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A case study is presented in this paper dealing with a steel braced frame office building located in Southern Italy and designed for gravity loads only. The building, erected in the early ‘60s, is investigated to assess its behavior with regard to both seismic and progressive collapse performance. At the same time, some possible retrofit strategies are outlined. To this aim, the results of both linear and nonlinear static and dynamic analyses are presented and discussed considering different column removal scenarios. Then, an integrated design procedure involving both robustness and seismic safety is developed using steel-braced frames and mega-truss outriggers. In this context, both seismic and progressive collapse performances after retrofit are investigated.

Here, we report a toxicity study, conducted on zebrafish larvae, of a series of coumarin and sulfamide compounds that were previously reported as inhibitors of human (h) metalloenzymes, carbonic anhydrases (CAs, EC 4.2.1.1). Due to the high relevance of hCA inhibitors as theragnostic agents, it is of pivotal importance to address safety issues that may arise from the initial in vivo toxicological assessment using zebrafish, a relevant model for biomedical research. None of the reported compounds showed adverse phenotypic effects or tissue damage on developing zebrafish larvae after 5 days of exposure. Our study suggests that the coumarin and sulfamide derivatives considered here are safe and suitable for further development and testing.

This paper deals with on-board integration of lithium-ion capacitors into plug-in hybrid electric vehicle applications. Power exchanges with the vehicle battery pack are controlled through a DC/DC bidirectional power converter, which is interposed between the DC-Link and a 125 V 73 F lithium-ion capacitor module. Specific energy management strategies have been evaluated and compared in this work with the aim of optimizing battery cycling life on different operative conditions (driving cycles and real driving mission profiles). Those evaluations are carried out in simulation environment, based on the use of detailed simulation models of a C-segment plug-in hybrid vehicle and lithium-ion capacitors. Models have been preliminary parametrized and validated by means of laboratory experimental activities. The obtained results highlighted the benefits of using hybrid energy storage systems, based on lithium-ion capacitors, in reducing power peaks for the battery pack and related impact on battery cycling life.

Molecular mimicry is one of the leading mechanisms by which infectious agents can induce autoimmunity. Whether a similar mechanism triggers an antitumor immune response is unexplored, and the role of antiviral T cells infiltrating the tumor has remained anecdotal. To address these questions, we first developed a bioinformatic tool to identify tumor peptides with high similarity to viral epitopes. Using peptides identified by this tool, we demonstrated that, in mice, preexisting immunity toward specific viral epitopes enhanced the efficacy of cancer immunotherapy via molecular mimicry in different settings. To understand whether this mechanism could partly explain immunotherapy responsiveness in humans, we analyzed a cohort of patients with melanoma undergoing anti-PD1 treatment who had a high IgG titer for cytomegalovirus (CMV). In this cohort of patients, we showed that high levels of CMV-specific antibodies were associated with prolonged progression-free survival and found that, in some cases, peripheral blood mononuclear cells (PBMC) could cross-react with both melanoma and CMV homologous peptides. Finally, T-cell receptor sequencing revealed expansion of the same CD8þ T-cell clones when PBMCs were expanded with tumor or homologous viral peptides. In conclusion, we have demonstrated that preexisting immunity and molecular mimicry could influence the response to immunotherapies. In addition, we have developed a free online tool that can identify tumor antigens and neoantigens highly similar to pathogen antigens to exploit molecular mimicry and cross-reactive T cells in cancer vaccine development.

Introduction: oncololytic adenoviruses (OAds), viruses constructed to replicate in tumor cells, improve the outcome of cancer therapy in some cases, such as sarcomas. However, the molecular heterogeneity of tumors requires specific and personalized cancer treatments in order to set up more adequate and effective therapies. Methods: by using the array Comparative Genomic Hybridization (array-CGH), a molecular approach method, we aimed to identify chromosomal aberrations or Copy Number Variants (CNVs) in three different tumor cell lines: HCT116, SW872 and A2058 selected for their Coxsackievirus and Adenovirus receptor (CAR) expression profile. Results: the cells showed several duplications of genes involved in replicative Adenovirus cycle (binding, internalization, escape) in the core transport, and in the escape of the viral DNA from the capsid. Conclusion: in this study, our aim was to identify chromosomal alterations in genes involved in the OAd replication cycle process. Array-CGH method could be useful to design a platform for a screening analysis in order to identify mutations that can contribute to oncolytic virotherapy approach generating a personalized strategy for tumor suppression.

The ?- and ?-class carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae, VchCA?, and VchCA?, were investigated for their activation with natural and non-natural amino acids and amines. The most effective VchCA? activators were L-tyrosine, histamine, serotonin, and 4-aminoethyl-morpholine, which had KAs in the range of 8.21-12.0 µM. The most effective VchCA? activators were D-tyrosine, dopamine, serotonin, 2-pyridyl-methylamine, 2-aminoethylpyridine, and 2-aminoethylpiperazine, which had KAs in the submicromolar - low micromolar range (0.18-1.37 µM). The two bacterial enzymes had very different activation profiles with these compounds, between each other, and in comparison to the human isoforms hCA I and II. Some amines were selective activators of VchCA?, including 2-pyridylmethylamine (KA of 180 nm for VchCA?, and more than 20 µM for VchCA? and hCA I/II). The activation of CAs from bacteria, such as VchCA?/? has not been considered previously for possible biomedical applications. It would be of interest to study in more detail the extent that CA activators are implicated in the virulence and colonisation of the host by such pathogenic bacteria, which for Vibrio cholerae, is highly dependent on the bicarbonate concentration and pH in the surrounding tissue.

Introduction: The hydration/dehydration of CO2 catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1) is a crucial physiological reaction for the survival of all living organisms because it is connected with numerous biosynthetic and biochemical pathways requiring CO2 or HCO3-, such as respiration, photosynthesis, carboxylation reactions, pH homeostasis, secretion of electrolytes, transport of CO2, bicarbonate, etc. Areas covered: The bacterial genome encodes CAs belonging to the ?-, ?-, and ?-CA classes able to ensure the survival and/or satisfying the metabolic needs of the bacteria, as demonstrated by in vivo and in vitro experiments. The discovery of new anti-infectives that target new bacterial pathways, such as those involving CAs, may lead to effective therapies against diseases subject to the antibiotic resistance. This aspect is important in pharmaceutical and biomedical research but received little attention till recently. Expert opinion: An overview of the potential use of CAs in biomedical applications, as drug targets, bioindicators, and within artificial organs is presented. The discovery of thermostable bacterial CAs allowed the use of CAs in biotechnological applications, but patents related to the use of bacterial CAs in the development of pharmacological agents are scarce.

The genome of Helicobacter pylori encodes for carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the ?- and ?-CA classes, which together with urease, have a pivotal role in the acid acclimation of the microorganism within the human stomach. Recently, in the exoproteome of H. pylori, a CA with no indication of the corresponding class was identified. Here, using the protonography and the mass spectrometry, a CA belonging to the ?-class was detected in the outer membrane vesicles (OMVs) generated by planktonic and biofilm phenotypes of four H. pylori strains. The amount of this metalloenzyme was higher in the planktonic OMVs (pOMVs) than in the biofilm OMVs (bOMVs). Furthermore, the content of ?-CA increases over time in the pOMVs. The identification of the ?-CA in pOMVs and bOMVs might shed new light on the role of this enzyme in the colonization, survival, persistence, and pathogenesis of H. pylori.

Reactive absorption promoted by carbonic anhydrase (CA, E.C. 4.2.1.1.) catalysis has been proposed for CO2 capture from exhaust gas as an alternative to the reactive absorption in amine solutions. Potassium carbonate solutions allow feasible CO2 capture assisted by CA. This paper reports on the characterization of a CA form supplied by Novozymes as a catalyst for CO2 capture in K2CO3 solutions at operating conditions relevant for industrial processes (2-3 M K2CO3, 298-313 K, 0-40% carbonate to bicarbonate conversion). CO2 absorption tests were carried out in a batch-stirred cell apparatus at constant gas volume and temperature by measuring gas pressure decay. The enhancement ratio between CO2 absorption rate with and without the enzyme at biocatalyst concentration above 0.3 kg m-3 ranged between 5 and 8 depending on the solvent composition and temperature. Active enzyme aggregates formed at protein concentration larger than 0.3 kg/m3 and their contribution to the absorption rate enhancement was remarkable. Assessment of enzyme kinetics in homogeneous solutions at enzyme concentration lower than 0.018 kg·m-3 showed that kcat/KM increased with both temperature and salt concentration. kcat/KM ranged between 9.0·103 and 7.0·104 m3·kg-1·s-1 in agreement with literature data on carbonic anhydrase kinetics. Reliability of the adopted method for kinetic characterization was confirmed. The activity of enzyme aggregates formed in the carbonate solvent was verified and CA aggregates can be used to select the proper CA based biocatalyst for CO2 capture application as an alternative to free and immobilized enzyme.

Post-combustion CO2 capture strategy asks for novel effective processes that can avoid the use of polluting solvents and that can be coupled with CO2 utilization processes. Recent research efforts are focused on the development of CO2 absorption processes promoted by the enzyme carbonic anhydrase [1]. This ubiquitous enzyme is able to catalyze the CO2 hydration reaction so it can be used to enhance CO2 absorption rate into aqueous solvents such as bicarbonate/carbonate solutions. The adoption of the biomimetic strategy for post-combustion CO2 capture is based on the use of environmental friendly solvent (enzyme aqueous solution). Moreover, it provides bicarbonate enriched solutions as intermediate product, such product might be processed in order to convert the captured carbon through further (enzymatic, microbial, photochemical, ...) processes in aqueous phase. The present contribution reports on recent study on the development of carbonic anhydrase biocatalysts through different immobilization techniques. The comparison was made between techniques based on enzyme attachment on solid particles and carrier free immobilization techniques. In both cases the use of paramagnetic solids was included in the development of the biocatalysts, so that magnetic field assisted separation technology may be considered for confinement/recovery of the biocatalyst in/from the reaction volume. The overview of experimental results highlighted advantages and drawbacks of two different CA attachment on activated paramagnetic nanoparticles and of immobilization through Cross Linked Enzyme Aggregates (CLEA) of CA prepared with inclusion of paramagnetic nanoparticles.