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Wenzhen Ge,1 Ning Wu,1 Chieh-I Chen,1 Timothy J Inocencio,1 Patrick R LaFontaine,2 Frank Seebach,3 Matthew Fury,4 James Harnett,1 Emily S Ruiz5 1Department of Health Economics and Outcomes Research, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 2Department of Global Health Economics & Outcomes Research, Sanofi, Cambridge, MA, USA; 3Department of Regulatory Affairs, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 4Department of Clinical Sciences, Oncology, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 5Department of Dermatology, Dana-Farber Cancer Institute, Boston, MA, USACorrespondence: Wenzhen Ge, Regeneron Pharmaceuticals, Inc, 1 Rockwood Road, Sleepy Hollow, NY, 10591, Tel +1 914-847-7000, Email wenzhen.ge@regeneron.comBackground: Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US.Patients and Methods: This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018– 2021). A clinical trial–like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan–Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort.Results: The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6– 9.0) months and 16.4 (13.3– 21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8– 29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age < 60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status < 3– 4 (HR range, 0.13– 0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without.Conclusion: These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.Keywords: cutaneous squamous cell carcinoma, cemiplimab, immune checkpoint inhibitor, real-world study, skin cancer

To address the issue of frequency stability in microgrids with limited communication resources and bandwidth, this paper proposed an event-triggered control method based on a cloud-edge collaborative architecture. Firstly, to address the limited communication resources, event-triggered detector is set up at the edge to upload state variables and update control instructions only when the frequency deviation exceeds a pre-set threshold. Secondly, a fractional-order PI–PD controller is designed at the cloud control center, which achieves higher control degrees of freedom and stronger robustness than traditional integer-order PID control schemes. Additionally, to obtain better control parameters, an optimized design method based on an improved Big Bang-Big Crunch method (BB-BC3) is proposed for the fractional-order PI–PD controller. At last, a simulation example is given to prove the validity of the proposed method. Simulation results show that compared to the integer-order PI–PD controller, the fractional-order PI–PD controller based on the BB-BC3 algorithm proposed in this paper reduces the peak value of the response curve by 5%, and shortens the setting time by 0.14 s. [ABSTRACT FROM AUTHOR]

Abstract There are many stars that are rotating spheroids in the Universe, and studying them is of very important significance. Since the times of Newton, many astronomers and physicists have researched gravitational properties of stars by considering the moment equations derived from Eulerian hydrodynamic equations. In this paper we study the scattering of spinors of the Dirac equation, and in particular investigate the scattering issue in the limit case of rotating Maclaurin spheroids. Firstly we give the metric of a rotating ellipsoid star, then write the Dirac equation under this metric, and finally derive the scattering solution to the Dirac equation and establish a relation between differential scattering cross-section, $$\sigma $$ σ , and stellar matter density, $$\mu $$ μ . It is found that the sensitivity of $$\sigma $$ σ to the change in $$\mu $$ μ is proportional to the density $$\mu $$ μ . Because of the weak gravitational field and the constant mass density, our results are reasonable. The results can be applied to white dwarfs, main sequence stars, red giants, supergiant stars and so on, as long as their gravitational fields are so weak that they can be treated in the Newtonan approximations, and the fluid is assumed to be incompressible. Notice that we take the star’s matter density to be its average density and the star is not taken to be compact. Obviously our results cannot be used to study neutron stars and black holes. In particular, our results are suitable for white dwarfs, which have average densities of about $$10^{5}$$ 105 –$$10^{6}$$ 106 g cm$$^{-3}$$ -3 , corresponding to a range of mass of about $$0.21{-}0.61 M_{\bigodot }$$ 0.21-0.61M⨀ and a range of radius of about $$6000{-}10,000$$ 6000-10,000 km.

