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.     

Well-Known and Novel Serum Biomarkers for Risk Stratification of Patients with Non-ischemic Dilated Cardiomyopathy

Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and increased risk of sudden cardiac death. In spite of all the therapeutic progress that has been made in recent years, dilated cardiomyopathy continues to be an important cause of cardiac transplant, being associated with an enormous cost burden for health care systems worldwide. Predicting the prognosis of patients with dilated cardiomyopathy is essential to individualize treatment. Late gadolinium enhancement-cardiac magnetic resonance imaging, microvolt T-wave alternans, and genetic testing have emerged as powerful tools in predicting sudden cardiac death occurrence and maximizing patient’s selection. Despite all these new diagnostic modalities, additional tests to complement or replace current tools are required for better risk stratification. Therefore, biomarkers are an easy and important tool that can help to detect patients at risk of adverse cardiovascular events. Additionally, identifying potential biomarkers involved in dilated cardiomyopathy can provide us important information regarding the diagnostic, prognostic, risk stratification, and response to treatment for these patients. Many potential biomarkers have been studied in patients with dilated cardiomyopathy, but only a few have been adopted in current practice. Therefore, the aim of our review is to provide the clinicians with an update on the well-known and novel biomarkers that can be useful for risk stratification of patients with non-ischemic dilated cardiomyopathy.     

NH3-NO/NO2 SCR for diesel exhausts after treatment: mechanism and modelling of a catalytic converter

We review herein the key mechanistic and kinetic features of the reactions involved in the NH₃-NO/NO₂ SCR system investigated by dynamic reactive experiments over a V-based commercial powdered catalyst, eventually leading to the proposal of an original redox scheme which accounts for stoichiometry, selectivity and intrinsic kinetics of the global SCR process.     

A universal design resource for rich Internet applications based on design patterns

Rich Internet applications have removed most of the constraints of Web 1.0 while giving users more responsiveness and advanced browsing and interaction experiences. These new horizons, however, raise many challenges for people with disabilities or using limited hardware and software technologies, whose risk to be excluded from the benefits deriving from advanced web applications. To address this problem, WCAG 2.0 guidelines have been released as the newest World Wide Web Consortium recommendation for accessible web content, and WAI-ARIA is a candidate recommendation which provides reference specifications for accessible rich Internet applications. However, both specifications contain a huge amount of information that often discourages most web designers from dealing with accessibility issues. Moreover, guidelines are suitable and usually adopted to judge a design solution a posteriori, but they do not suggest how to face a design problem constructively. This paper proposes a design pattern language for accessibility. The language can be regarded as a universal design resource for helping web designers create accessible rich Internet applications compliant with the most recent standards. Knowledge representation through design patterns reflects the problem-solving approach usually followed by software and web designers, while pattern organization in a structured language aims to guide web designers throughout the design process. The language has been implemented as an accessible rich Internet application itself, thus allowing designers with disabilities to participate in web design. In order to evaluate the design pattern language, a three-step process was carried out including: (1) a heuristic analysis with a group of human–computer interaction experts, (2) a survey study with a group of web designers, and (3) a validation on the field with two designers who have been requested to apply the language in real design cases.     

Disjunctive databases for representing repairs

This paper addresses the problem of representing the set of repairs of a possibly inconsistent database by means of a disjunctive database. Specifically, the class of denial constraints is considered. We show that, given a database and a set of denial constraints, there exists a (unique) disjunctive database, called canonical, which represents the repairs of the database w.r.t. the constraints and is contained in any other disjunctive database with the same set of minimal models. We propose an algorithm for computing the canonical disjunctive database. Finally, we study the size of the canonical disjunctive database in the presence of functional dependencies for both subset-based repairs and cardinality-based repairs.     

Approximation processes for resolvent operators

We introduce general sequences of linear operators obtained from classical approximation processes which are useful in the approximation of the resolvent operators of the generators of suitable C ₀-semigroups. The main aim is the representation of the resolvent operators in terms of classical approximation operators. Work performed under the auspices of PRIN 2006–07 “Kolmogorov equations” (coordinator G. Da Prato)     

Highly Conductive MXene/PEDOT:PSS-Integrated Poly(N-Isopropylacrylamide) Hydrogels for Bioinspired Somatosensory Soft Actuators

Sophisticated sensing and actuation capabilities of many living organisms in nature have inspired scientists to develop biomimetic somatosensory soft robots. Herein, the design and fabrication of homogeneous and highly conductive hydrogels for bioinspired somatosensory soft actuators are reported. The conductive hydrogels are synthesized by in situ copolymerization of conductive surface-functionalized MXene/Poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) ink with thermoresponsive poly(N-isopropylacrylamide) hydrogels. The resulting hydrogels are found to exhibit high conductivity (11.76 S m⁻¹), strain sensitivity (GF of 9.93), broad working strain range (≈560% strain), and high stability after over 300 loading–unloading cycles at 100% strain. Importantly, shape-programmable somatosensory hydrogel actuators with rapid response, light-driven remote control, and self-sensing capability are developed by chemically integrating the conductive hydrogels with a structurally colored polymer. As the proof-of-concept illustration, structurally colored hydrogel actuators are applied for devising light-driven programmable shape-morphing of an artificial octopus, an artificial fish, and a soft gripper that can simultaneously monitor their own motions via real-time resistance variation. This work is expected to offer new insights into the design of advanced somatosensory materials with self-sensing and actuation capabilities, and pave an avenue for the development of soft-matter-based self-regulatory intelligence via built-in feedback control that is of paramount significance for intelligent soft robotics and automated machines.     

Multimedia ontology population through semantic analysis and hierarchical deep features extraction techniques

Knowledge and Information Systems - The rapid increase of available data in different complex contexts needs automatic tasks to manage and process contents. Semantic Web technologies represent the...     

Atmospheric correction of optical imagery from MODIS and Reanalysis atmospheric products

In this paper we analyze the differences obtained in the atmospheric correction of optical imagery covering bands located in the Visible and Near Infra-Red (VNIR), Short-Wave Infra-Red (SWIR) and Themal-Infrared (TIR) spectral regions when atmospheric profiles extracted from different sources are used. In particular, three sensors were used, Compact High Resolution Imaging Spectrometer (CHRIS), Advanced Spaceborne Thermal Emission and Reflection radiometer (ASTER) and Landsat5 Thematic Mapper (TM), whereas four atmospheric profiles sources were considered: i) local soundings launched near the sensor overpass time, ii) Moderate Resolution Radiometer (MODIS) atmospheric profiles product (MOD07), iii) Atmospheric Correction Parameter Calculator (ACPC) generated by the National Center for Environmental Prediction (NCEP) and iv) Modified Atmospheric Profiles from Reanalysis Information (MAPRI), which includes data from NCEP and National Center of Atmospheric Research (NCAR) Reanalysis project but interpolated to 34 atmospheric levels and resampled to 0.5° × 0.5°. MODIS aerosol product (MOD04) was also used to extract Aerosol Optical Thickness (AOT) values at 550 nm. Analysis was performed for three test dates (12th July 2003, 18th July 2004 and 13th July 2005) over an agricultural area in Spain. Results showed that air temperature vertical profiles were similar for the four sources, whereas dew point temperature profiles showed significant differences at some particular levels. Atmospheric profiles were used as input to MODTRAN4 radiative transfer code in order to compute atmospheric parameters involved in atmospheric correction, with the aim of retrieving surface reflectances in the case of VNIR and SWIR regions, and Land Surface Temperature (LST) in the case of the TIR region. For the VNIR and SWIR region, significant differences depending on the atmospheric profile used were not found, particularly in the Visible region in which the AOT content is the main parameter involved in the atmospheric correction. In the case of TIR, differences depending on the atmospheric profile used were appreciable, since in this case the main parameter involved in the atmospheric correction is the water vapor content, which depends on the vertical profile. In terms of LST retrieval from ASTER data (2004 test case), all profiles provided satisfactory results compared to the ones obtained when using a local sounding, with errors of 0.3 K for ACPC and MAPRI cases and 0.7 K for MOD07. When retrieving LST from TM data (2005 test case), errors for MOD07 and MAPRI were 0.6 and 0.9 K respectively, whereas ACPC provided an error of 2 K. The results presented in this paper show that the different atmospheric profile sources are useful for accurate atmospheric correction when local soundings are not available. In particular, MOD07 product provides atmospheric information at the highest spatial resolution, 5 km, although its use is limited from 2000 to present, whereas MAPRI provides historical information from 1970 to present, but at lower spatial resolution.