On the Dichotomy between the Nodal and Antinodal Excitations in High-temperature Superconductors

Angle-resolved photoemission data on optimally- and under-doped high temperature superconductors reveal a dichotomy between the nodal and antinodal electronic excitations. In this paper we propose an explanation of this unusual phenomenon by employing the coupling between the quasiparticle and the commensurate/incommensurate magnetic excitations.Comment: 11 pages, 9 figure

Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention

The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy. Interestingly, response to HER-2 targeted therapies correlates with presence of immune response genes in the breast. Th1 cell production of the cytokines interferon gamma (IFNγ) and TNFα can enhance MHC class I expression, PD-L1 expression, augment apoptosis and tumor senescence, and enhances growth inhibition of many anti-breast cancer agents, including anti-estrogens and HER-2 targeted therapies. Recently, we have identified that a loss of anti-HER-2 CD4 Th1 in peripheral blood occurs during breast tumorigenesis and is dramatically diminished, even in Stage I breast cancers. The loss of anti-HER-2 Th1 response is specific and not readily reversed by standard therapies. In fact, this loss of anti-HER-2 Th1 response in peripheral blood correlates with lack of complete response to neoadjuvant therapy and diminished disease-free survival. This defect can be restored with HER-2 vaccinations in both DCIS and IBC. Correcting the anti-HER-2 Th1 response may have significant impact in improving response to HER-2 targeted therapies. Development of immune monitoring systems for anti-HER-2 Th1 to identify patients at risk for recurrence could be critical to improving outcomes, since the anti-HER-2 Th1 response can be restored by vaccination. Correction of the cellular immune response against HER-2 may prevent recurrence in high-risk patients with DCIS and IBC at risk of developing new or recurrent breast cancer.Fil: Nocera, Nadia F.. University of Pennsylvania; Estados UnidosFil: Lee, M. Catherine. H. Lee Moffitt Cancer Center; Estados UnidosFil: De La Cruz, Lucy M.. University of Pennsylvania; Estados UnidosFil: Rosemblit, Cinthia. University of Pennsylvania; Estados UnidosFil: Czerniecki, Brian J.. H. Lee Moffitt Cancer Center; Estados Unido

3D mesh processing using GAMer 2 to enable reaction-diffusion simulations in realistic cellular geometries

Recent advances in electron microscopy have enabled the imaging of single cells in 3D at nanometer length scale resolutions. An uncharted frontier for in silico biology is the ability to simulate cellular processes using these observed geometries. Enabling such simulations requires watertight meshing of electron micrograph images into 3D volume meshes, which can then form the basis of computer simulations of such processes using numerical techniques such as the Finite Element Method. In this paper, we describe the use of our recently rewritten mesh processing software, GAMer 2, to bridge the gap between poorly conditioned meshes generated from segmented micrographs and boundary marked tetrahedral meshes which are compatible with simulation. We demonstrate the application of a workflow using GAMer 2 to a series of electron micrographs of neuronal dendrite morphology explored at three different length scales and show that the resulting meshes are suitable for finite element simulations. This work is an important step towards making physical simulations of biological processes in realistic geometries routine. Innovations in algorithms to reconstruct and simulate cellular length scale phenomena based on emerging structural data will enable realistic physical models and advance discovery at the interface of geometry and cellular processes. We posit that a new frontier at the intersection of computational technologies and single cell biology is now open.Comment: 39 pages, 14 figures. High resolution figures and supplemental movies available upon reques

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes – NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases

Differentiation of mouse induced pluripotent stem cells (iPSCs) into nucleus pulposus-like cells in vitro.

A large percentage of the population may be expected to experience painful symptoms or disability associated with intervertebral disc (IVD) degeneration - a condition characterized by diminished integrity of tissue components. Great interest exists in the use of autologous or allogeneic cells delivered to the degenerated IVD to promote matrix regeneration. Induced pluripotent stem cells (iPSCs), derived from a patient's own somatic cells, have demonstrated their capacity to differentiate into various cell types although their potential to differentiate into an IVD cell has not yet been demonstrated. The overall objective of this study was to assess the possibility of generating iPSC-derived nucleus pulposus (NP) cells in a mouse model, a cell population that is entirely derived from notochord. This study employed magnetic activated cell sorting (MACS) to isolate a CD24(+) iPSC subpopulation. Notochordal cell-related gene expression was analyzed in this CD24(+) cell fraction via real time RT-PCR. CD24(+) iPSCs were then cultured in a laminin-rich culture system for up to 28 days, and the mouse NP phenotype was assessed by immunostaining. This study also focused on producing a more conducive environment for NP differentiation of mouse iPSCs with addition of low oxygen tension and notochordal cell conditioned medium (NCCM) to the culture platform. iPSCs were evaluated for an ability to adopt an NP-like phenotype through a combination of immunostaining and biochemical assays. Results demonstrated that a CD24(+) fraction of mouse iPSCs could be retrieved and differentiated into a population that could synthesize matrix components similar to that in native NP. Likewise, the addition of a hypoxic environment and NCCM induced a similar phenotypic result. In conclusion, this study suggests that mouse iPSCs have the potential to differentiate into NP-like cells and suggests the possibility that they may be used as a novel cell source for cellular therapy in the IVD

On the Nature of Fossil Galaxy Groups: Are they really fossils ?

We use SDSS-DR4 photometric and spectroscopic data out to redshift z~0.1 combined with ROSAT All Sky Survey X-ray data to produce a sample of twenty-five fossil groups (FGs), defined as bound systems dominated by a single, luminous elliptical galaxy with extended X-ray emission. We examine possible biases introduced by varying the parameters used to define the sample and the main pitfalls are discussed. The spatial density of FGs, estimated via the V/V_ MAX} test, is 2.83 x 10^{-6} h_{75}^3 Mpc^{-3} for L_x > 0.89 x 10^42 h_{75}^-2 erg/s consistent with Vikhlinin et al. (1999), who examined an X-ray overluminous elliptical galaxy sample (OLEG). We compare the general properties of FGs identified here with a sample of bright field ellipticals generated from the same dataset. These two samples show no differences in the distribution of neighboring faint galaxy density excess, distance from the red sequence in the color-magnitude diagram, and structural parameters such as a$_{4}$ and internal color gradients. Furthermore, examination of stellar populations shows that our twenty-five FGs have similar ages, metallicities, and $\alpha$-enhancement as the bright field ellipticals, undermining the idea that these systems represent fossils of a physical mechanism that occurred at high redshift. Our study reveals no difference between FGs and field ellipticals, suggesting that FGs might not be a distinct family of true fossils, but rather the final stage of mass assembly in the Universe.Comment: 18 pages, Accepted to A

Multiple shifts and fractional integration in the us and uk unemployment rates

This paper analyses the long-run behaviour of the US and UK unemployment rates by testing for possibly fractional orders of integration and multiple shifts using a sample of over 100 annual observations. The results show that the orders of integration are higher than 0 in both series, which implies long memory. If we assume that the underlying disturbances are white noise, the values are higher than 0.5, i.e., nonstationary. However, if the disturbances are autocorrelated, the orders of integration are in the interval (0, 0.5), implying stationarity and mean-reverting behaviour. Moreover, when multiple shifts are taken into account, unemployment is more persistent in the US than in the UK, implying the need for stronger policy action in the former to bring unemployment back to its original level

A Warp in Progress : H I and Radio Continuum Observations of the Spiral NGC 3145

Date of Acceptance: 16/06/2015We present VLA H I and 6 cm radio continuum observations of the spiral NGC 3145 and H I observations of its two companions, NGC 3143 and PGC 029578. In optical images NGC 3145 has stellar arms that appear to cross, forming "X"-features. Our radio continuum observations rule out shock fronts at 3 of the 4 "X"-features. In the middle-to-outer disk, the H I line-profiles of NGC 3145 are skewed. Relative to the disk, the gas in the skewed wing of the line-profiles has z-motions away from us on the approaching side of the galaxy and z-motions of about the same magnitude (about 40 km/s) towards us on the receding side. These warping motions imply that there has been a perturbation with a sizeable component perpendicular to the disk over large spatial scales. Two features in NGC 3145 have velocities indicating that they are out-of-plane tidal arms. One is an apparent branch of a main spiral arm; the velocity of the branch is 150 km/s greater than the spiral arm where they appear to intersect in projection. The other is an arm that forms 3 of the "X"-features. It differs in velocity by 56 km/s from the disk at the same projected location. Based on its SFR and H I properties, NGC 3143 is the more likely of the two companions to have interacted with NGC 3145 recently. A simple analytic model demonstrates that an encounter between NGC 3143 and NGC 3145 is a plausible explanation for the observed warping motions in NGC 3145.Peer reviewe

Spin waves and magnetic exchange interactions in the spin ladder compound RbFe2_2Se3_3

We report an inelastic neutron scattering study of the spin waves of the one-dimensional antiferromagnetic spin ladder compound RbFe$_2$Se$_3$. The results reveal that the products, $SJ$'s, of the spin $S$ and the magnetic exchange interactions $J$'s along the antiferromagnetic (leg) direction and the ferromagnetic (rung) direction are comparable with those for the stripe ordered phase of the parent compounds of the iron-based superconductors. The universality of the $SJ$'s implies nearly universal spin wave dynamics and the irrelevance of the fermiology for the existence of the stripe antiferromagnetic order among various Fe-based materials.Comment: 6 pages, 4 figure