p38α (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes.

In CNS lesions, "reactive astrocytes" form a prominent cellular response. However, the nature of this astrocyte immune activity is not well understood. In order to study astrocytic immune responses to inflammation and injury, we generated mice with conditional deletion of p38α (MAPK14) in GFAP+ astrocytes. We studied the role of p38α signaling in astrocyte immune activation both in vitro and in vivo, and simultaneously examined the effects of astrocyte activation in CNS inflammation. Our results showed that specific subsets of cytokines (TNFα, IL-6) and chemokines (CCL2, CCL4, CXCL1, CXCL2, CXCL10) are critically regulated by p38α signaling in astrocytes. In an in vivo CNS inflammation model of intracerebral injection of LPS, we observed markedly attenuated astrogliosis in conditional GFAPcre p38α(-/-) mice. However, GFAPcre p38α(-/-) mice showed marked upregulation of CCL2, CCL3, CCL4, CXCL2, CXCL10, TNFα, and IL-1β compared to p38αfl/fl cohorts, suggesting that in vivo responses to LPS after GFAPcre p38α deletion are complex and involve interactions between multiple cell types. This finding was supported by a prominent increase in macrophage/microglia and neutrophil recruitment in GFAPcre p38α(-/-) mice compared to p38αfl/fl controls. Together, these studies provide important insights into the critical role of p38α signaling in astrocyte immune activation

Enabling Thin and Flexible Solid-State Composite Electrolytes by the Scalable Solution Process

All solid-state batteries (ASSBs) have the potential to deliver higher energy densities, wider operating temperature range, and improved safety compared with today's liquid-electrolyte-based batteries. However, of the various solid-state electrolyte (SSE) classes - polymers, sulfides, or oxides - none alone can deliver the combined properties of ionic conductivity, mechanical, and chemical stability needed to address scalability and commercialization challenges. While promising strategies to overcome these include the use of polymer/oxide or sulfide composites, there is still a lack of fundamental understanding between different SSE-polymer-solvent systems and its selection criteria. Here, we isolate various SSE-polymer-solvent systems and study their molecular level interactions by combining various characterization tools. With these findings, we introduce a suitable Li7P3S11SSE-SEBS polymer-xylene solvent combination that significantly reduces SSE thickness (∼50 μm). The SSE-polymer composite displays high room temperature conductivity (0.7 mS cm-1) and good stability with lithium metal by plating and stripping over 2000 h at 1.1 mAh cm-2. This study suggests the importance of understanding fundamental SSE-polymer-solvent interactions and provides a design strategy for scalable production of ASSBs

Polariton Condensation and Lasing

The similarities and differences between polariton condensation in microcavities and standard lasing in a semiconductor cavity structure are reviewed. The recent experiments on "photon condensation" are also reviewed.Comment: 23 pages, 6 figures; Based on the book chapter in Exciton Polaritons in Microcavities, (Springer Series in Solid State Sciences vol. 172), V. Timofeev and D. Sanvitto, eds., (Springer, 2012

SD-208, a novel protein kinase D inhibitor, blocks prostate cancer cell proliferation and tumor Growth in Vivo by inducing G2/M cell cycle arrest

Protein kinase D (PKD) has been implicated in many aspects of tumorigenesis and progression, and is an emerging molecular target for the development of anticancer therapy. Despite recent advancement in the development of potent and selective PKD small molecule inhibitors, the availability of in vivo active PKD inhibitors remains sparse. In this study, we describe the discovery of a novel PKD small molecule inhibitor, SD-208, from a targeted kinase inhibitor library screen, and the synthesis of a series of analogs to probe the structure-activity relationship (SAR) vs. PKD1. SD-208 displayed a narrow SAR profile, was an ATP-competitive pan-PKD inhibitor with low nanomolar potency and was cell active. Targeted inhibition of PKD by SD-208 resulted in potent inhibition of cell proliferation, an effect that could be reversed by overexpressed PKD1 or PKD3. SD-208 also blocked prostate cancer cell survival and invasion, and arrested cells in the G2/M phase of the cell cycle. Mechanistically, SD-208-induced G2/M arrest was accompanied by an increase in levels of p21 in DU145 and PC3 cells as well as elevated phosphorylation of Cdc2 and Cdc25C in DU145 cells. Most importantly, SD-208 given orally for 24 days significantly abrogated the growth of PC3 subcutaneous tumor xenografts in nude mice, which was accompanied by reduced proliferation and increased apoptosis and decreased expression of PKD biomarkers including survivin and Bcl-xL. Our study has identified SD-208 as a novel efficacious PKD small molecule inhibitor, demonstrating the therapeutic potential of targeted inhibition of PKD for prostate cancer treatment

