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This was a single-institutional retrospective cohort study. Wound infections are common following spine metastasis surgery and can result in unplanned reoperations. A recent study published an online wound complication risk calculator but has not yet undergone external validation. Our aim was to evaluate the accuracy of this risk calculator in predicting 30-day wound infections and 30-day wound reoperations using our operative spine metastasis population. An internal operative database was used to identify patients between 2012 and 2022. The primary outcomes were 1) any surgical site infection and 2) wound-related revision surgery within 30 days following surgery. Patient details were manually collected from electronic medical records and entered into the calculator to determine predicted complication risk percentages. Predicted risks were compared to observed outcomes using receiver operator characteristic (ROC) curves with areas under the curve (AUC). A total of 153 patients were included. The observed 30-day postoperative wound infection incidence was 5% while the predicted wound infection incidence was 6%. In ROC analysis, good discrimination was found for the wound infection model (AUC = 0.737; P = 0.024). The observed wound reoperation rate was 5% and the predicted wound reoperation rate was 6%. ROC analysis demonstrated poor discrimination for wound reoperations (AUC = 0.559; P = 0.597). The online wound-related risk calculator was found to accurately predict wound infections but not wound reoperations within our metastatic spine surgery cohort. We suggest that the model may be clinically useful despite underlying population differences, but further work must be done to generate and validate accurate prediction tools. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the analytical precision of finite element analysis models of wind turbine bearings. In the finite element analysis models, balls were modeled as finite element meshes as a solid model or replaced by nonlinear springs as two kinds of spring models. In addition, test bench modeling was performed to calculate the displacement following the application of a turnover moment by means of a global model analysis and to calculate the contact stress by means of a sub-model analysis. The comparison of the results of the finite element analyses with the results of the bearing bench test showed that the analytical precision was 17% in the single-spring model, 9% in the Daidie spring model, and 3% in the finite element mesh ball model, indicating that the finite element mesh ball model exhibited the highest precision. [ABSTRACT FROM AUTHOR]

This article examines the engagement of North Korea in the Eurocurrency market in the 1970s. In the Cold War regime competition for economic prosperity, the communist regime turned to the City of London to raise capital for economic development. Despite the diplomatic efforts of South Korea against its rival, the judges were international banks. The failure to manage its indebtedness resulted in the retreat of the North in the Western financial market. Lost creditworthiness was hard to restore. The divergence in the access to foreign capital resulted in the different paths of economic growth of the two Koreas. [ABSTRACT FROM AUTHOR]

Blade coating of perovskite solar cells (PSCs) and modules has progressed considerably toward the industrial production of perovskite photovoltaics. Developing stable perovskite precursors is critical for achieving uniform coating over large areas. Here, the engineering of a perovskite precursor solution consisting of 2‐methoxyethanol (2‐Me) and 1,3‐dimethyl‐imidazolidinone (DMI) with superior intermediate phase stability that enables scalable production of efficient perovskite solar modules is reported. With this perovskite precursor solution, uniform and pinhole‐less perovskite film is deposited over a large area of > 100 cm2 and higher‐efficiency PSCs and modules are obtained. The best‐performing unit cell and module with n‐i‐p configuration reach power conversion efficiencies of 23.4% and 20.1%, respectively. Additionally, a series of non‐destructive metrology methods, such as spectroscopic ellipsometry, hyperspectral photoluminescence, electroluminescence, and laser beam‐induced current mapping, are employed to assess and guide the development the blade‐coated perovskite modules. This results show that rational engineering of precursor inks for blade coating is promising for the scalable production of efficient perovskite solar modules. [ABSTRACT FROM AUTHOR]

The high mobility group box 1 (HMGB1), a well-known danger-associated molecule pattern (DAMP) molecule, is a non-histone chromosomal protein localized in the nucleus under normal physiological conditions. HMGB1 exhibits diverse functions depending on its subcellular location. In the present study, we investigated the role of HMGB1-induced autophagy in the lipopolysaccharide (LPS)-treated BV2 microglial cell line in mediating the transition between the inflammatory and autophagic function of the nucleotide-binding oligomerization domain-containing 2 (NOD2), a cytoplasmic pattern-recognition receptor. The induction of the microtubule-associated protein 1 light chain 3 (LC3), an autophagy biomarker, was detected slowly in BV2 cells after the LPS treatment, and peak induction was detected at 12 h. Under these conditions, NOD2 level was significantly increased and the binding between HMGB1 and NOD2 and between HMGB1 and ATG16L1 was markedly enhanced and the temporal profiles of the LC3II induction and HMGB1-NOD2 and HMGB1-ATG16L1 complex formation coincided with the cytosolic accumulation of HMGB1. The LPS-mediated autophagy induction was significantly suppressed in BV2 cells after HMGB1 or NOD2 knock-down (KD), indicating that HMGB1 contributes to NOD2-mediated autophagy induction in microglia. Moreover, NOD2-RIP2 interaction-mediated pro-inflammatory cytokine induction and NF-κB activity were significantly enhanced in BV2 cells after HMGB1 KD, indicating that HMGB1 plays a critical role in the modulation of NOD2 function between pro-inflammation and pro-autophagy in microglia. The effects of the cell-autonomous pro-autophagic pathway operated by cytoplasmic HMGB1 may be beneficial, whereas those from the paracrine pro-inflammatory pathway executed by extracellularly secreted HMGB1 can be detrimental. Thus, the overall functional significance of HMGB1-induced autophagy is different, depending on its temporal activity. [ABSTRACT FROM AUTHOR]

Tannic acid (TA) is a polyphenolic compound that exerts protective effects under pathological conditions. The diverse mechanisms of TA can exert beneficial anti-oxidative, anti-inflammatory, and anti-cancer effects. Herein, we reported that TA affords robust neuroprotection in an animal model of stroke (transient middle cerebral artery occlusion; tMCAO) and exhibits Zn2+-chelating and anti-oxidative effects in primary cortical neurons. Following tMCAO induction, intravenous administration of TA (5 mg/kg) suppressed infarct formation by 32.9 ± 16.2% when compared with tMCAO control animals, improving neurological deficits and motor function. We compared the chelation activity under several ionic conditions and observed that TA showed better Zn2+ chelation than Cu2+. Furthermore, TA markedly decreased lactate dehydrogenase release following acute Zn2+ treatment and subsequently reduced the expression of p67 (a cytosolic component of NADPH oxidase), indicating the potential mechanism underlying TA-mediated Zn2+ chelation and anti-oxidative effects in primary cortical neurons. These findings suggest that anti-Zn2+ toxicity and anti-oxidative effects participate in the TA-mediated neuroprotective effects in the postischemic brain. [ABSTRACT FROM AUTHOR]

The ligand exchange process on gold nanorods (Au NRs) was explored by using laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS). Cetyltrimethylammonium bromide (CTAB) adsorbed on Au NRs was replaced with alkanethiol derivatives presenting different functional groups. The ligand exchange process was investigated under various conditions, such as in the presence of different functional groups in the ligands and with different concentrations of CTAB. The ligand-exchanged Au NRs were characterized by using a combination of UV–Vis spectroscopy and LDI-TOF-MS. Based on the results, it was revealed that LDI-TOF-MS analysis can provide crucial and distinct information about the degree of ligand exchange on Au NRs. [ABSTRACT FROM AUTHOR]

Background: Sudomotor dysfunction is common in patients with multiple system atrophy (MSA). Postganglionic sudomotor dysfunction in MSA, which can be assessed using quantitative sudomotor axon reflex testing (QSART), results from the degeneration of preganglionic sympathetic neurons and direct loss of postganglionic fibers. Objective: We investigate whether abnormal QSART responses in patients with MSA are associated with disease severity. Methods: In this retrospective study, patients with probable MSA who underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and autonomic function tests were included. Autonomic function test results were integrated divided into three sub-scores, including sudomotor, cardiovagal, and adrenergic sub-scores. The sudomotor sub-score represented postganglionic sudomotor function. Unified Multiple System Atrophy Rating Scale (UMSARS) Part I, Part II, and sum of Part I and II scores (Part I + II) to reflect disease severity and 18F-FDG-PET/CT results were collected. Results: Of 74 patients with MSA, 62.2%demonstrated abnormal QSART results. The UMSARS Part I + II score was significantly higher in the abnormal QSART group than in the normal QSART group (p = 0.037). In the regression analysis, both UMSARS Part I (β= 1.185, p = 0.013) and Part II (β= 1.266, p = 0.021) scores were significantly associated with the sudomotor sub-score. On 18F-FDG-PET/CT, the abnormal QSART group exhibited more severely decreased metabolic activity in the cerebellum and basal ganglia in patients with MSA-P and MSA-C, respectively. The sudomotor sub-score was significantly associated with regional metabolism in these areas. Conclusion: Patients with MSA and postganglionic sudomotor dysfunction may have worse disease severity and greater neuropathological burden than those without. [ABSTRACT FROM AUTHOR]

Perovskite solar cells in an n‐i‐p structure record high power conversion efficiency, but issues of insufficient thermal stability and the high cost of p‐type hole transporting materials have been raised as drawbacks. H2‐phthalocyanine (Pc) is introduced as a hole transport material to ensure the thermal stability and simultaneously have served surface passivation effects on hybrid halide perovskites as a Lewis base. Pyrrolic nitrogen in the Pc reacts with uncoordinated Pb2+ ions on the perovskite surface. Upon enhancing the interfacial interaction between phthalocyanine and the perovskite, the open circuit voltage in devices increases as compared to that of devices using a metal‐phthalocyanine complex. While the phthalocyanine‐applied device maintains superior thermal long‐term stability, the power conversion efficiency also exceeds 20%. [ABSTRACT FROM AUTHOR]

Abstract In recent years, much research has been conducted on wearable electronic devices based on human-friendly factors, and fibers having stretchability and electrical conductivity are required as a component technology of fiber-based wearable electronics. Here we demonstrate stretchable and electrically conductive polyurethane (PU)-silver/graphene composite fibers prepared by wet-spinning process, in which silver nanoparticles (AgNPs) and graphene nanoplatelets (GNPs) are added as conductive fillers. Although the aspect ratio of AgNPs is relatively small compared to nanowires and nanotubes, high conductivity and stretchability have been observed in PU-AgNPs composites, which depends on the volume fraction of AgNPs in the composites. In addition, the conductivity was improved by curing treatment and addition of a small amount of GNPs, and a high conductivity of 82,874 S m−1 was achieved with a ∼150% strain. Conventional yarn-like conductive threads consisting of six strands of PU-AgNPs/GNPs composite fibers showed a relatively low resistance change up to 30% strain and operated as stretchable conductor up to 100% stretch in a circuit. Thus, it is expected that the PU-AgNPs/GNPs composite fibers can be applicable to human costume, industrial robots, and wearable electronics such as adaptive sensor for body movement measurement or medical monitoring, and biological integration systems for rehabilitation or injury prevention. Graphical abstract Image 1 Highlights • Stretchable conductive polyurethane-silver/graphene composite fibers were prepared by wet-spinning. • High conductivity of 82,874 S m−1 was achieved with a ∼150% strain. • The composite fibers showed negligible resistance change up to 30% strain. • Their conductive threads were operated as stretchable conductor up to 100% stretch in a circuit. [ABSTRACT FROM AUTHOR]

We fabricated a conductive carbon nanosheet (CNS) film converted from brominated polystyrene (PS) and demonstrated that the CNS film can act as transparent electrode (TE) for polymeric photovoltaics (PPVs). The PS-converted CNS film was fabricated simply with spin-coating of a cost-effective PS solution, followed by stabilization via ion-beam irradiation and carbonization via heat treatment to convert PS to CNS. The analytical results revealed that the PS film was successfully stabilized by ion-beam irradiation and the conductive CNS with graphene-like structure was synthesized. The PPVs with the PS-converted CNS as a TE showed a feasible power conversion efficiency of ~0.61% under a standard 1 sun condition, thus, confirming that the ion-beam based CNS-formation approach and the PS-converted CNS can be useful in transparent electrode applications. • Conductive carbon nanosheet (CNS) films were fabricatd from polystyrene (PS). • The PS film was effectively stabilized by the ion-beam and converted to CNS by the carbonization process. • The PS-converted CNS served as a transparent electrode for polymeric photovoltaics. [ABSTRACT FROM AUTHOR]

Platycodin D (PD) is a major active component of the roots of Platycodon grandiflorum (Jacq.) A.DC. and possesses multiple biological and pharmacological properties, including anti-cancer activity. The aim of this study was to characterize PD-induced cytoplasmic vacuolation in human cancer cells and investigate the underlying mechanisms. PD-induced cancer cell death was associated with cytoplasmic pinocytic and autophagic vacuolation. Cellular energy levels were decreased by this compound, leading to the activation of AMP-activated protein kinase (AMPK). Additionally, compound C, an inhibitor of AMPK, completely prevented PD-induced vacuolation. These results suggest that PD induces cancer cell death, associated with excessive vacuolation through AMPK activation when cellular energy levels are low. Therefore, our findings provide a mechanistic rationale for a novel combinatorial approach using PD to treat cancer. [ABSTRACT FROM AUTHOR]

Whether thymectomy is beneficial in elderly patients with myasthenia gravis (MG) is unclear. Thus, we assessed whether conducting thymectomy in MG patients aged ≥ 50 years is beneficial. This retrospective cohort study included patients with MG between 1990 and 2018. Thymectomy and control cohorts were selected from among the population of MG patients with an age at onset of ≥ 45 years and elevated concentrations of acetylcholine-receptor antibodies. Patients with evidence of thymic malignancy were excluded. Of these patients, those who underwent thymectomy at the age of ≥ 50 years were designated as the thymectomy group and those who received only medical treatment were designated as the medical treatment group. We compared the Myasthenia Gravis Foundation of America post-intervention status between the thymectomy and medical treatment groups. Landmark analysis was conducted with the landmark set at 24 months. A total of 34 and 105 patients were classified into the thymectomy and medical treatment groups, respectively. Before landmark analysis, the thymectomy group had a higher cumulative incidence of pharmacologic remission (p = 0.009) and complete stable remission (p = 0.022) than the medical treatment group. After landmark analysis, the thymectomy group had a 2.22-fold (95% confidence interval 1.01-4.80) increased chance of achieving pharmacologic remission compared to the medical treatment group after adjustment for age, sex, and disease severity. No significant difference was observed in the rate of relapse after pharmacological remission between the thymectomy (16.7%) and medical treatment groups (21.4%). In conclusion, thymectomy may have a beneficial effect in elderly patients with non-thymomatous generalized MG. [ABSTRACT FROM AUTHOR]

Gastrodin (GAS) is a predominant bioactive constituent of the Chinese herbal medicine Tianma (Gastrodia elata Blume). Many authors have reported GAS has the beneficial effect on diverse diseases of the CNS, including epilepsy, Alzheimer's disease, Parkinson's disease, and cerebral ischemia. Here, we report GAS exhibited a robust neuroprotective effect in an Sprague-Dawley rat model of stroke (transient middle cerebral artery occlusion, tMCAO), and show that the underlying molecular mechanism involves its protective effect against Zn2+-toxicity and its anti-oxidative effects in astrocytes. Intraperitoneal administration of GAS (40 mg/kg) after MCAO reduced mean infarct volume to 30.1 ± 5.9% of that of MCAO controls and this neuroprotective effect was accompanied by neurological function recoveries which was measured using modified neurological severity score (mNSS). Interestingly, GAS induced up-regulation and nuclear translocation of Nrf2, and subsequently increased the expressions of anti-oxidative genes, such as, HO-1 and GCLM, in astrocytes. Furthermore, GAS co- or pre-treatment markedly suppressed Zn2+-induced cell death caused by excessive ROS production and PARP-1 induction. We found that GAS suppressed p67 expression and PAR formation in astrocytes, which might underlie the anti- Zn2+-toxicity and anti-oxidative effects of GAS in astrocytes. These findings indicate GAS protects astrocytes from Zn2+-induced toxicity and oxidative stress and these effects contribute to its neuroprotective effects in the postischemic brain. [ABSTRACT FROM AUTHOR]

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients possess multiple risk factors for osteoporosis, but few studies have evaluated bone mineral density (BMD) in CIDP patients.Methods: We retrospectively compared the BMD of CIDP patients with that of normal controls, and evaluated the clinical factors associated with osteoporosis.Results: Total BMD was lower in CIDP patients than in normal controls (P = 0.017). In a comparison of 16 osteoporotic CIDP patients with 25 non-osteoporotic patients, the cumulative prednisolone dose was lower (P = 0.022) and the duration from disease onset to BMD measurement was shorter (P = 0.014) in osteoporotic patients than in non-osteoporotic patients. Function, as measured by modified Rankin scale score within 3 years of the BMD measurement, was worse in osteoporotic than in non-osteoporotic patients (P = 0.008).Discussion: BMD in CIDP patients was significantly lower than in normal controls. Functional status rather than cumulative steroid dose was associated with osteoporosis. Muscle Nerve 58: 407-412, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT Mun, J.; Kim, S.-W., and Melby, J. A. 2018. A surrogate model for wave prediction based on an artificial neural network using high-fidelity synthetic hurricane modelling. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 876–880. Coconut Creek (Florida), ISSN 0749-0208. A surrogate model for significant wave height and period prediction is developed based on an artificial neural network with synthetic simulations of hurricanes. The neural networks between five input parameters and the wave height or wave period are trained by the Levenberg-Marquardt backpropagation algorithm. A back propagation is a form of supervising training algorithm and the weighting factors and the bias are updated by the back propagation training within a limited epoch. The data consists high intensity 446 storms on west region in Texas. The 14 save points in this area are analysed by the surrogate model. The performance of the static surrogate model for the significant waves is expressed as the correlation coefficient and the mean square error at the 14 save points. The minimum correlation coefficient and the mean square error are respectively 0.981 and 0.011. The predicted wave height and period are good agreement with the target values. [ABSTRACT FROM AUTHOR]

ABSTRACT Kim, S.-W.; Lee, A., and Mun, J., 2018. A Surrogate Modeling for Storm Surge Prediction Using an Artificial Neural Network. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 866–870. Coconut Creek (Florida), ISSN 0749-0208. A surrogate model for storm surge prediction is developed using on an artificial neural network with the measured tidal level in Korea peninsula. The 59 historical storms during 1978 to 2014 years are used in this modelling. Tidal data recorded for 15 years was applied. The neural network between seven input parameters (i.e., latitude, longitude, moving speed, heading direction, central pressure, radius of strong wind speed, maximum wind speed) and the storm surge is trained by Levenberg-Marquardt backpropagation algorithm. The type of network is a multilayer feedforward network. The data is divided by 70% for training, 15 % for validation and 15 % for test. The six save points in southern Korea are analysed by the surrogate model. The performance of the storm surge surrogate model is expressed as the correlation coefficient and mean square error at the six save points. The minimum and maximum correlation coefficients are respectively 0.861 and 0.979. The developed surrogate model satisfies high-accuracy and high-speed for predicting he storm surge based on an artificial intelligence method and a grid-free system. [ABSTRACT FROM AUTHOR]

4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn2+ toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects. Intraperitoneal administration of 4-HBA (20 mg/kg) in Sprague-Dawley rats 1 h after MCAO reduced infarct volumes to 27.1 ± 9.2% of that of MCAO controls and significantly ameliorated motor impairments and neurological deficits. Significant suppressions of Zn2+-induced cell death, ROS generation, and PARP-1 induction by 4-HBA were observed in primary cortical cultures. 4-HBA also protected astrocytes from Zn2+-induced toxicity and suppressing ROS generation by employing slightly different molecular mechanisms, i.e., suppressing PARP-1 induction and NAD depletion under acute Zn2+-treatment and suppressing p67 NADPH oxidase subunit induction under chronic Zn2+-treatment. Results indicate that the protective effects of 4-HBA against Zn2+-toxicity in neurons and astrocytes contribute to its robust neuroprotective effects in the postischemic brain. Considering the pleiotropic effects of 4-HBA, which have been reported in previous reports and added in the present study, it has therapeutic potential for the amelioration of ischemic brain damage. [ABSTRACT FROM AUTHOR]

Mun, J.; Kim, S.-W., and Melby, J. A. 2018. A surrogate model for wave prediction based on an artificial neural network using high-fidelity synthetic hurricane modelling. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 876–880. Coconut Creek (Florida), ISSN 0749-0208. A surrogate model for significant wave height and period prediction is developed based on an artificial neural network with synthetic simulations of hurricanes. The neural networks between five input parameters and the wave height or wave period are trained by the Levenberg-Marquardt backpropagation algorithm. A back propagation is a form of supervising training algorithm and the weighting factors and the bias are updated by the back propagation training within a limited epoch. The data consists high intensity 446 storms on west region in Texas. The 14 save points in this area are analysed by the surrogate model. The performance of the static surrogate model for the significant waves is expressed as the correlation coefficient and the mean square error at the 14 save points. The minimum correlation coefficient and the mean square error are respectively 0.981 and 0.011. The predicted wave height and period are good agreement with the target values. [ABSTRACT FROM AUTHOR]

