298 research outputs found
Shades of ambiguity: Maria Messina’s writing during the fascist era
Malgrado siano stati scritti durante gli anni di totalitarismo fascista, i miglioriromanzi di Maria Messina non sono mai stati studiati alla luce di questorilevante contesto storico. Senza prendere in considerazione la lorosituazione storica, le opere di Messina sembrano sfuocate e confondenti.Ma quando sono analizzate in relazione all’epoca, le opere assumono unsignificato nuovo e profondo. Questo articolo esamina l’ambiguità dellarappresentazione dei ruoli, delle aspirazioni e della caratterizzazione delledonne e degli uomini nei romanzi La casa nel vicolo (1921), Un fiore che nonfiorì (1923), Le pause della vita (1926) e L’amore negato (1928).Richiamando le dottrine fasciste del periodo, l’articolo dimostra comeMessina usava l’ironia, la parodia e la caricatura per rivelare i suoi verisentimenti spregiativi verso il regime fascista, nascosti sotto una facciatapro-fascista
Development of a high pressure liquid chromatographic method for the simultaneous analysis of sulphamethoxazole and trimethoprim and its application to biological fluids and dissolution rate studies on solid oral dosage forms
Co-trimoxazole, a combination of a 5-to-l ratio of Sulphamethoxazole (SMZ) and Trimethoprim (TMP) , is a highly effective, broad-spectrum antibacterial agent. Since its introduction in 1968, it has been extensively used in infections of the respiratory and urinary tracts. Co-trimoxazole was developed by the systematic investigation of a series of compounds whose mechanism of action was already known. As early as 1950 synergy between sulphonamides and 2,4-diaminopyrimidines was reported. This was to be expected as both groups of drugs exert their antibacterial activity by interfering with the same biochemical pathway in bacteria. TMP was chosen from among many 2,4-diaminopyrimidines tested because of its good antibacterial activity and low toxicity. SMZ was chosen from the sulphonamides available for combination with TMP because of similarity of their biological half-lives. The widespread use of the combination coupled with the fact that monitoring of the levels of all drugs in the body is becoming increasingly important has stimulated research into rapid and efficient methods for the analysis of TMP and SMZ in biological fluids. Another consequence of the immense popularity of the combination is the appearance on the market of several generic preparations of Co-trimoxazole. It is now generally recognized that drug products from different manufacturers which are chemically equivalent may not be therapeutically equivalent. This is due to the fact that the absorption rate and/or bioavailability (extent of absorption) of a poorly soluble drug may be markedly affected by its release rate from the product and by its subsequent dissolution rate in gastrointestinal fluids. Hence bioequivalence of these various products should be establishe
Neural Models of Normal and Abnormal Behavior: What Do Schizophrenia, Parkinsonism, Attention Deficit Disorder, and Depression Have in Common?
Defense Advanced Research Projects Agency and Office of Naval Research (N00014-95-1-0409); National Science Foundation (IRI-97-20333
Maria Messina : her works
Includes bibliographical references.In this thesis I examine the work of the tum-of-the century Sicilian writer, Maria Messina (1887-1944). Relatively prolific, she received attention from some of the major critics of her day. But her works were forgotten after her death until the early 1970s. Messina's works are significant for their contribution to the understanding of both women's literature and the position of the woman in a patriarchal society during the period of Fascist control of Italy. Although there is growing interest in Messina's works, no full-length study exists which combines a general overview of her writings in their historical and cultural context with an accurate biographical history, which also includes unpublished and rare documents by and on Messina. This thesis fills this gap. All available criticism of Messina's writings, both from the early Twentieth century and from the last twenty years has been taken into account. This comprises the overlooked and forgotten reviews from journals and newspapers as well as the recent German and American ones. The corpus of the known works by Messina has been increased by tracing unknown publications in literary journals of the 1910s and 1920s. Messina's known published correspondence has been increased by the discovery of her unpublished letters to Alessio DiGiovanni, which span the years 1910-40, and those to Enrico Bemporad. The former provide new knowledge of her life, cultural formation and social interaction. The latter serve as documents for her publishing history and her private life in general. A more historically accurate picture of Messina's life and work can now be formed, not only from the unpublished letters but also from the documents and certificates obtained from archives and municipal records. On the strength of internal and external evidence, not previously taken into account, a detailed biography and personality sketch of Messina and an assessment of her cultural and literary formation have now been provided. The literary analysis examined Messina's short stories and novels on a separate basis, while taking into account certain themes which were central to both genres. Rediscovered short stories were found to contribute greatly to a balanced understanding of Messina's subject matter: the tormented mother-child relationship, the dichotomy between greed and need, the ambivalent stance towards love. The analysis of the novels also revealed new insight into Messina's attitude towards the female condition within society. The present feminist-oriented criticism on Messina has tended to overlook her ambiguous representation of the career-woman. Nor has it been aware of the progressive weakening and elimination of the authoritative male figure. These aspects have been seen to be the externalisation of Messina's attitude towards Fascism. In her historical context, on one level Messina appears to accept and transmit Fascism's idealisation of the wife and mother and the glorification of the rural and traditional ways of life. On another level she denounces Fascist doctrine by ridiculing its cardinal symbol of the virile male. While considering Messina's writings as important literary and sociological documents of the condition of the woman in a critical historical moment, the analysis of the text is not oriented from the sole perspective of feminist criticism, which would have been too restrictive. It is instead conducted from a general critical perspective, moving from the texts themselves in order to assess their structural, thematic, stylistic and symbolic components. Research was carried out in the principal libraries of Italy and those in which Messina resided - Rome, Florence, Urbino, Naples, Palermo, Catania, Pistoia - for published and unpublished material written on and by Messina. Searches for biographical information and documents were carried out in all the centres in which Messina lived. Family members and descendents of her friends were contacted. The material obtained was used to compile a biographical history and analyses of her writings
