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Backgroud Smoking is a risk factor for cardiovascular diseases as well as pulmonary dysfunction. In particular, adolescent smoking has been reported to have a higher latent risk for cardiovascular disease. Despite the risk to and vulnerability of adolescents to smoking, the mechanisms underlying the effects of acute nicotine exposure on adolescents remain unknown. This study therefore evaluated the mechanism underlying the effects of linalyl acetate on cardiovascular changes in adolescent rats with acute nicotine exposure. Methods Parameters analyzed included heart rate (HR), systolic blood pressure, lactate dehydrogenase (LDH) activity, vascular contractility, and nitric oxide levels. Results Compared with nicotine alone, those treated with nicotine plus 10 mg/kg (p = 0.036) and 100 mg/kg (p = 0.023) linalyl acetate showed significant reductions in HR. Moreover, the addition of 1 mg/kg (p = 0.011), 10 mg/kg (p = 0.010), and 100 mg/kg (p = 0.011) linalyl acetate to nicotine resulted in significantly lower LDH activity. Nicotine also showed a slight relaxation effect, followed by a sustained recontraction phase, whereas nicotine plus linalyl acetate or nifedipine showed a constant relaxation effect on contraction of mouse aorta (p < 0.001). Furthermore, nicotine-induced increases in nitrite levels were decreased by treatment with linalyl acetate (p < 0.001). Conclusions Taken together, our findings suggest that linalyl acetate treatment resulted in recovery of cell damage and cardiovascular changes caused by acute nicotine-induced cardiovascular disruption. Our evaluation of the influence of acute nicotine provides potential insights into the effects of environmental tobacco smoke and suggests linalyl acetate as an available mitigating agent. [ABSTRACT FROM AUTHOR]

The retinoic acid receptor-related orphan receptor-α (RORα) is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer. Here, we show that hepatic RORα controls lipid homeostasis by negatively regulating transcriptional activity of peroxisome proliferators-activated receptor-γ (PPARγ) that mediates hepatic lipid metabolism. Liver-specific Rorα-deficient mice develop hepatic steatosis, obesity and insulin resistance when challenged with a high-fat diet (HFD). Global transcriptome analysis reveals that liver-specific deletion of Rorα leads to the dysregulation of PPARγ signaling and increases hepatic glucose and lipid metabolism. RORα specifically binds and recruits histone deacetylase 3 (HDAC3) to PPARγ target promoters for the transcriptional repression of PPARγ. PPARγ antagonism restores metabolic homeostasis in HFD-fed liver-specific Rorα deficient mice. Our data indicate that RORα has a pivotal role in the regulation of hepatic lipid homeostasis. Therapeutic strategies designed to modulate RORα activity may be beneficial for the treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) crystals have a multitude of forms, including semi-metals, semiconductors, and insulators, which are ideal for assembling isolated 2D atomic materials to create van der Waals (vdW) heterostructures. Recently, artificially-stacked materials have been considered promising candidates for nanoelectronic and optoelectronic applications. In this study, we report the vertical integration of layered structures for the fabrication of prototype non-volatile memory devices. A semiconducting-tungsten-disulfide-channel-based memory device is created by sandwiching high-density-of-states multi-layered graphene as a carrier-confining layer between tunnel barriers of hexagonal boron nitride (hBN) and silicon dioxide. The results reveal that a memory window of up to 20 V is opened, leading to a high current ratio (>103) between programming and erasing states. The proposed design combination produced layered materials that allow devices to attain perfect retention at 13% charge loss after 10 years, offering new possibilities for the integration of transparent, flexible electronic systems. [ABSTRACT FROM AUTHOR]

Endothelial cell (EC) activation and inflammation is a key step in the initiation and progression of many cardiovascular diseases. Targeted delivery of therapeutic reagents to inflamed EC using nanoparticles is challenging as nanoparticles do not arrest on EC efficiently under high shear stress. In this study, we developed a novel polymeric platelet-mimicking nanoparticle for strong particle adhesion onto ECs and enhanced particle internalization by ECs. This nanoparticle was encapsulated with dexamethasone as the anti-inflammatory drug, and conjugated with polyethylene glycol, glycoprotein 1b, and trans-activating transcriptional peptide. The multi-ligand nanoparticle showed significantly greater adhesion on P-selectin, von Willebrand Factor, than the unmodified particles, and activated EC in vitro under both static and flow conditions. Treatment of injured rat carotid arteries with these multi-ligand nanoparticles suppressed neointimal stenosis more than unconjugated nanoparticles did. These results indicate that this novel multi-ligand nanoparticle is efficient to target inflamed EC and inhibit inflammation and subsequent stenosis. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively ( p < 1 × 10). Of these, one locus on chromosome 1p31 (rs527409) was replicated in 266 children with KD and 600 normal controls (odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.85-4.54, P = 1.46 × 10); and a PELI1 locus on chromosome 2p13.3 (rs7604693) was replicated in 86 KD patients with CALs and 600 controls (OR = 2.70, 95% CI = 1.77-4.12, P = 2.00 × 10). These results implicate a locus in the 1p31 region and the PELI1 gene locus in the 2p13.3 region as susceptibility loci for KD and CALs, respectively. [ABSTRACT FROM AUTHOR]

Here, we prepared self-setting calcium phosphate cements (CPCs) based on α-tricalcium phosphate with the incorporation of sodium alginate, and their mechanical properties and in vitro cellular responses were investigated. The addition of alginate enhanced the hardening reaction of CPCs showing shorter setting times within a range of powder-to-liquid ratios. When immersed in a body simulating fluid the alginate-CPCs fully induced a formation of an apatite crystalline phase similar to that of bare CPCs. The compressive and tensile strengths of the CPCs were found to greatly improve during immersion in the fluid, and this improvement was more pronounced in the alginate-CPCs. As a result, the alginate-CPCs retained significantly higher strength values than the bare CPCs after 3-7 days of immersion. The rat bone marrow derived stromal cells (rBMSCs) cultured on the alginate-CPCs initially adhered to and then spread well on the cements surface, showed an on-going increase in the population with culture time, and differentiated into osteoblasts expressing bone-associated genes (collagen type I, osteopontin and bone sialoprotein) and synthesizing alkaline phosphatase. However, the stimulated level of osteogenic differentiation was not confirmative with the incorporation of alginate into the CPC composition based on the results. One merit of the use of alginate was its usefulness in forming CPCs into a variety of scaffold shapes including microspheres and fibers, which is associated with the cross-link of alginate under the calcium-containing solution. [ABSTRACT FROM AUTHOR]

In this study, a process was proposed which allows a base metal electrode to be burnt-out in an oxidative atmosphere for fabrication of multilayer ceramic device. To protect Cu in an oxidative atmosphere, the Cu powder was coated with borosilicate glass via a sol-gel process. The oxidation resistance and shrinkage of the glass-coated Cu were investigated. When a 10% glass-coated Cu was heated up to 500°C under an oxidative atmosphere, the Cu could survive without formation of copper oxide. The oxidation of the Cu was observed when heating at temperatures above 700°C. This might be due to exposure of Cu to oxidative atmosphere related to softening behavior of glass. The glass-coated Cu exhibited a shrinkage behavior which follows the shrinkage behavior of glass in the low temperature range and the shrinkage of pure Cu in the high temperature range. To measure the electrical conductivity of the glass-coated Cu electrode, the Cu pastes were prepared and printed onto alumina substrate. The binder-burn-out process of the glass-coated Cu was carried out at 550°C under an air atmosphere, and was then sintered at 1000°C under a nitrogen atmosphere. The electrical conductivity of the Cu electrode measured was above 10 /Ωcm which means that it can be used as the internal electrode of a multilayer device. [ABSTRACT FROM AUTHOR]

The marine alginate lyase from Streptomyces sp. ALG-5, which specifically degrades poly-G block of alginate, was functionally expressed as a His-tagged form with an Escherichia coli expression system. The recombinant alginate lyase expressed with pColdI at 15 °C exhibited the highest alginate-degrading activity. The recombinant alginate lyase was efficiently immobilized onto two types of magnetic nanoparticles, superparamagnetic iron oxide nanoparticle, and hybrid magnetic silica nanoparticle, based on the affinity between His-tag and Ni that displayed on the surfaces of nanoparticles. An alginate oligosaccharide mixture consisting of dimer and trimer was prepared by the immobilized alginate lyase. The immobilized enzymes were re-used repeatedly more than 10 times after magnetic separation. [ABSTRACT FROM AUTHOR]

In the present study, we confirmed the ability of M. hyopneumoniae to induce the secretion of large amount of proinflammatory cytokine and nitric oxide (NO) in murine macrophage RAW 264.7 cells. Moreover, M. hyopneumoniae-induced activation of the MAPK and NF-кB pathways by phosphorylation of ERK1/2, p38 and JNK/SAPK and by dissociation of IκB from NF-κB. Translocation of transcription factor NF-κB and its binding was confirmed through western blot and electromobility shift assay. From these results, we further hypothesized that these signal proteins were involved in M. hyopneumoniae-induced proinflammatory cytokines and NO productions in macrophages. Hence, we utilized specific blockers of MAPK and NF-κB to investigate the signaling pathway involvement in cytokine and NO production through pharmacological approaches. The results demonstrated significant inhibition of TNF-α, IL-1β, IL-6 and NO by MAPK inhibitors. NF-κB inhibitor PDTC significantly inhibited IL-1β and NO production. These findings contribute to the understanding of the mechanisms of immune reactivity and may ultimately prove useful in the development of new therapeutic strategies. In summary, we found critical evidence for the involvement of NF-κB and MAPK signaling pathways in the upregulation of proinflammatory cytokine and NO induced by M. hyopneumoniae. [ABSTRACT FROM AUTHOR]

