Search for Sub-eV Sterile Neutrinos at RENO.

We report a search result for a light sterile neutrino oscillation with roughly 2200 live days of data in the RENO experiment. The search is performed by electron antineutrino (ν[over ¯]_{e}) disappearance taking place between six 2.8 GW_{th} reactors and two identical detectors located at 294 m (near) and 1383 m (far) from the center of the reactor array. A spectral comparison between near and far detectors can explore reactor ν[over ¯]_{e} oscillations to a light sterile neutrino. An observed spectral difference is found to be consistent with that of the three-flavor oscillation model. This yields limits on sin^{2}2θ_{14} in the 10^{-4}≲|Δm_{41}^{2}|≲0.5 eV^{2} region, free from reactor ν[over ¯]_{e} flux and spectrum uncertainties. The RENO result provides the most stringent limits on sterile neutrino mixing at |Δm_{41}^{2}|≲0.002 eV^{2} using the ν[over ¯]_{e} disappearance channel.

Fuel-Composition Dependent Reactor Antineutrino Yield at RENO.

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

Measurement of Reactor Antineutrino Oscillation Amplitude and Frequency at RENO.

The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (ν[over ¯]_{e}) oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) ν[over ¯]_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the measured number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=[2.68±0.12(stat)±0.07(syst)]×10^{-3} eV^{2}.

Changes in the Microbial Composition of Microbrewed Beer during the Process in the Actual Manufacturing Line.

This study investigated changes in the microbial composition of microbrewed beer during the manufacturing processes and identified potential microbial hazards, effective critical quality control points, and potential contamination routes. Comprehensive quantitative (aerobic plate count, lactic acid bacteria, fungi, acetic acid bacteria, coliforms, and Bacillus cereus) and qualitative (Escherichia coli and eight foodborne pathogens) microbiological analyses were performed using samples of raw materials (malt and manufacturing water), semiprocessed products (saccharified wort, boiled wort, and samples taken during the fermentation and maturation process), and the final product obtained from three plants. The initial aerobic plate count and lactic acid bacteria counts in malt were 5.2 and 4.3 log CFU/g, respectively. These counts were reduced to undetectable levels by boiling but were present at 2.9 and 0.9 log CFU/ml in the final product. Fungi were initially present at 3.6 log CFU/g, although again, the microbes were eliminated by boiling; however, the level in the final product was 4.6 log CFU/ml. No E. coli or foodborne pathogens (except B. cereus) were detected. B. cereus was detected at all stages, although it was not present in the water or boiled wort (total detection rate » 16.4%). Results suggest that boiling of the wort is an effective microbial control measure, but careful management of raw materials and implementation of effective control measures after boiling are needed to prevent contamination of the product after the boiling step. The results of this study may constitute useful and comprehensive information regarding the microbiological quality of microbrewed beer.

Intrinsic dorsoventral patterning and extrinsic EGFR signaling genes control glial cell development in the Drosophila nervous system.

Dorsoventral patterning and epidermal growth factor receptor (EGFR) signaling genes are essential for determining neural identity and differentiation of the Drosophila nervous system. Their role in glial cell development in the Drosophila nervous system is not clearly established. Our study demonstrated that the dorsoventral patterning genes, vnd, ind, and msh, are intrinsically essential for the proper expression of a master glial cell regulator, gcm, and a differentiation gene, repo, in the lateral glia. In addition, we showed that esg is particularly required for their expression in the peripheral glia. These results indicate that the dorsoventral patterning and EGFR signaling genes are essential for identity determination and differentiation of the lateral glia by regulating proper expression of gcm and repo in the lateral glia from the early glial development. In contrast, overexpression of vnd, msh, spi, and Egfr genes repressed the expression of Repo in the ventral neuroectoderm, indicating that maintenance of correct columnar identity along the dorsoventral axis by proper expression of these genes is essential for restrictive formation of glial precursor cells in the lateral neuroectoderm. Therefore, the dorsoventral patterning and EGFR signaling genes play essential roles in correct identity determination and differentiation of lateral glia in the Drosophila nervous system.

Rubber friction on road surfaces: Experiment and theory for low sliding speeds.

