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International audience; We report the results of laboratory tests of the first version of the high-resolution fiber-fed spectrograph designed for the Special Astrophysical Observatory of the Russian Academy of Sciences (SAO RAS). During laboratory tests a spectral resolution of about 70 000 was achieved. The peak efficiency of the entire optical path of the spectrograph (without light losses at the CCD, primary mirror of the 6-m telescope, and in the atmosphere) at 620 nm and with the equivalent slit widths of the 1″.5 and 0″.75 are equal to 8% and 4%, respectively. The resolving power R = 70 000 and 100 000 can be reached with the sky aperture 0″.75 and 0″.4 respectively. In the current version of the spectrograph these regimes of operation are implemented by mechanic aperturing of the slit. A dedicated projecting camera has been developed and is currently manufactured to operate with a collimated 200-mm diameter beam, which will make it possible to increase the spectral resolution up to 100 000. A two-beam image slicer will be used to maintain the luminous efficiency of the instrument at least at the 6% level.

A number of piping components in the secondary system of nuclear power plants (NPPs) have been exposed to aging mechanisms such as FAC (Flow-Accelerated Corrosion), cavitation, flashing, LDIE (Liquid Droplet Impingement Erosion), and SPE (Solid Particle Erosion). Those mechanisms may lead to thinning, leaking, or the rupture of components. Due to the pipe ruptures caused by wall thinning of Surry Unit 2 in 1986 and Mihama Unit 3 in 2004, pipe wall thinning management has emerged as one of the most important issues in the nuclear industry. To manage the wall thinning of pipes caused by FAC and erosion, KEPCO-E & C has developed ToSPACE program. It can predict both FAC & erosion phenomena, and also be utilized in the pipe wall thinning management works such as susceptibility analysis, UT (Ultrasonic Test) data evaluation as well as establishment of long-term inspection plan. Even though the ToSPACE can predict the five aging mechanisms mentioned above, only the FAC prediction result using ToSPACE was compared herein with the experimental result using FACTS (Flow Accelerated Corrosion Test System) to verify the ToSPACE’s capability. In addition, the FAC prediction result using ToSPACE was also compared with that of CHECWORKS that is widely used all over the world.

Phase lag entropy, an electro-encephalography-based hypnotic depth indicator, calculates diversity in temporal patterns of phase relationship. We compared the performance of phase lag entropy with the bispectral index™ in 30 patients scheduled for elective surgery. We initiated a target-controlled infusion of propofol using the Schnider model, and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation scale every 30 s with each stepwise increase in the effect-site propofol concentration. Phase lag entropy and bispectral index values were recorded. The correlation coefficient and prediction probability between phase lag entropy or bispectral index and the sedation level or effect-site propofol concentration were analysed. We calculated baseline variabilities of phase lag entropy and bispectral index. In addition, we applied a non-linear mixed-effects model to obtain the pharmacodynamic relationships among the effect-site propofol concentration, phase lag entropy or bispectral index and sedation level. As sedation increased, phase lag entropy and bispectral index both decreased. The prediction probability values of phase lag entropy and bispectral index for sedation levels were 0.697 and 0.700 (p = 0.261) and for the effect-site concentration of propofol were 0.646 and 0.630 (p = 0.091), respectively. Baseline variability in phase lag entropy and bispectral index was 3.3 and 5.7, respectively. The predicted propofol concentrations, using the Schnider pharmacokinetic model, producing a 50% probability of moderate and deep sedation were 1.96 and 3.01 μg.ml-1 , respectively. Phase lag entropy was found to be useful as a hypnotic depth indicator in patients receiving propofol sedation.

Immunoscore can effectively predict prognosis in patients with colon cancer; however, its clinical application is limited. We modified the Immunoscore and created a tumor immune microenvironment (TIM) classification system for gastric carcinoma. Unlike previous studies that used small sample sizes or focused on particular immune-cell subtypes, our simplified system enables pathologists to classify gastric carcinomas intuitively using HE-stained sections.Samples from 326 patients with advanced gastric carcinoma were reviewed and analyzed by pathologists using simple determination and digital image analysis. Comprehensive results of cancer-panel sequencing, Epstein-Barr‒virus (EBV) status, and PD-L1, HER2, ATM, PTEN, MET, FGFR2, and EGFR immunohistochemistry were evaluated with respect to the TIM class.The TIM was classified as "hot" (n = 22), "immunosuppressed" (n = 178), "excluded" (n = 83), or "cold" (n = 43). TIM category was significantly associated with numbers of frameshift mutations (P 0.001) and high tumor mutational burden (P 0.004), and predicted overall survival. It was also significantly associated with age, histological type, degree of fibrosis, PD-L1 expression, loss of ATM and PTEN expression (P 0.001), sex, EBV positivity, and HER2 overexpression (P 0.04). "Hot" tumors were frequent in PD-L1 expressing and EBV-positive samples, and in those with ATM and PTEN loss. "Excluded" tumors were frequent in HER2-positive cases, whereas "cold" tumors were more frequent in younger patients with poorly cohesive histology and high fibrosis levels.TIM classification system for gastric carcinoma has prognostic significance and results in classes that are associated with molecular characteristics.

Traditionally, vascular interventions have been performed through the femoral artery.The purpose of this study was to evaluate risk factors affecting access-site complications in patients with hepatocellular carcinoma or peripheral arterial disease in lower extremity who underwent vascular intervention by accessing the common femoral artery (CFA).From December 2015 to November 2018, 287 patients underwent transarterial chemoembolization (TACE) or peripheral vascular intervention with ultrasound (US)-guided CFA access. Standard 18-gauge (G) access was used in 127 patients and Micropuncture® 21-G needles in 160 patients. Most access sites were managed with vascular closure devices and several were managed with manual compression. Within 24 hours after the procedure, all patients underwent US to evaluate the puncture site.Access-site complications occurred in 55 of 287 patients: 34 hematomas (11.9%), 20 pseudoaneurysms (7.0%), and 1 dissection (0.4%). In the crude model, risk factors related to access-site complications were the usage of 18-G needles (OR, 2.18; 95% CI, 1.17-4.07; P = 0.014), smoking (OR, 2.23; 95% CI, 1.16-4.27; P = 0.016), and approach route (OR, 3.23; 95% CI, 1.33-7.82; P = 0.009). Needle size (OR, 2.13; 95% CI, 1.10-4.12; P = 0.025) was the only factor associated with access-site complications in the adjusted model.Needle profile was the only factor associated with access-site complications in this study. Therefore, a needle with a smaller profile than an 18-G needle will reduce the incidence of complications at the access site.

Development of tungsten brazing technology for the upgraded Korea superconducting tokamak advanced research divertor was launched in early 2013. ITER grade tungsten block was brazed on the CuCrZr alloy in vacuum at 980 °C for 30 min using silver free brazing alloy. An OFHC-copper was used as an interlayer between tungsten and the CuCuZr. The brazing alloy is a 0.05 mm thickness of plate of which component is a Ni–Cu–Mn. It is found that the optimal loading on mock-up is about 20 kPa. Ultrasonic test and shear strength test were carried out to check the strength between tungsten and substrate material. And the joint conditions were analyzed by scanning electron microscopy. Tungsten-brazed mock-ups with a cooling tube were tested at the electron beam facility, Korea heat load test facility-electron beam in Korea Atomic Energy Research Institute. The high heat flux test was performed for tungsten-brazed mock-ups under heat flux of about 5 MW/ $\text{m}^{2}$ with more than 2000 cycles. All the tungsten-brazed mock-ups met the requirements and there was no delamination or failure at the bonding joints.

Tungsten (W) monoblock that consists of W according to ITER specifications, oxygen-free high conductive copper (Cu-OFHC), and CuCrZr has been designed in preparation for KSTAR upgrade for steady-state long-pulse operation with 27.5-MW heating power. Finite-element analysis has been performed by ANSYS Workbench. The hydraulic thermomechanical analysis is performed to investigate the optimal design parameters and the expected fatigue lifetime under the operating conditions with 5.4-MW/ $\text{m}^{2}$ incident heat flux at the divertor. For a single W monoblock, the optimization gives a W thickness of 5 mm, a side thickness of 2.5 mm, a thickness in the back part of 6 mm, and a Cu-OFHC interlayer thickness of 0.5 mm. For a mock-up consisting of five optimized W monoblocks, the thermal fatigue analysis is performed. As a result, the maximum value of equivalent total strain in the CuCrZr tube is found to be 0.266%, which corresponds to for a fatigue lifetime of 23 000 cycles.

This study investigates the association of PD-L1 expression and immune cell infiltrates and their impact on clinical outcome, in addition to their overlap with microsatellite instability (MSI), HER2 and ATM molecular subgroups of gastric cancer (GC). PD-L1 membrane expression on tumour cells (TC) and infiltrating immune cells (IC), CD3 + T-lymphocytes, CD8+ cytotoxic T-cells, ATM and HER2 were assessed by immunohistochemistry (IHC) in the ACRG (Asian Cancer Research Group) GC cohort (N = 380). EBV status was determined using in situ hybridization and MSI status was performed using PCR and MLH1 IHC. The PD-L1 segment was associated with increased T-cell infiltrates, while the MSI-high segment was enriched for PD-L1, CD3, and CD8. Multivariate analysis confirmed PD-L1 positivity, high CD3 and high CD8 as independent prognostic factors for both disease-free survival and overall survival (all p

Background Programmed death-ligand 1 (PD-L1) expression has been suggested as a potential predictive biomarker of response to anti-PD-1/PD-L1 therapy. In this study, we investigated whether the expression of PD-L1 in tumour cells is affected by neoadjuvant concurrent chemoradiotherapy (CCRT) or chemotherapy in oesophageal squamous cell carcinoma. Patients and methods Between 2004 and 2014, we collected the medical records of locally advanced oesophageal cancer patients consecutively diagnosed and treated with neoadjuvant CCRT or chemotherapy, followed by curative resection. PD-L1 expression in acquired tissue specimens was evaluated by immunohistochemistry using the H-score. The changes in PD-L1 expression between paired samples were evaluated and we also analysed PD-L1 expression in surgical tumour specimens to evaluate its prognostic role. Results Twenty-eight paired tumour tissues that were acquired before and after neoadjuvant therapy were available: 19 patients with CCRT and 9 with chemotherapy before complete oesophagectomy. The PD-L1 H-score increased significantly from baseline tumour tissues to surgical tumour tissues after neoadjuvant CCRT ( P = 0.007, median H-score from 28 to 52), whereas it decreased significantly after neoadjuvant chemotherapy ( P = 0.048, median H-score from 53 to 22). In a total of 73 patients, including 45 additional cases for the prognosis analysis, patients with higher PD-L1 H-scores (≥20) had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores ( Conclusions PD-L1 expression in tumour cells increased in oesophageal cancer patients who received neoadjuvant CCRT. Further studies with more cases are necessary to validate these findings.

A*02:687 showed one nucleotide difference with A*02:01:01:01 resulting in an amino acid change.

Molecular targets are emerging rapidly and the development of clinical tests that simultaneously screen for multiple targets has become especially important. We assessed the gene expression levels of three known targets in advanced gastric cancer, epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and N-methyl-N-nitrosoguanidine human osteosarcoma transforming gene (MET), using the nCounter® assay (NanoString Technologies, Seattle, WA, USA) and compared these results with protein overexpression, detected by immunohistochemistry, to evaluate the performance of this new technology. We investigated 42 formalin-fixed, paraffin-embedded tumor samples from patients with gastric cancer. A NanoString-based assay containing a 522 kinase gene panel was investigated. We analyzed the correlations between immunohistochemical findings and kinase gene expression levels of EGFR, HER2 and MET to validate this assay. EGFR, HER2, and MET overexpression were observed in 7 (16.6 %), 5 (11.9 %), and 3 (7.1 %) cases, respectively. For EGFR, HER2, and MET, the concordance rates between the NanoString-based assay results and the immunohistochemistry methods were 83.3, 97.6, and 100 %, respectively. Relative to immunohistochemistry findings, the NanoString-based assay sensitivities and specificities were 85.7 and 82.8 % for EGFR, 100 and 97.2 % for HER2, and 100 and 100 % for MET, respectively. We found a high concordance between immunohistochemistry- and nCounter-based assessments of EGFR, HER2, and MET in advanced gastric cancer. Judged against immunohistochemistry results, the NanoString assay had high sensitivities and high specificities. These results suggest that the nCounter assay provides a reliable, high-throughput assay to simultaneously screen for the overexpression of several target proteins.

Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive phenotype. Gα12 gep oncogene product couples to G-protein-coupled receptors, whose ligand levels are frequently increased in tumor microenvironments. Here, we report Gα12 overexpression in human HCC and the resultant induction of zinc-finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation. Gα12 expression was higher in HCC than surrounding non-tumorous tissue. Transfection of Huh7 cell with an activated mutant of Gα12 (Gα12QL) deregulated microRNA (miRNA or miR)-200b/a/429, -194-2/192 and -194-1/215 clusters in the miRNome. cDNA microarray analyses disclosed the targets affected by Gα12 gene knockout. An integrative network of miRNAs and mRNA changes enabled us to predict ZEB1 as a key molecule governed by Gα12. Decreases of miR-200a/b, -192 and -215 by Gα12 caused ZEB1 induction. The ability of Gα12 to decrease p53 levels, as a result of activating protein-1 (AP-1)/c-Jun-mediated mouse double minute 2 homolog induction, contributed to transcriptional deregulation of the miRNAs. Gα12QL induced ZEB1 and other epithelial-mesenchymal transition markers with fibroblastoid phenotype change. Consistently, transfection with miR-200b, -192 or -215 mimic prevented the ability of Gα12QL to increase tumor cell migration/invasion. In xenograft studies, sustained knockdown of Gα12 decreased the overall growth rate and average volume of tumors derived from SK-Hep1 cell (mesenchymal-typed). In HCC patients, miR-192, -215 and/or -200a were deregulated with microvascular invasion or growth advantage. In the HCC samples with higher Gα12 level, a correlation existed in the comparison of relative changes of Gα12 and ZEB1. In conclusion, Gα12 overexpressed in HCC causes ZEB1 induction by deregulating p53-responsive miRNAs, which may facilitate epithelial-mesenchymal transition and growth of liver tumor. These findings highlight the significance of Gα12 upregulation in liver tumor progression, implicating Gα12 as an attractive therapeutic target.

Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However, little is known about its actual incidence, clinical presentation, and the risk factors for its development among cancer patients. To answer these questions, we analyzed all cases that occurred during an 18-year period at our center. A case-control study was performed to identify risk factors for CMV GI disease. Electronic medical records were reviewed from individuals who were admitted and diagnosed with CMV GI disease during the period of January 1995 through March 2013 at a tertiary care center. Two CMV disease-free cancer patients were matched as controls. A total of 98 episodes of CMV GI disease were included in this study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with an increasing trend throughout the study period. According to multivariate analysis, male sex, low body mass index, lymphopenia, hematological malignancy, and steroid use and red blood cell transfusion within 1 month prior to the CMV disease were identified to be independent risk factors. Among these factors, RBC transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within 1 month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease in adult patients with cancer.

This study developed a drying method and a dryer that are optimized for shiitake mushrooms. They are mainly being cultivated and consumed as food and medicine in Korea, Japan, China, and Southeast Asia. They generally contain lots of moisture. For this reason, the use of a dryer causes problems such as decomposition and spoilage, and natural dry processing is preferred. To resolve these problems, various drying methods have been proposed (e.g. hot air drying, heat pump vacuum drying) but there has been a difficulty in maintaining a medium-temperature range of 30 to 40°C, the optimal temperature environments for retaining their main components. The study developed a 2-stage decompresses resistive heat pump dryer that can operate also in medium-temperature environments - existing decompresses heat pump dryers have been able to operate only in high-temperature environments. A dryer optimized for shiitake mushrooms that are being produced and distributed in large quantities was proposed, and the utility of the machine was proved through experiments.

A 5-GHz steady-state lower hybrid (LH) current drive (LHCD) system is planned to support steady-state and advanced tokamak operation on the Korea Superconducting Tokamak Advanced Research (KSTAR) e...

In and outboard plasma facing components (PFCs) of Korea Superconducting Tokamak Advanced Research (KSTAR) have been fully installed in 2010 for D-shaped diverted plasmas. Before the start of plasma operation, the PFCs were baked up to 200 by hot nitrogen gas circulation system to remove impurities including water. The surface temperature of the PFC tiles was monitored by 200 thermocouple sensors during the plasma operation [plasma shot or glow discharge cleaning (GDC)], and the temporal and spatial (poloidal) temperature profiles are obtained. Depending on the heat flux on each tile, the surface temperature shows time-dependent behavior. After 1-h morning He GDC, the temperature of the PFCs at the inboard side has reached to 40 . After an H-mode shot, the temperature of divertor tiles around the striking points was substantially increased. The time-averaged total heat flux after a few of L- and H-modes in 2010 was estimated to be approximately 0.010 .

Pollux is yellow giant with known regular surface magnetic field about 1 Gauss. An analysis of the periodic behavior of the magnetic field of Pollux was performed. For this purpose, we used literature data together with spectropolarimetric observations, which were carried out during 10 nights in 2010 at the Crimean Astrophysical Observatory, and spectropolarimetric observations, which were obtained at Bohyunsan Optical Astronomy Observatory during 4 nights in 2007. The radial velocity measurements of Pollux show variations with a period of 592.9 days due to the planetary companion. The rotational period of the Pollux equals to 491.5 days. Improved dipole parameters are presented. The centered dipole gives the angle between spin axis and line of sight, i ∼ 45°, and the angle between the spin and dipole axes, β ∼ 135°. We suppose that a few points that lie outside of the dipole magnetic field curve by more than three errors are the result of the emergence of magnetic unipolar spots on the stellar surface. We discuss the possibility of these events in comparison with solar-like star 61 Cyg A and the Sun. Numerical simulations of the magnetic geometry lead us to the conclusion that the spots may have an angular radius of ∼1.5° with the magnetic intensity ∼3000 G. Such active regions can be formed at the same latitudes as on the Sun near the 40° from the equator (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

T. Kim, Y. L. Oh, K. M. Kim and J. H. Shin Diagnostic dilemmas of hyalinizing trabecular tumours on fine needle aspiration cytology: a study of seven cases with BRAF mutation analysis Objective: Hyalinizing trabecular tumours (HTTs) are rare follicular-derived neoplasms that behave in an almost benign manner. HTT is frequently misdiagnosed as papillary carcinoma by fine needle aspiration (FNA) cytology or as papillary or medullary carcinoma on surgical resection. Methods: The authors examined FNA material from seven cases of histologically verified HTT. Cytological findings were reviewed and correlated with ultrasonographic and histological features. In addition, MIB-1 and calcitonin immunostaining was performed on surgical specimens, and BRAF mutation analysis on three pre-operative FNA specimens and seven histology specimens. Results: The original cytological diagnosis was either suspicious or positive for papillary carcinoma in all patients. The FNA-based differential diagnoses included HTT, papillary carcinoma or, less likely, medullary carcinoma in two patients. Aspirates showed oval to spindle-shaped cells with frequent intranuclear inclusions, isolated in loosely cohesive groups with a trabecular or syncytial pattern in a bloody background. Radiating arrangements of tumour cells surrounding hyaline stroma with serrated calcifications and a lack of papillary or sheet-like fragments may suggest HTT on FNA. Spherical calcified bodies and possible psammoma bodies were frequently found in three cases. Retrospectively, six of the seven cases showed membranous immunoreactivity for MIB-1, but none of the seven possessed the BRAF (V600E) mutation or showed calcitonin reactivity. Conclusions: Although the recognition of HTT on FNA cytology is difficult, because of its morphological similarities to papillary and medullary carcinoma, its characteristic cytological features along with ultrasonographic findings may suggest the diagnosis preoperatively and avoid surgical over-treatment.

Transgenic herbicide-resistant sweet potato plants [ Ipomoea batatas (L.) Lam.] produced through a biolistic transformation were used in this study. The objectives of this research were to (a) quantify resistance levels of transgenic sweet potato expressing the bar gene to glutamine synthetase (GS)-inhibitors, glufosinate and methionine sulfoximine, protoporphyrinogen oxidase (PPO)-inhibiting herbicide, oxyfluorfen and photosynthesis-inhibiting herbicide, paraquat; (b) compare the relative chlorophyll content, quantum yield, growth, and tuberous root yield between transgenic and wild-type sweet potato; (c) compare the response of transgenic and wild-type sweet potato plants to chilling and high temperature, and (d) compare amino acids, minerals and sugar contents of transgenic and wild-type sweet potato tubers. The transgenic sweet potato lines were 20–82-fold more resistant to glufosinate than the wild-type. The representative transgenic line 7171 also showed resistance to methionine sulfoximine, but was not resistant to oxyfluorfen and paraquat, which have different target sites. The stem length, number of leaves, petiole length, shoot fresh weight, and storage roots of transgenic lines were lower than those of the wild-type in field experiments. Reduced growth and root yield were not due to reduced quantum yield and relative chlorophyll contents. Glufosinate increased the ammonium accumulation in leaves of wild-type plants, but had minimal or no effect on leaves of transgenic line 7171. There were differences in mineral contents, free sugars, total amino acids, and free amino acids in the petiole and storage roots between wild-type and line 7171. There was no difference in drought tolerance between wild-type and line 7171, but the transgenic line was more tolerant to chilling temperature than wild-type plants. Follow-up research is required to elucidate the mechanisms underlying the growth and yield differences, different nutritional values, and differential response to low temperature between wild-type and transgenic sweet potato.

Background: Heat shock protein 90 (HSP90) possesses two major isoforms – HSP90α and HSP90β. They have essential roles in the protection against stressful conditions. They are also important for the re-establishment of cellular homeostasis. We investigated the clinical significance of HSP90α and HSP90β expression in patients with gastric cancer (GC). Methods: HSP90α and HSP90β expression levels were examined immunohistochemically in surgical specimens obtained from 186 GC patients. The correlations between their expression levels and clinicopathological parameters including patient survival were analyzed. Results: The frequencies of larger tumor size (maximum diameter ≥4 cm) and more prominent tumor invasion (≥pT3) in the high intensity HSP90α expression group were 73.4% and 68.8% higher, respectively, than those in the low intensity group (both P = 0.001). High HSP90α expression level was also significantly associated with lymphatic invasion, lymph node metastasis, and advanced stage (TNM stage ≥III) disease (P = 0.047, P = 0.046, and P = 0.004, respectively). Patients with high HSP90α expression levels demonstrated significantly worse survival than those with low HSP90α expression levels (P = 0.047). In contrast, survival did not differ significantly according to the intensity of HSP90β expression. Conclusions: Our results showed that HSP90α overexpression might be associated with disease progression and poorer survival in patients with GC. Therefore, HSP90α could be used as possible biomarker for the prognosis of GC.

Interferon tau (IFNT), a type I interferon, is known as a key signal molecule during pregnancy in ruminants because of the necessity in maternal recognition of pregnancy. It is produced in trophectoderm cells of the elongation bovine conceptus at Day 13-21, and peak production is at Day 15 to 17 of pregnancy. In addition, other studies show that it can affect embryonic development and quality. In this study, the effect of IFNT knockout in donor cells to bovine cloned embryonic development by somatic cell nuclear transfer (SCNT) was investigated. To proceed with this experiment, immature oocytes from ovaries at a local slaughterhouse were matured in vitro for 22h. To prepare the donor cell with IFNT knockout, somatic cells were transfected with Cas9 and single guide RNA targeting IFNT, and several single derived colonies with high proliferation were isolated for mutation assay. Finally, one colony that had mono-allelic mutation (4bp deletion) was selected and used as the donor cell for SCNT. A donor cell was injected into an enucleated oocyte. Reconstructed oocytes with the donor cell were fused by electrical shock, activated by chemical stimulation, and cultured for 7 days in chemically defined medium. For this study, control (n=94) and IFNT knockout groups (n=140) were compared with 4 replications. The results showed no significant difference between control and IFNT knockout groups not only in cleavage rate, but also in blastocyst formation rate (control: 15.7±8.3%, IFNT knockout group: 26.3±13.1%). In addition, the number of blastocyst cell was not different between control (88.2±27.0) and IFNT knockout group (88.0±21.1). Some IFNT mutated blastocysts from SCNT were randomly selected for confirmation of the deletion of IFNT, and all samples were positive for mutation. In conclusion, these data demonstrated that the disruption of IFNT did not affect embryonic development. In future study, we would transfer these embryos and check the effect of IFNT during pregnancy status. This work was supported by BK21 PLUS Program for Creative Veterinary Science, the National Research Foundation of Korea (2017R1A2B3004972), and the Technology Development Program (S2566872) by MSS.

