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Showing papers by "Korea Institute of Science and Technology Information published in 2017"


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1131 moreInstitutions (123)
TL;DR: The association of GRB 170817A, detected by Fermi-GBM 1.7 s after the coalescence, corroborates the hypothesis of a neutron star merger and provides the first direct evidence of a link between these mergers and short γ-ray bursts.
Abstract: On August 17, 2017 at 12∶41:04 UTC the Advanced LIGO and Advanced Virgo gravitational-wave detectors made their first observation of a binary neutron star inspiral. The signal, GW170817, was detected with a combined signal-to-noise ratio of 32.4 and a false-alarm-rate estimate of less than one per 8.0×10^{4} years. We infer the component masses of the binary to be between 0.86 and 2.26 M_{⊙}, in agreement with masses of known neutron stars. Restricting the component spins to the range inferred in binary neutron stars, we find the component masses to be in the range 1.17-1.60 M_{⊙}, with the total mass of the system 2.74_{-0.01}^{+0.04}M_{⊙}. The source was localized within a sky region of 28 deg^{2} (90% probability) and had a luminosity distance of 40_{-14}^{+8} Mpc, the closest and most precisely localized gravitational-wave signal yet. The association with the γ-ray burst GRB 170817A, detected by Fermi-GBM 1.7 s after the coalescence, corroborates the hypothesis of a neutron star merger and provides the first direct evidence of a link between these mergers and short γ-ray bursts. Subsequent identification of transient counterparts across the electromagnetic spectrum in the same location further supports the interpretation of this event as a neutron star merger. This unprecedented joint gravitational and electromagnetic observation provides insight into astrophysics, dense matter, gravitation, and cosmology.

7,327 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1195 moreInstitutions (139)
TL;DR: In this paper, the authors used the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to constrain the difference between the speed of gravity and speed of light to be between $-3
Abstract: On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is $5.0\times {10}^{-8}$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $-3\times {10}^{-15}$ and $+7\times {10}^{-16}$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1–1.4 per year during the 2018–2019 observing run and 0.3–1.7 per year at design sensitivity.

2,633 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1062 moreInstitutions (115)
TL;DR: The magnitude of modifications to the gravitational-wave dispersion relation is constrain, the graviton mass is bound to m_{g}≤7.7×10^{-23} eV/c^{2} and null tests of general relativity are performed, finding that GW170104 is consistent with general relativity.
Abstract: We describe the observation of GW170104, a gravitational-wave signal produced by the coalescence of a pair of stellar-mass black holes. The signal was measured on January 4, 2017 at 10∶11:58.6 UTC by the twin advanced detectors of the Laser Interferometer Gravitational-Wave Observatory during their second observing run, with a network signal-to-noise ratio of 13 and a false alarm rate less than 1 in 70 000 years. The inferred component black hole masses are 31.2^(8.4) _(−6.0)M_⊙ and 19.4^(5.3)_( −5.9)M_⊙ (at the 90% credible level). The black hole spins are best constrained through measurement of the effective inspiral spin parameter, a mass-weighted combination of the spin components perpendicular to the orbital plane, χ_(eff) = −0.12^(0.21)_( −0.30). This result implies that spin configurations with both component spins positively aligned with the orbital angular momentum are disfavored. The source luminosity distance is 880^(450)_(−390) Mpc corresponding to a redshift of z = 0.18^(0.08)_( −0.07) . We constrain the magnitude of modifications to the gravitational-wave dispersion relation and perform null tests of general relativity. Assuming that gravitons are dispersed in vacuum like massive particles, we bound the graviton mass to m_g ≤ 7.7 × 10^(−23) eV/c^2. In all cases, we find that GW170104 is consistent with general relativity.

2,569 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1113 moreInstitutions (117)
TL;DR: For the first time, the nature of gravitational-wave polarizations from the antenna response of the LIGO-Virgo network is tested, thus enabling a new class of phenomenological tests of gravity.
Abstract: On August 14, 2017 at 10∶30:43 UTC, the Advanced Virgo detector and the two Advanced LIGO detectors coherently observed a transient gravitational-wave signal produced by the coalescence of two stellar mass black holes, with a false-alarm rate of ≲1 in 27 000 years. The signal was observed with a three-detector network matched-filter signal-to-noise ratio of 18. The inferred masses of the initial black holes are 30.5-3.0+5.7M⊙ and 25.3-4.2+2.8M⊙ (at the 90% credible level). The luminosity distance of the source is 540-210+130 Mpc, corresponding to a redshift of z=0.11-0.04+0.03. A network of three detectors improves the sky localization of the source, reducing the area of the 90% credible region from 1160 deg2 using only the two LIGO detectors to 60 deg2 using all three detectors. For the first time, we can test the nature of gravitational-wave polarizations from the antenna response of the LIGO-Virgo network, thus enabling a new class of phenomenological tests of gravity.

