Search

This article from Fast Company highlights the winners of the Innovation by Design Awards, showcasing 20 projects that have been recognized for their excellence in various categories. These projects include a building made of living trees, an innovative earbud design, a rebranding of the crowdfunding platform Patreon, a provocative marketing campaign for Skims, a revolutionary building material, a compressed toilet paper packaging solution, an innovative office space in Detroit, and an app to help refugees settle in Poland. The article provides a brief overview of each project, emphasizing their unique features and contributions. Additionally, the article discusses partnerships between the Frank Lloyd Wright Foundation and design manufacturers, resulting in new products inspired by the architect's designs. These partnerships aim to appeal to a younger and more diverse audience, while also generating increased royalty income for the foundation. The document also includes a comprehensive list of designs and products recognized for their innovation and impact in various categories, along with the judges and finalists in each category. [Extracted from the article]

Adsorption equilibria of CO2, CH4, and their mixtures were measured on binderless pellets of NIST reference zeolite NaY (RM 8850) using a static gravimetric setup. The unary adsorption isotherms are reported at temperatures from 298 to 393 K up to a pressure of 3 MPa and compare favorably with independent results on RM 8850 powder. The competitive adsorption measurements were performed at temperatures from 298 to 353 K and up to 3 MPa for three premixed gas mixtures with CO2molar feed compositions of 0.25, 0.50, and 0.75. The results constitute the first competitive adsorption dataset reported for any of the NIST reference materials. RM 8850 shows a strong selectivity for CO2adsorption toward CH4. The experimental unary and binary adsorption isotherms are accurately modeled using the simplified statistical isotherm model (SSI). Notably, the agreement with the model improves only slightly (and within experimental uncertainties) when the whole dataset is used for parameter fitting as opposed to only using the unary data.

Neonates with congenital heart disease and ductal-dependent pulmonary blood flow (DD-PBF) require early intervention. Historically, this intervention was most often a surgical systemic-to-pulmonary shunt (SPS; eg, Blalock-Thomas-Taussig shunt). However, over the past two decades, an alternative to SPS has emerged in the form of transcatheter ductal artery stenting (DAS). While many reports have indicated safety and durability of the DAS approach, few studies compare outcomes between DAS and SPS. The reports that do exist are comprised primarily of small-cohort single-center reviews. Two multicenter retrospective studies suggest that DAS is associated with similar or superior survival compared with SPS. These studies offer the best evidence to-date, and yet both have important limitations. The authors describe herein the rationale and design of the COMPASS (COmparison of Methods for Pulmonary blood flow Augmentation: Shunt vs Stent [COMPASS]) Trial (NCT05268094, IDE G210212). The COMPASS Trial aims to randomize 236 neonates with DD-PBF to either DAS or SPS across approximately 27 pediatric centers in North America. The goal of this trial is to compare important clinical outcomes between DAS and SPS over the first year of life in a cohort of neonates balanced by randomization in order to assess whether one method of palliation demonstrates therapeutic superiority.

Le microbiote intestinal joue un rôle crucial dans la santé de l’hôte, car il fournit de l’énergie et des vitamines à partir de la fermentation d’aliments non digérés par les enzymes intestinales de l’hôte. Par conséquent, les animaux dépourvus de germes souffrent de graves problèmes de santé. Les produits du métabolisme bactérien sont captés et transformés par la muqueuse entérique/colique de l’hôte. Ainsi, les acides gras à chaîne courte et le succinate, les principaux métabolites bactériens produits, par exemple, à partir des régimes enrichis en fibres, sont essentiellement métabolisés par la muqueuse intestinale et n’apparaissent pas dans le sang périphérique. L’importance respective, pour la santé de l’hôte, des changements dans la composition génétique du microbiote et dans la fonction du microbiote en réponse à des aliments spécifiques fait l’objet d’un débat. Certains arguments suggèrent que le microbiote intestinal pourrait être un bioréacteur vital dont la fonction est stable et la composition variable. Ceci lui aurait permis, ainsi qu’à son hôte, de s’adapter à des sources alimentaires variable, ce qui a potentiellement joué un rôle dans l’évolution.

We performed time- and polarization-resolved extreme ultraviolet momentum microscopy on the topological Dirac semimetal candidate 1T-ZrTe2. Excited state band mapping uncovers the previously inaccessible linear dispersion of the Dirac cone above the Fermi level. We study the orbital texture of bands using linear dichroism in photoelectron angular distributions. These observations provide hints about the topological character of 1T-ZrTe2. Time-, energy-, and momentum-resolved nonequilibrium carrier dynamics reveal that intra- and interband scattering processes play a major role in the relaxation mechanism, leading to multivalley electron–hole accumulation near the Fermi level. We also show that electrons’ inverse lifetime has a linear dependence as a function of their excess energy. Our time- and polarization-resolved XUV photoemission results shed light on the excited state electronic structure of 1T-ZrTe2and provide valuable insights into the relatively unexplored field of quantum-state-resolved ultrafast dynamics in 3D topological Dirac semimetals.

The fabrication of nanostructured block copolymer (BCP) films endowed with lithium ion‐conducting gyroid (GYR) nanochannels is an appealing solution to build solid polymer electrolytes (SPEs) that combines high ionic conductivity (IC) with suitable mechanical properties. However, the formation of a well‐developed GYR structure remains challenging to achieve from the self‐assembly of polyelectrolyte BCP chains. To overcome this issue, large ion conducting gyroid grains were produced within freestanding polystyrene‐block‐poly(2‐vinylpyridine)‐block‐poly(ethylene oxide) (PS‐b‐P2VP‐b‐PEO) films by combining a solvent vapor annealing (SVA) treatment with an infiltration process. Here, the SVA treatment enabled the manufacture of SPEs entirely composed of a GYR structure while the infiltration process allowed for the incorporation of an appropriate Li salt (i.e., lithium iodoacetate, LiIAc) within the 3D‐interconected nanochannels via a Menshutkin reaction. By using this SVA‐Infiltration strategy, it has been demonstrated that the creation of ion conducting GYR nanochannels enhances the ion transportation capacity of pyridine‐containing SPEs since substantially lower ICs were measured from analog PS‐b‐P2VP‐b‐PEO/LiIAc films having a nominally disordered as‐cast state. Remarkably, zwitterionic pyridinium‐based moieties formed inside the interpenetrated nanochannels enable an efficient migration of Li+and I3−species, leading to an IC as high as 10−4S cm−1at 70°C.

•NGS-based stratification refines risk classification in T-ALL.•NGS classifier combined with MRD and WBC identifies a group of patients with a very high risk of relapse.

Of the approximately 25 directly imaged planets to date, all are younger than 500 Myr, and all but six are younger than 100 Myr (ref. 1). Eps Ind A (HD209100, HIP108870) is a K5V star of roughly solar age (recently derived as 3.7–5.7 Gyr (ref. 2) and 3.5−1.3+0.8Gyr (ref. 3)). A long-term radial-velocity trend4,5and an astrometric acceleration6,7led to claims of a giant planet2,8,9orbiting the nearby star (3.6384 ± 0.0013 pc; ref. 10). Here we report JWST coronagraphic images which reveal a giant exoplanet that is consistent with these radial and astrometric measurements but inconsistent with the previously claimed planet properties. The new planet has a temperature of approximately 275 K and is remarkably bright at 10.65 and 15.50 µm. Non-detections between 3.5 and 5.0 µm indicate an unknown opacity source in the atmosphere, possibly suggesting a high-metallicity, high carbon-to-oxygen ratio planet. The best-fitting temperature of the planet is consistent with theoretical thermal evolution models, which were previously untested at this temperature range. The data indicate that this is probably the only giant planet in the system, and therefore we refer to it as b, despite it having significantly different orbital properties than the previously claimed planet b.

This study investigates surface modifications of hydrogen-terminated milled nanodiamond (H-MND) drop-cast films by microwave (MW) and radio frequency (RF) nitrogen plasma exposures. The RF(N2) damaging plasma treatment results in the highest nitrogen adsorption (∼7.5 at. %) followed by MW(N2) (∼4.2 at. %) and RF(N2) nondamaging (∼3.8 at. %) plasma treatments. Upon MW(N2) plasma exposure, nitrogen predominantly adsorbs in C–N/C═N and NH states, whereas RF(N2) treatments result in mixed C–N/C═N, C≡N, and NH states, as revealed by electron spectroscopy. Crystalline edges strongly influence N, H, and O adsorption onto MND and act as active adsorption sites. The NH(ads) concentration is notably higher on MND surfaces compared to that on poly/single-crystalline surfaces, likely favored by the additional bonding configuration of hydrogen on the MND. NH(ads) species desorbed upon vacuum annealing in the 500–700 °C range, leaving CN adsorbed species onto the MND surfaces. The nitrogen and oxygen concentration monotonically decreases with annealing temperatures from 300 to 1000 °C. Upon high-temperature annealing, partial recovery of the MND surfaces occurs, depending on plasma exposure conditions. This study may be critical in all ex situ applications influenced by the near-surface physicochemical and electronic properties of nitrogen-terminated MND surfaces, such as NV centers in nanocrystals.

Determining lymphoma subtypes is a crucial step for better patient treatment targeting to potentially increase their survival chances. In this context, the existing gold standard diagnosis method, which relies on gene expression technology, is highly expensive and time-consuming, making it less accessibility. Although alternative diagnosis methods based on IHC (immunohistochemistry) technologies exist (recommended by the WHO), they still suffer from similar limitations and are less accurate. Whole Slide Image (WSI) analysis using deep learning models has shown promising potential for cancer diagnosis, that could offer cost-effective and faster alternatives to existing methods. In this work, we propose a vision transformer-based framework for distinguishing DLBCL (Diffuse Large B-Cell Lymphoma) cancer subtypes from high-resolution WSIs. To this end, we introduce a multi-modal architecture to train a classifier model from various WSI modalities. We then leverage this model through a knowledge distillation process to efficiently guide the learning of a mono-modal classifier. Our experimental study conducted on a lymphoma dataset of 157 patients shows the promising performance of our mono-modal classification model, outperforming six recent state-of-the-art methods. In addition, the power-law curve, estimated on our experimental data, suggests that with more training data from a reasonable number of additional patients, our model could achieve competitive diagnosis accuracy with IHC technologies. Furthermore, the efficiency of our framework is confirmed through an additional experimental study on an external breast cancer dataset (BCI dataset).

Les malpositions/malformations congénitales du pied affectent un à deux nouveau-nés sur mille. Elles sont liées à des contraintes posturales intra-utérines ou des facteurs génétiques et environnementaux. Le dépistage se réalise in uteroou à la naissance. Un diagnostic précoce permet une prise en charge optimale et plus efficace. Le traitement est conservateur, voire chirurgical en seconde intention. L’implication des parents est essentielle pour assurer son succès et le bien-être de l’enfant.

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure.

The assembly of the feeder machine joint has started under challenging conditions, making it difficult to meet the stringent requirements. The challenges of making machine joints and their surrounding support structure in an industrial environment must be successfully overcome. The quality of the worker skills and process control is managed through a rigorous training and qualification program as well as tool acceptance testing. Full-scale mock-ups provide candidate workers with valuable experience in an environment similar to the construction site. The first-of-a-kind assembly on the segmented superconducting busbars and surrounding structural parts is progressing using an approach in which risks are identified, assessed, and prioritized. Lessons learned during the construction of the ITER machine joints are implemented in subsequent assemblies. Status of the construction on the first-ever feeder joint assembly is reported.

In most mammals, new neurons are not only produced during embryogenesis but also after birth. Soon after adult neurogenesis was discovered, the influence of recruiting new neurons on cognitive functions, especially on memory, was documented. Likewise, the late process of neuronal production also contributes to affective functions, but this outcome was recognized with more difficulty. This review covers hypes and hopes of discovering the influence of newly-generated neurons on brain circuits devoted to affective functions. If the possibility of integrating new neurons into the adult brain is a commonly accepted faculty in the realm of mammals, the reluctance is strong when it comes to translating this concept to humans. Compiling data suggest now that new neurons are derived not only from stem cells, but also from a population of neuroblasts displaying a protracted maturation and ready to be engaged in adult brain circuits, under specific signals. Here, we discuss the significance of recruiting new neurons in the adult brain circuits, specifically in the context of affective outcomes. We also discuss the fact that adult neurogenesis could be the ultimate cellular process that integrates elements from both the internal and external environment to adjust brain functions. While we must be critical and beware of the unreal promises that Science could generate sometimes, it is important to continue exploring the potential of neural recruitment in adult primates. Reporting adult neurogenesis in humankind contributes to a new vision of humans as mammals whose brain continues to develop throughout life. This peculiar faculty could one day become the target of treatment for mental health, cognitive disorders, and elderly-associated diseases. The vision of an adult brain which never stops integrating new neurons isa real game changer for designing new therapeutic interventions to treat mental disorders associated with substantial morbidity, mortality, and social costs.

The use of adsorbents for direct air capture (DAC) of CO2is regarded as a promising and essential carbon dioxide removal technology to help meet the goals outlined by the 2015 Paris Agreement. A class of adsorbents that has gained significant attention for this application is ultramicroporous metal organic frameworks (MOFs). However, the necessary data needed to facilitate process scale evaluation of these materials is not currently available. Here, we investigate TIFSIX-3-Ni, a previously reported ultramicroporous MOF for DAC, and measure several physicochemical and equilibrium adsorption properties. We report its crystal structure, textural properties, thermal stability, specific heat capacity, CO2, N2, and H2O equilibrium adsorption isotherms at multiple temperatures, and Ar and O2isotherms at a single temperature. For CO2, N2, and H2O, we also report isotherm model fitting parameters and calculate heats of adsorption. We assess the manufacturability and process stability of TIFSIX-3-Ni by investigating the impact of batch reproducibility, binderless pelletization, humidity, and adsorption–desorption cycling (50 cycles) on its crystal structure, textural properties, and CO2adsorption. For pelletized TIFSIX-3-Ni, we also report its skeletal, pellet, and bed density, total pore volume, and pellet porosity. Overall, our data enable initial process modeling and optimization studies to evaluate TIFSIX-3-Ni for DAC at the process scale. They also highlight the possibility to pelletize TIFSIX-3-Ni and the limited stability of the MOF under humid and oxidative conditions as well as upon multiple adsorption–desorption cycles.

We report herein the synthesis of three detergents bearing a perfluorinated cyclohexyl group connected through a short, hydrogenated spacer (i.e., propyl, butyl, or pentyl) to a β-maltoside polar head that are, respectively, called FCymal-3, FCymal-4, and FCymal-5. Increasing the length of the spacer decreased the critical micellar concentration (CMC), as demonstrated by surface tension (SFT) and isothermal titration calorimetry (ITC), from 5 mM for FCymal-3 to 0.7 mM for FCymal-5. The morphology of the micelles was studied by dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and small-angle X-ray scattering (SAXS), indicating heterogeneous rod-like shapes. While micelles of FCymal-3 and -4 have similar hydrodynamic diameters of ∼10 nm, those of FCymal-5 were twice as large. We also investigated the ability of the detergents to solubilize lipid membranes made of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC). Molecular modeling indicated that the FCymal detergents generate disorder in lipid bilayers, with FCymal-3 being inserted more deeply into bilayers than FCymal-4 and -5. This was experimentally confirmed using POPC vesicles that were completely solubilized within 2 h with FCymal-3, whereas FCymal-5 required >8 h. A similar trend was noticed for the direct extraction of membrane proteins from E. colimembranes, with FCymal-3 being more potent than FCymal-5. An opposite trend was observed in terms of stabilization of the two model membrane proteins bacteriorhodopsin (bR) and SpNOX. In all three FCymal detergents, bR was stable for at least 2 months with no signs of aggregation. However, while the structural integrity of bR was fully preserved in FCymal-4 and -5, minor bleaching was observed in FCymal-3. Similarly, SpNOX exhibited the least activity in FCymal-3 and the highest activity in FCymal-5. By combining solubilizing and stabilizing potency, FCymal detergents push forward our expectations of the usefulness of fluorinated detergents for handling and investigating membrane proteins.

The ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as “maybe report” after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known.

Asphalt concrete layers deteriorate by traffic, environmental conditions, and material-related properties. While there have been studies on asphalt crack performance, research on fatigue life is still limited since they are mostly based on laboratory experiments. The main objective of this study is to assess the life span and crack performance of an innovative base layer material containing 40% RAP. It is accomplished by analysing the data collected from a constructed test pavement using a full-scale accelerated traffic load simulator MLS10. Significant instrumentation was embedded in the surface and base layers. Experimental campaigns were conducted with around 1 100 000 cumulative load passes applied to the base course under different climatic conditions. Based on the findings, the fatigue life and the crack position are determined for the base layer. Base course material with a recycled binder ratio of 40% survived 800 000 load cycles in severe thermal conditions before crack initiation.

Asphalt mixture is a complex heterogeneous material. Its mechanical behaviour strongly depends on its mastic characteristics. Thus, an analysis of mastic can predict the behaviour of its corresponding asphalt mix. This study focuses on numerical simulation of fatigue behaviour of bituminous mastic by using a heterogeneous multiscale approach. The fatigue equation, obtained from experimental tests was applied to the numerical models. Then, the fatigue damage was computed and presented through visual illustrations as well as the local damage distribution. A new numerical method was developed to determine the local damage failure in samples. Thereafter the local damage at the mesoscale scale can be related to global damage at the macroscopic scale. The results showed that the numerical values are close to the experimental data. Finally, the developed multiscale heterogeneous approach can be applied to the larger scale of given bituminous composites such as mortar and HMA models.

Incorporation of nanostructured photochromic WO3–x(NP-WO) in polymer optical fibers (POFs) made of polyethersulfone using a postdrawing coating method is reported. Upon ultraviolet (UV) irradiation, a higher coloring intensity of the cladding of nanostructured fibers is linked with a remarkably clear amplification (negative photochromism) of the transmission signal through the fiber. The postcoating method was thoroughly optimized by using poly(vinylpyrrolidone) (PVP) both as a dispersant agent and a cladding matrix for NP-WO. Modeling shows that the decrease of the real refractive index nin the transparency range of the POF (600–1200 nm) associated with the increase of the absorption coefficient kversus coloring under UV light allows the controllable “opening” of the fiber transmission. The fiber core negative photochromism implying the coloration under UV irradiation of the NP-WO-based fiber cladding represents a brand new optical effect, which could be used in various applications such as sensing, camouflage, or smart envelops.

Regulations will soon require seaports to provide Cold Ironing (CI) for ships at berth to reduce greenhouse gas emissions. Implementing CI usually involves the design of a renewable-based seaport microgrid. In this article, we propose a methodology for optimizing size and energy management of seaport microgrids, including CI, to minimize costs and CO2emissions. The methodology is applied to design the seaport microgrid of Martinique island. Novel contributions of this work are the use of solely linear programming for optimization, the load curve determination of single container ships at berth, and the consideration of a microgrid including storage in an island seaport. The results of the case study highlight that the microgrid would significantly reduce CO2emissions (up to 1.58 times) but may lead to higher costs compared to the current design where ship diesel generators are used. However, in future years, it should be noted that the current design will become prohibited in most ports due to stricter environmental regulations. Results also provide a comprehensive overview of three microgrid designs, each representing a distinct compromise between economic and environmental considerations while satisfying the power demand of the ships at berth and of the quayside loads. In particular, the least carbon-emitting solution maximizes the PV surface area at 10,600 m2. The storage capacity is set at 9.5 MWh. These components represent 7 and 2% of the life-cycle CO2emissions respectively. The remaining CO2emissions are due to the electricity imported from the main grid of Martinique. Even though the proposed methodology has been applied to a specific case study in this work, it is generic and transferrable to other cases and can serve as a valuable tool for port authorities.

This research offers fresh insights into the growth mechanism of cobalt nanoparticles in oleylamine from a precursor with nominal stoichiometry CoCl(PPh3)3, prompting a reevaluation of the model delineated in ″The five Shades of Oleylamine″ by Moisset et al. (Nanoscale2021, 13, 11289–11297) that explicated the cobalt sphere-to-rod morphological transition. While the crucial role of oleylamine is reconfirmed, X-ray photoelectron spectroscopy (XPS) discloses the significant involvement of the organophosphorus ligand of the Co(I) precursor. By scrutinizing aliquots from a tetradecane:oleylamine solution, XPS substantiates the disproportionation of Co(I) into Co(II) and Co° during the sphere growth stage in line with the tenets of Five Shades. Pure Co spheres are formed, with phosphorus-containing species disappearing from the XPS probed layers. However, further inspection of washed nanoparticles corroborates the formation of Co–P bonds, with the Co/P atomic ratio nearing 2 for the nanorods. In response to these findings, previously published data and electron diffraction patterns of the nanorods structure are reassessed, conclusively demonstrating that the nanorods are composed of Co2P, contrary to earlier assumptions of pure cobalt content. This leads to a revised depiction of the sphere-to-rod transition, placing emphasis on the role of organophosphorus ligands (triphenylphosphine and, possibly, its oxidation products) that were previously overlooked.

The directed self-assembly (DSA) of block copolymers (BCPs) is a promising next-generation lithography technique for high-resolution patterning. However, achieving lithographically applicable BCP organization such as out-of-plane lamellae requires proper tuning of interfacial energies between the BCP domains and the substrate, which remains difficult to address effectively and efficiently with high-χ BCPs. Here, we present the successful generation of anisotropic wetting by plasma treatment on patterned spin-on-carbon (SOC) substrates and its application to the DSA of a high-χ Si-containing material, poly(1,1-dimethylsilacyclobutane)-block-polystyrene (PDMSB-b-PS), with a 9 nm half pitch. Exposing the SOC substrate to different plasma chemistries promotes the vertical alignment of the PDMSB-b-PS lamellae within the trenches. In particular, a patterned substrate treated with HBr/O2plasma gives both a neutral wetting at the bottom interface and a strong PS-affine wetting at the sidewalls of the SOC trenches to efficiently guide the vertical BCP lamellae. Furthermore, prolonged exposure to HBr/O2plasma enables an adjustment of the trench width and an increased density of BCP lines on the substrate. Experimental observations are in agreement with a free energy configurational model developed to describe the system. These advances, which could be easily implemented in industry, could contribute to the wider adoption of self-assembly techniques in microelectronics, and beyond to applications such as metasurfaces, surface-enhanced Raman spectroscopy, and sensing technologies.

For decades, transition-metal catalysts based on noble metals have proven to be highly efficient for a wide range of organic transformations. However, due to their low abundance and highly volatile price the use of such metals is now critical for the economy. Thus, the use of more sustainable alternatives is mandatory and the more abundant first-row transition metals are becoming interesting challengers. Among them low-valent 3d transition metals appeared as the best candidates, as they are intrinsically more reactive than high-valent ones. However, this reactivity implies that these complexes are often generated in situ, putting further away the aspect of atom economy and low waste. To circumvent this and to get more insight on the mechanism of reaction, the concept of well-defined complexes has emerged. In this area, due to its historic development and the trouble associated with the preparation of other well-defined 3d transition-metal complexes, cobalt appears as an important player. In this review, after a definition of what is a low-valent complex and the presentation of the concept of a well-defined (pre)catalyst also known as the “single-component” strategy we will report the syntheses and applications in catalysis of low-valent well-defined cobalt complexes classified by their oxidation state and ligand environment.

