Apollo Lightcraft Project

This second year of the NASA/USRA-sponsored Advanced Aeronautical Design effort focused on systems integration and analysis of the Apollo Lightcraft. This beam-powered, single-stage-to-orbit vehicle is envisioned as the shuttlecraft of the 21st century. The five person vehicle was inspired largely by the Apollo Command Module, then reconfigured to include a new front seat with dual cockpit controls for the pilot and co-pilot, while still retaining the 3-abreast crew accommodations in the rear seat. The gross liftoff mass is 5550 kg, of which 500 kg is the payload and 300 kg is the LH2 propellant. The round trip cost to orbit is projected to be three orders of magnitude lower than the current space shuttle orbiter. The advanced laser-driven 5-speed combined-cycle engine has shiftpoints at Mach 1, 5, 11 and 25+. The Apollo Lightcraft can climb into low Earth orbit in three minutes, or fly to any spot on the globe in less than 45 minutes. Detailed investigations of the Apollo Lightcraft Project this second year further evolved the propulsion system design, while focusing on the following areas: (1) man/machine interface; (2) flight control systems; (3) power beaming system architecture; (4) re-entry aerodynamics; (5) shroud structural dynamics; and (6) optimal trajectory analysis. The principal new findings are documented. Advanced design efforts for the next academic year (1988/1989) will center on a one meter+ diameter spacecraft: the Lightcraft Technology Demonstrator (LTD). Detailed engineering design and analyses, as well as critical proof-of-concept experiments, will be carried out on this small, near-term machine. As presently conceived, the LTD could be constructed using state of the art components derived from existing liquid chemical rocket engine technology, advanced composite materials, and high power laser optics

Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair

Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and nonhistone proteins, which affect gene expression, cell cycle progression, cell migration, and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here, we show that the HDACi, vorinostat (Suberoylanilide hydroxamic acid, SAHA), induces DNA double-strand breaks (DSBs) in normal (HFS) and cancer (LNCaP, A549) cells. Normal cells in contrast to cancer cells repair the DSBs despite continued culture with vorinostat. In transformed cells, phosphorylated H2AX (γH2AX), a marker of DNA DSBs, levels increased with continued culture with vorinostat, whereas in normal cells, this marker decreased with time. Vorinostat induced the accumulation of acetylated histones within 30 min, which could alter chromatin structure-exposing DNA to damage. After a 24-h culture of cells with vorinostat, and reculture without the HDACi, γH2AX was undetectable by 2 h in normal cells, while persisting in transformed cells for the duration of culture. Further, we found that vorinostat suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, in cancer but not normal cells. Thus, the HDACi, vorinostat, induces DNA damage which normal but not cancer cells can repair. This DNA damage is associated with cancer cell death. These findings can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentrations that cause little or no normal cell death

Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.

Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer.Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Divertor currents optimization procedure for JET-ILW high flux expansion experiments

This paper deals with a divertor coil currents optimized procedure to design High Flux Expansion (HFE) configurations in the JET tokamak aimed to study the effects of flux expansion variation on the radiation fraction and radiated power re-distribution. A number of benefits of HFE configuration have been experimentally demonstrated on TCV, EAST, NSTX and DIII-D tokamaks and are under investigation for next generation devices, as DEMO and DTT. The procedure proposed here exploits the linearized relation between the plasma-wall gaps and the Poloidal Field (PF) coil currents. Once the linearized model is provided by means of CREATE-NL code, the divertor coils currents are calculated using a constrained quadratic programming optimization procedure, in order to achieve HFE configuration. Flux expanded configurations have been experimentally realized both in ohmic and heated plasma with and without nitrogen seeding. Preliminary results on the effects of the flux expansion variation on total power radiation increase will be also briefly discussed

The Antioxidant Protein Peroxiredoxin 4 Is Epigenetically Down Regulated in Acute Promyelocytic Leukemia

The antioxidant peroxiredoxin (PRDX) protein family comprises 6 members, which are implicated in a variety of cellular responses, including growth factor signal transduction. PRDX4 resides in the endoplasmic reticulum (ER), where it locally controls oxidative stress by reducing H2O2levels. We recently provided evidence for a regulatory function of PRDX4 in signal transduction from a myeloid growth factor receptor, the granulocyte colony-stimulating factor receptor (G-CSFR). Upon activation, the ligand-induced G-CSFR undergoes endocytosis and routes via the early endosomes where it physically interacts with ER-resident PRDX4. PRDX4 negatively regulates G-CSFR mediated signaling. Here, we investigated whether PRDX4 is affected in acute myeloid leukemia (AML); genomic alterations and expression levels of PRDX4 were investigated. We show that genomic abnormalities involving PRDX4 are rare in AML. However, we find a strong reduction in PRDX4 expression levels in acute promyelocytic leukemia (APL) compared to normal promyelocytes and different molecular subtypes of AML. Subsequently, the possible role of DNA methylation and histone modifications in silencing of PRDX4 in APLs was investigated. We show that the reduced expression is not due to methylation of the CpG island in the promoter region of PRDX4 but correlates with increased trimethylation of histone 3 lysine residue 27 (H3K27me3) and lysine residue 4 (H3K4me3) at the transcriptional start site (TSS) of PRDX4, indicative of a bivalent histone code involved in transcriptional silencing. These findings suggest that the control of G-CSF responses by the antioxidant protein PRDX4 may be perturbed in APL

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

Divertor currents optimization procedure for JET-ILW high flux expansion experiments

This paper deals with a divertor coil currents optimized procedure to design High Flux Expansion (HFE) configurations in the JET tokamak aimed to study the effects of flux expansion variation on the radiation fraction and radiated power re-distribution. A number of benefits of HFE configuration have been experimentally demonstrated on TCV, EAST, NSTX and DIII-D tokamaks and are under investigation for next generation devices, as DEMO and DTT. The procedure proposed here exploits the linearized relation between the plasma-wall gaps and the Poloidal Field (PF) coil currents. Once the linearized model is provided by means of CREATE-NL code, the divertor coils currents are calculated using a constrained quadratic programming optimization procedure, in order to achieve HFE configuration. Flux expanded configurations have been experimentally realized both in ohmic and heated plasma with and without nitrogen seeding. Preliminary results on the effects of the flux expansion variation on total power radiation increase will be also briefly discussed.EURATOM 63305