Kim, S.-W.; Lee, A., and Mun, J., 2018. A Surrogate Modeling for Storm Surge Prediction Using an Artificial Neural Network. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 866–870. Coconut Creek (Florida), ISSN 0749-0208. A surrogate model for storm surge prediction is developed using on an artificial neural network with the measured tidal level in Korea peninsula. The 59 historical storms during 1978 to 2014 years are used in this modelling. Tidal data recorded for 15 years was applied. The neural network between seven input parameters (i.e., latitude, longitude, moving speed, heading direction, central pressure, radius of strong wind speed, maximum wind speed) and the storm surge is trained by Levenberg-Marquardt backpropagation algorithm. The type of network is a multilayer feedforward network. The data is divided by 70% for training, 15 % for validation and 15 % for test. The six save points in southern Korea are analysed by the surrogate model. The performance of the storm surge surrogate model is expressed as the correlation coefficient and mean square error at the six save points. The minimum and maximum correlation coefficients are respectively 0.861 and 0.979. The developed surrogate model satisfies high-accuracy and high-speed for predicting he storm surge based on an artificial intelligence method and a grid-free system. [ABSTRACT FROM AUTHOR]

Aortic atheroma is a known cause of ischemic stroke. However, it is unclear whether ischemic stroke is caused by emboli from aortic atheroma or by accompanying atherosclerosis. In this study, we evaluated lesion patterns of patients with complex aortic plaque (CAP) to assume the underlying pathophysiology. Acute ischemic stroke patients who underwent transesophageal echocardiography were included. CAP was defined as a plaque in the proximal aorta ≥ 4 mm thick or with a mobile component. The diffusion-weighted imaging lesion patterns of patients with CAP were compared to those with large arterial atherosclerosis (LAA) or cardioembolism (CE). A total of 64 CAP patients, 127 LAA patients, and 80 CE patients were included. Small cortical pattern was more common in the CAP group (45.3%) than in the LAA (7.9%, p < 0.001) or the CE group (23.8%, p = 0.018). A large cortical pattern was more common in the CE group than in the CAP group ( p < 0.001), whereas subcortical only pattern tended to be more common in the CAP group than in the CE group ( p = 0.057). In multinominal analysis, the CAP group was more likely to have a small cortical lesion than the LAA group [odds ratio (OR) 14.63; 95% confidence interval (CI) 4.67-45.85] or the CE (OR 3.69, 95% CI 1.19-11.39) group. In conclusion, patients with CAP frequently had small cortical lesions or subcortical single lesion. These findings imply that ischemic stroke in aortic atheroma patients is associated with either small emboli or small artery disease. [ABSTRACT FROM AUTHOR]

4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata Blume (GEB), a traditional herbal medicine used in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in the brain, and in particular, its anti-inflammatory, anti-oxidative, and anti-zinc-toxic effects have been implicated in the postischemic brain. Here, the authors investigated the anti-oxidative effect of 4-HBA on astrocytes and sought to identify the underlying molecular mechanisms involved. 4-HBA dose-dependently suppressed H2O2-induced astrocyte cell death. More specifically, pre-incubation of C6 cells (an astrocyte cell line) with 100 μM 4-HBA for 6 hrs increased survival when cells were treated with H2O2 (100 μM, 1 hr) from 54.2±0.7% to 85.9±1.5%. In addition, 4-HBA was found to up-regulate and activate Nrf2, and subsequently, to induce the expressions of several anti-oxidative genes, such as, HO-1, NQO1, and GCLM. Notably, HO-1 was induced by 3.4-fold in 4-HBA-treated C6 cells, and siRNA-mediated HO-1 knockdown demonstrated that Nrf2 activation and HO-1 induction were responsible for the observed cytoprotective effect of 4-HBA. ERK and Akt signaling pathways were activated by 4-HBA in C6 cells, suggesting their involvements in protective effect of 4-HBA. In addition, 4-HBA-conditioned astrocyte culture medium was found to have neuroprotective effects on primary neuronal cultures or fresh C6 cells exposed to oxidative stress, and these effects seemed to be mediated by glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), which both accumulated in 4-HBA-treated astrocyte culture media. Thus, the 4-HBA-mediated activation of Nrf2 and induction of HO-1 in astrocytes were found to act via autocrine and paracrine mechanisms to confer protective effects. Furthermore, given the pleiotropic effects of 4-HBA with respect to its targeting of various brain cell types and functions, it would appear that 4-HBA has therapeutic potential for the prevention and amelioration of various brain diseases. [ABSTRACT FROM AUTHOR]

A non-metal approach for accessing α-oxo carbene surrogates for a C−C bond-forming bimolecular coupling between ynamides and nucleophilic arenes was developed. This acid-catalyzed coupling features mild temperature, which is critical for the required temporal chemoselectivity among nucleophiles. The scope of nucleophiles includes indoles, pyrroles, anilines, phenols and silyl enolethers. Furthermore, a direct test of SN2′ mechanism has been provided by employing chiral N,N′-dioxides which also enlightens the nature of the intermediates in related metal-catalyzed processes. [ABSTRACT FROM AUTHOR]

A non-metal approach for accessing α-oxo carbene surrogates for a C−C bond-forming bimolecular coupling between ynamides and nucleophilic arenes was developed. This acid-catalyzed coupling features mild temperature, which is critical for the required temporal chemoselectivity among nucleophiles. The scope of nucleophiles includes indoles, pyrroles, anilines, phenols and silyl enolethers. Furthermore, a direct test of SN2′ mechanism has been provided by employing chiral N,N′-dioxides which also enlightens the nature of the intermediates in related metal-catalyzed processes. [ABSTRACT FROM AUTHOR]

2-Hydroxy-4-trifluoromethylbenzoic acid (HTB) is a metabolite of triflusal (TF), and has been reported to exert anti-inflammatory effect. In this study, the authors investigated whether HTB has a neuroprotective effect against ischemic brain injuries. We showed that intravenous administration of HTB (5 mg/kg) 30 min before or 1, 3, or 6 h after middle cerebral artery occlusion (MCAO) reduced brain infarct to 10.4 ± 3.3%, 16.9 ± 2.3%, 22.2 ± 1.5% and 40.7 ± 7.5%, respectively, of that of treatment-naive MCAO controls, and the therapeutic time window extended to 9 h after MCAO (40.7 ± 7.5%). Furthermore, HTB suppressed infarct formation, protected motor activities, and ameliorated neurological deficits more effectively than by TF or salicylic acid (SA). HTB markedly suppressed microglial activation and proinflammatory cytokines expressions in the postischemic brain and in BV2 cells and suppressed LPS-induced nitrite production by inhibiting IkB degradation. In addition, HTB suppressed NMDA-induced neuronal cell death more effectively than TF or SA in primary cortical neuron cultures. Together, these results indicate that HTB has multi-modal protective effects against ischemic brain damage that encompass anti-inflammatory, anti-excitotoxicity, and anti-Zn 2+ -toxicity effects. [ABSTRACT FROM AUTHOR]

The keteniminium ions generated from the protonation of ynamides formed reversible adducts with counter anions and pyridine-N-oxides as well as halogenated solvents. Above 80 °C, the halonium ions selectively undergo a rate-limiting attack by pyridine-N-oxides, leading to (E)-haloenamides in good yields. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) is a hydrophobic polyphenol derived from the rhizome ofCurcuma longa. CUR confers protection in various pathological conditions, including many brain-related diseases, such as cerebral ischemia, intracerebral hemorrhage, or Alzheimer’s disease, and these effects have been attributed to its anti-inflammatory and anti-oxidative properties. In the present study, we found CUR induced the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in microglia, brain macrophage, and thus upregulated genes downstream of antioxidant response element, such as heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, glutamate-cysteine ligase modifier subunit, and ferritin light chain, and simultaneously downregulated lipopolysaccharide-induced inducible nitric oxide synthase expression. We showed that the anti-inflammatory effect of CUR in microglia is connected with its anti-oxidative effect in that CUR promotes Nrf2–p300 binding at the expense of p65–p300 binding. Since CUR is a dietary spice that is eaten on a daily basis, it appears that CUR could be used therapeutically to induce anti-oxidative effect and simultaneously ameliorate inflammatory conditions via up–downregulation of related genes. [ABSTRACT FROM AUTHOR]

Ethyl pyruvate (EP) is a simple aliphatic ester of pyruvic acid and has been shown to have robust protective effect in various pathological conditions. A variety of mechanisms have been reported to underlie the protective effects of EP, which include anti-inflammatory, anti-oxidative, and anti-apoptotic functions. Recently, we reported that EP suppressed high mobility group box 1 (HMGB1) release from primary microglial cells via direct Ca 2+ chelation. In the present study, we investigated whether and how EP chelates Zn 2+ in neurons when it is present at toxic levels. In cortical neurons treated with 40 μM of Zn 2+ for 24 h, both EP and pyruvate significantly suppressed neuronal cell death, although the potency of pyruvate was greater than that of EP, and that NAD replenishment contributed to the neuroprotective effects of both pyruvate and EP. However, when cortical neurons were exposed to acute treatment of Zn 2+ (400 μM, 15 min), EP, but not pyruvate, significantly suppressed neuronal death, despite the fact that NAD replenishment by EP was weaker than that by pyruvate. Spectrophotometric studies revealed that EP directly chelates Zn 2+ , and this was confirmed in physiological contexts, such as, NMDA-treated primary cortical cultures and OGD-subjected hippocampal slice cultures, in which EP suppressed intracellular Zn 2+ elevation and neuronal cell death. In addition, EP markedly reduced the expressions of PARP-1 and of the NADPH oxidase subunit in Zn 2+ -treated primary cortical neurons, well known Zn 2+ -induced downstream processes. Together, these results show EP suppresses Zn 2+ induced neurotoxicity via dual functions, chelating Zn 2+ and promoting NAD replenishment. [ABSTRACT FROM AUTHOR]

Objective: The role of lipopolysaccharide (LPS) and toll-like receptor 4 (TLR 4) in the pathogenesis of alcoholic liver disease (ALD) has been widely established. We evaluated the biological effects of probiotics (Lactobacillus rhamnosus R0011 and acidophilus R0052), KRG (Korea red ginseng), and urushiol (Rhus verniciflua Stokes) on ALD, including their effects on normal and high-fat diet in mice. Methods: One hundred C57BL/6 mice were classified into normal (N) and high-fat diet (H) groups. Each group was divided into 5 sub-groups: control, alcohol, alcohol+probiotics, alcohol+KRG, and alcohol+urushiol. A liver function test, histology, electron-microscopy, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-10, and TLR 4 were evaluated and compared. Results: In the N group, probiotics, KRG, and urushiol significantly reduced levels of TNF-α (12.3±5.1, 13.4±3.9, and 12.1±4.3 vs. 27.9±15.2 pg/mL) and IL-1β (108.4±39.4, 75.0±51.0, and 101.1±26.8 vs. 162.4±37.5 pg/mL), which were increased by alcohol. Alcohol-induced TLR 4 expression was reduced by probiotics and urushiol (0.7±0.2, and 0.8±0.1 vs. 1.0±0.3, p<0.001). In the H group, IL-10 was significantly increased by probiotics and KRG, compared with alcohol (25.3±15.6 and 20.4±6.2 vs. 7.6±5.6 pg/mL) and TLR 4 expression was reduced by probiotics (0.8±0.2 vs. 1.0±0.3, p = 0.007). Conclusions: Alcohol-induced TLR 4 expression was down-regulated by probiotics in the normal and high-fat diet groups. Probiotics, KRG, and urushiol might be effective in the treatment of ALD by regulating the gut-liver axis. [ABSTRACT FROM AUTHOR]

In this paper, the occurrence rate of caisson sliding of a vertical breakwater during a storm and the probabilistic distribution of the individual sliding distances are derived as functions of such important design variables as water depth, significant wave height, and caisson width. The expressions for various representative sliding distances such as the significant sliding distance are also derived. The derived statistical characteristics of individual sliding distances are then used for calculating the first passage probability of an allowable individual sliding distance during a storm. A method is also proposed to calculate the time-dependent first passage probability for the case where wave climate and mean water depth change with time. Finally, tentative design criteria for the allowable individual sliding distance are proposed. The proposed method is applied to fictitious breakwaters in different water depths near the Port of Hitachinaka in Japan. The time-dependent first passage probability is calculated for the next 50 years in which the wave height may increase due to climate change. The first passage probability increases as time elapses, as the water depth increases, and as the allowable individual sliding distance decreases. Comparison with a previous study that uses a performance-based design method shows that the allowable first passage probability should be in the range between 0.05 and 0.09. For the proposed method to be used in a practical design, however, more detailed study should be made to determine the allowable values of individual sliding distance, first passage probability, and representative sliding distance, by comparing with current design methods. [ABSTRACT FROM AUTHOR]

Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol. [ABSTRACT FROM AUTHOR]

Abstract: The effects of long-term sea-level rise and offshore wave-height increase due to climate change on the stability of caisson breakwaters constructed in different water depths are analyzed by using a time-dependent performance-based design method. An artificial neural network is combined with the wave transformation model to reduce the computation time in the Monte Carlo simulation. The breakwater is designed by the conventional safety-factor method, while its performance is evaluated by the expected sliding distance. In general, the stability of the breakwater is reduced if the climate change effects are included, but it shows different trends depending on water depth. Outside the surf zone, the effect of sea-level rise decreases with increasing water depth, whereas that of wave-height increase increases with water depth. Inside the surf zone, however, both effects decrease with decreasing water depth, with greater effect of wave-height increase than sea-level rise. In the design of a caisson breakwater of ordinary importance, it is not necessary to take into account the effect of sea-level rise, whereas the effect of wave-height increase should be taken into account if the breakwater is constructed far outside the surf zone. However, it should be noted that different results should be obtained if the breakwater were designed based on the expected sliding distance. [Copyright &y& Elsevier]