Calcium phosphate cements (CPCs) have recently gained great interest as injectable bone substitutes for use in dentistry and orthopedics. α-tricalcium phosphate (α-TCP) is a popularly used precursor powder for CPCs. When mixed with appropriate content of liquid and kept under aqueous conditions, α-TCP dissolves to form a calcium-deficient hydroxyapatite and then hardens to cement. In this study, α-TCP based cement (CP) and its composite cement with chitosan (Ch-CP) were prepared and the osteoclastic responses to the cements and their elution products were evaluated. Preliminary evaluation of the cements revealed that the CP and Ch-CP hardened within ~10 min at an appropriate powder-to-liquid ratio (PL) of 3.0. In addition, CP and Ch-CP were transformed into an apatite phase following immersion in a saline solution. Moreover, the osteoblastic cells were viable on the cements for up to 10 days. Mouse-derived bone marrow cells were isolated and activated with osteoclastic differentiation medium, and the effects of the CP and Ch-CP substrates and their ionic eluants on the osteoclastic activity were investigated. Osteoclastic cells were viable for up to 14 days on both types of cements, maintaining a higher cell growth level than the control culture dish. Multi-nucleated osteoclastic cells that were tartrate-resistant acid phosphatase (TRAP)-positive were clearly observed when cultured on the cement substrates as well as treated with the cement eluants. The TRAP activity was found to be significantly higher in cells influenced by the cement substrates and their eluants with respect to the control culture dish (Ch-CP > CP ≫ control). Overall, the osteoclastic differentiation was highly stimulated by the α-TCP based experimental cements in terms of both the substrate interaction and their elution products. [ABSTRACT FROM AUTHOR]

It has been suggested that oxidative stress is associated with the pathogenesis of osteoporosis. The objective of this study was to explore the association between a marker of oxidative stress and either bone turnover markers or bone mineral density (BMD) in postmenopausal women. In addition, the effects of oxidative stress on the formation of osteoclasts in human bone marrow cell culture were examined. We performed a cross-sectional analysis in healthy postmenopausal women aged 60–78 years ( n = 135, 68.2 ± 4.9). Oxidative stress was evaluated in the serum by measuring 8-hydroxy-2′-deoxyguanosine (8-OH-dG) levels. The biochemical markers of bone turnover and areal BMD were measured in all participants. Multivariate linear regression analysis revealed a negative association between 8-OH-dG levels and BMD of the lumbar spine, total hip, femoral neck, and trochanter and positive association with type I collagen C-telopeptide (ICTP) levels. The odds ratio of 8-OH-dG for osteoporosis was 1.54 (1.14–2.31, P = 0.003). In cultures of primary human marrow cells, HO caused concentration-dependent activation of TRAP-positive multinucleated giant cells. HO also increased the area of pits per osteoclast activity assay substrate. RT-PCR showed that HO stimulated the expression of M-CSF and RANKL and increased the RANKL/OPG ratio. The data support the view that oxidative stress is associated with increased bone resorption and low bone mass in otherwise healthy women. In addition, RANKL and M-CSF stimulation induced by oxidative stress may participate in osteoclastogenesis in human bone. [ABSTRACT FROM AUTHOR]

Fauna assemblages reflect their habitat relating to ecological function in an ecosystem. The functional groups are concerned with how a resource is processed by different species to provide a specific ecosystem service or function. We elucidated seasonal changes of coleopteran functional groups in forests, and evaluated their ecological roles related to available food resources. Coleopteran communities were collected weekly or biweekly using Malaise traps at nine study sites in Japanese red pine forests in Korea from late June to September 2005. Compositions of the functional groups were compared at the different sites and at sampling times with respect to taxa richness and abundance. Cluster analysis and non-metric multidimensional scaling were used to characterize spatial and temporal changes of functional groups. Herbivores and dead/live wood feeders regulating primary production in the pine forests were the dominant coleopteran groups in July, followed by detritivores and predators that dominated from July to August, resulting from the accumulation of detritus. Then, fungivores became dominant due to increased fungal biomass in the forest. Seasonal changes of coleopteran functional groups shifted from regulators of primary production to regulators of decomposition, reflecting their available food resources. In addition, abundance of detritivores and predators were dependent on total abundance of coleopterans, suggesting that these two groups reflect their habitat condition. [ABSTRACT FROM AUTHOR]

We evaluated the potential of a quartz crystal microbalance with dissipation monitoring (QCM-D) to provide a sensitive, label-free method for detecting the conformational rearrangement of glycoprotein gp120 upon binding to different ligands. This glycoprotein is normally found on the envelope of the HIV-1 virus and is involved in viral entry into host cells. It was immobilized on the surface of the sensing element of the QCM-D and was exposed to individual solutions of several different small-molecule inhibitors as well as to a solution of a soluble form of the host cell receptor to which gp120 binds. Instrument responses to ligand-triggered changes were in qualitative agreement with conformational changes as suggested by other biophysical methods. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The conversion of natural gas(methane) to syngas (reforming reaction) is regarded as alternative routes for production of great value compounds, such as synthetic liquid fuels and oxygenated compounds. The aim of this work is to investigate the highest activity catalyst among 30 catalyst candidates which consists of Ni-M [M (promoter) = Co, Fe, Ce] on γ-Al2O3, by combinatorial method for autothermal reforming. The catalyst candidates with different M/Ni molar ratio were prepared by the impregnation method. The consistent results were found between 32 channel reactors and single fixed bed reactor. It was found that the best catalyst is 5.54 wt%Ni-13.3wt% Ce/γ-Al2O3. [ABSTRACT FROM AUTHOR]

Abstract  In this study, we present in vitro cytotoxicity of iron oxide (Fe3O4) and manganese oxide (MnO) using live/dead cell assay, lactate dehydrogenase assay, and reactive oxygen species detection with variation of the concentration of nanoparticles (5–500 μg/ml), incubation time (18–96 h), and different human cell lines (lung adenocarcinoma, breast cancer cells, and glioblastoma cells). The surface of nanoparticles is modified with polyethyleneglycol-derivatized phospholipid to enhance the biocompatibility, water-solubility, and stability under an aqueous media. While the cytotoxic effect was negligible for 18 h incubation even at highest concentration of 500 μg/ml, MnO nanoparticle represented higher level of toxicity than those of Fe3O4 and the commercial medical contrast reagent, Feridex after 2 and 4 day incubation time. However, the cytotoxicity of Fe3O4 is equivalent or better than Feridex based on the live/dead cell viability assay. The engineered MnO and Fe3O4 exhibited excellent stability compared with Feridex for a prolonged incubation time. [ABSTRACT FROM AUTHOR]

A fuzzy logic controller (FLC) for mobile robots is designed in hierarchical structure. The designed FLC consists of two levels: the planner level and the motion control level. The planner level generates a path to the destination by avoiding obstacles. The singleton outputs of the planner are obtained by using lines and arc methods. The lower motion control level calculates the robot's wheel velocity so as to follow the path generated by the planner as to the current robot posture. The fuzzy singleton outputs are obtained by heuristics and tuned by evolutionary programming. The applicability of the controller is demonstrated by using robot soccer system. [ABSTRACT FROM AUTHOR]

The development of bioactive scaffolds with a designed pore configuration is of particular importance in bone tissue engineering. In this study, bone scaffolds with a controlled pore structure and a bioactive composition were produced using a robotic dispensing technique. A poly(ε-caprolactone) (PCL) and hydroxyapatite (HA) composite solution (PCL/HA = 1) was constructed into a 3-dimensional (3D) porous scaffold by fiber deposition and layer-by-layer assembly using a computer-aided robocasting machine. The in vitro tissue cell compatibility was examined using rat bone marrow stromal cells (rBMSCs). The adhesion and growth of cells onto the robotic dispensed scaffolds were observed to be limited by applying the conventional cell seeding technique. However, the initially adhered cells were viable on the scaffold surface. The alkaline phosphatase activity of the cells was significantly higher on the HA–PCL than on the PCL and control culture dish, suggesting that the robotic dispensed HA–PCL scaffold should stimulate the osteogenic differentiation of rBMSCs. Moreover, the expression of a series of bone-associated genes, including alkaline phosphatase and collagen type I, was highly up-regulated on the HA–PCL scaffold as compared to that on the pure PCL scaffold. Overall, the robotic dispensed HA–PCL is considered to find potential use as a bioactive 3D scaffold for bone tissue engineering. [ABSTRACT FROM AUTHOR]

The article presents a study on the connection between daily physical activity (PA) and the neighborhood environments (NE) of residents in Japan. The subjects were chosen through a random sampling method by sex and age in region with high and low residential density, land use mix-diversity and street connectivity. Residents' activities include cycling in female and walking in males. The study revealed that daily PA was high in women and in men, PA is high for those are into leisure walking.

Abstract  Rituximab is a chimeric monoclonal antibody directed against the phosphoprotein CD20. Because of its efficacy and acceptable toxicity profile, rituximab is now commonly used for the treatment of CD20-positive B-cell malignancies, including B-cell non-Hodgkin’s lymphoma. However, rituximab-induced acute thrombocytopenia is an extremely rare side effect. We report a case of acute thrombocytopenia occurring immediately after rituximab infusion in a mantle cell lymphoma patient with bone marrow involvement and massive splenomegaly. Although the mechanism of thrombocytopenia is still unclear, it is possible that tumor burden, bone marrow involvement, the presence of infusion-related symptoms, and mantle cell histology are related to this rare complication of rituximab therapy. Hence, rituximab should be used with caution in patients who have these factors, and clinicians must be aware of this rare, but serious, side effect. [ABSTRACT FROM AUTHOR]

We consider the general solution of quartic functional equations and prove the Hyers-Ulam- Rassias stability. Moreover, using the pullbacks and the heat kernels we reformulate and prove the stability results of quartic functional equations in the spaces of tempered distributions and Fourier hyperfunctions. [ABSTRACT FROM AUTHOR]

Some basal ganglia germinomas are difficult to diagnose in early stage of disease due to vague initial presentation without discernable mass lesion on brain imaging. We performed this study to determine the usefulness of 11C-methionine positron emission tomography (MET PET) for the diagnosis and monitoring of disease activity. MET PET was performed in three consecutive patients; they presented with cerebral hemiatrophy without definite mass lesions on brain image. The maximum standard tracer uptake values (max SUVs) were calculated and used for the quantitative evaluation of the abnormal MET uptake. A pathological diagnosis was made after stereotactic biopsy using MET PET/computed tomography. The max SUVs significantly decreased after treatment. Basal ganglia germinoma should be considered in the differential diagnosis of patients with progressive hemiparesis and hemiatrophy on magnetic resonance imaging. The MET PET was useful for diagnosis, and it can be valuable in evaluation of treatment effects and monitoring for tumor recurrence. [ABSTRACT FROM AUTHOR]

Iron, zinc, copper, lead, and cadmium were measured in livers of three shorebird species from Okgu Mudflat, Korea in the East Asian-Australian migration flyways. Iron concentrations in red-necked stints (Calidris ruficollis) (geomean = 1,322 μg/g dw) were higher than in terek sandpipers (Xenus cinereus) (467 μg/g dw), and great knots (Calidris tenuirostris) (158 μg/g dw). Copper concentrations in great knots (85.8 μg/g dw) were significantly higher than in red-necked stints (15.9 μg/g dw) and terek sandpipers (10.4 μg/g dw). However, significant differences in zinc concentrations were not found in livers among shorebird species. Iron, zinc, and copper concentrations from this study were within the range of other shorebird studies. We suggest that essential elements such as iron, zinc, and copper are within normal range and are maintained there by normal homeostatic mechanism. Lead and cadmium concentrations differed among shorebird species; red-necked stints (geomeans 27.8 μg/g dw and 4.69 μg/g dw, respectively) were higher than in terek sandpipers (12.9 and 0.44 μg/g dw, respectively), and great knots (5.43 and 0.29 μg/g dw, respectively). Some rednecked stints exceeded toxic levels of lead and cadmium for wild birds. In livers of red-necked stints from Okgu Mudflat, lead and cadmium concentrations were higher than previously reported in other shorebirds. [ABSTRACT FROM AUTHOR]

Abstract  Nicotine is the principal psychoactive ingredient in cigarette smoke, and has been associated with health problems in humans. However, the pure form of nicotine may prove to be a valuable pharmaceutical agent for the treatment of AD. However, the beneficial effects of nicotine remain a matter of much controversy. In order to clarify this issue, 12-month-old transgenic mice, expressing neuron-specific enolase (NSE)-controlled APPsw, were treated with low, middle, and high doses of nicotine for 6 months. Herein, we have concluded that the nicotine-treated groups evidenced improvements in behavior and increases in the nicotine acetylcholine receptor, nAchRα7. These findings provide experimental evidence that nicotine effects an improvement in impaired memory, and that this improvement is associated with an increase in nAchRα7. Thus, nicotine may prove a good preventative or therapeutic modality for AD patients. [ABSTRACT FROM AUTHOR]

Abstract   Background We investigated the relation between risk factors of coronary artery disease (CAD) and myocardial ischemia detected by 201Tl SPECT in elderly women. Methods 306 women aged ≥75 yr (79.1 ± 3.6 yr) who underwent pharmacologic 201Tl SPECT for suspected CAD based on symptoms or CAD risk factors were included. Coronary risk factors were evaluated by medical records, and included diabetes mellitus (DM), hypertension, hypercholesterolemia, cigarette smoking, greater age (≥80 yr), and obesity. Summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were calculated based on stress and redistribution SPECT images for semiquantification. Results The symptomatic group (n = 110) had a 34.5% perfusion defect rate. The asymptomatic group (n = 196) had a significantly lower perfusion defect rate of 16.8%. However, this significantly increased to 29.4% and 22.0% in the presence of diabetes mellitus (DM) and hypertension, respectively. In addition, the summed stress score of asymptomatic patients (12.4 ± 6.0) was not lower but comparable to that of symptomatic patients (10.0 ± 6.0). Conclusions In elderly women suspected of CAD, pharmacologic perfusion imaging can be used to identify myocardial ischemia in patients with angina as well as asymptomatic subjects with concurrent DM or hypertension. [ABSTRACT FROM AUTHOR]

The article offers an overview of the study which examines the stability of a quadratic functional equation in the spaces of generalized functions. Making use of the pullbacks, it reformulated the quadratic equation f (x + y + z) + f (x) + f (y) + f (z) = f(x + y) + f ( y + z ) + f ( z + x ) in the spaces of generalized functions. It also used the fundamental solution of the heat equation, it obtained the general solution and proved the Hyers-Ulam stability of this equation in spaces of generalized functions such as tempered distributions and Fourier hyperfunctions.

The aim of this phase II study was to evaluate the response rate to gemcitabine combined with cisplatin in patients with locally advanced, metastatic or recurrent biliary tract cancer who had received no prior chemotherapy. The treatment consisted of cisplatin 70 mg/m2 in intravenous infusion followed by gemcitabine 1,250 mg/m2 in 30-min intravenous infusion on days 1 and 8, repeated every 3 weeks until disease progression, unacceptable toxicity, patient’s refusal or up to 8 cycles. Thirty-nine patients with advanced biliary cancer were enrolled between March 2003 and August 2003. Fourteen patients (40%) had gall bladder cancer and 20 patients (57%) had cholangiocarcinoma. Thirty-two patients (91%) had metastatic disease at study entry with liver being the most commonly involved site of metastasis. About 84.5 and 94.2% of the initially planned dose were administered for gemcitabine and cisplatin, respectively. In the ITT population ( n = 35), six partial responses were observed for an objective response rate of 17.1% (95% CI; 4.7–29.6%). Ten patients (28.6%) had stable disease, 16 (45.7%) progressed, and three (8.6%) were not evaluable. For the 35 patients in the ITT population, the median overall survival time was 8.6 months (95% CI; 6.1–10.4 months). The median time to disease progression was 3.2 months (95% CI; 2.3–4.9 months) and the median time to treatment failure was 3.1 months (95% CI; 1.9–4.1 months). Among the six tumor responders, the median duration of tumor response was 7.3 months (95% CI; 5.6–11.0 months). The most common grade 3/4 maximum toxicities were nausea (3.4%) and vomiting (2.7%). The combination chemotherapy with gemcitabine and cisplatin in this trial demonstrated moderate antitumor activity with favorable toxicity profile. [ABSTRACT FROM AUTHOR]

Abstract  Singlet oxygen is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules and it also promotes deleterious processes such as cell death. Recently, we demonstrated that the control of redox balance and the cellular defense against oxidative damage are the primary functions of cytosolic NADP+dependent isocitrate dehydrogenase (IDPc) through supplying NADPH for antioxidant systems. In this report, we demonstrate that modulation of IDPc activity in HL-60 cells regulates singlet oxygen-induced apoptosis. When we examined the protective role of IDPc against singlet oxygen-induced apoptosis with HL-60 cells transfected with the cDNA for mouse IDPc in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPc expressed in target cells and their susceptibility to apoptosis. The results suggest that IDPc plays an important protective role in apoptosis of HL-60 cells induced by singlet oxygen. [ABSTRACT FROM AUTHOR]

This study presents the sintering behavior of silver/palladium electrode powders to which have been added TiO2 nanoparticles, and the effect this additive has on the ability of the electrode to match the characteristics of piezoelectric ceramics, Pb(Zr, Ti)O3. The densification (shrinkage) of the electrodes was investigated as a function of sintering temperature, and the reaction between the ceramic matrix and the electrodes was studied. The densification of the TiO2-enhanced electrode paste during the sintering process was explained with reference to a solid-state diffusion mechanism which integrated the TiO2 into the ceramic. Reactions occurred between the ceramic and electrode layers, resulting in reduced internal stress and enhanced mechanical adhesion. Based on these results, it is clear that high adhesive strength and good electrical conductivity of more than 104/Ω cm can be obtained in multilayer ferroelectric devices composed of stacks of ceramic and electrode layers provided the contain these nanoparticles. In the sintering process, interfacial diffusion of TiO2 occurred and, as a consequence, coarse grains of PZT were formed at the interface. [ABSTRACT FROM AUTHOR]

