On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85 þ21 −14 M ⊙ and 66 þ17 −18 M ⊙ (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M ⊙. We calculate the mass of the remnant to be 142 þ28 −16 M ⊙ , which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3 þ2.4 −2.6 Gpc, corresponding to a redshift of 0.82 þ0.28 −0.34. The inferred rate of mergers similar to GW190521 is 0.13 þ0.30 −0.11 Gpc −3 yr −1 .

Nearly a century after Einstein first predicted the existence of gravitational waves, a global network of Earth-based gravitational wave observatories [1, 2, 3, 4] is seeking to directly detect this faint radiation using precision laser interferometry. Photon shot noise, due to the quantum nature of light, imposes a fundamental limit on the attometre-level sensitivity of the kilometre-scale Michelson interferometers deployed for this task. Here, we inject squeezed states to improve the performance of one of the detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) beyond the quantum noise limit, most notably in the frequency region down to 150 Hz, critically important for several astrophysical sources, with no deterioration of performance observed at any frequency. With the injection of squeezed states, this LIGO detector demonstrated the best broadband sensitivity to gravitational waves ever achieved, with important implications for observing the gravitational-wave Universe with unprecedented sensitivity

In 2009-2010, the Laser Interferometer Gravitational-wave Observatory (LIGO) operated together with international partners Virgo and GEO600 as a network to search for gravitational waves of astrophysical origin. The sensitivity of these detectors was limited by a combination of noise sources inherent to the instrumental design and its environment, often localized in time or frequency, that couple into the gravitational-wave readout. Here we review the performance of the LIGO instruments during this epoch, the work done to characterize the detectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of LIGO to a variety of astrophysical sources.

Z. are inventors of two pending patent applications for use of BCL-X L PROTACs as senolytic and antitumor agents. R.H., G.Z., and D.Z. are co-founders of and have equity in Dialectic Therapeutics, which develops BCL-X L PROTACs to treat cancer.

Around the globe several observatories are seeking the first direct detection of gravitational waves (GWs). These waves are predicted by Einstein's general theory of relativity and are generated, for example, by black-hole binary systems. Present GW detectors are Michelson-type kilometre-scale laser interferometers measuring the distance changes between mirrors suspended in vacuum. The sensitivity of these detectors at frequencies above several hundred hertz is limited by the vacuum (zero-point) fluctuations of the electromagnetic field. A quantum technology--the injection of squeezed light--offers a solution to this problem. Here we demonstrate the squeezed-light enhancement of GEO600, which will be the GW observatory operated by the LIGO Scientific Collaboration in its search for GWs for the next 3-4 years. GEO600 now operates with its best ever sensitivity, which proves the usefulness of quantum entanglement and the qualification of squeezed light as a key technology for future GW astronomy

The Wnt signaling pathway is critically involved in both the development and homeostasis of tissues via regulation of their endogenous stem cells. Aberrant Wnt signaling has been described as a key player in the initiation of and/or maintenance and development of many cancers, via affecting the behavior of Cancer Stem Cells (CSCs). CSCs are considered by most to be responsible for establishment of the tumor and also for disease relapse, as they possess inherent drug-resistance properties. The development of new therapeutic compounds targeting the Wnt signaling pathway promises new hope to eliminate CSCs and achieve cancer eradication. However, a major challenge resides in developing a strategy efficient enough to target the dysregulated Wnt pathway in CSCs, while being safe enough to not damage the normal somatic stem cell population required for tissue homeostasis and repair. Here we review recent therapeutic approaches to target the Wnt pathway and their clinical applications.

Tyrosine kinase inhibitors (TKI) are widely used to treat patients with leukemia driven by BCR-ABL11 and other oncogenic tyrosine kinases2,3. Recent efforts focused on the development of more potent TKI that also inhibit mutant tyrosine kinases4,5. However, even effective TKI typically fail to eradicate leukemia-initiating cells6–8, which often cause recurrence of leukemia after initially successful treatment. Here we report on the discovery of a novel mechanism of drug-resistance, which is based on protective feedback signaling of leukemia cells in response to TKI-treatment. We identified BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukemia-initiating subclones. BCL6 is a known proto-oncogene that is often translocated in diffuse large B cell lymphoma (DLBCL)9. In response to TKI-treatment, BCR-ABL1 acute lymphoblastic leukemia (ALL) cells upregulate BCL6 protein levels by ~90-fold, i.e. to similar levels as in DLBCL (Fig. 1a). Upregulation of BCL6 in response to TKI-treatment represents a novel defense mechanism, which enables leukemia cells to survive TKI-treatment: Previous work suggested that TKI-mediated cell death is largely p53-independent. Here we demonstrate that BCL6 upregulation upon TKI-treatment leads to transcriptional inactivation of the p53 pathway. BCL6-deficient leukemia cells fail to inactivate p53 and are particularly sensitive to TKI-treatment. BCL6−/− leukemia cells are poised to undergo cellular senescence and fail to initiate leukemia in serial transplant recipients. A combination of TKI-treatment and a novel BCL6 peptide inhibitor markedly increased survival of NOD/SCID mice xenografted with patient-derived BCR-ABL1 ALL cells. We propose that dual targeting of oncogenic tyrosine kinases and BCL6-dependent feedback (Supplementary Fig. 1) represents a novel strategy to eradicate drug-resistant and leukemia-initiating subclones in tyrosine kinase-driven leukemia.

Focus on individual outsourcing decisions in IT research has often yielded contradictory findings and recommendations. To address these contradictions, we investigate a holistic, configurational approach with the prevailing universalistic or contingency perspectives in exploring the effects of IT outsourcing strategies on outsourcing success. Based on residual rights theory, we begin by identifying three dimensions of IT outsourcing strategies: degree of integration, allocation of control, and performance period. We then develop a model of fit-as-gestalt, drawing from literatures on strategy, governance, interorganizational relationships, and outsourcing. Next, based on data from 311 firms in South Korea, we test universalistic and contingency perspectives in explaining the relationship between IT outsourcing strategies and outsourcing success. We then identify three congruent patterns, or gestalts, of IT outsourcing strategies. We term these strategies independent, arm's-length, and embedded strategies. To establish the predictive validity of these gestalts and the viability of a configurational perspective, we then explore the effects of these congruent gestalts vis-à-vis noncongruent patterns on three dimensions of outsourcing success: strategic competence, cost efficiency, and technology catalysis. We also contrast the effects of each of the three gestalts on each of the three dimensions of outsourcing success. Our findings indicate the superiority of the configurational approach over universalistic and contingency perspectives in explaining outsourcing success.