Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

Characterization of poly(diethoxyphosphazene) by size exclusion chromatography and viscometry

Two samples of poly(diethoxyphosphazene) (PDEP) having very different molecular weights have been studied by viscometry and size exclusion chromatography in THF solution. The results obtained, together with light scattering data of these samples, allow the calculation of the Mark-Houwink constants a=0.65 and K=2.5 10^-4 in THF at 25°C. The method of calculation employed takes into account the great polydispersity of the samples. The characteristic ratio of the unperturbed dimensions was also calculated giving C_n = r²_o/n² 18, a value slightly higher than those previously reported for poly(dihexoxyphosphazene), C_n13 and poly (dichlorophosphazene), C_n13.5.     

Modelling the effects of human papillomavirus in cervical cells

Worldwide, cervical cancer is the second most common cancer in women, after breast cancer. The prevalence of this malignant disease is estimated at 1.4 million cases worldwide, causing about 290,000 deaths and 500,000 new cases per year, of which 80% correspond to women living in developing countries. In this work we propose a family of ordered models for basal cells of the cervix corresponding to different stages ranging from normal cells to the formation of precancerous lesions. We analyse the first member of the family analytically and for the second member we developed a non-standard numerical method in order to extract some biological information.     

A voltammetric study concerning the structural stability of Li-overstoichiometric Mg-doped LiCoO2 powders

The effect of Mg-doping and Li overstoichiometry on the structural stability of LiCoO₂ powders has been investigated with emphasis to voltammetric properties. Microparticle cyclic voltammetry (CV) conducted in caustic NaOH to best simulate a non-aqueous electrolyte shows a marked improvement of the structure stability of doped LiCoO₂. In contrast to the unsubstituted LiCoO₂ sample which shows voltammetric peaks associated to the well-known two-phase domain and monoclinic distortion reactions, in Li_1.08Mg_0.06CoO₂, LiMg_0.06CoO₂ and Li_1.08CoO₂ samples these peaks are strongly suppressed providing direct evidence for the existence of a stable solid solution with negligible phase transitions in the reversible intercalation region (3.8-4.2 V vs. Li) as well as in the overcharged region. The effect is higher with Mg-doping, irrespective of the Li overstoichiometry. However, the concomitant presence of Mg and Li excess in the structure is important for obtaining small particle sizes. Since Mg-doping induces a quasi metallic behavior in the samples, whereas the Li excess may provide an higher initial capacity, it is suggested that the Li_1.08Mg_0.06CoO₂ composition may be of interest as positive cathode for advanced Li-ion batteries.     

Communication across Viewpoints

A case situation arising in a normal interaction among people is the baseline for discussing properties of the theory of viewpoints. In particular we consider how to ensure agreement on the meaning of certain utterances by agents who have different perspectives on the situation, while maintaning other knowledge as private. We argue that communication should be modeled as adding facts to the common knowledge of agents. We introduce the principle of 'referent sharing' in communications and argue that common knowledge resulting from communication should only use constants whose referent is manifest to the parties involved.     

Repeated auctions for robust task execution by a robot team

We present empirical results of an auction-based algorithm for dynamic allocation of tasks to robots. The results have been obtained both in simulation and using real robots. A distinctive feature of our algorithm is its robustness to uncertainties and to robot malfunctions that happen during task execution, when unexpected obstacles, loss of communication, and other delays may prevent a robot from completing its allocated tasks. Therefore tasks not yet achieved are resubmitted for bids every time a task has been completed. This provides an opportunity to improve the allocation of the remaining tasks, enabling the robots to recover from failures and reducing the overall time for task completion.     

Filling gaps in diameter measurements on standing tree boles in the urban forest of Thessaloniki,Greece

Missing data are omnipresent in forestry research, and this poses problems in the analysis of primary data. Many statistical problems have been viewed as missing data problems. To cope with incomplete data, several methods are currently being used. They are all based on assumptions some of which might not be valid in a particular case. The choice mostly depends on the objective of the study. Considerable mensuration research is motivated by the need for yield projections that can support forest management decisions. This paper is focused on a new approach for filling gaps in diameter measurements on standing tree boles. Dealing with this problem, an attempt was made to examine the applicability of artificial neural network models for missing data estimation and to use the estimated values in the subsequent analysis. The procedure that should be followed in the development of such models is outlined. The results show good performance of the examined ANN models compared to regression treatments for missing data and ANN models demonstrate their adequacy and potential for filling gaps in diameter measurements on standing tree boles. The ANN models applied in this study are sufficiently general and have great potential to be applicable for estimating the missing values of many variables in environmental applications.     

A numerical modelling for the extraction of decay regions from color images of monuments

An innovative application focused on the segmentation of decay zones from images of stone materials is presented. The adopted numerical approach to extract decay regions from the color images of monuments provides a tool that helps experts analyze degraded regions by contouring them. In this way even if the results of the proposed procedure depend on the evaluation of experts, the approach can be a contribution to improving the efficiency of the boundary detection process. The segmentation is a process that allows an image to be divided into disjoint zones so that partitioned zones contain homogeneous characteristics. The numerical method, used to segment color images, is based on the theory of interface evolution, which is described by the eikonal equation. We adopted the fast marching technique to solve the upwind finite difference approximation of the eikonal equation. The fast marching starts from a seed point in the region of interest and generates a front which evolves according to a specific speed function until the boundary of the region is identified. We describe the segmentation results obtained with two speed functions, attained by the image gradient computation and color information about the object of interest. Moreover, we present the extension of the working modality of the method by introducing the possibility to extract the regions not only in a local way but also in a global way on the entire image. In this case, in order to improve the segmentation efficiency the application of the fast marching technique starts with more seed points defined as seed regions. The study case concerns the impressive remains of the Roman Theatre in the city of Aosta (Italy). In the image segmentation process the color space L^∗a^∗b^∗$L^{\ast }{a}^{\ast }{b}^{\ast }$ is utilized.