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The High-Resolution Rapid Refresh (HRRR) is a convection-allowing implementation of the Advanced Research version of the Weather Research and Forecasting (WRF-ARW) Model with hourly data assimilation that covers the conterminous United States and Alaska and runs in real time at the NOAA/National Centers for Environmental Prediction (NCEP). Implemented operationally at NOAA/NCEP in 2014, the HRRR features 3-km horizontal grid spacing and frequent forecasts (hourly for CONUS and 3-hourly for Alaska). HRRR initialization is designed for optimal short-range forecast skill with a particular focus on the evolution of precipitating systems. Key components of the initialization are radar-reflectivity data assimilation, hybrid ensemble-variational assimilation of conventional weather observations, and a cloud analysis to initialize stratiform cloud layers. From this initial state, HRRR forecasts are produced out to 18 h every hour, and out to 48 h every 6 h, with boundary conditions provided by the Rapid Refresh system. Between 2014 and 2020, HRRR development was focused on reducing model bias errors and improving forecast realism and accuracy. Improved representation of the planetary boundary layer, subgrid-scale clouds, and land surface contributed extensively to overall HRRR improvements. The final version of the HRRR (HRRRv4), implemented in late 2020, also features hybrid data assimilation using flow-dependent covariances from a 3-km, 36-member ensemble (“HRRRDAS”) with explicit convective storms. HRRRv4 also includes prediction of wildfire smoke plumes. The HRRR provides a baseline capability for evaluating NOAA’s next-generation Rapid Refresh Forecast System, now under development.

The land surface model (LSM) described in this manuscript was originally developed as part of the NOAA Rapid Update Cycle (RUC) model development effort; with ongoing modifications, it is now used as an option for the WRF community model. The RUC model and its WRF-based NOAA successor, the Rapid Refresh (RAP), are hourly updated and have an emphasis on short-range, near-surface forecasts including aviation-impact variables and preconvective environment. Therefore, coupling to this LSM (hereafter the RUC LSM) has been critical to provide more accurate lower boundary conditions. This paper describes changes made to the RUC LSM since earlier descriptions, including extension from six to nine levels, improved snow treatment, and new land-use data from MODIS. The RUC LSM became operational at the NOAA/National Centers for Environmental Prediction (NCEP) as part of the RUC from 1998–2012 and as part of the RAP from 2012 through the present. The simple treatments of basic land surface processes in the RUC LSM have proven to be physically robust and capable of realistically representing the evolution of soil moisture, soil temperature, and snow in cycled models. Extension of the RAP domain to encompass all of North America and adjacent high-latitude ocean areas necessitated further development of the RUC LSM for application in the tundra permafrost regions and over Arctic sea ice. Other modifications include refinements in the snow model and a more accurate specification of albedo, roughness length, and other surface properties. These recent modifications in the RUC LSM are described and evaluated in this paper.

The Rapid Refresh (RAP), an hourly updated assimilation and model forecast system, replaced the Rapid Update Cycle (RUC) as an operational regional analysis and forecast system among the suite of models at the NOAA/National Centers for Environmental Prediction (NCEP) in 2012. The need for an effective hourly updated assimilation and modeling system for the United States for situational awareness and related decision-making has continued to increase for various applications including aviation (and transportation in general), severe weather, and energy. The RAP is distinct from the previous RUC in three primary aspects: a larger geographical domain (covering North America), use of the community-based Advanced Research version of the Weather Research and Forecasting (WRF) Model (ARW) replacing the RUC forecast model, and use of the Gridpoint Statistical Interpolation analysis system (GSI) instead of the RUC three-dimensional variational data assimilation (3DVar). As part of the RAP development, modifications have been made to the community ARW model (especially in model physics) and GSI assimilation systems, some based on previous model and assimilation design innovations developed initially with the RUC. Upper-air comparison is included for forecast verification against both rawinsondes and aircraft reports, the latter allowing hourly verification. In general, the RAP produces superior forecasts to those from the RUC, and its skill has continued to increase from 2012 up to RAP version 3 as of 2015. In addition, the RAP can improve on persistence forecasts for the 1–3-h forecast range for surface, upper-air, and ceiling forecasts.

A stochastic parameter perturbation (SPP) scheme consisting of spatially and temporally varying perturbations of uncertain parameters in the Grell–Freitas convective scheme and the Mellor–Yamada–Nakanishi–Niino planetary boundary scheme was developed within the Rapid Refresh ensemble system based on the Weather Research and Forecasting Model. Alone the stochastic parameter perturbations generate insufficient spread to be an alternative to the operational configuration that utilizes combinations of multiple parameterization schemes. However, when combined with other stochastic parameterization schemes, such as the stochastic kinetic energy backscatter (SKEB) scheme or the stochastic perturbation of physics tendencies (SPPT) scheme, the stochastic ensemble system has comparable forecast performance. An additional analysis quantifies the added value of combining SPP and SPPT over an ensemble that uses SPPT only, which is generally beneficial, especially for surface variables. The ensemble combining all three stochastic methods consistently produces the best spread–skill ratio and generally outperforms the multiphysics ensemble. The results of this study indicate that using a single-physics suite ensemble together with stochastic methods is an attractive alternative to multiphysics ensembles and should be considered in the design of future high-resolution regional and global ensembles.

Lake-effect convective snowstorms frequently produce high-impact, hazardous winter weather conditions downwind of the North American Great Lakes. During lake-effect snow events, the lake surfaces can cool rapidly, and in some cases, notable development of ice cover occurs. Such rapid changes in the lake-surface conditions are not accounted for in existing operational weather forecast models, such as the National Oceanic and Atmospheric Administration’s (NOAA) High-Resolution Rapid Refresh (HRRR) model, resulting in reduced performance of lake-effect snow forecasts. As a milestone to future implementations in the Great Lakes Operational Forecast System (GLOFS) and HRRR, this study examines the one-way linkage between the hydrodynamic-ice model [the Finite-Volume Community Ocean Model coupled with the unstructured grid version of the Los Alamos Sea Ice Model (FVCOM-CICE), the physical core model of GLOFS] and the atmospheric model [the Weather Research and Forecasting (WRF) Model, the physical core model of HRRR]. The realistic representation of lake-surface cooling and ice development or its fractional coverage during three lake-effect snow events was achieved by feeding the FVCOM-CICE simulated lake-surface conditions to WRF (using a regional configuration of HRRR), resulting in the improved simulation of the turbulent heat fluxes over the lakes and resulting snow water equivalent in the downwind areas. This study shows that the one-way coupling is a practical approach that is well suited to the operational environment, as it requires little to no increase in computational resources yet can result in improved forecasts of regional weather and lake conditions.

The Rapid Update Cycle (RUC), an operational regional analysis-forecast system among the suite of models at the National Centers for Environmental Prediction (NCEP), is distinctive in two primary aspects: its hourly assimilation cycle and its use of a hybrid isentropic-sigma vertical coordinate. The use of a quasi-isentropic coordinate for the analysis increment allows the influence of observations to be adaptively shaped by the potential temperature structure around the observation, while the hourly update cycle allows for a very current analysis and short-range forecast. Herein, the RUC analysis framework in the hybrid coordinate is described, and some considerations for high-frequency cycling are discussed.

Various genetic markers such as IS-elements, DR-elements, variable number tandem repeats (VNTR), single nucleotide polymorphisms (SNPs) in housekeeping genes and other groups of genes are being used for genotyping. We propose a different approach. We suggest the type II toxin-antitoxin (TA) systems, which play a significant role in the formation of pathogenicity, tolerance and persistence phenotypes, and thus in the survival of Mycobacterium tuberculosis in the host organism at various developmental stages (colonization, infection of macrophages, etc.), as the marker genes. Most genes of TA systems function together, forming a single network: an antitoxin from one pair may interact with toxins from other pairs and even from other families. In this work a bioinformatics analysis of genes of the type II TA systems from 173 sequenced genomes of M. tuberculosis was performed. A number of genes of type II TA systems were found to carry SNPs that correlate with specific genotypes. We propose a minimally sufficient set of genes of TA systems for separation of M. tuberculosis strains at nine basic genotype and for further division into subtypes. Using this set of genes, we genotyped a collection consisting of 62 clinical isolates of M. tuberculosis. The possibility of using our set of genes for genotyping using PCR is also demonstrated.

A series of novel 5′-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of Mycobacterium smegmatis was completely inhibited by the most active compounds at a MIC99 of 67 μg/mL (mc2155) and a MIC99 of 6.7–67 μg/mL (VKPM Ac 1339). Several compounds also showed the ability to inhibit the growth of attenuated strains of Mycobacterium tuberculosis ATCC 25177 (MIC99 28–61 μg/mL) and Mycobacterium bovis ATCC 35737 (MIC99 50–60 μg/mL), as well as two virulent strains of M. tuberculosis; a laboratory strain H37Rv (MIC99 20–50 μg/mL) and a clinical strain with multiple drug resistance MS-115 (MIC99 20–50 μg/mL). Transmission electron microscopy (TEM) evaluation of M. tuberculosis H37Rv bacterial cells treated with one of the compounds demonstrated destruction of the bacterial cell wall, suggesting that the mechanism of action for these compounds may be related to their interactions with bacteria cell walls.

Carbocyclic nucleosides have long played a role in antiviral, antiparasitic, and antibacterial therapies. Recent results from our laboratories from two structurally related scaffolds have shown promising activity against both Mycobacterium tuberculosis and several parasitic strains. As a result, a small structure activity relationship study was designed to further probe their activity and potential. Their synthesis and the results of the subsequent biological activity are reported herein.

Levofloxacin (LFX) is a highly effective anti-tuberculosis drug with a pronounced bactericidal activity against Mycobacterium tuberculosis (Mtb). In this work, an “organic solvent-free” approach has been used for the development of polylactic-co-glycolic acid (PLGA) microparticles and scaffolds containing LFX at a therapeutically significant concentration, providing for its sustained release. To achieve the target, both nonpolar supercritical carbon dioxide and polar supercritical trifluoromethane have been used. By changing the composition, surface morphology, size, and internal structure of the polymer carriers, one can control the kinetics of the LFX release into phosphate buffered saline solutions and physiological media, providing for its acceptable burst and desirable concentration in the prolonged phase. The biocompatibility and bactericidal efficacy of PLGA/LFX carriers assessed both in vitro (against Mtb phagocytosed by macrophages) and in vivo (against inbred BALB/c mice aerogenically infected with Mtb) demonstrated their anti-tuberculosis activity comparable with that of the standard daily intragastric levofloxacin administration. These results make it possible to consider the developed compositions as a promising candidate for anti-tuberculosis control release formulations providing for the further evaluation of their activity against Mtb and their metabolism in vivo over long periods of tuberculosis infection.