Abstract: In this study, a risk assessment system has been developed by performing the reliability analysis for wave run-up and armor stability of inclined coastal structures for various scenarios of long-term sea level rise due to climate change. The change of probability of failure for armor stability and wave run-up due to sea level rise has been calculated against various design parameters such as size of armor units, structure slope, and freeboard of the structure. It is found that the effect of sea level rise is negligible outside the surf zone. Inside the surf zone, however, the effect increases with decreasing water depth so that more increase of probability of failure is calculated in smaller water depth for the same sea level rise. By comparing the results before and after the sea level rise, it is possible to evaluate how the sea level rise influences wave run-up and armor stability of the structure. The results of the present study could be used for maintenance or reinforcement planning of existing structures as well as in the design of new structures to cope with future sea level rise. [Copyright &y& Elsevier]

Abstract: Cerebral ischemia leads to brain injury via a complex series of pathophysiological events, and therefore, multi-drug treatments or multi-targeting drug treatments provide attractive options with respect to limiting brain damage. Previously, we reported that a novel multi-functional compound oxopropanoyloxy benzoic acid (OBA-09, a simple ester of pyruvate and salicylic acid) affords robust neuroprotective effects in the postischemic rat brain. OBA-09 exhibited anti-oxidative effects that appeared to be executed by OBA-09 and by the salicylic acid afforded by hydrolysis. Here, we report the anti-inflammatory effects of OBA-09. Microglial activation observed at 2 days post-middle cerebral artery occlusion (MCAO, 90min) and at 1 day after a LPS injection (0.5mg/kg, intravenously) in the brains of Sprague-Dawley rats were markedly suppressed by the administration of OBA-09 (10mg/kg). Inductions of proinflammatory markers (TNF-α, IL-1β, iNOS, and COX-2) were also suppressed by OBA-09 in both the LPS and MCAO models. Moreover, the anti-inflammatory effect of OBA-09 was accompanied by the suppression of infarct formation in the postischemic brain, but appeared to be independent of neuroprotection in LPS-treated rats. The inductions of proinflammatory markers were also inhibited by OBA-09 in LPS-treated BV2 cells (a microglia cell line) and in LPS-treated-primary neutrophils, possibly due to the suppression of NF-κB activity. Interestingly, the anti-inflammatory effect of OBA-09 was greater than that of equivalent co-treatment with pyruvate and salicylic acid. Together these results indicate that OBA-09 is a potent multi-modal neuroprotectant in the postischemic brain, and that its anti-inflammatory effect contributes to its neuroprotective function. [Copyright &y& Elsevier]

Kim, S.-W. and Suh, K.-D., 2013. Performance analysis of vertical breakwaters designed by partial safety factor method The partial safety factor method has been developed in Europe, Japan, and Korea to overcome the limitations of the deterministic method for design of the vertical breakwater. The practical engineers prefer the partial safety factor method because this method is relatively simple to use compared with other probabilistic methods. However, the partial safety factor method does not evaluate the displacement of the vertical breakwater, while only defining the boundary between safety and failure domains within a given target safety level. Therefore, it is required to examine the performance of the breakwater designed by the partial safety factor method in terms of caisson sliding distance. In the present study, the partial safety factors developed by an advanced research for vertical breakwaters are used with the target reliability indices of 2.33 and 2.0. The performance analysis of 12 cross-sections of five vertical breakwaters was conducted by the method based on the Monte-Carlo simulation. Especially, this method considers a technique to eliminate the unrealistic extreme values of the design variables. As a result, the breakwaters designed by the partial safety factor method with the target reliability index of 2.0 are found to be stable except for one cross-section with high uncertainty of wave height. On the other hand, all the breakwaters with the reliability index of 2.33 are found to be stable irrespective of any uncertainty of wave height. Finally, it is found that the vertical breakwaters designed with the reliability index of 2.33 satisfy the allowable exceedance probabilities for both repairable and ultimate limit states. [ABSTRACT FROM AUTHOR]

Abstract: During the last decade, partial safety factor systems have been adopted in the design standards of coastal structures, which are based on probabilistic theories but have a format similar to the traditional safety factor system. Tetrapod is one of the widely used breakwater armor units in the world. The previous partial safety factor system was developed based on limited wave and structure data in several locations. In this paper, a partial safety factor system for Tetrapod armor units is developed by performing reliability analysis and optimal code calibration for 116 breakwater cross-sections and wave conditions in 31 harbors in Korea. The partial safety factors associated with different ranges of the shape parameter of the Weibull extreme wave height distribution for different target probabilities of failure are proposed. For other types of extreme distributions, the skewness of the distribution should be calculated and the partial safety factors of the Weibull distribution of the same skewness could be used (the skewness of the Weibull distribution changes with the shape parameter). The developed system is applied to existing breakwaters to examine its applicability. [Copyright &y& Elsevier]

Abstract: Ethyl pyruvate (EP), a simple ester of pyruvic acid, has been shown to act as an anti-inflammatory molecule under various pathological conditions, such as, during cerebral ischemia and sepsis in animal models. Here, the authors investigated the novel molecular mechanism underlying the anti-oxidative effect of EP in primary astrocyte cultures, particularly with respect to nuclear factor E2-related factor 2 (Nrf2) activation and hemeoxygenase 1 (HO-1) induction. EP was found to induce Nrf2 translocation and the inductions of various genes downstream of Nrf2 and these resulted in the amelioration of the oxidative damage of H2O2. Furthermore, EP dose-dependently suppressed H2O2-induced astrocyte cell death (12h preincubation with 5mM EP increased cell survival after 1h exposure to 100μM H2O2 from 32.6±0.7% to 63±1.8%). HO-1 was markedly induced (4.9-fold) in EP-treated primary astrocyte cultures and Nrf2 was found to translocate from the cytosol to the nucleus and bind to the antioxidant response element (ARE) located on HO-1 promoter after EP treatment. siRNA-mediated HO-1 or Nrf2 knockdown and zinc protoporphyrin (ZnPP)-mediated inhibition of HO-1 activity showed that Nrf2 activation and HO-1 induction were responsible for the observed cytoprotective effect of EP, which was found to involve the ERK and Akt signaling pathways. Furthermore, EP-conditioned astrocyte culture media was found to have neuroprotective effects on primary neuronal cultures exposed to oxidative or excitotoxic stress, and this seemed to be mediated by glial cell line-derived neurotrophic factor (GDNF) and glutathione (GSH), which accumulated in EP-treated astrocyte culture media. Interestingly, we also found that in addition to HO-1, EP-induced Nrf2 activation increased the expressions of various anti-oxidant genes, including GST, NQO1, and GCLM. The study shows that EP-mediated Nrf2 activation and HO-1 induction in astrocytes act via autocrine and paracrine mechanisms to confer protective effects. [Copyright &y& Elsevier]

This paper presents a method to incorporate the effect of climate change on the performance-based design of a caisson breakwater and its application to the East Breakwater of the Port of Hitachinaka in Honshu, Japan. The up-to-date projection estimated a future sea-level rise of 0.25-0.6 m and a wave-height increase of 1.7 m (from 8.3 to 10 m) during the 21st century in this area. The influence of a sea-level rise on caisson sliding was minimal; the sea-level rise was much smaller than the water depth at the breakwater site. When the effects of climate change were not included, the performance-based design method calculated the same caisson width as that of the constructed breakwater, partly validating the consistency between conventional deterministic methods and performance-based design methods. The effects of climate change dictate an increase in caisson width of approximately 1.5 and 0.5 m for linear and parabolic increases of wave height, respectively, which are approximately 6.8 and 2.3% of the present caisson width of 22 m. Finally, it is recommended that the caisson breakwater be designed using the projected wave height and water level in 30 years from construction, if the deterministic design method is used and the effects of climate change are to be taken into account. [ABSTRACT FROM AUTHOR]

Abstract: High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In a previous report, we showed that HMGB1 is massively released during NMDA-induced acute damaging process in the postischemic brain and triggers inflammatory processes, like microglial activation. siRNA-mediated HMGB1 knockdown markedly reduced infarct volumes, confirming the crucial role played by HMGB1 in the postischemic brain. In the present study, we showed neuroprotective effects of glycyrrhizin (GL) in the postischemic rat brain after middle cerebral artery occlusion (MCAO). GL, a triterpene present in the roots and rhizomes of licorice, Glycyrrhiza glabra, has been shown to have anti-inflammatory and anti-viral effects. It has been reported that GL binds directly to HMGB1, and inhibits its chemoattractant and mitogenic activities. The administration of GL (10mg/kg) intravenously at 3 or 6h after MCAO reduced infarct volumes to 12.9±4.2% and 46.2±9.9%, respectively, of untreated control. This neuroprotective effect was accompanied by improvements in motor impairment and neurological deficits and suppressions of microglia activation and proinflammatory cytokine induction. Interestingly, GL almost completely blocked HMGB1 secretion in the postischemic brain and in lipopolysaccharide (LPS)-treated microglia cells. Furthermore, HMGB1 phosphorylation, which is the initial step for HMGB1 secretion, and the interaction between HMGB1 and protein kinase C (PKC) or calcium/calmodulin-dependent protein kinase IV (CaMKIV) were suppressed dose-dependently by GL. Here, we hypothesized that the blockage for the putative phosphorylation sites in HMGB1 by GL might be attributed to this suppression. In addition to the anti-inflammatory effects, we found that GL has anti-excitotoxic and anti-oxidative effects in neurons. Together these results indicate that GL has neuroprotective efficacy in the postischemic brain via its anti-inflammatory, anti-excitotoxic, and anti-oxidative effects and in particular, it exerts anti-inflammatory effect, at least in part, by inhibiting HMGB1 secretion. [Copyright &y& Elsevier]

Abstract: This paper presents two methods that evaluate the target reliability of caisson sliding of a vertical breakwater. First, the statistical characteristics and probability density function are obtained for the safety factors of the breakwaters designed by deterministic methods in the past. The first method calculates the probability density of reliability index by applying the Monte Carlo simulation to the safety factor for various combinations of uncertainties of load and resistance. The significant target reliability index is then calculated by averaging the highest one third of the reliability index. The second method uses the Chebyshev inequality which describes the lower limit of reliability index. Again the Monte Carlo simulation is used to calculate the probability density of the lower limit of reliability index. The maximum of the possible lower limits is then taken as the target reliability index. The application of the methods has given the target reliability indices close to one another and also close to the value used in a recently published design standard. [Copyright &y& Elsevier]

High mobility group box 1 (HMGB1) was originally identified as ubiquitously expressed nonhistone DNA-binding protein, but recently, it was found to act as an endogenous danger molecule, which signals danger and traumatic cell death. Previously, the authors showed that HMGB1 is massively released immediately after an ischemic insult and that it subsequently activates microglia and induces inflammation in the postischemic brain. Here, we showed the endogenous danger molecule-like function of HMGB1 in primary cortical cultures. HMGB1 was found to be accumulated in NMDA-treated primary cortical culture media, and media collected from these cultures were able to induce neuronal cell death when added to fresh primary cortical cultures. However, HMGB1-depleted NMDA-conditioned media produced by HMGB1 siRNA transfection or by preincubation with anti-HMGB1 antibody or with HMGB1 A box failed to induce neuronal cell death. Furthermore, siRNA-mediated HMGB1 knockdown substantially suppressed NMDA- or Zn-induced cell death. It was interesting to find that extracellular HMGB1-induced neuronal apoptosis, as evidenced by TUNEL staining and caspase 3 assay in combination with double immunofluorescence staining. A series of RAGE and HMGB1 co-immunoprecipitation experiments in the presence of SB203580 and PD98059 (p38 MAPK and ERK inhibitors, respectively) demonstrated that RAGE-p38 MAPK and RAGE-ERK pathway might underlie extracellular HMGB1-mediated neuronal apoptosis. These results together with our previous reports regarding microglial activation by extracellular HMGB1 indicate that HMGB1 functions as a novel danger signal, which aggravates brain damage via autocrine and paracrine manners. [ABSTRACT FROM AUTHOR]

Abstract: High mobility group box 1 (HMGB1) is a family of endogenous molecules that is released by necrotic cells and causes neuronal damages by triggering inflammatory processes. In the cerebral ischemic brain, sustained and regulated suppression of HMGB1 has been emerged as a therapeutic means to grant neuroprotection. HMGB1 consists of two HMG boxes (A and B) and an acidic C-terminal tail, and the A box peptide antagonistically competes with HMGB1 for its receptors. In the middle cerebral artery occlusion (MCAO) in rats, a murine model of transient cerebral ischemia, administration of HMGB1 A box intraparenchymally, after encapsulated in biodegradable gelatin microspheres (GMS), which enhances the stability of peptide inside and allows its sustained delivery, at 1 h, 3 h, or 6 h after MCAO, reduced mean infarct volumes by, respectively, 81.3%, 42.6% and 30.7% of the untreated MCAO-brain, along with remarkable improvement of neurological deficits. Furthermore, the administration of HMGB1 A box/GMS suppressed proinflammatory cytokine inductions more strongly than the injection of non-encapsulated HMGB1 A box. Given that insulted brains-like ischemia have enhanced gelatinase activity than the normal brain, our results suggest that GMS-mediated delivery of therapeutic peptides is a promising means to provide efficient neuroprotection in the postischemic brain. [ABSTRACT FROM AUTHOR]

