957 research outputs found
Clonality of B-cells in portal lymphoid infiltrates of HCV infected livers.
No full textReference Author: Facchetti
Partial inhibition and bilevel optimization in flux balance analysis
No full textMotivation: Within Flux Balance Analysis, the investigation of complex subtasks, such as finding the optimal perturbation of the network or finding an optimal combination of drugs, often requires to set up a bilevel optimization problem. In order to keep the linearity and convexity of these nested optimization problems, an ON/OFF description of the effect of the perturbation (i.e. Boolean variable) is normally used. This restriction may not be realistic when one wants, for instance, to describe the partial inhibition of a reaction induced by a drug.Results: In this paper we present a formulation of the bilevel optimization which overcomes the oversimplified ON/OFF modeling while preserving the linear nature of the problem. A case study is considered: the search of the best multi-drug treatment which modulates an objective reaction and has the minimal perturbation on the whole network. The drug inhibition is described and modulated through a convex combination of a fixed number of Boolean variables. The results obtained from the application of the algorithm to the core metabolism of E.coli highlight the possibility of finding a broader spectrum of drug combinations compared to a simple ON/OFF modeling.Conclusions: The method we have presented is capable of treating partial inhibition inside a bilevel optimization, without loosing the linearity property, and with reasonable computational performances also on large metabolic networks. The more fine-graded representation of the perturbation allows to enlarge the repertoire of synergistic combination of drugs for tasks such as selective perturbation of cellular metabolism. This may encourage the use of the approach also for other cases in which a more realistic modeling is required. © 2013 Facchetti and Altafini; licensee BioMed Central Ltd
Considerazioni sulla rilettura di CIE5992
No full textDal riesame congiunto di carattere archeologico, epigrafico, linguistico dell'iscrizione ceretana del periodo orientalizzante recente rinvenuta sotto il tumulo delle Ginestre, emergono spunti per lo studio delle pratiche funerarie etrusche in rapporto a aspetti finora poco esplorati della cosmologia e della religione degli Etruschi
Interni: Brandelli di memoria intorno a "La Traviata Norma"
No full textIn this text, Sergio Facchetti argues that the conflicts that led to the dissolution of the COM (Comitati Omosessuali Milanesi) were already present during the production of the theatrical pieceLa Traviata Norma. Remembering the houses interiors of three emblematic figures of the COM (Corrado Levi, Mario Mieli, Francesco Pertegato), the author tries to stress some of the cultural and social differences inside that gay group
Artificial metalloenzymes based on vancomycin for stereoselective catalysis in aqueous media
No full textBackground: Artificial metalloenzymes, stemming from the combination of transition metal catalysts embedded within a biological environment, have recently risen up as a promising approach to merge the reactivity of metal-based catalysis and the specificity of biocatalysis. Dalbapeptides, such as vancomycin, teicoplanin and ristocetin are variously substituted heptapeptides whose antibiotic activity depends on their binding to the D-Ala-D-Ala dimer of peptidoglycan precursors thus resulting in the inhibition of cell wall biosynthesis. In this system, indeed, the source of chirality is due to the presence not only of the aminoacidic chain, but also from the atropoisomerism of their structure. This interaction is stabilized by an array of hydrophobic interactions and five key hydrogen bonds and it is marked by such a low dissociation constant (KD = ~10-17 M).
Objective: starting from this background, dalbapeptides can be employed as an innovative alternative to the classical biotin/(strept)avidin second sphere coordination system.
Methods: In this context, aminoethylbenzensulfonamide ligands decorated with the D-Ala-D-Ala dimer at different positions of the phenyl ring were employed for the synthesis of the hybrid catalysts in association with an iridium centre. In the presence of vancomycin, a new class of artificial reductases was obtained and applied to the stereoselective synthesis of chiral cyclic in different aqueous media.
Results: An encouraging 48% (S) e.e. was obtained in the asymmetric reduction of the salsolidine precursor in NaOAc 0.1 M buffer at pH 5 whereas in the case of the most demanding isoquinoline substrates, the meta-artificial metalloenzyme afforded the product in an outstanding 71% (S) e.e. when applied to quinaldine.
Conclusion: The Van/ D-Ala-D-Ala dimer system resulted particularly sensitive to pH variations, thus indicating an interesting change in the conformational arrangement of Van. Indeed, the system shows remarkable potential for the synthesis of chiral sultam precursors under green reaction conditions
New platinum-based chemotherapeutics: a journey beyond cisplatin
No full textThe discovery of cisplatin and its later approved derivatives started a new era in the bioinorganic medicinal chemistry field but the persistence of severe side-effects along with the emerging of drug resistance evoke the need of a new generation of transition metal-based chemotherapeutics. The starting point of this journey was the preparation of diamine ligands derived from variously substituted N-methyl-2-aminomethyl imidazoles.1 By introducing differently-long saturated and unsaturated chains at N1, the lipophilicity and the consequent cytotoxicity of the corresponding Pt(II)-complexes was modulated whereas its substitution with the 1,2,5-oxadiazole moiety selectively introduced the ability to simultaneously interact with DNA and to interrupt STAT3 signalling pathway.2 Breaking the assumption that bifunctionality is necessary for antiproliferative activity, a series of monofunctional cationic platinum complexes were synthesised showing a potent cytotoxic effect toward triple-negative breast cancer cells and in cancer cell lines partially resistant to cisplatin. Moreover, the prominent stability of this class of platinum complexes suggested also a possible application for MSCs loading to use for advanced cell therapy.3 Moving forward in this field, the effect of the bidentate ligands on the biological activity was highlighted showing for the Pt-8-aminoquinoline series a different biological profile.4 In order to gain some mechanistic insights, the interaction of such platinum-based compounds with some model proteins was investigated through ESI-MS analysis.
Since an increasing interest has recently arisen in the development of platinum based theranostic agents, indeed, a series of cyclometalated anionic Pt(II) complexes carrying tetrabromocatechol or alizarine as O^O chelating ligands was developed. This last series of platinum complexes displayed enhanced cytotoxicity toward triple-negative breast cancer (TNBC) and they furthermore resulted emissive in solution.5 Moreover, fluorescence confocal analysis showed their localization in the perinuclear region of MDA-MB231 cells proving their ability to serve as luminescent theranostic probes
New artificial imine reductases based on an iridium/ vancomycin system for the asymmetric reduction of cyclic imines
No full textArtificial metalloenzymes, deriving from transition metal catalysts embedding within a biological environment, have recently risen up as a promising synthetic tool able to combine the reactivity of metal-based catalysis with the specificity of biocatalysis.1 Dalbapeptides, such as vancomycin, teicoplanin and ristocetin are variously substituted heptapeptides whose antibiotic activity relies on their binding to the D-Ala-D-Ala dimer of peptidoglycan precursors thus leading to an irreversible inhibition of cell wall biosynthesis. This interaction is marked by such a low dissociation constant (KD =~10-17M) that it makes vancomycin-based systems an innovative alternative to the classical biotin/(strept)avidin technology.2,3
In this context, a class of aminoethylbenzensulfonamide ligands functionalized with the D-Ala-D-Ala dimer were employed for the synthesis of hybrid catalysts in association with an iridium centre. In the presence of vancomycin, a new class of artificial reductases was obtained and applied to the Asymmetric Transfer Hydrogenation (ATH) of model imine substrates in different aqueous media. An encouraging 48% (S) e.e. was obtained in the asymmetric reduction of the salsolidine precursor in CH3COONa 0.1 M buffer at pH 5 whereas in the case of quinolines, the meta-artificial metalloenzyme afforded the product in a significant 70% (S) e.e. when applied to quinaldine. Moreover, an unprecedented 35% (R) e.e. in the enantioselective reduction of chiral sultam precursor 3-methylbenzo[d]isothiazole-1,1-dioxide was realized under green reaction conditions
Asymmetric reduction of cyclic imines by a new hybrid catalyst based on an iridium-vancomycin system
No full textThe so-called hybrid catalysts, derived from the combination of transition metal catalysts embedded within a biological environment have recently risen up as a promising approach able to merge the attractive properties of both metal-based catalysis and biocatalysis1-2. Dalbapeptides3, such as vancomycin, teicoplanin, ristocetin, are variously substituted heptapeptides whose antibiotic activity stems from their binding to the D-Ala-D-Ala dimer of peptidoglycan precursors thus resulting in the inhibition of cell wall biosynthesis. In this system, indeed, the source of chirality is due not only to the presence of the aminoacidic chain but also from the atropoisomerism of their structure. This interaction is marked by such a low dissociation constant (KD = ~10-17 M) that it makes dalbapeptides an innovative alternative to the classical biotin/(strept)avidin second sphere coordination system4-5.
In this context, aminoethylbenzensulfonamide ligands functionalized with the D-Ala-D-Ala dimer at different positions of the phenyl ring were employed for the synthesis of the hybrid catalysts (HyCat) in association with an iridium centre leading to reductases applied to the asymmetric transfer hydrogenation of cyclic imines.
An encouraging 48% (S) e.e. was obtained in the asymmetric reduction of the salsolidine precursor using the meta-Hycat in NaOAc 0.1 M buffer at pH 5. In the case of the most demanding isoquinoline substrates, the meta-HyCat afforded the product in an appreciable 70% (S) e.e. in the reduction of quinaldine
Errors in Italian as Second Language
No full textThis essay deals with a series of strategies that second or foreign language learners adopt in an effort to avoid making predictable errors. One of the most significant and least studied aspects in the academic field is the type of strategies that are put in place to make changes in the planning of the discourse, when the elements are not available to cope with the event, the communication need or when a speaker wants to change subject from a little-known conversational or textual sector. We intend to examine the concept of competence with respect to performance, the role and type of errors, ending up eliciting a taxonomy of interventions by learners, aimed at avoiding errors in oral and written production
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