MDF-DTA: A Multi-Dimensional Fusion Approach for Drug-Target Binding Affinity Prediction.

Drug-target affinity (DTA) prediction is an important task in the early stages of drug discovery. Traditional biological approaches are time-consuming, effort-consuming, and resource-consuming due to the large size of genomic and chemical spaces. Computational approaches using machine learning have emerged to narrow down the drug candidate search space.

Identification of oral therapeutics using an AI platform against the virus responsible for COVID-19, SARS-CoV-2.

This study introduces a sophisticated computational pipeline, , designed for the discovery of antiviral drugs based on their interactions within the human protein network. There is a pressing need for cost-effective therapeutics for infectious diseases (e.g.

Development and pharmacological evaluation of a new chemical series of potent pan-ERR agonists, identification of SLU-PP-915.

Estrogen-related receptors (ERR) are an orphan nuclear receptor sub-family that play a critical role in regulating gene transcription for several physiological processes including mitochondrial function, cellular energy utilization and homeostasis. They have also been implicated to play a role in several pathological conditions. Herein, we report the identification, synthesis, structure-activity relationships and pharmacological evaluation of a new chemical series of potent pan-ERR agonists.

Artificial intelligence for the discovery of novel antimicrobial agents for emerging infectious diseases.

The search for effective drugs to treat new and existing diseases is a laborious one requiring a large investment of capital, resources, and time. The coronavirus 2019 (COVID-19) pandemic has been a painful reminder of the lack of development of new antimicrobial agents to treat emerging infectious diseases. Artificial intelligence (AI) and other in silico techniques can drive a more efficient, cost-friendly approach to drug discovery by helping move potential candidates with better clinical tolerance forward in the pipeline.

Evaluation of a rapid biosensor tool for measuring PAH availability in petroleum-impacted sediment.

Decades of research have shown that the concentration of freely dissolved PAH (C in sediment correlates with PAH bioavailability and toxicity to aquatic organisms. Passive sampling techniques and models have been used for measuring and predicting C respectively, but these techniques require weeks for analytical chemical measurements and data evaluation. This study evaluated the performance of a portable, field-deployable antibody-based PAH biosensor method that can provide measurements of PAH C within a matter of minutes using a small volume of mechanically-extracted sediment porewater.

Review of Polycyclic Aromatic Hydrocarbons (PAHs) Sediment Quality Guidelines for the Protection of Benthic Life.

Polycyclic aromatic hydrocarbons (PAHs) in sediments can pose harm to the benthic community. Numerous sediment quality guidelines (SQGs) for the protection of benthic life are available to assess the risk of individual PAHs and PAH mixtures in sediments. Sediment quality guidelines are derived using empirical or mechanistic approaches.

Effects of mutations in mitochondrial dynamics-related genes on the mitochondrial response to ultraviolet C radiation in developing Caenorhabditis elegans.

We recently found that genes involved in mitochondrial dynamics and autophagy are required for removal of UVC-induced mitochondrial DNA damage. However, drp-1 and pink-1, unlike the autophagy and fusion genes tested, were not necessary for larval development after exposure. We hypothesized that increased fusion resulting from mutations in these genes facilitated recovery of mitochondrial function.

Mitochondria as a target of environmental toxicants.

Enormous strides have recently been made in our understanding of the biology and pathobiology of mitochondria. Many diseases have been identified as caused by mitochondrial dysfunction, and many pharmaceuticals have been identified as previously unrecognized mitochondrial toxicants. A much smaller but growing literature indicates that mitochondria are also targeted by environmental pollutants.

Effects of early life exposure to ultraviolet C radiation on mitochondrial DNA content, transcription, ATP production, and oxygen consumption in developing Caenorhabditis elegans.

Background: Mitochondrial DNA (mtDNA) is present in multiple copies per cell and undergoes dramatic amplification during development. The impacts of mtDNA damage incurred early in development are not well understood, especially in the case of types of mtDNA damage that are irreparable, such as ultraviolet C radiation (UVC)-induced photodimers.

Methods: We exposed first larval stage nematodes to UVC using a protocol that results in accumulated mtDNA damage but permits nuclear DNA (nDNA) repair.

UVC-induced mitochondrial degradation via autophagy correlates with mtDNA damage removal in primary human fibroblasts.

Mitochondrial DNA (mtDNA) is more susceptible than nuclear DNA to helix-distorting damage via exposure to environmental genotoxins, partially due to a lack of nucleotide excision repair. Thus, this damage is irreparable and persistent in mtDNA in the short term. We recently found that helix-distorting mtDNA damage induced by ultraviolet C radiation (UVC) is gradually removed in Caenorhabditis elegans and that removal is dependent upon autophagy and mitochondrial dynamics.

Analysis of DNA damage and repair in nuclear and mitochondrial DNA of animal cells using quantitative PCR.

This chapter was written as a guide to using the long-amplicon quantitative PCR (QPCR) assay for the measurement of DNA damage in mammalian as well as nonmammalian species such as Caenorhabditis elegans (nematodes), Drosophila melanogaster (fruit flies), and two species of fish (Fundulus heteroclitus and Danio rerio). Since its development in the early 1990s (Kalinowski et al., Nucleic Acids Res 20:3485-3494, 1992; Salazar and Van Houten, Mutat Res 385:139-149, 1997; Yakes and Van Houten, Proc Natl Acad Sci USA 94:514-519, 1997), the QPCR assay has been widely used to measure DNA damage and repair kinetics in nuclear and mitochondrial genomes after genotoxin exposure (Yakes and Van Houten, Proc Natl Acad Sci USA 94:514-519, 1997; Santos et al.

Involvement of autophagy and mitochondrial dynamics in determining the fate and effects of irreparable mitochondrial DNA damage.

Mitochondrial DNA (mtDNA) is different in many ways from nuclear DNA. A key difference is that certain types of DNA damage are not repaired in the mitochondrial genome. What, then, is the fate of such damage? What are the effects? Both questions are important from a health perspective because irreparable mtDNA damage is caused by many common environmental stressors including ultraviolet C radiation (UVC).

Mitochondrial dynamics and autophagy aid in removal of persistent mitochondrial DNA damage in Caenorhabditis elegans.

Mitochondria lack the ability to repair certain helix-distorting lesions that are induced at high levels in mitochondrial DNA (mtDNA) by important environmental genotoxins and endogenous metabolites. These lesions are irreparable and persistent in the short term, but their long-term fate is unknown. We report that removal of such mtDNA damage is detectable by 48 h in Caenorhabditis elegans, and requires mitochondrial fusion, fission and autophagy, providing genetic evidence for a novel mtDNA damage removal pathway.

Electronically signed documents in health care--analysis and assessment of data formats and transformation.

Objectives: Our objectives were to analyze and assess data formats for their suitability for conclusive and secure long-term archiving and to develop a concept for legally secure transformation of electronically signed documents that are not available in data formats appropriate for long-term archiving.

Methods: On the basis of literature review and Internet searches we developed general evaluation criteria to assess data formats with regard to their suitability for conclusive and secure long-term archiving. The assessment of data formats refers to format specifications and available literature.

Deduction of principles on long-term conservation of electronically signed documents by multi professional analyses.

Due to actual equalization of qualified electronic signatures with handwritten signatures and the legal acknowledgment of the electronic form, the opportunity to use electronic patient records instead of classic paper-based ones is given. The archiving of medical records over a period of 10 to 30 years represents an important factor in medical documentation which has to be assured for electronically signed documents as well. The ArchiSig project deduces principles on long-term conservation of electronically signed documents and corresponding technical components to be realized by the means of multi professional analyses.

[Clinical archiving--requirements and current solutions].

In this paper we summarize requirements for archiving in hospitals. Furthermore, we present solutions how digital archives can be built up. Archiving in hospitals requires medical documentation, which should take place preferably in a computer-based way.

Hospital portfolio analysis.

Portfolio analysis is a management technique that rationalizes the process of allocating funds to programs. Each program is screened based on financial performance and organizational relevance. A decision-making matrix prioritizes programs into an orderly form.

Payer segmentation: how to respond.

Knowing which payers are paying how much for which services will become critically important to hospitals as an increasing number of their payers negotiate fixed rates. Only by routinely assessing their payer composition can hospitals be assured that their profitable services remain profitable and their money losers don't place undue hardship on the bottom line.