Enhanced Phenotype Definition for Precision Isolation of Precursor Exhausted Tumor-Infiltrating CD8 T Cells.

In the context of adoptive T cell transfer (ACT) for cancer treatment, it is crucial to generate in vitro large amounts of tumor-specific CD8 T cells with high potential to persist in vivo. PD-1, Tim3, and CD39 have been proposed as markers of tumor-specific tumor-infiltrating CD8 T lymphocytes (CD8 TILs). However, these molecules are highly expressed by terminally differentiated exhausted CD8 T cells (Tex) that lack proliferation potential. Therefore, optimized strategies to isolate tumor-specific TILs with high proliferative potential, such as Tcf1+ precursor exhausted T cells (Tpe) are needed to improve in vivo persistence of ACT. Here we aimed at defining cell surface markers that would unequivocally identify Types for precision cell sorting increasing the purity of tumor-specific PD-1+ Tcf1+ Tpe from total TILs. Transcriptomic analysis of Tpe vs. Tex CD8 TIL subsets from B16 tumors and primary human melanoma tumors revealed that Tpes are enriched in Slamf6 and lack Entpd1 and Havcr2 expression, which encode Slamf6, CD39, and Tim3 cell surface proteins, respectively. Indeed, we observed by flow cytometry that CD39- Tim3- Slamf6+ PD-1+ cells yielded maximum enrichment for tumor specific PD-1+ Tcf1+ OT1 TILs in B16.OVA tumors. Moreover, this population showed higher re-expansion capacity upon an acute infection recall response compared to the CD39+ counterparts or bulk PD-1+ TILs. Hence, we report an enhanced sorting strategy (CD39- Tim3- Slamf6+ PD-1+) of Tpes. In conclusion, we show that optimization of CD8 TIL cell sorting strategy is a viable approach to improve recall capacity and in vivo persistence of transferred cells in the context of ACT

Reliability and validity of the Colombian version of the Revised Sociosexual Orientation Inventory

Sociosexuality refers to an individual’s disposition to have casual sex without establishing affective bonds and has been widely studied worldwide using the Revised Sociosexual Orientation Inventory (SOI-R; Penke & Asendorpf, 2008). Despite its many validations in different cultural contexts, no psychometric analyses of this instrument have been conducted in Spanish-speaking Latin American countries. To address this gap in the literature, we examined the psychometric properties of the SOI-R in Colombia. In a cross-sectional study with a large sample of participants (N = 812; 64% women), we conducted exploratory and confirmatory factor analyses to identify different factor structures and determine which had the best fit for our sample and examined the reliability of the scale. Results showed that a three-factor structure, with sociosexual behaviors, attitudes, and desire as first-order factors, and global sociosexuality as a second-order factor, had the best fit indexes. Each factor presented good reliability indexes. Replicating already established gender differences, we also found that men scored higher on each factor when compared to women. These findings show that the SOI-R is a reliable and valid instrument to assess sociosexuality in countries where sociosexuality research is underrepresented.info:eu-repo/semantics/publishedVersio

Relativistic quantum mechanics of a Dirac oscillator

The Dirac oscillator is an exactly soluble model recently introduced in the context of many particle models in relativistic quantum mechanics. The model has been also considered as an interaction term for modelling quark confinement in quantum chromodynamics. These considerations should be enough for demonstrating that the Dirac oscillator can be an excellent example in relativistic quantum mechanics. In this paper we offer a solution to the problem and discuss some of its properties. We also discuss a physical picture for the Dirac oscillator's non-standard interaction, showing how it arises on describing the behaviour of a neutral particle carrying an anomalous magnetic moment and moving inside an uniformly charged sphere.Comment: 19 pages, 1 figur

Halo based reconstruction of the cosmic mass density field

We present the implementation of a halo based method for the reconstruction of the cosmic mass density field. The method employs the mass density distribution of dark matter haloes and its environments computed from cosmological N-body simulations and convolves it with a halo catalog to reconstruct the dark matter density field determined by the distribution of haloes. We applied the method to the group catalog of Yang etal (2007) built from the SDSS Data Release 4. As result we obtain reconstructions of the cosmic mass density field that are independent on any explicit assumption of bias. We describe in detail the implementation of the method, present a detailed characterization of the reconstructed density field (mean mass density distribution, correlation function and counts in cells) and the results of the classification of large scale environments (filaments, voids, peaks and sheets) in our reconstruction. Applications of the method include morphological studies of the galaxy population on large scales and the realization of constrained simulations.Comment: Accepted for publication in MNRA

Model-free Rheo-AFM probes the viscoelasticity of tunable DNA soft colloids

Atomic force microscopy rheological measurements (Rheo‐AFM) of the linear viscoelastic properties of single, charged colloids having a star‐like architecture with a hard core and an extended, deformable double‐stranded DNA (dsDNA) corona dispersed in aqueous saline solutions are reported. This is achieved by analyzing indentation and relaxation experiments performed on individual colloidal particles by means of a novel model‐free Fourier transform method that allows a direct evaluation of the frequency‐dependent linear viscoelastic moduli of the system under investigation. The method provides results that are consistent with those obtained via a conventional fitting procedure of the force‐relaxation curves based on a modified Maxwell model. The outcomes show a pronounced softening of the dsDNA colloids, which is described by an exponential decay of both the Young's and the storage modulus as a function of the salt concentration within the dispersing medium. The strong softening is related to a critical reduction of the size of the dsDNA corona, down to ≈70% of its size in a salt‐free solution. This can be correlated to significant topological changes of the dense star‐like polyelectrolyte forming the corona, which are induced by variations in the density profile of the counterions. Similarly, a significant reduction of the stiffness is obtained by increasing the length of the dsDNA chains, which we attribute to a reduction of the DNA density in the outer region of the corona

An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma.

PD-1/PD-L1 pathway plays a role in inhibiting immune response. Therapeutic antibodies aimed at blocking the PD-1/PD-L1 interaction have entered clinical development and have been approved for a variety of cancers. However, the clinical benefits are reduced to a group of patients. The research in combined therapies, which allow for a greater response, is strongly encouraging. We previously characterized a polyphenol-rich extract from Caesalpinia spinosa (P2Et) with antitumor activity in both melanoma and breast carcinoma, as well as immunomodulatory activity. We hypothesize that the combined treatment with P2Et and anti-PD-L1 can improve the antitumor response through an additive antitumor effect. We investigated the antitumor and immunomodulatory activity of P2Et and anti-PD-L1 combined therapy in B16-F10 melanoma and 4T1 breast carcinoma. We analyzed tumor growth, hematologic parameters, T cell counts, cytokine expression, and T cell cytotoxicity. In the melanoma model, combined P2Et and anti-PD-L1 therapy has the following effects: decrease in tumor size; increase in the number of activated CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells; decrease in the number of suppressor myeloid cells; increase in PD-L1 expression; decrease in the frequency of CD8 <sup>+</sup> T cell expressing PD-1; improvement in the cytotoxic activity of T cells; and increase in the IFN γ secretion. In the breast cancer model, P2Et and PD-L1 alone or in combination show antitumor effect with no clear additive effect. This study shows that combined therapy of P2Et and anti-PD-L1 can improve antitumor response in a melanoma model by activating the immune response and neutralizing immunosuppressive mechanisms

Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.

Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-γ) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et's anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et's anti-tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells

Non-linear classifiers applied to EEG analysis for epilepsy seizure detection

This work presents a novel approach for automatic epilepsy seizure detection based on EEG analysis that exploits the underlying non-linear nature of EEG data. In this paper, two main contributions are presented and validated: the use of non-linear classifiers through the so-called kernel trick and the proposal of a Bag-of-Words model for extracting a non-linear feature representation of the input data in an unsupervised manner. The performance of the resulting system is validated with public datasets, previously processed to remove artifacts or external disturbances, but also with private datasets recorded under realistic and non-ideal operating conditions. The use of public datasets caters for comparison purposes whereas the private one shows the performance of the system under realistic circumstances of noise, artifacts, and signals of different amplitudes. Moreover, the proposed solution has been compared to state-of-the-art works not only for pre-processed and public datasets but also with the private datasets. The mean F1-measure shows a 10% improvement over the second-best ranked method including cross-dataset experiments. The obtained results prove the robustness of the proposed solution to more realistic and variable conditions. (C) 2017 Elsevier Ltd. All rights reserved

Reduced salivary oxytocin after an empathic induction task in Intimate Partner Violence perpetrators: Importance of socio-affective functions and its impact on prosocial behavior

Intimate Partner Violence (IPV) has been linked to difficulties in socio-affective functions. Nevertheless, the underlying psychobiological mechanisms that might be responsible for them remain unclear. Oxytocin (OXT) stands out as an important hormone that may favor the salience of social information, due to its relevance in empathy and prosocial behavior. Thus, the study of salivary OXT (sOXT) may provide further information about potential impairments in social cognition in IPV perpetrators. This study analyzed the effects of an empathic induction task, performed through negative emotion-eliciting videos, on endogenous sOXT levels, mood state, and emotional perception in 30 IPV perpetrators compared to 32 controls. Additionally, we explored their performance on prosocial behavior after the empathic induction task, using Hare''s donation procedure. Lower sOXT levels were found in IPV perpetrators after the task compared to controls, along with a general decreasing tendency in their sOXT levels. Additionally, IPV perpetrators exhibited no change in their mood state and perceived others'' emotions as more positive and less intense. Moreover, the mood state response and alexithymia traits, respectively, positively and negatively predicted the sOXT levels after the empathic induction task in the entire sample. Finally, we did not observe a lower appearance of prosocial behaviors in IPV perpetrators; however, higher sOXT levels after the empathic induction task were found in subjects who donated when considering the whole sample. In sum, IPV perpetrators exhibited differences in their sOXT levels when empa-thizing, compared to controls, with alexithymia and the emotional response potentially explaining the sOXT levels after the task. Furthermore, prosocial behavior was more related to these sOXT levels than to IPV. As our knowledge about the emotional processing of IPV perpetrators increases, we will be better able to develop and include coadjutant treatments in current psychotherapeutic programs, in order to focus on their emotional needs, which, in turn, would reduce the future risk of recidivism