Anti-TNF-α antibody allows healing of joint damage in polyarthritic transgenic mice

Anti-tumor-necrosis-factor-α (TNF-α) monoclonal antibody was used to treat Tg197 transgenic mice, which constitutively produce human TNF-α (hTNF-α) and develop a progressive polyarthritic disease. Treatment of both young (7- or 8-week-old) and aged (27- or 28-week-old) mice commenced when at least two limbs showed signs of moderate to severe arthritis. The therapeutic efficacy of anti-TNF-α antibody was assessed using various pathological indicators of disease progression. The clinical severity of arthritis in Tg197 mice was significantly reduced after anti-TNF-α treatment in comparison with saline-treated mice and in comparison with baseline assessments in both young and aged mice. The treatment with anti-TNF-α prevented loss of body weight. Inflammatory pathways as reflected by elevated circulating hTNF-α and local expression of various proinflammatory mediators were all diminished by anti-TNF-α treatment, confirming a critical role of hTNF-α in this model of progressive polyarthritis. More importantly, the amelioration of the disease was associated with reversal of existing structural damage, including synovitis and periosteal bone erosions evident on histology. Repair of cartilage was age dependent: reversal of cartilage degradation after anti-TNF-α treatment was observed in young mice but not in aged mice

Transport properties of copper phthalocyanine based organic electronic devices

Ambipolar charge carrier transport in Copper phthalocyanine (CuPc) is studied experimentally in field-effect transistors and metal-insulator-semiconductor diodes at various temperatures. The electronic structure and the transport properties of CuPc attached to leads are calculated using density functional theory and scattering theory at the non-equilibrium Green's function level. We discuss, in particular, the electronic structure of CuPc molecules attached to gold chains in different geometries to mimic the different experimental setups. The combined experimental and theoretical analysis explains the dependence of the mobilityand the transmission coefficient on the charge carrier type (electrons or holes) and on the contact geometry. We demonstrate the correspondence between our experimental results on thick films and our theoretical studies of single molecule contacts. Preliminary results for fluorinated CuPc are discussed.Comment: 18 pages, 16 figures; to be published in Eur. Phys. J. Special Topic

Electron quantum metamaterials in van der Waals heterostructures

In recent decades, scientists have developed the means to engineer synthetic periodic arrays with feature sizes below the wavelength of light. When such features are appropriately structured, electromagnetic radiation can be manipulated in unusual ways, resulting in optical metamaterials whose function is directly controlled through nanoscale structure. Nature, too, has adopted such techniques -- for example in the unique coloring of butterfly wings -- to manipulate photons as they propagate through nanoscale periodic assemblies. In this Perspective, we highlight the intriguing potential of designer sub-electron wavelength (as well as wavelength-scale) structuring of electronic matter, which affords a new range of synthetic quantum metamaterials with unconventional responses. Driven by experimental developments in stacking atomically layered heterostructures -- e.g., mechanical pick-up/transfer assembly -- atomic scale registrations and structures can be readily tuned over distances smaller than characteristic electronic length-scales (such as electron wavelength, screening length, and electron mean free path). Yet electronic metamaterials promise far richer categories of behavior than those found in conventional optical metamaterial technologies. This is because unlike photons that scarcely interact with each other, electrons in subwavelength structured metamaterials are charged, and strongly interact. As a result, an enormous variety of emergent phenomena can be expected, and radically new classes of interacting quantum metamaterials designed

Angle Dependent Van Hove Singularities in Slightly Twisted Graphene Bilayer

Recent studies show that two low-energy Van Hove singularities (VHSs) seen as two pronounced peaks in the density of states (DOS) could be induced in twisted graphene bilayer. Here, we report angle dependent VHSs of slightly twisted graphene bilayer studied by scanning tunneling microscopy and spectroscopy. We show that energy difference of the two VHSs follows \DeltaEvhs ~ \hbar{\nu}F\DeltaK between 1.0^{\circ} and 3.0^{\circ} (here {\nu}F ~ 1.1\times106 m/s is the Fermi velocity of monolayer graphene, \DeltaK = 2Ksin(\theta/2) is the shift between the corresponding Dirac points of the twisted graphene bilayer). This result indicates that the rotation angle between graphene sheets not results in significant reduction of the Fermi velocity, which quite differs from that predicted by band structure calculations. However, around a twisted angle \theta ~ 1.3^{\circ}, the observed \DeltaEvhs ~ 0.11 eV is much less than the expected value \hbar{\nu}F\DeltaK ~ 0.28 eV at 1.3^{\circ}. The origin of the reduction of \DeltaEvhs at 1.3^{\circ} is discussed.Comment: To appear in Phys. Rev. Lett. (2012

Dynamical CP violation at finite temperature

Based on the generalized Yang-Mills model, CP violation behavior at finite temperature is investigated, and it is shown that dynamical CP violation of the generalized Yang-Mills model at zero temperature can be restored at finite temperature.Comment: 6 page

Sonic Hedgehog Signaling Pathway Mediates Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via MAPK/ERK Signaling Pathway

Fibroblast-like synoviocytes (FLSs) are the major effector cells that lead to rheumatoid arthritis (RA) synovitis and joint destruction. Our previous studies showed that Sonic Hedgehog (SHH) signaling pathway is involved in aberrant activation of RA-FLSs and inhibition of SHH pathway decreases proliferation and migration of RA-FLSs. The objective of this study was to investigate if the SHH pathway mediates proliferation and migration of RA-FLSs via the mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) signaling pathway. SHH signaling was studied by using SHH agonist (Purmorphamine) and antagonist (Cyclopamine) targeting the Smoothened (SMO) in FLSs. U0126-EtOH was used to inhibit the MAPK/ERK signaling pathway. The phosphorylation of ERK 1/2 (p-ERKl/2) was examined by western blot. Cell viability was detected using cell proliferation and cytotoxicity kit-8 (CCK8), and cell cycle distribution and proliferating cells were evaluated by the flow cytometry. Cell migration was examined by Transwell assay. Results showed that, compared with the control group, Purmorphamine increased the levels of p-ERK1/2 in concentration-and time-dependent manners (P < 0.01). Co-treated with Purmorphamine and U0126-EtOH or Cyclopamine both decreased the levels of p-ERK1/2 (P < 0.05). RA-FLSs treated with Purmorphamine resulted in alteration of cell cycle distribution, increasing of proliferating cells, cell viability, and migration cells compared to controls (P < 0.01). However, the above phenomenon can be abolished by U0126-EtOH (P < 0.05). The findings suggest that SHH signaling pathway mediates proliferation and migration of RA-FLSs via MAPK/ERK pathway and may contribute to progression of RA. Targeting SHH signaling may have a therapeutic potential in patients with RA

An electric molecular motor

The computational investigations at California Institute of Technology were supported by National Science Foundation grant no. CBET-2005250 (W.-G.L. and W.A.G.).Macroscopic electric motors continue to have a large impact on almost every aspect of modern society. Consequently, the effort towards developing molecular motors that can be driven by electricity could not be more timely. Here we describe an electric molecular motor based on a [3]catenane , in which two cyclobis(paraquat-p-phenylene) (CBPQT4+) rings are powered by electricity in solution to circumrotate unidirectionally around a 50-membered loop. The constitution of the loop ensures that both rings undergo highly (85%) unidirectional movement under the guidance of a flashing energy ratchet , whereas the interactions between the two rings give rise to a two-dimensional potential energy surface (PES) similar to that shown by F0F1ATP synthase . The unidirectionality is powered by an oscillating voltage or external modulation of the redox potential . Initially, we focused our attention on the homologous [2]catenane, only to find that the kinetic asymmetry was insufficient to support unidirectional movement of the sole ring. Accordingly, we incorporated a second CBPQT4+ ring to provide further symmetry breaking by interactions between the two mobile rings. This demonstration of electrically driven continual circumrotatory motion of two rings around a loop in a [3]catenane is free from the production of waste products and represents an important step towards surface-bound electric molecular motors.Publisher PDFPeer reviewe

Addressing Antimicrobial Resistance in China: Policy Implementation in a Complex Context

The effectiveness of antibiotics in treating bacterial infections is decreasing in China because of the widespread development of resistant organisms. Although China has enacted a number of regulations to address this problem, but the impact is very limited. This paper investigates the implementation of these regulations through the lens of complex adaptive systems (CAS). It presents the findings from reviews of relevant policy documents and published papers. The paper identifies different types of agent and explores their interaction with regard to the use of antibiotics and their responses to changes of the regulations. It focuses particularly on the impact of perverse financial incentives on overall patterns of use of antibiotics. Implications for the possibilities of nonlinear results, interactive relationships, and new pathways of policy implementation are discussed. The paper concludes that policy-makers need to better understand the objectives, incentives and potential adaptive behaviors of the agents when they implement interventions to improve antibiotic use and reduce the risk of emergence of resistant organism