in T-ALL. Previously, glutaminolysis inhibition has been proposed to synergize with anti-Notch therapies in T-ALL models. In this work, we report that Notch1 upregulation in T-ALL induced a change in the metabolism of the important amino acid glutamine, preventing glutamine synthesis through the downregulation of glutamine synthetase (GS). Downregulation of GS was responsible for glutamine addiction in Notch1-driven T-ALL both in vitro and in vivo. Our results also confirmed an increase in glutaminolysis mediated by Notch1. Increased glutaminolysis resulted in the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway, a central controller of cell growth. However, glutaminolysis did not play any role in Notch1-induced glutamine addiction. Finally, the combined treatment targeting mTORC1 and limiting glutamine availability had a synergistic effect to induce apoptosis and to prevent Notch1-driven leukemia progression. Our results placed glutamine limitation and mTORC1 inhibition as a potential therapy against Notch1-driven leukemia.This work was supported by funds from the followinginstitutions: Agencia Estatal de Investigacion/Euro-pean Regional Development Fund, European Union(PGC2018-096244-B-I00, SAF2016-75442-R), Ministryof Science, Innovation and Universities of Spain,Spanish National Research Council—CSIC, InstitutNational de la Sante et de la Recherche Medicale—INSERM, Ligue Contre le Cancer—Gironde, Univer-site de Bordeaux, Fondation pour la Recherche Medi-cale, the Conseil Regional d’Aquitaine, SIRIC-BRIO,Fondation ARC and Institut Europeen de Chimie etBiologie. MJN was supported by a bourse d’excellencede la Federation Wallonie-Bruxelles (WBI) and a post-doctoral fellowship from Fondation ARC. We thankVincent Pitard (Flow Cytometry Platform, Universitede Bordeaux, France) for technical assistance in flowcytometry experiments. We thank Diana Cabrera(Metabolomics Platform, CIC bioGUNE, Spain) fortechnical assistance in metabolomics analysi

Development of an online p38α mitogen-activated protein kinase binding assay and integration of LC–HR-MS

A high-resolution screening method was developed for the p38α mitogen-activated protein kinase to detect and identify small-molecule binders. Its central role in inflammatory diseases makes this enzyme a very important drug target. The setup integrates separation by high-performance liquid chromatography with two parallel detection techniques. High-resolution mass spectrometry gives structural information to identify small molecules while an online enzyme binding detection method provides data on p38α binding. The separation step allows the individual assessment of compounds in a mixture and links affinity and structure information via the retention time. Enzyme binding detection was achieved with a competitive binding assay based on fluorescence enhancement which has a simple principle, is inexpensive, and is easy to interpret. The concentrations of p38α and the fluorescence tracer SK&F86002 were optimized as well as incubation temperature, formic acid content of the LC eluents, and the material of the incubation tubing. The latter notably improved the screening of highly lipophilic compounds. For optimization and validation purposes, the known kinase inhibitors BIRB796, TAK715, and MAPKI1 were used among others. The result is a high-quality assay with Z′ factors around 0.8, which is suitable for semi-quantitative affinity measurements and applicable to various binding modes. Furthermore, the integrated approach gives affinity data on individual compounds instead of averaged ones for mixtures

Advances in mass spectrometry-based post-column bioaffinity profiling of mixtures

In the screening of complex mixtures, for example combinatorial libraries, natural extracts, and metabolic incubations, different approaches are used for integrated bioaffinity screening. Four major strategies can be used for screening of bioactive mixtures for protein targets—pre-column and post-column off-line, at-line, and on-line strategies. The focus of this review is on recent developments in post-column on-line screening, and the role of mass spectrometry (MS) in these systems. On-line screening systems integrate separation sciences, mass spectrometry, and biochemical methodology, enabling screening for active compounds in complex mixtures. There are three main variants of on-line MS based bioassays: the mass spectrometer is used for ligand identification only; the mass spectrometer is used for both ligand identification and bioassay readout; or MS detection is conducted in parallel with at-line microfractionation with off-line bioaffinity analysis. On the basis of the different fields of application of on-line screening, the principles are explained and their usefulness in the different fields of drug research is critically evaluated. Furthermore, off-line screening is discussed briefly with the on-line and at-line approaches

Association between freedom of movement and health of nursing home residents with dementia:An exploratory longitudinal study

BackgroundLocked doors remain a common feature of dementia units in nursing homes (NHs) worldwide, despite the growing body of knowledge on the negative effects of restricted freedom on residents. To date, no previous studies have explored the health effects of opening locked NH units, which would allow residents to move freely within the building and enclosed garden. This study examines the association between increased freedom of movement and the health of NH residents with dementia.MethodsThis longitudinal, pre-post study involved a natural experiment in which NH residents with dementia (N = 46) moved from a closed to a semi-open location. Data on dimensions of positive health were collected at baseline (T0; one month before the relocation), at one (T1), four (T2) and nine (T3) months after the relocation. Linear mixed models were used to examine changes in positive health over time.ResultsCognition, quality of life and agitation scores improved significantly at T1 and T2 compared to the baseline, while mobility scores decreased. At T3, improvements in agitation and quality of life remained significant compared to the baseline. Activities of daily living (ADL) and depression scores were stable over time.ConclusionsIncreasing freedom of movement for NH residents with dementia is associated with improved health outcomes, both immediately and over time. These findings add to the growing evidence supporting the benefits of freedom of movement for the overall health of NH residents with dementia

Glutathione S-transferases as markers of salicylanilide resistance in isolates of Fasciola hepatica

A possible link between the level of glutathione S-transferase (GST, E.C. 2.5.1.18) activity and the development of salicylanilide resistance in Fasciola hepatica was investigated. Various isolates of F. hepatica with varying susceptibilities to salicylanilides were isolated and maintained in the laboratory. Individual flukes of these isolates were surveyed for their level of GST activity and a correlation between the level of GST activity and drug efficacy was found. In contrast to most other studies, a decrease in GST activity was associated with an increase in drug resistance. Evidence was collected to show that this may be a selective process since flukes which had survived exposure to rafoxanide and closantel in vivo (in sheep) had lower activity levels of GST than flukes from untreated sheep. Treatment with other flukicides (oxyclozanide, luxabendazole and triclabendazole) did not have this effect. Furthermore, in vivo treatment with closantel induced selection of particular isoenzymes in different isolates of F. hepatica having different degrees of susceptibility to closantel. However, no single isoenzyme or isoenzyme profile was associated with resistance and, in total, up to 8 different isoenzymes could be present in a single isolate. Thus, GST has some potential as a marker enzyme for salicylanilide resistance in F. hepatica. However, the precise role of GST in resistance is unclear and the extensive inter- and intra-isolate variation in activity levels and isoenzyme characteristics of this enzyme indicate the need for considerably more study before application in field situations