We study rubber friction for tire tread compounds on asphalt road surfaces. The road surface topographies are measured using a stylus instrument and atomic force microscopy, and the surface roughness power spectra are calculated. The rubber viscoelastic modulus mastercurves are obtained from dynamic mechanical analysis measurements and the large-strain effective modulus is obtained from strain sweep data. The rubber friction is measured at different temperatures and sliding velocities, and is compared to the calculated data obtained using the Persson contact mechanics theory. We conclude that in addition to the viscoelastic deformations of the rubber surface by the road asperities, there is an important contribution to the rubber friction from shear processes in the area of contact. The analysis shows that the latter contribution may arise from rubber molecules (or patches of rubber) undergoing bonding-stretching-debonding cycles as discussed in a classic paper by Schallamach.

Enhanced skin delivery of liquiritigenin and liquiritin-loaded liposome-in-hydrogel complex system.

OBJECTIVE: To study the permeation of liquiritigenin (LQG) and liquiritin (LQ) as licorice flavonoids into the skin, we prepared ceramide liposome-in-cellulose hydrogel complex system. METHODS: Liposome-in-hydrogel complex systems were developed by incorporating ceramide liposomes into cellulose hydrogels by the swelling method. We evaluated their physical and chemical properties, encapsulation efficiency and skin permeability using Franz Diffusion Cell. It was visually seen by CLSM images analysis. RESULTS: The ceramide liposome, consisting of biocompatible lipid membranes, remained stable for over 3 weeks. Encapsulation efficiencies for liquiritigenin and liquiritin-loaded liposome-in-hydrogel were 69.39% and 64.71%, respectively. Liposome-in-hydrogel complex systems (LQG: 56.55%, LQ: 66.99%) had greater skin permeability than control (LQG: 4.92%, LQ: 5.30%) or a single liposome systems (LQG: 43.34%, LQ: 48.97%) and hydrogel systems (LQG: 38.21%, LQ: 55.07%). CONCLUSION: Liposome-in-hydrogel system can be a potential drug delivery system for topical delivery of antioxidants such as licorice flavonoids to construct antioxidative skin barrier.

Cell death/proliferation roles for nc886, a non-coding RNA, in the protein kinase R pathway in cholangiocarcinoma.

We have recently identified nc886 (pre-miR-886 or vtRNA2-1) as a novel type of non-coding RNA that inhibits activation of protein kinase R (PKR). PKR's pro-apoptotic role through eukaryotic initiation factor 2 α (eIF2α) phosphorylation is well established in the host defense against viral infection. Paradoxically, some cancer patients have elevated PKR activity; however, its cause and consequence are not understood. Initially, we evaluated the expression of nc886, PKR and eIF2α in non-malignant cholangiocyte and cholangiocarcinoma (CCA) cells. nc886 is repressed in CCA cells and this repression is the cause of PKR's activation therein. nc886 alone is necessary and sufficient for suppression of PKR via direct physical interaction. Consistently, artificial suppression of nc886 in cholangiocyte cells activates the canonical PKR/eIF2α cell death pathway, suggesting a potential significance of the nc886 suppression and the consequent PKR activation in eliminating pre-malignant cells during tumorigenesis. In comparison, active PKR in CCA cells does not induce phospho-eIF2α nor apoptosis, but promotes the pro-survival nuclear factor-κB pathway. Thus, PKR has a dual life or death role during tumorigenesis. Similarly to the CCA cell lines, nc886 tends to be decreased but PKR tends to be activated in our clinical samples from CCA patients. Collectively from our data, we propose a tumor surveillance model for nc886's role in the PKR pathway during tumorigenesis.

Minimal clinically important differences in the Carpal Tunnel Questionnaire after carpal tunnel release.

Minimal clinically important difference is the smallest difference in the score of an outcome instrument that patients perceive as important. A prospective observational study was conducted involving 66 consecutive patients undergoing limited open carpal tunnel release. Patients completed the Carpal Tunnel Questionnaire (CTQ) before surgery and 3 months post-surgery. A transition item for patient satisfaction after 3 months of surgery was used as an anchor. Receiver operator characteristic curves were used to determine the minimal clinically important differences for the CTQ and its two subscales that best separated satisfied and unsatisfied patients. A 0.92 point change in the CTQ, a 1.14 point change in the symptom subscale, and a 0.74 point change in the function subscale indicated a clinically relevant threshold of satisfaction, and those values were greater than what could be accounted for by measurement errors.

Pharmacokinetics and the antiplatelet effect of a new clopidogrel formulation, clopidogrel besylate, in healthy subjects.

BACKGROUND: Clopidogrel, a thienopyridine derivative, is an inhibitor of platelet aggregation induced by adenosine diphosphate (ADP). We compared the pharmacokinetics and the antiplatelet effect of two clopidogrel formulations (clopidogrel besylate (test) and clopidogrel bisulfate (reference)). SUBJECTS AND METHODS: The study was conducted in 40 healthy subjects in a randomized, open-label, 2-period crossover manner. Each subject received a single loading dose of 150 mg clopidogrel on Day 1 followed by a daily dose of 75 mg clopidogrel from Day 2 to Day 7. After the first dose blood samples for pharmacokinetic analysis of clopidogrel and SR26334 were collected over 24 h. The pharmacodynamic variables, i.e., the inhibition of ADP-induced platelet aggregation, were measured over 264 h. RESULTS: No serious adverse events occurred during the study period. The mean plasma concentration-time profiles of clopidogrel and SR26334 for the two formulations were comparable. The 90% confidence intervals (CIs) for the log-transformed ratios for pharmacokinetic parameters (Cmax and AUC) of SR26334 fell within the predefined pharmacokinetic equivalence range of 80 - 125%. However, the upper limits of 90% CI of Cmax and AUC for clopidogrel exceeded the equivalence range. The two formulations showed similar antiplatelet profiles. The 90% CIs of DeltaEmax and DeltaAUEC of platelet aggregation inhibition fell within the equivalence range of 80 - 125%. CONCLUSION: Both clopidogrel formulations were well-tolerated. The study population showed no serious AEs. The test formulation proved pharmacokinetically non-inferior to the reference formulation. The test formulation showed an antiplatelet effect on ADP-induced platelet aggregation similar to the reference formulation. The two formulations were considered pharmacodynamically equivalent in terms of platelet aggregation inhibition.

BaTiO3 doped Na0.5K0.5NbO3 thin films deposited by using eclipse shutter enhanced pulsed laser deposition method.

We have investigated structural, electrical, and electro-mechanical properties of lead-free piezoelectric BaTiO3 doped Na0.5K0.5NbO3 (BTO-NKN) thin films deposited by pulsed laser deposition (PLD) methods. BTO-NKN thin films have been deposited on La0.5Sr0.5CoO3 (LSCO) bottom electrodes with LaAlO3 (LAO) substrates. X-ray diffraction data have shown that all the BTO-NKN and bottom electrodes are highly oriented with their c-axes normal to the substrates. In order to improve the morphology of BTO-NKN thin films, we have located an eclipse shutter between a target and a substrate. Root-mean-square roughness was changed from 91 nm to 21 nm with eclipse shutter enhanced PLD (E-PLD) method. Furthermore, the enhanced surface morphology leads to the improvement in electrical or electro-mechanical properties mainly due to increased density. Typical capacitance and d33 values of a BTO-NKN film deposited by E-PLD method are 1000 pF and 30 pmN, respectively.

Application of a new portable microscopic somatic cell counter with disposable plastic chip for milk analysis.

The somatic cell count (SCC) is one of the international standards for monitoring milk quality, and it is a useful indicator of mastitis. The current reference method for determining the SCC in raw milk is direct microscopic analysis, but this method requires well-trained staff to maintain its accuracy and reproducibility. To overcome these inconveniences, we developed a portable system (the C-reader system) that utilizes the capillary flow of a microfluidic chamber by surface modification of the hydrophilicity. The microfluidic technology of disposable microchips allows for low consumption of reagents, and a combination of ready-to-use reagents makes the daily work easier. The repeatability test of the C-reader using 10 composite bovine milk samples satisfied the recommended values for SCC equipment. In addition, an acceptable accuracy level of the natural logarithmic-transformed SCC [ln(SCC/1,000): +/- 0.059 to 0.112] was achieved using composite raw milk samples and various somatic cell standard solutions from the American Eastern Laboratory and the Korean National Veterinary Research and Quarantine Service. After testing 875 composite milk samples, the C-reader showed a high correlation coefficient (R2 = 0.935 to 0.964) and a low mean difference value in log-transformed SCC (-0.088 to 0.004) compared with 3 automatic commercialized somatic cell counters (Fossomatic 4000, Somacount 150, and Somascope). In conclusion, the C-reader system is a new, easy-to-use automatic on-farm method with acceptable repeatability and accuracy for measuring SCC in large dairies and smaller laboratories.

Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter.

One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation.

Mixture of N-carbamoyl-L-glutamate plus L-arginine can protect rats with liver cirrhosis from acute ammonia intoxication.

BACKGROUND/AIMS: We earlier reported that N-carbamoyl-L-glutamate (CG) plus L-arginine (Arg) protected normal and 70% hepatectomized rats from intoxication by a lethal or sub-lethal dose of ammonium acetate, respectively. In the present study, the protective effect of these compounds on cirrhotic rats was assessed. METHODS: CG plus Arg were administered prior to the injection of a sub-lethal dose of ammonium acetate into dimethylnitrosamine-induced cirrhotic rats. Control rats were given phosphate-buffered saline (PBS) instead of the mixture. The behavior of the rats was monitored until the time of sacrifice. Blood ammonia level, blood urea nitrogen (BUN) and liver carbamoylphosphate synthetase I (CPS I) activity were determined. RESULTS: Pretreatment of rats with the mixture of CG plus Arg could significantly lower the blood ammonia level (P<0.05), increase the activity of CPS I (P<0.05), improve abnormal behavior associated with ammonia intoxication (P<0.05), and increase BUN (P<0.05), as compared with the PBS-injected control group. There were significantly close correlations between (1) the increase of CPS I activity; (2) the improvement of abnormal behavior; (3) the increase of BUN; and (4) the decrease of the blood ammonia level. CONCLUSIONS: A mixture of CG plus Arg could protect rats with liver cirrhosis from acute ammonia intoxication.

Clinical significance of urinary vascular endothelial growth factor and microvessel density in patients with renal cell carcinoma.

OBJECTIVES: To investigate the urinary vascular endothelial growth factor (VEGF) levels from patients with renal cell carcinoma (RCC). Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. VEGF is thought to exert potent angiogenic activity. METHODS: Urine samples were obtained before radical nephrectomy from 27 patients with RCC and 10 control subjects with no evidence of cancer or inflammatory disease. VEGF was measured by enzyme-linked immunosorbent assay in the urine and corrected according to the 24-hour urine concentration of creatinine. The microvessel density was measured by immunohistochemical staining with CD31 monoclonal antibody. Nuclear morphometry was performed by photomicroscopy. RESULTS: The corrected urinary VEGF levels in patients with RCC were much higher than those in the normal control group (P = 0.039) and were more elevated in patients with higher stages of RCC (Stages III and IV versus Stages I and II; P = 0.024). A tendency was also noted for the VEGF levels to be higher according to cell grade. However, no statistical correlation was found between the corrected urinary VEGF and age, sex, tumor size, cell type, microvessel density, platelet count, or hemoglobin. The nuclear area was higher with more advanced-stage tumors (P = 0.043) and tended to increase according to the tumor cell grade. CONCLUSIONS: The results of this study indicate that urinary VEGF levels are increased in patients with RCC. However, they may not reflect the underlying angiogenic activity, and it may be that other angiogenic factors play a more prominent role.

Characterization of human IgE and mouse IgG1 responses to allergens in three mosquito species by immunoblotting and ELISA.

BACKGROUND: IgE-mediated allergic reactions caused by mosquito bites are a common problem all over the world. This study was undertaken to determine IgE levels in subjects, to elucidate human IgE and mouse IgG1 binding patterns and to investigate the cross-reactivity of salivary gland antigens with three mosquitoes. METHODS: Mosquito larvae of Aedes togoi, Culex tritaeniorhynchus and Culex pipiens pallens were collected and maintained in the laboratory. Salivary gland extracts (SGE) and whole-body extracts (WBE) were prepared from female mosquitoes of each species. Mosquito-specific IgE levels in 17 subjects were measured by ELISA. Polypeptide patterns were analyzed by SDS-PAGE. Immunoblotting was performed with sensitized human and immune mouse sera, and elucidated human IgE and mouse IgG1 binding patterns to SGE. For the determination of cross-reactivity to the three types of mosquitoes, ELISA inhibition tests were performed using sera from mice sensitized by biting of A. togoi. RESULTS: The 9 sera out of 12 with positive skin reactions to SGE of A. togoi by skin prick test showed significantly higher anti-mosquito SGE IgE levels than in those without skin reactions. Protein band patterns of the SGE and WBE of the three species were different from one another. Specific human IgE reacted to the protein in SGE of 30.5, 33, 37 and 57.5 kD from A. togoi, of 38, 43 an 68 kD from C. tritaeniorhynchus, and of 23, 33, 34, 43, 44, 60, 74 and 93 kD from C. pipiens pallens. There were specific mouse IgG1 reactions to the bands of 30.5, 33, 37 and 57.5 kD in the SGE of A. togoi. The ELISA inhibition studies disclosed almost no cross-reactivities between A. togoi, C. tritaeniorhynchus and C. pipiens pallens. CONCLUSIONS: Immunoblot analysis disclosed that allergenic proteins in the SGE of mosquitoes and their patterns were remarkably similar between human and mouse sera to the SGE of A. togoi. Species-shared allergens may not exist among the three mosquito species prevalent in Korea.

