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We demonstrate precise control of multiple FRET within LbL assemblies to produce simultaneous light emission with enhanced intensity from a single excitation with a blue wavelength. Three different fluorescent dyes were attached to neat polyelectrolytes and then incorporated into the LbL assembly. With designed deposition sequence, the layer of blue‐absorbing dyes was placed in the adjacent layer of green‐ and red‐emitting dyes, while the layers of emitting dyes were separated with each other beyond their Förster radius by inserting neat polyelectrolytes between them. The LbL assemblies not only allowed FRET from the absorbing dyes to the emitting dyes but also prohibited FRET between the emitting dyes to produce simultaneously enhanced green and red emission.

Ni-Fe-W alloys were obtained by electroplating using an ammoniacal citrate bath with a cation exchange membrane cell. The addition of 8 atom % iron to the Ni-W alloy removed surface microcracks on the deposits and increased the iron content, which was paralleled by an apparent increase in the tungsten content. To improve the microhardness, deposits were heat-treated at various temperatures. The maximum Vickers hardness value of 1350 was obtained after heat-treatment at . X-ray diffraction analysis revealed that the increasing annealing temperature induced both grain growth and precipitation of new phases, especially . Transmission electron microscopy and selected area diffraction observations revealed that annealing at led to a significant hardening of the deposits due to the precipitation of new phases with nanosized grains. However, as the annealing temperature was increased above , the microhardness began to fall with increasing grain size.

The intestinal epithelium undergoes a rapid turnover in addition to rapid exfoliation in response to bacterial infection, thus acting as an intrinsic defense against microbial intruders. It has long been questioned how mucosal pathogens can circumvent the intestinal defense systems. Our recent discovery of a bacterial ploy used by Shigella provided us with fresh insight. Shigella delivers OspE via the type III secretion system during multiplication within epithelial cells. This effector protein reinforces epithelial adherence to the basement membrane by interacting with integrin-linked kinase (ILK), a unique intracellular Ser/Thr kinase that links the cell-adhesion receptors, integrin, and growth factors to the actin cytoskeleton. The interaction between OspE and ILK increased formation of focal adhesions (FAs) and surface levels of b1-integrin, while suppressing phosphorylation of FAK and paxillin, thus suppressing rapid turnover of FAs, reducing cell motility and promoting cell adhesion to extracellular matrix. The impact of this OspE-ILK interplay was demonstrated both in vitro and in vivo by infecting polarized epithelial cell monolayers and guinea pig colons with Shigellapossessing or lacking the ospEgene. The findings thus establish a new class of virulence-associated factors, and provide new insight into the functioning of the intestinal barrier and bacterial strategies for circumventing it.

Integrin-mediated cell migration is central to many biologic and pathologic processes. During inflammation, tissue injury results from excessive infiltration and sequestration of activated leukocytes. Recombinant human activated protein C (rhAPC) has been shown to protect patients with severe sepsis, although the mechanism underlying this protective effect remains unclear. Here, we show that rhAPC directly binds to β1 and β3 integrins and inhibits neutrophil migration, both in vitro and in vivo. We found that human APC possesses an Arg-Gly-Asp (RGD) sequence, which is critical for the inhibition. Mutation of this sequence abolished both integrin binding and inhibition of neutrophil migration. In addition, treatment of septic mice with a RGD peptide recapitulated the beneficial effects of rhAPC on survival. Thus, we conclude that leukocyte integrins are novel cellular receptors for rhAPC and the interaction decreases neutrophil recruitment into tissues, providing a potential mechanism by which rhAPC may protect against sepsis.

Adhesion to extracellular ligands through integrins regulates cell shape, migration, growth, and survival. How integrins transmit signals in the outside-to-in direction remains unknown. Whereas in resting integrins the α and β subunit transmembrane domains are associated, ligand binding promotes dissociation and separation of these domains. Here we address whether such separation is required for outside-in signaling. By introduction of an intersubunit disulfide bond, we generated mutant integrin αIIbβ3 with blocked transmembrane separation that binds ligand, mediates adhesion, adopts an extended conformation after ligand binding, and forms antibody-induced macroclusters on the cell surface similarly to wild type. However, the mutant integrin exhibits a profound defect in adhesion-induced outside-in signaling as measured by cell spreading, actin stress-fiber and focal adhesion formation, and focal adhesion kinase activation. This defect was rescued by reduction of the disulfide bond. Our results demonstrate that the separation of transmembrane domains is required for integrin outside-in signal transduction.

