Digoxin, an Overlooked Agonist of RORγ/RORγT

Digoxin was one of the first identified RORγT receptor inverse agonists inhibiting the differentiation of Th17 cells. However, this compound exhibits inhibitory activity at relatively high concentrations that mediate cytotoxic effects. We previously identified several cardenolides that are structurally similar to digoxin that were able to induce RORγ/RORγT-dependent transcription. These observations encouraged us to reanalyze the effects of digoxin on RORγ/RORγT-dependent transcription at low, noncytotoxic concentrations. Digoxin induced RORγ/RORγT-dependent transcription in HepG2 and Th17 cells. Furthermore, analysis of the transcriptomes of Th17 cells cultured in the presence of digoxin revealed the induction of the expression of numerous Th17-specific genes, including IL17A/F, IL21, IL22, IL23R, CCR4, and CCR6. Thus, our study, which includes data obtained from intact cells, indicates that digoxin, similar to other cardenolides, is a potent RORγ/RORγT receptor activator and that its structure may serve as a starting point for the design of dedicated molecules that can be used in the development of adoptive cell therapy (ACT)

Smart port as a key to the future development of modern ports

Technological innovations gives the opportunity to create so-called Smart Ports. However, determining which technologies to choose, how to implement them remains a challenge. The research problem presented in the article is: Is the constant introduction and implementation of the concept of intelligent ports an irreversible trend determining the direction of development of modern seaports? The aim of the article is also to analyze projects introduced in the ports of the North Sea and Baltic Sea which are successively implementing the concept of a Smart Port. The article uses the method of analysis - mainly current analysis and prospective analysis

A modification of the using the properties of a new generation of cutting fluids based on fatty acid methyl esters

W pracy oceniono przydatność klasycznych dodatków uszlachetniających oraz modyfikacji chemicznej za pomocą siarkowania FAME do kształtowania właściwości użytkowych cieczy obróbkowych na bazie produktów roślinnych. Przedstawiono wyniki badań wpływu dodatków depresujących na właściwości niskotemperaturowe estru metylowego wyższych kwasów tłuszczowych oleju rzepakowego, a także zbadano właściwości smarne kompozycji FAME z wybranymi dodatkami AW/EP. Porównano właściwości tribologiczne siarkowanych estrów metylowych wyższych kwasów tłuszczowych oleju rzepakowego z kompozycjami FAME zawierającymi komercyjne dodatki smarne. Uzyskane wyniki wskazują, iż siarkowane FAME charakteryzują się lepszymi właściwościami przeciwzatarciowymi niż kompozycje FAME z dodatkami AW/EP, a wprowadzenie klasycznych wiskozatorów umożliwia uzyskanie optymalnych właściwości reologicznych w niskich temperaturach.The possibility of using vegetable-originated cutting fluid chemical modification by means of commercial additives or sulfurization processes is evaluated. The influence of depressants on the low-temperature characteristics of rapeseed oil FAME and the lubricity of FAME containing selected AW/EP additives are investigated. The tribological characteristics of sulfurized FAME and FAME containing commercial lubricating additives were compared. Obtained results have shown that sulfurized FAME has better antiseizure properties than FAME containing AW/EP additives. Application of the classic viscosity additives enables optimum rheological properties at low temperatures to be obtained

High speed rail - the current challenge to Polish rail transport

The increase of the role of rail transport in comparison with road and air ones was an important task for transport engineering in western Europe and Japan in the 1970s. Now the problem is not completely closed but the majority of the establishments formed in the beginning were successively solved. The main assumptions could be grouped into environmental protection and sustainability, decreasing the travel time connected with accessibility, safety, comfort for passengers, considering freight transport, as well. The high speed of the moving train was the main criteria of any engineer approach i.e. from the point of view of energy safety, limiting pollution, ability to transport thousands of people and tons of cargo. High Speed Rail - (HSR) means the speed between 250 to 400 km/h. This divides tracks into two groups: ordinary tracks and special ones, which results in two possible ways: adopting existing tracks or building new railways. Recently the program of HSR has been decided to put in motion in Poland. The situation here was very complicated. Many abandons such as complete lack of road highways, backwardness in air transport as well as rail transport, which means abandons in track conditions and rolling stock. At least, actually no existing haulage transport. In those circumstances, any rational first step was to be taken i.e. a technical diagnosis and an estimation of the existing railway system including culverts and bridges as important elements of trucks. The paper presented here contains a short survey of statical and dynamical field test results and FEM analyses as an extension to the train speeds 1.2ź350 = 420 km/h

Stadion Narodowy w Warszawie

Stadion Narodowy w Warszawie, powstający w niecce dawnego Stadionu X-lecia, jest największą i najnowocześniejszą inwestycją przygotowywaną na zbliżające się Mistrzostwa Europy w Piłce Nożnej UEFA Euro 2012. To tutaj w czasie trwania Mistrzostw mają zostać rozegrane trzy spotkania grupowe: mecz otwarcia wraz z oficjalną ceremonią, jeden ćwierćfinał i jeden półfinał