Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001

HIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years of infection, and therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that moderate protection is possible and that this protection may correlate with antibody-dependent cellular cytotoxicity (ADCC) activity. Our previous studies demonstrated that in an HIV vaccine phase I trial, the DP6-001 trial, a polyvalent Env DNA prime-protein boost formulation could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities. Here we report on the production and analysis of HIV-1 Env-specific human monoclonal antibodies (hMAbs) isolated from vaccinees in the DP6-001 trial. For this initial report, 13 hMAbs from four vaccinees in the DP6-001 trial showed broad binding to gp120 proteins of diverse subtypes both autologous and heterologous to vaccine immunogens. Equally cross-reactive Fc receptor-mediated functional activities, including ADCC and antibody-dependent cellular phagocytosis (ADCP) activities, were present with both immune sera and isolated MAbs, confirming the induction of nonneutralizing functional hMAbs by the DNA prime-protein boost vaccination. Elicitation of broadly reactive hMAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV vaccine design. IMPORTANCE: The roles of Fc receptor-mediated protective antibody responses are gaining more attention due to their potential contribution to the low-level protection against HIV-1 infection that they provided in the RV144 trial. At the same time, information about hMabs from other human HIV vaccine studies is very limited. In the current study, both immune sera and monoclonal antibodies from vaccinated humans showed not only high-level ADCC and ADCP activities but also cross-subtype ADCC and ADCP activities when a polyvalent DNA prime-protein boost vaccine formulation was used

Spectral Energy Distributions of Young Stars in IC 348: The Role of Disks in Angular Momentum Evolution of Young, Low-Mass Stars

Theoretical work suggests that a young star's angular momentum and rotation rate may be strongly influenced by magnetic interactions with its circumstellar disk. A generic prediction of these 'disk-locking' (DL) theories is that a disk-locked star will be forced to co-rotate with the Keplerian angular velocity of the inner edge of the disk. These theories have also been interpreted to suggest a correlation between young stars' rotation periods and the structural properties of their disks, such that slowly rotating stars possess close-in disks that enforce the star's slow rotation, whereas rapidly rotating stars possess anemic or evacuated inner disks that are unable to brake the stars and they spin up as they contract. To test these expectations, we model the SEDs of 33 young stars in IC 348 with known rotation periods and infrared excesses indicating the presence of disks. For each star, we match the observed spectral energy distribution, typically sampling 0.6-8.0 \mum, to a grid of 200,000 pre-computed star+disk radiative transfer models, from which we infer the disk's inner-truncation radius (R_trunc). We then compare this R_trunc to the disk's co-rotation radius (R_co), calculated from the star's rotation period. We do not find obvious differences in the disk R_trunc of slow vs. rapid rotators. This holds true both at the level of whether close-in disk material is present at all, and in analyzing the precise location of the inner disk edge relative to the R_co amongst the subset of stars with close-in disk material. One interpretation is that DL is unimportant for the IC 348 stars in our sample. Alternatively, if DL does operate, then it must operate on both the slow and rapid rotators, potentially producing both spin-up and spin-down torques, and the transition from the disk-locked state to the disk-released state must occur more rapidly than the stellar contraction timescale.Comment: 52 pages, 37 figures, 2 tables Accepted by Astronomical Journal, 02 June, 201

Application of area scaling analysis to identify natural killer cell and monocyte involvement in the GranToxiLux antibody dependent cell-mediated cytotoxicity assay

Several different assay methodologies have been described for the evaluation of HIV or SIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC). Commonly used assays measure ADCC by evaluating effector cell functions, or by detecting elimination of target cells. Signaling through Fc receptors, cellular activation, cytotoxic granule exocytosis, or accumulation of cytolytic and immune signaling factors have been used to evaluate ADCC at the level of the effector cells. Alternatively, assays that measure killing or loss of target cells provide a direct assessment of the specific killing activity of antibodies capable of ADCC. Thus, each of these two distinct types of assays provides information on only one of the critical components of an ADCC event; either the effector cells involved, or the resulting effect on the target cell. We have developed a simple modification of our previously described high-throughput ADCC GranToxiLux (GTL) assay that uses area scaling analysis (ASA) to facilitate simultaneous quantification of ADCC activity at the target cell level, and assessment of the contribution of natural killer cells and monocytes to the total observed ADCC activity when whole human peripheral blood mononuclear cells are used as a source of effector cells. The modified analysis method requires no additional reagents and can, therefore, be easily included in prospective studies. Moreover, ASA can also often be applied to pre-existing ADCC-GTL datasets. Thus, incorporation of ASA to the ADCC-GTL assay provides an ancillary assessment of the ability of natural and vaccine-induced antibodies to recruit natural killer cells as well as monocytes against HIV or SIV; or to any other field of research for which this assay is applied

