133 research outputs found
STUDIO DEL TRATTAMENTO TERMICO DI ACCIAI RAPIDI PER CILINDRI DI LAMINAZIONE A CALDO
In questo lavoro si propone lo studio del trattamento di tempra e rinvenimento di due acciai rapidi prodotti per colata centrifuga. La microstruttura dei materiali allo stato grezzo di colata è data da un reticolo più o meno interconnesso di carburi primari, in percentuale prossima al 10% in volume e da una matrice costituita da martensite e bainite. Le curve CCT evidenziano per entrambi un naso bainitico al di sotto dei 400°C per velocità di raffreddamento inferiori a 10°Cs-1. Gli acciai sono stati trattati termicamente secondo il processo impiegato a livello industriale. L’influenza della temperatura di austenitizzazione è stata valutata aumentando tale parametro da 1030 fino a 1200°C. Le relative curve di rinvenimento evidenziano un aumento sia della temperatura che della durezza di picco secondaria, differente nei due materiali considerati, indicando un effetto benefico sulla resistenza a caldo e la necessità di un rinvenimento a temperatura superiore per eliminare completamente l’austenite residua. In prossimità della temperatura più elevata (1200°C) si assiste alla rifusione di eutettici, individuando così in questo valore di temperatura un limite processuale invalicabile. Anche il tempo di austenitizzazione mostra un effetto sulla durezza dopo tempra correlabile alla differente propensione dei due materiali alla risolubilizzazione dei carburi
Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial
Background: Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC. Patients and methods: Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m2 day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m2 d1) and capecitabine (650-800 mg/m2 b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria. Results: Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m2 d1, d8; oxaliplatin 130 mg/m2 d1 and capecitabine 650 mg/m2 b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients. Conclusion: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigation
PROP1 overexpression in corticotrophinomas: evidence for the role of PROP1 in the maintenance of cells committed to corticotrophic differentiation
OBJECTIVE: The expression of transcription factors involved in early pituitary development, such as PROP1 and POU1F1, has been detected in pituitary adenoma tissues. In this study, we sought to characterize the transcriptional profiles of PROP1, POU1F1, and TBX19 in functioning and nonfunctioning pituitary adenomas in an attempt to identify their roles in tumorigenesis and hormone hypersecretion. METHODS: RT-qPCR analyses were performed to assess the transcriptional pattern of PROP1, POU1F1, TBX19, and hormone-producing genes in tissue samples of corticotrophinomas (n = 10), somatotrophinomas (n = 8), and nonfunctioning adenomas (n = 6). RESULTS: Compared with normal pituitary tissue, POU1F1 was overexpressed in somatotrophinomas by 3-fold. PROP1 expression was 18-fold higher in corticotrophinomas, 10-fold higher in somatotrophinomas, and 3-fold higher in nonfunctioning adenomas. TBX19 expression was 27-fold higher in corticotrophinomas. Additionally, the level of TBX19 mRNA positively correlated with that of pro-opiomelanocortin (r = 0.49, p = 0.014). CONCLUSIONS: Our data demonstrate that PROP1 is overexpressed in pituitary adenomas, mainly in corticotrophinomas. Together with previously published data showing that patients who harbor PROP1 loss-of-function mutations present a progressive decline in corticotrope function, our results support a role for PROP1 in pituitary tumor development and in the maintenance of cell lineages committed to corticotrophic differentiation
Application of the density dependent hadron field theory to neutron star matter
The density dependent hadron field (DDRH) theory, previously applied to
isospin nuclei and hypernuclei is used to describe -stable matter and
neutron stars under consideration of the complete baryon octet. The
meson-hyperon vertices are derived from Dirac-Brueckner calculations of nuclear
matter and extended to hyperons. We examine properties of density dependent
interactions derived from the Bonn A and from the Groningen NN potential as
well as phenomenological interactions. The consistent treatment of the density
dependence introduces rearrangement terms in the expression for the baryon
chemical potential. This leads to a more complex condition for the
-equilibrium compared to standard relativistic mean field (RMF)
approaches. We find a strong dependence of the equation of state and the
particle distribution on the choice of the vertex density dependence. Results
for neutron star masses and radii are presented. We find a good agreement with
other models for the maximum mass. Radii are smaller compared to RMF models and
indicate a closer agreement with results of non-relativistic Brueckner
calculations.Comment: 28 pages, 11 figure
Density dependent hadron field theory for neutron stars with antikaon condensates
We investigate and condensation in -equilibrated
hyperonic matter within a density dependent hadron field theoretical model. In
this model, baryon-baryon and (anti)kaon-baryon interactions are mediated by
the exchange of mesons. Density dependent meson-baryon coupling constants are
obtained from microscopic Dirac Brueckner calculations using Groningen and Bonn
A nucleon-nucleon potential. It is found that the threshold of antikaon
condensation is not only sensitive to the equation of state but also to
antikaon optical potential depth. Only for large values of antikaon optical
potential depth, condensation sets in even in the presence of negatively
charged hyperons. The threshold of condensation is always reached
after condensation. Antikaon condensation makes the equation of state
softer thus resulting in smaller maximum mass stars compared with the case
without any condensate.Comment: 20 pages, 7 figures; final version to appear in Physical Review
A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues
Purpose: Prostate-specific antigen (PSA)-based screening for prostate cancer (PC) has dramatically increased early diagnosis. Current imaging techniques are not optimal to stage early PC adequately. A promising alternative to PC imaging is peptide-based scintigraphy using radiolabelled bombesin (BN) analogues that bind to gastrin-releasing peptide receptors (GRPR) being overexpressed in PC. When labelled to appropriate radionuclides BN targeting of GRPRs may also provide applications for peptide radionuclide receptor therapy (PRRT). Assessment studies under identical experimental conditions allowing a reliable comparison of the potential of such analogues are lacking. This study was performed to evaluate and directly compare five promising radiolabelled BN analogues for their targeting efficacy for PC under standardised conditions. Methods: The BN agonists [111In]DOTA-PESIN, [111In]AMBA, [111In]MP2346 and [111In]MP2653 and one antagonist [99mTc]Demobesin-1 were evaluated in GRPR-overexpressing human PC-3 tumou
Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts
Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the68Ga-labelled bombesin analogue AMBA with metabolism-based tar
Illuminating the life of GPCRs
The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented
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