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For the stable and self-sufficient functioning of the DEMO fusion reactor, one of the most important parameters that must be demonstrated is the Tritium Breeding Ratio (TBR). The reliable assessment of the TBR with safety margins is a matter of fusion reactor viability. The uncertainty of the TBR in the neutronic simulations includes many different aspects such as the uncertainty due to the simplification of the geometry models used, the uncertainty of the reactor layout and the uncertainty introduced due to neutronic calculations. The last one can be reduced by applying high fidelity Monte Carlo simulations for TBR estimations. Nevertheless, these calculations have inherent statistical errors controlled by the number of neutron histories, straightforward for a quantity such as that of TBR underlying errors due to nuclear data uncertainties. In fact, every evaluated nuclear data file involved in the MCNP calculations can be replaced with the set of the random data files representing the particular deviation of the nuclear model parameters, each of them being correct and valid for applications. To account for the uncertainty of the nuclear model parameters introduced in the evaluated data file, a total Monte Carlo (TMC) method can be used to analyze the uncertainty of TBR owing to the nuclear data used for calculations. To this end, two 3D fully heterogeneous geometry models of the helium cooled pebble bed (HCPB) and water cooled lithium lead (WCLL) European DEMOs were utilized for the calculations of the TBR. The TMC calculations were performed, making use of the TENDL-2017 nuclear data library random files with high enough statistics providing a well-resolved Gaussian distribution of the TBR value. The assessment was done for the estimation of the TBR uncertainty due to the nuclear data for entire material compositions and for separate materials: structural, breeder and neutron multipliers. The overall TBR uncertainty for the nuclear data was estimated to be 3~4% for the HCPB and WCLL DEMOs, respectively.

The curcuminoid natural products have long been recognized for their medicinal properties and utilized for the treatment of many diseases. Curcuminoids are the major constituents of turmeric (Curcuma longa L.) and some other Curcuma species, including a number of other plant species. Curcuminoids include curcumin (~77%), demethoxycurcumin (~18%), and bisdemethoxycurcumin (~5%), and they exhibit many interesting biological activities such as antioxidant, anti-inflammatory, anticancer, and antiplatelet activities. The cause of thrombosis is commonly associated with platelet aggregation. The effect of curcumin has been reported to reduce platelet aggregation and to increase prostacyclin (PGI2) as the main factor, and it inhibited the induction of platelet aggregation for adenosine diphosphate (ADP), epinephrine (adrenaline), and collagen. Platelets play a main role in hemostasis in the main defense mechanism in biological systems (in vivo). However, hyper-activated platelets increase thrombosis and could develop various cardiovascular diseases such as coronary artery disease, myocardial infarction, and stroke. Conventional anti-platelet drugs such as aspirin, clopidogrel bisulfate, and abciximab have already been proven to treat and prevent cardiovascular diseases, but these drugs also have side effects like bleeding. We decided to use curcumin and its analogs as starting materials in order to prevent side effects. However, curcumin has poor absorption in vivo, thus we studied improving its physical properties. It remains unknown whether the activity of curcumin is based on its presumably promiscuous scaffold, or if it results from the Michael acceptor properties of the α,β-unsaturated 1,3-diketone moiety central to its structure. The keto-enol tautomerism and E/Z enol stereoisomerism of curcumin result in dynamic equilibria of isomers, which hinder the evaluation of the structure-activity relationships (SARs) of substituted curcumins. We studied the relationship between curcumin-derived pyrazoles of the 1,3-dicarbonyl with various hydrazines and curcuminester of the phenol position. Curcumin-derived pyrazoles were synthesized in order to minimize the metal chelation properties of curcumin. We designed and synthesized new curcumin derivatives. First, known compounds (curcumin, bisdemethoxycurcumin, curcumin-derived pyrazole, and bisdemethoxycurcumin-derived pyrazole) were separated Figure 1. Approaches of curcumin analogs.

Synthesis of a new series of pyrimidinyl-imidazo(2,1-b)thiazole derivatives is described. Their antiproliferative activity against A375 human melanoma cell line was tested and the effect of substituents on the pyrimidinyl ring side chain was investigated. The biological results indicated that most of the newly synthesized compounds showed mo- derate activity against A375, compared with Sorafenib. Among all of these derivatives, the cyclic sulfamide derivatives IIIa, IIIb, and IIIe showed the most potent antiproliferative activity against A375 human melanoma cell line. The IC50 values of compounds IIIa,b were in nanomolar scale. In addition, compound IIIe (IC50 = 1.9 µM) also demon- strated more potent antiproliferative activity compared with Sorafenib (IC50 = 5.6 µM).

Synthesis of a new series of diarylureas and amides having pyrrolo[2,3-d]pyrimidine scaffold is described. Their in vitro antiproliferative activities against A375 human melanoma cell line and HS 27 fibroblast cell line were tested and the effect of substituents on pyrrolo[2,3-d]pyrimidine was investigated. The newly synthesized compounds, except N-acetyl derivatives (Id, Ie, and Im), generally showed superior or similar activity against A375 to Sorafenib. Among all of these derivatives, compounds Iq and Ir having imidazole and morpholine moieties, respectively, showed the most potent antiproliferative activity against A375.

Isothermal vapor–liquid equilibria were measured for the binary systems difluoromethane (HFC-32)+1,1,1,2,3,3,3-heptafluoropropane (HFC-22ea) and 1,1-difluoroethane (HFC-152a)+1,1,1,2,3,3,3-heptafluoropropane at 283.15 and 303.15 K and 1,1,1,2-tetrafluoroethane (HFC-134a)+1,1,1,2,3,3,3-heptafluoropropane at 303.15 and 323.15 K in an apparatus in which both phases were recirculated. The experimental data were correlated with the Peng–Robinson equation of state using the Wong–Sandler mixing rules. Azeotropic behavior has not been found in any of the three mixtures.

Compounds (IIIb), (IIIf), (IVb), and (IVd)—(IVg) exhibit higher activity against A375P human melanoma cell line than the reference compound sorafenib.

A series of 18 new imidazo[2,1- b ]thiazole derivatives was synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 15 , 16 , 18 , 22 , 26 – 28 , and 31 showed superior potency against A375P to sorafenib. In addition, compounds 26 and 27 showed selectivity toward melanoma cell lines than for other cancer types. Both compounds exerted sub-micromolar IC 50 values over 7 (including A375P) and 6 melanoma cell lines, respectively. In silico studies are also reported. ADME profiling, in silico toxicity, drug-likeness, and drug-score data of compounds 26 and 27 are promising.

Title compounds, e.g. (VIII), are investigated for their antiproliferative activity against A375 human melanoma cell lines.

Synthesis of novel amides and esters prodrugs of olmesartan is described. Their in vitro stability in rat plasma was tested. The results showed that the ester derivative IIa with n-octyl substituted dioxolone moiety was rapidly converted into olmesartan within 30 min. The pharmacokinetic parameters of IIa were studied and compared with those of olmesartan medoxomil. Compound IIa is proposed to be a promising prodrug of olmesartan.