Induced Surface Enhancement in Coral Pt Island Films Attached to Nanostructured Ag Electrodes

Coral Pt islands films are deposited via electrochemical reduction on silica-coated nanostructured Ag electrodes. From these devices surface-enhanced (resonance) Raman [SE­(R)­R] signals of molecules exclusively attached to Pt are obtained with intensity up to 50% of the value determined for Ag. SE­(R)­R spectroscopic investigations are carried out with different probe molecules, silica-coating thicknesses, and excitation lines. Additionally, field enhancement calculations on Ag–SiO₂–Pt support geometries are performed to elucidate the influence of the Pt island film nanostructure on the observed Raman intensities. It is concluded that the nonperfect coating of the Pt island film promotes the efficiency of the induced Pt SER activity. Comparison with similar measurements on Ag–SiO₂–Au electrodes further suggests that the chemical nature of the deposited metal island film plays a minor role for the SE­(R)­R intensity

Tunable Plasmon Coupling in Distance-Controlled Gold Nanoparticles

Plasmons are resonant excitations in metallic films and nanoparticles. For small enough static distances of metal nanoparticles, additional plasmon-coupled modes appear as a collective excitation between the nanoparticles. Here we show, by combining poly­(<i>N</i>-isopropylacrylamide) micro- and nanospheres and Au nanoparticles, how to design a system that allows controllably and reversibly switching on and off, and tuning the plasmon-coupled mode

iORFV (D1701) reduces antigen cross-presentation by liver sinus endothelial cells (LSEC) but enhances activation of T-cells.

<p>Activation of CD8+ T cells (B3Z) was measured by IL-2 secretion.</p

iORFV NZ2 is a more potent inhibitor of HBV than strain D1701 in HBV-transgenic mice.

<p>iORFV D1701, iORFV NZ2 or placebo was administered i.p. every third day, three times in total, to HBV-transgenic mice expressing 10⁷–10⁸ HBV genome equivalents per ml plasma (n = 7 per group). HBV-specific DNA from plasma was analyzed by quantitative PCR and from livers by dot-blot hybridization as described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074605#pone.0074605-Weber1" target="_blank">[11]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074605#pone.0074605-Chromczynski1" target="_blank">[18]</a>. The figure shows means ± standard error of means (SEM) relative to placebo-treated animals where mean HBV-DNA content was set 100%. Treatment with iORFV reduced non-chromosomal HBV-DNA in the livers as compared to placebo animals <b>(a)</b> and in the plasma with the exception of the lowest dose of iORFV D1701 <b>(b)</b>. iORFV NZ-2 was more potent in terms of its potential to inhibit HBV replication compared to strain D1701 with the two lower dosages resulting in significantly higher reduction of HBV-DNA (one-way ANOVA and <i>post hoc</i> analysis [Newman-Keuls Multiple Comparison Test] *p<0.05, **p<0.01). <b>c)</b> Immunohistological analysis of HBcAg expression in the livers of placebo-treated animals. Diffuse cytoplasmic staining in periportal areas [arrows, central veins (CV)] indicates viral capsids and ongoing HBV replication in placebo-treated mice. Cytoplasmic HBcAg as well as nuclear HBcAg-specific stain (for empty capsids) was strongly reduced in both iORFV (NZ2)-treated <b>d)</b> and iORFV (D1701)-treated mice <b>e)</b>. Figures provide typical examples of the respective group of animals treated with a dose of 1.5×10⁶ TCID₅₀ iORFV NZ 2 or D1701, respectively.</p

Both ORFV strains induce cytokines suppressing HCV replication in an <i>in vitro</i> replicon system.

<p>Figures shows relative fluorescence units (RFU) as a measure for HCV replication. <b>a)</b> 20 µl (dose 1.6×10⁵ TCID₅₀) iORFV strain D1701 or NZ2 was added to whole blood and incubated for 3 days (see methods). Supernatants of cultured blood cells were added to replicon cells and HCV replication was determined three days later. Statistical analyses were performed using the one-way ANOVA and as <i>post hoc</i> analysis the Bonferroni Test. *p<0.05 vs. placebo. RFU-value from placebo (PBS) - treated supernatants was set as 100%. ConA served as a positive control. <b>b)</b> Cell viability of replicon-bearing cells was not affected after addition of supernatants from iORFV-incubated human blood cells. <b>c)</b> iORFV inhibits HCV replication in a dose-dependent manner. D 1701 or NZ2 were used for incubation with whole blood at doses ranging from 1.6×10⁵ TCID₅₀ to 1.6×10³ TCID₅₀. Values (n = 3) show means ± standard error of means (SEM).</p

Treatment with inactivated ORFV reduces HBV core antigen (HBcAg) in HBV-transgenic mice (n = 7/group).

*<p>Scores of anti-HbcAg stain: Nuclei: grade 3: the majority of nuclei in the liver specimens revealed intense immunostaining; grade 2: the number of positive nuclei was slightly reduced predominantly at the periphery of the liver lobule; grade 1: further reduction of positive nuclei was observed. Cytoplasm: grade 3: strong staining of numerous hepatocytes was observed around the central veins; grade 2: the cytoplasmic staining was reduced; grade 1: a further reduction or even absence of cytoplasmic immunostaining was observed. The histological slides were cross-checked by an independent pathologist and the results confirmed.</p><p>The severity of HBcAG-specific stain was quantified according to a scoring from 1 to 3*.</p

Metal–Semiconductor Nanoparticle Hybrids Formed by Self-Organization: A Platform to Address Exciton–Plasmon Coupling

Hybrid nanosystems composed of excitonic and plasmonic constituents can have different properties than the sum of of the two constituents, due to the exciton–plasmon interaction. Here, we report on a flexible model system based on colloidal nanoparticles that can form hybrid combinations by self-organization. The system allows us to tune the interparticle distance and to combine nanoparticles of different sizes and thus enables a systematic investigation of the exciton–plasmon coupling by a combination of optical spectroscopy and quantum-optical theory. We experimentally observe a strong influence of the energy difference between exciton and plasmon, as well as an interplay of nanoparticle size and distance on the coupling. We develop a full quantum theory for the luminescence dynamics and discuss the experimental results in terms of the Purcell effect. As the theory describes excitation as well as coherent and incoherent emission, we also consider possible quantum optical effects. We find a good agreement of the observed and the calculated luminescence dynamics induced by the Purcell effect. This also suggests that the self-organized hybrid system can be used as platform to address quantum optical effects

Strain Control of Exciton–Phonon Coupling in Atomically Thin Semiconductors

Semiconducting transition metal dichalcogenide (TMDC) monolayers have exceptional physical properties. They show bright photoluminescence due to their unique band structure and absorb more than 10% of the light at their excitonic resonances despite their atomic thickness. At room temperature, the width of the exciton transitions is governed by the exciton–phonon interaction leading to strongly asymmetric line shapes. TMDC monolayers are also extremely flexible, sustaining mechanical strain of about 10% without breaking. The excitonic properties strongly depend on strain. For example, exciton energies of TMDC monolayers significantly redshift under uniaxial tensile strain. Here, we demonstrate that the width and the asymmetric line shape of excitonic resonances in TMDC monolayers can be controlled with applied strain. We measure photoluminescence and absorption spectra of the A exciton in monolayer MoSe₂, WSe₂, WS₂, and MoS₂ under uniaxial tensile strain. We find that the A exciton substantially narrows and becomes more symmetric for the selenium-based monolayer materials, while no change is observed for atomically thin WS₂. For MoS₂ monolayers, the line width increases. These effects are due to a modified exciton–phonon coupling at increasing strain levels because of changes in the electronic band structure of the respective monolayer materials. This interpretation based on steady-state experiments is corroborated by time-resolved photoluminescence measurements. Our results demonstrate that moderate strain values on the order of only 1% are already sufficient to globally tune the exciton–phonon interaction in TMDC monolayers and hold the promise for controlling the coupling on the nanoscale

Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure–activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound <b>24</b>, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported

Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure–activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound <b>24</b>, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported