• Connolly Demant opublikował 1 rok, 3 miesiące temu

    A central challenge in neuroscience is how the brain organizes the information necessary to orchestrate behaviour. Arguably, this whole-brain orchestration is carried out by a core subset of integrative brain regions, a 'global workspace’, but its constitutive regions remain unclear. We quantified the global workspace as the common regions across seven tasks as well as rest, in a common 'functional rich club’. To identify this functional rich club, we determined the information flow between brain regions by means of a normalized directed transfer entropy framework applied to multimodal neuroimaging data from 1,003 healthy participants and validated in participants with retest data. This revealed a set of regions orchestrating information from perceptual, long-term memory, evaluative and attentional systems. We confirmed the causal significance and robustness of our results by systematically lesioning a generative whole-brain model. Overall, this framework describes a complex choreography of the functional hierarchical organization of the human brain.Interacting pedestrians in a crowd spontaneously adjust their footsteps and align their respective stepping phases. This self-organization phenomenon is known as synchronization. However, it is unclear why and how synchronization forms spontaneously under different density conditions, or what functional benefit synchronization offers for the collective motion of humans. Here, we conducted a single-file crowd motion experiment that directly tracked the alternating movement of both legs of interacting pedestrians. We show that synchronization is most likely to be triggered at the same density at which the flow rate of pedestrians reaches a maximum value. We demonstrate that synchronization is established in response to an insufficient safety distance between pedestrians, and that it enables pedestrians to realize efficient collective stepping motion without the occurrence of inter-person collisions. These findings provide insights into the collective motion behaviour of humans and may have implications for understanding pedestrian synchronization-induced wobbling, for example, of bridges.In strongly correlated materials, quasiparticle excitations can carry fractional quantum numbers. An intriguing possibility is the formation of fractionalized, charge-neutral fermions-for example, spinons1 and fermionic excitons2,3-that result in neutral Fermi surfaces and Landau quantization4,5 in an insulator. Although previous experiments in quantum spin liquids1, topological Kondo insulators6-8 and quantum Hall systems3,9 have hinted at charge-neutral Fermi surfaces, evidence for their existence remains inconclusive. Here we report experimental observation of Landau quantization in a two-dimensional insulator, monolayer tungsten ditelluride (WTe2), a large-gap topological insulator10-13. Using a detection scheme that avoids edge contributions, we find large quantum oscillations in the material’s magnetoresistance, with an onset field as small as about 0.5 tesla. Despite the huge resistance, the oscillation profile, which exhibits many periods, mimics the Shubnikov-de Haas oscillations in metals. At ultralow temperatures, the observed oscillations evolve into discrete peaks near 1.6 tesla, above which the Landau quantized regime is fully developed. Such a low onset field of quantization is comparable to the behaviour of high-mobility conventional two-dimensional electron gases. Our experiments call for further investigation of the unusual ground state of the WTe2 monolayer, including the influence of device components and the possible existence of mobile fermions and charge-neutral Fermi surfaces inside its insulating gap.A large proportion of patients with cancer are unresponsive to treatment with immune checkpoint blockade and other immunotherapies. Here, we report a mathematical model of the time course of tumour responses to immune checkpoint inhibitors. The model takes into account intrinsic tumour growth rates, the rates of immune activation and of tumour-immune cell interactions, and the efficacy of immune-mediated tumour killing. For 124 patients, four cancer types and two immunotherapy agents, the model reliably described the immune responses and final tumour burden across all different cancers and drug combinations examined. In validation cohorts from four clinical trials of checkpoint inhibitors (with a total of 177 patients), the model accurately stratified the patients according to reduced or increased long-term tumour burden. We also provide model-derived quantitative measures of treatment sensitivity for specific drug-cancer combinations. The model can be used to predict responses to therapy and to quantify specific drug-cancer sensitivities in individual patients.Therapeutic genome editing requires effective and targeted delivery methods. The delivery of Cas9 mRNA using adeno-associated viruses has led to potent in vivo therapeutic efficacy, but can cause sustained Cas9 expression, anti-Cas9 immune responses and off-target edits. Lentiviral vectors have been engineered to deliver nucleases that are expressed transiently, but in vivo evidence of their biomedical efficacy is lacking. Here, we show that the lentiviral codelivery of Streptococcus pyogenes Cas9 mRNA and expression cassettes that encode a guide RNA that targets vascular endothelial growth factor A (Vegfa) is efficacious in a mouse model of wet age-related macular degeneration induced by Vegfa. A single subretinal injection of engineered lentiviruses knocked out 44% of Vegfa in retinal pigment epithelium and reduced the area of choroidal neovascularization by 63% without inducing off-target edits or anti-Cas9 immune responses. Engineered lentiviruses for the transient expression of nucleases may form the basis of new treatments for retinal neovascular diseases.The prognostic value of electrocardiograms (ECGs) has been reported in predialysis patients but not in incident hemodialysis patients with overhydration and electrolyte disturbances, both of which potentially affect ECG results. We performed a retrospective multicenter cohort study involving incident