Transfer printing of vertical-type microscale light-emitting diode array onto flexible substrate using biomimetic stamp.

We report the transfer printing of GaN-based microscale vertical-type light-emitting diodes (µ-VLEDs) using a functional layer and a biomimetic stamp. An oxide-based functional layer is inserted onto the structure of a µ-VLED and used to separate the chip from the µ-VLED wafer by absorbing the pulse of a UV pulse laser during pick-up of the transfer printing process. Polydimethylsiloxane (PDMS)-based biomimetic stamps have been fabricated to mimic the gecko lizard cilia for improved adhesion and repeatability. The biomimetic stamp has an adhesion force of 25.6 N/cm2, which is 12 times the adhesion of a flat stamp; an adhesion force of 10 N/cm2 or more was maintained after 100,000 repeated adhesion tests. A flexible 10 × 10 prototype array on a polyimide substrate was fabricated, and its bending test results indicated that the strain effect on the forward voltage and the output power was less than 1%. The stable bending test results of the prototype indicate that µ-VLEDs using biomimetic stamps allow the necessary stability for practical transfer printing.

Grading system for migrated lumbar disc herniation on sagittal magnetic resonance imaging: an agreement study.

PURPOSE: Migrated lumbar disc herniations (LDHs) in the sagittal plane are common. Disc migration grading can be applied as a useful measurement tool in the diagnosis, treatment, and outcome evaluation of migrated LDH. No study has evaluated the reliability of migrated LDH grading. We evaluated the reliability and functionality of the current magnetic resonance imaging (MRI) grading system for migrated LDH. METHODS: We assessed a six-level grading system developed based on sagittal MRI and graded according to the direction (rostral and caudal) and degree (low, high, and very high) of disc migration. One-hundred and one migrated LDHs treated with minimally invasive endoscopic discectomy were analyzed independently by two experienced radiologists. Intraobserver and interobserver agreements were assessed by kappa statistics. RESULTS: The most common migrated LDH grade was grade 4 (30.94%; caudal, low-grade migration). Rostral and caudal migrations were more common in the upper and lower lumbar levels, respectively. Interobserver agreement in the grading of migrated LDH was good at both the first (kappa = 0.737) and second assessment (kappa = 0.657). The intraobserver agreement for reader 1 was very good (kappa = 0.827) and for reader 2 was good (kappa = 0.620). CONCLUSIONS: The current grading system for migrated LDH was found to be reliable and functional with good interobserver and intraobserver agreement. It may be useful in the interpretation of disc migration patterns and outcomes of various minimally invasive surgical procedures.

Surface modulation and back reflection from foil targets irradiated by a Petawatt femtosecond laser pulse at oblique incidence.

A significant level of back reflected laser energy was measured during the interaction of ultra-short, high contrast PW laser pulses with solid targets at 30° incidence. 2D PIC simulations carried out for the experimental conditions show that at the laser-target interface a dynamic regular structure is generated during the interaction, which acts as a grating (quasi-grating) and reflects back a significant amount of incident laser energy. With increasing laser intensity above 1018 W/cm2 the back reflected fraction increases due to the growth of the surface modulation to larger amplitudes. Above 1020 W/cm2 this increase results in the partial destruction of the quasi-grating structure and, hence, in the saturation of the back reflection efficiency. The PIC simulation results are in good agreement with the experimental findings, and, additionally, demonstrate that in presence of a small amount of pre-plasma this regular structure will be smeared out and the back reflection reduced.

Passive and post-exercise cold-water immersion augments PGC-1α and VEGF expression in human skeletal muscle.

PURPOSE: We tested the hypothesis that both post-exercise and passive cold water immersion (CWI) increases PGC-1α and VEGF mRNA expression in human skeletal muscle. METHOD: Study 1 Nine males completed an intermittent running protocol (8 × 3-min bouts at 90 % [Formula: see text], interspersed with 3-min active recovery (1.5-min at 25 % and 1.5-min at 50 % [Formula: see text]) before undergoing CWI (10 min at 8 °C) or seated rest (CONT) in a counterbalanced, randomised manner. Study 2 Ten males underwent an identical CWI protocol under passive conditions. RESULTS: Study 1 PGC-1α mRNA increased in CONT (~3.4-fold; P < 0.001) and CWI (~5.9-fold; P < 0.001) at 3 h post-exercise with a greater increase observed in CWI (P < 0.001). VEGFtotal mRNA increased after CWI only (~2.4-fold) compared with CONT (~1.1-fold) at 3 h post-exercise (P < 0.01). Study 2 Following CWI, PGC-1α mRNA expression was significantly increased ~1.3-fold (P = 0.001) and 1.4-fold (P = 0.0004) at 3 and 6 h, respectively. Similarly, VEGF165 mRNA was significantly increased in CWI ~1.9-fold (P = 0.03) and 2.2-fold (P = 0.009) at 3 and 6 h post-immersion. CONCLUSIONS: Data confirm post-exercise CWI augments the acute exercise-induced expression of PGC-1α mRNA in human skeletal muscle compared to exercise per se. Additionally CWI per se mediates the activation of PGC-1α and VEGF mRNA expression in human skeletal muscle. Cold water may therefore enhance the adaptive response to acute exercise.

Comparison of live performance and meat quality parameter of cross bred (korean native black pig and landrace) pigs with different coat colors.

Five hundred and forty crossbred (Korean native black pig×Landrace) F2 were selected at a commercial pig farm and then divided into six different coat color groups: (A: Black, B: White, C: Red, D: White spot in black, E: Black spot in white, F: Black spot in red). Birth weight, 21st d weight, 140th d weight and carcass weight varied among the different coat color groups. D group (white spot in black coat) showed a significantly higher body weight at each weigh (birth weight, 140th d weight and carcass weight) than did the other groups, whereas the C group (red coat color) showed a significantly lower body weight at finishing stage (140th d weight and carcass weight) compared to other groups. Meat quality characteristics, shear force, cooking loss and meat color were not significantly different among the different coat color groups, whereas drip loss was significantly higher in F than in other groups. Most blood characteristics were not significantly different among the different groups, except for the red blood cells.

Laser-driven proton acceleration enhancement by nanostructured foils.

Nanostructured thin plastic foils have been used to enhance the mechanism of laser-driven proton beam acceleration. In particular, the presence of a monolayer of polystyrene nanospheres on the target front side has drastically enhanced the absorption of the incident 100 TW laser beam, leading to a consequent increase in the maximum proton energy and beam charge. The cutoff energy increased by about 60% for the optimal spheres' diameter of 535 nm in comparison to the planar foil. The total number of protons with energies higher than 1 MeV was increased approximately 5 times. To our knowledge this is the first experimental demonstration of such advanced target geometry. Experimental results are interpreted and discussed by means of 2(1/2)-dimensional particle-in-cell simulations.

Gamma-ray flash generation in irradiating a thin foil target by a single-cycle tightly focused extreme power laser pulse.

We present a regime where an ultraintense laser pulse interacting with a foil target results in high γ-photon conversion efficiency, obtained via three-dimensional quantum-electrodynamics particle-in-cell simulations. A single-cycle laser pulse is used under the tight-focusing condition for obtaining the λ^{3} regime. The simulations employ a radially polarized laser as it results in higher γ-photon conversion efficiency compared to both azimuthal and linear polarizations. A significant fraction of the laser energy is transferred to positrons, while a part of the electromagnetic wave escapes the target as attosecond single-cycle pulses.

High-repetition rate solid target delivery system for PW-class laser-matter interaction at ELI Beamlines.

L3-HAPLS (High-repetition-rate Advanced Petawatt Laser System) at ELI (Extreme Light Infrastructure) Beamlines currently delivers 0.45 PW pulses (12 J in 27 fs) at 3.3 Hz repetition rate. A fresh target surface for every shot was placed at the laser focus using an in-house tape target system designed to withstand large laser intensities and energies. It has been tested for different material thicknesses (25 and 7.6 µm), while L3-HAPLS delivered laser shots for energies ranging from 1 to 12 J. A technical description of the tape target system is given. The device can be used in diverse geometries needed for laser-matter interaction studies by providing an ≈300° free angle of view on the target in the equatorial plane. We show experimental data demonstrating the shot-to-shot stability of the device. An x-ray crystal spherical spectrometer was set up to measure the Kα yield stability, while a GHz H-field probe was used to check the shot-to-shot electromagnetic pulse generation. Finally, we discuss short and mid-term future improvements of the tape target system for efficient user operation.

Effects of castration on atherosclerosis in Yucatan minipigs with genetic hypercholesterolemia.

BACKGROUND: Low plasma testosterone, either spontaneous or as a result of androgen deprivation therapy for prostate cancer, is associated with an increased risk of cardiovascular events. The underlying mechanism in humans is not understood. Experimental studies in mice have shown that castration facilitates atherogenesis and may increase signs of plaque vulnerability. Pigs used for translational atherosclerosis research have frequently been castrated for practical or commercial reasons, but the effect of castration on atherosclerosis has never been systematically evaluated in pigs. OBJECTIVE: To study the effect of castration on atherosclerotic plaque burden and type in genetically modified minipigs with hypercholesterolemia. METHODS: Newborn male Yucatan minipigs with transgenic overexpression of a human gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 were randomized to undergo orchiectomy (n = 8) or serve as controls (n = 6). Minipigs were started on high-fat diet at 3 months of age and the amount and composition of atherosclerotic lesions were analyzed at 12 months of age. Plasma lipid profiles and behavioral parameters were also assessed. RESULTS: Plasma lipids were slightly affected to a more atherogenic profile by orchiectomy, but atherosclerotic lesion size was unaltered in the LAD, thoracic aorta, abdominal aorta, and iliac arteries. The distribution of lesion types (xanthomas, pathological intimal thickening and fibroatheromas) were also not statistically different between groups in any of the examined vascular territories. The abdominal aorta developed the most advanced stages of disease with reproducible fibroatheroma formation, and here it was found that the area of necrotic core was significantly increased in orchiectomized pigs compared with controls. Orchiectomy also reduced aggressive behavior. CONCLUSIONS: Castration does not alter the burden of atherosclerosis in hypercholesterolemic Yucatan minipigs, but may increase necrotic core area in fibroatheromas.

Identification of Plasmodium dipeptidyl aminopeptidase allosteric inhibitors by high throughput screening.

Dipeptidyl aminopeptidases (DPAPs) are cysteine proteases that cleave dipeptides from the N-terminus of protein substrates and have been shown to play important roles in many pathologies including parasitic diseases such as malaria, toxoplasmosis and Chagas's disease. Inhibitors of the mammalian homologue cathepsin C have been used in clinical trials as potential drugs to treat chronic inflammatory disorders, thus proving that these enzymes are druggable. In Plasmodium species, DPAPs play important functions at different stages of parasite development, thus making them potential antimalarial targets. Most DPAP inhibitors developed to date are peptide-based or peptidomimetic competitive inhibitors. Here, we used a high throughput screening approach to identify novel inhibitor scaffolds that block the activity of Plasmodium falciparum DPAP1. Most of the hits identified in this screen also inhibit Plasmodium falciparum DPAP3, cathepsin C, and to a lesser extent other malarial clan CA proteases, indicating that these might be general DPAP inhibitors. Interestingly, our mechanism of inhibition studies indicate that most hits are allosteric inhibitors, which opens a completely new strategy to inhibit these enzymes, study their biological function, and potentially develop new inhibitors as starting points for drug development.

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice.

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ-db/db (db/db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates (db/+) were used. Supplementation of the SBE (0.171 g/100g diet), SSE (0.154 g/100g diet), and RG (0.005 g/100g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.

Novel deletion mutation of HLA-B*40:02 gene in acquired aplastic anemia.

Despite prevalence of clonal evolution in patients with aplastic anemia (AA), somatic mutation of human leukocyte antigen (HLA) gene is rarely reported. Herein, we reported a case of acquired AA (aAA) harboring a new four-base-pair deletion mutation within exon 4 of HLA-B*40:02 leading to frameshift and premature stop codon. The HLA-B*40:02 mutant allele was detected in the patient's peripheral blood sample not in patient's buccal epithelial cells. The patient received allogenic hematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donor. On day 30 after HSCT, the mutant HLA allele was not detected by high-resolution sequence-based HLA typing. Serial chimerism analyses showed mixed chimeric status indicative of coexisting donor and recipient hematopoietic cells. Our data could provide additional support in view of pathophysiology of aAA that somatic mutation of HLA-B*40:02 allele is one of the possible origin of clonal escape to evade immune attack in patient with aAA.

CR-39 track detector for multi-MeV ion spectroscopy.

We present the characteristics of track formation on the front and rear surfaces of CR-39 produced by laser-driven protons and carbon ions. A methodological approach, based on bulk etch length, is proposed to uniquely characterize the particle tracks in CR-39, enabling comparative description of the track characteristics in different experiments. The response of CR-39 to ions is studied based on the energy dependent growth rate of the track diameter to understand the intrinsic particle stopping process within the material. A large non-uniformity in the track diameter is observed for CR-39 with thickness matching with the stopping range of particles. Simulation and experimental results show the imprint of longitudinal range straggling for energetic protons. Moreover, by exploiting the energy dependence of the track diameter, the energy resolution (δE/E) of CR-39 for few MeV protons and Carbon ion is found to be about 3%.

RESPONSE OF DOSEMETERS IN FIELDS GENERATED BY LASER-ACCELERATED PROTONS.

