Las terrazas del río Sil en el tramo Carucedo-Os Peares, SE de Galicia

[ES] Se describen los sistemas de terrazas del Río Sil desde el Bierzo hasta la confluencia con el Miño. En este tramo el río se encaja profundamente sobre las principales superficies de erosión del SE gallego (R400, R600, R800, RlOOO y R1200). Junto a los niveles de terraza con depósitos se observa la presencia de superficies terraza y aplanamientos de mayor extensión, siempre asociados al encajamiento fluvial. Se analiza la morfometría y los perfiles longitudinales de la red; así como la distribución de las terrazas y aplanamientos incluidos en el encajamiento. Se reconocen algunos cambios en la evolución de la red simultáneos a la sedimentación de las fosas terciarias (Monforte de Lemos, Quiroga, A Rúa-O Barco). La antigüedad de la red y un descenso generalizado en el nivel de base del Sistema Miño-Sil, podría justificar estos acontecimientos. Sin embargo, existen indicios de cierto control tectónico. Por último se propone un modelo evolutivo del tramo estudiado, para la etapa posterior a la formación del aplanamiento RlOOO.

Unraveling efficiency-limiting processes in organic solar cells by ultrafast spectroscopy - impact of chemical structure and morphology on photophysics and efficiency

Diese Arbeit widmet sich der Untersuchung der photophysikalischen Prozesse, die in Mischungen von Elektronendonoren mit Elektronenakzeptoren zur Anwendung in organischen Solarzellen auftreten. Als Elektronendonoren werden das Copolymer PBDTTT-C, das aus Benzodithiophen- und Thienothiophene-Einheiten besteht, und das kleine Molekül p-DTS(FBTTh2)2, welches Silizium-überbrücktes Dithiophen, sowie fluoriertes Benzothiadiazol und Dithiophen beinhaltet, verwendet. Als Elektronenakzeptor finden ein planares 3,4:9,10-Perylentetracarbonsäurediimid-(PDI)-Derivat und verschiedene Fullerenderivate Anwendung. PDI-Derivate gelten als vielversprechende Alternativen zu Fullerenen aufgrund der durch chemische Synthese abstimmbaren strukturellen, optischen und elektronischen Eigenschaften. Das gewichtigste Argument für PDI-Derivate ist deren Absorption im sichtbaren Bereich des Sonnenspektrums was den Photostrom verbessern kann. Fulleren-basierte Mischungen übertreffen jedoch für gewöhnlich die Effizienz von Donor-PDI-Mischungen.rnUm den Nachteil der PDI-basierten Mischungen im Vergleich zu den entsprechenden Fulleren-basierten Mischungen zu identifizieren, werden die verschiedenen Donor-Akzeptor-Kombinationen auf ihre optischen, elektronischen und strukturellen Eigenschaften untersucht. Zeitaufgelöste Spektroskopie, vor allem transiente Absorptionsspektroskopie (TA), wird zur Analyse der Ladungsgeneration angewendet und der Vergleich der Donor-PDI Mischfilme mit den Donor-Fulleren Mischfilmen zeigt, dass die Bildung von Ladungstransferzuständen einen der Hauptverlustkanäle darstellt.rnWeiterhin werden Mischungen aus PBDTTT-C und [6,6]-Phenyl-C61-buttersäuremethylesther (PC61BM) mittels TA-Spektroskopie auf einer Zeitskala von ps bis µs untersucht und es kann gezeigt werden, dass der Triplettzustand