hemodialysis patients and examined whether ECG parameters immediately before hemodialysis initiation can predict subsequent cardiovascular disease (CVD) using Cox proportional hazards models. We explored potential effect modifications by several electrolytes on the predictive power of ECG abnormalities. Among the 618 enrolled patients, 16%, 10%, 46%, and 22% showed a PR interval ≥ 200 ms, QRS interval ≥120 ms, QTc interval ≥ 450/460 ms (male/female), and left ventricular hypertrophy (LVH) by voltage criteria, respectively. Over a median 3-year follow-up, 19% and 16% of the patients developed atherosclerotic and nonatherosclerotic CVD, respectively. The Cox regression model results revealed that the sum of the number of abnormalities in PR, QRS, and QT intervals was a significant risk factor for nonatherosclerotic CVD (hazard ratios (HRs) [95% confidence interval (CI)] 1.58 [1.24-2.01] per number of abnormalities). The predictive value of LVH for atherosclerotic CVD was attenuated over time. At up to 36 months, although the proportional hazards assumption was met, LVH was significantly associated with atherosclerotic CVD (HR [95% CI] 1.89 [1.15-3.11]). The adjusted HR was particularly high (HR [95% CI] 4.02 [1.68-9.60]) among patients who were in the lowest tertile of serum magnesium levels (P for interaction = 0.04). PR, QRS, and QT prolongation additively predicted nonatherosclerotic CVD, while LVH predicted atherosclerotic CVD in the short term.Advancements in human pluripotent stem cell technology offer a unique opportunity for the neuroimmunology field to study host-virus interactions directly in disease-relevant cells of the human central nervous system (CNS). Viral encephalitis is most commonly caused by herpesviruses, arboviruses and enteroviruses targeting distinct CNS cell types and often leading to severe neurological damage with poor clinical outcomes. Furthermore, different neurotropic viruses will affect the CNS at distinct developmental stages, from early prenatal brain development to the aged brain. With the unique flexibility and scalability of human pluripotent stem cell technology, it is now possible to examine the molecular mechanisms underlying acute infection and latency, determine which CNS subpopulations are specifically infected, study temporal aspects of viral susceptibility, perform high-throughput chemical or genetic screens for viral restriction factors and explore complex cell-non-autonomous disease mechanisms. Therefore, human pluripotent stem cell technology has the potential to address key unanswered questions about antiviral immunity in the CNS, including emerging questions on the potential CNS tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Low-dimensional van der Waals materials have been extensively studied as a platform with which to generate quantum effects. Advancing this research, topological quantum materials with van der Waals structures are currently receiving a great deal of attention. Here, we use the concept of designing topological materials by the van der Waals stacking of quantum spin Hall insulators. Most interestingly, we find that a slight shift of inversion centre in the unit cell caused by a modification of stacking induces a transition from a trivial insulator to a higher-order topological insulator. Based on this, we present angle-resolved photoemission spectroscopy results showing that the real three-dimensional material Bi4Br4 is a higher-order topological insulator. Our demonstration that various topological states can be selected by stacking chains differently, combined with the advantages of van der Waals materials, offers a playground for engineering topologically non-trivial edge states towards future spintronics applications.Conductive and stretchable electrodes that can be printed directly on a stretchable substrate have drawn extensive attention for wearable electronics and electronic skins. Printable inks that contain liquid metal are strong candidates for these applications, but the insulating oxide skin that forms around the liquid metal particles limits their conductivity. This study reveals that hydrogen doping introduced by ultrasonication in the presence of aliphatic polymers makes the oxide skin highly conductive and deformable. X-ray photoelectron spectroscopy and atom probe tomography confirmed the hydrogen doping, and first-principles calculations were used to rationalize the obtained conductivity. The printed circuit lines show a metallic conductivity (25,000 S cm-1), excellent electromechanical decoupling at a 500% uniaxial stretching, mechanical resistance to scratches and long-term stability in wide ranges of temperature and humidity. The self-passivation of the printed lines allows the direct printing of three-dimensional circuit lines and double-layer planar coils that are used as stretchable inductive strain sensors.Moiré superlattices in twisted van der Waals materials have recently emerged as a promising platform for engineering electronic and optical properties. A major obstacle to fully understanding these systems and harnessing their potential is the limited ability to correlate direct imaging of the moiré structure with optical and electronic properties. Here we develop a secondary electron microscope technique to directly image stacking domains in fully functional van der Waals heterostructure devices. After demonstrating the imaging of AB/BA and ABA/ABC domains in multilayer graphene, we employ this technique to investigate reconstructed moiré patterns in twisted WSe2/WSe2 bilayers and directly correlate the increasing moiré periodicity with the emergence of two distinct exciton species in photoluminescence measurements. These states can be tuned individually through electrostatic gating and feature different valley coherence properties. We attribute our observations to the formation of an array of two intralayer exciton species that reside in alternating locations in the superlattice, and open up new avenues to realize tunable exciton arrays in twisted van der Waals heterostructures, with applications in quantum optoelectronics and explorations of novel many-body systems.

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