In laser-driven acceleration, ultra-short and intense laser pulses are focussed on targets to generate beams of ionising radiation. One of the most important issues to be addressed is personal monitoring. While traditional dosemeters were designed primarily for measurements in continuous fields, dosemeters for laser laboratories must be capable of working in pulsed fields of pulse length below 1 ps, in a single-shot regime up to the repetition rate of 1 kHz. Responses of conventional dosemeters (films, polyallyldiglycol carbonate, electronic personal dosemeter) to proton bunches of up to 30 MeV energy produced by South Korean PW laser system at the Advanced Photonics Research Institute, Gwangju Institute of Science and Technology were studied, both by means of Monte Carlo simulations and experimentally.

Calmidazolium and arachidonate activate a calcium entry pathway that is distinct from store-operated calcium influx in HeLa cells.

Agonists that deplete intracellular Ca2+ stores also activate Ca2+ entry, although the mechanism by which store release and Ca2+ influx are linked is unclear. A potential mechanism involves 'store-operated channels' that respond to depletion of the intracellular Ca2+ pool. Although SOCE (store-operated Ca2+ entry) has been considered to be the principal route for Ca2+ entry during hormonal stimulation of non-electrically excitable cells, recent evidence has suggested that alternative pathways activated by metabolites such as arachidonic acid are responsible for physiological Ca2+ influx. It is not clear whether such messenger-activated pathways exist in all cells, whether they are truly distinct from SOCE and which metabolites are involved. In the present study, we demonstrate that HeLa cells express two pharmacologically and mechanistically distinct Ca2+ entry pathways. One is the ubiquitous SOCE route and the other is an arachidonate-sensitive non-SOCE. We show that both these Ca2+ entry pathways can provide long-lasting Ca2+ elevations, but that the channels are not the same, based on their differential sensitivity to 2-aminoethoxydiphenyl borate, LOE-908 [(R,S)-(3,4-dihydro-6,7-dimethoxy-isochinolin-1-yl)-2-phenyl-N,N-di[2-(2,3,4-trimethoxyphenyl)ethyl]acetamid mesylate] and gadolinium. In addition, non-SOCE and not SOCE was permeable to strontium. Furthermore, unlike SOCE, the non-SOCE pathway did not require store depletion and was not sensitive to displacement of the endoplasmic reticulum from the plasma membrane using jasplakinolide or ionomycin pretreatment. These pathways did not conduct Ca2+ simultaneously due to the dominant effect of arachidonate, which rapidly curtails SOCE and promotes Ca2+ influx via non-SOCE. Although non-SOCE could be activated by exogenous application of arachidonate, the most robust method for stimulation of this pathway was application of the widely used calmodulin antagonist calmidazolium, due to its ability to activate phospholipase A2.

2-Aminoethoxydiphenyl borate (2-APB) antagonises inositol 1,4,5-trisphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channels.

The action of 2-aminoethoxydiphenyl borate (2-APB) on Ca(2+) signalling in HeLa cells and cardiac myocytes was investigated. Consistent with other studies, we found that superfusion of cells with 2-APB rapidly inhibited inositol 1,4,5-trisphosphate (InsP(3))-mediated Ca(2+) release and store-operated Ca(2+) entry (SOC). In addition to abrogating hormone-evoked Ca(2+) responses, 2-APB could antagonise Ca(2+) signals evoked by a membrane permeant InsP(3) ester. 2-APB also slowed the recovery of intracellular Ca(2+) signals consistent with an effect on Ca(2+) ATPases. The inhibitory action of 2-APB on InsP(3) receptors (InsP(3)Rs), SOC channels and Ca(2+) pumps persisted for several minutes after washout of the compound. Application of 2-APB to unstimulated cells had no effect on subsequent Ca(2+) responses suggesting that it has a use-dependent action. Mitochondria in cells treated with 2-APB showed a rapid and slowly reversible swelling. 2-APB did not cause the mitochondria to depolarise, but it reduced the extent of mitochondrial calcium uptake. Although 2-APB has been demonstrated not to affect voltage-operated Ca(2+) channels or ryanodine receptors, we found that it gave a concentration-dependent long-lasting inhibition of Ca(2+) signalling in electrically-stimulated cardiac myocytes, where InsP(3)Rs and SOC channels do not play a significant role. Our data suggest that 2-APB has multiple cellular targets, a use-dependent action, is difficult to reverse and may affect Ca(2+) signalling in cell types where InsP(3) and SOC are not active.

Inhibition of cytokine-induced vascular cell adhesion molecule-1 expression; possible mechanism for anti-atherogenic effect of Agastache rugosa.

Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) play an important role during the early stages of atherogenesis. Agastache rugosa has an anti-atherogenic effect in low density lipoprotein receptor -/- mice. Moreover, A. rugosa reduced macrophage infiltration and VCAM-1 expression has been localized in aortic endothelium that overlies early foam cell lesions. This study ascertained that tilianin (100 microM), a major component of A. rugosa, inhibits the tumor necrotic factor-alpha (TNF-alpha)-induced expression of VCAM-1 by 74% in cultured human umbilical vein endothelial cells (HUVECs). Also, tilianin (100 microM) reduced TNF-alpha-induced activation of nuclear factor-kappaB in HUVECs.

Dietary hematein ameliorates fatty streak lesions in the rabbit by the possible mechanism of reducing VCAM-1 and MCP-1 expression.

Hematein is a compound isolated from Caesalpinia sappan that has been used in oriental medicine as both an analgesic and an anti-inflammatory agent. In this study, we examined the anti-atherogenic potential of hematein using cholesterol-fed New Zealand White (NZW) rabbits. NZW rabbits were divided into a hematein-supplemented (0.05% in diet) group (n=6), a probucol-supplemented (0.25% in diet) group (n=6), and a control group (n=6). After 8 weeks of treatments, the extent of the atherosclerotic lesions was significantly reduced in the hematein-supplemented group and the probucol-supplemented group without changing plasma lipoprotein levels. Hematein and probucol prevented the up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) expression on the descending aorta induced by cholesterol diet. In culture, hematein also significantly inhibited the secretion of soluble VCAM-1 and of monocyte chemotactic protein-1 (MCP-1) respectively induced by tumor necrotic factor alpha (TNF-alpha) and mildly oxidized low density lipoprotein in human umbilical vein endothelial cell (HUVEC) culture. Also, hematein inhibited monocyte adhesion to endothelial cell and the activation of NF-kappaB in HUVECs stimulated with TNF-alpha. The results of the present study suggest that the anti-atherogenic effect of hematein is not related to control of the plasma lipid profile but probably related to the inhibition of VCAM-1 and MCP-1 expression resulting in an amelioration of lesion development in the rabbit.

Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice.

The protective effects of an aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), on acetaminophen (APAP)-induced hepatotoxicities and the possible protective mechanisms involved were investigated in mice. Pretreatment with CK prior to the administration of APAP significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. APAP-induced hepatotoxicity was also essentially prevented as evidenced by liver histopathology. Hepatic glutathione levels and glutathione-S-transferase activities were not affected by treatment with CK alone, but pretreatment with CK protected the APAP-induced depletion of hepatic glutathione levels. The effects of CK on cytochrome P450 (P450) 1A2 and 2E1, the major isozymes involved in APAP bioactivation, were investigated. In microsomal incubations, CK effectively inhibited P450 lA2-dependent methoxyresorufin O-deethylase activities and the P450 2E1-dependent p-nitrophenol and aniline hydroxylase. The results suggest that the protective effects of CK against the APAP-induced hepatotoxicity may, at least in part, be due to its ability to block P450-mediated APAP bioactivation.

Lipid-lowering and antioxidative activities of 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate in cholesterol-fed rats.

BACKGROUND: Polyphenols appear to have antioxidant activities and may mediate lipid lowering. METHODS: Four groups of rats, a high-cholesterol control (HC), HC+lovastatin, HC+3,4-di(OH)-cinnamate, and HC+3,4-di(OH)-hydrocinnamate, were given a semi-synthetic diet. The cinnamate derivative or lovastatin (0.1 g/100 g) supplements were given for 6 weeks. RESULTS: The plasma total cholesterol concentration was significantly lowered by the 3,4-di(OH)-cinnamate supplement compared to the control or lovastatin group. The 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate supplements significantly lowered both the hepatic cholesterol and triglyceride levels, while lovastatin only lowered the hepatic cholesterol. The hepatic HMG-CoA reductase activities were significantly lower in the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate groups than in the control or lovastatin group. The ACAT activity was only significantly lower in the lovastatin group compared to the other groups. With regards the hepatic antioxidant enzyme system, the CAT activity was significantly higher in the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate groups compared to the control or lovastatin group. The two cinnamate derivatives resulted in an increased hepatic GSH-Px activity. Meanwhile, all the supplements significantly lowered the hepatic thiobarbituric acid reactive substances (TBARS) content. However, the 3,4-di(OH)-cinnamate and 3,4-di(OH)-hydrocinnamate supplements did not alter the neutral sterol and total fecal sterol. CONCLUSIONS: Both cinnamate derivatives were potent in lipid-lowering and altering the antioxidative enzyme. Furthermore, these results also suggest that 3,4-di(OH)-cinnamate is more effective than 3,4-di(OH)-hydrocinnamate in its lipid-lowering action.