des Polymers über die nicht-geminale Rekombination freier Ladungen auf einer sub-ns Zeitskala bevölkert wird. Hochentwickelte Methoden zur Datenanalyse, wie multivariate curve resolution (MCR), werden angewendet um überlagernde Datensignale zu trennen. Zusätzlich kann die Regeneration von Ladungsträgern durch Triplett-Triplett-Annihilation auf einer ns-µs Zeitskala gezeigt werden. Darüber hinaus wird der Einfluss des Lösungsmitteladditivs 1,8-Diiodooctan (DIO) auf die Leistungsfähigkeit von p-DTS(FBTTh2)2:PDI Solarzellen untersucht. Die Erkenntnisse von morphologischen und photophysikalischen Experimenten werden kombiniert, um die strukturellen Eigenschaften und die Photophysik mit den relevanten Kenngrößen des Bauteils in Verbindung zu setzen. Zeitaufgelöste Photolumineszenzmessungen (time-resolved photoluminescence, TRPL) zeigen, dass der Einsatz von DIO zu einer geringeren Reduzierung der Photolumineszenz führt, was auf eine größere Phasentrennung zurückgeführt werden kann. Außerdem kann mittels TA Spektroskopie gezeigt werden, dass die Verwendung von DIO zu einer verbesserten Kristallinität der aktiven Schicht führt und die Generation freier Ladungen fördert. Zur genauen Analyse des Signalzerfalls wird ein Modell angewendet, das den gleichzeitigen Zerfall gebundener CT-Zustände und freier Ladungen berücksichtigt und optimierte Donor-Akzeptor-Mischungen zeigen einen größeren Anteil an nicht-geminaler Rekombination freier Ladungsträger.rnIn einer weiteren Fallstudie wird der Einfluss des Fullerenderivats, namentlich IC60BA und PC71BM, auf die Leistungsfähigkeit und Photophysik der Solarzellen untersucht. Eine Kombination aus einer Untersuchung der Struktur des Dünnfilms sowie zeitaufgelöster Spektroskopie ergibt, dass Mischungen, die ICBA als Elektronenakzeptor verwenden, eine schlechtere Trennung von Ladungstransferzuständen zeigen und unter einer stärkeren geminalen Rekombination im Vergleich zu PCBM-basierten Mischungen leiden. Dies kann auf die kleinere Triebkraft zur Ladungstrennung sowie auf die höhere Unordnung der ICBA-basierten Mischungen, die die Ladungstrennung hemmen, zurückgeführt werden. Außerdem wird der Einfluss reiner Fullerendomänen auf die Funktionsfähigkeit organischer Solarzellen, die aus Mischungen des Thienothienophen-basierenden Polymers pBTTT-C14 und PC61BM bestehen, untersucht. Aus diesem Grund wird die Photophysik von Filmen mit einem Donor-Akzeptor-Mischungsverhältnis von 1:1 sowie 1:4 verglichen. Während 1:1-Mischungen lediglich eine co-kristalline Phase, in der Fullerene zwischen den Seitenketten von pBTTT interkalieren, zeigen, resultiert der Überschuss an Fulleren in den 1:4-Proben in der Ausbildung reiner Fullerendomänen zusätzlich zu der co kristallinen Phase. Transiente Absorptionsspektroskopie verdeutlicht, dass Ladungstransferzustände in 1:1-Mischungen hauptsächlich über geminale Rekombination zerfallen, während in 1:4 Mischungen ein beträchtlicher Anteil an Ladungen ihre wechselseitige Coulombanziehung überwinden und freie Ladungsträger bilden kann, die schließlich nicht-geminal rekombinieren.

MECHANISM-BASED STRATEGIES TO ENHANCE THE ACTIONS OF A

Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which play a role in the survival of malignant cells. The chaperone function of HSP90 is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, treatment with 17-AAG results in the elevation of the levels of antiapoptotic proteins HSP70 and HSP27, which may lead to cell death resistance. The increase in HSP70 and HSP27 protein levels is due to the activation of the transcription factor HSF-1 binding to the promoter region of HSP70 and HSP27 genes. HSF-1 binding subsequently promotes HSP70 and HSP27 gene expression. Based on this, I hypothesized that inhibition of transcription/translation of HSP or client proteins would enhance 17-AAG-mediated cytotoxicity. Multiple myeloma (MM) cell lines MM.1S, RPMI-8226, and U266 were used as a model. To test this hypothesis, two different strategies were used. For the first approach, a transcription inhibitor was combined with 17-AAG. The established transcription inhibitor Actinomycin D (Act D), used in the clinic, intercalates into DNA and blocks RNA elongation. Stress inducible (HSP90á, HSP70 and HSP27) and constitutive (HSP90â and HSC70) mRNA and protein levels were measured using real time RT-PCR and immunoblot assays. Treatment with 0.5 µM 17-AAG for 8 hours resulted in the induction of all HSP transcript and protein levels in the MM cell lines. This induction of HSP mRNA levels was diminished by 0.05 µg/mL Act D for 12 hours in the combination treatment, except for HSP70. At the protein level, Act D abrogated the 17-AAG-mediated induction of all HSP expression levels, including HSP70. Cytotoxic evaluation (Annexin V/7-AAD assay) of Act D in combination with 17-AAG suggested additive or more than additive interactions. For the second strategy, an agent that affected bioenergy production in addition to targeting transcription and translation was used. Since ATP is necessary for the proper folding and maturation of client proteins by HSP90, ATP depletion should lead to a decrease in client protein levels. The transcription and translation inhibitor 8-Chloro-Adenosine (8-Cl-Ado), currently in clinical trials, is metabolized into its cytotoxic form 8-Cl-ATP causing a parallel decrease of the cellular ATP pool. Treatment with 0.5 µM 17-AAG for 8 hours resulted in the induction of all HSP transcript and protein levels in the three MM cell lines evaluated. In the combination treatment, 10 µM 8-Cl-Ado for 20 hours did not abrogate the induction of HSP mRNA or protein levels. Since cellular bioenergy is necessary for the stabilization of oncoproteins by HSP90, immunoblot assays analyzing for expression levels of client proteins such as STAT3, Raf-1, and Akt were performed. Immunoblot assays detecting for the phosphorylation status of the translation repressor 4E-BP1, whose activity is modulated by upstream kinases sensitive to changes in ATP levels, were also performed. The hypophosphorylated state of 4E-BP1 leads to translation repression. Data indicated that treatment with 17-AAG alone resulted in a minor (<10%) change in STAT3, Raf-1, and Akt protein levels, while no change was observed for 4E-BP1. The combination treatment resulted in more than 50% decrease of the client protein levels and hypophosphorylation of 4E-BP1 in all MM cell lines. Treatment with 8-Cl-Ado alone resulted in less than 30% decrease in client protein levels as well as a decrease in 4E-BP1 phosphorylation. Cytotoxic evaluation of 8-Cl-Ado in combination with 17-AAG resulted in more than additive cytotoxicity when drugs were combined in a sequential manner. In summary, these data suggest that the mechanism-based combination of agents that target transcription, translation, or decrease cellular bioenergy with 17-AAG results in increase cytotoxicity when compared to the single agents. Such combination strategies may be applied in the clinic since these drugs are established chemotherapeutic agents or currently in clinical trials.

Sediments and tephra layers from the southern Tyrrhenian abyssal plain near Marsili Seamount

From the south-eastern Tyrrhenian deep-sea floor, four sediment cores of "Meteor" cruise 22 (1971) are described. These cores were taken in the basin between the Aeolian Islands and the Marsili Seamount, an elevation of more tha 3000 m above the sea floor. The sedimentation of the deep-sea basin is distinguished by a sequence of turbidites with a high sedimentation rate. The composition of the clastic material and the position of the cores in the mouth area of the morphologically very pronounced Stromboli Canyon suggest an interpretation of the turbidite sequence as fan of this canyon onto the deep-sea floor. A white rhyolitic pumice-tephra at the base of the 4 m thick sequence of turbidites in core M22-102 has been correlated with the Pelato eruption of the island of Liparo in the 6th century A.D. At the foot of the Marsili Seamount - apparently in morphologically elevated positions - the influence of the turbidite sedimentation increases, the rate of sedimentation is lower and stratigraphic omissions are probable. Here, rather compacted globigerina marls have been found in only 15 -25 cm depth. In addition, volcanic material in the form of lapilli layers, palagonitized ashes and detrital volcanic sands of the Marsili Seamount have been encountered in this area. An up to 3 cm thick layer of completely palagonitized basaltic ash intercalates with the marls at the base of two cores. Layers of very fresh olivine basaltic lapilli in core 103 and palagonitized lapilli of latitic composition in core 104 testify to an explosive submarine volcanism of the Marsili Seamount. According to the stratigraphy of core 103, the latest manifestations of this basaltic volcanism belong to the late Pleistocene (Emiliana huxleyi-zone of Nannoplankton stratigraphy) The basaltic lapilli are glassy to perhyaline with phenocrysts or microphenocrysts predominantely of olivine. The petrological character of the basaltic volcanites with high MgO, Ni, Cr and high MgO/FeO- and Ni/Co-ratios exhibits primitive basaltic features. These basalts clearly differ from basalts of the ocean floors, mid-ocean ridges and marginal basins. Prominent features are a missing iron-enrichment trend and low TiO2. Al2O3 tends to be high, as well as K2O and related trace elements (Ba, Sr). In spite of silica undrsaturation and high color index, the Marsili basalt exhibit some analogies with the calcalkaline basalts of the Aeolian arc, as well as the undersaturated basalts of some other circumoceanic areas.

Influence of the epoxy/amine stoichiometry on the thermomechanical properties of nanocomposites based on high Tg epoxy and organophilic clays.

