Autoimmune thyroid disease (AITD) can cause enormous health burdens; however, trustworthy biomarkers in identifying the onset and progression of AITD are limited. In this study, we attempted to ...discover new potential serum biomarkers to discriminate AITD using mass spectrometry (MS). In the biomarker study cohort, 20 patients with Graves' disease (GD), 20 patients with Hashimoto's thyroiditis (HT), and 20 healthy controls were enrolled for a liquid chromatographic-tandem MS assessment. A novel biomarker, keratin 1 (KRT1), was selected for further evaluation in the validation cohort, including 125 patients with GD, 34 patients with HT, and 77 controls. Relationships of serum KRT1 with AITD-related immunomodulatory cytokines were also analyzed using enzyme-linked immunosorbent assays (ELISAs). In the MS analysis, KRT1 was the single marker overexpressed in GD, while it was underexpressed in HT. In the ELISA analysis of the validation cohort, KRT1 was consistently upregulated in GD, while it was not downregulated in HT. There were significant associations of KRT1 levels with thyroid function in GD, AITD, and overall subjects. Additionally, a significant association of KRT1 levels with thyroid-stimulating hormone receptor antibody (TSHRAb) levels was observed. Moreover, there were significant associations of KRT1 with osteopontin (OPN) and B-cell activating factor (BAFF) levels in GD. Serum KRT1 levels were upregulated in GD and were associated with thyroid function and TSHRAb levels. Moreover, KRT1 was correlated with the BAFF and OPN levels in GD patients. Further molecular-based research to elucidate the role of KRT1 in the pathogenesis of AITD is needed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report the application of machine learning methods for predicting the effective diffusivity (D
) of two-dimensional porous media from images of their structures. Pore structures are built using ...reconstruction methods and represented as images, and their effective diffusivity is computed by lattice Boltzmann (LBM) simulations. The datasets thus generated are used to train convolutional neural network (CNN) models and evaluate their performance. The trained model predicts the effective diffusivity of porous structures with computational cost orders of magnitude lower than LBM simulations. The optimized model performs well on porous media with realistic topology, large variation of porosity (0.28-0.98), and effective diffusivity spanning more than one order of magnitude (0.1 ≲ D
< 1), e.g., >95% of predicted D
have truncated relative error of <10% when the true D
is larger than 0.2. The CNN model provides better prediction than the empirical Bruggeman equation, especially for porous structure with small diffusivity. The relative error of CNN predictions, however, is rather high for structures with D
< 0.1. To address this issue, the porosity of porous structures is encoded directly into the neural network but the performance is enhanced marginally. Further improvement, i.e., 70% of the CNN predictions for structures with true D
< 0.1 have relative error <30%, is achieved by removing trapped regions and dead-end pathways using a simple algorithm. These results suggest that deep learning augmented by field knowledge can be a powerful technique for predicting the transport properties of porous media. Directions for future research of machine learning in porous media are discussed based on detailed analysis of the performance of CNN models in the present work.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic ...malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this paper, a novel sliding-mode-observer-based adaptive controller is developed for the servo actuators with friction. The LuGre dynamic friction model is adopted for adaptive friction ...compensation. A sliding-mode observer is proposed to estimate the internal friction state of LuGre model. Based on the estimated friction state, adaptation laws are designed to compensate the unknown friction and load torque. The stability of the adaptive controller with sliding-mode observer is analyzed. The position tracking performance has been verified through both simulation and experimental results
Non-reciprocal devices, which allow non-reciprocal signal routing, serve as fundamental elements in photonic and microwave circuits and are crucial in both classical and quantum information ...processing. The radiation-pressure-induced coupling between light and mechanical motion in travelling-wave resonators has been exploited to break the Lorentz reciprocity, enabling non-reciprocal devices without magnetic materials. Here, we experimentally demonstrate a reconfigurable non-reciprocal device with alternative functions as either a circulator or a directional amplifier via optomechanically induced coherent photon-phonon conversion or gain. The demonstrated device exhibits considerable flexibility and offers exciting opportunities for combining reconfigurability, non-reciprocity and active properties in single photonic devices, which can also be generalized to microwave and acoustic circuits.
A link between sex hormones and B-cell activating factor (BAFF), a crucial immunoregulator of autoimmune thyroid disease (AITD), may exist. The study aimed to elucidate the role of estrogen (E2) in ...regulating BAFF in Graves' disease (GD). In clinical samples, serum BAFF levels were higher in women than in men in both the GD and control groups. serum BAFF levels were associated with thyroid-stimulating hormone receptor antibody levels and thyroid function only in women and not in men. BAFF transcripts in peripheral blood mononuclear cells were higher in women with GD than those in the control group. Among GD patients with the AA genotype of rs2893321, women had higher BAFF transcripts and protein levels than men. In the progression of a spontaneous autoimmune thyroiditis (SAT) murine model, NOD.H-2h4, serum free thyroxine and BAFF levels were higher in female than in male mice. Moreover, exogenous E2 treatment increased serum BAFF levels in male SAT mice. Meanwhile, female SAT mice exhibited higher thyroid BAFF transcripts levels than either the E2-treated or untreated male SAT mouse groups. Our results showed that E2 might be implicated in modulating BAFF expression, and support a possible mechanism for the higher incidence of AITD in women.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper presents an online image-based visual servoing (IBVS) controller for a 6-degrees-of-freedom (DOF) robotic system based on the robust model predictive control (RMPC) method. The controller ...is designed considering the robotic visual servoing system's input and output constraints, such as robot physical limitations and visibility constraints. The proposed IBVS controller avoids the inverse of the image Jacobian matrix and hence can solve the intractable problems for the classical IBVS controller, such as large displacements between the initial and the desired positions of the camera. To verify the effectiveness of the proposed algorithm, real-time experimental results on a 6-DOF robot manipulator with eye-in-hand configuration are presented and discussed.
We seek the best stroke sequences of a finite-size swimming predator chasing a non-motile point or finite-size prey at low Reynolds number. We use optimal control to seek the globally optimal ...solutions for the former and reinforcement learning (RL) for general situations. The predator is represented by a squirmer model that can translate forward and laterally, rotate and generate a stresslet flow. We identify the predator's best squirming sequences to achieve the time-optimal (TO) and efficiency-optimal (EO) predation. For a point prey, the TO squirmer executing translational motions favours a two-fold $L$-shaped trajectory that enables it to exploit the disturbance flow for accelerated predation; using a stresslet mode expedites significantly the EO predation, allowing the predator to catch the prey faster yet with lower energy consumption and higher predatory efficiency; the predator can harness its stresslet disturbance flow to suck the prey towards itself; compared to a translating predator, its compeer combining translation and rotation is less time-efficient, and the latter occasionally achieves the TO predation via retreating in order to advance. We also adopt RL to reproduce the globally optimal predatory strategy of chasing a point prey, qualitatively capturing the crucial two-fold attribute of a TO path. Using a numerically emulated RL environment, we explore the dependence of the optimal predatory path on the size of prey. Our results might provide useful information that help in the design of synthetic microswimmers such as in vivo medical microrobots capable of capturing and approaching objects in viscous flows.
Autophagy is a genetically well-controlled cellular process that is tightly controlled by a set of core genes, including the family of autophagy-related genes (ATG). Autophagy is a "double-edged ...sword" in tumors. It can promote or suppress tumor development, which depends on the cell and tissue types and the stages of tumor. At present, tumor immunotherapy is a promising treatment strategy against tumors. Recent studies have shown that autophagy significantly controls immune responses by modulating the functions of immune cells and the production of cytokines. Conversely, some cytokines and immune cells have a great effect on the function of autophagy. Therapies aiming at autophagy to enhance the immune responses and anti-tumor effects of immunotherapy have become the prospective strategy, with enhanced antigen presentation and higher sensitivity to CTLs. However, the induction of autophagy may also benefit tumor cells escape from immune surveillance and result in intrinsic resistance against anti-tumor immunotherapy. Increasing studies have proven the optimal use of either ATG inducers or inhibitors can restrain tumor growth and progression by enhancing anti-tumor immune responses and overcoming the anti-tumor immune resistance in combination with several immunotherapeutic strategies, indicating that induction or inhibition of autophagy might show us a prospective therapeutic strategy when combined with immunotherapy. In this article, the possible mechanisms of autophagy regulating immune system, and the potential applications of autophagy in tumor immunotherapy will be discussed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Silicon photodiodes are the foundation of light-detection technology; yet their rigid structure and limited area scaling at low cost hamper their use in several emerging applications. A detailed ...methodology for the characterization of organic photodiodes based on polymeric bulk heterojunctions reveals the influence that charge-collecting electrodes have on the electronic noise at low frequency. The performance of optimized organic photodiodes is found to rival that of low-noise silicon photodiodes in all metrics within the visible spectral range, except response time, which is still video-rate compatible. Solution-processed organic photodiodes offer several design opportunities exemplified in a biometric monitoring application that uses ring-shaped, large-area, flexible, organic photodiodes with silicon-level performance.
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