Nanomembrane‐Based,Thermal‐Transport Biosensor for Living Cells

Knowledge of materials' thermal‐transport properties, conductivity and diffusivity, is crucial for several applications within areas of biology, material science and engineering. Specifically, a microsized, flexible, biologically integrated thermal transport sensor is beneficial to a plethora of applications, ranging across plants physiological ecology and thermal imaging and treatment of cancerous cells, to thermal dissipation in flexible semiconductors and thermoelectrics. Living cells pose extra challenges, due to their small volumes and irregular curvilinear shapes. Here a novel approach of simultaneously measuring thermal conductivity and diffusivity of different materials and its applicability to single cells is demonstrated. This technique is based on increasing phonon‐boundary‐scattering rate in nanomembranes, having extremely low flexural rigidities, to induce a considerable spectral dependence of the bandgap‐emission over excitation‐laser intensity. It is demonstrated that once in contact with organic or inorganic materials, the nanomembranes' emission spectrally shift based on the material's thermal diffusivity and conductivity. This NM‐based technique is further applied to differentiate between different types and subtypes of cancer cells, based on their thermal‐transport properties. It is anticipated that this novel technique to enable an efficient single‐cell thermal targeting, allow better modeling of cellular thermal distribution and enable novel diagnostic techniques based on variations of single‐cell thermal‐transport properties.     

A comprehensive study on the size-dependent hygrothermal analysis of exponentially graded microplates on elastic foundations

Abstract

In this paper, the effects of hygrothermal conditions on various behaviors, such as bending, free vibration, mechanical and thermal buckling, of exponentially graded microplates lying on two-parameter elastic foundations are investigated. The trigonometric four-variable plate theory incorporated to the modified couple stress theory (MCST) is employed to derive the equations of motion. The present MCST contains an internal material length scale parameter, thus it can capture the size effect. The microplate is assumed to be subjected to a temperature rise and moisture concentration which are varied linearly through the thickness of the plate. Based on an exponential law, the material properties of the microplate are graded only in z direction. The equations of motion are solved analytically to obtain the displacements, stresses, eigenfrequencies and critical buckling load and temperature of the microplates. The present results are validated by comparing them with those previously published. The numerical examples reveal that considering the size effect and/or the elastic foundations leads to an increment in plate stiffness and thereby leads to a decrement in the deflection and an increment in eigenfrequency and buckling loads. It is also shown that the size effect is negligible for the thicker plate.     

Constrained model predictive control for time-varying delay systems: Application to an active car suspension

This study investigates the problem of robust model predictive control (RMPC) for active suspension systems with time-varying delays and input constraints. The uncertainty is of convex polytopic type. Based on the Lyapunov-Krasovskii functional method, sufficient stability conditions of the time-varying delays systems are derived by linear matrix inequalities (LMIs) terms. At each time set, a feasible state feedback is obtained by minimizing an upper bound of the ‘worst-case’ quadratic objective function over an infinite horizon subject to constraints on inputs. Finally, a quarter-vehicle model is exploited to demonstrate the effectiveness of the proposed method.     

Intelligent system for visual web content analytics: A new approach and case study

The accuracy of searches for visual data elements, as well as other types of information, depends on the terms used by the user in the input query to retrieve the relevant results and to reduce the irrelevant ones. Most of the results that are returned are relevant to the query terms, but not to their meaning. For example, certain types of web contents hold hidden information that traditional search engines are unable to retrieve. Searching for the mathematical construct of 1/x using Google will not result in the retrieval of the documents that contain the mathematically equivalent expressions (i.e. x^?1). Because conventional search engines fall short of providing math-search capabilities. One of these capabilities is the ability of these search engines to detect the mathematical equivalence between users’ quires and math contents. In addition, users sometimes need to use slang terms, either to retrieve slang-based visual data (e.g. social media content) or because they do not know how to write using classical form. To solve such a problem, this paper proposed an AI-based system for analysing multilingual slang web contents so as to allow a user to retrieve web slang contents that are relevant to the user’s query. The proposed system presents an approach for visual data analytics, and it also enables users to analyse hundreds of potential search results/web pages by starting an informed friendly dialogue and presenting innovative answers.     

Synthesis and Anti-Cancer Activity of New Pyrazolinyl-Indole Derivatives: Pharmacophoric Interactions and Docking Studies for Identifying New EGFR Inhibitors

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the ¹H NMR, ¹³C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells’ growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.     

The Role of Antibodies in the Treatment of SARS-CoV-2 Virus Infection,and Evaluating Their Contribution to Antibody-Dependent Enhancement of Infection

Antibodies play a crucial role in the immune response, in fighting off pathogens as well as helping create strong immunological memory. Antibody-dependent enhancement (ADE) occurs when non-neutralising antibodies recognise and bind to a pathogen, but are unable to prevent infection, and is widely known and is reported as occurring in infection caused by several viruses. This narrative review explores the ADE phenomenon, its occurrence in viral infections and evaluates its role in infection by SARS-CoV-2 virus, which causes coronavirus disease 2019 (COVID-19). As of yet, there is no clear evidence of ADE in SARS-CoV-2, though this area is still subject to further study.     

Detection of Porphyrins in Hair Using Capillary Liquid Chromatography-Mass Spectrometry

Unlike humans, some animals have evolved a physiological ability to deposit porphyrins, which are pigments produced during heme synthesis in cells, in the skin and associated integument such as hair. Given the inert nature and easiness of collection of hair, animals that present porphyrin-based pigmentation constitute unique models for porphyrin analysis in biological samples. Here we present the development of a simple, rapid, and efficient analytical method for four natural porphyrins (uroporphyrin I, coproporphyrin I, coproporphyrin III and protoporphyrin IX) in the Southern flying squirrel Glaucomys volans, a mammal with hair that fluoresces and that we suspected has porphyrin-based pigmentation. The method is based on capillary liquid chromatography-mass spectrometry (CLC-MS), after an extraction procedure with formic acid and acetonitrile. The resulting limits of detection (LOD) and quantification (LOQ) were 0.006–0.199 and 0.021–0.665 µg mL⁻¹, respectively. This approach enabled us to quantify porphyrins in flying squirrel hairs at concentrations of 3.6–353.2 µg g⁻¹ with 86.4–98.6% extraction yields. This method provides higher simplicity, precision, selectivity, and sensitivity than other methods used to date, presenting the potential to become the standard technique for porphyrin analysis.     

A novel energy‐aware routing mechanism for SDN‐enabled WSAN

Energy consumption is one of the most important design constraints when building a wireless sensor and actuator network since each device in the network has a limited battery capacity, and prolonging the lifetime of the network depends on saving energy. Overcoming this challenge requires a smart and reconfigurable network energy management strategy. The Software‐Defined Networking (SDN) paradigm aims at building a flexible and dynamic network structure, especially in wireless sensor networks. In this study, we propose an SDN‐enabled wireless sensor and actuator network architecture that has a new routing discovery mechanism. To build a flexible and energy‐efficient network structure, a new routing decision approach that uses a fuzzy‐based Dijkstra's algorithm is developed in the study. The proposed architecture can change the existing path during data transmission, which is the key property of our model and is achieved through the adoption of the SDN approach. All the components and algorithms of the proposed system are modeled and simulated using the Riverbed Modeler software for more realistic performance evaluation. The results indicate that the proposed SDN‐enabled structure with fuzzy‐based Dijkstra's algorithm outperforms the one using the regular Dijkstra's and the ZigBee‐based counterpart, in terms of the energy consumption ratio, and the proposed architecture can provide an effective cluster routing while prolonging the network lifetime.     

Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro,In Vivo and Clinical Studies

Chemoradiation-induced mucositis is a debilitating condition of the gastrointestinal tract eventuating from antineoplastic treatment. It is believed to occur primarily due to oxidative stress mechanisms, which generate Reactive Oxygen Species (ROS). The aim of this scoping review was to assess the role of oxidative stress in the development of Oral Mucositis (OM). Studies from the literature, published in MEDLINE and SCOPUS, that evaluated the oxidative stress pathways or antioxidant interventions for OM, were retrieved to elucidate the current understanding of their relationship. Studies failing inclusion criteria were excluded, and those suitable underwent data extraction, using a predefined data extraction table. Eighty-nine articles fulfilled criteria, and these were sub-stratified into models of study (in vitro, in vivo, or clinical) for evaluation. Thirty-five clinical studies evaluated antioxidant interventions on OM’s severity, duration, and pain, amongst other attributes. A number of clinical studies sought to elucidate the protective or therapeutic effects of compounds that had been pre-determined to have antioxidant properties, without directly assessing oxidative stress parameters (these were deemed “indirect evidence”). Forty-seven in vivo studies assessed the capacity of various compounds to prevent OM. Findings were mostly consistent, reporting reduced OM severity associated with a reduction in ROS, malondialdehyde (MDA), myeloperoxidase (MPO), but higher glutathione (GSH) and superoxide dismutase (SOD) activity or expression. Twenty-one in vitro studies assessed potential OM therapeutic interventions. The majority demonstrated successful a reduction in ROS, and in select studies, secondary molecules were assessed to identify the mechanism. In summary, this review highlighted numerous oxidative stress pathways involved in OM pathogenesis, which may inform the development of novel therapeutic targets.     

Blocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma

Simple SummaryMembrane-associated PCNA is expressed on the surface of human MM cell lines and primary MM cells. Mab 14-25-9 interacts with membrane-associated PCNA and blocks its binding to NK-expressed NKp44, thus activating NK function. We showed that mAb 14-25-9 can serve as an immune checkpoint blocker, enhancing the function of NK cells on target human MM cell lines and primary cells.AbstractMultiple Myeloma (MM) is a devastating malignancy that evades immune destruction using multiple mechanisms. The NKp44 receptor interacts with PCNA (Proliferating Cell Nuclear Antigen) and may inhibit NK cells’ functions. Here we studied in vitro the expression and function of PCNA on MM cells. First, we show that PCNA is present on the cell membrane of five out of six MM cell lines, using novel anti-PCNA mAb developed to recognize membrane-associated PCNA. Next, we stained primary bone marrow (BM) mononuclear cells from MM patients and showed significant staining of membrane-associated PCNA in the fraction of CD38⁺CD138⁺ BM cells that contain the MM cells. Importantly, blocking of the membrane PCNA on MM cells enhanced the activity of NK cells, including IFN-γ-secretion and degranulation. Our results highlight the possible blocking of the NKp44-PCNA immune checkpoint by the mAb 14-25-9 antibody to enhance NK cell responses against MM, providing a novel treatment option.