Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Effects of melatonin receptor expression on prognosis and survival in oral squamous cell carcinoma patients.

Melatonin receptors can inhibit breast and prostate cancers; however, little is known regarding their effects on oral squamous cell carcinoma. In this study, we collected specimens from 81 patients with oral squamous cell carcinoma and analysed clinicopathological data retrospectively. In addition, the expression of the melatonin receptor was analysed immunohistochemically. Survival rates were calculated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed based on the Cox proportional-hazards model. Further, an in vitro study was performed using YD15 cells. The cells were transfected with siRNA targeting melatonin receptor 1A and 1B for evaluating the malignancy of melatonin receptors by western blotting, trypan blue-exclusion, colony-forming, wound-healing, and invasion assays. Survival decreased as melatonin receptor expression and clinical and pathological tumour-node-metastasis stages increased. A Cox proportional-hazard model showed that melatonin receptor 1A may serve as a significant predictor of the survival rate of patients with oral squamous cell carcinoma [hazard ratio = 1.423, 95% confidence interval (CI) = 1.019-1.988, p = 0.038]. Melatonin receptor 1A and 1B knockdown significantly suppressed proliferation, migration ability, and invasion ability of YD15 cells in vitro. Our findings reveal that inhibiting melatonin receptor expression may suppress oral squamous cell carcinoma development.

Clinical characteristics and differences of 802 acral tumours, categorized by anatomical sites.

BACKGROUND: Acral skin tumours are common, but information in the literature regarding their incidence is scarce. AIM: To investigate the clinical characteristics and differences in incidence of benign and malignant acral tumours by anatomical site. METHODS: A retrospective review was conducted of 802 patients with acral skin tumours confirmed by skin biopsy between January 2010 and December 2019. Age, sex, duration, symptoms and sites were obtained from medical records and photographs. RESULTS: The mean age of onset was 43.8 years, the male/female ratio was 1 : 1.41, and the mean duration was 68.8 months. Most tumours were asymptomatic (66.7%). In total, 802 acral tumours were identified: 512 (63.8%) were benign and 290 (36.2%) were malignant. The most common benign tumours were benign melanocytic lesions (n = 239), and the most common malignant tumours were melanoma (n = 234). The most common site was the sole (n = 408). Benign melanocytic lesions, melanoma and epidermal cysts were more frequent on the foot, whereas pyogenic granuloma, glomus tumours, haemangiomas and mucous cysts were more frequent on the hand. Glomus tumours, fibromas, mucous cysts and osteomas were more frequent on the nail portion, and benign melanocytic lesions and epidermal cysts were more frequent on the non-nail portion. CONCLUSION: This study reports the incidence of various benign and malignant acral tumours according to site, and we believe the results will be helpful in making a clinical diagnosis.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

A large-aperture strip-grid beam splitter for partially combined two millimeter-wave diagnostics on Korea Superconducting Tokamak Advanced Research.

A large-aperture beam splitter has been developed for simultaneous operation of two millimeter-wave diagnostics employing different probe beams in the frequency and polarization, microwave imaging reflectometer (∼85 GHz X-mode), and collective scattering system (300 GHz O-mode), on the Korea Superconducting Tokamak Advanced Research device. The beam splitter was designed based on a polarizer concept (i.e., grid of metal strips on a thin dielectric sheet), and this can be an optimal solution for these two diagnostics. Fabrication of the strips with uniform sub-millimeter width and spacing on a large dielectric sheet was achieved with an etching technique, and the laboratory test results on the reflection and transmission ratio are in good agreement with design values.

Surfactant protein D alleviates eosinophil-mediated airway inflammation and remodeling in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Surfactant protein D (SPD) is a member of the collectin family that lines the airway epithelial cells with host defense. However, the role of SPD in the pathogenesis of aspirin-exacerbated respiratory disease (AERD) is still unclear. METHODS: The serum SPD level was measured in patients with AERD (n = 336), those with aspirin-tolerant asthma (ATA, n = 442), and healthy controls (HC, n = 104). Polymorphisms of SFTPD in the study subjects were analyzed. The effect of LTE4 on SPD production through eosinophil infiltration was investigated in BALB/c mice. The protective function of SPD against eosinophils inducing inflammation and remodeling was assessed in vitro/vivo. The potential efficacy of nintedanib against airway remodeling through the production of SPD was evaluated. RESULTS: The serum SPD level was significantly lower (P < .001) in AERD compared with ATA patients, and negatively correlated with fall in FEV1 (%) after lysine-aspirin bronchoprovocation test and/or the urinary LTE4 level. In addition, polymorphism of SFTPD at rs721917 was significantly different in the study subjects (odds ratio, 1.310; 95% confidence intervals, 2.124-3.446; P = .002). LTE4-exposed mice showed an increased eosinophil count with a decreased SPD level in bronchoalveolar lavage fluid. Eosinophils increased α-smooth muscle actin expression in airway epithelial cells, which was attenuated by SPD treatment. Furthermore, nintedanib protected the airway epithelial cells against eosinophils by enhancing the production of SPD. CONCLUSION: The decreased level of SPD in AERD was associated with airway inflammation/remodeling under the eosinophilic condition, suggesting that modulation of SPD may provide a potential benefit in AERD.

Background model for the NaI(Tl) crystals in COSINE-100.

The COSINE-100 dark matter search experiment is an array of NaI(Tl) crystal detectors located in the Yangyang Underground Laboratory (Y2L). To understand measured backgrounds in the NaI(Tl) crystals we have performed Monte Carlo simulations using the Geant4 toolkit and developed background models for each crystal that consider contributions from both internal and external sources, including cosmogenic nuclides. The background models are based on comparisons of measurement data with Monte Carlo simulations that are guided by a campaign of material assays and are used to evaluate backgrounds and identify their sources. The average background level for the six crystals (70 kg total mass) that are studied is 3.5 counts/day/keV/kg in the (2-6) keV energy interval. The dominant contributors in this energy region are found to be 210 Pb and 3 H.

Expression of the glutamine metabolism-related proteins glutaminase 1 and glutamate dehydrogenase in canine mammary tumours.

Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumour growth and glutamine metabolism. Because of their similarities, canine mammary carcinomas are useful for studying human breast cancer. Accordingly, we investigated the correlations between the expression of glutamine metabolism-related proteins and the pathological features of canine mammary tumours. We performed immunohistochemical and western blot analysis of 39 mammary tumour tissues. In immunohistochemical analysis, the expression of glutaminase 1 (GLS1) in the epithelial region increased according to the histological grade (P < .005). In the stromal region, complex-type tumours displayed significantly higher GLS1 intensity than simple-type tumours. However, glutamate dehydrogenase expression did not show the same tendencies as GLS1. The western blot results were consistent with the immunohistochemical findings. These results suggest that the expression of GLS1 is correlates with clinicopathological factors in canine mammary tumours and shows a similar pattern to human breast cancer.

Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods.

Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4-5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate adoption of defined approaches for skin sensitisation assessments.

Detecting Dark Photons with Reactor Neutrino Experiments.

We propose to search for light U(1) dark photons, A^{'}, produced via kinetically mixing with ordinary photons via the Compton-like process, γe^{-}→A^{'}e^{-}, in a nuclear reactor and detected by their interactions with the material in the active volumes of reactor neutrino experiments. We derive 95% confidence-level upper limits on ε, the A^{'}-γ mixing parameter, ε, for dark-photon masses below 1 MeV of ε<1.3×10^{-5} and ε<2.1×10^{-5}, from NEOS and TEXONO experimental data, respectively. This study demonstrates the applicability of nuclear reactors as potential sources of intense fluxes of low-mass dark photons.

Human DBR1 modulates the recycling of snRNPs to affect alternative RNA splicing and contributes to the suppression of cancer development.

The contribution of RNA processing to tumorigenesis is understudied. Here, we report that the human RNA debranching enzyme (hDBR1), when inappropriately regulated, induces oncogenesis by causing RNA processing defects, for example, splicing defects. We found that wild-type p53 and hypoxia-inducible factor 1 co-regulate hDBR1 expression, and insufficient hDBR1 leads to a higher rate of exon skipping. Transcriptomic sequencing confirmed the effect of hDBR1 on RNA splicing, and metabolite profiling supported the observation that neoplasm is triggered by a decrease in hDBR1 expression both in vitro and in vivo. Most importantly, when modulating the expression of hDBR1, which was found to be generally low in malignant human tissues, higher expression of hDBR1 only affected exon-skipping activity in malignant cells. Together, our findings demonstrate previously unrecognized regulation and functions of hDBR1, with immediate clinical implications regarding the regulation of hDBR1 as an effective strategy for combating human cancer.

Sterile Neutrino Search at the NEOS Experiment.

An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.

Solitary perturbations in the steep boundary of magnetized toroidal plasma.

Solitary perturbations (SPs) localized both poloidally and radially are detected within ~100 µs before the partial collapse of the high pressure gradient boundary region (called pedestal) of magnetized toroidal plasma in the KSTAR tokamak device. The SP develops with a low toroidal mode number (typically unity) in the pedestal ingrained with quasi-stable edge-localized mode (QSM) which commonly appears during the inter-collapse period. The SPs have smaller mode pitch and different (often opposite) rotation velocity compared to the QSMs. Similar solitary perturbations are also frequently observed before the onset of complete pedestal collapse, suggesting a strong connection between the SP generation and the pedestal collapse.

Ion gyroscale fluctuation measurement with microwave imaging reflectometer on KSTAR.

Ion gyroscale turbulent fluctuations with the poloidal wavenumber kθ ∼ 3 cm-1 have been measured in the core region of the neutral beam (NB) injected low confinement (L-mode) plasmas on Korea superconducting tokamak advanced research. The turbulence poloidal wavenumbers are deduced from the frequencies and poloidal rotation velocities in the laboratory frame, measured by the multichannel microwave imaging reflectometer. Linear and nonlinear gyrokinetic simulations also predict the unstable modes with the normalized wavenumber kθρs ∼ 0.4, consistent with the measurement. Comparison of the measured frequencies with the intrinsic mode frequencies from the linear simulations indicates that the measured ones are primarily due to the E × B flow velocity in the NB-injected fast rotating plasmas.

New compact and efficient local oscillator optic system for the KSTAR electron cyclotron emission imaging system.

Electron cyclotron emission imaging (ECEI) diagnostic on Korean Superconducting Tokamak Advanced Research utilizes quasi-optical heterodyne-detection method to measure 2D (vertical and radial) Te fluctuations from two toroidally separated poloidal cross section of the plasma. A cylindrical lens local oscillator (LO) optics with optical path length (OPL) 2-2.5 m has been used in the current ECEI system to couple the LO source to the 24 vertically aligned array of ECE detectors. For efficient and compact LO optics employing the Powell lens is proposed so that the OPL of the LO source is significantly reduced from ∼2.0 m to 0.4 m with new optics. The coupling efficiency of the LO source is expected to be improved especially at the edge channels. Results from the optical simulation together with the laboratory test of the prototype optics will be discussed in this paper.

Compact ECEI system with in-vessel reflective optics for WEST.

An electron cyclotron emission imaging (ECEI) diagnostic system for WEST (W Environment for Steady state Tokamak) is under development to study the MHD instabilities affected by tungsten impurities. The system will provide 2-D Te fluctuation images (width × height = ∼18 cm × âˆ¼ 34 cm at low field side and ∼13 cm × âˆ¼ 39 cm at high field side) from a poloidal cross section with high spatial (≤1.7 cm) and temporal (≤2 µs) resolutions. While the key concept and electronic structure are similar to that of prior ECEI systems on other tokamak devices such as KSTAR, DIII-D, or ASDEX-U, part of the imaging optics have to be placed inside the vacuum vessel in order to resolve issues on limited installation space and longer beam path to the detector position. The in-vessel optics consisting of two large curvature-radius mirrors are expected to withstand the extreme heating on long-pulse operation scenario (∼1000 s). The out-vessel optical housing is constructed as compact as possible to remove easily from the installation site in case of necessity. Commissioning of the system is scheduled on the second experimental WEST campaign end of 2017.