Search

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias

Abstract The NEXT-White detector, a high-pressure gaseous xenon time projection chamber, demonstrated the excellence of this technology for future neutrinoless double beta decay searches using photomultiplier tubes (PMTs) to measure energy and silicon photomultipliers (SiPMs) to extract topology information. This analysis uses 83m Kr data from the NEXT-White detector to measure and understand the energy resolution that can be obtained with the SiPMs, rather than with PMTs. The energy resolution obtained of (10.9 ± 0.6)%, full-width half-maximum, is slightly larger than predicted based on the photon statistics resulting from very low light detection coverage of the SiPM plane in the NEXT-White detector. The difference in the predicted and measured resolution is attributed to poor corrections, which are expected to be improved with larger statistics. Furthermore, the noise of the SiPMs is shown to not be a dominant factor in the energy resolution and may be negligible when noise subtraction is applied appropriately, for high-energy events or larger SiPM coverage detectors. These results, which are extrapolated to estimate the response of large coverage SiPM planes, are promising for the development of future, SiPM-only, readout planes that can offer imaging and achieve similar energy resolution to that previously demonstrated with PMTs.

Abstract Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from $$^{83\textrm{m}}$$ 83 m Kr calibration electron captures ( $$E\sim 45$$ E ∼ 45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias $$< 1~$$ < 1 mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks ( $$E\ge ~1.5$$ E ≥ 1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Q $$_{\beta \beta }$$ β β in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation.

Gaze cues play a vital role in conveying critical information about objects and locations necessary for survival, such as food sources, predators, and the attentional states of conspecific and heterospecific individuals. During referential intentional communication, the continuous alternation of gaze between a communicative partner and a specific object or point of interest attracts the partner's attention towards the target. This behaviour is considered by many as essential for understanding intentions and is thought to involve mental planning. Here, we investigated the behavioural responses of seven bottlenose dolphins (Tursiops truncatus) that were given an impossible task in the presence of two experimenters (a ‘commanding experimenter’ and a ‘non-commanding experimenter’), whose attentional state towards the dolphins varied. We found that the dolphins spontaneously displayed gaze alternation, specifically triadic referential pointing, only when the human commanding experimenter was facing them. However, they ceased to alternate their gaze between the impossible object and the commanding experimenter when the experimenter had their back turned. Notably, the dolphins' behaviour differed from general pointing and gaze, as their triadic sequence occurred within a narrow time window. These findings suggest that the dolphins were sensitive to human attentional cues and utilized their own gaze cue (pointing) as a salient signal to attract the attention of the commanding experimenter towards a specific location.

Abstract Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory condition resulting from monoallelic NLRP3 variants that facilitate IL-1β production. Although these are gain-of-function variants characterized by hypersensitivity to cell priming, patients with CAPS and animal models of the disease may present inflammatory flares without identifiable external triggers. Here we find that CAPS-associated NLRP3 variants are forming constitutively active inflammasome, which induce increased basal cleavage of gasdermin D, IL-18 release and pyroptosis, with a concurrent basal pro-inflammatory gene expression signature, including the induction of nuclear receptors 4 A. The constitutively active NLRP3-inflammasome of CAPS is responsive to the selective NLRP3 inhibitor MCC950 and its activation is regulated by deubiquitination. Despite their preactivated state, the CAPS inflammasomes are responsive to activation of the NF-κB pathway. NLRP3-inflammasomes with CAPS-associated variants affect the immunometabolism of the myeloid compartment, leading to disruptions in lipids and amino acid pathways and impaired glycolysis, limiting IL-1β production. In summary, NLRP3 variants causing CAPS form a constitutively active inflammasome inducing pyroptosis and IL-18 release without cell priming, which enables the host’s innate defence against pathogens while also limiting IL-1β–dependent inflammatory episodes through immunometabolism modulation.

El Convenio Ramsar tiene entre sus orientaciones que los estados dispongan de un inventario de humedales, cuya elaboración, en el caso de España, está coordinada por el Estado central, que aprobó unas directrices mediante el Real Decreto 435/2004 para que las Comunidades Autónomas elaborasen sus propios inventarios. Los objetivos son la descripción de los criterios utilizados para incluir un humedal en el Inventario Español de Zonas Húmedas, analizar el proceso de inventariación para el caso de la Región de Murcia, así como la utilidad del inventario nacional en la planificación y gestión del territorio. La metodología empleada en el proceso de elaboración del Inventario de la Región de Murcia en 2017 fue tomar como punto de partida el Inventario del año 2000, evaluar los humedales que cumplían el Real Decreto mencionado, revisar sus límites e incorporar otros humedales que cumpliendo los criterios no habían sido inventariados hasta esa fecha. El resultado fue la incorporación de 53 humedales y complejos de humedales en el Inventario Español de Zonas Húmedas, que se están teniendo en cuenta en la planificación hidrológica de la cuenca del río Segura, en la evaluación de impacto ambiental, con especial atención en los procesos de revisión del planeamiento municipal, así como en la incorporación en la red de espacios protegidos del Mar Menor de algunos humedales periféricos que no habían sido inventariados. Por tanto, se puede concluir que la elaboración de inventarios de humedales en España en general, y en la Región de Murcia en particular, permite dotar de herramientas de planificación y gestión de humedales, que favorece la conservación de estos espacios naturales.

