Fluctuation symmetries for work and heat

We consider a particle dragged through a medium at constant temperature as described by a Langevin equation with a time-dependent potential. The time-dependence is specified by an external protocol. We give conditions on potential and protocol under which the dissipative work satisfies an exact symmetry in its fluctuations for all times. We also present counter examples to that exact fluctuation symmetry when our conditions are not satisfied. Finally, we consider the dissipated heat which differs from the work by a temporal boundary term. We explain when and why there can be a correction to the standard fluctuation theorem due to the unboundedness of that temporal boundary. However, the corrected fluctuation symmetry has again a general validity.Comment: 10 pages, 4 figures (v2: minor typographic corrections

Household food security status in South Africa

The Human Sciences Research Council has established a policy research initiative to monitor household food security and to identify and evaluate policy options. In this special edition, a selection of articles from this project is assembled. While deep chronic hunger has fallen with the expansion of the social grants, under-nutrition is a very serious and widespread challenge. This special edition draws together the best available evidence on household food security with the aim of stimulating wider debate.food security, social grants, smallholder and subsistence production, poverty, Consumer/Household Economics,

Identification of long non-coding RNAs involved in neuronal development and intellectual disability

Recently, exome sequencing led to the identification of causal mutations in 16–31% of patients with intellectual disability (ID), leaving the underlying cause for many patients unidentified. In this context, the noncoding part of the human genome remains largely unexplored. For many long non-coding RNAs (lncRNAs) a crucial role in neurodevelopment and hence the human brain is anticipated. Here we aimed at identifying lncRNAs associated with neuronal development and ID. Therefore, we applied an integrated genomics approach, harnessing several public epigenetic datasets. We found that the presence of neuron-specific H3K4me3 confers the highest specificity for genes involved in neurodevelopment and ID. Based on the presence of this feature and GWAS hits for CNS disorders, we identified 53 candidate lncRNA genes. Extensive expression profiling on human brain samples and other tissues, followed by Gene Set Enrichment Analysis indicates that at least 24 of these lncRNAs are indeed implicated in processes such as synaptic transmission, nervous system development and neurogenesis. The bidirectional or antisense overlapping orientation relative to multiple coding genes involved in neuronal processes supports these results. In conclusion, we identified several lncRNA genes putatively involved in neurodevelopment and CNS disorders, providing a resource for functional studies

Learning Interpretable Models Through Multi-Objective Neural Architecture Search

Monumental advances in deep learning have led to unprecedented achievements across a multitude of domains. While the performance of deep neural networks is indubitable, the architectural design and interpretability of such models are nontrivial. Research has been introduced to automate the design of neural network architectures through neural architecture search (NAS). Recent progress has made these methods more pragmatic by exploiting distributed computation and novel optimization algorithms. However, there is little work in optimizing architectures for interpretability. To this end, we propose a multi-objective distributed NAS framework that optimizes for both task performance and introspection. We leverage the non-dominated sorting genetic algorithm (NSGA-II) and explainable AI (XAI) techniques to reward architectures that can be better comprehended by humans. The framework is evaluated on several image classification datasets. We demonstrate that jointly optimizing for introspection ability and task error leads to more disentangled architectures that perform within tolerable error.Comment: 14 pages main text, 5 pages references, 17 pages supplementa

De Novo Proteins Designed From Evolutionary Principles

Protein engineering has rapidly developed into a powerful method for the optimization, alteration, and creation of protein functions. Current protein engineering methods fall into the category of either high-throughput directed evolution techniques, or engineering through the use of computational models of protein structure. Despite significant innovation in both of these categories, neither is capable of handling the most difficult and desirable protein engineering goals. The combination of these two categories is an area of active research, and the development and testing of combination methods is the focus of this dissertation. Chapters 2 and 3 describe the development of a computational framework for de novo protein design called SEWING (Structural Extension WIth Native-fragment Graphs). In contrast to existing methods of de novo design, which attempt to design proteins that match a designer-supplied target topology, SEWING generates large numbers of diverse protein structures. We show that this strategy is highly effective at creating diverse helical backbones. Experimental characterization of SEWING designs shows that the experimental structures match the design models with sub-angstrom root mean square deviation (RMSD). Chapter 3 extends this methodology to the creation of protein interfaces. Using this method, several de novo designed proteins are created that bind their designated target. Chapter 4 describes the combination of directed evolution and computational modeling through the improvement of directed evolution techniques. In this chapter, a web tool called SwiftLib is developed, which allows rapid generation of degenerate codon libraries. SwiftLib allows protein engineers to determine optimal degenerate codon primers for the incorporation of desired sequences, such as sequence profiles generated from computational modeling and evolutionary data. Together, these chapters outline the creation of tools for the engineering of protein functions, and provide additional evidence that computational modeling and evolutionary principles can be combined for the improvement of protein engineering methods.Doctor of Philosoph

Current and future directions in frailty research.

The concept of frailty has been evolving dramatically for the past 30 years. Through its evolution, a variety of single and multidimensional models have been used to describe frailty. This article reviews the current literature related to the defining dimensions of frailty and identifies the gaps in the literature requiring additional research. A detailed literature review was performed to identify key dimensions and models currently being used to define frailty, classify interventions that have been developed to reverse frailty, and identify potential areas for future research within this field. Despite the large body of research defining the dimensions of frailty, no consensus exists on a comprehensive, operational definition. A standardized definition will be critical to design effective interventions at earlier stages along the continuum of frailty and interpret findings from evaluation studies. Identified gaps in the literature include studies supporting the utility of expanding the definition of frailty to incorporate social determinants, studies evaluating the role of obesity in the development of frailty, and the need for longitudinal studies for defining the pathways to developing frailty. This review highlights the need for an accurate definition of frailty and for longitudinal research to explore the development of frailty and evaluate the effectiveness of the frailty reversal interventions that may avert or delay adverse outcomes within this susceptible population. These future research needs are discussed within the context of the growing pressures to bring down health care costs, and the role of comparative effectiveness research and cost-effectiveness research in identifying interventions with the potential to help slow the growth of health care spending among the elderly

Super-orbital re-entry in Australia - laboratory measurement, simulation and flight observation

There are large uncertainties in the aerothermodynamic modelling of super-orbital re-entry which impact the design of spacecraft thermal protection systems (TPS). Aspects of the thermal environment of super-orbital re-entry flows can be simulated in the laboratory using arc- and plasma jet facilities and these devices are regularly used for TPS certification work [5]. Another laboratory device which is capable of simulating certain critical features of both the aero and thermal environment of super-orbital re-entry is the expansion tube, and three such facilities have been operating at the University of Queensland in recent years[10]. Despite some success, wind tunnel tests do not achieve full simulation, however, a virtually complete physical simulation of particular re-entry conditions can be obtained from dedicated flight testing, and the Apollo era FIRE II flight experiment [2] is the premier example which still forms an important benchmark for modern simulations. Dedicated super-orbital flight testing is generally considered too expensive today, and there is a reluctance to incorporate substantial instrumentation for aerothermal diagnostics into existing missions since it may compromise primary mission objectives. An alternative approach to on-board flight measurements, with demonstrated success particularly in the ‘Stardust’ sample return mission, is remote observation of spectral emissions from the capsule and shock layer [8]. JAXA’s ‘Hayabusa’ sample return capsule provides a recent super-orbital reentry example through which we illustrate contributions in three areas: (1) physical simulation of super-orbital re-entry conditions in the laboratory; (2) computational simulation of such flows; and (3) remote acquisition of optical emissions from a super-orbital re entry event