On the strict topology in non-archimedean spaces of continuous functions

The strict topology, on the space C(X,E) of all continuous functions on a toplogical space X with values in a non-Archimedean locally convex space E, is introduced and several of its properties are investigated. The dual spaces of C(X,E), under the strict topology and under the bounding convergence topology, turn out to be certain spaces of E\u27-valued measures

Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes

AbstractInteractions of the hydrophobic anticancer drug tamoxifen (TAM) with lipid model membranes were studied using calcein-encapsulated vesicle leakage, attenuated total reflection Fourier transform infrared (FTIR) spectroscopy, small-angle neutron scattering (SANS), atomic force microscopy (AFM) based force spectroscopy, and all-atom molecular dynamics (MD) simulations. The addition of TAM enhances membrane permeability, inducing calcein to translocate from the interior to the exterior of lipid vesicles. A large decrease in the FTIR absorption band’s magnitude was observed in the hydrocarbon chain region, suggesting suppressed bond vibrational dynamics. Bilayer thickening was determined from SANS data. Force spectroscopy measurements indicate that the lipid bilayer area compressibility modulus KA is increased by a large amount after the incorporation of TAM. MD simulations show that TAM decreases the lipid area and increases chain order parameters. Moreover, orientational and positional analyses show that TAM exhibits a highly dynamic conformation within the lipid bilayer. Our detailed experimental and computational studies of TAM interacting with model lipid membranes shed new light on membrane modulation by TAM

Discontinuous unbinding of lipid multibilayers

We have observed a discontinuous unbinding transition of lipid bilayer stacks composed of phosphatidylethanolamine and phosphatidylglycerol using X-ray diffraction. The unbinding is reversible and coincides with the main (Lβ→Lα) transition of the lipid mixture. Interbilayer interaction potentials deduced from the diffraction data reveal that the bilayers in the Lβ phase are only weakly bound. The unbinding transition appears to be driven by an abrupt increase in steric repulsion resulting from increased thermal undulations of the bilayers upon entering the fluid Lαphase

Influence of ceramide on lipid domain stability studied with small-angle neutron scattering: The role of acyl chain length and unsaturation

Ceramides and diacylglycerols are groups of lipids capable of nucleating and stabilizing ordered lipid domains, structures that have been implicated in a range of biological processes. Previous studies have used fluorescence reporter molecules to explore the influence of ceramide acyl chain structure on sphingolipid-rich ordered phases. Here, we use small-angle neutron scattering (SANS) to examine the ability of ceramides and diacylglycerols to promote lipid domain formation in the well-characterized domain- forming mixture DPPC/DOPC/cholesterol. SANS is a powerful, probe-free technique for interrogating membrane heterogeneity, as it is differentially sensitive to hydrogen\u27s stable isotopes protium and deuterium. Specifcally, neutron contrast is generated through selective deuteration of lipid species, thus enabling the detection of nanoscopic domains enriched in deuterated saturated lipids dispersed in a matrix of protiated un- saturated lipids. Using large unilamellar vesicles, we found that upon replacing 10 mol % DPPC with either C16:0 or C18:0 ceramide, or 16:0 diacylglycerol (dag), lipid domains persisted to higher temperatures. However, when DPPC was replaced with short chain (C6:0 or C12:0) or very long chain (C24:0) ceramides, or ceramides with unsaturated acyl chains of any length (C6:1(3), C6:1(5), C18:1, and C24:1), as well as C18:1-dag, lipid domains were destabilized, melting at lower temperatures than those in the DPPC/DOPC/cholesterol system. These results show how ceramide acyl chain length and unsaturation influence lipid domains, and have implications for how cell membranes might modify their function through the generation of different ceramide species

Problems associated with direct displacement-based design of concrete bridges with single-column piers, and some suggested improvements

Currently available displacement-based design (DBD) procedures for bridges are critically evaluated with a view to identifying extensions and/or modifications of the procedure, for it to be applicable to final design of a fairly broad class of bridges. An improved direct DBD procedure is presented, including a suite of comprehensive design criteria and proper consideration of the degree of fixity of the pier top. The design of an overpass bridge (originally designed to a current European Code), applying the improved ‘direct’ displacement-based design (DDBD) procedure is presented and both ‘conventional’ and displacement-based designs are assessed using non-linear response-history analysis (NLRHA); comparisons are made in terms of both economy and seismic performance of the different designs. It is seen that DDBD provided a more rational base shear distribution among piers and abutments when compared to the force-based design procedure and adequately captured the displacement pattern, closely matching the results of the more rigorous NLRHA

Bovine Spongiform Encephalopathy and Public Health

Η σπογγιόμορφη εγκεφαλοπάθεια των βοοειδών είναι μεταδοτική εκφυλιστική νόσος του κεντρικού νευρικού συστήματος και ανήκει σε ομάδα  ασθενειών, οι οποίες προσβάλλουν τον άνθρωπο και διάφορα είδη ζώων και έχουν παρόμοια ιστοπαθολογική εικόνα. Ο βλαπτικός παράγοντας της BSE, αλλά και όλων των άλλων σπογγιόμορφων εγκεφαλοπαθειών, δεν έχει πλήρως διευκρινιστεί. Η επικρατέστερη σήμερα άποψη είναι ότι αυτός αποτελείται κυρίως ή και μόνον από μη φυσιολογική πρωτεΐνη, που ονομάστηκε prion. Στις διάφορες παρατηρήσεις ο βλαπτικός παράγοντας γίνεται αντιληπτός με τη μορφή πρωτεϊνικών κυλίνδρων, οι οποίοι αποτελούνται από συγκεντρώσεις ή πολυμερισμένη μορφή του βλαπτικού παράγοντα και ονομάστηκε πρωτεΐνη prion (prion protein - PrP). Αποδείχθηκε ότι υπάρχουν δυο ισόμορφες της PrP. Η μία που σημειώνεται ως PrF παράγεται από αρκετά κύτταρα του ανθρώπου και των ζώων και αποτελεί κυτταρικό δομικό στοιχείο. Η δεύτερη που σημειώνεται ως PrPst παρουσιάζει ιδιαίτερες ιδιότητες, που την καθιστούν παθολογική και υπεύθυνη για τη δημιουργία των σπογγιόμορφων εγκεφαλοπαθειών. Ο αναδιπλασιασμός της PrPM φαίνεται ότι διενεργείται στα λυσοσώματα κυττάρων του νευρικού συστήματος και των δενδριτικών, καθώς και λοιπών κυττάρων του δικτυωτού των λεμφοκυτογόνων οργάνων με μετατροπή της PrPc σε PrPsc. Όπως φαίνεται η BSE προκλήθηκε στα βοοειδή εξαιτίας της κατανάλωσης από αυτά κρεαταλεύρων και οστεαλεύρων, που προέρχονταν από πρόβατα μολυσμένα από τη scrapie. Αναφορικά με την παθογένεια φαίνεται από πειραματικά δεδομένα ότι αρχικά η PrPsr εισέρχεται με την τροφή και εγκαθίσταται στα διάφορα λεμφοκυτογόνα όργανα όπου και γίνεται ο πρώτος αναδιπλασιασμός της. Πιστεύεται ότι, από τα λεμφοκυτογόνα όργανα, μεταφέρεται με τα νεύρα στο κεντρικό νευρικό σύστημα, όπου και δημιουργεί τις χαρακτηριστικές αλλοιώσεις της κενοτοπιώδους εκφύλισης των νευρικών κυττάρων και τη σπογγίωση, οπότε και εμφανίζεται κλινικά η νόσος. Τα νευρικά συμπτώματα χαρακτηρίζονται κυρίως από αλλαγή στη συμπεριφορά των ζώων και από κινητικές ανωμαλίες. Η διάγνωση της νόσου γίνεται με την παρατήρηση των ιστοπαθολογικών αλλοιώσεων, την ανίχνευση ινιδίων συνδεμένων με τη scrapie-SAF και την ανοσοϊστοχημική ανίχνευση των μορίων της PrPsc σε ιστολογικές τομές ή με ηλεκτροφόρηση (Western blotting test). Η BSE αποδείχθηκε ότι μπορεί να μεταδοθεί σε άλλα ζώα και υπάρχει η πιθανότητα να μεταδίδεται και στον άνθρωπο με την τροφική αλυσίδα. Ύστερα από αυτά και σ' όλο το διάστημα που διέρρευσε, απότην εμφάνιση της μέχρι σήμερα, λήφθηκαν μέτρα, τόσο από τη Μ. Βρεττανία, όσο και από την ΕΕ για την εκρίζωση της νόσου και την προστασία της δημόσιας υγείας. Τα μέτρα αυτά θα πρέπει να τηρούνται από τις επίσημες αρχές και επιπρόσθετα θα πρέπει να ενημερωθεί ο καταναλωτής για την πιθανή επικινδυνότητα των διαφόρων ζωικών προϊόντων.Bovine Spongiform Encephalopathy (BSE) is a transmissible degenerative disease of the central nervous system. It belongs to a group of diseases which affect man and various kinds of animals and they have a similar histopathological appearance. The harmful agent of BSE and all the others spongiform encephalopathies have not been totally clarified. Today according to the predominant opinion this agent is consisted mainly or/and only of an abnormal protein, which is called prion. In various observations the harmful agent appears like proteinaceous cylinders which are consisted of aggregations or polymerized forms of the agent and it is called prion-protein (PrP). It has been proved that there are two isoforms of PrP. The first of them, called PrPc, is produced from many cells of man and animals and consists a cellular structural element. The second, called PrPs t, due to its specific properties, it is considered to be pathological and responsible for the spongiform encephalopathies. The replication of PrPsc seems to take place in the lysosomes of central nervous system cells, dendritic, and other reticular cells of the lymphatic organs through transformation of PrPc into PrPsc. It appears BSE caused by feeding meat and bone meals to cattle which were originated from scrapie infected sheep. Refering to the pathogenesis originating from experimental data it seems that initially the PrF* enters the body by food and afterwards is settled in various lymphoid organs where the first replication takes place. It is believed that BSE is transmitted through the nerves to the CNS, where it creates the characteristic lesions of vacuolar degeneration of the neurons and finally the spongiosis. Then the clinical signs are expressed. The nervous signs characterised by behavioural alterations of the animals and kinetic abnormalities. The diagnosis of the disease is made by the observation of the histopathological lesions, the detection of Scrapie Associated Fibrils-SAF by EM, the immunohistochemical detection of prpsc i n histological samples or by electrophoresis (Western blotting test). BSE was proved to be transmissible to other animals and there is a possibility that it could be done to man through the food chain. According to the above in these years, from the appearance of the disease until now, have been taken bans from Great Britain as well as from E.U. for the eradication of the disease and the protection of the public health. These instructions should be followed by the authorities and additionally the consumers ought to be informed for the possible danger of various animal products

Interaction of Aspirin (Acetylsalicylic Acid) with Lipid Membranes

We studied the interaction of Aspirin (acetylsalicylic acid) with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core

Interaction between a cationic surfactant-like peptide and lipid vesicles and its relationship to antimicrobial activity

We investigate the properties of an antimicrobial surfactant-like peptide (Ala)6(Arg), A6R, containing a cationic headgroup. The interaction of this peptide with zwitterionic (DPPC) lipid vesicles is investigated using a range of microscopic, X-ray scattering, spectroscopic, and calorimetric methods. The β-sheet structure adopted by A6R is disrupted in the presence of DPPC. A strong effect on the small-angle X-ray scattering profile is observed: the Bragg peaks from the DPPC bilayers in the vesicle walls are eliminated in the presence of A6R and only bilayer form factor peaks are observed. All of these observations point to the interaction of A6R with DPPC bilayers. These studies provide insight into interactions between a model cationic peptide and vesicles, relevant to understanding the action of antimicrobial peptides on lipid membranes. Notably, peptide A6R exhibits antimicrobial activity without membrane lysis