Complementary Metal Oxide Semiconductor (CMOS) and Micro-Electro-Mechanical System (MEMS) devices play significant roles in emerging research fields such as artificial intelligence (AI) ....
Clathrin-mediated endocytosis occurs via the assembly of clathrin-coated pits (CCPs) that invaginate and pinch off to form clathrin-coated vesicles (CCVs). It is well known that adaptor protein 2 ...(AP2) complexes trigger clathrin assembly on the plasma membrane, and biochemical and structural studies have revealed the nature of these interactions. Numerous endocytic accessory proteins collaborate with clathrin and AP2 to drive CCV formation. However, many questions remain as to the molecular events involved in CCP initiation, stabilization, and curvature generation. Indeed, a plethora of recent evidence derived from cell perturbation, correlative light and EM tomography, live-cell imaging, modeling, and high-resolution structural analyses has revealed more complexity and promiscuity in the protein interactions driving CCP maturation than anticipated. After briefly reviewing the evidence supporting prevailing models, we integrate these new lines of evidence to develop a more dynamic and flexible model for how redundant, dynamic, and competing protein interactions can drive endocytic CCV formation and suggest new approaches to test emerging models.
Abstract
The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and ...metastatic progression of cancer cells. C-MET can be activated by either hepatocyte growth factor (HGF), or its natural isoform NK1. Here, we report the cryo-EM structures of c-MET/HGF and c-MET/NK1 complexes in the active state. The c-MET/HGF complex structure reveals that, by utilizing two distinct interfaces, one HGF molecule is sufficient to induce a specific dimerization mode of c-MET for receptor activation. The binding of heparin as well as a second HGF to the 2:1 c-MET:HGF complex further stabilize this active conformation. Distinct to HGF, NK1 forms a stable dimer, and bridges two c-METs in a symmetrical manner for activation. Collectively, our studies provide structural insights into the activation mechanisms of c-MET, and reveal how two isoforms of the same ligand use dramatically different mechanisms to activate the receptor.
Metastasis is the main cause of death in individuals with cancer. Immune checkpoint blockade (ICB) can potentially reverse CD8+ cytotoxic T lymphocytes (CTLs) dysfunction, leading to significant ...remission in multiple cancers. However, the mechanism underlying the development of CTL exhaustion during metastatic progression remains unclear. Here, we established an experimental pulmonary metastasis model with melanoma cells and discovered a critical role for melanoma‐released exosomes in metastasis. Using genetic knockdown of nSMase2 and Rab27a, 2 key enzymes for exosome secretion, we showed that high levels of effector‐like tumor‐specific CD8+ T cells with transitory exhaustion, instead of terminal exhaustion, were observed in mice without exosomes; these cells showed limited inhibitory receptors and strong proliferation and cytotoxicity. Mechanistically, the immunosuppression of exosomes depends on exogenous PD‐L1, which can be largely rescued by pretreatment with antibody blockade. Notably, we also found that exosomal PD‐L1 acts as a promising predictive biomarker for ICB therapies during metastasis. Together, our findings suggest that exosomal PD‐L1 may be a potential immunotherapy target, suggesting a new curative therapy for tumor metastasis.
We demonstrate a crucial role for tumor‐released exosomes in promoting metastatic progression. We provide extensive evidence that exosomes from tumor cells act alone as contributors to driving tumor‐specific CD8+ T cell exhaustion in vivo. We also find that exosomal PD‐L1 acts as a promising predictive biomarker for ICB therapies during metastasis.
In this paper, we propose a vectorized noncircular MUSIC (VNCM) algorithm based on the concept of the coarray, which can construct the difference and sum (diff-sum) coarray, for direction finding of ...the noncircular (NC) quasi-stationary sources. Utilizing both the NC property and the concept of the Khatri-Rao product, the proposed method can be applied to not only the ULA but also sparse arrays. In addition, we utilize the quasi-stationary characteristic instead of the spatial smoothing method to solve the coherent issue generated by the Khatri-Rao product operation so that the available degree of freedom (DOF) of the constructed virtual array will not be reduced by half. Compared with the traditional NC virtual array obtained in the NC MUSIC method, the diff-sum coarray achieves a higher number of DOFs as it comprises both the difference set and the sum set. Due to the complementarity between the difference set and the sum set for the coprime array, we choose the coprime array with multiperiod subarrays (CAMpS) as the array model and summarize the properties of the corresponding diff-sum coarray. Furthermore, we develop a diff-sum coprime array with multiperiod subarrays (DsCAMpS) whose diff-sum coarray has a higher DOF. Simulation results validate the effectiveness of the proposed method and the high DOF of the diff-sum coarray.
Complex fracture networks are commonly generated in subsurface reservoirs, and the first and primary task is to understand their transport characteristics and properties. Like pumping test ...interpretation, the well‐testing interpretation is an effective means for transport characteristics analysis and parameter estimations, this work attempts to propose a parameter inversion approach for complex fracture networks based on well‐testing interpretation. Given that non‐unique solutions and computational inefficiencies are obstacles to practical interpretation, especially when complex fractures are existing, a new deep reinforcement learning (DRL) based approach is proposed for automatic curve matching on complex fractured networks well‐testing interpretation. Based on twin delayed deep deterministic policy gradient (TD3) algorithm, the proposed DRL approach is successfully applied to automatic matching of complex fractured networks' well test curves. In addition, to improve the training efficiency, a surrogate model of the well test model based on bidirectional GRU (Bi‐GRU) neural network was established. After episodic training, the agent finally converged to an optimal curve matching policy through interaction with the surrogate model. The results show that the average relative error of the curve's parameter interpretation is 4.34%. Additionally, the results from the case studies show that the proposed DRL approach has a high calculation speed.
Plain Language Summary
Complex fracture networks are commonly generated in subsurface reservoirs, and the first and primary task is to understand their transport characteristics and properties. Like pumping test interpretation, the well‐testing interpretation is an effective means for transport characteristics analysis and parameter estimations. Thus, a new deep reinforcement learning based approach is proposed for automatic curve matching on complex fractured networks well‐testing interpretation.
Key Points
Automatic interpretation method improves the accuracy of understanding the characteristics and properties of complex fracture networks
An automatic interpretation method for complex fractured networks based on reinforcement learning is proposed
Using agents for curve matching significantly reduces the nonunique solutions and computation cost in parameter inversion
During the COVID-19 epidemic, the prevalence of neck pain among college students has increased due to the shift from offline to online learning and increasing academic and employment pressures. ...Therefore, this systematic review aimed to identify the personal, occupational, and psychological factors associated with the development of neck pain to promote the development of preventive strategies and early intervention treatment.
Seven electronic databases were searched from inception to December 2022 for cross-sectional studies, cohort studies, case---control studies, and randomized controlled trials (RCTs) on neck pain. The quality of the selected studies were assessed by American Agency for Healthcare Research and Quality (AHRQ) or the Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the effects of the included risk factors on neck pain.
Thirty studies were included, including 18,395 participants. And a total of 33 potentially associated risk factors were identified. Ultimately, 11 risk factors were included in the meta-analysis after assessing, and all results were statistically significant (P < 0.05). The factors supported by strong evidence mainly include the improper use of the pillow (OR = 2.20, 95% CI: 1.39 to 3.48), lack of exercise (OR = 1.88, 95% CI: 1.53 to 2.30), improper sitting posture (OR = 1.97, 95% CI: 1.39 to 2.78), history of neck and shoulder trauma (OR = 2.32, 95% CI: 1.79 to 3.01), senior grade (OR = 2.86, 95% CI: 2.07 to 3.95), staying up late (OR = 1.80, 95% CI: 1.35 to 2.41), long-time electronic product usage daily (OR = 1.53, 95% CI: 1.33 to 1.76), long-time to bow head (OR = 2.04, 95% CI: 1.58 to 2.64), and emotional problems (OR = 2.09; 95% CI: 1.66 to 2.63). Risk factors supported by moderate evidence were high stress (OR = 1.61, 95% CI: 1.02 to 2.52) and female gender (OR = 1.69, 95% CI: 1.52 to 1.87).
This study obtained 11 main risk factors affecting college students neck pain, including improper use of the pillow, lack of exercise, improper sitting posture, history of neck and shoulder trauma, senior grade, staying up late, long-term electronic product usage daily, long time to bow head, high stress, emotional problems and female gender.
This paper presents a 210-GHz transceiver with OOK modulation in a 32-nm SOI CMOS process (f T /f max = 250/320 GHz). The transmitter (TX) employs a 2 × 2 spatial combining array consisting of a ...double-stacked cross-coupled voltage controlled oscillator (VCO) at 210 GHz with an on-off-keying (OOK) modulator, a power amplifier (PA) driver, a novel balun-based differential power distribution network, four PAs, and an on-chip 2 × 2 dipole antenna array. The noncoherent receiver (RX) utilizes a direct detection architecture consisting of an on-chip antenna, a low-noise amplifier (LNA), and a power detector. The VCO generates measured -13.5-dBm output power, and the PA shows a measured 15-dB gain and 4.6-dBm P sat . The LNA exhibits a measured in-band gain of 18 dB and minimum in-band noise figure (NF) of 11 dB. The TX achieves an EIRP of 5.13 dBm at 10 dB back-off from saturated power. It achieves an estimated EIRP of 15.2 dBm when the PAs are fully driven. This is the first demonstration of a fundamental frequency CMOS transceiver at the 200-GHz frequency range.
As the second-generation high-temperature superconducting conductors, rare earth–barium–copper–oxide (REBCO) coated conductor (CC) tapes have good potential as high-field and high-energy ...superconductors. In superconducting applications, several joints are required for conjugating comparatively short REBCO CC tapes. Soldering lap joints are the simplest and most commonly applied REBCO CC joints. In addition to joint resistance, the mechanical behavior and electromechanical properties are also crucial for superconducting applications. In this paper, the electromechanical properties and mechanical behaviors of soldering lap joints at 77 K under a self-field were studied. The mechanical behavior was addressed by using a full three-dimensional multilayer elastic–plastic finite element model (FEM) with REBCO CC tape main layers and solder connecting layers. Then, the electromechanical properties were analyzed by using Gao’s strain-Ic degradation general model on the basis of the FEM results. Both the mechanical behavior and electromechanical properties were verified by experimental results. The effects of soldering lap conditions including lap length, soldering thickness and lap style on the electromechanical properties and mechanical behaviors were discussed. The results indicate that shorter overlap lengths and a thinner solder can reduce the premature degradation of Ic due to stress concentrations nearby the joint edges; moreover, the irreversible critical strain is significantly higher in the back-to-back joint approach compared to the widely used face-to-face joint approach.
Van der Waals (vdW) heterostructures provide a unique opportunity to develop various electronic and optoelectronic devices with specific functions by designing novel device structures, especially for ...bioinspired neuromorphic optoelectronic devices, which require the integration of nonvolatile memory and excellent optical responses. Here, we demonstrate a programmable optoelectronic synaptic floating‐gate transistor based on multilayer graphene/h‐BN/MoS2 vdW heterostructures, where both plasticity emulation and modulation were successfully realized in a single device. The dynamic tunneling process of photogenerated carriers through the as‐fabricated vdW heterostructures contributed to a large memory ratio (105) between program and erase states. Our device can work as a functional or silent synapse by applying a program/erase voltage spike as a modulatory signal to determine the response to light stimulation, leading to a programmable operation in optoelectronic synaptic transistors. Moreover, an ultra‐low energy consumption per light spike event (~2.5 fJ) was obtained in the program state owing to a suppressed noise current by program operation in our floating‐gate transistor. This study proposes a feasible strategy to improve the functions of optoelectronic synaptic devices with ultra‐low energy consumption based on vdW heterostructures designed for highly efficient artificial neural networks.
A neuromorphic optoelectronic floating‐gate transistor based on multilayer graphene/h‐BN/MoS2 vdW heterostructure exhibits programmable synaptic plasticity due to the unique light‐induced carrier tunneling through vdW heterostructure. Ultra‐low energy consumption for the electrical response to light stimulation is also realized under a low Vds at program state, demonstrating its great potential in building efficient artificial neural networks based on vdW heterostructures.
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