In layered silicate-epoxy nanocomposites organic modification of the silicates makes them compatible with the epoxy which intercalates into the clay galleries. The effect of clay dispersion on epoxies of high Tg is not clear. Decreases of the epoxy Tg have been frequently reported. The presence of clay may cause stoichiometry imbalances that conduces to the formation of imperfect networks

Synthesis and spectroscopic characterization of site-specific 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine oligodeoxyribonucleotide adducts

The aim of the present study is to determine the chemical structure and conformation of DNA adducts formed by incubation of the bioactive form of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-acetoxy-PhIP, with a single-stranded 11mer oligodeoxyribonucleotide. Using conditions optimized to give the C8-dG-PhIP adduct as the major product, sufficient material was synthesized for NMR solution structure determination. The NMR data indicate that in duplex DNA this adduct exists in equilibrium between two different conformational states. In the main conformer, the covalently bound PhIP molecule intercalates in the helix, whilst in the minor conformation the PhIP ligand is probably solvent exposed. In addition to the C8-dG-PhIP adduct, at least eight polar adducts are found after reaction of N-acetoxy-PhIP with the oligonucleotide. Three of these were purified for further characterization and shown to exhibit lowest energy UV absorption bands in the range 342–347 nm, confirming the presence of PhIP or PhIP derivative. Accurate mass determination of two of the polar adducts by negative ion MALDI-TOF MS revealed ions consistent with a spirobisguanidino-PhIP derivative and a ring-opened adduct. The third adduct, which has the same mass as the C8-dG-PhIP oligonucleotide adduct, may contain PhIP bound to the N2 position of guanine.

Solution structure of the 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine C8-deoxyguanosine adduct in duplex DNA

The carcinogenic heterocyclic amine (HA) 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed during the cooking of various meats. To enable structure/activity studies aimed at understanding how DNA damaged by a member of the HA class of compounds can ultimately lead to cancer, we have determined the first solution structure of an 11-mer duplex containing the C8-dG adduct formed by reaction with N-acetoxy-PhIP. A slow conformational exchange is observed in which the PhIP ligand either intercalates into the DNA helix by denaturing and displacing the modified base pair (main form) or is located outside the helix in a minimally perturbed B-DNA duplex (minor form). In the main base-displaced intercalation structure, the minor groove is widened, and the major groove is compressed at the lesion site because of the location of the bulky PhIP-N-methyl and phenyl ring in the minor groove; this distortion causes significant bending of the helix. The PhIP phenyl ring interacts with the phosphodiester-sugar ring backbone of the complementary strand and its fast rotation with respect to the intercalated imidazopyridine ring causes substantial distortions at this site, such as unwinding and bulging-out of the strand. The glycosidic torsion angle of the [PhIP]dG residue is syn, and the displaced guanine base is directed toward the 3′ end of the modified strand. This study contributes, to our knowledge, the first structural information on the biologically relevant HA class to a growing body of knowledge about how conformational similarities and differences for a variety of types of lesions can influence protein interactions and ultimately biological outcome.

Topoisomerase 1 (Top1)-associated Genome Instability in Yeast: Effects of Persistent Cleavage Complexes or Increased Top1 Levels

Topoisomerase 1 (Top1), a Type IB topoisomerase, functions to relieve transcription- and replication-associated torsional stress in DNA. Top1 cleaves one strand of DNA, covalently associates with the 3’ end of the nick to form a Top1-cleavage complex (Top1cc), passes the intact strand through the nick and finally re-ligates the broken strand. The chemotherapeutic drug, Camptothecin, intercalates at a Top1cc and prevents the crucial re-ligation reaction that is mediated by Top1, resulting in the conversion of a nick to a toxic double-strand break during DNA replication or the accumulation of Top1cc. This mechanism of action preferentially targets rapidly dividing tumor cells, but can also affect non-tumor cells when patients undergo treatment. Additionally, Top1 is found to be elevated in numerous tumor tissues making it an attractive target for anticancer therapies. We investigated the effects of Top1 on genome stability, effects of persistent Top1-cleavage complexes and elevated Top1 levels, in Saccharomyces cerevisiae. We found that increased levels of the Top1cc resulted in a five- to ten-fold increase in reciprocal crossovers, three- to fifteen fold increase in mutagenesis and greatly increased instability within the rDNA and CUP1 tandem arrays. Increased Top1 levels resulted in a fifteen- to twenty-two fold increase in mutagenesis and increased instability in rDNA locus. These results have important implications for understanding the effects of CPT and elevated Top1 levels as a chemotherapeutic agent.