Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro

Increasing outbreaks of new pathogenic viruses have promoted the exploration of novel alternatives to time-consuming vaccines. Thus, it is necessary to develop a universal approach to halt the spread of new and unknown viruses as they are discovered. One such promising approach is to target lipid membranes, which are common to all viruses and bacteria. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reaffirmed the importance of interactions between the virus envelope and the host cell plasma membrane as a critical mechanism of infection. Metadichol®, a nanolipid emulsion of long-chain alcohols, has been demonstrated as a strong candidate that inhibits the proliferation of SARS-CoV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce viral infectivity, including that of coronaviruses (such as SARS-CoV-2) by modifying their lipid-dependent attachment mechanism to human host cells. The receptor ACE2 mediates the entry of SARS-CoV-2 into the host cells, whereas the serine protease TMPRSS2 primes the viral S protein. In this study, Metadichol® was found to be 270 times more potent an inhibitor of TMPRSS2 ( E C 50 = 96 ng / mL ) than camostat mesylate ( E C 50 = 26000 ng / mL ). Additionally, it inhibits ACE with an EC50 of 71 ng/mL, but it is a very weak inhibitor of ACE2 at an EC50 of 31 μg/mL. Furthermore, the live viral assay performed in Caco-2 cells revealed that Metadichol® inhibits SARS-CoV-2 replication at an EC90 of 0.16 μg/mL. Moreover, Metadichol® had an EC90 of 0.00037 μM, making it 2081 and 3371 times more potent than remdesivir ( E C 50 = 0.77 μ M ) and chloroquine ( E C 50 = 1.14 μ M ), respectively.

Design and Development of AI based Approach for Histopathology Cancer Screening and Identification

Cancer is a heterogeneous disorder comprising various types and sub-types. Early detection, screening, and diagnosis of cancer types are necessary for facilitating cancer research in early diagnosis, management, and the evolution of successful therapies. Existing methodologies were only able to classify and diagnose a single variety of cancer based on a homogeneous dataset but more focused on predicting patient survivability then cure. This research defines a machine learning-based methodology to develop an universal approach in diagnosis, detection, symptoms-based prediction, and screening of histopathology cancer, their types, and sub types using a heterogeneous dataset based on images and scans. In this architecture, we use VGG-19 based 3D-Convolutional Neural Network for deep feature extraction and later perform regression using a random forest algorithm. We create a heterogeneous dataset consisting of results from laboratory tests, imaging tests and biopsy reports, not only relying on clinical images. Initially, we categorize tumors and lesions as benign or malignant and classify the malignant lesions into their sub-types, detecting their severity and growth rate. Our system is designed to predict risk at multiple time-points, leverage optional risk factors if they are available and produce predictions that are consistent across mammography machines. We found the classification accuracy for categorizing tumors as cancerous to be 95% whereas the accuracy for classification of malignant lesions into their sub-types to be 94%..

Operationalizing the Exposome Using Passive Silicone Samplers

The exposome, which is defined as the cumulative effect of environmental exposures and corresponding biological responses, aims to provide a comprehensive measure for evaluating non-genetic causes of disease. Operationalization of the exposome for environmental health and precision medicine has been limited by the lack of a universal approach for characterizing complex exposures, particularly as they vary temporally and geographically. To overcome these challenges, passive sampling devices (PSDs) provide a key measurement strategy for deep exposome phenotyping, which aims to provide comprehensive chemical assessment using untargeted high-resolution mass spectrometry for exposome-wide association studies. To highlight the advantages of silicone PSDs, we review their use in population studies and evaluate the broad range of applications and chemical classes characterized using these samplers. We assess key aspects of incorporating PSDs within observational studies, including the need to preclean samplers prior to use to remove impurities that interfere with compound detection, analytical considerations, and cost. We close with strategies on how to incorporate measures of the external exposome using PSDs, and their advantages for reducing variability in exposure measures and providing a more thorough accounting of the exposome. Continued development and application of silicone PSDs will facilitate greater understanding of how environmental exposures drive disease risk, while providing a feasible strategy for incorporating untargeted, high-resolution characterization of the external exposome in human studies.

Universal approach to in situ light-coupled NMR spectroscopy without fibre optics

In situ illumination of liquid-state nuclear magnetic resonance (NMR) samples makes it possible for a wide range of light-dependent chemical and biological phenomena to be studied by the powerful analytical technique. However, the position of an NMR sample deep within the bore of the spectrometer magnet renders such illumination challenging. Here, we demonstrate a photo-NMR insert device (NMRtorch) where a lighthead containing an LED array is attached directly to the top of an NMRtorch tube. The wall of the tube itself acts as a light guide, illuminating the sample from the outside. We explore how this new setup performs in a number of photo-NMR applications, including photoisomerisation and photo-chemically induced dynamic nuclear polarisation (photo-CIDNP), and demonstrate the potential for ultraviolet (UV) degradation studies with continuous online NMR assessment. This setup enables users of any typical liquid-state spectrometer to easily perform in situ photo-NMR experiments, using a wide range of wavelengths.

Unspoken Modernity: Bamboo-Reinforced Concrete, China 1901-40

Engineering science in the China of 1901-40 had unique characteristics that disrupt the idea of a universal approach to its history.1 The following case study describes the ideas and trials of introducing bamboo into the seemingly globalised technology of reinforced concrete—an innovation developed across the borders of mechanical, naval, civil, and aeronautical engineering. The article showcases a way of knowing and working by twentieth century engineers that has not been fully acknowledged, and is not only a phenomenon of China. While bamboo was a complicated and somewhat marginal object for engineering, it did make the European concrete technology more viable in the construction sites of China, and stimulate engineers’ experimental and resourceful spirit in mobilising both craft and scientific knowledge. It also opened up a challenge to engineering science of the time.

Full Text Search Setup on a Website

ntroduction. When implementing the search for text fragments on the site, approaches are used that are different in complexity and performance. There is also a sequence of related tasks: choosing a text indexing option, sending a text for indexing, selecting texts for indexing specifically from the CMS database, choosing a search engine, and others. These approaches do not always provide satisfactory search results. Purpose. The purpose of the article is to the description of existing solutions for full-text search on a website, their advantages, and disadvantages. Development of a full-text search algorithm using the Elasticsearch system. Methods. Analysis of approaches to the implementation of full-text search on a website, varying in complexity and performance. Identification of flaws and vulnerabilities in more primitive approaches and the development of more advanced and complex algorithms that eliminate the identified deficiencies. Step-by-step implementation of full-text search using third-party systems. Results. A method for implementing full-text search using Elasticsearch is described. The advantage of the new approach is the asynchronous sending of the page content and its address to a specific service responsible for communication with Elasticsearch. This allows you not to block the normal work with the CMS and not depend on the availability of the indexing service. The approach described in the article is flexible and adaptable for various website architectures. Asynchronous processing of indexing requests ensures high query execution speed and system fault tolerance. Conclusions. The article discusses various approaches to implementing full-text search on a website, their advantages and disadvantages. Based on the analysis, a more flexible and universal approach to the implementation of a full-text search system has been developed. A solution is proposed with step-by-step implementation and setup of advanced full-text search using Elasticsearch.

Optical, Thermal, and Mechanical Properties of (Y1-xScx)2O3 Transparent Ceramics

Sesquioxides such as Y2O3 and Sc2O3 are important optical materials, but the fabrication of their transparent ceramics remains a challenge due to the ultra-high melting point of over 2400 oC. In this work, a series of (Y1-xScx)2O3 transparent ceramics were successfully fabricated by a simple vacuum sintering process without any sintering additives, and the effect of Scandium (Sc) content on the crystal structure and optical/thermal/mechanical properties were evaluated. Y2O3 and Sc2O3 form a complete solid solution with a cubic bixbyite structure. The formation of (Y1-xScx)2O3 solid solution promotes the densification of ceramics, leading to the realization of high transparency close to the theoretical transmittance over a wide wavelength range of 0.35-8 mm. In particular, the in-line transmittance in the range of 0.6-6 mm remains above 80% for (Y1-xScx)2O3 with x = 0.23-0.31, while the pristine Y2O3 and Sc2O3 are opaque. Moreover, the mechanical properties including Vickers hardness (Hv), fracture toughness (KIC), and biaxial strength (δb) are evidently enhanced due to the solid solution strengthening, while the thermal conductivity is reduced due to the reduction of photon free path. This study demonstrates that forming of solid solution is a facile and universal approach for preparing sesquioxides transparent ceramics with high optical and mechanical quality.

Enterprise capital - Definition, theory and determinants of the structure

Purpose of the study: The main goal of the article is to define the company's capital, the concept of which in the literature is insignificant and broad. The subject of the research is also the characteristics of the capital structure and the factors that determine it. Methodology: The main research method was a critical review of the literature in the field of shaping the capital structure of enterprises, also in the perspective of the evolution of the theory of the optimal capital structure and the factors determining it. Main findings: The most common definition of capital describes this concept as a source of financing for the activities of an enterprise, and therefore equates it with the balance sheet concept of liabilities. The sources of origin of funds financing business activities forces the managers to search for their optimal structure ensuring the proper relationship between the planned profit and the acceptable level of risk. The literature presents many theories of capital structure and factors shaping it. When shaping the share of equity and borrowed capital in the total of liabilities, one should take into account the business sector of the enterprise, its environment and the risk appetite of the managers. Application of the study: The presented attempt to define the company's capital is in line with the considerations on this subject so far and aims to standardize this concept in the literature. The cross-section of the theory of capital structure allows for a historical approach to this issue and confirmation of the multidimensionality of the presented issues. The presented factors shaping the capital structure of enterprises specify the areas on which managers should focus when looking for an optimal relationship of equity and foreign capital. Originality/Novelty of the study: The issue of defining capital and its optimal structure is not new in the literature. However, it requires permanent analysis, which is conditioned by the volatility of macroeconomic and microeconomic conditions. Difficulties in a universal approach to this subject also force detailed research in specific industries and economic conditions.