bluuebunny/crossref_metadata_2025 huggingface dataset:
Building Footprints Extraction from Oblique Imagery
Authors: Nex F. , Rupnik E. , Remondino F.
Published: October 2013

Abstract. Nowadays, multi-camera aerial platforms combining nadir and oblique cameras are experiencing a revival and several companies have proposed new image acquisition systems. Due to their various advantages, oblique imagery have found their place in numerous companies and civil applications. However, the automatic processing of such image blocks still remains a topic of research. Camera configuration indeed poses a challenge on the traditional photogrammetric pipeline used in commercial software but, on the other hand, gives the opportunity to exploit the additional information provided by the oblique views and allows a more reliable feature extraction. In particular, the information that can be provided in correspondence of building façades can open new possibilities for the building detection and footprint extraction. In this paper, a methodology for the automated extraction of building footprints from oblique imagery is presented. The extraction is performed using dense point clouds generated using an image matching algorithm. The developed methodology and the achieved results are described in detail showing the advantages and opportunities offered by oblique aerial systems for cartographic and mapping purposes.
Reconstruction of façades in point clouds from multi aspect oblique ALS
Authors: Tuttas S. , Stilla U.
Published: October 2013

Abstract. In this paper an approach is described which allows the reconstruction of windows in façades from airborne laser scanning (ALS) data taken in oblique view. A challenge is the sparse sampling of the façades by ALS compared to terrestrial laser scanning. In a first step windows are detected by a search for measurements of laser pulses which pass the windows (voyeur effect) and reflect behind the façade (indoor points). For a general study exploiting this side effect two different cases are considered: (i) a city model with faces of the façade is available and the point cloud has to be co-registered, (ii) a city model is not available and façade planes has to be automatically derived from the point cloud itself. Then, in both cases indoor points are mapped to a raster on the façade plane to accumulate hypotheses for the position of windows. Based on the points lying around these positions rectangular windows are reconstructed on the façade wall. Finally, the outlines of the windows are adapted by considering all windows of one façade. For a selection of eleven façades a quality analysis was performed showing a detection rate of 67%, a false alarm rate of 9% and an error of window sizes varying from a few centimeter to about one meter.
Application of GA-SVM method with parameter optimization for landslide development prediction
Authors: Li X. Z. , Kong J. M.
Published: October 2013

Abstract. Prediction of landslide development process is always a hot issue in landslide research. So far, many methods for landslide displacement series prediction have been proposed. Support vector machine (SVM) has been proved to be a novel algorithm with good performance. However, the performance strongly depends on the right selection of the parameters (C and γ) of SVM model. In this study, we presented an application of GA-SVM method with parameter optimization in landslide displacement rate prediction. We selected a typical large-scale landslide in some hydro - electrical engineering area of Southwest China as a case. On the basis of analyzing the basic characteristics and monitoring data of the landslide, a single-factor GA-SVM model and a multi-factor GA-SVM model of the landslide were built. Moreover, the models were compared with single-factor and multi-factor SVM models of the landslide. The results show that, the four models have high prediction accuracies, but the accuracies of GA-SVM models are slightly higher than those of SVM models and the accuracies of multi-factor models are slightly higher than those of single-factor models for the landslide prediction. The accuracy of the multi-factor GA-SVM models is the highest, with the smallest RSME of 0.0009 and the biggest RI of 0.9992.
The transient distributions of nuclear weapon-generated tritium and its decay product 3 He in the Mediterranean Sea, 1952–2011, and their oceanographic potential
Authors: Roether W. , Jean-Baptiste P. , Fourré E. , Sültenfuß J.
Published: October 2013

Abstract. We present a comprehensive account of tritium and 3He in the Mediterranean Sea since the appearance of the tritium generated by the atmospheric nuclear-weapon testing in the 1950s and early 1960s, based on essentially all available observations. Tritium in surface waters rose to 20–30 TU in 1964 (TU = 1018 × [3H]/H]), a factor of about 100 above the natural level, and thereafter declined 30-fold up to 2011. The decline was largely due to radioactive tritium decay, which produced significant amounts of its stable daughter 3He. We present the scheme by which we separate the tritiugenic part of 3He and the part due to release from the sea floor (terrigenic part). We show that the tritiugenic component can be quantified throughout the Mediterranean waters, typically to a ± 0.15 TU equivalent, mostly because the terrigenic part is low in 3He. This fact makes the Mediterranean unique in offering a potential for the use of tritiugenic 3He as a tracer. The transient distributions of the two tracers are illustrated by a number of sections spanning the entire sea and relevant features of their distributions are noted. By 2011, the 3He concentrations in the top few hundred metres had become low, in response to the decreasing tritium concentrations combined with a flushing out by the general westward drift of these waters. Tritium-3He ages in Levantine Intermediate Water (LIW) were obtained repeated in time at different locations, defining transit times from the LIW source region east of Rhodes. The ages show an upward trend with the time elapsed since the surface-water tritium maximum, which arises because the repeated observations represent increasingly slower moving parts of the full transit time spectrum of LIW. The transit time dispersion revealed by this new application of tritium-3He dating is considerable. We find mean transit times of 12 ± 2 yr up to the Strait of Sicily, 18 ± 3 yr up to the Tyrrhenian Sea, and 22 ± 4 yr up into the Western Mediterranean. Furthermore, we present full Eastern Mediterranean sections of terrigenic 3He and tritium-3He age in 1987, the latter one similarly showing an effect of the transit time dispersion. We conclude that the available tritium and 3He data, particularly if combined with other tracer data, are useful for constraining the subsurface circulation and mixing of the Mediterranean Sea.
Undermining ‘data’: A critical examination of a core term in scientific inquiry
Authors: Markham Annette N.
Published: October 2013

