Enzyme promiscuity in amino acid oxidases: a tool for sustainable processes.

Enzymatic promiscuity is the ability of enzymes to catalyze additional reactions different from those for which they have evolved. This phenomenon plays a key role in the divergent evolution of novel enzymes. Amino acid oxidases (AAOs) are a group of FAD containing enzymes that catalyze the oxidative deamination of amino acids. AAOs evolved to fulfill very different physiological roles, by reshaping of their functional and structural features. Thus these enzymes represent an ideal model to understand the mechanisms that originated molecular biodiversity in modern enzyme families. In addition, their strict enantioselectivity renders AAOs interesting biocatalysts for the production of optically pure amino acids, valuable compounds widely used in the pharmaceutical and food industries. Through extensive literature and database search we identified two novel L-amino acid oxidases (LAAOs). Detailed structural and functional characterization showed that the first one, the aminoacetone oxidase from S. oligofermentans (SoAAO), is not a canonical LAAO, since it does no possess the typical features of these enzymes, and has only a low promiscuous activity on L-amino acids. Its preferred substrate is aminoacetone that is converted to 2,5-dimethylpyrazine. Thus we propose that SoAAO could act as a scavenger of aminoacetone (a prooxidant metabolite), protecting the cell from oxidative damage. The second one, L-amino acid deaminase from P. myxofaciens (PmaLAAD), resembles more closely the typical LAAOs: it is a membrane associated protein active on large hydrophobic L-amino acids. PmaLAAD does not use molecular oxygen, but a cytochrome b-like protein, as a direct electron acceptor. We propose that PmaLAAD is involved in catabolic utilization of L-amino acids to fuel the electron-transfer chain of Proteus membranes. Comparison of the 3D structure of the two proteins with other LAAOs reveals that SoAAO diverged very early from this group of flavoenzymes, originating a novel structural group, while PmaLAAD has a clear evolutionary link with LAAOs. In conclusion, the characterization of two novel microbial LAAOs allowed us to define their structure/function relationships, to clarify their physiological role and to obtain new insights on the underlying mechanisms of the molecular evolution of AAOs

The Politics of the Unspoken in Max Horkheimer

Max Horkheimer has a special place in German critical theory. Unlike Adorno and others who lean on Hegelian paradigm, Horkheimer draws upon Schopenhauer’s metaphysics. Schopenhauer gives us a critique of representation which Horkheimer understands to be of a piece with instrumental rationality and so a critique of capitalism. This thesis argues that Horkheimer’s use of critique of representation is a break with Kantian First Critique notions of time, space and causation. It presents a deep linguistic reading of such a critique of representation and its categories as predicational or propositional language. From the standpoint of this linguistic reading, the study explores a Horkheimer-inspired politics based on the Kantian conception of hope and the Judaic prohibition of the image of God. This notion of hope is for Horkheimer conceived as a longing for the totally other. We explore these thematic as a philosophy of political practice to conclude with a theoretical framework for a politics of emancipation inspired by Horkheimer’s thought

Self-funded social impact investment: an interdisciplinary analysis of the Sardex mutual credit system

Sardex is an electronic B2B mutual credit system that has been operating on the island of Sardinia since 2009 as a complementary currency. In contrast to other funding mechanisms, it allows private funding driving social and environmental impact to be endogenously generated within a given geographically limited socio-economic context, rather than injected from exogenous sources. By drawing on different strands of monetary theory, sociology and anthropology, we argue that mutual credit is central to a form of social finance and social impact investment that we identify with sustainable development, i.e. stable and constructive integration of market activity with democratic institutions and socio-cultural values and structures. The empirical basis of the paper consists of approximately thirty semi-structured in-depth interviews of Sardex circuit members and founders over 4 years. We conclude that Sardex as a collective social enterprise is best understood through an interdisciplinary perspective that demonstrates its sustainability through the different levels of its workings and its strengths as a hybrid multilayered system

Effects of axial torsion on sp carbon atomic nanowires

Ab-initio calculations within Density Functional Theory combined with experimental Raman spectra on cluster-beam deposited pure carbon films provide a consistent picture of sp-carbon chains stabilized by sp^3 or sp^2 terminations, the latter being sensitive to torsional strain. This unexplored effect promises many exciting applications since it allows one to modify the conductive states near the Fermi level and to switch on and off the on-chain pi-electron magnetism.Comment: in print in Phys Rev Let

Stakeholder Oriented Analysis for Information Intensive Applications: A Case Study

We present an approach to Requirements Elicitation based on AWARE, a goal oriented technique conceived for Web applications. The approach integrates a goal-oriented analysis of the needs of each stakeholder class with a subsequent phase of function-oriented analysis. Goal-oriented analysis facilitates an active participation of users and, therefore, can be considered as a substantial step towards user acceptance of the system. Our approach introduces the use of predefined diagrams of user’s needs and confirmation/disconfirmation interviews, that easies and fastens user interaction. The approach was tested on an Information Intensive Application, namely a collaborative document management system for a fast growing Management Consulting organization. The system will support both marketing activities and consulting work on the whole life cycle of consulting projects. In our case study the goal-oriented approach actually encouraged active participation of future users in the dynamic and unstructured environment typical to a Management Consulting organization. The active user participation helped analyst to maximize the potential value supplied to each professional and to minimize the future effort required to use the system. The consulting organization is currently implementing the system and decided to adopt the approach also for their customers

An HMM–ensemble approach to predict severity progression of ICU treatment for hospitalized Covid–19 patients

COVID–19–related pneumonia requires different modalities of Intensive Care Unit (ICU) interventions at different times to facilitate breathing, depending on severity progression. The ability for clinical staff to predict how patients admitted to hospital will require more or less ICU treatment on a daily basis is critical to ICU management. For real datasets that are sparse and incomplete and where the most important state transitions (dismissal, death) are rare, a standard Hidden Markov Model (HMM) approach is insufficient, as it is prone to overfitting. In this paper we propose a more sophisticated ensemble-based approach that involves training multiple HMMs, each specialized in a subset of the state transitions, and then selecting the more plausible predictions either by selecting or combining the models. We have validated the approach on a live dataset of about 1,000 patients from a partner hospital. Our results show that rare events, as well as the transitions to the most severe treatments outperform state of the art approaches

Data-Driven, AI-Based Clinical Practice:Experiences, Challenges, and Research Directions

Clinical practice is evolving rapidly, away from the traditional but inefficient detect-and-cure approach, and towards a Preventive, Predictive, Personalised and Participative (P4) vision that focuses on extending people's wellness state. This vision is increasingly data-driven, AI-based, and is underpinned by many forms of "Big Health Data" including periodic clinical assessments and electronic health records, but also using new forms of self-assessment, such as mobile-based questionnaires and personal wearable devices. Over the last few years, we have been conducting a fruitful research collaboration with the Infectious Disease Clinic of the University Hospital of Modena having the main aim of exploring specific opportunities offered by data-driven AI-based approaches to support diagnosis, hospital organization and clinical research. Drawing from this experience, in this paper we provide an overview of the main research challenges that need to be addressed to design and implement data-driven healthcare applications. We present concrete instantiations of these challenges in three real-world use cases and summarise the specific solutions we devised to address them and, finally, we propose a research agenda that outlines the future of research in this field.</p

Data-driven, AI-based clinical practice: experiences, challenges, and research directions

Clinical practice is evolving rapidly, away from the traditional but inefficient detect-and-cure approach, and towards a Preventive, Predictive, Personalised and Participative (P4) vision that focuses on extending people’s wellness state. This vision is increasingly data-driven, AI-based, and is underpinned by many forms of "Big Health Data" including periodic clinical assessments and electronic health records, but also using new forms of self-assessment, such as mobile-based questionnaires and personal wearable devices. Over the last few years, we have been conducting a fruitful research collaboration with the Infectious Disease Clinic of the University Hospital of Modena having the main aim of exploring specific opportunities offered by data-driven AI-based approaches to support diagnosis, hospital organization and clinical research. Drawing from this experience, in this paper we provide an overview of the main research challenges that need to be addressed to design and implement data-driven healthcare applications. We present concrete instantiations of these challenges in three real-world use cases and summarise the specific solutions we devised to address them and, finally, we propose a research agenda that outlines the future of research in this field

The concept of care complexity: a qualitative study

Background: Hospital organisations based on the level of care intensity have clearly revealed a concept, that of care complexity, which has been widely used for decades in the healthcare field. Despite its wide use, this concept is still poorly defined and it is often confused with and replaced by similar concepts such as care intensity or workload. This study aims to describe the meaning of care complexity as perceived by nurses in their day-to-day experience of hospital clinical care, rehabilitation, home care, and organisation. Design and methods: Fifteen interviews were conducted with nurses belonging to clinical-care areas and to heterogeneous organisational areas. The interview was of an unstructured type. The participants were selected using a propositional methodology. Colaizzi’s descriptive phenomenological method was chosen for the analysis of the interviews. Results: The nurses who were interviewed predominantly perceive the definition of care complexity as coinciding with that of workload. Nevertheless, the managerial perspective does not appear to be exclusive, as from the in-depth interviews three fundamental themes emerge that are associated with the concept of care complexity: the patient, the nurse and the organisation. Conclusions: The study highlights that care complexity consists of both quantitative and qualitative aspects that do not refer only to the organisational dimension. The use of the terminology employed today should be reconsidered: it appears to be inappropriate to talk of measurement of care complexity, as this concept also consists of qualitative – thus not entirely quantifiable – aspects referring to the person being cared for. In this sense, reference should instead be made to the evaluation of care complexity, which would also constitute a better and more complete basis for defining the nursing skills required in professional nursing practice