Phase locking of coupled lasers with many longitudinal modes

Detailed experimental and theoretical investigations on two coupled fiber lasers, each with many longitudinal modes, reveal that the behavior of the longitudinal modes depends on both the coupling strength as well as the detuning between them. For low to moderate coupling strength only longitudinal modes which are common for both lasers phase-lock while those that are not common gradually disappear. For larger coupling strengths, the longitudinal modes that are not common reappear and phase-lock. When the coupling strength approaches unity the coupled lasers behave as a single long cavity with correspondingly denser longitudinal modes. Finally, we show that the gradual increase in phase-locking as a function of the coupling strength results from competition between phase-locked and non phase-locked longitudinal modes.Comment: 3 pages, 4 figures, submitted to opt. let

Fiber amplification of radially and azimuthally polarized laser light

The results on amplifying either radially or azimuthally polarized light with a fiber amplifier are presented. Experimental results reveal that more than 85% polarization purity can be retained at the output even with 40dB amplification, and that efficient conversion of the amplified light to linear polarization can be obtained.Comment: 3 pages, 4 figures, submitted to optics letter

Benzylic Dehydroxylation of Echinocandin antifungal drugs restores efficacy against resistance conferred by mutated Glucan Synthase

Each year, infections caused by fungal pathogens claim the lives of about 1.6 million people and affect the health of over a billion people worldwide. Among the most recently developed antifungal drugs are the echinocandins, which noncompetitively inhibit β-glucan synthase, a membrane-bound protein complex that catalyzes the formation of the main polysaccharide component of the fungal cell wall. Resistance to echinocandins is conferred by mutations in FKS genes, which encode the catalytic subunit of the β-glucan synthase complex. Here, we report that selective removal of the benzylic alcohol of the nonproteinogenic amino acid 3S,4S-dihydroxy-l-homotyrosine of the echinocandins anidulafungin and rezafungin, restored their efficacy against a large panel of echinocandin-resistant Candida strains. The dehydroxylated compounds did not significantly affect the viability of human-derived cell culture lines. An analysis of the efficacy of the dehydroxylated echinocandins against resistant Candida strains, which contain mutations in the FKS1 and/or FKS2 genes of the parental strains, identified amino acids of the Fks proteins that are likely to reside in proximity to the l-homotyrosine residue of the bound drug. This study describes the first example of a chemical modification strategy to restore the efficacy of echinocandin drugs, which have a critical place in the arsenal of antifungal drugs, against resistant fungal pathogens.The authors thank J. Berman and D. Perlin for providing Candida strains. This work was supported by the Israel Science Foundation Grant 179/19 (Micha Fridman). TG acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00 and from the “la Caixa” Foundation under the agreements LCF/PR/GN18/50310010 and LCF/PR/HR21/00737. They also thank E. Ainbinder. O. Singer, and Y. Fried from the Stem Cell Unit of Life Science Core Facilities, the Weizmann Institute of Science. They especially thank H. Barr, head of HTS and Medicinal Chemistry Units at the Maurice and Vivienne Wohl Institute for Drug Discovery, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science.Peer ReviewedPostprint (published version

6′′‐Thioether Tobramycin Analogues: Towards Selective Targeting of Bacterial Membranes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91322/1/ange_201200761_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91322/2/5750_ftp.pd

Branched aminoglycosides: biochemical studies and antibacterial activity of neomycin B derivatives

Abstract-The C5 00 -OH group in neomycin B was glycosylated with a variety of mono-and di-saccharides to probe the effect of introduction of additional binding elements on antibacterial activity and interaction with the aminoglycosides modifying enzyme APH(3 0 )-IIIa. The designed structures show antibacterial activity superior to that of neomycin B against pathogenic and resistant strains, while in parallel they demonstrate poor substrate activity with APH(3 0 )-IIIa

Poacic Acid, a Plant-Derived Stilbenoid, Augments Cell-Wall Chitin Production, but Its Antifungal Activity Is Hindered by this Polysaccharide and by Fungal Essential Metals

Climate and environmental changes have modified the habitats of fungal pathogens, inflicting devastating effects on livestock and crop production. Additionally, drug-resistant fungi are increasing worldwide, driving the urgent need to identify new molecular scaffolds for development of antifungal agents for humans, animals, and plants. Poacic acid (PA), a plant-derived stilbenoid, was recently discovered to be a novel molecular scaffold that inhibits the growth of several fungi. Its antifungal activity has been associated with perturbation of the production/assembly of fungal cell wall β-1,3-glucan, but its mode of action is not resolved. In this study, we investigated the antifungal activity of PA and its derivatives on a panel of yeast. PA had a fungistatic effect on S. cerevisiae and a fungicidal effect on plasma membrane-damaged Candida albicans mutants. Live cell fluorescent microscopy experiments revealed that PA increases chitin production and modifies its cell wall distribution. Chitin production and cell growth returned to normal after prolonged incubation. The antifungal activity of PA was reduced in the presence of exogenous chitin, suggesting that potentiation of chitin production is a stress response that helps the yeast cell overcome the effect of this antifungal stilbenoid. Growth inhibition was also reduced by metal ions, indicating that PA affects metal homeostasis. These findings suggest that PA has a complex antifungal mechanism of action that involves perturbation of cell wall β-1,3-glucan production/assembly, chitin production, and metal homeostasis