Omi/HtrA2 is a mitochondrial serine protease that is released into the cytosol during apoptosis to antagonize inhibitors of apoptosis (IAPs) and contribute to caspase-independent cell death. Here, we demonstrate that Omi/HtrA2 directly cleaves various IAPs in vitro, and the cleavage efficiency is determined by its IAP-binding motif, AVPS. Cleavage of IAPs such as c-IAP1 substantially reduces its ability to inhibit and ubiquitylate caspases. In contrast to the stoichiometric anti-IAP activity by Smac/DIABLO, Omi/HtrA2 cleavage of c-IAP1 is catalytic and irreversible, thereby more efficiently inactivating IAPs and promoting caspase activity. Elimination of endogenous Omi by RNA interference abolishes c-IAP1 cleavage and desensitizes cells to apoptosis induced by TRAIL. In addition, overexpression of cleavage-site mutant c-IAP1 makes cells more resistant to TRAIL-induced caspase activation. This IAP cleavage by Omi is independent of caspase. Taken together, these results indicate that unlike Smac/DIABLO, Omi/HtrA2's catalytic cleavage of IAPs is a key mechanism for it to irreversibly inactivate IAPs and promote apoptosis.

There has been a striking realization that physics resolving the black hole information paradox could imply postmerger gravitational wave echoes. We here report on evidence for echoes from the LIGO compact binary merger events, GW151226, GW170104, GW170608, GW170814, as well as the neutron star merger GW170817. There is a signal for each event with a p-value of order 1% or sometimes significantly less. Our study begins with the comparison of echoes from a variety of horizonless exotic compact objects. Next we investigate the effects of spin. The identification of the more generic features of echoes then leads to the development of relatively simple windowing methods, in both time and frequency space, to extract a signal from noise. The time delay between echoes is inversely related to the spacing between the spectral resonances, and it is advantageous to look directly for this resonance structure. We find time delays for the first four events that are consistent with a simple model that accounts for mass and spin of the final object, while for the neutron star merger the final mass and spin are constrained.

We construct a minimal viable extension of the standard model (SM) with classical scale symmetry. Its scalar sector contains a complex singlet in addition to the SM Higgs doublet. The scale-invariant and CP-symmetric Higgs potential generates radiative electroweak symmetry breakingà la Coleman-Weinberg, and gives a natural solution to the hierarchy problem, free from fine-tuning. Besides the 125 GeV SM-like Higgs particle, it predicts a new CP-even Higgs (serving as the pseudo-Nambu-Goldstone boson of scale symmetry breaking) and a CP-odd scalar singlet (providing the dark matter candidate) at weak scale. We systematically analyze experimental constraints from direct LHC Higgs searches and electroweak precision tests, as well as theoretical bounds from unitarity, triviality and vacuum stability. We demonstrate the viable parameter space, and discuss implications for new Higgs and dark matter (DM) searches at the upcoming LHC runs and for the on-going direct detections of DM. 1 After the SM is extended with singlet right-handed neutrinos, their dimension-3 heavy Majorana mass-term provides another soft breaking of scale invariance. Our present construction will naturally generate this Majorana mass term via spontaneous symmetry breaking. 2 The SM Higgs sector with a 125 GeV Higgs boson is free from triviality bound, but suffers a vacuum stability bound at the scale µ 10 12 GeV [8]. We will analyze both triviality and vacuum stability bounds for the present model.

Astrophysical black hole candidates, although long thought to have a horizon, could be horizonless ultra-compact objects. This intriguing possibility is motivated by the black hole information paradox and a plausible fundamental connection with quantum gravity. Asymptotically free quadratic gravity is considered here as the UV completion of general relativity. A classical theory that captures its main features is used to search for solutions as sourced by matter. We find that sufficiently dense matter produces a novel horizonless configuration, the 2-2-hole, which closely matches the exterior Schwarzschild solution down to about a Planck proper length of the would-be horizon. The 2-2-hole is characterized by an interior with a shrinking volume and a seemingly innocuous timelike curvature singularity. The interior also has a novel scaling behavior with respect to the physical mass of the 2-2-hole. This leads to an extremely deep gravitational potential in which particles get efficiently trapped via collisions. As a generic static solution, the 2-2-hole may then be the nearly black endpoint of gravitational collapse. There is a considerable time delay for external probes of the 2-2-hole interior, and this determines the spacing of echoes in a post-merger gravitational wave signal.Comment: 35 pages, 11 figures, added section IIID: A brick wall and entrop