Enhanced Potency of Bivalent Small Molecule gp41 Inhibitors
Low molecular weight peptidomimetic inhibitors with hydrophobic pocket binding properties and moderate fusion inhibitory activity against HIV-1 gp41-mediated cell fusion were elaborated by increasing the available surface area for interacting with the heptad repeat-1 (HR1) coiled coil on gp41. Two types of modifications were tested: 1) increasing the overall hydrophobicity of the molecules with an extension that could interact in the HR1 groove, and 2) forming symmetrical dimers with two peptidomimetic motifs that could potentially interact simultaneously in two hydrophobic pockets on the HR1 trimer. The latter approach was more successful, yielding 40–60 times improved potency against HIV fusion over the monomers. Biophysical characterization, including equilibrium binding studies by fluorescence and kinetic analysis by Surface Plasmon Resonance, revealed that inhibitor potency was better correlated to off-rates than to binding affinity. Binding and kinetic data could be fit to a model of bidentate interaction of dimers with the HR1 trimer as an explanation for the slow off-rate, albeit with minimal cooperativity due to the highly flexible ligand structures. The strong cooperativity observed in fusion inhibitory activity of the dimers implied accentuated potency due to the transient nature of the targeted intermediate. Optimization of monomer, dimer or higher order structures has the potential to lead to highly potent non-peptide fusion inhibitors by targeting multiple hydrophobic pockets
Modulation of the conductance of a 2,2′-bipyridine-functionalized peptidic ion channel by Ni2+
An α-helical amphipathic peptide with the sequence H2N-(LSSLLSL)3-CONH2 was obtained by solid phase synthesis and a 2,2′-bipyridine was coupled to its N-terminus, which allows complexation of Ni2+. Complexation of the 2,2′-bipyridine residues was proven by UV/Vis spectroscopy. The peptide helices were inserted into lipid bilayers (nano black lipid membranes, nano-BLMs) that suspend the pores of porous alumina substrates with a pore diameter of 60 nm by applying a potential difference. From single channel recordings, we were able to distinguish four distinct conductance states, which we attribute to an increasing number of peptide helices participating in the conducting helix bundle. Addition of Ni2+ in micromolar concentrations altered the conductance behaviour of the formed ion channels in nano-BLMs considerably. The first two conductance states appear much more prominent demonstrating that the complexation of bipyridine by Ni2+ results in a considerable confinement of the observed multiple conductance states. However, the conductance levels were independent of the presence of Ni2+. Moreover, from a detailed analysis of the open lifetimes of the channels, we conclude that the complexation of Ni2+ diminishes the frequency of channel events with larger open times
Cortical Columnar Organization Is Reconsidered in Inferior Temporal Cortex
The object selectivity of nearby cells in inferior temporal (IT) cortex is often different. To elucidate the relationship between columnar organization in IT cortex and the variability among neurons with respect to object selectivity, we used optical imaging technique to locate columnar regions (activity spots) and systematically compared object selectivity of individual neurons within and across the spots. The object selectivity of a given cell in a spot was similar to that of the averaged cellular activity within the spot. However, there was not such similarity among different spots (>600 μm apart). We suggest that each cell is characterized by 1) a cell-specific response property that cause cell-to-cell variability in object selectivity and 2) one or potentially a few numbers of response properties common across the cells within a spot, which provide the basis for columnar organization in IT cortex. Furthermore, similarity in object selectivity among cells within a randomly chosen site was lower than that for a cell in an activity spot identified by optical imaging beforehand. We suggest that the cortex may be organized in a region where neurons with similar response properties were densely clustered and a region where neurons with similar response properties were sparsely clustered
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Structure and Interactions of HIV-1 gp41 CHR-NHR Reverse Hairpin Constructs Reveal Molecular Determinants of Antiviral Activity
Engineered reverse hairpin constructs containing a partial C-heptad repeat (CHR) sequence followed by a short loop and full-length N-heptad repeat (NHR) were previously shown to form trimers in solution and to be nanomolar inhibitors of HIV-1 Env mediated fusion. Their target is the in situ gp41 fusion intermediate, and they have similar potency to other previously reported NHR trimers. However, their design implies that the NHR is partially covered by CHR, which would be expected to limit potency. An exposed hydrophobic pocket in the folded structure may be sufficient to confer the observed potency, or they may exist in a partially unfolded state exposing full length NHR. Here we examined their structure by crystallography, CD and fluorescence, establishing that the proteins are folded hairpins both in crystal form and in solution. We examined unfolding in the milieu of the fusion reaction by conducting experiments in the presence of a membrane mimetic solvent and by engineering a disulfide bond into the structure to prevent partial unfolding. We further examined the role of the hydrophobic pocket, using a hairpin-small molecule adduct that occluded the pocket, as confirmed by X-ray footprinting. The results demonstrated that the NHR region nominally covered by CHR in the engineered constructs and the hydrophobic pocket region that is exposed by design were both essential for nanomolar potency and that interaction with membrane is likely to play a role in promoting the required inhibitor structure. The design concepts can be applied to other Class 1 viral fusion proteins
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