Tracking autophagy during proliferation and differentiation of trypanosoma brucei

Autophagy is a lysosome-dependent degradation mechanism that sequesters target cargo into autophagosomal vesicles. The Trypanosoma brucei genome contains apparent orthologues of several autophagy-related proteins including an ATG8 family. These ubiquitin-like proteins are required for autophagosome membrane formation, but our studies show that ATG8.3 is atypical. To investigate the function of other ATG proteins, RNAi compatible T. brucei were modified to function as autophagy reporter lines by expressing only either YFP-ATG8.1 or YFP-ATG8.2. In the insect procyclic lifecycle stage, independent RNAi down-regulation of ATG3 or ATG7 generated autophagy-defective mutants and confirmed a pro-survival role for autophagy in the procyclic form nutrient starvation response. Similarly, RNAi depletion of ATG5 or ATG7 in the bloodstream form disrupted autophagy, but did not impede proliferation. Further characterisation showed bloodstream form autophagy mutants retain the capacity to undergo the complex cellular remodelling that occurs during differentiation to the procyclic form and are equally susceptible to dihydroxyacetone-induced cell death as wild type parasites, not supporting a role for autophagy in this cell death mechanism. The RNAi reporter system developed, which also identified TOR1 as a negative regulator controlling YFP-ATG8.2 but not YFP-ATG8.1 autophagosome formation, will enable further targeted analysis of the mechanisms and function of autophagy in the medically relevant bloodstream form of T. brucei

Learning gain - annotated bibliography

The purpose of this literature search was to produce an annotated bibliography outlining the new literature and research that has emerged on learning gain within higher education since the RAND report was published in 2015. Using some of the key themes from the RAND report, this bibliography organises the literature into: (1) ways of measuring learning gain, (2) limitations to measuring learning gain, (3) benefits to student learning gain and (4) the purpose of measuring learning gain. This research found that four main areas emerge from the current literature. These are: (1) the use of current data sources to measure learning gain, (2) the limitations of using assessment grades to measure learning gain, (3) the development of current teaching practice to impact student learning and (4) the inclusion of learning gain within the Teaching Excellence Framework (TEF). From this research it is clear that recent discussion of learning gain focuses on many of the key areas of the RAND report. In addition, the search further highlights the significant variations of measuring learning gain and the implications and issues around it

Individual behavioral rules sustain the cell allocation pattern in the combs of honey bee colonies (Apis mellifera)

In the beeswax combs of honey bees, the cells of brood, pollen, and honey have a consistent spatial pattern that is sustained throughout the life of a colony. This spatial pattern is believed to emerge from simple behavioral rules that specify how the queen moves, where foragers deposit honey/pollen and how honey/pollen is consumed from cells. Prior work has shown that a set of such rules can explain the formation of the allocation pattern starting from an empty comb. We show that these rules cannot maintain the pattern once the brood start to vacate their cells, and we propose new, biologically realistic rules that better sustain the observed allocation pattern. We analyze the three resulting models by performing hundreds of simulation runs over many gestational periods and a wide range of parameter values. We develop new metrics for pattern assessment and employ them in analyzing pattern retention over each simulation run. Applied to our simulation results, these metrics show alteration of an accepted model for honey/pollen consumption based on local information can stabilize the cell allocation pattern over time. We also show that adding global information, by biasing the queen's movements towards the center of the comb, expands the parameter regime over which pattern retention occurs.Comment: Accepted to Journal of Theoretical Biolog

Distributed CSMA with pairwise coding

We consider distributed strategies for joint routing, scheduling, and network coding to maximize throughput in wireless networks. Network coding allows for an increase in network throughput under certain routing conditions. We previously developed a centralized control policy to jointly optimize for routing and scheduling combined with a simple network coding strategy using max-weight scheduling (MWS) [9]. In this work we focus on pairwise network coding and develop a distributed carrier sense multiple access (CSMA) policy that supports all arrival rates allowed by the network subject to the pairwise coding constraint. We extend our scheme to optimize for packet overhearing to increase the number of beneficial coding opportunities. Simulation results show that the CSMA strategy yields the same throughput as the optimal centralized policy of [9], but at the cost of increased delay. Moreover, overhearing provides up to an additional 25% increase in throughput on random topologies.United States. Dept. of Defense. Assistant Secretary of Defense for Research & EngineeringUnited States. Air Force (Air Force Contract FA8721-05-C-0002

