A new class of ignition designs is proposed for inertial confinement fusion experiments. These designs are based on the hot-spot ignition approach, but instead of a conventional target that is ...comprised of a spherical shell with a thin frozen deuterium-tritium (DT) layer, a liquid DT sphere inside a wetted-foam shell is used, and the lower-density central region and higher-density shell are created dynamically by appropriately shaping the laser pulse. These offer several advantages, including simplicity in target production (suitable for mass production for inertial fusion energy), absence of the fill tube (leading to a more-symmetric implosion), and lower sensitivity to both laser imprint and physics uncertainty in shock interaction with the ice-vapor interface. The design evolution starts by launching an ∼ 1 -Mbar shock into a DT sphere. After bouncing from the center, the reflected shock reaches the outer surface of the sphere and the shocked material starts to expand outward. Supporting ablation pressure ultimately stops such expansion and subsequently launches a shock toward the target center, compressing the ablator and fuel, and forming a shell. The shell is then accelerated and fuel is compressed by appropriately shaping the drive laser pulse, forming a hot spot using the conventional or shock ignition approaches. This Letter demonstrates the feasibility of the new concept using hydrodynamic simulations and discusses the advantages and disadvantages of the concept compared with more-traditional inertial confinement fusion designs.
This study aimed to determine whether the multi-kinase inhibitor dasatinib would provide an effective therapy for myeloproliferative diseases (MPDs) involving c-Cbl mutations. These mutations, which ...occur in the RING finger and linker domains, abolish the ability of c-Cbl to function as an E3 ubiquitin ligase and downregulate activated protein tyrosine kinases. Here we analyzed the effects of dasatinib in a c-Cbl RING finger mutant mouse that develops an MPD with a phenotype similar to the human MPDs. The mice are characterized by enhanced tyrosine kinase signaling resulting in an expansion of hematopoietic stem cells, multipotent progenitors and cells within the myeloid lineage. Since c-Cbl is a negative regulator of c-Kit and Src signaling we reasoned that dasatinib, which targets these kinases, would be an effective therapy. Furthermore, two recent studies showed dasatinib to be effective in inhibiting the in vitro growth of cells from leukemia patients with c-Cbl RING finger and linker domain mutations. Surprisingly we found that dasatinib did not provide an effective therapy for c-Cbl RING finger mutant mice since it did not suppress any of the hematopoietic lineages that promote MPD development. Thus we conclude that dasatinib may not be an appropriate therapy for leukemia patients with c-Cbl mutations. We did however find that dasatinib caused a marked reduction of pre-B cells and immature B cells which correlated with a loss of Src activity. This study is therefore the first to provide a detailed characterization of in vivo effects of dasatinib in a hematopoietic disorder that is driven by protein tyrosine kinases other than BCR-ABL.
Background African Potato (hypoxis hemerocallidea), is used for enhancing immune system in Southern Africa. It is among the plants of intense commercial and scientific interest; hence, the aim of ...this study was to describe its chemistry and pharmacology. Methods PubMed, Cochrane Controlled Trials Register (CENTRAL) and Google Scholar were searched independently for relevant literature. The last search occurred in October 2018. Other research material was obtained from Google. The following search terms were used, but not limited to: "African Potato", "hypoxis", "hemerocallidea", "rooperol." Articles that were explaining the chemistry and pharmacology of hypoxis hemerocallidea were included. Results Thirty articles from PubMed, Cochrane and Google Scholar were eligible. Three webpages were included from Google. Results showed that the tuberous rootstock (corm) of African Potato is used traditionally to treat wasting diseases, testicular tumours, insanity, barrenness, impotency, bad dreams, intestinal parasites, urinary infection, cardiac disease and enhancing immunity. The plant contains hypoxoside, which is converted rapidly to a potent antioxidant, rooperol in the gut. The corm contains sterols, sterol glycosides, stanols, terpenoids, saponins, cardiac glycosides, tannins and reducing sugars. A dose of 15 mg/kg/day of hypoxoside is reportedly therapeutic. Preclinical studies of African Potato have shown immunomodulation, antioxidant, antinociceptive, hypoglycaemic, anti-inflammatory, anticonvulsant, antibacterial, uterolytic, antimotility, spasmolytic and anticholinergic effects. The common side effects of African Potato are nausea and vomiting, which subside over time. In vitro, African Potato demonstrated inhibitory effects on CYP1A2, 2C9, 2D6, 3A4, 3A5, CYP19-metabolism and induction of P-glycoprotein. In vivo, it did not alter the pharmacokinetics of efavirenz or lopinavir/ritonavir. Conclusion African Potato is mainly used as an immunostimulant. The exact mechanisms of action for all the pharmacological actions are unknown. More research is required to substantiate claims regarding beneficial effects. There are many research gaps that require investigation including pharmacokinetic interactions with conventional drugs, especially those used in HIV/AIDS. Keywords: African potato, Hypoxis hemerocallidea, Pharmacology, Pharmacokinetics, Chemistry, Traditional medicine
Nanoscale control of the polymerization of silicon and oxygen determines the structures and properties of a wide range of siloxane-based materials, including glasses, ceramics, mesoporous molecular ...sieves and catalysts, elastomers, resins, insulators, optical coatings, and photoluminescent polymers. In contrast to anthropogenic and geological syntheses of these materials that require extremes of temperature, pressure, or pH, living systems produce a remarkable diversity of nanostructured silicates at ambient temperatures and pressures and at near-neutral pH. We show here that the protein filaments and their constituent subunits comprising the axial cores of silica spicules in a marine sponge chemically and spatially direct the polymerization of silica and silicone polymer networks from the corresponding alkoxide substrates in vitro, under conditions in which such syntheses otherwise require either an acid or base catalyst. Homology of the principal protein to the well known enzyme cathepsin L points to a possible reaction mechanism that is supported by recent site-directed mutagenesis experiments. The catalytic activity of the "silicatein" (silica protein) molecule suggests new routes to the synthesis of silicon-based materials.
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