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Detection of X-ray emission at a location coincident with the kilonova transient of the gravitational-wave event GW170817 provides the missing observational link between short gamma-ray bursts and gravitational waves from neutron-star mergers. When neutron stars collide Merging neutron stars are potential sources of gravitational waves and have long been predicted to produce jets of material as part of a low-luminosity transient known as a 'kilonova'. There is growing evidence that neutron-star mergers also give rise to short, hard gamma-ray bursts. A group of papers in this issue report observations of a transient associated with the gravitational-wave event GW170817—a signature of two neutron stars merging and a gamma-ray flash—that was detected in August 2017. The observed gamma-ray, X-ray, optical and infrared radiation signatures support the predictions of an outflow of matter from double neutron-star mergers and present a clear origin for gamma-ray bursts. Previous predictions differ over whether the jet material would combine to form light or heavy elements. These papers now show that the early part of the outflow was associated with lighter elements whereas the later observations can be explained by heavier elements, the origins of which have been uncertain. However, one paper (by Stephen Smartt and colleagues) argues that only light elements are needed for the entire event. Additionally, Eleonora Troja and colleagues report X-ray observations and radio emissions that suggest that the 'kilonova' jet was observed off-axis, which could explain why gamma-ray-burst detections are seen as dim. A long-standing paradigm in astrophysics is that collisions—or mergers—of two neutron stars form highly relativistic and collimated outflows (jets) that power γ-ray bursts of short (less than two seconds) duration 1 , 2 , 3 . The observational support for this model, however, is only indirect 4 , 5 . A hitherto outstanding prediction is that gravitational-wave events from such mergers should be associated with γ-ray bursts, and that a majority of these bursts should be seen off-axis, that is, they should point away from Earth 6 , 7 . Here we report the discovery observations of the X-ray counterpart associated with the gravitational-wave event GW170817. Although the electromagnetic counterpart at optical and infrared frequencies is dominated by the radioactive glow (known as a ‘kilonova’) from freshly synthesized rapid neutron capture (r-process) material in the merger ejecta 8 , 9 , 10 , observations at X-ray and, later, radio frequencies are consistent with a short γ-ray burst viewed off-axis 7 , 11 . Our detection of X-ray emission at a location coincident with the kilonova transient provides the missing observational link between short γ-ray bursts and gravitational waves from neutron-star mergers, and gives independent confirmation of the collimated nature of the γ-ray-burst emission.

Despite diversity in genetic events in oncogenesis, cancer cells exhibit a common set of functional characteristics. Otto Warburg discovered that cancer cells have consistently higher rates of glycolysis than normal cells. The underlying mechanisms leading to the Warburg phenomenon include mitochondrial changes, upregulation of rate-limiting enzymes/proteins in glycolysis and intracellular pH regulation, hypoxia-induced switch to anaerobic metabolism, and metabolic reprogramming after loss of p53 function. The regulation of energy metabolism can be traced to a “triad” of transcription factors: c-MYC, HIF-1 and p53. Oncogenetic changes involve a nonrandom set of gene deletions, amplifications and mutations, and many oncogenes and tumor suppressor genes cluster along the signaling pathways that regulate c-MYC, HIF-1 and p53. Glycolysis in cancer cells has clinical implications in cancer diagnosis, treatment and interaction with diabetes mellitus. Many drugs targeting energy metabolism are in development. Future advances in technology may bring about transcriptome and metabolome-guided chemotherapy.

The advanced molybdenum-based rare process experiment (AMoRE) aims to search for neutrinoless double beta decay (\\[0\\nu \\beta \\beta \\]) of \\[^{100}\\]Mo with \\[\\sim 100\\,\\hbox {kg}\\] of \\[^{100}\\]Mo-enriched molybdenum embedded in cryogenic detectors with a dual heat and light readout. At the current, pilot stage of the AMoRE project we employ six calcium molybdate crystals with a total mass of 1.9 kg, produced from \\[^{48}\\]Ca-depleted calcium and \\[^{100}\\]Mo-enriched molybdenum (\\[^{48{{\\text {depl}}}\\hbox {Ca}^{100}\\hbox {MoO}_{4}\\]). The simultaneous detection of heat (phonon) and scintillation (photon) signals is realized with high resolution metallic magnetic calorimeter sensors that operate at milli-Kelvin temperatures. This stage of the project is carried out in the Yangyang underground laboratory at a depth of 700 m. We report first results from the AMoRE-Pilot \\[0\\nu \\beta \\beta \\] search with a 111 kg day live exposure of \\[^{48{{\\text {depl}}}\\hbox {Ca}^{100}\\hbox {MoO}_{4}\\] crystals. No evidence for \\[0\\nu \\beta \\beta \\] decay of \\[^{100}\\]Mo is found, and a upper limit is set for the half-life of \\[0\\nu \\beta \\beta \\] of \\[^{100}\\]Mo of \\[T^{0\\nu }_{1/2} > 9.5\\times 10^{22}~\\hbox {years}\\] at 90% C.L. This limit corresponds to an effective Majorana neutrino mass limit in the range \\[\\langle m_{\\beta \\beta }\\rangle \\le (1.2-2.1)\\,\\hbox {eV}\\].

AMoRE is an international project to search for the neutrinoless double beta decay of 100 Mo using a detection technology consisting of magnetic microcalorimeters (MMCs) and molybdenum-based scintillating crystals. Data collection has begun for the current AMORE-I phase of the project, an upgrade from the previous pilot phase. AMoRE-I employs thirteen 48 depl . Ca 100 MoO 4 crystals and five Li 2 100 MoO 4 crystals for a total crystal mass of 6.2 kg. Each detector module contains a scintillating crystal with two MMC channels for heat and light detection. We report the present status of the experiment and the performance of the detector modules.

Magnetic flux quantization is one of the defining properties of a superconductor. We report the observation of half-integer magnetic flux quantization in mesoscopic rings of superconducting β-Bi₂Pd thin films. The half-quantum fluxoid manifests itself as a π phase shift in the quantum oscillation of the superconducting critical temperature. This result verifies unconventional superconductivity of β-Bi₂Pd and is consistent with a spin-triplet pairing symmetry. Our findings may have implications for flux quantum bits in the context of quantum computing.

Uncontrolled growth and diffused invasion are major causes of mortality in patients with malignant gliomas. Nodal has been shown to have a central role in the tumorigenic signaling pathways of malignant melanoma. In this study, we show that grade IV human glioma cell lines expressed different levels of Nodal, paralleled to the potential for cell invasiveness. Treatment of glioma cell lines with recombinant Nodal (rNodal) increased matrix metalloproteinase 2 (MMP-2) secretion and cell invasiveness. The ectopic expression of Nodal in GBM glioma cells that expressed Nodal at low level resulted in increased MMP-2 secretion, enhanced cell invasiveness, raised cell proliferation rates in vitro , increased tumor growth in vivo , and was associated with poor survival in a mice xenograft model. In contrast, the knockdown of Nodal expression in U87MG glioma cells with high Nodal expression level had reduced MMP-2 secretion, less cell invasiveness, lower tumor growth in vivo and longer lifespan in mice with U87MG/shNodal cell xenografts. In addition, Nodal knockdown promoted the reversion of malignant glioma cells toward a differentiated astrocytic phenotype. Furthermore, our data support the notion that Nodal may regulate glioma progression through the induction of the leukemia inhibitory factor (LIF) and Cripto-1 through activated Smad.

SummaryThe mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk.IntroductionIt is unclear whether subsequent fractures or a certain location and sequence of subsequent fractures are associated with mortality risk in the elderly. We aimed to investigate the relationship between subsequent fractures and mortality risk.MethodsUsing the Korean National Health Insurance Research Database, we analyzed the cohort data of 24,756 patients aged > 60 years who sustained fractures between 2002 and 2013. Cox regression was used to assess the mortality risk associated with the number, locations, and sequences of subsequent fractures.ResultsMortality hazard ratios (HRs) for women and men were shown to be associated with the number of subsequent fractures (one, 1.63 (95% confidence interval [CI], 1.48–1.80) and 1.42 (95% CI, 1.28–1.58); two, 1.75 (95% CI, 1.47–2.08) and 2.03 (95% CI, 1.69–2.43); three or more, 2.46(95% CI, 1.92–3.15) and 1.92 (95% CI, 1.34–2.74), respectively). For women, the mortality risk was high when hip (HR, 2.49; 95% CI, 1.80–3.44) or vertebral (HR, 1.40; 95% CI, 1.03–1.90) fracture occurred as a second fracture. Compared with a single hip fracture, there was a high mortality risk in the group with hip fracture after the first vertebral fracture (HR, 2.90; 95% CI, 1.86–4.54), followed by vertebral fracture after the first hip fracture (HR, 1.90; 95% CI, 1.12–3.22).ConclusionThe mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk.

The annual modulation signal observed by the DAMA experiment is a long-standing question in the community of dark matter direct detection. This necessitates an independent verification of its existence using the same detection technique. The COSINE-100 experiment has been operating with 106 kg of low-background NaI(Tl) detectors providing interesting checks on the DAMA signal. However, due to higher backgrounds in the NaI(Tl) crystals used in COSINE-100 relative to those used for DAMA, it was difficult to reach final conclusions. Since the start of COSINE-100 data taking in 2016, we also have initiated a program to develop ultra-pure NaI(Tl) crystals for COSINE-200, the next phase of the experiment. The program includes efforts of raw powder purification, ultra-pure NaI(Tl) crystal growth, and detector assembly techniques. After extensive research and development of NaI(Tl) crystal growth, we have successfully grown a few small-size (0.61–0.78 kg) thallium-doped crystals with high radio-purity. A high light yield has been achieved by improvements of our detector assembly technique. Here we report the ultra-pure NaI(Tl) detector developments at the Institute for Basic Science, Korea. The technique developed here will be applied to the production of NaI(Tl) detectors for the COSINE-200 experiment.

The Korea Invisible Mass Search (KIMS) collaboration has developed low-background NaI(Tl) crystals that are suitable for the direct detection of WIMP dark matter. Building on experience accumulated during the KIMS-CsI programs, the KIMS-NaI experiment will consist of a 200 kg NaI(Tl) crystal array surrounded by layers of shielding structures and will be operated at the Yangyang underground laboratory. The goal is to provide an unambiguous test of the DAMA/LIBRA annual modulation signature. Measurements of six prototype crystals show progress in the reduction of internal contamination from radioisotopes. Based on our understanding of these measurements, we expect to achieve a background level in the final detector configuration that is less than 1 count/day/keV/kg for recoil energies around 2 keV. The annual modulation sensitivity for the KIMS-NaI experiment shows that an unambiguous 7 σ test of the DAMA/LIBRA signature would be possible with a 600 kg year exposure with this system.

Tripartite motif 24 protein (TRIM24) is a plant homeodomain/bromodomain histone reader, recently associated with poor overall survival of breast-cancer patients. At a molecular level, TRIM24 is a negative regulator of p53 levels and a co-activator of estrogen receptor. However, the role of TRIM24 in breast tumorigenesis remains largely unknown. We used an isogenic human mammary epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue, and found that ectopic expression of TRIM24 in immortalized HMECs (TRIM24 iHMECs) greatly increased cellular proliferation and induced malignant transformation. Subcutaneous injection of TRIM24 iHMECs in nude mice led to growth of intermediate to high-grade tumors in 60–70% of mice. Molecular analysis of TRIM24 iHMECs revealed a glycolytic and tricarboxylic acid cycle gene signature, alongside increased glucose uptake and activated aerobic glycolysis. Collectively, these results identify a role for TRIM24 in breast tumorigenesis through reprogramming of glucose metabolism in HMECs, further supporting TRIM24 as a viable therapeutic target in breast cancer.