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The magneto-optical Faraday and Kerr effects are widely used in modern optical devices. In this Letter, we propose an all-dielectric metasurface composed of perforated magneto-optical thin films, which can support the highly confined toroidal dipole resonance and provide full overlap between the localized electromagnetic field and the thin film, and consequently enhance the magneto-optical effects to an unprecedented degree. The numerical results based on the finite element method show that the Faraday and Kerr rotations can reach -13.59° and 8.19° in the vicinity of toroidal dipole resonance, which are 21.2 and 32.8 times stronger than those in the equivalent thickness of thin films. In addition, we design an environment refractive index sensor based on the resonantly enhanced Faraday and Kerr rotations, with sensitivities of 62.96 nm/RIU and 73.16 nm/RIU, and the corresponding maximum figures of merit 132.22°/RIU and 429.45°/RIU, respectively. This work provides a new, to the best of our knowledge, strategy for enhancing the magneto-optical effects at nanoscale, and paves the way for the research and development of magneto-optical metadevices such as sensors, memories, and circuits.
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In this paper, simultaneous zero refractive indices (ZRIs) for both sound and light are realized on the basis of a 2D triangular lattice phoxonic crystal (PxC) with C6v symmetry. For the phononic mode, accidental phononic Dirac degeneracy at the center of Brillouin zone (BZ) occurs at a relatively high frequency which leads to the failure of the efficient medium theory; hence, it is no longer applicable to the realization of acoustic ZRI. We thus turn to a low-frequency phononic Dirac cone located at K point, the corner of the BZ, which shows in-phase pressure field oscillations in expanded unit cells. Using zone folding, we further reveal the cause for the characteristic of acoustic ZRI. For the photonic mode, a low-frequency photonic Dirac-like cone can be achieved by adjusting the geometric parameter due to the high contrast permittivity between scatterers and the matrix. When the phononic and photonic low-frequency Dirac dispersions coexist, the PxC can be mapped into a zero-index material for both sound and light at the same time. The new mechanism for simultaneously controlling sound and light helps to achieve acousto-optic synchronous cloaking and unidirectional transmission, which are numerically demonstrated.
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We propose a width-tunable topological pseudospin-dependent waveguide (TPDW) which can manipulate the optical beam width using a heterostructure of all-dielectric photonic crystals (PhCs). The heterostructure can be realized by introducing a PhC featuring double Dirac cones into the other two PhCs with different topological indices. The topological pseudospin-dependent waveguide states (TPDWSs) achieved from the TPDW exhibit unidirectional transport and immunity against defects. As a potential application of our work, using these characteristics of TPDWSs, we further design a topological pseudospin-dependent beam expander which can expand a narrow beam into a wider one at the communication wavelength of 1.55â µm and is robust against three kinds of defects. The proposed TPDW with widely adjustable width can better dock with other devices to achieve stable and efficient transmission of light. Meanwhile, all-dielectric PhCs have negligible losses at optical wavelengths, which provides the prospect of broad application in photonic integrated devices.
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Enhancement of weak Casimir forces is extremely important for their practical detection and subsequent applications in variety of scientific and technological fields. We study the lateral Casimir forces acting on the rotating particles with small radius of 50 nm as well as that with large radius of 500 nm near the hyperbolic metamaterial made of silicon carbide (SiC) nanowires. It is found that the lateral Casimir force acting on the small particle of 50 nm near hyperbolic metamaterial with appropriate filling fraction can be enhanced nearly four times comparing with that acting on the same particle near SiC bulk in the previous study. Such enhancement is caused by the coupling between the resonance mode excited by nanoparticle and the hyperbolic mode supported by hyperbolic metamaterial. The results obtained in this study provide an efficient method to enhance the interaction of nanoscale objects.
