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The rational bottom-up synthesis of atomically defined graphene nanoribbon (GNR) heterojunctions represents an enabling technology for the design of nanoscale electronic devices. Synthetic strategies used thus far have relied on the random copolymerization of two electronically distinct molecular precursors to yield GNR heterojunctions. Here we report the fabrication and electronic characterization of atomically precise GNR heterojunctions prepared through late-stage functionalization of chevron GNRs obtained from a single precursor. Post-growth excitation of fully cyclized GNRs induces cleavage of sacrificial carbonyl groups, resulting in atomically well-defined heterojunctions within a single GNR. The GNR heterojunction structure was characterized using bond-resolved scanning tunnelling microscopy, which enables chemical bond imaging at T  = 4.5 K. Scanning tunnelling spectroscopy reveals that band alignment across the heterojunction interface yields a type II heterojunction, in agreement with first-principles calculations. GNR heterojunction band realignment proceeds over a distance less than 1 nm, leading to extremely large effective fields. Bottom-up fabrication of GNR heterojunctions exhibiting atomically perfect heterojunction interfaces can be obtained from a single molecular precursor via post-growth modification

Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children’s Hospital from January 2022 to June 2023. The median age was 85 (range: 2–188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2–7) days. We observed independent factors related to PICU admission, including CRP ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39–4.56, p = 0.002), albumin ≤ 30 (g/L) (OR 3.18, 95% CI 1.63–6.02, p = 0.001), absolute lymphocyte count ≤ 2 (× 10 9 /L) (OR 2.18, 95% CI 1.29–3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38–4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28–4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤ 2 (× 10 9 /L) (OR 2.48, 95% CI 1.10–5.61, p = 0.029), albumin ≤ 30 (g/L) (OR 2.53, 95% CI 1.22–5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12–4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.

Non-destructive techniques of in-situ stress measurement from oriented cored rocks have great potential to be developed as a cost cost-effective and reliable alternative to the conventional overcoring and hydraulic fracturing methods. The tangent modulus method (TMM) is one such technique that can be applied to oriented cored rocks to measure in-situ stresses. Like the deformation rate analysis (DRA), the rock specimen is subjected to two cycles of uniaxial compression and the stress-tangent modulus curve for the two cycles is obtained from the stress–strain curve. A bending point in the tangent modulus curve of the first cycle is observed, separating it from the tangent modulus curve of the second cycle. The point of separation between the two curves is assumed to be the previously applied maximum stress. A number of experiments were conducted on coal and coal measured rocks (sandstone and limestone) to understand the effect of loading conditions and the time delay. The specimens were preloaded, and cyclic compressions were applied under three different modes of loading, four different strain rates, and time delays of up to one week. The bending point in the stress-tangent modulus curves occurred approximately at the applied pre-stress levels under all three loading modes, and no effect of loading rate was observed on the bending points in TMM. However, a clear effect of time delay was observed on the TMM, contradicting the DRA results. This could be due to the sensitivity of TMM and the range of its applicability, all of which need further investigation for the in-situ stress measurement.

Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal polyglutamine expansion in the amino-terminal end of the huntingtin protein (Htt) and characterized by progressive striatal and cortical pathology. Previous reports have shown that Htt is essential for embryogenesis, and a recent study by our group revealed that the pathogenic form of Htt (mHtt) causes impairments in multiple stages of striatal development. In this study, we have examined whether HD-associated striatal developmental deficits are reflective of earlier maturational alterations occurring at the time of neurulation by assessing differential roles of Htt and mHtt during neural induction and early neurogenesis using an in vitro mouse embryonic stem cell (ESC) clonal assay system. We demonstrated that the loss of Htt in ESCs (KO ESCs) severely disrupts the specification of primitive and definitive neural stem cells (pNSCs, dNSCs, respectively) during the process of neural induction. In addition, clonally derived KO pNSCs and dNSCs displayed impaired proliferative potential, enhanced cell death and altered multi-lineage potential. Conversely, as observed in HD knock-in ESCs (Q111 ESCs), mHtt enhanced the number and size of pNSC clones, which exhibited enhanced proliferative potential and precocious neuronal differentiation. The transition from Q111 pNSCs to fibroblast growth factor 2 (FGF2)-responsive dNSCs was marked by potentiation in the number of dNSCs and altered proliferative potential. The multi-lineage potential of Q111 dNSCs was also enhanced with precocious neurogenesis and oligodendrocyte progenitor elaboration. The generation of Q111 epidermal growth factor (EGF)-responsive dNSCs was also compromised, whereas their multi-lineage potential was unaltered. These abnormalities in neural induction were associated with differential alterations in the expression profiles of Notch, Hes1 and Hes5. These cumulative observations indicate that Htt is required for multiple stages of neural induction, whereas mHtt enhances this process and promotes precocious neurogenesis and oligodendrocyte progenitor cell elaboration.

Huntington's disease (HD) is a neurodegenerative disease caused by abnormal polyglutamine expansion in the huntingtin protein (Htt). Although both Htt and the HD pathogenic mutation (mHtt) are implicated in early developmental events, their individual involvement has not been adequately explored. In order to better define the developmental functions and pathological consequences of the normal and mutant proteins, respectively, we employed embryonic stem cell (ESC) expansion, differentiation and induction experiments using huntingtin knock-out (KO) and mutant huntingtin knock-in (Q111) mouse ESC lines. In KO ESCs, we observed impairments in the spontaneous specification and survival of ectodermal and mesodermal lineages during embryoid body formation and under inductive conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves cell survival, but failed to correct defects in germ layer specification. In addition, we observed ensuing impairments in the specification and maturation of neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling pathways. Moreover, in Q111 ESCs, we observed differential developmental stage-specific alterations in lineage specification and maturation. We also observed changes in Notch/STAT3 expression and activation. Our observations underscore essential roles of Htt in the specification of ectoderm, endoderm and mesoderm, in the specification of neural and non-neural organ-specific lineages, as well as cell survival during early embryogenesis. Remarkably, these developmental events are differentially deregulated by mHtt, raising the possibility that HD-associated early developmental impairments may contribute not only to region-specific neurodegeneration, but also to non-neural co-morbidities.

The identification of crack stress thresholds and damage evolution from circumferential strain control triaxial tests are presented in this paper. As underground excavations become deeper to exploit mineral resources or construct civil projects, it has become increasingly important to determine the full stress–strain and damage evolution behaviours of brittle rock. Therefore, post-peak reaction of Class II rock or ‘snap-back’ behaviour must be captured to show the response of the material under self-sustaining failure. To investigate this, a series of triaxial compression tests were carried out for a granite sourced from over 1000 m depth. The tests were controlled using the feedback of lateral strain gauges attached to the Hoek cell membrane, to allow for constant, slow dilation of the specimen. The test results were then input to existing methods along with two new techniques, to identify the crack stress thresholds of crack closure, crack initiation and damage. It was found that although the crack closure threshold is comparable for axial and lateral control testing, the crack initiation and damage thresholds are significantly higher for the tests conducted in this study compared to most existing research. This result highlights the importance of the circumferential strain control method in triaxial tests when determining the post-peak behaviour and damage evolution of brittle rock. This was made easier with the strain gauged membrane proposed in this study, which provides reliable measurements throughout the duration of rock testing. Therefore, full stress–strain and damage evolution data can be obtained for use in damage-plasticity constitutive models.

The smoothed particle hydrodynamics (SPH) method was recently extended to simulate granular materials by the authors and demonstrated to be a powerful continuum numerical method to deal with the post-flow behaviour of granular materials. However, most existing SPH simulations of granular flows suffer from significant stress oscillation during the post-failure process, despite the use of an artificial viscosity to damp out stress fluctuation. In this paper, a new SPH approach combining viscous damping with stress/strain regularisation is proposed for simulations of granular flows. It is shown that the proposed SPH algorithm can improve the overall accuracy of the SPH performance by accurately predicting the smooth stress distribution during the post-failure process. It can also effectively remove the stress oscillation issue in the standard SPH model without having to use the standard SPH artificial viscosity that requires unphysical parameters. The predictions by the proposed SPH approach show very good agreement with experimental and numerical results reported in the literature. This suggests that the proposed method could be considered as a promising continuum alternative for simulations of granular flows.

Grain crushing and pore collapse are the principal micromechanisms controlling the physics of compaction bands in porous rocks. Several constitutive models have been previously used to predict the formation and propagation of these bands. However, they do not account directly for the physical processes of grain crushing and pore collapse. The parameters of these previous models were mostly tuned to match the predictions of compaction localization; this was usually done without validating whether the assigned parameters agree with the full constitutive behavior of the material. In this study a micromechanics‐based constitutive model capable of tracking the evolving grain size distribution due to grain crushing is formulated and used for a theoretical analysis of compaction band formation in porous rocks. Linkage of the internal variables to grain crushing enables us to capture both the material behavior and the evolving grain size distribution. On this basis, we show that the model correctly predicts the formation and orientation of compaction bands experimentally observed in typical high‐porosity sandstones. Furthermore, the connections between the internal variables and their underlying micromechanisms allow us to illustrate the significance of the grain size distribution and pore collapse on the formation of compaction bands. Key Points We provide a novel continuum theory for the prediction of compaction bands This continuum theory is the first one explicitly linked to micromechanics The localization is linked to competing grain crushing and pore collapse effects

H1 linker histone proteins are essential for the structural and functional integrity of chromatin and for the fidelity of additional epigenetic modifications. Deletion of H1c, H1d and H1e in mice leads to embryonic lethality by mid-gestation with a broad spectrum of developmental alterations. To elucidate the cellular and molecular mechanisms underlying H1 linker histone developmental functions, we analyzed embryonic stem cells (ESCs) depleted of H1c, H1d and H1e subtypes (H1-KO ESCs) by utilizing established ESC differentiation paradigms. Our study revealed that although H1-KO ESCs continued to express core pluripotency genes and the embryonic stem cell markers, alkaline phosphatase and SSEA1, they exhibited enhanced cell death during embryoid body formation and during specification of mesendoderm and neuroectoderm. In addition, we demonstrated deregulation in the developmental programs of cardiomyocyte, hepatic and pancreatic lineage elaboration. Moreover, ectopic neurogenesis and cardiomyogenesis occurred during endoderm-derived pancreatic but not hepatic differentiation. Furthermore, neural differentiation paradigms revealed selective impairments in the specification and maturation of glutamatergic and dopaminergic neurons with accelerated maturation of glial lineages. These impairments were associated with deregulation in the expression profiles of pro-neural genes in dorsal and ventral forebrain-derived neural stem cell species. Taken together, these experimental observations suggest that H1 linker histone proteins are critical for the specification, maturation and fidelity of organ-specific cellular lineages derived from the three cardinal germ layers.

In this study, we investigate the influence of material properties on the mobility of granular flow through granular column collapse experiments using the Smooth Particle Hydrodynamics method and a continuum constitutive model capable of describing the nonlinear responses of granular materials. Numerical simulations are systematically compared with available experimental data and well-established empirical laws to validate the capability of this numerical approach for simulating the dynamics of granular flow. Based on this validation, a series of numerical experiments is conducted to investigate the effects of strength properties (i.e. friction and dilation), density and stiffness properties (i.e. Young’s modulus and Poisson’s ratio) on the run-out distance and energy evolution of granular flows, which were unclear or contradictorily reported in previous experimental studies. We found that as the friction angle increases, the material is less mobilised and hence the run-out distance is shorter. In addition, a denser state (i.e. more dilation) facilitates its mobilisation associated with a greater volume expansion during the collapse. The density and stiffness properties of granular materials, nonetheless, have negligible effects on the deposit morphology and run-out distance of granular flow. To further quantify the effects of material properties, the run-out scaling law of granular flow, which describes the relationship between the run-out distance and the initial geometry of granular columns, is analysed and shown to be significantly influenced by the friction and dilation of the materials.