In Korea, Tetrapods have been widely used to protect rubble mound breakwaters against erosion due to wave action. The deterministic design method has been used based on Hudson or van der Meer formula. In this study, we have performed reliability analyses for thus designed Tetrapod armors of 12 trade harbors and 8 coastal harbors in Korea. It is found that there is a linear relationship between the safety factor and the probability of failure; the larger the safety factor, the smaller the probability of failure. It is also found that the probability of failure during 50-year service lifetime is about 60% for the Tetrapod armors designed by the deterministic design method with the safety factor of 1.0. This finding seems to be natural since the encounter probability that a breakwater will experience storm waves greater than the design wave during its lifetime is 63% if the lifetime is set equal to the design return period. The results of this study could provide a guideline for determining the target probability of failure of Tetrapod armors in the future. A similar approach could be used for armor units other than Tetrapods. [ABSTRACT FROM AUTHOR]

In calculating the partial safety factors of breakwater armor stones, it has been assumed that all the design variables are independent of one another. However, some of them are not independent but are correlated to each other. In the present study, the partial safety factors are calculated by considering the correlation between wave height and wave steepness. Smaller partial safety factors and smaller armor weight are obtained if the correlation is taken into account. The reduction becomes prominent as the probability of failure decreases (or the design armor weight increases). The correlation between wave height and steepness in real sea is also estimated by using the wave hindcasting data around the Korean Peninsula. [ABSTRACT FROM AUTHOR]

Abstract: αB-crystallin is a member of the small heat shock proteins, which is abundantly expressed in various vertebrate tissues including the central nervous system. In our previous report, we showed αB-crystallin induction in activated astrocytes in the postischemic brain and in H2O2-treated primary astrocyte cultures. To investigate the functional significance of αB-crystallin induction in astrocytes, we generated a stable C6 astroglioma cell line overexpressing αB-crystallin. In these cells, hydrogen peroxide-induced apoptosis was reduced by 60% compared to parent cells. Furthermore, the repression of αB-crystallin expression by αB-crystallin siRNA transfection suppressed this protective effect, indicating that αB-crystallin is responsible for the protection against H2O2-induced apoptosis in C6 astroglioma cells. Similar level of aggravation in H2O2-induced apoptosis was observed in primary astrocyte cultures when αB-crystallin expression was suppressed by αB-crystallin siRNA transfection, confirming the importance of αB-crystallin. In addition, the induction of caspase-3 activity after H2O2 treatment was markedly suppressed in αB-crystallin-overexpressing cells, and immunoprecipitation proved binding between αB-crystallin and partially processed caspase-3 (a p24 intermediate). These results indicate that αB-crystallin confers protection against hydrogen peroxide-induced astrocytes apoptosis in part by inhibiting caspase-3 activation. [Copyright &y& Elsevier]

Reliability design methods have been developed for breakwater designs since the mid-1980s. The reliability design method is classified into three categories depending on the level of probabilistic concepts being employed, i.e. Level 1, 2, and 3 methods. Each method gives results in different forms, but all of them can be expressed in terms of probability of failure so that the difference can be compared among the different methods. In this study, we apply the reliability design methods to the stability of armor blocks and sliding of caissons of the breakwater of Donghae Harbor located in the east coast of Korea, which was constructed by traditional deterministic design methods to be damaged in 1987 and reinforced in 1991. Analyses are made for the breakwaters before the damage and after the reinforcement. The allowable probability of failure of a Tetrapod armor layer of 50 year's lifetime is proposed as 40% for existing stability formulas, whilst that for caisson sliding as 20% with the failure criterion for the cumulative sliding distance over the lifetime of 0.1 m. The probability of failure before the damage is much higher than the allowable value for both stability of armor blocks and sliding of caissons, indicating that the breakwater was under-designed. The probability of failure for the reinforced breakwater is lower than the allowable value, indicating that the breakwater became stable after the reinforcement. On the other hand, the results of different reliability design methods were in fairly good agreement, confirming that there is not much difference among the different methods. [ABSTRACT FROM AUTHOR]

αB-crystallin (α-BC), a member of the small heat-shock proteins (sHSP), is constitutively expressed in the vertebrate lens and in non-ocular tissues including the central nervous system (CNS). In this study we investigated the expression of α-BC in the rat brain after middle cerebral artery occlusion (MCAO). α-BC transcript and protein were transiently expressed 4 h after MCAO/reperfusion in the pyramidal neurons in the peri-infarct region of the ischemic hemisphere. Beginning 2 days after MCAO, significant α-BC induction appeared in reactive astrocytes in the penumbra, and this induction was sustained for several days. In addition, levels of MAPKAPK-2, one of the α-BC upstream kinases, and its phosphorylated form were upregulated gradually and peaked 4 days after ischemia/reperfusion injury. The immunohistochemical study indicated that α-BC was co-localized with MAPKAPK-2 and p-MAPKAPK-2. Furthermore, p38β MAPK, an upstream kinase of MAPKAPK-2, which has been known to be involved in compensatory responses to stress, was also co-localized with α-BC in the penumbra. Our results suggest that the p38β-dependent α-BC induction in neurons and astrocytes in the penumbra may play an important role in the postischemic brain. [ABSTRACT FROM AUTHOR]

A self-calibration algorithm is described that allows testing the out-of-plane error motion of two-dimensional profiling stages by using a flat artifact whose accuracy is unknown. The algorithm suppresses artifact-related calibration errors in consideration of the geometrical congruence of three separate profile measurements taken with different orientations of a single artifact. Usefulness of the self-calibration algorithm is verified through computer simulation as well as actual experimental testing. Test results show that the calibration accuracy is free from artifact imperfection and only minimally affected by random measurement errors encountered during the process of calibration. [Copyright &y& Elsevier]

A new method of thermal stabilization that uses gallium as an isothermal heat exchanger is presented. Gallium maintains a fixed temperature near 29 °C when it melts, and the resultant temperature sustains extremely good stability against ambient change of temperature and pressure. This thermo-physical property allows gallium to be utilized as an isothermal medium that is capable of performing precise thermal stabilization at near room temperature without intensive care on temperature sensing and heat control. In this investigation, an isothermal gallium chamber is designed and an ultraprecision level of temperature stabilization to ±1 mK is demonstrated with the aid of Fabry–Perot interferometry. [Copyright &y& Elsevier]

The activation of p38 mitogen-activated protein kinase (MAPK) has been implicated in the pathological changes accompanying inflammatory and apoptotic processes of various cell types including neurons. In a kainic acid (KA)-induced mouse seizure model, p38 MAPK is induced in reactive astrocytes in the CA3 region of the hippocampus where severe neuronal loss occurs. Here we report the delayed and protracted activation of p38 MAPK in the CA3 region of the hippocampus of mice treated with KA. In this model, the inhibition of p38 MAPK isoforms by SB203580, a specific inhibitor, attenuated neuronal loss in the CA3 and CA1 regions of the hippocampus, which was accompanied by the suppression of the p38 MAPK activation as well as astrogliosis. Thus, the delayed and sustained induction of p38 MAPK plays a crucial role in the neuronal damage of KA-induced brain seizures. [Copyright &y& Elsevier]