A novel strategy for the targeted analysis of protein and peptide metabolites

The detection and quantitation of exogenously administered biological macromolecules (e.g. vaccines, peptide and protein therapeutics) and their metabolites is frequently complicated by the presence of a complex endogenous mixture of closely related compounds. We describe a method that incorporates stable isotope labeling of the compound of interest allowing the selective screening of the intact molecule and all metabolites using a modified precursor ion scan. This method involves monitoring the low molecular weight fragment ions produced during MS/MS that distinguish isotopically labelled material from related endogenous compounds. All isotopically labelled substances can be selected using this scanning technique for further analysis whilst other unlabelled and irrelevant substances are ignored. The potential for this technique to be used in metabolism and pharmacokinetic experiments is discussed with specific examples looking at the metabolism of α-synuclein in serum and the brain

Determining eigenstates and thermal states on a quantum computer using quantum imaginary time evolution

The accurate computation of Hamiltonian ground, excited, and thermal states on quantum computers stands to impact many problems in the physical and computer sciences, from quantum simulation to machine learning. Given the challenges posed in constructing large-scale quantum computers, these tasks should be carried out in a resource-efficient way. In this regard, existing techniques based on phase estimation or variational algorithms display potential disadvantages; phase estimation requires deep circuits with ancillae, that are hard to execute reliably without error correction, while variational algorithms, while flexible with respect to circuit depth, entail additional high-dimensional classical optimization. Here, we introduce the quantum imaginary time evolution and quantum Lanczos algorithms, which are analogues of classical algorithms for finding ground and excited states. Compared to their classical counterparts, they require exponentially less space and time per iteration, and can be implemented without deep circuits and ancillae, or high-dimensional optimization. We furthermore discuss quantum imaginary time evolution as a subroutine to generate Gibbs averages through an analog of minimally entangled typical thermal states. Finally, we demonstrate the potential of these algorithms via an implementation using exact classical emulation as well as through prototype circuits on the Rigetti quantum virtual machine and Aspen-1 quantum processing unit.Comment: 18 pages, 7 figures; improved figures and tex

Kinetics of antigen expression and epitope presentation during virus infection

Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.NHMRC (National Health and Medical Research Council of Australia

All-Electrical Skyrmionic Bits in a Chiral Magnetic Tunnel Junction

Topological spin textures such as magnetic skyrmions hold considerable promise as robust, nanometre-scale, mobile bits for sustainable computing. A longstanding roadblock to unleashing their potential is the absence of a device enabling deterministic electrical readout of individual spin textures. Here we present the wafer-scale realization of a nanoscale chiral magnetic tunnel junction (MTJ) hosting a single, ambient skyrmion. Using a suite of electrical and multi-modal imaging techniques, we show that the MTJ nucleates skyrmions of fixed polarity, whose large readout signal - 20-70% relative to uniform states - corresponds directly to skyrmion size. Further, the MTJ exploits complementary mechanisms to stabilize distinctly sized skyrmions at zero field, thereby realizing three nonvolatile electrical states. Crucially, it can write and delete skyrmions using current densities 1,000 times lower than state-of-the-art. These results provide a platform to incorporate readout and manipulation of skyrmionic bits across myriad device architectures, and a springboard to harness chiral spin textures for multi-bit memory and unconventional computing.Comment: 8 pages, 5 figure

Defining the 'Social' in 'Social Entrepreneurship': Altruism and Entrepreneurship

Abstract. What is social entrepreneurship? In, particular, what’s so social about it? Understanding what social entrepreneurship is enables researchers to study the phenomenon and policy-makers to design measures to encourage it. However, such an understanding is lacking partly because there is no universally accepted definition of entrepreneurship as yet. In this paper, we suggest a definition of social entrepreneurship that intuitively accords with what is generally accepted as entrepreneurship and that captures the way in which entrepreneurship may be altruistic. Based on this we provide a taxonomy of social entrepreneurship and identify a number of real cases from Asia illustrating the different forms it could take. Keywords: social entrepreneurship, definition, taxonomy, altruism Social entrepreneurship is a concept that has captured the imagination of many researchers and policy-makers in recent years. Social entrepreneurship suggests that entrepreneurship may be aimed at benefiting society rather than merely maximising individual profits. It appears to promise an altruistic form of capitalism that does not evaluate all human activities in business terms. It enables a bridge to be built between enterprise and benevolence (Roberts and Woods, 2005). The history of the term ‘social entrepreneurship ’ can be traced to the publication of a Demos thinktank report entitled The Rise of the Social Entrepreneur (Leadbeater, 1997) in the United Kingdom and probably a little earlier in the United States to the publication of New Social Entrepreneurs by the Roberts Foundation (Emerson and Twerksy, 1996). Prior to this, some of the activities under the rubric of social entrepreneurship were either termed ‘community development ’ or those in ‘social purpose organizations’. There is considerable use of the term in popular literature although academic literature on it is thin (Taylor, Hobbs, Nilsson, O’Halloran and Preisser, 2000). Recent interest saw a call for papers for a special issue on social entrepreneurship (Honig an

Configurational Thermodynamics of Alloyed Nanoparticles with Adsorbates

Changes in the chemical configuration of alloyed nanoparticle (NP) catalysts induced by adsorbates under working conditions, such as reversal in core–shell preference, are crucial to understand and design NP functionality. We extend the cluster expansion method to predict the configurational thermodynamics of alloyed NPs with adsorbates based on density functional theory data. Exemplified with PdRh NPs having O-coverage up to a monolayer, we fully detail the core–shell behavior across the entire range of NP composition and O-coverage with quantitative agreement to in situ experimental data. Optimally fitted cluster interactions in the heterogeneous system are the key to enable quantitative Monte Carlo simulations and design