The article focuses on the stability of cubic functional equation in the spaces of generalized functions. It is proved that the Hyers-Ulam-Rassias stability theorem cubic functional equation of the cubic functional equation f ( ax + y ) + f ( ax - y ) = af ( x + y ) + af ( x - y ) + 2a(a2 - 1 ) f ( x ) for fixed integer a with a ≠ 0, ± 1 in the spaces of Schwartz tempered distributions and Fourier hyperfunctions. It is mentioned that in 1940, questions concerning the stability of group homomorphisms was solved by Hyers, assuming that G1 and G2 are Banach spaces. It is said that in 1978, Rassias generalized Hyers' result to the unbounded Cauchy difference.

The article presents a study which delineates the association between the perception of resident on the neighborhood's environments and walking time in objectively different regions of Japan. The subjects of the study were participants of health promotion program that focused on walking activity in the street. The results suggested that the perception of the neighborhood's environmental factors which correlates on walking time differs the differential regional physical environment.

A practical neutral aromatic nitration process using nitrogen dioxide in the presence of FeCl3 · 6H2O under 40–100 psig of oxygen was developed, and nitration of several aromatic compounds, including the deactivated nitrobenzene, was performed in a successful manner. The correlation of reaction rate with equivalents nitrogen dioxide, oxygen pressure, amount of catalyst and temperature was investigated through the nitration of benzene. Following the optimization of reaction conditions, the nitration of benzene was scaled up to 476 mol. Furthermore, inorganic solid catalysts with pore size over 5 Å and surface area over 100 m2/g were applied to newly developed neutral nitration. [ABSTRACT FROM AUTHOR]

Abstract  The complexity of Alzheimer’s disease (AD) has made it difficult to examine its underlying mechanisms. A gene microarray offers a solution to the complexity through parallel analysis of most of the genes expressed in the hippocampal tissues from AD-transgenic and age-matched control littermates. This study examined the potential effect of APPsw over-expression on the modulation of genes for AD. To accomplish this, an oligonucleotide array was used with the large-scale screening of the hippocampus mRNA from 12-month-old APPsw-transgenic and control mice. There was a total of 116 differentially expressed genes, 59 up-regulated and 57 down-regulated, in the hippocampal region of the transgenic mice compared with the control mice. Initially, two of each of the down-regulated (Xlr3b and Mup3) and up-regulated genes (Serpina9 and Ccr6) were chosen for further investigation if the magnitude of change in these genes on the oligonucleotide array would correspond to those in the RT-PCR analysis from APPsw-transgenic mice. We also found that the changes in the differentially expressed genes are reliable. Thus, these genes might associate with AD neuropathology in neurodegenerative process of AD, although relevance of long lists altered genes should be evaluated in a future study. [ABSTRACT FROM AUTHOR]

The article investigates the "doughnut effect" in Cy3-labeled protein microarrays using scanning near-field optical microscope. The study has emphasized on the micron sized spots of human Immunoglobin G protein, with and without a Cy3 dye labeling, which have been fabricated on glass substrates by an immobilization method that has made use of calixcrown derivatives termed Prolinker.

Insulin-degrading enzyme (IDE) is a 110-kDa thiol zinc-methalloendopeptidase that can cleave small Aβ peptides and the APP intracellular domain (AICD). The aim of this study was to examine aging-related correlation of IDE with γ-secretase-generated products involving insulin and glucose levels in transgenic brains expressing neuron-specific enolase (NSE)-controlled human mutant presenilin-2 (hPS2m). Herein, we concluded that the levels of IDE expression in transgenic brains were decreased relative to those of control mice at 15 months of age. In parallel, inhibition in the IDE expression at this age underlies to the levels-up of Aβ-42, AICD, γ-secretase, and glucose with a level-down of insulin. Thus, IDE expression is critical target for the therapeutic trials. [ABSTRACT FROM AUTHOR]

