University of Notre Dame

About: University of Notre Dame is a education organization based out in Notre Dame, Indiana, United States. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 22238 authors who have published 55201 publications receiving 2032925 citations. The organization is also known as: University of Notre Dame du Lac & University of Notre Dame, South Bend.

Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.

Abstract: A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.

Acute and chronic toxicity of imidazolium-based ionic liquids on Daphnia magna

Abstract: Room-temperature ionic liquids (ILs) are considered to be green chemicals that may replace volatile organic solvents currently used by industry. However, IL effects on aquatic organisms and ecosystems are currently unknown. We studied the acute effects of imidazolium-based ILs on survival of the crustacean Daphnia magna and their chronic effects on number of first-brood neonates, total number of neonates, and average brood size. Lethal concentrations of imidazolium ILs with various anions (X-) ranged from a median lethal concentration (LC50) of 8.03 to 19.91 mg L(-1), whereas salts with a sodium cation (Na+ X-) were more than an order of magnitude higher (NaPF6 LC50, 9,344.81 mg L(-1); NaBF4 LC50, 4765.75 mg L(-1)). Thus, toxicity appeared to be related to the imidazolium cation and not to the various anions (e.g., Cl-, Br-, PF6-, and BF4-). The toxicity of imidazolium-based ILs is comparable to that of chemicals currently used in manufacturing and disinfection processes (e.g., ammonia and phenol), indicating that these green chemicals may be more harmful to aquatic organisms than current volatile organic solvents. We conducted 21-d chronic bioassays of individual D. magna exposed to nonlethal IL concentrations at constant food-resource levels. Daphnia magna produced significantly fewer total neonates, first-brood neonates, and average neonates when exposed to lower concentrations (0.3 mg L(-1)) of imidazolium-based ILs than in the presence of Na-based salts at higher concentrations (400 mg L(-1)). Such reductions in the reproductive output of Daphnia populations could cascade through natural freshwater ecosystems. The present study provides baseline information needed to assess the potential hazard that some ILs may pose should they be released into freshwater ecosystems.

Two degrees of separation in complex food webs.

Abstract: Feeding relationships can cause invasions, extirpations, and population fluctuations of a species to dramatically affect other species within a variety of natural habitats. Empirical evidence suggests that such strong effects rarely propagate through food webs more than three links away from the initial perturbation. However, the size of these spheres of potential influence within complex communities is generally unknown. Here, we show for that species within large communities from a variety of aquatic and terrestrial ecosystems are on average two links apart, with >95% of species typically within three links of each other. Species are drawn even closer as network complexity and, more unexpectedly, species richness increase. Our findings are based on seven of the largest and most complex food webs available as well as a food-web model that extends the generality of the empirical results. These results indicate that the dynamics of species within ecosystems may be more highly interconnected and that biodiversity loss and species invasions may affect more species than previously thought.

The Logical Status of Diagrams

Abstract: Acknowledgements 1. Introduction 2. Preliminaries 3. Venn-I 4. Venn-II 5. Venn-II and L0 6. Diagrammatic versus linguistic representation 7. Conclusion Appendix References Index.

Biometric Recognition Using 3D Ear Shape

Abstract: Previous works have shown that the ear is a promising candidate for biometric identification. However, in prior work, the preprocessing of ear images has had manual steps and algorithms have not necessarily handled problems caused by hair and earrings. We present a complete system for ear biometrics, including automated segmentation of the ear in a profile view image and 3D shape matching for recognition. We evaluated this system with the largest experimental study to date in ear biometrics, achieving a rank-one recognition rate of 97.8 percent for an identification scenario and an equal error rate of 1.2 percent for a verification scenario on a database of 415 subjects and 1,386 total probes.