Baculoviral inhibitor of apoptosis repeat-containing (Birc)6 gene͞ BIRC6 (Bruce͞APOLLON) encodes an inhibitor of apoptosis and a chimeric E2͞E3 ubiquitin ligase in mammals. The physiological role of Bruce in antiapoptosis is unknown. Here, we show that deletion of the C-terminal half of Bruce, including the UBC domain, causes activation of caspases and apoptosis in the placenta and yolk sac, leading to embryonic lethality. This apoptosis is associated with up-regulation and nuclear localization of the tumor suppressor p53 and activation of mitochondrial apoptosis, which includes upregulation of Bax, Bak, and Pidd, translocation of Bax and caspase-2 onto mitochondria, release of cytochrome c and apoptosis-inducing factor, and activation of caspase-9 and caspase-3. Mutant mouse embryonic fibroblasts are sensitive to multiple mitochondrial death stimuli but resistant to TNF. In addition, eliminating p53 by RNA interference rescues cell viability induced by Bruce ablation in human cell line H460. This viability preservation results from reduced expression of proapoptotic factors Bax, Bak, and Pidd and from prevention of activation of caspase-2, -9, and -3. The amount of second mitochondrial-derived activator of caspase and Omi does not change. We conclude that p53 is a downstream effector of Bruce, and, in response to loss of Bruce function, p53 activates Pidd͞caspase-2 and Bax͞Bak, leading to mitochondrial apoptosis. P rogrammed cell death or apoptosis is critical for development and homeostasis in metazoans (1). The inhibitor of apoptosis (IAP) proteins antagonize cell death by suppressing active caspases. This inhibition can be reversed by IAP antagonists Reaper, Grim, and Hid in flies and the second mitochondrial-derived activator of caspase (Smac)͞Diablo family of proteins in vertebrates (2-5). Despite their well known anti-death function in vitro, IAPs have not been shown to be required for apoptosis inhibition in vertebrate development. Gene ablation of baculoviral IAP repeat-containing (Birc)4 (XIAP), the most potent caspase inhibitory IAP in cultured cells, does not perturb mouse development (6). In addition, Birc1a (Naip)-deficient mice do not manifest developmental abnormalities or spinal muscular atrophy, even though the deletion of BIRC1 (NAIP) correlates with the severity of this disease in a significant proportion of spinal muscular atrophy patients (7,8). Although tissue-specific ablation of Birc5 (survivin) in mice has demonstrated that Birc5 is required for thymocyte development (9) and the resistance of keratinocytes to UVB-induced apoptosis (10), Birc5-null embryos die primarily because of deficient mitotic division instead of apoptosis (11,12). Taken together, the physiological function of mammalian IAP family proteins in antagonizing apoptosis remains elusive in vivo.Birc6 (Bruce) is a large mouse IAP with a molecular mass of 528 kDa (13). Similar to other IAPs, Bruce promotes cell survival. It inhibits apoptosis by binding to caspases through its BIR domain, and its caspase inhibitory activity...

We study gravitational interaction of Higgs boson through the unique dimension-4 operator ξH † HR , with H the Higgs doublet and R the Ricci scalar curvature. We analyze the effect of this dimensionless nonminimal coupling ξ on weak gauge boson scattering in both Jordan and Einstein frames. We explicitly establish the longitudinal-Goldstone boson equivalence theorem with nonzero ξ coupling in both frames, and analyze the unitarity constraints. We study the ξ-induced weak boson scattering cross sections at O(1 − 30)TeV scales, and propose to probe the Higgs-gravity coupling via weak boson scattering experiments at the LHC (14 TeV) and the next generation pp colliders (50 − 100 TeV). We further extend our study to Higgs inflation, and quantitatively derive the perturbative unitarity bounds via coupled channel analysis, under large field background at the inflation scale. We analyze the unitarity constraints on the parameter space in both the conventional Higgs inflation and the improved models in light of the recent BICEP2 data.

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m χ) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m χ are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ SI χN at 90% confidence level are derived as 2 × 10 −32 ∼ 7 × 10 −35 cm 2 for TI analysis at m χ ∼ 50-180 MeV=c 2 , and 3 × 10 −32 ∼ 9 × 10 −38 cm 2 for AM analysis at m χ ∼ 75 MeV=c 2-3.0 GeV=c 2 .

We report results of a search for light Dark Matter WIMPs with CDEX-1 experiment at the China Jinping Underground Laboratory, based on 53.9 kg-days of data from a p-type point-contact germanium detector enclosed by a NaI(Tl) crystal scintillator as anti-Compton detector. The event rate and spectrum above the analysis threshold of 475 eVee are consistent with the understood background model. Part of the allowed regions for WIMP-nucleus coherent elastic scattering at WIMP mass of 6-20 GeV are probed and excluded. Independent of interaction channels, this result contradicts the interpretation that the anomalous excesses of the CoGeNT experiment are induced by Dark Matter, since identical detector techniques are used in both experiments. PACS numbers: 95.35.+d, 98.70.Vc