1,979 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1151 moreInstitutions (125)
TL;DR: In this article, a GW signal from the merger of two stellar-mass black holes was observed by the two Advanced Laser Interferometer Gravitational-Wave Observatory detectors with a network signal-to-noise ratio of 13.5%.
Abstract: On 2017 June 8 at 02:01:16.49 UTC, a gravitational-wave (GW) signal from the merger of two stellar-mass black holes was observed by the two Advanced Laser Interferometer Gravitational-Wave Observatory detectors with a network signal-to-noise ratio of 13. This system is the lightest black hole binary so far observed, with component masses of ${12}_{-2}^{+7}\,{M}_{\odot }$ and ${7}_{-2}^{+2}\,{M}_{\odot }$ (90% credible intervals). These lie in the range of measured black hole masses in low-mass X-ray binaries, thus allowing us to compare black holes detected through GWs with electromagnetic observations. The source's luminosity distance is ${340}_{-140}^{+140}\,\mathrm{Mpc}$, corresponding to redshift ${0.07}_{-0.03}^{+0.03}$. We verify that the signal waveform is consistent with the predictions of general relativity.

1,268 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1319 moreInstitutions (78)
02 Nov 2017-Nature
TL;DR: A measurement of the Hubble constant is reported that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data.
Abstract: On 17 August 2017, the Advanced LIGO1 and Virgo2 detectors observed the gravitational-wave event GW170817—a strong signal from the merger of a binary neutron-star system3. Less than two seconds after the merger, a γ-ray burst (GRB 170817A) was detected within a region of the sky consistent with the LIGO–Virgo-derived location of the gravitational-wave source4, 5, 6. This sky region was subsequently observed by optical astronomy facilities7, resulting in the identification8, 9, 10, 11, 12, 13 of an optical transient signal within about ten arcseconds of the galaxy NGC 4993. This detection of GW170817 in both gravitational waves and electromagnetic waves represents the first ‘multi-messenger’ astronomical observation. Such observations enable GW170817 to be used as a ‘standard siren’14, 15, 16, 17, 18 (meaning that the absolute distance to the source can be determined directly from the gravitational-wave measurements) to measure the Hubble constant. This quantity represents the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Here we report a measurement of the Hubble constant that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data. In contrast to previous measurements, ours does not require the use of a cosmic ‘distance ladder’19: the gravitational-wave analysis can be used to estimate the luminosity distance out to cosmological scales directly, without the use of intermediate astronomical distance measurements. We determine the Hubble constant to be about 70 kilometres per second per megaparsec. This value is consistent with existing measurements20, 21, while being completely independent of them. Additional standard siren measurements from future gravitational-wave sources will enable the Hubble constant to be constrained to high precision.

892 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy3  +719 moreInstitutions (86)
Abstract: The second-generation of gravitational-wave detectors are just starting operation, and have already yielding their first detections. Research is now concentrated on how to maximize the scientific potential of gravitational-wave astronomy. To support this effort, we present here design targets for a new generation of detectors, which will be capable of observing compact binary sources with high signal-to-noise ratio throughout the Universe.

796 citations


Journal ArticleDOI
TL;DR: In this article, the authors present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions, showing that the integrated yields of strange and multi-strange particles relative to pions increases significantly with the event charged-particle multiplicity.
Abstract: At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed. Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions, is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions, but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results, indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.

500 citations


Journal ArticleDOI
S. Hirose1, T. Iijima1, I. Adachi2, K. Adamczyk  +190 moreInstitutions (61)
TL;DR: The first measurement of the tau lepton polarization P-tau(D*) in the decay (B) over bar -> D* tau(-) (v) over b (tau) as well as a new measurement of the ratio of the branching fractions was reported in this paper.
Abstract: We report the first measurement of the tau lepton polarization P-tau(D*) in the decay (B) over bar -> D* tau(-) (v) over bar (tau) as well as a newmeasurement of the ratio of the branching fractions R(D*) = B((B) over bar -> D* tau(-) (v) over bar (tau)) / B((B) over bar -> D* l(-) (v) over bar (l)), where l(-) denotes an electron or a muon, and the tau is reconstructed in the modes tau(-) -> pi(-) v(tau) and tau(-) -> rho(-) v(tau). We use the full data sample of 772 x 10(6) B (B) over bar pairs recorded with the Belle detector at the (KEKB) over bar electron-positron collider. Our results, P-tau(D*) = -0.38 +/- 0.51 (stat)(-0.16)(+0.21) (syst) and R(D*) = 0.270 +/- 0.035 (stat)(- 0.025)(+0.028) (syst), are consistent with the theoretical predictions of the standard model.

374 citations


Journal ArticleDOI
TL;DR: A pan-cancer mechanism of pro-inflammatory signals from the tumor stimulates an inflammatory response in the adjacent endothelium, and the authors find that NAT presents a unique state, potentially due to inflammatory response of the NAT to the tumour tissue.
Abstract: Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies. However, little is known about the transcriptomic profile of NAT, how it is influenced by the tumor, and how the profile compares with non-tumor-bearing tissues. Here, we integrate data from the Genotype-Tissue Expression project and The Cancer Genome Atlas to comprehensively analyze the transcriptomes of healthy, NAT, and tumor tissues in 6506 samples across eight tissues and corresponding tumor types. Our analysis shows that NAT presents a unique intermediate state between healthy and tumor. Differential gene expression and protein–protein interaction analyses reveal altered pathways shared among NATs across tissue types. We characterize a set of 18 genes that are specifically activated in NATs. By applying pathway and tissue composition analyses, we suggest a pan-cancer mechanism of pro-inflammatory signals from the tumor stimulates an inflammatory response in the adjacent endothelium.

340 citations


Journal ArticleDOI
S. Wehle, C. Niebuhr, S. Yashchenko, Iki Adachi1  +239 moreInstitutions (64)
TL;DR: The result is consistent with standard model (SM) expectations, where the largest discrepancy from a SM prediction is observed in the muon modes with a local significance of 2.6σ.
Abstract: We present a measurement of angular observables and a test of lepton flavor universality in the B -> K(+)l(+)l(-) decay, where l is either e or mu. The analysis is performed on a data sample corresponding to an integrated luminosity of 711 fb(-1) containing 772 x 10(6) B (B) over bar pairs, collected at the Upsilon(4S) resonance with the Belle detector at the asymmetric-energy e(+)e(-) collider KEKB. The result is consistent with standard model (SM) expectations, where the largest discrepancy from a SM prediction is observed in the muon modes with a local significance of 2.6 sigma.

Journal ArticleDOI
TL;DR: EGFR TKI-resistant SCLCs are branched out early from the LADC clones that harbor completely inactivated RB1 and TP53, and they share a common clonal origin and undergoBranched evolutionary trajectories.
Abstract: Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied for nine tumors acquired at various time points from four patients to reconstruct their clonal evolutionary history and to detect genetic predictors for small-cell transformation. The findings were validated by immunohistochemistry in 210 lung cancer tissues. Results We identified that EGFR TKI-resistant LADCs and SCLCs share a common clonal origin and undergo branched evolutionary trajectories. The clonal divergence of SCLC ancestors from the LADC cells occurred before the first EGFR TKI treatments, and the complete inactivation of both RB1 and TP53 were observed from the early LADC stages in sequenced tumors. We extended the findings by immunohistochemistry in the early-stage LADC tissues of 75 patients treated with EGFR TKIs; inactivation of both Rb and p53 was strikingly more frequent in the small-cell-transformed group than in the nontransformed group (82% v 3%; odds ratio, 131; 95% CI, 19.9 to 859). Among patients registered in a predefined cohort (n = 65), an EGFR mutant LADC that harbored completely inactivated Rb and p53 had a 43× greater risk of small-cell transformation (relative risk, 42.8; 95% CI, 5.88 to 311). Branch-specific mutational signature analysis revealed that apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-induced hypermutation was frequent in the branches toward small-cell transformation. Conclusion EGFR TKI-resistant SCLCs are branched out early from the LADC clones that harbor completely inactivated RB1 and TP53. The evaluation of RB1 and TP53 status in EGFR TKI-treated LADCs is informative in predicting small-cell transformation.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, Richard J. Abbott2, T. D. Abbott3  +1064 moreInstitutions (117)
TL;DR: This work performs a search for the isotropic stochastic gravitational-wave background using data from Advanced Laser Interferometer Gravitational Wave Observatory's (aLIGO) first observing run, and constrain the dimensionless energy density of gravitational waves to be Ω_{0}<1.7×10^{-7} with 95% confidence.
Abstract: A wide variety of astrophysical and cosmological sources are expected to contribute to a stochastic gravitational-wave background. Following the observations of GW150914 and GW151226, the rate and mass of coalescing binary black holes appear to be greater than many previous expectations. As a result, the stochastic background from unresolved compact binary coalescences is expected to be particularly loud. We perform a search for the isotropic stochastic gravitational-wave background using data from Advanced Laser Interferometer Gravitational Wave Observatory’s (aLIGO) first observing run. The data display no evidence of a stochastic gravitational-wave signal. We constrain the dimensionless energy density of gravitational waves to be Ω 0 < 1.7 × 10 − 7 with 95% confidence, assuming a flat energy density spectrum in the most sensitive part of the LIGO band (20–86 Hz). This is a factor of ∼ 33 times more sensitive than previous measurements. We also constrain arbitrary power-law spectra. Finally, we investigate the implications of this search for the background of binary black holes using an astrophysical model for the background.

Journal ArticleDOI
TL;DR: The study reveals that research using Google Trends has increased dramatically in the last decade, and in the process, the focus of research has shifted to forecasting changes, whereas in the past the focus had been on merely describing and diagnosing research trends, such as surveillance and monitoring.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1137 moreInstitutions (125)
TL;DR: In this paper, the authors presented a search for GWs from the remnant of the binary neutron star merger GW170817 using data from Advanced LIGO and Advanced Virgo.
Abstract: The first observation of a binary neutron star (NS) coalescence by the Advanced LIGO and Advanced Virgo gravitational-wave (GW) detectors offers an unprecedented opportunity to study matter under the most extreme conditions. After such a merger, a compact remnant is left over whose nature depends primarily on the masses of the inspiraling objects and on the equation of state of nuclear matter. This could be either a black hole (BH) or an NS, with the latter being either long-lived or too massive for stability implying delayed collapse to a BH. Here, we present a search for GWs from the remnant of the binary NS merger GW170817 using data from Advanced LIGO and Advanced Virgo. We search for short- (lesssim1 s) and intermediate-duration (lesssim500 s) signals, which include GW emission from a hypermassive NS or supramassive NS, respectively. We find no signal from the post-merger remnant. Our derived strain upper limits are more than an order of magnitude larger than those predicted by most models. For short signals, our best upper limit on the root sum square of the GW strain emitted from 1–4 kHz is ${h}_{\mathrm{rss}}^{50 \% }=2.1\times {10}^{-22}\,{\mathrm{Hz}}^{-1/2}$ at 50% detection efficiency. For intermediate-duration signals, our best upper limit at 50% detection efficiency is ${h}_{\mathrm{rss}}^{50 \% }=8.4\times {10}^{-22}\,{\mathrm{Hz}}^{-1/2}$ for a millisecond magnetar model, and ${h}_{\mathrm{rss}}^{50 \% }=5.9\times {10}^{-22}\,{\mathrm{Hz}}^{-1/2}$ for a bar-mode model. These results indicate that post-merger emission from a similar event may be detectable when advanced detectors reach design sensitivity or with next-generation detectors.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1141 moreInstitutions (125)
TL;DR: In this paper, the mass of the dynamical ejecta can be estimated without a direct electromagnetic observation of the kilonova, using GW measurements and a phenomenological model calibrated to numerical simulations of mergers with dynamical ejecteda.
Abstract: The source of the gravitational-wave (GW) signal GW170817, very likely a binary neutron star merger, was also observed electromagnetically, providing the first multi-messenger observations of this type. The two-week-long electromagnetic (EM) counterpart had a signature indicative of an r-process-induced optical transient known as a kilonova. This Letter examines how the mass of the dynamical ejecta can be estimated without a direct electromagnetic observation of the kilonova, using GW measurements and a phenomenological model calibrated to numerical simulations of mergers with dynamical ejecta. Specifically, we apply the model to the binary masses inferred from the GW measurements, and use the resulting mass of the dynamical ejecta to estimate its contribution (without the effects of wind ejecta) to the corresponding kilonova light curves from various models. The distributions of dynamical ejecta mass range between = - - - M M ej 10 10  3 2 for various equations of state, assuming that the neutron stars are rotating slowly. In addition, we use our estimates of the dynamical ejecta mass and the neutron star merger rates inferred from GW170817 to constrain the contribution of events like this to the r-process element abundance in the Galaxy when ejecta mass from post-merger winds is neglected. We find that if 10% of the matter dynamically ejected from binary neutron star (BNS) mergers is converted to r-process elements, GW170817-like BNS mergers could fully account for the amount of r-process material observed in the Milky Way.

Journal ArticleDOI
Arnauld Albert1, Michel André2, M. Anghinolfi3, Miguel Ardid4  +1987 moreInstitutions (227)
TL;DR: In this paper, the authors search for high-energy neutrinos from the binary neutron star merger in the GeV-EeV energy range using the Antares, IceCube, and Pierre Auger Observatories.
Abstract: The Advanced LIGO and Advanced Virgo observatories recently discovered gravitational waves from a binary neutron star inspiral. A short gamma-ray burst (GRB) that followed the merger of this binary was also recorded by the Fermi Gamma-ray Burst Monitor (Fermi-GBM), and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory (INTEGRAL), indicating particle acceleration by the source. The precise location of the event was determined by optical detections of emission following the merger. We searched for high-energy neutrinos from the merger in the GeV–EeV energy range using the Antares, IceCube, and Pierre Auger Observatories. No neutrinos directionally coincident with the source were detected within ±500 s around the merger time. Additionally, no MeV neutrino burst signal was detected coincident with the merger. We further carried out an extended search in the direction of the source for high-energy neutrinos within the 14 day period following the merger, but found no evidence of emission. We used these results to probe dissipation mechanisms in relativistic outflows driven by the binary neutron star merger. The non-detection is consistent with model predictions of short GRBs observed at a large off-axis angle.

Journal ArticleDOI
TL;DR: This approach for product planning will contribute to the systematic identification of product opportunities from large-scale customer-generated social media data and will be used as a real-time monitoring tool for changing customer needs analysis in rapidly evolving product environments.

Journal ArticleDOI
TL;DR: Deep hybrid capture and amplicon sequencing of five important mTOR pathway genes shows that brain somatic mutations in TSC1 and TSC2 cause FCD and that in utero application of the CRISPR-Cas9 system is useful for generating neurodevelopmental disease models of somatic mutation in the brain.
Abstract: Focal cortical dysplasia (FCD) is a major cause of the sporadic form of intractable focal epilepsies that require surgical treatment. It has recently been reported that brain somatic mutations in MTOR account for 15%–25% of FCD type II (FCDII), characterized by cortical dyslamination and dysmorphic neurons. However, the genetic etiologies of FCDII-affected individuals who lack the MTOR mutation remain unclear. Here, we performed deep hybrid capture and amplicon sequencing (read depth of 100×–20,012×) of five important mTOR pathway genes—PIK3CA, PIK3R2, AKT3, TSC1, and TSC2—by using paired brain and saliva samples from 40 FCDII individuals negative for MTOR mutations. We found that 5 of 40 individuals (12.5%) had brain somatic mutations in TSC1 (c.64C>T [p.Arg22Trp] and c.610C>T [p.Arg204Cys]) and TSC2 (c.4639G>A [p.Val1547Ile]), and these results were reproducible on two different sequencing platforms. All identified mutations induced hyperactivation of the mTOR pathway by disrupting the formation or function of the TSC1-TSC2 complex. Furthermore, in utero CRISPR-Cas9-mediated genome editing of Tsc1 or Tsc2 induced the development of spontaneous behavioral seizures, as well as cytomegalic neurons and cortical dyslamination. These results show that brain somatic mutations in TSC1 and TSC2 cause FCD and that in utero application of the CRISPR-Cas9 system is useful for generating neurodevelopmental disease models of somatic mutations in the brain.

Journal ArticleDOI
TL;DR: It is shown that the potency of a drug to reverse cancer-associated gene expression changes positively correlates with that drug’s efficacy in preclinical models of breast, liver and colon cancers and may be complementary to the traditional target-based approach in connecting diseases to potentially efficacious drugs.
Abstract: The decreasing cost of genomic technologies has enabled the molecular characterization of large-scale clinical disease samples and of molecular changes upon drug treatment in various disease models. Exploring methods to relate diseases to potentially efficacious drugs through various molecular features is critically important in the discovery of new therapeutics. Here we show that the potency of a drug to reverse cancer-associated gene expression changes positively correlates with that drug's efficacy in preclinical models of breast, liver and colon cancers. Using a systems-based approach, we predict four compounds showing high potency to reverse gene expression in liver cancer and validate that all four compounds are effective in five liver cancer cell lines. The in vivo efficacy of pyrvinium pamoate is further confirmed in a subcutaneous xenograft model. In conclusion, this systems-based approach may be complementary to the traditional target-based approach in connecting diseases to potentially efficacious drugs.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy3  +1036 moreInstitutions (119)
TL;DR: In this paper, the results of searches for gravitational waves from 200 pulsars using data from the first observing run of the Advanced LIGO detectors were presented, and they were able to set the most constraining upper limits yet on their gravitational-wave amplitudes and ellipticities.
Abstract: We present the result of searches for gravitational waves from 200 pulsars using data from the first observing run of the Advanced LIGO detectors. We find no significant evidence for a gravitational-wave signal from any of these pulsars, but we are able to set the most constraining upper limits yet on their gravitational-wave amplitudes and ellipticities. For eight of these pulsars, our upper limits give bounds that are improvements over the indirect spin-down limit values. For another 32, we are within a factor of 10 of the spin-down limit, and it is likely that some of these will be reachable in future runs of the advanced detector. Taken as a whole, these new results improve on previous limits by more than a factor of two.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy3  +1030 moreInstitutions (114)
TL;DR: In this paper, the effects of possible systematic errors in the waveform models on estimates of its source parameters were investigated and no evidence for a systematic bias relative to the statistical error of the original parameter recovery of GW150914 due to modeling approximations or modeling inaccuracies was found.
Abstract: Parameter estimates of GW150914 were obtained using Bayesian inference, based on three semi-analytic waveform models for binary black hole coalescences. These waveform models differ from each other in their treatment of black hole spins, and all three models make some simplifying assumptions, notably to neglect sub-dominant waveform harmonic modes and orbital eccentricity. Furthermore, while the models are calibrated to agree with waveforms obtained by full numerical solutions of Einstein's equations, any such calibration is accurate only to some non-zero tolerance and is limited by the accuracy of the underlying phenomenology, availability, quality, and parameter-space coverage of numerical simulations. This paper complements the original analyses of GW150914 with an investigation of the effects of possible systematic errors in the waveform models on estimates of its source parameters. To test for systematic errors we repeat the original Bayesian analysis on mock signals from numerical simulations of a series of binary configurations with parameters similar to those found for GW150914. Overall, we find no evidence for a systematic bias relative to the statistical error of the original parameter recovery of GW150914 due to modeling approximations or modeling inaccuracies. However, parameter biases are found to occur for some configurations disfavored by the data of GW150914: for binaries inclined edge-on to the detector over a small range of choices of polarization angles, and also for eccentricities greater than ~0.05. For signals with higher signal-to-noise ratio than GW150914, or in other regions of the binary parameter space (lower masses, larger mass ratios, or higher spins), we expect that systematic errors in current waveform models may impact gravitational-wave measurements, making more accurate models desirable for future observations.

Journal ArticleDOI
TL;DR: The bulky nature of the triarylboron endows the D-A dyads with inherent steric "locking" for a highly twisted arrangement, leading to a small energy difference between singlet and triplet excited states (ΔEST) and thus exhibiting very efficient TADF with microsecond-range lifetimes.
Abstract: A synthetic approach to highly efficient thermally activated delayed fluorescence (TADF) is proposed that uses ortho donor (D)–acceptor (A) compounds (PXZoB, DPAoB, and CzoB), wherein the acceptor is based on triarylboron and the donor is phenoxazine (PXZ), diphenylamine (DPA), or carbazole (Cz). Combined with the ortho D–A connectivity, the bulky nature of the triarylboron endows the D–A dyads with inherent steric “locking” for a highly twisted arrangement, leading to a small energy difference between singlet and triplet excited states (ΔEST) and thus exhibiting very efficient TADF with microsecond-range lifetimes. In sharp contrast, the corresponding para D–A derivatives, DPApB and CzpB, only display short-lived, normal fluorescence. Organic light-emitting diodes (OLEDs) incorporating the proposed ortho D–A compounds as emitters display orange, greenish-blue, and pure blue emission and exhibit high external quantum efficiency (ηEQE). In particular, the pure blue OLEDs based on the proposed ortho D–A emi...

Journal ArticleDOI
Jaroslav Adam1, Jovan Milosevic2, Gabor Biro3, Edmundo Javier Garcia-Solis4  +1049 moreInstitutions (103)
TL;DR: In this article, the authors presented results on the inclusive J/$psi$ cross section in Pn-Pb and pp collisions at the ALICE detector at the CERN LHC.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy3  +1015 moreInstitutions (113)
TL;DR: Directed searches for narrowband gravitational waves from astrophysically interesting objects yield median frequency-dependent limits on strain amplitude at the most sensitive detector frequencies between 130-175 Hz, which represents a mean improvement of a factor of 2 across the band compared to previous searches of this kind.
Abstract: We employ gravitational-wave radiometry to map the stochastic gravitational wave background expected from a variety of contributing mechanisms and test the assumption of isotropy using data from the Advanced Laser Interferometer Gravitational Wave Observatory's (aLIGO) first observing run. We also search for persistent gravitational waves from point sources with only minimal assumptions over the 20-1726 Hz frequency band. Finding no evidence of gravitational waves from either point sources or a stochastic background, we set limits at 90% confidence. For broadband point sources, we report upper limits on the gravitational wave energy flux per unit frequency in the range F_{α,Θ}(f)<(0.1-56)×10^{-8} erg cm^{-2} s^{-1} Hz^{-1}(f/25 Hz)^{α-1} depending on the sky location Θ and the spectral power index α. For extended sources, we report upper limits on the fractional gravitational wave energy density required to close the Universe of Ω(f,Θ)<(0.39-7.6)×10^{-8} sr^{-1}(f/25 Hz)^{α} depending on Θ and α. Directed searches for narrowband gravitational waves from astrophysically interesting objects (Scorpius X-1, Supernova 1987 A, and the Galactic Center) yield median frequency-dependent limits on strain amplitude of h_{0}<(6.7,5.5, and 7.0)×10^{-25}, respectively, at the most sensitive detector frequencies between 130-175 Hz. This represents a mean improvement of a factor of 2 across the band compared to previous searches of this kind for these sky locations, considering the different quantities of strain constrained in each case.

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Shreyasi Acharya1, Dagmar Adamová2, Madan M. Aggarwal3, G. Aglieri Rinella4  +1044 moreInstitutions (101)
TL;DR: In this article, the production cross sections for prompt charmed mesons were measured at mid-rapidity in proton-proton collisions at a centre-of-mass energy of 7~{\mathrm {TeV}} with the ALICE detector at the Large Hadron Collider.
Abstract: The production cross sections for prompt charmed mesons $$\mathrm{D^0}$$ , $$\mathrm{D^+}$$ , $$\mathrm{D^{*+}}$$ and $$\mathrm{D_s^+}$$ were measured at mid-rapidity in proton–proton collisions at a centre-of-mass energy $$\sqrt{s}=7~{\mathrm {TeV}}$$ with the ALICE detector at the Large Hadron Collider (LHC). D mesons were reconstructed from their decays $$\mathrm{D}^0 \rightarrow \mathrm{K}^-\pi ^+$$ , $$\mathrm{D}^+\rightarrow \mathrm{K}^-\pi ^+\pi ^+$$ , $$\mathrm{D}^{*+} \rightarrow \mathrm{D}^0 \pi ^+$$ , $$\mathrm{D_s^{+}\rightarrow \phi \pi ^+\rightarrow K^-K^+\pi ^+}$$ , and their charge conjugates.With respect to previous measurements in the same rapidity region, the coverage in transverse momentum ( $$p_\mathrm{T}$$ ) is extended and the uncertainties are reduced by a factor of about two. The accuracy on the estimated total $$\mathrm{c}{\overline{\mathrm{c}}}$$ production cross section is likewise improved. The measured $$p_\mathrm{T}$$ -differential cross sections are compared with the results of three perturbative QCD calculations.

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J. Abadie1, B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2  +876 moreInstitutions (88)
TL;DR: In this paper, an all-sky search for periodic gravitational waves in the frequency band 20−475 Hz and with a frequency time derivative in the range of [−1.0,+0.1]×10−8
Abstract: We report on an all-sky search for periodic gravitational waves in the frequency band 20–475 Hz and with a frequency time derivative in the range of [−1.0,+0.1]×10−8 Hz/s. Such a signal could be produced by a nearby spinning and slightly nonaxisymmetric isolated neutron star in our galaxy. This search uses the data from Advanced LIGO’s first observational run, O1. No periodic gravitational wave signals were observed, and upper limits were placed on their strengths. The lowest upper limits on worst-case (linearly polarized) strain amplitude h0 are ∼4×10−25 near 170 Hz. For a circularly polarized source (most favorable orientation), the smallest upper limits obtained are ∼1.5×10−25. These upper limits refer to all sky locations and the entire range of frequency derivative values. For a population-averaged ensemble of sky locations and stellar orientations, the lowest upper limits obtained for the strain amplitude are ∼2.5×10−25.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy3  +997 moreInstitutions (112)
TL;DR: The results from an all-sky search for short-duration gravitational waves in the data of the first run of the Advanced LIGO detectors between September 2015 and January 2016 are presented in this article.
Abstract: We present the results from an all-sky search for short-duration gravitational waves in the data of the first run of the Advanced LIGO detectors between September 2015 and January 2016. The search algorithms use minimal assumptions on the signal morphology, so they are sensitive to a wide range of sources emitting gravitational waves. The analyses target transient signals with duration ranging from milliseconds to seconds over the frequency band of 32 to 4096 Hz. The first observed gravitational-wave event, GW150914, has been detected with high confidence in this search; the other known gravitational-wave event, GW151226, falls below the search’s sensitivity. Besides GW150914, all of the search results are consistent with the expected rate of accidental noise coincidences. Finally, we estimate rate-density limits for a broad range of non-binary-black-hole transient gravitational-wave sources as a function of their gravitational radiation emission energy and their characteristic frequency. These rate-density upper limits are stricter than those previously published by an order of magnitude.

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Jaroslav Adam1, Dagmar Adamová2, Madan M. Aggarwal3, G. Aglieri Rinella4  +1043 moreInstitutions (100)
TL;DR: In this paper, the authors measured the pseudorapidity of particles in Pb-Pb collisions at a range from 3.5$ to 5$ and found that for the most central (0-5%) collisions, the density was $21\,400\pm 1\,300$ while for the more peripheral (80-90%) collisions it was $230\pm 38$.

Journal ArticleDOI
Jaroslav Adam1, Dagmar Adamová2, Madan M. Aggarwal3, G. Aglieri Rinella4  +1008 moreInstitutions (95)
TL;DR: A detailed study of pseudorapidity densities and multiplicity distributions of primary charged particles produced in proton-proton collisions, at $\sqrt{s} =$ 0.76, 7 and 8 TeV, in the pseudoreapidity range $|\eta|<2$ was carried out using the ALICE detector.
Abstract: A detailed study of pseudorapidity densities and multiplicity distributions of primary charged particles produced in proton-proton collisions, at $\sqrt{s} =$ 0.9, 2.36, 2.76, 7 and 8 TeV, in the pseudorapidity range $|\eta|<2$, was carried out using the ALICE detector. Measurements were obtained for three event classes: inelastic, non-single diffractive and events with at least one charged particle in the pseudorapidity interval $|\eta|<1$. The use of an improved track-counting algorithm combined with ALICE's measurements of diffractive processes allows a higher precision compared to our previous publications. A KNO scaling study was performed in the pseudorapidity intervals $|\eta|<$ 0.5, 1.0 and 1.5. The data are compared to other experimental results and to models as implemented in Monte Carlo event generators PHOJET and recent tunes of PYTHIA6, PYTHIA8 and EPOS.