Dendritic-Cell (DC)-Based Immunotherapy: Tumor Endothelial Marker 8 (TEM8) Gene Expression of DC Vaccines Correlates with Clinical Outcome

ABSTRACT\ud Previous studies have shown that tumor-endothelial markers (TEMs) are upregulated in immunosuppressive, pro-angiogenic dendritic cells (DCs) found in tumor microenvironments. \ud We reported that pro-angiogenic monocyte-derived DCs (Mo-DCs), utilized for therapeutic vaccination of cancer patients upon maturation, markedly differ in their ability to up-regulate tumor-endothelial marker 8 (TEM8) gene\ud expression. A DC vaccination trial of 17 advanced cancer patients (13 melanoma and 4 renal cell carcinoma), carried out at the Cancer Institute of Romagna (I.R.S.T.) in Meldola, highlighted a significant correlation between delayed-type hypersensitivity test (DTH) and overall survival (OS). In the study, relative TEM8 mRNA and protein expression levels (mature (m) vs. immature (i) DCs), in DCs obtained for therapeutic vaccines were evaluated by quantitative real-time RT-PCR and cytofluorimetric analysis, respectively. mDCs from six healthy donors were included for comparison purposes. Eight non-progressing patients, all DTH-positive, had a mean fold increase\ud (mfi) of 1.97 in TEM8 expression. Similarly, a TEM8 mRNA mfi = 2.7 was found in healthy donor mDCs. Conversely, mDCs from nine progressing patients, all but one with negative DTH, had a TEM8 mRNA mfi of 12.88. Thus, mDC TEM8 expression levels would seem to identify (p = 0.0018) patients who could benefit from DC therapeutic vaccination

A first unbiased global determination of polarized PDFs and their uncertainties

We present a first global determination of spin-dependent parton distribution functions (PDFs) and their uncertainties using the NNPDF methodology: NNPDFpol1.1. Longitudinally polarized deep-inelastic scattering data, already used for the previous NNPDFpol1.0 PDF set, are supplemented with the most recent polarized hadron collider data for inclusive jet and $W$ boson production from the STAR and PHENIX experiments at RHIC, and with open-charm production data from the COMPASS experiment, thereby allowing for a separate determination of the polarized quark and anti-quark PDFs, and an improved determination of the medium- and large-$x$ polarized gluon PDF. We study the phenomenological implications of the NNPDFpol1.1 set, and we provide predictions for the longitudinal double-spin asymmetry for semi-inclusive pion production at RHIC.Comment: 36 pages, 16 figures. Final version to be published in Nucl. Phys. B. Small textual improvements and minor typos correcte

A tight-binding model for MoS2_2 monolayers

We propose an accurate tight-binding parametrization for the band structure of MoS$_2$ monolayers near the main energy gap. We introduce a generic and straightforward derivation for the band energies equations that could be employed for other monolayer dichalcogenides. A parametrization that includes spin-orbit coupling is also provided. The proposed set of model parameters reproduce both the correct orbital compositions and location of valence and conductance band in comparison with ab initio calculations. The model gives a suitable starting point for realistic large-scale atomistic electronic transport calculations.Comment: 35 pages, 8 figure

Noise-driven cooperative dynamics between vegetation and topography in riparian zones

Riparian ecosystems exhibit complex biotic and abiotic dynamics, where the triad vegetation-sediments-stream determines the ecogeomorphological features of the river landscape. Random fluctuations of the water stage are a key trait of this triad, and a number of behaviors of the fluvial environment can be understood only taking into consideration the role of noise. In order to elucidate how randomness shape riparian transects, a stochastic model that takes into account the main links between vegetation, sediments, and the stream is adopted, emphasizing the capability of vegetation to alter the plot topography. A minimalistic approach is pursued, and the probability density function of vegetation biomass is analytically evaluated in any transect plot. This probability density function strongly depends on the vegetation-topography feedback. We demonstrate how the vegetation-induced modifications of the bed topography create more suitable conditions for the survival of vegetation in a stochastically dominated environment

Wind fluctuations affect the mean behaviour of naturally ventilated systems

We study the dynamics of a naturally ventilated room in which a point source provides a steady source of buoyancy and which is affected by an opposing unsteady wind. The wind is modelled as a stochastic forcing, which aims at simulating realistic velocity fluctuations as observed in the lower atmosphere. Our main finding is the occurrence of a "noise-induced transition", namely a structural change of the mean behaviour of the system: the warm-cold air interface does not fluctuate around the elevation exhibited when wind is constant, but oscillations occur around a new (significantly lower) interface elevation. We provide the physical explanation for such a counter-intuitive behaviour and show its dependence on (i) wind characteristics (intensity and timescale of fluctuations) and (ii) relative strength of wind over thermal loads. A realistic example case shows that the behaviour highlighted here has potentially major implications in the design and management of naturally ventilated buildings

Transport–diffusion models with nonlinear boundary conditions and solution by generalized collocation methods

AbstractThis paper deals with the derivation of a class of nonlinear transport and diffusion models implemented with nonlinear boundary conditions. Mathematical tools to treat the initial-boundary value problems are developed, based on generalized collocation methods, focused on the treatment of nonlinear boundary conditions in one space dimension. Applications refer to a problem of interest in applied sciences

Polarized Parton Distributions at an Electron-Ion Collider

We study the potential impact of inclusive deep-inelastic scattering data from a future electron-ion collider (EIC) on longitudinally polarized parton distribution (PDFs). We perform a PDF determination using the NNPDF methodology, based on sets of deep-inelastic EIC pseudodata, for different realistic choices of the electron and proton beam energies. We compare the results to our current polarized PDF set, NNPDFpol1.0, based on a fit to fixed-target inclusive DIS data. We show that the uncertainties on the first moments of the polarized quark singlet and gluon distributions are substantially reduced in comparison to NNPDFpol1.0, but also that more measurements may be needed to ultimately pin down the size of the gluon contribution to the nucleon spin.Comment: 11 pages, 6 figures. Two plots in Fig.5 added and discussion of extrapolation uncertainties expanded. Final version, published in Phys. Lett.

Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients

BACKGROUND: We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. METHODS: Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL) or – homogenate (ATH) and 50 μg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC) (range 4.5 – 82 × 10(6)) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2–26 × 10(6)). Subcutaneous interleukin-2 (3 × 10(6 )IU) was administered from days 3 to 7 of each treatment cycle. RESULTS: Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SD (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3 – 45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3–14) for the 11 DTH-negative patients (P < 0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%). CONCLUSION: Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival