Nanomechanical In Situ Monitoring of Proteolysis of Peptide by Cathepsin B

Characterization and control of proteolysis of peptides by specific cellular protease is a priori requisite for effective drug discovery. Here, we report the nanomechanical, in situ monitoring of proteolysis of peptide chain attributed to protease (Cathepsin B) by using a resonant nanomechanical microcantilever immersed in a liquid. Specifically, the detection is based on measurement of resonant frequency shift arising from proteolysis of peptides (leading to decrease of cantilever's overall mass, and consequently, increases in the resonance). It is shown that resonant microcantilever enables the quantification of proteolysis efficacy with respect to protease concentration. Remarkably, the nanomechanical, in situ monitoring of proteolysis allows us to gain insight into the kinetics of proteolysis of peptides, which is well depicted by Langmuir kinetic model. This implies that nanomechanical biosensor enables the characterization of specific cellular protease such as its kinetics

An optical-frequency synthesizer using integrated photonics

Optical-frequency synthesizers, which generate frequency-stable light from a single microwave-frequency reference, are revolutionizing ultrafast science and metrology, but their size, power requirement and cost need to be reduced if they are to be more widely used. Integrated-photonics microchips can be used in high-coherence applications, such as data transmission, highly optimized physical sensors and harnessing quantum states, to lower cost and increase efficiency and portability. Here we describe a method for synthesizing the absolute frequency of a lightwave signal, using integrated photonics to create a phase-coherent microwave-to-optical link. We use a heterogeneously integrated iii–v/silicon tunable laser, which is guided by nonlinear frequency combs fabricated on separate silicon chips and pumped by off-chip lasers. The laser frequency output of our optical-frequency synthesizer can be programmed by a microwave clock across 4 terahertz near 1,550 nanometres (the telecommunications C-band) with 1 hertz resolution. Our measurements verify that the output of the synthesizer is exceptionally stable across this region (synthesis error of 7.7 × 10^(−15) or below). Any application of an optical-frequency source could benefit from the high-precision optical synthesis presented here. Leveraging high-volume semiconductor processing built around advanced materials could allow such low-cost, low-power and compact integrated-photonics devices to be widely used

Highly effective peginterferon α-2a plus ribavirin combination therapy for chronic hepatitis C in hemophilia in Korea

Background/AimsChronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon α-2a plus ribavirin for CHC in hemophilia.MethodsPatients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests.ResultsEleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naïve patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis.ConclusionsPeginterferon α-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events

Demography of SDSS early-type galaxies from the perspective of radial color gradients

We have investigated the radial g-r color gradients of early-type galaxies in the Sloan Digital Sky Survey (SDSS) DR6 in the redshift range 0.00<z<0.06. The majority of massive early-type galaxies show a negative color gradient (red-cored) as generally expected for early-type galaxies. On the other hand, roughly 30 per cent of the galaxies in this sample show a positive color gradient (blue-cored). These "blue-cored" galaxies often show strong H beta absorption line strengths and/or emission line ratios that are indicative of the presence of young stellar populations. Combining the optical data with Galaxy Evolution Explorer (GALEX) UV photometry, we find that all blue-cored galaxies show UV-optical colors that can only be explained by young stellar populations. This implies that most of the residual star formation in early-type galaxies is centrally concentrated. Blue-cored galaxies are predominantly low velocity dispersion systems. A simple model shows that the observed positive color gradients (blue-cored) are visible only for a billion years after a star formation episode for the typical strength of recent star formation. The observed effective radius decreases and the mean surface brightness increases due to this centrally-concentrated star formation episode. As a result, the majority of blue-cored galaxies may lie on different regions in the Fundamental Plane from red-cored ellipticals. However, the position of the blue-cored galaxies on the Fundamental Plane cannot be solely attributed to recent star formation but require substantially lower velocity dispersion. We conclude that a low-level of residual star formation persists at the centers of most of low-mass early-type galaxies, whereas massive ones are mostly quiescent systems with metallicity-driven red cores.Comment: 15 pages, 19 figures, accepted for publication in ApJ

Clinical Outcomes and Prognostic Factors of Up-Front Autologous Stem Cell Transplantation in Patients with Extranodal Natural Killer/T Cell Lymphoma

AbstractLimited data exist on up-front autologous stem cell transplantation (ASCT) in extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and 19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary therapy were identified. Poor-risk characteristics included advanced stage (50%), high-intermediate to high-risk International Prognostic Index (25.8%), and group 3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant responses included complete remission in 61.3% and partial remission in 38.7% of patients, and final post-transplantation response included complete remission in 78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3-year overall survival (OS) was 60.0%. Patients with limited disease had significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6% versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis showed NKPI and pretransplant response were independent prognostic factors influencing survival, particularly NKPI in limited disease and pretransplant response in advanced disease. Radiotherapy was an independent factor for reduced progression and survival in patients with limited disease, but anthracycline-based chemotherapy was a poor prognostic factor for progression in patients with advanced disease. Up-front ASCT is an active treatment in ENKTL patients responding to primary therapy

A Case of Placenta Increta Presenting as Delayed Postabortal Intraperitoneal Bleeding in the First Trimester

Placenta increta is an uncommon and life-threatening complication of pregnancy characterized by complete or partial absence of the decidua basalis. Placenta increta usually presents with vaginal bleeding during difficult placental removal in the third-trimester. Although placenta increta may complicate first and early second-trimester pregnancy loss, the diagnosis can be very difficult during early pregnancy and thus the lesion is difficult to identify. We encountered with a woman who was diagnosed with placenta increta after receiving emergency hysterectomy due to intraperitoneal bleeding 2 months after an uncomplicated dilatation and curettage in the first trimester. Therefore, we report this case with a brief review of the literature

Effects of corn gluten hydrolyzates, branched chain amino acids, and leucine on body weight reduction in obese rats induced by a high fat diet

In this study, we compared corn gluten hydrolyzates, BCAAs, and leucine for their effects on body weight reduction in high fat-induced obese rats in order to determine the major active components in the corn gluten hydrolyzates. After obesity was induced for 13 weeks with high fat diet, the overweight-induced SD rats (n = 64) were stratified according to body weight, randomly blocked into eight treatments, and raised for 8 weeks. Four groups were changed to a normal diet and the other groups remained on the high fat diet. Each of the groups within both diets was fed either casein, corn gluten hydrolyzates, leucine, or branched chain amino acids, respectively. Daily food intake, body weight gain, and food efficiency ratio were significantly lower in the corn gluten hydrolyzate groups compared to the other groups, regardless of the high fat diet or normal fat diet. The rats fed the corn gluten hydrolyzates diet had the lowest perirenal fat pad weights whereas muscle weight was significantly increased in the corn gluten hydrolyzates groups. Plasma triglyceride, hepatic total lipid, and total cholesterol contents were significantly reduced in the corn gluten hydrolyzates groups. Other lipid profile measurements were not significantly changed. Plasma triglyceride and hepatic total lipid were also significantly reduced in the BCAA and leucine groups. Leptin levels were significantly lower and adiponectin was significantly higher in the corn gluten hydrolyzates groups. Fasting blood glucose, insulin, C-peptide, and HOMA-IR levels were also significantly reduced in the corn gluten hydrozylates groups, regardless of fat level

EC-18, a Synthetic Monoacetyldiacylglyceride, Inhibits Hematogenous Metastasis of KIGB-5 Biliary Cancer Cell in Hamster Model

EC-18 (monoacetyldiacylglyceride) stimulates T cell production of IL-2, IL-4, IL-12, IFN-γ, and GM-CSF in vitro. To study the effects of these cytokines stimulated by EC-18 on cancer cells, we applied hamster biliary cancer model, a difficult cancer to treat. Cancer (KIGB-5) cells were given intravenously to produce hematogenous metastatic lung lesions which were treated with EC-18 at 10, 25, and 50 mg/kg/day respectively. The fourth group was untreated control. At 4th, 8th, and 12th week the lungs were examined. EC-18 treated groups showed only a few microscopic lung lesions and no evidence of metastatic lesion with highest dose whereas widespread gross lung lesions were observed in untreated control. To investigate whether the anti-tumor effect of EC-18 is associated with suppression of tumor cell Toll-like receptor 4 (TLR-4) expression in addition to stimulation of the immune cells, KIGB-5 cells were exposed to LPS with or without EC-18. TLR-4 mRNA and protein expression, measured by reverse transcriptase PCR (RT-PCR), real-time quantitative PCR and western blot analysis, showed suppression of TLR-4 expression in KIGB-5 cells treated with EC-18 compared with control. In conclusion, EC-18 has a significant anti-tumor effect in this experimental model of biliary cancer suggesting potential for clinical application to this difficult cancer

Prevalence of the Major Mental Disorders among the Korean Elderly

With a rapidly aging society, geriatric mental health is emerging as important public health concern. Despite the short history of psychiatric epidemiology in Korea, recently, epidemiologic data regarding geriatric psychiatric problems has started to accumulate. In the current study, we reviewed epidemiological findings regarding geriatric mental health in Korea. It was found that up to 10% of the elderly suffer from dementia, and 10% to 20% from depressive disorder. Further, prevalence estimates of Alzheimer's disease ranged from 4.2% to 9.0%, and vascular dementia from 1.0% to 4.8%. Annual incidence rates for Alzheimer's were 2.7% to 3.4% whereas that for vascular dementia was found to be as low as 0.3%. The prevalence of major depressive disorder was 4.2% to 9.1%, while that of clinically significant depressive symptom was between 9.1% and 33.0%. Finally, those with alcohol use disorders were found to comprise up to 13.6% of elderly population and additionally, 22% to 58% of the elderly were found to have sleep difficulties. Thus major mental disorders are already prevalent among the Korean elderly and are likely to increase rapidly

Prognostic Factors and Clinical Outcomes of High-Dose Chemotherapy followed by Autologous Stem Cell Transplantation in Patients with Peripheral T Cell Lymphoma, Unspecified: Complete Remission at Transplantation and the Prognostic Index of Peripheral T Cell Lymphoma Are the Major Factors Predictive of Outcome

AbstractHigh-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) offers a rescue option for T cell lymphoma patients with poor prognosis. However, the effectiveness of HDT/ASCT in patients with various peripheral T cell subtypes, optimal transplant timing, and the prognostic factors that predict better outcomes, have not been identified. We retrospectively investigated the clinical outcomes and prognostic factors for HDT/ASCT in 64 Korean patients with peripheral T cell lymphoma, unspecified (PTCL-U) between March 1995 and February 2007. The median age at transplantation was 44 years (range: 15-63 years). According to the age-adjusted International Prognostic Index (a-IPI) and the prognostic index of PTCL (PIT), 8 patients (12.5%) were in the high-risk group and 16 (26.6%) had the 2-3 PIT factors, respectively. After a median follow-up of 29.7 months, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 53.0% ± 7.5% and 44.3% ± 7.0%, respectively. Univariate analysis showed that poor performance status, high lactate dehydrogenase (LDH) levels, high a-IPI score, high PIT classes, failure to achieve complete response (CR) at transplantation, and nonfrontline transplantation were associated with poor OS. Multivariate analysis showed that failure to achieve CR at transplantation (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.78-7.93) and 2-3 PIT factors (HR 3.76; 95% CI 1.02-5.42) were independent prognostic factors for OS. Failure to achieve CR at transplantation and high PIT are negative predictable factors for survival following HDT/ASCT in patients with PTCL-U