Nonparametric approach for uncertainty-based multidisciplinary design optimization considering limited data

Uncertainty-based multidisciplinary design optimization (UMDO) has been widely acknowledged as an advanced methodology to address competing objectives and reliable constraints of complex systems by coupling relationship of disciplines involved in the system. UMDO process consists of three parts. Two parts are to define the system with uncertainty and to formulate the design optimization problem. The third part is to quantitatively analyze the uncertainty of the system output considering the uncertainty propagation in the multidiscipline analysis. One of the major issues in the UMDO research is that the uncertainty propagation makes uncertainty analysis difficult in the complex system. The conventional methods are based on the parametric approach could possibly cause the error when the parametric approach has ill-estimated distribution because data is often insufficient or limited. Therefore, it is required to develop a nonparametric approach to directly use data. In this work, the nonparametric approach for uncertainty-based multidisciplinary design optimization considering limited data is proposed. To handle limited data, three processes are also adopted. To verify the performance of the proposed method, mathematical and engineering examples are illustrated.     

Corrugated Heterojunction Metal‐Oxide Thin‐Film Transistors with High Electron Mobility via Vertical Interface Manipulation

A new strategy is reported to achieve high‐mobility, low‐off‐current, and operationally stable solution‐processable metal‐oxide thin‐film transistors (TFTs) using a corrugated heterojunction channel structure. The corrugated heterojunction channel, having alternating thin‐indium‐tin‐zinc‐oxide (ITZO)/indium‐gallium‐zinc‐oxide (IGZO) and thick‐ITZO/IGZO film regions, enables the accumulated electron concentration to be tuned in the TFT off‐ and on‐states via charge modulation at the vertical regions of the heterojunction. The ITZO/IGZO TFTs with optimized corrugated structure exhibit a maximum field‐effect mobility >50 cm² V^?1 s^?1 with an on/off current ratio of >10⁸ and good operational stability (threshold voltage shift <1 V for a positive‐gate‐bias stress of 10 ks, without passivation). To exploit the underlying conduction mechanism of the corrugated heterojunction TFTs, a physical model is implemented by using a variety of chemical, structural, and electrical characterization tools and Technology Computer‐Aided Design simulations. The physical model reveals that efficient charge manipulation is possible via the corrugated structure, by inducing an extremely high carrier concentration at the nanoscale vertical channel regions, enabling low off‐currents and high on‐currents depending on the applied gate bias.     

The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure

Recently, we reported that ciprofloxacin, an antimicrobial agent with gamma-aminobutyric acid (GABA(A)) receptor antagonist properties, significantly increases hepatic regenerative activity in animal models of alcohol-induced liver disease and cirrhosis. In the present study, we documented the effects of ciprofloxacin on survival and hepatic regeneration in a D-galactosamine (D-gal)-induced model of acute hepatic injury in rats. One hundred nineteen adult, male Sprague-Dawley rats (n = 19-20/group) were treated with intraperitoneal D-gal (total dose: 2.5 g/kg), followed by gastric gavage with either saline, ciprofloxacin (10, 50, or 100 mg/kg), norfloxacin (250 mg/kg), or intraperitoneal putrescine (300 micromol/kg), a potent hepatic growth promoter. Mortality rates were then documented over a 4-day period. An additional 45 rats (n = 15/group) received a sublethal dose of D-gal (1.0 g/kg), followed by gastric gavage with either saline or ciprofloxacin (100 mg/kg), or intraperitoneal putrescine (300 micromol/kg). In these rats, hepatic regenerative activity was documented at 12, 24, and 60 hours post-D-gal by 3H-thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) staining. In the survival study, a dose-response effect of ciprofloxacin on survival was observed (ciprofloxacin: 10 mg/kg, 10%; 50 mg/kg, 26%; and 100 mg/kg, 35%) with the results in the 100-mg/kg-treated group being significant when compared with the 5% survival rate in saline-treated controls (P < .05). Survival figures in the norfloxacin- and putrescine-treated groups were not significantly improved (15% and 25%, respectively). In the regeneration study, compared with the D-gal + saline-treated control group, DNA synthesis rates at 60 hours were increased in the D-gal + ciprofloxacin and D-gal + putrescine groups (10.2 +/- 3.3 vs. 18.2 +/- 5.1 and 18.8 +/- 6.8 x 10(3) dpm/mg DNA respectively; P < .05). The results of PCNA staining also supported enhanced hepatic regeneration in the ciprofloxacin-treated group at 60 hours (saline, 13.4 +/- 3.7; ciprofloxacin, 47.4 +/- 7.3; and putrescine, 8.4% +/- 2.8% hepatocytes staining positive). Ciprofloxacin at a dose of 100 mg/kg significantly improves survival and hepatic regenerative activity in this animal model of acute hepatic injury.     

Effects of hepatic stimulator substance, herbal medicine, selenium/vitamin E, and ciprofloxacin on cirrhosis in the rat

BACKGROUND & AIMS: Cirrhosis is a potentially lethal condition for which there is no proven effective therapy. The aim of this study was to compare the effects of hepatic stimulator substance, traditional Chinese herbal medicine, selenium plus vitamin E, and ciprofloxacin treatment on biochemical and histological features of fibrosis in rats with carbon tetrachloride (CCl4)/ethanol-induced cirrhosis. METHODS: One hundred twenty adult Wistar rats were divided into six study groups (20 rats/group): healthy controls, CCl4/ethanol-injured rats left untreated, and CCl4/ethanol-injured rats treated for 4 weeks with either hepatic stimulator substance, traditional Chinese herbal medicine, a combination of selenium plus vitamin E, or ciprofloxacin. After the 4-week treatment, rats were killed and the following parameters of hepatic fibrosis were determined: hepatic hydroxyproline and proline levels, serum hyaluronic acid concentrations, and histological staining of hepatic tissue. RESULTS: Hepatic fibrosis was significantly improved in all four treated groups compared with the untreated CCl4/ethanol-injured controls. Improvements were most striking in the groups treated with traditional Chinese herbal medicine and ciprofloxacin. CONCLUSIONS: The data indicate that hepatic stimulator substance, traditional Chinese herbal medicine, selenium plus vitamin E, and ciprofloxacin significantly decrease the amount of hepatic fibrosis caused by CCl4/ethanol injury in rats.     

Reliability-based design optimization of a pick-up device of a manganese nodule pilot mining robot using the Coandă effect

Design of a pick-up device using the Coandă effect in a deep-sea mining robot is vital to develop a reliable and sustainable deep-sea mining system. One of the crucial performance metrics of this device is the collection efficiency since it affects the mining efficiency of the entire system. However, the collection efficiency is significantly affected by the uncertainties of shape, size and mass of manganese nodules on the seabed. In this study, reliability-based design optimization (RBDO) was performed to improve the reliability of the collection efficiency of the pick-up device under these environmental uncertainties. First, a computational model based on the Coandă effect that predicts the collection efficiency of the pick-up device was developed. Next, RBDO based on the Akaike information criterion method was employed to design the pick-up device by using this model. The results demonstrated that the proposed design methodology significantly improved the design of the pick-up device for the pilot mining robot.

     

Hamartoma of the breast, an underrecognized breast lesion. A clinicopathologic and radiographic study of 25 cases

This study investigated the clinical, radiographic, and pathologic features of breast hamartoma. The patients ranged in age from 18 to 89 years, with a mean age of 45 years, and a median age of 43 years. Seventy-five percent of the patients were asymptomatic, other than reporting a breast lump. In two patients, the lesions recurred at 7 and 18 months after the initial resection. The clinical diagnoses were fibroadenoma in 10 cases, carcinoma in 5 cases, hamartoma in 4 cases, and phyllodes tumor and lipoma in 2 other cases. Mammograms were available in 12 cases, the majority of which showed a well-defined mass of homogeneous density. Grossly, these lesions were oval to round, well-circumscribed masses, ranging in size from 1 to 7 cm in maximum dimension (mean, 3.9 cm). The microscopic appearance of these tumors corresponded to their gross appearance. Lesions that were grossly firm, rubbery, and white consisted largely of dense fibroconnective tissue with variable amounts of glandular elements with little adipose tissue. Softer, pale, yellow lesions contained more adipose tissue. A consistent and important diagnostic feature was the presence of both lobules and ducts, in contrast to fibroadenoma in which lobules are often absent or rare. The current trend of mammographic breast screening has made us aware that mammary hamartomas are not uncommon. These lesions may go unrecognized by the pathologists because they show all the constituents of normal breast tissue and may be reported as "no pathological diagnosis" or "normal breast tissue," which are inappropriate diagnoses for a lesion that presents as a palpable and a well-circumscribed mass.     

Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT)

BACKGROUND: Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV). METHODS: 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens: 3 mega units (MU) interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 24 weeks; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV-RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment. FINDINGS: Sustained virological response at 24 weeks after treatment, was found in 119 (43%) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=O.055), and 53 (19%) of the 278 patients treated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years or less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95% Cl 1.4-4.8; p=0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Discontinuation of therapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given for 24 weeks (8%). INTERPRETATION: An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile. Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks.     

A comparative trial of recombinant interferon alpha 2A versus alpha 2 beta on myelosuppression in healthy adult volunteers

BACKGROUND/AIMS: Recombinant interferon (r-IFN) is an antiviral agent used to treat patients with chronic viral hepatitis patients. Unfortunately, the use is often limited due to its myelosuppressive properties. Currently, there are two forms of r-IFN commercially available: r-IFN alpha-2a and rIFN alpha-2b. Although both are thought to be equally effective, a comparative study of their myelosuppressive properties has not been undertaken. MATERIALS AND METHODS: In the present study, three groups of healthy adult volunteers (n = 6/group) were randomized to receive a two week course of either r-IFN alpha-2a or r-IFN alpha-2b (5 million units, subcutaneously, thrice weekly) or no treatment. All subjects were then followed for an additional two week post treatment; observation period. RESULTS: The results of the study revealed that both forms of r-IFN alpha caused a significant and similar decrease in white blood cell counts (maximum declines of 37.9 +/- 6.8% for alpha-2a and 39.5 +/- 6.0% for alpha-2b at day 4) and platelet counts (maximum declines of 19.5 +/- 8.6% for alpha-2a and 20.2 +/- 8.4% for alpha-2b at day 2) from baseline values. Following discontinuation of therapy, white blood cell and platelet counts returned to pretreatment levels. Hemoglobin levels remained unchanged throughout the study period. CONCLUSION: The results of this study indicate that r-IFN alpha causes a prompt and significant decrease in white blood cell and platelet counts. However, no differences exist between r-IFN alpha-2a and r-IFN alpha-2b in terms of their myelosuppressive properties in humans.