The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function

Proximal tubule epithelial cells (PTEC) of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC) as the model system. We demonstrate that PTEC express three inhibitory molecules: (i) cell surface PD-L1 that induces MoDC expression of PD-L1; (ii) intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii) soluble HLA-G (sHLA-G) that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.

Graphene with patterned fluorination: Morphology modulation and implications

Recent years have witnessed a large volume of works on the modification of graphene; however, an understanding of the associated morphology or mechanical properties changes is still lacking, which is vital for its engineering implementation. By taking the C4F fluorination as an example, we find that the morphology of both graphene sheet (GS) and graphene nanoribbon (GNR) can be effectively tailored by fluorination patterning via molecular dynamics simulations. The fluorine atom produces out-of-plane forces which trigger several intriguing morphology changes to monolayer graphene, including zigzag, folded, ruffle, nanoscroll, and chain structures. Notably, for multilayer GNR, the delamination and climbing phenomena of the surface layer are observed. Further studies show that the fluorination pattern can also be utilized to modulate the mechanical properties of graphene, e.g., about 40% increase of the effective yield strain is observed for the examined GNR with fluorination patterns. This study not only demonstrates the significant impacts on the morphology of graphene from fluorination but also suggests an effective avenue to tailor the morphology and thus mechanical properties of GS and GNR.

Switching period randomisation for multilevel converter modulation

The spectral energy associated with the carrier and sidebands of naturally sampled carrier based PWM can be spread by randomising the carrier (switch) half-period Tc = 1/2fc. So long as the switch duty cycle each period still correctly reflects the value of the modulating fundamental waveform as sampled during that switch period, then the fundamental component will remain undistorted. Natural sampling will ensure this occurs. Carrier based PWM can be extended to (m+1) level multilevel converter waveform generation by creating m triangular carriers, each with an equal 2*pi/m phase displacement. Alternatively the carrier disposition strategy calls for m amplitude displaced triangular carriers, each of amplitude 1/m and frequency mfc. Randomising these carrier sub-periods T0> = 1/2mfc is shown to generate (m+ 1) level PWM waveforms where the first (m-1) carrier groups are cancelled, while the remaining carrier and sidebands at multiples of mfc are spectrally spread. Numerous five level simulation and experimentally gathered randomised PWM waveforms are presented, showing the effects of the variation of the degree of randomisation, modulation depth and pulse number.

Phase accumulated carrier pulse width modulation

An alternative approach to digital PWM generation uses an accumulator rather than a counter to generate the carrier. This offers several advantages. The resolution and gain of the pulse width modulator remain constant regardless of the module clock frequency and PWM output frequency. The PWM resolution also becomes fixed at the register width. Even at high PWM frequencies, the resolution remains high when averaged over a number of PWM cycles. An inherent dithering of the PWM waveform introduced over successive cycles blurs the switching spectra without distorting the modulating waveform. The technique also lends itself to easily generating several phase shifted PWM waveforms suitable for multilevel converter modulation. Several example waveforms generated using both simulation and FPGA hardware are presented.

Novel modulation strategy for a CLC resonant dual active bridge

This paper proposes a novel modulation strategy for a phase controlled Capacitor-Inductor-Capacitor (CLC) Resonant Dual Active Bridge (RDAB). The proposed modulation strategy improves the soft turn-on, Zero-Current-Switching (ZCS) and Zero-Voltage-Switching (ZVS) range of the converter while only minimally increasing the required reactive currents in the ac link. A mathematical analysis of the proposed modulation scheme is presented along with a theoretical loss comparison between several modulation strategies. The proposed modulation strategy was implemented and the experimental results are presented.

mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats

Background Methamphetamine is a highly addictive central nervous system stimulant with increasing levels of abuse worldwide. Alterations to mRNA and miRNA expression within the mesolimbic system can affect addiction-like behaviors and thus play a role in the development of drug addiction. While many studies have investigated the effects of high-dose methamphetamine, and identified neurotoxic effects, few have looked at the role that persistent changes in gene regulation play following methamphetamine self-administration. Therefore, the aim of this study was to identify RNA changes in the ventral tegmental area following methamphetamine self-administration. We performed microarray analyses on RNA extracted from the ventral tegmental area of Sprague–Dawley rats following methamphetamine self-administration training (2 h/day) and 14 days of abstinence. Results We identified 78 miRNA and 150 mRNA transcripts that were differentially expressed (fdr adjusted p < 0.05, absolute log2 fold change >0.5); these included genes not previously associated with addiction (miR-125a-5p, miR-145 and Foxa1), loci encoding receptors related to drug addiction behaviors and genes with previously recognized roles in addiction such as miR-124, miR-181a, DAT and Ret. Conclusion This study provides insight into the effects of methamphetamine on RNA expression in a key brain region associated with addiction, highlighting the possibility that persistent changes in the expression of genes with both known and previously unknown roles in addiction occur.

Performance modulation of α-MnO2 nanowires by crystal facet engineering

Modulation of material physical and chemical properties through selective surface engineering is currently one of the most active research fields, aimed at optimizing functional performance for applications. The activity of exposed crystal planes determines the catalytic, sensory, photocatalytic, and electrochemical behavior of a material. In the research on nanomagnets, it opens up new perspectives in the fields of nanoelectronics, spintronics, and quantum computation. Herein, we demonstrate controllable magnetic modulation of α-MnO 2 nanowires, which displayed surface ferromagnetism or antiferromagnetism, depending on the exposed plane. First-principles density functional theory calculations confirm that both Mn- and O-terminated α-MnO2(1 1 0) surfaces exhibit ferromagnetic ordering. The investigation of surface-controlled magnetic particles will lead to significant progress in our fundamental understanding of functional aspects of magnetism on the nanoscale, facilitating rational design of nanomagnets. Moreover, we approved that the facet engineering pave the way on designing semiconductors possessing unique properties for novel energy applications, owing to that the bandgap and the electronic transport of the semiconductor can be tailored via exposed surface modulations.

Modulation of protease expression in prostate cancer cells after androgen deprivation

Understanding mechanisms associated with the emergence of castration resistant prostate cancer cells (CRPC) after androgen deprivation therapy (ADT) is essential to create new therapeutic agents to counteract this aggressive form of prostate cancer (PCa). Because proteases are involved in almost all cancer associated mechanisms such as cell proliferation, invasion and metastasis, we are interested in their modulation in PCa after ADT and their involvement in CRPC.