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Silicones find use in a myriad of applications from sealants and adhesives to cooking utensils and medical implants. However, state-of-the-art silicone parts fall short in terms of shape complexity and reprocessability. Advances in three-dimensional printing and the discovery of vitrimers have recently opened opportunities for shaping and recycling of silicone objects. Here, we report the 3D printing via direct ink writing of silicone vitrimers into complex-shaped parts with high strength and room-temperature reprocessability. The reprocessing properties of the printed objects result from the adaptive nature of the silicone vitrimer, which can deform under stress without losing its network connectivity. Rheological and mechanical experiments reveal that printable inks can be tuned to generate strong parts with high creep resistance and room-temperature reprocessability, two properties that are usually challenging to reconcile in vitrimers. By combining printability, high strength, and room-temperature reprocessability, the reported silicone vitrimers represent an attractive sustainable alternative to currently available elastomers in a broad range of established and prospective applications.

Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia.

In arid and semiarid regions, agricultural producers, including cashew growers, grapple with the challenges of cultivating crops in harsh environmental conditions. To address this issue, conditioning materials capable of maintaining soil moisture levels even during droughts presents a promising solution. Herein, we synthesized a superabsorbent hydrogel composite comprised of starch-grafted-poly(sodium acrylate) embedded with 20% (w/w) kaolin (KAO), designed to enhance the quality of cashew seedlings. Characterization of the composite through Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses confirmed its successful synthesis. The incorporation of KAO influenced the thermal, morphological, and swelling properties of the composite, as a result of the interaction between the clay and starch. Moreover, the composite exhibited improved water absorption capacity and kinetics, demonstrating a superabsorbent behavior. Our findings demonstrated that the addition of just 1% (w/w) of the composite effectively enhanced soil moisture retention. Notably, the placement of the composite within the soil column proved critical in extending the interval between irrigation cycles. Field experiments revealed that cashew seedlings cultivated in soil conditioned with the composite positioned deeper in the pot exhibited notable improvements in morphological parameters such as plant height, stem diameter, and leaf count, especially over prolonged cultivation periods. Besides, these seedlings displayed increased vigor and overall quality, essential for the establishment of robust and healthy cashew orchards. Overall, this study underscores the potential of this composite as a promising and cost-effective soil conditioning material for enhancing cashews and other crop yields in arid and semiarid regions with limited water availability.

Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies.

This paper presents robust control design conditions for uncertain sampled-data systems. We transform such systems into interval or polytopic uncertain hybrid dynamic models, which we then use to analyse and design H2conditions. The numerical examples in this paper demonstrate the efficacy of the proposed methods.

This work analyzed the volume fraction of the sigma phase in a superduplex stainless steel UNS S32760. Two electrochemical testing methodologies were applied for this purpose. Firstly the DL-EPR test was performed in three different electrolytic solutions. The LSV-KOH test was also used, a recent methodology proposal for analyzing these alloys. Seven specimens were solution annealed at 1100 °C for 60 min and heat-treated at 850 and 950 °C for 5, 20, and 60 min to promote the formation of different fractions of the sigma phase. The sigma phase volume fraction present in these specimens was determined by quantitative metallography. The DL-EPR analyses in all three conditions proved to be limited in quantifying the sigma phase, especially in specimens heat-treated at 950 °C. On the other hand, from the analyses with the LSV-KOH technique, it was possible to construct a reference curve between the sigma volume fractions and the electrochemical response of the LSV-KOH test (charge density), obtaining a linear regression coefficient of 0.97. This curve can then be applied to quantify the sigma phase. For comparison, the best regression coefficient obtained for DL-EPR was 0.53. Accompanied by the quantitative analysis, a qualitative analysis of the sigma phase can be made from a deeper analysis of the LSV-KOH voltammograms. In these analyses, it was possible to infer whether the sigma phase morphology is lamellar or in blocks. From the results obtained, it was possible to show that the LSV-KOH test is more precise in quantifying the sigma phase and allows a morphological analysis.

Although several meta-analyses have suggested the efficacy of non-invasive brain stimulation (NIBS) mainly in prefrontal brain areas to treat mental disorders, no synthetic approach has been performed for other psychiatric disorders rather than depression. The objective is to assess the available evidence of NIBS in the treatment of anxiety disorders.

Biological living materials, such as animal bones and plant stems, are able to self-heal, regenerate, adapt and make decisions under environmental pressures. Despite recent successful efforts to imbue synthetic materials with some of these remarkable functionalities, many emerging properties of complex adaptive systems found in biology remain unexplored in engineered living materials. Here, we describe a three-dimensional printing approach that harnesses the emerging properties of fungal mycelia to create living complex materials that self-repair, regenerate and adapt to the environment while fulfilling an engineering function. Hydrogels loaded with the fungus Ganoderma lucidumare three-dimensionally printed into lattice architectures to enable mycelial growth in a balanced exploration and exploitation pattern that simultaneously promotes colonization of the gel and bridging of air gaps. To illustrate the potential of such mycelium-based living complex materials, we three-dimensionally print a robotic skin that is mechanically robust, self-cleaning and able to autonomously regenerate after damage.

Introduction: Increasing interest has been seen in understanding the anatomy and biomechanics involved in the Deep Gluteal Syndrome, therefore the main objective of our paper was to define the anatomy of the deep gluteal space concerning the important osseous, muscular and neurological structures.Methods: 12 cadaveric models (24 hemipelvises) were used. We proceeded with classical anatomic dissection and evaluated numerous osseous, musculotendinous and neurologic structures and their relationships. We also determined the femoral anteversion and neck-shaft angles.Results: We found that 15.4% of lower limbs examined presented variations in the sciatic nerve (SN) emergence, and this was significantly longer in men. The distance from the SN to the trochanteric region was also significantly lower in males. The average ischiofemoral distance (IFD) was 2.5 ± 1.3 cm, at the same time that the structures comprised in that space showed superior areas, such as the quadratus femoris (QF) with 5.0 ± 1.1 cm and the SN with 1.4 ± 0.3 cm widths. Besides that, we also evaluated the distance from the SN to the lesser trochanter (LT) and the ischial tuberosity (IT), in the ischiofemoral space, reaching average values of 1.1 ± 0.7 cm and 1.5 ± 0.6 cm respectively. Regarding the relationship between the proximal hamstring insertion, we verified that the LT was at an average distance of 1.6 ± 1.1 cm, that the SN was only 0.2 ± 0.3 cm lateral to it, and the PN is just 2.6 ± 1.2 cm proximal to it.Conclusions: Our study confirmed the extreme variation in the SN origin that can contribute to the Piriformis syndrome. The IFD obtained in our study showed that this distance was small for the structures contained in this space. The proximal hamstring insertion showed a significantly more extended footprint in males, which puts the pudendal nerve (PN) at higher risk of iatrogenic injury.

ABSTRACTParkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggests the involvement of autophagy as well as lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to be the major lysosomal protease involved in SNCA degradation, its deficiency has been linked to the presence of insoluble SNCA conformers in the brain of mice and humans as well as to the transcellular transmission of SNCA aggregates. We here postulate that SNCA degradation can be enhanced by the application of the recombinant human proform of CTSD (rHsCTSD). Our results reveal that rHsCTSD is efficiently endocytosed by neuronal cells, correctly targeted to lysosomes and matured to an enzymatically active protease. In dopaminergic neurons derived from induced pluripotent stem cells (iPSC) of PD patients harboring the A53T mutation within the SNCAgene, we confirm the reduction of insoluble SNCA after treatment with rHsCTSD. Moreover, we demonstrate a decrease of pathological SNCA conformers in the brain and within primary neurons of a ctsd-deficient mouse model after dosing with rHsCTSD. Boosting lysosomal CTSD activity not only enhanced SNCA clearance in human and murine neurons as well as tissue, but also restored endo-lysosome and autophagy function. Our findings indicate that CTSD is critical for SNCA clearance and function. Thus, enzyme replacement strategies utilizing CTSD may also be of therapeutic interest for the treatment of PD and other synucleinopathies aiming to decrease the SNCA burden.Abbreviations:aa: amino acid; SNCA/α-synuclein: synuclein alpha; APP: amyloid beta precursor protein; BBB: blood brain barrier; BF: basal forebrain; CBB: Coomassie Brilliant Blue; CLN: neuronal ceroid lipofuscinosis; CNL10: neuronal ceroid lipofuscinosis type 10; Corr.: corrected; CTSD: cathepsin D; CTSB: cathepsin B; DA: dopaminergic; DA-iPSn: induced pluripotent stem cell-derived dopaminergic neurons; dox: doxycycline; ERT: enzyme replacement therapy; Fx: fornix, GBA/β-glucocerebrosidase: glucosylceramidase beta; h: hour; HC: hippocampus; HT: hypothalamus; i.c.: intracranially; IF: immunofluorescence; iPSC: induced pluripotent stem cell; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LSDs: lysosomal storage disorders; MAPT: microtubule associated protein tau; M6P: mannose-6-phosphate; M6PR: mannose-6-phosphate receptor; MB: midbrain; mCTSD: mature form of CTSD; neurofil.: neurofilament; PD: Parkinson disease; proCTSD: proform of CTSD; PRNP: prion protein; RFU: relative fluorescence units; rHsCTSD: recombinant human proCTSD; SAPC: Saposin C; SIM: structured illumination microscopy; T-insol: Triton-insoluble; T-sol: Triton-soluble; TEM: transmission electron microscopy, TH: tyrosine hydroxylase; Thal: thalamus

ABSTRACTThere is strong theoretical and empirical support for the use of digital games for learning. Despite their research support, digital games are not widely used in mathematics classrooms. One main contributor to this lack of adoption is the paucity of extant research on the extent to which mathematics teachers are using digital games, how teachers are using digital games in the mathematics classroom, and what barriers hinder their use of digital games. To begin answering these questions, the Digital Game Usage in the Mathematics Classroom Surveywas developed. Pilot data were collected to evaluate the reliability and validity of the survey. The results of the pilot study are discussed along with recommendations for future research and survey instrument usage.

The article discusses fossil mammal specimens discovered in the Andes mountains of central Chile and the Tinguiririca River Valley. They include an array of new species, as well as South America's oldest known rodent remains. Some of the fossils document the existence of an ancient grassland that predates such ecosystems elsewhere in the world. INSETS: Cast of Characters;African Immigrants;Teeth Tell All;Late to Rise

Focuses on palaeontological research in Madagascar for information about Mesozoic era mammals in the Southern hemisphere. Conditions which make Madagascar an ideal place for this study; Discoveries of various mammals, including the rhynchosaurs and traversodontids, both of which have changed notions of mammalian evolution; Goals of these studies; Description of various findings, including several fossils. INSETS: LIVING IN MIXED COMPANY;Modern-Day Mystery.

Stapled peptides have the ability to mimic α-helices involved in protein binding and have proved to be effective pharmacological agents for disrupting protein–protein interactions. DNA-binding proteins such as transcription factors bind their cognate DNA sequences viaan α-helix interacting with the major groove of DNA. We previously developed a stapled peptide based on the bacterial alternative sigma factor RpoN capable of binding the RpoN DNA promoter sequence and inhibiting RpoN-mediated expression in Escherichia coli. We have elucidated a structure–activity relationship for DNA binding by this stapled peptide, improving DNA binding affinity constants in the high nM range. Lead peptides were shown to have low toxicity as determined by their low hemolytic activity at 100 μM and were shown to have anti-virulence activity in a Galleria mellonellamodel of Pseudomonas aeruginosainfection. These findings support further preclinical development of stapled peptides as antivirulence agents targeting P. aeruginosa.

Antibiotics with fundamentally new mechanisms of action such as the armeniaspirols, which target the ATP-dependent proteases ClpXP and ClpYQ, must be developed to combat antimicrobial resistance. While the mechanism of action of armeniaspirol against Gram-positive bacteria is understood, little is known about the structure–activity relationship for its antibiotic activity. Based on the preliminary data showing that modifications of armeniaspirol's N-methyl group increased antibiotic potency, we probed the structure–activity relationship of N-alkyl armeniaspirol derivatives. A series of focused derivatives were synthesized and evaluated for antibiotic activity against clinically relevant pathogens including methicillin-resistant Staphylococcus aureusand vancomycin-resistant Enterococcus. Replacement of the N-methyl with N-hexyl, various N-benzyl, and N-phenethyl substituents led to substantial increases in antibiotic activity and potency for inhibition of both ClpYQ and ClpXP. Docking studies identified binding models for ClpXP and ClpYQ that were consistent with the inhibition data. This work confirms the role of ClpXP and ClpYQ in the mechanism of action of armeniaspirol and provides important lead compounds for further antibiotic development.

Oranchuk, DJ, Storey, AG, Nelson, AR, Neville, JG, and Cronin, JB. Variability of multiangle isometric force-time characteristics in trained men. J Strength Cond Res36(1): 284–288, 2022—Measurements of isometric force, rate of force development (RFD), and impulse are widely reported. However, little is known about the variability and reliability of these measurements at multiple angles, over repeated testing occasions in a homogenous, resistance-trained population. Thus, understanding the intersession variability of multiangle isometric force-time characteristics provides the purpose of this article. Three sessions of isometric knee extensions at 40°, 70°, and 100° of flexion were performed by 26 subjects across 51 limbs. All assessments were repeated on 3 occasions separated by 5–8 days. Variability was qualified by doubling the typical error of measurement (TEM), with thresholds of 0.2–0.6 (small), 0.6–1.2 (moderate), 1.2–2.0 (large), 2.0–4.0 (very large), and >4.0 (extremely large). In addition, variability was deemed large when the intraclass correlation coefficient (ICC) was <0.67 and coefficient of variation (CV) >10%; moderate when ICC >0.67 or CV <10% (but not both); and small when both ICC >0.67 and CV <10%. Small to moderate between-session variability (ICC = 0.68–0.95, CV = 5.2–18.7%, TEM = 0.24–0.49) was associated with isometric peak force, regardless of angle. Moderate to large variability was seen in early-stage (0–50 ms) RFD and impulse (ICC = 0.60–0.80, CV = 22.4–63.1%, TEM = 0.62–0.74). Impulse and RFD at 0–100 ms, 0–200 ms, and 100–200 ms were moderately variable (ICC = 0.71–0.89, CV = 11.8–42.1%, TEM = 0.38–0.60) at all joint angles. Isometric peak force and late-stage isometric RFD and impulse measurements were found to have low intersession variability regardless of joint angle. However, practitioners need to exercise caution when making inferences about early-stage RFD and impulse measures due to moderate-large variability.

Mixed depression is probably different in terms of clinical course and response to treatment. Repetitive transcranial magnetic stimulation (rTMS) is well established in non-mixed depression, and theta-burst stimulation (TBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, TBS has not been adequately studied in mixed states. This study was a double-blind, six-week, sham-controlled, and randomized clinical trial of bilateral TBS targeting the right and left dorsolateral prefrontal cortex, respectively. Adults with bipolar and major depressive disorder experiencing an acute mixed depression were eligible if they had not benefited from a first- or second-line treatment for acute unipolar or bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments. Out of 100 patients included, 90 composed modified intention-to-treat sample, which was patients that completed at least one week of the intervention. There were no significant differences in Montgomery-Asberg depression rating scale score changes (least squares mean difference between groups at week 3, −0.06 [95% CI, − 3.39 to 3.51; P= 0.97] in favor of sham TBS). Response and remission rates per MADRS were also not statistically different among active and sham groups (35.7% vs. 43.7%, and 28.5% vs. 37.5% respectively at week 6, ps> 0.51). No other analyses from baseline to weeks 3 or 6 revealed significant time x group interaction or mean differences among groups in the mITT sample. Bilateral TBS targeting the DLPFC is not efficacious as an add-on treatment of acute bipolar and unipolar mixed depression. ClinicalTrials.govIdentifier: NCT04123301

Vat photopolymerization 3D printing provides new opportunities for the fabrication of tissue scaffolds and medical devices. However, for the manufacturing of biodegradable elastomers, it usually requires the use of organic solvents to dissolve the solid photoinitators and achieve low resin viscosity, making this process environmentally unfriendly and not optimal for biomedical applications. Here, we report solvent-free 3D printing of biodegradable elastomers by digital light processing with well-defined photoinitiator–polymer conjugates. Being in liquid state at room temperature, the macrophotoinitiators enabled high-quality 3D printing in the absence of any organic solvents that are usually used in digital light 3D printing. This allowed the systematic investigation of structure–property relationships of 3D-printed biodegradable elastomers without the interference from reactive diluents. The developed macrophotoinitiators were compatible with various photopolymers and could be applied for solvent-free fabrication of biodegradable shape-memory devices. This work offers new perspectives for the solvent-free additive manufacturing of bioresorbable medical implants and other functional devices.

Crop pollination is one of Nature’s Contributions to People (NCP) that reconciles biodiversity conservation and agricultural production. NCP benefits vary across space, including among distinct political-administrative levels within nations. Moreover, initiatives to restore ecosystems may enhance NCP provision, such as crop pollination delivered by native pollinators. We mapped crop pollination demand (PD), diversity of pollinator-dependent crops, and vegetation deficit (VD) (vis-a-vis Brazilian legal requirements) across all 5570 municipalities in Brazil. Pollinator-dependent crops represented ∼55% of the annual monetary value of agricultural production and ∼15% of the annual crop production. Municipalities with greater crop PD (i.e., higher degree of pollinator dependence of crop production) also had greater VD, associated with large properties and monocultures. In contrast, municipalities with a greater diversity of pollinator-dependent crops and predominantly small properties presented a smaller VD. Our results support that ecological restoration prompted by legal requirements offers great potential to promote crop productivity in larger properties. Moreover, conservation of vegetation remnants could support food security in small properties. We provided the first steps to identify spatial patterns linking biodiversity conservation and pollination service. Using Brazilian legal requirements as an example, we show that land-use management policies may be successfully used to ensure agricultural sustainability and crop production.

