Angiogenesis is a multistep process and various molecules are involved in regulating it. Extracellular vesicles are cell-derived particles, secreted from several types of cells and are known to ...mediate cell-to-cell communication. These vesicles contain different bio-molecules including nucleic acids, proteins, and lipids, which are transported between cells and regulate physiological and pathological conditions in the recipient cell. Exosomes, 30-150 nm extracellular vesicles, and their key roles in tumorigenesis via promoting angiogenesis are of great recent interest. In solid tumors, the suitable blood supply is the hallmark of their progression, growth, and metastasis, so it can be supported by angiogenesis. Tumor cells abundantly release exosomes containing different kinds of biomolecules such as angiogenic molecules that contribute to inducing angiogenesis. These exosomes can be trafficked between tumor cells or between tumor cells and endothelial cells. The protein and nucleic acid cargo of tumor derived-exosomes can deliver to endothelial cells mostly by endocytosis, and then induce angiogenesis. Tumor derived-exosomes can be used as biomarker for cancer diagnosis. Targeting exosome-induced angiogenesis may serve as a promising tool for cancer therapy. Taken together, tumor derived-exosomes are the major contributors in tumor angiogenesis and a supposed target for antiangiogenic therapies. However, further scrutiny is essential to investigate the function of exosomes in tumor angiogenesis and clinical relevance of targeting exosomes for suppressing angiogenesis.
The solid tumor microenvironment possesses a hypoxic condition, which promotes aggressiveness and resistance to therapies. Hypoxic tumor cells undergo broadly metabolic and molecular adaptations and ...communicate with surrounding cells to provide conditions promising for their homeostasis and metastasis. Extracellular vesicles such as exosomes originating from the endosomal pathway carry different types of biomolecules such as nucleic acids, proteins, and lipids; participate in cell-to-cell communication. The exposure of cancer cells to hypoxic conditions, not only, increases exosomes biogenesis and secretion but also alters exosomes cargo. Under the hypoxic condition, different signaling pathways such as HIFs, Rab-GTPases, NF-κB, and tetraspanin are involved in the exosomes biogenesis. Hypoxic tumor cells release exosomes that induce tumorigenesis through promoting metastasis, angiogenesis, and modulating immune responses. Exosomes from hypoxic tumor cells hold great potential for clinical application and cancer diagnosis. Besides, targeting the biogenesis of these exosomes may be a therapeutic opportunity for reducing tumorigenesis. Exosomes can serve as a drug delivery system transferring therapeutic compounds to cancer cells. Understanding the detailed mechanisms involved in biogenesis and functions of exosomes under hypoxic conditions may help to develop effective therapies against cancer.
In this paper, we present a machine learning model to estimate the blood pressure (BP) of a person using only his photoplethysmogram (PPG) signal. We propose algorithms to better detect some critical ...points of the PPG signal, such as systolic and diastolic peaks, dicrotic notch and inflection point. These algorithms are applicable to different PPG signal morphologies and improve the precision of feature extraction. We show that the logarithm of dicrotic notch reflection index, the ratio of low- to high-frequency components of heart rate (HR) variability signal, and the product of HR multiplied by the modified Normalized Pulse Volume (mNPV) are the key features in accurately estimating the BP using PPG signal. Our proposed method has achieved higher accuracies in estimating BP compared to the previously reported methods that only use PPG signal. For the systolic BP, the achieved correlation coefficient between the estimated values and the real values is 0.78, the mean absolute error of the estimated values is 8.22 mmHg, and their standard deviation is 10.38 mmHg. For the diastolic BP, the achieved correlation coefficient between the estimated and the real values is 0.72, the mean absolute error of the estimated values is 4.17 mmHg, and their standard deviation is 4.22 mmHg. The achieved results fall within Grade A for diastolic, Grade C for systolic and Grade B for mean BP based on BHS standard.
