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Abstract Background A brain glucose metabolism pattern related to phenoconversion in patients with idiopathic/isolated REM sleep behaviour disorder (iRBDconvRP) was recently identified. However, the validation of the iRBDconvRP in an external, independent group of iRBD patients is needed to verify the reproducibility of such pattern, so to increase its importance in clinical and research settings. The aim of this work was to validate the iRBDconvRP in an independent group of iRBD patients. Methods Forty iRBD patients (70 ± 5.59 years, 19 females) underwent brain [18F]FDG-PET in Seoul National University. Thirteen patients phenoconverted at follow-up (7 Parkinson disease, 5 Dementia with Lewy bodies, 1 Multiple system atrophy; follow-up time 35 ± 20.56 months) and 27 patients were still free from parkinsonism/dementia after 62 ± 29.49 months from baseline. We applied the previously identified iRBDconvRP to validate its phenoconversion prediction power. Results The iRBDconvRP significantly discriminated converters from non-converters iRBD patients (p = 0.016; Area under the Curve 0.74, Sensitivity 0.69, Specificity 0.78), and it significantly predicted phenoconversion (Hazard ratio 4.26, C.I.95%: 1.18–15.39). Conclusions The iRBDconvRP confirmed its robustness in predicting phenoconversion in an independent group of iRBD patients, suggesting its potential role as a stratification biomarker for disease-modifying trials.

Background Calcium ions play a pivotal role in cell proliferation, differentiation, and migration. Under basal conditions, the calcium level is tightly regulated; however, cellular activation by growth factors increase the ion level through calcium pumps in the plasma membrane and endoplasmic reticulum for calcium signaling. Orai1 is a major calcium channel in the cell membrane of non-excitable cells, and its activity depends on the stromal interaction molecule 1 (Stim1). Several groups reported that the store-operated calcium entry (SOCE) can be modulated through phosphorylation of Stim1 by protein kinases such as extracellular signal-regulated kinase (ERK), protein kinase A (PKA), and p21-activated kinase (PAK). PKC is a protein kinase that is activated by calcium and diacylglycerol (DAG), but it remains unclear what role activated PKC plays in controlling the intracellular calcium pool. Objectives Here, we investigated whether PKC-β controls intracellular calcium dynamics through Stim1. Methods Several biochemical methods such as immune-precipitation, site directed mutagenesis, in vitro kinase assay were employed to investigate PKC interaction with and phosphorylation of Stim1. Intracellular calcium mobilization, via Stim1 mediated SOCE channel, were studied using in the presence of PKC activator or inhibitor under a confocal microscope. Results Our data demonstrate that PKC interacts with and phosphorylates Stim1 in vitro. phosphorylation of Stim1 at its C-terminal end appears to be important in the regulation of SOCE activity in HEK293 and HeLa cells. Additionally, transient intracellular calcium mobilization assays demonstrate that the SOCE activity was inhibited by PKC activators or activated by PKC inhibitors. Conclusion In sum, our data suggest a repressive role of PKC in regulating calcium entry through SOCE.

This study aimed to assess the long-term outcomes of video-assisted mediastinoscopic lymphadenectomy (VAMLA) combined with video-assisted thoracic surgery (VATS) for left-sided lung cancer pulmonary resection.We retrospectively reviewed 1194 consecutive patients who underwent VATS anatomical resection for left-sided lung cancer between January 2007 and December 2016. Using propensity score-based inverse probability of treatment weighting (IPTW), perioperative outcomes and long-term survival outcomes were compared.Among 1194 patients, 295 (24.7%) underwent additional VAMLA (VATS + VAMLA group) and 899 patients (75.3%) underwent VATS only (VATS group). The proportion of patients with advanced N stage were higher in the VATS + VAMLA group (24.7%) than in the VATS group (18.3%). After IPTW adjustment, all baseline profiles between the two groups became similar. The long-term overall survival (OS) and recurrence-free survival (RFS) rates were similar between the VATS + VAMLA group and the VATS group (5-year OS, 77.8% versus 79.3%, p = 0.957; 5-year RFS, 69.6% versus 70.1%, p = 0.498). However, among patients with borderline pulmonary function (FEV1 ≤ 60% or DLCO ≤ 60%), the VATS + VAMLA group (n = 23) had a better prognosis than the VATS group (n = 36) (5-year OS, 67.4% versus 46.7%, respectively; p = 0.047; 5-year RFS, 74.6% versus 53.5%, respectively; p = 0.027).VAMLA might be a good complement to VATS for left-sided lung cancer, wherein optimal mediastinal lymph node dissection is not feasible under one-lung ventilation, such as when patients have borderline pulmonary function.

Background DNA mutations of diverse types provide the raw material required for phenotypic variation and evolution. In the case of crop species, previous research aimed to elucidate the changing patterns of repetitive sequences, single-nucleotide polymorphisms (SNPs), and small InDels during domestication to explain morphological evolution and adaptation to different environments. Additionally, structural variations (SVs) encompassing larger stretches of DNA are more likely to alter gene expression levels leading to phenotypic variation affecting plant phenotypes and stress resistance. Previous studies on SVs in rice were hampered by reliance on short-read sequencing limiting the quantity and quality of SV identification, while SV data are currently only available for cultivated rice, with wild rice largely uncharacterized. Here, we generated two genome assemblies for O. rufipogon using long-read sequencing and provide insights on the evolutionary pattern and effect of SVs on morphological traits during rice domestication. Results In this study, we identified 318,589 SVs in cultivated and wild rice populations through a comprehensive analysis of 13 high-quality rice genomes and found that wild rice genomes contain 49% of unique SVs and an average of 1.76% of genes were lost during rice domestication. These SVs were further genotyped for 649 rice accessions, their evolutionary pattern during rice domestication and potential association with the diversity of important agronomic traits were examined. Genome-wide association studies between these SVs and nine agronomic traits identified 413 candidate causal variants, which together affect 361 genes. An 824-bp deletion in japonica rice, which encodes a serine carboxypeptidase family protein, is shown to be associated with grain length. Conclusions We provide relatively accurate and complete SV datasets for cultivated and wild rice accessions, especially in TE-rich regions, by comparing long-read sequencing data for 13 representative varieties. The integrated rice SV map and the identified candidate genes and variants represent valuable resources for future genomic research and breeding in rice.

We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 − 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 − 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p

Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis. Adult human tissues from diverse sites around the body are used to reconstruct cellular phylogenies from early development, using somatic mutations as an internal barcode.

Whether prior radiotherapy (RT) affects the response of EGFR-mutated non-small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitor (TKI) remains elusive.Patients with EGFR-mutated NSCLC treated with EGFR TKIs who recurred after curative treatment at Asan Medical Center, Seoul, Korea were included. The progression-free survival (PFS) and overall survival (OS) from the initiation of EGFR TKI in patients who recurred after definitive RT were analyzed and compared to the outcomes of RT-naïve patients with advanced NSCLC treated with EGFR TKIs from previously reported prospective clinical trial results.A total of 60 patients who recurred after definitive RT were included. The median age was 70 years (range, 38-88), with 24 patients (40.0%) being males. Among the 60 patients, 52 patients (86.7%) had exon 19 deletion or L858R mutation, with 49 patients (81.7%) receiving gefitinib as the first-line EGFR TKI. The median PFS and OS from the initiation of EGFR TKI were 10.4 months (95% confidence interval [CI], 7.4-13.2) and 21.3 months (95% CI, 13.4-28.8), respectively.The EGFR TKI efficacy in EGFR-mutated patients with NSCLC who recurred after RT was comparable with that in historic controls of RT-naïve patients with advanced NSCLC treated with EGFR TKIs, indicating that RT may not affect EGFR TKI efficacy.

Various liquefaction vulnerability indices (LVIs) have been proposed to quantify the severity of liquefaction, and used to create the liquefaction hazard map. In producing the liquefaction hazard map, the spatial variability of LVI is important because the number of available in-situ data is typically limited, and the values at the unmeasured locations are predicted using kriging operations that consider the spatial correlation of observed values. In addition, the liquefaction hazard map may vary significantly depending on how LVI was spatially interpolated. This study aims to evaluate the spatial variability of soil properties based on cone penetration test (CPT) data, and to investigate the changes in geostatistical properties of LVIs depending on shaking intensity. A simplified CPT-based procedure was used to calculate the factor of safety against liquefaction, and the geostatistical properties of LVI according to shaking intensity were evaluated using the parameters of semivariogram. In addition, the LVIs at unmeasured locations were predicted using two geostatistical modeling approaches, and their results were compared to investigate the accuracy of geostatistical approaches in predicting LVIs according to the peak ground acceleration (PGA).

Microbial bioconversion of a given substrate is considered an efficient and eco-friendly tool for value-added industrial compound generation from natural products. Among natural products, unsaturated fatty acids have been used as substrates to produce various functional hydroxy fatty acids. In this study, we report the production of 7,10-dihydroxy-8(E)-hexadecenoic acid (DHD) from palmitoleic acid by a new strain, Pseudomonas aeruginosa KNU-2B. KNU-2B efficiently produced DHD from palmitoleic acid and required a strong alkaline condition for maximum DHD production. The maximum DHD amount produced under pH 10.0 and 48-h incubation at 27 °C and 150 rpm was 219.5 mg/100 mL culture. Other important nutritional factors were also investigated to obtain optimum DHD production.

Silicon carbide (SiC) is well known as an excellent material for high performance optical applications because it offers many advantages over other commonly used glasses and metals. The excellent attributes of SiC include high strength, high hardness, low density, high thermal resistance, and low coefficient of thermal expansion. The effect of CO2 laser and its tool path on SiCwere investigated. The process started by creating laser pre-cracks on the desired pattern. Subsequently, laser assisted polishing was conducted on the same tool path. The surface showed a sharp increase in material removal in the areas with laser pre-cracks. This high difference in material removal was used not only to fabricate a ⌀ 1100 mm concave mirror with 127 μm in depth but also to generate macro and micro patterns. Grooves from 2 mm to 200 μm in width and 5 μm to 20 μm depth were successfully generated.

Artificial muscle is one of the more prominent topics in modern robotics as it can be applied to robotic arms, electric vehicles and wearable robots (Shahinpoor et al. in Smart Mater Struct 7:15–30, 1998; Jani et al. in Mater Des 56:1078–1113, 2014). The advantages of Shape Memory Alloy (SMA) artificial muscle are lightness and high energy density. The high energy density allows the actuator to make powerful motions. Meanwhile, SMA wire contracts 6% of its length, which means that the required displacement cannot be achieved by a simple connection. To resolve these disadvantages, the SMA wires are coiled in a diamond-shaped structure. If the electric current is given by contracting wires in the longitudinal direction, the actuator can exert force and displacement in the diagonal direction. As the crossed tendon finds its minimal length when actuated, the rotation angle converges to 90°. Parameters related with the rotating motion were selected, such as SMA wires’ diameter and length, distance between the crossed part and elbow part, size of the diamond-shaped structure, friction, etc. To determine the maximum force of the actuator, a graphical method was used, which is similar to the yield strength determination (0.2% offset). Because the robotic elbow joint is connected by the tendon, the connections between links are flexible, and without motor it does not generate any sound or noise during operation. The robotic elbow joint using the SMA actuator is designed and analyzed, which can rotate 86.7° and generates maximum 56.3 N force.

This paper investigates how people perceive the same material differently according to sex and nationality and what types of materials they prefer. We surveyed the sense of and preference for materials through questionnaires. The survey used five specimens made of zirconia, alumina, aluminum alloy, titanium alloy, and polycarbonate, and was conducted in four cities: Seoul and Ansan (Korea), Atlanta (USA), and Arusha (Tanzania). The survey consisted of three tests (a tactile test, a visual with tactile test, and an acoustic test). Except for the visual with the tactile test, the tests were conducted without any visual information. Using a statistical method, it was found that people feel the same materials differently depending on their sex and nationality. Furthermore, evaluation items which are correlated with material preferences such as roughness, coldness, familiarity, stiffness and color brightness levels were found, with these results showing that the evaluation items related to the preferences differ depending on the person’s sex and nationality.

A specific type II restriction endonuclease T.Smu451I has been purified to electrophoretic homogeneity from the frozen cells of soil bacterium Sphingobacterium multivorum 451 (formerly Flavobacterium multivorum 451), using ultrasonic grinding, nucleic acid removal by streptomycin sulfate, protein precipitation by ammonium sulfate and phosphocellulose P-11, DEAE-Cellulose DE-52, Hepharin-Sepharose CL-6B chromatography, and elucidated several characteristics of T.Smu451I. The molecular weight of the enzyme determined by gel filtration and SDS-polyacrylamide gel electrophoresis was calculated to be 45,000 ± 2000 D (dimer) and 23,000 ± 1000 D (monomer), respectively. The isoelectric point (pI) of T.Smu451I is 5.4. T.Smu451I recognizes pentanucleotide palindromic sequences 5'-GGNC↓C-3' and cleaves between C and C in position shown by arrow to produce 3'-cohesive terminus of trinucleotide. Therefore, T.Smu451I is a neoschizomer of T.AsuI.

Background The role of surgical intervention as a treatment for pulmonary metastasis (PM) from hepatocellular carcinoma (HCC) has not been established. In this study, we investigated the clinical outcomes of pulmonary metastasectomy. Using propensity score matching (PSM) analysis, we compared the results according to the surgical approach: video-assisted thoracic surgery (VATS) versus the open method. Methods A total of 134 patients (115 men) underwent pulmonary metastasectomy for isolated PM of HCC between January 1998 and December 2010 at Seoul Asan Medical Center. Of these, 84 underwent VATS (VATS group) and 50 underwent thoracotomy or sternotomy (open group). PSM analysis between the groups was used to match them based on the baseline characteristics of the patients. Results During the median follow-up period of 33.4 months (range, 1.8–112.0), 113 patients (84.3%) experienced recurrence, and 100 patients (74.6%) died of disease progression. There were no overall survival rate, disease-free survival rate, and pulmonary-specific disease-free survival rate differences between the VATS and the open groups (p = 0.521, 0.702, and 0.668, respectively). Multivariate analysis revealed local recurrence of HCC, history of liver cirrhosis, and preoperative alpha-fetoprotein level as independent prognostic factors for overall survival (hazard ratio, 1.729/2.495/2.632, 95% confidence interval 1.142–2.619/1.571–3.963/1.554–4.456; p = 0.010/ Conclusions Metastasectomy can be considered a potential alternative for selected patients. VATS metastasectomy had outcomes comparable to those of open metastasectomy.

Background IL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited. Methods This study investigated the immunohistochemical expression of IL4Rα and IL13Rα1 in 89 soft-tissue sarcomas of the extremities, superficial trunk, and retroperitoneum. Immunohistochemical staining for IL4Rα and IL13Rα1 were scored according to a combination of staining intensity and staining area in tissue microarray samples. Positivity for the immunohistochemical expression of IL4Rα and IL13Rα1 were determined using receiver operating curve analysis. Statistical analysis was performed using regression analysis and a chi-square test. Results In human soft-tissue sarcomas, immunohistochemical expression of IL4Rα was significantly associated with IL13Rα1 expression. Nuclear and cytoplasmic expression of IL4Rα and IL13Rα1 were significantly associated with shorter survival of soft-tissue sarcoma patients in univariate analysis. Multivariate analysis indicated that nuclear expression of IL4Rα and IL13Rα1 were independent indicators of shorter overall survival (IL4Rα; p = 0.002, IL13Rα1; p = 0.016) and relapse-free survival (IL4Rα; p = 0.022, IL13Rα1; p p p Conclusions This study suggests IL4Rα and IL13Rα1 are associated with the progression of soft-tissue sarcoma, and the expression of IL4Rα and IL13Rα1 might be novel prognostic indicators of soft-tissue sarcoma patients.

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infections with multi-drug resistance needs effective and alternative control strategies. In this study we investigated the adjuvant effect of a novel furan fatty acid, 7,10-epoxyoctadeca-7,9-dienoic acid (7,10-EODA) against multidrug-resistant S. aureus (MDRSA) strain 01ST001 by disc diffusion, checker board and time kill assays. Further the membrane targeting action of 7,10-EODA was investigated by spectroscopic and confocal microscopic studies. 7,10-EODA exerted synergistic activity along with β-lactam antibiotics against all clinical MRSA strains, with a mean fractional inhibitory concentration index below 0.5. In time-kill kinetic study, combination of 7,10-EODA with oxacillin, ampicillin, and penicillin resulted in 3.8–4.2 log10 reduction in the viable counts of MDRSA 01ST001. Further, 7,10-EODA dose dependently altered the membrane integrity (p

Although the proximal humerus is a common site of osteochondroma, osteochondroma arising from the lesser tuberosity of the proximal humerus is rare. Because of the anatomy of the shoulder, mechanical impingement can occur via direct contact of the protruding lesser tuberosity against the glenoid rim or coracoid. In younger patients, this may cause isolated tearing of the subscapularis. In this study, is presented a rare case of osteochondroma on the lesser tuberosity that caused a subscapularis tear after shoulder impingement in a 34-year-old male. This case was managed using an arthroscopic approach. One year after the surgery, the patient had recovered a normal range of motion, with the resolution of impingement symptoms and the tearing of the subscapularis. Level of evidence IV.

Though inter-subspecific hybrids from indica and japonica rice have gained great success for yield increases over the recent decade, there are severe sterility problems in such hybrids. To overcome hybrid sterility, we previously obtained the line PL-(S5-n + f5-n) in the genetic background of an elite indica restorer line 9311, via breeding strategy for construction of wide compatibility line, which was proven to be an effective strategy in improving the seed setting rate of indica-japonica hybrid rice. Here, a novel strategy for developing japonica-compatible indica lines was employed by introducing the japonica allele pf12-j into 9311. The obtained NIL-(pf12-j) could significantly improve pollen and embryo-sac fertility by 29.7% and 28.6% in indica-japonica hybrids, thus leading to 20.9% improvement of spikelet fertility. In addition, we achieved the pyramiding line PL-(S5-n + f5-n + pf12-j) by a combinational strategy using both wide compatibility line and japonica-compatible indica line. Compared to PL-(S5-n + f5-n) with 38.9% increase of spikelet fertility, the pyramiding line PL-(S5-n + f5-n + pf12-j) showed 49.7% increase of spikelet fertility, suggesting cumulative effect of wide compatibility alleles S5-n + f5-n and japonica allele pf12-j to shape normal fertility of inter-subspecies hybrid. Interestingly, these lines also showed compatibility to indica. Hence, our results demonstrate that the two strategies could be simultaneously applied for indica-japonica hybrid breeding, and S5-n + f5-n + pf12-j are the optional allelic combination for overcoming hybrid sterility. This finding will greatly enhance our understanding for breeding indica-japonica hybrid rice by molecular-assisted selection strategy.

Background Animal studies are pivotal in allowing experimentation to identify efficacious treatment protocols for resolution of peri-implantitis. The purpose of this investigation was to characterize an expedited dog peri-implantitis model clinically, radiographically, and microbiologically. Methods Eight hound dogs underwent extractions (week 0) and implant (3.3 × 8.5 mm) placement with simultaneous surgical defect creation and ligature placement for induction of peri-implantitis (week 10). Ligatures were replaced at 6 weeks (week 16) and removed after 9 weeks (week 19) when supporting bone loss involved approximately 50% of the peri-implant bone. Microbial samples from the defects and healthy control implant sites collected at week 19 were analyzed utilizing a microarray. Clinical measures of inflammation were obtained and radiographic bone loss was measured from periapical radiographs. Radiographic depth and width measurements of bony defect were repeated at weeks 10 (baseline), 16, and 19. Canonical analysis of principal coordinates was used to visualize overall differences in microbial abundance between peri-implantitis and healthy implants. Results This accelerated disease protocol led to intrabony defect creation with a mean depth and width of 4.3 mm and 3.5 mm, respectively after 9 weeks of ligature placement. Microbial identification revealed 59 total bacteria in peri-implant sites, 21 of which were only present in peri-implant sites as compared to healthy controls. Overall microbial beta diversity (microbial between-sample compositional diversity) differed between peri-implantitis and healthy implants (p = 0.009). Conclusions Within the limitations of this study, this protocol led to expedited generation of peri-implant defects with a microbial profile indicative of a shift to disease and defect patterns conducive to regenerative treatment. However, the possibility of potential spontaneous resolution of lesions due to the lack of a chronicity interval as compared to chronic disease models need to be further clarified and considered during preclinical peri-implantitis model selection. Electronic supplementary material The online version of this article (10.1186/s12903-019-0837-y) contains supplementary material, which is available to authorized users.

We analyzed the antimicrobial potential of a novel furan fatty acid, 7,10-epoxyoctadeca-7,9-dienoic acid (7,10-EODA) against methicillin-resistant and -sensitive S. aureus (MRSA and MSSA). The anti-staphylococcal activity of 7,10-EODA and its consequences on cell physiology was determined by disc diffusion, broth microdilution, and flow cytometry. Anti-virulence activity of 7,10-EODA was evaluated by bioassays. 7,10-EODA was anti-staphylococcal with minimum inhibitory concentration (MIC) range of 125-250 mg/L. 7,10-EODA exhibited a dose response and inhibited MRSA 01ST001 by 90.5% and ATCC 29213 (MSSA) by 85.3% at 125 mg/L. MIC of 7,10-EODA permeabilized >95 % of MRSA 01ST001 cells to small molecules. Sublethal dose of 7,10-EODA was non-toxic but markedly reduced the hemolytic, coagulase, and autolytic activities of MRSA and MSSA at 15.6 mg/L. The results provide a lead for the utilization of natural furan fatty acids as novel anti-MRSA agents.

The manufacturing process of long fiber thermoplastic is initiated by supplying reinforced fiber wound in a spool dispenser. If problems such as tangling or kinking occur in the apparatus used for supplying the reinforced fiber in the long-fiber thermoplastic direct process, the productivity of the long-fiber thermoplastic decreases. Therefore, it is important to enhance the supply stability of reinforced fiber. In general, the increase in supply stability can be achieved by maintaining a steady balloon shape that is controlled by the unwinding velocity or tensile force of the reinforced fiber. In this research, the range of suitable tensile force was determined under the assumption that the unwinding velocity remained constant. The reinforced fiber was assumed to be inextensible, homogeneous, and isotropic and to have uniform density. The transient-state unwinding equation of motion to analyze the unwinding motion of reinforced fiber can be derived by using Hamilton’s principle for an open system in which mass can change within a control volume. In the process of solving the transient-state unwinding equation of motion, the exact two-point boundary conditions are adopted for each time step.

The use of computed tomography (CT) in the diagnosis of urinary tract infection (UTI) has rapidly increased recently at acute stage, but the CT findings associated with bacteremia in UTI patients are unknown. 189 UTI patients were enrolled who underwent a CT scan within 24 h after hospital admission. We classified CT findings into eight types: a focal or multifocal wedge-shaped area of hypoperfusion, enlarged kidneys, perinephric fat stranding, ureteritis or pyelitis, complicated renal cyst, renal papillary necrosis, hydronephrosis, and renal and perirenal abscess. A retrospective analysis was conducted to evaluate the CT findings associated with bacteremia. The mean age of these patients was 60 ± 17.2 years, and 93.1 % were women. Concurrent bacteremia was noted in 40.2 % of the patients. Abnormal CT findings were noted in 96.3 % of the patients and 62.4 % had two or more abnormal findings. The most frequent abnormal CT finding was a focal or multifocal wedge-shaped area of hypoperfusion (77.2 %), followed by perinephric fat stranding (29.1 %). Perinephric fat stranding, hydronephrosis, and the presence of two or more abnormal CT findings were significantly associated with bacteremia in patients with community-acquired UTI. In the multivariate logistic regression analysis, age [odds ratio (OR) 1.03; 95 % confidence interval (CI) 1.009-1.062], two or more abnormal CT findings (OR 3.163; 95 % CI 1.334-7.498), and hydronephrosis (OR 13.160; 95 % CI 1.048-165.282) were significantly associated with bacteremia. Physicians should be aware that appropriate early management is necessary to prevent fatality in patients with these CT findings.

Periosteum contains enriched pools of osteogenic progenitors and is highly proliferative, thus giving this tissue a pivotal role in maintaining the diameter of the diaphyseal cortex and in recovery from fractures. Although periosteal proliferation has not been detected in normal bone, intense periosteal proliferation has been observed in pathologic states such as fracture, inflammation, and bone tumors. However, the mechanism by which periosteal osteoprogenitor proliferation is regulated remains poorly understood. To investigate this regulation mechanism, osteoblast/osteocyte-specific conditional knockout mice were developed lacking Smad4 and Osx, two factors that are essential for osteoblast differentiation and matrix mineralization. In Smad4 (Col) and Osx (Col) mice, osteocalcin, Dmp-1, and sclerostin expression were significantly decreased in the cortical bone. Interestingly, although Cre activity was not observed in the periosteum, the proliferation of periosteal osteoprogenitors was enhanced in Smad4 (Col) and Osx (Col) mice, as assessed by 5'-bromo-2'deoxyuridine incorporation and proliferating cell nuclear antigen localization. Since Wnt signaling is a major factor affecting periosteal proliferation, we evaluated Wnt signaling in the periosteum. The expression levels of β-catenin and Lef-1 were increased in the periosteal osteoprogenitors. Moreover, the mRNA levels of β-catenin, cyclin D1, Lef-1, and Axin2, all of which are Wnt target genes, were significantly increased in the periosteum of both Smad4 (Col) and Osx (Col) mice. These results indicated that extracellular proteins secreted by mature osteoblasts and osteocytes suppress the proliferation of periosteal osteoprogenitors by blocking Wnt signaling in a paracrine manner. Our data suggest a new concept of periosteal bone healing and periosteal bone formation.

The study and transmission of East Asian medicine had gathered the attention of researchers in various fields in the Western world, especially in the United States. This study reviews various research papers and summarizes key issues in the spread of East Asian medicine in the United States. The propagation of East Asian medicine in the United States is summarized through the key words of who, when, why, and how. In terms of ‘Who’, Chinese researchers emphasize the role of Chinese parties, while non-Chinese researchers stress the process of internalization. The question of ‘When’ is also controversial. The oldest origin disputed goes back to the 13th century but Bach Franklin’s year 1825 and William Osler’s year 1892 seem more meaningful to Americans. This is because acupuncture was first introduced to the American medical community in 1825. Also, Osler is a relatively interesting figure, as he is the founder of the Johns Hopkins University School of Medicine. Reasons for the question of ‘Why’ are mostly practical as the desire for better treatment techniques propelled East Asian medicine’s inclusion. Yet historically, the yearning for Chinese culture was partially involved as well as academic reasons. As far as ‘How’, Sometimes East Asian medicine was spread through books and records, and direct experience of actual practice. Also, institutionalization of the acupuncturist system and the establishment of educational institutions in America show that East Asian medicine has surpassed the point of mere curiosity, and has grown into a substantial part of American society.

Munemasa (Finite Fields Appl. 4, 252–260, 1998) considered the orthogonal array of strength 2 that has a property very close to being an orthogonal array of strength 3. This result was based on his proof that a very few trinomials of degree at most 2m are divisible by a given trinomial of degree m. Dewar et al. (Des. Codes Cryptogr. 45, 1–17, 2007) proved that no trinomial of degree at most 2m is divisible by a given pentanomial f of degree m, provided that f is not in a finite list of exceptions. This result then led to produce the orthogonal arrays of strength 3, and they concluded their paper with some open questions. With regard to one of these questions, Panario et al. (Des. Codes Cryptogr. 63, 425–445, 2012) gave a characterization of divisibility for binomials and trinomials over F 3. In our work, division of tetranomials of degree at most 2m by a given type II pentanomial of degree m over F 2 is considered. It is related with the orthogonal arrays of strength 4 and will contribute to the question posed by Dewar et al.

Background The analgesic effects of dexamethasone have been reported previously, and the present study determined the effects of preoperative dexamethasone on postoperative pain in patients who received thoracotomy. Methods Forty patients participated in this randomized, double-blind study. All patients received either dexamethasone via a 0.1 mg/kg intravenous bolus before anesthetic induction or an equal volume of saline. Postoperative analgesia was provided to both groups via epidural patient-controlled analgesia (PCA), which consisted of 250 μg of sufentanil in 250 mL of ropivacaine (0.18%) for 72 h. The primary outcome was the cumulative consumption of epidural PCA at postoperative 24 and 72 h. The secondary outcomes were the pain intensity scores during resting and coughing at postoperative 24 and 72 h, quality of recovery, total amount of rescue analgesics required, and length of hospital stay. Results No significant differences was observed in the consumption of epidural PCA between the control and dexamethasone infusion groups at 24 h (63.6 [55.9–72.7] vs. 68.5 [60.2–89.0] ml, P = 0.281) and 72 h (199.4 [172.4–225.1] vs. 194.7 [169.1–252.2] ml, P = 0.890). Moreover, there was no significant difference in the pain intensity scores during resting and coughing at postoperative 24 and 72 h, quality of recovery, total amount of rescue analgesics required, and length of hospital stay. Conclusion A single intravenous administration of dexamethasone during the preoperative period does not reduce opioid consumption and post-thoracotomy pain. Trial registration The study was registered at http://cris.nih.go.kr (KCT0000359) and was conducted from December 2011 to October 2012.

We investigated non-equilibrium atomic dynamics in a moving optical lattice via observation of atomic resonance fluorescence spectrum. A three-dimensional optical lattice was generated in a phase-stabilized magneto-optical trap (MOT) and the lattice was made to move by introducing a detuning between the counter-propagating trap lasers. A non-equilibrium steady states (NESS's) of atoms was then established in the hybrid of the moving optical lattice and the surrounding MOT. A part of atoms were localized and transported in the moving optical lattice and the rest were not localized in the lattice while trapped as a cold gas in the MOT. These motional states coexisted with continuous transition between them. As the speed of the lattice increased, the population of the non-localized state increased in a stepwise fashion due to the existence of bound states at the local minima of the lattice potential. A deterministic rate-equation model for atomic populations in those motional states was introduced in order to explain the experimental results. The model calculations then well reproduced the key features of the experimental observations, confirming the existence of an NESS in the cold atom system., 12 pages, 7 figures

Background PARP1 facilitates the recovery of DNA-damaged cells by recruiting DNA damage response molecules such as γH2AX and BRCA1/2, and plays a role in resistance to antitumor therapies. Therefore, PARP inhibition being evaluated as an anti-cancer therapy. However, there are limited studies regrading PARP inhibition in osteosarcoma. Methods We evaluated the expression of DNA damage response molecules in 35 human osteosarcomas and investigated the effects of co-treatment of the PARP inhibitor, olaparib, and doxorubicin in osteosarcoma cells. Results The expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 were significantly associated with shorter survival of osteosarcoma patients. In osteosarcoma cells, knock-down of PARP1 and treatment of olaparib significantly inhibited proliferation of cells and induced apoptosis. Moreover, the anti-tumor effect was more significant with co-treatment of olaparib and doxorubicin in vitro and in vivo. Conclusions This study suggests that combined use of a PARP inhibitor with doxorubicin, a DNA damaging agent, might be effective in the treatment of osteosarcoma patients, especially in the poor-prognostic subgroups of osteosarcoma expressing PARP1, γH2AX, or BRCA1/2.

The recent advances in photocatalysis have opened a variety of new possibilities for energy and biomedical applications. In particular, plasmonic photocatalysis using hybridization of semiconductor materials and metal nanoparticles has recently facilitated the rapid progress in enhancing photocatalytic efficiency under visible or solar light. One critical underlying aspect of photocatalysis is that it generates and releases reactive oxygen species (ROS) as intermediate or final products upon light excitation or activation. Although plasmonic photocatalysis overcomes the limitation of UV irradiation, synthesized metal/semiconductor nanomaterial photocatalysts often bring up biohazardous and environmental issues. In this respect, this review article is centered in identifying natural photosensitizing organic materials that can generate similar types of ROS as those of plasmonic photocatalysis. In particular, we propose the idea of plasmonic photocatalyst-like fluorescent proteins for ROS generation under visible light irradiation. We recapitulate fluorescent proteins that have Type I and Type II photosensitization properties in a comparable manner to plasmonic photocatalysis. Plasmonic photocatalysis and protein photosensitization have not yet been compared systemically in terms of ROS photogeneration under visible light, although the phototoxicity and cytotoxicity of some fluorescent proteins are well recognized. A comprehensive understanding of plasmonic photocatalyst-like fluorescent proteins and their potential advantages will lead us to explore new environmental, biomedical, and defense applications.

The East Sea (Japan Sea), a small marginal sea in the northwestern Pacific, is ventilated deeply down to the bottom and sensitive to changing surface conditions. Addressing the response of this marginal sea to the hydrological cycle and atmospheric forcing would be helpful for better understanding present and future environmental changes in oceans at the global and regional scales. Here, we present an analysis of observations revealing a slowdown of the long-term deepening in water boundaries associated with changes of water formation rate. Our results indicate that bottom (central) water formation has been enhanced (reduced) with more (less) oxygen supply to the bottom (central) layer since the 2000s. This paper presents a new projection that allows a three-layered deep structure, which retains bottom water, at least until 2040, contrasting previous results. This projection considers recent increase of slope convections mainly due to the salt supply via air-sea freshwater exchange and sea ice formation and decrease of open-ocean convections evidenced by reduced mixed layer depth in the northern East Sea, resulting in more bottom water and less central water formations. Such vigorous changes in water formation and ventilation provide certain implications on future climate changes.

Sugar derivatives are critically important in nutritional, pharmaceutical, and some non-food industries. Amino sugars are more important as essential components of many drugs, antibiotics, and biopolymers. Hence, a novel amino sugar compound is worthy of investigation for identification and production. A novel amino sugar compound was identified from crude extracts of Korean pine seed embryos. This new compound was isolated from extracts using traditional purification steps. The pure compound was white in color with a melting point of 145°C. HPLC, TLC, FT-IR, and NMR analyses of the compound indicated a trisaccharide form of amino mannose that was polymerized with β-(1→2) glycosidic bonding. Computer-aided NMR spectral analysis of the trisaccharide of 2-dehydro-2-mannosamine exhibited a 96% match with the 13C-NMR spectrum of the new compound.

Next-generation sequencing (NGS) technique applies to genome sequencing, genome resequencing, transcriptome profiling (RNA-Seq) and epigenome characterization. In this study, we built valuable genetic off-line databases related to silk synthesis of wild silkworm B. mandarina, using comparative transcriptional studies between B. mandarina and the domestic silkworm, on the NGS platform. It contains 12,298 coding DNA sequence (CDS) showing differential expressed in the silk gland of B. mandarina and B. mori. The other database contains 31 CDS that are estimated to be specifically expressed in the silk gland of B. mandarina.

In ancient society, royal court was the core of authority and as such, almost all of the national resources were available to it. In terms of medicine, it was where the best medical techniques were applied. Especially since producing offspring is very important for the preservation of the throne, the medical treatment related to such an affair would have been the most efficient methods available in the era. This study focuses on the record of pregnancy and childbirth in the royal court of Joseon dynasty (a Korean kingdom that lasted for approximately five centuries, from July 1392 to October 1897) to analyze what medical treatment was used in the period. The pregnancy and childbirth related to the royal family was systematically managed by the state with a specific kind of treatment manual and protocol. Compound use of natural herbal medicine was common among diverse treatment methods. It seems that the oral medication of herbal medicines served to minimize miscarriages and post-natal aftereffects, and for this purpose Angelica Gigantis Radix and Cnidii Rhizoma were frequently used.

We study the Gauss map G of surfaces of revolution in the 3-dimensional Euclidean space $${{\mathbb {E}}^3}$$ with respect to the so-called Cheng–Yau operator $$\square $$ acting on the functions defined on the surfaces. As a result, we establish the classification theorem that the only surfaces of revolution with Gauss map G satisfying $$\square G=AG$$ for some $$3\times 3$$ matrix A are the planes, right circular cones, circular cylinders, and spheres.

This paper presents a study on applicability of predicting toe bearing capacities from cone penetration test (CPT) for PHC (pretensioned spun high-strength concrete) driven piles into deep sandy deposits in the Nakdong River deltaic area west of Busan City in South Korea. Using toe bearing capacities obtained from pile driving analyzer (PDA) tests as reference values, which were reliably calibrated by on-site O-cell tests, the applicability of the CPT-based methods was evaluated using a statistical rank index (RI). A total of 82 piezocone penetration test soundings and 190 PDA test piles were used for reliability analysis in this study. Three correction steps were applied to obtain reliable PDA and CPT data sets before ranking is carried out. The RI index is combined from four criteria: (1) the best-fit line, (2) the arithmetic mean and standard deviation, (3) the cumulative probabilities, and (4) the log-normal and histogram distributions. Based on these criteria the performance of some SPT-based methods in the literature is evaluated.

The aim of this retrospective, multicenter study was to develop a recurrence risk-scoring model in patients with curatively resected stage I lung adenocarcinoma (ADC). Clinicopathologic and outcome data for a development cohort of 1,700 patients with pathologic stage I ADC from four institutions resected between January 2000 and December 2009 were evaluated. A phantom study was performed for correction of inter-institutional differences in positron emission tomography-standardized uptake value (PET-SUV). A nomogram for recurrence prediction was developed using Cox proportional hazards regression. This model was validated in a cohort of 460 patients in two other hospitals. The recurrence rate was 21.0 % for the development cohort and 22.1 % for the validation cohort. In multivariable analysis, three independent predictors for recurrence were identified: pathologic tumor size (hazard ratio [HR] 1.03, 95 % CI 1.017–1.048; p

Rotigotine is a dopamine receptor agonist indicated for the treatment of Parkinson's disease and moderate-to-severe restless legs syndrome. Continuous transdermal delivery of rotigotine via a silicon-based patch maintains stable plasma concentrations over 24 h. The objective of the study was to evaluate the pharmacokinetics, safety, and tolerability of a multiple-dose schedule of rotigotine transdermal patch in Japanese and Caucasian subjects. In this open-label, repeated-dose, parallel-group study (ClinicalTrials.gov: NCT01854216), healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by gender, body mass index, and age. Subjects underwent a 9-day patch application period. 12 Japanese and 12 Caucasian subjects were included in the pharmacokinetic analyses. Mean apparent doses (actual amount of drug delivered) increased proportionally with rotigotine nominal dosages (1, 2, and 4 mg/24 h) and were similar for both ethnic groups, with large inter-individual variability. Mean plasma concentration-time profiles for unconjugated rotigotine were similar in both ethnic groups at day 3 for each dosage. Peak concentrations (C max,ss) and area under the concentration-time curves from pre-dose to the concentration measured 24 h after administration of patch (AUC(0-24,ss)) showed similar exposure in both groups; higher values in Japanese subjects were explained by differences in body weight. For total rotigotine, C max,ss and AUC(0-24,ss) values were higher in Caucasian subjects and could be explained by small differences in apparent dose. Rotigotine was generally well tolerated following multiple applications up to 4 mg/24 h. These findings suggest similar dosage requirements for rotigotine transdermal system in Japanese and Caucasian populations.

When a thin cable is unwound from a spool dispenser, factors that influence balloon shapes are initial tensile force, unwinding velocity, balloon height, package radius, and fluid condition. Historically, a thin cable’s unwinding motion has been analyzed using transient- and steady-state unwinding equations of motion. The transient-state unwinding equation of motion can be derived by using Hamilton’s principle for an open system in which mass can change within a control volume. In the process of solving the transient-state unwinding equation of motion, two-point boundary conditions are exactly adopted for each time step. The steady-state unwinding equation of motion can be derived by using a perturbation scheme from the transient-state unwinding equation of motion. To find a solution for the steady-state unwinding equation of motion, the shooting method is utilized, but due to insufficient boundary conditions at the lift-off point, finding a unique solution is impossible. Therefore, analysis of the unwinding motion of a thin cable should be performed using the transient-state unwinding equation of motion.

The optic nerve sheath diameter (ONSD) is considered as an indirect marker for intracranial pressure (ICP). However, the optimal cut-off value for an abnormal ONSD indicating elevated ICP and its associated factors have been unclear. Thus, we investigated normative values for the ONSD using ultrasonography and investigate the potential factors affecting it. We prospectively recruited healthy volunteers between September 2016 and March 2017. A total of 585 individuals were included, in which the mean ONSD was 4.11 mm [95% confidence interval (CI), 4.09–4.14 mm]. Although ONSD was correlated with sex (p = 0.015), height (p = 0.003), and eyeball transverse diameter (ETD) (p p

Background Shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, induces necroptosis in various cancer types, but the mechanisms underlying the anticancer activity of shikonin in lung cancer are not fully understood. This study was designed to clarify whether shikonin causes necroptosis in non-small cell lung cancer (NSCLC) cells and to investigate the mechanism of action. Methods Multiplex and caspase 8 assays were used to analyze effect of shikonin on A549 cells. Cytometry with annexin V/PI staining and MTT assays were used to analyze the mode of cell death. Western blotting was used to determine the effect of shikonin-induced necroptosis and autophagy. Xenograft and orthotopic models with A549 cells were used to evaluate the anti-tumor effect of shikonin in vivo. Results Most of the cell death induced by shikonin could be rescued by the specific necroptosis inhibitor necrostatin-1, but not by the general caspase inhibitor Z-VAD-FMK. Tumor growth was significantly lower in animals treated with shikonin than in the control group. Shikonin also increased RIP1 protein expression in tumor tissues. Autophagy inhibitors, including methyladenine (3-MA), ATG5 siRNA, and bafilomycin A, enhanced shikonin-induced necroptosis, whereas RIP1 siRNA had no effect on the apoptotic potential of shikonin. Conclusions Our data indicated that shikonin treatment induced necroptosis and autophagy in NSCLC cells. In addition, the inhibition of shikonin-induced autophagy enhanced necroptosis, suggesting that shikonin could be a novel therapeutic strategy against NSCLC.

Some esophageal cancer patients may have residual nodal metastases following pathologic complete response (pCR) of the primary tumor after neoadjuvant chemoradiotherapy (CRT). This study examines the prognosis according to lymph node metastases in pathologic T0 patients who received neoadjuvant CRT followed by surgery for esophageal squamous cell carcinoma (SCC). Prospectively-collected data from patients who underwent protocol-based esophageal resection and reconstruction after neoadjuvant CRT for esophageal SCC from 2000 to 2010 at the Asan Medical Center, Seoul, Korea, were retrospectively studied. Overall survival (OS), recurrence-free survival (RFS), and risk factors for ypT0N1 were analyzed and compared with ypT0N0. A total of 211 patients underwent prospective, protocol-based esophageal resection and reconstruction after neoadjuvant CRT for esophageal SCC. Of these, 123 patients had a pCR of the primary tumor and were enrolled in this study. Lymph node status was ypT0N0 in 103 patients and ypT0N1 in 20 patients. The two groups did not show significant differences in sex, initial clinical stage, tumor location, and histologic grade. Recurrence occurred in 13 patients (12.6 %) with ypT0N0 and six patients (30.0 %) with ypT0N1, respectively (p = 0.083). Five-year OS and RFS of ypT0N1 were 42.8 ± 13.9 and 41.7 ± 12.8 %, respectively. Survival was compared between the two groups using a log-rank test, and there were no significant differences for OS or RFS. Residual lymph node metastases did not significantly influence prognosis in pathologic T0 patients who received neoadjuvant CRT followed by surgery for esophageal SCC.