Adenosine receptors (ADORs) in the enteric nervous system may be of importance in the control of motor and secretomotor functions. Gene expression and distribution of neural adenosine A1, A2a, A2b, or A3 receptors (Rs) in the human intestine was investigated using immunochemical, Western blotting, RT‐PCR, and short‐circuit current (Isc) studies. Adenosine A1R, A2aR, A2bR, or A3R mRNAs were differentially expressed in neural and nonneural layers of the jejunum, ileum, colon, and cecum and in HT‐29, T‐84, T98G, and Bon cell lines. A1R, A2aR, A2bR, and A3R immunoreactivities (IRs) were differentially expressed in PGP 9.5‐immunoreactive neurons. A2bR IR occurs exclusively in 50% of submucosal vasoactive intestinal peptide (VIP) neurons (interneurons, secretomotor or motor neurons) in jejunum, but not colon; A2aR is also found in other neurons. A3R IR occurs in 57% of substance P‐positive jejunal submucosal neurons (putative intrinsic primary afferent neurons) and less than 10% of VIP neurons. Western blots revealed bands for A3R at 44 kDa, 52 kDa, and 66 kDa. A2aR and A2bR are coexpressed in enteric neurons and epithelial cells. 5′‐N‐methylcarboxamidoadenosine or carbachol evoked an increase in Isc. A2bR IR is more prominent than A2aR IR in myenteric neurons, nerve fibers, or glia. A1R is expressed in jejunal myenteric neurons and colonic submucosal neurons. Regional differences also exist in smooth muscle expression of ADOR IR(s). It is concluded that neural and nonneural A1, A2a, A2b, and A3Rs may participate in the regulation of neural reflexes in the human gut. Clear cell and regional differences exist in ADOR gene expression, distribution, localization, and coexpression. J. Comp. Neurol. 439:46–64, 2001. © 2001 Wiley‐Liss, Inc.

The incidence of osteoporosis and diabetes mellitus (DM) is known to increase with aging. DM is associated with osteoporotic fractures and decreased bone mineral metabolism. However, no studies have compared the effects of DM on the changes in bone mineral density (BMD) and osteoporotic fracture after epidural steroid injections (ESIs). The present study aimed to analyze the relationship between ESI and BMD changes in elderly women with and without DM. The medical records of elderly women who underwent ESI were retrospectively analyzed. All patients had radiographic and BMD assessments performed before and after receiving lumbar ESIs. A total of 172 patients were divided into two groups according to the presence of DM. The duration of BMD monitoring was 16.1 and 16.8 months in the non-DM and DM groups, respectively. The mean total number of ESIs was 3.4 and 3.2, and the mean cumulative administered dose of glucocorticoids (dexamethasone) was 17 and 16 mg in the non-DM and DM groups, respectively. There were no significant differences between baseline and posttreatment BMD in the lumbar spine, total femur, and femoral neck region in either group. The incidence of osteoporotic fractures at the hip joint and thoracolumbar spine was not significantly different in both groups. ESIs could be used without concerns regarding osteoporosis and fractures in elderly women with DM if low doses of glucocorticoids are used.

Background:We sought to evaluate the role of ergonovine provocation testing with echocardiographic monitoring of ventricular wall motion for non-invasive diagnosis of coronary vasospasm (CVS).Methods:Clinical data of patients who underwent ergonovine echocardiography in three tertiary referral hospitals in South Korea from January 1991 to December 2015 were analyzed.Results:Ergonovine echocardiography was performed in 15,105 patients (mean age 53?11 years; 6661 women 44.1%) after exclusion of significant coronary arterial stenosis. Premature termination developed in 0.3% and a positive result was observed in 2230 patients (14.8%) with development of regional wall motion abnormality on echocardiography in 99.6% (2220/2230): the remaining ten patients showed ST-segment displacement only (>0.1 mV) in electrocardiography. The most common electrocardiographic changes associated with the positive test was no obvious changes (n=1163, 52.2%), followed by ST segment elevation (n=632, 28.3%) and depression (n=242, 10.8%). The frequency of arrhythmias was 0.4% (n=61), with atrioventricular block (n=22) and sinus bradycardia (n=21) being the predominant arrhythmias. The frequency of positive tests varied significantly according to the clinical diagnosis (variant angina 31.3%; atypical chest pain 3.6%; effort angina 14.4%; acute coronary syndrome 32.3%; aborted sudden death 15.4%; syncope 9.1%). There was no mortality or development of myocardial infarction during the test. The 10-year overall (96.8?0.2% vs. 91.6?0.6%, p<0.0001) and cardiovascular mortality-free survival rates (99.3?0.1% vs. 96.8?0.4%, p<0.0001) were lower in patients with positive ergonovine echocardiography (Figure A & B).Conclusions:Ergonovine echocardiography is highly feasible and safe for the diagnosis of CVS and can be a rational diagnostic strategy in diverse clinical situations, replacing the invasive spasm provocation test, which has been overlooked unfairly.