Abstract This article presents the development of a liquid-level sensor using fiber optic Bragg gratings (FBG). The sensor comprises a carbon-fiber-reinforced polymers (CFRP) diaphragm packaging an embedded FBG to measure strain. A mathematical analysis determines the FBG response to the pressure exerted by a liquid column over the packaged sensor. The experimental arrangement consists of an acrylic tube with a sensor at the bottom. FBG signals were acquired using a DI 410 optical interrogator manufactured by HBM. A finite element simulation with Ansys was performed to determine the most reposeful position from the FBG sensor. The experimental results show the analysis of eight repetitions of the water column ranging from 10 cm to 60 cm using 10 cm steps. The sensor showed a linear response, with a coefficient of determination of 0.999, and a sensitivity of 4.1 pm/cm; and the maximum standard deviation is 0.64 pm. Although water is used in the calibration process, other liquids could also be used, obtaining a different angular coefficient depending on the density of the liquid used.

Introducción: en el hospital Dr. Agostinho Neto se carece de datos sobre las características de la neumonía adquirida en la comunidad en pacientes maternas desde la perspectiva de la microbiología. Los estudios microbiológicos influyen en la toma de decisiones diagnósticas y terapéuticas en casos de neumonía adquirida en la comunidad. Objetivo: precisar el perfil microbiológico de la neumonía adquirida en la comunidad en pacientes maternas egresadas en la unidad de cuidados intensivos del hospital Dr. Agostinho Neto durante el periodo 2015-2022. Métodos: se realizó un estudio descriptivo, retrospectivo y transversal. Se estudiaron todas las gestantes y puérperas con esta neumonía (n = 91). Se estudiaron las siguientes variables: edad biológica y gestacional y caracterizadoras de la neumónica: clínicas (forma clínica, prescripción de fármacos antimicrobianos, respuesta terapéutica) y microbiológicas (medios diagnóstico microbiológico utilizados, germen causal). Los datos se resumieron mediante análisis de frecuencias y porcentajes. Resultados: el germen más usual fue el streptococcus pneumoniae (56.0 %) y el medio diagnóstico más utilizado fue el cultivo del esputo. El 76.9 % de las pacientes era gestante y el 23.1 % era puérperas. El 94.5 % se egresó viva y falleció el 5.5 % (1 por H1N1 y 4 por virus SARS-Cov-2). El 100 % se trató con fármacos antimicrobianos antivirales, cefalosporinas y macrólidos. Conclusiones: se caracterizó el perfil microbiológico de la neumonía adquirida en la comunidad en pacientes maternas.

Abstract The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess prevalence of MPXV in high-risk populations of GBMSM, trans women (TW) and non-binary people without symptoms or with unrecognized monkeypox (Mpox) symptoms, using a self-sampling strategy. Anal and pharyngeal swabs are tested by MPXV real-time PCR and positive samples are tested for cytopathic effect (CPE) in cell culture. 113 individuals participated in the study, 89 (78.76%) were cis men, 17 (15.04%) were TW. The median age was 35.0 years (IQR: 30.0–43.0), 96 (85.02%) individuals were gay or bisexual and 72 (63.72%) were migrants. Seven participants were MPXV positive (6.19% (95% CI: 1.75%–10.64%)). Five tested positive in pharyngeal swabs, one in anal swab and one in both. Six did not present symptoms recognized as MPXV infection. Three samples were positive for CPE, and showed anti-vaccinia pAb staining by FACS and confocal microscopy. This suggests that unrecognized Mpox cases can shed infectious virus. Restricting testing to individuals reporting Mpox symptoms may not be sufficient to contain outbreaks.

Abstract The NEXT experiment aims at the sensitive search of the neutrinoless double beta decay in 136Xe, using high-pressure gas electroluminescent time projection chambers. The NEXT-White detector is the first radiopure demonstrator of this technology, operated in the Laboratorio Subterráneo de Canfranc. Achieving an energy resolution of 1% FWHM at 2.6 MeV and further background rejection by means of the topology of the reconstructed tracks, NEXT-White has been exploited beyond its original goals in order to perform a neu- trinoless double beta decay search. The analysis considers the combination of 271.6 days of 136Xe-enriched data and 208.9 days of 136Xe-depleted data. A detailed background modeling and measurement has been developed, ensuring the time stability of the radiogenic and cosmogenic contributions across both data samples. Limits to the neutrinoless mode are obtained in two alternative analyses: a background-model-dependent approach and a novel direct background-subtraction technique, offering results with small dependence on the background model assumptions. With a fiducial mass of only 3.50 ± 0.01 kg of 136Xe-enriched xenon, 90% C.L. lower limits to the neutrinoless double beta decay are found in the T 1 / 2 0 ν $$ {T}_{1/2}^{0\nu } $$ > 5.5 × 1023 − 1.3 × 1024 yr range, depending on the method. The presented techniques stand as a proof-of-concept for the searches to be implemented with larger NEXT detectors.

Abstract The ability to attribute attentional states to other individuals is a highly adaptive socio-cognitive skill and thus may have evolved in many social species. However, whilst humans excel in this ability, even chimpanzees appear to not accurately understand how visual attention works, particularly in regard to the function of eyes. The complex socio-ecological background and socio-cognitive skill-set of bottlenose dolphins (Tursiops sp.), alongside the specialised training that captive dolphins typically undergo, make them an especially relevant candidate for an investigation into their sensitivity to human attentional states. Therefore, we tested 8 bottlenose dolphins on an object retrieval task. The dolphins were instructed to fetch an object by a trainer under various attentional state conditions involving the trainer’s eyes and face orientation: ‘not looking’, ‘half looking’, ‘eyes open’, and ‘eyes closed’. As the dolphins showed an increased latency to retrieve the object in conditions where the trainer’s head and eyes cued a lack of attention to the dolphin, particularly when comparing ‘eyes open’ vs ‘eyes closed’ conditions, we demonstrate that dolphins can be sensitive to human attentional features, namely the functionality of eyes. This study supports growing evidence that dolphins possess highly complex cognitive abilities, particularly those in the social domain.

IntroductionGranulocytes are innate immune cells that play a key role in pathogen elimination. Recent studies revealed the diversity of granulocytes in terms of phenotype and function. In particular, a subset of granulocytes identified as low-density granulocytes (LDG) has been described in physiological conditions and with increased frequencies in several pathological contexts. However, the properties of LDG are still controversial as they vary according to the pathophysiological environment. Here we investigated the heterogeneity of granulocyte populations and the potential differences in phenotype and immunomodulatory capacity between LDG and normal density granulocytes (NDG) in people living with HIV-1 (PLWH).MethodsTo this end, we developed an optimized method to purify LDG and NDG from a single blood sample, and performed in-depth, comparative phenotypic characterization of both granulocyte subtypes. We also assessed the impact of purification steps on the expression of cell surface markers on LDG by immunophenotyping them at different stages of isolation.ResultsWe identified 9 cell surface markers (CD16, CD32, CD89, CD62L, CD177, CD31, CD10, CXCR4 and CD172α) differentially expressed between LDG and NDG. Noteworthy, markers that distinguish the two subsets include receptors for the Fc part of IgG (CD16, CD32) and IgA (CD89). Importantly, we also highlighted that the purification procedure affects the expression of several cell surface markers (i.e.CD63, CD66b, …) which must be taken into account when characterizing LDG. Our work sheds new light on the properties of LDG in PLWH and provides an extensive characterization of this granulocyte subset in which Fc receptors are key discriminatory markers.

Episodic memory describes the conscious reimagining of our memories and is often considered to be a uniquely human ability. As these phenomenological components are embedded within its definition, major issues arise when investigating the presence of episodic memory in non-human animals. Importantly, however, when we as humans recall a specific experience, we may remember details from that experience that were inconsequential to our needs, thoughts, or desires at that time. This 'incidental' information is nevertheless encoded automatically as part of the memory and is subsequently recalled within a holistic representation of the event. The incidental encoding and unexpected question paradigm represents this characteristic feature of human episodic memory and can be employed to investigate memory recall in non-human animals. However, without evidence for the associated phenomenology during recall, this type of memory is termed 'episodic-like memory'. Using this approach, we tested seven Eurasian jays (Garrulus glandarius) on their ability to use incidental visual information (associated with observed experimenter made 'caches') to solve an unexpected memory test. The birds performed above chance levels, suggesting that Eurasian jays can encode, retain, recall, and access incidental visual information within a remembered event, which is an ability indicative of episodic memory in humans.

O objetivo deste artigo é expor o cerne das críticas de Paul Natorp ao psicologismo. Expomos os argumentos que levam Natorp a concluir que o conhecimento não pode ter fundamento subjetivo, mas deve ter fundamento objetivo. Argumentamos que, segundo Natorp, o problema do psicologismo é fundamentalmente metodológico. O psicologismo confunde o estudo das leis do conhecimento com o estudo da legalidade da vida psíquica. Assim, o problema da gênese se confunde com o problema da validade.

ABSTRACTThe annual “Antibody Industrial Symposium”, co-organized by LabEx MAbImprove and MabDesign, held its 10th anniversary edition in Montpellier, France, on June 28–29, 2022. The meeting focused on new results and concepts in antibody engineering (naked, mono- or multi-specific, conjugated to drugs or radioelements) and also on new cell-based therapies, such as chimeric antigenic receptor (CAR)-T cells. The symposium, which brought together scientists from academia and industry, also addressed issues concerning the production of these molecules and cells, and the necessary steps to ensure a strong intellectual property protection of these new molecules and approaches. These two days of exchanges allowed a rich discussion among the various actors in the field of therapeutic antibodies.

Background & aimsIncreased hepatocyte death contributes to the pathology of acute and chronic liver diseases. However, the role of hepatocyte pyroptosis and extracellular inflammasome release in liver disease is unknown.MethodsWe used primary mouse and human hepatocytes, hepatocyte-specific leucine 351 to proline Nlrp3KICreA mice, and GsdmdKO mice to investigate pyroptotic cell death in hepatocytes and its impact on liver inflammation and damage. Extracellular NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes were isolated from mutant NLRP3-YFP HEK cells and internalisation was studied in LX2 and primary human hepatic stellate cells. We also examined a cohort of 154 adult patients with biopsy-proven non-alcoholic fatty liver disease (Sir Charles Gairdner Hospital, Nedlands, Western Australia).ResultsWe demonstrated that primary mouse and human hepatocytes can undergo pyroptosis upon NLRP3 inflammasome activation with subsequent release of NLRP3 inflammasome proteins that amplify and perpetuate inflammasome-driven fibrogenesis. Pyroptosis was inhibited by blocking caspase-1 and gasdermin D activation. The activated form of caspase-1 was detected in the livers and in serum from patients with non-alcoholic steatohepatitis and correlated with disease severity. Nlrp3KICreA mice showed spontaneous liver fibrosis under normal chow diet, and increased sensitivity to liver damage and inflammation after treatment with low dose lipopolysaccharide. Mechanistically, hepatic stellate cells engulfed extracellular NLRP3 inflammasome particles leading to increased IL-1β secretion and α-smooth muscle actin expression. This effect was abrogated when cells were pre-treated with the endocytosis inhibitor cytochalasin B.ConclusionsThese results identify hepatocyte pyroptosis and release of inflammasome components as a novel mechanism to propagate liver injury and liver fibrosis development.Lay summaryOur findings identify a novel mechanism of inflammation in the liver. Experiments in cell cultures, mice, and human samples show that a specific form of cell death, called pyroptosis, leads to the release of complex inflammatory particles, the NLRP3 inflammasome, from inside hepatocytes into the extracellular space. From there they are taken up by other cells and thereby mediate inflammatory and pro-fibrogenic stress signals. The discovery of this mechanism may lead to novel treatments for chronic liver diseases in the future.

The uses of natural compounds, such as essential oils (EOs), are limited due to their instability to light, oxygen and temperature, factors that affect their application. Therefore, improving stability becomes necessary. The objective of this study was to prepare inclusion complexes of Litsea cubeba essential oil (LCEO) with β-cyclodextrin (β-CD) using physical mixing (PM), kneading (KN) and co-precipitation (CP) methods and to evaluate the efficiency of the complexes and their physicochemical properties using ATR-FTIR, FT-Raman, DSC and TG. The study also assessed cytotoxicity against human colorectal and cervical cancer cells and antifungal activity against Aspergillus flavus and Fusarium verticillioides. The complexation efficiency results presented significant evidence of LCEO:β-CD inclusion complex formation, with KN (83%) and CP (73%) being the best methods used in this study. All tested LCEO:β-CD inclusion complexes exhibited toxicity to HT-29 cells. Although the cytotoxic effect was less pronounced in HeLa tumor cells, LCEO-KN was more active against Hela than non-tumor cells. LCEO-KN and LCEO-CP inclusion complexes were efficient against both toxigenic fungi, A. flavus and F. verticillioides. Therefore, the molecular inclusion of LCEO into β-CD was successful, as well as the preliminary biological results, evidencing that the β-CD inclusion process may be a viable alternative to facilitate and increase future applications of this EO as therapeutic medication, food additive and natural antifungal agent.

Summary: Background: Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. Methods: In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). Findings: SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8+ T-cell proliferation. Administration of sSIGLEC5r (0.8 mg/kg) had adverse effects in mouse endotoxemia models. Additionally, plasma sSIGLEC5 levels of septic patients were higher than HVs and ROC analysis revealed it as a mortality marker with an AUC of 0.713 (95% CI, 0.656–0.769; p