Cadmium (Cd) resistance is associated with the suppression of autophagy in H460 lung cancer cells, which is regulated by phospho(p)serine-glycogen synthase kinase (GSK) 3αβ. However, the involvement of multidrug resistance (MDR) in this signaling pathway and its underlying mechanisms remain to be elucidated. In this study, we used Cd-resistant cells (RH460), developed from H460 lung cancer cells, to demonstrate that the induction of MDR-associated protein (MRP1) in response to Cd is enhanced in H460 cells compared to RH460. Treating RH460 cells with Cd induced large cytoplasmic vacuoles, which was inhibited by the autophagy inhibitor 3-methyladenine. MRP1 was detected in the nuclear-rich membrane fractions and redistributed from the perinuclear to the cytoplasmic compartment following exposure to Cd. Cd-induced MRP1, p-Ser/p-Tyr GSK3αβ, and LC3-II were all suppressed by the GSK3 inhibitor SB216763, but increased by lithium. Furthermore, MRP1 was upregulated by the Ser/Thr phosphatase inhibitor okadaic acid and downregulated by the tyrosine phosphatase inhibitor vanadate, suggesting that MRP1 protein was stabilized by p-Ser GSK3αβ. In addition, co-immunoprecipitation and co-localization analyzes revealed a physical interaction between MRP1 and p-Ser GSK3αβ. Genetic knockdown of GSK3β decreased Cd-induced MRP1 mRNA and protein levels, whereas its overexpression upregulated MRP1 protein expression. MRP1 also co-localized with lysosomal membrane protein-2, which may cause lysosomal membrane permeabilization and the subsequent release of cathepsins into the cytosol. In mice chronically injected with Cd, MRP1 localized to the perinuclear region of bronchial and alveolar epithelial cells. Collectively, these data suggest that Cd toxicity is regulated by the transcriptional regulation, stabilization, and subcellular redistribution of MRP1 via the posttranslational modification of GSK3αβ. Therefore, the serine phosphorylation of GSK3αβ plays a critical role in MRP1-induced cell death.

The role of non-surgical treatments (NS), such as chemoradiotherapy or radiotherapy, for clinical T1N0M0 esophageal cancer (cT1N0M0 EC) has not been well delineated. The aim of this study was to evaluate and compare the feasibility and efficacy of NS and Surgical treatment (S) in cT1N0M0 EC patients.The medical records of patients who received treatment for cT1N0M0 EC at Asan Medical Center between 2003 and 2012 were retrospectively reviewed. The baseline characteristics, treatment outcomes and complications, and survival were compared.There were 264 S and 20 NS patients with respective median ages of 69.5 and 63.0. The main histologic finding was squamous cell carcinoma in both groups (97 and 100 %, respectively). The Eastern Cooperative Oncology Group performance status and Charlson comorbidity index score were poorer in the NS group. With a median follow-up of 49.0 months, 37 S patients (14 %) and 3 NS patients (15 %) exhibited recurrence. The first sites of recurrence for S and NS patients were locoregional (21 vs. 3 patients), distant (6 vs. 0), and both locoregional and distant (9 vs. 0), respectively. The median time-to-recurrence could not be calculated in either group (log-rank test P = 0.831). The estimated median overall survival was 64.4 months (95 % CI 37.2-91.6 months) in the NS group and could not be calculated in the S group (P = 0.056).Non-surgical treatments can be an effective alternative to S for patients with cT1N0M0 EC unfit for radical surgery. The role of NS for early stage EC needs to be further verified with prospective randomized trials.

Lipases with abnormal functionalities such as high thermostability and optimal activity at extreme conditions gain special attentions because of their applicability in the restricted reaction conditions. In particular, coldactive lipases have gained special attentions in various industrial fields such as washer detergent, pharmaceutical catalyst, and production of structured lipid. However, production of cold-active lipase is mostly found from psychrophilic microorganisms. Recently we found a novel cold-active lipase from Pichia lynferdii Y-7723 which is mesophilic yeast strain. In this study, we purified the cold active lipase and the enzyme was further characterized in several parameters. The enzyme was purified with 33 purification fold using chromatographic techniques and the purified lipase represented maximum lipolytic activity at 15°C and the maximum activity was highly dependent on pH.

A crack identification method using an equivalent bending stiffness for cracked beam and committee of neural networks is presented. The equivalent bending stiffness is constructed based on an energy method for a straight thin-walled pipe, which has a through-the-thickness crack, subjected to bending. Several numerical analysis for a steel cantilever pipe using the equivalent bending stiffness are carried out to extract the natural frequencies and mode shapes of the cracked beam. The extracted modal properties are used in constructing a training patterns of a neural network. The input to the neural network consists of the modal properties and the output is composed of the crack location and size. Multiple neural networks are constructed and each individual network is trained independently with the different initial synaptic weights. Then, the estimated crack locations and sizes from different neural networks are averaged. Crack detection is carried out for 16 damage cases using the proposed method, and the identified crack locations and sizes agree reasonably well with the exact values.

Melanoma that involves the upper gastrointestinal (GI) tract is rare and studies relating to endoscopic and pathologic findings with clinical outcomes are lacking. We reviewed the gross and microscopic patterns of the upper GI tract in primary and metastatic melanoma, and examined their association with clinical outcomes. Twenty-nine cases of primary esophageal (n = 19) and metastatic gastric and/or duodenal melanoma (n = 10) that were detected during upper GI endoscopy between 1995 and 2011 were retrospectively analyzed. Three types of gross patterns were recognized—nodular pattern in 7 cases, mass-forming pattern in 18 cases, and flat pigmented pattern in 4 cases. In primary esophageal melanoma, 13 patients (68.4 %) underwent surgery and 9 received palliative therapy. Of all cases, 22 patients (75.9 %) died of disease progression; the median overall survival period was 12 months (interquartile range [IQR] 4.5–24.5 months), and from recognition of upper GI tract melanoma the median overall survival period was 9 months (IQR 3.5–17.0 months). In primary esophageal cases, skin melanoma stage better discriminated the patients with good prognosis than the esophageal cancer stage. The flat pigmented gross pattern proved to be a good prognostic factor in primary and metastatic GI tract melanomas (p = 0.016 and p = 0.046, respectively). Melanoma of the GI tract is a highly aggressive disease with a poor prognosis, both in primary and metastatic cases. However, in primary esophageal melanoma, careful inspection of the mucosa during endoscopic examination followed by surgical resection may result in extended survival.