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DNA Strand Displacement (DSD) systems model basic reaction rules, such as toehold-mediated strand displacement and 4-way branch migration, that modify complexes of bound DNA strands. DSD systems have been widely used to design and reason about the correctness of molecular programs, including implementations of logic circuits, neural networks, and Chemical Reaction Networks. Such implementations employ a valuable toolkit of mechanisms - sequences of basic reaction rules - that achieve catalysis, reduce errors (e.g., due to leak), or simulate simple computational units such as logic gates, both in solution and on surfaces. Expanding the DSD toolkit of DSD mechanisms can lead to new and better ways of programming with DNA. Here we introduce a new mechanism, which we call controlled reconfiguration. We describe one example where two single-stranded DSD complexes interact, changing the bonds in both complexes in a way that would not be possible for each independently on its own via the basic reaction rules allowed by the model. We use coupled reconfiguration to refer to instances of controlled reconfiguration in which two reactants change each other in this way. We note that our DSD model disallows pseudoknots and that properties of our coupled reconfiguration construction rely on this restriction of the model. A key feature of our coupled reconfiguration example, which distinguishes it from mechanisms (such as 3-way strand displacement or 4-way branch migration) that are typically used to implement molecular programs, is that the reactants are single-stranded. Leveraging this feature, we show how to use coupled reconfiguration to implement Chemical Reaction Networks (CRNs), with a DSD system that has both single-stranded signals (which represent the species of the CRN) and single-stranded fuels (which drive the CRN reactions). Our implementation also has other desirable properties; for example it is capable of implementing reversible CRNs and uses just two distinct toeholds. We discuss drawbacks of our implementation, particularly the reliance on pseudoknot-freeness for correctness, and suggest directions for future research that can provide further insight on the capabilities and limitations of controlled reconfiguration., LIPIcs, Vol. 238, 28th International Conference on DNA Computing and Molecular Programming (DNA 28), pages 3:1-3:19

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

BackgroundThe last two decades have seen substantial expansion of childhood vaccination programmes in low and middle income countries (LMICs). Here we quantify the health impact of these programmes by estimating the deaths and disability-adjusted life years (DALYs) averted by vaccination with ten antigens in 98 LMICs between 2000 and 2030.MethodsIndependent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B (HepB), Haemophilus influenzae type b (Hib), human papillomavirus (HPV), Japanese encephalitis (JE), measles, Neisseria meningitidis serogroup A (MenA), Streptococcus pneumoniae, rotavirus, rubella, yellow fever. Using standardized demographic data and vaccine coverage estimates for routine and supplementary immunization activities, the impact of vaccination programmes on deaths and DALYs was determined by comparing model estimates from the no vaccination counterfactual scenario with those from a default coverage scenario. We present results in two forms: deaths/DALYs averted in a particular calendar year, and in a particular annual birth cohort.FindingsWe estimate that vaccination will have averted 69 (2.5-97.5% quantile range 52-88) million deaths between 2000 and 2030 across the 98 countries and ten pathogens considered, 35 (29-45) million of these between 2000-2018. From 2000-2018, this represents a 44% (36-57%) reduction in deaths due to the ten pathogens relative to the no vaccination counterfactual. Most (96% (93-97%)) of this impact is in under-five age mortality, notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 122 (96-147) million deaths will be averted by vaccination, of which 58 (39-75) and 38 (26-52) million are due to measles and Hepatitis B vaccination, respectively. We estimate that recent increases in vaccine coverage and introductions of additional vaccines will result in a 72% (61-79%) reduction in lifetime mortality caused by these 10 pathogens in the 2018 birth cohort.InterpretationIncreases in vaccine coverage and the introduction of new vaccines into LMICs over the last two decades have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained.

Legislatures are increasingly developing novel, tradeable statutory entitlements, such as transferable licences or allowances, to respond to a range of social and environmental issues. However, the statutes that establish such entitlements commonly overlook the nature and scope of the legal interests, personal or proprietary, which may exist in relation to an entitlement. As a result, courts are increasingly dealing with issues that stem from the uncertain legal nature of statutory entitlements. Issues that have arisen include whether a statute dealing with property transfers is applicable to a particular statutory entitlement, whether a regulator must pay compensation for withdrawing an entitlement or whether a statutory entitlement is capable of supporting rights that are enforceable against third parties. To determine the legal nature of statutory entitlements, courts undertake a property analysis that involves considering the attributes of a statutory entitlement against particular indicia of property. In this article, we focus on the diff erent conceptions of property and its indicia in the United States, Australia, the United Kingdom and Canada. This comparative analysis illustrates the distinct approaches being adopted to resolve the uncertain legal nature of statutory entitlements. Using emissions trading schemes as a case study, we explore how the diff erent property analyses adopted impact the rights and liabilities of parties as well as the functioning of statutory entitlement schemes.

This report provides an evaluation of the implementation of the Polluter Pays Principle (PPP) – a principle of international environmental law – in the context of pollution from sugarcane farming affecting Australia’s Great Barrier Reef (GBR). The research was part of an experiment to test methods for evaluating the effectiveness of environmental laws. Overall, we found that whilst the PPP is reflected to a limited extent in Australian law (more so in Queensland law, than at the national level), the behaviour one might expect in terms of implementing the principle was largely inadequate. Evidence of a longer term, explicit commitment to the PPP was particularly weak.

The concept of environmental justice is well developed in North America, but is still at the evolutionary stage in most other jurisdictions around the globe. This paper seeks to explore two jurisdictions where incidents of environmental justice are likely to be seen in the future as a result of manufacturing and mining practices. The discussion will centre upon avenues to environmental justice for both private citizens and the public at large. The first jurisdiction considered is China, where environmental liability claims brought by Chinese citizens have increased at an annual average of 25% (Yang 2011). Manufacturing is at the core of the Chinese economy and is responsible for some of the unprecedented economic growth in the region. Less discussed are the industry impacts on water and air pollution levels and the associated implications of these pollutants on local communities. China introduced the Tort Liability Law (TLL) in 2010, which may provide avenues to justice for private citizens. The other jurisdiction considered by the paper is Australia, where the mining boom has buffered the Australian economy from the global financial crisis. There is some limited case law in Australia where private citizens have made a claim in toxic torts; however the framework is underdeveloped in terms of the significant risks facing indigenous and local communities in mining areas and also by comparison to the developments of the TLL framework in China. This paper traces the regulatory responses to the affects of major industries on communities in China and Australia. From this it examines the need for environmental justice avenues that align with rule of law principles.

This study is an investigation into methods of developing ergonomic guidelines for automotive assembly tasks involving insertion of small parts. The study was conducted in four major parts: 1) a method of determining and evaluating subjective exertion limits was modified and tested, 2) a large dataset was collected from an industrial population in 10 simulated assembly line tasks, 3) a smaller dataset was collected from a student population to assess hand dominance effects, and 4) strength data obtained was compared with a strength prediction model to determine if the model could predict manual insertion forces. The traditional method of psychophysical data collection requires participants to extrapolate sensations from a relativity short session to judge if the task could be done for a much longer period. Maximum acceptable limits (MALs) are typically derived from having participants adjust a weight, resistance, or frequency to an acceptable level. The present study evaluated a relatively new method of collecting MAL data for simple, single-digit exertions where participants were asked to determine an MAL by self-adjusting and then regulating to maintain the exertion level. Results showed that MAL values obtained from a series of self-regulated exertions were independent of both analysis method and duration (5 minutes vs. 25 minutes) used for evaluation, and that the method was repeatable both within and between sessions. Ergonomic guidelines are often obtained from the strength capacity for a certain task, as it is important to ensure that workers possess sufficient strength to accomplish a task. As task demands increase, however, a larger percentage of a worker's strength capability in required, and other factors, such as performance and worker comfort, tend to be compromised. In this work, both strength capacity and subjective limits were obtained for a variety of simulated tasks to facilitate development of guidelines for the specific tasks. The relationship between these two measures (maximum force, acceptable force) was determined, and acceptable limits were found to be approximately 55% of population strength capacity, with correlations (R2) ranging from 0.40 to 0.60 depending on the task, suggesting the subjective limits and strength capacity are related in these tasks. Hand dominance was found to have a small (5%), but significant (p = 0.006) effect on strength capability, and no significant effect on subjective limit. Biomechanical strength prediction models can be used to assess loads placed on the human performing various tasks. One of the more popular models, Three-Dimensional Static Strength Prediction Program, is often used for heavy material handling tasks, such as lifting or pushing. The tasks studied presently, however, are manual insertions, requiring localized force application rather than whole body exertion. The prediction capabilities of this strength prediction model were compared with strength values obtained from the simulated assembly tasks. Results indicated that the model was not successful when predicting localized force, accounting for only 40% of the observed variance in strength (R2 = 0.4) Master of Science

There is a considerable effort to find novel compounds to combat the growing threat of antibiotic resistant bacteria. Spider silk has been considered as a potential source of antimicrobial compounds and was tested for its ability to affect the growth of bacteria. We explored the relationship between the egg case silk of the western black widow spider,Latrodectus hesperusand various bacteria.Antibacterial properties of the egg case silk were tested using several methods. When placed in various growth media, egg case silk was observed to elicit bacterial growth. DNA from a diverse population of bacteria was detected on the surface of the silk using next generation sequencing. When evaluated for its antibacterial properties, the egg case silk was shown to significantly inhibit the growth ofBacillus megaterium. However, the doubling time ofEscherichia colidecreased while other species appeared to be unaffected by the silk.Staphylococcus aureuswas shown to be able to attach itself onto surface of the silk while also showing evidence of replication and biofilm formation. We concluded that egg case silk does not have antibiotic properties and could play host to a microbiome.&nbsp

There is a significant presence of Mn-II in terrestrial and marine environments that can beoxidized from soluble manganese (Mn-II) into insoluble Mn-III/IV by bacteria. The Mn oxides play an important role in the fate of other vital elements that are required for different biogeochemical reactions such as carbon, sulfur, iron, and others. The oxidation mechanism employed by bacteria is unclear. The marine bacterium Erythrobactersp. SD-21 is known to produce a Mn-oxidizing protein called MopA. This protein has the potential to be utilized in the field of bio remediation focusing on the treatment of contaminated sources. Previous purification attempts have provided samples of heterologously expressed MopA with incomplete purification or no activity. The purpose of this project is to derive an active and pure sample of MopA through different purification methods. The current purification protocol involves nickel affinity chromatography with a desalting process. Such a method has provided an active but not so pure sample of MopA. Additional purification by an ion exchange chromatography is being investigated. The 250-kDa native MopA is identified by SDS-PAGE. Mn oxidizing activity is quantified through a colorimetric LBB assay and the concentration of the protein is determined by absorbance. Additional purification will allow future studies on the mechanism of Mnoxidation by MopA.

Sinorhizobium melilotiis an alpha-proteobacterium that forms a nitrogen-fixing symbiosis with its plant hostMedicago sativa. This symbiosis is an alternative to manufactured nitrogen fertilizers which contribute to greenhouse gas emissions. The ExoS/ChvI two-component signaling pathway inS. melilotiregulates genes that are required for a successful symbiosis. Small regulatory RNAs (sRNAs) are short transcripts that play an important role in regulating gene expression in bacteria. Previous northern blot research aimed to investigate ChvI regulation of 28 sRNA genes using total RNA from cells harvested from rich media. However, 18 sRNAs remained undetected in the previous study. Here, we use RNA enriched for the small RNA fraction and total RNA from cells grown in multiple conditions, including stress conditions, to increase the chances of detecting sRNA gene expression. Also, 44 additional sRNA genes not previously tested by northern analysis are examined in this study. To detect ChvI regulation of sRNA genes, northern analysis was done using RNA extracted from threeS. melilotistrains (chvIpartial loss-of-function mutant,chvIgain-of-function mutant, and wildtype). An sRNA was determined to be regulated by ChvI if the sRNA showed a reciprocal change in expression in thechvImutants compared to wildtype. Here, we show that three previously undetected sRNA genes are likely be regulated by ChvI and one of the 44 sRNA genes not previously tested by northern analysis is also likely to be regulated by ChvI. We also confirmed that two previously detected sRNA genes are indeed regulated by ChvI.&nbsp