Yi-Che Lee,1–3 Chih-Ting Huang,4 Fong-Yu Cheng,5 Shih-Yuan Hung,3,6 Tsun-Mei Lin,7 Yen-Chang Tsai,4 Chih-I Chen,8 Hao-Kuang Wang,9 Chi-Wei Lin,10 Hung-Hsiang Liou,11 Min-Yu Chang,3 Hsi-Hao Wang,3 Yuan-Yow Chiou4,12 1Division of Nephrology, Department of Internal Medicine, E-DA Dachang Hospital/ I-Shou University, Kaohsiung, Taiwan; 2School of Medicine, College of Medicine; 3Division of Nephrology, Department of Internal Medicine, E-DA Hospital/ I-Shou University, Kaohsiung, Taiwan; 4Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Chemistry, Chinese Culture University, Taipei, Taiwan; 6School of Medicine for International Students; 7Department of Laboratory Medicine; 8Division of Colorectal Surgery, Department of Surgery; 9Department of Neurosurgery; 10Department of Medical Education, E-DA Hospital/ I-Shou University, Kaohsiung, Taiwan; 11Division of Nephrology, Department of Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan; 12Department of Pediatrics, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Yi-Che LeeDivision of Nephrology, Department of Internal Medicine, E-DA Hospital/I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan, ROCTel +886-7-6150011 ext. 5121Email pipijer@gmail.com Yuan-Yow ChiouInstitute of Clinical Medicine, Department of Pediatrics, National Cheng Kung University Hospital, Medical College, No. 138, Sheng-Li Road, Tainan City 701, Taiwan, ROCTel +886-6-2353535 ext. 4184Fax +886-6-2753083Email yuanyow@mail.ncku.edu.twPurpose: Vitamin D is a novel potential therapeutic agent for peritoneal dialysis (PD)-related peritoneal fibrosis, but it can induce hypercalcemia and vascular calcification, which limits its applicability. In this study, we create nanotechnology-based drug delivery systems to investigate its therapeutics and side effects.Materials and methods: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino-(polyethylene glycol)2000] (DSPE-PEG) and L-α-phosphatidylcholine (PC), which packages with 1α,25(OH)2D3, were used to construct vitamin D nanoliposomes. To confirm the function and safety of vitamin D nanoliposomes, peritoneal mesothelial cells were treated with TGF-β1 and the reverse was attempted using vitamin D nanoliposomes. Antibodies (Ab) against the peritoneum-glycoprotein M6A (GPM6A) Ab were conjugated with vitamin D nanoliposomes. These particles were implanted into mice by intraperitoneal injection and the animals were monitored for the distribution and side effects induced by vitamin D.Results: Vitamin D nanoliposomes were taken up by the mesothelial cells over time without cell toxicity and it also provided the same therapeutic effect in vitro. In vivo study, fluorescent imaging showed vitamin D nanoliposomes allow specific peritoneum target effect and also ameliorate vitamin D side effect.Conclusion: Nanoliposomes vitamin D delivery systems for the prevention of PD-related peritoneal damage may be a potential clinical strategy in the future.Keywords: peritoneal dialysis, nanoliposome, vitamin D, fibrosis