Pin1 binds mitotically phosphorylated Thr231–Pro232 and Thr212–Pro213 sites on tau, and a Pin1 deficiency in mice leads to tau hyperphosphorylation. The aim of this study was to determine if the dephosphorylation or inhibition of tau and GSK3β phosphorylation induces the Pin1 phosphorylation. To test this, human SK-N-MC cells were stably transfected with a fusion gene containing neuron-specific enolase (NSE)-controlled APPsw gene(NSE/APPsw), to induce Aβ-42. The stable transfectants were then transiently transfected with NSE/Splice, lacking human tau (NSE/Splice), or NSE/hTau, containing human tau, into the cells. The NSE/Splice- and NSE/hTau-cells were then treated with lithium. We concluded that (i) there was more C99-β APP accumulation than C83-βAPP in APPsw-tansfectant and thereby promoted Aβ-42 production in transfectants. (ii) the inhibition of tau and GSK3β phosphorylations correlated with increase in Pin1 activation in NSE/hTau- cells. Thus, these observations suggest that Pin1 might have an inhibitive role in phosphorylating tau and GSK3β for protecting against Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Mutations in genes for Alzheimer’s disease (AD) result in a modulating of gene expressions in the brains of patients with AD. The aim of this study was to identify genes whose expression is modulated due to the over-expression of human mutant presenilin-2 (N141I) (hPS2m) in transgenic mice, which has previously been produced by us. To test this, GeneFishingTM DEG101 technique was performed on large-scale screen of mRNA from transgenic and non-transgenic brains. A total of 40 transcriptional products corresponding to cDNA were compared between two brains, and 17 showed a differential expression between the samples in all sets of experiments. However, all showed significant homology to known genes. Initially, a cloning corresponding to human selenoprotein M (hSelM) was chosen for investigation further because SelM induced by sodium selenite, a pro-oxidant, may have a functional role in catalyze the free radicals. We found that mouse SelM had significantly suppressed on its transcriptional products in transgenic brains. In parallel, suppression of endogenous was not observed in transgenic brains. Moreover, the levels of green fluorescence on hSelM fusion protein with EGFP were suppressed in the cells transfected with hPS2m, and its levels had actually increased by treatments of sodium selenite. Thus, the results indicate that SelM might play a suppressive or protective role in the pathology of patients with AD and it will be necessary to investigate further on functional roles of other up- and down-regulated gene in future. [ABSTRACT FROM AUTHOR]

Pt thin films of various thicknesses (30 nm ∼ 200 nm) were deposited on Si wafers with SiO2, Ti, TiO2, or IrO2 buffer layers at various temperatures (room temperature ∼ 200 °C) by a direct current magnetron sputtering process. The Pt films showed a strong (111)-preferred texture irrespective of the thickness, under-layer, and growth temperature. The authors previously reported [J-E. Lim, D-Y. Park, J.K. Jeong, G. Darlinski, H.J. Kim, and C.S. Hwang, App!. Phys. Lett. 81, 3224 (2002)] that the films were composed of three kinds of grains with slightly different (111) lattice parameters (bulklike, 1.0% and 2.1% larger). This study details the microstructural variations of the Pt films according to the variations of experimental parameters. The different deposition conditions produced slightly different crystalline structures, but the three different (111) lattice parameters were always found. Epitaxial (200) Pt films on a (200) MgO substrate and a highly (111) textured Au thin film on a SiO2/Si did not show the same splitting in the lattice parameter. The grains with 1.0% and 2.1% larger (111) lattice parameter almost disappeared after postannealing at 1000 °C. However, surface chemical binding of the Pt film before and after annealing was unchanged. Therefore, it is believed that the lattice parameter splitting in the (111) textured Pt film originated from the interfacial grains with the distorted crystal structure due probably to growth stress. [ABSTRACT FROM AUTHOR]

The role of the subunits of phosphoinositide (PI) 3-kinase in NF-κB activation in silica-stimulated RAW 264.7 cells was investigated. Results indicate that PI3-kinase activity was increased in response to silica. The p85&agr; subunit of PI3-kinase interacted with tyrosine-phosphorylated IκB-&agr; in silica-stimulated cells. PI3-kinase specific inhibitors, such as wortmannin and LY294003, substantially blocked both silica-induced PI3-kinase and NF-κB activation. The inhibition of NF-κB activation by PI3-kinase inhibitors was also observed in pervanadate-stimulated but not in LPS-stimulated cells. Furthermore, tyrosine phosphorylation of NF-κB p65 was enhanced in cells stimulated with silica, pervanadate or LPS, and wortmannin substantially inhibited the phosphorylation event induced by the first two stimulants but not LPS. Antioxidants, such as superoxide dismutase (SOD), N-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), blocked silica-induced PI3-kinase activation, suggesting that reactive oxygen species may be important regulatory molecules in NF-κB activation by mediating PI3-kinase activation. Our data suggest that p85 and p110 subunits of PI3-kinase play a role in NF-κB activation through interaction with tyrosine-phosphorylated IκB-&agr; and contributing to tyrosine phosphorylation of p65 NF-κB. [ABSTRACT FROM AUTHOR]