In this paper, in order to control a nonlinear dynamic system via multi-model controller, we propose a systematic approach to determine the nominal local linear models. These models are selected from ...the local models bank and results in a reduced nominal models set that provides enough information to design a multi-model controller. To determine the initial local models bank, gap metric is used so that the distance between two successive local models is smaller than a threshold value. Then, a systematic approach that aims to get a reduced nominal models bank is developed. Based on this approach, first, a binary gap matrix is defined by combining gap metric and stability information. Then, several rows of this matrix are selected such that the sum of them becomes a non-zero vector. The proposed approach along with a designed robust controller is validated on a pH neutralization regarding to its highly nonlinear behavior.
The Volt/Var optimization (VVO) problem is used for scheduling the voltage regulation and reactive power compensation equipment in distribution networks to minimize power loss and voltage violation. ...In order to solve the VVO problem for a forthcoming time horizon, it is necessary to predict some parameters such as load demand and renewable energy production. The prediction of these parameters is always accompanied by uncertainty that robust optimization can be used to solve this concern. This paper presents a scenario‐based robust Volt/Var optimization (RVO) method that significantly reduces the number of scenarios required for the worst‐case approach. Solving the VVO problem with the worst‐case scenarios reduces the computational burden and maintains the voltage security of the distribution network against the severe events. The proposed RVO is formulated based on a mixed‐integer second‐order cone programming (MISOCP) model in which Volt/Var control (VVC) equipment is scheduled over a two‐stage strategy. The proposed method is validated using modified 33‐bus and 69‐bus IEEE test systems. The results demonstrate that the proposed RVO method maintains the network's voltage profile within the acceptable range against uncertainties.
This paper proposes a new RVO approach based on worst‐case scenarios that can coordinate the voltage and reactive power control equipment at different time stages to reduce voltage violation. Instead of using numerous scenarios to realize a specific robustness rate in the proposed method, only two scenarios (determined according to the worst‐case robust optimization approach) has been selected.
Immune escape, a process by which tumor cells evade immune surveillance, remains a challenge for cancer therapy. Tumor cells produce extracellular vesicles (EVs) that participate in immune escape by ...transferring bioactive molecules between cells. EVs refer to heterogeneous vesicles that participate in intercellular communication. EVs from tumor cells usually carry tumor antigens and have been considered a source of tumor antigens to induce anti-tumor immunity. However, evidence also suggests that these EVs can accelerate immune escape by carrying heat shock proteins (HSPs), programmed death-ligand 1 (PD-L1), etc. to immune cells, suppressing function and exhausting the immune cells pool. EVs are progressively being evaluated for therapeutic implementation in cancer therapies. EVs-based immunotherapies involve inhibiting EVs generation, using natural EVs, and harnessing engineering EVs. All approaches are associated with advantages and disadvantages. The EVs heterogeneity and diverse physicochemical properties are the main challenges to their clinical applications.
Although EVs are criminal; they can be useful for overcoming immune escape. This review discusses the latest knowledge on EVs population and sheds light on the function of tumor-derived EVs in immune escape. It also describes EVs-based immunotherapies with a focus on engineered EVs, followed by challenges that hinder the clinical translation of EVs that are essential to be addressed in future investigations. Video Abstract.
This paper develops a novel instrumented urethral catheter with an array of force sensors for measuring the distributed pressure in a human urethra. The catheter and integrated portions of the force ...sensors are fabricated by the use of 3D printing using a combination of both soft and hard polymer substrates. Other portions of the force sensors consisting of electrodes and electrolytes are fabricated separately and assembled on top of the 3D-printed catheter to create a soft flexible device. The force sensors use a novel supercapacitive (iontronic) sensing mechanism in which the contact area between a pair of electrodes and a paper-based electrolyte changes in response to force. This provides a highly sensitive measure of force that is immune to parasitic noise from liquids. The developed catheter is tested using a force calibration test rig, a cuff-based pressure application device, an extracted bladder and urethra from a sheep and by dipping inside a beaker of water. The force sensors are found to have a sensitivity of 30–50 nF/N, which is 1000 times larger than that of traditional capacitive force sensors. They exhibit negligible capacitance change when dipped completely in water. The pressure cuff tests and the extracted sheep tissue tests also verify the ability of the sensor array to work reliably in providing distributed force measurements. The developed catheter could help diagnose ailments related to urinary incontinence and inadequate urethral closure pressure.
Image retargeting is the task of making images capable of being displayed on screens with different sizes. This work should be done so that high-level visual information and low-level features such ...as texture remain as intact as possible to the human visual system. At the same time, the output image may have different dimensions. Thus, simple methods such as scaling and cropping are not adequate for this purpose. In recent years, researchers have tried to improve the existing retargeting methods, and they have introduced new ones. However, a specific method cannot be utilized to retarget all types of images. In other words, different images require different retargeting methods. Image retargeting has a close relationship to image saliency detection, which is a relatively new image processing task. Earlier saliency detection methods were based on local and global but low-level image information. These methods are called bottom-up processes. On the other hand, newer approaches are top-down and mixed methods that consider the high level and semantic knowledge of the image too. In this paper, we introduce the proposed methods in both saliency detection and retargeting. For the saliency detection, the use of image context and semantic segmentation are examined, and a novel mixed bottom-up and top-down saliency detection method is introduced. After saliency detection, a modified version of an existing retargeting technique is utilized for retargeting the images. The results suggest that the proposed image retargeting pipeline has excellent performance compared to other tested methods. Also, the subjective evaluations on the Pascal dataset can be used as a retargeting quality assessment dataset for further research.
Eukaryotic cells produce extracellular vesicles (EVs) mediating intercellular communication. These vesicles encompass many bio-molecules such as proteins, nucleic acids, and lipids that are ...transported between cells and regulate pathophysiological actions in the recipient cell. Exosomes originate from multivesicular bodies inside cells and microvesicles shed from the plasma membrane and participate in various pathological conditions. Retroviruses such as Human Immunodeficiency Virus -type 1 (HIV-1) and Human T-cell leukemia virus (HTLV)-1 engage exosomes for spreading and infection. Exosomes from virus-infected cells transfer viral components such as miRNAs and proteins that promote infection and inflammation. Additionally, these exosomes deliver virus receptors to target cells that make them susceptible to virus entry. HIV-1 infected cells release exosomes that contribute to the pathogenesis including neurological disorders and malignancy. Exosomes can also potentially carry out as a modern approach for the development of HIV-1 and HTLV-1 vaccines. Furthermore, as exosomes are present in most biological fluids, they hold the supreme capacity for clinical usage in the early diagnosis and prognosis of viral infection and associated diseases. Our current knowledge of exosomes' role from virus-infected cells may provide an avenue for efficient retroviruses associated with disease prevention. However, the exact mechanism involved in retroviruses infection/ inflammation remains elusive and related exosomes research will shed light on the mechanisms of pathogenesis.
There remains a vital necessity for new therapeutic approaches to combat metastatic cancers, which cause globally over 8 million deaths per year. Mesenchymal stem cells (MSCs) display aptitude as new ...therapeutic choices for cancer treatment. Exosomes, the most important mediator of MSCs, regulate tumor progression. The potential of harnessing exosomes from MSCs (MSCs-Exo) in cancer therapy is now being documented. MSCs-Exo can promote tumor progression by affecting tumor growth, metastasis, immunity, angiogenesis, and drug resistance. However, contradictory evidence has suggested that MSCs-Exo suppress tumors through several mechanisms. Therefore, the exact association between MSCs-Exo and tumors remains controversial. Accordingly, the applications of MSCs-Exo as novel drug delivery systems and standalone therapeutics are being extensively explored. In addition, engineering MSCs-Exo for targeting tumor cells has opened a new avenue for improving the efficiency of antitumor therapy. However, effective implementation in the clinical trials will need the establishment of standards for MSCs-Exo isolation and characterization as well as loading and engineering methods. The studies outlined in this review highlight the pivotal roles of MSCs-Exo in tumor progression and the promising potential of MSCs-Exo as therapeutic drug delivery vehicles for cancer treatment.
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