Functional proteomics.

Background: With the increase in the number of genome sequencing projects, there is a concomitant exponential growth in the number of protein sequences whose function is still unknown. Functional proteomics constitutes an emerging research area in the proteomic field whose approaches are addressed towards two major targets: the elucidation of the biological function of unknown proteins and the definition of cellular mechanisms at the molecular level. Methods: The identification of interacting proteins in stable complexes in vivo is essentially achieved by affinity-based procedures. The basic idea is to express the protein of interest with a suitable tag to be used as a bait to fish its specific partners out from a cellular extract. Individual components within the multi-protein complex can then be identified by mass spectrometric methodologies. Results and conclusions: The association of an unknown protein with partners belonging to a specific protein complex involved in a particular mechanism is strongly suggestive of the biological function of the protein. Moreover, the identification of protein partners interacting with a given protein will lead to the description of cellular mechanisms at the molecular level. The next goal will be to generate animal models bearing a tagged form of the bait protein

Nrf2 in neoplastic and non-neoplastic liver diseases

Activation of the Keap1/Nrf2 pathway, the most important cell defense signal, triggered to neutralize the harmful effects of electrophilic and oxidative stress, plays a crucial role in cell survival. Therefore, its ability to attenuate acute and chronic liver damage, where oxidative stress represents the key player, is not surprising. On the other hand, while Nrf2 promotes proliferation in cancer cells, its role in non-neoplastic hepatocytes is a matter of debate. Another topic of uncertainty concerns the nature of the mechanisms of Nrf2 activation in hepatocarcinogenesis. Indeed, it remains unclear what is the main mechanism behind the sustained activation of the Keap1/Nrf2 pathway in hepatocarcinogenesis. This raises doubts about the best strategies to therapeutically target this pathway. In this review, we will analyze and discuss our present knowledge concerning the role of Nrf2 in hepatic physiology and pathology, including hepatocellular carcinoma. In particular, we will critically examine and discuss some findings originating from animal models that raise questions that still need to be adequately answered

Achieving macro- and micro-roughness on Ti alloy by etching without prior sandblasting: a surface characterization

INTRODUCTION: Etching is currently the most popular method used to texture the surface of dental implants. Sandblasting prior to etching (SLA) is the only method to achieve a macro- and micro-surface texture with a Sa in the 1-2 μm range, a ‘moderately rough’ surface considered to be an optimized surface. However, SLA surfaces harbor remnant particles from the sandblasting process [l]. Some manufacturers consider the residual alumina particles as a foreign material worth getting rid of. Subsequently, they forgo an optimized moderately rough surface and stick to a ‘minimally rough’ micro-roughened surface displaying a Sa < 1 μm [l]. It has been recently claimed [2] that acid etching is typically not an appropriate treatment for α-β alloys because its biphasic nature leads to an enrichment of the Vanadium-rich β-phase on the surface. The aim of the present paper is to show that it is feasible to achieve an optimized ‘moderately rough’ macro- and micro-textured surface on titanium alloy (Ti6Al4V) through etching only, without any prior sandblasting and to characterize the resulting surface

Interaction Proteomics

The term proteome is traditionally associated with the identification of a large number of proteins within complex mixtures originating from a given organelle, cell or even organism. Current proteome investigations are basically focused on two major areas, expression proteomics and functional proteomics. Both approaches rely on the fractionation of protein mixtures essentially by two-dimensional polyacrylamide gel electrophoresis (2D-gel) and the identification of individual protein bands by mass spectrometric techniques (2D-MS). Functional proteomics approaches are basically addressing two main targets, the elucidation of the biological function of unknown proteins and the definition of cellular mechanisms at the molecular level. In the cell many processes are governed not only by the relative abundance of proteins but also by rapid and transient regulation of activity, association and localization of proteins and protein complexes. The association of an unknown protein with partners belonging to a specific protein complex involved in a particular process would then be strongly suggestive of its biological function. The identification of interacting proteins in stable complexes in a cellular system is essentially achieved by affinity-based procedures. Different strategies relying on this simple concept have been developed and a brief overview of the main approaches presently used in functional proteomics studies is describe

Partial purification and MALDI-TOF MS analysis of UN1, a tumor antigen membrane glycoprotein.

UN1 is a membrane glycoprotein that is expressed in immature human thymocytes, a subpopulation of peripheral T lymphocytes, the HPB acute lymphoblastic leukemia (ALL) T-cell line and fetal thymus. We previously reported the isolation of a monoclonal antibody (UN1 mAb) recognizing the UN1 protein that was classified as "unclustered" at the 5th and 6th International Workshop and Conference on Human Leukocyte Differentiation Antigens. UN1 was highly expressed in breast cancer tissues and was undetected in non-proliferative lesions and in normal breast tissues, indicating a role for UN1 in the development of a tumorigenic phenotype of breast cancer cells. In this study, we report a partial purification of the UN1 protein from HPB-ALL T cells by anion-exchange chromatography followed by immunoprecipitation with the UN1 mAb and MALDI-TOF MS analysis. This analysis should assist in identifying the amino acid sequence of UN

Dedicated versus mainstreaming approaches in local climate plans in Europe

Cities are gaining prominence committing to respond to the threat of climate change, e.g., by developing local climate plans or strategies. However, little is known regarding the approaches and processes of plan development and implementation, or the success and effectiveness of proposed measures. Mainstreaming is regarded as one approach associated with (implementation) success, but the extent of integration of local climate policies and plans in ongoing sectoral and/or development planning is unclear. This paper analyses 885 cities across the 28 European countries to create a first reference baseline on the degree of climate mainstreaming in local climate plans. This will help to compare the benefits of mainstreaming versus dedicated climate plans, looking at policy effectiveness and ultimately delivery of much needed climate change efforts at the city level. All core cities of the European Urban Audit sample were analyzed, and their local climate plans classified as dedicated or mainstreamed in other local policy initiatives. It was found that the degree of mainstreaming is low for mitigation (9% of reviewed cities; 12% of the identified plans) and somewhat higher for adaptation (10% of cities; 29% of plans). In particular horizontal mainstreaming is a major effort for local authorities; an effort that does not necessarily pay off in terms of success of action implementation. This study concludes that climate change issues in local municipalities are best tackled by either, developing a dedicated local climate plan in parallel to a mainstreamed plan or by subsequently developing first the dedicated and later a mainstreaming plan (joint or subsequent “dual track approach”). Cities that currently provide dedicated local climate plans (66% of cities for mitigation; 26% of cities for adaptation) may follow-up with a mainstreaming approach. This promises effective implementation of tangible climate actions as well as subsequent diffusion of climate issues into other local sector policies. The development of only broad sustainability or resilience strategies is seen as critical.We thank the many council representatives that supported the datacollection. Special thanks to Birgit Georgi who helped in setting up this large net work of researchers across the EU-28. We also thank the EU COST Action TU 0902 (ledbyRichardDawson) that established the core research network and the positive engagement and interaction of th emembers of this group. OH is Fellow of the Tyndall Centre for Climate Change Research and was funded by the UK EPSRC LC Transforms: Low Carbon Transitions of Fleet Operations in Metropolitan Sites Project (grant number EP/N010612/1). EKL was supported by the Ministry of Education, Youth and Sports, Czechia, within the National Sustainability Program I (NPU I) (grant number LO1415). DG ac-knowledges support by the Ministry of Education, University and Research (MIUR), Italy ("Departments of Excellence" grant L. 232/2016). HO was supported by the Ministry of Education and Research, Estonia (grantnumberIUT34-17). MO acknowledges funding from the Ministry of Economy and Competitiveness (MINECO), Spain (grant number IJCI-2016-28835). SS acknowledges that CENSE's research is partially funded by the Science Foundation, Portugal (grant number UID/AMB/04085/2019). The paper reflects only the views of the authors. The European Union, the European Environment Agency or other supporting bodies are not liable for any use that may be made of the information that is provided in this manuscript

