Programmed cell death regulates a number of biological phenomena, and the apoptotic signal must itself be tightly controlled to avoid inappropriate cell death. We established a genetic screen to search for molecules that inhibit the apoptotic signal from the Fas receptor. Here we report the isolation of a gene, LFG, that protects cells uniquely from Fas but not from the mechanistically related tumor necrosis factor ␣ death signal. LFG is widely distributed, but remarkably is highly expressed in the hippocampus. LFG can bind to the Fas receptor, but does not regulate Fas expression or interfere with binding of an agonist antibody. Furthermore LFG does not inhibit binding of FADD to Fas.

Activation of the NF-#cB/Rel family of transcription factors is regulated by a cytoplasmic inhibitor, IkBa. Activity of I#cBa is in turn modulated by phosphorylation and proteolysis. It has been postulated that phosphorylation of I,cBa leads to its dissociation from NF-#cB, and free IkBa is targeted for rapid degradation. However, this phosphorylation-mediated dissociation event has not been demonstrated in vivo. We demonstrate that, contrary to this hypothesis, phosphorylation of IKBa induced by tumor necrosis factor a in HeLa cells does not induce dissociation. We propose a model in which (i) induced phosphorylation ofIdcBa does not result in its dissociation from NF-KB, (ii) phosphorylation of IcBa serves as a signal for degradation, and (iii) degradation of IK#Ba occurs while it is still complexed with NF-KB.

Fusion fast ignition (FI) initiated by laser-driven ion beams is a promising concept examined in this paper. FI based on a beam of quasi-monoenergetic ions (protons or heavier ions) has the advantage of a more localized energy deposition, which minimizes the required total beam energy, bringing it close to the ≈10 kJ minimum required for fuel densities ∼500 g cm−3. High-current, laser-driven ion beams are most promising for this purpose. Because they are born neutralized in picosecond timescales, these beams may deliver the power density required to ignite the compressed DT fuel, ∼10 kJ/10 ps into a spot 20 µm in diameter. Our modelling of ion-based FI include high fusion gain targets and a proof of principle experiment. That modelling indicates the concept is feasible, and provides confirmation of our understanding of the operative physics, a firmer foundation for the requirements, and a better understanding of the optimization trade space. An important benefit of the scheme is that such a high-energy, quasi-monoenergetic ignitor beam could be generated far from the capsule (⩾1 cm away), eliminating the need for a reentrant cone in the capsule to protect the ion-generation laser target, a tremendous practical benefit. This paper summarizes the ion-based FI concept, the integrated ion-driven FI modelling, the requirements on the ignitor beam derived from that modelling, and the progress in developing a suitable laser-driven ignitor ion beam.

The c-Rel protein is able to associate in vitro and in vivo with the TATA-binding protein (TBP) of the TFIID complex. Coexpression of TBP with c-Rel augments transactivation from the kappa B site in Drosophila Schneider cells. DNA-binding mutants of TBP not only fail to cooperate, but they repress transactivation by c-Rel. There may be a direct communication between kappa B enhancer binding proteins and basal transcription factors which leads to enhanced transcription.

We report here that the major ad-binding complx in murine mature B cells is composed of a p50-Rd heterodimer, whereas the major inducible form in pre-B cells is a p50-65 heterodimer. Treatment of a pre-B-cell line with ioopolysaccharide changes the subunit composition of #cB-bin complexes from p50-p65 to p50-Rel. This (vol/vol) heat-inactivated fetal bovine serum, 50 pM 2-mercaptoethanol, 1250 units of penicillin G, and streptomycin sulfate (0.5 mg/ml). Rel antiserum 5075 has been described (24). Anti-p65 serum was raised against N-terminal 19-aa peptide (MDDLF-PLIFPSEPAQASGP). Anti-p50 sera were raised against a glutathione S-transferase-p50 fusion protein, whose gene is constructed by cloning murine NFKBI-p5O (Apa I digested, Klenow fragment filled-in, EcoRI linker added, and finally the 1.4-kb EcoRI fragment cont N-terminal Rel homology domain generated) into EcoRI site of pGEX-2TK (a gift from W. Kaelin, Dana-Farber Cancer Institute and Harvard University Medical School).Metabo Laeling and Imnun etation. Approximately 107 cells were incubated with methionine/cysteinefree Dulbecco's modified Eagle's medium (1 ml) containing 10% dialyzed fetal bovine serum, 50 pM 2-mercaptoethanol, nonessential amino acids (GIBCO), and 2 mM glutamine.[35S]Methionine/cysteine was added at 1 mCi/ml (1 Ci = 37 GBq) and further incubated for 2 h. After rinsing with phosphate-buffered saline, the cells were lysed in IP buffer (20 mM Tris HCl, pH 7.5/100 mM NaCl/1 mM EDTA/0.2% Nonidet P-40/0.2% deoxycholate). SDS was added to 0.5% and the cell lysates were then boiled for 5 mnm and diluted 1:5 with the IP buffer. After preclearing with protein A-Sepharose (Pharmacia), affinity-purified Rel antiserum and protein A-Sepharose were added and further incubated for 4 h. The Sepharose beads were rinsed five times with the IP buffer, and the Rel proteins bound to the Sepharose were released by boiling in SDS sample buffer and resolved by SDS/PAGE. Eectropoetic Mobfllt Shift Assay (EMSAs). Approximately 2 x 108 cells were used to prepare cellular extracts from 70Z/3 and WEHI231 cells (24,25). The protein concentration of extracts was =5 mg/ml. EMSAs were performed as described (24 5056The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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A record fuel hot-spot pressure P hs ¼ 56 AE 7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, LM15119ER (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laserdrive nonuniformity and target-positioning error reduces target performance. DOI: 10.1103/PhysRevLett.117.025001 The spherical concentric layers of a direct-drive inertial confinement fusion (ICF) target nominally consist of a central region of a near-equimolar deuterium and tritium (DT) vapor surrounded by a cryogenic DT-fuel layer and a thin, nominally plastic (CH) ablator. The outer surface of the ablator is uniformly irradiated with multiple laser beams having a peak overlapped intensity of <10 15 watts=cm 2 . The resulting laser-ablation process causes the target to accelerate and implode. As the DT-fuel layer decelerates, the initial DT vapor and the fuel mass thermally ablated from the inner surface of the ice layer are compressed and form a central hot spot, in which fusion reactions occur. ICF relies on the 3.5-MeV DT-fusion alpha particles depositing their energy in the hot spot, causing the hotspot temperature to rise sharply and a thermonuclear burn wave to propagate out through the surrounding nearly degenerate, cold, dense DT fuel, producing significantly more energy than was used to heat and compress the fuel. Ignition is predicted to occur when the product of the temperature and areal density of the hot spot reach a minimum of 5 keV × 0.3 g=cm 2 [1-3]. Currently, the 192-beam, 351-nm, 1.8-MJ National Ignition Facility (NIF) [4] is configured for indirectdrive-ignition experiments using laser-driven hohlraums to accelerate targets via x-ray ablation. Approximately 26 kJ of thermonuclear fusion energy has been recorded on the NIF using indirect-drive ICF targets [5], where alpha heating has boosted the fusion yield by a factor of ∼2.5 from that caused by the implosion system alone [6,7]. The indirect-drive NIF implosions have achieved over 60% of the Lawson parameter Pτ required for ignition, where P is the pressure and τ is the confinement time [6]. Here P and τ are estimated without accounting for alpha heating to assess the pure hydrodynamic performance. The goal of achieving laboratory fusion and progress made with direct-drive ICF over the last decade motivate direct-drive implosions on NIF [8,9]. Hot-spot formation for spherically symmetric, direct-drive, DT-layered implosions is st...