There are many rotating spheroids in the universe, and many astronomers and physicists have used theoretical methods to study the characteristics of stellar gravity since Newton's time. This paper derives the solutions of eight scattering states (ϕ(0),χ(0),ϕ(1),χ(1),ϕ(2)$$ \Big({\phi}^{(0)},{\chi}^{(0)},{\phi}^{(1)},{\chi}^{(1)},{\phi}^{(2)} $$,χ(2),ϕ(3)$$ {\chi}^{(2)},{\phi}^{(3)} $$, andχ(3))$$ {\chi}^{(3)}\Big) $$ for the Dirac equation with positive‐energy E=im$$ E= im $$, and establishes the relationship between the differential scattering cross section σi(p,θ,φ)$$ {\sigma}_i\left(p,\theta, \varphi \right) $$ and the stellar density μ$$ \mu $$. It is found that: (1) For the eight scattering states, their average scattering cross‐sections σi‾$$ \overline{\sigma_i} $$ are proportional to μ2$$ {\mu}^2 $$, and depend on the star's radius, and the higher the stellar density μ$$ \mu $$, the greater the sensitivity of σi‾$$ \overline{\sigma i} $$ to the change of μ$$ \mu $$; (2) For the four scattering states χ(i),i=0,1,2,3$$ {\chi}^{(i)},i=0,1,2,3 $$, their average scattering amplitudes f‾(p,θ)$$ \overline{f}\left(p,\theta \right) $$ and σ‾(p,θ)$$ \overline{\sigma}\left(p,\theta \right) $$ depend on the mass m$$ m $$ of the particles; while for the other four scattering states ϕ(i)$$ {\phi}^{(i)} $$, i=0,1,2,3$$ i=0,1,2,3 $$, then f‾$$ \overline{f} $$ and σ‾$$ \overline{\sigma} $$ are independent of m$$ m $$. This study links the gravitational characteristics of stars with the scattering cross section, creating a new method for studying the gravitational characteristics, which helps to reveal the mystery of the gravity of rotating ellipsoidal stars. [ABSTRACT FROM AUTHOR]

Planning for autonomous vehicles to merge into high‐density traffic flows within limited mileage is quite challenging. Specifically, the driving trajectory will inevitably have intersections with other vehicles whose driving intentions can't be directly observed. Herein, a two‐stage algorithm framework that is decomposed into the longitudinal and lateral planning processes for online merging planning is proposed. An improved particle filter is used to estimate the driving models of surrounding vehicles for predicting their future driving intentions. Based on Monte Carlo tree search (MCTS), different action spaces are evaluated for longitudinal merging gap selection and lateral interactive merging operation, while heuristic pruning is used to reduce the computation cost. Moreover, the coefficients related to the driving styles are introduced, and their influences on merging performance are analyzed. Finally, the proposed algorithm is implemented in a two‐lane simulation environment. The results show that the proposal has outperformed other baseline methods. [ABSTRACT FROM AUTHOR]

In this article, we consider the resilience problem in the presence of communication faults encountered in distributed secondary voltage and frequency control of an islanded alternating current microgrid. Such faults include the partial failure of communication links and some classes of data manipulation attacks. This practical and important yet challenging issue has been taken into limited consideration by existing approaches, which commonly assume that the measurement or communication between the distributed generations (DGs) is ideal or satisfies some restrictive assumptions. To achieve communication resilience, a novel adaptive observer is first proposed for each individual DG to estimate the desired reference voltage and frequency under unknown communication faults. Then, to guarantee the stability of the closed-loop system, voltage and frequency restoration, and accurate power sharing regardless of unknown communication faults, sufficient conditions are derived. Some simulation results are presented to verify the effectiveness of the proposed secondary control approach. [ABSTRACT FROM AUTHOR]

As an indispensable branch of machine learning (ML), reinforcement learning (RL) plays a prominent role in the decision-making process of autonomous driving (AD), which enables autonomous vehicles (AVs) to learn an optimal driving strategy through continuous interaction with the environment. This paper proposes a deep reinforcement learning (DRL)-based motion planning strategy for AD tasks in the highway scenarios where an AV merges into two-lane road traffic flow and realizes the lane changing (LC) maneuvers. We integrate the DRL model into the AD system relying on the end-to-end learning method. An improved DRL algorithm based on deep deterministic policy gradient (DDPG) is developed with well-defined reward functions. In particular, safety rules (SR), safety prediction (SP) module and trauma memory (TM) as well as the dynamic potential-based reward shaping (DPBRS) function are adopted to further enhance safety and accelerate learning of the LC behavior. For validation, the proposed DSSTD algorithm is trained and tested on the dual-computer co-simulation platform. The comparative experimental results show that our proposal outperforms other benchmark algorithms in both driving safety and efficiency. [ABSTRACT FROM AUTHOR]

