COVIDomic: A multi-modal cloud-based platform for identification of risk factors associated with COVID-19 severity.

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in December 2019 in Wuhan, China. It was quickly established that both the symptoms and the disease severity may vary from one case to another and several strains of SARS-CoV-2 have been identified. To gain a better understanding of the wide variety of SARS-CoV-2 strains and their associated symptoms, thousands of SARS-CoV-2 genomes have been sequenced in dozens of countries. In this article, we introduce COVIDomic, a multi-omics online platform designed to facilitate the analysis and interpretation of the large amount of health data collected from patients with COVID-19. The COVIDomic platform provides a comprehensive set of bioinformatic tools for the multi-modal metatranscriptomic data analysis of COVID-19 patients to determine the origin of the coronavirus strain and the expected severity of the disease. An integrative analytical workflow, which includes microbial pathogens community analysis, COVID-19 genetic epidemiology and patient stratification, allows to analyze the presence of the most common microbial organisms, their antibiotic resistance, the severity of the infection and the set of the most probable geographical locations from which the studied strain could have originated. The online platform integrates a user friendly interface which allows easy visualization of the results. We envision this tool will not only have immediate implications for management of the ongoing COVID-19 pandemic, but will also improve our readiness to respond to other infectious outbreaks.

Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology, and Target Identification of Thiowurtzine, a Potent Inhibitor of the Opioid Receptors and the Ion Channels.

The number of candidate molecules for new non-narcotic analgesics is extremely limited. Here, we report the identification of thiowurtzine, a new potent analgesic molecule with promising application in chronic pain treatment. We describe the chemical synthesis of this unique compound derived from the hexaazaisowurtzitane (CL-20) explosive molecule. Then, we use animal experiments to assess its analgesic activity in vivo upon chemical, thermal, and mechanical exposures, compared to the effect of several reference drugs. Finally, we investigate the potential receptors of thiowurtzine in order to better understand its complex mechanism of action. We use docking, molecular modeling, and molecular dynamics simulations to identify and characterize the potential targets of the drug and confirm the results of the animal experiments. Our findings finally indicate that thiowurtzine may have a complex mechanism of action by essentially targeting the mu opioid receptor, the TRPA1 ion channel, and the Cav voltage-gated calcium channel.

Sensor data fusion for responsive high resolution ultrasonic temperature measurement using piezoelectric transducers.

Ultrasonic temperature measurement allows for responsive measurements across an entire ultrasonic pathway, unlike most conventional temperature sensors that respond to the temperature at the point of their placement only after a notable response time. The high cost of required ultrasonic instrumentation can be reduced substantially by using ultrasonic oscillating temperature sensors (UOTS) consisting of inexpensive narrowband piezo transducers and driving electronics. An UOTS produces sustained oscillations at a frequency that relates to the temperature of the medium between the transducers. The existence of thermal hysteresis in UOTS readings, observed experimentally and apparently related to the fundamental properties of piezoelectric materials, makes conversion of the output frequency readings to the temperature values ambiguous. This makes it complicated to calibrate and use UOTS on their own. In the reported experiment (heating, then naturally cooling of a water vessel equipped with both UOTS and conventional sensors), this hysteresis was solved by fusing UOTS data with conventional temperature sensor readings. As the result, the combination of one UOTS plus one conventional reference sensor allowed improving both the temperature resolution and responsiveness of the latter and ambiguity of the readings of the former. Data fusion effectively led to calibrating the UOTS at every change of the conventional sensor's reading, removing any concerns related to the thermal expansion/contraction of the ultrasonic pathway itself and/or hysteresis of piezoelectric transducers.

Combined Antibacterial Effects of Goat Cathelicidins With Different Mechanisms of Action.

Being essential components of innate immune system, animal antimicrobial peptides (AMPs) also known as host-defense peptides came into sharp focus as possible alternatives to conventional antibiotics due to their high efficacy against a broad range of MDR pathogens and low rate of resistance development. Mammalian species can produce a set of co-localized AMPs with different structures and mechanisms of actions. Here we examined the combined antibacterial effects of cathelicidins, structurally diverse family of host-defense peptides found in vertebrate species. As a model we have used structurally distinct cathelicidins expressed in the leukocytes of goat Capra hircus. The recombinant analogs of natural peptides were obtained by heterologous expression in bacterial system and biological activities as well as the major mechanisms of antibacterial action of the peptides were investigated. As the result, the marked synergistic effect against wide panel of bacterial strains including extensively drug-resistant ones was observed for the pair of membranolytic α-helical amphipathic peptide ChMAP-28 and Pro-rich peptide mini-ChBac7.5Nα targeting a bacterial ribosome. ChMAP-28 was shown to damage the outer bacterial membrane at sub-inhibitory concentrations that could facilitate Pro-rich peptide translocation into the cell. Finally, resistance changes under a long-term continuous selective pressure of each individual peptide and the synergistic combination of both peptides were tested against Escherichia coli strains. The combination was shown to keep a high activity after the 26-days selection experiment in contrast to mini-ChBac7.5Nα used alone and the reference antibiotic polymyxin B. We identified the point mutation leading to amino acid substitution V102E in the membrane transport protein SbmA of the mini-ChBac7.5Nα-resistant strain obtained by selection. The experiments revealed that the presence of sub-inhibitory concentrations of ChMAP-28 restored the activity of mini-ChBac7.5Nα against this strain and clinical isolate with a weak sensitivity to mini-ChBac7.5Nα. The obtained results suggest a potential medical application of synergistic combinations of natural cathelicidins, which allows using a lower therapeutic dose and minimizes the risk of resistance development.

Chloroflexus islandicus sp. nov., a thermophilic filamentous anoxygenic phototrophic bacterium from a geyser.

A novel, thermophilic filamentous anoxygenic phototrophic bacterium, strain isl-2T, was isolated from the Strokkur Geyser, Iceland. Strain isl-2T formed unbranched multicellular filaments with gliding motility. The cells formed no spores and stained Gram-negative. The existence of pili was described in a species of the genus Chloroflexus for the first time, to our knowledge. Optimal growth occurred at a pH range of 7.5-7.7 and at a temperature of 55 °C. Strain isl-2T grew photoheterotrophically under anaerobic conditions in the light and chemoheterotrophically under aerobic conditions in the dark. The major cellular fatty acids were C18 : 1ω9, C16 : 0, C18 : 0 and C18 : 0-OH. The major quinone was menaquinone-10. The photosynthetic pigments were bacteriochlorophylls c and a as well as ß- and γ-carotenes. The results of phylogenetic analysis of the 16S rRNA gene sequences placed strain isl-2T into the genus Chloroflexus of the phylum Chloroflexi with Chloroflexus aggregans DSM 9485T as the closest relative (97.0 % identity). The whole-genome sequence of isl-2T was determined. Average nucleotide identity values obtained for isl-2T in comparison to available genomic sequences of other strains of members of the genus Chloroflexus were 81.4 % or less and digital DNA-DNA hybridisation values 22.8 % or less. The results of additional phylogenetic analysis of the PufLM and BchG amino acid sequences supported the separate position of the isl-2T phylotype from the phylotypes of other members of the genus Chloroflexus. On the basis of physiological and phylogenetic data as well as genomic data, it was suggested that isl-2T represents a novel species within the genus Chloroflexus, with the proposed name Chloroflexus islandicus sp. nov. The type strain of the species is isl-2T (=VKM B-2978T,=DSM 29225T,=JCM 30533T).

Filamentous anoxygenic phototrophic bacteria from cyanobacterial mats of Alla hot springs (Barguzin Valley, Russia).

