1,721,348 research outputs found
Development of a novel two-hybrid system for the identification of cyclic peptide induced protein-protein association
No full textChemically-induced protein association is involved in key regulatory pathways throughout the body. Many natural products exert their downstream effect by the stabilisation of naturally occurring interactions, either by an allosteric effect or by the direct binding of two distinct protein partners. The targeting of these interactions by small-molecules is a relatively under developed field, with the inhibition of existing protein-protein interactions (PPIs) a more investigated target. One such method to investigate PPI inhibition is a bacterial reverse two-hybrid system (RTHS), which has been successfully coupled to a split-intein based library of cyclic peptides to identify novel inhibitors (split-intein circular ligation of peptides and proteins, SICLOPPS). Here, the existing RTHS technology was rebuilt to enable the screening of cyclic peptides for their ability to induce dimerisation of two target proteins.The well-studied mTOR-FKBP12 interaction, with heterodimerisation induced by the natural product rapamycin, was used to build and validate a novel two-hybrid system. This utilises the tetracycline repressor to reverse the transcriptional control from the RTHS, leading to a selectable phenotype upon dimerisation. Rapamycin addition successfully results in the association of these target proteins, leading to the downstream expression of two essential reporter genes and a fluorescent protein. This rapamycin-dependent interaction can be identified both by an agarbased growth assay, and a liquid media-based fluorescent assay.A large number of SICLOPPS libraries were screened with little success at replicating the action of brapamycin. The SICLOPPS technology was optimised and expanded, enabling an improved screening platform for the future
Supplement to The World Bank Economic Review
No full textThis volume contains the Papers and
Proceedings of the 26th Annual Bank Conference on
Development Economics (ABCDE) held on June 15–16, 2015, in
Mexico City. The theme of the conference was
"Productivity, Growth, and the Law," and it was
hosted jointly by the Bank of Mexico and the World Bank. The
2015 ABCDE Organizing Committee was composed of Kaushik Basu
(World Bank, Chair), Asli Demirguc¸-Kunt and Indermit Gill
(World Bank), Alberto Torres and Laura Juarez (Bank of
Mexico), and Andrew Foster (Brown University)
Structural fire performance of axially and rotationally restrained stainless steel columns
No full textPerformance of axially restrained carbon and stainless steel perforated beams at elevated temperatures
No full textThis article compares the fire performance of axially restrained perforated carbon and austenitic stainless steel composite beams with circular and rectangular web openings. Finite element models, validated against experimental tests from the literature, were used to perform parametric analysis. The beams were analysed under various levels of load ratio and axial restraint stiffness covering the ranges which may exist in practice. It is concluded that austenitic stainless steel perforated beams show a more ductile fire response compared to carbon steel beams of similar geometry. It is shown that despite stainless steel’s higher thermal expansion, the beams exhibit lower thermal-induced peak compressive forces than carbon steel beams giving rise to lower levels of thermal-induced compressive force on the adjacent cold structures. The load ratio was found to determine the relative survivability of stainless steel and carbon steel beams, where at load ratios lower than 0.6, stainless steel beams show superior fire resistance than their carbon steel counterparts. The article also assesses the applicability and accuracy of the Steel Construction Institute method for the design of carbon and stainless steel perforated beams, and recommendations for future improvements are made.</p
Timothy Edmunds - Anthony Foster - Andrew Cottey (eds.): The Challenge of Military Reform in Postcommunist Europe. Building the Professional Armed Forces
No full textTimothy Edmunds - Anthony Foster - Andrew Cottey (eds.): The Challenge of Military Reform in
Postcommunist Europe. Building the Professional Armed Forces. 1st ed. Palgrave, London 2002, 10
+ 260 s., ISBN 0-333-94621-9
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
A numerical investigation into stripping failure of bolt assemblies at elevated temperatures
No full textA detailed finite element (FE) study is presented investigating the factors affecting the failure modes of high strength and stainless steel bolt assemblies under tensile force at ambient and elevated temperatures. Axisymmetric FE models incorporating key behavioural aspects including surface interaction and damage modelling of steel at elevated temperatures were developed. In practice, stripping failure is generally undesired because it results in premature failure of the bolt which can deteriorate rotational capacity of connections and hence compromise the robustness of steel frames. Yet, stripping failure has not been previously investigated in the open literature. In this study, the examined stainless steel bolt assemblies displayed an outstanding ductile response even when stripping failure was observed. Parameters that can govern the failure modes of bolt assemblies at elevated temperatures include the thread length in the grip (Lt), and the relative strength and friction between the mating threads. At ambient temperature, stripping was observed at certain Lt lengths depending on the nut dimension deviation from the basic profile. The Lt stripping failure threshold reduces with temperature for high strength bolt assemblies while the value fluctuates without a discernible pattern for stainless steel types. Increasing the relative strength and friction coefficient can reduce the Lt length threshold, with the former having the greatest influence. It was also found that larger bolt sizes are more vulnerable to thread stripping failure
Selecting suitable bolt parameters to achieve ductility at elevated temperatures
No full textA detailed FE study is presented investigating the factors affecting failure modes of bolt assemblies under tensile force at ambient and elevated temperatures. Axissymmetric FE models incorporating important behavioural aspects including surface interaction and damage modelling were developed. Stripping failure is generally undesirable because it results in premature failure of the bolt, which can deteriorate the rotational capacity of connections and robustness of steel frames. The paper discusses how the thread length in the grip 퐿푡 can affect the failure mode of bolt assemblies at elevated temperatures. This paper concludes that at ambient temperature, stripping can occur at certain 퐿푡 length dependent upon the nut dimension deviation from the basic profile; this length reduces with temperature
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