Alternative medicine | EPFL Graph Search

Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability or evidence of effectiveness. Unlike modern medicine, which employs the scientific method to test plausible therapies by way of responsible and ethical clinical trials, producing repeatable evidence of either effect or of no effect, alternative therapies reside outside of medical science and do not originate from using the scientific method, but instead rely on testimonials, anecdotes, religion, tradition, superstition, belief in supernatural "energies", pseudoscience, errors in reasoning, propaganda, fraud, or other unscientific sources. Frequently used terms for relevant practices are New Age medicine, pseudo-medicine, unorthodox medicine, holistic medicine, fringe medicine, and unconventional medicine, with little distinction from quackery. Some alternative practices are based on theories that contradict the established sci

Gestion dynamique des échelles de données raster dans un environnement interactif

Benoit Le Bocey

Scale and resolution have long been key issues of geography. In recent years, the rapid development of desktop or Internet Geographic Information Systems (GIS) has forced a more precise consideration of these concepts. This research focuses on fitting the resolution of morphologic and thematic raster data, to the scale chosen to represent them in a GIS. To better adapt this resolution, reference aggregation methods based on the type of data are proposed. In the case of morphological raster data, this reference method is visually and statistically compared with two other alternative methods potentially used in existing interfaces. The feasibility of this research's concepts has been tested with an interactive web interface created for this purpose. This work demonstrates that it is necessary to adjust carefully the resolution of raster data to the display scale chosen by the user.

2010

On the replication of adeno-associated virus in the presence or absence of viral helper functions

Anika Ekrut

Adeno-associated virus (AAV) is a small non-enveloped virus and as a member of the parvovirus family, it contains a single stranded DNA genome. AAV's life cycle in vitro is strongly dependent not only on cellular factors but also on helper functions provided by other viruses, for example adenovirus, herpes virus and, to a certain extent, papillomavirus (HPV). Although AAVs are wide spread throughout the human population, no disease is yet associated with them. Accordingly, AAV became attractive as a vector for gene therapy studies, but even though the virus is well studied in vitro and now used in clinical trials as a vector, not much is known about AAV infection in vivo. AAV was initially isolated from humans together with its helper adenovirus. However, adenovirus-independent replication of AAV has been reported for a number of cellular situations, including differentiating keratinocytes with or without the presence of HPV, and in cells with an activated DNA damage response due to genotoxic agents. In the work reported here we have undertaken a systematic study of these alternative helper activities with a view to evaluating their contribution to natural infections by AAV. We used three different systems of cultured keratinocytes and showed that in each case in vitro differentiation was achieved. In two of these, the cells were from HPV-induced lesions. We found that AAV replicates efficiently in differentiating monolayer foreskin keratinocytes in the presence but not in the absence of adenovirus. Likewise naturally HPV-infected cervical keratinocytes only support the full life cycle of AAV if adenovirus is present. Even though HPV can provide certain helper functions, it is less efficient as a helper than adenovirus. We also exploited osteosarcoma cells, which are particularly well infected by AAV. Our results indicate that U2OS osteosarcoma cells are semi-permissive for AAV growth. Induction of a DNA damage response in these cells, or in HPV-containing keratinocytes, stimulates AAV genome amplification. Although AAV replication in the absence of helper virus can readily be demonstrated, this is either at a relatively low level or limited to part of the AAV growth cycle. We conclude that although these alternative helper systems can contribute to the natural history of AAV, the presence of an efficient helper virus seems likely to be needed for AAV to persist in the human population.

EPFL2009

Design and Evaluation of New Quinazolin-4(3H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa

Eduard Vico Oton

P. aeruginosa (PA) continues to pose a threat to global public health due to its high levels of antimicrobial resistance (AMR). The ongoing AMR crisis has led to an alarming shortage of effective treatments for resistant microbes, and hence there is a pressing demand for the development of novel antimicrobial interventions. The potential use of antivirulence therapeutics to tackle bacterial infections has attracted considerable attention over the past decades as they hamper the pathogenicity of target microbes with reduced selective pressure, minimizing the emergence of resistance. One such approach is to interfere with the PA pqs quorum sensing system which upon the interaction of PqsR, a Lys-R type transcriptional regulator, with its cognate signal molecules 4-hydroxy-2-heptylquinoline (HHQ) and 2-heptyl-3-hydroxy-4-quinolone (PQS), governs multiple virulence traits and host-microbe interactions. In this study, we report the hit identification and optimization of PqsR antagonists using virtual screening coupled with whole cell assay validation. The optimized hit compound 61 ((R)-2-(4-(3-(6-chloro-4-oxoquinazolin-3(4H)-yl)-2-hydroxypropoxy)phenyl)acetonitrile) was found to inhibit the expression of the PA P-pqsA promoter controlled by PqsR with an IC50 of 1 mu M. Using isothermal titration calorimetry, a K-d of 10 nM for the P-qsR ligand binding domain (PqsR(LBD)) was determined for 61. Furthermore, the crystal structure of 61 with PqsR(LBD) was attained with a resolution of 2.65 angstrom. Compound 61 significantly reduced levels of pyocyanin, PQS, and HHQ in PAO1-L, PA14 lab strains and PAK6085 clinical isolate. Furthermore, this compound potentiated the effect of ciprofloxacin in early stages of biofilm treatment and in Galleria mellonella infected with PA. Altogether, this data shows 61 as a potent PqsR inhibitor with potential for hit to lead optimization toward the identification of a PA QS inhibitor which can be advanced into preclinical development.

AMER CHEMICAL SOC2021