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Societal Impact Statement Table grape production is a traditional practice in southeastern Spain, where locals have produced fresh grapes and raisins for centuries. Many of these vines are now centenary, and they represent a useful source of diversity for developing future table grape varieties with improved traits. Genetic analysis showed that many of the local varieties identified in this study were traditional varieties from Western Mediterranean countries. Others were not identified, and they might be old grape varieties of previous importance in the region. The conservation and characterization of these varieties could be key to ensuring current and future vineyard sustainability. Summary Current worldwide table grape production focuses on a reduced number of Vitis vinifera L. varieties. However, traditional farmers have grown many table grape varieties for centuries, as they provided a steady source of fresh fruit and raisins. These ancient living genotypes potentially store a genetic diversity that can be used now to ensure future grape production. Here we focused on the study of grapevines found across Almería, one of the Spanish regions with longer tradition in table grape production. After an exhaustive inspection, we located 220 old (some centenary) vines producing grapes consumed by owners or in abandoned areas no longer devoted to agriculture. Some of these vines were identified by comparing their simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) genetic profiles with available data from international databases. We found that, while grape growers' efforts focused on the cultivation of traditional grape varieties from Western Mediterranean regions, they also cultivated few exogenous varieties if they provided additional fruit features. Other vines were found to have genetic profiles that did not match reference datasets. Interestingly, some of them were found in multiple locations, suggesting they are endangered varieties with some previous relevance in the region. Besides, first‐degree relationships support the autochthonous origin of many of these unidentified genotypes. Locals kept a high number of different grapevine varieties, now considered reservoirs of genetic diversity. Traditional farming practices have been useful to prevent the loss of this diversity, which now needs to be preserved and further studied to contribute to the sustainability of viticultural systems.

La vida se desarrolla bajo la influencia sistemática de factores socializadores, en los distintos contextos que influyen en lo afectivo y lo cognitivo a través del desarrollo de la personalidad de los estudiantes. En ello la orientación profesional y la dialéctica aplicada en los últimos cursos, urge de acciones precisas al actuar como un todo único en todas las formaciones psicológicas por las que pasa el estudiante en el tránsito del preuniversitario a la universidad. En este artículo se propone una metodología de orientación profesional, como vía de solución, a las regularidades que han incidido negativamente, durante varios cursos en los distintos indicadores de la eficiencia, en el proceso docente educativo de la escuela, al incorporarse de la enseñanza preuniversitaria a la universitaria. Todo ello influye en el bienestar de los estudiantes, las familias y la comunidad, al verse afectadas cuando ocurre una deserción o ausencias prolongadas del estudiante a la docencia. Es allí donde la orientación profesional, debe desempeñar el rol esencial, por los distintos agentes educativos desde el preuniversitario en la continuidad de estudio dentro del mismo sistema. Con la instrumentación de esta propuesta se puede solucionar la problemática planteada, con la participación de los distintos agentes del proceso docente educativo.

In waste recycling plants, measuring the waste volume and weight at the beginning of the treatment process is key for a better management of resources. This task can be conducted by using orthophoto images, but it is necessary to remove from those images the objects, such as containers or trucks, that are not involved in the measurement process. This work proposes the application of deep learning for the semantic segmentation of those irrelevant objects. Several deep architectures are trained and compared, while three semi-supervised learning methods (PseudoLabeling, Distillation and Model Distillation) are proposed to take advantage of non-annotated images. In these experiments, the U-net++ architecture with an EfficientNetB3 backbone, trained with the set of labelled images, achieves the best overall multi Dice score of 91.23%. The application of semi-supervised learning methods further boosts the segmentation accuracy in a range between 1.31% and 2.59%, on average.

Resistive switching (RS) devices are electronic components which exhibit a resistive state that can be adjusted to different nonvolatile levels via electrical stressing, fueling the development of future resistive memories (ReRAM) and enabling innovative solutions for several applications. Most works so far have used voltage-based driving schemes for both WRITE and READ operations. However, results from current-driven WRITE operations have shown high uniformity in switching performance, and thus constitute a valid alternative to consider, but current-driven READ operations have rarely been explored. In this context, here we tested a current-based READ/WRITE memory driving scheme on commercial self-directed channel (SDC) devices, while operating constantly at low current levels between tenths of nA and 1.5 uA. We propose a novel method to carry out efficient READ operations exploiting the transient response of the voltage on the current-driven ReRAM memory cells. For READ operations performed at 100 nA, we calculated the cumulative probability distribution of the standard deviation of the measured voltage ( $\sigma _{\mathrm {V}}$ ) on the devices and we observed a ratio $\sigma _{\mathrm {V-HRS}}/\sigma _{\mathrm {V-LRS}} \sim 10\times $ . Moreover, the HRS and LRS states were distinguishable in all the tested devices with less than 0.5% error. Finally, the calculated energy consumption ( $E_{\mathrm {SET}} \approx 10$ nJ, $E_{\mathrm {RESET}} \approx 30$ nJ, and $E_{\mathrm {READ}}$ between 80–400 pJ) was competitive even when the duration of the READ/WRITE current pulses was suboptimal in the millisecond range. Therefore, the presented results validate the promising characteristics and the power-efficiency of the proposed READ method for current-driven ReRAM circuits and applications.

Inspired by the behavior of natural systems, Cellular Automata (CA) tackle the demanding long-distance information transfer of conventional computers by the massive parallel computation performed by a set of locally-coupled dynamical nodes. Although CA are envisioned as powerful deterministic computers, their intrinsic capabilities are expanded after the memristor’s probabilistic switching is introduced into CA cells, resulting in new hybrid deterministic and probabilistic memristor-based CA (MemCA). In the proposed MemCA hardware realization, memristor devices are incorporated in both the cell and rule modules, composing the very first all-memristor CA hardware, designed with mixed CMOS/Memristor circuits. The proposed implementation accomplishes high operating speed and reduced area requirements, exploiting also memristor as an entropy source in every CA cell. MemCA’s functioning is showcased in deterministic and probabilistic operation, which can be externally modified by the selection of programming voltage amplitude, without changing the design. Also, the proposed MemCA system includes a reconfigurable rule module implementation that allows for spatial and temporal rule inhomogeneity.

The aeronautic industry is facing many challenges regarding the lifetime, weight and accuracy that aircraft skins must comply to meet stringent structural and aerodynamic requirements. Currently, mechanical milling of aircraft skin parts of 2024-T3 aluminum alloy is displacing the highly pollutant chemical milling. Consequently, flexible and reconfigurable vacuum holding fixtures are being increasingly employed, because they are adaptable to several part geometries, but, since their rigidity is extremely reduced, the low stiffness of parts limits severely their deployment. Aiming to harness the full potential of these holding systems for aluminum alloy skin parts, a complete analysis of final thickness achieved and cutting force is developed. Thin floor parts of different geometries are pocket milled, simply screwed at their corners, emulating a skin part supported by four vacuum cups. Process forces are continuously monitored, and final thickness is measured. It has been proven that the reduction of mass and stiffness during milling causes a corresponding reduction of the natural frequencies of the parts. Also, as long as natural frequencies are not excited, final thickness error is almost constant and not affected by the tool position, but only by the initial geometry and fixtures distribution of the part. Additionally, a new cutting force model for skin parts is empirically calculated. Unlike models designed for fully supported parts, this model is designed for skins held in flexible fixtures. It has a relative error of 5.6% and it allows to optimize the trajectory, geometry and support distribution, thus boosting the use of flexible fixtures.

This study analyzes the effects of the punch-through stop (PTS) layer and well depth in a bulk FinFET SRAM cell on the fraction of charge generated by an ion impact that is collected by the FinFET channel. More than 1700 3D TCAD simulations have been performed to obtain a detailed map of the sensitivity areas in a full cell 6-T SRAM 22 nm bulk-FinFET process. The influence of the well depth on the charge collected by the drain devices of the SRAM cell has been studied, and it has been concluded that the collected charge can be reduced down to 300% simply by modifying the depth of the well, without affecting the performance of the cell. Different PTS layer depths have been analyzed in order to calculate which value minimizes the impact of the charge generated by an ion during its track along the FinFET body. The simulations carried out allow to conclude that the incorporation of a PTS layer not only reduces the leakage current, but also reduces the amount of charge, delivered by the ion, that reaches the drain region. Simulation results also show that the fraction of the charge generated by the ion impact, which is collected by the drain, mainly depends on the depth of the wells, whereas the PTS layer hardly modifies the collected charge.

Abstract Much evidence suggests a role for human milk oligosaccharides (HMOs) in establishing the infant microbiota in the large intestine, but the response of particular bacteria to individual HMOs is not well known. Here twelve bacterial strains belonging to the genera Bifidobacterium, Enterococcus, Limosilactobacillus, Lactobacillus, Lacticaseibacillus, Staphylococcus and Streptococcus were isolated from infant faeces and their growth was analyzed in the presence of the major HMOs, 2′-fucosyllactose (2′FL), 3-fucosyllactose (3FL), 2′,3-difucosyllactose (DFL), lacto-N-tetraose (LNT) and lacto-N-neo-tetraose (LNnT), present in human milk. Only the isolated Bifidobacterium strains demonstrated the capability to utilize these HMOs as carbon sources. Bifidobacterium infantis Y538 efficiently consumed all tested HMOs. Contrarily, Bifidobacterium dentium strains Y510 and Y521 just metabolized LNT and LNnT. Both tetra-saccharides are hydrolyzed into galactose and lacto-N-triose (LNTII) by B. dentium. Interestingly, this species consumed only the galactose moiety during growth on LNT or LNnT, and excreted the LNTII moiety. Two β-galactosidases were characterized from B. dentium Y510, Bdg42A showed the highest activity towards LNT, hydrolyzing it into galactose and LNTII, and Bdg2A towards lactose, degrading efficiently also 6′-galactopyranosyl-N-acetylglucosamine, N-acetyl-lactosamine and LNnT. The work presented here supports the hypothesis that HMOs are mainly metabolized by Bifidobacterium species in the infant gut.

ABSTRACT The gastrointestinal microbiota members produce α-l-fucosidases that play key roles in mucosal, human milk, and dietary oligosaccharide assimilation. Here, 36 open reading frames (ORFs) coding for putative α-l-fucosidases belonging to glycosyl hydrolase family 29 (GH29) were identified through metagenome analysis of breast-fed infant fecal microbiome. Twenty-two of those ORFs showed a complete coding sequence with deduced amino acid sequences displaying the highest degree of identity with α-l-fucosidases from Bacteroides thetaiotaomicron, Bacteroides caccae, Phocaeicola vulgatus, Phocaeicola dorei, Ruminococcus gnavus, and Streptococcus parasanguinis. Based on sequence homology, 10 α-l-fucosidase genes were selected for substrate specificity characterization. The α-l-fucosidases Fuc18, Fuc19A, Fuc35B, Fuc39, and Fuc1584 showed hydrolytic activity on α1,3/4-linked fucose present in Lewis blood antigens and the human milk oligosaccharide (HMO) 3-fucosyllactose. In addition, Fuc1584 also hydrolyzed fucosyl-α-1,6-N-acetylglucosamine (6FN), a component of the core fucosylation of N-glycans. Fuc35A and Fuc193 showed activity on α1,2/3/4/6 linkages from H type-2, Lewis blood antigens, HMOs and 6FN. Fuc30 displayed activity only on α1,6-linked l-fucose, and Fuc5372 showed a preference for α1,2 linkages. Fuc2358 exhibited a broad substrate specificity releasing l-fucose from all the tested free histo-blood group antigens, HMOs, and 6FN. This latest enzyme also displayed activity in glycoconjugates carrying lacto-N-fucopentaose II (Lea) and lacto-N-fucopentaose III (Lex) and in the glycoprotein mucin. Fuc18, Fuc19A, and Fuc39 also removed l-fucose from neoglycoproteins and human α-1 acid glycoprotein. These results give insight into the great diversity of α-l-fucosidases from the infant gut microbiota, thus supporting the hypothesis that fucosylated glycans are crucial for shaping the newborn microbiota composition. IMPORTANCE α-l-Fucosyl residues are frequently present in many relevant glycans, such as human milk oligosaccharides (HMOs), histo-blood group antigens (HBGAs), and epitopes on cell surface glycoconjugate receptors. These fucosylated glycans are involved in a number of mammalian physiological processes, including adhesion of pathogens and immune responses. The modulation of l-fucose content in such processes may provide new insights and knowledge regarding molecular interactions and may help to devise new therapeutic strategies. Microbial α-l-fucosidases are exoglycosidases that remove α-l-fucosyl residues from free oligosaccharides and glycoconjugates and can be also used in transglycosylation reactions to synthesize oligosaccharides. In this work, α-l-fucosidases from the GH29 family were identified and characterized from the metagenome of fecal samples of breastfed infants. These enzymes showed different substrate specificities toward HMOs, HBGAs, naturally occurring glycoproteins, and neoglycoproteins. These novel glycosidase enzymes from the breast-fed infant gut microbiota, which resulted in a good source of α-l-fucosidases, have great biotechnological potential.

In this work, a versatile mathematical framework for multi-state probabilistic modeling of Resistive Switching (RS) devices is proposed for the first time. The mathematical formulation of memristor and Markov jump processes are combined and, by using the notion of master equations for finite-states, the inherent probabilistic time-evolution of RS devices is sufficiently modeled. In particular, the methodology is generic enough and can be applied for N states; as a proof of concept, the proposed framework is further stressed for both a two-state RS paradigm, namely N = 2, and a multi-state device, namely N = 4. The presented I-V results demonstrate in a qualitative and quantitative manner, adequate matching with other modeling approaches.

The huge quantity of nodes and interconnections in modern binary circuits leads to extremely high levels of energy consumption. The interconnection complexity and other issues of binary circuits encourage researchers to consider multiple-valued logic (MVL) alternatives. Features of Carbon Nanotube Field-Effect Transistors (CNTFETs) make this technology a potential candidate to implement MVL circuits. In this article, a new systematic methodology is proposed to design ternary logic block circuits based on CNTFETs. The methodology is applied to the design of two basic logic circuits, a half adder and a 1-digit multiplier, which are evaluated through HSPICE simulations. Simulation results indicate improvements over current equivalents in transistor count and PDP mean with the half adder version of 19.2%, and 74.07% respectively, and with the 1-digit multiplier of 24.67% and 81.12% respectively.

In this article, we present a new method to mitigate the effect of the charge collected by trigate FinFET devices after an ionizing particle impact. The method is based on the creation of an internal structure that generates an electrical field that drives the charge generated by the ion track out of the sensitive device terminals. This electrical field is generated with the insertion of complementary doped regions near the active region of the device. We analyze the influence of the distance of those regions to the device, their depth into the substrate and their doping concentration to determine the optimal implementation which minimizes the collected charge. The impact on the device performance in terms of leakage current, threshold voltage, maximum transconductance and subthreshold voltage swing has also been investigated. Our results show that the added structures introduce negligible effects in performance degradation and total leakage current, at the cost of a small increase in area. The simulations performed with technology computer-aided design numerical (TCAD) tools in 22nm bulk FinFET technology show that the amount of charge collected by the device terminals can be reduced up to 50% for a linear energy transfer (LET) of 60 MeV-cm2/mg.

CAD is a 1.5 MDa hexameric protein with four enzymatic domains responsible for initiating de novo biosynthesis of pyrimidines nucleotides: glutaminase, carbamoyl phosphate synthetase, aspartate transcarbamoylase (ATC), and dihydroorotase. Despite its central metabolic role and implication in cancer and other diseases, our understanding of CAD is poor, and structural characterization has been frustrated by its large size and sensitivity to proteolytic cleavage. Recently, we succeeded in isolating intact CAD-like particles from the fungus Chaetomium thermophilum with high yield and purity, but their study by cryo-electron microscopy is hampered by the dissociation of the complex during sample grid preparation. Here we devised a specific crosslinking strategy to enhance the stability of this mega-enzyme. Based on the structure of the isolated C. thermophilum ATC domain, we inserted by site-directed mutagenesis two cysteines at specific locations that favored the formation of disulfide bridges and covalent oligomers. We further proved that this covalent linkage increases the stability of the ATC domain without damaging the structure or enzymatic activity. Thus, we propose that this cysteine crosslinking is a suitable strategy to strengthen the contacts between subunits in the CAD particle and facilitate its structural characterization.

Reseña sobre el libro El desastre de Annual a través de la prensa. Entre la prensa de aquella época destacaron algunos periodistas que utilizaron el libro como recurso o plataforma para profundizar en las crónicas y reportajes que hicieron y enviaban desde el lugar de los hechos: Melilla, Nador, Monte Arruit, Igueriben… el Protectorado español

Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1–3 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNFα and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators.

Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host–microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.

El turismo de Sol y Playa es una de las actividades económicas más importantes en Andalucía. Sin embargo, las playas turísticas pueden ser entornos peligrosos para los bañistas debido a la presencia de bancos de medusas y otros organismos gela­tinosos, como Physalia physalis. Dada la naturaleza del problema, realizamos un estudio integrado sobre el impacto de las medu­sas y otros organismos gelatinosos en la costa andaluza: en primer lugar, estudiamos la percepción de los usuarios de playas y la prensa local sobre la presencia de medusas; y, en segundo lugar, analizamos la distribución espacial y temporal de los avistamien­tos de medusas y otros organismos gelatinosos mediante el uso de Sistemas de Información Geográfica. Los resultados muestran que tanto los usuarios de la playa como la prensa local perciben las floraciones de medusas como un problema de creciente im­portancia. Encontramos que los avistamientos de medusas se concentraron en la temporada de verano y fueron más abundantes en el mar Mediterráneo, entre las provincias de Málaga y Granada. Pelagia noctiluca fue la medusa más avistada y se concentró en los meses de verano. Le sigue Physalia physalis, un hidrozoo marino más abundante en primavera y en el Océano Atlántico, aunque también aparece en el Mar Mediterráneo, como consecuencia de la fuerza de las borrascas atlánticas. Concluimos que la investigación sobre las floraciones de medusas y otros organismos gelatinosos potencialmente peligrosos para los usuarios de playas es crucial para el manejo integrado de la zona costera en áreas turísticas.

Thin floor machining is a challenging and demanding issue, due to vibrations that create poor surface quality. Several technologies have been developed to overcome this problem. Ad hoc fixtures for a given part geometry lead to meeting quality tolerances, but since they lack flexibility, they are expensive and not suitable for low manufacturing batches. On the contrary, flexible fixtures consisting of vacuum cups adaptable to a diversity of part geometries may not totally avoid vibrations, which greatly limits its use. The present study analyses the feasibility of thin floor milling in terms of vibration and roughness, in the cases where milling is conducted without back support, a usual situation when flexible fixtures are employed, so as to define the conditions for a stable milling in them and thus avoid the use of ad hoc fixtures. For that purpose, the change of modal parameters due to material removal and its influence on chatter appearance have been studied, by means of stability lobe diagrams and Fourier Transform analysis. Additionally, the relationship between surface roughness and chatter frequency, tooth passing frequency, and spindle frequency have been studied. Ploughing effect has also been observed during milling, and the factors that lead to the appearance of this undesirable effect have been analyzed, in order to avoid it. It has been proven that finish milling of thin floors without support in the axial direction of the mill can meet aeronautic tolerances and requirements, providing that proper cutting conditions and machining zones are selected.

Intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of analyzing whether human gut bacteria improve the inefficient replication of human rotavirus in mice, we performed fecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. We showed that a simple antibiotic treatment, irrespective of FMT, resulted in viral shedding for 6 days after challenge with the human rotavirus G1P[8] genotype Wa strain (RVwa). Rotavirus titers in feces were also significantly higher in antibiotic-treated animals with or without FMT but they were decreased in animals subject to self-FMT, where a partial re-establishment of specific bacterial taxons was evidenced. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members of Lactobacillus, Bilophila, Mucispirillum, and Oscillospira, recovered after self-FMT. In antibiotic-treated and FMT animals where the virus replicated more efficiently, differences were observed in gene expression of immune mediators, such as IL1β and CXCL15, as well as in the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human rotavirus infectivity in mice.

Precise control and study of molecules is challenging due to the variety of internal degrees of freedom and local coordinates that are typically not controlled in an experiment. Employing quantum gas microscopy to position and resolve the atoms in Rydberg macrodimer states solves most of these challenges and enables unique access to the molecular frame. Here, we demonstrate this approach and present photoassociation studies in which the molecular orientation relative to an applied magnetic field, the polarization of the excitation light, and the initial atomic state are fully controlled. The observed dependencies allow for an electronic structure tomography of the molecular state. We additionally observe an orientation-dependent Zeeman shift, and we reveal a significant influence on it caused by the hyperfine interaction of the macrodimer state. Finally, we demonstrate control over the electrostatic binding potential by engineering a gap between two crossing pair potentials. Our results establish macrodimers as the most sensitive tool to benchmark Rydberg interaction potentials, and they open new perspectives for improving Rydberg dressing schemes.

The gut microbiota has emerged as a key factor in the pathogenesis of intestinal viruses, including enteroviruses, noroviruses and rotaviruses (RVs), where stimulatory and inhibitory effects on infectivity have been reported. With the aim of determining whether members of the microbiota interact with RVs during infection, a combination of anti-RV antibody labeling, fluorescence-activated cell sorting and 16S rRNA amplicon sequencing was used to characterize the interaction between specific bacteria and RV in stool samples of children suffering from diarrhea produced by G1P[8] RV. The genera Ruminococcus and Oxalobacter were identified as RV binders in stools, displaying enrichments between 4.8- and 5.4-fold compared to samples nonlabeled with anti-RV antibodies. In vitro binding of the G1P[8] Wa human RV strain to two Ruminococcus gauvreauii human isolates was confirmed by fluorescence microscopy. Analysis in R. gauvreauii with antibodies directed to several histo-blood group antigens (HBGAs) indicated that these bacteria express HBGA-like substances on their surfaces, which can be the target for RV binding. Furthermore, in vitro infection of the Wa strain in differentiated Caco-2 cells was significantly reduced by incubation with R. gauvreauii. These data, together with previous findings showing a negative correlation between Ruminococcus levels and antibody titers to RV in healthy individuals, suggest a pivotal interaction between this bacterial group and human RV. These results reveal likely mechanisms of how specific bacterial taxa of the intestinal microbiota could negatively affect RV infection and open new possibilities for antiviral strategies.

Periodic driving has emerged as a powerful tool in the quest to engineer new and exotic quantum phases. While driven many-body systems are generically expected to absorb energy indefinitely and reach an infinite-temperature state, the rate of heating can be exponentially suppressed when the drive frequency is large compared to the local energy scales of the system—leading to long-lived “prethermal” regimes. In this work, we experimentally study a bosonic cloud of ultracold atoms in a driven optical lattice and identify such a prethermal regime in the Bose-Hubbard model. By measuring the energy absorption of the cloud as the driving frequency is increased, we observe an exponential-in-frequency reduction of the heating rate persisting over more than 2 orders of magnitude. The tunability of the lattice potentials allows us to explore one- and two-dimensional systems in a range of different interacting regimes. Alongside the exponential decrease, the dependence of the heating rate on the frequency displays features characteristic of the phase diagram of the Bose-Hubbard model, whose understanding is additionally supported by numerical simulations in one dimension. Our results show experimental evidence of the phenomenon of Floquet prethermalization and provide insight into the characterization of heating for driven bosonic systems.

In finishing processes, the quality of aluminum parts is mostly influenced by static and dynamic phenomena. Different solutions have been studied toward a stable milling process attainment. However, the improvements obtained with the tuning of process parameters are limited by the system stiffness and external dampers devices interfere with the machining process. To deal with this challenge, this work analyzes the suitability of elastomer layers as passive damping elements directly located under the part to be machined. Thus, exploiting the sealing properties of nitrile butadiene rubber (NBR), a suitable flexible vacuum fixture is developed, enabling a proper implementation in the manufacturing process. Two different compounds are characterized under axial compression and under finishing operations. The compression tests present the effect of the feed rate and the strain accumulative effect in the fixture compressive behavior. Despite the higher strain variability of the softer rubber, different milling process parameters, such as the tool feed rate, can lead to a similar compressive behavior of the fixture regardless the elastomer hardness. On the other hand, the characterization of these flexible fixtures is completed over AA2024 floor milling of rigid parts and compared with the use of a rigid part clamping. These results show that, as the cutting speed and the feed rate increases, due to the strain evolution of the rubber, the part quality obtained tend to equalize between the flexible and the rigid clamping of the workpiece. Due to the versatility of the NBR for clamping different part geometries without new fixture redesigns, this leads to a competitive advantage of these flexible solutions against the classic rigid vacuum fixtures. Finally, a model to predict the grooving forces with a bull-nose end mill regardless of the stiffness of the part support is proposed and validated for the working range.

Closed generic quantum many-body systems may fail to thermalize under certain conditions even after long times, a phenomenon called many-body localization (MBL). Numerous studies support the stability of the MBL phase in strongly disordered one-dimensional systems. However, the situation is much less clear when a small part of the system is ergodic, a scenario which also has important implications for the existence of many-body localization in higher dimensions. Here we address this question experimentally using a large-scale quantum simulator of ultracold bosons in a two-dimensional optical lattice. We prepare two-component mixtures of varying relative population and implement a disorder potential which is experienced only by one of the components. The second nondisordered “clean” component plays the role of a bath of adjustable size that is collisionally coupled to the “dirty” component. Our experiments show how the dynamics of the dirty component, which, when on its own, show strong evidence of localization, become affected by the coupling to the clean component. For a high clean population, the clean component appears to behave as an effective bath for the system which leads to its delocalization, while for a smaller clean population, the ability of the bath to destabilize the system becomes strongly reduced. Our results reveal how a finite-sized quantum system can bring another one towards thermalization, in a regime of complex interplay between disorder, tunneling, and intercomponent interactions. They provide a new benchmark for effective theories aiming to capture the complex physics of MBL in the weakly localized regime.

Extracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas.

Coherent many-body quantum dynamics lies at the heart of quantum simulation and quantum computation. Both require coherent evolution in the exponentially large Hilbert space of an interacting many-body system. To date, trapped ions have defined the state of the art in terms of achievable coherence times in interacting spin chains. Here, we establish an alternative platform by reporting on the observation of coherent, fully interaction-driven quantum revivals of the magnetization in Rydberg-dressed Ising spin chains of atoms trapped in an optical lattice. We identify partial many-body revivals at up to about ten times the characteristic time scale set by the interactions. At the same time, single-site-resolved correlation measurements link the magnetization dynamics with interspin correlations appearing at different distances during the evolution. These results mark an enabling step towards the implementation of Rydberg-atom-based quantum annealers, quantum simulations of higher-dimensional complex magnetic Hamiltonians, and itinerant long-range interacting quantum matter.

Noroviruses (NoVs) are the main etiologic agents of acute epidemic gastroenteritis and probiotic bacteria have been reported to exert a positive effect on viral diarrhea. The protruding (P) domain from NoVs VP1 capsid protein has the ability to assemble into the so-called P-particles, which retain the binding ability to host receptors. We purified the P-domains from NoVs genotypes GI.1 and GII.4 as 6X(His)-tagged proteins and determined that, similar to native domains, they were structured into P-particles that were functional in the recognition of the specific glycoconjugated receptors, as established by surface plasmon resonance experiments. We showed that several lactic acid bacteria (probiotic and non-probiotic) and a Gram-negative probiotic strain have the ability to bind P-particles on their surfaces irrespective of their probiotic status. The binding of P-particles (GI.1) to HT-29 cells in the presence of selected strains showed that bacteria can inhibit P-particle attachment in competitive exclusion experiments. However, pre-treatment of cells with bacteria or adding bacteria to cells with already attached P-particles enhanced the retention of the particles. Although direct viral binding and blocking of viral receptors have been postulated as mechanisms of protection against viral infection by probiotic bacteria, these results highlight the need for a careful evaluation of this hypothesis. The work presented here investigates for the first time the probiotic-NoVs-host interactions and points up the NoVs P-particles as useful tools to overcome the absence of in vitro cellular models to propagate these viruses.

Mesenchymal stromal cell (MSC) immunosuppressive properties have been applied to treat graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplants (HSCTs). We have previously demonstrated that MSC infusions early after haplo-HSCT prevent GVHD in a haploidentical-HSCT mouse model. Now, we investigated the impact that MSCs' immunosuppressive properties have on the graft-versus-leukemia (GVL) effect. First, to mimic a chronic myeloid leukemia (CML) relapse after a haploidentical HSCT, lethally irradiated mice were coinfused with haploidentical donor bone marrow cells plus syngenic hematopoietic progenitors transduced with a retroviral vector encoding both the BCR/ABL oncogene and the D NGFR marker gene. As expected, a CML-like myeloproliferative syndrome developed in all the recipient animals. The addition of haploidentical splenocytes to the transplanted graft prevented CML development by a GVL effect, and all transplanted recipients died of GVHD. This GVL mouse model allowed us to investigate the impact of MSCs infused to prevent GVHD on days 0, 7, and 14 after HSCT, on the GVL effect, expecting an increase in leukemic relapse. Strikingly, a high mortality of the recipients was observed, caused by GVHD, and only few leukemic cells were detected in the recipient animals. In contrast, GVHD prevention by MSCs in the absence of BCR/ABL leukemic cells resulted in a significant survival of the recipients. In vitro data pointed to an inability of MSCs to control strong CTLs responses against BCR/ABL . Our results show that, although an evident increase in leukemic relapses induced by MSCs could not be detected, they showed a reduced efficacy in preventing GVHD that precluded us to draw clear conclusions on MSCs' impact over GVL effect.