Cerebellar dysfunction relates to various psychiatric disorders, including autism spectrum and depressive disorders. However, the physiological aspect is less advanced. Here, we investigate the immune-triggered hyperexcitability in the cerebellum on a wider scope. Activated microglia via exposure to bacterial endotoxin lipopolysaccharide or heat-killed Gram-negative bacteria induce a potentiation of the intrinsic excitability in Purkinje neurons, which is suppressed by microglia-activity inhibitor and microglia depletion. An inflammatory cytokine, tumor necrosis factor alpha (TNF-α), released from microglia via toll-like receptor 4, triggers this plasticity. Our two-photon FRET ATP imaging shows an increase in ATP concentration following endotoxin exposure. Both TNF-α and ATP secretion facilitate synaptic transmission. Region-specific inflammation in the cerebellum in vivoshows depression- and autistic-like behaviors. Furthermore, both TNF-α inhibition and microglia depletion revert such behavioral abnormality. Resting-state functional MRI reveals overconnectivity between the inflamed cerebellum and the prefrontal neocortical regions. Thus, immune activity in the cerebellum induces neuronal hyperexcitability and disruption of psychomotor behaviors in animals.

Hydrazine fuel-cell technology holds great promise for clean energy, not only because of the greater energy density of hydrazine compared to hydrogen but also due to its safer handling owing to its liquid state. However, current technologies involve the use of precious metals (such as platinum) for hydrazine oxidation, which hinders the further application of hydrazine fuel-cell technologies. In addition, little attention has been devoted to the management of gas, which tends to become stuck on the surface of the electrode, producing overall poor electrode efficiencies. In this study, we utilized a nano-hill morphology of vertical graphene, which efficiently resolves the issue of the accumulation of gas bubbles on the electrode surface by providing a nano-rough-edged surface that acts as a superaerophobic electrode. The growth of the vertical graphene nano-hills was achieved and optimized by a scalable plasma-enhanced chemical vapor deposition method. The resulting metal-free graphene-based electrode showed the lowest onset potential (−0.42 V vs saturated calomel electrode) and the highest current density of all the carbon-based materials reported previously for hydrazine oxidation.

Laser interference lithography (LIL) is a technique that allows maskless patterning of large areal periodic nano/micro structures. The LIL pattern is often used as an etch barrier to pattern SiO2intermediate layer in the fabrication process of high aspect ratio silicon nano/micro structures by deep reactive ion etching process (DRIE) with SiO2etch barrier. In this study, a method to fabricate high aspect ratio nanograting structures by direct DRIE process of silicon substrate using LIL pattern without intermediate layer was developed as a simple and cost-effective fabrication process. To fabricate high aspect ratio silicon nanograting with high pattern fidelity, a simulation method to predict the cross sectional profile of photoresist (PR) pattern after exposure and development processes was investigated, and the LIL processing conditions were selected to obtain optimized cross sectional profile of PR pattern without residual layer based on the simulation results. To minimize the side wall defects during the DRIE process due to the deterioration of LIL pattern etch barrier, the processing conditions of DRIE process including etching gas, etching gas ratio, passivation time and power were optimized. Finally, a silicon nanograting with a grating pitch of 780 nm and height of 2.42 μm (aspect ratio: 6) was fabricated via the developed direct DRIE process with LIL pattern.

Opposing effects of Giprotein α and βγ subunits on the abundance of the second messenger cAMP enable neutrophil migration.

We have demonstrated high performance operation of planar-type tunnel field-effect transistors (TFETs) using Ge/III-V materials. It is found that solid-phase Zn diffusion can realize steep-profile and defect-less p+/n source junctions. We have demonstrated the operation of high Ion/Ioffand low SS planar-type InGaAs tunnel FETs with Zn-diffused source junctions. The small S.S. of 64 mV/dec and large Ion/Ioffratio over106has been realized in the planar-type III-V TFETs. It is also shown that tensile strain in Si channels (sSi) combined with the Ge source can enhance the tunneling current because of the reduced effective energy bandgap. The fabricated Ge/sSOI (1.1 %) TFETs show high Ion/Ioffratio over 107and steep minimum subthreshold slope (SS) of 28 mV/dec.

Novel device architectures offer improved scalability but come at the price of increased layout sensitivity and reduced effectiveness of stressors. This work focuses on stress effects in n-type FinFETs with gate-first or gate-last stacks, and relies mainly on TCAD results. On n-FinFETs, tensile stressed Contact Etch-Stop Layers (t-CESL) are less effective than on planar FETs when a gate-first scheme is used. For gate-last schemes, CESL is as effective as on planar FETs, moreover a strong boost is expected when compared to gate-first schemes. CESL becomes very ineffective for layouts with narrow fin pitches with merged fins. Tensile stressed gates are shown to be an effective stressor on gate-first n-FinFETs, but not on gate-last: in the latter case a mobility degradation is predicted. Si:C source/drain stressors are very effective and show similar width dependence as on planar FETs. Significant mobility enhancement is predicted both in isolated and tight-pitch fin configurations.