Determination and geographical distribution of Orientia tsutsugamushi serotypes in Korea by nested polymerase chain reaction.

Field rodents and chigger mites were collected at 30 locations in Korea in October and November 1997-1999 to determine the serotypes of Orientia tsutsugamushi and their geographical distribution. A nested polymerase chain reaction was performed with the spleen tissues from 546 field-striped mice (Apodemus agrarius) and 104 pools of chigger mites. The positivity rate of O. tsutsugamushi was 45.6% in A. agrarius and 39.4% in the chigger mite pools. Two serotypes, Boryong and Karp, were found in these samples; the former was predominant (78.3% in the mice and 82.9% in the chigger mite pools), with wide distribution throughout the country, including Cheju-do. The latter was confined to the middle of the Korean peninsula, with positivity rates of 15.7% in the mice and 12.2% in the chigger mite pools. The double infection of Karp and Boryong serotypes was found in 15 (6.0%) A. agrarius mice. Gilliam serotype was not detected at any of the study locations. The Boryong and Kuroki serotypes were identical in amino acid sequence of the 56-kDa protein, although they differed in virulence to BALB/c mice.

Clinical significance of urinary vascular endothelial growth factor in patients with superficial bladder tumors.

Vascular endothelial growth factor (VEGF) is an important mediator of tumor angiogenesis and has been shown to be excreted in the urine of bladder cancer patient. The goal of this study was to evaluate urinary VEGF levels of patients with superficial bladder transitional cell carcinoma (TCC) and to determine its predictive value for recurrence. Pre-operative urinary VEGF levels were determined in 31 patients with superficial bladder TCC and 10 control patients. A quantitative enzyme immunoassay was used to measure urinary VEGF levels and the urine VEGF concentration was corrected by the creatinine concentration in a 24-h urine specimen. The corrected urinary VEGF levels were higher in patients than controls (p=0.003). Ten of 31 patients had TCC recurrences during this study. Corrected urinary VEGF levels were significantly higher in recurrent vs. non-recurrent patients (p=0.001). A cut-off value of 0.32 (corrected urinary VEGF levels) was valuable for predicting recurrences in this prospective study. However, there was no statistical correlation between VEGF levels and tumor stage (Ta or T1), tumor size or tumor grade. Pre-operative urinary VEGF levels are associated with a risk of recurrence in patient with superficial bladder TCC. Quantification of urinary VEGF may prove to be a valuable, non-invasive indicator of carcinoma recurrence in patients with superficial bladder TCC. Urinary VEGF may be a therapeutic target for intravesical therapy. However, because of the small number of cases, further studies with larger number of patients will be needed to clarify this issue.

Intravascular ultrasound findings of coronary wall morphology in a child with Kawasaki disease.

Intravascular ultrasound (IVUS) imaging was performed to assess the coronary wall morphology in detail at 22 months after the onset of Kawasaki disease in a girl who had developed coronary aneurysms at 4 yr of age. The sites of persistent aneurysms demonstrated a dilated lumen with a marked symmetrical or asymmetrical thickening of the intima-media complex. This pathologic finding was also present in angiographically normal vessels near an aneurysm but with a mild thickening. Coronary artery calcification was observed at one site in the aneurysms. The sites of normal coronary artery far from an aneurysm showed normal intravascular ultrasound findings with no measurable intima-media complex. Our case indicates that the healing process may continue via cell proliferation, with extension to the proximity of the coronary aneurysms. IVUS is useful to evaluate the coronary wall morphology and may be valuable in the long-term follow-up of coronary lesions due to Kawasaki disease.