Single vortex-antivortex pair in an exciton polariton condensate

In a homogeneous two-dimensional system at non-zero temperature, although there can be no ordering of infinite range, a superfluid phase is predicted for a Bose liquid. The stabilization of phase in this superfluid regime is achieved by the formation of bound vortex-antivortex pairs. It is believed that several different systems share this common behaviour, when the parameter describing their ordered state has two degrees of freedom, and the theory has been tested for some of them. However, there has been no direct experimental observation of the phase stabilization mechanism by a bound pair. Here we present an experimental technique that can identify a single vortex-antivortex pair in a two-dimensional exciton polariton condensate. The pair is generated by the inhomogeneous pumping spot profile, and is revealed in the time-integrated phase maps acquired using Michelson interferometry, which show that the condensate phase is only locally disturbed. Numerical modelling based on open dissipative Gross-Pitaevskii equation suggests that the pair evolution is quite different in this non-equilibrium system compared to atomic condensates. Our results demonstrate that the exciton polariton condensate is a unique system for studying two-dimensional superfluidity in a previously inaccessible regime

In situ evidence for the structure of the magnetic null in a 3D reconnection event in the Earth's magnetotail

Magnetic reconnection is one of the most important processes in astrophysical, space and laboratory plasmas. Identifying the structure around the point at which the magnetic field lines break and subsequently reform, known as the magnetic null point, is crucial to improving our understanding reconnection. But owing to the inherently three-dimensional nature of this process, magnetic nulls are only detectable through measurements obtained simultaneously from at least four points in space. Using data collected by the four spacecraft of the Cluster constellation as they traversed a diffusion region in the Earth's magnetotail on 15 September, 2001, we report here the first in situ evidence for the structure of an isolated magnetic null. The results indicate that it has a positive-spiral structure whose spatial extent is of the same order as the local ion inertial length scale, suggesting that the Hall effect could play an important role in 3D reconnection dynamics.Comment: 14 pages, 4 figure

Complementary cooperation, minimal winning coalitions, and power indices

We introduce a new simple game, which is referred to as the complementary weighted multiple majority game (C-WMMG for short). C-WMMG models a basic cooperation rule, the complementary cooperation rule, and can be taken as a sister model of the famous weighted majority game (WMG for short). In this paper, we concentrate on the two dimensional C-WMMG. An interesting property of this case is that there are at most $n+1$ minimal winning coalitions (MWC for short), and they can be enumerated in time $O(n\log n)$, where $n$ is the number of players. This property guarantees that the two dimensional C-WMMG is more handleable than WMG. In particular, we prove that the main power indices, i.e. the Shapley-Shubik index, the Penrose-Banzhaf index, the Holler-Packel index, and the Deegan-Packel index, are all polynomially computable. To make a comparison with WMG, we know that it may have exponentially many MWCs, and none of the four power indices is polynomially computable (unless P=NP). Still for the two dimensional case, we show that local monotonicity holds for all of the four power indices. In WMG, this property is possessed by the Shapley-Shubik index and the Penrose-Banzhaf index, but not by the Holler-Packel index or the Deegan-Packel index. Since our model fits very well the cooperation and competition in team sports, we hope that it can be potentially applied in measuring the values of players in team sports, say help people give more objective ranking of NBA players and select MVPs, and consequently bring new insights into contest theory and the more general field of sports economics. It may also provide some interesting enlightenments into the design of non-additive voting mechanisms. Last but not least, the threshold version of C-WMMG is a generalization of WMG, and natural variants of it are closely related with the famous airport game and the stable marriage/roommates problem.Comment: 60 page

Experimental and theoretical investigation of ligand effects on the synthesis of ZnO nanoparticles

ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence

Electric Field-Tuned Topological Phase Transition in Ultra-Thin Na3Bi - Towards a Topological Transistor

The electric field induced quantum phase transition from topological to conventional insulator has been proposed as the basis of a topological field effect transistor [1-4]. In this scheme an electric field can switch 'on' the ballistic flow of charge and spin along dissipationless edges of the two-dimensional (2D) quantum spin Hall insulator [5-9], and when 'off' is a conventional insulator with no conductive channels. Such as topological transistor is promising for low-energy logic circuits [4], which would necessitate electric field-switched materials with conventional and topological bandgaps much greater than room temperature, significantly greater than proposed to date [6-8]. Topological Dirac semimetals(TDS) are promising systems in which to look for topological field-effect switching, as they lie at the boundary between conventional and topological phases [3,10-16]. Here we use scanning probe microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES) to show that mono- and bilayer films of TDS Na3Bi [3,17] are 2D topological insulators with bulk bandgaps >400 meV in the absence of electric field. Upon application of electric field by doping with potassium or by close approach of the STM tip, the bandgap can be completely closed then re-opened with conventional gap greater than 100 meV. The large bandgaps in both the conventional and quantum spin Hall phases, much greater than the thermal energy kT = 25 meV at room temperature, suggest that ultrathin Na3Bi is suitable for room temperature topological transistor operation

CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene