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The ALFA-tag is a highly versatile tool for nanobody-based bioscience applications

Specialized epitope tags are widely used for detecting, manipulating or purifying proteins, but often their versatility is limited. Here, we introduce the ALFA-tag, a rationally designed epitope tag that serves a remarkably broad spectrum of applications in life sciences while outperforming established tags like the HA-, FLAG®- or myc-tag. The ALFA-tag forms a small and stable α-helix that is func

Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases : A systematic literature review for the 2019 update of EULAR recommendations

Aim To present a systematic literature review (SLR) on efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD), aiming to provide a basis for updating the EULAR evidence-based recommendations. Methods An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Outcome was determined by

The Gaia-ESO survey: Calibrating a relationship between age and the [C/N] abundance ratio with open clusters?

Context. In the era of large high-resolution spectroscopic surveys such as Gaia-ESO and APOGEE, high-quality spectra can contribute to our understanding of the Galactic chemical evolution by providing abundances of elements that belong to the different nucleosynthesis channels, and also by providing constraints to one of the most elusive astrophysical quantities: stellar age. Aims. Some abundance

Alignment limit in three Higgs-doublet models

The LHC Higgs data are showing a gradual inclination towards the standard model (SM) result, and realization of a SM-like limit becomes essential for beyond the SM scenarios to survive. Considering the accuracy that can be achieved in future colliders, models beyond the standard model that acquire the alignment limit with a SM-like Higgs boson can surpass others in the long run. Using a convenient

Field Measurements for Verification of the Impact of Renovation and Maintenance Measures on Buildings : - regarding Energy Efficiency, Indoor Environment and Moisture Safety

Renovating the European building stock has for almost two decades been a matter of importance to the European Union. Reduction of energy use for existing buildings can be achieved through applying energy efficiency renovation measures. Besides this, there is quite a large renovation need in Sweden due to building materials and services reaching (or having passed) the end of their service life.IncoRenovating the European building stock has for almost two decades been a matter of importance to the European Union. Reduction of energy use for existing buildings can be achieved through applying energy efficiency renovation measures. Besides this, there is quite a large renovation need in Sweden due to building materials and services reaching (or having passed) the end of their service life.Inco

Ventilation measures for heritage office buildings in temperate climate for improvement of energy performance and IEQ

Heritage buildings are usually culturally protected as well as naturally ventilated. As such, it is difficult to control the airflow, which depends on the temperature outdoors as well as the wind. This causes issues with the thermal comfort and the indoor air quality. In this study, status determinations were conducted for 12 heritage buildings with offices, across Sweden. Field measurements on te

Discovery of a class of calcium sensing receptor positive allosteric modulators; 1-(benzothiazol-2-yl)-1-phenylethanols

1-(Benzothiazol-2-yl)-1-(4-chlorophenyl)ethanol (1) was identified as a positive allosteric modulator (PAM) of the CaSR in a functional cell-based assay. This compound belongs to a class of compounds that is structurally distinct from other known positive allosteric modulators, for example, the phenylalkylamines cinacalcet, a modified analog (13) potently suppressed parathyroid hormone (PTH) relea

Complete regioselective addition of grignard reagents to pyrazine N-oxides, toward an efficient enantioselective synthesis of substituted piperazines

(Figure presented) A conceptually new one-pot strategy for the synthesis of protected substituted piperazines via the addition of Grignard reagents to pyrazine N-oxides is presented. This strategy is high yielding (33-91% over three steps), step-efficient, and fast. The synthesized N,N-diprotected piperazines are convenient to handle and allow for orthogonal deprotection at either nitrogen for sel

Discovery of selective nonpeptidergic neuropeptide FF2 receptor agonists

We report the discovery and initial characterization of a novel class of selective NPFF2 agonists. HTS screening using R-SAT, a whole cell based functional assay, identified a class of aryliminoguanidines as NPFF1 and NPFF2 ligands. Subsequent optimization led to molecules exhibiting selective NPFF2 agonistic activity. Systemic administration showed that selective NPFF2 agonists (1 and 3) are acti

Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators

Herein we describe the discovery of ACP-105 (1), a novel and potent nonsteroidal selective androgen receptor modulator (SARM) with partial agonist activity relative to the natural androgen testosterone. Compound 1 was developed from a series of compounds found in a HTS screen using the receptor selection and amplification technology (R-SAT). In vivo, 1 improved anabolic parameters in a 2-week chro

Temporary in situ aluminum and zinc tethering in Diels-Alder reactions

(formula presented) Temporary tethering using aluminum or zinc in Diels-Alder reactions made possible the use of otherwise "noncompatible" combinations of dienes and dienophiles, resulting in the one-step formation of substituted cyclohexene 1,2-bis-methanols. Excellent regioselectivity and also significant stereoselectivity were obtained.

Efficient Solution-Phase Parallel Synthesis of 4-Substituted N-Protected Piperidines

Practical conditions for the synthesis of 4-substituted N-protected piperidines through CuCN·2LiBr-catalyzed organozinc additions to 1-acylpyridinium salts and subsequent hydrogen-transfer hydrogenation have been established. The reaction sequence is performed at room temperature and provides 4-substituted N-protected piperidines in excellent overall yields without the isolation of intermediate di

Discovery of potent and selective small-molecule PAR-2 agonists

Proteinase activated receptor-2 plays a crucial role in a wide variety of conditions with a strong inflammatory component. We present the discovery and characterization of two structurally different, potent, selective, and metabolically stable small-molecule PAR-2 agonists. These ligands may be useful as pharmacological tools for elucidating the complex physiological role of the PAR-2 receptors as