SINFONIA Project Mass Appraisal: Beyond The Value Of Energy Performance In Buildings

Energy retrofit of existing buildings stock is today a major urban challenge and opportunity. Although a market appreciation of green buildings is generally recognized, specificities related to different countries, contexts and sectors still need further investigation. Moreover, the energy retrofit carries with it multiple elements, ranging from monetary savings to personal fulfillment of living greener. The ongoing European smart city project SINFONIA offers the chance to analyze a double international case study, and to estimate expected positive effects on dwellings\u2019 value, due to energy retrofit measures undertaken at the district level. This paper, starting from previous similar experiences, designs an operational approach based on spatial hedonic price method and analytic hierarchy process. Finally, it suggests how to develop a spatialized mass appraisal by linking results with a geographical information system. Such approach will contribute to assess the socio-economic impact of SINFONIA project and to evaluate the effectiveness of further smart city initiatives

Multiple-benefits from buildings\u2019 refurbishment: Evidence from smart city projects in Europe

Given the necessity of strengthening the transition towards a smarter, more sustainable low-carbon future, Smart Cities are considered a powerful tool. However, Smart City projects involving the refurbishment of existing buildings carry key barriers to implementation. The most prominent ones are: (i) a wide time discrepancy between appreciable environmental and economic benefits and immediate costs of action and (ii) economic benefits that might not accrue to who bears the cost of the intervention. This research provides a clue to solving this impasse based on the concept of multiple-benefits evaluation stemming from a shift in perspective from mitigation costs to development opportunities. We considered the costs of interventions on the European building stock under the Smart City projects to assess the multiple-benefits delivered to society. Starting from the monetary aspects of single projects, we identified multipliers to assess three different types of multiple-benefits: (i) Energy savings; (ii) Health and well-being; and iii.) Employment. Our findings indicate that in a time span of 14 years (2005\u20132018), an amount of about 260 million Euros invested in such projects lead to: (i) an accumulated saving potential of approximately 40 kilotons of oil equivalent, corresponding to 465 GWh; (ii) a reduction in air pollution corresponding to a value of 3 million Euros in avoided costs; and (iii) the creation of around 1,000 jobs with an average duration of 5 years. Considering that most of such investments occurred during the latest economic recession, the impact of the aforementioned multi-benefits appears to be not negligible

New Tasks in Old Jobs: Drivers of Change and Implications for Job Quality

This overview report summarises the findings of 20 case studies looking at recent changes in the task content of five manufacturing occupations (car assemblers, meat processing workers, hand-packers, chemical products plant and machine operators and inspection engineers) as a result of factors such as digital transformations, globalisation and offshoring, increasing demand for high quality standards and sustainability. It also discusses some implications in terms of job quality and working life. The study reveals that the importance of physical tasks in manufacturing is generally declining due to automation; that more intensive use of digitally controlled equipment, together with increasing importance of quality standards, involve instead a growing amount of intellectual tasks for manual industrial workers; and that the amount of routine task content is still high in the four manual occupations studied. Overall, the report highlights how qualitative contextual information can complement existing quantitative data, offering a richer understanding of changes in the content and nature of jobs

Recent BES Results on Hadron Spectroscopy

We present recent results from the BES experiment on the observation of the Y(2175) in J/\psi\to \phi f_0(980) \eta, study of \eta(2225) in J/\psi\to \gamma \phi \phi, and the production of X(1440) recoiling against an \omega or a \phi in J/\psi hadronic decays. The observation of \psi(2S) radiative decays is also presented.Comment: 5 page

HUMAN AROMATIC L-AMINO ACID DECARBOXYLASE: WHEN STRUCTURE AND MOBILITY DRIVE EFFICIENT CATALYSIS. IMPLICATIONS FOR AADC DEFICIENCY

