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Engineered botulinum neurotoxin B with improved binding to human receptors has enhanced efficacy in preclinical models

Although botulinum neurotoxin serotype A (BoNT/A) products are common treatments for various disorders, there is only one commercial BoNT/B product, whose low potency, likely stemming from low affinity toward its human receptor synaptotagmin 2 (hSyt2), has limited its therapeutic usefulness. We express and characterize two full-length recombinant BoNT/B1 proteins containing designed mutations E119

Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes

Background: Sex differences are known to impact muscle phenotypes, metabolism, and disease risk. Skeletal muscle stem cells (satellite cells) are important for muscle repair and to maintain functional skeletal muscle. Here we studied, for the first time, effects of sex on DNA methylation and gene expression in primary human myoblasts (activated satellite cells) before and after differentiation int

Defining the Sharing Economy for Sustainability

(1) Background: The sharing economy has emerged as a phenomenon widely described by academic literature to promote more sustainable consumption practices such as access over ownership. However, there exists great semantic confusion within academic literature surrounding the term “sharing economy,” which threatens the realisation of its purported sustainability potential. (2) Objective: The aim of (1) Background: The sharing economy has emerged as a phenomenon widely described by academic literature to promote more sustainable consumption practices such as access over ownership. However, there exists great semantic confusion within academic literature surrounding the term “sharing economy,” which threatens the realisation of its purported sustainability potential. (2) Objective: The aim of

The importance of geographical distance to different types of R&D collaboration in the pharmaceutical industry

Innovation within companies is generated by a combination of different types of knowledge from external and geographically dispersed sources. Although the geographical dimension of collaboration has previously been investigated, studies have not distinguished between different types of knowledge involved in collaboration. This article analyses how the number of collaborations between pharmaceutica

The viscoelastic signature underpinning polymer deformation under shear flow

Entangled polymers are deformed by a strong shear flow. The shape of the polymer, called the form factor, is measured by small angle neutron scattering. However, the real-space molecular structure is not directly available from the reciprocal-space data, due to the phase problem. Instead, the data has to be fitted with a theoretical model of the molecule. We approximate the unknown structure using

A colorful death : A study of the social life of colors in Late Bronze Age grave goods

The study of burials can include, among other things, examinations of grave goods, architecture, osteological and organic remains, context and location, socio-religious and ritual importance, sacred landscape, socio-economic relevance, and so on. One area that has not been investigated in depth regarding the objects placed in the graves is the aspect of color: does their color in general or specifi

Addition of n-Alcohols Induces a Variety of Liquid-Crystalline Structures in Surfactant-Rich Cores of Dispersed Block Copolymer/Surfactant Nanoparticles

Poly(acrylamide)-b-complex salts made from a symmetric poly(acrylate-b-acrylamide) block copolymer, where the acrylate charges are neutralized by cationic surfactant counterions, form kinetically stable aqueous dispersions of hierarchical aggregates with a liquid-crystalline complex salt core and a diffuse hydrated shell. By the addition of suitable amounts of long-chain alcohols, such as octanol

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ABSTRACT Introduction: Scientists from many disciplines have studied population, church and burials from the Early Medieval churchyard Västerhus/Westerhus in Middle Sweden. Archaeology, anthropology, odontology and demography of this population have been investigated. The present project group has, above all, investigated teeth, bones and bone chemistry. But also many archaeological questions have

Pirqei deRabbi Eliezer : Structure, Coherence, Intertextuality

In Pirqei deRabbi Eliezer: Structure, Coherence, Intertextuality Katharina E. Keim offers a description of the literary character of Pirqei deRabbi Eliezer, an enigmatic work of the late-eighth-to-early-ninth centuries CE. Katharina E. Keim explores the work’s distinctive literary features through an analysis of its structure and coherence. These literary features, when taken together with the wor

Harnessing androgen receptor pathway activation for targeted alpha particle radioimmunotherapy of breast cancer

Purpose: The impact of androgen receptor (AR) activity Results: D-Norgestrel and DHT activated the AR pathway, in breast cancer biology is unclear. We characterized and while 17b-Estradiol did not. Competitive binding for AR tested a novel therapy to an AR-governed target in breast protein showed similar affinity between DHT and D-Norges-cancer. trel, indicating direct AR–ligand interaction. In vi

Uncertainty quantification, propagation and characterization by Bayesian analysis combined with global sensitivity analysis applied to dynamical intracellular pathway models

Motivation: Dynamical models describing intracellular phenomena are increasing in size and complexity as more information is obtained from experiments. These models are often over-parameterized with respect to the quantitative data used for parameter estimation, resulting in uncertainty in the individual parameter estimates as well as in the predictions made from the model. Here we combine Bayesia