Cells sense and respond to scaffold pore geometry and mechanical stimuli. Many fabrication methods used in bone tissue engineering render structures with poorly controlled pore geometries. Given that cell–scaffold interactions are complex, drawing a conclusion on how cells sense and respond to uncontrolled scaffold features under mechanical loading is difficult. In this study, monodisperse templated scaffolds (MTSC) were fabricated and used as well-defined porous scaffolds to study the effect of dynamic culture conditions on bone-like tissue formation. Human bone marrow-derived stromal cells were cultured on MTSC or conventional salt-leached scaffolds (SLSC) for up to 7 weeks, either under static or dynamic conditions (wall shear stress [WSS] using spinner flask bioreactors). The influence of controlled spherical pore geometry of MTSC subjected to static or dynamic conditions on osteoblast cell differentiation, bone-like tissue formation, structure, and distribution was investigated. WSS generated within the two idealized geometrical scaffold features was assessed. Distinct response to fluid flow in osteoblast cell differentiation were shown to be dependent on scaffold pore geometry. As revealed by collagen staining and microcomputed tomography images, dynamic conditions promoted a more regular extracellular matrix (ECM) formation and mineral distribution in both scaffold types compared with static conditions. The results showed that regulation of bone-related genes and the amount and the structure of mineralized ECM were dependent on scaffold pore geometry and the mechanical cues provided by the two different culture conditions. Under dynamic conditions, SLSC favored osteoblast cell differentiation and ECM formation, whereas MTSC enhanced ECM mineralization. The spherical pore shape in MTSC supported a more trabecular bone-like structure under dynamic conditions compared with MTSC statically cultured or to SLSC under either static or dynamic conditions. These results suggest that cell activity and bone-like tissue formation is driven not only by the pore geometry but also by the mechanical environment. This should be taken into account in the future design of complex scaffolds, which should favor cell differentiation while guiding the formation, structure, and distribution of the engineered bone tissue. This could help to mimic the anatomical complexity of the bone tissue structure and to adapt to each bone defect needs.Impact statementAging of the human population leads to an increasing need for medical implants with high success rate. We provide evidence that cell activity and the amount and structure of bone-like tissue formation is dependent on the scaffold pore geometry and on the mechanical environment. Fabrication of complex scaffolds comprising concave and planar pore geometries might represent a promising direction toward the tunability and mimicry the structural complexity of the bone tissue. Moreover, the use of fabrication methods that allow a systematic fabrication of reproducible and geometrically controlled structures would simplify scaffold design optimization.

The Anninghe Fault (ANHF) is a major left‐lateral strike‐slip fault in southwestern China and one of the main seismogenic fault zones with a history of strong earthquakes. To understand the frictional properties of natural granitic gouges from the principal slip zone, we conducted hydrothermal friction experiments using both saw‐cut and ring shear methods. These experiments were performed at temperatures (T) of 25–600°C, pore pressures (Pf) of zero (dry), 30 and 100 MPa, sliding velocities (V) of 0.01–100 μm/s and effective normal stresses (σneff${\sigma }_{\mathrm{n}}^{\text{eff}}$) of 68, 100, and 200 MPa. The (apparent) friction coefficient is low (μ< 0.5) at high T(600°C), high Pf(100 MPa) and low V(<1 μm/s); but high (μ> 0.6) under all other T, Pfand Vconditions. Under high Pf, the velocity dependence of friction, (a‐b), displays three regimes with increasing temperature, from positive below ∼100°C to negative at 100–300°C (at V= 1–3 μm/s) or else 100–450°C (at V= 30–100 μm/s), becoming positive again above 300–450°C. At low Pf, the negative (a‐b) expands to the range ∼300–600°C. Microstructural observations and microphysical interpretation imply that the frictional weakening and transitions in (a‐b) are related to competition between dilatant granular flow and deformation of the fine‐grained gouge by intergranular pressure solution accompanied by healing phenomena (leading to cavitation‐creep‐like behavior). Our results provide a possible explanation for the distribution of earthquakes at different depths in the continental crust, in particular for the depth range of the seismogenic zone between 4 and 24 km along the ANHF. The left‐lateral Anninghe Fault (ANHF), bounding the Tibetan Plateau in China, accommodates part of the distributed convergence between the Indian and Eurasian plates. It has accommodated numerous historical earthquakes during the last few centuries. However, the mechanisms controlling the frictional behavior of natural granitic fault rocks (gouges) collected from ANHF are poorly understood. Laboratory friction experiments were performed at a wide range of temperatures (T), velocities (V) and shear displacements (X), employing varying pore fluid pressure (Pf). The gouges showed potentially unstable shearing behavior at 100–450°C (corresponding to 4–18 km depth), extending up to 600°C (24 km depth) at low Pf(≤30 MPa) and low V(0.04 μm/s). Low frictional strength obtained in large displacement experiments at 600°C indicates a transition from brittle to ductile and seismic‐aseismic (velocity‐strengthening) behavior. Based on microstructural analysis and a microphysical model, we infer that the observed behavior is due to competition between brittle/frictional flow of the granular gouge and creep involving stress‐driven dissolution of the finely crushed constituent grains. Our results offer a possible explanation for the distribution of earthquakes at different depths between 4 and 24 km along the ANHF. New experiments confirm a low friction coefficient (μ= 0.37) for granitic gouge at high temperature hydrothermal conditionsThe temperature range characterized by velocity‐weakening narrows with decreasing velocity and with increasing pore fluid pressurePressure solution is a key deformation mechanism controlling the velocity dependence of friction in fine‐grained granite gouge New experiments confirm a low friction coefficient (μ= 0.37) for granitic gouge at high temperature hydrothermal conditions The temperature range characterized by velocity‐weakening narrows with decreasing velocity and with increasing pore fluid pressure Pressure solution is a key deformation mechanism controlling the velocity dependence of friction in fine‐grained granite gouge

Microcapsules made of synthetic polymers are used for the release of cargo in agriculture, food, and cosmetics but are often difficult to be degraded in the environment. To diminish the environmental impact of microcapsules, we use the biofilm-forming ability of bacteria to grow cellulose-based biodegradable microcapsules. The present work focuses on the design and optimization of self-grown bacterial cellulose capsules. In contrast to their conventionally attributed pathogenic role, bacteria and their self-secreted biofilms represent a multifunctional class of biomaterials. The bacterial strain used in this work, Gluconacetobacter xylinus, is able to survive and proliferate in various environmental conditions by forming biofilms as part of its lifecycle. Cellulose is one of the main components present in these self-secreted protective layers and is known for its outstanding mechanical properties. Provided enough nutrients and oxygen, these bacteria and the produced cellulose are able to self-assemble at the interface of any given three-dimensional template and could be used as a novel stabilization concept for water-in-oil emulsions. Using a microfluidic setup for controlled emulsification, we demonstrate that bacterial cellulose capsules can be produced with tunable size and monodispersity. Furthermore, we show that successful droplet stabilization and bacterial cellulose formation are functions of the bacteria concentration, droplet size, and surfactant type. The obtained results represent the first milestone in the production of self-assembled biodegradable cellulose capsules to be used in a vast range of applications such as flavor, fragrance, agrochemicals, nutrients, and drug encapsulation.

The increasing use of lightweight composite materials in structural applications requires the development of new damage monitoring technologies to ensure their safe use and prevent accidents. Although several molecular strategies have been proposed to report damage in polymers through mechanochromic responses, these approaches have not yet been translated into lightweight bioinspired composites for load-bearing applications. Here, we report on the development of bioinspired laminates of alternating polymer and nacre-like layers that combine optical translucency, high fracture toughness, and damage-reporting capabilities. The composites signal damage via a fluorescence color change that arises from the force activation of mechanophore molecules embedded in the material’s polymer phase. A quantitative correlation between the applied strain and the fluorescence intensity was successfully established. We demonstrate that optical imaging of mechanically loaded composites allows for the localized detection of damage prior to fracture. This fluorescence-based self-reporting mechanism offers a promising approach for the early detection of damage in lightweight structural composites and can serve as a useful tool for the analysis of fracture processes in bulk transparent materials.

Le vitiligo est une dépigmentation auto-immune de la peau, dont le traitement reste difficile. Les stéroïdes topiques, les inhibiteurs de la calcineurine et la photothérapie sont couramment utilisés. Récemment, les inhibiteurs topiques des Janus Kinases (JAKi), tels que le ruxolitinib et le tofacitinib, ont été évalués dans les cas résistants. Nous rapportons ici une réponse clinique spectaculaire d’un vitiligo facial traité par tofacitinib topique à 2 % chez un patient atteint d’un lupus cutané déclenché par une photothérapie.

The skin of humanoid robots often lacks human tactility and the inherent self-repair capability of biological tissues. Recently, researchers have grown a living, self-healing skin on a robot finger by subsequent culturing of human dermal and epidermal cells. Here, we highlight the significance of this study alongside challenges toward developing biohybrid robots equipped with sensate and adaptive living robotic skins.

ABSTRACTCTSD (cathepsin D) is one of the major lysosomal proteases indispensable for the maintenance of cellular proteostasis by turning over substrates of endocytosis, phagocytosis and autophagy. Consequently, CTSD deficiency leads to a strong impairment of the lysosomal-autophagy machinery. In mice and humans CTSD dysfunction underlies the congenital variant (CLN10) of neuronal ceroid lipofuscinosis (NCL). NCLs are distinct lysosomal storage disorders (LSDs) sharing various hallmarks, namely accumulation of protein aggregates and ceroid lipofuscin leading to neurodegeneration and blindness. The most established and clinically approved approach to treat LSDs is enzyme replacement therapy (ERT) aiming to replace the defective hydrolase with an exogenously applied recombinant protein. Here we reveal that recombinant human pro-CTSD produced in a mammalian expression system can be efficiently taken up by a variety of cell models, is correctly targeted to lysosomes and processed to the active mature form of the protease. In proof-of-principle experiments we provide evidence that recombinant human CTSD (rhCTSD) can improve the biochemical phenotype of CTSD-deficient hippocampal slice cultures in vitroand retinal cells in vivo. Furthermore, we demonstrate that dosing of rhCTSD in the murine CLN10 model leads to a correction of lysosomal hypertrophy, storage accumulation and impaired autophagic flux in the viscera and central nervous system (CNS). We establish that direct delivery of the recombinant protease to the CNS is required for improvement of neuropathology and lifespan extension. Together these data support the continuation of the pre-clinical studies for the application of rhCTSD in the treatment of NCL.Abbreviations:AIF1/IBA1: allograft inflammatory factor 1; BBB: blood brain barrier; CNS: central nervous system; CTSB: cathepsin B; CTSD: cathepsin D; CTSL: cathepsin L; ERT: enzyme replacement therapy; GFAP: glial fibrillary acidic protein; INL: inner nuclear layer; LAMP1: lysosomal-associated membrane protein 1; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; LDL: low-density lipoprotein; LRP1: low density lipoprotein receptor-related protein 1; LSD: lysosomal storage disorder; MEFs: mouse embryonic fibroblasts; M6P: mannose 6-phosphate; mCTSD: mature CTSD; NCL: neuronal ceroid lipofuscinosis; ONL: outer nuclear layer; PB: phosphate buffer; proCTSD: pro-cathepsin D; LRPAP1: low density lipoprotein receptor-related protein associated protein 1; rhCTSD: human recombinant CTSD; SAPC: saposin C; SAPD: saposin D; ATP5G1: ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C1 (subunit 9); SQSTM1/p62: sequestosome 1; TPP1: tripeptidyl peptidase I.

We report a versatile method to form bacterial cellulose coatings through simple dip-coating of 3D objects in suspensions of cellulose-producing bacteria. The adhesion of cellulose-secreting bacteria on objects was promoted through surface roughness and chemistry. Immobilized bacteria secreted highly porous hydrogels with high water content directly from the surface of a variety of materials. The out-of-plane orientation of cellulose fibers present in this coating leads to high mechanical stability and energy dissipation with minimal cellulose concentration. The conformal, biocompatible, and lubricious nature of the in situgrown cellulose surfaces makes the coated 3D objects attractive for biomedical applications.

Calcium looping, a CO2capture technique based on the cyclic carbonation and calcination of CaO, is a promising short- to midterm solution to reduce CO2emissions. However, CaO suffers from sintering under industrially relevant operating conditions, which reduces rapidly its cyclic CO2uptake capacity. Here, we report the design and manufacture of a hierarchical, porous (HP) CaO-based CO2sorbent. The hierarchically porous sorbent is created through the assembly of calcium carbonate nanoparticles and monodisperse oil droplets generated via microfluidic emulsification. The structure of the sorbent is stabilized by an Al2O3coating via atomic layer deposition (ALD). The sorbent outperformed the CO2uptake of the reference limestone by ca. 140%. The improved CO2uptake capacity is attributed to (i) the stabilization of the micro- and mesoporous structure of the material by the formation of Ca–Al mixed oxides, that is, Ca12Al14O33and Ca3Al2O6, and (ii) an improved mass transport within the sorbent particles owing to the HP structure of the material.

The barocaloric effect (BCE) is characterized as thermal responses (variations of temperature or entropy) in a material resulting from compression. Several materials exhibit a BCE suitable for development of solid-state cooling devices, typically associated with pressure-induced phase transitions. A giant BCE has been observed for natural rubber (NR), which makes it a cheap and environmentally friendly candidate for such a purpose. The reason for the significant BCE in NR is still elusive, considering that there is no evidence of phase transitions in the process. The present study uses a combination of classical molecular dynamics (MD) simulations and a thermodynamic analysis to investigate the origin of the giant BCE in NR. MD simulations of adiabatic compression cycles for NR were carried out under varied applied pressures and initial temperatures and were able to capture the BCE. A detailed analysis of the results helped us to elucidate the structural transformations and resulting energy changes in the material under compression. MD results for isothermal compression along with the thermodynamic analysis showed that the high compressibility of NR combined with an unusual decrease in the potential energy at the molecular level upon compression favors significantly the BCE (quantified by isothermal entropy changes and adiabatic temperature changes in the process), a feature not commonly seen in other materials. These findings can be extended to other polymers and are certainly going to be useful toward the design of materials with an enhanced BCE.

Cutaneous adverse effects of immunotherapies are being seen with increasing frequency in general practice. While anti-PD1 lichenoid reactions are well known, only a few cases of bullous lichen planus have so far been reported in the medical literature. Herein we described a case of secondary bullous lichen planus associated with nivolumab and we present a systematic review of all anti-P1-induced cases reported in the literature.

Constraining strain localization and the growth of shear fabrics within brittle fault zones at sub‐seismic slip rates is important for understanding fault strength and frictional stability. We conducted direct shear experiments on simulated sandstone‐derived fault gouges at an effective normal stress of 40 MPa, a pore pressure of 15 MPa, and a temperature of 100°C. Using a passive strain marker and X‐ray Computed Tomography, we analyzed the spatial distribution of deformation in gouges deformed in the strain‐hardening, subsequent strain‐softening, and then steady‐state regimes at displacement rates of 1, 30, and 1,000 µm/s. We developed a machine‐learning‐based automatic boundary detection method to recognize the shear fabrics and quantify displacement partitioning between each fabric element. Our results show fabrics oriented along R1and Y (including boundary) shears are the two major fabric elements. At rates of 1 and 30 µm/s, the relative amount of displacement on R1shears is displacement dependent, increasing to ∼20% of the total displacement up to the strain‐softening stage, then decreasing to ∼10%–18% at the steady state. This trend is absent at the high rate where ∼18% of the displacement occurs on R1shears throughout all investigated stages. At all rates, the relative amount of displacement on Y shears increases linearly with displacement to a total of larger than 50% at the steady state. Our study provides constraints on the development of the active slip zone, which is an important factor controlling heating and weakening associated with small‐magnitude earthquakes with limited displacement (mm‐dm), such as induced seismicity. In the past few decades, several studies have focused on the mechanical behavior of simulated fault zones to understand earthquake nucleation. However, minor attention has been paid to the microstructural characterization of fault‐zone gouges due to the difficulties in quantifying deformation. An understanding of brittle fault‐zone fabrics and their development provides crucial constraints on the mechanical strength and stability of faults. We conducted laboratory experiments on simulated sandstone‐derived fault gouges with a passive strain marker under the conditions relevant to earthquake nucleation to explore the development and evolution of shear zone fabrics and their relations to fault strength. We combined X‐ray Computed Tomography (XCT) and a custom‐designed machine‐learning‐based automatic boundary detection method to analyze the spatial distribution of gouge deformation and to quantify displacement partitioning between deformation features. The results show that our samples have similar evolution of the shear fabrics, partitioning of displacement, and mechanical response with increasing shear strain at all tested nucleation velocities. The evolution of the mechanical behavior from strain‐hardening, to softening, to steady‐state stages is related to the transformation of R1to shear‐parallel shear bands. Up to 50% of the total displacement can be accommodated within shear‐parallel shear bands, facilitating strain weakening of the materials. We performed 3‐D analyses on the evolution of shear zone fabrics within sandstone‐derived fault gouges utilizing the X‐ray CT techniqueOur samples show similar evolution of shear fabrics, slip partitioning, and mechanical response with shear strain at all tested velocitiesUp to 50% of the total imposed displacement can be accommodated within shear‐parallel shear bands during earthquake nucleation We performed 3‐D analyses on the evolution of shear zone fabrics within sandstone‐derived fault gouges utilizing the X‐ray CT technique Our samples show similar evolution of shear fabrics, slip partitioning, and mechanical response with shear strain at all tested velocities Up to 50% of the total imposed displacement can be accommodated within shear‐parallel shear bands during earthquake nucleation

IMPORTANCE: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. OBSERVATIONS: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. CONCLUSIONS AND RELEVANCE: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.

The digital fabrication of oxide glasses by three-dimensional (3D) printing represents a major paradigm shift in the way glasses are designed and manufactured, opening opportunities to explore functionalities inaccessible by current technologies. The few enticing examples of 3D printed glasses are limited in their chemical compositions and suffer from the low resolution achievable with particle-based or molten glass technologies. Here, we report a digital light-processing 3D printing platform that exploits the photopolymerization-induced phase separation of hybrid resins to create glass parts with complex shapes, high spatial resolutions and multi-oxide chemical compositions. Analogously to conventional porous glass fabrication methods, we exploit phase separation phenomena to fabricate complex glass parts displaying light-controlled multiscale porosity and dense multicomponent transparent glasses with arbitrary geometry using a desktop printer. Because most functional properties of glasses emerge from their transparency and multicomponent nature, this 3D printing platform may be useful for distinct technologies, sciences and arts.

This work presents the stability analysis and design of a lateral controller for a nonlinear ground vehicle applying the concept of polynomial sum of squares relaxations. The system is approximated by a polynomial vector field that describes the lateral vehicle dynamics. The resulting polynomial system falls on a class of non-affine in input system, which makes the control synthesis more involved. This issue is circumvented by an input-affine approximation, simplifying the stability analysis and the design procedure of a polynomial state-feedback controller able to enlarge the region of attraction (RoA). We also compare the estimated region of attraction with the standard LQR optimal controller.

Polysaccharide-based materials have been claimed as efficient supports for different species used in catalysis, such as transition metal ions. Overall, the immobilization of metal ions on these materials brings several attractive aspects in terms of economy and catalytic activity. In this study, we demonstrated the facile immobilization of Cu2+ions on alginate-based microspheres (Alg–Cu2+) viaa straightforward ion exchange process. The prepared microspheres were characterized in detail by different techniques. As assessed, the ion-exchange process promoted some change in the properties of the microspheres, which was ascribed to the strong interaction forces established between the alginate matrix and Cu2+ions. The catalytic activity of Alg–Cu2+was investigated towards the one-pot synthesis of 4-organylselanyl-1H-pyrazole derivatives viacyclocondensation reactions of diketones and hydrazines, followed by direct selenation reactions. In general lines, the starting reagents were efficiently converted viaone-pot reactions to different derivatives in moderate to excellent yields. Moreover, the Alg–Cu2+catalysts still maintained satisfactory catalytic activity even after five consecutive runs. These results indicate that the Alg–Cu2+microspheres prepared in this study are a promising heterogeneous catalytic system for the synthesis of this class of substituted pyrazoles.

Adsorption heat pumps offer a clean, zero-emission technology for universally applicable cooling or heating utilizing water as a refrigerant and waste or renewable heat as driving energy instead of electricity. Despite their attractive environmentally friendly prospects, the broader application of such classes of heat pumps has not yet been possible, mainly because of the low power density of adsorption heat exchangers and the corresponding large size and high cost of the adsorption heat pumps. We report an inexpensive route for the fabrication of zeolite coatings with high adsorption power density based on the bottom-up assembly of colloids directed by magnetic and capillary forces. Such an assembly process relies on the chaining of oil droplets under an external magnetic field during deposition of the coating, followed by the formation of a percolating network of bridged adsorbent particles upon drying. This results in vertically open channels and thermal bridges that facilitate directed mass and heat transport across the structured zeolite coating during sorption cycles. By reaching up to 3.3-fold higher performance than their unstructured counterparts using readily available zeolite as an adsorbent material, the architectured coatings produced through this facile, upscalable approach hold great potential for next-generation adsorption heat pumps.

Chlorite is abundant at hypocentral depths in subduction zones and is likely to play a key role in controlling megathrust slow slip and catastrophic rupture. However, no data exist on the frictional properties of chlorite(‐rich) fault rocks under the hydrothermal conditions relevant for the subduction seismogenic zone. We report results from experiments conducted under such conditions, using chlorite powders prepared from single crystal clinochlore (Mg‐chlorite), as well as limited experiments using a stack of single crystal sheets. Shear experiments were carried out at effective normal stresses (σn) of 100 to 400 MPa, pore fluid pressures (Pf) of 50 to 220 MPa, and at temperatures (T) of 22 to 600 °C, using stepped displacement rates (v) from 0.3 to 100 μm/s. The gouges are characterized by a coefficient of friction (μ) of 0.2–0.3 at T≤ 400 °C and 0.3–0.4 at 500–600 °C, while (a‐b) values showed positive values for nearly all conditions tested, except at 300 °C. Microstructures of gouges sheared at T≤ 300 °C show evidence for widespread comminution, compared with a lower porosity at 600 °C. Experiments using a stack of single crystal sheets showed μ≤ 0.008 at low displacements (<3 mm) followed by hardening, while microstructures are suggestive of slip along (001), folding and tear of cleavage planes, and gouge production. Our results have important implications for the mechanisms controlling megathrust fault slip under greenschist facies conditions in a subduction zone and shed new light on the strain accommodation mechanisms within sheared gouges versus single crystals composed of phyllosilicates. Chlorite gouges show a low friction coefficient (μ= 0.2–0.4) and velocity strengthening behavior, except at ~300 °CFault slip of chlorite‐rich gouge may be velocity‐neutral or unstable at hypocentral depths around 300 °C in a subduction zoneA stack of cleaved chlorite single crystals shows extremely low μvalues (≤ 0.01) at low displacements (<3 mm)

Mechanosensing is ubiquitous in natural systems. From the skin ridges of our finger tips to the microscopic ion channels in cells, mechanosensors allow organisms to probe their environment and gather information needed for processing, decision making, and actuation. Despite technological advances in synthetic mechanosensing, it remains challenging to achieve this functionality at the scale of large stiff structures where both the amount of data to sense locally and the diversity of input stresses that the sensors have to withstand require highly tunable systems. Filtered sensing using mechanical displacement is an effective strategy developed by organisms to cope with large sets of stimuli. Inspired by this biological strategy, we fabricate bistable elements that can passively filter mechanical inputs, translate them into electrical signals, and be reset to their original sensing state using an external magnetic field. These multiple functionalities are achieved using hierarchically structured composites that can be arranged in large-area arrays. The filtering capability and fast passive response of our mechanosensors are experimentally demonstrated using simple electrical circuits and magnets. Thanks to their scalability and applicability to a wide range of material systems, these low-power sensors are avenues for the fabrication of load-bearing structures that are able to sense, compute, communicate, and autonomously adapt in response to external magneto-mechanical stimuli.

Tuning the optical properties of suspensions by controlling the orientation and spatial distribution of suspended particles with magnetic fields is an interesting approach to creating magnetically controlled displays, microrheology sensors, and materials with tunable light emission. However, the relatively high concentration of magnetic material required to manipulate these particles very often reduces the optical transmittance of the system. In this study, we describe a simple method of generating particles with magnetically tunable optical properties via sol–gel deposition and functionalization of a continuous layer of silica on ultrahigh magnetically responsive (UHMR) alumina microplatelets. UHMR microplatelets with tunable magnetic response in the range of 15–36 G are obtained by the electrostatic adsorption of 2 to 13% of superparamagnetic iron oxide nanoparticles (SPIONs) on the alumina surface. The magnetized platelets are coated with a 20–50 nm layer of SiO2through the controlled hydrolysis and condensation reactions of tetraethylorthosilicate (TEOS) in an NH3/ethanol mixture. Finally, the silica surface is covalently modified with an organic fluorescent dye by conventional silane chemistry. Because of the anisotropic shape of the particles, control of their orientation and distribution using magnetic fields and field gradients enables easy tuning of the optical properties of the suspension. This strategy allows us to gain both spatial and temporal control over the fluorescence emission from the particle surface, making the multifunctional platelets interesting building blocks for the manipulation of light in colloid-based smart optical devices and sensors.

Hemoglobin SC is the second most common variant of sickle-cell disease worldwide, after hemoglobin SS. The objectives of the study were to describe the clinical and laboratory characteristics of hemoglobin SC disease in children from a newborn screening program and treated at a blood center.

In this contribution, we a report a facile synthesis and stabilization of copper nanoparticles (CuNPs) in a superporous hydrogel based on chitosan (Cs) and poly(vinyl alcohol) (PVA). The functional groups of Cs and PVA stabilized the CuNPs and, as a result, several properties (e.g.thermal, morphological and liquid uptake) of the final materials exhibited remarkable improvements in terms of stability and catalytic activity. The metallic nature of CuNPs was confirmed by XRD and XPS analyses. From the XRD data, the Cu nanoparticle size was estimated to range from 3 to 7 nm. Moreover, EDS mapping analysis revealed that the CuNPs are homogeneously distributed throughout the hydrogel surface. The Cs/PVA-CuNP hydrogel was found to be an excellent catalyst for the synthesis of 1,2,3-triazoles using phenyl azide and phenylacetylene as model substrates under mild optimized conditions (>90% yield). Reuse studies revealed that this original CuNP-containing catalyst can be employed in at least 5 consecutive cycloaddition reactions without demonstrating a clear loss of efficiency. Moreover, the copper leaching from the hydrogel matrix was negligible during these consecutive reactions under the investigated conditions. The Cs/PVA-CuNP hydrogel could also efficiently catalyze cycloaddition reactions involving different substituted azide and alkyne precursors.

Inpatient palliative care consultation has been demonstrated to improve quality of life as well as decrease hospital readmissions, intensive care unit transfers, and hospital costs for people with a life limiting illness. The clinical teaching units (CTUs) at London Health Sciences Centre (LHSC) routinely admit patients with noncurable cancer as well as end-stage heart, lung, liver, or kidney disease. However, the use of inpatient palliative care consultations for CTU patients remains unexamined. We conducted a descriptive study of all patients referred from LHSC CTU from both University and Victoria hospital to inpatient palliative care over a 1-year period from August 2013 to July 2014. The purpose of this study was to characterize the population and identify possible areas for quality improvement. In a 1-year period, 638 patients were referred from CTU to the inpatient palliative care consultation service. Of referrals, 55% died during their admission. Based on data collected, we conclude that many patients are referred early in their admission to CTU and patients are referred for a variety of noncancer diseases, suggesting knowledge and appreciation of the benefit of early palliative care consultation for malignant and nonmalignant disease. However, when further analyzed, there is indication that patients with noncancer diagnoses are referred statistically significantly later than those with a cancer diagnosis. The CTUs are sites of core medical training, and therefore, it is imperative that we model early integration of palliative care in order to continue to improve care of patients at end of life.

Fibre-reinforced polymer structures are often used when stiff lightweight materials are required, such as in aircraft, vehicles and biomedical implants. Despite their very high stiffness and strength1, such lightweight materials require energy- and labour-intensive fabrication processes2, exhibit typically brittle fracture and are difficult to shape and recycle3,4. This is in stark contrast to lightweight biological materials such as bone, silk and wood, which form by directed self-assembly into complex, hierarchically structured shapes with outstanding mechanical properties5–11, and are circularly integrated into the environment. Here we demonstrate a three-dimensional (3D) printing approach to generate recyclable lightweight structures with hierarchical architectures, complex geometries and unprecedented stiffness and toughness. Their features arise from the self-assembly of liquid-crystal polymer molecules into highly oriented domains during extrusion of the molten feedstock material. By orienting the molecular domains with the print path, we are able to reinforce the polymer structure according to the expected mechanical stresses, leading to stiffness, strength and toughness that outperform state-of-the-art 3D-printed polymers by an order of magnitude and are comparable with the highest-performance lightweight composites1,12. The ability to combine the top-down shaping freedom of 3D printing with bottom-up molecular control over polymer orientation opens up the possibility to freely design and realize structures without the typical restrictions of current manufacturing processes.

Partial circulatory support is a promising concept for the treatment of heart failure patients. A better understanding of induced hemodynamic changes is essential for optimizing treatment efficacy. Computational fluid dynamics (CFD) is an alternative method to gain insight into flow phenomena difficult to obtain in vivo. In 10 patients implanted with a Circulite Synergy Micro-pump (HeartWare, Framingham, Massachusetts) (a continuous flow partial circulatory assist device connecting the left atrium to the right subclavian artery), transient CFD simulations were performed. Patients were divided into two groups depending on their cardiac output (CO; high CO group: 5.5 ± 1.1 L/min, low CO group: 1.7 ± 0.7 L/min). The partial assist device provided a supporting flow of 1.5 ± 0.8 L/min. Support was highest at diastole and decreased during systole because of a collision of the blood flows from the partial assist device and the CO. Reversed flow counteracting the flow of the device was significantly higher for the high CO group (mean flow in peak systole: −2.18 ± 1.08 vs.0.23 ± 0.59 L/min; p= 0.002) showing an inverse correlation between CO and amount of reversed flow during peak systole (R= −0.7; p< 0.02). The flow collision lead to higher total pressures at the point of collision and consequently in the Circulite outflow graft. The CFD simulations allow quantifying hemodynamic alterations in patients with partial support consisting of a flow collision, thereby reducing effectiveness of the circulatory support. Partial support in heart failure patients alternates their hemodynamics not only in providing support for the circulation but also inducing unfavorable changes in flow patterns.

The alignment of anisotropic particles during ink deposition directly affects the microstructure and properties of materials manufactured by extrusion-based 3D printing. Although particle alignment in diluted suspensions is well described by analytical and numerical models, the dynamics of particle orientation in the highly concentrated inks typically used for printing viadirect ink writing (DIW) remains poorly understood. Using cellulose nanocrystals (CNCs) as model building blocks of increasing technological relevance, we study the dynamics of particle alignment under the shear stresses applied to concentrated inks during DIW. With the help of in situpolarization rheology, we find that the time period needed for particle alignment scales inversely with the applied shear rate and directly with the particle concentration. Such dependences can be quantitatively described by a simple scaling relation and qualitatively interpreted in terms of steric and hydrodynamic interactions between particles at high shear rates and particle concentrations. Our understanding of the alignment dynamics is then utilized to estimate the effect of shear stresses on the orientation of particles during the printing process. Finally, proof-of-concept experiments show that the combination of shear and extensional flow in 3D printing nozzles of different geometries provides an effective means to tune the orientation of CNCs from fully aligned to core–shell architectures. These findings offer powerful quantitative guidelines for the digital manufacturing of composite materials with programmed particle orientations and properties.

Nasal CPAP is the “gold standard” treatment for OSA. However, oronasal masks are frequently used in clinical practice. The aim of this study was to perform a meta-analysis of all randomized and nonrandomized trials that compared nasal vs oronasal masks on CPAP level, residual apnea-hypopnea index (AHI), and CPAP adherence to treat OSA.