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Abstract Quantum Reservoir Computing (QRC) offers potential advantages over classical reservoir computing, including inherent processing of quantum inputs and a vast Hilbert space for state exploration. Yet, the relation between the performance of reservoirs based on complex and many-body quantum systems and non-classical state features is not established. Through an extensive analysis of QRC based on a transverse-field Ising model we show how different quantum effects, such as quantum coherence and correlations, contribute to improving the performance in temporal tasks, as measured by the Information Processing Capacity. Additionally, we critically assess the impact of finite measurement resources and noise on the reservoir’s dynamics in different regimes, quantifying the limited ability to exploit quantum effects for increasing damping and noise strengths. Our results reveal a monotonic relationship between reservoir performance and coherence, along with the importance of quantum effects in the ergodic regime.

A massagem infantil é uma terapia complementar que tem suscitado um interesse crescente na comunidade científica pelos seus potenciais benefícios no alívio sintomático de condições pediátricas frequentes. O seu mecanismo fisiopatológico ainda não está completamente estabelecido, porém é uma prática que favorece a comunicação e o vínculo com os cuidadores, promovendo uma sensação de conforto e bem-estar do lactente. Segundo a literatura mais recente, a massagem infantil parece ser promissora no alívio da dor, na diminuição da icterícia, no tratamento adjuvante da obstipação funcional, na melhoria da qualidade do sono e no crescimento e desenvolvimento infantis. Assim, como terapêutica não farmacológica, parece ter benefícios, sendo praticamente desprovida de efeitos adversos. Contudo, atualmente, ainda existem poucos estudos randomizados acerca desta temática, pelo que a qualidade da evidência é baixa, constituindo uma limitação para a sua recomendação universal na prática clínica.

The process of training an artificial neural network involves iteratively adapting its parameters so as to minimize the error of the network’s prediction, when confronted with a learning task. This iterative change can be naturally interpreted as a trajectory in network space–a time series of networks–and thus the training algorithm (e.g., gradient descent optimization of a suitable loss function) can be interpreted as a dynamical system in graph space. In order to illustrate this interpretation, here we study the dynamical properties of this process by analyzing through this lens the network trajectories of a shallow neural network, and its evolution through learning a simple classification task. We systematically consider different ranges of the learning rate and explore both the dynamical and orbital stability of the resulting network trajectories, finding hints of regular and chaotic behavior depending on the learning rate regime. Our findings are put in contrast to common wisdom on convergence properties of neural networks and dynamical systems theory. This work also contributes to the cross-fertilization of ideas between dynamical systems theory, network theory and machine learning.

The retinal pigment epithelium (RPE) is an essential component of the retina that plays multiple roles required to support visual function. These include light onset- and circadian rhythm-dependent tasks, such as daily phagocytosis of photoreceptor outer segments. Mitochondria provide energy to the highly specialized and energy-dependent RPE. In this study, we examined the positioning of mitochondria and how this is influenced by the onset of light. We identified a population of mitochondria that are tethered to the basal plasma membrane pre- and post-light onset. Following light onset, mitochondria redistributed apically and interacted with melanosomes and phagosomes. In a choroideremia mouse model that has regions of the RPE with disrupted or lost infolding of the plasma membrane, the positionings of only the non-tethered mitochondria were affected. This provides evidence that the tethering of mitochondria to the plasma membrane plays an important role that is maintained under these disease conditions. Our work shows that there are subpopulations of RPE mitochondria based on their positioning after light onset. It is likely they play distinct roles in the RPE that are needed to fulfil the changing cellular demands throughout the day.

Abstract Although adoptive T cell therapy provides the T cell pool needed for immediate tumor debulking, the infused T cells generally have a narrow repertoire for antigen recognition and limited ability for long-term protection. Here, we present a hydrogel that locally delivers adoptively transferred T cells to the tumor site while recruiting and activating host antigen-presenting cells with GMCSF or FLT3L and CpG, respectively. T cells alone loaded into these localized cell depots provided significantly better control of subcutaneous B16-F10 tumors than T cells delivered through direct peritumoral injection or intravenous infusion. T cell delivery combined with biomaterial-driven accumulation and activation of host immune cells prolonged the activation of the delivered T cells, minimized host T cell exhaustion, and enabled long-term tumor control. These findings highlight how this integrated approach provide both immediate tumor debulking and long-term protection against solid tumors, including against tumor antigen escape.

Adeno-associated virus (AAV) vectors are currently the most efficient option for intracranial gene therapies to treat neurodegenerative disease. Increased efficacy and safety will depend upon robust and specific expression of therapeutic genes into target cell-types within the human brain. In this study, we set out with two objectives: (1) to identify capsids with broader transduction of the striatum upon intracranial injection in mice and (2) to test a truncated human choline acetyltransferase (ChAT) promoter that would allow efficient and selective transduction of cholinergic neurons. We compared AAV9 and an engineered capsid, AAV-S, to mediate widespread reporter gene expression throughout the striatum. We observed that AAV-S transduced a significantly greater area of the injected hemisphere primarily in the rostral direction compared with AAV9 (CAG promoter). We tested AAV9 vectors packaging a reporter gene expression cassette driven by either the ChAT or CAG promoter. Specificity of transgene expression of ChAT neurons over other cells was 7-fold higher, and efficiency was 3-fold higher for the ChAT promoter compared with the CAG promoter. The AAV-ChAT transgene expression cassette should be a useful tool for the study of cholinergic neurons in mice, and the broader transduction area of AAV-S warrants further evaluation of this capsid.

Immunotherapy has emerged as a promising strategy to eradicate cancer cells. Particularly, the development of cancer vaccines to induce a potent and sustained antigen-specific T cell response has become a center of attention. Herein, we describe a novel immunotherapy based on magnetic nanoparticles (MNP) covalently modified with the OVA254-267 antigen and a CpG oligonucleotide via disulfide bonds. The MNP-CpG-COVA significantly enhances dendritic cell activation and CD8+ T cell antitumoral response against B16-OVA melanoma cells in vitro. Notably, the immune response induced by the covalently modified MNP is more potent and sustained over time than that triggered by the free components, highlighting the advantage of nanoformulations in immunotherapies. What is more, the nanoparticles are stable in the blood after in vivo administration and induce potent levels of systemic tumor-specific effector CD8 + T cells. Overall, our findings highlight the potential of covalently functionalized MNP to induce robust immune responses against mouse melanoma.

In this work, the authors identify Genipin as a small iridoid able to prevent alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage.

Dissipation induced by interactions with an external environment typically hinders the performance of quantum computation, but in some cases can be turned out as a useful resource. We show the potential enhancement induced by dissipation in the field of quantum reservoir computing introducing tunable local losses in spin network models. Our approach based on continuous dissipation is able not only to reproduce the dynamics of previous proposals of quantum reservoir computing, based on discontinuous erasing maps but also to enhance their performance. Control of the damping rates is shown to boost popular machine learning temporal tasks as the capability to linearly and non-linearly process the input history and to forecast chaotic series. Finally, we formally prove that, under non-restrictive conditions, our dissipative models form a universal class for reservoir computing. It means that considering our approach, it is possible to approximate any fading memory map with arbitrary precision.

Inherited retinal diseases (IRDs) encompass a diverse group of genetic disorders that lead to progressive visual impairment and blindness. Over the years, considerable strides have been made in understanding the underlying molecular mechanisms of IRDs, laying the foundation for novel therapeutic interventions. Gene therapy has emerged as a compelling approach for treating IRDs, with notable advancements achieved through targeted gene augmentation. However, several setbacks and limitations persist, hindering the widespread clinical success of gene therapy for IRDs. One promising avenue of research is the development of new genome editing tools. Cutting-edge technologies such as CRISPR-Cas9 nucleases, base editing and prime editing provide unprecedented precision and efficiency in targeted gene manipulation, offering the potential to overcome existing challenges in gene therapy for IRDs. Furthermore, traditional gene therapy encounters a significant challenge due to immune responses to viral vectors, which remain crucial obstacles in achieving long-lasting therapeutic effects. Nanotechnology has emerged as a valuable ally in the quest to optimize gene therapy outcomes for ocular diseases. Nanoparticles engineered with nanoscale precision offer improved gene delivery to specific retinal cells, allowing for enhanced targeting and reduced immunogenicity. In this review, we discuss recent advancements in gene therapy for IRDs and explore the setbacks that have been encountered in clinical trials. We highlight the technological advances in genome editing for the treatment of IRDs and how integrating nanotechnology into gene delivery strategies could enhance the safety and efficacy of gene therapy, ultimately offering hope for patients with IRDs and potentially paving the way for similar advancements in other ocular disorders.

Abstract Time-series processing is a major challenge in machine learning with enormous progress in the last years in tasks such as speech recognition and chaotic series prediction. A promising avenue for sequential data analysis is quantum machine learning, with computational models like quantum neural networks and reservoir computing. An open question is how to efficiently include quantum measurement in realistic protocols while retaining the needed processing memory and preserving the quantum advantage offered by large Hilbert spaces. In this work, we propose different measurement protocols and assess their efficiency in terms of resources, through theoretical predictions and numerical analysis. We show that it is possible to exploit the quantumness of the reservoir and to obtain ideal performance both for memory and forecasting tasks with two successful measurement protocols. One repeats part of the experiment after each projective measurement while the other employs weak measurements operating online at the trade-off where information can be extracted accurately and without hindering the needed memory, in spite of back-action effects. Our work establishes the conditions for efficient time-series processing paving the way to its implementation in different quantum technologies.

The emergence of drug resistance significantly hampers the treatment of human infections, including those caused by fungal pathogens such as Candida species. Candida glabrata ranks as the second most common cause of candidiasis worldwide, supported by rapid acquisition of resistance to azole and echinocandin antifungals frequently prompted by single nucleotide polymorphisms (SNPs) in resistance associated genes, such as PDR1 (azole resistance) or FKS1/2 (echinocandin resistance). To determine the frequency of polymorphisms and genome rearrangements as the possible genetic basis of C. glabrata drug resistance, we assessed genomic variation across 94 globally distributed isolates with distinct resistance phenotypes, whose sequence is deposited in GenBank. The genomes of three additional clinical isolates were sequenced, in this study, including two azole resistant strains that did not display Gain-Of-Function (GOF) mutations in the transcription factor encoding gene PDR1. Genomic variations in susceptible isolates were used to screen out variants arising from genome diversity and to identify variants exclusive to resistant isolates. More than half of the azole or echinocandin resistant isolates do not possess exclusive polymorphisms in PDR1 or FKS1/2, respectively, providing evidence of alternative genetic basis of antifungal resistance. We also identified copy number variations consistently affecting a subset of chromosomes. Overall, our analysis of the genomic and phenotypic variation across isolates allowed to pinpoint, in a genome-wide scale, genetic changes enriched specifically in antifungal resistant strains, which provides a first step to identify additional determinants of antifungal resistance. Specifically, regarding the newly sequenced strains, a set of mutations/genes are proposed to underlie the observed unconventional azole resistance phenotype.

Mutations in the hexose transporter, CgHXT4/6/7, contribute to increased antifungal (azole) resistance in the fungal pathogen, Candida glabrata, potentially by influencing azole accumulation.

Abstract The excavations undertaken at the Campo de Hockey site in 2008 led to the identification of a major Neolithic necropolis in the former Island of San Fernando (Bay of Cádiz). This work presents the results of the latest studies, which indicate that the site stands as one of the oldest megalithic necropolises in the Iberian Peninsula. The main aim of this work is to present with precision the chronology of this necropolis through a Bayesian statistical model that confirms that the necropolis was in use from c. 4300 to 3800 cal BC. The presence of prestige grave goods in the earliest and most monumental graves suggest that the Megalithism phenomenon emerged in relation to maritime routes linked to the distribution of exotic products. We also aim to examine funerary practices in these early megalithic communities, and especially their way of life and the social reproduction system. As such, in addition to the chronological information and the Bayesian statistics, we provide the results of a comprehensive interdisciplinary study, including anthropological, archaeometric and genetic data.

The implementation of machine learning concepts using optoelectronic and photonic components is rapidly advancing. Here, we use the recently introduced notion of optical dendritic structures, which aspires to transfer neurobiological principles to photonics computation. In real neurons, plasticity—the modification of the connectivity between neurons due to their activity—plays a fundamental role in learning. In the current work, we investigate theoretically and experimentally an artificial dendritic structure that implements a modified Hebbian learning model, called input correlation (ICO) learning. The presented optical fiber-based dendritic structure employs the summation of the different optical intensities propagating along the optical dendritic branches and uses Gigahertz-bandwidth modulation via semiconductor optical amplifiers to apply the necessary plasticity rules. In its full deployment, this optoelectronic ICO learning analog can be an efficient hardware platform for ultra-fast control.

This study investigates the internal architecture of Asian hornet nests (AHNs) using advanced imaging techniques, such as CT scanning and X-ray radiography, to understand their construction and function. The primary objective and significance of this study centre on drawing inspiration from the creative way Asian hornets construct their nests, with a particular focus on the architecture, design, functionality, and building materials of these nests. The architectural principles governing the construction of these nests, such as the arrangement of hexagonal cells, pedicels for load bearing, and adhesive materials, serve as a source of inspiration for innovative and sustainable design practices. The pedicels in Asian hornet nests play a crucial role in transferring load and ensuring stability. Additionally, AHNs’ adhesion to tree branches is essential for preventing collapse, and the pedicels provide necessary structural support. The knowledge gained from studying AHNs’ internal architecture could be applied directly to the architecture and civil engineering fields to improve structure stability and durability. The microstructure analysis of the paper-like material that hornets produce to build their nests indicates a complex and heterogeneous structure, composed of various plant fragments and fibres. This unique composition creates intricate grooves and pores, which are essential for regulating temperature and humidity levels within the outer envelope of the nest. The study of Asian hornet nests’ internal structure demonstrated that nature’s engineering principles inspire the design of durable and resilient structures in the construction industry. Civil engineers can incorporate similar principles into their designs to enhance the structural integrity and performance of buildings, bridges, and other infrastructure.

Chitin/chitosan and collagen are two of the most important bioactive compounds, with applications in the pharmaceutical, veterinary, nutraceutical, cosmetic, biomaterials, and other industries. When extracted from non-edible parts of fish and shellfish, by-catches, and invasive species, their use contributes to a more sustainable and circular economy. The present article reviews the scientific knowledge and publication trends along the marine chitin/chitosan and collagen value chains and assesses how researchers, industry players, and end-users can bridge the gap between scientific understanding and industrial applications. Overall, research on chitin/chitosan remains focused on the compound itself rather than its market applications. Still, chitin/chitosan use is expected to increase in food and biomedical applications, while that of collagen is expected to increase in biomedical, cosmetic, pharmaceutical, and nutritional applications. Sustainable practices, such as the reuse of waste materials, contribute to strengthen both value chains; the identified weaknesses include the lack of studies considering market trends, social sustainability, and profitability, as well as insufficient examination of intellectual property rights. Government regulations, market demand, consumer preferences, technological advancements, environmental challenges, and legal frameworks play significant roles in shaping both value chains. Addressing these factors is crucial for seizing opportunities, fostering sustainability, complying with regulations, and maintaining competitiveness in these constantly evolving value chains.

Testing shear-resisting plates in steel connections is one of the most challenging laboratory undertakings in steel construction, as the most common experimental layout design includes simulating the connection with its adjoining members. This significant hindrance gained particular magnitude as the need to test prototypes of topologically optimised shear cover plates became more pressing. Indeed, new code-compliant topology optimisation approaches for steel construction have recently been offered, and physically non-linear analyses have been demonstrated to be vital for assessing these elements. Hence, a rapid and reliable experimental process has become a fundamental necessity. To answer this need, a novel layout is herein proposed, in which topologically optimised and previously numerically examined bolted shear plates of a well-known steel joint were tested. The results allowed for the definition of the material trilinear model for use in subsequent numerical analysis, as well as the validation of the numerical simulation results. The discrepancy between the previously mathematically anticipated and empirically determined ultimate resistance did not exceed 1.7%.

El hallazgo de parásitos procedentes de contextos arqueológicos nos permite conocer las condiciones socio-económicas y los hábitos alimentarios de las poblaciones pasadas, aportando una visión novedosa en el estudio de dichas sociedades. Pese a su probado interés en la contribución al conocimiento de los estudios arqueológicos, antropológicos y biológicos, apenas se han llevado a cabo investigaciones paleoparasitológicas en España. Este trabajo presenta los resultados de los análisis paleoparasitológicos desarrollados sobre restos esqueletizados de ocho individuos procedentes de la necrópolis romana de Dianium (Dénia, Alicante, España), fechada entre los siglos III a V d.C. Este análisis se ha realizado mediante visualización por microscopía óptica de campo claro. Los resultados han evidenciado la presencia de Ascaris lumbricoides en uno de los individuos. Estos resultados se han integrado con los hallazgos paleopatológicos y antropológicos. La presencia de este parásito se vincula a la falta de higiene, derivada de contaminación ambiental y alimentaria. ABSTRACT: The discovery of parasites remains from archaeological contexts allows us to learn about the socio-economic conditions and eating habits of past populations, providing a bioarchaeological insight into the study of these societies. Despite its proven interest in contributing to the knowledge of archaeological, anthropological and biological studies, very little palaeoparasitological research has been carried out in Spain. This paper presents the palaeoparasitological and anthropological results carried out on Upper and Lower Imperial Roman material from the study of eight skeletonized individuals found at the site of Dianium (Alicante, Spain). Given that these materials were found in previous archaeological campaigns, the sampling was carried out in the laboratory. This is the first time such a is conducted on a Spanish archaeological site. Analysis of ancient parasites were carried out using bright-field optical microscopy. The results showed the presence of Ascaris lumbricoides in one of the individuals. The presence of this parasite is linked to a lack of hygiene, derived from environmental and food contamination. The presence of parasites is related to evidence of bone pathologies. Likewise, the presence of this parasite may be due to the use of human faeces as fertilizer in Roman times. The low number of parasitological evidences may be due to the nature of the materials, as well as the taphonomic processes that took place.

Skin pigmentation is imparted by melanin and is crucial for photoprotection against UVR. Melanin is synthesized and packaged into melanosomes within melanocytes and is then transferred to keratinocytes (KCs). Although the molecular players involved in melanogenesis have been extensively studied, those underlying melanin transfer remain unclear. Previously, our group proposed that coupled exocytosis/phagocytosis is the predominant mechanism of melanin transfer in human skin and showed an essential role for RAB11B and the exocyst tethering complex in this process. In this study, we show that soluble factors present in KC-conditioned medium stimulate melanin exocytosis from melanocytes and transfer to KCs. Moreover, we found that these factors are released by differentiated KCs but not by basal layer KCs. Furthermore, we found that RAB3A regulates melanin exocytosis and transfer stimulated by KC-conditioned medium. Indeed, KC-conditioned medium enhances the recruitment of RAB3A to melanosomes in melanocyte dendrites. Therefore, our results suggest the existence of two distinct routes of melanin exocytosis: a basal route controlled by RAB11B and a RAB3A-dependent route, stimulated by KC-conditioned medium. Thus, this study provides evidence that soluble factors released by differentiated KCs control skin pigmentation by promoting the accumulation of RAB3A-positive melanosomes in melanocyte dendrites and their release and subsequent transfer to KCs.

Skin pigmentation ensures efficient photoprotection and relies on the pigment melanin, which is produced by epidermal melanocytes and transferred to surrounding keratinocytes. While the molecular mechanisms of melanin synthesis and transport in melanocytes are now well characterized, much less is known about melanin transfer and processing within keratinocytes. Over the past few decades, distinct models have been proposed to explain how melanin transfer occurs at the cellular and molecular levels. However, this remains a debated topic, as up to four different models have been proposed, with evidence presented supporting each. Here, we review the current knowledge on the regulation of melanin exocytosis, internalization, processing, and polarization. Regarding the different transfer models, we discuss how these might co-exist to regulate skin pigmentation under different conditions, i.e., constitutive and facultative skin pigmentation or physiological and pathological conditions. Moreover, we discuss recent evidence that sheds light on the regulation of melanin exocytosis by melanocytes and internalization by keratinocytes, as well as how melanin is stored within these cells in a compartment that we propose be named the melanokerasome. Finally, we review the state of the art on the molecular mechanisms that lead to melanokerasome positioning above the nuclei of keratinocytes, forming supranuclear caps that shield the nuclear DNA from UV radiation. Thus, we provide a comprehensive overview of the current knowledge on the molecular mechanisms regulating skin pigmentation, from melanin exocytosis by melanocytes and internalization by keratinocytes to processing and polarization within keratinocytes. A better knowledge of these molecular mechanisms will clarify long-lasting questions in the field that are crucial for the understanding of skin pigmentation and can shed light on fundamental aspects of organelle biology. Ultimately, this knowledge can lead to novel therapeutic strategies to treat hypo- or hyper-pigmentation disorders, which have a high socio-economic burden on patients and healthcare systems worldwide, as well as cosmetic applications.

Abstract Numerous genomes are sequenced and made available to the community through the NCBI portal. However, and, unlike what happens for gene function annotation, annotation of promoter sequences and the underlying prediction of regulatory associations is mostly unavailable, severely limiting the ability to interpret genome sequences in a functional genomics perspective. Here we present an approach where one can download a genome of interest from NCBI in the GenBank Flat File (.gbff) format and, with a minimum set of commands, have all the information parsed, organized and made available through the platform web interface. Also, the new genomes are compared with a given genome of reference in search of homologous genes, shared regulatory elements and predicted transcription associations. We present this approach within the context of Community YEASTRACT of the YEASTRACT + portal, thus benefiting from immediate access to all the comparative genomics queries offered in the YEASTRACT + portal. Besides the yeast community, other communities can install the platform independently, without any constraints. In this work, we exemplify the usefulness of the presented tool, within Community YEASTRACT, in constructing a dedicated database and analysing the genome of the highly promising oleaginous red yeast species Rhodotorula toruloides currently poorly studied at the genome and transcriptome levels and with limited genome editing tools. Regulatory prediction is based on the conservation of promoter sequences and available regulatory networks. The case-study examined is focused on the Haa1 transcription factor—a key regulator of yeast resistance to acetic acid, an important inhibitor of industrial bioconversion of lignocellulosic hydrolysates. The new tool described here led to the prediction of a RtHaa1 regulon with expected impact in the optimization of R. toruloides robustness for lignocellulosic and pectin-rich residue biorefinery processes.

Mafalda Cavalheiro et al. use single-cell force spectroscopy and RNA-seq to examine the adhesion process of Candida glabrata, an opportunistic human fungal pathogen, to various medical surfaces. Their results suggest that the adhesion forces of C. glabrata to medical material are stronger than those presented for epithelial cells, and highlight the underlying molecular pathways related to adhesion and biofilm formation in this species.

One of the main contributing factors to uncertainty for ground-based global irradiance measurements is the angular response of the pyranometer. Since it depends on the angle of incidence, the measurement uncertainty will depend on the time of day and time of the year, as well as the site latitude and local climate. This work explores the geographical and seasonal distribution of the angle of incidence impact on the measurement accuracy of the global horizontal irradiance. Based on direct irradiance estimates from the ERA5 reanalysis, a model for the angle of incidence uncertainty, based on latitude and the fraction of diffuse irradiation, is proposed and validated, considering empirical estimates of the GHI component closure from the Baseline Surface Radiation Network. Results show that the model is accurately estimating the angle of incidence uncertainty at mid and high latitudes.

Production of large quantities of hepatocytes remains a major challenge for a number of clinical applications in the biomedical field. Directed differentiation of human pluripotent stem cells (hPSCs) into hepatocyte-like cells (HLCs) provides an advantageous solution and a number of protocols have been developed for this purpose. However, these methods usually follow different steps of liver development in vitro, which is time consuming and requires complex culture conditions. In addition, HLCs lack the full repertoire of functionalities characterising primary hepatocytes. Here, we explore the interest of forward programming to generate hepatocytes from hPSCs and to bypass these limitations. This approach relies on the overexpression of three hepatocyte nuclear factors (HNF1A, HNF6, and FOXA3) in combination with different nuclear receptors expressed in the adult liver using the OPTi-OX platform. Forward programming allows for the rapid production of hepatocytes (FoP-Heps) with functional characteristics using a simplified process. We also uncovered that the overexpression of nuclear receptors such as RORc can enhance specific functionalities of FoP-Heps thereby validating its role in lipid/glucose metabolism. Together, our results show that forward programming could offer a versatile alternative to direct differentiation for generating hepatocytes in vitro.

Gallium nitride is a wide bandgap semiconductor which is generally expected to replace some silicon-based technologies, despite some of its properties still requiring further investigation. Here, using a two-temperature model coupled to molecular dynamics simulations, the authors investigate and predict the effects of strongly ionising radiation in gallium nitride, revealing the mechanism behind its unusual resistance to radiation.

Most attempts to delineate quantum machine-learning-related computing capabilities of continuous variables states have relied on non-Gaussian resources. Here, the authors show that linear systems with continuous-variable Gaussian states are a promising platform for the implementation of quantum reservoir computers with universal approximation capabilities

In this study, cladodes of Opuntia ficus indica (OFIC), chemically modified with NaOH (OFICM), have been prepared, characterized, and tested as an effective biomass to remove Pb(II) and/or Cd(II) from aqueous media. At an optimum pH of 4.5, the adsorption capacity, qe, of treated OFICM was almost four times higher than that of untreated OFIC. The maximum adsorption capacities (qmax) in the single removal of Pb(II) and Cd(II) were 116.8 and 64.7 mg g−1, respectively. These values were 12.1% and 70.6% higher than those for the corresponding qmax in binary removal, which indicates the strong inhibitive effect of Pb(II) on the co-cation Cd(II) in a binary system. Structural and morphological characterization have been carried out by FTIR, SEM/EDX, and point of zero charge (pHPZC) measurements. The SEM/EDX results confirmed that the metals are adsorbed on the surface. The presence of C-O, C=O, and COO- functional groups were identified by FTIR on both OFIC and OFICM surfaces. On the other hand, we found that the adsorption processes followed the pseudo-second-order kinetics for both single and binary systems, with a fast biosorption rate of Pb(II) and Cd(II). The equilibrium data (adsorption isotherms) were better described by Langmuir and modified-Langmuir models for single and binary systems, respectively. A good regeneration of OFICM was obtained with an eluent of 0.1 M HNO3. Therefore, OFICM can be efficiently reused to remove Pb or Cd, up to three times.

Candida glabrata is a prominent pathogenic yeast which exhibits a unique ability to survive the harsh environment of host immune cells. In this study, we describe the role of the transcription factor encoded by the gene CAGL0F09229g, here named CgTog1 after its Saccharomyces cerevisiae ortholog, as a new determinant of C. glabrata virulence. Interestingly, Tog1 is absent in the other clinically relevant Candida species (C. albicans, C. parapsilosis, C. tropicalis, C. auris), being exclusive to C. glabrata. CgTog1 was found to be required for oxidative stress resistance and for the modulation of reactive oxygen species inside C. glabrata cells. Also, CgTog1 was observed to be a nuclear protein, whose activity up-regulates the expression of 147 genes and represses 112 genes in C. glabrata cells exposed to H2O2, as revealed through RNA-seq-based transcriptomics analysis. Given the importance of oxidative stress response in the resistance to host immune cells, the effect of CgTOG1 expression in yeast survival upon phagocytosis by Galleria mellonella hemocytes was evaluated, leading to the identification of CgTog1 as a determinant of yeast survival upon phagocytosis. Interestingly, CgTog1 targets include many whose expression changes in C. glabrata cells after engulfment by macrophages, including those involved in reprogrammed carbon metabolism, glyoxylate cycle and fatty acid degradation. In summary, CgTog1 is a new and specific regulator of virulence in C. glabrata, contributing to oxidative stress resistance and survival upon phagocytosis by host immune cells.

Mozambique is one of the largest energy producers in the Southern African Development Community. Substantial efforts have been undertaken in recent years to increase energy access for poverty reduction in the country, however, most efforts seem to be concentrated to rural areas ignoring the existence of urban energy poverty, and despite all the efforts made, almost 70% of the Mozambican population still lives without modern energy services. The study assesses the extent of energy poverty and the impact of the different dimensions of energy poverty in Mozambique using the multidimensional energy poverty index approach and Mozambican demographic and health surveys data for households. It concludes that Mozambique has improved from acute energy poverty in 2009 to moderate energy poverty in 2015. Increased inequalities, however, accompanied this improvement. Energy poverty is a rural and an urban phenomenon since 34% of urban households are energy poor, suggesting that energy poverty in the country is a problem of lack of access and a lack of capacity to afford energy services to fulfill basic needs. Therefore, coordinated political actions between the various economic sectors and policies that focus on meeting the population´s basic needs, on technical, financial, and infrastructural issues may upgrade the use of electricity and its impacts on human development. Finally, we propose changes to the method to highlight the relevance of productive uses of energy for energy poverty alleviation. We also suggest the introduction of energy affordability measures in the Multidimensional Energy Poverty Index framework to identify the causes of energy poverty.

The uptake of cholesterol from the host is closely linked to the proliferation of pathogenic fungi and protozoa during infection. For some pathogenic fungi, cholesterol uptake is an important strategy for decreasing susceptibility to antifungals that inhibit ergosterol biosynthesis. In this study, we show that Candida glabrata ERG25, which encodes an enzyme that demethylates 4,4-dimethylzymosterol, is required for cholesterol uptake from host serum. Based on the screening of C. glabrata conditional knockdown mutants for each gene involved in ergosterol biosynthesis, ERG25 knockdown was found to decrease lethality of infected mice. ERG25 knockdown impairs the plasma membrane localization of the sterol importer Aus1p, suggesting that the accumulated 4,4-dimethylzymosterol destabilizes the lipid domain with which Aus1p functionally associates. ERG25 knockdown further influences the structure of the membrane compartment of Can1p (MCC)/eisosomes (ergosterol-rich lipid domains), but not the localization of the membrane proteins Pma1p and Hxt1p, which localize to sterol-poor domains. In the sterol-rich lipid domain, Aus1p-contining domain was mostly independent of MCC/eisosomes, and the nature of these domains was also different: Ausp1-contining domain was a dynamic network-like domain, whereas the MCC/eisosomes was a static dot-like domain. However, deletion of MCC/eisosomes was observed to influence the localization of Aus1p after Aus1p was transported from the endoplasmic reticulum (ER) through the Golgi apparatus to the plasma membrane. These findings suggest that ERG25 plays a key role in stabilizing sterol-rich lipid domains, constituting a promising candidate target for antifungal therapy.

The immunosuppressive tumour microenvironment impairs immunotherapy in poorly immunogenic cancer. Here, the authors load an alginate gel with GM-CSF, CpG oligonucleotides and doxorubicin-iRGD to promote immunogenic death of tumour cells and improve immunotherapy efficacy in triple negative breast cancer models.

Alpha-synuclein (aSyn) plays a central role in Parkinson’s disease (PD) and has been extensively studied in the brain. This protein is part of the synuclein family, which is also composed of beta-synuclein (bSyn) and gamma-synuclein (gSyn). In addition to its neurotoxic role, synucleins have important functions in the nervous system, modulating synaptic transmission. Synucleins are expressed in the retina, but they have been poorly characterized. However, there is evidence that they are important for visual function and that they can play a role in retinal degeneration. This study aimed to profile synucleins in the retina of naturally aged mice and to correlate their patterns with specific retinal cells. With aging, we observed a decrease in the thickness of specific retinal layers, accompanied by an increase in glial reactivity. Moreover, the aSyn levels decreased, whereas bSyn increased with aging. The colocalization of both proteins was decreased in the inner plexiform layer (IPL) of the aged retina. gSyn presented an age-related decrease at the inner nuclear layer but was not significantly changed in the ganglion cell layer. The synaptic marker synaptophysin was shown to be preferentially colocalized with aSyn in the IPL with aging. At the same time, aSyn was found to exist at the presynaptic endings of bipolar cells and was affected by aging. Overall, this study suggests that physiological aging can be responsible for changes in the retinal tissue, implicating functional alterations that could affect synuclein family function.

Se estudian los avatares sufridos por el patrimonio bibliográfico de los dominicos valencianos durante los siglos XIX y XX a partir del seguimiento de cada uno de los cuatro volúmenes manuscritos del Necrologio del padre Teixidor: su primitiva ubicación en la librería del convento de Predicadores de Valencia, su traslado a las Baleares en la época napoleónica, su diverso destino en el periodo desamortizador, el retorno de varios volúmenes a manos de los religiosos tras la Restauración y las nuevas incautaciones y reubicaciones producidas durante y después de la guerra civil española.

Marine microbiomes are prolific sources of bioactive natural products of potential pharmaceutical value. This study inspected two culture collections comprising 919 host-associated marine bacteria belonging to 55 genera and several thus-far unclassified lineages to identify isolates with potentially rich secondary metabolism and antimicrobial activities. Seventy representative isolates had their genomes mined for secondary metabolite biosynthetic gene clusters (SM-BGCs) and were screened for antimicrobial activities against four pathogenic bacteria and five pathogenic Candida strains. In total, 466 SM-BGCs were identified, with antimicrobial peptide- and polyketide synthase-related SM-BGCs being frequently detected. Only 38 SM-BGCs had similarities greater than 70% to SM-BGCs encoding known compounds, highlighting the potential biosynthetic novelty encoded by these genomes. Cross-streak assays showed that 33 of the 70 genome-sequenced isolates were active against at least one Candida species, while 44 isolates showed activity against at least one bacterial pathogen. Taxon-specific differences in antimicrobial activity among isolates suggested distinct molecules involved in antagonism against bacterial versus Candida pathogens. The here reported culture collections and genome-sequenced isolates constitute a valuable resource of understudied marine bacteria displaying antimicrobial activities and potential for the biosynthesis of novel secondary metabolites, holding promise for a future sustainable production of marine drug leads.

ABSTRACT Introduction: Arteriovenous fistulas (AVF) are the first choice vascular access for hemodialysis. However, they present a high incidence of venous stenosis leading to thrombosis. Although training in interventional nephrology may improve accessibility for treatment of venous stenosis, there is limited data on the safety and efficacy of this approach performed by trained nephrologists in low-income and developing countries. Methods: This study presents the retrospective results of AVF angioplasties performed by trained nephrologists in a Brazilian outpatient interventional nephrology center. The primary outcome was technical success rate (completion of the procedure with angioplasty of all stenoses) and secondary outcomes were complication rates and overall AVF patency. Findings: Two hundred fifty-six angioplasties were performed in 160 AVF. The technical success rate was 88.77% and the main cause of technical failure was venous occlusion (10%). The incidence of complications was 13.67%, with only one patient needing hospitalization and four accesses lost due to the presence of hematomas and/or thrombosis. Grade 1 hematomas were the most frequent complication (8.2%). The overall patency found was 88.2 and 80.9% at 180 and 360 days after the procedure, respectively. Conclusion: Our findings suggest that AVF angioplasty performed by trained nephrologists has acceptable success rates and patency, with a low incidence of major complications as well as a low need for hospitalization.

The design of new dual-purpose thermal desalination plants is a combinatory problem because the optimal process configuration strongly depends on the desired targets of electricity and freshwater. This paper proposes a mathematical model for selecting the optimal structure, the operating conditions, and sizes of all system components of dual-purpose thermal desalination plants. Electricity is supposed to be generated by a combined-cycle heat and power plant (CCHPP) with the following candidate structures: (a) one or two gas turbines; (b) one or two additional burners in the heat recovery steam generator; (c) the presence or missing a medium-pressure steam turbine; (d) steam generation and reheating at low pressure. Freshwater is supposed to be obtained from two candidate thermal processes: and (e) a multi-effect distillation (MED) or a multi-stage flash (MSF) system. The number of effects in MED and stages in MSF are also discrete decisions. Different case studies are presented to show the applicability of the model for same cost data. The proposed model is a powerful tool in optimizing new plants (or plants under modernization) and/or improving existing plants for desired electricity generation and freshwater production. No articles addressing the optimization involving the discrete decisions mentioned above are found in the literature.

The mismatch between photovoltaic generation and residential load leads to relative modest rates of self-consumption of solar electricity unless expensive storage solutions are locally available. One alternative to batteries is the aggregation of demand of different prosumers, as the collective load diagram might be better adapted to the solar resource. This hypothesis is tested for empirical data from 18 dwellings and 3 small businesses in the city of Lisbon, Portugal. Results show that a relatively low number of dwellings and a local small shop with a PV system without any storage will reach 90% self-consumption rates at a much lower cost than an individually owned PV system with 1 kWh/kWp storage system. Keywords: Photovoltaics, Self-consumption, Demand aggregation, Solar community

Introduction: Coding variants in apolipoprotein L-1 (APOL1) are associated with an increased risk of end-stage kidney disease (ESRD) in African American individuals under a recessive model of inheritance. The effect of the APOL1 risk alleles on kidney disease has been observed in studies in African American and African populations. Despite the 130 million individuals of recent African ancestry in South America, the impact of APOL1 has not been explored. Methods: In this case-control study, we tested APOL1 genotype in 106 Brazilian HD (hemodialysis) patients with African ancestry and compared risk allele frequency with 106 healthy first-degree relatives. The association of risk alleles and ESRD was calculated with a linear mixed model and was adjusted for relatedness and additional confounders. In a broader survey, the age of dialysis initiation and APOL1 variants were analyzed in 274 HD patients. Results: Two APOL1 risk alleles were 10 times more common in patients with ESRD than in controls (9.4% vs. 0.9%; odds ratio [OR]: 10.95, SE = 1.49, P = 0.0017). Carriers of 2 risk alleles initiated dialysis 12 years earlier than patients with zero risk alleles. Conclusion: The APOL1 risk variants were less frequent in dialysis patients of African ancestry in Brazil than in the United States. Nonetheless, carriers of 2 risk variants had 10-fold higher odds of ESRD. Age of dialysis initiation was markedly lower in 2-risk allele carriers, suggesting a more aggressive disease phenotype. The Brazilian population represents an opportunity to identify different sets of genetic modifiers or environmental triggers that might be present in more extensively studied populations. Keywords: age of dialysis initiation, APOL1, APOL1-associated kidney disease, end-stage kidney disease, genetics, South America

Pastrana conserva uno de los conjuntos más relevantes de artesonados renacentistas en España, trazados por Alonso de Covarrubias y ejecutados por Cristóbal de Nieva y Justo de Vega en 1549-50. Con la llegada del Renacimiento, los techos de madera habían adoptado formas al romano y tramas geométricas con teselaciones de polígonos presentes en restos de la antigüedad. Mientras en el resto de Europa estos patrones poblaban techos planos, el oficio y conocimiento geométrico de los carpinteros peninsulares, herederos de la tradición visigoda e hispanomusulmana, permitió su ejecución sobre techos poliédricos, en un desarrollo que supera la mera copia de formas importadas de Italia. El artículo analiza los diferentes trazados presentes en Pastrana y las variadas estrategias para encajar las teselaciones planas en la configuración de los paños inclinados, especialmente en el diseño de los cuartos de limas.

From 1990–2019, a total of 15,442 New Marine Natural Products from Invertebrates (NMNPIs) were reported. The 2010s saw the most prolific decade of biodiscovery, with 5630 NMNPIs recorded. The phyla that contributed most biomolecules were the Porifera (sponges) (47.2%, 2659 NMNPIs) and the Cnidaria (35.3%, 1989 NMNPIs). The prevalence of these two phyla as the main sources of NMNPIs became more pronounced in the 2010s. The tropical areas of the Pacific Ocean yielded more NMNPIs, most likely due to the remarkable biodiversity of coral reefs. The Indo-Burma biodiversity hotspot (BH) was the most relevant area for the biodiscovery of NMNPIs in the 2010s, accounting for nearly one-third (1819 NMNPIs) of the total and surpassing the top BH from the 1990s and the 2000s (the Sea of Japan and the Caribbean Islands, respectively). The Chinese exclusive economic zone (EEZ) alone contributed nearly one-quarter (24.7%) of all NMNPIs recorded during the 2010s, displacing Japan’s leading role from the 1990s and the 2000s. With the biodiscovery of these biomolecules steadily decreasing since 2012, it is uncertain whether this decline has been caused by lower bioprospecting efforts or the potential exhaustion of chemodiversity from traditional marine invertebrate sources.