Antitumor Effects of Vitamin D Analogs on Hamster and Mouse Melanoma Cell Lines in Relation to Melanin Pigmentation

Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH)₂D₃) limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity. We therefore examined the effect of secosteroidal analogs, both classic (1,25(OH)₂D₃ and 25(OH)D₃), and novel relatively non-calcemic ones (20(OH)D₃, calcipotriol, 21(OH)pD, pD and 20(OH)pL), on proliferation, colony formation in monolayer and soft-agar, and mRNA and protein expression by melanoma cells. Murine B16-F10 and hamster Bomirski Ab cell lines were shown to be effective models to study how melanogenesis affects anti-melanoma treatment. Novel Vitamin D analogs with a short side-chain and lumisterol-like 20(OH)pL efficiently inhibited rodent melanoma growth. Moderate pigmentation sensitized rodent melanoma cells towards Vitamin D analogs, and altered expression of key genes involved in Vitamin D signaling, which was opposite to the effect on heavily pigmented cells. Interestingly, melanogenesis inhibited ligand-induced Vitamin D receptor translocation and ligand-induced expression of VDR and CYP24A1 genes. These findings indicate that melanogenesis can affect the anti-melanoma activity of Vitamin D analogs in a complex manner.     

Parallel quicksort

A parallel version of quicksort on a CRCW PRAM is developed. The algorithm uses n processors and a linear space to sort n keys in the expected time O(log n) with large probability.     

Volatile organo-halogen trace analysis in beverages by thin-layer headspace enrichment and electron-capture gas-chromatography

Applicability of thin-layer headspace (TLHS) procedure giving an aqueous concentrate and also classical purge and trap (PT) in off-line mode to isolate and enrich volatile organohalogen compounds in common beverages was tested. Both enrichment tech-niques were used in combination with gas chromatography – electron capture detection (GC-ECD). TLHS, combined with direct aqueous injection (DAI)-GC-ECD, proved applicable in the determination of volatile organohalogen compounds in all studied beverages, while the PT in a version with no preliminary sample pre-treatment was of limited applicability. Detection limits of the TLHS-based procedure were in the order of 1 ppt. Content of volatile organohalogen compounds in a number of beverages available on the Polish market including mineral waters, beers, juices, carbonated and non-carbonated soft drinks, etc. was determined by means of TLHS-DAI-GC-ECD.     

Investigation and Elaboration of Methods of Multicolor Optical Thermometry

The various complex mathematical transformations previously proposed for eliminating methodological errors of multicolor radiation pyrometry are mainly reduced to the determination of such combinations of wavelengths or corrections of registered brightness for the spectral distribution of the radiating capacity of the object being thermometered at which its equivalent radiating capacity is equal to unity. Mathematical formulas of the determining parameters of multicolor pyrometry of radiation have been obtained. Engineering techniques for calculating the critical values of the determining and adjustable parameters at which the application of multicolor optical thermometry is excluded because of large errors have been developed. Algorithms of a priori and a posteriori calibration systems of multicolor pyrometry of radiation of objects with practically any spectral distribution of the radiating capacity are proposed.     

Meningocerebral lesions in children with iatrogenic AIDS

This study is focused on structural modifications of leptomeninges and cerebral matter in children deceased because of iatrogenic AIDS. Although we do not evidence the specific lesions of AIDS, we have noticed edema, hyperemia, hematic extravasation, microlesions of the small vessel walls, perivascular infiltrations with lymphocytes, macrophages and even plasmocytes, moderate tigrolysis, mild demyelination, gliosis and sidero-calcic deposits. We do not consider these lesions as specific to HIV-infected patients.     

Automatic recognition of gait-related health problems in the elderly using machine learning

This paper proposes a system for the early automatic recognition of health problems that manifest themselves in distinctive form of gait. Purpose of the system is to prolong the autonomous living of the elderly at home. When the system identifies a health problem, it automatically notifies a physician and provides an explanation of the automatic diagnosis. The gait of the elderly user is captured using a motion-capture system, which consists of body-worn tags and wall-mounted sensors. The positions of the tags are acquired by the sensors and the resulting time series of position coordinates are analyzed with machine-learning algorithms in order to recognize a specific health problem. Novel semantic features based on medical knowledge for training a machine-learning classifier are proposed in this paper. The classifier classifies the user’s gait into: 1) normal, 2) with hemiplegia, 3) with Parkinson’s disease, 4) with pain in the back and 5) with pain in the leg. The studies of 1) the feasibility of automatic recognition and 2) the impact of tag placement and noise level on the accuracy of the recognition of health problems are presented. The experimental results of the first study (12 tags, no noise) showed that the k-nearest neighbors and neural network algorithms achieved classification accuracies of 100%. The experimental results of the second study showed that classification accuracy of over 99% is achievable using several machine-learning algorithms and 8 or more tags with up to 15 mm standard deviation of noise. The results show that the proposed approach achieves high classification accuracy and can be used as a guide for further studies in the increasingly important area of Ambient Assisted Living. Since the system uses semantic features and an artificial-intelligence approach to interpret the health state, provides a natural explanation of the hypothesis and is embedded in the domestic environment of the elderly person; it is an example of the semantic ambient media for Ambient Assisted Living.     

Interpretation of long-chain structure from dilute solution properties of ultrahigh molecular weight polymers

Summary Systematic studies on solution properties of ultrahigh molecular weight polymers showed the existence of some special features as compared to usual length polymers. The paper discusses the possible appearance of branched structures in the polymerization process, structures able to influence the mentioned features. From experimental data on poly(methyl methacrylate), poly(butyl methacrylate) and polyacrylonitrile it appears that branching can be excluded, and the very high molecular weight domain considered may be responsible for the modifications observed in the molecular weight dependences on 2>, A₂ or [].     

Target Score—A Proteomics Data Selection Tool Applied to Esophageal Cancer Identifies GLUT1-Sialyl Tn Glycoforms as Biomarkers of Cancer Aggressiveness

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms.