2,092 research outputs found
Efficient Bayesian Nonparametric Modelling of Structured Point Processes
This paper presents a Bayesian generative model for dependent Cox point
processes, alongside an efficient inference scheme which scales as if the point
processes were modelled independently. We can handle missing data naturally,
infer latent structure, and cope with large numbers of observed processes. A
further novel contribution enables the model to work effectively in higher
dimensional spaces. Using this method, we achieve vastly improved predictive
performance on both 2D and 1D real data, validating our structured approach.Comment: Presented at UAI 2014. Bibtex: @inproceedings{structcoxpp14_UAI,
Author = {Tom Gunter and Chris Lloyd and Michael A. Osborne and Stephen J.
Roberts}, Title = {Efficient Bayesian Nonparametric Modelling of Structured
Point Processes}, Booktitle = {Uncertainty in Artificial Intelligence (UAI)},
Year = {2014}
THE EXAMINATION OF SHOCK WAVE ATTENUATION IN RUNNING SHOES
Various sports footwear companies have produced different types of running shoes to “mimic” barefoot walking or running such as FiveFingers and Rush shoes. There is limited evidence suggesting these shoes are able to reduce vertical ground reaction forces while standing, walking or running. The purpose of this study was to examine the vertical ground reaction forces between the minimalist shoes and traditional well-cushioned shoes. All shoes underwent both static and dynamic performance testing on top of an AMTI force platform. The results indicated that the Vibram minimalist shoe provided the highest amount of vertical ground reaction forces during the dynamic testing but the lowest amount of vertical ground reaction forces during the static testing. The study provides a preliminary understanding of vertical ground reaction forces in minimalist running shoes
THE EXAMINATION OF ANKLE JOINT MOTION BETWEEN BAREFOOT AND MINIMALIST RUNNING SHOES DURING GAIT CYCLES
Studying gait analysis with particular running shoes is extremely important because the ankle and foot serve as the foundation of structural balance, support, and propulsion. In this study Vibram FiveFingers and Nike Free Run minimalist shoes were chosen because of their popularity and uniqueness. During the testing each participant ran 30 s at the speed of 3 m/s on a flat treadmill for the FiveFingers shoe, Free Run shoe, and barefoot condition. The gait cycles of heel strike, mid support and toe off were examined. In this study no statistical significant increase or decrease in dorsiflexion or plantarflexion angles was observed in the Nike Free Run or Vibram FiveFingers in any phase of gait. This study suggests that both types of minimalist footwear do “mimic” barefoot running because they do not hinder a runner’s range of motion in the ankle joint while running
Ensemble Concerts: Men\u27s Glee Club Winter Concert, December 13, 1972
Capen AuditoriumWednesday EveningDecember 13, 19728:15 p.m
Ensemble Concerts: Men\u27s Glee Club Spring Concert, May 16, 1972
Capen AuditoriumTuesday EveningMay 16,19728:15 p.m
Ensemble Concerts: Men\u27s Glee Club Spring Concert, May 9, 1973
Capen AuditoriumWednesday EveningMay 9, 19738:15 p.m
Ensemble Concerts: Men\u27s Glee Club, December 14, 1971
Capen AuditoriumTuesday EveningDecember 14, 19718:15 p.m
Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF
Background
To develop antibacterial agents having novel modes of action against bacterial cell wall biosynthesis, we targeted the essential MurF enzyme of the antibiotic resistant pathogen Pseudomonas aeruginosa. MurF catalyzes the formation of a peptide bond between D-Alanyl-D-Alanine (D-Ala-D-Ala) and the cell wall precursor uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (UDP-MurNAc-Ala-Glu-meso-A2pm) with the concomitant hydrolysis of ATP to ADP and inorganic phosphate, yielding UDP-N-acetylmuramyl-pentapeptide. As MurF acts on a dipeptide, we exploited a phage display approach to identify peptide ligands having high binding affinities for the enzyme.
Results
Screening of a phage display 12-mer library using purified P. aeruginosa MurF yielded to the identification of the MurFp1 peptide. The MurF substrate UDP-MurNAc-Ala-Glumeso-A2pm was synthesized and used to develop a sensitive spectrophotometric assay to quantify MurF kinetics and inhibition. MurFp1 acted as a weak, time-dependent inhibitor of MurF activity but was a potent inhibitor when MurF was pre-incubated with UDP-MurNAc-Ala-Glu-meso-A2pm or ATP. In contrast, adding the substrate D-Ala-D-Ala during the pre-incubation nullified the inhibition. The IC50 value of MurFp1 was evaluated at 250 ÎĽM, and the Ki was established at 420 ÎĽM with respect to the mixed type of inhibition against D-Ala-D-Ala.
Conclusion
MurFp1 exerts its inhibitory action by interfering with the utilization of D-Ala-D-Ala by the MurF amide ligase enzyme. We propose that MurFp1 exploits UDP-MurNAc-Ala-Glu-meso-A2pm-induced structural changes for better interaction with the enzyme. We present the first peptide inhibitor of MurF, an enzyme that should be exploited as a target for antimicrobial drug development
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