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BACKGROUND: Although computer-aided detection (CAD) software employed with Artificial Intelligence (AI) system has been developed aiming to assist tuberculosis (TB) triage, screening, and diagnosis, its clinical performance for tuberculosis screening remains unknown. OBJECTIVE: To evaluate performance of an CAD software for detecting TB on chest X-ray images at a pilot active TB screening project. METHODS: A CAD software scheme employed with AI was used to screen chest X-ray images of participants and produce probability scores of cases being positive for TB. CAD-generated TB detection scores were compared with on-site and senior radiologists via several performance evaluation indices including area under the ROC curves (AUC), specificity, sensitive, and positive predict value. Pycharm CE and SPSS statistics software packages were used for data analysis. RESULTS: Among 2,543 participants, eight TB patients were identified from this screening pilot program. The AI-based CAD system outperformed the onsite (AUCâ=â0.740) and senior radiologists (AUCâ=â0.805) either using thresholds of 30% (AUCâ=â0.978) and 50% (AUCâ=â0.859) when taking the final diagnosis as the ground truth. CONCLUSIONS: The AI-based CAD software successfully detects all TB patients as identified from this study at a threshold of 30%. It demonstrates feasibility and easy accessibility to carry out large scale TB screening using this CAD software equipped in medical vans with chest X-ray imaging machine.
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Tuberculose Pulmonar , Tuberculose , Inteligência Artificial , Humanos , Projetos Piloto , Tuberculose/diagnóstico por imagem , Tuberculose Pulmonar/diagnóstico por imagem , Raios XRESUMO
Purpose: To investigated the changes of gut microbiome and fecal metabolome during anti-tuberculosis chemotherapy with isoniazid (H)-rifampin (R)-pyrazinamide (Z)-ethambutol (E). Patients and methods: (1) In this study, we recruited 168 stool specimens from 49 healthy volunteers without M. tuberculosis (Mtb), 30 healthy volunteers with latently infected by Mtb, 41 patients with active tuberculosis (ATB), 28 patients with 2-month HRZE treatment and 20 patients with 2-month HRZE followed by 4-month HR treatment. (2) We used 16S rRNA sequencing and an untargeted Liquid Chromatograph Mass Spectrometer-based metabolomics to investigate the changes of gut microbiome and the alteration of fecal metabolome, respectively, during anti-TB chemotherapy. Results: Mtb infection can reduce the diversity of intestinal flora of ATB patients and change their taxonomic composition, while the diversity of intestinal flora of ATB patients were restored during anti-TB chemotherapy. Especially, family Veillonellacea and Bateroidaceae and their genera Veillonella and Bacteroides significantly increased in the gut microbiota during anti-TB chemotherapy. Additionally, Mtb infection dynamically regulates fecal metabolism in ATB patients during anti-TB chemotherapy. Interestingly, the altered abundance of fecal metabolites correlated with the altered gut microbiota, especially the change of gut Clostridium, Bacteroides and Prevotella was closely related to the change of fecal metabolites such as Trans-4-Hydroxy-L-proline and Genistein caused by Mtb infection or anti-TB chemotherapy. Conclusion: Anti-TB chemotherapy with HRZE can disrupt both gut microbiotas and metabolome in ATB patients. Some specific genera and metabolites are depleted or enriched during anti-TB chemotherapy. Therefore, revealing potential relevance between gut microbiota and anti-TB chemotherapy will provide potential biomarkers for evaluating the therapeutic efficacy in ATB patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01003-2.
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Evolutionary trajectories are deemed largely irreversible. In a newly diverged protein, reversion of mutations that led to the functional switch typically results in loss of both the new and the ancestral functions. Nonetheless, evolutionary transitions where reversions are viable have also been described. The structural and mechanistic causes of reversion compatibility versus incompatibility therefore remain unclear. We examined two laboratory evolution trajectories of mammalian paraoxonase-1, a lactonase with promiscuous organophosphate hydrolase (OPH) activity. Both trajectories began with the same active-site mutant, His115Trp, which lost the native lactonase activity and acquired higher OPH activity. A neo-functionalization trajectory amplified the promiscuous OPH activity, whereas the re-functionalization trajectory restored the native activity, thus generating a new lactonase that lacks His115. The His115 revertants of these trajectories indicated opposite trends. Revertants of the neo-functionalization trajectory lost both the evolved OPH and the original lactonase activity. Revertants of the trajectory that restored the original lactonase function were, however, fully active. Crystal structures and molecular simulations show that in the newly diverged OPH, the reverted His115 and other catalytic residues are displaced, thus causing loss of both the original and the new activity. In contrast, in the re-functionalization trajectory, reversion compatibility of the original lactonase activity derives from mechanistic versatility whereby multiple residues can fulfill the same task. This versatility enables unique sequence-reversible compositions that are inaccessible when the active site was repurposed toward a new function.
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Arildialquilfosfatase/genética , Evolução Molecular Direcionada , Arildialquilfosfatase/metabolismo , Epistasia Genética , Evolução Molecular , Humanos , Monoéster Fosfórico Hidrolases/metabolismoRESUMO
In this study, we investigate the spontaneous emission of a quantum emitter nearby black phosphorus (BP) sheet. The spontaneous emission can be modulated mechanically by rotating the BP sheet when the quantum emitter is placed parallel to the sheet. The spontaneous emission is dependent on the electron doping and rotation angle of BP with respect to the x-axis. The Purcell factor decreases with the increase in rotation angle under smaller electron doping. The Purcell factor increases with the increase in rotation angle under larger electron doping. The spontaneous emission of quantum emitter nearby two types of BP ribbon arrays tailored along armchair (type I) and zigzag (type II) directions is studied in detail. The spontaneous emission of quantum emitter parallel to type I is enhanced compared with that parallel to BP sheet. The spontaneous emission decreases remarkably for the quantum emitter parallel to type II compared with that parallel to BP sheet. The spontaneous emission can be flexibly modulated by rotating BP ribbon arrays mechanically in two types. The results obtained in this study provide a new method to actively modulate the spontaneous emission.
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Enhancing the light-matter interactions in two-dimensional materials via optical metasurfaces has attracted much attention due to its potential to enable breakthrough in advanced compact photonic and quantum information devices. Here, we theoretically investigate a strong coupling between excitons in monolayer WS2 and quasi-bound states in the continuum (quasi-BIC). In the hybrid structure composed of WS2 coupled with asymmetric titanium dioxide nanobars, a remarkable spectral splitting and typical anticrossing behavior of the Rabi splitting can be observed, and such strong coupling effect can be modulated by shaping the thickness and asymmetry parameter of the proposed metasurfaces, and the angle of incident light. It is found that the balance of line width of the quasi-BIC mode and local electric field enhancement should be considered since both of them affect the strong coupling, which is crucial to the design and optimization of metasurface devices. This work provides a promising way for controlling the light-matter interactions in strong coupling regime and opens the door for the future novel quantum, low-energy, distinctive nanodevices by advanced meta-optical engineering.
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The dual beam guides for transverse-electric and transverse-magnetic polarizations of electromagnetic (EM) wave and elastic wave in defect-free phoxonic crystals are reported. The realization for phoxonic virtual waveguides relies on dual ï¬at equifrequency contours (EFCs) enabling self-collimation for EM and elastic waves. As a possible application of our work, the enhanced acousto-optic (AO) interaction in this kind of defect-free phoxonic waveguide, just as it does in defect-based waveguides, is further studied. Results show that obvious shifts of the transmission peaks of EM waves exist for both polarizations during one period of the elastic wave, and single-phonon exchange dominates the AO interaction. This kind of phoxonic virtual waveguide provides an effective platform to enhance AO interaction and exhibits some advantage over defect-based waveguides by properly manipulating the photonic and phononic dispersion surfaces.
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One of the main research topics related to Alzheimer's disease is the aggregation of the amyloid-ß peptide, which was shown to follow different pathways for the two major alloforms of the peptide, Aß40 and the more toxic Aß42. Experimental studies emphasized that oligomers of specific sizes appear in the early aggregation process in different quantities and might be the key toxic agents for each of the two alloforms. We use transition networks derived from all-atom molecular dynamics simulations to show that the oligomers leading to the type of oligomer distributions observed in experiments originate from compact conformations. Extended oligomers, on the other hand, contribute more to the production of larger aggregates thus driving the aggregation process. We further demonstrate that differences in the aggregation pathways of the two Aß alloforms occur as early as during the dimer stage. The higher solvent-exposure of hydrophobic residues in Aß42 oligomers contributes to the different aggregation pathways of both alloforms and also to the increased cytotoxicity of Aß42.
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Peptídeos beta-Amiloides/química , Agregados Proteicos , Agregação Patológica de Proteínas , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica MolecularRESUMO
We have previously performed empirical valence bond calculations of the kinetic activation barriers, Δ Gcalc, for the deprotonation of complexes between TIM and the whole substrate glyceraldehyde-3-phosphate (GAP, Kulkarni et al. J. Am. Chem. Soc. 2017 , 139 , 10514 - 10525 ). We now extend this work to also study the deprotonation of the substrate pieces glycolaldehyde (GA) and GA·HPi [HPi = phosphite dianion]. Our combined calculations provide activation barriers, Δ Gcalc, for the TIM-catalyzed deprotonation of GAP (12.9 ± 0.8 kcal·mol-1), of the substrate piece GA (15.0 ± 2.4 kcal·mol-1), and of the pieces GA·HPi (15.5 ± 3.5 kcal·mol-1). The effect of bound dianion on Δ Gcalc is small (≤2.6 kcal·mol-1), in comparison to the much larger 12.0 and 5.8 kcal·mol-1 intrinsic phosphodianion and phosphite dianion binding energy utilized to stabilize the transition states for TIM-catalyzed deprotonation of GAP and GA·HPi, respectively. This shows that the dianion binding energy is essentially fully expressed at our protein model for the Michaelis complex, where it is utilized to drive an activating change in enzyme conformation. The results represent an example of the synergistic use of results from experiments and calculations to advance our understanding of enzymatic reaction mechanisms.
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Biocatálise , Triose-Fosfato Isomerase/metabolismo , Ligantes , Estrutura Molecular , Conformação Proteica , Termodinâmica , Triose-Fosfato Isomerase/químicaRESUMO
Conformational changes are crucial for the catalytic action of many enzymes. A prototypical and well-studied example is loop opening and closure in triosephosphate isomerase (TIM), which is thought to determine the rate of catalytic turnover in many circumstances. Specifically, TIM loop 6 "grips" the phosphodianion of the substrate and, together with a change in loop 7, sets up the TIM active site for efficient catalysis. Crystal structures of TIM typically show an open or a closed conformation of loop 6, with the tip of the loop moving â¼7 Å between conformations. Many studies have interpreted this motion as a two-state, rigid-body transition. Here, we use extensive molecular dynamics simulations, with both conventional and enhanced sampling techniques, to analyze loop motion in apo and substrate-bound TIM in detail, using five crystal structures of the dimeric TIM from Saccharomyces cerevisiae. We find that loop 6 is highly flexible and samples multiple conformational states. Empirical valence bond simulations of the first reaction step show that slight displacements away from the fully closed-loop conformation can be sufficient to abolish most of the catalytic activity; full closure is required for efficient reaction. The conformational change of the loops in TIM is thus not a simple "open and shut" case and is crucial for its catalytic action. Our detailed analysis of loop motion in a highly efficient enzyme highlights the complexity of loop conformational changes and their role in biological catalysis.
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Saccharomyces cerevisiae/enzimologia , Triose-Fosfato Isomerase/química , Simulação de Dinâmica Molecular , Estrutura Molecular , Triose-Fosfato Isomerase/metabolismoRESUMO
Simultaneously obtaining high photon emission rate and collection efficiency is highly desirable for applications of single photon sources. However, it remains great challenging and is seldom reported before. Here, we demonstrate that highly enhanced radiation of the emitter and efficient collection of the emitted photons can be simultaneously fulfilled in a hybrid photonic-plasmonic cavity which comprises of an Au nanorod dimer and a photonic crystal nanobeam cavity with a collecting waveguide, where the resonance wavelength of nanobeam cavity is red-detuned from that of the Au nanorod dimer. Our calculations show that the spontaneous emission rate of a single emitter can be enhanced by 5060 -folds, correspondingly, the far-field radiation efficiency and collection efficiency into a dielectric waveguide reaches ~97% and ~67%, respectively. The proposed mechanism paves the way towards the practical applications in ultra-bright on-chip single photon sources and plasmon-based nanolasers.
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ß-Phosphoglucomutase (ß-PGM) has served as an important model system for understanding biological phosphoryl transfer. This enzyme catalyzes the isomerization of ß-glucose-1-phosphate to ß-glucose-6-phosphate in a two-step process proceeding via a bisphosphate intermediate. The conventionally accepted mechanism is that both steps are concerted processes involving acid-base catalysis from a nearby aspartate (D10) side chain. This argument is supported by the observation that mutation of D10 leaves the enzyme with no detectable activity. However, computational studies have suggested that a substrate-assisted mechanism is viable for many phosphotransferases. Therefore, we carried out empirical valence bond (EVB) simulations to address the plausibility of this mechanistic alternative, including its role in the abolished catalytic activity of the D10S, D10C and D10N point mutants of ß-PGM. In addition, we considered both of these mechanisms when performing EVB calculations of the catalysis of the wild type (WT), H20A, H20Q, T16P, K76A, D170A and E169A/D170A protein variants. Our calculated activation free energies confirm that D10 is likely to serve as the general base/acid for the reaction catalyzed by the WT enzyme and all its variants, in which D10 is not chemically altered. Our calculations also suggest that D10 plays a dual role in structural organization and maintaining electrostatic balance in the active site. The correct positioning of this residue in a catalytically competent conformation is provided by a functionally important conformational change in this enzyme and by the extensive network of H-bonding interactions that appear to be exquisitely preorganized for the transition state stabilization.
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Simulação por Computador , Proteínas Mutantes/genética , Fosfoglucomutase/genética , Animais , Catálise , Domínio Catalítico , Humanos , Ligação de Hidrogênio , Transferases Intramoleculares/metabolismo , Conformação Proteica , Eletricidade Estática , Especificidade por Substrato , TermodinâmicaRESUMO
Triosephosphate isomerase (TIM) is a proficient catalyst of the reversible isomerization of dihydroxyacetone phosphate (DHAP) to d-glyceraldehyde phosphate (GAP), via general base catalysis by E165. Historically, this enzyme has been an extremely important model system for understanding the fundamentals of biological catalysis. TIM is activated through an energetically demanding conformational change, which helps position the side chains of two key hydrophobic residues (I170 and L230), over the carboxylate side chain of E165. This is critical both for creating a hydrophobic pocket for the catalytic base and for maintaining correct active site architecture. Truncation of these residues to alanine causes significant falloffs in TIM's catalytic activity, but experiments have failed to provide a full description of the action of this clamp in promoting substrate deprotonation. We perform here detailed empirical valence bond calculations of the TIM-catalyzed deprotonation of DHAP and GAP by both wild-type TIM and its I170A, L230A, and I170A/L230A mutants, obtaining exceptional quantitative agreement with experiment. Our calculations provide a linear free energy relationship, with slope 0.8, between the activation barriers and Gibbs free energies for these TIM-catalyzed reactions. We conclude that these clamping side chains minimize the Gibbs free energy for substrate deprotonation, and that the effects on reaction driving force are largely expressed at the transition state for proton transfer. Our combined analysis of previous experimental and current computational results allows us to provide an overview of the breakdown of ground-state and transition state effects in enzyme catalysis in unprecedented detail, providing a molecular description of the operation of a hydrophobic clamp in triosephosphate isomerase.
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Fosfato de Di-Hidroxiacetona/metabolismo , Gliceraldeído 3-Fosfato/metabolismo , Simulação de Dinâmica Molecular , Triose-Fosfato Isomerase/metabolismo , Biocatálise , Fosfato de Di-Hidroxiacetona/química , Gliceraldeído 3-Fosfato/química , Interações Hidrofóbicas e Hidrofílicas , Conformação Molecular , Saccharomyces cerevisiae/enzimologia , Termodinâmica , Triose-Fosfato Isomerase/química , Triose-Fosfato Isomerase/genéticaRESUMO
We report the properties of dual phononic-photonic band gaps and localized modes of eightfold lithium niobate (LiNbO3) phoxonic quasicrystals (PhXQCs). Complete and large phoxonic band gaps are easily achieved despite the low refractive index of LiNbO3 substrate. Point defect intentionally introduced can form localized modes within both forbidden and transparency bands over a wide range of geometric parameters. Further analysis indicates that the localized modes within transparency bands originate from the intrinsic high-order rotational symmetry of quasiperiodic structures, which resemble whispering gallery modes. LiNbO3 PhXQCs provide a good candidate to enhance phononic-photonic interaction and show considerable advantage over the periodic counterparts.
