Research And Implementation Of Drug Target Interaction Confidence Measurement Method Based On Causal Intervention

The identification and discovery of drug-target Interaction (DTI) is an important step in the field of Drug research and development, which can help scientists discover new drugs and accelerate the development process. KnowledgeGraph and the related knowledge graph Embedding (KGE) model develop rapidly and show good performance in the field of drug discovery in recent years. In the task of drug target identification, the lack of authenticity and accuracy of the model will lead to the increase of misjudgment rate and the low efficiency of drug development. To solve the above problems, this study focused on the problem of drug target link prediction with knowledge mapping as the core technology, and adopted the confidence measurement method based on causal intervention to measure the triplet score, so as to improve the accuracy of drug target interaction prediction model. By comparing with the traditional Softmax and Sigmod confidence measurement methods on different KGE models, the results show that the confidence measurement method based on causal intervention can effectively improve the accuracy of DTI link prediction, especially for high-precision models. The predicted results are more conducive to guiding the design and development of followup experiments of drug development, so as to improve the efficiency of drug development.Comment: 8 pages,11 figure

Observation and analysis of diving beetle movements while swimming

The fast swimming speed, flexible cornering, and high propulsion efficiency of diving beetles are primarily achieved by their two powerful hind legs. Unlike other aquatic organisms, such as turtle, jellyfish, fish and frog et al., the diving beetle could complete retreating motion without turning around, and the turning radius is small for this kind of propulsion mode. However, most bionic vehicles have not contained these advantages, the study about this propulsion method is useful for the design of bionic robots. In this paper, the swimming videos of the diving beetle, including forwarding, turning and retreating, were captured by two synchronized high-speed cameras, and were analyzed via SIMI Motion. The analysis results revealed that the swimming speed initially increased quickly to a maximum at 60% of the power stroke, and then decreased. During the power stroke, the diving beetle stretched its tibias and tarsi, the bristles on both sides of which were shaped like paddles, to maximize the cross-sectional areas against the water to achieve the maximum thrust. During the recovery stroke, the diving beetle rotated its tarsi and folded the bristles to minimize the cross-sectional areas to reduce the drag force. For one turning motion (turn right about 90 degrees), it takes only one motion cycle for the diving beetle to complete it. During the retreating motion, the average acceleration was close to 9.8 m/s2 in the first 25 ms. Finally, based on the diving beetle's hind-leg movement pattern, a kinematic model was constructed, and according to this model and the motion data of the joint angles, the motion trajectories of the hind legs were obtained by using MATLAB. Since the advantages of this propulsion method, it may become a new bionic propulsion method, and the motion data and kinematic model of the hind legs will be helpful in the design of bionic underwater unmanned vehicles

Combined signature of N7-methylguanosine regulators with their related genes and the tumor microenvironment: a prognostic and therapeutic biomarker for breast cancer

BackgroundIdentifying predictive markers for breast cancer (BC) prognosis and immunotherapeutic responses remains challenging. Recent findings indicate that N7-methylguanosine (m7G) modification and the tumor microenvironment (TME) are critical for BC tumorigenesis and metastasis, suggesting that integrating m7G modifications and TME cell characteristics could improve the predictive accuracy for prognosis and immunotherapeutic responses.MethodsWe utilized bulk RNA-sequencing data from The Cancer Genome Atlas Breast Cancer Cohort and the GSE42568 and GSE146558 datasets to identify BC-specific m7G-modification regulators and associated genes. We used multiple m7G databases and RNA interference to validate the relationships between BC-specific m7G-modification regulators (METTL1 and WDR4) and related genes. Single-cell RNA-sequencing data from GSE176078 confirmed the association between m7G modifications and TME cells. We constructed an m7G-TME classifier, validated the results using an independent BC cohort (GSE20685; n = 327), investigated the clinical significance of BC-specific m7G-modifying regulators by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, and performed tissue-microarray assays on 192 BC samples.ResultsImmunohistochemistry and RT-qPCR results indicated that METTL1 and WDR4 overexpression in BC correlated with poor patient prognosis. Moreover, single-cell analysis revealed relationships between m7G modification and TME cells, indicating their potential as indicators of BC prognosis and treatment responses. The m7G-TME classifier enabled patient subgrouping and revealed significantly better survival and treatment responses in the m7Glow+TMEhigh group. Significant differences in tumor biological functions and immunophenotypes occurred among the different subgroups.ConclusionsThe m7G-TME classifier offers a promising tool for predicting prognosis and immunotherapeutic responses in BC, which could support personalized therapeutic strategies

Propagation Characteristics of Ultrasonic Weld-guided Waves in Friction Stir Welding Joint of Same Material

Abstract(#br)Friction stir welding (FSW) is an important technology for manufacturing large-scale aluminum alloy propellant tank. Due to stress corrosion and cyclic loads, the key FSW joints require online monitoring to ensure the structural integrity and service safety of long-term storage propellant tanks. FSW joints in the propellant tank are regarded as a type of circumferential or longitudinal long and narrow region. In order to detect the flaws with high efficiency and fewer sensors, the propagation characteristics of ultrasonic guided waves in the FSW joint of same material is investigated in this paper. The weld of a FSW joint is characterized by concave cross-sectional shape and different microstructure-mechanical parameters. The micro-structure, micro-hardness, and Young’s modulus of a real FSW joint are analyzed, and a two-dimensional semi-analytical finite-element (SAFE) method is employed to study the effects of different parameters on the modal characteristics of weld-guided waves in the FSW joint. In the studied fundamental modes (symmetric (S0), anti-symmetric (A0), and shear-horizontal (SH0)), an almost non-leaky A0-like weld-guided wave at a certain frequency range from 100 kHz to 210 kHz is discovered in the welded zone of a specific FSW model and shows a potential for long-distance detection. Parametric simulation results show that A0-like, SH0-like and S0-like modes at 120 kHz always exist when the weld width is changed while the moduli of the welded zone and base metal zone are maintained the same. Additionally, the simulations demonstrate that some weld-guided waves only exist if the modulus value of the welded zone is lower than that of the base metal zone when the cross section is geometrically continuous (i.e. the shoulder plunge depth is zero). Comparing with weld-guided waves affected by weld width, the weld-guided waves affected by the modulus change shows less obvious energy leakage during propagation. The experiments are conducted to validate the existence of A0-like weld-guided mode with a primary energy trapping effect

Optical sensing interface based on nano-opto-electro-mechanical systems

A novel optical sensing interface based on nano-opto-electro-mechanical systems (NOEMS) is proposed, in which the light can be coupled with quantum tunneled electrons via weak mechanical coupling. By taking optical pump power and mechanical coupling strength as varying parameters, respectively, bifurcation diagrams of three involved dynamical states of the NOEMS, i.e., optical, electrical and mechanical mode, are calculated, from which an effective coupling region for tunneled electrons and light is revealed. Self-oscillation, transient dynamics and the threshold of the NOEMS are further characterized, and it is found that the effective coupling region has a special transient time. The work sheds light in developing ultra-sensitive photon detectors using physical mechanisms rather than the conventional PN junction based

Retreat, Adapt, Defend - Urban Design Response to Sea Level Rise in 5 Coastal Georgia Communities

Information on this record corrected per JIRA ticket LDC-1043, 11/16/2021This studio is part of a Georgia Conservancy Blueprints initiative assessing impacts of climate change and sea level rise for Coastal Georgia. The studio was organized into five teams to address issues five cities: Savannah, Tybee Island, Brunswick, Darien and St. Marys. Student teams visited each city, meeting with local officials and leaders of non-profit organization who were involved in adapting to climate change.The Georgia Conservanc

Interactions between depositional regime and climate proxies in the northern South China Sea since the Last Glacial Maximum

Sedimentary deposits from the northern South China Sea (SCS) can provide important constraints on past changes in ocean currents and the East Asian summer monsoon (EASM) in this region. However, the interpretation of such records spanning the last deglaciation is complicated because sea-level change may also have influenced the depositional processes and patterns. Here, we present new records of grain size, clay mineralogy, and magnetic mineralogy spanning the past 24 kyr from both shallow and deep-water sediment cores in the northern SCS. Our multi-proxy comparison among multiple cores helps constrain the influence of sea-level change, providing confidence in interpreting the regional climate-forced signals. After accounting for the influence of sea-level change, we find that these multi-proxy records reflect a combination of changes in (a) the strength of the North Pacific Intermediate Water inflow, (b) the EASM strength, and (c) the Kuroshio Current extent. Overall, this study provides new insights into the roles of varying terrestrial weathering and oceanographic processes in controlling the depositional record on the northern SCS margin in response to climate and sea-level fluctuations