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The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C) Cdh1 E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in Drosophila eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/C Cdh1 represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.

Copper ferrocyanide-functionalized magnetic nano-adsorbents were successfully synthesized by electrostatic coating of citric acid coated Fe3O4 nanoparticles with polyethyleneimine, and immobilizing copper and ferrocyanide on the surfaces of polyethyleneimine-coated nanoparticles. Radioactive cesium (Cs) adsorption tests were conducted to investigate the effectiveness of the copper ferrocyanide-functionalized magnetic nano-adsorbents toward the removal of radioactive Cs.

Collagen sponges are often used as dermal substitutes in the treatment of burns, trauma, infections, and wounds. Dermal substitutes that can be applied in a one-stage operation are particularly important for dermal regeneration. Some protocols for the production of collagen sponges have been developed, but many issues remain, including low yield, contraction, and expense. In this study, the effectiveness of two skin substitutes was evaluated. Specifically, we compared two thin matrices, i.e., the newly developed INSUREGRAF® 1.2 mm and the widely used Matriderm® 1 mm Single Layer, with respect to their biochemical and mechanical properties, safety, and efficacy. We examined the rate of contractibility and biocompatibility using in vitro and in vivo models. The INSUREGRAF had an interconnected pore structure, which affects cell attachment and proper vascularization. Accordingly, this novel collagen sponge type has the potential to promote skin tissue regeneration and is especially suitable for full-thickness skin defects as a one-stage operation substitute.

Unsaturated fatty acids exert diverse biological processes dependent on their overall shape due to cis and trans isomerism. Hence selective detection of fatty acids by their molecular shape is of interest but is a challenging goal. Disclosed here is a polymerized liposome that selectively senses bent fatty acids over linear fatty acids, with a turn-on type fluorescence change as well as a distinct color change from blue to red. The use of two different liposome components that contain monoamine and triamine moieties is found to be critical for the color change. Furthermore, the color change can be correlated with a distinct stoichiometry between the molar ratio of the total liposome components and an analyte cis-fatty acid, oleic acid, in a ratio of 1 : 2. The colorimetric response also shows good linearity up to the equivalent point, which enables the monitoring of the content change of cis-fatty acids in commercial cooking oil upon heating at 200 °C.

Hedgehog (Hh) signaling culminates in the conversion of the latent transcription factor Cubitus interruptus (Ci)/Gli into its activator form (Ci(A)/Gli(A)), but the underlying mechanism remains poorly understood. Here we demonstrate that Hh stimulates the phosphorylation of Ci by the Ser/Thr kinase Fused (Fu) and that Fu-mediated phosphorylation of Ci promotes its activation. We find that Fu directly phosphorylates Ci on Ser218 and Ser1230, which primes its further phosphorylation by CK1 on adjacent sties. These phosphorylation events alter Ci binding to the pathway inhibitor Suppressor of fused (Sufu) and facilitate the recruitment of Transportin and the transcriptional coactivator CBP. Furthermore, we provide evidence that Sonic hedgehog (Shh) activates Gli2 by stimulating its phosphorylation on conserved sites through the Fu family kinases ULK3 and mFu/STK36 in a manner depending on Gli2 ciliary localization. Hence, Fu family kinase-mediated phosphorylation of Ci/Gli serves as a conserved mechanism that activates the Hh pathway transcription factor.

Tissue engineering aims to repair or replace damaged tissues or organs using biomedical scaffolds cultured with cells. The scaffolds composed of biomaterials should guide the cells to mature into functional tissues or organs. An ideal scaffold to regenerate hard tissues should have mechanical stability as well as biocompatibilities. It has been well known that gelatin can provide outstanding biological activities, but its low mechanical stability can be one of obstacles to be used in hard tissue regeneration. To overcome the issue, we used PVA, which can reinforce the low mechanical stability of the gelatin. The gelatin/PVA scaffolds have been fabricated using a low temperature 3D-printing process. By manipulating various weight fractions of PVA/gelatin, we can obtain the optimal mixture ratio in aspect of the physical and biological properties of the scaffolds. As a result, a weight fraction of 5:5 showed appropriate mechanical strength and enhanced cell activities, such as cell proliferation and differentiation. The gelatin/PVA scaffold showed potential for future application as biomedical scaffold in soft and hard tissue regeneration.

Objectives We evaluated the ability of new sepsis (S3) criteria (compared with previous definitions of sepsis [S1] and burn sepsis criteria) to accurately determine the mortality in severe burns patients with sepsis. Design This was retrospective cohort study. Setting The Burn ICU of Burn Center, Hangang Sacred Heart Hospital, Hallym University, Seoul, Korea. Patients A total of 1,185 adult patients (mean age, 49.1 yr) were admitted between January 2009 and December 2015. Interventions The 1,185 patients enrolled in the present study and were then re-evaluated based on S1, burn sepsis, and S3 criteria, following which 565 patients, 812 patients, and 809 patients were diagnosed with sepsis based on S1, burn sepsis, S3 criteria, respectively. Measurements and main results For diagnostic performance, sensitivity, specificity, predictive value, and likelihood ratio were calculated. The area under the curve of the receiver operating characteristic curve was calculated to determine the accuracy of mortality prediction. The optimal cutoff value of Sequential Organ Failure Assessment score was calculated by the decision tree method. Total body surface area burned was 33.4%. Patients were identified with sepsis using S1 (812), S3 (809), and burn sepsis (565) criteria. Overall mortality was 20.3%, highest (82.2%) and lowest (26.5%) occurred with new septic shock (SH3) and S3, respectively. The sensitivity and specificity for burn sepsis (84.6% and 61.8%) and SH3 (63.1% and 96.5%) were reported. Area under the curve values for Sequential Organ Failure Assessment scores were the highest in all sepsis categories. With Sequential Organ Failure Assessment score greater than or equal to 6 (with infection), the accuracy was 0.86 (95% CI, 0.82-0.89). Conclusions The S3 criteria failed to show superior prognostic accuracy for mortality in severely burned patients. Sequential Organ Failure Assessment score greater than or equal to 6 may be a better criterion for the diagnosis of sepsis in burns patients.

Background Diagnosing acute kidney injury quickly is imperative since it is known as an independent risk factor for mortality in burn patients. We evaluated the diagnostic power of creatinine, cystatin, serum and urine neutrophil gelatinase-associated lipocalin at different time periods and observed the changes from baseline for each biomarker. Methods This was a prospective observation study from January 2015 to February 2016. A total of 84 patients were enrolled consecutively. Serum creatinine, serum cystatin C, and serum and urine neutrophil gelatinase-associated lipocalin were measured at admission, 7th, 14th, 21st, and 28th days after admission. All samples were collected until acute kidney injury developed. Results Acute kidney injury developed in 35 patients. The mean age was 49.6 years with a male predominance. The median urine neutrophil gelatinase-associated lipocalin was the lowest (11.6 ng/dL) at admission, and the highest at 85.5 ng/dL on day 7. Mean creatinine level was the highest (0.88 mg/dL) at admission and the median creatinine level was the lowest (0.56 mg/dL) on the 14th day. The area under the curve of creatinine levels was the highest with 0.857 during the 1st week. The area under the curve of urine neutrophil gelatinase-associated lipocalin was the highest with 0.803 during the 5th week. Conclusions Within 1 week of acute kidney injury, creatinine level was the optimal biomarker for diagnosis while urine neutrophil gelatinase-associated lipocalin showed better diagnostic performance following the 4- week period.

Hedgehog (Hh) transduces signals by promoting cell surface accumulation and activation of the G-protein-coupled receptor (GPCR)-family protein Smoothened (Smo) in Drosophila, but the molecular mechanism underlying the regulation of Smo trafficking remains poorly understood. Here, we identified the Cul4–DDB1 E3 ubiquitin ligase complex as being essential for Smo ubiquitylation and cell surface clearance. We found that the C-terminal intracellular domain of Smo recruits Cul4–DDB1 through the β subunit of trimeric G protein (Gβ), and that Cul4–DDB1–Gβ promotes the ubiquitylation of both Smo and its binding partner G-protein-coupled-receptor kinase 2 (Gprk2) and induces the internalization and degradation of Smo. Hh dissociates Cul4–DDB1 from Smo by recruiting the catalytic subunit of protein kinase A (PKA) to phosphorylate DDB1, which disrupts its interaction with Gβ. Inactivation of the Cul4–DDB1 complex resulted in elevated Smo cell surface expression, whereas an excessive amount of Cul4–DDB1 blocked Smo accumulation and attenuated Hh pathway activation. Taken together, our study identifies an E3 ubiquitin ligase complex targeting Smo for ubiquitylation and provides new insight into how Hh signaling regulates Smo trafficking and cell surface expression.

This prospective observational study was performed to analyze the clinical outcomes of patients with massive burns treated using cultured epithelial autografts (CEAs) and to determine the association of this treatment with survival outcomes. During 2006-2013, total 177 massive-burns subjects treated with (96 subjects) or without (81 subjects) CEAs. Data were analyzed using the independent t test or chi-square test. Multivariate logistic regression, Kaplan-Meier survival, and Cox regression analyses were performed to evaluate the factors that influenced mortality. Age, percentage of total body surface area burned, incidence of inhalation injury, allograft-application rate, Abbreviated Burn Severity Index score, length of hospital stay, and mortality significantly differed between the CEA and noncultured epithelial autograft groups. Mortality and other clinical parameters did not differ between the sheet-type and spray-type CEA groups. Allograft application (odds ratio, 4.44; p

PURPOSE: To determine epidemiological trends among burns patients admitted to our burns center during 2003-2012, and the usefulness of the Abbreviated Burns Severity Index (ABSI) for predicting burns-related mortality. METHODS: We retrospectively reviewed the data of 4481 burns patients. We analyzed the epidemiological trends and ABSI scores using Student t-test and one-way analysis of variance (continuous variables), chi-square test (categorical variables) and stepwise logistic-regression analysis (predictors of mortality). RESULTS: The mean age and male-to-female ratio were 39.9±19.7 years and 2.88, respectively. ABSI scores decreased from 7.7±3.0 in 2003 to 6.9±3.0 in 2012. Mortality rate improved from 24.5% in 2003 to 15.8% in 2012. Burns were caused by flames (67.3%), scalding (22.0%) and electrical (7.5%), chemical (1.6%) and contact (1.5%) injuries. Scalding and flames were the most common causes in patients aged ≤20 years and ≥21 years, respectively. Female sex, inhalation injury, full-thickness burns, large total body surface area (TBSA) burned and old age predicted mortality. ABSI scores 14 were associated with 0.7% and >90% mortality, respectively. CONCLUSIONS: The mortality of major burns has decreased but remains high. ABSI scores predict burns-related mortality. Language: en

This study was to re-evaluate inhalation injury as a prognostic factor in burn patients and to determine the factors that should be considered when refining the definition of inhalation injury. A total of 192 burn patients (152 men, 40 women; mean age, 46.1±13.8 years) who were suspected to have an inhalation injury and underwent bronchoscopy between January 2010 and June 2012 were included in this prospective observational study. All patients underwent bronchoscopy within 24h of sustaining the burn. The bronchoscopic findings were classified as normal, mild, moderate, and severe. Mechanical ventilation was administered, when required. Age, percentage of TBSA burned, ABSI score, requirement of mechanical ventilation and PF ratio, but not inhalation injury, COHb level, and bronchoscopic grades, significantly differed between the survivors and non-survivors (p

Purpose To estimate long-term outcomes after treatment modification in patients with chronic hepatitis B (CHB) treated with entecavir (ETV) and telbivudine (LdT). Materials and methods The study enrolled 131 nucleos(t)ide analogue (NA)-naive CHB patients treated with ETV or LdT. During the 3-year study, NA treatment history including the incidence, the type of treatment modification, reasons for the modification, and overall complete virologic response (CVR) rate were retrospectively evaluated using the patients' medical records. Results Among the 131 patients, 84 and 47 were initially treated with ETV and LdT, respectively. During the course of 3-year study, 82 patients in the ETV group (97.6%) maintained initial treatment whereas only 19 in the LdT group (40.4%). In the LdT group, 26 patients (92.9%) switched to another NA and another NA was added in 2 (7.1%) patients. An assessment of the CVR rate at 3 years, including treatment modification, showed that 89.3% and 95.7% of patients in the ETV and LdT groups, respectively, had undetectable serum hepatitis B virus DNA levels (p=0.329). Among LdT patients with treatment modification, the cumulative incidence rate of a CVR for rescue therapy was significantly higher in the tenofovir than in the ETV group (p=0.009). Conclusion During the 3-year study, there were no significant differences in the CVR between the ETV and LdT groups if appropriate rescue therapy was considered.

Pruritus, a common, chronically disabling condition is often refractory to treatment. The pruritus sensation is mediated in the spinal cord and post-burn pruritus is considered a form of neuropathic pain. We investigated cold pack therapy as a treatment modality for post-burn pruritus.We studied 23 patients with severe pruritus scoring at least 5 on the visual analogue scale (VAS) and refractory to antihistamine and gabapentin administration. Each cold pack therapy lasted more than 20min. Patients participated in more than three sessions daily for 4 consecutive weeks. The numerical rating scale (NRS), 5-D Itch Scale, Leuven Itch Scale, and perfusion units were evaluated before, within 30min after, 2, and 4 weeks cold pack therapy.In all patients, the NRS was 9.37±1.47 pre-therapy, 3.48±2.19 at 2 weeks, and 2.78±2.13 at 4 weeks following therapy, the pre-scores being significantly different (p0.001). Pruritus severity and consequences scores (Leuven Itch Scale) were improved after therapy compared to pre-therapy. Perfusion unit (PU) scores were statistically insignificant compared to PU scores measured before the application of cold pack therapy. Degree, direction, and disability scores (5-D Itch scale) significantly differed (p.05).Cold pack therapy, a non-invasive, non-pharmacological treatment modality significantly reduces post-burn pruritus and could be useful in burn patients.

There is no consensus whether patients who underwent endoscopic common bile duct (CBD) stone removal should be followed up periodically and whether patients with gallbladder (GB) stones should undergo cholecystectomy. Thus, this study aimed to investigate the recurrence rate of CBD stones and the difference in recurrence rate according to cholecystectomy. We conducted a population-based study using the National Health Insurance database. Patients diagnosed with CBD stones and with procedure registry of endoscopic stone removal were included. The primary outcome was the recurrence rate of CBD stones. The secondary outcome was the difference in recurrence rate of CBD stones according to cholecystectomy. A total of 46,181 patients were identified. The mean follow-up was 4.2 years. The first CBD stone recurrence occurred in 5228 (11.3%) patients. The cumulative first recurrence rate was low. However, the second and third recurrence rates were 23.4 and 33.4%, respectively. The cumulative second and third recurrence rates were high and gradually increased with time. The recurrence rate in the non-cholecystectomy group was higher than that in the cholecystectomy group (p

Inhalation injury is known to be an important factor in predicting mortality in burns patients. However, the diagnosis is complicated by the heterogeneous presentation and inability to determine the severity of inhalation injury. The purpose of this study was to identify clinical features of inhalation injury that affect mortality and the values that could predict the outcome more precisely in burns patients with inhalation injury. This retrospective observational study included 676 burns patients who were over 18 years of age and hospitalized in the Burns Intensive Care Unit between January 2012 and December 2015. We analyzed variables that are already known to be prognostic factors (age, percentage of total body surface area (%TBSA) burned, and inhalation injury) and factors associated with inhalation injury (carboxyhemoglobin and PaO2/FiO2 [PF] ratio) by univariate and multivariate logistic regression. Age group (odds ratio [OR] 1.069, p

Purpose The purpose of this study was to develop a new prediction model to reflect the risk of mortality and severity of disease and to evaluate the ability of the developed model to predict mortality among adult burn patients. Methods This study included 2009 patients aged more than 18 years who were admitted to the intensive care unit (ICU) within 24 hours after a burn. We divided the patients into two groups; those admitted from January 2007 to December 2013 were included in the derivation group and those admitted from January 2014 to September 2017 were included in the validation group. Shrinkage methods with 10-folds cross-validation were performed to identify variables and limit overfitting of the model. The discrimination was analyzed using the area under the curve (AUC) of the receiver operating characteristic curve. The Brier score, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were also calculated. The calibration was analyzed using the Hosmer-Lemeshow goodness-of-fit test (HL test). The clinical usefulness was evaluated using a decision-curve analysis. Results The Hangang model showed good calibration with the HL test (χ2 = 8.785, p = 0.361); the highest AUC and the lowest Brier score were 0.943 and 0.068, respectively. The NRI and IDI were 0.124 (p-value = 0.003) and 0.079 (p-value

The purpose of this study is to clarify the clinical significance of serum transthyretin (TTR) in massively burned patients in nutrition support and clinical severity.A retrospective study was performed with 204 patients admitted to Hangang Sacred Heart Hospital's Burn Center September 2010-September 2012 with burn wounds20% of total body surface area (TBSA) burned. Serum TTR, C-reactive protein (CRP), lactic acid, and an NST index (calculated by dividing real caloric intake by estimated caloric need for 7 days) were analyzed on a weekly basis for 5 weeks after admission.When we classified patients with severity according to mortality, percentage of TBSA burned, serum lactic acid, and CRP, mean serum TTR level was significantly higher in the less severe patient group than in the severe patient group in each week for every severity index. And the serum TTR level did not show significant differences by NST index in both the severe patient group and the less severe patient group. In a multivariate logistic regression, percentage TBSA burned, TTR, and lactic acid had an independent association with mortality.Serum TTR did not show a significant difference by nutrition support in massively burned patients with20% of TBSA burned. But serum TTR was significantly different by the severity of the patient and independently associated with mortality. Hence, serum TTR level can be 1 of the useful biomarkers for comprehending the severity of the illness in massively burned patients.

PURPOSE This study examined 2-year outcome of consecutive therapy using entecavir (ETV) followed by telbivudine (LdT) in subjects with undetectable hepatitis B virus (HBV) DNA level and normal alanine aminotransferase level after the initial 6 months of ETV treatment. MATERIALS AND METHODS Sixty subjects were randomized to continue with ETV or switch to LdT. Significant difference in baseline characteristics was not found between the two groups. Persistent HBV DNA level of 20-60 IU/mL in three consecutive samples collected three months apart or singly measured HBV DNA level of >60 IU/mL was defined as virological rebound. RESULTS During 96 weeks of follow-up, all subjects of the ETV-only group (n=30) resulted in undetectable HBV DNA level. On the other hand, 83.3% (n=25) of the LdT-switched group showed treatment success. Virological rebound time varied from week 24 to 84 after switching to LdT. HBV DNA level was 180 to 2940 IU/mL at rebound time. All subjects with virological rebound (n=5) showed drug-resistant mutation: three had mutation rtM204I, and two had mutation rtM204V. Consecutive treatment using ETV followed by LdT showed virological rebound in 16.7% of subjects during 96 weeks of follow-up. HBV DNA negativity during initial ETV therapy could not be achieved in patients who switched to LdT. CONCLUSION Consecutive treatment using ETV followed by lamivudine was ineffective for treating chronic hepatitis B. LdT was found as a more potent antiviral agent than lamivudine. However, this conclusion requires larger-scale, long-term prospective reviews of the treatment effects of ETV-LdT switch therapy.

The Hippo (Hpo) tumor suppressor pathway is an evolutionarily conserved signaling pathway that controls tissue growth and organ size in species ranging from Drosophila to human, and its malfunction has been implicated in many types of human cancer. In this study, we conducted a kinome screen and identified Happyhour (Hppy)/MAP4K3 as a novel player in the Hpo pathway. Our biochemical study showed that Hppy binds and phosphorylates Wts. Our genetic experiments suggest that Hppy acts in parallel and partial redundantly with Misshapen (Msn)/MAP4K4 to regulate Yki nuclear localization and Hpo target gene expression in Drosophila wing imaginal discs. Furthermore, we showed that cytoskeleton stress restricts Yki nuclear localization through Hppy and Msn when Hpo activity is compromised, thus providing an explanation for the Wts-dependent but Hpo-independent regulation of Yki in certain contexts. Our study has unraveled an additional layer of complexity in the Hpo signaling pathway and laid down a foundation for exploring how different upstream regulators feed into the core Hpo pathway.

We address the clinical application of the suspension type cultured epithelial autografts (CEAs), Keraheal™ (MCTT, Seoul, Korea), along with the effects, application method, merits and demerits thereof. From February 2007 to June 2010, 29 burn patients with extensive burns, participated in the suspension type of CEA clinical test. A widely meshed autograft (1:4-6 ratio) was applied to the wound bed and the suspension type CEA was sprayed with a Tissomat cell sprayer, followed by a Tissucol spray, a fibrin sealant. The patients' (men/women=26/3) median (interquartile ranges) age was 42 (30-49) years old, the burned TBSA was 55 (44-60) %, and the full thickness burn area was 40 (30-46.5) %. The area of Keraheal™ applied was 800 (400-1200) cm(2). The take rate was 96 (90.5-99) % and 100 (98.5-100) % at 2 and 4 weeks after treatment with Keraheal™, respectively. The Vancouver burn scar scale was 5 (4-6.5), 4 (3-6), and 3 (2-4) at 8, 12 and 24 weeks after the Keraheal™ application. Widely meshed autograft must be applied in massive burns but it's take rate is greatly reduced. The CEAs enhance the take rate of a wide meshed autograft in massive burns and allow for grafting wide meshed autograft together with acellular dermal matrix in some cases.

This paper describes a method of road tracking by using a vision and laser with extracting road boundary (road lane and curb) for navigation of intelligent transport robot in structured road environments. Road boundary information plays a major role in developing such intelligent robot. For global navigation, we use a global positioning system achieved by means of a global planner and local navigation accomplished with recognizing road lane and curb which is road boundary on the road and estimating the location of lane and curb from the current robot with EKF(Extended Kalman Filter) algorithm in the road assumed that it has prior information. The complete system has been tested on the electronic vehicles which is equipped with cameras, lasers, GPS. Experimental results are presented to demonstrate the effectiveness of the combined laser and vision system by our approach for detecting the curb of road and lane boundary detection.

In this paper, we propose a design method of Reed-Solomon (23, 17) decoder for UWB using direct decoding method. The direct decoding algorithm is more efficient for the case of relatively small error correction capability. The proposed decoder requires only 9 multipliers in obtaining the error-locator polynomial and the error-evaluator polynomial, whereas other decoders need about 20 multipliers. Thus, the attractive feature of this decoder is its remarkable simplicity from the point of view of hardware implementation. Futhermore, the proposed decoder has very simple control circuit and short decoding delay. Therefore this decoder can be implemented by simple hardware and also save buffer memory which stores received sequence.

This study investigates the effects of frequency of exposure to banner ads and ad clutter in web pages upon online users’ psychological responses. In a 7 (frequency 1 through 7) × 2 (clutter vs. non-clutter) between-participants factorial experiment, participants (N = 250) were randomly assigned to one of fourteen news websites, each with 20 separate pages of news stories and animated banner ads downloaded from various websites. Results indicated that frequency of exposure is a powerful psychological cue affecting users’ memory, attitudes, and behavior. However, contrary to expectation, banner clutter does not lead to negative effects on recall, attitudes, and behavior. Negative impact of banner clutter was significant only on ad recognition.

Summary The establishment of Drosophila embryonic dorsal-ventral (DV) polarity relies on serine proteolytic activity in the perivitelline space between the embryonic membrane and the eggshell [1]. Gastrulation Defective cleaves and activates Snake, which processes and activates Easter, which cleaves Spatzle to form the activating ligand for the Toll receptor. Ventral restriction of ligand formation depends on the Pipe sulfotransferase, which is expressed in ventral cells of the follicular epithelium surrounding the developing oocyte [2]. Pipe modifies components of the developing eggshell to produce a ventral cue embedded in the vitelline membrane [3]. This ventral cue is believed to promote one or more of the proteolysis steps in the perivitelline space. By examining the processing of transgenic, tagged versions of the perivitelline proteins during DV patterning, we find that the proteolysis of Easter by Snake is the first Pipe-dependent step and therefore the key ventrally restricted event in the protease cascade. We also find that Snake and Easter associate together in a complex in both wild-type and pipe mutant-derived embryos. This observation suggests a mechanism in which the sulfated target of Pipe promotes a productive interaction between Snake and Easter, perhaps by facilitating conformational changes in a complex containing the two proteins.

In efforts to prevent and reduce joint contracture and scar formation after burn, we used the acellular human dermis (AlloDerm) as a dermal replacement in the acute stage. A total of 64 patients received AlloDerm graft selectively on joint areas during the study period from March, 2005 to July, 2007. From January to March, 2008, a total of 31 patients returned to our burn center to examine the functional results by measuring range of motion of joints. Additionally, the quality of grafted skin condition criteria of skin elasticity, scar thickness, trans-epidermal water loss, melanin and erythema level was measured in a total of 11 patients among them. By analyzing the limitation level of 55 joints excluding hand areas, we found that 24 joints (43.6%) showed no limitations, 12 joints (21.8%) showed limitations below 10%, 16 joints (29.1%) showed limitations between 10 and 19% and 3 joints (5.5%) showed limitations over 20%. The scar thickness of non-AlloDerm applied areas was 2.5+/-0.9 mm and AlloDerm applied areas was 1.8+/-0.7 mm (p = 0.396). Trans-epidermal water loss for non-AlloDerm applied areas was 20.9+/-7.7 g/h/m(2) and AlloDerm applied areas was 10.8+/-3.4 g/h/m(2) (p

Continuous renal replacement therapy (CRRT) is administered to critically ill patients with renal injuries as renal replacement or renal support. We aimed to identify predictors of mortality among burn patients receiving CRRT, and to investigate clinical differences according to acute kidney injury (AKI) status. This retrospective observational study evaluated 216 Korean burn patients who received CRRT at a burn intensive care unit. Patients were categorized by AKI status. Data were collected regarding arterial pH, laboratory results, ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio), and urine production. Among surviving patients, CRRT duration and the sequential organ failure assessment score were 6.5 days and 4.7 in the non-AKI group and 23.4 days and 7.4 in the AKI group, respectively (p = 0.003 and p = 0.008). On logistic regression analyses, mortality was significantly associated with a pH of 5.0 mEg/L (p = 0.045), creatinine levels of >2.0 mg/dL (p = 0.011), lactate levels of >2 mmol/L (p2 mmol/L, and a platelet count of 2 mg/dL. In the non-AKI group, poor outcomes were associated with lactate levels of >1.5 mmol/L, a PF ratio of 1.2 mg/dL. Duration of the CRRT application and the requirement for either renal replacement or renal support at the initiation of CRRT application are important considerations depending on its application.

This paper reports on measurement method for the fiber optic strain monitoring of overhead contact line systems of trains, We used FBG (Fiber Bragg Grating) sensors to measure the strain variation of overhead contact line. FBG sensors can sensitively measure the variation of strain and! or temperature by the shift wavelength of reflected wave according to the lattice variation during the measurement. FBG sensor were attached on the contact line and connected to the monitoring system with optical fibers. The monitering system with FBG sensors showed very good sensitivity to measuring strain variation and this system could be applied to the overhead contact line of KTX (Korea Train eXpress).

Drosophila embryonic dorsal-ventral polarity is defined by a maternally encoded signal transduction pathway. Gastrulation Defective, Snake, and Easter comprise a serine protease cascade that operates in the perivitelline space to generate active ligand for the Toll receptor, which resides in the embryonic membrane. Toll is activated only on the ventral side of the embryo. Spatial regulation of this pathway is initiated by the ventrally restricted expression of the sulfotransferase Pipe in the follicular epithelium that surrounds the developing oocyte. Pipe is thought to modify a target molecule that is secreted and localized within the ventral region of the egg and future embryo, where it influences the activity of the pathway such that active Toll ligand is produced only ventrally. A potential substrate for Pipe is encoded by nudel, which is expressed throughout the follicle cell layer and encodes a large, multi-functional secreted protein that contains a serine protease domain as well as other structural features characteristic of extracellular matrix proteins. A previous mosaic analysis suggested that the protease domain of Nudel is not a target for Pipe activity as its expression is not required in pipe-expressing cells, but failed to rule out such a role for other functional domains of the protein. To investigate this possibility, we carried out a mosaic analysis of additional nudel alleles, including some that affect the entire protein. Our analysis demonstrated that proteolytically processed segments of Nudel are secreted into the perivitelline space and stably localized, as would be expected for the target of Pipe, However, we found no requirement for nudel to be expressed in ventral, pipe-expressing follicle cells, thereby eliminating Nudel as an essential substrate of Pipe sulfotransferase activity.

본 연구에서는 장기간 보관 중인 장비의 신뢰도를 유지하기 위한 2단계 주기적 검사모형을 제안하였다. 제안된 모형은 불완전한 간이검사와 완전한 정밀검사를 단계적으로 사용하여 고장이 발견되거나 검사 후 저장신뢰도가 미리 정해진 값 이하로 떨어질 때 장비에 대한 오버홀을 수행한다. 제안된 모형을 사용하여 오버홀까지의 단위시간당 기대비용을 유도하고 이를 최소화하기 위한 절차를 구하였으며, 고장시간이 지수분포 및 와이블분포를 따를 경우 제안된 모형을 1단계 주기적 검사모형과 비용함수의 다양한 모수값에 대하여 비교하였다. 또한 실제 운용 중인 유도탄 시스템에 제안된 검사정책을 적용하여 현재 사용 중인 검사정책과의 비교를 수행하였다. 【In this thesis we propose a two-stage periodic inspection model for maintaining the reliability of a system in long-term storage. There are two types of tests available; a fallible test and an error-free test. The system is overhauled at detection of failure or when the storage reliability after inspection becomes less than or equal to the prespecified value. The expected cost per unit time until overhaul is derived and a procedure for minimizing the expected cost is suggested. The two-stage periodic inspection model is compared with the one-stage periodic inspection model for various parameters of the cost function when the failure time follows exponential and Weibull distributions. The proposed model is then applied to an existing missile system for comparison with the current inspection policy.】

Undoped GaN epilayers were grown on sapphire (0 0 0 1) substrates using different H 2 /N 2 carrier gas ratios (0%, 50%, 70%, 80%, and 100% N 2 content in the mixtures) in metal organic vapor phase epitaxy (MOVPE). Growth was observed in situ by reflectometry. Additionally experiments were carried out in which growth was stopped in the high-temperature growth step for the same carrier gas mixtures. The morphology development was correlated with the structural and electrical characteristics of the layers.

AlN growth was performed on c -plane sapphire substrates by metalorganic vapor phase epitaxy (MOVPE) using trimethylaluminium (TMAl) and ammonia. The influence of the carrier gases H 2 and N 2 and their mixtures on the surface morphology and structural characteristics was investigated as well as the influence of the growth temperature of the total source partial pressure and of the TMAl substrate pretreatment. It was found that smoother layers and better structural characteristics are obtained for lower source partial pressures. Decreasing of growth temperature led to improvement of surface morphology, and increasing of nitrogen in gas phase led to improvement structural quality of the layer. A pretreatment of the substrate leads to rougher layers.

This paper reports on new approaches for growth control of GaN-based heterostructures for high frequency and high power application. First in situ methods are presented and their further development discussed [1]. The development leads to a greatly improved observation of growth parameter influences in the MOVPE of GaN. A new growth process is introduced which enhances growth reproducibility [2]. This new growth process is then optimized with respect to the envisaged application. To this end process modeling will be employed. The application envisaged is the AlxGa1-xN/GaN high electron mobility transistor (HEMT). At last device results will be presented. All in all it will be shown how fundamental research can drive technology and how basic knowledge can be employed for process development with respect to device applications.

The efficacy of adefovir add-on therapy in treatmentexperienced patients with chronic hepatitis B (CHB) is debatable. This study aimed to evaluate the efficacy of adefovir add-on therapy in CHB patients with antiviral resistance to lamivudine/entecavir sequential therapy. CHB patients who exhibited documented resistance to lamivudine and switched to entecavir 1.0 mg monotherapy were evaluated and 19 of them showed active viral replication (HBV DNA levels ≥ 10⁵ copies/mL) or a history of treatment failure to lamivudine/ entecavir sequential therapy. Adefovir 10 mg/day has been added to these 19 patients and the virologic parameters were monitored every three months for 96 weeks. A primary responder was defined as patient who had a decline in serum HBV DNA ≥ 1 log10 copies/mL after 12 weeks of therapy, compared with the pretreatment value. In 19 CHB patients, 10(52.6%) patients were HBeAg positive, 7 (36.8%) had cirrhosis. The mean duration of previous entecavir therapy was 84.4 ± 22.5 weeks. The mean HBV DNA levels and ALT at baseline were 6.17 ± 0.96 log10 copies/mL, 53 ± 35 IU/L. The reduction of serum HBV DNA levels from baseline was 2.27 ± 1.34, 2.77 ± 1.41, and 3.09 ± 1.37 log10 copies/mL, at 24, 48 and 96 weeks, respectively. The rate of undetectable serum HBV DNA was 10.5% (2/19), 26.3% (5/19), and 31.5% (6/19) and ALT levels were normalized in 5 (55.6%), 6(66.7%), and 6(66.7%) of 9 patients with elevated ALT at baseline. Initial HBV DNA level was the only independent factor that was inversely associated with serum HBV DNA negativity at 96 weeks. Among 7 primary non-responders, 6 patients achieved serum HBV-DNA level < 4 log10 copies/mL at 96 weeks. Until 96 weeks, viral breakthrough was not detected in 19 patients. The adefovir add-on therapy may be helpful, even if not sufficient enough, for CHB patients with antiviral resistance to lamivudine/entecavir sequential therapy.

We investigated the structural properties of GaN epilayers grown on strained sapphire (0001) substrate by metal-organic chemical vapor deposition (MOCVD). To minimize the mismatch in lattice constants and thermal expansion coefficients between the sapphire substrate and the GaN epilayer, we imposed the strain onto the sapphire (0001) substrate using high-energy O + , Cl + , and As + ion implantation. The strained sapphire surfaces result in the different behaviors of defect generation in the GaN epilayer. Not only the ionic species but also the thickness of the low-temperature GaN buffer layer on sapphire affected the structural quality of the GaN epilayer. The present results show that O + ion-implanted substrate can provide an improved GaN epilayer using only a thin (∼5 nm) buffer layer rather than using a thicker one.

Constitutive activation of the telomerase is a key step in the development of human cancers. Interferon-gamma (IFN-gamma) signaling induces growth arrest in many tumors through multiple regulatory mechanisms. In this study, we show that IFN-gamma signaling represses telomerase activity and human telomerase reverse transcriptase (hTERT) transcription, and suggest that this signaling is mediated by IRF-1. Ectopic expression of IRF-1 attenuated hTERT promoter activity. Murine embryonic fibroblasts (MEFs) genetically deficient in IRF-1 (IRF-1(-/-)) showed an elevated level (15 times) of hTERT promoter activity as compared to the hTERT promoter activity of wild-type MEFs. The telomerase activity and hTERT expression in IRF-1(-/-) MEFs were downregulated by IRF-1 transfection. Interestingly, less extent of telomerase repression was observed in HPV E6 and E7 negative, p53 mutant HT-3 cells than in HPV 18 E6 and E7 positive HeLa cells (intact p53). These findings provide evidence that IRF-1 is a potential mediator of IFN-gamma-induced attenuation of telomerase activity and hTERT expression.

In an effort to improve the initial nucleation and crystal quality of the GaN epilayer, N-ion implantation on the sapphire (0001) substrate has been attempted. As a result of implantation with 55 keV nitrogen ions (N+), to a dose ranging from 1×1015 to 1×1017 cm-2, prior to GaN epilayer growth, the formation of a thin and disordered AlN phase was observed. The presence of the N-ion-implanted surface decreased internal free energies in the growth of the GaN epilayer, and the misfit strain was relieved to allow the formation of the AlN phase on the N-ion-implanted sapphire substrate. Through the estimation of the lattice strain value for GaN epilayers, it was confirmed that the reduction of strain was achieved with the N-ion-implanted surface with the ion dose of 1×1016 cm-2. The present results show that N-ion implantation of the sapphire (0001) surface can improve the properties of GaN epilayers grown by metalorganic chemical vapor deposition (MOCVD).

GaN growth was carried out on Al/sub 2/O/sub 3/(0001) which was ion beam pre-treated to reduce the stain and dislocation density in the film. The ion dose was fixed to 1/spl times/10/sup 16/ ions/cm/sup 2/ and the ion energy used was 800eV and 5.5keV. The 800eV ion beam was reactive N/sub 2//sup +/ ions and the 5.5keV ion beam was from a normal ion implanter. Both ion beam pretreatments resulted in the formation of a disordered amorphous phase on the substrate surface. The GaN buffer and main growth was carried out by MOCVD,the strain was monitored using Raman spectra and dislocations were observed by TEM. The Raman shift clearly showed that the strain in the film was decreased by ion beam pre-treatment of sapphire prior to GaN deposition. The defect density in the film was reduced by up to 55% with ion beam pretreatment.

Objective. The coxsackievirus and adenovirus receptor (CAR) is known to be a primary receptor for attachment during adenovirus infection of target cells and thus is closely related to adenoviral infection efficiency. To extend this notion to human ovarian cancer, we investigated the difference in expression levels of CAR in human ovarian cancer cell lines and whether their adenoviral sensitivities are enhanced by transient transfection of the CAR gene. Methods. Adenoviral infection efficiency was examined by flow cytometry analysis, β-galactosidase staining, and β-galactosidase activity assay. Expression of the CAR-specific mRNA and protein was analyzed by reverse transcription polymerase chain reaction and flow cytometry, respectively. Results. Expression of CAR in human ovarian cancer cell lines (SKOV3, 2774, PA-1, and OVCAR3) appeared to be correlated with their susceptibilities to adenovirus-mediated gene delivery. The 2774 and PA-1 cells expressing an easily detectable level of CAR on the cell surface showed a higher susceptibility to infection with both AdCMVGFP and AdRSVβgal than SKOV3 and OVCAR3 cells, both of which had hardly detectable levels of CAR. Ectopic expression of the CAR gene by transient transfection of these ovarian cancer cells resulted in a dramatic increase in their adenoviral sensitivities. Conclusion. These data show that the expression of CAR is closely related to susceptibility to adenovirus infection in human ovarian cancer cells. These results indicate that the CAR gene can be a useful tool in boosting the efficiency of adenoviral vector-mediated gene therapy against human ovarian cancer.

We have investigated the effects of N + -implanted sapphire (0 0 0 1) substrate on a GaN epilayer grown by metal–organic chemical vapor deposition (MOCVD). As a result of implantation with 55 keV nitrogen ions (N + ) to a dose ranging from 1×10 15 to 1×10 17 cm −2 prior to GaN epilayer growth, the N + -implanted sapphire surface was chemo-physically modified and a thin disordered AlN phase was observed. The N + -implanted substrate’s surface had decreased internal free energies during the growth of the GaN epilayer, and the misfit strain was relieved through the formation of an AlN phase on the N + -implanted sapphire (0 0 0 1) substrate. Crystallographical and optical properties of GaN epilayer grown on N + -implanted sapphire (0 0 0 1) substrate with the ion dose of 1×10 16 cm −2 were found to be improved, indicating decreased internal stress and generation of dislocations in the GaN epilayer. The present results show that N + -implantation pre-treatment of the sapphire (0 0 0 1) substrate surface can be used to improve the properties of GaN epilayers grown by MOCVD.