The design of bifunctional compounds is a promising approach toward the development of strong analgesics with reduced side effects. We here report the optimization of the previously published lead peptide KGFF09, which contains opioid receptor agonist and neuropeptide FF receptor antagonist pharmacophores and is shown to induce potent antinociception and reduced side effects. We evaluated the novel hybrid peptides for their in vitroactivity at MOP, NPFFR1, and NPFFR2 and selected four of them (DP08/14/32/50) for assessment of their acute antinociceptive activity in mice. We further selected DP32and DP50and observed that their antinociceptive activity is mostly peripherally mediated; they produced no respiratory depression, no hyperalgesia, significantly less tolerance, and strongly attenuated withdrawal syndrome, as compared to morphine and the recently FDA-approved TRV130. Overall, these data suggest that MOP agonist/NPFF receptor antagonist hybrids might represent an interesting strategy to develop novel analgesics with reduced side effects.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5–7. This hampers the accuracy of global land carbon–climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9–2.0 °C] in air and 0.4 °C [CI 0.2–0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22–38%] (n= 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n= 9) and continued for at least 25 years (n= 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

In this work, we present the conception and study of gallium nitride (GaN) nanostructures on a gallium arsenide (GaAs) substrate with (111)A orientation. The nanostructures were designed by GaN droplet epitaxy and studied in situby X-ray photoelectron spectroscopy and ex situby atomic force microscopy, scanning electron microscopy, and transmission electron microscopy. These studies were coupled with kinetic Monte Carlo simulations to precisely understand the phenomena occurring during the nitridation and to find the optimum conditions for complete nitridation of gallium droplets. The HRTEM observation showed a cubic (zinc blende) crystal structure of the GaN nanodots for a nitridation at 300 °C. Ramping the temperature from 100 to 350 °C during droplet nitridation enabled to obtain a very high density (>1011cm–2) of GaN nanodots with the zinc blende crystallinity.

Le spectre des syndromes de prédisposition aux leucémies de l’enfant s’est significativement enrichi au cours des dernières décennies. Ils impliquent principalement les gènes CEBPA, ETV6, GATA2, IKZF1, PAX5, RUNX1, SAMD9/SAMD9L, TP53, les gènes de la voie RAS-MAPK, le système de réparation des mésappariements de l’ADN, les gènes impliqués dans la maladie de Fanconi, ainsi que la trisomie 21. Les contextes clinicobiologiques conduisant à la suspicion d’une prédisposition sont très hétérogènes et appellent à des stratégies d’exploration variées. L’étude des caractéristiques initiales des leucémies pédiatriques inclut des techniques de type séquençage à haut débit ayant augmenté la fréquence des situations de suspicion d’une anomalie constitutionnelle prédisposante. L’identification d’un syndrome de prédisposition aux leucémies peut avoir un impact important sur le choix de la chimiothérapie, l’indication de greffe de cellules souches hématopoïétiques et le dépistage des malformations et pathologies associées. Le diagnostic d’un syndrome de prédisposition peut également permettre de proposer une étude familiale et un conseil génétique. Leur diagnostic et la prise en soins doivent reposer sur des filières adaptées et pluridisciplinaires.

Premature hair graying occurs owing to the depletion of melanocyte stem cells in the hair follicle, which can be accelerated by stress caused by genetic or environmental factors. However, the connection between stress and melanocyte stem cell loss is not fully understood. MicroRNAs are molecules that control gene expression by regulating mRNA stability and translation and are produced by the enzyme Dicer, which is repressed under stress. In this study, using 2 mouse genetic models and human and mouse cell lines, we found that the inactivation of Dicer in melanocytes leads to misplacement of these cells within the hair follicle, resulting in a lack of melanin transfer to keratinocytes in the growing hair and the exhaustion of the melanocyte stem cell pool. We also show that miR-92b, which regulates ItgaVmRNA and protein levels, plays a role in altering melanocyte migration. Overall, our findings suggest that the Dicer–miR92b–ItgaV pathway serves as a major signaling pathway linking stress to premature hair greying.

