PROGETTAZIONE, SINTESI E VALUTAZIONE DELL'ATTIVITA' ANTIMICOBATTERICA ED ANTIFUNGINA DI NUOVI DERIVATI ETEROCICLICI

2000/2001XIV Ciclo1970Versione digitalizzata della tesi di dottorato cartacea

Cellulose/biochar aerogels with excellent mechanical and thermal insulation properties

Aiming at investigating the use of alternative materials for the production of thermal insulation and, mainly, to replace the carbon structures (graphene and nanotubes), extensively used in the development of aerogels, the present study had the objective to produce cellulose/biochar aerogels and to evaluate their properties. The aerogels were produced from Pinus elliottii cellulose fibers and biochar produced from these fibers. The materials were characterized in their physical, thermal and mechanical properties. They were extremely light and porous, with a density between 0.01 and 0.027 g cm−3 and porosity between 93 and 97%. Several percentages of biochars were added to the cellulose suspension (0–100% w/w). The use of 40 wt% biochar provided a 60% increase in the compressive strength of the aerogel in relation to the cellulose aerogel. Besides that, the addition of this carbonaceous structure did not influence significantly the thermal conductivity of the aerogels, which presented a thermal conductivity of 0.021–0.026 W m−1 K−1. The materials produced in the present research present a great potential to be used as insulators due to the low thermal conductivity found, which was very similar to the thermal conductivity of the air and also of commercial materials such as polyurethane foam and expanded polystyrene

Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: preliminary data and computational analysis

This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 \u3bcg/mL (0.37-0.75 \u3bcM) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans

Improving selectivity preserving affinity: New piperidine-4-carboxamide derivatives as effective sigma-1-ligands

We report the design, synthesis and binding evaluation against \u3c31 and \u3c32 receptors of a series of new piperidine-4-carboxamide derivatives variously substituted on the amide nitrogen atom. Specifically, we assessed the effects exerted on \u3c3 receptor affinity by substituting the N-benzylcarboxamide group present on a series of compounds previously synthesized in our laboratory with different cyclic or linear moieties. The synthesized compounds 2a-o were tested to estimate their affinity and selectivity toward \u3c31 and \u3c32 receptors. Very high \u3c31 affinity (Ki\ua0=\ua03.7\ua0nM) and Ki\u3c32/Ki\u3c31 selectivity ratio (351) were found for the tetrahydroquinoline derivative 2k, featuring a 4-chlorobenzyl moiety linked to the piperidine nitrogen atom

Production of carbon foams from rice husk

The production of a material with rigid, multifunctional three-dimensional porous structure at a low cost is still challenging to date. In this work, a light and rigid carbon foam was prepared using rice husk as the basic element through a simple fermentation process followed by carbonization. For the fermentation process, the amount of biological yeast (7.5 g for the carbon foam CA-1P and 5 g for the carbon foam CA-2P) was used to evaluate its influence on the morphology of the foams. In order to prove that the heat treatment made in the foam alters the hydrophilic character of the rice husk foam, a chemical treatment with steam deposition was carried out. The foams were characterized by the following analyzes: apparent density, micrograph, thermogravimetry, contact angle, water sorption capacity and thermal conductivity. Visually, the CA-1P foams presented a structure with larger pores due to the greater amount of yeast used in its formulation. The heat treatment of rice potato foams proved to be as efficient as the chemical treatment for water contact angle above 90º, proving the ability of the foams to repel water/moisture. The thermal conductivity of the foams (0.029 and 0.026 W m-1 K-1 for CA-1P and CA-2P, respectively) was close to the conductivity of polyurethane foams (0.032 W m-1 K-1). Thus, the method used in the production of the carbon foams produced from the rice husk proved to be effective. In addition, the foams produced have the potential to be used for thermal insulation

Computer-assisted design, synthesis, binding and cytotoxicity assessments of new 1-(4-(aryl(methyl)amino)butyl)-heterocyclic sigma 1 ligands

In this work we applied a blend of computational and synthetic techniques with the aim to design, synthesize, and characterize new \u3c31 receptor (\u3c31R) ligands. Starting from the structure of previously reported, high-affinity benzoxazolone-based \u3c31 ligands, the threedimensional homology model of the \u3c31R was exploited for retrieving the molecular determinants to fulfill the optimal pharmacophore requirements. Accordingly, the benzoxazolone moiety was replaced by other heterocyclic scaffolds, the relevant conformational space in the \u3c31R binding cavity was explored, and the effect on \u3c31R binding affinity was ultimately assessed. Next, the compounds designed in silico were synthesized, and their affinity and selectivity toward \u3c31 and \u3c32 receptors were tested. Finally, a representative series of best \u3c31R binders were assayed for cytotoxic activity on the SH-SY5Y human neuroblastoma cell line. Specifically, the new 4-phenyloxazolidin-2-one derivatives 2b (i.e., (R)-2b and (S)-2b) emerged as potential leads for further development as \u3c31R agents, as they were found endowed with the highest \u3c31R affinity (Ki\u3c31 values in the range 0.95-9.3 nM), and showed minimal cytotoxic levels exhibited in the selected, cell-based test, in line with a \u3c31R agonist behavior

Origin of Co-Expression Patterns in E.coli and S.cerevisiae Emerging from Reverse Engineering Algorithms

BACKGROUND: The concept of reverse engineering a gene network, i.e., of inferring a genome-wide graph of putative gene-gene interactions from compendia of high throughput microarray data has been extensively used in the last few years to deduce/integrate/validate various types of "physical" networks of interactions among genes or gene products. RESULTS: This paper gives a comprehensive overview of which of these networks emerge significantly when reverse engineering large collections of gene expression data for two model organisms, E. coli and S. cerevisiae, without any prior information. For the first organism the pattern of co-expression is shown to reflect in fine detail both the operonal structure of the DNA and the regulatory effects exerted by the gene products when co-participating in a protein complex. For the second organism we find that direct transcriptional control (e.g., transcription factor-binding site interactions) has little statistical significance in comparison to the other regulatory mechanisms (such as co-sharing a protein complex, co-localization on a metabolic pathway or compartment), which are however resolved at a lower level of detail than in E. coli. CONCLUSION: The gene co-expression patterns deduced from compendia of profiling experiments tend to unveil functional categories that are mainly associated to stable bindings rather than transient interactions. The inference power of this systematic analysis is substantially reduced when passing from E. coli to S. cerevisiae. This extensive analysis provides a way to describe the different complexity between the two organisms and discusses the critical limitations affecting this type of methodologies

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Alignment of the CMS muon system with cosmic-ray and beam-halo muons

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe CMS muon system has been aligned using cosmic-ray muons collected in 2008 and beam-halo muons from the 2008 LHC circulating beam tests. After alignment, the resolution of the most sensitive coordinate is 80 microns for the relative positions of superlayers in the same barrel chamber and 270 microns for the relative positions of endcap chambers in the same ring structure. The resolution on the position of the central barrel chambers relative to the tracker is comprised between two extreme estimates, 200 and 700 microns, provided by two complementary studies. With minor modifications, the alignment procedures can be applied using muons from LHC collisions, leading to additional significant improvements.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR(Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)