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.
Low-dose organochlorine (OC) pesticides have recently been associated with type 2 diabetes in several non-Asian general populations. As there is currently epidemic type 2 diabetes in Asia, we ...investigated the associations between OC pesticides and type 2 diabetes in Koreans. Among subjects who participated in a community-based health survey, we randomly selected 40 diabetic patients and 40 normal controls. Ten OC pesticides (beta-hexachlorocyclohexane, hexachlorobenzene, heptachlor epoxide, p,p′-DDE, p,p′-DDD, p,p′-DDT, o,p′-DDT, oxychlordane, trans-nonachlor, and mirex) detectable in ≥
70% of controls were analyzed in relation to diabetes. Most OC pesticides showed strong associations with type 2 diabetes after adjusting for age, sex, BMI, alcohol consumption, and cigarette smoking. Compared with subjects in the lowest tertile of each OC pesticide, adjusted odds ratios (ORs) in the 3rd tertile ranged from 3.1 (95% CI 0.8–12.1) for heptachlor epoxide to 26.0 (95% CI 1.3–517.4) for oxychlordane. In the case of chemicals belonging to the DDT family, adjusted ORs in the 3rd tertile were in the range of 10.6 (95% CI 1.3–84.9) for p,p′-DDT to 12.7 (95% CI 1.9–83.7) for p,p′-DDE. In this exploratory study with small sample, low-dose background exposure to OC pesticides was strongly associated with prevalent type 2 diabetes in Koreans even though absolute concentrations of OC pesticides were no higher than in other populations. Asians may be more susceptible to adverse effects of OC pesticides than other races.
X-ray free-electron lasers enable the investigation of the structure and dynamics of diverse systems, including atoms, molecules, nanocrystals and single bioparticles, under extreme conditions. Many ...imaging applications that target biological systems and complex materials use hard X-ray pulses with extremely high peak intensities (exceeding 10
watts per square centimetre). However, fundamental investigations have focused mainly on the individual response of atoms and small molecules using soft X-rays with much lower intensities. Studies with intense X-ray pulses have shown that irradiated atoms reach a very high degree of ionization, owing to multiphoton absorption, which in a heteronuclear molecular system occurs predominantly locally on a heavy atom (provided that the absorption cross-section of the heavy atom is considerably larger than those of its neighbours) and is followed by efficient redistribution of the induced charge. In serial femtosecond crystallography of biological objects-an application of X-ray free-electron lasers that greatly enhances our ability to determine protein structure-the ionization of heavy atoms increases the local radiation damage that is seen in the diffraction patterns of these objects and has been suggested as a way of phasing the diffraction data. On the basis of experiments using either soft or less-intense hard X-rays, it is thought that the induced charge and associated radiation damage of atoms in polyatomic molecules can be inferred from the charge that is induced in an isolated atom under otherwise comparable irradiation conditions. Here we show that the femtosecond response of small polyatomic molecules that contain one heavy atom to ultra-intense (with intensities approaching 10
watts per square centimetre), hard (with photon energies of 8.3 kiloelectronvolts) X-ray pulses is qualitatively different: our experimental and modelling results establish that, under these conditions, the ionization of a molecule is considerably enhanced compared to that of an individual heavy atom with the same absorption cross-section. This enhancement is driven by ultrafast charge transfer within the molecule, which refills the core holes that are created in the heavy atom, providing further targets for inner-shell ionization and resulting in the emission of more than 50 electrons during the X-ray pulse. Our results demonstrate that efficient modelling of X-ray-driven processes in complex systems at ultrahigh intensities is feasible.
Pathologic alterations in podocytes lead to failure of an essential component of the glomerular filtration barrier and proteinuria in chronic kidney diseases. Elevated levels of saturated free fatty ...acid (FFA) are harmful to various tissues, implemented in the progression of diabetes and its complications such as proteinuria in diabetic nephropathy. Here, we investigated the molecular mechanism of palmitate cytotoxicity in cultured mouse podocytes. Incubation with palmitate dose-dependently increased cytosolic and mitochondrial reactive oxygen species, depolarized the mitochondrial membrane potential, impaired ATP synthesis and elicited apoptotic cell death. Palmitate not only evoked mitochondrial fragmentation but also caused marked dilation of the endoplasmic reticulum (ER). Consistently, palmitate upregulated ER stress proteins, oligomerized stromal interaction molecule 1 (STIM1) in the subplasmalemmal ER membrane, abolished the cyclopiazonic acid-induced cytosolic Ca(2+) increase due to depletion of luminal ER Ca(2+). Palmitate-induced ER Ca(2+) depletion and cytotoxicity were blocked by a selective inhibitor of the fatty-acid transporter FAT/CD36. Loss of the ER Ca(2+) pool induced by palmitate was reverted by the phospholipase C (PLC) inhibitor edelfosine. Palmitate-dependent activation of PLC was further demonstrated by following cytosolic translocation of the pleckstrin homology domain of PLC in palmitate-treated podocytes. An inhibitor of diacylglycerol (DAG) kinase, which elevates cytosolic DAG, strongly promoted ER Ca(2+) depletion by low-dose palmitate. GF109203X, a PKC inhibitor, partially prevented palmitate-induced ER Ca(2+) loss. Remarkably, the mitochondrial antioxidant mitoTEMPO inhibited palmitate-induced PLC activation, ER Ca(2+) depletion and cytotoxicity. Palmitate elicited cytoskeletal changes in podocytes and increased albumin permeability, which was also blocked by mitoTEMPO. These data suggest that oxidative stress caused by saturated FFA leads to mitochondrial dysfunction and ER Ca(2+) depletion through FAT/CD36 and PLC signaling, possibly contributing to podocyte injury.
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.
The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 ... GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.
Objectives: Histone deacetylase (HDAC) is an important therapeutic target in cancer. Two of the main anticancer mechanisms of HDAC inhibitors are induction of terminal differentiation and inhibition ...of cell proliferation. To investigate the role of HDAC in maintenance of self‐renewal and cell proliferation, we treated mesenchymal stem cells (MSCs) that originated from adipose tissue or umbilical cord blood with valproic acid (VPA) and sodium butyrate (NaBu).
Materials and methods: Human MSCs were isolated from mammary fat tissue and cord blood. We performed MTT assay and flow cytometry‐based cell cycle analysis to assess self‐renewal of MSCs. In vitro differentiation assays into osteogenic, adipogenic, neurogenic and chondrogenic lineages were conducted to investigate MSC multipotency. Immunocytochemistry, Western blot and reverse transcription‐polymerase chain reaction were used to interrogate molecular pathways.
Results: VPA and NaBu flattened the morphology of MSCs and inhibited their growth. VPA and NaBu activated the transcription of p21CIP1/WAF1 by increasing the acetylation of histone H3 and H4 and eventually blocked the cell cycle at G2/M phase. The expression level of p16INK4A, a cdk inhibitor that is closely related to cellular senescence, was not changed by HDAC inhibitor treatment. We performed controlled differentiation into bone, fat, cartilage and nervous tissue to elucidate the role of HDAC in the pluripotency of MSC to differentiate into functional tissues. VPA and NaBu decreased the efficiency of adipogenic, chondrogenic, and neurogenic differentiation as visualized by specific staining and reverse transcription‐polymerase chain reaction. In contrast, osteogenic differentiation was elevated by HDAC inhibitor treatment.
Conclusion: HDAC activity is essential for maintaining the self‐renewal and pluripotency of MSCs.
Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a ...reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.
Background: To investigate the association between tumor markers cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) and clinicopathological parameters and patient outcomes in breast ...cancer. Materials and methods: A total of 740 patients with stages I–III breast cancer had preoperative CA 15-3 and CEA concentrations measured. Univariate and multivariate analyses were used to investigate associations between marker concentration and clinicopathological parameters and patient outcomes. Results: Among 740 patients, elevated preoperative levels of CA 15-3 and CEA were identified in 92 (12.4%) and 79 (10.7%) patients, respectively. Tumor size (>5 cm), node metastases (≥4), and advanced stage (≥III) were associated with higher preoperative levels. Elevated CA 15-3 and CEA levels were associated with poor disease-free survival (DFS, P = 0.0014, P = 0.0001, respectively) and overall survival (OS, P = 0.018, P = 0.015) even in stage-matched analysis. Patients with normal levels of both CA 15-3 and CEA showed better DFS and OS than those with elevated group. In multivariate analysis, age (<35 years), tumor size (>2 cm), node metastases, estrogen receptor expression, and elevated CA 15-3 and CEA preoperative values were independent prognostic factors for DFS. Conclusion: High preoperative CA 15-3 and CEA levels may reflect tumor burden and are associated with advanced disease and poor outcome. Measuring preoperative levels of CA 15-3 and CEA can be helpful for predicting outcomes.
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