Regulation of Inflammatory Gene Expression in PBMCs by Immunostimulatory Botanicals

Many hundreds of botanicals are used in complementary and alternative medicine for therapeutic use as antimicrobials and immune stimulators. While there exists many centuries of anecdotal evidence and few clinical studies on the activity and efficacy of these botanicals, limited scientific evidence exists on the ability of these botanicals to modulate the immune and inflammatory responses. Using botanogenomics (or herbogenomics), this study provides novel insight into inflammatory genes which are induced in peripheral blood mononuclear cells following treatment with immunomodulatory botanical extracts. These results may suggest putative genes involved in the physiological responses thought to occur following administration of these botanical extracts. Using extracts from immunostimulatory herbs (Astragalus membranaceus, Sambucus cerulea, Andrographis paniculata) and an immunosuppressive herb (Urtica dioica), the data presented supports previous cytokine studies on these herbs as well as identifying additional genes which may be involved in immune cell activation and migration and various inflammatory responses, including wound healing, angiogenesis, and blood pressure modulation. Additionally, we report the presence of lipopolysaccharide in medicinally prepared extracts of these herbs which is theorized to be a natural and active component of the immunostimulatory herbal extracts. The data presented provides a more extensive picture on how these herbs may be mediating their biological effects on the immune and inflammatory responses

Produktion und radiochemische Abtrennung von 147^{147}Gd zur Markierung und in vivo SPET-Evaluierung von Magnetopharmaka

There is a continuing interest in specific gadolinium compounds to be used in macroscopic amounts as MRI contrast agents in medical research. Their biodistributions are usually measured in animals using $^{153}$Gd (T$_{1/2}$ = 241.6 d) labelled analogues, which, however, cannot be used in humans. Fortunately, there is $^{147}$Gd, which may be able to bridge MRI and SPECT imaging techniques. The introduction of a new radionuclide for use in humans requires several development steps. With this aim nuclear data measurements were performed and a suitable target system for irradiations was developed. Furthermore a chemical separation procedure was worked out and SPET-phantom measurements, dosimetry and finally synthesis of two already known magnetopharmaceuticals with $^{147}$Gd were performed. Excitation functions were measured by the stacked-foil technique for the $^{147}$($^{3}$He,xn)-processes overthe energy range of 12 to 36 MeV, and the $^{144}$Sm($\alpha$,xn)-reactions over the energy range of 12 to 27 MeV. Thin samples of 96.5% enriched $^{147}$Sm$_{2}$O$_{3}$3 or 86.6% enriched $^{144}$Sm$_{2}$O$_{3}$ of 10 mm diameter and 2-5 mg/cm$^{2}$ thickness were prepared via a sedimentation method. Thick target yields of $^{147}$Gdwere calculated from the measured excitation functions and the levels of radiogadolinium impurities were determined experimentally. The optimum energy range at the compact cyclotron CV28 for the production of $^{147}$Gd via the $^{144}$($^{3}$He,3n)-process was found to be E3$_{He}$ = 36 $\rightarrow$ 13 MeV and via the $^{147}$Sm($\alpha$,n)-reaction as E$_{\alpha}$ = >27-13 MeV. The expected thick target yield of $^{147}$Gd over the respective energy ranges is 10 MBq/$\mu$Ah for the $^{3}$He-induced reaction and 4.8 MBq/$\mu$Ah for the $\alpha$-induced reaction. A target system was constructed which allowed irradiation of the target material Sm$_{2}$O$_{3}$ with 15 $\mu$A beams of 36 MeV $^{3}$He- or 27 MeV $\alpha$-particles. A separation technique involving cementation with Na-amalgam followed byan ion exchange process was developed to separate the n.c.a. gadolinium from the bulk of Sm$_{2}$O$_{3}$ target material and from the n.c.a. europium isotopes. The final purification of $^{147}$Gd was done using a small glass column (3 mm x 120 mm) or an HPLC column (8 mm x 300 mm) filledwith a cation exchanger. Using 97% enriched $^{147}$Sm and the separation technique described here about 60-70% $^{147}$Gd of high radionuclidic and chemical purity could be achieved. The chemical separation procedure developed also allowed an almost quantitative (>90%) recovery of the enriched target material for cyclic use. First SPET-phantom measurements were performed with the radiochemically isolated $^{147}$Gd. The measurement conditions of the TRIONIX 88 tomograph were optimized for this new SPET-nuclide. Especially the choice of suitable collimators, energy-window and reconstruction algorithms was important to compare $^{147}$Gd with commonly used SPET nuclides. Best results could be obtained with a middle- (MEUR) as weil as a high-energy (HEGP) collimator and the Butterworth reconstruction algorithm. Dosimetric calculations were done using available literature pharmacokinetic data of similar pharmaceuticals. The expected dose was compared with commonly used SPET radionuclides. Finally two commonly used magnetopharmaceuticals (Gd-DTAP, (Gd-DTPAkPolylysine) were synthesised and characterised. For $^{147}$Gd-DTPA an on-line process using a cation-exhange column was developed which gave a product of high radiochemical purity and yield (> 95%). For ($^{147}$Gd-DTPA)$_{n}$-Polylysine two classical routes, namely the mixed anhydrid and the bisanhydrid methods were performed. Both resulted in about 30% Gd-lysin-coupling (Gd carrier addded) via the DTPA-bridge. This was shown by NMR-measurements

Cross section measurements of alpha-induced reactions on (92,94)Mo and (112)Sn for p-process studies

The (92)Mo(alpha, n)(95)Ru, (94)Mo(alpha, n)(97)Ru, and (112)Sn(alpha, gamma)(116)Te cross sections were measured at the upper end of the p-process Gamow window between 8.2 and 11.1 MeV. Our results are slightly lower than global Hauser-Feshbach calculations from the code NON-SMOKER, but still within the uncertainty of the prediction. The (112)Sn(alpha, gamma)(116)T, cross section agrees well with a recently measured thick-target cross section in the same energy range. For the (92,94)Mo(alpha, n) reactions the present data close to the reaction thresholds could eliminate previous uncertainties within a factor of 20, and we can present now useful comparisons to statistical model calculations with different optical potentials.Peer reviewe

A virtual “Werkstatt” for digitization in the sciences

Data is central in almost all scientific disciplines nowadays. Furthermore, intelligent systems have developed rapidly in recent years, so that in many disciplines the expectation is emerging that with the help of intelligent systems, significant challenges can be overcome and science can be done in completely new ways. In order for this to succeed, however, first, fundamental research in computer science is still required, and, second, generic tools must be developed on which specialized solutions can be built. In this paper, we introduce a recently started collaborative project funded by the Carl Zeiss Foundation, a virtual manufactory for digitization in the sciences, the "Werkstatt", which is being established at the Michael Stifel Center Jena (MSCJ) for data-driven and simulation science to address fundamental questions in computer science and applications. The Werkstatt focuses on three key areas, which include generic tools for machine learning, knowledge generation using machine learning processes, and semantic methods for the data life cycle, as well as the application of these topics in different disciplines. Core and pilot projects address the key aspects of the topics and form the basis for sustainable work in the Werkstatt