A multi-wavelength study of the young star V1118 Orionis in outburst

Abriged version for astroph: The young late-type star V1118 Orionis was in outburst from 2005 to 2006. We followed the outburst with optical and near-infrared photometry; the X-ray emission was further probed with observations taken with XMM-Newton and Chandra during and after the outburst. In addition, we obtained mid-infrared photometry and spectroscopy with Spitzer at the peak of the outburst and in the post-outburst phase. The spectral energy distribution of V1118 Ori varied significantly over the course of the outburst. The optical flux showed the largest variations, most likely due to enhanced emission by a hot spot. The latter dominated the optical and near-infrared emission at the peak of the outburst, while the disk emission dominated in the mid-infrared. The X-ray flux correlated with the optical and infrared fluxes, indicating that accretion affected the magnetically active corona and the stellar magnetosphere. The thermal structure of the corona was variable with some indication of a cooling of the coronal temperature in the early phase of the outburst with a gradual return to normal values. Color-color diagrams in the optical and infrared showed variations during the outburst, with no obvious signature of reddening due to circumstellar matter. Using MC realizations of star+disk+hotspot models to fit the SED in ``quiescence'' and at the peak of the outburst, we determined that the mass accretion rate varied from about 2.5E-7 Msun/yr to 1E-6 Msun/yr; in addition the fractional area of the hotspot increased significantly as well. The multi-wavelength study of the V1118 Ori outburst helped us to understand the variations in spectral energy distributions and demonstrated the interplay between the disk and the stellar magnetosphere in a young, strongly accreting star.Comment: Accepted in A&A, Tables will be published onlin

POISSON project - II - A multi-wavelength spectroscopic and photometric survey of young protostars in L 1641

Characterising stellar and circumstellar properties of embedded young stellar objects (YSOs) is mandatory for understanding the early stages of the stellar evolution. This task requires the combination of both spectroscopy and photometry, covering the widest possible wavelength range, to disentangle the various protostellar components and activities. As part of the POISSON project, we present a multi-wavelength spectroscopic and photometric investigation of embedded YSOs in L1641, aimed to derive the stellar parameters and evolutionary stages and to infer their accretion properties. Our database includes low-resolution optical-IR spectra from the NTT and Spitzer (0.6-40 um) and photometric data covering a spectral range from 0.4 to 1100 um, which allow us to construct the YSOs spectral energy distributions (SEDs) and to infer the main stellar parameters. The SED analysis allows us to group our 27 YSOs into nine Class I, eleven Flat, and seven Class II objects. However, on the basis of the derived stellar properties, only six Class I YSOs have an age of ~10^5 yr, while the others are older 5x10^5-10^6 yr), and, among the Flat sources, three out of eleven are more evolved objects (5x10^6-10^7 yr), indicating that geometrical effects can significantly modify the SED shapes. Inferred mass accretion rates (Macc) show a wide range of values (3.6x10^-9 to 1.2x10^-5 M_sun yr^-1), which reflects the age spread observed in our sample. Average values of mass accretion rates, extinction, and spectral indices decrease with the YSO class. The youngest YSOs have the highest Macc, whereas the oldest YSOs do not show any detectable jet activity in either images and spectra. We also observe a clear correlation among the YSO Macc, M*, and age, consistent with mass accretion evolution in viscous disc models.Comment: 61 pages, 16 figures; A&A in pres

Intrapartum Antibiotic Prophylaxis and Early-Onset Neonatal Sepsis Patterns

Objective: To compare the relative effects of intrapartum antibiotic prophylaxis regimens on patterns of early-onset neonatal sepsis. Methods: We performed an historical cohort study of 17 187 infants born at our center from September 1993 to February 2000. A risk-based strategy was employed prior to July 1996 and a screening-based strategy was utilized thereafter. Ampicillin was utilized prior to March 1995 and penicillin was used thereafter. Results: There were 75 cases of neonatal sepsis, 34 (4.10/1000) in the risk-based era and 41 (4.63/1000) in the screening-based era (p = 0.62). There were fewer ampicillin-resistant isolates during the risk-based than the screening-based era (32 versus 61%; p = 0.014). The only significant change in organism-specific sepsis rates was an increase in the rate of infection caused by coagulase-negative staphylococci in the screening-based era (0.36 versus 1.46/1000; p = 0.018), but 75% of infants infected with these organisms were not exposed to ß-lactam antibiotics within 72 h prior to delivery. For the risk- and screening-based eras, respectively, the rates of Gram-negative sepsis (1.21 versus 1.46/1000; p = 0.65) and the proportions of Gram-negative pathogens that were ampicillin-resistant (70 versus 77%; p = 1.0) were similar. The drug employed for prophylaxis did not appear to affect the pattern of sepsis cases. Conclusion: In our patient population, coagulase-negative staphylococci have become the most common cause of early-onset neonatal sepsis. The cause of this shift in pathogen prevalence is uncertain and seemingly unrelated to intrapartum antibiotic exposure

Transfer Matrices and Partition-Function Zeros for Antiferromagnetic Potts Models. V. Further Results for the Square-Lattice Chromatic Polynomial

We derive some new structural results for the transfer matrix of square-lattice Potts models with free and cylindrical boundary conditions. In particular, we obtain explicit closed-form expressions for the dominant (at large |q|) diagonal entry in the transfer matrix, for arbitrary widths m, as the solution of a special one-dimensional polymer model. We also obtain the large-q expansion of the bulk and surface (resp. corner) free energies for the zero-temperature antiferromagnet (= chromatic polynomial) through order q^{-47} (resp. q^{-46}). Finally, we compute chromatic roots for strips of widths 9 <= m <= 12 with free boundary conditions and locate roughly the limiting curves.Comment: 111 pages (LaTeX2e). Includes tex file, three sty files, and 19 Postscript figures. Also included are Mathematica files data_CYL.m and data_FREE.m. Many changes from version 1: new material on series expansions and their analysis, and several proofs of previously conjectured results. Final version to be published in J. Stat. Phy

The context influences doctors' support of shared decision-making in cancer care

Most cancer patients in westernised countries now want all information about their situation, good or bad, and many wish to be involved in decision-making. The attitudes to and use of shared decision-making (SDM) by cancer doctors is not well known. Australian cancer clinicians treating breast, colorectal, gynaecological, haematological, or urological cancer were surveyed to identify their usual approach to decision-making and their comfort with different decision-making styles when discussing treatment with patients. A response rate of 59% resulted in 624 complete surveys, which explored usual practice in discussing participation in decision-making, providing information, and perception of the role patients want to play. Univariate and multivariate analyses were performed to identify predictors of use of SDM. Most cancer doctors (62.4%) reported using SDM and being most comfortable with this approach. Differences were apparent between reported high comfort with SDM and less frequent usual practice. Multivariate analysis showed that specialisation in breast or urological cancers compared to other cancers (AOR 3.02), high caseload of new patients per month (AOR 2.81) and female gender (AOR 1.87) were each independently associated with increased likelihood of use of SDM. Barriers exist to the application of SDM by doctors according to clinical situation and clinician characteristics

Spanning forests and the q-state Potts model in the limit q \to 0

We study the q-state Potts model with nearest-neighbor coupling v=e^{\beta J}-1 in the limit q,v \to 0 with the ratio w = v/q held fixed. Combinatorially, this limit gives rise to the generating polynomial of spanning forests; physically, it provides information about the Potts-model phase diagram in the neighborhood of (q,v) = (0,0). We have studied this model on the square and triangular lattices, using a transfer-matrix approach at both real and complex values of w. For both lattices, we have computed the symbolic transfer matrices for cylindrical strips of widths 2 \le L \le 10, as well as the limiting curves of partition-function zeros in the complex w-plane. For real w, we find two distinct phases separated by a transition point w=w_0, where w_0 = -1/4 (resp. w_0 = -0.1753 \pm 0.0002) for the square (resp. triangular) lattice. For w > w_0 we find a non-critical disordered phase, while for w < w_0 our results are compatible with a massless Berker-Kadanoff phase with conformal charge c = -2 and leading thermal scaling dimension x_{T,1} = 2 (marginal operator). At w = w_0 we find a "first-order critical point": the first derivative of the free energy is discontinuous at w_0, while the correlation length diverges as w \downarrow w_0 (and is infinite at w = w_0). The critical behavior at w = w_0 seems to be the same for both lattices and it differs from that of the Berker-Kadanoff phase: our results suggest that the conformal charge is c = -1, the leading thermal scaling dimension is x_{T,1} = 0, and the critical exponents are \nu = 1/d = 1/2 and \alpha = 1.Comment: 131 pages (LaTeX2e). Includes tex file, three sty files, and 65 Postscript figures. Also included are Mathematica files forests_sq_2-9P.m and forests_tri_2-9P.m. Final journal versio

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc