Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model

Combining currently available antibiotics to optimize their use is a promising strategy to reduce treatment failures against biofilm-associated infections. Nevertheless, most assays of such combinations have been performed in vitro on planktonic bacteria exposed to constant concentrations of antibiotics over only 24 h and the synergistic effects obtained under these conditions do not necessarily predict the behavior of chronic clinical infections associated with biofilms. To improve the predictivity of in vitro combination assays for bacterial biofilms, we first adapted a previously described Hollow-fiber (HF) infection model by allowing a Staphylococcus aureus biofilm to form before drug exposure. We then mimicked different concentration profiles of amikacin and vancomycin, similar to the free plasma concentration profiles that would be observed in patients treated daily over 5 days. We assessed the ability of the two drugs, alone or in combination, to reduce planktonic and biofilm-embedded bacterial populations, and to prevent the selection of resistance within these populations. Although neither amikacin nor vancomycin exhibited any bactericidal activity on S. aureus in monotherapy, the combination had a synergistic effect and significantly reduced the planktonic bacterial population by -3.0 to -6.0 log10 CFU/mL. In parallel, no obvious advantage of the combination, as compared to amikacin alone, was demonstrated on biofilm-embedded bacteria for which the addition of vancomycin to amikacin only conferred a further maximum reduction of 0.3 log10 CFU/mL. No resistance to vancomycin was ever found whereas a few bacteria less-susceptible to amikacin were systematically detected before treatment. These resistant bacteria, which were rapidly amplified by exposure to amikacin alone, could be maintained at a low level in the biofilm population and even suppressed in the planktonic population by adding vancomycin. In conclusion, by adapting the HF model, we were able to demonstrate the different bactericidal activities of the vancomycin and amikacin combination on planktonic and biofilm-embedded bacterial populations, suggesting that, for biofilm-associated infections, the efficacy of this combination would not be much greater than with amikacin monotherapy. However, adding vancomycin could reduce possible resistance to amikacin and provide a relevant strategy to prevent the selection of antibiotic-resistant bacteria during treatments

Generování vzorků bicích souprav pomocí strojového učení

V této práci jsme navrhli nástroj pro interaktivní generování vzorků pro jednotlivé údery bicích nástrojů (one-shot samples) pomocí variačních autoenkodérů (VAE), v kontextu produkce elektronické hudby. Prozkoumali jsme reprezentace používané pro úlohu generování zvuku a vybrali dvě nejlépe vyhovující. Dále jsme sesbírali vlastní datovou sadu téměř 16,000 volně dostupných vzorků, které jsme setřídili do 9 kategorií bicích nástrojů. Sérií pokusů jsme pak došli k modelu, který rekonstruuje a generuje vzorky s postačující kvalitou, ačkoliv stále obsahují jeden šumový artefakt. Na základě pokusů s PCA a konvexními kombinacemi jsme zjistili, že natrénovaný latentní prostor má interpretovatelnou a tedy ovladatelnou topologii.In this thesis, we designed an interactive generative tool based on the Variational Autoencoder (VAE) to synthesise new and interesting drum one-shot samples for electronic music production. We researched audio representations used in audio generation tasks and selected two that suited our settings the best. Furthermore, we created our own dataset of almost 16,000 freely available samples organised into 9 drum categories. Through a series of experiments, we were able to achieve a model that was reconstructing and generating quality samples; however, they contained a specific noise artefact we could not get rid of. Based on the results of PCA and convex combinations methods we found out that the latent space has "meaningful" properties.Ústav formální a aplikované lingvistikyInstitute of Formal and Applied LinguisticsMatematicko-fyzikální fakultaFaculty of Mathematics and Physic

Synapse of the Self

http://deepblue.lib.umich.edu/bitstream/2027.42/108409/1/backol_1398957977.pd

Distinguishing between natural and cultural taphonomic agents in skeletal assemblages from human sacrifice sites in Pre-Columbian northern coastal Peru

This study expands upon traditional taphonomic techniques to distinguish between natural and cultural agents of modification among several Pre-Columbian human sacrificial sites from the north coast of Peru. The definition of taphonomy used here goes beyond traditional usage to include research issues in bioarchaeology and modern forensics. For the purposes of this research, taphonomy is thus defined broadly as the study and description of all postmortem processes, both natural and culturally-derived, which affect the subsequent recovery, condition and interpretation of skeletal remains. The use of both established techniques as well as innovative methodologies provide a fresh look on sample size estimation, element representation, disarticulation, and orientations. Unusual patterns of element loss, dismemberment, trauma, and dispersal, and grouping/positioning is quantified and graphically illustrated, and then compared to known patterns of taphonomic activity, which are then either confirmed or excluded. In addition, these techniques give additional insight into the overall level of taphonomic winnowing present. The resulting patterns were attributed almost exclusively to cultural rather than natural modifications. It was therefore possible to exclude both carnivore and fluvial activity from playing a central role at any of the included sites. In addition, the overall picture created by the taphonomic patterns both identified and elaborated upon several specific ritual activities practiced by these prehistoric cultures of Northern Peru. This included the deliberate removal of the cranial vault, a practice that was found to extend through the Moche III to the later Transitional period. Evidence from the Templo Nuevo suggested that the cranial vault was displayed or utilized for a period of time after removal. The deliberate removal of phalanges was also found to be present at the Moche III Plaza 3C and Transitional era Templo Nuevo, again illustrating cultural continuity. Also of note is the earliest evidence for the deliberate opening of the chest cavity involving cut marks on the manubrium from the Templo Nuevo, a practice that continued on into the later Chimu/Lambayeque periods. However, disarticulation patterns at Plaza 3C illustrate a focus on the torso area that could extend the practice even further in time to the Moche III era

Generating Drum Kit Samples using Machine Learning

In this thesis, we designed an interactive generative tool based on the Variational Autoencoder (VAE) to synthesise new and interesting drum one-shot samples for electronic music production. We researched audio representations used in audio generation tasks and selected two that suited our settings the best. Furthermore, we created our own dataset of almost 16,000 freely available samples organised into 9 drum categories. Through a series of experiments, we were able to achieve a model that was reconstructing and generating quality samples; however, they contained a specific noise artefact we could not get rid of. Based on the results of PCA and convex combinations methods we found out that the latent space has "meaningful" properties