Alpha1-acid glycoprotein post-translational modifications: a comparative two dimensional electrophoresis based analysis

Alpha1-acid glycoprotein (AGP) is an immunomodulatory protein expressed by hepatocytes in response to the systemic reaction that follows tissue damage caused by inflammation, infection or trauma. A proteomic approach based on two dimensional electrophoresis, immunoblotting and staining of 2DE gels with dyes specific for post-translational modifications (PTMs) such as glycosylation and phosphorylation has been used to evaluate the differential interspecific protein expression of AGP purified from human, bovine and ovine sera. By means of these techniques, several isoforms have been identified in the investigated species: they have been found to change both with regard to the number of isoforms expressed under physiological condition and with regard to the quality of PTMs (i.e. different oligosaccharidic chains, presence/absence of phosphorilations). In particular, it is suggested that bovine serum AGP may have one of the most complex pattern of PTMs among serum proteins of mammals studied so far

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes.

Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies

The landscape of combining immune checkpoint inhibitors with novel Therapies: Secret alliances against breast cancer

this review focuses on the immune checkpoint inhibitors (ICIs) in the context of breast cancer (BC) management. these innovative treatments, by targeting proteins expressed on both tumor and immune cells, aim to overcome tumor-induced immune suppression and reactivate the immune system. the potential of this approach is the subject of numerous clinical studies. here, we explore the key studies and emerging therapies related to ICIs providing a detailed analysis of their specific and combined use in BC treatment

Brettanomyces bruxellensis yeasts: impact on wine and winemaking

Yeasts belonging to the Brettanomyces/Dekkera genus are non-conventional yeasts, which affect winemaking by causing wine spoilage all over the world. This mini-review focuses on recent results concerning the presence of Brettanomyces bruxellensis throughout the wine processing chain. Here, culture-dependent and independent methods to detect this yeast on grapes and at the very early stage of wine production are encompassed. Chemical, physical and biological tools, devised for the prevention and control of such a detrimental species during winemaking are also presented. Finally, the mini-review identifies future research areas relevant to the improvement of wine safety and sensory profiles

THE CONCEPT OF LAW AND EFFICACY

Jedno od značenja izraza ‘učinkovitost’ odnosi se na činjenicu da se adresati pravnih normi stvarno ponašaju onako kako to od njih zahtijevaju pravne norme. To se značenje izraza obično koristi u filozofskopravnim raspravama glede toga je li učinkovitost bitan element pojma prava. Prema pravnom pozitivizmu, učinkovitost je u nekim slučajevima i na određene načine uvjet važenja (vrijeđenja) pravnih normi i pravnih sustava. S druge strane, pravni je realizam sklon potpunom poistovjećivanju pravnog važenja s učinkovitosti ili njegovu svođenju na učinkovitost. Prema tome, u oba je filozofskopravna pravca učinkovitost u pravilu uključena u oblikovanje njihovih pojmova prava. Međutim, dok pravnopozitivističko shvaćanje ne utječe na najuobičajenije značenje važenja pravne norme (pripadanje pravne norme pravnom sustavu), a utvrđivanjem učinkovitosti kao kriterija postojanja pravnog sustava ne dodaje mnogo objašnjenju pojma prava, pravnorealističko se shvaćanje suočava s ozbiljnim prigovorima glede svoje objašnjavalačke prikladnosti.One of the senses of the term ‘efficacy’ refers to the fact that norm-addresses actually behave as is required of them by legal norms. This sense of the term is one which is generally used within the jurisprudential discussions about whether efficacy is the essential element of the concept of law. According to legal positivism, efficacy is in some cases and in certain ways the condition of legal validity of both legal norms and legal systems. On the other hand, legal realism tends to entirely identify legal validity or reduce it to efficacy. Thus, in both jurisprudential approaches, efficacy tends to play a role in shaping their respective concepts of law. However, while the legal positivistic view does not affect the most standard sense of legal validity of the legal norm (i.e. the legal norms’ membership in the legal system), and does not add much to the explanation of the concept of law by identifying efficacy as the criterion of legal systems’ existence, the legal realistic view is faced with some serious objections regarding its explanatory adequacy

Modelling of metal nano-particle condensation and growth in a reactive atmosphere

The control of the particle size distribution of metal nanoparticles produced via aerosol condensation is a technologically relevant open problem, constrained by the limits of the construction materials and by the desire to minimise carrier gas consumption. As reactive impurities can be present in the carrier gas, we have reviewed the physical chemistry and reactivity of nano-particles and developed a quantitative, continuous model of the nucleation and particle growth processes in the presence of a reactive impurity. The model has been applied to nickel as the metal and oxygen as the impurity, but could equally well be applied to other metals and other impurities such as nitrogen, sulphur, or the halogens. In certain conditions oxygen is only stochastically present in the nucleating nickel droplets, resulting in oxide inclusions that cannot be described by a continuous model. In other conditions the oxidation occurs simultaneously with the metal condensation and can be studied qualitatively using the developed continuous model. The model indicates that the concentration of a reactive contaminant in the gas phase could be used as an additional operating parameter to control the final particle size

Feasibility of the integration of a Molten Carbonate Fuel Cell System and an Integrated Gasification Combined Cycle

IGCC (Integrated Gasification Combined Cycle) power plants look promising for the environmentally- friendly, large-scale production of electrical energy from low-cost fossil feedstocks such as coal or refinery residues. In IGCC plants hydrogen is an intermediate product, as a syngas component, between the thermochemical section and the power section, which is a conventional combined cycle modified to handle this low-density fuel. Replacing the conventional power section with a fuel cell, the IGFC (Integrated Gasification Fuel Cell) configuration promises lower emissions, higher efficiency and possibility to scale down to smaller sizes. To explore the challenges and the feasibility of such an integration we have proposed putting a pilot-scale fuel-cell system into operation within an existing, conventional IGCC, creating a hybrid fuel-cell-IGCC. Two innovative configurations have been proposed and optimised for a pilot-scale MCFC\u2013GT (Molten Carbonate Fuel-Cell\u2013Gas Turbine) system, based on a typical syngas for IGCC plants such as that in operation at ISAB Energy Srl. The system has been modelled using the LIBPF process simulation library