Conditional protein rescue (CPR) by binding-induced protective shielding

The rational regulation of protein concentration remains an elusive problem in synthetic biology. Several strategies have been developed at the transcriptional level, but these suffer from suboptimal response kinetics due to slow turnover of any protein already synthesized. The direct fusion of degradation tags to a protein of interest (POI) results in rapid fluctuations in protein concentration, and several degradation tags have been developed that function conditionally on the presence of a small molecule. However, no solutions currently exist that allow the intracellular concentration of a POI to be regulated by the cellular environment. Please click Additional Files below to see the full abstract

Frogs and Feeling Communities:A Study in History of Emotions and Environmental History

This article offers an overview of some approaches from the history of emotions that environmental historians could employ in order to sharpen engagement with emotion, and applies some of these approaches to a long history of human–frog interactions, by way of example. We propose that emotions have played a key role in the constitution of human communities, as well as enabling or inhibiting particular kinds of human thoughts and actions in relation with the living planet. In tracing human–frog relations over time we tease apart the complex historic relationships between cultural frameworks, scientific expectations and conventions, and the texts and images emerging from these contexts, which operate explicitly or implicitly to train and discipline the emotional selves of human adults and children

Topology Optimization Algorithms for Additive Manufacturing

Topology optimization is a powerful free-form design tool that couples finite element analysis with mathematical programming to systematically design for any number of engineering problems. Additive manufacturing (AM), specifically 3D printing, is a manufacturing process where material is added through deposition or melting in a layer-by-layer fashion. Additively manufactured parts are `built' from the bottom up, allowing production of intricate designs without extra effort on the part of the engineer or technician -- complexity is often said to be `free'. This dissertation seeks to leverage the full potential of this burgeoning manufacturing technology by developing several new design algorithms based on topology optimization. These include multi-material projection methods appropriate for multiphase 3D printers, an overhang-prevention projection method capable of designing components that do not need sacrificial anchors in metal AM processes, and models for simultaneously optimizing topology and objects embedded in process. These algorithms are demonstrated on several design examples and shown to produce solutions with capabilities that exceed existing designs and/or that require less post-processing in fabrication. Targeting the capabilities of the Polyjet Stratasys 3D printers, a topology optimization algorithm is developed for the design of multi-material compliant mechanisms in which the algorithm ultimately designs both the topology of the part and the placement of each material -- one stiff, one more compliant. Results -- obtained through development of a both a new multi-material model and through development of a robust topology optimization technique for the elimination of one-node hinges -- show the ability to place both soft and stiff material and lead to dramatic improvements in performance of compliant mechanisms. One of the manufacturing challenges in metal powder-based 3D printing technologies is material curling due to internal stress development from the heating and cooling cycle during the printing process. To counteract this phenomena, sacrificial support material is introduced to anchor the part to the build plate, which must then be removed chemically or mechanically in post-production: a time consuming process. Components requiring no post-printing material removal are achieved through development of a topology optimization algorithm to design components to respect a designer-prescribed maximum overhang angle, such that the optimized part can be manufactured without using sacrificial support anchors. Solutions are shown to satisfy the prescribed overhang constraint, along with minimum feature length scale constraints as needed. Finally, an algorithm is developed considering the ability to embed discrete objects such as stiffeners or actuators within a monolithic printed part. Herein, a hybrid continuum-truss topology optimization algorithm is developed to leverage this potential capability, where the algorithm designs not only the continuum phase, but also places discrete truss members within this phase. With an eye towards future AM capabilities, the algorithm is demonstrated on the more contemporary design problem of strut-and-tie models in reinforced concrete design. It is shown that the algorithm is especially useful for designing within complex design domains in which the flow of forces is not obvious. While an exciting direction, it is noted that further advancements in 3D printing technology are needed to allow for such printed topologies

Structural Topology Optimization: Moving Beyond Linear Elastic Design Objectives

Topology optimization is a systematic, free-form approach to the design of structures. It simultaneously optimizes material quantities and system connectivity, enabling the discovery of new, high-performance structural concepts. While powerful, this design freedom has a tendency to produce solutions that are unrealizable or impractical from a structural engineering perspective. Examples include overly complex topologies that are expensive to construct and ultra-slender subsystems that may be overly susceptible to imperfections. This paper summarizes recent tools developed by the authors capable of mitigating these shortcomings through consideration of (1) constructability, (2) nonlinear mechanics, and (3) uncertainties

The Effect of Hospital Nurse Staffing on Patient Health Outcomes: Evidence from California's Minimum Staffing Regulation

Hospitals are currently under pressure to control the cost of medical care, while at the same time improving patient health outcomes. These twin concerns are at play in an important and contentious decision facing hospitals—choosing appropriate nurse staffing levels. Intuitively, one would expect nurse staffing ratios to be positively associated with patient outcomes. If so, this should be a key consideration in determining nurse staffing levels. A number of recent studies have examined this issue, however, there is concern about whether a causal relationship has been established. In this paper we exploit an arguably exogenous shock to nurse staffing levels. We look at the impact of California Assembly Bill 394, which mandated minimum levels of patients per nurse in the hospital setting. When the law was passed, some hospitals already had acceptable staffing levels, while others had nurse staffing ratios that did not meet mandated standards. Thus changes in hospital-level staffing ratios from the pre- to post-mandate periods are driven in part by the legislation. We find persuasive evidence that AB394 did have the intended effect of decreasing patient/nurse ratios in hospitals that previously did not meet mandated standards. However, our analysis suggests that patient outcomes did not disproportionately improve in these same hospitals. That is, we find no evidence of a causal impact of the law on patient safety.

Multiple-Material Topology Optimization of Compliant Mechanisms Created via Polyjet 3D Printing

Compliant mechanisms are able to transfer motion, force, and energy using a monolithic structure without discrete hinge elements. The geometric design freedoms and multi-material capability offered by the PolyJet 3D printing process enables the fabrication of compliant mechanisms with optimized topology. The inclusion of multiple materials in the topology optimization process has the potential to eliminate the narrow, weak, hinge-like sections that are often present in single-material compliant mechanisms. In this paper, the authors propose a design and fabrication process for the realization of 3-phase, multiple-material compliant mechanisms. The process is tested on a 2D compliant force inverter. Experimental and theoretical performance of the resulting 3-phase inverter is compared against a standard 2-phase design.Mechanical Engineerin

Professional views on the management of sex offenders in the community

Sex offender registration and community notification schemes form an increasingly important part of public policy relevant to the management of known sex offenders in the community. Critics of these policies not only point to the lack of empirical evidence that is currently available to support their impact on reoffending, but also the disproportionate and potentially iatrogenic effects that they have on offenders. However, there have been few attempts to understand these issues from the perspective of those practitioners who work on a daily basis with sex offenders in the community. These professionals are uniquely placed to contribute to an understanding of effective risk management and, as such, this article presents an analysis of the perspectives of a group of experienced practitioners and how this practice-based wisdom might inform the development of sex offender public policy

Changes in Asthma Mortality in England and Wales since 2001

The number of deaths from asthma in England and Wales has not changed significantly over the last decade. This lack of improvement has received attention from both national asthma guidelines and the media. We examined asthma death data from the Office for National Statistics, stratified by age band. Every 5-year age band below the age of 80 years has seen a large reduction in mortality between 2001 and 2017, whereas numbers of asthma deaths have increased by 81% for people aged 80 years or above. This increase in older people dying from asthma requires explanation

Place based learning in Skills in Schools and science teacher education programmes: student perspectives to moving learning online due to Covid-19

The development of science teachers requires lab-based, inquiry based and place-based learning in universities and schools. This is inherent to understanding the nature of learning science and associated pedagogy. Place based learning requires the development of teaching skills through working in a community of practice.1 In March 2020, with the outbreak of Covid-19 and lockdown, teacher education programmes had to adapt to a blended learning approach. This project explores that journey across three teacher development programmes within one Higher Education Institute (HEI). The programmes were SKE (Subject Knowledge Enhancement), Skills and Schools and PGCE Secondary Science. It unpicks how the participants responded to that provision and how the TEL (technology enhanced learning) pedagogy evolved. This paper discusses the approaches taken in overcoming the challenges to deliver place-based learning online, whilst maintaining the essence of social learning and collaborative learning.2 It draws on Salmon’s five stage model of e-learning to describe the process and presents insights from a student perspective, drawn from feedback and focus groups.3 The HEI TEL strategy was to make use of MS Teams and Blackboard VLE. Laboratory work and school experiences made use of a combination of videos, home labs and group meetings and taught sessions, which will be discussed. The unique contribution of this research is that it is a collaborative project that can allow some comparisons to be drawn. Offering lessons to be learnt in improving online provision and TEL pedagogy. The research questions focus on the participants perceptions of learning and reflections on learning