Sublayering in standard network architectures

There are several reasons for grouping functions in layers of a structured standard architecture, and subdivision of layers (sublayering) is used in several cases. To show the relevance of this tool, this paper lists some applications in which this technique has been used to solve specific problems. This list is organized in three parts, for three different modalities: the horizontal subdivision operated in a vertical sequence of layers (e.g. the OSI model), the vertical subdivision of functions performed over a kernel providing the minimal layer functionality (e.g. the functions activated on an optional basis in the Session protocol) and the grouping of functions which are not used at the same time, but may be activated subsequently with mutual exclusion (such as the establishment, the data transfer and the clearing phase of a connection). The paper shows how different the modalities and the results obtained with this technique can be; the effects may range from influencing only the local implementation, to requiring an additional protocol in the layer.     

Iron Availability in Tissue Microenvironment: The Key Role of Ferroportin

Body iron levels are regulated by hepcidin, a liver-derived peptide that exerts its function by controlling the presence of ferroportin (FPN), the sole cellular iron exporter, on the cell surface. Hepcidin binding leads to FPN internalization and degradation, thereby inhibiting iron release, in particular from iron-absorbing duodenal cells and macrophages involved in iron recycling. Disruption in this regulatory mechanism results in a variety of disorders associated with iron-deficiency or overload. In recent years, increasing evidence has emerged to indicate that, in addition to its role in systemic iron metabolism, FPN may play an important function in local iron control, such that its dysregulation may lead to tissue damage despite unaltered systemic iron homeostasis. In this review, we focus on recent discoveries to discuss the role of FPN-mediated iron export in the microenvironment under both physiological and pathological conditions.     

Antimetastatic and Antitumor Activities of Orally Administered NAX014 Compound in a Murine Model of HER2-Positive Breast Cancer

The natural isoquinoline alkaloid Berberine (BBR) has been shown to possess several therapeutic effects, including anticancer activity. Different BBR derivatives have been designed and synthesized in order to obtain new compounds with enhanced anticancer efficacy. We previously showed that intraperitoneal (IP) administration of the BBR-derived NAX014 compound was able to counteract HER-2 overexpressing mammary tumors onset and progression in transgenic mice. However, the IP administration was found to induce organ toxicity at doses higher than 2.5 mg/Kg. In this study, we evaluated the effect of intragastric (IG) administration of 20 mg/kg of NAX014 on both safety and anticancer efficacy in HER-2/neu transgenic mice. Furthermore, cancer cell dissemination and migration, tumor cell senescence and immunological changes were examined. Our results demonstrated that IG NAX014 administration delayed the onset of mammary tumors with no negative effects on health and survival. NAX014 reduced HER-2 overexpressing BC cells migration in vitro and the frequency of lung metastasis in HER-2/neu transgenic mice. A statistically significant increase of senescence-associated p16 expression was observed in tumors from NAX014-treated mice, and the induction of cell senescence was observed in HER-2 overexpressing BC cells after in vitro treatment with NAX014. Although NAX014 did not modulate the presence of tumor-infiltrating lymphocytes, the level of circulating TNF-α and VEGF was found to be reduced in NAX014-treated mice. The overall results address the NAX014 compound as potential tool for therapeutic strategies against HER-2 overexpressing breast cancer.     

New Frontiers about the Role of Human Microbiota in Immunotherapy: The Immune Checkpoint Inhibitors and CAR T-Cell Therapy Era

Microbiota is considered an independent organ with the capability to modulate tumor growth and response to therapies. In the chemo-free era, the use of new immunotherapies, more selective and effective and less toxic, led to the extension of overall survival of patients, subject to their ability to not stop treatment. This has focused scientists’ attention to optimize responses by understanding and changing microbiota composition. While we have obtained abundant data from studies in oncologic and hematologic patients receiving conventional chemotherapy, we have less data about alterations in intestinal flora in those undergoing immunotherapy, especially based on Chimeric Antigen Receptor (CAR) T-cells. Actually, we know that the efficacy of Programmed Cell Death 1 (PD-1), PD-1 ligand, and Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is improved by probiotics rich in Bifidobacterium spp., while compounds of Bacteroidales and Burkholderiales protect from the development of the anti-CTLA-4-induced colitis in mouse models. CAR T-cell therapy seems to not be interfering with microbiota; however, the numerous previous therapies may have caused permanent damage, thus obscuring the data we might have obtained. Therefore, this review opens a new chapter to transfer known acquisitions to a typology of patients destined to grow.     

Power generation of microbial fuel cells (MFCs) with low cathodic platinum loading

This study aims at investigating the effects of platinum (Pt) loadings on the cathodic reactions in Single Chamber Microbial Fuel Cells (SCMFCs) and developing cost-effective MFC operational protocols. The power generation of SCMFCs was examined with different Pt loadings (0.005–1 mgPt/cm²) on cathodes. The results showed that the power generation of the SCMFCs with 0.5–1 mgPt/cm² were the highest in the tests, decreased 10–15% at 0.01–0.25 mgPt/cm², and decreased further 10–15% at 0.005 mgPt/cm². The SCMFCs with Pt-free cathode (graphite) had the lowest power generation. In addition, the power generation of SCMFCs with different Pt loadings were compared in raw wastewater (Chemical oxygen demand (COD): 0.36 g/L) and wastewater enriched with sodium acetate (COD: 2.95 g/L). The solution conductivity in SCMFCs decreased with the degradation of organic substrates. Daily polarization curves (V–I) showed a decrease in current generation and an increase in ohmic losses over the operational period (8 days). The SCMFCs (with 0.5–1 mgPt/cm² at cathode) fed with wastewater and sodium acetate (NaOAc) reached the highest power generation (786 mW/m²), while the SCMFCs (with 0.5–1 mgPt/cm² at cathode) fed only with wastewater obtained the lower power generation (81 mW/m²). The study demonstrated that lowering the Pt loadings in two magnitude orders (1 to 0.01, 0.5 to 0.005 mgPt/cm²) only reduced the power generation of 15–30%, and this reduction of the power generation become less substantial with the decrease in the solution conductivity of SCMFCs.     

Chemical hydrogels based on a hyaluronic acid-graft-α-elastin derivative as potential scaffolds for tissue engineering

In this work hyaluronic acid (HA) functionalized with ethylenediamine (EDA) has been employed to graft α-elastin. In particular a HA-EDA derivative bearing 50 mol% of pendant amino groups has been successfully employed to produce the copolymer HA-EDA-g-α-elastin containing 32% w/w of protein. After grafting with α-elastin, remaining free amino groups reacted with ethylene glycol diglycidyl ether (EGDGE) for producing chemical hydrogels, proposed as scaffolds for tissue engineering. Swelling degree, resistance to chemical and enzymatic hydrolysis, as well as preliminary biological properties of HA-EDA-g-α-elastin/EGDGE scaffold have been evaluated and compared with a HA-EDA/EGDGE scaffold. The presence of α-elastin grafted to HA-EDA improves attachment, viability and proliferation of primary rat dermal fibroblasts and human umbilical artery smooth muscle cells. Biological performance of HA-EDA-g-α-elastin/EGDGE scaffold resulted comparable to that of a commercial collagen type I sponge (Antema®), chosen as a positive control.     

The role played by the alpha-helix in the unfolding pathway and stability of azurin: switching between hierarchic and nonhierarchic folding

The role played by the alpha-helix in determining the structure, the stability and the unfolding mechanism of azurin was addressed by studying a helix-depleted azurin variant produced by site-directed mutagenesis. The protein structure was investigated by CD, 1D (1)H NMR, fluorescence spectroscopy measurements and MD simulations, whilst EPR, UV-visible and cyclic voltammetry experiments were carried out to investigate the geometry and the properties of the Cu(II) site. The effects of the alpha-helix depletion on the thermal stability and the unfolding pathway of the protein were determined by DSC, UV/visible and fluorescence measurements at increasing temperature. The results show that, in the absence of the alpha-helix segment, the overall protein structure is maintained, and that only the Cu site is slightly modified. In contrast, the protein stability is diminished by about 60% with respect to the wild-type azurin. Moreover, the unfolding pathway of the mutant azurin involves the presence of detectable intermediates. In comparison with previous studies concerning other small beta-sheet cupredoxins, the results as a whole support the hypothesis that the presence of the alpha-helix can switch the folding of azurin from a hierarchic to a nonhierarchic mechanism in which the highly conserved beta-sheet core provides a scaffold for cooperative folding of the wild-type protein.     

Evolution and control of oxygen order in a cuprate superconductor

The disposition of defects in metal oxides is a key attribute exploited for applications from fuel cells and catalysts to superconducting devices and memristors. The most typical defects are mobile excess oxygens and oxygen vacancies, which can be manipulated by a variety of thermal protocols as well as optical and d.c. electric fields. Here we report the X-ray writing of high-quality superconducting regions, derived from defect ordering, in the superoxygenated layered cuprate, La?CuO(4+y). Irradiation of a poor superconductor prepared by rapid thermal quenching results first in the growth of ordered regions, with an enhancement of superconductivity becoming visible only after a waiting time, as is characteristic of other systems such as ferroelectrics, where strain must be accommodated for order to become extended. However, in La?CuO(4+y), we are able to resolve all aspects of the growth of (oxygen) intercalant order, including an extraordinary excursion from low to high and back to low anisotropy of the ordered regions. We can also clearly associate the onset of high-quality superconductivity with defect ordering in two dimensions. Additional experiments with small beams demonstrate a photoresist-free, single-step strategy for writing functional materials.     

Patient dose in digital projection radiography

In projection radiography, two types of digital imaging systems are currently available, computed radiography (CR) and direct radiography (DR): a difference between them can be stated in terms of dose and image quality. In the Radiology Emergency Department of our hospital, a flat-panel DR equipment (Siemens Axiom Aristos FX) and two CR systems (Kodak CR-850) are employed. In 2006, five standard radiographic examinations (abdomen, chest, lumbar spine, pelvis, skull) were considered: doses delivered to patients in terms of both entrance skin dose (ESD) and effective dose (E) were calculated and compared in order to study the dosimetric discrepancies between CR and DR. Assessment of image quality is undertaken by Consultant Radiologists to ensure that the quality criteria for diagnostic radiographic images of the European guidelines were met. Results showed that both ESD and E in DR are lower than that in CR; all images met the criteria in the European Guidelines for both modalities and were used for reporting by the radiologists. Since the operators are the same and the image quality is comparable in both modalities, this study shows that in the considered examinations, DR can perform better than CR from a dosimetric point of view.     

Unified theory for confinement of RC solid and hollow circular columns

Hollow bridge piers are incorporated in tall bridges to maximize the structural efficiency of the strength-mass and stiffness-mass ratios. Column jacketing with fiber reinforced polymer (FRP) composite materials has been extensively studied in recent years but it is uncertain how FRP jackets may perform when retrofitting hollow concrete columns since the topic has been little researched.A confinement model for circular hollow sections is proposed which can be extended to the case of solid sections. The model is able to estimate confinement effectiveness and to plot stress–strain relationships, which are different in the case of solid and hollow sections.