585 research outputs found

    EFFETTO DI INCLUSIONI METALLICHE NEI PROCESSI DI ANODIZZAZIONE DI LEGHE DI ALLUMINIO

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    La necessità di lavorare mediante asportazione di truciolo leghe di alluminio ha da tempo portato allo sviluppo di leghe specifiche, far cui le più diffuse contengono piombo. Tali leghe devono ora essere superate a causa delle restrizioni legate alla presenza del piombo, motivate principalmente da ragioni ambientali. Diverse leghe sono state sviluppate cercando di sostituire il piombo con il manganese, il ferro, il nichel o l’indio. Un altro promettente sostituto del piombo per queste applicazioni è il berillio, oggetto di studio negli ultimi anni come alligante dell’alluminio. Molto spesso per applicazioni che spaziano dalla motoristica alla attrezzatura sportiva alla componentistica per l’elettronica, i componenti in lega di alluminio devono essere modificati superficialmente per migliorarne sia la resistenza alla corrosione che le proprietà tribologiche. Uno dei trattamenti più diffusi è l’anodizzazione. La presenza però di una particolare microstruttura, contenente isole di metallo elettrochimicamente più nobile (Pb o Bi) può notevolmente influenzare la qualità dell’ossido anodico e di conseguenza le proprietà di resistenza alla corrosione del componente anodizzato. Tale aspetto non è stato ancora sufficientemente analizzato scientificamente. In questo studio sono stati considerati campioni di diverse leghe di alluminio contenenti sia Pb che Bi, sottoposti a trattamenti di anodizzazione. Sono state studiate le difettosità riscontrate nell’ossido individuate mediante microscopia elettronica ed ottica, collegandole al comportamento corrosivo e alla microstruttura del materiale (dimensioni e distribuzione delle isole di Pb o di Bi). Sono state eseguite prove elettrochimiche di vario tipo al fine di comprendere il meccanismo di degrado. Lo scopo finale del lavoro sperimentale è quello di fornire informazioni utili all’ottimizzazione di nuove leghe di alluminio, lavorabili per asportazione di truciolo esenti piombo, che mantengano buone proprietà protettive dell’ossido anodico

    Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer

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    The role of oxidative stress in prostate cancer has been increasingly recognised. Acute and chronic inflammations generate reactive oxygen species that result in damage to cellular structures. Haeme oxygenase-1 (HO-1) has cytoprotective effects against oxidative damage. We hypothesise that modulation of HO-1 expression may be involved in the process of prostate carcinogenesis and prostate cancer progression. We thus studied HO-1 expression and localisation in 85 samples of organ-confined primary prostate cancer obtained via radical prostatectomy (Gleason grades 4–9) and in 39 specimens of benign prostatic hyperplasia (BPH). We assessed HO-1 expression by immunohistochemical staining. No significant difference was observed in the cytoplasmic positive reactivity among tumours (84%), non-neoplastic surrounding parenchyma (89%), or BPH samples (87%) (P=0.53). Haeme oxygenase-1 immunostaining was detected in the nuclei of prostate cancer cells in 55 of 85 (65%) patients but less often in non-neoplastic surrounding parenchyma (30 of 85, 35%) or in BPH (9 of 39, 23%) (P<0.0001). Immunocytochemical and western blot analysis showed HO-1 only in the cytoplasmic compartment of PC3 and LNCaP prostate cancer cell lines. Treatment with hemin, a well-known specific inducer of HO-1, led to clear nuclear localisation of HO-1 in both cell lines and highly induced HO-1 expression in both cellular compartments. These findings have demonstrated, for the first time, that HO-1 expression and nuclear localisation can define a new subgroup of prostate cancer primary tumours and that the modulation of HO-1 expression and its nuclear translocation could represent new avenues for therapy

    Intermittent docetaxel chemotherapy as first-line treatment for metastatic castration-resistant prostate cancer patients

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    Aims: The intermittent administration of chemotherapy is a means of preserving patients' quality of life (QL). The aim of this study was to verify whether the intermittent administration of docetaxel (DOC) improves the patients' QL. Patients &amp; methods: All patients received DOC 70 mg/m every 3 weeks for eight cycles. The patients were randomized to receive DOC continuously or with a fixed 3-month interval after the first four DOC courses. Results: The study involved 148 patients. There was no difference in QL between the groups receiving intermittent or continuous treatment. Intermittence had no detrimental effects on disease control. Conclusion: Although feasible and not detrimental, our results showed that true intermittent chemotherapy in metastatic castration-resistant prostate cancer patients failed to improve the patients' QL

    Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets

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    While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes

    Functional Analyses of the Three Simian Hemorrhagic Fever Virus Nonstructural Protein 1 Papain-Like Proteases

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    The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural polyprotein 1a is predicted to encode three papain-like proteases (PLP1α, PLP1β, and PLP1γ). Catalytic residues and cleavage sites for each of the SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with each other as well as with those of other arteriviruses, and the predicted catalytic residues were shown to be proximal by homology modeling of the SHFV nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal structures. The functionality of the predicted catalytic Cys residues and cleavage sites was tested by analysis of the autoproteolytic products generated in in vitro transcription/translation reactions done with wild-type or mutant SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy analysis of selected immunoprecipitated cleavage products. The data showed that each of the three SHFV PLP1s is an active protease. Cys63 was identified as the catalytic Cys of SHFV PLP1α and is adjacent to an Ala instead of the canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1γ is able to cleave at both downstream and upstream nsp1 junction sites. Although intermediate precursor polyproteins as well as alternative products generated by each of the SHFV PLP1s cleaving at sites within the N-terminal region of nsp1β were produced in the in vitro reactions, Western blotting of SHFV-infected, MA104 cell lysates with SHFV nsp1 protein-specific antibodies detected only the three mature nsp1 proteins

    Treatment Outcome of metastatic lesions from renal cell carcinoma underGoing Extra-cranial stereotactic body radioTHERapy: The together retrospective study

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    Objectives: stereotactic body radiation therapy (SBRT) use has increased overtime for the management of metastatic renal cell carcinoma (mRCC) patients, with a likely good control of irradiated lesions. We planned a retrospective multicenter Italian study, with the aim of investigating the outcome of treatment with SBRT for non-brain secondary lesions in mRCC patients. Methods: all consecutive metastatic non-brain lesions from mRCC that underwent SBRT at nine Italian institutions from January 2015 to June 2017 were considered. The primary endpoint of the study was the lesion-PFS, calculated from SBRT initiation to the local progression of the irradiated lesion. Results: 57 extracranial metastatic lesions from 48 patients with primary mRCC were treated with SBRT. At the median follow-up of 26.4 months, the median lesion-PFS was not reached (43 censored); 72.4% of lesions were progression-free at 40 months, with significantly better lesion-PFS for small metastatic lesions (&lt;14 mm). SBRT was safe and the 1-year local disease control was 87.7%. After SBRT, 18 patients (37.5%) permanently interrupted systemic therapy. Conclusions: consistently with the previous literature, our findings support the use of SBRT in selected mRCC patients

    Effect of D222G Mutation in the Hemagglutinin Protein on Receptor Binding, Pathogenesis and Transmissibility of the 2009 Pandemic H1N1 Influenza Virus

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    Influenza viruses isolated during the 2009 H1N1 pandemic generally lack known molecular determinants of virulence associated with previous pandemic and highly pathogenic avian influenza viruses. The frequency of the amino acid substitution D222G in the hemagglutinin (HA) of 2009 H1N1 viruses isolated from severe but not mild human cases represents the first molecular marker associated with enhanced disease. To assess the relative contribution of this substitution in virus pathogenesis, transmission, and tropism, we introduced D222G by reverse genetics in the wild-type HA of the 2009 H1N1 virus, A/California/04/09 (CA/04). A dose-dependent glycan array analysis with the D222G virus showed a modest reduction in the binding avidity to human-like (α2-6 sialylated glycan) receptors and an increase in the binding to avian-like (α2-3 sialylated glycan) receptors in comparison with wild-type virus. In the ferret pathogenesis model, the D222G mutant virus was found to be similar to wild-type CA/04 virus with respect to lethargy, weight loss and replication efficiency in the upper and lower respiratory tract. Moreover, based on viral detection, the respiratory droplet transmission properties of these two viruses were found to be similar. The D222G virus failed to productively infect mice inoculated by the ocular route, but exhibited greater viral replication and weight loss than wild-type CA/04 virus in mice inoculated by the intranasal route. In a more relevant human cell model, D222G virus replicated with delayed kinetics compared with wild-type virus but to higher titer in human bronchial epithelial cells. These findings suggest that although the D222G mutation does not influence virus transmission, it may be considered a molecular marker for enhanced replication in certain cell types.Centers for Disease Control and Prevention (U.S.)United States. National Institutes of Health (merit award R37 GM057073-13)Singapore-MIT Alliance for Research and Technolog

    Rebooting an Old Script by New Means: Teledildonics—The Technological Return to the ‘Coital Imperative’

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    Teledildonics, a form of digital-mediated sexual interaction, opens new possibilities for the understanding of sexual activity. At first glance, it disrupts conventional preconditions and assumptions about sexual interaction, by allowing the dimension of touch despite the physical distance between partners and, ultimately, promoting a sexual dimension definitely disconnected from the reproductive model of sexuality. However, by scrutinizing the design and functionality of the devices, as well as the discourses presented by three commercial companies—LovePalz, Lovense and Kiiroo—I suggest that this technology reinforces the ‘coital imperative’, by equating sexual interaction with penetration of the vagina by the penis. Although permitting other formulations, specifically for non-heterosexual couples, the penetrative act remains a presupposition. In spite of structurally disrupting the reproductive model of sex, teledildonics promotes its strongest corollary.info:eu-repo/semantics/publishedVersio
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