The article from Writer's Digest discusses the challenges and complexities of including song lyrics in writing projects. The author shares their experience of navigating the legalities and permissions required to reprint lyrics in a book about Modest Mouse's album. The article provides practical advice on how to obtain rights to song lyrics, emphasizing the importance of starting early, understanding ownership, negotiating fees, and sealing the deal with music publishers. It highlights the need to respect copyright laws and the creative process while incorporating song lyrics into literary works. [Extracted from the article]

The local microenvironment has recently been found to play a major role in the electrocatalytic activity of nanomaterials. Modulating the microenvironment by adding alkali metal cations into the electrolyte can be used to either suppress hydrogen or oxygen evolution, thereby extending the electrochemical window of energy storage systems, or to tune the selectivity of electrocatalysts. MXenes are a large family of two-dimensional transition metal carbides, nitrides, and carbonitrides that have shown potential for use in electrochemical energy storage applications. Due to their negatively charged surfaces, MXenes can accommodate cations and water molecules between the layers. Nevertheless, the nature of the aqueous microenvironment in the MXene interlayer space is poorly understood. Here, we apply Fourier transform infrared spectroscopy (FTIR) to probe the hydrogen bonding of intercalated water in Ti3C2Txas a function of intercalated cation and relative humidity. Substantial changes in the FTIR spectra after cation exchange demonstrate that the hydrogen bonding of water molecules confined between the MXene layers is strongly cation-dependent. Furthermore, the IR absorbance of the confined water correlates with resistivity estimated by 4-point probe measurements and interlayer distance calculated from XRD patterns. This work demonstrates that cation intercalation strongly modulates the confined microenvironment, which can be used to tune the activity or selectivity of electrochemical reactions in the interlayer space of MXenes in the future.

BACKGROUND: UVB radiation triggers skin photoaging by inducing excess cellular oxidants, contributing to senescence, and overproducing matrix metalloproteinase-1 (MMP-1), causing skin wrinkles. Senescence also impedes skin wound closure. Passion fruit seeds (PFS) boast abundant piceatannol (PCT), recognized for its antioxidant and anti-aging properties.OBJECTIVE: To study potential of PFS extract in diminishing photoaging, accelerating wound healing, and enhancing SIRT1 production in human keratinocytes (HaCaT cells).METHODS: The PFS extract was assessed for PCT using HPLC analysis. The antioxidant effects, reduced senescence-associated β-galactosidase (SA-β-gal) activity, and MMP-1 production were measured in HaCaT cells exposed to UVB using a DCFA-DA assay, SA-β-gal activity, and flow cytometry/immunofluorescent including MMP-1 mRNA expression, respectively. The effect of wound healing acceleration was evaluated, including EGFR mRNA expression. Additionally, SIRT1 enhancement was investigated using flow cytometry and immunofluorescent techniques, which also included the assessment of SIRT1 mRNA expression.RESULTS: The PFS extract, which is rich in PCT, effectively diminished cellular oxidants and aging. It decreased UVB-induced cellular oxidants, senescence, and MMP-1 production at both protein and mRNA levels. Moreover, the extract enhanced wound closure by boosting cell migration and increasing EGFR mRNA expression. Additionally, SIRT1 production and expression, associated with cellular rejuvenation, increased in extract-treated cells.CONCLUSIONS: PFS extract exhibits potential for skincare and wound healing applications, offering a natural strategy to combat skin aging effects and support tissue repair.

An efficient synthetic route to access rilpivirine hydrochloride was designed and demonstrated on a multikilogram scale. The synthetic route uses two subsequent aromatic nucleophilic substitutions, conducted under carefully optimized conditions to access the target in a 39% overall yield over four steps from (E)-3-(4-amino-3,5-dimethylphenyl)acrylonitrile hydrochloride 5. The procedures developed were demonstrated on multikilogram scale in our pilot plant, and the product was obtained with a purity of 99.6% by HPLC with no single impurity above 0.10%. The challenges associated with polymorph control and impurity control in an active pharmaceutical ingredient (API) are also discussed. Overall, our process toward Rilpivirine is shorter than most processes described and displays smooth reaction conditions. This work showcases the use of a Boc protecting group as a handle to achieve a more selective nucleophilic aromatic substitution process. It also illustrates the importance of solvent choice in process development to make the chemistry applicable on a large scale under safe conditions.

