Search results for "CEI"

Using the Rasch model to assess a University Service on the Basis of Students Opinions

2008

In this paper we use the Rasch model (RM) as a tool to measure the perceived quality of student services at the Reception Office of an Italian university faculty. This paper has both a substantive and a methodological aim. The former is concerned with measuring the service quality of the Reception Office, while the latter concerns the definition and validation of an instrument for measuring perceived quality. The sample comprised 273 students enrolled at the Faculty of Economics at the University of Palermo (Aiello F. Il modello di Rasch per la costruzione di uno strumento di misura della qualit`a di un Servizio. Ph.D. Thesis, University of Palermo, Palermo, 2005). The RM is applied to prod…

Optimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal…

2013

The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 subs…

Peptides Derived from Apoptotic Bax and Bid Reproduce the Poration Activity of the Parent Full-Length Proteins

2005

Bax and Bid are proapoptotic proteins of the Bcl-2 family that regulate the release of apoptogenic factors from mitochondria. Although they localize constitutively in the cytoplasm, their apoptotic function is exerted at the mitochondrial outer membrane, and is related to their ability to form transbilayer pores. Here we report the poration activity of fragments from these two proteins, containing the first alpha-helix of a colicinlike hydrophobic hairpin (alpha-helix 5 of Bax and alpha-helix 6 of Bid). Both peptides readily bind to synthetic lipid vesicles, where they adopt predominantly alpha-helical structures and induce the release of entrapped calcein. In planar lipid membranes they fo…

Tuning and Predicting Biological Affinity: Aryl Nitriles as Cysteine Protease Inhibitors

2012

A series of aryl nitrile-based ligands were prepared to investigate the effect of their electrophilicity on the affinity against the cysteine proteases rhodesain and human cathepsin L. Density functional theory calculations provided relative reactivities of the nitriles, enabling prediction of their biological affinity and cytotoxicity and a clear structure-activity relationship.

Cyclodextrin and Adamantane Host-Guest Interactions of Modified Hyperbranched Poly(ethylene imine) as Mimetics for Biological Membranes

2011

Quenching of fluorescein-conjugated lipids by antibodies. Quantitative recognition and binding of lipid-bound haptens in biomembrane models, formatio…

1992

Three model biomembrane systems, monolayers, micelles, and vesicles, have been used to study the influence of chemical and physical variables of hapten presentation at membrane interfaces on antibody binding. Hapten recognition and binding were monitored for the anti-fluorescein monoclonal antibody 4–4-20 generated against the hapten, fluorescein, in these membrane models as a function of fluorescein-conjugated lipid architecture. Specific recognition and binding in this system are conveniently monitored by quenching of fluorescein emission upon penetration of fluorescein into the antibody's active site. Lipid structure was shown to play a large role in affecting antibody quenching. Interes…

Structure, interdomain dynamics, and pH-dependent autoactivation of pro-rhodesain, the main lysosomal cysteine protease from African trypanosomes

2021

AbstractRhodesain is the lysosomal cathepsin L-like cysteine protease ofT. brucei rhodesiense, the causative agent of Human African Trypanosomiasis. The enzyme is essential for the proliferation and pathogenicity of the parasite as well as its ability to overcome the blood-brain barrier of the host. Lysosomal cathepsins are expressed as zymogens with an inactivating pro-domain that is cleaved under acidic conditions. A structure of the uncleaved maturation intermediate from a trypanosomal cathepsin L-like protease is currently not available. We thus established the heterologous expression ofT. brucei rhodesiensepro-rhodesain inE. coliand determined its crystal structure. The trypanosomal pr…

The discovery of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines

2021

Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense which seriously affects human health in Africa. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work herein describes the design and syntheses of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines, with compound 13, the 4-(2-methoxyphenyl)-6-(pyridine-3-yl)pyrimidin-2-amine demonstrating an IC50 value of 0.38 μM and a promising off-target ADME-Tox profile in vitro. In silico molecular target investigations showed rhodesain to be a pu…

In vitro and in silico studies of polycondensed diazine systems as anti-parasitic agents

2012

Abstract Parasitic diseases caused by protozoarian agents are still relevant today more than ever. Recently, we synthesized several polycondensed diazine derivatives by means 1,3-dipolar cycloaddition reactions. A broad selection of these compounds were submitted to in vitro biological screening against Plasmodium falciparum , Leishmania infantum , Trypanosoma brucei , and Trypanosoma cruzi , resulting active at micromolar level. Induced Fit Docking/MM-GBSA studies were performed giving interesting indications about the probable mechanism of action of the most active compounds

Donne imprenditrici nella produzione e nel commercio dell'olio betico (I-III Sec. D.C.)

1999

Las inscripciones pictóricas (tituli picti) y los sellos de las ánforas olearias Dressel 20 nos aportan el testimonio de las implicaciones de muchos personajes femeninos en la producción y comercio del aceite de oliva entre la Bética (actual Andalucía, España) y Roma, gestionado por la Annona (I-III d.C.). Las mujeres, sean nacidas libres o libertas, desarrollan papeles de responsabilidad, utilizando grandes capitales privados, a veces asociadas con familiares.