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We report the preparation and spectroscopic characterization of a highly elusive copper site bound exclusively to oxygen donor atoms within a protein scaffold. Despite copper generally being considered unsuitable for use in MRI contrast agents, which in the clinic are largely Gd(III) based, the designed copper coiled coil displays relaxivity values equal to, or superior than, those of the Gd(III) analog at clinical field strengths. The creation of this new-to-biology proteinaceous CuOx-binding site demonstrates the power of the de novo peptide design approach to access chemistry for abiological applications, such as for the development of MRI contrast agents.
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Meios de Contraste , Cobre , Cobre/metabolismo , Meios de Contraste/química , Imageamento por Ressonância Magnética , Sítios de Ligação , PeptídeosRESUMO
Cryptococcosis is a potentially lethal fungal infection of humans caused by organisms within the Cryptococcus neoformans/gattii species complex. Whilst C. neoformans is a relatively common pathogen of immunocompromised individuals, C. gattii is capable of acting as a primary pathogen of immunocompetent individuals. Within the host, both species undergo morphogenesis to form titan cells: exceptionally large cells that are critical for disease establishment. To date, the induction, defining attributes, and underlying mechanism of titanisation have been mainly characterized in C. neoformans. Here, we report the serendipitous discovery of a simple and robust protocol for in vitro induction of titan cells in C. gattii. Using this in vitro approach, we reveal a remarkably high capacity for titanisation within C. gattii, especially in strains associated with the Pacific Northwest Outbreak, and characterise strain-specific differences within the clade. In particular, this approach demonstrates for the first time that cell size changes, DNA amplification, and budding are not always synchronous during titanisation. Interestingly, however, exhibition of these cell cycle phenotypes was correlated with genes associated with cell cycle progression including CDC11, CLN1, BUB2, and MCM6. Finally, our findings reveal exogenous p-Aminobenzoic acid to be a key inducer of titanisation in this organism. Consequently, this approach offers significant opportunities for future exploration of the underlying mechanism of titanisation in this genus.
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Cryptococcus gattii , Cryptococcus neoformans , Proteínas Fúngicas , Humanos , Hospedeiro Imunocomprometido , Componente 6 do Complexo de Manutenção de MinicromossomoRESUMO
[This corrects the article DOI: 10.1371/journal.ppat.1010321.].
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Silicon planar waveguides are designed to maximize the wavelength conversion efficiency via the use of Raman-enhanced four-wave mixing in the telecom band. By investigating the dispersion properties of various rib waveguide structures, the optimum etch depth and width are selected to obtain efficient phase-matching for a continuous-wave pump at 1545â nm. The design benefits from good fabrication tolerance in the structural parameters, which are well within the precision of standard lithography and etching processes. Using the optimized waveguides, simulations show that it is possible to reach conversion efficiencies as high as â¼45â dB for waveguide lengths as short as 4.6â cm, with a pump power of only 130â mW. This enhancement in the conversion efficiency is about 50â dB higher than conventional values for FWM in integrated silicon photonic systems, highlighting the benefits of exploiting the coupling between the two nonlinear processes.
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This joint issue of Optics Express and Optical Materials Express showcases 29 articles that report the latest advancements in nonlinear optics. These articles include contributions from authors who participated in the Optica Nonlinear Optics Topical Meeting, which took place in Honolulu, Hawaii, from July 10th to July 14th, 2023. The conference was organized by Optica (formerly known as OSA). As an introduction, the editors provide a summary of these articles, which cover a broad range of topics in nonlinear optics, spanning from fundamental nonlinear optical concepts to novel nonlinear effects, and from innovative nonlinear materials to topics such as ultrafast optics, machine learning empowered nonlinear optics, and unconventional applications. This diverse array of contributions reflects the dynamic and interdisciplinary nature of contemporary research in the field of nonlinear optics while showcasing some of the most recent developments.
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Low-temperature deposited polycrystalline silicon waveguides are emerging as a flexible platform that allows for dense optoelectronic integration. Here, the optical transmission properties of poly-silicon waveguides have been characterized from the near-to-mid-infrared wavelength regime, extending the optical transmission well beyond previous reports in the telecom band. The poly-Si waveguides with a dimension of 3â µm × â¼0.6â µm have been produced from pre-patterned amorphous silicon waveguides that are post-processed through laser melting, reflowing, and crystallization using a highly localized laser induced heat treatment at a wavelength of 532 nm. Low optical transmission losses (<3â dBâ cm-1) have been observed at 1.55â µm as well as across the wavelength range of 2-2.25â µm, aided by the relatively large waveguide heights that are enabled by the deposition process. The results demonstrate the suitability of low-temperature poly-silicon waveguides to find wide ranging applications within integrated mid-infrared systems.
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A strong Raman enhancement to the four-wave mixing (FWM) conversion efficiency is obtained in a silicon core fiber (SCF) when pumped with a continuous-wave (CW) source in the telecom band. By tapering the SCFs to alter the core diameter and length, the role of phase-matching on the conversion enhancement is investigated, with a maximum Raman enhancement of â¼15â dB obtained for an SCF with a zero dispersion wavelength close to the pump. Simulations show that by optimizing the tapered waist diameter to overlap the FWM phase-matching with the peak Raman gain, it is possible to obtain large Raman enhanced FWM conversion efficiencies of up to â¼2â dB using modest CW pump powers over wavelengths covering the extended telecom bands.
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Herein we report unprecedented location-dependent, size-selective binding to designed lanthanide (Ln3+ ) sites within miniature protein coiled coil scaffolds. Not only do these engineered sites display unusual Ln3+ selectivity for moderately large Ln3+ ions (Nd to Tb), for the first time we demonstrate that selectivity can be location-dependent and can be programmed into the sequence. A 1â nm linear translation of the binding site towards the N-terminus can convert a selective site into a highly promiscuous one. An X-ray crystal structure, the first of a lanthanide binding site within a coiled coil to be reported, coupled with CD studies, reveal the existence of an optimal radius that likely stems from the structural constraints of the coiled coil scaffold. To the best of our knowledge this is the first report of location-dependent metal selectivity within a coiled coil scaffold, as well as the first report of location-dependent Ln3+ selectivity within a protein.
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Elementos da Série dos Lantanídeos/química , Peptídeos/química , Sequência de Aminoácidos , Sítios de Ligação , Íons/química , Elementos da Série dos Lantanídeos/metabolismo , Modelos Moleculares , Peptídeos/metabolismo , Conformação Proteica em alfa-HéliceRESUMO
We report nonlinear optical characterization of cm-long polycrystalline silicon (poly-Si) waveguides at telecom wavelengths. Laser post-processing of lithographically-patterned amorphous silicon deposited on silica-on-silicon substrates provides low-loss poly-Si waveguides with surface-tension-shaped boundaries. Achieving optical losses as low as 4 dB cm-1 enabled us to demonstrate effects of self-phase modulation (SPM) and two-photon absorption (TPA). Analysis of the spectral broadening and nonlinear losses with numerical modeling reveals the best fit values of the Kerr coefficient n2=4.5×10-18 m W-1 and TPA coefficient ßTPA=9.0×10-12 m2 W-1, which are within the range reported for crystalline silicon. On-chip low-loss poly-Si paves the way for flexible integration of nonlinear components in multi-layered photonic systems.
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A novel technique for realization of configurable/one-time programmable (OTP) silicon photonic circuits is presented. Once the proposed photonic circuit is programmed, its signal routing is retained without the need for additional power consumption. This technology can potentially enable a multi-purpose design of photonic chips for a range of different applications and performance requirements, as it can be programmed for each specific application after chip fabrication. Therefore, the production costs per chip can be reduced because of the increase in production volume, and rapid prototyping of new photonic circuits is enabled. Essential building blocks for the configurable circuits in the form of erasable directional couplers (DCs) were designed and fabricated, using ion implanted waveguides. We demonstrate permanent switching of optical signals between the drop port and through the port of the DCs using a localized post-fabrication laser annealing process. Proof-of-principle demonstrators in the form of generic 1×4 and 2×2 programmable switching circuits were fabricated and subsequently programmed.
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We report the fabrication of low-loss, low temperature deposited polysilicon waveguides via laser crystallization. The process involves pre-patterning amorphous silicon films to confine the thermal energy during the crystallization phase, which helps to control the grain growth and reduce the heat transfer to the surrounding media, making it compatible with CMOS integration. Micro-Raman spectroscopy, Secco etching and X-ray diffraction measurements reveal the high crystalline quality of the processed waveguides with the formation of millimeter long crystal grains. Optical losses as low as 5.3 dB/cm have been measured, indicating their suitability for the development of high-density integrated circuits.
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Few-layer molybdenum disulfide (MoS2) has an electronic band structure that is dependent on the number of layers and, therefore, is a very promising material for an array of optoelectronic, photonic, and lasing applications. In this Letter, we make use of a side-polished optical fiber platform to gain access to the nonlinear optical properties of the MoS2 material. We show that the nonlinear response can be significantly enhanced via resonant coupling to the thin film material, allowing for the observation of optical modulation and spectral broadening in the telecom band. This route to access the nonlinear properties of two-dimensional materials promises to yield new insights into their photonic properties.
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Reported here is the fabrication of tapered silicon core fibers possessing a nano-spike input that facilitates their seamless splicing to conventional single mode fibers. A proof-of-concept 30 µm cladding diameter fiber-based device is demonstrated with nano-spike coupling and propagation losses below 4 dB and 2 dB/cm, respectively. Finite-element-method-based simulations show that the nano-spike coupling losses could be reduced to below 1 dB by decreasing the cladding diameters down to 10 µm. Such efficient and robust integration of the silicon core fibers with standard fiber devices will help to overcome significant barriers for all-fiber nonlinear photonics and optoelectronics.
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We correct an error of the nonlinear refractive index used in our original paper.
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Although metal ion binding to naturally occurring l-amino acid proteins is well documented, understanding the impact of the opposite chirality (d-)amino acids on the structure and stereochemistry of metals is in its infancy. We examine the effect of a d-configuration cysteine within a designed l-amino acid three-stranded coiled coil in order to enforce a precise coordination number on a metal center. The d chirality does not alter the native fold, but the side-chain re-orientation modifies the sterics of the metal binding pocket. l-Cys side chains within the coiled-coil structure have previously been shown to rotate substantially from their preferred positions in the apo structure to create a binding site for a tetra-coordinate metal ion. However, here we show by X-ray crystallography that d-Cys side chains are preorganized within a suitable geometry to bind such a ligand. This is confirmed by comparison of the structure of ZnII Cl(CSL16D C)32- to the published structure of ZnII (H2 O)(GRAND-CSL12AL16L C)3- . Moreover, spectroscopic analysis indicates that the CdII geometry observed by using l-Cys ligands (a mixture of three- and four-coordinate CdII ) is altered to a single four-coordinate species when d-Cys is present. This work opens a new avenue for the control of the metal site environment in man-made proteins, by simply altering the binding ligand with its mirror-imaged d configuration. Thus, the use of non-coded amino acids in the coordination sphere of a metal promises to be a powerful tool for controlling the properties of future metalloproteins.
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Here, we describe novel polyion complex (PIC) particles for the delivery of Polymyxin B (Pol-B), an antimicrobial peptide currently used in the clinic as a last resort antibiotic against multidrug-resistant gram-negative bacteria. A range of conditions for the controlled assembly of Pol-B with poly(styrene sulphonate) (PSS) has been identified which let us prepare stable colloidal PIC particles. This way, PIC particles containing different Pol-B:PSS ratios have been prepared and their stability under simulated physiological conditions (i.e. pH, osmotic pressure and temperature) characterised. Furthermore, preliminary evaluation of the antimicrobial activity of these Pol-B containing PIC particles has been performed, by monitoring their effect on the growth of Pseudomonas aeruginosa, an opportunistic gram-negative bacterium.
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A programmable fiber long-period grating (LPG) is experimentally demonstrated in a liquid core optical fiber with a low insertion loss. The LPG is dynamically formed by a temperature gradient in real time through a micro-heater array. The transmission spectrum of the LPG can be completely reconfigured by digitally changing the grating period, index contrast, length, and design. The phase shift inside the LPG can also be readily defined to enable advanced spectrum shaping. Owing to the high thermo-optic coefficient of the liquid core, it is possible to achieve high coupling efficiencies with driving powers as low as a few tens of milliwatts. The proposed thermo-programmable device provides a potential design solution for dynamic all-fiber optics components.
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We propose and demonstrate a novel approach to obtaining small-core polysilicon waveguides from the silicon fiber platform. The fibers were fabricated via a conventional drawing tower method and, subsequently, tapered down to achieve silicon core diameters of â¼1 µm, the smallest optical cores for this class of fiber to date. Characterization of the material properties have shown that the taper process helps to improve the local crystallinity of the silicon core, resulting in a significant reduction in the material loss. By exploiting the combination of small cores and low losses, these tapered fibers have enabled the first observation of nonlinear transmission within a polycrystalline silicon waveguide of any type. As the fiber drawing method is highly scalable, it opens a route for the development of low-cost and flexible nonlinear silicon photonic systems.
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For decades now, silicon has been the workhorse of the microelectronics revolution and a key enabler of the information age. Owing to its excellent optical properties in the near- and mid-infrared, silicon is now promising to have a similar impact on photonics. The ability to incorporate both optical and electronic functionality in a single material offers the tantalizing prospect of amplifying, modulating and detecting light within a monolithic platform. However, a direct consequence of silicon's transparency is that it cannot be used to detect light at telecommunications wavelengths. Here, we report on a laser processing technique developed for our silicon fibre technology through which we can modify the electronic band structure of the semiconductor material as it is crystallized. The unique fibre geometry in which the silicon core is confined within a silica cladding allows large anisotropic stresses to be set into the crystalline material so that the size of the bandgap can be engineered. We demonstrate extreme bandgap reductions from 1.11 eV down to 0.59 eV, enabling optical detection out to 2,100 nm.
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The nonlinear absorption properties of a germanium-on-silicon waveguide have been characterized across the two-photon absorption (TPA) transmission window. The results show that the TPA parameters in germanium waveguides are much stronger than the peak values in silicon, in good agreement with selected measurements conducted in bulk materials. Exploiting the large nonlinear absorption near the bandedge, efficient all-optical modulation is achieved with a modulation depth of â¼8 dB and a response time <5 ps.