Anomalous Diffusion at Edge and Core of a Magnetized Cold Plasma

Progress in the theory of anomalous diffusion in weakly turbulent cold magnetized plasmas is explained. Several proposed models advanced in the literature are discussed. Emphasis is put on a new proposed mechanism for anomalous diffusion transport mechanism based on the coupled action of conductive walls (excluding electrodes) bounding the plasma drain current (edge diffusion) together with the magnetic field flux "cutting" the area traced by the charged particles in their orbital motion. The same reasoning is shown to apply to the plasma core anomalous diffusion. The proposed mechanism is expected to be valid in regimes when plasma diffusion scales as Bohm diffusion and at high $B/N$, when collisions are of secondary importance.Comment: 9 pages, 4 figure

Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates

There is a remarkable heterogeneity in the functional profile (quality) of T cell responses. Importantly, the magnitude and/or quality of a response required for protection may be different depending on the infection. Here, we assessed the capacity of different Toll like receptor (TLR)-binding compounds to influence T helper cell (Th)1 and CD8+ T cell responses when used as adjuvants in nonhuman primates (NHP) with HIV Gag as a model antigen. NHP were immunized with HIV Gag protein emulsified in Montanide ISA 51, an oil-based adjuvant, with or without a TLR7/8 agonist, a TLR8 agonist, or the TLR9 ligand cytosine phosphate guanosine oligodeoxynucleotides (CpG ODN), and boosted 12 wk later with a replication-defective adenovirus-expressing HIV-Gag (rAD-Gag). Animals vaccinated with HIV Gag protein/Montanide and CpG ODN or the TLR7/8 agonist had higher frequencies of Th1 responses after primary immunization compared to all other vaccine groups. Although the rAD-Gag boost did not elevate the frequency of Th1 memory cytokine responses, there was a striking increase in HIV Gag-specific CD8+ T cell responses after the boost in all animals that had received a primary immunization with any of the TLR adjuvants. Importantly, the presence and type of TLR adjuvant used during primary immunization conferred stability and dramatically influenced the magnitude and quality of the Th1 and CD8+ T cell responses after the rAD-Gag boost. These data provide insights for designing prime-boost immunization regimens to optimize Th1 and CD8+ T cell responses

Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC

BLUF Domain Function Does Not Require a Metastable Radical Intermediate State

BLUF (blue light using flavin) domain proteins are an important family of blue light-sensing proteins which control a wide variety of functions in cells. The primary light-activated step in the BLUF domain is not yet established. A number of experimental and theoretical studies points to a role for photoinduced electron transfer (PET) between a highly conserved tyrosine and the flavin chromophore to form a radical intermediate state. Here we investigate the role of PET in three different BLUF proteins, using ultrafast broadband transient infrared spectroscopy. We characterize and identify infrared active marker modes for excited and ground state species and use them to record photochemical dynamics in the proteins. We also generate mutants which unambiguously show PET and, through isotope labeling of the protein and the chromophore, are able to assign modes characteristic of both flavin and protein radical states. We find that these radical intermediates are not observed in two of the three BLUF domains studied, casting doubt on the importance of the formation of a population of radical intermediates in the BLUF photocycle. Further, unnatural amino acid mutagenesis is used to replace the conserved tyrosine with fluorotyrosines, thus modifying the driving force for the proposed electron transfer reaction; the rate changes observed are also not consistent with a PET mechanism. Thus, while intermediates of PET reactions can be observed in BLUF proteins they are not correlated with photoactivity, suggesting that radical intermediates are not central to their operation. Alternative nonradical pathways including a keto–enol tautomerization induced by electronic excitation of the flavin ring are considered

3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR

SrFe12O19 based ceramics with ultra-low dielectric loss in the millimetre-wave band

The following article appeared in Applied Physics Letters, 112,143501 and may be found at https://doi.org/10.1063/1.5022271. This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing.Non-reciprocal devices such as isolators and circulators, based mainly on ferromagnetic materials, require extremely low dielectric loss in order for strict power-link budgets to be met for millimetre (mm)-wave and terahertz (THz) systems. The dielectric loss of commercial SrFe12O19 hexaferrite was significantly reduced to below 0.002 in the 75 - 170 GHz band by thermal annealing. While the overall concentration of Fe2+ and oxygen vacancy defects is relatively low in the solid, their concentration at the surface is significantly higher, allowing for a surface sensitive technique such as XPS to monitor the Fe3+/Fe2+ redox reaction. Oxidation of Fe2+ and a decrease in oxygen vacancies is found at the surface on annealing, which is reflected in the bulk sample by a small change in unit cell volume. The significant decrease in dielectric loss property can be attributed to the decreased concentration of charged defects such as Fe2+ and oxygen vacancies through annealing process, which demonstrated that thermal annealing could be effective in improving the dielectric performance of ferromagnetic materials for various applications

Efficient hydrolytic hydrogen evolution from sodium borohydride catalyzed by polymer immobilized ionic liquid‐stabilized platinum nanoparticles

Platinum nanoparticles stabilized by imidazolium‐based phosphine‐decorated Polymer Immobilized Ionic Liquids (PPh2‐PIIL) catalyze the hydrolytic evolution of hydrogen from sodium borohydride with remarkable efficiency, under mild conditions. The composition of the polymer influences efficiency with the catalyst based on a polyethylene glycol modified imidazolium monomer (PtNP@PPh2‐PEGPIILS) more active than its N‐alkylated counterpart (PtNP@PPh2‐N‐decylPIILS). The maximum initial TOF of 169 moleH2.molcat−1.min−1 obtained at 30 °C with a catalyst loading of 0.08 mol% is among the highest to be reported for the aqueous phase hydrolysis of sodium borohydride catalyzed by a PtNP‐based system. Kinetic studies revealed that the apparent activation energy (Ea) of 23.9 kJ mol−1 for the hydrolysis of NaBH4 catalyzed by PtNP@PPh2‐PEGPIILS is significantly lower than that of 35.6 kJ mol−1 for PtNP@PPh2‐N‐decylPIILS. Primary kinetic isotope effects kH/kD of 1.8 and 2.1 obtained with PtNP@PPh2‐PEGPIILS and PtNP@PPh2‐N‐decylPIILS, respectively, for the hydrolysis with D2O support a mechanism involving rate determining oxidative addition or σ‐bond metathesis of the O−H bond. Catalyst stability and reuse studies showed that PtNP@PPh2‐PEGPIILS retained 70 % of its activity across five runs; the gradual drop in conversion appears to be due to poisoning of the catalyst by the accumulated metaborate product as well as the increased viscosity of the reaction mixture