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An 8.5-Gb/s/pin (Gb/s) 12-Gb LPDDR5 SDRAM is implemented in a second-generation 10-nm DRAM process with a hybrid-bank architecture that provides a power-optimized bank solution depending on the bank modes (4B/4BG, 16B-merged bank, 8B-split bank). Based on the specified bank modes, vertical and horizontal skew-cancel schemes for high density and an RBUS-based DBI ac to minimize data transition are newly proposed. Thus, the switching power of RBUS DBI ac is saved by 8.9% compared to that of DBI ac “OFF.” To improve the rank interleaving efficiency with a current increase, partially enabled WCK (PE-WCK) mode is proposed, which minimizes the number of enabled circuits for maintaining the WCK2CK synchronization. Therefore, the current can be saved by 62% without a timing constraint compared to the WCK always-ON mode. To achieve high-speed operation beyond 6.4 Gb/s, speed-boosting techniques, namely, the two-step duty corrector, active resonant load (ARL), and one-tap decision feedback equalizer (DFE) with offset calibration, are newly adopted. In the coarse step in the two-step duty corrector, the value of the duty error decreases to below 5% by suppressing the dc signal. In the fine step, the remaining duty error is further reduced within 2.5 ps by the duty cycle monitor (DCM) and duty cycle adjustor (DCA). Moreover, the skew increase beyond 6.4 Gb/s due to the bandwidth limit by the heavy loading of four-phase WCK signals is alleviated by the ARL, where the four-phase skew is within 5 ps irrespective of process, voltage, and temperature (PVT) variations. The direct feedback DFE enables fast feedback (< 118 ps) for tap coefficient control, and offset calibration reduces the three-sigma offset of the four dynamic latches in DQ within 5 mV.

Energy efficiency in mobile devices is a pivotal criteria from the overall system point of view, Although the 7,5Gb/s 8Gb LPDDR5 [1], with low-power schemes (internal data copy, dynamic-voltage-frequency scaling (DVFS), and a deep-sleep mode (DSM)), achieves improved energy efficiency compared to the previous LPDDR4X [2], the market demands for higher density and speed gradually increase for high-end applications including hand-held artificial intelligence (AI) and advanced driver assistance system (ADAS), To achieve higher density and speed in a power-efficient manner, this paper proposes a 8,5Gb/s 12Gb LPDDR5 with a hybrid bank architecture (split/merged bank), a skew-tolerant scheme, bus-based ROBI AC, and speed-boosting techniques based on 2nd generation 10nm DRAM process, Adopting a hybrid bank architecture and skew-tolerant scheme enables high speed and power-optimization for each bank-mode in high density memories, Moreover, bus-based RDBI AC achieves 2,1 % current gain and command-based WCK control scheme achieves 36mA saving at WCK-always-on mode, The speed-boosting techniques (duty-cycle correction (DCC), an active-resonant load, and at-tap DFE receiver) provide improved operating speeds from 7,5Gb/s to 8,5Gb/s@VDD2H = 1, 05V, where the read/write DQ valid windows are 0,60UI and 0.64UI (1UI = 118ps).

Zr-Ti alloy powders were successfully synthesized by magnesium thermal reduction of metal chlorides. The evaporated and mixed gasses of were injected to liquid magnesium and the chloride components were reduced by magnesium leading to the formation of . The released Zr and Ti atoms were then condensed to particle forms inside the mixture of liquid magnesium and magnesium chloride, which could be dissolved fully in post process by 1~5% HCl solution at room temperature. By the fraction-control of individually injected and gasses, the final compositions of produced alloy powders were changed in the ranges of Zr-0 wt.%~20 wt.%Ti and their purity and particle size were about 99.4% and the level of several micrometers, respectively.

Melanin synthesis is regulated by melanocyte specific enzymes and related transcription factors. β-carboline alkaloids including harmaline and harmalol are widely distributed in the environment including several plant families and alcoholic beverages. Presently, melanin content and tyrosinase activity were increased in melanoma cells by harmaline and harmalol in concentration- and time-dependent manners. Increased protein levels of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 were also evident. In addition, immunofluorescence and Western blot analyses revealed harmaline and harmalol increased cAMP response element binding protein phosphorylation and microphthalmia-associated transcription factor expression. In addition to studying the signaling that leads to melanogenesis, roles of the p38 MAPK pathways by the harmaline and harmalol were investigated. Harmaline and harmalol induced time-dependent phosphorylation of p38 MAPK. Harmaline and harmalol stimulated melanin synthesis and tyrosinase activity, as well as expression of tyrosinase and TRP-1 and TRP-2 indicating that these harmaline and harmalol induce melanogenesis through p38 MAPK signaling.

Minimal hepatitis encephalopathy (MHE) is a liver cirrhosis complication that does not show symptoms of overt hepatitis encephalopathy (OHE) but can be detected using specific complementary neuropsychological and neurophysiological evaluations. Patients with MHE show abnormalities in cognitive functions, which can increase the risk of automobile accidents. The aim of this study was to compare the cognitive functioning of patients with MHE to patients with other liver disease and to compare their driving abilities, using a driving simulator and the Stim(2) software. Thirty-eight participants, who were not diagnosed with OHE but were diagnosed with chronic hepatitis and liver cirrhosis, took part in the study. The results indicate that patients with MHE show reduced level of cognitive functioning, which may affect their ability to drive safely. We cautiously predict that any future guidelines based on this knowledge may help reduce the incidence of traffic accidents caused by drivers with decreased with driving abilities.

The aim of this study was to isolate chicken feather-degrading bacteria with high keratinolytic activity and to investigate cultural conditions affecting keratinolytic enzyme production by a selected isolate. A chicken feather-degrading bacterial strain CH3 was isolated from poultry wastes. Isolate CH3 degraded whole chicken feather completely within 3 days. On the basis of phenotypical and 16S rDNA studies, isolate CH3 was identified as Bacillus thuringiensis CH3. This strain is the first B. thuringiensis described as a feather degrader. The bacterium grew with an optimum at pH 8.0 and 37℃, where maximum keratinolytic activity was also observed. The composition of optimal medium for keratinolytic enzyme production was feather 0.1%, sucrose 0.7%, casein 0.3%, K2HPO4 0.03%, KH2PO4 0.04%, MgCl2 0.01% and NaCl 0.05%, respectively. The keratinolytic enzyme had a pH and temperature optima 9.0 and 45℃, respectively. The keratinolytic activity was inhibited ethylenediaminetetraacetic acid, phenylmethylsulfonyl fluoride, and metal ions like Hg2+, Cu2+ and Zn2+. The enzyme activated by Fe2+, dithiothreitol and 2-mercaptoethanol.

The flesh and skin of Anguilla japonica and Conger myriaster were investigated for their antioxidant activity. Ethyl acetate and diethyl ether extracts (4 mg/mL) after extracting with methanol were tested for 2,2-diphenyl-1-picrylhidrazyl (DPPH) free radical scavenging (FRS) activity for flesh and skin of each eel species. The values were compared with α-tocopherol and butylated hydroxytoluene (BHT). Extracts showing positive results, when tested for DPPH FRS, were examined for dose effect, hydrogen peroxide (H2O2), hydroxyl radical and superoxide scavenging assays and heat stability. All extracts of A. japonica showed a dose-dependent DPPH FRS and significant hydroxyl radical scavenging activities (>65%). The diethyl ether extract of the flesh of A. japonica showed the highest superoxide scavenging activity. Diethyl ether extracts of A. japonica were heat stable, and ethyl acetate extracts were stable up to 75C. Thus, it can be concluded that A. japonica is rich with heat stable and nonpolar antioxidants.

Transforming growth factor-betas (TGF-betas) have significant effects on testis development. The pattern of TGF-beta expression in aging testis has not been established to date. We examined age-related changes in the expression of TGF-beta and its receptors in the testis using Western blot analysis. TGF-beta1 expression increased continuously in aging rat testis, whereas no age-associated changes were observed for TGF-beta3. Strong expression of TGF-beta2, as well as type I and II receptors was observed in 12-month-old testis, but following this time, expression decreased dramatically. Interestingly, TGF-beta2 and -beta3 displayed strong and similar expression patterns in liver, regardless of age, suggesting that the down-regulation of TGF-beta2 is testis-specific. We observed significant induction of p53 and p21WAF1 in 18-month-old testis that appeared to correspond with aging. Moreover, caloric restriction (CR) prevented age-related decrease in TGF-beta2 expression. Using immunohistochemistry, we showed that all TGF-beta1, -beta2, and -beta3 proteins are expressed primarily in interstitial cells, which are located in the space between adjoining seminiferous tubules. Our data collectively indicate that aging in the testis is regulated by differential expression of TGF-beta proteins, and decreased levels of TGF-beta2 contribute to the aging process.

Background: Interindividual genetic differences in susceptibility to chemical carcinogens are among the most important host factors in human cancer. The present study was undertaken to reveal the association between the polymorphism of CYP2E1 (CYP2E1/PstI and CYP2E1/DraI) with genetic susceptibility to gastric cancer development in Koreans. Methods: In the present study, 120 gastric cancer patients and 145 controls with no history of tumors were analyzed. CYP2E1 was determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP), or PCR and direct gel electrophoresis. Results: The overall genotype distribution of CYP2E1 was not significantly different from that of controls. However, the genotype distribution of the patient subgroups with a history of heavy cigarette smoking (>30 pack/year) in the CYP2E1/PstI and CYP2E1/DraI polymorphisms were significantly different from those of non-smoking patients (P = 0.0122 and P = 0.0029, respectively). The difference was also noticeable in the younger patient subgroup (aged ≤50 years) compared with normal controls (P = 0.0414) in the CYP2E1/PstI. The relative risk estimation for the combination of the CYP2E1/PstI and CYP2E1/DraI polymorphisms revealed that the odds ratio for individuals with homozygotes of rare alleles (c2/c2, C/C) was 5.6 (95% confidence interval = 0.9–39.1). Conclusions: : These results suggest the possible involvement of the CYP2E1 polymorphism in smoking-induced gastric cancer development in Koreans as one of the risk factors which increases genetic susceptibility.

Various reports on the prevalence of gastroesophageal reflux disease (GERD) and uninvestigated dyspepsia have been conducted in Western countries. We sought to determine the frequency of GERD symptoms and uninvestigated dyspepsia in Korea. Telephone interviews were conducted with 1,044 individuals. Of all subjects, 7.1% reported that GERD symptoms were present at least once a week, and 3.8% at least twice a week. The prevalence of heartburn according to educational level and acid regurgitation according to age was significantly different (P < 0.05). The prevalence of uninvestigated dyspepsia was reported as 12.2%. Dyspepsia was divided into subgroups of 34% ulcer-like, 56% dysmotility-like, and 10% nonspecific. The occurrence of dyspepsia did not vary according to age, gender, educational level and household income. As frequency of GERD symptoms increased, quality of life significantly decreased. We concluded that GERD symptoms and uninvestigated dyspepsia were prevalent in Korea. The prevalence was similar to that of other Asian countries.

Molecular changes associated with cellular senescence in human diploid fibroblasts (HDF), IMR-90, were analyzed by two-dimensional differential proteome analysis. A high percentage of replicative senescent cells were positive for senescence-associated beta-galactosidase activity, and displayed elevated levels of p21 and p53 proteins. Comparison of early population doubling level (PDL) versus replicative senescent cells among the 1000 spots resolved on gels revealed that the signal intensities of six spots were increased fivefold, whereas those of four spots were decreased. Proteome analysis data demonstrated that connective tissue growth factor (CTGF) is an age-associated protein. Up-regulation of CTGF expression in senescent cells was further confirmed by Western blotting and RT-PCR. We postulate that CTGF expression is controlled, in part, by transforming growth factor-beta (TGF-beta), in view of the high levels of TGF-beta isoforms as well as type I and II receptors detected only in late PDL of HDF cells. To verify this hypothesis, we stimulated early PDL cells with TGF-beta1 as well as stress inducing agents such as hydrogen peroxide. As expected, CTGF expression and Smad protein phosphorylation were dramatically increased up to observed levels in normal replicative senescent cells. In vivo experiments disclosed that CTGF, pSmad, and p53 were constitutively expressed at basal levels in up to 18-month-old rat liver, and expression was significantly up-regulated in 24-month-old rat tissue. However, expression patterns were not altered at all periods examined in livers of caloric-restricted rats. In view of both in vitro and in vivo data, we propose that the TGF-beta/Smad pathway functions in the induction of CTGF, a novel biomarker protein of cellular senescence in human fibroblasts.

The diagnosis of refractory ascites means a poor prognosis for patients with liver cirrhosis. The definition of refractory ascites has already been established, but using the dosage of diuretics that correlates with the definition of refractory ascites in an out-patient department will lower the compliance of the patient, as well as causing serious complications, such as hepatic encephalopathy and hyponatremia, as the dosage of diuretics is increased. Due to this fact, it is very difficult to apply this definition of refractory ascites to patients in a domestic out-patient department. In this study, in situations where there are difficulties in applying the diuretics dosage according to definition of refractory ascites, we tried to find out whether measuring the value of urine sodium after the administration of intravenous furosemide can be the standard in early differentiation of the response to diuretics treatment.We reviewed 16 cases of liver cirrhosis with ascites and classified them into two groups by the response to diuretics. The diuretics-responsive ascites group was 8 cases and the diuretics-unresponsive ascites group consisted of 8 cases. After admission, we examined the patients' CBC, biochemical liver function test, spot urine sodium, and 24 hour creatinine clearance. After the beginning of the experiment, all diuretic therapy was stopped for 3 days. Daily we examined the patients' CBC, biochemical liver function test, and in the 3rd experiment day, we measured 24-hour urine volume and sodium. In the 4th experiment day, after sampling for ADH, plasma renin activity and plasma aldosterone level, we administrated the furosemide 80 mg I.V, and measured the amount of 8 hour urine volume and sodium.The plasma aldosterone level was significantly higher in the diuretics- unresponsive ascites group than in the diuretics-responsive ascites group. In the 4th experiment day, the amount of urine volume and sodium was very significantly lower in the diuretics-unresponsive ascites group than in the diuretics-responsive ascites group (1297.5 +/-80.9 vs 2003.7 +/-114.6 ml, p0.005, 77.3 +/-8.2 vs 211.8 +/-12.6 mEq, p0.001).In out-patient departments, the measurement of urine sodium 8 hours after administrating 80 mg of intravenous furosemide, will help in differentiating ascites patients with lower treatment response to diuretics.

It is important to evaluate the general status of the liver including the structural and inflammatory aspects, as well as the functional aspects, in order to determine a patient's treatment modality and prognosis.55 Child-Pugh class A liver cirrhosis patients confirmed by liver biopsy have been categorized into 4 groups based on the shunt index and p-value(Y= 3.3431-0.8160 ALT/AST ratio-0.0343 X prothrombin time+2.6963 X shunt index, p = e(y)/(e(y)+1)), which was obtained by Thallium- 201 scan; group I - shunt index less than 0.3 and p-value less than 0.7; group II - shunt index less than 0.3 and p-value more than 0.7; group III - shunt index more than 0.3 and p-value less than 0.7; and group IV - shunt index more than 0.3 and p-value more than 0.7. Statistical analyses used were ANOVA, paired t-test, and Chi-square test.1. The laboratory data after a 5-year follow-up also showed a significant difference between four groups. 2. In group IV, the Child-Pugh class after 5 years worsened, and complications of liver cirrhosis such as esophageal varix, ascites, and hepatic encephalopathy occurred more frequently. 3. In group II, the laboratory data after a 5-year follow-up indicated some improvement.It can be seen that even early in patients with initially the same cirrhosis, the course of the illness can progress to a variety of different situations. The measurement of shunt index and the p-value of cirrhosis will be more helpful in the follow-up evaluation and predicting its prognostic index in liver cirrhosis patients.

This study was designed to determine the relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced cirrhotic rats.Cirrhotic rats(n=6) were induced by intramuscular injection of CCl4 in olive oil(two time per weeks) for 12 weeks. Controls (n=6) were injected intramuscularly with the same dose of olive oil for 12 weeks. We evaluated the amount of portosystemic shunt by thallium-201 per rectal scintigraphy. After intravenous bolus injection of propranolol (2mg/kg) to rats, the serum propranolol concentrations were analyzed by a HPLC-fluorimetric detector system. Pharmacokinetic parameters such as C0, AUC, t1/2(beta), and CLp were determined in each group. Then, a small amount of heptic tissue was obtained and subjected to determination of the hepatic collagen content by quantitating 4-hydroxyproline and were inspected by microscope after hematoxylin and eosin stain.In liver biopsy, liver fibrosis progressed in CCl4-induced cirrhotic rats. The serum concentrations of propranolol were significantly (p0.01) elevated in CCl4-induced cirrhotic rats. Mean amount of 4-hydroxyproline, mean H/L ratio, and mean AUC in CCl4-induced cirrhotic rats was significantly (p0.01) higher than that in control rats. There was a relationship between AUC, H/L ratio, and amount of 4-hydroxyproline.H/L ratio may help in the selection of drug dosage (especially blood flow dependent drug) in pre-clinical studies for chronic liver disease during the drug development process.

Background & Aims: Various reports on the prevalence of gastroesophageal reflux disease (GERD) and functional dyspepsia have been conducted according to countries, survey methods and diagnosis criteria. However, detailed population-based data in Korea are lacking. The aim of this study was to determine the prevalence of upper gastrointestinal (GI) symptoms such as GERD and dyspeptic symptoms in Korea, as well as the impact of these symptoms on quality of life. Methods: The telephone survey, conducted by Galhip Korea, targeted a stratified probability random sample of the Republic of Korea. A reliable and valid questionnaire was asked about upper GI symptoms according to ROME II criteria, soeiodemographic association, physician visit and quality of life. In measuring quality of life, the Korean version o[ the EQ-SD, which underwent cross-cultural adaptation and validation, was used. Results: A total of 3,600 people were selected, and among them, 1,044 people responded to all questions. The response rate was 29%. 3.5% of the responders experienced heartburn more than twice a week, 3.4% once a week, 5.8% once a month, and 12.3% once in two momhs. And 2.6% of the responders experienced acid regurgitation more than twice a week, 1.9% once a week, 5.5% once a month, and 14.3% once in two months. A statistically significant difference was found in the quality of life according to the frequency of heartburn and acid regurgitation (p

Pernicious anemia is an autoimmune disease characterized by a gastric mucosal defect which results in an insufficiency of intrinsic factor to facilitate the absorption of the physiologic amount of cobalamin. Increased risk of cancers of the stomach has been reported for patients with pernicious anemia. We report here a case of a 65 year old woman who had been diagnosed as having pernicious anemia 16 months previously, was receiving monthly vitamin B12 injections, and developed early gastric cancer type IIa by routine follow-up gastroscopic examination. This patient underwent endoscopic mucosal resection for an early gastric cancer lesion with a free resection margin.