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We report numerically large and complete photonic and phononic band gaps that simultaneously exist in eight-fold phoxonic quasicrystals (PhXQCs). PhXQCs can possess simultaneous photonic and phononic band gaps over a wide range of geometric parameters. Abundant localized modes can be achieved in defect-free PhXQCs for all photonic and phononic polarizations. These defect-free localized modes exhibit multiform spatial distributions and can confine simultaneously electromagnetic and elastic waves in a large area, thereby providing rich selectivity and enlarging the interaction space of optical and elastic waves. The simulated results based on finite element method show that quasiperiodic structures formed of both solid rods in air and holes in solid materials can simultaneously confine and tailor electromagnetic and elastic waves; these structures showed advantages over the periodic counterparts.
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Streptomycin-resistant (SM-resistant) Mycobacterium tuberculosis (M. tuberculosis) is a major concern in tuberculosis (TB) treatment. However, the mechanisms underlying streptomycin resistance remain unclear. This study primarily aimed to perform preliminary screening of genes associated with streptomycin resistance through conjoint analysis of multiple genomics. Genome-wide methylation, transcriptome, and proteome analyses were used to elucidate the associations between specific genes and streptomycin resistance in M. tuberculosis H37Rv. Methylation analysis revealed that 188 genes were differentially methylated between the SM-resistant and normal groups, with 89 and 99 genes being hypermethylated and hypomethylated, respectively. Furthermore, functional analysis revealed that these 188 differentially methylated genes were enriched in 74 pathways, with most of them being enriched in metabolic pathways. Transcriptome analysis revealed that 516 genes were differentially expressed between the drug-resistant and normal groups, with 263 and 253 genes being significantly upregulated and downregulated, respectively. KEGG analysis indicated that these 516 genes were enriched in 79 pathways, with most of them being enriched in histidine metabolism. The methylation level was negatively related to mRNA abundance. Proteome analysis revealed 56 differentially expressed proteins, including 14 upregulated and 42 downregulated proteins. Moreover, three hub genes (coaE, fadE5, and mprA) were obtained using synthetic analysis. The findings of this study suggest that an integrated DNA methylation, transcriptome, and proteome analysis can provide important resources for epigenetic studies in SM-resistant M. tuberculosis H37Rv.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Metilação de DNA , Transcriptoma , Proteoma/metabolismo , Estreptomicina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/genéticaRESUMO
BACKGROUND: Rifampicin (RIF) and multidrug-resistant tuberculosis (TB) are major public health threats. As conventional phenotypic drug susceptibility testing requires two-eight weeks, molecular diagnostic assays are widely used to determine drug resistance. METHODS: Clinical Mycobacterium tuberculosis isolates with consistent drug susceptibility results, tested using microbroth dilution and proportion methods in Löwenstein-Jensen medium from patients with TB in Guangdong province were utilized to evaluate MeltPro TB and whole-genome sequencing (WGS) assays in detecting resistance to RIF, isoniazid (INH), ethambutol (EMB), fluoroquinolones (FQ), and streptomycin (SM). Solid phenotypic drug susceptibility testing was used as the gold standard to evaluate the detection capacity of MeltPro TB on clinical sputum samples of patients with TB. RESULTS: Similar to WGS, MeltPro TB successfully detected RIF, INH, and SM resistance with sensitivities of 86.3, 84.8, and 86.6 %, respectively. However, the resistant isolate detection rates were only 58.1 and 69.6 % for EMB and FQ-resistant strains. For clinical specimens, MeltPro TB still showed good detectable rates of RIF and INH resistance, with sensitivities of 82.4 % and 95.2 %, respectively. Detectable rates of FQ and EMB resistance were low: 77.8 % and 35.3 %, respectively. CONCLUSIONS: MeltPro TB can detect known DNA mutations associated with drug resistance in Mycobacterium tuberculosis strains with comparable efficacy to WGS. For FQ and EMB resistance testing, MeltPro TB requires optimization and is unsuitable for general use. MeltPro TB can be used for diagnosis of RIF and multidrug-resistant tuberculosis to rapidly initiate appropriate anti-TB drug therapy.