The term ‘data’ functions as a powerful frame for discourse about how knowledge is derived and privileges certain ways of knowing over others. Through its ambiguity, the term can foster a self–perpetuating sensibility that ‘data’ is incontrovertible, something to question the meaning or the veracity of, but not the existence of. This article critically examines the concept of ‘data’ within larger questions of research method and frameworks for scientific inquiry. The current dominance of the term ‘data’ and ‘big data’ in discussions of scientific inquiry as well as everyday advertising focuses our attention on only certain aspects of the research process. The author suggests deliberately decentering the term, to explore nuanced frames for describing the materials, processes, and goals of inquiry.
Caracterização fisiológica de sorgo sacarino em diferentes intensidades de irrigação
Authors: Moreira Luciano Rezende , Ervilha Jardélcio Damião Carvalho , Coutinho Paulo Henrique , Vidigal Juliana Gonçalves , Ogliari Juares , Miranda Glauco Vieira , Pereira Lucas Felisberto
Published: October 2013

O sorgo [Sorghum bicolor (L.) Moench] é uma planta de origem africana, da mesma família do milho. O sorgo tipo sacarino é utilizado como matéria prima para bionergia (etanol) e apresenta elevada eficiência no uso da água. Este trabalho teve como objetivo caracterizar cultivares de sorgo sacarino quanto às características fisiológicas em diferentes intensidades de irrigação, analisar trocas gasosas e fluorescência de clorofila a fim de subsidiar programas de melhoramento genético direcionados à obtenção de genótipos produtivos de sorgo em situações de déficit hídrico. Foram avaliados quatro cultivares, tolerantes à seca: Rio, Ramada, BRS 501, BRS 506. O tratamento consistiu de três disponibilidades de água no solo: 80%, 60% e 40% da capacidade de campo (c.c.). Foram avaliadas a condutância estomática (gs), a taxa de fotossíntese líquida (A), a transpiração foliar (E) e a eficiência intrínseca do uso da água (EIUA, A/gs). Também foi determinada a eficiência quântica ideal (Fv/Fm) do fotossistema II (FSII), o rendimento quântico basal dos processos fotoquímicos no FSII (Fo/Fm) e a eficiência fotoquímica no FSII (Fv/Fo). A disponibilidade hídrica não causou alteração (P > 0,05) na transpiração dos cultivares Ramada e BRS 501, mas afetou (P < 0,05) os cultivares Rio e BRS 506 que responderam positivamente ao aumento da irrigação. Resultado semelhante ocorreu com a fotossíntese, já que as diferentes disponibilidades hídricas influenciaram positivamente apenas os cultivares Rio e BRS 506. Com o incremento da irrigação houve um acréscimo (P < 0,05) na condutância estomática dos cultivares avaliados. Os resultados referentes à fluorescência da clorofila mostraram superioridade dos cultivares BRS 506, Rio e Ramada com valores maiores (P < 0,05) de Fv/Fm e Fv/Fo. Os distintos níveis de disponibilidade hídrica e os diferentes cultivares não promoveram (P > 0,05) alteração na EIUA. Esta metodologia, comum às outras culturas, pode ser utilizada para sorgo sacarino para estabelecer disponibilidades hídricas em novos experimentos que tenham a finalidade de discriminar cultivares tolerantes à seca.
Análise do telos estético do empresariado da Região Norte Fluminense sobre Design
Authors: Neves Alan Rene Lopes , Oliveira Joelma Alves de , Maciel Marcos Antonio Esquef
Published: October 2013

Diante das expectativas de um novo cenário de desenvolvimento da Região Norte Fluminense e do surgimento de um mercado econômico mais competitivo e exigente, busca-se por meio deste artigo identificar o grau de entendimento dos empreendedores sobre a relevância do Design como ferramenta estratégica para os seus negócios. Com este intuito, o trabalho em questão analisa diferentes fontes teóricas no que tange ao assunto bem como apresenta uma pesquisa junto ao empresariado que lhes possibilita perceber não só a aplicabilidade do Design em suas empresas mas também sua importância como fator de desenvolvimento econômico da região e do país.
Otimização geométrica de treliças planas utilizadas em coberturas metálicas
Authors: Oliveira Sergio Rafael Cortes de , Falcón Gines Arturo Santos
Published: October 2013

Na concepção de projetos estruturais, os profissionais modernos buscam minimizar o consumo de material, o que diminui custos, mas sem comprometer a eficiência do sistema. Este trabalho visa implementar um programa de otimização geométrica para identificação da solução ótima de uma treliça em alumínio, objetivando minimizar seu peso. E busca ressaltar a importância de projetar sistemas mais racionais, sustentáveis e com boa relação custo-benefício. Os resultados da pesquisa mostraram o potencial da otimização diante da considerável redução de peso obtida. Foram feitas avaliações complementares para verificar a influência das áreas e da eliminação de restrições na geometria final do problema.
Impacto da fertirrigação com água residuária da suinocultura em um latossolo vermelho-amarelo
Authors: Condé Marisa Senra , Almeida Neto Onofre Barroca de , Homem Bruno Grossi Costa , Ferreira Igor Machado , Silva Mateus Diniz
Published: October 2013

O objetivo do trabalho foi avaliar o efeito da aplicação de Água Residuária de Suínos (ARS) sobre as propriedades químicas e físicas de um Latossolo Vermelho-Amarelo distrófico. O experimento foi realizado em condições de campo, com os seguintes tratamentos: T1 = 0; T2 = 50; T3 = 100; T4 = 150 m3.ha.ano-1 de ARS. A ARS promoveu aumento da acidez do solo na camada de 20-40 cm, e diminuição da quantidade de fósforo adsorvido à argila em ambas as camadas, 0-20 e 20-40 cm. A porcentagem de argila dispersa em água aumentou na camada de 20-40 cm, indicando que a aplicação permanente da ARS pode propiciar riscos de redução da permeabilidade do solo.
Informing Practice: Mathematical Practices That Promote Twenty-First Century Skills
Authors: Suh Jennifer , Seshaiyer Padmanabhan
Published: October 2013

Skills that students will need in the twenty-first century, such as financial literacy, are explored in this classroom-centered research article.
Responding to Students' Work on a Rich Task
Authors: Kuper Emily G. , Kimani Patrick M.
Published: October 2013

Students engage in a fractions task involving 2/3 men and 3/5 women, and teachers analyze their thinking.
An Unplanned Path
Authors: McGarvey Lynn M. , Sterenberg Gladys Y. , Long Julie S.
Published: October 2013

As a means of identifying potential new elementary school trailblazers, examine the significant points along the professional journeys of two teachers.
Theologies of the Land and State of Israel: The Role of the Secular in Jewish and Christian Understandings
Authors: Langer Ruth
Published: October 2013

Christians and Jews have tended to approach theological understandings of Israel through different categorizations of what constitutes appropriate topics for theology. Separation of religious and political realities has been an aspect of Christian culture since the fourth century, but it was never a native separation for Judaism. Thus, contemporary Christian theologians have attempted to develop understandings of Jewish relationship to the land that excludes its political aspects. From a Jewish perspective, this amounts to a recasting of Judaism according to a foreign set of values, one that devalues the potential (if not yet actualized) theological meanings inherent in contemporary Jewish sovereignty over its historical homeland. Progress in dialogue about Israel requires confronting this difference directly.
Founding Father of Jewish-Christian Relations: The Rev. James Parkes (1896-1981)
Authors: Eckardt Alice
Published: October 2013

No abstract is available.
Has the Papacy 'Owned' Vatican Guilt for the Church's Role in the Holocaust?
Authors: Madigan Kevin
Published: October 2013

No abstract is available.
Saints in the Christian Tradition: Unraveling the Canonization Process
Authors: Gribble, C.S.C. Richard
Published: October 2013

Contemporary people, both Christian and non-Christian like, find the Roman Catholic process of declaring saints, known as canonization, to be both interesting and mystifying. This essay seeks to unravel the apparent mystery by providing a historical chronicle that describes the development and evolution of this process. Beginning in the Patristic Church, when persecution was normative, martyrs to the faith were exalted by local peoples and with time declared saints. Later, when martyrdoms subsided greatly, men and women who demonstrated "heroic virtue" were placed on a par with martyrs and also declared saints. By the late medieval period, after some abuses in the declaration of saints were noted, the process of canonization became more centralized in the office of the Pope. Processes to determine heroic virtue and to verify miracles, which became a necessary element to both beatification and canonization, were also developed. By the time of the early 20th century and the formalization of Canon Law in 1917, a rigorous process to declare men and women as saints was present. In the post-Vatican II era, this process has been streamlined and become more formalized through documents published by Popes John Paul II and Benedict XVI.
David Rudolph. A Jew to the Jews: Jewish Contours of Pauline Flexibility in 1 Corinthians 9:19-23
Authors: Kensky Meira Z.
Published: October 2013

No abstract is available.
Devorah Schoenfeld. Isaac on Jewish & Christian Altars: Polemic and Exegesis in Rashi and the Glossa Ordinaria
Authors: Resnick Irven M.
Published: October 2013

No abstract is available.
David H. Price. Johannes Reuchlin and the Campaign to Destroy Jewish Books
Authors: Walton Michael T.
Published: October 2013

No abstract is available.
Neutralization of LC- and RC-Disturbances with Left-Handed and NGD Effects
Authors: Ravelo B.
Published: October 2013

This paper focus is on the neutralization technique of the unwanted physical disturbances in the radio frequencies (RF) and digital electronic structures. Most of parasitic effects induced in these systems can be modeled by RC- and LC- passive networks. For canceling these disturbing effects, we can proceed with the transfer function neutralization in the considered operating frequency bands. This neutralization concept is developed by using first, a left-handed (LH) and negative group delay (NGD) circuits inspired from metamaterials. The fundamental theoretical approach illustrating the RC- and LC-effects transfer function neutralization is described. Synthesis relations enabling to determine the elements of the LH and NGD circuit correctors in function of the perturbation parameters are established. Numerical and experimental demonstrators are presented to validate the technique proposed. This later is particularly useful for the improvement of the analogue and digital signal integrity degraded by electromagnetic interferences.
Nick Sagan Reflects on Voyager 1 and the Golden Record
Authors: Showstack Randy
Published: October 2013

When scientists confirmed on 12 September that NASA's Voyager 1 spacecraft had entered interstellar space (Eos, 94(39), 339, doi:10.1002/2013EO390003), the probe was acknowledged as the first human‐made object to travel into that realm. The probe and its twin, Voyager 2, each carry a 12‐inch gold‐plated copper disk, known as the Golden Record.
New Ambassador Award Recognizes Outreach and Societal Impact
Authors: McKenzie Judith Ann
Published: October 2013

AGU has created a new award that honors members whose achievements extend beyond those recognized by traditional scientific discipline awards. The award furthers AGU's strategic goals to promote collaboration and innovation, inform society about Earth and space science, and build the global talent pool.
Proposed Bylaws Changes Open for Comment
Authors: Enderlein Cheryl
Published: October 2013

AGU members are invited to comment on proposed changes to AGU's bylaws. The updates reflect changes required by Washington, D. C., law and changes enacted by the AGU Board of Directors and Council during the transition in 2010–2012 to a new governance structure. Members can view and comment on the proposed changes at http://sites.agu.org/leadership/agu‐bylaws‐comment‐period/. The comment period is open until 18 November.
Di Baldassarre Receives 2012 Hydrologic Sciences Early Career Award: Citation
Authors: Montanari Alberto
Published: October 2013

It is a great pleasure for me to introduce Giuliano Di Baldassarre as the recipient of the AGU Hydrologic Sciences Early Career Award.
Climates, Landscapes, and Civilizations
Authors: Schultz Colin
Published: October 2013

Humans are now the dominant driver of global climate change. From ocean acidification to sea level rise, changes in precipitation patterns, and rising temperatures, global warming is presenting us with an uncertain future. However, this is not the first time human civilizations have faced a changing world. In the AGU monograph Climates, Landscapes, and Civilizations, editors Liviu Giosan, Dorian Q. Fuller, Kathleen Nicoll, Rowan K. Flad, and Peter C. Clift explore how some ancient peoples weathered the shifting storms while some faded away. In this interview, Eos speaks with Liviu Giosan about the decay of civilizations, ancient adaptation, and the surprisingly long history of humanity's effect on the Earth.
Effects of space weather on satellite components
Authors: Balcerak Ernie
Published: October 2013

Space weather can affect satellite performance and cause “anomalies,” unexplained problems ranging from a minor temporary glitch to a complete failure of a component. Understanding these effects requires looking at the relationship between space weather conditions and anomalies. However, data on commercial satellite anomalies have not often been made available for scientists to study.
Large‐scale atmospheric circulation affects particulate matter levels
Authors: Balcerak Ernie
Published: October 2013

Particulate matter in the air, which can come from both natural and anthropogenic sources, can be detrimental to human health. Air quality standards in Europe and elsewhere regulate emission of air pollutants from human sources, but in some locations, particulate matter levels are still high. Among the natural factors that can influence particulate matter concentrations are large‐scale atmospheric circulation patterns, such as the North Atlantic Oscillation (NAO). Understanding the relationship between NAO variability and particulate matter can help scientists understand particulate matter trends and potentially predict areas likely to be affected by pollution episodes. This is especially important because climate models suggest that the winter mean state of the NAO is likely to shift in coming years.
Sediment wedges not stabilizing West Antarctic Ice Sheet
Authors: Balcerak Ernie
Published: October 2013

The stability of the West Antarctic Ice Sheet is uncertain as climate changes. An ice sheet such as the West Antarctic Ice Sheet that is grounded well below sea level on a bed that slopes toward the interior of the sheet is believed to be unstable: When the grounding zone, where the grounded sheet transitions into floating ice, retreats inland, it can lead to massive amounts of ice becoming ungrounded and floating into the ocean unless something such as a wedge of sediment stabilizes the ice sheet. It has been proposed that such a sediment wedge stabilizes the grounding zone of the Whillans Ice Stream, one of the large ice streams flowing from the West Antarctic Ice Sheet. However, most understanding of ice sheet stability at grounding zones comes from models and remote observation rather than field‐based observations.
Parts of Amazon on the verge of forest‐to‐grassland shift
Authors: Schultz Colin
Published: October 2013

The stability of the Amazon rainforest and the ecosystem's resilience to widespread deforestation may be much lower than previously thought. The replacement of stands of trees with grassland changes evapotranspiration rates and atmospheric moisture convergence, which, in turn, reduce regional rainfall. This feedback effect could drive further deforestation. Previous research indicated that a dramatic shift from forest to grassland could overtake the Amazon when the total deforested area hits 40% to 50% of the forest's current size. New research by Pires and Costa, however, found that the deforestation needed to trigger this equilibrium shift is much lower, closer to just 10%.
Breath Figure Arrays: Unconventional Fabrications, Functionalizations, and Applications
Authors: Bai Hua , Du Can , Zhang Aijuan , Li Lei
Published: October 2013

A breath figure (BF) is the water droplet array that forms when moisture comes in contact with a cold substrate. This water droplet array has been widely utilized in the past two decades as a versatile soft template for the fabrication of polymeric porous films. Accordingly, the ordered pores on the polymer films formed with such a method are named a breath figure array (BFA).The BF templating technique is undergoing rapid development. Several unconventional BF processes have been established to prepare porous films with unique morphologies or primary materials, and various newly developed functionalization techniques have significantly improved the performance of polymeric films with BFA, leading to novel applications, including templates, biosensors, and separation membranes. These recent achievements will be described in this Minireview.
Promotion of Förster Resonance Energy Transfer in a Saponite Clay Containing Luminescent Polyhedral Oligomeric Silsesquioxane and Rhodamine Dye
Authors: Olivero Francesco , Carniato Fabio , Bisio Chiara , Marchese Leonardo
Published: October 2013

A new hybrid photostable saponite clay with embedded donor–acceptor dyes was prepared and characterized in this work. The saponite is intercalated with a luminescent polyhedral oligomeric silsesquioxane, which transfers the photoexcitation energy directly to an acceptor dye (rhodamine B). The obtained composite material was characterized by means of XRD, TEM microscopy, and UV/Vis and photoluminescence spectroscopy. A physicochemical study showed that the system behaved as an efficient Förster resonance energy transfer pair, owing to the very good spectral overlap of donor emission (λem=510–540 nm) and acceptor absorption in the λ=530–570 nm range. The hybrid material represents the first example of a photonic antenna based on a synthetic saponite clay and can be considered a step forward in the search for new, efficient, and stable materials suitable for light‐harvesting applications.
Palladium‐Catalyzed Cross‐Dehydrogenative Functionalization of C(sp2)H Bonds
Authors: Wu Yinuo , Wang Jun , Mao Fei , Kwong Fuk Yee
Published: October 2013

The catalytic cross‐dehydrogenative coupling (CDC) reaction has received intense attention in recent years. The attractive feature of this coupling process is the formation of a CC bond from two CH moieties under oxidative conditions. In this Focus Review, recent advances in the palladium‐catalyzed CDC reactions of C(sp2)H bond are summarized, with a focus on the period from 2011 to early 2013.
Macrocyclic Bis(phenanthroline‐pyrrole): A Convenient One‐Pot Synthesis, Structure(s), Spectroscopic, and Redox Properties, and the Binding of Amine Guests, Protons, and Lanthanide Ions
Authors: McSkimming Alex , Shrestha Sumi , Bhadbhade Mohan M. , Thordarson Pall , Colbran Stephen B.
Published: October 2013

This paper reports a convenient, one‐pot, easily scalable and readily modifiable synthesis of a novel large‐ring bis(1,10‐phenanthrolinyl‐2,5‐pyrrole) macrocycle, H2LMC and describes its spectroscopic and electrochemical properties, protonation, cooperative amine binding, electrocatalysis of the oxidation of primary amines, photosensitization of the decomposition of dichloromethane, and the first lanthanide complexes of the hexaaza‐dianion LMC2− including the novel dimer, [(NO3)(LMC)Eu(μ‐OH)Eu(LMC)(H2O)2]⋅2py.
Chitosan‐Capped Mesoporous Silica Nanoparticles as pH‐Responsive Nanocarriers for Controlled Drug Release
Authors: Hu Xiaoxi , Wang Yun , Peng Bo
Published: October 2013

Herein, we present a straightforward synthesis of pH‐responsive chitosan‐capped mesoporous silica nanoparticles (MSNs). These MCM‐41‐type MSNs could be used as nanocapsules to accommodate guest molecules. Subsequently, (3‐glycidyloxypropyl)trimethoxysilane was grafted onto the surface of the MSNs, which served as a bridge to link between MSNs and chitosan, which is ubiquitous in nature and commercially available. Owing to the pH‐responsive and biocompatible features of chitosan, the loading and release of an anti‐cancer drug, doxorubicin hydrochloride, were carried out in vitro, in which the composite chitosan‐capped MSNs (CS‐MSNs) showed excellent environmental response. As the pH value of the media decreased, the degree of drug release correspondingly increased. Moreover, thanks to the perfect biocompatibility of chitosan, the CS‐MSNs exhibited lower cytotoxicity than that of the naked MSNs in an MTT assay. In addition, the in vitro kill potency against MCF‐7 breast‐cancer cells was enhanced over time, as well as with increasing concentration of the drug‐loaded CS‐MSNs. These results indicate that CS‐MSNs are promising candidates for pH‐responsive drug delivery in cancer therapy.
Discovery and Biological Characterization of the Auromomycin Chromophore as an Inhibitor of Biofilm Formation in Vibrio cholerae
Authors: Peach Kelly C. , Cheng Andrew T. , Oliver Allen G. , Yildiz Fitnat H. , Linington Roger G.
Published: October 2013

Bacterial biofilms pose a significant challenge in clinical environments due to their inherent lack of susceptibility to antibiotic treatment. It is widely recognized that most pathogenic bacterial strains in the clinical setting persist in the biofilm state, and are the root cause of many recrudescent infections. The discovery and development of compounds capable of either inhibiting biofilm formation or initiating biofilm dispersal might provide new therapeutic avenues for reducing the number of hospital‐acquired, biofilm‐mediated infections. We detail here the application of our recently reported image‐based, high‐throughput screen to the discovery of microbially derived natural products with inhibitory activity against Vibrio cholerae biofilm. Examination of a prefractionated library of microbially derived marine natural products has led to the identification of a new biofilm inhibitor that is structurally unrelated to previously reported inhibitors and is one of the most potent inhibitors of V. cholerae reported to date. Combination of this compound with sub‐MIC concentrations of a number of clinically relevant antibiotics was shown to improve the inhibitory efficacy of this new compound compared to monotherapy treatments, and provides evidence for the potential therapeutic benefit of biofilm inhibitors in treating persistent biofilm‐mediated infections.
Base‐Pairing Behavior of a Carbocyclic Janus‐AT Nucleoside Analogue Capable of Recognizing A and T within a DNA Duplex
Authors: Largy Eric , Liu Wenbo , Hasan Abid , Perrin David M.
Published: October 2013

Janus‐type nucleosides are heterocycles with two faces, each of which is designed to complement the H‐bonding interactions of natural nucleosides comprising a canonical Watson–Crick base pair. By intercepting all of the hydrogen bonds contained within the base pair, oligomeric Janus nucleosides are expected to achieve sequence‐specific DNA recognition through the formation of J‐loops that will be more stable than D‐loops, which simply replaces one base‐pair with another. Herein, we report the synthesis of a novel Janus‐AT nucleoside analogue, JAT, affixed on a carbocyclic analogue of deoxyribose that was converted to the corresponding phosphoramidite. A single JAT was successfully incorporated into a DNA strand by solid phase for targeting both A and T bases, and characterized through biophysical and computational methods. Experimental UV‐melting and circular dichroism data demonstrated that within the context of a standard duplex, JAT associates preferentially with T over A, and much more poorly with C and G. Density functional theory calculations confirm that the JAT structure is well suited to associate only with A and T thereby highlighting the importance of the electronic structure in terms of H‐bonding. Finally, molecular dynamics simulations validated the observation that JAT can substitute more effectively as an A‐analogue than as a T‐analogue without substantial distortion of the B‐helix. Overall, this new Janus nucleotide is a promising tool for the targeting of A–T base pairs in DNA, and will lead to the development of oligo‐Janus‐nucleotide strands for sequence‐specific DNA recognition.
Ribosomal Protein S5e is Implicated in Translation Initiation through its Interaction with the N‐Terminal Domain of Initiation Factor eIF2α
Authors: Sharifulin Dmitri , Babaylova Elena , Kossinova Olga , Bartuli Yulia , Graifer Dmitri , Karpova Galina
Published: October 2013

A key step of translation initiation in eukaryotes is formation of the 48S preinitiation complex (PIC) containing the 40S ribosome, a set of eukaryotic initiation factors (eIFs), mRNA, and initiator Met‐tRNA interacting with mRNA start codon; however, the PIC structure remains substantially unknown. Here, we apply formaldehyde‐induced protein–protein crosslinks to identify contacts between ribosomal protein S5e (rpS5e, “e” stands for “eukaryotic”) and eIFs within the mammalian PIC, assembled on either model canonical or IRES‐containing mRNA. Using immunoblotting and mass spectrometry, we show that with both types of mRNA, rpS5e crosslinks to eIF2α. Comparative analysis of peptides resulting from trypsinolysis of the crosslinked proteins before and after crosslink reversal reveals crosslinked peptides in the N‐terminal parts of rpS5e and eIF2α. Application of these data to a model PIC structure obtained with the use of available structures indicates that eIF2α undergoes major conformation rearrangements to enable contacts of the factor with rpS5e. These contacts are suggested to maintain the correct positioning of eIF2α relative to other PIC components; this could be essential for start‐codon selection by the PIC.
Bicyclic Peptide Inhibitor of Urokinase‐Type Plasminogen Activator: Mode of Action
Authors: Roodbeen Renée , Paaske Berit , Jiang Longguang , Jensen Jan K. , Christensen Anni , Nielsen Jakob T. , Huang Mingdong , Mulder Frans A. A. , Nielsen Niels Chr. , Andreasen Peter A. , Jensen Knud J.
Published: October 2013

The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptide‐based inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase‐type plasminogen activator (uPA), based on the established monocyclic peptide, upain‐2. It was successfully converted to a bicyclic peptide, without loss of inhibitory properties. The aim was to produce a peptide cyclised by an amide bond with an additional stabilising across‐the‐ring covalent bond. We expected this bicyclic peptide to exhibit a lower entropic burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain‐2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain‐2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also investigated the solution structures of the bicyclic peptide by NMR spectroscopy to map possible conformations. An X‐ray structure of the bicyclic‐peptide–uPA complex confirmed an interaction similar to that for the previous upain‐1/upain‐2–uPA complexes. These physical studies of the peptide–protease interactions will aid future designs of bicyclic peptide protease inhibitors.
Effects of Charge and Charge Distribution on the Cellular Uptake of Multivalent Arginine‐Containing Peptide–Polymer Conjugates
Authors: Koschek Katharina , Dathe Margitta , Rademann Jörg
Published: October 2013

Copolymers of N‐(2‐hydroxypropyl)methacrylamide (HPMA) and N‐methacryloyl‐β‐alaninyl‐S‐benzyl thioester were prepared by employing free radical or RAFT conditions and denominated as “NCL polymers”. The copolymer with a polydispersity index of 1.2–1.3 was used for the direct conjugation of unprotected peptides and peptide mixtures bearing differentially loaded side chains by native chemical ligation reactions conducted in aqueous buffer. Uptake into human HeLa cells was correlated with the overall surface charge and the ζ potentials of the peptide–polymer conjugates. Most notable were the differential effects found for various multivalent peptide–polymer conjugates containing arginine residues. Although positive ζ potentials were required for cellular uptake of the peptide–polymer conjugates, this sole charge effect was strongly dominated by the effect exerted by the relative distribution of arginine residues. Polymers conjugated with nona‐arginine peptides were over‐proportionally taken up, relative to their surface charge, compared to polymers with random distribution of single arginine residues. In view of these findings, peptide–polymer compositions suitable for efficient cellular uptake with negligible toxicity at polymer concentrations relevant for intracellular functional studies were determined.
A Single Mutation at the Ferredoxin Binding Site of P450 Vdh Enables Efficient Biocatalytic Production of 25‐Hydroxyvitamin D3
Authors: Yasutake Yoshiaki , Nishioka Taiki , Imoto Noriko , Tamura Tomohiro
Published: October 2013

Vitamin D3 hydroxylase (Vdh) from Pseudonocardia autotrophica is a cytochrome P450 monooxygenase that catalyzes the two‐step hydroxylation of vitamin D3 (VD3) to produce 25‐hydroxyvitamin D3 (25(OH)VD3) and 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2VD3). These hydroxylated forms of VD3 are useful as pharmaceuticals for the treatment of conditions associated with VD3 deficiency and VD3 metabolic disorder. Herein, we describe the creation of a highly active T107A mutant of Vdh by engineering the putative ferredoxin‐binding site. Crystallographic and kinetic analyses indicate that the T107A mutation results in conformational change from an open to a closed state, thereby increasing the binding affinity with ferredoxin. We also report the efficient biocatalytic synthesis of 25(OH)VD3, a promising intermediate for the synthesis of various hydroxylated VD3 derivatives, by using nisin‐treated Rhodococcus erythropolis cells containing VdhT107A. The gene‐expression cassette encoding Bacillus megaterium glucose dehydrogenase‐IV was inserted into the R. erythropolis chromosome and expressed to avoid exhaustion of NADH in a cytoplasm during bioconversion. As a result, approximately 573 μg mL−1 25(OH)VD3 was successfully produced by a 2 h bioconversion.
Mycobacterial Phenolic Glycolipids with a Simplified Lipid Aglycone Modulate Cytokine Levels through Toll‐Like Receptor 2
Authors: Elsaidi Hassan R. H. , Barreda Daniel R. , Cairo Christopher W. , Lowary Todd L.
Published: October 2013

Phenolic glycolipids (PGLs) are virulence factors present in the cell walls of many pathogenic mycobacteria. PGLs have been implicated in various aspects of mycobacterial disease, but there are limited structure–activity data available for these molecules. We report here the preparation of seven synthetic PGL analogues, differing from the native compounds in the replacement of the complex phenolic lipid moiety with a p‐methoxyphenyl group. The ability of these compounds to stimulate or inhibit the production of cytokines (TNF‐α, IL‐1β, IL‐6, MCP‐1) and nitric oxide (NO) was then evaluated by ELISA‐based assays. None of the compounds stimulated the production of these biological signalling molecules. In contrast, they each displayed concentration‐dependent inhibitory activity, related to the methylation pattern of the molecule and mediated by Toll‐like receptor 2. Additional studies revealed that native PGL‐I from Mycobacterium leprae and a synthetic PGL‐I analogue containing a simplified lipid domain had enhanced inhibitory activities relative to the corresponding analogues containing the p‐methoxyphenyl aglycone; however, the natural lipid phenolthiocerol was only weakly active. These studies reveal that synthetic molecules of this type can be used as probes for PGL function. Moreover, their ease of synthesis relative to the natural glycolipids, as well as their more favourable aqueous solubility, should allow for more thorough structure–activity relationship studies.
Position of Cu Atoms at the Pt(111) Electrode Surfaces Controls Electrosorption of (H)SO4(2)− from H2SO4 Electrolytes
Authors: Tymoczko Jakub , Schuhmann Wolfgang , Bandarenka Aliaksandr S.
Published: October 2013

Selective positioning of monolayer amounts of foreign atoms at the surface and subsurface regions of metal electrodes is a promising way to fine‐tune the properties of the electrode/electrolyte interface. The latter is critical as it largely governs the adsorption of electrolyte components and reaction intermediates and, therefore, controls many key electrocatalytic processes. Using model Pt(111) single‐crystal electrodes, we demonstrate how the relative position of Cu atoms at the surface drastically changes the adsorption energies for (bi)sulfate anions. Our measurements involve pseudomorphic overlayers of Cu on Pt(111) as well as Cu–Pt(111) surface and sub‐surface alloys, where Cu atoms were located either in the first or in the second atomic layers of Pt, respectively. In the case of Cu–Pt(111) surface alloys, specific adsorption of the anions starts earlier compared to the unmodified Pt(111) surface. In contrast, placing Cu atoms into the second atomic layer weakens the binding between the surface and the anions. Surprisingly, Cu pseudomorphic overlayers do not reveal any specific adsorption of (bi)sulfates (within the region of the overlayer stability). Taking into account that electrified interfaces between Pt(111) electrodes and sulfate‐containing electrolytes often play the role of benchmark systems in fundamental physico‐chemical and, particularly, electrocatalytic studies, our findings demonstrate a promising and relatively easy route of tuning the properties of these interfaces.
The Formation and Role of Oxide Layers on Pt during Hydrazine Oxidation in Protic Ionic Liquids
Authors: Walsh Darren A. , Ejigu Andinet , Muhammad Sayyar , Licence Peter
Published: October 2013

The electrochemistry of platinum is studied in the protic ionic liquids dimethylethylammonium trifluoromethanesulfonate, diethylmethylammonium trifluoromethanesulfonate and diethylmethylammonium bis(trifluoromethanesulfonyl)imide. Oxide layers form on platinum due to trace water oxidation in the ionic liquids at potentials of about 1.0 V and the oxide growth kinetics change as the potential increases Above 60 °C, multilayers of oxide form in each ionic liquid at high potentials. The hydrazine oxidation reaction was used as a probe of the reactivity of the oxide layers and significant differences in the behaviour of the [TfO]−‐based ionic liquids and [dema][Tf2N] are observed during hydrazine oxidation. Specifically, significant “activation” of the Pt electrode towards hydrazine oxidation is observed in the [TfO]−‐based liquids whereas the electrode appears to be poisoned rapidly in [dema][Tf2N]. The electrochemically formed oxide layers are sensitive to the presence of hydrazine dissolved in dimethylethylammonium trifluoromethanesulfonate and immersion of the “activated” oxide‐coated Pt in a hydrazine/ionic liquid solution for extended periods of time results in deactivation of the platinum surface.
Biotin‐Labeled Electropolymerized Network of Gold Nanoparticles for Amperometric Immunodetection of Human Fibrinogen
Authors: Díez Paula , Gamella María , Martínez‐Ruíz Paloma , Lanzone Valentina , Sánchez Alfredo , Sánchez Enrique , Garcinuño Belit , Villalonga Reynaldo , Pingarrón José M.
Published: October 2013

Water‐soluble gold nanoparticles (3.1±0.6 nm) with polymerization ability and affinity to streptavidin are prepared by reducing HAuCl4 in the presence of the capping ligands 2‐mercaptoethanesulfonic acid, biotin–cysteamine, and p‐aminothiophenol. This colloid, HAuCl4, is used to modify gold electrodes by forming a 3D electropolymerized network of bis‐aniline‐cross‐linked nanoparticles on the metal surface. The modified electrode is used as a scaffold for the assembly of an amperometric immunosensor system to detect human fibrinogen. The immunosensor shows excellent analytical characteristics, with a dynamic range of detection between 0.018 and 2.208 μg mL−1, a detection limit of 4 ng mL−1, and a half‐maximal inhibitory concentration (IC50) of 177 ng mL−1. The immunosensor is markedly stable, retaining full analytical capacity after 45 days of storage at 4 °C.
Investigating Spectral Characteristics and Spatial Variability of Dissolved Organic Matter Leached from Wetland in Semi‐Arid Region to Differentiate Its Sources and Fate
Authors: Guo Xu‐Jing , Li Qiang , Jiang Jin‐Yuan , Dai Ben‐Lin
Published: October 2013

Dissolved organic matter (DOM) collected from different sampling sites in Lake Wuliangsuhai (Inner Mongolia Autonomous Region of China) was investigated using UV–Vis absorption and fluorescence spectroscopy. The three indices, SUVA280 and two spectral slopes (S275–295 and S350–400), were used to detect the change in the aromatic structure of DOM. DOM aromaticity was lower at sites W1 and W3, where industrial wastewater and domestic sewage, and agricultural drainage, contributed respectively. The humification index also indicated a low humification degree at sites W1 and W3, and high humification degree in other sites with relatively better water quality. Fluorescence regional integration (FRI) analysis has been used to quantitatively analyse fluorescence excitation–emission matrix spectra. The results showed that external contaminants can influence the distribution of Pi,n values from the FRI analysis. Serious pollution area obtained a relatively high Pp value. A significant negative correlation between Ph/Pp and f450/500 indicated the terrestrial or autochthonous sources of DOM. Therefore, the spectroscopic techniques combined with regional integration analysis can be used as a useful tool for investigating and assessing the lake ecological environment.
Probing Binding and Cellular Activity of Pyrrolidinone and Piperidinone Small Molecules Targeting the Urokinase Receptor
Authors: Mani Timmy , Liu Degang , Zhou Donghui , Li Liwei , Knabe William Eric , Wang Fang , Oh Kyungsoo , Meroueh Samy O.
Published: October 2013

The urokinase receptor (uPAR) is a cell‐surface protein that is part of an intricate web of transient and tight protein interactions that promote cancer cell invasion and metastasis. Here, we evaluate the binding and biological activity of a new class of pyrrolidinone and piperidinone compounds, along with derivatives of previously‐identified pyrazole and propylamine compounds. Competition assays revealed that the compounds displace a fluorescently labeled peptide (AE147‐FAM) with inhibition constant (Ki) values ranging from 6 to 63 μM. Structure‐based computational pharmacophore analysis followed by extensive explicit‐solvent molecular dynamics (MD) simulations and free energy calculations suggested the pyrazole‐based and piperidinone‐based compounds adopt different binding modes, despite their similar two‐dimensional structures. In cells, pyrazole‐based compounds showed significant inhibition of breast adenocarcinoma (MDA‐MB‐231) and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but piperidinone‐containing compounds exhibited no cytotoxicity even at concentrations of 100 μM. One pyrazole‐based compound impaired MDA‐MB‐231 invasion, adhesion, and migration in a concentration‐dependent manner, while the piperidinone inhibited only invasion. The pyrazole derivative inhibited matrix metalloprotease‐9 (gelatinase) activity in a concentration‐dependent manner, while the piperidinone showed no effect suggesting different mechanisms for inhibition of cell invasion. Signaling studies further highlighted these differences, showing that pyrazole compounds completely inhibited ERK phosphorylation and impaired HIF1α and NF‐κB signaling, while pyrrolidinones and piperidinones had no effect. Annexin V staining suggested that the effect of the pyrazole‐based compound on proliferation was due to cell killing through an apoptotic mechanism. The compounds identified represent valuable leads in the design of further derivatives with higher affinities and potential probes to unravel the protein–protein interactions of uPAR.