Alkaline hydrotherms of the Baikal rift zone are unique systems to study the diversity of thermophilic bacteria. In this study, we present data on the phototrophic bacterial community of cyanobacterial mats from the alkaline Alla hot spring. Using a clonal analysis approach, this study evaluated the species diversity, the proportion of oxygenic and anoxygenic phototrophs and their distribution between various areas of the spring. Novel group-specific PCR primers were designed and applied to detect representatives of the Chloroflexus and Roseiflexus genera in mat samples. For the first time, the presence of Roseiflexus-like bacteria was detected in the Baikal rift zone.

Shikimic acid: review of its analytical, isolation, and purification techniques from plant and microbial sources.

Shikimic acid properties and its available analytical techniques are discussed. Plants having the highest content of shikimic acid are shown. The existing isolation methods are analyzed and the most optimal approaches to extracting this acid from natural sources (plants and microorganisms) are considered.

Diffractive-refractive correction units for plastic compact zoom lenses.

A method of designing a plastic zoom lens with a diffractive-refractive hybrid corrector, comprising one diffractive lens and one refractive lens, is described. The efficiency of this method is demonstrated by designing a compact zoom lens for a mobile phone. This zoom design, incorporating lenses made only of two commercial optical plastics (polymethylmethacrylate and polycarbonate), provides high optical performance.

Ultrasonic sensing of temperature of liquids using inexpensive narrowband piezoelectric transducers.

We investigated the possibility of substantially reducing the cost of minimally invasive ultrasonic non-destructive evaluation (NDE) of liquids, in particular, temperature sensing, using inexpensive narrowband transducers. Although designed for operation in air, ultrasonic transducers enclosed in an aluminum case could be submerged in water and were found to be suitable for this application; however, their responses changed substantially when submerged. The test cell developed was complemented by an amplifier to operate as an oscillator and some other support electronics to supervise the sensor's operation. The sensor was tested in temperatures ranging from 26 to 32°C at a nominal central frequency of 330 kHz and showed a sensitivity of around 280 Hz/K.

Ultrasonic monitoring of foamed polymeric tissue scaffold fabrication.

Polymeric tissue scaffolds are central to many regenerative medicine therapies offering a new approach to medicine. As the number of these regenerative therapies increases there is a pressing need for an improved understanding of the methods of scaffold fabrication. Of the many approaches to processing scaffolds, supercritical fluid fabrication methods have a distinct advantage over other techniques as they do not require the use of organic solvents, elevated processing temperatures or leaching processes. The work presented here is centred on the development of a new approach to monitoring supercritical scaffold fabrication based on determination of the scaffold acoustic impedance to inform protocols for scaffold fabrication. The approach taken uses an ultrasonic pulse-echo reflectometer enabling non-invasive monitoring of the supercritical environment on-line. The feasibility of this approach was investigated for two scaffolds of different molecular weight. Acoustic results demonstrate that differences in the physical properties of the two scaffolds could be resolved, particularly during the foaming process which correlated with findings from time-lapsed imaging and micro X-ray computed tomography (micro X-ray CT) images. Thus, this work demonstrates the feasibility of ultrasonic pulse-echo reflectometry to non-invasively study supercritical scaffold fabrication on-line providing a greater understanding of the scaffold fabrication process.

High-accuracy data acquisition architectures for ultrasonic imaging.

This paper proposes a novel architecture for a data acquisition system intended to support the next generation of ultrasonic imaging instruments operating at or above 100 MHz. Existing systems have relatively poor signal-to-noise ratios and are limited in terms of their maximum data sampling rate, both of which are improved by a combination of embedded averaging and embedded interleaved sampling. "On-the-fly" pipelined operation minimizes control overheads for signal averaging. A two-clock sampling timing system provides for effective sampling rates that are a factor of 20 or more above the basic sampling rate of the analog-to-digital converter (ADC). The system uses commercial field-programmable gate array devices operated at clock frequencies commensurable with the ADC clock. Implementation is via the Xilinx Xtreme digital signal processing development kit, available at low cost. Sample rates of up to 2160 MHz have been achieved in combination with up to 16384 coherent averages using the above-mentioned off-the-shelf hardware.

Cloning, sequencing, expression, and characterization of protealysin, a novel neutral proteinase from Serratia proteamaculans representing a new group of thermolysin-like proteases with short N-terminal region of precursor.

The gene of Serratia proteamaculans proteinase, protealysin, was cloned, sequenced, and expressed in Escherichia coli. The gene encoded a precursor of 341 amino acids (AAs) with a significant homology to thermolysin-like proteinases (TLPs). The molecular weight of the purified mature active recombinant protein was 32 kDa, the N-terminal amino acid sequence was AKTSTGGEVI. The optimum pH for azocasein hydrolysis by protealysin was seven and it was completely inhibited by o-phenanthroline. The enzyme hydrolyzed 3-(2-furyl)acryloyl-glycyl-L-leucine amide, the standard substrate for TLPs, with k(cat)/K(m) ratio of (2.52 +/- 0.02) x 10(2) M(-1) s(-1). Protealysin maturation removes 50 AA from the N-terminus of the precursor. The removed region had no similarity with the preprosequence of thermolysin (232 AA) but was homologous to some other TLPs. These proteins shared a conserved 7-AA motif near the initial methionine. Such motif was also found in some nonproteolytic putative proteins; two of them were eukaryotic.

Errors and uncertainties in the measurement of ultrasonic wave attenuation and phase velocity.

This paper presents an analysis of the error generation mechanisms that affect the accuracy of measurements of ultrasonic wave attenuation coefficient and phase velocity as functions of frequency. In the first stage of the analysis we show that electronic system noise, expressed in the frequency domain, maps into errors in the attenuation and the phase velocity spectra in a highly nonlinear way; the condition for minimum error is when the total measured attenuation is around 1 Neper. The maximum measurable total attenuation has a practical limit of around 6 Nepers and the minimum measurable value is around 0.1 Neper. In the second part of the paper we consider electronic noise as the primary source of measurement error; errors in attenuation result from additive noise whereas errors in phase velocity result from both additive noise and system timing jitter. Quantization noise can be neglected if the amplitude of the additive noise is comparable with the quantization step, and coherent averaging is employed. Experimental results are presented which confirm the relationship between electronic noise and measurement errors. The analytical technique is applicable to the design of ultrasonic spectrometers, formal assessment of the accuracy of ultrasonic measurements, and the optimization of signal processing procedures to achieve a specified accuracy.

New architectures for feedthrough SAW recursive devices.

This paper presents an analysis of a new type of feedthrough recursive surface acoustic wave (SAW) device. The device combines a conventional SAW structure with positive feedback in a way that allows use of selective properties of the SAW structure, control of the central frequency and bandwidth, achieving significantly higher quality factors for given dimensions of the structure, and reduction of the sidelobe level. Several possible implementations are discussed from a simple one that uses external circuitry to the most advanced that includes digital supervisory control. Equations are presented that relate the central frequency, bandwidth, and sidelobe level to the parameters of the SAW structure and feedback loop. The simulation results were found to be in good agreement with experimental data. These data show the control of the central frequency within 1%, a 10-fold increase in the quality factor compared to the original SAW structure, and a reduction of the side-lobe level by 20 dB irrespective of the influence of second order effects and random manufacturing fluctuations.

The influence of fabrication errors on the stopband magnitude responses of SAW devices.

This article is devoted to the analysis of the influence of manufacturing errors on the magnitude responses of surface acoustic wave (SAW) devices. Analytical analysis of these random errors provides statistical distributions of the relevant responses and their parameters. It allows significant reduction in the modeling computations compared to the Monte Carlo method, and it provides possibilities for further analytical analysis. After the application of the statistical analysis to different potential structures of SAW devices, it is possible to choose the least sensitive one during the design process without the need of costly trials. Experimental analysis confirmed the existence of some of the features predicted both theoretically and by modeling. The experimental procedure for the evaluation of the fabrication error variances is described. The application of these results to the design process of the SAW devices allows simplification of the requirements for the manufacturing equipment and/or improvement of the devices' parameters, especially stopband suppression.