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Background Inflammatory bowel disease (IBD) represents a group of chronic immune-mediated diseases of the gastrointestinal tract, characterized by recurrent inflammation and consequential damage of the gastrointestinal tract. Histone deacetylases (HDACs) are a family of mostly ubiquitous enzymes that remove acetyl groups from lysines on histone proteins to regulate gene transcription. HDAC6, which is localized to the cytoplasm, appears to be a promising candidate in IBD treatment. The purpose of the current study was to examine the anti-inflammatory effects of CKD-506, a novel histone deacetylase 6 (HDAC6) inhibitor, on human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells and to explore the relationship between CKD-506 and gut epithelial barrier function. Methods Lipopolysaccharide (LPS)-stimulated human PBMCs from inflammatory bowel disease (IBD) patients were treated with CKD-506, and tumor necrosis factor-alpha (TNF-α) expression was measured using enzyme-linked immunosorbent assay. The proliferation of CD4+ T cells from IBD patients was evaluated using flow cytometric analysis. The effects of CKD-506 on gut barrier function in a cell line and colon organoids, with examinations of mRNA production, goblet cell differentiation, and E-cadherin recovery, were investigated using quantitative reverse transcription PCR, immunofluorescence, and FITC-dextran permeability assay. Results TNF-α secretion, a pivotal pro-inflammatory mediator in IBD, of LPS-triggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. E-cadherin mRNA expression and goblet cell differentiation increased significantly and dose-dependently in HT-29 cells in response to CKD-506, and inhibition of E-cadherin loss after TNF-α stimulation was significantly reduced both in HT-29 cells and gut organoids. Caco-2 cells treated with CKD-506 showed a significant reduction of barrier permeability in a dose-dependent manner. Conclusion The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4+ T cells and improved gut barrier function, indicating its potential as a promising and competent candidate for small-molecule medicine for IBD treatment.

Few data are available on the gender-related differences in the prognostic impact of diabetes in people with heart failure. This study was performed to investigate whether there is a gender difference in the association between diabetes and long-term clinical outcomes in people hospitalized for heart failure.A total of 3162 people hospitalized with heart failure (aged 67.4 ± 14.1 years, 50.4% females) from the data set of the nationwide registry were analysed. The primary endpoint was a composite of all-cause mortality and heart failure readmission.People with diabetes (30.5% for males vs. 31.1% for females, P = 0.740) were older and had more unfavourable risk factors and laboratory findings than those without diabetes in both genders. During a median follow-up period of 549 days, there were 1418 cases of composite events (44.8%). In univariable analysis, the coexistence of diabetes was significantly associated with a higher incidence of composite events in both genders (P 0.05 each for males and females). In multivariable analysis, the prognostic impact of diabetes on the development of composite events remained significant in females even after controlling for potential confounders (hazard ratio 1.43, 95% confidence intervals 1.12-1.84; P = 0.004). However, an independent association between diabetes and composite events was not seen in males in the same multivariable analysis (P 0.05).In people with heart failure, the impact of diabetes on long-term mortality and heart failure readmission seems to be stronger in females than in males. More careful and intensive management is needed especially in females with heart failure and diabetes.

The oriental armyworm, Mythimna separata is an important crop pest in eastern Asia. Nocturnal insects, including nocturnal moths, have phototactic behavior to an artificial light source. Phototactic behavior in insects is species-specific in response to different wavelengths of light sources. Our previous study showed that green (520 nm) light emitting diode (LED) light resulted in a significantly higher phototactic behavior in M. separata moths compared to the other wavelength LED lights. The goal of the present study is to investigate the influence of green light illumination on biological characteristics of different developmental stages in M. separata. Our results revealed that when different developmental stages of M. separata were exposed to the green light illumination in a dark period, several biological characteristics in all developmental stages except for egg stage were positively changed, but those of F1 generation M. separata which are next generation of the adults exposed to the green light did not significantly change compared with the control level. These findings suggest that green light illumination at night (or dark period) has a positive effect on the development and longevity of M. separata.

Background Ischemic heart disease (IHD) is a major underlying etiology in patients with heart failure (HF). Although the impact of IHD on HF is evolving, there is a lack of understanding of how IHD affects long-term clinical outcomes and uncertainty about the role of IHD in determining the risk of clinical outcomes by gender. Purpose This study aims to evaluate the gender difference in impact of IHD on long-term clinical outcomes in patients with heart failure reduced ejection fraction (HFrEF). Methods Study data were obtained from the nationwide registry which is a prospective multicenter cohort and included patients who were hospitalized for HF composed of 3,200 patients. A total of 1,638 patients with HFrEF were classified into gender (women 704 and men 934). The primary outcome was all-cause death during follow-up and the composite clinical events of all-cause death and HF readmission during follow-up were also obtained. HF readmission was defined as re-hospitalization because of HF exacerbation. Results 133 women (18.9%) were died and 168 men (18.0%) were died during follow-up (median 489 days; inter-quartile range, 162–947 days). As underlying cause of HF, IHD did not show significant difference between genders. Women with HFrEF combined with IHD had significantly lower cumulative survival rate than women without IHD at long-term follow-up (74.8% vs. 84.9%, Log Rank p=0.001, Figure 1). However, men with HFrEF combined with IHD had no significant difference in survival rate compared with men without IHD (79.3% vs. 83.8%, Log Rank p=0.067). After adjustment for confounding factors, Cox regression analysis showed that IHD had a 1.43-fold increased risk for all-cause mortality independently only in women. (odds ratio 1.43, 95% confidence interval 1.058–1.929, p=0.020). On the contrary to the death-free survival rates, there were significant differences in composite clinical events-free survival rates between patients with HFrEF combined with IHD and HFrEF without IHD in both genders. Figure 1 Conclusions IHD as predisposing cause of HF was an important risk factor for long-term mortality in women with HFrEF. Clinician need to aware of gender-based characteristics in patients with HF and should manage and monitor them appropriately and gender-specifically. Women with HF caused by IHD also should be treated more meticulously to avoid a poor prognosis. Acknowledgement/Funding None

Background HDAC6 is a stress-inducible gene and highly expressed in pathological conditions as well as inflammatory bowel disease. Immuno-modulatory functions of HDAC6 inhibitors are well established and proposed therapeutic effects for autoimmune diseases through regulation of Treg cell function and inflammation. Moreover, HDAC6 inhibitors regulate inflammatory cytokines and chemokines, neutrophil activities, and epithelial regeneration in colitis models. CKD-506, a potent and selective oral HDAC6 inhibitor, is generally safe and well-tolerated in human, and is now investigating the efficacy in patients with rheumatoid arthritis. Herein, for future investigation with IBD, we identified molecular action mechanisms of CKD-506 involved in anti-colitis effects. Methods Mouse peritoneal macrophages or Raw264.7 cells were transfected with HDAC6 overexpression plasmid or empty vector as control. Cells were cultured in the presence or absence of 0.03~3 μM CKD-506, and the expression and production of inflammatory mediators were determined by RT–PCR and ELISA respectively. For reporter assays, Raw264.7 cells were transfected with pNF-kB-luc or pAP-1-luc plasmid and luciferase activity in cell lysates was determined by a luminometer. Signalling molecules in HDAC6 overexpressed cells were checked by immunoblot analysis. For the efficacy test of CKD-506, we used DSS-, TNBS-, Piroxicam (IL-10−/−)-, and adaptive T-cell transfer (RAG1−/−)-mediated colitis animal models. Colitis animals were treated with 1 to 100 mg/kg of CKD-506 and analysed disease activities and inflammatory mediators. Results In vivo, CKD-506 strongly inhibited disease activities in DSS-, TNBS-, Piroxicam-, and adaptive T-cell transfer-mediated colitis. In the chemical-induced colitis model, the expression of cell adhesion molecules and chemokines such as IP-10 and also infiltration of immune cells to colon tissues were reduced in CKD-506 treated mice. In vitro, HDAC6 overexpression strongly induced ROS and NADPH oxidase activity in Raw264.7 cells and CKD-506 significantly and dose-dependently inhibited HDAC6-mediated ROS and NADPH activity. Moreover, CKD-506 inhibited the production of pro-inflammatory cytokines and chemokines which are up-regulated in HDAC6 overexpressed mouse peritoneal macrophages or Raw264.7 cells. In promoter assay, HDAC6 overexpression highly induced NF-kB and AP-1 activity and CKD-506 strongly and dose-dependently inhibited both signalling pathways. Conclusion These data provide insight that CKD-506, a selective HDAC6 inhibitor, has anti-inflammatory and anti-colitis effects through regulation of NF-kB and AP-1 signalling pathway. Therefore, CKD-506 may provide beneficial effects in patients with Crohn’s disease and ulcerative colitis.

Reverse transcription-polymerase chain reaction (RT-PCR) was developed for the detection of viruses from Daphne odora plants in this study. Five sets of primers were designed for the specific detection of five different viruses, Daphne virus Y (DVY, Potyvirus), Cucumber mosaic virus (CMV, Cucumovirus), Daphne virus S (DVS, Carlavirus), Cycas necrotic stunt virus (CNSV, Nepovirus), and Watermelon mosaic virus (WMV, Potyvirus) in collected Daphne plants. RT-PCR could successfully detect the viruses from the Daphne plants. Two potyviruses (DVY and WMV), CNSV, CMV and DVS were frequently detected in >85% samples examined in this study. CNSV was the most prevalent virus (78%), and the infection rate for the three viruses WMV, CMV and DVS was >60%. These results demonstrate that virus diseases on Daphne plants are extremely severe and widespread in Korea. It is especially notable that mixed virus infections with more than three different viruses were very common and 12% of Daphne plants were infected by the five viruses. The results suggest that five primer sets developed in this study can successfully detect the target viruses and can be useful for the monitoring of virus incidence and indexing of the virus-free Daphne plants.

The pattern of leukocyte locomotion can be changed in many pathological situations, but its accurate analysis is difficult because of technological limitation. In the present study, by using a newly developed time-lapse videomicroscopic technique, we have analyzed the locomotive patterns of leukocytes in a stable concentration gradient of chemokines. Granulocytes, monocytes, and lymphocytes were purified from adult human peripheral blood. Locomotive behavior of the leukocytes was analyzed by an optical assay using a microchannel producing a stable concentration gradient of chemokines. Videomicroscopic analysis showed distinct locomotive patterns of granulocytes, monocytes, and lymphocytes. Granulocytes were intrinsically motile, vigorously moving in random direction without any chemokine stimulation. Upon stimulation with CXCL8/IL-8, the speed of migration was increased from 13.3 +/- 2.8 to 19.4 +/- 2.5 microm/min (P = 0.002, n = 100) and they moved toward the chemokine, although many cells still wandered very much. Stimulation with CCL5/RANTES or CXCL12/SDF-1alpha induced similar changes in locomotive pattern. On the other hand, most lymphocytes did not polarize or move spontaneously without chemokine stimulation. Stimulation with CXCL12 induced directional migration in 37% of the lymphocytes at a speed of 9.6 +/- 1.6 microm/min (n = 100). The movement pattern of monocytes was similar to that of granulocytes in that they tend to become polarized and move spontaneously, but they moved at a very slow speed ranging from 3.9 to 4.2 microm/min even with chemokine stimulation. The new optical assay may be useful for many diagnostic as well as basic studies.

The effects of BiFeO3 (BF) doping on the phase transition temperatures especially of lead-free piezoelectric materials were studied. Up to 20 mole% of BFO was doped in (Bi0.5Na0.5)TiO3 (BNT) and BaTiO3 (BT) ceramics synthesized by solid state reactions. In BNT, ferroelectric transition temperature (TC) increased with doping but depolarization temperature (Td) was almost independent of BF contents. In BT, however, TC decreased with BF doping.

Recently perovskite niobates were paid much attention as lead-free piezoelectric materials to replace lead-based Pb(Zr,Ti)O3 or relaxor systems which cause much environmental problems. Piezoelectric and ferroelectric properties of electromechanical coupling coefficient and quality factor in (K0.5Na0.5)NbO3 ceramic were studied. Dielectric properties of niobates including Ag ion; AgNbO3 and (Ag0.5Na0.5)NbO3 were studied. Phase transitions and dielectric relaxations were studied from the frequency and temperature dependent dielectric constant measurements. The piezoelectric properties were hardly observed in silver niobate systems.

This study was conducted to improve the control performance of a current variable-rate controller for granular fertilizers. Simulation model was developed. Optimized proportional, integral and derivative gains were determined by simulation model using 2nd order PID gain learning algorithm, and these control gains were evaluated through the field tests. Important results of this study are as follows; 1. Principles of pre-existing variable-rate application of granular fertilizers were investigated. 2. Simulation model of a PID controller that could simulate the control system was developed by using Matlab/Simulink program. The program was to determine PID control coefficients through the simulation model and 2nd order PID gain learning algorithm. 3. PID control coefficients obtained from the simulation were applied to the developed model. When the step input was given, Maximum overshoot were 1.96%, rise time were 0.05 sec, settling time were 0.06 sec and steady state error were 0.21 % respectively. 4. The simulation model was verified through field tests. The errors of maximum overshoot were 10%, rise time were 0.11 sec, settling time were 0.40 sec and steady state error were 8% because of loads and noises. Rise time was decreased to one third of that of the pre-existing system. 5. If the speed of a fertilizing machine is and the maximum rotation speed of a discharging roller is 64 rpm, rise time would be 0.26 sec and fertilizing machine would cover the distance of with settling time of 0.4 sec, fertilizing machine would cover the distance of .

This study was conducted to design and fabricate a controller for variable-rate application of granular fertilizer based on physical and chemical information, to analyze the performance of the controller and characteristics of a discharger. The result of the study are summarized as follows: 1. The charge ratios of discharger by accumulation heights of fertilizer in hopper were examined, and the variations in charge ratio were and for the fertilizers Super 21 and Sinsedae, respectively. The charge ratio also decreased as the rotational speed of discharger increased. 2. The coefficient of variation of discharge amount by rotational speed and discharge time of discharger were in the range of and for the fertilizer of Super 21 and Sinsedae. Except the rotational speed of 12 rpm, the coefficient of variation for discharge amount were relatively small with 4% more or less 3. In order to evaluate the rotational speed of discharger, the control signal in the range of was subdivided into the 50 steps by 0.1V. The regression equation for the rotational speed of discharger was Y

Most of tractors in the world have manual gear transmission, and some of small tractors have hydrostatic trans-mission(HST). Since the HST is expensive and has low power efficiency, it is being used for only small garden tractors. The continuously variable transmission(CVT) is an alternative to the HST or power-shift gear transmissions. The driver of the CVT tractor doesn`t have to operate a shift lever since the CVT controller automatically controls the speed of tractor. Thus, it is much easier to operate the CVT tractor. For the easy and stable control of the CVT tractor, an appropriate control algorithm should be developed and the dynamic modeling should be carried out before making the prototype of CVT controller. This study was conducted to develop a simulation model of the CVT control system needed to develop a PID control algorithm. The simulation model consisted of variator dynamics, hydraulic system and control computer. And the simulation model was verified by experiment. The results obtained in this study can be utilized in the design of CVT tractors for practical use, but a lot of field tests and improvement of softwares would be necessary.

There are several different types of continuously variable transmission(CVT) such as toroidal drive, belt drive, hydrostatic drive, hydro-mechanical drive. The toroidal CVT is an alternative to the manual transmission, HST, power-shift gear trans-missions or other CVTs. The driver of the CVT tractor doesn`t have to operate a shia lever since the CVT controller automatically controls the speed of tractor. Thus, it is much easier to operate the CVT tractor. The fuel efficiency of CVT tractor can be increased since the controller responds quickly to the change in external load on the wheel during field operation. This study was conducted to develop the hardwares and softwares for the toroidal CVT controller which control the variator and the range clutches. The hardware consisted of a measurement system, hydraulic system and computer. And the PID controller was developed using the simulation model of the CVT control system. Through the simulation, the control coefficients for the PID controller were selected. Finally, the performance of the CVT control system was evaluated by step response test and torque response test. The settling time of the CVT control system appeared to be fast enough for field operations.

Thrombopoietin (TPO) is one of the most promising stimulants for ex vivo expansion of haematopoietic stem cells. Previously, we have found that TPO induces a characteristic pattern of apoptosis during ex vivo expansion of human cord blood (CB) CD34+ cells and that the TPO-induced apoptotic cells belong to megakaryocyte (MK) lineage. In this study, we have examined the maturation of MK and platelet production in association with the TPO-induced apoptosis. CD34+ cells, purified from human CB, were expanded in serum-free conditions stimulated with TPO. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) assay and electron microscopy (EM). Simultaneous measurement of DNA content and immunophenotyping revealed that the cells with higher DNA content (>8 N) constituted less than 5% of the CD41+ fractions until day 14, implying premature apoptosis of MKs before full polyploidization. Nevertheless, EM observation showed not only platelet territories but also newly produced platelets in which granules and microfilaments could be identified. Furthermore, flow cytometry demonstrated that the platelet fraction expressed P-selectin and an activation motif on GPIIb/IIIa recognized by monoclonal antibody PAC-1 upon stimulation with adenosine diphosphate (ADP). In addition, periodic acid-Schiff (PAS)-positive materials and nonspecific esterase activities could be demonstrated. Therefore, it is suggested that platelet production and the accompanying processes, rather than apoptosis only, be hastened during the ex vivo expansion of CB CD34+ cells when using TPO.

The interrelationship between defect chemistry, non-stoichiometry, grain boundary transport and chemical stability of proton conducting perovskites (doped alkaline earth cerates and zirconates) has been investigated. Non-stoichiometry, defined as the deviation of the A : M molar ratio in AMO3 from 1 : 1, dramatically impacts conductivity, sinterability and chemical stability with respect to reaction with CO2. In particular, alkaline earth deficiency encourages dopant incorporation onto the A-atom site, rather than the intended M-atom site, reducing the concentration of oxygen vacancies. Transport along grain boundaries is, in general, less favorable than transport through the bulk, and thus only in fine-grained materials does microstructure impact the overall electrical properties. The chemical stability of high conductivity cerates is enhanced by the introduction of Zr. The conductivity of BaCe0.9−x Zr x M0.1O3 perovskites monotonically decreases with increasing x (increasing Zr content), with the impact of Zr substitution increasing in the order M = Yb → Gd → Nd. Furthermore, the magnitude of the conductivity follows the same sequence for a given zirconium content. This result is interpreted in terms of dopant ion incorporation onto the divalent ion site.

This study was conducted to develop a low-cost, precise metering device for automated nutrient-solution mixing systems. The metering device consisted of a supply pump, cylinder, level sensors, and a solenoid valve. The level of solution in the cylinder was kept constant to maintain a uniform discharge rate. The supply and discharge of the solution was controlled with a microcomputer. Test results indicate that the deviation in accuracy for the four metering devices developed was ±0.3%, which is significantly less than that of commercial metering pumps.

The low temperature pressureless sintering of a nanosized Si3N4 powder with doped sintering additives was investigated. The microstructural evolution during sintering at different temperatures was analyzed using x-ray diffraction and scanning electron microscopy. The effect of using nanosized Si3N4 powder as a catalyst to accelerate the α→β–Si3N4 transformation of a commercial Si3N4 powder with larger particle sizes was also investigated. Finally, two stage sintering was used to study the feasibility of controlling the microstructure and the mechanical properties of the nanosized silicon nitride.

The characteristics of nanosized silicon nitride powders with doped Y2O3 and Al2O3 fabricated by a plasma-reacted chemical process were investigated. The chemical compositions of the powders were analyzed by wet chemical analysis. The morphology and the size distribution were determined by transmission electron microscopy (TEM). TEM with energy dispersive spectroscopy (EDS) was used to verify the existence of sintering additives in each individual particle. The crystal structure of the powders was identified by the selected area diffraction pattern (SADP). X-ray diffraction (XRD) technique was used for phase analysis and the measurement of degree of crystallinity. The characteristics of chemical bonding was analyzed by using Fourier transform infrared spectroscopy (FTIR).

The coat protein (CP) genes of the genomic RNA of two Korean isolates of sweet potato feathery mottle potyvirus (SPFMV), SPFMV-K1 and SPFMV-K2, were cloned and their complete nucleotide sequences were determined. Sequence comparisons of the two Korean isolates showed 97.8% amino acid identity in the CP cistron, and 79.9% to 99.0% identity with those of 6 other known SPFMV strains. Of 74 amino acid changes totally among the SPFMV strains, 39 changes were located at the N-terminal region. Pairwise amino acid sequence comparison revealed sequence similarities of 48.6 to 70.2% between SPFMV and 20 other potyviruses, indicating SPFMV to be a quite distinct species. Multiple alignment of the CP cistrons from other potyviruses showed that most of the conserved amino acid residues of the genus Potyvirus are well preserved in the corresponding locations.

The aim of this study was to determine the clinical characteristics of patients with resistant hypertension (RH) and predictors among elderly Korean hypertensives. This prospective, multi-center, observational study evaluated 2439 elderly hypertensive patients between December 2008 and November 2011, who visited secondary hypertension clinics for high blood pressure (BP). Patients were categorized as resistant if their BP was ≥140/90 mm Hg and if they reported using antihypertensive medications from three different drug classes, including a diuretic or drugs from ≥4 antihypertensive drug classes, regardless of BP. Characteristics of patients with RH were compared with those of patients who were controlled with one or two antihypertensive medications after 6-month antihypertensive treatment. In comparison with 837 patients with non-RH, 404 patients with RH were more likely to be aware of their status of high BP before enrollment and have a high baseline systolic BP ≥160 mm Hg, microalbuminuria, high body mass index (BMI) ≥24 kg m(-2) and diabetes mellitus (DM). In drug-naive patients, awareness of hypertension at baseline was the only independent predictor for RH. In elderly Korean hypertensives, BMI (≥24 kg m(-2)), baseline systolic BP (≥160 mm Hg), microalbuminuria, DM and awareness of hypertension showed an association with RH.

We sought to find the therapeutic effect of 5Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected pharyngeal motor cortex in post-stroke dysphagic patients.Eighteen patients with unilateral hemispheric stroke oropharyngeal dysphagia that lasted more than 1 month were randomly divided into two groups. They all performed videofluoroscopic swallowing study (VFSS) before rTMS intervention. The experimental group (EG) received 5Hz rTMS over contra-lesional pharyngeal motor cortex for 10 min per day for 2 weeks. The control group (CG) received sham stimulation under the same condition. Videofluoroscopic swallowing study were performed again just after treatment cessation and 2 weeks afterward. The evaluation was performed using videofluoroscopic dysphagia scale (VDS) and penetration-aspiration scale (PAS).Mean baseline VDS and PAS of EG was 33.6 ± 12.1 and 3.41 ± 2.32 respectively and the scores were reduced to 25.3 ± 9.8 and 1.93 ± 1.52 just after 2 weeks intervention (P0.05). This effect lasted for up to 2 weeks after treatment. However, there was no change in the CG. Baseline prevalence of aspiration, pharyngeal residue, delayed triggering of pharyngeal swallowing and abnormal pharyngeal transit time (PTT) in EG was 66.7%, 66.7%, 33.3%, and 44.4%, respectively. After rTMS, the prevalence of aspiration and pharyngeal residue was reduced to 33.3% and 33.3%, respectively. However, the prevalence of delayed triggering and abnormal PTT was not changed.A 5Hz high-frequency rTMS on contra-lesional pharyngeal motor cortex might be beneficial for post-stroke dysphagic patients. This intervention can be used as a new treatment method in post-stroke patients with dysphagia.

The effects on cardiac function of slowed frequency produced by a sinus node inhibitor (zatebradine, or UL-FS 49) were studied in the conscious rabbit under control conditions (n=16) and after heart failure was produced by rapid atrial pacing for an average of 18.5 days (n=8). Echocardiography was used to verify severe left ventricular (LV) dysfunction, and high-fidelity micromanometry and cardiac output measurements (Doppler echo) were performed. Echocardiographic fractional shortening was 40.3±4.1% (SD) in controls; in heart failure it was 18.0±1.6%, and the LV was enlarged. In controls, as heart rate (HR) was decreased from 279 beats per minute (bpm) by incremental doses of zatebradine (up to 0.75 mg/kg), maximal changes occurred when the heart reached 218 bpm with a maximum decrease of the first derivative of LV pressure (LV dP/dtmax) of 15.9%; LV enddiastolic pressure (EDP) increased from 4.3 to 8.4 mmHg along with a significant decrease in cardiac index (CI) of 15.2%, while LV systolic pressure (SP) was stable. In heart failure, LV dP/dtmax and CI were markedly reduced compared to controls and with reduction of HR from 257 to 221 with reduction of HR from 257 to 221 bpm LV dP/dtmax was unchanged, LVEDP increased slightly (NS), LVSP was unchanged and CI fell by 13.5% at the highest dose. In subgroups (control n=9, failure n=6), in order to eliminate the hemodynamic effects of cardiac slowing by zatebradine the sinus rate present before zatebradine was matched by atrial pacing; this procedure eliminated all hemodynamic abnormalities accompanying cardiac slowing in both groups. In conclusion, slowed HR due to a sinus node inhibitor was well tolerated in severe heart failure, and all negative hemodynamic responses in both controls and in heart failure were due entirely to a negative forcefrequency effect, without a direct depressant action of zatebradine on the myocardium.

The complete nucleotide sequence of the genomic RNA of odontoglossum ringspot tobamovirus (ORSV) was determined. The RNA genome of ORSV is 6618 nucleotides long and contains five open reading frames (ORFs 1 to 5) coding for proteins of M(r) 126 K, 181 K, 34 K, 18 K and 52 K, respectively. This is the longest RNA of the known viruses of the Tobamovirus genus. The sequences of the ORSV RNA encoded proteins exhibit high homology to the proteins of the members of the Tobamovirus genus. The genomic organization and sequence analysis showed that ORSV is more closely related to tobacco mild green mosaic virus (TMGMV), pepper mild mottle virus (PMMV), tomato mosaic virus (ToMV) and TMV than to cucumber green mottle mosaic virus (CGMMV) and sunn-hemp mosaic virus (SHMV).

Recently we biochemically determined the molecular recognition and regulatory mechanisms of how beetle’s larvae recognize Gram-positive bacteria and fungi via Toll signaling cascade. The biochemical analysis of newly identified molecules provides us how beetles recognize invading pathogenic microbes and how they defend their bodies using elegant innate immunity. Here, we will focus on reviewing the biochemical analyses and biological functions of newly identified molecules involved in insect Toll signaling cascade.

BACKGROUND AND STUDY AIMS: Oral sodium phosphate (NaP) solution is widely used for colonoscopy bowel preparation and it may cause aphthous ulcers in the colon. Our aim was to evaluate whether oral NaP solution is associated with gastric mucosal lesions. METHODS: A total of 20 070 individuals underwent esophagogastroduodenoscopy (EGD) with colonoscopy, and 4271 individuals underwent EGD without colonoscopy, for cancer screening. Oral NaP solutions were used for bowel preparation prior to colonoscopy. Hemorrhagic gastropathy was graded using a five-point scale for erosive mucosal injury. The effect of NaP bowel preparation on hemorrhagic gastropathy was estimated using multiple logistic regression analysis with odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: The incidence of hemorrhagic gastropathy was 1.6 % (70/4271) in the EGD only group and 4.0 % (809/20 070) in the EGD with colonoscopy group ( P < 0.001, unadjusted OR 2.55, 95 %CI 1.99 - 3.27). The ORs for mild (grade 1 - 2), moderate (grade 3), and severe (grade 4) hemorrhagic gastropathy according to NaP use were 1.92 (95 %CI 1.45 - 2.54), 4.72 (95 %CI 2.65 - 8.47), and 5.99 (95 %CI 1.46 - 24.63), respectively. After adjustment for confounding factors, NaP solution was a significant risk factor for acute hemorrhagic gastropathy in the multivariate analysis (OR 1.92, 95 %CI 1.34-2.74). In addition, male sex, a body mass index (kg/m 2 ) of less than 20, concurrent use of antihypertensive or nonsteroidal anti-inflammatory drugs, and duodenal ulcers were independently associated with the development of hemorrhagic gastropathy. HELICOBACTER PYLORI infection and atrophic gastritis were negatively associated with hemorrhagic gastropathy. CONCLUSION: Oral NaP bowel preparation for colonoscopy was associated with hemorrhagic gastropathy.

We have completed the genomic sequence of a potyvirus, freesia mosaic virus (FreMV), and compared it to those of other known potyviruses. The full-length genome sequence of FreMV consists of 9,489 nucleotides. The large protein contains 3,077 amino acids, with an AUG start codon and UAA stop codon, containing one open reading frame typical of a potyvirus polyprotein. The polyprotein of FreMV-Kr gives rise to eleven proteins (P1, HC-pro, P3, PIPO, 6K1, CI, 6K2, VPg, NIa, NIb and CP), and putative cleavage sites of each protein were identified by sequence comparison to those of other known potyviruses. Phylogenetic analysis of the polyprotein revealed that FreMV-Kr was most closely related to PeMoV and was related to BtMV, BaRMV and PeLMV, which belong to the BCMV subgroup. This is the first information on the complete genome structure of FreMV, and the sequence information clearly supports the status of FreMV as a member of a distinct species in the genus Potyvirus.

Electrical stimulation (ES) can be used to correct foot drop and toe drag during hemiplegic walking. This study designed to make potable electrical stimulation system according to correct foot drop of hemiplegic walking. A right hemiplegic patient was participated and electrical stimulator was mounted on the motor point of the tibialis anterior (TA) of hemiplegic patient. In order to validate the use of this system, we performed gait analysis of hemiplegic walking with and without electrical stimulation. A potable electrical stimulation system could correct the drag foot successfully.

Herbicide-tolerant Zoysia grass (Zoysta japonica Steud.) has been generated previously through Agrobacterium tumefaciensmediated transformation. The genetically modified (GM) Zoysia grass survived Basta spraying and grew to maturity normally while the wild-type (WT) grass stopped growing and died. GM Zoysia grass will permit more efficient weed control for various turf grass plantings such as home lawns, golf courses, and parks. We examined the environmental/biodiversity risks of herbicide-tolerant GM Zoysia before applying to regulatory agencies for approval for commercial release. The GM and WT Zoysia grass' substantial trait equivalence, ability to cross-pollinate, and gene flow in confined and unconfined test fields were selectively analyzed for environmental/biodiversity effects. No difference between GM and WT Zoysia grass in substantial traits was found. To assess the potential for cross-pollination and gene flow, a non-selective herbicide, Basta, was used. Results showed that unintended cross-pollination with and gene flow from GM Zoysia grass were not detected in neighboring weed species examined, but were observed in WT Zoysia grass (on average, 6% at proximity, 1,2% at a distance of 0.5 m and 0.12% at a radius of 3 m, and 0% at distances over 3 m). On the basis of these initial studies, we conclude that the GM Zoysia grass generated in our laboratory and tested in the Nam Jeju County field does not appear to pose a significant risk when cultivated outside of test fields.

Three Korean girls with ethylmalonic encephalopathy, the first Asian cases, were identified. In all three cases, we observed slight improvement in motor functions, cognitive behaviours and chronic mucoid diarrhoea after treatment with riboflavin and/or coenzyme Q10 treatment. The precise pathogenesis of ethylmalonic encephalopathy has not been fully elucidated, but riboflavin treatment may be helpful.

Thrombopoietin (TPO) is one of the most promising stimulants for ex vivo expansion of haematopoietic stem cells. Previously, we have found that TPO induces a characteristic pattern of apoptosis during ex vivo expansion of human cord blood (CB) CD34+ cells and that the TPO-induced apoptotic cells belong to megakaryocyte (MK) lineage. In this study, we have examined the maturation of MK and platelet production in association with the TPO-induced apoptosis. CD34+ cells, purified from human CB, were expanded in serum-free conditions stimulated with TPO. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) assay and electron microscopy (EM). Simultaneous measurement of DNA content and immunophenotyping revealed that the cells with higher DNA content (8 N) constituted less than 5% of the CD41+ fractions until day 14, implying premature apoptosis of MKs before full polyploidization. Nevertheless, EM observation showed not only platelet territories but also newly produced platelets in which granules and microfilaments could be identified. Furthermore, flow cytometry demonstrated that the platelet fraction expressed P-selectin and an activation motif on GPIIb/IIIa recognized by monoclonal antibody PAC-1 upon stimulation with adenosine diphosphate (ADP). In addition, periodic acid-Schiff (PAS)-positive materials and nonspecific esterase activities could be demonstrated. Therefore, it is suggested that platelet production and the accompanying processes, rather than apoptosis only, be hastened during the ex vivo expansion of CB CD34+ cells when using TPO.

Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, plays important roles in early haematopoiesis. Previously, we have demonstrated that TPO induces a characteristic pattern of apoptosis during ex vivo expansion of cord blood (CB) CD34+ cells. In this study, we have demonstrated that the TPO-induced apoptotic cells belong to the megakaryocytic (MK) lineage and that initially expanding MK progenitors declined along with the appearance of TPO-induced apoptosis. Human CB CD34+ cells were expanded in serum-free conditions with TPO. Multidimensional flow cytometry using simultaneous measurement of apoptosis and immunophenotyping showed that the TPO-induced apoptotic cells appeared in CD61+ fractions. Immunocytochemical analysis of the fluorescent activated cell-sorted fractions showed that the apoptosis-associated CD44low fraction expressed CD61. Clonogenic assay revealed 7.4 +/- 0.50-fold increase of total megakaryocyte colony-forming units (CFU-MKs) during the initial 9 d. Thereafter, the number of CFU-MKs decreased in parallel with the increase of apoptosis. When the MK colonies were subdivided according to size, the proportion of large colonies progressively decreased, while that of medium and small colonies increased. In particular, from d 6 small colonies became predominant. These results suggested that the MK progenitors matured as they expanded during ex vivo expansion with TPO and then proceeded to apoptosis.

In order to determine the detection limit for chemically treated virions by gel electrophoresis, reverse transcription-polymerase chain reaction (RT-PCR) and infectivity assay, tobacco mosaic virus (TMV) exposed to various concentrations of chemicals was studied. When virions were exposed to 0.2 N HCl for 30 mins, partially degraded TMV particles were observed by gel electrophoresis. Under the same exposure, a major RT-PCR amplified DNA product corresponding to the target size of 806 bp, which decreased as a function of time, could be detected for up to 60 mins of exposure. When virions were treated with NaOH (0.02 N or higher normality) for 5 mins, partially degraded virions were detected by gel electrophoresis, exhibiting multiple band patterns. Exposure of the virions to 0.1 N NaOH for 5 mins revealed severely degraded viral RNA, but disappearance of the amplified RT-PCR products was apparent during 30-60 mins of exposure. Therefore, these data showed clearly the difference in the detection limit of gel electrophoresis and that of RT-PCR for the degraded viral RNA. In addition, the infectivity assay showed that the number of local lesions in Nicotiana rustica were significantly reduced by more than 95% when the virus was exposed to 0.2 N HCl for 15 mins or 0.1 N NaOH for 10 mins. From these results we conclude that loss of infectivity was not related to that of PCR product. Other chemical disinfectants such as phenol or formalin were also found to be effective to reduce the virus infectivity, but a corresponding degradation of viral RNA was detected by neither gel electrophoresis nor RT-PCR.

Biomechanical and biological factors can co-dependently influence the establishment of implant-tissue integration; thus, concurrent evaluation of these factors should provide a better understanding of osseointegration. This study aimed to establish and validate an in vivo rat model frequently used in molecular/cellular biology for implant biomechanical studies. We tested the hypotheses that the implant push-in test assesses the degree of osseointegration by the breakpoint load at the implant-tissue interface and that it sensitively differentiates between the effects of different implant surface topographies. The implant push-in test, which produces a consistent load-displacement measurement, was used to test miniature cylindrical titanium implants placed at the distal edge of the adult rat femur. The push-in test values obtained at each post-implantation healing point (weeks 0, 2, 4, and 8) significantly increased in a time-dependent manner. The implant surface after the push-in test was associated with remnant tissues containing host-derived elements, such as calcium, phosphate, and sulfate. In this model, acid-etched implants (average roughness, 0.159 μm) showed significantly greater push-in test values than did turned implants (average roughness, 0.063 μm) throughout the experimental period (p < 0.0001). These results support the validity of the push-in test in rats, which may be used as a rapid and sensitive biomechanical assay system for implant osseointegration research.

We investigated the phenotypic changes of human umbilical cord blood (CB) CD34+ cells during ex vivo expansion using thrombopoietin (TPO), flt3-ligand (FL), and/or granulocyte-colony stimulating factor (G-CSF). During ex vivo expansion of CD34+ cells isolated from human CB for up to 5 weeks, surface expression of molecules on the cultured cells including CD64 (Fc gammaRI), CD32 (Fc gammaRII), CD16 (Fc gammaRII), CD11b (MAC-1) and CD18 (beta2-integrin) was analysed by flow cytometry along with simultaneous measurement of apoptosis by 7-aminoactinomycin D staining method. CD64, CD32 and/or CD18 expressing cells appeared in the cultures both with and without the addition of G-CSF until the tenth day. However, without G-CSF, CD16+ fractions did not appear and CD11b+ fractions were not maintained. With G-CSF, the CD16+ or CD11b+ fractions appeared only from the second week. These results suggest that G-CSF is necessary for the late stage of myeloid maturation during which CD16 and CD11b are expressed.

The insufficient number of haemopoietic stem cells (HSCs) in cord blood (CB) is the major potential limitation to widespread use of CB for marrow replacement. Cytokine-mediated ex vivo expansion has been proposed as a means of increasing the number of CB HSCs for transplantation. However, the biology of CB HSCs during cytokine-mediated ex vivo expansion, such as apoptosis or expression of adhesion molecules, has not yet been elucidated. We have investigated the patterns of apoptosis and CD44 expression on human CB CD34+ cells during ex vivo expansion. CD34+ cells isolated from human CB were cultured in a stroma-free liquid culture system with thrombopoietin (TPO), flt3-ligand (FL), stem cell factor (SCF), and/or granulocyte-colony stimulating factor (G-CSF). During the culture, for up to 5 weeks, apoptosis was measured by staining with 7-amino-actinomycin D (7-AAD) along with concurrent immunophenotyping of CD34 and CD44 with three-colour flow cytometry. In the cultures with TPO, an apoptotic fraction with down-regulated CD44 appeared from the fourth day up to the second week. G-CSF also induced apoptosis but in a different manner; the apoptotic fraction without down-regulation of CD44 appeared unremittingly for up to 5 weeks. FL did not induce apoptosis or down-regulation of CD44. These findings show that apoptosis is indeed involved in the regulation of CB CD34+ cells in ex vivo expansion and the patterns of apoptosis are dependent on the type of cytokines used. The distinct patterns of apoptosis suggest different mechanisms of TPO and G-CSF in inducing apoptosis, which still remains to be elucidated.

The 3'-terminal regions of the genomic RNAs of two Korean isolates of the lily symptomless Carlavirus (LSV), LSV-Ko and LSV-KII, were cloned and their nucleotide sequences were determined. The nucleotide sequence analysis and protein analysis by the Western blot revealed that E. coli expressed a 32-kDa protein that is the viral coat protein (CP) for the LSV. The two Korean strains share 98.4% and 98.3% sequence identities at the nucleotide and amino acid levels, respectively. The CP gene of LSV-Ko showed 99.1% and 87.0% nucleotide sequence identities, and 99.0% and 96.6% amino acid sequence identities with those of the Netherlands and the Japanese LSV strains, respectively. A pairwise amino acid sequence comparison revealed a sequence similarity of 29.6% to 69.8% between LSV-Ko and other species of the carlavirus. The 16 kDa protein of LSV-Ko shares 17.6% to 42.7% amino acid similarity with those of 8 other the carlaviruses, and they are variable in the N-terminal region. The Cys repeated zinc finger nucleic acid binding domain was found in the 16 kDa protein for all of the LSV strains. Sequence comparisons of the 7 kDa protein of LSV in the strain level showed significant identities from 100.0% to 98.4%. LSV-Ko shares 21.9% to 42.2% amino acid similarity with those of 8 other carlaviruses, 4 members of the potexviruses, and a closterovirus. LSV is closely related to blueberry scorch virus (BISV) based upon the phylogenetic tree analyses of the three proteins, indicating LSV to be a quite distinct member of the genus Carlavirus.

Trichuriasis is an intestinal infection found in human beings which is caused by Trichuris trichiura, more commonly known as whipworm because of its whip-like appearance. It is characterized by the invasion of the colonic mucosa by the adult Trichuris and produces minor inflammatory changes at the sites of localization. It is prevalent throughout the world, especially in tropical areas. Its diagnosis is usually made by identification of the typical eggs in the stool; adult whipworm is rarely seen during colonoscopy. Colonoscopy can directly diagnose trichuriasis, confirming the threadlike form of worms with an attenuated end. The worms can be overlooked, particularly if colon preparation is imperfect. Attenuated whip-like ends of whipworms, which are embedded in the colonic mucosa, were removed with biopsy forceps. We report on 5 cases of whipworm infection that were diagnosed on total colonoscopy.

The 3'-terminal regions of the genomic RNAs of two Korean isolates of sweet potato feathery mottle potyvirus (SPFMV) were cloned and their nucleotide sequences of full-length coat protein (CP) gene and 3' noncoding region (NCR) were determined. The CP of the two Korean isolates contained 315 amino acid residues. The CP cistron sequences of the Korean isolates exhibit 72.7% to 98.7% nucleotide sequence identity and 79.9% to 99.0% amino acid identity when compared with those of 8 other known SPFMV strains. Pairwise comparison revealed sequence similarities of 47.4% to 62.1% at the nucleotide level, and 48.6% to 70.2% at the amino acid level between SPFMV and 21 other potyviruses. SPFMV CP has extensive amino acid sequence similarity to the other members of the genus Potyvirus throughout its central and C-terminal regions. The 3' NCR of the SPFMV showed 42.5% to 99.1% nucleotide sequence identities among the strains. The 3' NCR of SPFMV revealed 19.9% to 63.6% sequence similarities to those of 21 other potyviruses. These results support the assignment of SPFMV as a distinct member of the genus Potyvirus of the family Potyviridae.

The 3′-terminal 1855 nucleotides (nts) of a Korean isolate of odontoglossum ringspot tobamovirus (ORSV-Cy) were cloned and sequenced. The sequence contained two open reading frames, which encode the cell-to-cell movement protein (MP) and coat protein genes, and are 912 nts and 477 nts long, respectively. The MP gene contained a conserved sequence motif of tobamoviruses and putative assembly origin of the viral RNA locating between 1117 nts and 1292 nts from the 3′-end. The 3′ untranslated region (UTR) of the virus comprises 414 nts, includes nine pseudoknots and a tRNA-like structure domain containing aminoacyl acceptor arm and the anticodon hairpin loop coding for histidine.

It is unclear whether nonpulsatile perfusion adversely affects the brain. This study compared cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) betwen pulsatile and nonpulsatile cardiopulmonary bypass (CPB) in rabbits at 27 degrees C.In experiment A, 24 anesthetized New Zealand white rabbits underwent pulsatile CPB at 27 degrees C, using alpha-stat acid-base management. Animals were randomized to three groups based upon the duration of the period of systolic ejection (100, 120, 140 ms) and were perfused for 20 min at each of three pulse rates (150, 200, 250 pulse/min), generating nine arterial pressure waveforms. Arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (radiolabeled microspheres), and CMRO2 (Fick) were measured at the end of each 20-min period. In experiment B, 16 anesthetized rabbits were randomized to pulsatile (120-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 27 degrees C. AFter 1 h, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF and CMRO2 were measured.In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all nine waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile bypass, 30 +/- 4 versus 32 +/- 5 ml.100 g-1.min-1, respectively. CMRO2 did not differ between pulsatile and nonpulsatile bypass, 1.7 +/- 0.2 versus 1.6 +/- 0.2 ml.100 g-1.min-1, respectively.During CPB in rabbits at 27 degrees C, neither CBF nor CMRO2 is affected by flow character.