Complexation of Secondary Amides to Chromium(III): the X-Ray Structure of a Molecule with Two Modes of Monodentate Organic Amide Co-ordination

The X-ray crystal structure of the dimer [Cr{H(chba-Et)}(py)_2]_(2)·2py [H_(4)(chba-Et)= 1,2-bis(3,5-dichloro-2-hydroxybenzamido) ethane, py = pyridine] establishes, for the first time, the existence of N-co-ordination of an organic amide to Cr^III, the N-atom and carbonyl O-atom of two separate amide groups being co-ordinated to each Cr^III centre [Cr–N 2.030(6) and Cr–O 1.976(5)Å]; the potentially tetra-anionic chelating ligand leads to a variety of co-ordination modes

A new mechanism for exchange processes observed in the compounds [M(η-C_5H_5)_2(exo-η-RCH = CH_2)H], M = Nb and Ta

Dynamic n.m.r. studies of the exchange processes in the complexes [M(η-C_5H_5)(exo-η-RCH=CH_2)H], M = Nb, Ta, lead to the proposal of a new mechanism involving intermediates with agostic bonding

Integrated seismic and energy retrofitting of existing buildings: A state-of-the-art review

Ageing of the building stock is an issue affecting many regions in the world. This means a large proportion of existing buildings being considered energy inefficient, with associated high energy use for heating and cooling. Through renovation, it is possible to improve their energy-efficiency, hence reducing their significant impact on the total energy household and associated greenhouse gas emissions. In seismic regions, additionally, recent earthquakes have caused significant economic losses, largely due to the vulnerability of older buildings not designed to modern standards. Addressing seismic and energy performance by separate interventions is the common approach currently taken, however to achieve better cost-effectiveness, safety and efficiency, a novel holistic approach to building renovation is an emerging topic in the scientific literature. Proposed solutions range from integrated exoskeleton solutions, over strengthening and insulation solutions for the existing building envelope or their replacement with better materials, to integrated interventions on horizontal elements like roof and floor slabs. To identify pathways to combined seismic and energy retrofitting of buildings, a state-of-the-art review of all materials and solutions investigated to date is presented. This is followed by a critical analysis of their effectiveness, invasiveness, building use disruption as well as their impact on the environment. The assessment of current combined retrofitting research highlights a great potential for their application, with a potential to provide cost-effective renovation solutions for regions with moderate to high seismic risk. Still, to-date there is a lack of experimental research in this field, a need for further work on truly integrated technologies and their validation through applications on existing large-scale buildings. Moreover, there is a need for adequate design methods, regulations and incentives that further the implementation of integrated retrofitting approaches

Experimental and numerical evaluation of coring effects in reinforced concrete columns

The knowledge of in-situ material properties is the first step in the assessment process of existing structures and, where needed, in the design of the consequent strengthening interventions. In order to achieve this goal, destructive (DT; e.g., cores) and non-destructive (NDT; e.g., ultrasonic, rebound) test methods are generally adopted, either alone or combined. Although many literature papers and guidelines propose to minimize the number of cores in the estimation of the concrete strength in reinforced concrete structures, the European and Italian codes prescribe that the estimation of in-situ strength has to be mainly based on cores drilled from the structure (DT). In this framework, the paper reports results of an experimental program aimed at evaluating the effects of core tests on RC columns, as well as the effectiveness of the structural restoration of drilling holes. Specifically, three sets of column specimens have been considered: (i) drilled columns, (ii) drilled and subsequently restored columns, and (iii) reference not drilled (as-built) columns. Compression tests have been carried out on each column and the results have been compared with the prediction based on codes or other literature approaches. This helped to recognize the main phenomena affecting the column members behavior under axial loads. At the same time, the authors calibrated detailed finite element models based on the experimental results of the tests carried out on column specimens. An advanced Fem tool was used to set-up 3D models. Numerical simulations aimed at better understanding the failure mechanism, especially in the presence of the hole related to the core extraction. The role of longitudinal and transverse reinforcement has been evaluated, highlighting that concrete crushing in the areas around the hole causes the early buckling of rebars, leading to premature failure of drilled column specimens

Behavior and Strengthening of RC Beam-Column Joints: Experimental Program and First Results of the Research Activity in the Framework of DPC-ReLUIS Project (Research Line 2)

The 2005-2008 DPC-Reluis Project, funded by the Italian Department of Civil Protection (DPC), is made up of ten Research Lines (RL). RL 2 specifically focuses on the seismic performance of existing RC buildings and is, in turn, organised in nine different Tasks. In the paper, the design of the research activities being carried out within the Task 7 by the four involved Research Units (RU UNIBAS, RU UNIUD, RU UNISA, and RU UNINA) and some first results are reported. Main objective of Task 7 is to investigate on the experimental behaviour of beam-column joints without or with strengthening, thus providing a contribution to a more reliable evaluation of the seismic vulnerability of Reinforced Concrete existing buildings. To this purpose the main activities carried out have been devoted to design and set up of wide experimental programs on beam-column joints relevant to typical existing RC buildings having different Earthquake Resistant Design (ERD) level, to make a literature review of the state of the art on the subject, to perform numerical simulations based on some analytical models available in literature in order to fully understand the mechanical behaviour. Further, some results of the tests already carried out are reported, analysed and compared in order to understand the failure mechanism and evaluate the seismic performance of joints with and without ERD

ACLY nuclear translocation in human macrophages drives proinflammatory gene expression by NF-κB acetylation

Macrophage stimulation by pathogen-associated molecular patterns (PAMPs) like lipopolysaccharide (LPS) or lipoteichoic acid (LTA) drives a proinflammatory phenotype and induces a metabolic reprogramming to sustain the cell’s function. Nevertheless, the relationship between metabolic shifts and gene expression remains poorly explored. In this context, the metabolic enzyme ATP citrate lyase (ACLY), the producer of citrate-derived acetyl-coenzyme A (CoA), plays a critical role in supporting a proinflammatory response. Through immunocytochemistry and cytosol-nucleus fractionation, we found a short-term ACLY nuclear translocation. Protein immunoprecipitation unveiled the role of nuclear ACLY in NF-κB acetylation and in turn its full activation in human PBMC-derived macrophages. Notably, sepsis in the early hyperinflammatory phase triggers ACLY-mediated NF-κB acetylation. The ACLY/NF-κB axis increases the expression levels of proinflammatory genes, including SLC25A1—which encodes the mitochondrial citrate carrier—and ACLY, thus promoting the existence of a proinflammatory loop involving SLC25A1 and ACLY genes

Mesothelin-specific CD8+ T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients

Tumor-specific CD8+ T cells can potentially be activated by two distinct mechanisms of major histocompatibility complex class I–restricted antigen presentation as follows: direct presentation by tumor cells themselves or indirect presentation by professional antigen-presenting cells (APCs). However, controversy still exists as to whether indirect presentation (the cross-priming mechanism) can contribute to effective in vivo priming of tumor-specific CD8+ T cells that are capable of eradicating cancer in patients. A clinical trial of vaccination with granulocyte macrophage–colony stimulating factor–transduced pancreatic cancer lines was designed to test whether cross-presentation by locally recruited APCs can activate pancreatic tumor-specific CD8+ T cells. Previously, we reported postvaccination delayed-type hypersensitivity (DTH) responses to autologous tumor in 3 out of 14 treated patients. Mesothelin is an antigen demonstrated previously by gene expression profiling to be up-regulated in most pancreatic cancers. We report here the consistent induction of CD8+ T cell responses to multiple HLA-A2, A3, and A24-restricted mesothelin epitopes exclusively in the three patients with vaccine-induced DTH responses. Importantly, neither of the vaccinating pancreatic cancer cell lines expressed HLA-A2, A3, or A24. These results provide the first direct evidence that CD8 T cell responses can be generated via cross-presentation by an immunotherapy approach designed to recruit APCs to the vaccination site

Structural Analysis of Papain-Like NlpC/P60 Superfamily Enzymes with a Circularly Permuted Topology Reveals Potential Lipid Binding Sites

NlpC/P60 superfamily papain-like enzymes play important roles in all kingdoms of life. Two members of this superfamily, LRAT-like and YaeF/YiiX-like families, were predicted to contain a catalytic domain that is circularly permuted such that the catalytic cysteine is located near the C-terminus, instead of at the N-terminus. These permuted enzymes are widespread in virus, pathogenic bacteria, and eukaryotes. We determined the crystal structure of a member of the YaeF/YiiX-like family from Bacillus cereus in complex with lysine. The structure, which adopts a ligand-induced, “closed” conformation, confirms the circular permutation of catalytic residues. A comparative analysis of other related protein structures within the NlpC/P60 superfamily is presented. Permutated NlpC/P60 enzymes contain a similar conserved core and arrangement of catalytic residues, including a Cys/His-containing triad and an additional conserved tyrosine. More surprisingly, permuted enzymes have a hydrophobic S1 binding pocket that is distinct from previously characterized enzymes in the family, indicative of novel substrate specificity. Further analysis of a structural homolog, YiiX (PDB 2if6) identified a fatty acid in the conserved hydrophobic pocket, thus providing additional insights into possible function of these novel enzymes