Search

In the present study, a piecewise-integrated composite bumper beam for passenger cars is proposed, and the design innovation process for a composite bumper beam regarding a bumper test protocol suggested by the Insurance Institute for Highway Safety is carried out with the help of machine learning models. Several elements in the bumper FE model have been assigned to be references in order to collect training data, which allow the machine learning model to study the method of predicting loading types for each finite element. Two-dimensional and three-dimensional implementations are provided by machine learning models, which determine the stacking sequences of each finite element in the piecewise-integrated composite bumper beam. It was found that the piecewise-integrated composite bumper beam, which is designed by a machine learning model, is more effective for reducing the possibility of structural failure as well as increasing bending strength compared to the conventional composite bumper beam. Moreover, the three-dimensional implementation produces better results compared with results from the two-dimensional implementation since it is preferable to choose loading-type information, which is achieved from surroundings when the target elements are located either at corners or junctions of planes, instead of using information that comes from the identical plane of target elements.

Flaviviral infections including dengue virus are an increasing clinical problem worldwide. Dengue infection triggers host production of the type 1 IFN, IFN alpha, one of the strongest and broadest acting antivirals known. However, dengue virus subverts host IFN signaling at early steps of IFN signal transduction. This subversion allows unbridled viral replication which subsequently triggers ongoing production of IFN which, again, is subverted. Identification of downstream IFN antiviral effectors will provide targets which could be activated to restore broad acting antiviral activity, stopping the signal to produce endogenous IFN at toxic levels. To this end, we performed a targeted functional genomic screen for IFN antiviral effector genes (IEGs), identifying 56 IEGs required for antiviral effects of IFN against fully infectious dengue virus. Dengue IEGs were enriched for genes encoding nuclear receptor interacting proteins, including HELZ2, MAP2K4, SLC27A2, HSP90AA1, and HSP90AB1. We focused on HELZ2 (Helicase With Zinc Finger 2), an IFN stimulated gene and IEG which encodes a promiscuous nuclear factor coactivator that exists in two isoforms. The two unique HELZ2 isoforms are both IFN responsive, contain ISRE elements, and gene products increase in the nucleus upon IFN stimulation. Chromatin immunoprecipitation-sequencing revealed that the HELZ2 complex interacts with triglyceride-regulator LMF1. Mass spectrometry revealed that HELZ2 knockdown cells are depleted of triglyceride subsets. We thus sought to determine whether HELZ2 interacts with a nuclear receptor known to regulate immune response and lipid metabolism, AHR, and identified HELZ2:AHR interactions via co-immunoprecipitation, found that AHR is a dengue IEG, and that an AHR ligand, FICZ, exhibits anti-dengue activity. Primary bone marrow derived macrophages from HELZ2 knockout mice, compared to wild type controls, exhibit enhanced dengue infectivity. Overall, these findings reveal that IFN antiviral response is mediated by HELZ2 transcriptional upregulation, enrichment of HELZ2 protein levels in the nucleus, and activation of a transcriptional program that appears to modulate intracellular lipid state. IEGs identified in this study may serve as both (1) potential targets for host directed antiviral design, downstream of the common flaviviral subversion point, as well as (2) possible biomarkers, whose variation, natural, or iatrogenic, could affect host response to viral infections.

Silicon is known as one of the widely used materials in electronic fields for its excellent semiconductive characteristics. However, these characteristics are vulnerable to internal defects, which randomly exist in any materials. In the present study, defects in single crystalline silicon thin film were investigated by atomistic simulation of nano-indentation at zero temperature. The Tersoff potential and the spherical indenter were applied to the model of silicon. The symmetric axis parameter method is novelly proposed to identify defects in the diamond cubic structure. Under the nanoindentation condition, the ring slip appears close to the indentation region on the free surface and propagates along with [110]/(111). The dislocation is initiated closely to the ring slip and emitted on the (111) plane by the dissociation into two partial dislocations. It was found that the symmetric axis parameter method successfully separated the perfect dislocations, the partial dislocations and the stacking fault from perfect structure, i.e., diamond cubic structure, even though it was not able to distinguish between glide set and shuffle set dislocations.

The dislocation evolution in substrate/film systems with Ag and Cu was investigated by the molecular dynamics simulation of nanoindentation. Film thickness in the range from 2 to 5 nm with the crystalline direction (001), which is the same as that of the substrate, was modelled in the present study. It was observed that the slip of the misfit dislocations in the interface is determined by indentation force and lattice constants of the substrate and the film. It was also shown that the crystal direction and the initial indentation position relative to misfit dislocation have a major role in the form of dislocation structures. The hardness of the bulk Cu is observed to be higher than that of the bulk Ag, as expected, however, it was also observed that soft film coating on the hard substrate cannot increase the hardness of the overall substrate/film system. On the contrary, the hard film, which is thicker than 4 nm, coating on the soft substrate increases the hardness of the overall substrate/film system.

Endomyocardial biopsy (EMB) is one of the reliable methods for the diagnosis of various cardiac diseases. However, EMB can cause various complications. The purpose of this study is to evaluate the complication of transfemoral EMB with both fluoroscopic and two-dimensional (2-D) echocardiographic guidance. A total of 228 patients (148 men; 46.0±14.6 yr-old) who underwent EMB at Kyungpook National University Hospital from January 2002 to June 2012 were included. EMB was performed via the right femoral approach with the guidance of both echocardiography and fluoroscopy. Overall, EMB-related complications occurred in 21 patients (9.2%) including one case (0.4%) with cardiac tamponade requiring emergent pericardiocentesis, four cases (1.8%) with small pericardial effusion without pericardiocentesis, two cases (0.9%) with hemodynamically unstable ventricular tachycardia (VT), one case (0.4%) with nonsustained VT, one case (0.4%) with tricuspid regurgitation, twelve cases (5.3%) with right bundle branch block. There was no occurrence of either EMB-related death or cardiac surgery. Left ventricular ejection fraction was significantly lower (32.0±18.7% vs 42.0±19.1%, P=0.023) and left ventricular end-diastolic dimension was larger (60.0±10.0 mm vs 54.2±10.2 mm, P=0.013) in patients with EMB related complications than in those without. It is concluded that transfemoral EMB with fluoroscopic and 2-D echocardiographic guidance is a safe procedure with low complication rate.

Background and Objectives: Rapid diagnosis of ST-segment elevation myocardial infarction (STEMI) is essential for the appropriate management of patients. We investigated the prevalence, etiologies and predictors of false-positive diagnosis of STEMI and subsequent inappropriate catheterization laboratory activation in patients with presumptive diagnosis of STEMI., Subjects and Methods: Four hundred fifty-five consecutive patients (62±13 years, 345 males) with presumptive diagnosis of STEMI between August 2008 and November 2010 were included., Results: A false-positive diagnosis of STEMI was made in 34 patients (7.5%) with no indication of coronary artery lesion. Common causes for the false-positive diagnosis were coronary spasm in 10 patients, left ventricular hypertrophy in 5 patients, myocarditis in 4 patients, early repolarization in 3 patients, and previous myocardial infarction and stress-induced cardiomyopathy in 2 patients each. In multivariate logistic regression analysis, symptom-to-door time >12 hours {odds ratio (OR) 4.995, 95% confidence interval (CI) 1.384-18.030, p=0.014}, presenting symptom other than chest pain (OR 7.709, 95% CI 1.255-39.922, p=0.027), absence of Q wave (OR 9.082, CI 2.631-31.351, p<0.001) and absence of reciprocal changes on electrocardiography (ECG) (OR 17.987, CI 5.295-61.106, p<0.001) were independent predictors of false-positive diagnosis of STEMI., Conclusion: In patients whom STEMI was planned for primary coronary intervention, the false-positive diagnosis of STEMI was not rare. Correct interpretation of ECGs and consideration of ST-segment elevation in conditions other than STEMI may reduce inappropriate catheterization laboratory activation.

Purpose: The purpose of this study was to investigate the relationship among family support, stress and quality of life according to the phases of illness in breast cancer patients., Methods: A descriptive correlational study was employed with 121 breast cancer patients. The data was collected by using self reported questionnaire. Self reported data was collected by using the Family support scale, Perceived Stress Scale (PSS), and EORTC QLQ-BR23. Phases of illness consisted 1st phase, 2nd phase, 3rd phase., Results: The score of family supporting, stress and quality of life showed a statically differences according to the phase of illness. Family supporting and stress had negative relation in the first, second and third phase. Family supporting and quality of life in function area had positive relation in the first, second phase. There was no relation between family supporting and quality of life in symptom area. Stress, quality of life in symptom area and quality of life in function area had correlation in the first, third phase., Conclusion: This study suggest that the new nursing implementation should be considered according to the phase of illness in order to improve the family supporting and quality of life and reduce the stress in breast cancer patients through this study results.

After cutaneous injury, a variety of cell types are activated to reconstitute the epithelial and dermal components of the skin. beta-Catenin plays disparate roles in keratinocytes and fibroblasts, inhibiting keratinocyte migration and activating fibroblast proliferation, suggesting that beta-catenin could either inhibit or enhance the healing process. How beta-catenin functions in concert with other signaling pathways important in the healing process is unknown. Wound size was examined in mice expressing conditional null or conditional stabilized alleles of beta-catenin, regulated by an adenovirus expressing cre-recombinase. The size of the wounds in the mice correlated with the protein level of beta-catenin. Using mice expressing these conditional alleles, we found that the wound phenotype imparted by Smad3 deficiency and by the injection of TGFbeta before wounding is mediated in part by beta-catenin. TGFbeta was not able to regulate proliferation in beta-catenin null fibroblasts, whereas keratinocyte proliferation rate was independent of beta-catenin. When mice are treated with lithium, beta-catenin-mediated signaling was activated in cutaneous wounds, which healed with a larger size. These results demonstrate a crucial role for beta-catenin in regulating cutaneous wound size. Furthermore, these data implicate mesenchymal cells as playing a critical role regulating wound size.

Beta-catenin is a critical regulator of cell behavior during embryogenesis and neoplastic processes. It also plays a crucial role in repair by modulating dermal fibroblast activity during the proliferative phase of cutaneous wound healing. We hypothesize that growth factors liberated during the initial phase of wound healing convey signals to induce activation of beta-catenin-mediated TCF-dependent signaling during the proliferative phase. Dermal fibroblasts were isolated and cultured from mice containing a beta-galactosidase reporter responsive to beta-catenin-TCF transactivation (TCF-beta-gal). Cells were stimulated with growth factors present at the initial phase of wound healing. EGF and TGF-beta1 significantly increased beta-catenin protein levels and transcriptional activity, whereas beta-catenin mRNA expression was unaffected. This increase was attributed to inactivation of GSK-3beta, a kinase important for beta-catenin destabilization. Subcutaneous injection of EGF or TGF-beta1 before wounding of TCF-beta-gal mice resulted in larger scars and fibroblasts within these wounds that strongly stained for beta-galactosidase, indicating significant beta-catenin transcriptional activity in vivo. Thus, beta-catenin-mediated signaling is activated downstream of growth factors released during the initial phase of wound repair, and may act during the proliferative phase of wound healing to integrate signals from initial phase factors into the expression of genes important during the later, remodeling phase.

A tyrosinase-directed therapeutic approach for malignant melanoma therapy uses the depigmenting phenolic agents such as 4-hydroxyanisole (4-HA) to form cytotoxic o-quinones. However, renal and hepatic toxicity was reported as side effects in a recent 4-HA clinical trial. In search of novel therapeutics, the cytotoxicity of the isomers 4-HA, 3-HA and 2-HA were investigated. In the following, the order of the HAs induced hepatotoxicity in mice, as measured by increased in vivo plasma transaminase activity, or in isolated rat hepatocytes, as measured by trypan blue exclusion, was 3-HA > 2-HA > 4-HA. Hepatocyte GSH depletion preceded HA induced cytotoxicity and a 4-MC-SG conjugate was identified by LC/MS/MS mass spectrometry analysis when 3-HA was incubated with NADPH/microsomes/GSH. 3-HA induced hepatocyte GSH depletion or GSH depletion when 3-HA was incubated with NADPH/microsomes was prevented by CYP 2E1 inhibitors. Dicumarol (an NAD(P)H: quinone oxidoreductase inhibitor) potentiated 3-HA- or 4-methoxycatechol (4-MC) induced toxicity whereas sorbitol (an NADH generating nutrient) greatly prevented cytotoxicity indicating a quinone-mediated cytotoxic mechanism. Ethylendiamine (an o-quinone trap) largely prevented 3-HA and 4-MC-induced cytotoxicity indicating that o-quinone was involved in cytotoxicity. Dithiothreitol (DTT) greatly reduced 3-HA and 4-MC induced toxicity. The ferric chelator deferoxamine slightly decreased 3-HA and 4-MC induced cytotoxicity whereas the antioxidants pyrogallol or TEMPOL greatly prevented the toxicity suggesting that oxidative stress contributed to 3-HA induced cytotoxicity. In summary, ring hydroxylation but not O-demethylation/epoxidation seems to be the bioactivation pathway for 3-HA in rat liver. The cytotoxic mechanism for 3-HA and its metabolite 4-MC likely consists cellular protein alkylation and oxidative stress. These results suggest that 3-HA is not suitable for treatment of melanoma., (Copyright 2002 Elsevier Science B.V.)

A tyrosinase-directed therapeutic approach for treating malignant melanoma uses depigmenting phenolic prodrugs such as 4-hydroxyanisole (4-HA) for oxidation by melanoma tyrosinase to form cytotoxic o-quinones. However, in a recent clinical trial, both renal and hepatic toxicity were reported as side effects of 4-HA therapy. In the following, 4-HA (200 mg/kg i.p.) administered to mice caused a 7-fold increase in plasma transaminase toxicity, an indication of liver toxicity. Furthermore, 4-HA induced-cytotoxicity toward isolated hepatocytes was preceded by glutathione (GSH) depletion, which was prevented by cytochrome p450 inhibitors that also partly prevented cytotoxicity. The 4-HA metabolite formed by NADPH/microsomes and GSH was identified as a hydroquinone mono-glutathione conjugate. GSH-depleted hepatocytes were much more prone to cytotoxicity induced by 4-HA or its reactive metabolite hydroquinone (HQ). Dicumarol (an NAD(P)H/quinone oxidoreductase inhibitor) also potentiated 4-HA- or HQ-induced toxicity whereas sorbitol, an NADH-generating nutrient, prevented the cytotoxicity. Ethylenediamine (an o-quinone trap) did not prevent 4-HA-induced cytotoxicity, which suggests that the cytotoxicity was not caused by o-quinone as a result of 4-HA ring hydroxylation. Deferoxamine and the antioxidant pyrogallol/4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (TEMPOL) did not prevent 4-HA-induced cytotoxicity, therefore excluding oxidative stress as a cytotoxic mechanism for 4-HA. A negligible amount of formaldehyde was formed when 4-HA was incubated with rat microsomal/NADPH. These results suggest that the 4-HA cytotoxic mechanism involves alkylation of cellular proteins by 4-HA epoxide or p-quinone rather than involving oxidative stress.

Fibroproliferative processes are a group of disorders in which there is excessive proliferation of spindle (mesenchymal fibroblast-like) cells. They range from hypertrophic scars to neoplasms such as aggressive fibromatosis. Cells from these disorders share cytologic similarity with fibroblasts present during the proliferative phase of wound healing, suggesting that they represent a prolonged wounding response. A critical role for beta-catenin in mesenchymal cells in fibroproliferative processes is suggested by its high rate of somatic mutation in aggressive fibromatosis. Using a Tcf-reporter mouse we found that beta-catenin protein level and Tcf-transcriptional activity are elevated in fibroblasts during the proliferative phase of healing. We generated a transgenic mouse in which stabilized beta-catenin is expressed in mesenchymal cells under control of a tetracycline-regulated promoter. Fibroblasts from the transgenic mice exhibited increased proliferation, motility, and invasiveness when expressing stabilized beta-catenin and induced tumors after induction of the transgene when grafted into nude mice. Mice developed aggressive fibromatoses and hyperplastic gastrointestinal polyps after 3 months of transgene induction and healed with hyperplastic cutaneous wounds compared with control mice, which demonstrates an important function for beta-catenin in mesenchymal cells and shows a central role for beta-catenin in wound healing and fibroproliferative disorders.