Synthesis and biological properties of β-turned Aβ31-35 constrained analogues

A series of constrained pentapeptide analogues of the fragment Aβ31–35 has been prepared using solid phase synthesis protocols. The results of conformational studies and surface plasmon resonance (SPR) experiments seem to indicate that the affinity of these constrained analogues for immobilized Aβ25–35 peptide could be related to their ability to adopt a Leu34N-Ile31O β-turn-like folded conformation.This work has been supported by the Spanish Ministry of Education and Science (SAF 2006-01205) and the Comunidad de Madrid (GR/SAL/0846/2004). Work at Universitat Pompeu Fabra was supported by Generalitat de Catalunya (SGR2005-00494). We thank Dr. M.L. Jimeno and Dr. M. Martı´n-Martı´nez for NMR and molecular modeling studies, respectively. J.L.B. and C.J.C. thank the Spanish Ministry of Education and Science for predoctoral fellowships

Disposition of Federally Owned Surpluses

PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions

Top-quark physics at the CLIC electron-positron linear collider

Abstract The Compact Linear Collider (CLIC) is a proposed future high-luminosity linear electron-positron collider operating at three energy stages, with nominal centre-of-mass energies $$\sqrt{s}$$ s = 380 GeV, 1.5 TeV, and 3 TeV. Its aim is to explore the energy frontier, providing sensitivity to physics beyond the Standard Model (BSM) and precision measurements of Standard Model processes with an emphasis on Higgs boson and top-quark physics. The opportunities for top-quark physics at CLIC are discussed in this paper. The initial stage of operation focuses on top-quark pair production measurements, as well as the search for rare flavour-changing neutral current (FCNC) top-quark decays. It also includes a top-quark pair production threshold scan around 350 GeV which provides a precise measurement of the top-quark mass in a well-defined theoretical framework. At the higher-energy stages, studies are made of top-quark pairs produced in association with other particles. A study of t̄tH production including the extraction of the top Yukawa coupling is presented as well as a study of vector boson fusion (VBF) production, which gives direct access to high-energy electroweak interactions. Operation above 1 TeV leads to more highly collimated jet environments where dedicated methods are used to analyse the jet constituents. These techniques enable studies of the top-quark pair production, and hence the sensitivity to BSM physics, to be extended to higher energies. This paper also includes phenomenological interpretations that may be performed using the results from the extensive top-quark physics programme at CLIC.</jats:p

Detector Technologies for CLIC

The Compact Linear Collider (CLIC) is a high-energy high-luminosity linear electron-positron collider under development. It is foreseen to be built and operated in three stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. It offers a rich physics program including direct searches as well as the probing of new physics through a broad set of precision measurements of Standard Model processes, particularly in the Higgs-boson and top-quark sectors. The precision required for such measurements and the specific conditions imposed by the beam dimensions and time structure put strict requirements on the detector design and technology. This includes low-mass vertexing and tracking systems with small cells, highly granular imaging calorimeters, as well as a precise hit-time resolution and power-pulsed operation for all subsystems. A conceptual design for the CLIC detector system was published in 2012. Since then, ambitious R&D programmes for silicon vertex and tracking detectors, as well as for calorimeters have been pursued within the CLICdp, CALICE and FCAL collaborations, addressing the challenging detector requirements with innovative technologies. This report introduces the experimental environment and detector requirements at CLIC and reviews the current status and future plans for detector technology R&D.Comment: 152 pages, 116 figures; published as CERN Yellow Report Monograph Vol. 1/2019; corresponding editors: Dominik Dannheim, Katja Kr\"uger, Aharon Levy, Andreas N\"urnberg, Eva Sickin

The Compact Linear Collider (CLIC) - 2018 Summary Report

The Compact Linear Collider (CLIC) is a TeV-scale high-luminosity linear $e^+e^-$ collider under development at CERN. Following the CLIC conceptual design published in 2012, this report provides an overview of the CLIC project, its current status, and future developments. It presents the CLIC physics potential and reports on design, technology, and implementation aspects of the accelerator and the detector. CLIC is foreseen to be built and operated in stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. CLIC uses a two-beam acceleration scheme, in which 12 GHz accelerating structures are powered via a high-current drive beam. For the first stage, an alternative with X-band klystron powering is also considered. CLIC accelerator optimisation, technical developments and system tests have resulted in an increased energy efficiency (power around 170 MW) for the 380 GeV stage, together with a reduced cost estimate at the level of 6 billion CHF. The detector concept has been refined using improved software tools. Significant progress has been made on detector technology developments for the tracking and calorimetry systems. A wide range of CLIC physics studies has been conducted, both through full detector simulations and parametric studies, together providing a broad overview of the CLIC physics potential. Each of the three energy stages adds cornerstones of the full CLIC physics programme, such as Higgs width and couplings, top-quark properties, Higgs self-coupling, direct searches, and many precision electroweak measurements. The interpretation of the combined results gives crucial and accurate insight into new physics, largely complementary to LHC and HL-LHC. The construction of the first CLIC energy stage could start by 2026. First beams would be available by 2035, marking the beginning of a broad CLIC physics programme spanning 25-30 years