Novel Inducers of the Envelope Stress Response BaeSR in Salmonella Typhimurium: BaeR Is Critically Required for Tungstate Waste Disposal

The RpoE and CpxR regulated envelope stress responses are extremely important for SalmonellaTyphimurium to cause infection in a range of hosts. Until now the role for BaeSR in both the Salmonella Typhimurium response to stress and its contribution to infection have not been fully elucidated. Here we demonstrate stationary phase growth, iron and sodium tungstate as novel inducers of the BaeRregulon, with BaeR critically required for Salmonella resistance to sodium tungstate. We show that functional overlap between the resistance nodulation-cell division (RND) multidrug transporters, MdtA, AcrD and AcrB exists for the waste disposal of tungstate from the cell. We also point to a role for enterobactinsiderophores in the protection of enteric organisms from tungstate, akin to the scenario in nitrogen fixing bacteria. Surprisingly, BaeR is the first envelope stress response pathway investigated in S. Typhimurium that is not required for murine typhoid in either ityS or ityR mouse backgrounds. BaeR is therefore either required for survival in larger mammals such as pigs or calves, an avian host such as chickens, or survival out with the host altogether where Salmonella and related enterics must survive in soil and water

Military Contractors Who Comply with Elements of Government Contractor Defense are Immune from Products Liability Suits Stemming from Design Defects.

In Boyle v. United Technologies Corp., the United States Supreme Court held military contractors who comply with the elements of the government contractor defense are immune from products liability suits stemming from design defects. Lower courts consider the government contractor defense to be a combination of two separate defenses. The first is the well-settled contract specification defense which eliminates liability for contractors who properly follow client supplied specifications. The second defense is the doctrine of shared sovereign immunity shielding the contractor from liability based on public policy concerns. In Boyle, the Court held defective design of military equipment will not result in liability under state law when the United States approved reasonably precise specifications. Immunity would exist so long as the equipment conformed to those specifications and the supplier warned the United States of dangers in using the equipment that were known to the supplier but not to the United States. The majority decided the conflict based on the language of a provision of the Federal Tort Claims Act (FTCA), which provides discretionary functions of the government are within the exceptions that prohibit suit under the act. The problems in Boyle arise because the Court legislatively altered tort law and gave a cloak of immunity to government contractors whose products have design defects. First, the displacement of state tort law, implementing broad immunity for government contractors, does not clarify a confusing area of law. Second, the majority created a formulation of the immunity, which is quite liberal in its requirements, yet arguably narrow in its application. Finally, the Court should have allowed Congress to legislate a more equitable affirmative defense in military products liability cases

MEMS 411: Mini-Golf Robot

The following report details the design and construction of a mini-golf robot overthree months. The robot was designed under the standards provided by theASME Fall 2023 Design Challenge. The robot would need to traverse the mini-golfcourse, completing it in under 10 minutes with the assistance of an attached strikermechanism. It was necessary that the robot could position itself precisely withrespect to the goofball, while also staying stationary while striking the object. Therobot design timeline followed the guidelines of the engineering design process, withconcept generation, concept selection, prototype embodiment and design refinementall playing important roles in ensuring the design of the vehicle was best suited tothe goals it was supposed to complete. The final prototype performance goals ofthe vehicle, determined by our customer, Dr. J. Jackson Potter, were for the deviceto a) climb over a long wooden board that is 3.5” tall and 1.5” thick, b) climb onto,over, and back down from a sheet of 1/2”-thick plywood whose bottom surfaceis 3.5” above the ground, and c) position itself next to three golf balls (withoutdisturbing them) and ”aim” in a specified direction before removing the ball andcontinuing to the next ball in ¡ 1 minute, all while carrying extra weight in theshape of a wooden striker template. The group was able to complete prototypegoal number 3 successfully but failed to complete prototype goals 1 or 2. Thisreport outlines the full process of the creation and assembly of the vehicle

The Role of Legal Services in the Antipoverty Program

Large-scale adaptive radiations might explain the runaway success of a minority of extant vertebrate clades. This hypothesis predicts, among other things, rapid rates of morphological evolution during the early history of major groups, as lineages invade disparate ecological niches. However, few studies of adaptive radiation have included deep time data, so the links between extant diversity and major extinct radiations are unclear. The intensively studied Mesozoic dinosaur record provides a model system for such investigation, representing an ecologically diverse group that dominated terrestrial ecosystems for 170 million years. Furthermore, with 10,000 species, extant dinosaurs (birds) are the most speciose living tetrapod clade. We assembled composite trees of 614-622 Mesozoic dinosaurs/birds, and a comprehensive body mass dataset using the scaling relationship of limb bone robustness. Maximum-likelihood modelling and the node height test reveal rapid evolutionary rates and a predominance of rapid shifts among size classes in early (Triassic) dinosaurs. This indicates an early burst niche-filling pattern and contrasts with previous studies that favoured gradualistic rates. Subsequently, rates declined in most lineages, which rarely exploited new ecological niches. However, feathered maniraptoran dinosaurs (including Mesozoic birds) sustained rapid evolution from at least the Middle Jurassic, suggesting that these taxa evaded the effects of niche saturation. This indicates that a long evolutionary history of continuing ecological innovation paved the way for a second great radiation of dinosaurs, in birds. We therefore demonstrate links between the predominantly extinct deep time adaptive radiation of non-avian dinosaurs and the phenomenal diversification of birds, via continuing rapid rates of evolution along the phylogenetic stem lineage. This raises the possibility that the uneven distribution of biodiversity results not just from large-scale extrapolation of the process of adaptive radiation in a few extant clades, but also from the maintenance of evolvability on vast time scales across the history of life, in key lineages

msmsEval: tandem mass spectral quality assignment for high-throughput proteomics

BACKGROUND: In proteomics experiments, database-search programs are the method of choice for protein identification from tandem mass spectra. As amino acid sequence databases grow however, computing resources required for these programs have become prohibitive, particularly in searches for modified proteins. Recently, methods to limit the number of spectra to be searched based on spectral quality have been proposed by different research groups, but rankings of spectral quality have thus far been based on arbitrary cut-off values. In this work, we develop a more readily interpretable spectral quality statistic by providing probability values for the likelihood that spectra will be identifiable. RESULTS: We describe an application, msmsEval, that builds on previous work by statistically modeling the spectral quality discriminant function using a Gaussian mixture model. This allows a researcher to filter spectra based on the probability that a spectrum will ultimately be identified by database searching. We show that spectra that are predicted by msmsEval to be of high quality, yet remain unidentified in standard database searches, are candidates for more intensive search strategies. Using a well studied public dataset we also show that a high proportion (83.9%) of the spectra predicted by msmsEval to be of high quality but that elude standard search strategies, are in fact interpretable. CONCLUSION: msmsEval will be useful for high-throughput proteomics projects and is freely available for download from . Supports Windows, Mac OS X and Linux/Unix operating systems

Evaluation of seismic assessment procedures for determining deformation demands in RC wall buildings

This work evaluates the performance of a number of seismic assessment procedures when applied to a case study reinforced concrete (RC) wall building. The performance of each procedure is evaluated through its ability to accurately predict deformation demands, specifically, roof displacement, inter-storey drift ratio and wall curvatures are considered as the key engineering demand parameters. The different procedures include Direct Displacement-Based Assessment, nonlinear static analysis and nonlinear dynamic analysis. For the latter two approaches both lumped and distributed plasticity modelling are examined. To thoroughly test the different approaches the case study building is considered in different configurations to include the effects of unequal length walls and plan asymmetry. Recommendations are made as to which methods are suited to different scenarios, in particular focusing on the balance that needs to be made between accurate prediction of engineering demand parameters and the time and expertise required to undertake the different procedures. All methods are shown to have certain merits, but at the same time a number of the procedures are shown to have areas requiring further development. This work also highlights a number of key aspects related to the seismic response of RC wall buildings that may significantly impact the results of an assessment. These include the influence of higher-mode effects and variations in spectral shape with ductility demands