Optimal routing and scheduling for a simple network coding scheme

We consider jointly optimal routing, scheduling, and network coding strategies to maximize throughput in wireless networks. While routing and scheduling techniques for wireless networks have been studied for decades, network coding is a relatively new technique that allows for an increase in throughput under certain topological and routing conditions. In this work we introduce k-tuple coding, a generalization of pairwise coding with next-hop decodability, and fully characterize the region of arrival rates for which the network queues can be stabilized under this coding strategy. We propose a dynamic control policy for routing, scheduling, and k-tuple coding, and prove that our policy is throughput optimal subject to the k-tuple coding constraint. We provide analytical bounds on the coding gain of our policy, and present numerical results to support our analytical findings. We show that most of the gains are achieved with pairwise coding, and that the coding gain is greater under 2-hop than 1-hop interference. Simulations show that under 2-hop interference our policy yields median throughput gains of 31% beyond optimal scheduling and routing on random topologies with 16 nodes.National Science Foundation (U.S.) (grant CNS-0915988)United States. Office of Naval Research (grant N00014-12-1-0064)United States. Office of Naval Research. Multidisciplinary University Research Initiative (grant number W911NF-08-1-0238)United States. Air ForceUnited States. Dept. of Defense (Contract No. FA8721-05-C-0002

Why is the BME attainment gap such a wicked problem?

This paper outlines a research process which followed a case study approach (Yin 2009) to explore the Black and Minority Ethnic (BME) student attainment gap, and responses to it, at Sheffield Hallam University. A mixed methodology was envisaged, which would triangulate institutional data, measures of student engagement, focus groups and researcher reflections to construct an analysis of interventions aimed at enhancing confidence and belonging for BME students. This discussion focuses on the challenges experienced by the research team and uses the notion of a 'wicked problem' to help understand the limitations faced. 'Wicked problems' (Rittel 1972, see Conklin 2005) are entrenched in social complexity, which increases in line with the diversity of the associated stakeholders. These problems have the ability to divide opinion, provide limited solutions and to lay blame for lack of results. This research examining the BME attainment gap can be critiqued using this notion of a 'wicked problem' noting that, without recognition, this issue has the potential to become ubiquitous and almost unsolvable

An overlay architecture for throughput optimal multipath routing

Legacy networks are often designed to operate with simple single-path routing, like shortest-path, which is known to be throughput suboptimal. On the other hand, previously proposed throughput optimal policies (i.e., backpressure) require every device in the network to make dynamic routing decisions. In this work, we study an overlay architecture for dynamic routing such that only a subset of devices (overlay nodes) need to make dynamic routing decisions. We determine the essential collection of nodes that must bifurcate traffic for achieving the maximum multicommodity network throughput. We apply our optimal node placement algorithm to several graphs and the results show that a small fraction of overlay nodes is sufficient for achieving maximum throughput. Finally, we propose a heuristic policy (OBP), which dynamically controls traffic bifurcations at overlay nodes. In all studied simulation scenarios, OBP not only achieves full throughput, but also reduces delay in comparison to the throughput optimal backpressure routing.United States. Air Force (Contract FA8721-05-C-0002)National Science Foundation (U.S.) (Grant CNS-0915988)United States. Office of Naval Research (Grant N00014-12-1-0064)United States. Army Research Office. Multidisciplinary University Research Initiative (Grant W911NF-08-1-0238)European Social Fund (WiNC Project of the Action:Supporting Postdoctoral Researchers

Access to Higher Education: Do schools “grant” success?

University education can lead to upward income mobility for low-income students. Being exposed to other student’s life experiences that are different from their own may highlight activities and actions that they may want to consider aiding their success. According to the U.S. Bureau of Labor Statistics, the median weekly earnings in 2019 for all workers in the U.S. was $969. Of those, U.S. workers who held bachelor’s degrees earned$1,248. In 2016, the Brookings Institute found that Pell Grant recipients and first-generation student loan borrowers attended universities that had lower graduation rates and higher loan default rates in comparison to other loan borrowers. Using hypothesis tests including t-test, simple linear regression, chi-square analyses, among others, this researcher seeks to investigate relationships that may alert the reader to the needs of Pell Grant recipients and first-generation students at post-secondary institutions. For example, do Pell Grant recipients and first-generation students have lower graduation rates and higher loan default rates even at the same university? The goal is to increase graduation rates and decrease loan default rates while also enabling Pell grant recipients to leave with the least amount of debt. The College Scorecard dataset includes demographics of schools serving low-income students including Title IV participation status, the percentage of undergraduate Pell recipients, being a 2-year or 4-year institution, public or private ownership of the institution, whether the university awards Associate’s, Bachelor’s, or Graduate degrees, the proportion of STEM-focused majors, the net revenue per full-time student, the instructional expenditures per full-time student, the proportion of full-time faculty, and the average faculty salary. Through analyzing these variables, the reader can gain insight into the possible non-academic needs of Pell Grant recipients and first-generation students