We introduce a top-down fabricated metamaterial composed of three-dimensional, chiral, plasmonic nanostructures for visible and near-infrared wavelengths. Based on a combined spectroscopic and ...interferometric characterization, the entire complex transmission response in terms of a Jones matrix is disclosed. Particularly, the polarization output state of light after propagation through the nanostructures can be decoded from the measurements for any excitation configuration. We experimentally found a rotation of the polarization azimuth of linearly polarized light exceeding 50° at wavelengths around 1.08 μm. This corresponds to a specific rotation which is significantly larger than that of any linear, passive, and reciprocal medium reported to date.
Adaptive immune responses are induced in liver after major stresses such as hemorrhagic shock (HS) and trauma. There is emerging evidence that the inflammasome, the multiprotein platform that induces ...caspase-1 activation and promotes interleukin (IL)-1β and IL-18 processing, is activated in response to cellular oxidative stress, such as after hypoxia, ischemia and HS. Additionally, damage-associated molecular patterns, such as those released after injury, have been shown to activate the inflammasome and caspase-1 through the NOD-like receptor (NLR) NLRP3. However, the role of the inflammasome in organ injury after HS and trauma is unknown. We therefore investigated inflammatory responses and end-organ injury in wild-type (WT) and caspase-1(-/-)mice in our model of HS with bilateral femur fracture (HS/BFF). We found that caspase-1(-/-) mice had higher levels of systemic inflammatory cytokines than WT mice. This result corresponded to higher levels of liver damage, cell death and neutrophil influx in caspase-1(-/-) liver compared with WT, although there was no difference in lung damage between experimental groups. To determine if hepatoprotection also depended on NLRP3, we subjected NLRP3(-/-) mice to HS/BFF, but found inflammatory responses and liver damage in these mice was similar to WT. Hepatoprotection was also not due to caspase-1-dependent cytokines, IL-1β and IL-18. Altogether, these data suggest that caspase-1 is hepatoprotective, in part through regulation of cell death pathways in the liver after major trauma, and that caspase-1 activation after HS/BFF does not depend on NLRP3. These findings may have implications for the treatment of trauma patients and may lead to progress in prevention or treatment of multiple organ failure (MOF).
Within the past several years a tremendous progress regarding optical nano-antennas could be witnessed. It is one purpose of optical nano-antennas to resonantly enhance light-matter interactions at ...the nanoscale, e.g. the interaction of an external illumination with molecules. In this specific, but in almost all schemes that take advantage of resonantly enhanced electromagnetic fields in the vicinity of nano-antennas, the precise knowledge of the spectral position of resonances is of paramount importance to fully exploit their beneficial effects. Thus far, however, many nano-antennas were only optimized with respect to their far-field characteristics, i.e. in terms of their scattering or extinction cross sections. Although being an emerging feature in many numerical simulations, it was only recently fully appreciated that there exists a subtle but very important difference in the spectral position of resonances in the near-and the far-field. With the purpose to quantify this shift, Zuloaga et al. suggested a Lorentzian model to estimate the resonance shift. Here, we devise on fully analytical grounds a strategy to predict the resonance in the near-field directly from that in the far-field and disclose that the issue is involved and multifaceted, in general. We outline the limitations of our theory if more sophisticated optical nano-antennas are considered where higher order multipolar contributions and higher order antenna resonances become increasingly important. Both aspects are highlighted by numerically studying relevant nano-antennas.
The human Plasma Proteome Project pilot phase aims to analyze serum and plasma specimens to elucidate specimen characteristics by various proteomic techniques to ensure sufficient sample quality for ...the HUPO main phase. We used our proprietary peptidomics technologies to analyze the samples distributed by HUPO. Peptidomics summarizes technologies for visualization, quantitation, and identification of the low‐molecular‐weight proteome (<15 kDa), the “peptidome.” We analyzed all four HUPO specimens (EDTA plasma, citrate plasma, heparin plasma, and serum) from African‐ and Asian‐American donors and compared them to in‐house collected Caucasian specimens. One main finding focuses on the most suitable method of plasma specimen collection. Gentle platelet removal from plasma samples is beneficial for improved specificity. Platelet contamination or activation of platelets by low temperature prior to their removal leads to distinct and multiple peptide signals in plasma samples. Two different specimen collection protocols for platelet‐poor plasma are recommended. Further emphasis is placed on the differences between plasma and serum on a peptidomic level. A large number of peptides, many of them in rather high abundance, are only present in serum and not detectable in plasma. This ex vivo generation of multiple peptides hampers discovery efforts and is caused by a variety of factors: the release of platelet‐derived peptides, other peptides derived from cellular components or the clot, enzymatic activities of coagulation cascades, and other proteases. We conclude that specimen collection is a crucial step for successful peptide biomarker discovery in human blood samples. For analysis of the low‐molecular‐weight proteome, we recommend the use of platelet‐depleted EDTA or citrate plasma.
Hemorrhagic shock due to trauma (HS/T) induces an inflammatory response that can contribute to end-organ injury. The pathways involved in the initiation and propagation of HS/T-induced inflammation ...are incompletely understood. Here, we hypothesized that the DNA sensor TLR9 would have a role in inflammatory signaling after HS/T. Using mice expressing a nonfunctional, mutant form of TLR9, we identified a role of TLR9 in driving the initial cytokine response and liver damage in a model of hemorrhagic shock and bilateral femur fracture. Circulating DNA levels were found to correlate with the degree of tissue damage. Experiments using chimeric mice show that TLR9 on both bone marrow-derived cells and parenchymal cells are important for the TLR9-mediated liver and tissue damage, as well as systemic inflammation after HS/T. These data suggest that release of DNA may be a driver of the inflammatory response to severe injury as well as a marker of the extent of tissue damage. One of the sensors of DNA in the setting of HS/T seems to be TLR9.
The use of laryngeal masks in the surgical treatment of infantile lacrimal duct stenosis is controversial due to the potential risk of aspiration.
This study investigates airway procedures in ...children aged <6 years for surgery of lacrimal duct stenosis in a tertiary care university hospital.
After institutional approval, airway procedures, duration of anesthesiological measures, and airway-related complications were retrospectively analyzed. Patients were divided into two groups according to the airway procedures used (endotracheal tube ET vs. laryngeal mask LMA airway). Associations were calculated using the Chi-square test or Mann-Whitney U-test.
Clinical data of 84 patients (ET
= 36 42.9% vs. LMA
= 48 57.1%) were analyzed. There were no significant differences in surgical treatment, age distribution, and pre-existing conditions between the groups. None of the patients showed evidence of tracheal aspiration or changes in measured oxygen saturation. LMA airway shortened time for anesthesia induction (
= 0.006) and time for recovery/emergence period (
= 0.03). In contrast, the time to discharge from the recovery room was significantly prolonged using LMA (
= 0.001). A total of 7 adverse events were recorded. Five of these were directly or indirectly related to ET (laryngo-/bronchospasm; muscle relaxant residual).
LMA airway for infantile lacrimal duct stenosis seems to be a safe procedure and should be used in appropriate pediatric patients due to its lower invasiveness, low complication rate, and time savings.
Pediatric extracorporeal membrane oxygenation (ECMO) support is often the ultimate therapy for neonatal and pediatric patients with congenital heart defects after cardiac surgery. The impact of ...lactate clearance in pediatric patients during ECMO therapy on outcomes has been analyzed. Materials
We retrospectively analyzed data from 41 pediatric vaECMO patients between January 2006 and December 2016. Blood lactate and lactate clearance have been recorded prior to ECMO implantation and 3, 6, 9 and 12 h after ECMO start. Receiver operating characteristic (ROC) analysis was used to identify cut-off levels for lactate clearance.
Lactate levels prior to ECMO therapy (9.8 mmol/L vs. 13.5 mmol/L;
= 0.07) and peak lactate levels during ECMO support (10.4 mmol/L vs. 14.7 mmol/L;
= 0.07) were similar between survivors and nonsurvivors. Areas under the curve (AUC) of lactate clearance at 3, 9 h and 12 h after ECMO start were significantly predictive for mortality (
= 0.017,
= 0.049 and
= 0.006, respectively). Cut-off values of lactate clearance were 3.8%, 51% and 56%. Duration of ECMO support and respiratory ventilation was significantly longer in survivors than in nonsurvivors (
= 0.01 and
< 0.001, respectively).
Dynamic recording of lactate clearance after ECMO start is a valuable tool to assess outcomes and effectiveness of ECMO application. Poor lactate clearance during ECMO therapy in pediatric patients is a significant marker for higher mortality.
The properties of several cinnamic acid compounds used as matrices for matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were investigated as standard dried ...droplet (DD) and vacuum sublimed preparations. The differences between both preparation methods were analyzed with regard to matrix grain size, internal ion energy, initial velocity, analyte intensity, and analyte incorporation depth. Some of the used cinnamic acid derivatives exhibit clearly reduced grain sizes as sublimed preparations compared with standard DD approaches. In these cases higher effective temperatures could be measured accompanied by increased analyte intensities, which can be explained by stronger volatilization processes caused by a hindered heat dissipation resulting in a raised analyte transfer into the gas phase. For all sublimed compounds, a strong increase of the initial ion velocity compared with DD preparations could be measured. Higher initial ion velocities correlate with a decrease in internal ion energy which might be attributed to the very uniform crystal morphology exhibited by sublimed compounds. For sublimed matrices without reduced grain size, at least slightly higher analyte intensities could be detected at raised laser fluences. Analyte accumulation in the uppermost matrix layers or the detected higher ion stability can be explanations for these results.
The differences between standard dried droplet and vacuum sublimed surface preparations were analyzed for several cinnamic acid compounds used as matrices for MALDI-TOF MS.
Background: Bacteriorhodopsin (bR) from
Halobacterium salinarum is a proton pump that converts the energy of light into a proton gradient that drives ATP synthesis. The protein comprises seven ...transmembrane helices and
in vivo is organized into purple patches, in which bR and lipids form a crystalline two-dimensional array. Upon absorption of a photon, retinal, which is covalently bound to Lys216 via a Schiff base, is isomerized to a 13-
cis,15-
anti configuration. This initiates a sequence of events – the photocycle – during which a proton is transferred from the Schiff base to Asp85, followed by proton release into the extracellular medium and reprotonation from the cytoplasmic side.
Results: The structure of bR in the ground state was solved to 1.9 Å resolution from non-twinned crystals grown in a lipidic cubic phase. The structure reveals eight well-ordered water molecules in the extracellular half of the putative proton translocation pathway. The water molecules form a continuous hydrogen-bond network from the Schiff-base nitrogen (Lys216) to Glu194 and Glu204 and includes residues Asp85, Asp212 and Arg82. This network is involved both in proton translocation occurring during the photocycle, as well as in stabilizing the structure of the ground state. Nine lipid phytanyl moieties could be modeled into the electron-density maps. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis of single crystals demonstrated the presence of four different charged lipid species.
Conclusions: The structure of protein, lipid and water molecules in the crystals represents the functional entity of bR in the purple membrane of the bacteria at atomic resolution. Proton translocation from the Schiff base to the extracellular medium is mediated by a hydrogen-bond network that involves charged residues and water molecules. These authors contributed equally to this work.