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Purpose: To develop and validate a predictive combined model for metastasis in patients with clear cell renal cell carcinoma (ccRCC) by integrating multimodal data. Materials and methods: In this retrospective study, the clinical and imaging data (CT and ultrasound) of patients with ccRCC confirmed by pathology from three tertiary hospitals in different regions were collected from January 2013 to January 2023. We developed three models, including a clinical model, a radiomics model, and a combined model. The performance of the model was determined based on its discriminative power and clinical utility. The evaluation indicators included area under the receiver operating characteristic curve (AUC) value, accuracy, sensitivity, specificity, negative predictive value, positive predictive value and decision curve analysis (DCA) curve. Results: A total of 251 patients were evaluated. Patients (n = 166) from Shandong University Qilu Hospital (Jinan) were divided into the training cohort, of which 50 patients developed metastases; patients (n = 37) from Shandong University Qilu Hospital (Qingdao) were used as internal testing, of which 15 patients developed metastases; patients (n = 48) from Changzhou Second People's Hospital were used as external testing, of which 13 patients developed metastases. In the training set, the combined model showed the highest performance (AUC, 0.924) in predicting lymph node metastasis (LNM), while the clinical and radiomics models both had AUCs of 0.845 and 0.870, respectively. In the internal testing, the combined model had the highest performance (AUC, 0.877) for predicting LNM, while the AUCs of the clinical and radiomics models were 0.726 and 0.836, respectively. In the external testing, the combined model had the highest performance (AUC, 0.849) for predicting LNM, while the AUCs of the clinical and radiomics models were 0.708 and 0.804, respectively. The DCA curve showed that the combined model had a significant prediction probability in predicting the risk of LNM in ccRCC patients compared with the clinical model or the radiomics model. Conclusion: The combined model was superior to the clinical and radiomics models in predicting LNM in ccRCC patients. [ABSTRACT FROM AUTHOR]

Preoperative correction path planning is an important preparation for obtaining the desired correction. However, a convenient and effective model has not been proposed to characterize the correction path features, especially how to visualize the growth process of the bone cross-section has not been investigated. In this paper, a new characterization approach of the correction path features and corresponding evaluation indexes are proposed for the tibia deformity correction. We represent the growth process of new bone cross-section by a series of continuous and discrete circles. Based on the definition and assumptions of the bone cross-section, three evaluation indexes are proposed to assist the clinician in critically comparing and analyzing the feasibility of preoperatively correction approaches. A motor-driven parallel external fixator (MD-PEF) is developed to verify the proposed characterization approach. Finally, the features of the generated correction paths are compared and analyzed based on three correction methods. The results show that the proposed method can well present the growth process of bone cross-section and can detect the overlap phenomenon between bone cross-sections. And the approach of joint adjustment for equal bone distraction can generate a smooth correction path, uniform distraction rate and effectively avoid the overlap of bone cross-sections. This study is an important addition to facilitating the development of deformity correction techniques. [ABSTRACT FROM AUTHOR]

The Dualistic Model of Passion (DMP) divides passion into two categories: Harmonious Passion and Obsessive Passion. These categories are based on how individuals internalize their activities, and they have different characteristics and roles. Harmonious Passion is generally considered healthier and more stable than Obsessive Passion, and it has a more positive impact on the individual. Over the last two decades, the DMP and the Dualistic Scale of Passion(DSP) have been commonly used to examine the effects of Harmonious Passion and Obsessive Passion on individual achievement and burnout in the domains of work, study, and sport et al. Future research could integrate perseverance and passion to develop a scale that better predicts individual achievement. Furthermore, researchers could investigate additional techniques for intervening in passion based on the dynamic variability of passion, using autonomy as a starting point to regulate the type and intensity of passion. [ABSTRACT FROM AUTHOR]

A novel frequency domain behavioral modeling method for gallium‐nitride (GaN) devices is presented in this article. By utilizing a multi‐dimensional polynomial function, the proposed technique interpolates DC‐bias voltage and temperature based on the Canonical section‐wise piecewise linear (CSWPL) model framework. A detailed description of the model's theory is provided. With data from 10‐W GaN devices, the model was implemented in commercial software and validated through both DC and radio frequency (RF) tests. A robust predictive ability is demonstrated by the obtained results, thus proving the accuracy of the developed modeling method. This model is superior to the standard CSWPL model in that it is capable of predicting transistor behavior at different bias voltages and temperatures using a single set of parameters, thereby greatly reducing the complexity of the model and the time required for extraction. [ABSTRACT FROM AUTHOR]

This paper presents a novel poly‐harmonic distortion (PHD) model that incorporates the DC input and output bias voltages using Gaussian process regression (GPR). Simulation tests were conducted using a 10‐W gallium nitride (GaN) HEMT transistor from Wolfspeed, and the model implementation test was performed in the Keysight Advanced Design System environment. The results showed that the GPR‐based PHD model exhibited good performance in predicting both fundamental and harmonic behaviors over a wide range of bias variations with significant advantages over basic linear regression methods. Additionally, the model accurately predicted load‐pull simulations. The measurement test was conducted using a 6‐W GaN device, and the results showed a mean error of 2.22% and 4.54% for the fundamental and second harmonic of the reflected wave, respectively. [ABSTRACT FROM AUTHOR]

In deep space exploration, the high-speed separation process of spacecraft is fraught with uncertainty and uncontrollability. To accurately simulate and analyze this process, a series of ground tests are typically required. In this study, a cable-driven mechanism is proposed to simulate this process. Given the high initial velocity of the spacecraft, the cable force undergoes violent fluctuations. Thus, a detailed study of the mechanism governing the forcetransmission characteristics is essential to enhance the accuracy of cable force application. Three key parameters, such as slack time, peak cable force, and average relative error, are proposed to illustrate force-transmission characteristics. The effects of parameters such as thrust, pre-tension, and Young's modulus on force-transmission characteristics are also investigated. An input force planning algorithm is proposed to improve the accuracy of the cable force. High-speed separation tests are conducted within certain upper and lower bounds, and the experimental and simulation data demonstrate good agreement, confirming the accuracy of the proposed model. [ABSTRACT FROM AUTHOR]

Aims The mechanisms underlying ageing-induced vascular remodelling remain unclear. This study investigates the role and underlying mechanisms of the cytoplasmic deacetylase sirtuin 2 (SIRT2) in ageing-induced vascular remodelling. Methods and results Transcriptome and quantitative real-time PCR data were used to analyse sirtuin expression. Young and old wild-type and Sirt2 knockout mice were used to explore vascular function and pathological remodelling. RNA-seq, histochemical staining, and biochemical assays were used to evaluate the effects of Sirt2 knockout on the vascular transcriptome and pathological remodelling and explore the underlying biochemical mechanisms. Among the sirtuins, SIRT2 had the highest levels in human and mouse aortas. Sirtuin 2 activity was reduced in aged aortas, and loss of SIRT2 accelerated vascular ageing. In old mice, SIRT2 deficiency aggravated ageing-induced arterial stiffness and constriction–relaxation dysfunction, accompanied by aortic remodelling (thickened vascular medial layers, breakage of elastin fibres, collagen deposition, and inflammation). Transcriptome and biochemical analyses revealed that the ageing-controlling protein p66Shc and metabolism of mitochondrial reactive oxygen species (mROS) contributed to SIRT2 function in vascular ageing. Sirtuin 2 repressed p66Shc activation and mROS production by deacetylating p66Shc at lysine 81. Elimination of reactive oxygen species by MnTBAP repressed the SIRT2 deficiency–mediated aggravation of vascular remodelling and dysfunction in angiotensin II–challenged and aged mice. The SIRT2 coexpression module in aortas was reduced with ageing across species and was a significant predictor of age-related aortic diseases in humans. Conclusion The deacetylase SIRT2 is a response to ageing that delays vascular ageing, and the cytoplasm–mitochondria axis (SIRT2–p66Shc–mROS) is important for vascular ageing. Therefore, SIRT2 may serve as a potential therapeutic target for vascular rejuvenation. [ABSTRACT FROM AUTHOR]

Granzyme A from killer lymphocytes cleaves gasdermin B (GSDMB) and triggers pyroptosis in targeted human tumor cells, eliciting antitumor immunity. However, GSDMB has a controversial role in pyroptosis and has been linked to both anti- and protumor functions. Here, we found that GSDMB splicing variants are functionally distinct. Cleaved N-terminal (NT) fragments of GSDMB isoforms 3 and 4 caused pyroptosis, but isoforms 1, 2, and 5 did not. The nonfunctional isoforms have a deleted or modified exon 6 and therefore lack a stable belt motif. The belt likely contributes to the insertion of oligomeric GSDMB-NTs into the membrane. Consistently, noncytotoxic GSDMB-NTs blocked pyroptosis caused by cytotoxic GSDMB-NTs in a dominant-negative manner. Upon natural killer (NK) cell attack, GSDMB3-expressing cells died by pyroptosis, whereas GSDMB4-expressing cells died by mixed pyroptosis and apoptosis, and GSDMB1/2-expressing cells died only by apoptosis. GSDMB4 partially resisted NK cell-triggered cleavage, suggesting that only GSDMB3 is fully functional. GSDMB1-3 were the most abundant isoforms in the tested tumor cell lines and were similarly induced by interferon-γ and the chemotherapy drug methotrexate. Expression of cytotoxic GSDMB3/4 isoforms, but not GSDMB1/2 isoforms that are frequently up-regulated in tumors, was associated with better outcomes in bladder and cervical cancers, suggesting that GSDMB3/4-mediated pyroptosis was protective in those tumors. Our study indicates that tumors may block and evade killer cell-triggered pyroptosis by generating noncytotoxic GSDMB isoforms. Therefore, therapeutics that favor the production of cytotoxic GSDMB isoforms by alternative splicing may improve antitumor immunity. Cytotoxic pores require the right splice: Granzyme A (GzmA) is one of the cytotoxic granule proteins killer lymphocytes deploy to kill targeted tumor cells. Whereas GzmA-dependent cytotoxicity is reported to depend on pyroptosis activated by cleavage of gasdermin B (GSDMB), controversy has arisen over whether all splice variants of GSDMB can support formation of cytotoxic pores. Kong and Xia et al. assessed the ability of GSDMB isoforms to induce tumor cell death and found that only the GSDMB3 and GSDMB4 splice variants retaining exon 6 supported pyroptosis. The other GSDMB isoforms interfered with pyroptosis through a dominant negative mechanism. These findings better define the structural requirements for GzmA-dependent pyroptosis involved in antitumor immunity and reveal a mechanism by which some tumor cells can evade this killing pathway through modified splicing of GSDMB mRNA. —IRW [ABSTRACT FROM AUTHOR]

In this work, a harmonic included canonical piecewise linear (CPL) function based quadratic poly‐harmonic distortion (QPHD) model is presented. The proposed model employs the framework of the standard QPHD model, making use of the CPL functions for interpolation of the amplitude of the dominant input signal. Compared with the standard QPHD model, the model described in this work is able to predict transistor behavior at different levels of input powers with one single set of model coefficients. The harmonic information has also been added in this model to make it more complete. The model is validated in terms of both DC and RF behavior through simulated data of a 10 W gallium nitride (GaN) high‐electron‐mobility transistor (HEMT) over a wide range of load conditions and power levels. In addition, the model is implemented in advanced design system (ADS) with frequency‐defined device (FDD), and applied for a broadband power amplifier (PA) design. Chebyshev low‐pass topology is used for both input and output matching network design. Finally, a broadband PA is implemented with an average power added efficiency of 66.23%, an average power of 41.09 dBm, and an average gain of 13.09 dB across the operating frequency range from 0.6 to 1.7 GHz. The simulation results of the harmonic included CPL‐QPHD model are highly matched with the measurement results of the designed PA, demonstrating the feasibility of applying the proposed model for broadband PA design. [ABSTRACT FROM AUTHOR]

Cable-driven parallel robot (CDPR) is a type of high-performance robot that integrates cable-driven kinematic chains and parallel mechanism theory. It inherits the high dynamics and heavy load capacities of the parallel mechanism and significantly improves the workspace, cost and energy efficiency simultaneously. As a result, CDPRs have had irreplaceable roles in industrial and technological fields, such as astronomy, aerospace, logistics, simulators, and rehabilitation. CDPRs follow the cutting-edge trend of rigid-flexible fusion, reflect advanced lightweight design concepts, and have become a frontier topic in robotics research. This paper summarizes the kernel theories and developments of CDPRs, covering configuration design, cable-force distribution, workspace and stiffness, performance evaluation, optimization, and motion control. Kinematic modeling, workspace analysis, and cable-force solution are illustrated. Stiffness and dynamic modeling methods are discussed. To further promote the development, researchers should strengthen the investigation in configuration innovation, rapid calculation of workspace, performance evaluation, stiffness control, and rigid-flexible coupling dynamics. In addition, engineering problems such as cable materials, reliability design, and a unified control framework require attention. [ABSTRACT FROM AUTHOR]

Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery. [ABSTRACT FROM AUTHOR]

During the landing process of a probe, the backshell separation stage is full of uncertainty and risk. To mitigate this, it is necessary to simulate spacecraft separation prior to launch to verify safety and performance. A high-acceleration cable-driven parallel mechanism is normally used to simulate the force state required for the backshell to separate. Unfortunately, little attention has been paid to research the cable force on the end-effector, especially under high acceleration. In this article, a dynamic model of the cable-force transmission is proposed. The influences of disturbing force/moment on the position and orientation of the end-effector and axial force are analyzed. Indices for evaluating the performance of the cable-force transmissions are proposed. The factors affecting the performance are also explored. Finally, the experimental results are used to verify the correctness of the proposed dynamic model. The deviation caused by the disturbing force/moment is basically consistent with the desired deviation. The increase in the disturbing force/moment correspondingly reduces the resultant force of the end-effector. A series of experiments provide guidance and a theoretical basis for a ground simulation experiment of spacecraft separation. [ABSTRACT FROM AUTHOR]

Specific satellites with ultralong wings play a crucial role in many fields. However, external disturbance and self-rotation could result in undesired vibrations of the flexible wings, which affect the normal operation of the satellites. In severe cases, the satellites would be damaged. Therefore, it is imperative to conduct vibration suppression for these flexible structures. Utilizing fuzzy-proportional integral derivative control and deep reinforcement learning (DRL), two active control methods are proposed in this article to rapidly suppress the vibration of flexible structures with quite small controllable force based on a cable-driven parallel robot. Inspired by the output law of DRL, a new control method named Tang and Sun control is innovatively presented based on the Lyapunov theory. To verify the effectiveness of these three control methods, three groups of simulations with different initial disturbances are implemented for each method. Besides, to enhance the contrast, a passive pretightening scheme is also tested. First, the dynamic model of the cable-driven parallel robot which comprises four cables and a flexible structure is established using the finite element method. Then, the dynamic behavior of the model under the controllable cable force is analyzed by the Newmark-ß method. Finally, these control methods are implemented by numerical simulations to evaluate their performance, and the results are satisfactory, which validates the controllers' ability to suppress vibrations. [ABSTRACT FROM AUTHOR]

Epigenetic bad actors in liver fibrosis: The molecular processes that lead to fibrogenesis in nonalcoholic steatohepatitis (NASH) are complex and not completely understood. Zhang et al. used single-cell omics analysis of multiple species to show that epigenetic dysregulation of hepatic endothelial cells promoted the maladaptation of these cells from a sinusoidal to vascular phenotype. The vascularly maladapted cells stimulated fibrosis via a HDAC2-DNMT1-IGFBP7-TH17 pathway, and HDAC2 and DNMT1 inhibitors targeting this pathway mitigated fibrosis in a minipig NASH model. This provides a valuable resource for studying NASH pathogenesis and suggests a potential strategy to block the liver fibrosis promoted by maladaptive vascularization in this disease. Chronic hepatic diseases such as nonalcoholic steatohepatitis (NASH) suppress liver regeneration and lead to fibrosis and cirrhosis. Decoding the cellular and molecular network underlying this fibrotic maladaptation might aid in combatting NASH, a growing health challenge with no approved therapies. Here, we used multiomics analysis of human cirrhotic liver, a Western diet– and carbon tetrachloride (CCl4)–induced minipig NASH model, and genetically modified mice to unravel the landscape of the vascular adaptome at the single-cell level, in which endothelial cells (ECs) and TH17 cells jointly contribute to liver cirrhosis. We found that epigenetics-dependent hepatic vascular maladaptation enriches fibrogenic TH17 cells to promote liver fibrosis in mice, minipigs, and human patients with cirrhosis. Further analysis of humans, minipigs, and mice suggested that cross-talk between histone deacetylase 2 (HDAC2) and DNA methyltransferase 1 (DNMT1) promoted liver EC maladaptation to promote production of angiocrine IGFBP7 and ADAMTS1 in extracellular vesicles, recruiting fibrogenic TH17 cells to the liver. Pharmacological targeting of HDAC2 and DNMT1 alleviated fibrosis in a minipig NASH model. We conclude that epigenetically reprogrammed vascular adaptation contributes to liver fibrosis. Targeting of a vascular adaptation node might block maladaptive vascularization to promote liver regeneration in NASH. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is a major and common disease that poses a threat to human health. Recent studies suggested that epicardial fat may have an important role in the pathogenesis of CAD. Therefore, the association between epicardial fat volume (EFV) and left ventricular function with CAD was investigated in the present study. A total of 61 patients with suspected CAD who underwent CT scanning were enrolled. Baseline data, parameters of left heart function and EFV of the subjects were collected and analyzed. The degree of coronary artery lesions was assessed using the Gensini score. Pearson's correlation analysis and a logistic regression model were applied to assess the association between EFV and risk factors for CAD, the Gensini score and left ventricular function index. A total of 29 female and 32 male subjects with a median age of 63 years were enrolled. The median body mass index (BMI) of the subjects was 23.37 kg/m2 and the median EFV was 86.41 cm3. It was revealed that risk factors of CAD, specially hypertension, diabetes mellitus, dyslipidemia, history of myocardial infarction and smoking, had no significant association with the EFV (P>0.05); however, the EFV was significantly positively correlated with the BMI (r=0.479, P<0.0001), interventricular septal thickness (r=0.436, P=0.004), left ventricular posterior wall thickness (r=0.350, P=0.0058), left ventricular end diastolic diameter (r=0.265, P=0.0388), left ventricular mass (r=0.445, P=0.0003) and left ventricular mass index (r=0.371, P=0.0035). However, no correlation was identified between the EFV and the Gensini score (r=0.131, P=0.3137). In conclusion, the EFV measured by cardiac CT scanning was positively correlated with the BMI and left ventricular function, but was not associated with the presence of CAD according to the Gensini scores. [ABSTRACT FROM AUTHOR]

Ever since a GGGGCC hexanucleotide repeat expansion mutation in C9ORF72 was identified as the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), three competing but nonexclusive hypotheses to explain how this mutation causes diseases have been proposed and are still under debate. Recent studies in the field have tried to understand how the repeat expansion disrupts cellular physiology, which has suggested interesting convergence of these hypotheses on downstream, functional defects in cells, such as nucleocytoplasmic transport disruption, membrane-less organelle defects, and DNA damage. These studies have not only provided an integrated view of the disease mechanism but also revealed novel cell biology implicated in neurodegeneration. Furthermore, some of the discoveries have given rise to new ideas for therapeutic development. Here, we review the research progress on cellular pathophysiology of C9ORF72-mediated ALS and FTD and its therapeutic implication. We suggest that the repeat expansion drives pathogenesis through a combination of downstream defects, of which some can be therapeutic targets. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases have become the leading cause of human death. Aging is an independent risk factor for cardiovascular diseases. Cardiac aging is associated with maladaptation of cellular metabolism, dysfunction (or senescence) of cardiomyocytes, a decrease in angiogenesis, and an increase in tissue scarring (fibrosis). These events eventually lead to cardiac remodeling and failure. Senescent cardiomyocytes show the hallmarks of DNA damage, endoplasmic reticulum stress, mitochondria dysfunction, contractile dysfunction, hypertrophic growth, and senescence-associated secreting phenotype (SASP). Metabolism within cardiomyocytes is essential not only to fuel the pump function of the heart but also to maintain the functional homeostasis and participate in the senescence of cardiomyocytes. The senescence of cardiomyocyte is also regulated by the non-myocytes (endothelial cells, fibroblasts, and immune cells) in the local microenvironment. On the other hand, the senescent cardiomyocytes alter their phenotypes and subsequently affect the non-myocytes in the local microenvironment and contribute to cardiac aging and pathological remodeling. In this review, we first summarized the hallmarks of the senescence of cardiomyocytes. Then, we discussed the metabolic switch within senescent cardiomyocytes and provided a discussion of the cellular communications between dysfunctional cardiomyocytes and non-myocytes in the local microenvironment. We also addressed the functions of metabolic regulators within non-myocytes in modulating myocardial microenvironment. Finally, we pointed out some interesting and important questions that are needed to be addressed by further studies. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription 3 (STAT3) is implicated in inflammation processing, but the mechanism of its regulation mostly remains limited to Janus kinase (JAK)-mediated phosphorylation. Although AMP-activated protein kinase (AMPK)-mediated STAT3 inactivation has got documented, the molecular signaling cascade connecting STAT3 inactivation and the anti-inflammatory role of AMPK is far from established. In the present study, we addressed the interplay between AMPK and STAT3, and revealed the important role of STAT3 inactivation in the anti-inflammatory function of AMPK in lipopolysaccharide-stressed macrophages and mice. Firstly, we found that pharmacological inhibition of STAT3 can improve the anti-inflammatory effect of AMPK in wild-type mice, and the expression of STAT3 in macrophage of mice is a prerequisite for the anti-inflammatory effect of AMPK. As to the molecular signaling cascade linking AMPK to STAT3, we disclosed that AMPK suppressed STAT3 not only by attenuating JAK signaling but also by activating nuclear factor erythroid-2-related factor-2 (Nrf2), a redox-regulating transcription factor, which consequently increased the expression of small heterodimer protein (SHP), thus repressing the transcriptional activity of STAT3. In summary, this study provided a unique set of evidence showing the relationship between AMPK and STAT3 signaling and explored a new mechanism of AMPK-driven STAT3 inactivation that involves Nrf2-SHP signaling cascade. These findings expand our understanding of the interplay between pro- and anti-inflammatory signaling pathways and are beneficial for the therapeutic development of sepsis treatments. [ABSTRACT FROM AUTHOR]

To detect the changes in the liver function in both male and female OVE26 mice from young to adults for better understanding of type 1 diabetes‐induced hepatic changes, OVE26 mice and wild‐type FVB mice were raised in the same environment without any intervention, and then killed at 4, 12, 24 and 36 weeks for examining liver's general properties, including pathogenic and molecular changes. The influence of diabetes on the bodyweight of male and female mice was different. Both male and female OVE26 mice did not obtain serious liver injury or non‐alcoholic fatty liver disease, manifested by mild elevation of plasma alanine transaminase, and less liver lipid content along with significantly suppressed lipid synthesis. Uncontrolled diabetes also did not cause hepatic glycogen accumulation in OVE26 mice after 4 weeks. Oxidative stress test showed no change in lipid peroxidation, but increased protein oxidation. Changed endoplasmic reticulum stress and apoptosis along with increased antioxidant capacity was observed in OVE26 mice. In conclusion, uncontrolled type 1 diabetes did not cause hepatic lipid deposition most likely because of reduced lipids synthesis in response to insulin deficiency. Enhanced antioxidant capacity might not only prevent the occurrence of severe acute liver injury but also the self‐renewal, leading to liver dysfunction. [ABSTRACT FROM AUTHOR]

Summary: In this paper, a dynamic model of a seven-joints manipulator operated in a zero-g simulation system is established. The errors of the friction, the suspension force, and the flexible deformation of arms are considered. Furthermore, the unloading ratio, which can evaluate the performance of the simulation system, is presented. It can reflect the level of similarity between the system and the space environment directly and effectively. The results of experimental and theoretical analyses verify the correctness of the model. It helps us to get the joint torques when the actual space manipulator without the torque sensor operates in this system and guarantees the safety of the experiments. [ABSTRACT FROM AUTHOR]

In this paper, to solve the problem of variable stiffness of cable-driven parallel robots (CDPR), a new static stiffness analysis and cable tension distribution method are proposed for studying the CDPRs’ controllable stiffness. First, a three-dimensional Hessian matrix of the structure matrix to position differential is deduced by introducing a line vector and differential transform, and a static stiffness model is established for analyzing the relationship between cable tension and the stiffness of the robots. Furthermore, a calculation algorithm for cable tension polygons based on Graham's Scan is introduced that effectively obtains the cable tension feasible region (CTFR) of CDPRs. Next, a method involving “the relationship between the external force and the pose change value of the moving-platform” is proposed to measure the variation of system stiffness. The CDPR's controllable stiffness is also analyzed based on the CTFR by considering the variation of each driving-cable's tension and each component of the moving-platform's pose. The results of experimental and theoretical analyses verify the correctness and efficacy of the proposed method. In addition, they show that the proposed method is computationally efficient and easily establishes the relationship between cable tension and the CDPR's controllable stiffness. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase (PON) gene cluster (PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene (PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type (WT) control. The same protective tendency was also observed with an Apoe background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family. [ABSTRACT FROM AUTHOR]

Background and Aim: To evaluate image quality and radiation dosage in coronary CT angiography using 80-kVp tube voltage combined with low-concentration contrast media (CM) and iterative reconstruction (IR) for coronary CT angiography (CCTA) and employing dual-source CT without heart-rate control.Methods: 154 patients were randomly assigned to Group A (Control Group, 120-kVp tube voltage, high-concentration CM and filtered back projection reconstruction) and Group B (Low-Dose Group, 80 kVp, low-concentration CM and iterative construction). Two experienced radiologists double-blindly evaluated the following parameters: CT attenuation, signal-noise ratio (SNR), contrast-noise ratio (CNR), radiation dose, size-specific dose estimates (SSDE) and total iodine intake. Pearson correlation analysis was used to assess the relationship between SSDE and BMI.Results: 98.1% vessel segments in Group A and 97.6% in Group B passed diagnostics, indicating no significant differences; the average aorta scores and CT attenuation values showed no significant differences between groups. Similar SNR and CNR results were obtained for the two groups, although values were slightly lower in Group A compared with Group B. The Effective Dose in Group B was 63% lower than that in Group A (P<.001). SSDE results were significantly different between the two groups (P<.001) but did not correlate with BMI. Finally, the total iodine intake in Group B was 22.9% lower than that in Group A.Conclusions: Coronary CTA conducted with a low tube voltage of 80 kVp, a low-concentration CM and IR without heart rate control can achieve images of similar quality to those obtained using standard procedures, significantly reducing the associated radiation dose and iodine intake. [ABSTRACT FROM AUTHOR]

In this paper, a geometrical expression to delineate the sum of tensions (i.e. minimum 1-norm tensions) of 2-DoF planar cable-driven parallel manipulators (CDPMs) is proposed and proofed, which can be used to reduce calculation time of workspace determination. Furthermore, this paper also presents a systematic analysis on the relation between cable tension and workspace by means of convex analysis. In order to obtain wrench-feasible workspace, a unified and feasible algorithm is adopted in simulation examples of spatial CDPMs with different configurations, which demonstrate that the proposed method is valid and straightforward to calculate workspace. [ABSTRACT FROM AUTHOR]

Inertia strongly influences the dynamic performance of parallel manipulators, and ignorance of inertia is apt to result in negative phenomena such as vibrations, overshoot, and slow response. This study analyzes the inertia-decoupling characteristic of Stewart platform. Because the inertia matrix of the Stewart platform is usually non-diagonal, inertia coupling occurs between its legs. Herein, decoupling to inertia is implemented, and independent control channels are determined. The influence of decoupled inertia on the control system is analyzed using the Adams simulation software, and the inertia index of the Stewart platform is proposed. Experiments are conducted on a prototype of the Stewart platform to verify the eigenvalue characteristic of decoupled inertia. The distribution of inertia index in the operational workspace is provided, and the influence of dimensional parameters on inertia index is discussed. Finally, dimensional optimization is realized with a set of optimized dimensions for good dynamic performance. [ABSTRACT FROM AUTHOR]

Optimum design is a key approach to make full use of potential advantages of a parallel manipulator. The optimum design of multi-parameter parallel manipulators(more than three design parameters), such as Stewart manipulator, relies on analysis based and algorithm based optimum design methods, which fall to be accurate or intuitive. To solve this problem and achieve both accurate and intuition, atlas based optimum design of a general Stewart parallel manipulator is established, with rational selection of design parameters. Based on the defined spherical usable workspace(SUW), primary kinematic performance indices of the Stewart manipulator, involving workspace and condition number are introduced and analyzed. Then, corresponding performance atlases are drawn with the established non-dimensional design space, and impact of joint distribution angles on the manipulator performance is analyzed and illustrated. At last, an example on atlas based optimum design of the Stewart manipulator is accomplished to illustrate the optimum design process, considering the end-effector posture. Deduced atlases can be flexibly applied to both quantitative and qualitative analysis to get the desired optimal design for the Stewart manipulator with respect to related performance requirements. Besides, the established optimum design method can be further applied to other multi-parameter parallel manipulators. [ABSTRACT FROM AUTHOR]

SIRT1, a mammalian ortholog of yeast silent information regulator 2 (Sir2), is an NAD-dependent protein deacetylase that plays a critical role in the regulation of vascular function. The current study aims to investigate the functional significance of deacetylase activity of SIRT1 in heart. Here we show that the early postnatal hearts expressed the highest level of SIRT1 deacetylase activity compared to adult and aged hearts. We generated transgenic mice with cardiac-specific expression of a dominant-negative form of the human SIRT1 (SIRT1H363Y), which represses endogenous SIRT1 activity. The transgenic mice displayed dilated atrial and ventricular chambers, and died early in the postnatal period. Pathological, echocardiographic and molecular phenotype confirmed the presence of dilated cardiomyopathy. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling analysis revealed a greater abundance of apoptotic nuclei in the hearts of transgenic mice. Furthermore, we show that cardiomyocyte apoptosis caused by suppression of SIRT1 activity is, at least in part, due to increased p53 acetylation and upregulated Bax expression. These results indicate that dominant negative form of SIRT1 (SIRT1H363Y) overexpression in mouse hearts causes cardiomyocyte apoptosis and early-onset heart failure, suggesting a critical role of SIRT1 in preserving normal cardiac development during the early postnatal period. [ABSTRACT FROM AUTHOR]

SIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial cells. Inhibition of NFAT signaling may be an attractive target to regulate inflammation in atherosclerosis. However, whether NFAT transcriptional activity is suppressed by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT-mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1 suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore, SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that suppression of NFAT transcriptional activity is involved in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Io, and that the negative regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory effects in atherosclerosis. [ABSTRACT FROM AUTHOR]

With the advantage of large workspace, low energy consumption and small inertia, the cable-driven parallel manipulator (CDPM) is suitable for heavy workpieces in rapid velocity and acceleration. We present a workspace analysis approach to solve force and torque equilibriums of completely restrained CDPMs. By this approach, not only the distribution but also the value of tensions driven by cables is investigated together. Two new indices, all cable tension distribution index (ACTDI) and area of the global quality workspace (AG) are proposed to evaluate the quality of the workspace. By concentrating on the workspace and its quality combined with the tension characteristics, these criteria are used to determine the optimal workspace in CDPMs. To verify the capacity of the proposed method, simulation examples are presented and the results demonstrate the approach’s effectiveness. In the end, the dimensional design for a planar CDPM is discussed with the indices of workspace quality. [ABSTRACT FROM AUTHOR]

Tumour-associated macrophages ( TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy. [ABSTRACT FROM AUTHOR]