37,129 research outputs found
Evaluation of the extended pre-school provision for vulnerable two year olds pilot programme: final report
No full textIn August 2006 the Scottish Government invited Glasgow, Dundee and North Ayrshire local authorities to take part in a £2 million Extended Pre-School Provision for Vulnerable 2 Year Olds Pilot Programme. The pilot programme was to run for a two year period with the key aim of providing positive preschool experiences one year early for vulnerable children and supporting their parents. Local authorities were encouraged to develop their own models of delivery within the broad aims of the project. A research team from the Department of Psychology, University of Strathclyde, headed by Dr Lisa Woolfson was contracted to carry out an evaluation of the programme in the second year of the pilot. The research study ran from April 2007 to September 2008 and evaluated children who participated in the pilot programme between August 2007 and June 2008, the second year of the pilot programme. Aims We aimed to explore the impact of the extended pilot programme on cognitive, social, emotional and behavioural developmental child outcomes, as well as the impact on participating parents. In addition we aimed to identify recruitment criteria and admission procedures used by the participating local authorities as well as staffing, numbers of children, attendance rates and practical issues around programme set-up and delivery
Fragment-linking peptide design yields a high-affinity ligand for microtubule-based transport
No full textSynthetic peptides are attractive candidates to manipulate protein-protein interactions inside the cell as they mimic natural interactions to compete for binding. However, protein-peptide interactions are often dynamic and weak. A challenge is to design peptides which make improved interactions with the target. Here, we devise a fragment-linking strategy - ‘mash-up’ design - to deliver a high-affinity ligand, KinTag, for the kinesin-1 motor. Using structural insights from natural micromolaraffinity cargo-adaptor ligands, we have identified and combined key binding features in a single, high-affinity ligand. An X-ray crystal structure demonstrates interactions as designed and reveals only a modest increase in interface area. Moreover, when genetically encoded, KinTag promotes transport of lysosomes with higher efficiency than natural sequences, revealing a direct link between motor-adaptor binding affinity and organelle transport. Together, these data demonstrate a fragment-linking strategy for peptide design and its application in a synthetic motor ligand to direct cellular cargo transport.<br/
De novo coiled-coil peptides as scaffolds for disrupting protein-protein interactions
No full textProtein-protein interactions (PPIs) play pivotal roles in the majority of biological processes. Therefore, improved approaches to target and disrupt PPIs would provide tools for chemical biology and leads for therapeutic development. PPIs with α-helical components are appealing targets given that the secondary structure is well understood and can be mimicked or stabilised to render small-molecule and constrained-peptide-based inhibitors. Here we present a strategy to target α-helix-mediated PPIs that exploits de novo coiled-coil assemblies and test this using the MCL-1/NOXA-B PPI. First, computational alanine scanning is used to identify key α-helical residues from NOXA-B that contribute to the interface. Next, these residues are grafted onto the exposed surfaces of de novo designed homodimeric or heterodimeric coiled-coil peptides. The resulting synthetic peptides selectively inhibit a cognate MCL-1/BID complex in the mid-nM range. Furthermore, the heterodimeric system affords control as inhibition occurs only when both the grafted peptide and its designed partner are present. This establishes proof of concept for exploiting peptides stabilised in de novo coiled coils as inhibitors of PPIs. This dependence on supramolecular assembly introduces new possibilities for regulation and control
1ST MEASUREMENT OF GAMMA(D(S)(+)-]MU+NU)/GAMMA(D(S)(+)-]PHI-PI+)
No full textComplete Author List:
ACOSTA D, ATHANAS M, MASEK G, PAAR H, BEAN A, GRONBERG J, KUTSCHKE R, MENARY S, MORRISON RJ, NAKANISHI S, NELSON HN, NELSON TK, RICHMAN JD, RYD A, TAJIMA H, SCHMIDT D, SPERKA D, WITHERELL MS, PROCARIO M, YANG S, BALEST R, CHO K, DAOUDI M, FORD WT, JOHNSON DR, LINGEL K, LOHNER M, RANKIN P, SMITH JG, ALEXANDER JP, BEBEK C, BERKELMAN K, BESSON D, BROWDER TE, CASSEL DG, CHO HA, COFFMAN DM, DRELL PS, EHRLICH R, GALIK RS, GARCIASCIVERES M, GEISER B, GITTELMAN B, GRAY SW, HARTILL DL, HELTSLEY BK, JONES CD, JONES SL, KANDASWAMY J, KATAYAMA N, KIM PC, KREINICK DL, LUDWIG GS, MASUI J, MEVISSEN J, MISTRY NB, NG CR, NORDBERG E, OGG M, PATTERSON JR, PETERSON D, RILEY D, SALMAN S, SAPPER M, WORDEN H, WURTHWEIN F, AVERY P, FREYBERGER A, RODRIGUEZ J, STEPHENS R, YELTON J, CINABRO D, HENDERSON S, KINOSHITA K, LIU T, SAULNIER M, SHEN F, WILSON R, YAMAMOTO H, ONG B, SELEN M, SADOFF AJ, AMMAR R, BALL S, BARINGER P, COPPAGE D, COPTY N, DAVIS R, HANCOCK N, KELLY M, KWAK N, LAM H, KUBOTA Y, LATTERY M, NELSON JK, PATTON S, PERTICONE D, POLING R, SAVINOV V, SCHRENK S, WANG R, ALAM MS, KIM IJ, NEMATI B, ONEILL JJ, SEVERINI H, SUN CR, ZOELLER MM, CRAWFORD G, DAUBENMIER CM, FULTON R, FUJINO D, GAN KK, HONSCHEID K, KAGAN H, KASS R, LEE J, MALCHOW R, MORROW F, SKOVPEN Y, SUNG M, WHITE C, WHITMORE J, WILSON P, BUTLER F, FU X, KALBFLEISCH G, LAMBRECHT M, ROSS WR, SKUBIC P, SNOW J, WANG PL, WOOD M, BORTOLETTO D, BROWN DN, FAST J, MCILWAIN RL, MIAO T, MILLER DH, MODESITT M, SCHAFFNER SF, SHIBATA EI, SHIPSEY IPJ, WANG PN, BATTLE M, ERNST J, KROHA H, ROBERTS S, SPARKS K, THORNDIKE EH, WANG CH, DOMINICK J, SANGHERA S, SHELKOV V, SKWARNICKI T, STROYNOWSKI R, VOLOBOUEV I, ZADOROZHNY P, ARTUSO M, HE D, GOLDBERG M, HORWITZ N, KENNETT R, MONETI GC, MUHEIM F, MUKHIN Y, PLAYFER S, ROZEN Y, STONE S, THULASIDAS M, VASSEUR G, ZHU G, BARTELT J, CSORNA SE, EGYED Z, JAIN V, SHELDON P, AKERIB DS, BARISH B, CHADHA M, CHAN S, COWEN DF, EIGEN G, MILLER JS, OGRADY C, URHEIM J, WEINSTEIN A
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Recommended from our members
Identifying idiolect in forensic authorship attribution: an n-gram textbite approach
No full textForensic authorship attribution is concerned with identifying authors of disputed or anonymous documents, which are potentially evidential in legal cases, through the analysis of linguistic clues left behind by writers. The forensic linguist “approaches this problem of questioned authorship from the theoretical position that every native speaker has their own distinct and individual version of the language [. . . ], their own idiolect” (Coulthard, 2004: 31). However, given the diXculty in empirically substantiating a theory of idiolect, there is growing concern in the Veld that it remains too abstract to be of practical use (Kredens, 2002; Grant, 2010; Turell, 2010). Stylistic, corpus, and computational approaches to text, however, are able to identify repeated collocational patterns, or n-grams, two to six word chunks of language, similar to the popular notion of soundbites: small segments of no more than a few seconds of speech that journalists are able to recognise as having news value and which characterise the important moments of talk. The soundbite oUers an intriguing parallel for authorship attribution studies, with the following question arising: looking at any set of texts by any author, is it possible to identify ‘n-gram textbites’, small textual segments that characterise that author’s writing, providing DNA-like chunks of identifying material
Gaps in intervals of N-expansions
No full textFor N ∈ N≥2 and α ∈ R such that 0 < α ≤ N − 1, the continued fraction map Tα: [α, α+1] → [α, α+1) is defined as Tα (x):= N/x−d(x), where d: [α, α+1] → N is defined by d(x):= ⌊N/x − α⌋. A maximal open interval (a, b) ⊂ Iα is called a gap of Iα if for almost every x ∈ Iα there is an n0 (x) ∈ N such that xn /∈ (a, b) for all n ≥ n0 . In this paper, all conditions are given in which Iα is gapless. For α =√N − 1 it is shown that the number of gaps is a finite, monotonically non-decreasing and unbounded function of N.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Applied Probabilit
Challenge in R&D Management : Tata Steel A Case Study
No full textThe purpose of R&D management is to promote innovation as
well as wealth creation. The paper traces the history of R&D managementhow it has changed from the first generation when only innovation was the main objective to the fifth generation where IT plays an important role. It is now necessary to understand the needs of market for conducting worthwhile research. The author shares his experience of R&D management at Tata Steel. The experience shows that by adopting judicious R&D strategy it is possible to face the challenges of reconciling innovation with wealth
creation is possible by a judicious R&D strategy
A 2 h periodic variation in the low-mass X-ray binary Ser X-1
No full textSpectroscopy of the low-mass X-ray binary Ser X-1 using the Gran Telescopio Canarias have revealed a ?2 h periodic variability that is present in the three strongest emission lines. We tentatively interpret this variability as due to orbital motion, making it the first indication of the orbital period of Ser X-1. Together with the fact that the emission lines are remarkably narrow, but still resolved, we show that a main-sequence K dwarf together with a canonical 1.4 M? neutron star gives a good description of the system. In this scenario, the most likely place for the emission lines to arise is the accretion disc, instead of a localized region in the binary (such as the irradiated surface or the stream-impact point), and their narrowness is due instead to the low inclination (?10°) of Ser X-1
Measurement of the D+/- production asymmetry in 7 TeV pp collisions
No full textThe asymmetry in the production cross-section \sigma of D+/- mesons, A_P = (\sigma(D+) - \sigma(D-))/(\sigma(D+) + \sigma(D-)), is measured in bins of pseudorapidity \eta and transverse momentum p_T within the acceptance of the LHCb detector. The result is obtained with a sample of D+ -> K_S pi+ decays corresponding to an integrated luminosity of 1.0 fb^-1, collected in pp collisions at a centre of mass energy of 7 TeV at the Large Hadron Collider. When integrated over the kinematic range 2.0 K_S pi+ decay is negligible. No significant dependence on \eta or p_T is observed
- …
