Life extending control for rocket engines

The concept of life extending control is defined. A brief discussion of current fatigue life prediction methods is given and the need for an alternative life prediction model based on a continuous functional relationship is established. Two approaches to life extending control are considered: (1) the implicit approach which uses cyclic fatigue life prediction as a basis for control design; and (2) the continuous life prediction approach which requires a continuous damage law. Progress on an initial formulation of a continuous (in time) fatigue model is presented. Finally, nonlinear programming is used to develop initial results for life extension for a simplified rocket engine (model)

Impiego di batteri lattici autoctoni per il miglioramento igienico-sanitario del Pecorino Siciliano DOP

Il Pecorino Siciliano DOP \ue8 considerato il pi\uf9 antico formaggio prodotto in Sicilia e, probabilmente, d\u2019Europa. Le citazioni storiche sulla sua antica origine risalgono al IX secolo a.C. in uno dei passi pi\uf9 famosi dell\u2019odissea di Omero, quando Ulisse incontra Polifemo. In seguito, anche Aristotele e Plinio esaltano il gusto unico di questo formaggio. In particolare, proprio Plinio, nella sua opera \u201cNaturalis Historia\u201d, redige una carta dei formaggi nella quale vengono citati, tra i migliori pecorini,quelli provenienti da Agrigento. Fra le caratteristiche peculiari del Pecorino Siciliano DOP vanno annoverati il sapore leggermente piccante e l\u2019incantevole profumo di pascolo. Il Pecorino Siciliano DOP \ue8 un formaggio a pasta dura, semicotto, prodotto con latte intero crudo di pecora. L\u2019areale di produzione si estende su tutta la regione Sicilia. La forma \ue8 cilindrica a facce piane o lievemente concave, pesa dai 4 ai 12 kg, lo scalzo \ue8 di 10-18 cm. La crosta \ue8 bianca-giallognola,con la superficie rugosa per la modellatura lasciata dal canestro in giunco dove avviene la formatura, spesso viene cappata con olio. La pasta \ue8 compatta, di colore bianco o giallo paglierino, con occhiatura scarsa. Il sapore \ue8 piccante e caratteristico, l\u2019aroma \ue8 intenso. La stagionatura minima prevista dal disciplinare \ue8 di 4 mesi. Il Pecorino Siciliano ha acquisito la certificazione DO nel 1955 e la DOP nel 1996 con regolamento CE n. 1107/96 della Commissione del 12 giugno 1996 (Gazzetta Ufficiale Comunit\ue0 Europea L 148 del 21/6/1996). Attualmente, le attivit\ue0 di promozione, valorizzazione e vigilanza sono affidate al Consorzio di tutela del Pecorino Siciliano DOP, che \ue8 stato riconosciuto dal ministero delle Politiche agricole, alimentari e forestali (Mi- Paaf) dal 2005 a oggi. L\u2019elevata eterogeneit\ue0 del prodotto osservata nelle forme presenti sul mercato \ue8 dovuta sia ai metodi di produzione artigianali sia al vecchissimo disciplinare di produzione, risalente al 1956. Ci\uf2 ha indotto il consorzio di tutela a intraprendere una proficua collaborazione tecnico-scientifica con l\u2019Universit\ue0 degli Studi di Palermo prima e l\u2019Istituto Zooprofilattico Sperimentale della Sicilia, il Corfilac e l\u2019Universit\ue0 di Catania successivamente, con l\u2019obiettivo di migliorare la qualit\ue0 igienico-sanitaria del formaggio Pecorino Siciliano DOP e ridurre l\u2019eccessiva variabilit\ue0 qualitativa fra le forme ottenute da differenti caseificazioni

Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

The bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells

Mapping the ν⊙\nu_\odot Secular Resonance for Retrograde Irregular Satellites

Constructing dynamical maps from the filtered output of numerical integrations, we analyze the structure of the $\nu_\odot$ secular resonance for fictitious irregular satellites in retrograde orbits. This commensurability is associated to the secular angle $\theta = \varpi - \varpi_\odot$, where $\varpi$ is the longitude of pericenter of the satellite and $\varpi_\odot$ corresponds to the (fixed) planetocentric orbit of the Sun. Our study is performed in the restricted three-body problem, where the satellites are considered as massless particles around a massive planet and perturbed by the Sun. Depending on the initial conditions, the resonance presents a diversity of possible resonant modes, including librations of $\theta$ around zero (as found for Sinope and Pasiphae) or 180 degrees, as well as asymmetric librations (e.g. Narvi). Symmetric modes are present in all giant planets, although each regime appears restricted to certain values of the satellite inclination. Asymmetric solutions, on the other hand, seem absent around Neptune due to its almost circular heliocentric orbit. Simulating the effects of a smooth orbital migration on the satellite, we find that the resonance lock is preserved as long as the induced change in semimajor axis is much slower compared to the period of the resonant angle (adiabatic limit). However, the librational mode may vary during the process, switching between symmetric and asymmetric oscillations. Finally, we present a simple scaling transformation that allows to estimate the resonant structure around any giant planet from the results calculated around a single primary mass.Comment: 11 pages, 13 figure

Selected lactic acid bacteria as a hurdle to the microbial spoilage of cheese: application on a traditional raw ewes’ milk cheese.

To evaluate the efficacy of lactic acid bacteria (LAB) to improve the hygienic safety of a traditional raw milk cheese, the raw ewes’ milk protected denomination of origin (PDO) Pecorino Siciliano cheese was used as a model system. Different Pecorino Siciliano curds and cheeses were used as sources of autochthonous LAB subsequently used as starter and non-starter LAB. These were screened for their acidification capacity and autolysis. Starter LAB showing the best performance were genotypically differentiated and identified: two strains of Lactococcus lactis subsp. lactis were selected. From the nonstarter LAB, Enterococcus faecalis, Lactococcus garvieae and Streptococcus macedonicus strains were selected. The five cultures were used in individual or dual inocula to produce experimental cheeses in a dairy factory for which production was characterised by high numbers of undesirable bacteria. At 5- month of ripening, the experimental cheeses produced with LAB were characterised by undetectable levels of enterobacteria and pseudomonads and the typical sensory attributes

Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms

Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1-H4HRs. H1HR acts by Gαq activating IP(3)/Ca(2+), whereas H2HR activates Gα(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCα and protein kinase A (PKA) phosphorylation; and (3) PKCα silencing on H1HR-stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCα phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCα siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts

A large factory-scale application of selected autochthonous lactic acid bacteria for PDO Pecorino Siciliano cheese production

The main hypothesis of this study was that the autochthonous lactic acid bacteria (LAB) selected for their dairy traits are able to stabilize the production of PDO (Protected Denomination of Origin) Pecorino Siciliano cheese, preserving its typicality. The experimental plan included the application of a multistrain lactic acid bacteria (LAB) culture, composed of starter (Lactococcus lactis subsp. lactis CAG4 and CAG37) and non starter (Enterococcus faecalis PSL71, Lactococcus garviae PSL67 and Streptococcus macedonicus PSL72) strains, during the traditional production of cheese at large scale level in six factories located in different areas of Sicily. The cheese making processes were followed from milk to ripened cheeses and the effects of the added LAB were evaluated on the microbiological, chemico-physical and sensorial characteristics of the final products. Results highlighted a high variability for all investigated parameters and the dominance of LAB cocci in bulk milk samples. The experimental curds showed a faster pH drop than control curds and the levels of LAB estimated in 5-month ripened experimental cheeses (7.59 and 7.27 Log CFU/g for rods and cocci, respectively) were higher than those of control cheeses (7.02 and 6.61 Log CFU/g for rods and cocci, respectively). The comparison of the bacterial isolates by randomly amplified polymorphic DNA (RAPD)-PCR evidenced the dominance of the added starter lactococci over native milk and vat LAB, while the added non starter LAB were found at almost the same levels of the indigenous strains. The sensory evaluation showed that the mixed LAB culture did not influence the majority of the sensory attributes of the cheeses and that each factory produced cheeses with unique characteristics. Finally, the multivariate statistical analysis based on all parameters evaluated on the ripened cheeses showed the dissimilarities and the relationships among cheeses. Thus, the main hypothesis of the work was accepted since the quality parameters of the final cheeses were stabilized, but all cheeses maintained their local typicality

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0–2.5 μM) of OCA were added to culture media and, after 3–10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 μM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients

Secular dynamics of planetesimals in tight binary systems: Application to Gamma-Cephei

The secular dynamics of small planetesimals in tight binary systems play a fundamental role in establishing the possibility of accretional collisions in such extreme cases. The most important secular parameters are the forced eccentricity and secular frequency, which depend on the initial conditions of the particles, as well as on the mass and orbital parameters of the secondary star. We construct a second-order theory (with respect to the masses) for the planar secular motion of small planetasimals and deduce new expressions for the forced eccentricity and secular frequency. We also reanalyze the radial velocity data available for Gamma-Cephei and present a series of orbital solutions leading to residuals compatible with the best fits. Finally, we discuss how different orbital configurations for Gamma-Cephei may affect the dynamics of small bodies in circunmstellar motion. For Gamma-Cephei, we find that the classical first-order expressions for the secular frequency and forced eccentricity lead to large inaccuracies around 50 % for semimajor axes larger than one tenth the orbital separation between the stellar components. Low eccentricities and/or masses reduce the importance of the second-order terms. The dynamics of small planetesimals only show a weak dependence with the orbital fits of the stellar components, and the same result is found including the effects of a nonlinear gas drag. Thus, the possibility of planetary formation in this binary system largely appears insensitive to the orbital fits adopted for the stellar components, and any future alterations in the system parameters (due to new observations) should not change this picture. Finally, we show that planetesimals migrating because of gas drag may be trapped in mean-motion resonances with the binary, even though the migration is divergent.Comment: 11 pages, 9 figure