Simultaneous approximation of a smooth function and its derivatives by deep neural networks with piecewise-polynomial activations.

This paper investigates the approximation properties of deep neural networks with piecewise-polynomial activation functions. We derive the required depth, width, and sparsity of a deep neural network to approximate any Hölder smooth function up to a given approximation error in Hölder norms in such a way that all weights of this neural network are bounded by 1. The latter feature is essential to control generalization errors in many statistical and machine learning applications.

Intermittent High-Frequency Percussive Ventilation Therapy in 3 Patients with Severe COVID-19 Pneumonia.

BACKGROUND High-frequency percussive ventilation (HFPV) is a method that combines mechanical ventilation with high-frequency oscillatory ventilation. This report describes 3 cases of patients with severe COVID-19 pneumonia who received intermittent adjunctive treatment with HFPV at a single center without requiring admission to the Intensive Care Unit (ICU). CASE REPORT Case 1 was a 60-year-old woman admitted to the hospital 14 days after the onset of SARS-CoV-2 infection symptoms, and cases 2 and 3 were men aged 65 and 72 years who were admitted to the hospital 10 days after the onset of SARS-CoV-2 infection symptoms. All 3 patients presented with clinical deterioration accompanied by worsening lung lesions on computed tomography (CT) scans after 21 days from the onset of symptoms. SARS-CoV-2 infection was confirmed in all patients by real-time reverse transcription-polymerase chain reaction (RT-PCR) assay from nasal swabs. All 3 patients had impending respiratory failure when non-invasive intermittent HFPV therapy was initiated. After therapy, the patients had significant clinical improvement and visibly decreased lung lesions on followup CT scans performed 4-6 days later. CONCLUSIONS The 3 cases described in this report showed that the use of intermittent adjunctive treatment with HFPV in patients with severe pneumonia due to infection with SARS-CoV-2 improved lung function and may have prevented clinical deterioration. However, recommendations on the use of intermittent HFPV as an adjunctive treatment in COVID-19 pneumonia requires large-scale controlled clinical studies. In the pandemic context, with a shortage of ICU beds, avoiding ICU admission by using adjunctive therapies on the ward is a useful option.

Novel Copper-Containing Cytotoxic Agents Based on 2-Thioxoimidazolones.

A series of 73 ligands and 73 of their Cu+2 and Cu+1 copper complexes with different geometries, oxidation states of the metal, and redox activities were synthesized and characterized. The aim of the study was to establish the structure-activity relationship within a series of analogues with different substituents at the N(3) position, which govern the redox potentials of the Cu+2/Cu+1 redox couples, ROS generation ability, and intracellular accumulation. Possible cytotoxicity mechanisms, such as DNA damage, DNA intercalation, telomerase inhibition, and apoptosis induction, have been investigated. ROS formation in MCF-7 cells and three-dimensional (3D) spheroids was proven using the Pt-nanoelectrode. Drug accumulation and ROS formation at 40-60 µm spheroid depths were found to be the key factors for the drug efficacy in the 3D tumor model, governed by the Cu+2/Cu+1 redox potential. A nontoxic in vivo single-dose evaluation for two binuclear mixed-valence Cu+1/Cu+2 redox-active coordination compounds, 72k and 61k, was conducted.

Copper Coordination Compounds as Biologically Active Agents.

Copper-containing coordination compounds attract wide attention due to the redox activity and biogenicity of copper ions, providing multiple pathways of biological activity. The pharmacological properties of metal complexes can be fine-tuned by varying the nature of the ligand and donor atoms. Copper-containing coordination compounds are effective antitumor agents, constituting a less expensive and safer alternative to classical platinum-containing chemotherapy, and are also effective as antimicrobial, antituberculosis, antimalarial, antifugal, and anti-inflammatory drugs. 64Сu-labeled coordination compounds are promising PET imaging agents for diagnosing malignant pathologies, including head and neck cancer, as well as the hallmark of Alzheimer's disease amyloid-ß (Aß). In this review article, we summarize different strategies for possible use of coordination compounds in the treatment and diagnosis of various diseases, and also various studies of the mechanisms of antitumor and antimicrobial action.

Discovering relationships between nuclear receptor signaling pathways, genes, and tissues in Transcriptomine.

We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biology in these pathways using this tool. Transcriptomine currently contains about 45 million data points encompassing more than 2000 experiments in a reference library of nearly 550 data sets retrieved from public archives and systematically curated. To make the underlying data points more accessible to bench biologists, we classified experimental small molecules and gene manipulations into signaling pathways and experimental tissues and cell lines into physiological systems and organs. Incorporation of these mappings into Transcriptomine enables the user to readily evaluate tissue-specific regulation of gene expression by nuclear receptor signaling pathways. Data points from animal and cell model experiments and from clinical data sets elucidate the roles of nuclear receptor pathways in gene expression events accompanying various normal and pathological cellular processes. In addition, data sets targeting non-nuclear receptor signaling pathways highlight transcriptional cross-talk between nuclear receptors and other signaling pathways. We demonstrate with specific examples how data points that exist in isolation in individual data sets validate each other when connected and made accessible to the user in a single interface. In summary, Transcriptomine allows bench biologists to routinely develop research hypotheses, validate experimental data, or model relationships between signaling pathways, genes, and tissues.

Improving the discoverability, accessibility, and citability of omics datasets: a case report.

Although omics datasets represent valuable assets for hypothesis generation, model testing, and data validation, the infrastructure supporting their reuse lacks organization and consistency. Using nuclear receptor signaling transcriptomic datasets as proof of principle, we developed a model to improve the discoverability, accessibility, and citability of published omics datasets. Primary datasets were retrieved from archives, processed to extract data points, then subjected to metadata enrichment and gap filling. The resulting secondary datasets were exposed on responsive web pages to support mining of gene lists, discovery of related datasets, and single-click citation integration with popular reference managers. Automated processes were established to embed digital object identifier-driven links to the secondary datasets in associated journal articles, small molecule and gene-centric databases, and a dataset search engine. Our model creates multiple points of access to reprocessed and reannotated derivative datasets across the digital biomedical research ecosystem, promoting their visibility and usability across disparate research communities.

Use of input impedance to determine changes in the resistance of arterial vessels at different levels in feline femoral bed.

In many studies, the functional state of vessels of different caliber was determined by fitting the lumped parameters of a mathematical model of the bed in order to fit the vascular input impedance (Z in) data. However, reliability of the results obtained in such a way remains uncertain. In this study, we employed a mathematical model with seven lumped parameters and Z in experimental data to analyze the distribution of resistance across the arterial bed of the hind limb in anesthetized cats, to test reliability of this distribution and to describe the process of ascending arterial dilation followed occlusion of iliac artery. The vascular bed was divided into three segments: large arteries, medium-sized arterial vessels and precapillary resistance vessels together with venous part of the bed. Based on the data of Z in measured in a wide frequency range (from 0 to 150 Hz) we showed that pharmacologically induced constriction and dilation of the arterial microvessels were reflected in the model by the changes in the resistance of distal precapillary vessels only, whereas the local constriction or dilation of femoral and iliac arteries as well as artificial stenosis of the femoral artery resulted exclusively in the changes of the resistance describing the state of large arteries. Using the input impedance method we could demonstrate and quantitatively describe the process of ascending arterial dilation during the post-occlusion (reactive) hyperemia. All these results prove that the model of vascular bed with seven lumped elements used in combination with input hydraulic impedance data can be an effective tool permitted to quantitatively analyze the functional state of arterial vessels of different caliber and to describe the changes in resistance of arterial vessels during vascular reactions.