Sharing Ghost Variables in a Collection of Abstract Domains

International audienceWe propose a framework in which we share ghost variables across a collection of abstract domains allowing precise proofs of complex properties. In abstract interpretation, it is often necessary to be able to express complex properties while doing a precise analysis. A way to achieve that is to combine a collection of domains, each handling some kind of properties, using a reduced product. Separating domains allows an easier and more modular implementation, and eases soundness and termination proofs. This way, we can add a domain for any kind of property that is interesting. The reduced product, or an approximation of it, is in charge of refining abstract states, making the analysis precise. In program verification, ghost variables can be used to ease proofs of properties by storing intermediate values that do not appear directly in the execution. We propose a reduced product of abstract domains that allows domains to use ghost variables to ease the representation of their internal state. Domains must be totally agnostic with respect to other existing domains. In particular the handling of ghost variables must be entirely decentralized while still ensuring soundness and termination of the analysis

PERT: A Method for Expression Deconvolution of Human Blood Samples from Varied Microenvironmental and Developmental Conditions

The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the actual constituent populations are often perturbed from those of the reference profiles due to gene expression changes in cells associated with microenvironmental or developmental effects. Existing deconvolution algorithms do not account for these changes and give incorrect results when benchmarked against those measured by well-established flow cytometry, even after batch correction was applied. We introduce PERT, a new probabilistic expression deconvolution method that detects and accounts for a shared, multiplicative perturbation in the reference profiles when performing expression deconvolution. We applied PERT and three other state-of-the-art expression deconvolution methods to predict cell frequencies within heterogeneous human blood samples that were collected under several conditions (uncultured mono-nucleated and lineage-depleted cells, and culture-derived lineage-depleted cells). Only PERT's predicted proportions of the constituent populations matched those assigned by flow cytometry. Genes associated with cell cycle processes were highly enriched among those with the largest predicted expression changes between the cultured and uncultured conditions. We anticipate that PERT will be widely applicable to expression deconvolution strategies that use profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular phenotypic identity

P16-37. HIV controllers with weak CD8+ T cell responses maintain a tight control of infection despite carrying infectious viruses

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Assessment of Transformed Properties In Vitro and of Tumorigenicity In Vivo in Primary Keratinocytes Cultured for Epidermal Sheet Transplantation

Epidermal keratinocytes are used as a cell source for autologous and allogenic cell transplant therapy for skin burns. The question addressed here is to determine whether the culture process may induce cellular, molecular, or genetic alterations that might increase the risk of cellular transformation. Keratinocytes from four different human donors were investigated for molecular and cellular parameters indicative of transformation status, including (i) karyotype, (ii) telomere length, (iii) proliferation rate, (iv) epithelial-mesenchymal transition, (v) anchorage-independent growth potential, and (vi) tumorigenicity in nude mice. Results show that, despite increased cell survival in one keratinocyte strain, none of the cultures displayed characteristics of cell transformations, implying that the culture protocol does not generate artefacts leading to the selection of transformed cells. We conclude that the current protocol does not result in an increased risk of tumorigenicity of transplanted cells

Light-induced strain and its correlation with the optical absorption at charged domain walls in polycrystalline ferroelectrics

Photostrictive materials have a growing interest because of their great potential as light-driven actuators, among other optomechanical applications. In this context, the optical control of macroscopic strain in ferroelectrics has recently attracted remarkable attention as an effective alternative to the conventional electric control of strain. Here, a clear correlation between optical absorption and light-induced strain in polycrystalline BaTiO3 is shown. Specifically, the grain size and the sample thickness dependence of optical absorption when the material is irradiated with energy photons lower than the band gap evidence that light absorption at charged domain walls is the core of the observed photo-response in ferroelectrics. The photoinduced electronic reconstruction phenomenon is proposed as the primary physical mechanism for light absorption at charged domain walls. Results open a new pathway to designing ferroelectric-based devices with new functionalities like thickness gradient-based photo-controlled nanoactuators

Sepsis in PD-1 light

Increasing evidence suggests that after the first pro-inflammatory hours, sepsis is characterized by the occurrence of severe immunosuppression. Several mechanisms have been reported to participate in sepsis-induced immune alterations affecting both innate and adaptive immunity. Of these, the concept of ‘cell exhaustion’ has gained a lot of interest because some parallels can be drawn with the cancer field in which immunostimulation approaches through blocking immune checkpoints currently obtain remarkable success. Herein, perspectives regarding co-inhibitory receptors’ contribution to lymphocyte exhaustion in sepsis will be discussed in the context of a recently published study investigating the potential of PD-1 molecule expression (i.e. PD-1 on lymphocytes, PD-L1 on monocytes) to predict mortality in septic shock patients

Tumor-infiltrating lymphocytes in patients receiving trastuzumab/pertuzumab-based chemotherapy : a TRYPHAENA Substudy

Background: There is an urgent requirement to identify biomarkers to tailor treatment in human epidermal growth factor receptor 2 (HER2)-amplified early breast cancer treated with trastuzumab/pertuzumab-based chemotherapy. Methods: Among the 225 patients randomly assigned to trastuzumab/pertuzumab concurrently or sequentially with an anthracycline-containing regimen or concurrently with an anthracycline-free regimen in the Tryphaena trial, we determined the percentage of tumor-infiltrating lymphocytes (TILs) at baseline in 213 patients, of which 126 demonstrated a pathological complete response (pCR; ypT0/is ypN0), with 28 demonstrating event-free survival (EFS) events. We investigated associations between baseline TIL percentage and either pCR or EFS after adjusting for clinicopathological characteristics using logistic and Cox regression models, respectively. To understand TIL biology, we evaluated associations between baseline TILs and baseline tumor gene expression data (800 gene set by NanoString) in a subset of 173 patients. All statistical tests were two-sided. Results: Among the patients with measurable TILs at baseline, the median level was 14.1% (interquartile range = 7.1%-32.4%). After adjusting for clinicopathological characteristics, baseline percentage TIL was not associated with pCR (adjusted odds ratio [aOR] for every 10-percentage unit increase in TILs = 1.12, 95% confidence interval [CI] = 0.95 to 1.31, P = .17). At a median follow-up of 4.7 years, for every increase in baseline TILs of 10%, there was a 25% reduction in the hazard for an EFS event (aOR = 0.75, 95% CI = 0.56 to 1.00, P = .05) after adjusting for baseline clinicopathological characteristics and pCR. Additionally, genes associated with epithelial-mesenchymal transition, angiogenesis, and T-cell inhibition such as SNAIL1, ZEB1, NOTCH3, and B7-H3 were statistically significantly inversely correlated with percentage TIL. Conclusions: Baseline TIL percentage provides independent prognostic information in patients treated with trastuzumab/pertuzumab-based neoadjuvant chemotherapy. However, further validation is required