Fingerprint Adversarial Presentation Attack in the Physical Domain

With the advent of the deep learning era, Fingerprint-based Authentication Systems (FAS) equipped with Fingerprint Presentation Attack Detection (FPAD) modules managed to avoid attacks on the sensor through artificial replicas of fingerprints. Previous works highlighted the vulnerability of FPADs to digital adversarial attacks. However, in a realistic scenario, the attackers may not have the possibility to directly feed a digitally perturbed image to the deep learning based FPAD, since the channel between the sensor and the FPAD is usually protected. In this paper we thus investigate the threat level associated with adversarial attacks against FPADs in the physical domain. By materially realising fakes from the adversarial images we were able to insert them into the system directly from the “exposed” part, the sensor. To the best of our knowledge, this represents the first proof-of-concept of a fingerprint adversarial presentation attack. We evaluated how much liveness score changed by feeding the system with the attacks using digital and printed adversarial images. To measure what portion of this increase is due to the printing itself, we also re-printed the original spoof images, without injecting any perturbation. Experiments conducted on the LivDet 2015 dataset demonstrate that the printed adversarial images achieve ∼ 100% attack success rate against an FPAD if the attacker has the ability to make multiple attacks on the sensor (10) and a fairly good result (∼ 28%) in a one-shot scenario. Despite this work must be considered as a proof-of-concept, it constitutes a promising pioneering attempt confirming that an adversarial presentation attack is feasible and dangerous

Fabrication and Characterization of Quinary High Entropy-Ultra-High Temperature Diborides” Ceramics

Due to their inherently chemical complexity and their refractory nature, the obtainment of highly dense and single-phase High Entropy (HE) diborides represents a very hard target to achieve. In this framework, homogeneous (Hf0.2Nb0.2Ta0.2Mo0.2Ti0.2)B2, (Hf0.2Zr0.2Ta0.2Mo0.2Ti0.2)B2, and (Hf0.2Zr0.2Nb0.2Mo0.2Ti0.2)B2 ceramics with high relative densities (97.4, 96.5 and 98.2 %, respectively) are successfully produced by Spark Plasma Sintering (SPS) using powders prepared by Self-propagating High-temperature Synthesis (SHS). Although the latter technique does not lead to the complete conversion of initial precursors into the prescribed HE phases, such goal is fully reached after SPS (1950°C/20min/20 MPa). The three HE products show similar, even better in some cases, mechanical properties compared to ceramics with the same nominal composition attained using alternative processing methods. Superior Vickers hardness and elastic modulus values are found for the (Hf0.2Nb0.2Ta0.2Mo0.2Ti0.2)B2 and (Hf0.2Zr0.2Ta0.2Mo0.2Ti0.2)B2 systems, i.e. 28.1 GPa/538.5 GPa and 28.08 GPa/498.1 GPa, respectively, in spite of the correspondingly higher residual po-rosities (1.2 and 2.2 vol.%, respectively). In contrast, the third ceramic, not containing Tantalum, displays lower values of these two properties (25.1 GPa/404.5 GPa). However, the corresponding fracture toughness (8.84 MPa m1/2) is relatively higher. This fact can be likely ascribed to the smaller residual porosity (0.3 vol.%) of the sintered material

Optical properties of bulk high-entropy diborides for solar energy applications

So far, the studies regarding the innovative High-Entropy Borides (HEBs), which belong to the more general class of Ultra-high temperature ceramics (UHTCs), have been entirely confined to their fabrication or characterization from the microstructural, mechanical and oxidation resistance viewpoints. In this work, the optical properties of two members of HEBs, i.e. (Hf0.2Zr0.2Ta0.2Mo0.2Ti0.2)B2 and (Hf0.2Nb0.2Ta0.2Mo0.2Ti0.2)B2, are evaluated for the first time to assess their possible utilization in the thermal solar energy field. The bulk samples (96.5 % and 97.4 % dense, respectively) are obtained as single-phase products by Spark Plasma Sintering (1950 °C/20 min/20 MPa) starting from powders previously synthesized by Self-propagating High-temperature Synthesis (SHS). The optical characterization, whose results are discussed by comparing HEBs to the individual borides, shows that they are characterized by intrinsic spectral selectivity and low thermal emittance, resulting therefore interesting for high-temperature solar absorbers applications