L’enzima Decarbossilasi degli L-amino acidi aromatici (AADC) è responsabile della sintesi di due neurotrasmettitori essenziali: la dopamina e la serotonina. AADC deve la sua attività catalitica alla chimica del suo cofattore, il piridossale 5’-fosfato (PLP). La struttura cristallografica dell’enzima da mammifero (precisamente da maiale che ha il 90% di identità con l’enzima umano) nella sua forma olo venne risolta venti anni fa e tale risoluzione aprì la strada ad importanti studi strutturali. Dieci anni dopo venne pubblicata la struttura umana di AADC nella sua forma apo evidenziando quali cambiamenti conformazionali avvengono quando il PLP viene legato dall’enzima. Le strutture apo e olo AADC hanno avuto notevole importanza per la comprensione della patogenicità di varianti enzimatiche associate alla malattia chiamata ‘Deficit da AADC’ (AADCd, OMIM#608643). Questa malattia autosomica recessiva molto rara è dovuta prevalentemente a mutazioni missenso sul gene AADC. I pazienti affetti da AADCd mostrano un’amAromatic L-Amino Acid Decarboxylase (AADC) is the enzyme responsible for the synthesis of two essential neurotransmitter dopamine and serotonin from L-Dopa and L-hydroxytryptophan. AADC owes its specific catalytic activity to the chemistry of its cofactor, pyrydoxal-5’-phosphate (PLP). Almost 20 years ago, the crystal structure of a mammalian holoAADC (porcine, sharing 90% of sequence identity) was solved and the availability of its 3D structure paved the way to structural studies. Moreover, 10 years later, human apoAADC structure was published, shedding light on the conformational rearrangement occurring on the apo enzyme upon addition of PLP. Importantly, apo and holoAADC structures provided crucial insights for the comprehension of the pathogenicity of a number of AADC deficiency associated variants. AADC deficiency (OMIM#608643) is a rare autosomal recessive inborn disease due to missense mutations in the AADC gene. Patients bearing these mutations show mild to severe phenotypes, whose destiny is often fatal. Due to the rarity of the disease and to the heterogeneous response to the treatments, medications are not often satisfactory. In the past years, some efforts on human recombinant AADC pathogenic variants have tried to provide support to the research on AADC deficiency by means of biochemical and biophysical approaches determining the impact of the amino acid substitutions on the enzyme features. Here, a further contribution to the comprehension of the AADC deficiency is provided. The crystal structure of human holoAADC has been solved under different conditions, both in its native and ligand bound form. The combination of crystallographic studies, molecular dynamics simulations (MD) and site directed mutagenesis uncovered novel aspects of the AADC structure-function relationship. Moreover, the characterization of 21 novel identified pathogenic variants (spread on each AADC domain, N-terminal, Large and C-terminal Domains) led to the widening of the range of enzymatic phenotypes associated to AADC deficiency. The proposed combination of biochemical and kinetic studies permitted to determine correlations between structural and functional signals. Enzymatic phenotypes span from variants characterized by a mild phenotypes to variants (mainly located at the NTD-CTD interface) whose dramatic structural defects lead to a catalytic incompetence. In addition, MD simulations and in solutions data point out a critical role for the loop3 element that contains the essential catalytic residue Tyr332. A group of variants affecting loop3 has been identified as catalytically incompetent and their structural features have been dissected thanks also to the solving of the crystal structure of pathogenic variant L353P, which constitutes the first solved structure of an AADC variant. Altogether, this study on human AADC provides new elements for the comprehension of the structure-function relationship of AADC with a particular focus on protein dynamics and mobility. Lastly, structural details might represent the basis for both the designing of novel specific inhibitors and for a better comprehension of the molecular aspects of the variants associated with the AADC deficiency

Compound heterozygosis in AADC deficiency and its complex phenotype in terms of AADC protein population

Aromatic amino acid decarboxylase (AADC) deficiency is a rare monogenic disease due to mutations in the ddc gene producing AADC, a homodimeric pyridoxal 5 '-phosphate-dependent enzyme. The disorder is often fatal in the first decade and is characterized by profound motor impairments and developmental delay. In the last two years, there has been a net rise in the number of patients and variants identified, maybe also pushed by the ongoing gene therapy trials. The majority of the identified genotypes are compound heterozygous (about 70%). Efforts are underway to reach early diagnosis, find possible new markers/new fast methods, and predict clinical outcome. However, no clear correlation of genotype-to-phenotype exists to date. Nevertheless, for homozygous patients, reliable results have been obtained using genetic methods combined with available computational tools on crystal structures corroborated by biochemical investigations on recombinant homodimeric AADC variants that have been obtained and characterized in solution. For these variants, the molecular basis for the defect has been suggested and validated, since it correlates quite well with mildness/severity of the homozygous phenotype. Instead, prediction for compound heterozygous patients is more difficult since complementation effects could happen. Here, by analyzing the existing literature on compound heterozygosity in AADC deficiency and other genetic disorders, we highlight that, in order to assess pathogenicity, the measurement of activity of the AADC heterodimeric variant should be integrated by bioinformatic, structural, and functional data on the whole protein constellation theoretically present in such patients. A wider discussion on symptomatic heterozygosity in AADC deficiency is also presented