Search

Macro placement is a crucial and complex task in chip design. In recent years, reinforcement learning (RL) has emerged as a promising approach for autonomously generating effective macro placement on a grid-based chip canvas. However, existing RL-based macro placers encounter challenges when handling macros of varying sizes and preplaced blocks, due to using coarse-grained grids leads to wastage of placement space, while employing fine-grained grids results in an exponentially growing solution space and significant computational overhead. This brief proposes a legalization-aided RL-based macro placement (LAMPlace) for mixed-size designs with preplaced blocks. LAMPlace leverages RL to generate a global macro placement that allows possible overlap, followed by a macro legalization algorithm to ensure the legality of macro placement. LAMPlace can effectively address macros of various sizes and preplaced blocks because the action mask generation algorithm in RL is well coupled with the macro legalization algorithm. Compared with the state-of-the-art works, experimental results on publicly mixed-size placement benchmarks show that LAMPlace is effective.

The role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.colienhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the immunosuppressive activities of regulatory T cells (Tregs) and the antitumor activities of and CD8+T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM.

This study investigates the influence of modification on the microstructure and properties of Mn–Si–Cr alloy steel. The results indicate that the as-cast microstructure of Mn–Si–Cr alloy steel is composed of black acicular bainitic ferrite lath and white retained austenite. The microstructure of the alloy steel changes to martensite, austenite, and carbide after quenching and partitioning treatment. After rare-earth magnesium modification and compound modification, the as-cast microstructure of Mn–Si–Cr steel becomes more refined and displays a more regular arrangement. Furthermore, the martensite and austenite grains in the modified samples show refinement, and the arrangement of martensite is more systematic. Additionally, the amount of austenite decreases, and the amount of carbides increases after quenching and partitioning heat treatment. In comparison with the unmodified samples, the modified samples show negligible changes in hardness. However, the impact toughness of modified quenched and partitioned steel increases by 20 %. Moreover, the wear resistance of compound modified quenched and partitioned steel is 38 % higher than that of the unmodified sample. The compound modified sample steel exhibits excellent wear resistance and comprehensive mechanical properties.

Uniform symmetric bodies can be observed floating asymmetrically under certain circumstances. Previous explanations of this are mostly abstract and lack experimental verification, making their understanding and application difficult. This article presents in detail alternative insights into the floating equilibria of uniform prisms and parabolic cylinders. The intrinsic characteristics of the equilibrium curves are investigated, and several equilibria different from those in the literature are found. The inflection points in the equilibrium curves are analyzed quantitatively due to their significance for floating states. Furthermore, experiments have been conducted for the square prism which validate the derived equilibrium curve, and provide a practical impression of the asymmetric floating phenomenon of symmetric bodies. These results have the potential to be applied in naval and ocean engineering, such as in the design of vessels and floating offshore structures.

Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match those of long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiological and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals (rs7629500) in the 3′ untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23–3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

The Bessel beam, owing to its unique properties (keeping the intensity distribution unchanged during transmission, focusing energy on the central spot, self-reconstruction, etc.), has received extensive attention. In this study, a new type of combined axicon (CA) is designed that can generate a high-quality zero-order terahertz quasi-Bessel beam. The simulation and experimental results show that the quasi-Bessel beam generated by the CA has an obvious projection distance and sidelobe suppression effect. And the projection distance, length of the non-diffracting region, and sidelobe-suppression ratio of the beam can be modulated as required, which is not possible with ordinary axicon. The CA consists of a local negative axicon tightly bonded to an ordinary axicon. The quasi-Bessel beam generated by the CA exhibits enhanced intensity on the central axis. The influence of different parameters has been investigated, and the results have been explained using geometric optical. We believe that this element has broad application prospects in non-destructive testing, laser cutting, and microscopic imaging.

Optical delay line (ODL) plays a crucial role in various detection techniques such as terahertz time-domain spectroscopy (THz-TDS), and optical pump detection. This letter proposes a novel multi-mirror array optical delay line (MMAODL) structure suitable for THz-TDS systems, which consists of a laser collimator, a rotating disk, a multi mirror array, a pyramid prism, and a plane mirror. Based on the principle of ray tracing, a theoretical mathematical model of MMAODL was constructed. Combined with simulation, the working angle of MMAODL was obtained to be 13 deg, and the theoretical delay time was 228.71 ps. Using the THz TDS system, the actual time length of the 8-cycle MMAODL structure, calibrated by the FP standard, was tested and demonstrated to be 228.47 ps, and the time-domain error of the collected signal was found to be approximately 0.014 ps. When an 8-cycle MMAODL is combined with a 4000-rpm motor, the theoretical waveform reproduction rate can reach 533 Hz, which simultaneously meets the requirements of a THz-TDS system for long delay time and high scanning frequency.

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P< 5 × 10−8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66–7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P= 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

A facile method, refluxing with hydrothermal process, was used to synthesize the fluorinated graphene sheets (FGS) with high F/C ratio. Then, the surface of aluminum hydride (AlH3) was coated with FGS by means of liquid self-assembly process. The structure and performance of FGS were characterized through fourier transform infrared spectra (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM) and elemental analyzer. FTIR spectra show that the FGS have obvious absorption peak of CF bond. Raman spectra display many defects on FGS. XPS spectra and elemental analysis also prove the existence of CF bond, and the content of fluorine is more than 25%. From SEM photos we can see that FGS have thin layers with some curled wrinkles. TEM photos demonstrate intuitively the FGS has a few layers. At last, the aluminum hydride (AlH3) was coated with FGS by means of liquid self-assembly process, and AlH3samples before and after treated were characterized through hydrogen content (H%) analysis, X-ray diffraction (XRD), FTIR, SEM and differential thermal analysis (DTA), ect. The results demonstrate that there is only a little FGS on the surface of AlH3, which won't affect the effective H% and release efficiency of hydrogen. AlH3@FGS also reduces the mechanical sensitivity of solid propellant with AlH3, which will remarkably promote the application of AlH3in the novel high-energy solid propellant.

Aluminum alloy wires with higher strength and better electrical conductivity are demanded in electrical engineering. Pre-torsion was employed to process aluminum alloy wire for the improvement of its properties. Uniaxial tensile and electrical tests show that simultaneous improvements of strength and electrical conductivity were achieved in the pre-torsioned aluminum alloy wire at a maximum shear strain of 0.27. Microstructural observations reveal that pre-torsion induces the formation of nanoscale rod-shaped β′ particles and the sizes of nanoscale precipitates increase with the maximum shear strain of pre-torsion. Based on the experimental results, a theoretical model is proposed to reveal the underlying mechanisms. The small nanoscale precipitates can contribute to the improvement of strength and electrical conductivity. The large size of nanoscale precipitates leads to the low strength and poor electrical conductivity. This is attributed to the weak strengthening and strong electron scattering in large nanoscale precipitates.

In this paper, we establish a unified framework to study the almost sure global convergence and the expected convergence rates of a class of mini-batch stochastic (projected) gradient (SG) methods, including two popular types of SG: stepsize diminishedSG and batch size increasedSG. We also show that the standard variance uniformly bounded assumption, which is frequently used in the literature to investigate the convergence of SG, is actually not required when the gradient of the objective function is Lipschitz continuous. Finally, we show that our framework can also be used for analyzing the convergence of a mini-batch stochastic extragradient method for stochastic variational inequality.

The K2CO3/18-crown-6-catalyzed H/D exchange of heretoarenes in high atom % deuterium incorporation is disclosed. The use of a weak base as a catalyst leads to excellent site selectivity and broad functional group tolerance. Control experiments indicated that the use of bromide, which enhances the adjacent C–H bond reactivity, as a removable directing group is essential. Moreover, conversion of bromide to other functional groups is also performed to construct other useful deuterated compounds.

This contribution summarizes the significant progress in a variety of topic areas related to internal tropical cyclone (TC) intensity change processes over 2018–2022 from the WMO Tenth International Workshop on Tropical Cyclones (IWTC-10). These topic areas include surface and boundary layer processes; TC internal structure and microphysical processes; and, radiation interactions with TCs. Recent studies better frame the uncertainty in the surface drag and enthalpy coefficients at high wind speeds. These parameters greatly impact TC intensity and it is therefore important that more direct measurements of these boundary layer parameters are made. Particularly significant scientific strides have been made in TC boundary layers. These advancements have been achieved through improved coupled models, large-eddy simulations, theoretical advancements, and detailed observations. It is now clear that the research field needs to better represent the eddy viscosity throughout the depth of the boundary layer. Furthermore, detailed study of coherent structures in TC boundary layers will likely be a propitious direction for the research community. Meanwhile, in-depth observational field campaigns and assiduous data analysis have made significant headway into verifying theory and modeling studies of intensification processes related to TC vortex alignment, efficient latent heating distributions, and overall 3D structure. Substantial efforts have also been made to better understand the intricate roles radiative processes play in TC evolution and intensity change. Finally, some promising progress has been made in the development of time-dependent theories of TC intensification and the predictability of internal TC intensity change. Overall, there have been well-earned gains in the understanding of intensity change processes intrinsic to the TC system, but the journey is not complete. This paper highlights some of the most relevant and important research areas that are still shedding new light into internal factors governing TC intensity change.

Background: Identification of emerging molecular biomarkers on circulating tumor cells (CTCs) represents an attractive feature of liquid biopsy that facilitates precision and tailored medicine in the management of metastatic castration-resistant prostate cancer (mCRPC). Prostein is an androgen-regulated transmembrane protein with high prostate specificity. Prostein-positive circulating tumor cell (CTC) was recently suggested to have diagnostic potential; however, no study has been conducted to evaluate its prognostic value in mCRPC. Methods: CTCs from mCRPC patients were enumerated using the CellSearch System. Prostein-positive CTCs were identified by immunostaining results. The relationships between prostein expression on CTCs and PSA response rate, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (PFS), and overall survival (OS) were tested by Fisher’s exact test or evaluated using Kaplan–Meier and multivariate Cox analyses. Results: Prostein-positive CTCs were identified in 31 of 87 baseline samples from mCRPC patients and 16 of 51 samples collected at the first follow-up visit. PSA response rates were significantly lower in baseline prostein-positive patients (0%, 0/31) than in prostein-negative patients (19.6%, 11/56) (p= 0.007). The 31 prostein-positive patients had significantly shorter PSA-PFS (p&lt; 0.001), radiographic PFS (p&lt; 0.001), and OS (p= 0.018), compared to the 56 prostein-negative patients at baseline. The association with PSA-PFS maintained its significance (p= 0.028) in multivariate analyses. Analyzing prostein expression at the first follow-up as well as the conversion of prostein expression from baseline to follow-up samples not only confirmed the association with PSA-PFS, but also demonstrated prognostic significance with OS. Conclusion: Our study provides the first evidence to support the potential of prostein expression on CTCs to serve as a novel prognostic marker in mCRPC patients. Future large-scale prospective studies are needed to validate our findings.

Background: U-osteotomy with Taylor Spatial Frame correction is a rarely reported treatment method particularly well-suited for severe rigid equinus deformity in adults. The purpose of this study was to evaluate the effectiveness and efficacy of deformity correction and clinical outcome using this technique.Methods: We present a retrospective review of 30 feet in 26 patients who received U-osteotomy with Taylor Spatial Frame. Radiologic outcomes were measured using the anterior tibiotalar angle (TTA) with conventional weightbearing radiographs. Functional assessments included American Orthopaedic Foot & Ankle Society (AOFAS) ankle and hindfoot scores and patient satisfaction using Likert scale.Results: The etiology included trauma (9), neglected or relapsed clubfoot (6), spina bifida (5), poliomyelitis (4), Charcot-Marie-Tooth disease (4), and iatrogenic (2). All patients had equinus deformity with TTA more than 140 degrees (median 157.5, 141-177). There were varus deformity in 19 feet, limb length discrepancy in 6 legs, and genu procurvatum deformity in 2 legs. The duration of gradual correction was 53.6±13.5 days (33-73 days), and the external fixation time was 147.8±25.2 days (98-203 days). At last follow-up, TTA in all patients improved significantly (P< .001) to 113.5 degrees (111.8-116.0). All patients had plantigrade feet, except for 2 cases of residual mild equinovarus deformity, 2 cases of residual mild hindfoot varus deformity, 1 case of moderate hindfoot varus recurrence. The AOFAS scores significantly improved (P< .001) from 51.0 points (29.0-66.0) to 76.0 points (69.5-88.0). Eighteen patients were very satisfied, 6 patients were somewhat satisfied, and 2 patients were somewhat dissatisfied.Conclusion: Using minimally invasive U-osteotomy with Taylor Spatial Frame to gradually correct the adult severe rigid equinus deformity proved to be an effective and relatively safe method associated with high patient satisfaction rates.Level of Evidence: Level IV, case series.

Terahertz (THz) imaging has broad application prospects in nondestructive testing (NDT). However, compared to visible light, it has a low resolution and limited depth of field (DOF) due to its long wavelength. To address these limitations, a 3-D point spread function (PSF) based on a simulated THz time-domain spectroscopy (THz-TDS) system combined with the Lucy–Richardson method is proposed for image defocus restoration. The experimental results show that the contrast of THz images at different defocus positions is 2–5 times higher than that of the original image after restoration using the proposed method, and the resolution is improved by approximately 60%–80%. Moreover, the maximum contrast enhancement at the boundaries of tiny features can reach 1.81 times. For a hole-defect sample, the relative error of the defect area at different depths is < 5%. The proposed method solves the problem of defocus in THz images, enhances the resolution of these images, and facilitates NDT.

The Transformer architecture and transfer learning have marked a quantum leap in natural language processing, improving the state of the art across a range of text-based tasks. This paper examines how these advancements can be applied to and improve code search. To this end, we pre-train a BERT-based model on combinations of natural language and source code data and fine-tune it on pairs of StackOverflow question titles and code answers. Our results show that the pre-trained models consistently outperform the models that were not pre-trained. In cases where the model was pre-trained on natural language “and” source code data, it also outperforms an information retrieval baseline based on Lucene. Also, we demonstrated that the combined use of an information retrieval-based approach followed by a Transformer leads to the best results overall, especially when searching into a large search pool. Transfer learning is particularly effective when much pre-training data is available and fine-tuning data is limited. We demonstrate that natural language processing models based on the Transformer architecture can be directly applied to source code analysis tasks, such as code search. With the development of Transformer models designed more specifically for dealing with source code data, we believe the results of source code analysis tasks can be further improved.

A palladium-catalyzed domino cyclization/ring-opening reaction between 8H-indeno[1,2-c]thiophen-8-ols and N-(2-bromophenyl)propiolamide derivatives is reported. The reaction features a highly stereospecific point chirality to axial chirality transfer process, which enables the synthesis of molecules containing two chiral axes from the compounds with only one stereogenic center.

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P< 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P= 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P< 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

Despite several synthetic approaches that have been developed for α-deuterated amino acids, the synthesis of β-deuterated amino acids has remained a challenge. Herein, we disclose a palladium catalyzed H/D exchange protocol for a β-deuterated N-protected amino amide, which can be converted to a β-deuterated amino acid simply by removal of protecting groups. This protocol is highly efficient, simply manipulated, and appliable for deuterium-labeling of many amino amides. In addition, deuterium labeling of phenylalanine derivatives was also successful when pivalic acid served as an additive to promote the H/D exchange process.

The study investigates the rapid intensification (RI) of tropical cyclones (TCs) in the Northwestern Pacific. We found that rapid changes in the maximum wind speed (Vmax) and the minimum central pressure (Pmin) are not always concurrent. RI cases can be categorized into three types: (a) RIv, only Vmaxstrengthens rapidly; (b) RIp, only Pmindecreases rapidly; (c) RIpv, rapid changes in Vmaxand Pminoccur concurrently. At the onset of RI, RIv‐type TCs exhibit the weakest intensity and the smallest size, with deep convection concentrated in the inner‐core region; RIp‐type TCs are characterized by the strongest cyclone intensity and the largest outer‐core size, with strong convection covering the inner‐ and outer‐core regions; RIpv‐type TCs show moderate intensity, size, and convection distribution. For RIpv, significant strengthening of wind profile is concentrated in the inner‐core region, while for RIpit is more prominent in the outer‐core. The rapid intensification (RI) of tropical cyclones (TCs) continues to pose challenges in both operational forecasting and scientific research. The maximum wind speed (Vmax) and the minimum central pressure (Pmin) are two commonly used TC intensity indicators. In most of existing studies, one single indicator (usually Vmax) is used to investigate the RI process. Whether there is a difference between RI cases defined by 24‐hr strengthening of Vmaxand 24‐hr deepening of Pminis an issue deserving discussion. The study found that rapid changes in Vmaxand Pminare not always concurrent. In the cases where only Vmaxstrengthens rapidly, the outer‐core size of TC expands slowly. While in the cases where only Pmindeepens rapidly, the enhancement of outer circulation is distinctive. Since the Pmin, as an integral variable, reflects TC information of both the intensity and the size, RI cases classified via these two commonly used indicators (Vmaxand Pmin) could help us further understand the relationship between TC intensity and size. Rapid changes in the maximum wind speed (Vmax) and the minimum central pressure (Pmin) are not always concurrent in tropical cyclones (TCs)TCs that only experience a rapid increase in Vmax(RIv) tend to have a significantly weaker lifetime maximum intensityThe evident expansion of the outer circulation occurs in TCs of which only Pmindeepens rapidly (RIp) Rapid changes in the maximum wind speed (Vmax) and the minimum central pressure (Pmin) are not always concurrent in tropical cyclones (TCs) TCs that only experience a rapid increase in Vmax(RIv) tend to have a significantly weaker lifetime maximum intensity The evident expansion of the outer circulation occurs in TCs of which only Pmindeepens rapidly (RIp)

Automatic program repair (APR) aims to reduce the cost of manually fixing software defects. However, APR suffers from generating a multitude of overfitting patches, those patches that fail to correctly repair the defect beyond making the tests pass. This paper presents a novel overfitting patch detection system called ODS to assess the correctness of APR patches. ODS first statically compares a patched program and a buggy program in order to extract code features at the abstract syntax tree (AST) level, for the single programming language Java. Then, ODS uses supervised learning with the captured code features and patch correctness labels to automatically learn a probabilistic model. The learned ODS model can then finally be applied to classify new and unseen program repair patches. We conduct a large-scale experiment to evaluate the effectiveness of ODS on patch correctness classification based on 10,302 patches from Defects4J, Bugs.jar and Bears benchmarks. The empirical evaluation shows that ODS is able to correctly classify 71.9 percent of program repair patches from 26 projects, which improves the state-of-the-art. ODS is applicable in practice and can be employed as a post-processing procedure to classify the patches generated by different APR systems.

ABSTRACTThe resistance of melanoma to BRAF inhibitors remains a tough clinical challenge. In order to explore the underlying mechanism of drug resistance in melanoma, we established the resistant cell line to vemurafenib, and assessed the changes of drug-resistant cells on proliferation, apoptosis, oxidative stress and tumor stemness. Our results suggest that phosphoenolpyruvate carboxykinase1 (PCK1) is activated and inhibits the oxidative stress caused by vemurafenib in drug-resistant cells. Long term treatment of vemurafenib increases the expression of PCK1 which reduces the production of reactive oxygen species (ROS) by activating PI3K/Akt pathway. After the inhibition of PCK1 by 3-mercaptopropionic acid (3-MPA), the therapeutic sensitivity of vemurafenib is restored. In conclusion, this study disclosed that drug-resistant cells appeared to regulate their own proliferation, oxidative stress and tumor dryness by activating Akt/PCK1/ROS pathway, and shed new insights into acquiring drug resistance in melanoma.

Additive of 1-adamantanecarbonitrile is used to strengthen the poly(ethylene oxide) based solid polymer electrolytes (SPEs).LiF-based integral cathode/SPE and Li/SPE interfaces are generated.The NMC811/Li all-solid-state performs stable cycle at 45 °C (1000, 80%).

This paper studies a full-duplex (FD) amplify-and-forward relaying, where a fixed-wing unmanned aerial vehicle (UAV) is dispatched as a mobile relay to serve a source-destination communication pair so as to satisfy their service requirement. Here, the UAV relay flies in a circular path and hence it must continuously change its heading of flight which leads to a bank angle of the aircraft. In order to ensure flight safety, therefore, a bank angle limit is imposed on the UAV relay. By considering a practical FD relaying, namely, there exists both residual loop interference (RLI) and processing time-delay at the relay side, novel signal to interference plus noise ratio (SINR) received at the destination is analyzed, giving a closed-form expression in addition to a concise lower-bound. Armed with the SINR analysis, the size of data received by the destination during a period of flight time of the UAV is calculated, leading to a closed-form lower-bound of the size of data. Taking bank angle limit into consideration and using the calculated lower-bound of the size of data, an optimization problem with the purpose of energy conservation is solved, leading to a novel method for joint adjustment of the UAV's flight parameters. Computer simulation experiments are conducted, and the results demonstrated that the proposed optimization method performs better in terms of energy conservation compared to the benchmark techniques regardless of the value of RLI and/or the service requirement of the source-destination communication pair.

To ensure the safety, comfort, and effectiveness of lower limb rehabilitation exoskeleton robots in the rehabilitation training process, compliance is a prerequisite for human–machine interaction safety. First, under the premise of considering the mechanical structure of the lower limb rehabilitation exoskeleton robot (LLRER), when conducting the dynamic transmission of the exoskeleton knee joint, the soft axis is added to ensure that the rotation motion and torque are flexibly transmitted to any position to achieve flexible force transmission. Second, to realize the active compliance control of LLRER, the sliding mode impedance closed-loop controller is developed based on the kinematics and dynamics model of LLRER, and the stability of the designed control system is verified by Lyapunov method. Then the experiment is designed to track the collected bicycle rehabilitation motion data stably, and the algorithm and dynamic model are verified to satisfy the experimental requirements. Finally, aiming at the transmission efficiency and response performance of the soft shaft in the torque transmission process of the knee joint, the soft shaft transmission performance test is carried out to test the soft shaft transmission performance and realize the compliance of the LLRER, so as to ensure that the rehabilitation training can be carried out in a safe and comfortable interactive environment. Through the design of rehabilitation exercise training, it is verified that the LLRER of flexible transmission under sliding mode impedance control has good adaptability in the actual environment, and can achieve accurate and flexible control. During the experiment, the effectiveness of monitoring rehabilitation training is brought through the respiratory belt.

This paper introduces a rigid-flexible coupling wearable exoskeleton robot for lower limb, which is designed in light of gait biomechanics and beneficial for low limb movement disorders by implementing gait training. The rationality of the proposed mechanism is shown with the implementation of the dynamic simulation through MSC ADAMS. For the purposes of lightweight, the exoskeleton mechanism is optimized through finite element analysis. It can be concluded from performance evaluation experiment, the mechanism has certain advantages over existing exoskeleton robots, namely, comfortable, lightweight, low cost, which can be utilized for rehabilitation training in medical institutions or as a daily-walking ancillary equipment for patients.

Supplemental Digital Content is available in the text.

Aryl bromide is one of the most important compounds in organic chemistry, because it is widely used as synthetic building blocks enabling quick access to a wide array of bioactive molecules, organic materials, and polymers via the versatile cutting-edge transformations of C–Br bond. Direct C–H bond functionalization of aryl bromide is considered to be an efficient way to prepare functionalized aryl bromides; however, it is rarely explored possibly due to the relatively low reactivity of aryl bromide toward C–H bond activation. We herein report a palladium-catalyzed coupling reaction between aryl iodide and aryl bromide for preparing brominated biaryl compounds via a silver-mediated C–H bond activation pathway.

Yersinia pestisis a Gram-negative bacterium that is the causative agent of plague and is widely recognized as a potential biological weapon. Due to the high fatality rate of plague when diagnosis is delayed, the development of rapid, sensitive, specific, and cost-effective methods is needed for its diagnosis. The Y. pestislow calcium response V (LcrV) protein has been identified as a potential microbial biomarker for the diagnosis of plague. In this paper, we present a highly sensitive, paper-based, vertical flow immunoassay (VFI) prototype for the detection of LcrV and the diagnosis of plague. An antigen-capture assay using monoclonal antibodies is employed to capture and detect the LcrV protein, using a colorimetric approach. In addition, the effect of miniaturizing the VFI device is explored based on two different sizes of VFI platforms, denoted as “large VFI” and “mini VFI.” Also, a comparative analysis is performed between the VFI platform and a lateral flow immunoassay (LFI) platform to exhibit the improved assay sensitivity suitable for point-of-care (POC) diagnostics. The analytical sensitivity or limit of detection (LOD) in the mini VFI is approximately 0.025 ng/mL, that is, 10 times better than that of the large VFI platform or 80 times over a standard lateral flow configuration. The low LOD of the LcrV VFI appears to be highly suitable for testing clinical samples and potentially diagnosing plague at earlier time points. In addition, optimization of the gold nanoparticle (AuNP) concentration, nanomaterial plasmonic properties, and flow velocity analysis could improve the performance of the VFI. Furthermore, we developed automated image analysis software that shows potential for integrating the diagnostic system into a smartphone. These methods and findings demonstrate that the VFI platform is a highly sensitive device for detecting the LcrV and potentially many other biomarkers.

Photocatalytic carbon dioxide reduction (CO2RR) is considered to be a promising sustainable and clean approach to solve environmental issues. Polyoxometalates (POMs), with advantages in fast, reversible, and stepwise multiple-electron transfer without changing their structures, have been promising catalysts in various redox reactions. However, their performance is often restricted by poor thermal or chemical stability. In this work, two transition-metal-modified vanadoborate clusters, [Co(en)2]6[V12B18O54(OH)6]·17H2O (V12B18–Co) and [Ni(en)2]6[V12B18O54(OH)6]·17H2O (V12B18–Ni), are reported for photocatalytic CO2reduction. V12B18–Co and V12B18–Ni can preserve their structures to 200 and 250 °C, respectively, and remain stable in polar organic solvents and a wide range of pH solutions. Under visible-light irradiation, CO2can be converted into syngas and HCOO–with V12B18–Co or V12B18–Ni as catalysts. The total amount of gaseous products and liquid products for V12B18–Co is up to 9.5 and 0.168 mmol g–1h–1. Comparing with V12B18–Co, the yield of CO for V12B18–Ni declines by 1.8-fold, while that of HCOO–increases by 35%. The AQY of V12B18–Co and V12B18–Ni is 1.1% and 0.93%, respectively. These values are higher than most of the reported POM materials under similar conditions. The density functional theory (DFT) calculations illuminate the active site of CO2RR and the reduction mechanism. This work provides new insights into the design of stable, high-performance, and low-cost photocatalysts for CO2reduction.

This paper investigates an in-band full-duplex (IBFD) relaying, where a fixed-wing unmanned aerial vehicle (UAV) is dispatched as an amplify-and-forward relay to forward data from a source to a destination. By considering ideal and practical IBFD cases, new received signal-to-noise ratio (SNR) expressions at the destination are derived. Armed with the newly derived SNR expressions and the existing one in literature, three different lower-bounds of the size of data received by the destination are calculated. Using the three lower-bounds of the size of data, an optimization problem corresponding to energy minimization of the IBFD relaying system subject to a total data-bit constraint in addition to a mission completion time (MCT) constraint is solved, leading to three sets of solutions. Computer simulation experiments are conducted and the accuracy of the derived SNR expressions and the three sets of solutions of the optimization problem are compared. The results demonstrated that the newly derived SNR expressions are more accurate than the existing one in literature and are more suitable to be utilized for energy minimization, and the proposed optimization method can complete the relaying task with the minimum energy and MCT. When the residual loop-interference channel power is equal to -100dB, the scheme of ideal IBFD only consumes up to 2.5% of the energy of the compared schemes regardless of the value of the total data-bit constraint.