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Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.
The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response
Intensity-Based Registration of Freehand 3D Ultrasound and CT-scan Images of the Kidney
This paper presents a method to register a pre-operative Computed-Tomography
(CT) volume to a sparse set of intra-operative Ultra-Sound (US) slices. In the
context of percutaneous renal puncture, the aim is to transfer planning
information to an intra-operative coordinate system. The spatial position of
the US slices is measured by optically localizing a calibrated probe. Assuming
the reproducibility of kidney motion during breathing, and no deformation of
the organ, the method consists in optimizing a rigid 6 Degree Of Freedom (DOF)
transform by evaluating at each step the similarity between the set of US
images and the CT volume. The correlation between CT and US images being
naturally rather poor, the images have been preprocessed in order to increase
their similarity. Among the similarity measures formerly studied in the context
of medical image registration, Correlation Ratio (CR) turned out to be one of
the most accurate and appropriate, particularly with the chosen non-derivative
minimization scheme, namely Powell-Brent's. The resulting matching transforms
are compared to a standard rigid surface registration involving segmentation,
regarding both accuracy and repeatability. The obtained results are presented
and discussed
Observation of Dirac plasmons in a topological insulator
Plasmons are the quantized collective oscillations of electrons in metals and
doped semiconductors. The plasmons of ordinary, massive electrons are since a
long time basic ingredients of research in plasmonics and in optical
metamaterials. Plasmons of massless Dirac electrons were instead recently
observed in a purely two-dimensional electron system (2DEG)like graphene, and
their properties are promising for new tunable plasmonic metamaterials in the
terahertz and the mid-infrared frequency range. Dirac quasi-particles are known
to exist also in the two-dimensional electron gas which forms at the surface of
topological insulators due to a strong spin-orbit interaction. Therefore,one
may look for their collective excitations by using infrared spectroscopy. Here
we first report evidence of plasmonic excitations in a topological insulator
(Bi2Se3), that was engineered in thin micro-ribbon arrays of different width W
and period 2W to select suitable values of the plasmon wavevector k. Their
lineshape was found to be extremely robust vs. temperature between 6 and 300 K,
as one may expect for the excitations of topological carriers. Moreover, by
changing W and measuring in the terahertz range the plasmonic frequency vP vs.
k we could show, without using any fitting parameter, that the dispersion curve
is in quantitative agreement with that predicted for Dirac plasmons.Comment: 11 pages, 3 figures, published in Nature Nanotechnology (2013
Three Ways of Combining Genotyping and Resequencing in Case-Control Association Studies
We describe three statistical results that we have found to be useful in case-control genetic association testing. All three involve combining the discovery of novel genetic variants, usually by sequencing, with genotyping methods that recognize previously discovered variants. We first consider expanding the list of known variants by concentrating variant-discovery in cases. Although the naive inclusion of cases-only sequencing data would create a bias, we show that some sequencing data may be retained, even if controls are not sequenced. Furthermore, for alleles of intermediate frequency, cases-only sequencing with bias-correction entails little if any loss of power, compared to dividing the same sequencing effort among cases and controls. Secondly, we investigate more strongly focused variant discovery to obtain a greater enrichment for disease-related variants. We show how case status, family history, and marker sharing enrich the discovery set by increments that are multiplicative with penetrance, enabling the preferential discovery of high-penetrance variants. A third result applies when sequencing is the primary means of counting alleles in both cases and controls, but a supplementary pooled genotyping sample is used to identify the variants that are very rare. We show that this raises no validity issues, and we evaluate a less expensive and more adaptive approach to judging rarity, based on group-specific variants. We demonstrate the important and unusual caveat that this method requires equal sample sizes for validity. These three results can be used to more efficiently detect the association of rare genetic variants with disease
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Measurement of masses in the [Formula: see text] system by kinematic endpoints in pp collisions at [Formula: see text].
A simultaneous measurement of the top-quark, W-boson, and neutrino masses is reported for [Formula: see text] events selected in the dilepton final state from a data sample corresponding to an integrated luminosity of 5.0 fb-1 collected by the CMS experiment in pp collisions at [Formula: see text]. The analysis is based on endpoint determinations in kinematic distributions. When the neutrino and W-boson masses are constrained to their world-average values, a top-quark mass value of [Formula: see text] is obtained. When such constraints are not used, the three particle masses are obtained in a simultaneous fit. In this unconstrained mode the study serves as a test of mass determination methods that may be used in beyond standard model physics scenarios where several masses in a decay chain may be unknown and undetected particles lead to underconstrained kinematics
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Search for physics beyond the standard model in events with Ď„ leptons, jets, and large transverse momentum imbalance in pp collisions at [Formula: see text].
A search for physics beyond the standard model is performed with events having one or more hadronically decaying Ď„ leptons, highly energetic jets, and large transverse momentum imbalance. The data sample corresponds to an integrated luminosity of 4.98 fb-1 of proton-proton collisions at [Formula: see text] collected with the CMS detector at the LHC in 2011. The number of observed events is consistent with predictions for standard model processes. Lower limits on the mass of the gluino in supersymmetric models are determined
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Measurement of jet multiplicity distributions in [Formula: see text] production in pp collisions at [Formula: see text].
The normalised differential top quark-antiquark production cross section is measured as a function of the jet multiplicity in proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] at the LHC with the CMS detector. The measurement is performed in both the dilepton and lepton+jets decay channels using data corresponding to an integrated luminosity of 5.0[Formula: see text]. Using a procedure to associate jets to decay products of the top quarks, the differential cross section of the [Formula: see text] production is determined as a function of the additional jet multiplicity in the lepton+jets channel. Furthermore, the fraction of events with no additional jets is measured in the dilepton channel, as a function of the threshold on the jet transverse momentum. The measurements are compared with predictions from perturbative quantum chromodynamics and no significant deviations are observed
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Search for supersymmetry in hadronic final states with missing transverse energy using the variables αT and b-quark multiplicity in pp collisions at [Formula: see text].
An inclusive search for supersymmetric processes that produce final states with jets and missing transverse energy is performed in pp collisions at a centre-of-mass energy of 8 TeV. The data sample corresponds to an integrated luminosity of 11.7 fb-1 collected by the CMS experiment at the LHC. In this search, a dimensionless kinematic variable, αT, is used to discriminate between events with genuine and misreconstructed missing transverse energy. The search is based on an examination of the number of reconstructed jets per event, the scalar sum of transverse energies of these jets, and the number of these jets identified as originating from bottom quarks. No significant excess of events over the standard model expectation is found. Exclusion limits are set in the parameter space of simplified models, with a special emphasis on both compressed-spectrum scenarios and direct or gluino-induced production of third-generation squarks. For the case of gluino-mediated squark production, gluino masses up to 950-1125 GeV are excluded depending on the assumed model. For the direct pair-production of squarks, masses up to 450 GeV are excluded for a single light first- or second-generation squark, increasing to 600 GeV for bottom squarks
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Probing color coherence effects in pp collisions at [Formula: see text].
A study of color coherence effects in pp collisions at a center-of-mass energy of 7[Formula: see text] is presented. The data used in the analysis were collected in 2010 with the CMS detector at the LHC and correspond to an integrated luminosity of 36 pb[Formula: see text]. Events are selected that contain at least three jets and where the two jets with the largest transverse momentum exhibit a back-to-back topology. The measured angular correlation between the second- and third-leading jet is shown to be sensitive to color coherence effects, and is compared to the predictions of Monte Carlo models with various implementations of color coherence. None of the models describe the data satisfactorily
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