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

Multiple solutions for asteroid orbits: Computational procedure and applications

We describe the Multiple Solutions Method, a one-dimensional sampling of the six-dimensional orbital confidence region that is widely applicable in the field of asteroid orbit determination. In many situations there is one predominant direction of uncertainty in an orbit determination or orbital prediction, i.e., a ``weak'' direction. The idea is to record Multiple Solutions by following this, typically curved, weak direction, or Line Of Variations (LOV). In this paper we describe the method and give new insights into the mathematics behind this tool. We pay particular attention to the problem of how to ensure that the coordinate systems are properly scaled so that the weak direction really reflects the intrinsic direction of greatest uncertainty. We also describe how the multiple solutions can be used even in the absence of a nominal orbit solution, which substantially broadens the realm of applications. There are numerous applications for multiple solutions; we discuss a few problems in asteroid orbit determination and prediction where we have had good success with the method. In particular, we show that multiple solutions can be used effectively for potential impact monitoring, preliminary orbit determination, asteroid identification, and for the recovery of lost asteroids

Immunolocalization of estrogen receptor beta in the epididymis of mature and immature pigs.

A growing body of evidence suggests a role of estrogens in the male reproduction via their specific estrogen receptors (ERalpha/ERbeta). Estrogen receptor distribution along the genital tract tissues has been described in different species, but it is unknown in the pig. Therefore, the aim of the present study was to localize ERbeta in the epididymis of mature and immature pigs (aged 2 and 18 months, respectively). Immunohistochemistry was carried out on paraffin-embedded tissues using a mouse anti-human monoclonal IgG against ERbeta as the primary antibody, and a goat anti-mouse biotinylated IgG as the secondary antibody. Avidin-biotin-peroxidase complex was then applied followed by diaminobenzidine. In immature pigs, the epithelial cells from the caput, corpus and cauda epididymis showed no or very weak immunoreactivity for ERbeta, whereas they were all strongly immmunoreactive in mature pigs. A various intensity of immunostaining from weak to strong in the smooth muscle cells as well as in the connective tissue cells were detected in the epididymis of both, young and adult pigs. This is the first report on the cellular localization of ERbeta protein in porcine epidydimis. The present study demonstrated that (1) irrespectively of the epididymal region, the epithelial cells of caput, corpus and cauda epididymis of mature pigs revealed a strong immunoreactivity for ERbeta, and (2) ERbeta expression in the epididymal epithelium is regulated by puberty. Finally, although the biological activity of ERbeta has not yet been established, the results of the present study suggest its involvement in estrogen modulation of pig epididymal function

Anatomical, histomorphological and molecular classification of cholangiocarcinoma

Cholangiocarcinoma constitutes a heterogeneous group of malignancies that can emerge at any point of the biliary tree. Cholangiocarcinoma is classified into intrahepatic, perihilar and distal based on its anatomical location. Histologically, conventional perihilar/distal cholangiocarcinomas are mucin-producing adenocarcinomas or papillary tumours; intrahepatic cholangiocarcinomas are more heterogeneous and can be sub-classified according to the level or size of the displayed bile duct. Cholangiocarcinoma develops through multistep carcinogenesis and is preceded by dysplastic and in situ lesions. Definition and clinical significance of precursor lesions, including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm, are discussed in this review. A main challenge in diagnosing cholangiocarcinoma is the fact that tumour tissue for histological examination is difficult to obtain. Thus, a major clinical obstacle is the establishment of the correct diagnosis at a tumour stage that is amenable to surgery which still represents the only curable therapeutic option. Current standards, methodology and criteria for diagnosis are discussed. Cholangiocarcinoma represents a heterogeneous tumour with regard to molecular alterations. In intrahepatic subtype, mainly two distinctive morpho-molecular groups can currently be discriminated. Large-duct type intrahepatic cholangiocarcinoma shows a high mutation frequency of oncogenes and tumour suppressor genes, such as KRAS and TP53 while Isocitrate Dehydrogenase 1/2 mutations and Fibroblast Growth Factor Receptor 2-fusions are typically seen in small-duct type tumours. It is most important to ensure the separation of the given anatomical subtypes and to search for distinct subgroups within the subtypes on a molecular and morphological basis

Composition of Ragusano Cheese During Aging

Ragusano cheese is a brine-salted pasta filata cheese. Composition changes during 12 mo of aging were determined. Historically, Ragusano cheese has been aged in caves at 14 to 16 degrees C with about 80 to 90% relative humidity. Cheeses (n = 132) included in our study of block-to-block variation were produced by 20 farmhouse cheese makers in the Hyblean plain region of the Province of Ragusa in Sicily. Mean initial cheese block weight was about 14 kg. The freshly formed blocks of cheese before brine salting contained about 45.35% moisture, 25.3% protein, and 25.4% fat, with a pH of 5.25. As result of the brining and aging process, a natural rind forms. After 12 mo of aging, the cheese contained about 33.6% moisture, 29.2% protein, 30.0% fat, and 4.4% salt with a pH of 5.54, but block-to-block variation was large. Both soluble nitrogen content and free fatty acid (FFA) content increased with age. The pH 4.6 acetate buffer and 12% TCA-soluble nitrogen as a percentage of total nitrogen were 16 and 10.7%, respectively, whereas the FFA content was about 643 mg/100 g of cheese at 180 d. Five blocks of cheese were selected at 180 d for a study of variation within block. Composition variation within block was large; the center had higher moisture and lower salt in moisture content than did the outside. Composition variation within blocks favored more proteolysis and softer texture in the center

H3 histamine receptor-mediated activation of protein kinase calpha inhibits the growth of cholangiocarcinoma in vitro and in vivo

Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The D-myo-inositol 1,4,5-trisphosphate (IP(3))/Ca(2+)/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(alpha)-(-)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP(3) and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKC alpha was visualized by immunofluorescence in cell smears and immunoblotting for PKC alpha in cytosol and membrane fractions. Following knockdown of PKC alpha, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKC alpha, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP(3) levels and PKC alpha phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKC alpha expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKC alpha prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKC alpha expression was increased. RAMH inhibits cholangiocarcinoma growth by PKC alpha-dependent ERK1/2 dephosphorylation. Modulation of PKC alpha by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res 2009;7(10):1704-13

Peribiliary glands as a niche of extra-pancreatic precursors yielding insulin-producing cells in experimental and human diabetes

Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, towards pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) towards insulin-producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N=12) or 120 mg/kg (N=12) of streptozotocin. Liver, pancreas and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepato-pancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with up-regulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepato-pancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures towards pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the patho-physiology and complications of this disease. This article is protected by copyright. All rights reserved

Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells-newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies