Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings

Cataloged from PDF version of article.Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon alpha (IFN alpha) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity

Electromigration-Induced Propagation of Nonlinear Surface Waves

Due to the effects of surface electromigration, waves can propagate over the free surface of a current-carrying metallic or semiconducting film of thickness h_0. In this paper, waves of finite amplitude, and slow modulations of these waves, are studied. Periodic wave trains of finite amplitude are found, as well as their dispersion relation. If the film material is isotropic, a wave train with wavelength lambda is unstable if lambda/h_0 < 3.9027..., and is otherwise marginally stable. The equation of motion for slow modulations of a finite amplitude, periodic wave train is shown to be the nonlinear Schrodinger equation. As a result, envelope solitons can travel over the film's surface.Comment: 13 pages, 2 figures. To appear in Phys. Rev.

Shortcuts in Stochastic Systems and Control of Biophysical Processes

The biochemical reaction networks that regulate living systems are all stochastic to varying degrees. The resulting randomness affects biological outcomes at multiple scales, from the functional states of single proteins in a cell to the evolutionary trajectory of whole populations. Controlling how the distribution of these outcomes changes over time-via external interventions like time-varying concentrations of chemical species-is a complex challenge. In this work, we show how counterdiabatic (CD) driving, first developed to control quantum systems, provides a versatile tool for steering biological processes. We develop a practical graph-theoretic framework for CD driving in discrete-state continuous-time Markov networks. Though CD driving is limited to target trajectories that are instantaneous stationary states, we show how to generalize the approach to allow for nonstationary targets and local control-where only a subset of system states is targeted. The latter is particularly useful for biological implementations where there may be only a small number of available external control knobs, insufficient for global control. We derive simple graphical criteria for when local versus global control is possible. Finally, we illustrate the formalism with global control of a genetic regulatory switch and local control in chaperone-assisted protein folding. The derived control protocols in the chaperone system closely resemble natural control strategies seen in experimental measurements of heat shock response in yeast and E. coli

Intestinal microbiota in patients with spinal cord injury

Human intestinal flora comprises thousands of bacterial species. Growth and composition of intestinal microbiota is dependent on various parameters, including immune mechanisms, dietary factors and intestinal motility. Patients with spinal cord injury (SCI) frequently display neurogenic bowel dysfunction due to the absence of central nervous system control over the gastrointestinal system. Considering the bowel dysfunction and altered colonic transit time in patients with SCI, we hypothesized the presence of a significant change in the composition of their gut microbiome. The objective of this study was to characterize the gut microbiota in adult SCI patients with different types of bowel dysfunction. We tested our hypothesis on 30 SCI patients (15 upper motor neuron [UMN] bowel syndrome, 15 lower motor neuron [LMN] bowel syndrome) and 10 healthy controls using the 16S rRNA sequencing. Gut microbial patterns were sampled from feces. Independent of study groups, gut microbiota of the participants were dominated by Blautia, Bifidobacterium, Faecalibacterium and Ruminococcus. When we compared all study groups, Roseburia, Pseudobutyrivibrio, Dialister, Marvinbryantia and Megamonas appeared as the genera that were statistically different between groups. In comparison to the healthy group, total bacterial counts of Pseudobutyrivibrio, Dialister and Megamonas genera were significantly lower in UMN bowel dysfunction group. The total bacterial count of Marvinbryantia genus was significantly lower in UMN bowel dysfunction group when compared to the LMN group. Total bacterial counts of Roseburia, Pseudobutyrivibrio and Megamonas genera were significantly lower in LMN bowel dysfunction group when compared to healthy groups. Our results demonstrate for the first time that butyrate-producing members are specifically reduced in SCI patients when compared to healthy subjects. The results of this study would be of interest since to our knowledge, microbiome-associated studies targeting SCI patients are non-existent and the results might help explain possible implications of gut microbiome in SCI. Copyright © 2016 Gungor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Advanced load-shift system: an experimental validation of the ac-dc converter as shunt active power filter

This paper presents a load-shift system with advanced functionalities to interface the power grid (PG). When compared with the conventional approach, an advanced load-shift system (aLSS) permits the compensation of power quality (PQ) problems for the grid-side, namely problems related to current harmonics, current imbalance, and power factor. The proposed aLSS is composed by a bidirectional ac-dc converter to interface the PG and by a bidirectional dc-dc converter to interface an energy storage system (ESS). Since the main innovation is related with the PG interface, the focus of this work is on the analysis of the ac-dc converter, which is based on a three-phase four-leg converter. A theoretical study and the details concerning the control algorithm are presented and discussed along the paper. A laboratory prototype of the proposed aLSS was developed and the details of implementation are described in the paper. Experimental results obtained with the developed prototype prove that the aLSS contributes for the technology progress in this area, validating a new concept of operation concerning the PQ on the PG side.This work has been supported by FCT – Fundação para a Ciência e Tecnologia with-in the Project Scope: UID/CEC/00319/2019. This work has been supported by the FCT Project QUALITY4POWER PTDC/EEI-EEE/28813/2017, and by the FCT Project newERA4GRIDs PTDC/EEI-EEE/30283/2017

Flexible and fragmentable tandem photosensitive nanocrystal skins

We proposed and demonstrated the first account of large-area, semi-transparent, tandem photosensitive nanocrystal skins (PNSs) constructed on flexible substrates operating on the principle of photogenerated potential buildup, which avoid the need for applying an external bias and circumvent the currentmatching limitation between junctions. We successfully fabricated and operated the tandem PNSs composed of single monolayers of colloidal water-soluble CdTe and CdHgTe nanocrystals (NCs) in adjacent junctions on a Kapton polymer tape. Owing to the usage of a single NC layer in each junction, noise generation was significantly reduced while keeping the resulting PNS films considerably transparent. In each junction, photogenerated excitons are dissociated at the interface of the semi-transparent Al electrode and the NC layer, with holes migrating to the contact electrode and electrons trapped in the NCs. As a result, the tandem PNSs lead to an open-circuit photovoltage buildup equal to the sum of those of the two single junctions, exhibiting a total voltage buildup of 128.4 mV at an excitation intensity of 75.8 μW cm⁻² at 350 nm. Furthermore, we showed that these flexible PNSs could be bent over 3.5 mm radius of curvature and cut out in arbitrary shapes without damaging the operation of individual parts and without introducing any significant loss in the total sensitivity. These findings indicate that the NC skins are promising as building blocks to make low-cost, flexible, large-area UV/visible sensing platforms with highly efficient full-spectrum conversion

Highly Efficient Nonradiative Energy Transfer from Colloidal Semiconductor Quantum Dots to Wells for Sensitive Noncontact Temperature Probing

This study develops and shows highly efficient exciton-transferring hybrid semiconductor nanocrystal films of mixed dimensionality comprising quasi 0D and 2D colloids. Through a systematic study of time-resolved and steady-state photoluminescence spectroscopy as a function of the donor-to-acceptor molar concentration ratio and temperature, a high-efficiency nonradiative energy transfer (NRET) process from CdZnS/ZnS core/shell quantum dots (QDs) directed to atomically flat CdSe nanoplatelets (NPLs) in their solid-state thin films is uncovered. The exciton funneling in this system reaches transfer efficiency levels as high as 90% at room temperature. In addition, this study finds that with decreasing temperature exciton transfer efficiency is increased to a remarkable maximum level of ≈94%. The enhancement in the dipole-dipole coupling strength with decreasing temperature is well accounted by increasing photoluminescence quantum yield of the donor and growing spectral overlap between the donor and the acceptor. Furthermore, NRET efficiency exhibits a highly linear monotonic response with changing temperature. This makes the proposed QD-NPL composites appealing for noncontact sensitive temperature probing based on NRET efficiencies as a new metric. These findings indicate that combining colloidal nanocrystals of different dimensionality enables efficient means of temperature probing at an unprecedented sensitivity level at nanoscale through almost complete exciton transfer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction

Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients. © 2017 Gucluler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited