Targeting lentiviral vectors to antigen-specific immunoglobulins

Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell Populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient rnethod to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and hi vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral Surface. This engineered vector could specifically bind to cells expressing Surface immunoglobulin recognizing CD20 (αCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing αCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin-specific cells to deliver a therapeutic effect. Such targeting lentivectors also Could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology

Bimodal Expansion of the Lymphatic Vessels Is Regulated by the Sequential Expression of IL-7 and Lymphotoxin α1β2 in Newly Formed Tertiary Lymphoid Structures.

Lymphangiogenesis associated with tertiary lymphoid structure (TLS) has been reported in numerous studies. However, the kinetics and dynamic changes occurring to the lymphatic vascular network during TLS development have not been studied. Using a viral-induced, resolving model of TLS formation in the salivary glands of adult mice we demonstrate that the expansion of the lymphatic vascular network is tightly regulated. Lymphatic vessel expansion occurs in two distinct phases. The first wave of expansion is dependent on IL-7. The second phase, responsible for leukocyte exit from the glands, is regulated by lymphotoxin (LT)βR signaling. These findings, while highlighting the tight regulation of the lymphatic response to inflammation, suggest that targeting the LTα1β2/LTβR pathway in TLS-associated pathologies might impair a natural proresolving mechanism for lymphocyte exit from the tissues and account for the failure of therapeutic strategies that target these molecules in diseases such as rheumatoid arthritis

The analysis of facial beauty: an emerging area of research in pattern analysis

Much research presented recently supports the idea that the human perception of attractiveness is data-driven and largely irrespective of the perceiver. This suggests using pattern analysis techniques for beauty analysis. Several scientific papers on this subject are appearing in image processing, computer vision and pattern analysis contexts, or use techniques of these areas. In this paper, we will survey the recent studies on automatic analysis of facial beauty, and discuss research lines and practical application

A dimensionally continued Poisson summation formula

We generalize the standard Poisson summation formula for lattices so that it operates on the level of theta series, allowing us to introduce noninteger dimension parameters (using the dimensionally continued Fourier transform). When combined with one of the proofs of the Jacobi imaginary transformation of theta functions that does not use the Poisson summation formula, our proof of this generalized Poisson summation formula also provides a new proof of the standard Poisson summation formula for dimensions greater than 2 (with appropriate hypotheses on the function being summed). In general, our methods work to establish the (Voronoi) summation formulae associated with functions satisfying (modular) transformations of the Jacobi imaginary type by means of a density argument (as opposed to the usual Mellin transform approach). In particular, we construct a family of generalized theta series from Jacobi theta functions from which these summation formulae can be obtained. This family contains several families of modular forms, but is significantly more general than any of them. Our result also relaxes several of the hypotheses in the standard statements of these summation formulae. The density result we prove for Gaussians in the Schwartz space may be of independent interest.Comment: 12 pages, version accepted by JFAA, with various additions and improvement

Pulsars as Fantastic Objects and Probes

Pulsars are fantastic objects, which show the extreme states of matters and plasma physics not understood yet. Pulsars can be used as probes for the detection of interstellar medium and even the gravitational waves. Here I review the basic facts of pulsars which should attract students to choose pulsar studies as their future projects.Comment: Invited Lecture on the "First Kodai-Trieste Workshop on Plasma Astrophysics", Kodaikanal Obs, India. Aug.27-Sept.7th, 2007. In: "Turbulence, Dynamos, Accretion Disks, Pulsars and Collective Plasma Processes". Get a copy from: http://www.springerlink.com/content/978-1-4020-8867-

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Measurement of the CP-Violating Asymmetry Amplitude sin2β\beta

We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.033 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.017 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes

A search for the decay B+→K+ννˉB^+ \to K^+ \nu \bar{\nu}

We search for the rare flavor-changing neutral-current decay $B^+ \to K^+ \nu \bar{\nu}$ in a data sample of 82 fb$^{-1}$ collected with the {\sl BABAR} detector at the PEP-II B-factory. Signal events are selected by examining the properties of the system recoiling against either a reconstructed hadronic or semileptonic charged-B decay. Using these two independent samples we obtain a combined limit of ${\mathcal B}(B^+ \to K^+ \nu \bar{\nu})<5.2 \times 10^{-5}$ at the 90% confidence level. In addition, by selecting for pions rather than kaons, we obtain a limit of ${\mathcal B}(B^+ \to \pi^+ \nu \bar{\nu})<1.0 \times 10^{-4}$ using only the hadronic B reconstruction method.Comment: 7 pages, 8 postscript figures, submitted to Phys. Rev. Let