Fundamental differences in physiology of Bordetella pertussis dependent on the two-component system Bvg revealed by gene essentiality studies.

The identification of genes essential for a bacterium's growth reveals much about its basic physiology under different conditions. Bordetella pertussis, the causative agent of whooping cough, adopts both virulent and avirulent states through the activity of the two-component system, Bvg. The genes essential for B. pertussis growth in vitro were defined using transposon sequencing, for different Bvg-determined growth states. In addition, comparison of the insertion indices of each gene between Bvg phases identified those genes whose mutation exerted a significantly different fitness cost between phases. As expected, many of the genes identified as essential for growth in other bacteria were also essential for B. pertussis. However, the essentiality of some genes was dependent on Bvg. In particular, a number of key cell wall biosynthesis genes, including the entire mre/mrd locus, were essential for growth of the avirulent (Bvg minus) phase but not the virulent (Bvg plus) phase. In addition, cell wall biosynthesis was identified as a fundamental process that when disrupted produced greater fitness costs for the Bvg minus phase compared to the Bvg plus phase. Bvg minus phase growth was more susceptible than Bvg plus phase growth to the cell wall-disrupting antibiotic ampicillin, demonstrating the increased susceptibility of the Bvg minus phase to disruption of cell wall synthesis. This Bvg-dependent conditional essentiality was not due to Bvg-regulation of expression of cell wall biosynthesis genes; suggesting that this fundamental process differs between the Bvg phases in B. pertussis and is more susceptible to disruption in the Bvg minus phase. The ability of a bacterium to modify its cell wall synthesis is important when considering the action of antibiotics, particularly if developing novel drugs targeting cell wall synthesis

Autonomous Tennis Ball Collector

Practicing tennis often involves hitting many tennis balls from one side of the court to the other without an opponent to hit the balls back. In training sessions like these, the task of collecting the balls is laborious when performed manually. The objective of this project is to develop a robotic tennis ball collector that can automatically collect the balls from one side of the court so that the player can rest rather than collect the balls manually. This document outlines the process of designing such a robot. Included in this report is background research, prototype, and concept modeling, along with a finalized design, and a complete timeline of our process. We will also detail the manufacturing process and the design verification. In the conclusion we will provide you with recommendations for future projects. Throughout our research, we discovered many similar products, but none met all of the customer’s requirements, thus opening a window for our product. After copious design consideration, we selected the strongest idea that satisfied our customers’ needs and are moving forward with structural modeling and preliminary analysis on it. After the structural prototype revealed issues in the design we went back to work and finalized a design that we felt confident with and still satisfied all the requirements. As seen in this report the final design utilizes structural framing materials to build the robot and allows for ease of attachment for all the electrical components. The final step in the design process was to test the verification prototype to ensure that it met all our specifications. Unfortunately, our design did not pass as many of the tests as we would have liked, and this is detailed in that section. While at the conclusion of this project, we did not complete as much as we hoped, there is a good foundation in place for the project to continue as our sponsor so desires

Tunable Localized Surface Plasmon-Enabled Broadband Light-Harvesting Enhancement for High-Efficiency Panchromatic Dye-Sensitized Solar Cells

In photovoltaic devices, light harvesting (LH) and carrier collection have opposite relations with the thickness of the photoactive layer, which imposes a fundamental compromise for the power conversion efficiency (PCE). Unbalanced LH at different wavelengths further reduces the achievable PCE. Here, we report a novel approach to broadband balanced LH and panchromatic solar energy conversion using multiple-core–shell structured oxide-metal-oxide plasmonic nanoparticles. These nanoparticles feature tunable localized surface plasmon resonance frequencies and the required thermal stability during device fabrication. By simply blending the plasmonic nanoparticles with available photoactive materials, the broadband LH of practical photovoltaic devices can be significantly enhanced. We demonstrate a panchromatic dye-sensitized solar cell with an increased PCE from 8.3% to 10.8%, mainly through plasmon-enhanced photoabsorption in the otherwise less harvested region of solar spectrum. This general and simple strategy also highlights easy fabrication, and may benefit solar cells using other photoabsorbers or other types of solar-harvesting devices.Eni-MIT Energy Initiative Founding Member ProgramNational Science Foundation (U.S.) (ECCS Award 1028568)United States. Air Force Office of Scientific Research (AFOSR MURI Award FA9550-12-1-0488

Evolution of oceanic near surface stratification in response to an autumn storm

Understanding the processes that control the evolution of the ocean surface boundary layer (OSBL) is a prerequisite for obtaining accurate simulations of air-sea fluxes of heat and trace gases. Observations of the rate of dissipation of turbulent kinetic energy (ɛ), temperature, salinity, current structure and wave-field over a period of 9.5 days in the NE Atlantic during the Ocean Surface Mixing, Ocean Submesoscale Interaction Study (OSMOSIS), are presented. The focus of this study is a storm which passed over the observational area during this period. The profiles of ɛ in the OSBL are consistent with profiles from large eddy simulation (LES) of Langmuir turbulence. In the transition layer (TL), at the base of the OSBL, ɛ was found to vary periodically at the local inertial frequency. A simple bulk model of the OSBL and a parametrisation of shear driven turbulence in the TL are developed. The parametrisation of ɛ is based on assumptions about the momentum balance of the OSBL and shear across the TL. The predicted rate of deepening, heat budget and the inertial currents in the OSBL were in good agreement with the observations, as is the agreement between the observed value of ɛ and that predicted using the parametrisation. A previous study reported spikes of elevated dissipation related to enhanced wind-shear alignment at the base of the OSBL after this storm. The spikes in dissipation are not predicted by this new parametrisation, implying that they are not an important source of dissipation during the storm

Defining and assessing research quality in a transdisciplinary context

Research increasingly seeks both to generate knowledge and to contribute to real-world solutions, with strong emphasis on context and social engagement. As boundaries between disciplines are crossed, and as research engages more with stakeholders in complex systems, traditional academic definitions and criteria of research quality are no longer sufficient-there is a need for a parallel evolution of principles and criteria to define and evaluate research quality in a transdisciplinary research (TDR) context. We conducted a systematic review to help answer the question: What are appropriate principles and criteria for defining and assessing TDR quality? Articles were selected and reviewed seeking: arguments for or against expanding definitions of research quality, purposes for research quality evaluation, proposed principles of research quality, proposed criteria for research quality assessment, proposed indicators and measures of research quality, and proposed processes for evaluating TDR. We used the information from the review and our own experience in two research organizations that employ TDR approaches to develop a prototype TDR quality assessment framework, organized as an evaluation rubric. We provide an overview of the relevant literature and summarize the main aspects of TDR quality identified there. Four main principles emerge: relevance, including social significance and applicability; credibility, including criteria of integration and reflexivity, added to traditional criteria of scientific rigor; legitimacy, including criteria of inclusion and fair representation of stakeholder interests, and; effectiveness, with criteria that assess actual or potential contributions to problem solving and social change

Estimating the association between systemic Interleukin-6 and mortality in the dialysis population. Re-analysis of the global fluid study, systematic review and meta-analysis

Background: Systemic inflammation, measured as circulating Interleukin-6 (IL-6) levels, is associated with cardiovascular and all-cause mortality in chronic kidney disease. However, this has not been convincingly demonstrated in a systematic review or a meta-analysis in the dialysis population. We provide such evidence, including a re-analysis of the GLOBAL Fluid Study.Methods: Mortality in the GLOBAL fluid study was re-analysed using Cox proportional hazards regression with IL-6 levels as a covariate using a continuous non-logarithmic scale. Literature searches of the association of IL-6 levels with mortality were conducted on MEDLINE, EMBASE, PyschINFO and CENTRAL. All studies were assessed for risk of bias using the QUIPS tool. To calculate a pooled effect size, studies were grouped by use of IL-6 scale and included in the meta-analysis if IL-6 was analysed as a continuous linear covariate, either per unit or per 10 pg/ml, in both unadjusted or adjusted for other patient characteristics (e.g. age, comorbidity) models. Funnel plot was used to identify potential publication bias. Results: Of 1886 citations identified from the electronic search, 60 were included in the qualitative analyses, and 12 had sufficient information to proceed to meta-analysis after full paper screening. Random effects meta-analysis of 11 articles yielded a pooled hazard ratio (HR) per pg/ml of 1.03, (95% CI 1.01, 1.03), = 81%. When the analysis was confined to seven articles reporting a non-adjusted HR the result was similar: 1.03, per pg/ml (95% CI: 1.03, 1.06), =92%. Most of the heterogeneity could be attributed to three of the included studies. Publication bias could not be determined due to the limited number of studies.Conclusion: This systematic review confirms the adverse association between systemic IL-6 levels and survival in people treated with dialysis. The heterogeneity that we observed may reflect differences in study case mix. Systematic Review Registration: PROSPERO - CRD42020214198

Creating a Conversation: Insights from the Development of a Decision Aid

The authors share lessons learned from their development ofStatin Choice, a decision aid for patients with diabetes who are considering using statins to reduce their cardiovascular risk

Discovery of High-Affinity Protein Binding Ligands – Backwards

BACKGROUND: There is a pressing need for high-affinity protein binding ligands for all proteins in the human and other proteomes. Numerous groups are working to develop protein binding ligands but most approaches develop ligands using the same strategy in which a large library of structured ligands is screened against a protein target to identify a high-affinity ligand for the target. While this methodology generates high-affinity ligands for the target, it is generally an iterative process that can be difficult to adapt for the generation of ligands for large numbers of proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a class of peptide-based protein ligands, called synbodies, which allow this process to be run backwards--i.e. make a synbody and then screen it against a library of proteins to discover the target. By screening a synbody against an array of 8,000 human proteins, we can identify which protein in the library binds the synbody with high affinity. We used this method to develop a high-affinity synbody that specifically binds AKT1 with a K(d)<5 nM. It was found that the peptides that compose the synbody bind AKT1 with low micromolar affinity, implying that the affinity and specificity is a product of the bivalent interaction of the synbody with AKT1. We developed a synbody for another protein, ABL1 using the same method. CONCLUSIONS/SIGNIFICANCE: This method delivered a high-affinity ligand for a target protein in a single discovery step. This is in contrast to other techniques that require subsequent rounds of mutational improvement to yield nanomolar ligands. As this technique is easily scalable, we believe that it could be possible to develop ligands to all the proteins in any proteome using this approach