In this article, we study the distributed resilient cooperative control problem for directed networked Lagrangian systems under denial-of-service (DoS) attacks. The DoS attacks will block the communication channels between the agents. Compared with the existing methods for the linear networked systems, the considered nonlinear networked Lagrangian systems with asymmetric channels under DoS attacks are more challenging and still not well explored. In order to solve this problem, a novel resilient cooperative control scheme is proposed by using the sampling control approach. Sufficient conditions are first derived in the absence of DoS attacks according to a multidimensional small-gain scheme. Then, in the presence of DoS attacks, the proposed resilient scheme works in a switching manner. Inspired by multidimensional small-gain techniques, the Lyapunov approach is used to analyze the closed-loop system, which enables us to establish sufficient stability conditions for the control gains in terms of the duration and frequency of the DoS attacks. [ABSTRACT FROM AUTHOR]

We propose a novel, computationally efficient, and robust light detection and ranging (LiDAR)-only odometry framework based on truncated least squares termed T-LOAM. Our method focuses on alleviating the impact of outliers to allow robust navigation in sparse, noisy, or cluttered scenarios where degeneration occurs. As preprocessing, the multiregion ground extraction and dynamic curved-voxel clustering methods are proposed to accomplish the segmentation of 3D point clouds and filter out unstable objects. A novel feature extraction module is tailored to discriminate four peculiar features: edge features, sphere features, planar features, and ground features. As frontend, a hierarchical feature-based LiDAR-only odometry performs precise motion estimates through the truncated least squares method for directly processing various features. The preprocessing model and motion estimation precision have been evaluated on the KITTI odometry benchmark as well as various campus scenarios. The experimental results have demonstrated the real-time capability and superior precision of the proposed T-LOAM over other state-of-the-art algorithms. [ABSTRACT FROM AUTHOR]

To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, a humanized decoy antibody (ACE2‐Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin‐converting enzyme 2 (ACE2). First, we demonstrated that ACE2‐Fc could specifically abrogate virus replication by blocking the entry of SARS‐CoV‐2 spike‐expressing pseudotyped virus into both ACE2‐expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS‐CoV‐2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2‐Fc to reduce the angiotensin II‐mediated cytokine cascade. Furthermore, this Fc domain of ACE2‐Fc was shown to activate NK cell degranulation after co‐incubation with Spike‐expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2‐Fc as an effective treatment for COVID‐19. Synopsis: Currently, there is no effective strategy to fight against the COVID‐19 pandemic. We aim to design and develop a humanized decoy antibody to block SARS‐CoV‐2 infection. The ACE2‐Fc fusion protein can form a dimer that mimics a humanized antibody and specifically binds to the SARS‐CoV‐2 Spike protein.The ACE2‐Fc fusion protein abrogates virus replication by blocking SARS‐CoV‐2 entry in clinical isolates.The peptidase activity of ACE2‐Fc enables the decoy antibody to reduce angiotensin II‐mediated cytokine cascade.After binding to Spike‐expressing target cells, ACE2‐Fc activates degranulation of NK cells. [ABSTRACT FROM AUTHOR]

Background Evidence from biochemical, epidemiological and genetic findings indicates that cholesterol levels are linked to amyloid-β (Aβ) production and Alzheimer's disease (AD). Oxysterols, which are cholesterol-derived ligands of the liver X receptors (LXRs) and oxysterol binding proteins, strongly regulate the processing of amyloid precursor protein (APP). Although LXRs have been studied extensively, little is known about the biology of oxysterol binding proteins. Oxysterol-binding protein 1 (OSBP1) is a member of a family of sterol-binding proteins with roles in lipid metabolism, regulation of secretory vesicle generation and signal transduction, and it is thought that these proteins may act as sterol sensors to control a variety of sterol-dependent cellular processes. Results We investigated whether OSBP1 was involved in regulating APP processing and found that overexpression of OSBP1 downregulated the amyloidogenic processing of APP, while OSBP1 knockdown had the opposite effect. In addition, we found that OSBP1 altered the trafficking of APP-Notch2 dimers by causing their accumulation in the Golgi, an effect that could be reversed by treating cells with OSBP1 ligand, 25-hydroxycholesterol. Conclusion These results suggest that OSBP1 could play a role in linking cholesterol metabolism with intracellular APP trafficking and Aβ production, and more importantly indicate that OSBP1 could provide an alternative target for Aβ-directed therapeutic.

Phasor measurement unit can monitor the variation of phase angle of power grid in real time, which is of great significance to ensure the safe and stable operation of power grid. Among them, the virtual phasor measurement algorithm based on discrete Fourier transform (DFT) has been widely used because of its simple principle and relatively easy implementation. However, the existing virtual phasor measurement algorithm only gives the dynamic error reduction effect under the fixed offset angle, and does not give the rule of the reduction effect with the different offset angle. The relationship between anti-harmonic interference capability and response speed with the different offset angles is not analysed. Therefore, this study deduces the pattern of dynamic error reduction effect, anti-harmonic interference ability and response speed with the different offset angles. The dynamic error reduction effect of the algorithm is the best when the offset angle is π/2, and the anti-harmonic interference ability of the algorithm is the strongest when the offset angle is π/3. The response speed of the algorithm increases linearly with the increase of the offset angle. On this basis, the correctness of the algorithm is verified by numerical simulation experiments. [ABSTRACT FROM AUTHOR]

Klotho is an age-extending, cognition-enhancing protein found to be down-regulated in aged mammals when age-related diseases start to appear. Low levels of Klotho occur in neurodegenerative diseases, kidney disease and many cancers. Many normal and pathologic processes involve the proteolytic shedding of membrane proteins. Transmembrane (TM) Klotho contains two homologous domains, KL1 and KL2 with homology to glycosidases. After shedding by ADAM 10 and 17, a shed Klotho isoform is released into serum and urine by the kidney, and into the CSF by the choroid plexus. We previously reported that human Klotho contains two major cleavage sites. However, the exact cleavage site responsible for the cleavage between the KL1 and KL2 domains remains unknown for the human Klotho, and both sites are unknown for mouse Klotho. In this study, we aimed to identify the cleavage sites leading to the shed forms of human and mouse Klotho. Mutations in the region close to the TM domain of mouse Klotho result in the reduced shedding of the 130 kD (KL1+KL2) and 70 kD (KL1) fragments, suggesting that the cleavage site lies within the mutated region. We further identified the cleavage sites responsible for the cleavage between KL1 and KL2 of human and mouse Klotho. Moreover, mutated Klotho proteins have similar subcellular localization patterns as wild type Klotho. Finally, in an FGF23 functional assay, all Klotho mutants with a nine amino acid deletion can also function as an FGFR1 co-receptor for FGF23 signaling, however, the signaling activity was greatly reduced. The study provides new and important information on Klotho shedding, and paves the way for studies aimed to distinguish between the distinct roles of the various isoforms of Klotho. [ABSTRACT FROM AUTHOR]

This paper investigates a problem of designing an adaptive asymptotic cooperative control scheme for nonlinear time-varying multiagent systems, which can simultaneously tolerate unknown actuator failures and unknown control directions. To address such the problem, we propose a conditional inequality, which allows multiple piecewise Nussbaum functions to acquire the control robustness. Benefiting from this robustness, a part of failure uncertainties and system errors are compensated for, while the remaining parts are handled by adaptive control technique. Moreover, structural properties of the proposed adaptive laws are utilized so that Barbalat’s lemma is applicable to make all the followers asymptotically converge to the leader based on the neighborhood information. [ABSTRACT FROM AUTHOR]

The efficient fixation of CO 2 without co-catalyst and solvent under metal-free condition is still an urgent topic in sustainable chemistry. In this work, a series of dialkylpyrazolium ionic liquids are employed to promote the cycloaddition of CO 2 and PO to produce PC. They would be easily synthesized by a simple one-pot reaction. The effect of alkyl chain length in cation and different anion is explored. Diethylpyrazolium iodide presents the excellent catalytic activity with the product yield of 96% and selectivity of 99% in a benign condition. Moreover, the catalyst could be reused for at least five times without significant loss of catalytic activity. An intensive structure-activity research testifies that the cycloaddition of CO 2 with PO is activated by a synergistic effect from both cation and anion of ILs. To confirm it, the detailed mechanism is investigated by density functional theory associated with the non-covalent interactions and atoms in molecule analysis. Besides the electrostatic interaction between cation of ionic liquid and PO, the noncovalent interaction, especially for hydrogen bond, plays a vital role in promoting the reaction. [ABSTRACT FROM AUTHOR]

Most existing control results for pure-feedback stochastic systems are limited to a condition that tracking errors are bounded in probability. Departing from such bounded results, this paper proposes an asymptotic fuzzy neural network control for pure-feedback stochastic systems. The control goal is realized by proposing a novel semi-Nussbaum function-based technique and employing it in adaptive backstepping controller design. The proposed Nussbaum function is integrated with adaptive control technique to guarantee that the tracking error is asymptotically stable in probability. [ABSTRACT FROM PUBLISHER]

To achieve satisfying motion/force objectives, it is required for the multiarm robot manipulation to tackle unknown nonlinearities and uncertainties. Existing control schemes have a requirement that the deadzone nonlinearity in the sensor channel could be ignored. However, the sensor deadzone is widely spread in real world applications; and its existence significantly limits the robotic performances. Moreover, the kinematics and dynamics of the manipulated object cannot be accurately known as the prior knowledge. Hence, such robotic systems may not be perfectly controlled by conventional approaches. In this paper, a coordinated motion/force control method is presented to handle unknown sensor deadzone and object’s uncertainty. The proposed method ensures the motion and internal force errors be bounded in a small neighborhood around the origin. Finally, comparative studies are presented to show the effectiveness and robustness of the proposed scheme. [ABSTRACT FROM AUTHOR]

This paper presents a saturated Nussbaum function based approach for robotic systems with unknown actuator dynamics. To eliminate the effect of the control shock from the traditional Nussbaum function, a new type of the saturated Nussbaum function is developed with the idea of time-elongation. Moreover, by exploiting properties of the proposed Nussbaum function, a promising theorem is established to deal with unknown multiple actuator nonlinearities. In what follows, the proposed theorem is integrated with the adaptive control technique such that the stability analysis of the robotic system is completed. It thus guarantees that the state of the robotic system asymptotically converges to the desired trajectory. Finally, comparative studies are carried out to validate the effectiveness and the superiority of the proposed approach. [ABSTRACT FROM PUBLISHER]

To isolate the mounted object from the vibration sources, it is required that the qualities of the actuators in an active vibration isolation system are highly promising. Therefore, it is unreasonable to ignore actuator nonlinearity to realize the excellent performances of the vibration isolation. In this paper, the problem of unknown actuator backlash in the vibration isolation system is investigated. To handle the lines–segments backlash nonlinearity, an adaptive smooth backlash inverse is employed to compensate the deleterious effect. Moreover, a promising controller is proposed to ensure that the motion of the moving platform converges to desired values. Based on Lyapunov’s second method, all of the involved signals in the closed-loop system are proved to be stable. Finally, comparative studies involving active vibration isolation with actuator backlash are constructed and carried out to validate the effectiveness of the proposed control scheme. [ABSTRACT FROM PUBLISHER]

To achieve an excellent dual-arm coordination of the humanoid robot, it is essential to deal with the nonlinearities existing in the system dynamics. The literatures so far on the humanoid robot control have a common assumption that the problem of output hysteresis could be ignored. However, in the practical applications, the output hysteresis is widely spread; and its existing limits the motion/force performances of the robotic system. In this paper, an adaptive neural control scheme, which takes the unknown output hysteresis and computational efficiency into account, is presented and investigated. In the controller design, the prior knowledge of system dynamics is assumed to be unknown. The motion error is guaranteed to converge to a small neighborhood of the origin by Lyapunov’s stability theory. Simultaneously, the internal force is kept bounded and its error can be made arbitrarily small. [ABSTRACT FROM PUBLISHER]

The gene ankyrin repeat domain 1 (Ankrd1) is an enigmatic gene and may exert pleiotropic function dependent on its expression level, subcellular localization and even types of pathological stress, but it remains unclear how these factors influence the fate of cardiomyocytes. Here we attempted to investigate the role of CARP on cardiomyocyte hypertrophy. In neonatal rat ventricular cardiomyocytes (NRVCs), angiotensin II (Ang II) increased the expression of both calpain 1 and CARP, and also induced cytosolic translocation of CARP, which was abrogated by a calpain inhibitor. In the presence of Ang-II in NRVCs, infection with a recombinant adenovirus containing rat Ankrd1 cDNA (Ad-Ankrd1) enhanced myocyte hypertrophy, the upregulation of atrial natriuretic peptide and β-myosin heavy chain genes and calcineurin proteins as well as nuclear translocation of nuclear factor of activated T cells. Cyclosporin A attenuated Ad-Ankrd1-enhanced cardiomyocyte hypertrophy. Intra-myocardial injection of Ad-Ankrd1 in mice with transverse aortic constriction (TAC) markedly increased the cytosolic CARP level, the heart weight/body weight ratio, while short hairpin RNA targeting Ankrd1 inhibited TAC-induced hypertrophy. The expression of calcineurin was also significantly increased in Ad-Ankrd1-infected TAC mice. Olmesartan (an Ang II receptor antagonist) prevented the upregulation of CARP in both Ang II-stimulated NRVCs and hearts with pressure overload. These findings indicate that overexpression of Ankrd1 exacerbates pathological cardiac remodeling through the enhancement of cytosolic translocation of CARP and upregulation of calcineurin. [ABSTRACT FROM AUTHOR]

We developed cobalt and carbon complex materials as counter electrodes (CEs) for dye-sensitized solar cells (DSSCs) to replace conventional platinum (Pt) CEs. Co12 and Co15, both of which are basic cobalt derivatives, showed good redox potential with a suitable open-circuit voltage (VOC); however, their poor electrical conductivity engendered a low short-circuit current (JSC) and fill factor (FF). Mixing them with carbon black (CB) improved the electrical conductivity of the CE; in particular, JSC and FF were considerably improved. Further improvement was achieved by combining cobalt derivatives and CB through thermal sintering to produce a novel CoCB material as a CE. CoCB had good electrical conductivity and electrocatalytic capability, and this further enhanced both JSC and VOC. The optimized device exhibited a power conversion efficiency (PCE) of 7.44%, which was higher than the value of 7.16% for a device with a conventional Pt CE. The conductivity of CoCB could be further increased by mixing it with PEDOT:PSS, a conducting polymer. The device's JSC increased to 18.65 mA/cm2, which was considerably higher than the value of 14.24 mA/cm2 for the device with Pt CEs. The results demonstrate the potential of the cobalt and carbon complex as a CE for DSSCs. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we employed CRISPR/Cas9 editing technology to introduce the EGFR C797S mutation into an NSCLC cell line harboring EGFR L858R/T790M to establish a cellular model for the investigation of the resistance mechanism associated with the acquired C797S mutation and to explore strategies to battle this type of TKI resistance. Transcriptome and proteome analyses revealed that the differentially expressed genes/proteins in the cells harboring the EGFR C797S mutation are associated with elevated expression of AXL. Furthermore, we presented evidence that inhibition of AXL is effective in slowing the growth of NSCLC cells harboring EGFR C797S. Our findings suggest that AXL inhibition could be a second-line or a potential adjuvant treatment for NSCLC harboring the EGFR C797S mutation. Oncogenic mutations of epidermal growth factor receptor (EGFR) are responsive to targeted tyrosine kinase inhibitor (TKI) treatment in non-small-cell lung cancer (NSCLC). However, NSCLC patients harboring activating EGFR mutations inevitably develop resistance to TKIs. The acquired EGFR C797S mutation is a known mechanism that confers resistance to third-generation EGFR TKIs such as AZD9291. In this work, we employed CRISPR/Cas9 genome-editing technology to knock-in the EGFR C797S mutation into an NSCLC cell line harboring EGFR L858R/T790M. The established cell model was used to investigate the biology and treatment strategy of acquired EGFR C797S mutations. Transcriptome and proteome analyses revealed that the differentially expressed genes/proteins in the cells harboring the EGFR C797S mutation are associated with a mesenchymal-like cell state with elevated expression of AXL receptor tyrosine kinase. Furthermore, we presented evidence that inhibition of AXL is effective in slowing the growth of NSCLC cells harboring EGFR C797S. Our findings suggest that AXL inhibition could be a second-line or a potential adjuvant treatment for NSCLC harboring the EGFR C797S mutation. [ABSTRACT FROM AUTHOR]

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae), is an important transmission vector of the citrus greening disease Candidatus Liberibacter asiaticus (CLas). The D. citri midgut exhibits an important tissue barrier against CLas infection. However, the molecular mechanism of the midgut response to CLas infection has not been comprehensively elucidated. In this study, we identified 778 differentially expressed genes (DEGs) in the midgut upon CLas infection, by comparative transcriptome analyses, including 499 upregulated DEGs and 279 downregulated DEGs. Functional annotation analysis showed that these DEGs were associated with ubiquitination, the immune response, the ribosome, endocytosis, the cytoskeleton and insecticide resistance. KEGG enrichment analysis revealed that most of the DEGs were primarily involved in endocytosis and the ribosome. A total of fourteen DEG functions were further validated by reverse transcription quantitative PCR (RT-qPCR). This study will contribute to our understanding of the molecular interaction between CLas and D. citri. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the efficacy and tolerability of weekly oral cyclophosphamide in combination with alternate-day prednisone (CP) as salvage therapy for patients with relapsed multiple myeloma (MM) after autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: We retrospectively reviewed the medical records of all patients identified in our clinical database as having received CP as treatment for relapsed MM after ASCT at Princess Margaret Hospital between July 1998 and May 2004. The CP regimen consisted of oral cyclophosphamide at 500 mg once weekly and oral prednisone at 100 mg on alternate days. RESULTS: A total of 66 patients received the CP regimen, with a median of 2.0 prior therapies (range, 1.0-5.0) from time of diagnosis to initiation of CP. The median time from relapse after ASCT to start of CP therapy was 1.5 months (range, 0.0-23.5 months). Because of nonsecretory disease in 7 patients, only 59 patients were evaluable for response. The median duration of CP treatment was estimated at 5.8 months (95% confidence interval [CI], 4.6-7.8 months). With a median follow-up of 15.9 months (range, 1.4-67.2 months), 36 patients (61%) responded to treatment, 24 (41%) of whom had a partial response. The 1-year progression-free survival of all evaluable patients was estimated at 66% (95% CI, 54%-80%), with a median progression-free survival of 18.6 months (95% CI, 13.9-29.9 months). The median overall survival from time of initiation of CP was estimated at 28.6 months (95% CI, 22.1-not available months). CONCLUSION: Our data show that CP is an effective, well-tolerated, and convenient regimen as salvage therapy for MM after ASCT. [ABSTRACT FROM AUTHOR]