The p53 gene is a tumour suppressor gene with many roles in cellular reprogramming, senescence, or cancers. Knockdown of p53 in somatic cells improves generation of induced pluripotent stem cells and developmental competence of cloned embryos. In this study, we hypothesised that disruption of p53 in bovine somatic cells using CRISPR-Cas9 may improve reprogramming and result in increased blastocyst formation. For the study, ovary-derived immature bovine cumulus-oocyte complexes were matured in vitro. To prepare the donor cells with disruption of p53, primary cells from the skin tissue were transfected with spCas9 and single guide RNA for bovine p53. Two days later, genomic DNA was extracted and the mutation was evaluated on the target region using the T7E1 enzyme. Several single cell colonies were isolated to investigate the mutation and sequencing for mutation positive colonies was performed. One colony with high proliferative activity and heterozygotic mutation (−7bp deletion) was selected and used as the donor cell for somatic cell nuclear transfer. The donor cell was microinjected into an enucleated oocyte. Reconstructed oocytes were fused by electrical pulse, activated by chemical stimulation, and cultured in chemically defined media for 7 days at 5% CO2 and 5% O2. Data were subjected to ANOVA and least significant different test to determine differences between experimental groups by using SAS software (SAS Institute Inc., Cary, NC, USA). Statistical significance was determined when the P-value was less than 0.05. Blastocyst formation rate (13.5±7.6%) from the mutated cell line was significantly lower than wild type cells (43.9±12.1%). Moreover, total cell number (115.4±13.3) of the blastocysts from knockout cells was significantly decreased compared with the control group (143.6±22.5). Some randomly selected blastocysts derived from mutated cells were subjected to mutation assay to confirm deletion of p53. As expected, all the samples were positive to mutation. These data did not support our hypothesis that p53 disruption could improve blastocyst formation competence of bovine cloned embryos. In the future, the reason for impaired embryonic development of clones of p53 deleted somatic cells will be further investigated. This work was supported by BK21 PLUS Program for Creative Veterinary Science, the National Research Foundation of Korea (2017R1A2B3004972), and the Technology Development Program (S2566872) by MSS.

Background Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. Methods In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Findings Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Interpretation Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Funding Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT).

Version-4 of the Goddard Earth Observing System (GEOS-4) General Circulation Model (GCM) was employed to assess the influence of potential changes in aerosols on the regional circulation, ambient temperatures, and precipitation in four selected regions: India and Africa (current paper), as well as North and South America (companion paper). Ensemble-simulations were carried out with the GCM to assess the aerosol direct and indirect effects, hereafter ADE and AIE. Each simulation was started from the NCEP-analyzed initial conditions for 1 May and was integrated through May-June-July-August of each year: 1982–1987 to provide an ensemble set of six simulations. In the first set, called experiment (#1), climatological aerosols were prescribed. The next two experiments (#2 and #3) had two sets of simulations each: one with 2X and other with 1/2X the climatological aerosols over each of the four selected regions. In experiment #2, the anomaly regions were advectively restricted (AR), i.e., the large-scale prognostic fields outside the aerosol anomaly regions were prescribed while in experiment #3, the anomaly regions were advectively Interactive (AI) as is the case in a normal GCM integrations, but with the same aerosols anomalies as in experiment #2. Intercomparisons of circulation, diabatic heating, and precipitation difference fields showed large disparities among the AR and AI simulations, which raised serious questions about the proverbial AR assumption, commonly invoked in regional climate simulation studies. Consequently AI simulation mode was chosen for the subsequent studies. Two more experiments (#4 and #5) were performed in the AI mode in which ADE and AIE were activated one at a time. The results showed that ADE and AIE work in concert to make the joint influences larger than sum of each acting alone. Moreover, the ADE and AIE influences were vastly different for the Indian and Africa regions, which suggest an imperative need to include them rationally in climate models. We also found that the aerosol induced increase of tropical cirrus clouds would potentially offset any cirrus thinning that may occur due to warming in response to CO2 increase.

PURPOSE: Mandibular growth rotation is an important phenomenon in human facial growth. However, changes in the vertical height of the dentition, the inclination of the occlusal plane, and subsequent mandibular rotation during growth, are only poorly established. This study was designed to examine the inter-relation among occlusal plane rotation, mandibular growth rotation, and the establishment of tooth axis during growth and development. MATERIALS AND METHODS: The materials used consisted of 351 lateral cephalograms from 39 children who belonged to a longitudinal growth study. We observed their growth changes in the developmental stages from first molar eruption (Initial stage) until the completion of permanent dentition (Final stage). We measured values regarding the posture of the lower face, including mandibular rotation, occlusal plane, and tooth axis. The tangent law was applied for the sagittal organization of the mandibular teeth by geometrical analyses. RESULTS: Results showed that mandibular growth rotation is associated with occlusal plane rotation, which is caused by greater vertical height increase in the molars than in the anterior incisors. It was also shown that the mandibular incisors followed the tangent law, but the long axis of the posterior mandibular teeth exhibited almost the same angle, approximately 15° with the direction of the tangent. This tooth axis arrangement was very much dependent upon occlusal plane rotation and mandibular rotation during growth. CONCLUSION: The results of this cephalometric study could help dentists to determine a more suitable organization of occlusion in the sagittal plane, as required in orthodontics, prosthodontics, and implant dentistry.