LOCSET phase locking : operation, diagnostics, and applications

The aim of this dissertation is to discuss the theoretical and experimental work recently done with the Locking of Optical Coherence via Single-detector Electronic-frequency Tagging (LOCSET) phase locking technique developed and employed here are AFRL. The primary objectives of this effort are to detail the fundamental operation of the LOCSET phase locking technique, recognize the conditions in which the LOCSET control electronics optimally operate, demonstrate LOCSET phase locking with higher channel counts than ever before, and extend the LOCSET technique to correct for low order, atmospherically induced, phase aberrations introduced to the output of a tiled array of coherently combinable beams. The experimental work performed for this effort resulted in the coherent combination of 32 low power optical beams operating with unprecedented LOCSET phase error performance of λ/71 RMS in a local loop beam combination configuration. The LOCSET phase locking technique was also successfully extended, for the first time, into an Object In the Loop (OIL) configuration by utilizing light scattered off of a remote object as the optical return signal for the LOCSET phase control electronics. Said LOCSET-OIL technique is capable of correcting for low order phase aberrations caused by atmospheric turbulence disturbances applied across a tiled array output

How to sequence 10,000 bacterial genomes and retain your sanity: an accessible, efficient and global approach

Non-typhoidal Salmonella(NTS)are typically associated with enterocolitis and linked to the industrialisation of food production. In recent years, NTS has been associated with invasive disease (iNTS disease) causing an estimated 77,000 deaths each year worldwide; 80% of mortality occurs in sub-Saharan Africa. New clades of S. Typhimurium and S. Enteritidis have been identified, which are characterised by genomic degradation, altered prophage repertoires and novel multidrug resistant plasmids. To understand how these clades are contributing to the burden and severity of iNTS disease, it is crucial to expand genome-based surveillance to cover more countries, and incorporate historical isolates to generate an evolutionary timeline of the development of iNTS. We developedand validateda robust and inexpensive method for large-scale collection and sequencing of bacterial genomes. The “10,000 Salmonella genomes” project established a worldwide research collaboration to generate information relevant to the epidemiology, drug resistance and virulence factors of Salmonellae using a whole-genome sequencing approach. By streamlining collection of isolates and developing an efficient logistics pipeline, we gathered 10,419 clinical and environmental isolates from collections in low and middle-income countries within six months. Genome sequences are now available for isolates from 51 countries/territories dating from 1949 to 2017, with ~80 % representing African and Latin-American datasets. Our method can be applied to other large sample collections that require maximisation of resources within a limited timeframe. Detailed genome analyses are in progress and it is hoped that the resulting data will contribute to public health control strategies in low and middle-income countries

<i>Salmonella enterica</i>serovar Typhimurium ST313 sublineage 2.2 has emerged in Malawi with a characteristic gene expression signature and a fitness advantage

AbstractInvasive non-typhoidalSalmonella(iNTS) disease is a serious bloodstream infection that targets immune-compromised individuals, and causes significant mortality in sub-Saharan Africa.Salmonella entericaserovar Typhimurium ST313 causes the majority of iNTS in Malawi, and we performed an intensive comparative genomic analysis of 608 isolates obtained from fever surveillance at the Queen Elizabeth Hospital, Blantyre between 1996 and 2018. We discovered that following the upsurge of the well-characterisedS.Typhimurium ST313 lineage 2 from 1999 onwards, two new multidrug-resistant sublineages designated 2.2 and 2.3, emerged in Malawi in 2006 and 2008, respectively. The majority ofS.Typhimurium isolates from human bloodstream infections in Malawi now belong to sublineage 2.2 or 2.3. To identify factors that characterised the emergence of the prevalent ST313 sublineage 2.2, we performed genomic and functional analysis of two representative strains, D23580 (lineage 2) and D37712 (sublineage 2.2). Comparative genomic analysis showed that the chromosome of ST313 lineage 2 and sublineage 2.2 were broadly similar, only differing by 29 SNPs and small indels and a 3kb deletion in the Gifsy-2 prophage region that spanned thesseIpseudogene. Lineage 2 and sublineage 2.2 have unique plasmid profiles that were verified by long read sequencing. The transcriptome was initially explored in 15 infection-relevant conditions and within macrophages. Differential gene expression was subsequently investigated in depth in the four most importantin vitrogrowth conditions. We identified up-regulation of SPI2 genes in non-inducing conditions, and down-regulation of flagellar genes in D37712, compared to D23580. Following phenotypic confirmation of transcriptional differences, we discovered that sublineage 2.2 had increased fitness compared with lineage 2 during mixed-growth in minimal media. We speculate that this competitive advantage is contributing to the continuing presence of sublineage 2.2 in Malawi.</jats:p

An accessible, efficient and global approach for the large-scale sequencing of bacterial genomes

We have developed an efficient and inexpensive pipeline for streamlining large-scale collection and genome sequencing of bacterial isolates. Evaluation of this method involved a worldwide research collaboration focused on the model organism Salmonella enterica, the 10KSG consortium. Following the optimization of a logistics pipeline that involved shipping isolates as thermolysates in ambient conditions, the project assembled a diverse collection of 10,419 isolates from low- and middle-income countries. The genomes were sequenced using the LITE pipeline for library construction, with a total reagent cost of less than USD$10 per genome. Our method can be applied to other large bacterial collections to underpin global collaborations

Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

Bloodstream infections caused by nontyphoidal Salmonella are a major public health concern in Africa, causing ~49,600 deaths every year. The most common Salmonella enterica pathovariant associated with invasive nontyphoidal Salmonella disease is Salmonella Typhimurium sequence type (ST)313. It has been proposed that antimicrobial resistance and genome degradation has contributed to the success of ST313 lineages in Africa, but the evolutionary trajectory of such changes was unclear. Here, to define the evolutionary dynamics of ST313, we sub-sampled from two comprehensive collections of Salmonella isolates from African patients with bloodstream infections, spanning 1966 to 2018. The resulting 680 genome sequences led to the discovery of a pan-susceptible ST313 lineage (ST313 L3), which emerged in Malawi in 2016 and is closely related to ST313 variants that cause gastrointestinal disease in the United Kingdom and Brazil. Genomic analysis revealed degradation events in important virulence genes in ST313 L3, which had not occurred in other ST313 lineages. Despite arising only recently in the clinic, ST313 L3 is a phylogenetic intermediate between ST313 L1 and L2, with a characteristic accessory genome. Our in-depth genotypic and phenotypic characterization identifies the crucial loss-of-function genetic events that occurred during the stepwise evolution of invasive S. Typhimurium across Africa

LOCSET Phase Locking: Operation, Diagnostics, and Applications

The aim of this dissertation is to discuss the theoretical and experimental work recently done with the Locking of Optical Coherence via Single-detector Electronic-frequency Tagging (LOCSET) phase locking technique developed and employed here are AFRL. The primary objectives of this effort are to detail the fundamental operation of the LOCSET phase locking technique, recognize the conditions in which the LOCSET control electronics optimally operate, demonstrate LOCSET phase locking with higher channel counts than ever before, and extend the LOCSET technique to correct for low order, atmospherically induced, phase aberrations introduced to the output of a tiled array of coherently combinable beams. The experimental work performed for this effort resulted in the coherent combination of 32 low power optical beams operating with unprecedented LOCSET phase error performance of λ/71 RMS in a local loop beam combination configuration. The LOCSET phase locking technique was also successfully extended, for the first time, into an Object In the Loop (OIL) configuration by utilizing light scattered off of a remote object as the optical return signal for the LOCSET phase control electronics. Said LOCSET-OIL technique is capable of correcting for low order phase aberrations caused by atmospheric turbulence disturbances applied across a tiled array output

Power scaling of a hybrid microstructured Yb-doped fiber amplifier

Hybrid microstructured fibers, utilizing both air holes and high index cladding structures, provide important advantages over conventional fiber including robust fundamental mode operation with large core diameters (>30 mu m) and spectral filtering (i.e. amplified spontaneous emission and Raman suppression). This work investigates the capabilities of a hybrid fiber designed to suppress stimulated Brillouin scattering (SBS) and modal instability (MI) by characterizing these effects in a counter-pumped amplifier configuration as well as interrogating SBS using a pump-probe Brillouin gain spectrum (BGS) diagnostic suite. The fiber has a 35 mu m annularly gain tailored core, the center doped with Yb and the second annulus comprised of un-doped fused silica, designed to optimize gain in the fundamental mode while limiting gain to higher order modes. A narrow-linewidth seed was amplified to an MI-limited 820 W, with near-diffraction-limited beam quality, an effective linewidth similar to 1 GHz, and a pump conversion efficiency of 78%. Via a BGS pump-probe measurement system a high resolution spectra and corresponding gain coefficient were obtained. The primary gain peak, corresponding to the Yb doped region of the core, occurred at 15.9 GHz and had a gain coefficient of 1.92x10(-11) m/W. A much weaker BGS response, due to the pure silica annulus, occurred at 16.3 GHz. This result demonstrates the feasibility of power scaling hybrid microstructured fiber amplifiersThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

400-W near diffraction-limited single-frequency all-solid photonic bandgap fiber amplifier

An ytterbium-doped large-mode area photonic bandgap fiber is used to demonstrate 400 W of single-frequency output at 1064 nm with excellent beam quality and minimal stimulated Brillouin scattering. The fiber possesses all-solid microstructures embedded in the cladding and a core composed of phosphosilicate with a diameter of ∼50  μm. As the signal power is pushed beyond 450 W, there is degradation in the beam quality due to the modal instability. We briefly discuss techniques to alleviate this problem in future designs. To the best of our knowledge, the 400-W single-frequency near diffraction-limited output far exceeds the current state-of-the-art from such type of fiber amplifier

400-W near diffraction-limited single-frequency all-solid photonic bandgap fiber amplifier

An ytterbium-doped large-mode area photonic bandgap fiber is used to demonstrate 400 W of single-frequency output at 1064 nm with excellent beam quality and minimal stimulated Brillouin scattering. The fiber possesses all-solid microstructures embedded in the cladding and a core composed of phosphosilicate with a diameter of ∼50  μm. As the signal power is pushed beyond 450 W, there is degradation in the beam quality due to the modal instability. We briefly discuss techniques to alleviate this problem in future designs. To the best of our knowledge, the 400-W single-frequency near diffraction-limited output far exceeds the current state-of-the-art from such type of fiber amplifier

Media 1: 400-W near diffraction-limited single-frequency all-solid photonic bandgap fiber amplifier

Originally published in Optics Letters on 15 May 2015 (ol-40-10-2297