Variants of uncertain significance (VUS) are a significant issue for the molecular diagnosis of rare diseases. The publication of episignatures as effective biomarkers of certain Mendelian neurodevelopmental disorders has raised hopes to help classify VUS. However, prediction abilities of most published episignatures have not been independently investigated yet, which is a prerequisite for an informed and rigorous use in a diagnostic setting. We generated DNA methylation data from 101 carriers of (likely) pathogenic variants in ten different genes, 57 VUS carriers, and 25 healthy controls. Combining published episignature information and new validation data with a k-nearest-neighbour classifier within a leave-one-out scheme, we provide unbiased specificity and sensitivity estimates for each of the signatures. Our procedure reached 100% specificity, but the sensitivities unexpectedly spanned a very large spectrum. While ATRX, DNMT3A, KMT2D, and NSD1signatures displayed a 100% sensitivity, CREBBP-RSTSand one of the CHD8signatures reached <40% sensitivity on our dataset. Remaining Cornelia de Lange syndrome, KMT2A, KDM5Cand CHD7signatures reached 70–100% sensitivity at best with unstable performances, suffering from heterogeneous methylation profiles among cases and rare discordant samples. Our results call for cautiousness and demonstrate that episignatures do not perform equally well. Some signatures are ready for confident use in a diagnostic setting. Yet, it is imperative to characterise the actual validity perimeter and interpretation of each episignature with the help of larger validation sample sizes and in a broader set of episignatures.

Purpose: The acquisition of good quality ultrasound (US) images requires good acoustic coupling between the ultrasound probe and the patient’s skin. In practice, this good coupling is achieved by the operator applying a force to the skin through the probe. This force induces a deformation of the tissues underlying the probe. The distorted images deteriorate the quality of the reconstructed 3D US image. Methods: In this work, we propose two methods to correct these deformations. These methods are based on the construction of a biomechanical model to predict the mechanical behavior of the imaged soft tissues. The originality of the methods is that they do not use external information (force or position value from sensors, or elasticity value from the literature). The model is parameterized thanks to the information contained in the image. This is allowed thanks to the optimization of two key parameters for the model which are the indentation d and the elasticity ratio α. Results: The validation is performed on real images acquired on a gelatin-based phantom using an ultrasound probe inducing an increasing vertical indentation using a step motor. The results showed a good correction of the two methods for indentations less than 4 mm. For larger indentations, one of the two methods (guided by the similarity score) provides a better quality of correction, presenting a Euclidean distance between the contours of the reference image and the corrected image of 0.71 mm. Conclusion: The proposed methods ensured the correction of the deformed images induced by a linear probe pressure without using any information coming from sensors (force or position), or generic information about the mechanical parameters. The corrected images can be used to obtain a corrected 3D US image.

Safety, privacy, efficiency and cybersecurity (SPEC) properties are mandatory in vehicular networks. Owing to intrinsic limitations, the V2X framework and related communicating autonomous vehicles are inadequate. We explore the CMX framework (Coordinated Mobility for X = SPEC), Next Generation Vehicles (NGVs), and protocols for safety-critical inter-vehicle communications and agreements that solve problems left open in the V2X framework. Then, we focus on cyberattacks and physical attacks against isolated NGVs and cohorts of NGVs. The cyberphysical security analysis investigates more than 20 attacks and demonstrates that the goal set for CMX is verified. In the presence of attacks, safety is never compromised, possibly at the expense of diminished efficiency.

AbstractA specific simulation mode has been implemented in the TRIPOLI-4® Monte Carlo code to deal with subcritical or critical configurations together with the use of variance reduction techniques usually dedicated to shielding studies. This multiple mode enables a coupling between the fixed-source criticality (or the criticality) mode with the shielding mode, within the Monte Carlo code, with the aims to simplify the calculation and help users run the code. Test cases with a fuel assembly in borated water are presented to illustrate the use of this feature in a subcritical case. An experimental setup is then investigated in a critical case. It is based on the Criticality Accident Alarm System benchmark experiment conducted in the SILENE critical assembly facility. Stability and efficiency issues are examined, and promising results are presented and discussed in both cases.

Genetic alterations are the cornerstone of risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and their accurate identification is critical for optimal treatment. Most cases with ABL-class fusion are classified as high-risk yet display good responses to tyrosine kinase inhibitors (TKIs). Current clinical protocols recommend adding a TKI to chemotherapy as soon as possible, making it mandatory to rapidly identify these alterations. We investigated here whether the identification of immunophenotypic features associated with these molecular alterations could be a valuable screening tool. CD36 expression was shown to be a characteristic feature of ABL-or JAK-class kinase fusions. The main genetic subgroups clustering in the subset with Philadelphia (Ph)-like features were also found to display specific immunophenotypic characteristics. A predictive multiparameter scoring system was generated, segregating genetic subtypes with aberrant kinase activation (PAX5/CRLF2alt, BCR::ABL1, ABL/JAK-class). The most robust markers identified were the TSLPR with CD19/22/9/38/81/304 and CD49f. As TKI adjunction is currently limited to the ABL-class kinase fusions, immunophenotypes distinguishing ABLfrom JAK-class were also investigated. The flow cytometry method reported here, accessible to most hematology departments, is thus a new useful tool to quickly screen for Ph-like kinase fusion with a good sensitivity (95%) and specificity (96%).