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  • 1
    Publication Date: 2007-11-10
    Description: Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrated a correlation between the arrival directions of cosmic rays with energy above 6 x 10(19) electron volts and the positions of active galactic nuclei (AGN) lying within approximately 75 megaparsecs. We rejected the hypothesis of an isotropic distribution of these cosmic rays with at least a 99% confidence level from a prescribed a priori test. The correlation we observed is compatible with the hypothesis that the highest-energy particles originate from nearby extragalactic sources whose flux has not been substantially reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pierre Auger Collaboration -- Abraham, J -- Abreu, P -- Aglietta, M -- Aguirre, C -- Allard, D -- Allekotte, I -- Allen, J -- Allison, P -- Alvarez, C -- Alvarez-Muniz, J -- Ambrosio, M -- Anchordoqui, L -- Andringa, S -- Anzalone, A -- Aramo, C -- Argiro, S -- Arisaka, K -- Armengaud, E -- Arneodo, F -- Arqueros, F -- Asch, T -- Asorey, H -- Assis, P -- Atulugama, B S -- Aublin, J -- Ave, M -- Avila, G -- Backer, T -- Badagnani, D -- Barbosa, A F -- Barnhill, D -- Barroso, S L C -- Bauleo, P -- Beatty, J -- Beau, T -- Becker, B R -- Becker, K H -- Bellido, J A -- Benzvi, S -- Berat, C -- Bergmann, T -- Bernardini, P -- Bertou, X -- Biermann, P L -- Billoir, P -- Blanch-Bigas, O -- Blanco, F -- Blasi, P -- Bleve, C -- Blumer, H -- Bohacova, M -- Bonifazi, C -- Bonino, R -- Boratav, M -- Brack, J -- Brogueira, P -- Brown, W C -- Buchholz, P -- Bueno, A -- Busca, N G -- Caballero-Mora, K S -- Cai, B -- Camin, D V -- Caruso, R -- Carvalho, W -- Castellina, A -- Catalano, O -- Cataldi, G -- Cazon-Boado, L -- Cester, R -- Chauvin, J -- Chiavassa, A -- Chinellato, J A -- Chou, A -- Chye, J -- Clark, P D J -- Clay, R W -- Colombo, E -- Conceicao, R -- Connolly, B -- Contreras, F -- Coppens, J -- Cordier, A -- Cotti, U -- Coutu, S -- Covault, C E -- Creusot, A -- Cronin, J -- Dagoret-Campagne, S -- Daumiller, K -- Dawson, B R -- de Almeida, R M -- De Donato, C -- de Jong, S J -- De La Vega, G -- de Mello Junior, W J M -- de Mello Neto, J R T -- De Mitri, I -- de Souza, V -- Del Peral, L -- Deligny, O -- Selva, A Della -- Fratte, C Delle -- Dembinski, H -- Di Giulio, C -- Diaz, J C -- Dobrigkeit, C -- D'Olivo, J C -- Dornic, D -- Dorofeev, A -- Dos Anjos, J C -- Dova, M T -- D'Urso, D -- Duvernois, M A -- Engel, R -- Epele, L -- Erdmann, M -- Escobar, C O -- Etchegoyen, A -- Facal San Luis, P -- Falcke, H -- Farrar, G -- Fauth, A C -- Fazzini, N -- Fernandez, A -- Ferrer, F -- Ferry, S -- Fick, B -- Filevich, A -- Filipcic, A -- Fleck, I -- Fonte, R -- Fracchiolla, C E -- Fulgione, W -- Garcia, B -- Garcia Gamez, D -- Garcia-Pinto, D -- Garrido, X -- Geenen, H -- Gelmini, G -- Gemmeke, H -- Ghia, P L -- Giller, M -- Glass, H -- Gold, M S -- Golup, G -- Albarracin, F Gomez -- Berisso, M Gomez -- Herrero, R Gomez -- Goncalves, P -- Goncalves do Amaral, M -- Gonzalez, D -- Gonzalez, J G -- Gonzalez, M -- Gora, D -- Gorgi, A -- Gouffon, P -- Grassi, V -- Grillo, A -- Grunfeld, C -- Guardincerri, Y -- Guarino, F -- Guedes, G P -- Gutierrez, J -- Hague, J D -- Hamilton, J C -- Hansen, P -- Harari, D -- Harmsma, S -- Harton, J L -- Haungs, A -- Hauschildt, T -- Healy, M D -- Hebbeker, T -- Heck, D -- Hojvat, C -- Holmes, V C -- Homola, P -- Horandel, J -- Horneffer, A -- Horvat, M -- Hrabovsky, M -- Huege, T -- Iarlori, M -- Insolia, A -- Ionita, F -- Italiano, A -- Kaducak, M -- Kampert, K H -- Keilhauer, B -- Kemp, E -- Kieckhafer, R M -- Klages, H O -- Kleifges, M -- Kleinfeller, J -- Knapik, R -- Knapp, J -- Koang, D-H -- Kopmann, A -- Krieger, A -- Kromer, O -- Kumpel, D -- Kunka, N -- Kusenko, A -- La Rosa, G -- Lachaud, C -- Lago, B L -- Lebrun, D -- Lebrun, P -- Lee, J -- Leigui de Oliveira, M A -- Letessier-Selvon, A -- Leuthold, M -- Lhenry-Yvon, I -- Lopez, R -- Lopez Aguera, A -- Lozano Bahilo, J -- Maccarone, M C -- Macolino, C -- Maldera, S -- Malek, M -- Mancarella, G -- Mancenido, M E -- Mandat, D -- Mantsch, P -- Mariazzi, A G -- Maris, I C -- Martello, D -- Martinez, J -- Martinez Bravo, O -- Mathes, H J -- Matthews, J -- Matthews, J A J -- Matthiae, G -- Maurizio, D -- Mazur, P O -- McCauley, T -- McEwen, M -- McNeil, R R -- Medina, M C -- Medina-Tanco, G -- Meli, A -- Melo, D -- Menichetti, E -- Menschikov, A -- Meurer, Chr -- Meyhandan, R -- Micheletti, M I -- Miele, G -- Miller, W -- Mollerach, S -- Monasor, M -- Monnier Ragaigne, D -- Montanet, F -- Morales, B -- Morello, C -- Moreno, E -- Moreno, J C -- Morris, C -- Mostafa, M -- Muller, M A -- Mussa, R -- Navarra, G -- Navarro, J L -- Navas, S -- Nellen, L -- Newman-Holmes, C -- Newton, D -- Thi, T Nguyen -- Nierstenhofer, N -- Nitz, D -- Nosek, D -- Nozka, L -- Oehlschlager, J -- Ohnuki, T -- Olinto, A -- Olmos-Gilbaja, V M -- Ortiz, M -- Ostapchenko, S -- Otero, L -- Pakk Selmi-Dei, D -- Palatka, M -- Pallotta, J -- Parente, G -- Parizot, E -- Parlati, S -- Pastor, S -- Patel, M -- Paul, T -- Pavlidou, V -- Payet, K -- Pech, M -- Pekala, J -- Pelayo, R -- Pepe, I M -- Perrone, L -- Petrera, S -- Petrinca, P -- Petrov, Y -- Ngoc, Dieppham -- Ngoc, Dongpham -- Pham Thi, T N -- Pichel, A -- Piegaia, R -- Pierog, T -- Pimenta, M -- Pinto, T -- Pirronello, V -- Pisanti, O -- Platino, M -- Pochon, J -- Porter, T A -- Privitera, P -- Prouza, M -- Quel, E J -- Rautenberg, J -- Reucroft, S -- Revenu, B -- Rezende, F A S -- Ridky, J -- Riggi, S -- Risse, M -- Riviere, C -- Rizi, V -- Roberts, M -- Robledo, C -- Rodriguez, G -- Rodriguez Frias, D -- Rodriguez Martino, J -- Rodriguez Rojo, J -- Rodriguez-Cabo, I -- Ros, G -- Rosado, J -- Roth, M -- Rouille-d'Orfeuil, B -- Roulet, E -- Rovero, A C -- Salamida, F -- Salazar, H -- Salina, G -- Sanchez, F -- Santander, M -- Santo, C E -- Santos, E M -- Sarazin, F -- Sarkar, S -- Sato, R -- Scherini, V -- Schieler, H -- Schmidt, F -- Schmidt, T -- Scholten, O -- Schovanek, P -- Schussler, F -- Sciutto, S J -- Scuderi, M -- Segreto, A -- Semikoz, D -- Settimo, M -- Shellard, R C -- Sidelnik, I -- Siffert, B B -- Sigl, G -- De Grande, N Smetniansky -- Smialkowski, A -- Smida, R -- Smith, A G K -- Smith, B E -- Snow, G R -- Sokolsky, P -- Sommers, P -- Sorokin, J -- Spinka, H -- Squartini, R -- Strazzeri, E -- Stutz, A -- Suarez, F -- Suomijarvi, T -- Supanitsky, A D -- Sutherland, M S -- Swain, J -- Szadkowski, Z -- Takahashi, J -- Tamashiro, A -- Tamburro, A -- Tascau, O -- Tcaciuc, R -- Thomas, D -- Ticona, R -- Tiffenberg, J -- Timmermans, C -- Tkaczyk, W -- Todero Peixoto, C J -- Tome, B -- Tonachini, A -- Torresi, D -- Travnicek, P -- Tripathi, A -- Tristram, G -- Tscherniakhovski, D -- Tueros, M -- Tunnicliffe, V -- Ulrich, R -- Unger, M -- Urban, M -- Valdes Galicia, J F -- Valino, I -- Valore, L -- van den Berg, A M -- van Elewyck, V -- Vazquez, R A -- Veberic, D -- Veiga, A -- Velarde, A -- Venters, T -- Verzi, V -- Videla, M -- Villasenor, L -- Vorobiov, S -- Voyvodic, L -- Wahlberg, H -- Wainberg, O -- Waldenmaier, T -- Walker, P -- Warner, D -- Watson, A A -- Westerhoff, S -- Wieczorek, G -- Wiencke, L -- Wilczynska, B -- Wilczynski, H -- Wileman, C -- Winnick, M G -- Wu, H -- Wundheiler, B -- Xu, J -- Yamamoto, T -- Younk, P -- Zas, E -- Zavrtanik, D -- Zavrtanik, M -- Zech, A -- Zepeda, A -- Ziolkowski, M -- Kegl, B -- New York, N.Y. -- Science. 2007 Nov 9;318(5852):938-43.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17991855" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-10-14
    Description: Recently, there has been renewed interest in the coupling between geometry and topological defects in crystalline and striped systems. Standard lore dictates that positive disclinations are associated with positive Gaussian curvature, whereas negative disclinations give rise to negative curvature. Here, we present a diblock copolymer system exhibiting a striped columnar...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2015-06-21
    Description: The oft-repeated claim that Earth’s biota is entering a sixth "mass extinction" depends on clearly demonstrating that current extinction rates are far above the "background" rates prevailing in the five previous mass extinctions. Earlier estimates of extinction rates have been criticized for using assumptions that might overestimate the severity of the extinction crisis. We assess, using extremely conservative assumptions, whether human activities are causing a mass extinction. First, we use a recent estimate of a background rate of 2 mammal extinctions per 10,000 species per 100 years (that is, 2 E/MSY), which is twice as high as widely used previous estimates. We then compare this rate with the current rate of mammal and vertebrate extinctions. The latter is conservatively low because listing a species as extinct requires meeting stringent criteria. Even under our assumptions, which would tend to minimize evidence of an incipient mass extinction, the average rate of vertebrate species loss over the last century is up to 114 times higher than the background rate. Under the 2 E/MSY background rate, the number of species that have gone extinct in the last century would have taken, depending on the vertebrate taxon, between 800 and 10,000 years to disappear. These estimates reveal an exceptionally rapid loss of biodiversity over the last few centuries, indicating that a sixth mass extinction is already under way. Averting a dramatic decay of biodiversity and the subsequent loss of ecosystem services is still possible through intensified conservation efforts, but that window of opportunity is rapidly closing.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 4
    Publication Date: 2011-03-09
    Description: Anaerobic digestion is the most successful bioenergy technology worldwide with, at its core, undefined microbial communities that have poorly understood dynamics. Here, we investigated the relationships of bacterial community structure (〉400,000 16S rRNA gene sequences for 112 samples) with function (i.e., bioreactor performance) and environment (i.e., operating conditions) in a yearlong monthly time series of nine full-scale bioreactor facilities treating brewery wastewater (〉20,000 measurements). Each of the nine facilities had a unique community structure with an unprecedented level of stability. Using machine learning, we identified a small subset of operational taxonomic units (OTUs; 145 out of 4,962), which predicted the location of the facility of origin for almost every sample (96.4% accuracy). Of these 145 OTUs, syntrophic bacteria were systematically overrepresented, demonstrating that syntrophs rebounded following disturbances. This indicates that resilience, rather than dynamic competition, played an important role in maintaining the necessary syntrophic populations. In addition, we explained the observed phylogenetic differences between all samples on the basis of a subset of environmental gradients (using constrained ordination) and found stronger relationships between community structure and its function rather than its environment. These relationships were strongest for two performance variables—methanogenic activity and substrate removal efficiency—both of which were also affected by microbial ecology because these variables were correlated with community evenness (at any given time) and variability in phylogenetic structure (over time), respectively. Thus, we quantified relationships between community structure and function, which opens the door to engineer communities with superior functions.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2019
    Description: 〈p〉Although tunable signaling by G protein–coupled receptors can be exploited through medicinal chemistry, a comparable pharmacological approach has been lacking for the modulation of signaling through dimeric receptors, such as those for cytokines. We present a strategy to modulate cytokine receptor signaling output by use of a series of designed C2-symmetric cytokine mimetics, based on the designed ankyrin repeat protein (DARPin) scaffold, that can systematically control erythropoietin receptor (EpoR) dimerization orientation and distance between monomers. We sampled a range of EpoR geometries by varying intermonomer angle and distance, corroborated by several ligand-EpoR complex crystal structures. Across the range, we observed full, partial, and biased agonism as well as stage-selective effects on hematopoiesis. This surrogate ligand strategy opens access to pharmacological modulation of therapeutically important cytokine and growth factor receptor systems.〈/p〉
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2019
    Description: 〈p〉The evolution of flight in birds involves (i) decoupling of the primitive mode of quadrupedal locomotor coordination, with a new synchronized flapping motion of the wings while conserving alternating leg movements, and (ii) reduction of wing digits and loss of functional claws. Our observations show that hoatzin nestlings move with alternated walking coordination of the four limbs using the mobile claws on their wings to anchor themselves to the substrate. When swimming, hoatzin nestlings use a coordinated motion of the four limbs involving synchronous or alternated movements of the wings, indicating a versatile motor pattern. Last, the proportions of claws and phalanges in juvenile hoatzin are radically divergent from those in adults, yet strikingly similar to those of 〈i〉Archaeopteryx.〈/i〉 The locomotor plasticity observed in the hoatzin suggests that transitional forms that retained claws on the wings could have also used them for locomotion.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 7
    Publication Date: 2014-08-06
    Description: The sodium-coupled neutral amino acid transporter 2 (SNAT2) translocates small neutral amino acids into the mammary gland to promote cell proliferation during gestation. It is known that SNAT2 expression increases during pregnancy, and in vitro studies indicate that this transporter is induced by 17β-estradiol. In this study, we elucidated the...
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    Electronic ISSN: 1091-6490
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  • 8
    Publication Date: 2014-08-06
    Description: AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target effects. To eliminate...
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    Electronic ISSN: 1091-6490
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  • 9
    Publication Date: 1997-01-17
    Description: Transmembrane receptors for hormones, neurotransmitters, light, and odorants mediate their cellular effects by activating heterotrimeric guanine nucleotide-binding proteins (G proteins). Crystal structures have revealed contact surfaces between G protein subunits, but not the surfaces or molecular mechanism through which Galphabetagamma responds to activation by transmembrane receptors. Such a surface was identified from the results of testing 100 mutant alpha subunits of the retinal G protein transducin for their ability to interact with rhodopsin. Sites at which alanine substitutions impaired this interaction mapped to two distinct Galpha surfaces: a betagamma-binding surface and a putative receptor-interacting surface. On the basis of these results a mechanism for receptor-catalyzed exchange of guanosine diphosphate for guanosine triphosphate is proposed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Onrust, R -- Herzmark, P -- Chi, P -- Garcia, P D -- Lichtarge, O -- Kingsley, C -- Bourne, H R -- CA-54427/CA/NCI NIH HHS/ -- GM-27800/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1997 Jan 17;275(5298):381-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0450, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8994033" target="_blank"〉PubMed〈/a〉
    Keywords: Aluminum Compounds/pharmacology ; Animals ; Binding Sites ; COS Cells ; Fluorides/pharmacology ; Guanosine 5'-O-(3-Thiotriphosphate)/metabolism ; Guanosine Diphosphate/metabolism ; Models, Molecular ; Mutation ; Phenotype ; *Protein Conformation ; Retinaldehyde/pharmacology ; Rhodopsin/*metabolism/pharmacology ; Rod Cell Outer Segment/metabolism ; Transducin/*chemistry/metabolism
    Print ISSN: 0036-8075
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  • 10
    Publication Date: 2018-10-10
    Description: The increased prevalence of drug-resistant human pathogenic fungal diseases poses a major threat to global human health. Thus, new drugs are urgently required to combat these infections. Here, we demonstrate that acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway, is a promising new target for...
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