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The code ingests Zeek logs derived from network packet captures, applies a DBSCAN model, Gower distance to build a feature set as input into a transformer model that will output anomaly scores and provides the option to set a threshold as to what’s considered an anomaly.
The RIPK1-RIPK3 necrosome is an amyloid signaling complex that initiates TNF-induced necroptosis, serving in human immune defense, cancer, and neurodegenerative diseases. RIPK1 and RIPK3 associate through their RIP homotypic interaction motifs with consensus sequences IQIG (RIPK1) and VQVG (RIPK3). Using solid-state nuclear magnetic resonance, we determined the high-resolution structure of the RIPK1-RIPK3 core. RIPK1 and RIPK3 alternately stack (RIPK1, RIPK3, RIPK1, RIPK3, etc.) to form heterotypic β sheets. Two such β sheets bind together along a compact hydrophobic interface featuring an unusual ladder of alternating Ser (from RIPK1) and Cys (from RIPK3). The crystal structure of a four-residue RIPK3 consensus sequence is consistent with the architecture determined by NMR. In conclusion, the RIPK1-RIPK3 core is the first detailed structure of a hetero-amyloid and provides a potential explanation for the specificity of hetero- over homo-amyloid formation and a structural basis for understanding the mechanisms of signal transduction.
Purpose: To develop an advanced testbed that combines a 3D motion stage and ultrasound phantom to optimize and validate 2D and 3D tracking algorithms for real-time motion management during radiation therapy. Methods: A Siemens S2000 Ultrasound scanner utilizing a 9L4 transducer was coupled with the Washington University 4D Phantom to simulate patient motion. The transducer was securely fastened to the 3D stage and positioned to image three cylinders of varying contrast in a Gammex 404GS LE phantom. The transducer was placed within a water bath above the phantom in order to maintain sufficient coupling for the entire range of simulated motion. A programmed motion sequence was used to move the transducer during image acquisition and a cine video was acquired for one minute to allow for long sequence tracking. Images were analyzed using a normalized cross-correlation block matching tracking algorithm and compared to the known motion of the transducer relative to the phantom. Results: The setup produced stable ultrasound motion traces consistent with those programmed into the 3D motion stage. The acquired ultrasound images showed minimal artifacts and an image quality that was more than suitable for tracking algorithm verification. Comparisons of a block matching tracking algorithm with the known motion trace for the three features resulted in an average tracking error of 0.59 mm. Conclusion: The high accuracy and programmability of the 4D phantom allows for the acquisition of ultrasound motion sequences that are highly customizable; allowing for focused analysis of some common pitfalls of tracking algorithms such as partial feature occlusion or feature disappearance, among others. The design can easily be modified to adapt to any probe such that the process can be extended to 3D acquisition. Further development of an anatomy specific phantom better resembling true anatomical landmarks could lead to an even more robust validation. This work is partially funded by NIH grant R01CA190298.
The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. OBJECTIVES: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. METHODS: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. RESULTS: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. CONCLUSION: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
This study aimed to characterize a novel adenovirus (AdV) isolated from diseased Muscovy ducks in China. After the AdV was successfully propagated in duck embryo fibroblasts, the morphological and physicochemical properties of the virions were studied by electron microscopy and different tests. The results of the analyses were in conformity with AdV properties. The full genome sequence was determined and analyzed. The new isolate (named CH-GD-12-2014) shared over 91% sequence identity with duck AdV-2 representing the species Duck aviadenovirus B. The most important distinguishing feature between the two DAdV strains was the presence of a second fiber gene in the Chinese isolate. Phylogeny reconstruction confirmed the affiliation of the virus with goose and duck AdVs in the genus Aviadenovirus. Experimental infection resulted in embryo death, and intramuscular inoculation provoked morbidity and mortality among ducks and chickens. - Highlights: • A duck adenovirus type 3 was isolated and the complete genome of DAdV-3 was obtained. • Physicochemical properties and electron microscopy were researched. • Pathogenicity of duck adenovirus type 3 was researched.
A 4-oxalocrotonate tautomerase (4-OT) trimer has been isolated from Burkholderia lata, and a kinetic, mechanistic, and structural analysis has been performed. The enzyme is the third described oligomer state for 4-OT along with a homo- and heterohexamer. The 4-OT trimer is part of a small subset of sequences (133 sequences) within the 4-OT subgroup of the tautomerase superfamily (TSF). The TSF has two distinct features: members are composed of a single β–α–β unit (homo- and heterohexamer) or two consecutively joined β–α–β units (trimer) and generally have a catalytic amino-terminal proline. The enzyme, designated as fused 4-OT, functions as a 4-OT where the active site groups (Pro-1, Arg-39, Arg-76, Phe-115, Arg-127) mirror those in the canonical 4-OT from Pseudomonas putida mt-2. Inactivation by 2-oxo-3-pentynoate suggests that Pro-1 of fused 4-OT has a low pK a enabling the prolyl nitrogen to function as a general base. A remarkable feature of the fused 4-OT is the absence of P 3 rotational symmetry in the structure (1.5 Å resolution). The asymmetric arrangement of the trimer is not due to the fusion of the two β–α–β building blocks because an engineered “unfused” variant that breaks the covalent bond between the two units (to generate a heterohexamer) assumes the same asymmetric oligomerization state. Furthermore, it remains unknown how the different active site configurations contribute to the observed overall activities and whether the asymmetry has a biological purpose or role in the evolution of TSF members.
Botulinum neurotoxin-producing clostridia are diverse in the types of toxins they produce as well as in their overall genomic composition. They are globally distributed, with prevalent species and toxin types found within distinct geographic regions, but related strains containing the same toxin types may also be located on distinct continents. The mechanisms behind the spread of these bacteria and the independent movements of their bont genes may be understood through examination of their genetic backgrounds. The generation of 15 complete genomic sequences from bacteria isolated in Argentina, Australia, and Africa allows for a thorough examination of genome features, including overall relationships, bont gene cluster locations and arrangements, and plasmid comparisons, in bacteria isolated from various areas in the southern hemisphere. Insights gained from these examinations provide an understanding of the mechanisms behind the independent movements of these elements among distinct species.
Background: Of the > 2600 Salmonella serovars, Salmonella enterica serovar I 4,[5],12:i:- (serovar I 4,[5],12:i:-) has emerged as one of the most common causes of human salmonellosis and the most frequent multidrug-resistant (MDR; resistance to ≥3 antimicrobial classes) nontyphoidal Salmonella serovar in the U.S. Serovar I 4,[5],12:i:- isolates have been described globally with resistance to ampicillin, streptomycin, sulfisoxazole, and tetracycline (R-type ASSuT) and an integrative and conjugative element with multi-metal tolerance named Salmonella Genomic Island 4 (SGI-4). Results: We analyzed 13,612 serovar I 4,[5],12:i:- strain sequences available in the NCBI Pathogen Detection database to determine global distribution, animal sources, presence of SGI-4, occurrence of R-type ASSuT, frequency of antimicrobial resistance (AMR), and potential transmission clusters. Genome sequences for serovar I 4,[5],12:i:- strains represented 30 countries from 5 continents (North America, Europe, Asia, Oceania, and South America), but sequences from the United States (59%) and the United Kingdom (28%) were dominant. The metal tolerance island SGI-4 and the R-type ASSuT were present in 71 and 55% of serovar I 4,[5],12:i:- strain sequences, respectively. Sixty-five percent of strain sequences were MDR which correlates to serovar I 4,[5],12:i:- being the most frequent MDR serovar. The distribution of serovar I 4,[5],12:i:- strain sequences in the NCBI Pathogen Detection database suggests that swine-associated strain sequences were the most frequent food-animal source and were significantly more likely to contain the metal tolerance island SGI-4 and genes for MDR compared to all other animal-associated isolate sequences. Conclusions: Our study illustrates how analysis of genomic sequences from the NCBI Pathogen Detection database can be utilized to identify the prevalence of genetic features such as antimicrobial resistance, metal tolerance, and virulence genes that may be responsible for the successful emergence of bacterial foodborne pathogens.
Intracellular pathogens must egress from the host cell to continue their infectious cycle. Apicomplexans are a phylum of intracellular protozoans that have evolved members of the membrane attack complex and perforin (MACPF) family of pore forming proteins to disrupt cellular membranes for traversing cells during tissue migration or egress from a replicative vacuole following intracellular reproduction. Previous work showed that the apicomplexan Toxoplasma gondii secretes a perforin-like protein (TgPLP1) that contains a C-terminal Domain (CTD) which is necessary for efficient parasite egress. However, the structural basis for CTD membrane binding and egress competency remained unknown. Here, we present evidence that TgPLP1 CTD prefers binding lipids that are abundant in the inner leaflet of the lipid bilayer. Additionally, solving the high-resolution crystal structure of the TgPLP1 APCβ domain within the CTD reveals an unusual double-layered β-prism fold that resembles only one other protein of known structure. Three direct repeat sequences comprise subdomains, with each constituting a wall of the β-prism fold. One subdomain features a protruding hydrophobic loop with an exposed tryptophan at its tip. Spectrophotometric measurements of intrinsic tryptophan fluorescence are consistent with insertion of the hydrophobic loop into a target membrane. Using CRISPR/Cas9 gene editing we show that parasite strains bearing mutations in the hydrophobic loop, including alanine substitution of the tip tryptophan, are equally deficient in egress as a strain lacking TgPLP1 altogether. Taken together our findings suggest a crucial role for the hydrophobic loop in anchoring TgPLP1 to the membrane to support its cytolytic activity and egress function.
The purpose of this report is to document updates on the apparatus to simulate commercial vacuum drying procedures at the Nuclear Energy Work Complex at Sandia National Laboratories. Validation of the extent of water removal in a dry spent nuclear fuel storage system based on drying procedures used at nuclear power plants is needed to close existing technical gaps. Operational conditions leading to incomplete drying may have potential impacts on the fuel, cladding, and other components in the system during subsequent storage and disposal. A general lack of data suitable for model validation of commercial nuclear canister drying processes necessitates well-designed investigations of drying process efficacy and water retention. Scaled tests that incorporate relevant physics and well-controlled boundary conditions are essential to provide insight and guidance to the simulation of prototypic systems undergoing drying processes. This report documents a new test apparatus, the Advanced Drying Cycle Simulator (ADCS). This apparatus was built to simulate commercial drying procedures and quantify the amount of residual water remaining in a pressurized water reactor (PWR) fuel assembly after drying. The ADCS was constructed with a prototypic 17×17 PWR fuel skeleton and waterproof heater rods to simulate decay heat. These waterproof heaters are the next generation design to heater rods developed and tested at Sandia National Laboratories in FY20. This report describes the ADCS vessel build that was completed late in FY22, including the receipt of the prototypic length waterproof heater rods and construction of the fuel basket and the pressure vessel components. In addition, installations of thermocouples, emissivity coupons, pressure and vacuum lines, pressure transducers, and electrical connections were completed. Preliminary power functionality testing was conducted to demonstrate the capabilities of the ADCS. In FY23, a test plan for the ADCS will be developed to implement a drying procedure based on measurements from the process used for the High Burnup Demonstration Project. While applying power to the simulated fuel rods, this procedure is expected to consist of filling the ADCS vessel with water, draining the water with applied pressure and multiple helium blowdowns, evacuating additional water with a vacuum drying sequence at successively lower pressures, and backfilling the vessel with helium. Additional investigations are expected to feature failed fuel rod simulators with engineered cladding defects and guide tubes with obstructed dashpots to challenge the drying system with multiple water retention sites.
The purpose of this report is to document updates on testing of the apparatus built to simulate commercial drying procedures for spent nuclear fuel at the Nuclear Energy Work Complex at Sandia National Laboratories. Validation of the extent of water removal in a dry spent nuclear fuel storage system based on drying procedures used at nuclear power plants is needed to close existing technical gaps. Operational conditions leading to incomplete drying may have potential impacts on the fuel, cladding, and other components in the system during subsequent storage and disposal. A general lack of data suitable for model validation of commercial nuclear canister drying processes necessitates well-designed investigations of drying process efficacy and water retention that incorporate relevant physics and well-controlled boundary conditions. This report documents testing updates for the Advanced Drying Cycle Simulator (ADCS). This apparatus was built to simulate commercial drying procedures and quantify the amount of residual water remaining in a pressurized water reactor (PWR) fuel assembly after drying. The ADCS was constructed with a prototypic 17×17 PWR fuel skeleton and waterproof heater rods to simulate decay heat. These waterproof heaters are the next generation design to heater rods developed and tested at Sandia National Laboratories in FY20. This report describes preliminary testing of the ADCS through measurement and analysis of the thermal response of the system to a subset of commercial drying conditions that exclude the introduction of water, namely simulated decay heats and pressures relevant to commercial drying. This test series, referred to as a “dry” test series in this report, spans three uniform waterproof heater rod powers (representing spent fuel decay heats), four helium fill pressures, and six vacuum levels. This test series was conducted to cover the range of expected ADCS testing conditions for upcoming “wet” testing, where water will be introduced and a simulated commercial drying cycle will be performed. The dry test conditions were derived from the commercial drying conditions seen in the High Burnup Demonstration and the vacuum drying conditions chosen for a smaller scale Dashpot Drying Apparatus tested at Sandia National Laboratories in FY22. For a given uniform power and pressure/vacuum level, the ADCS was operated at constant power and pressure and allowed to reach steady state conditions. The thermal data obtained from these tests were analyzed, and the results can inform computational models built to simulate commercial drying processes by providing baseline thermal data prior to the introduction of water. Following the preliminary dry tests, a test plan for the ADCS will be developed to implement a drying procedure that begins with the introduction of water to the system and is based on measurements from the drying process used for the High Burnup Demonstration Project. While applying power to the simulated fuel rods, this procedure is expected to consist of filling the ADCS vessel with water, draining the water with applied pressure and multiple helium blowdowns, evacuating additional water with a vacuum drying sequence at successively lower pressures, and backfilling the vessel with helium. Additional investigations are expected to feature failed fuel rod simulators with engineered cladding defects and guide tubes with obstructed dashpots to challenge the drying system with multiple water retention sites. The data from these investigations is expected to inform the efficacy of commercial drying operations through the quantification of residual water in a prototypic-length dry storage canister.
Accurate short-term precipitation forecast is extremely important for urban flood warning and natural disaster prevention. In this paper, we present an innovative deep learning model named ISA-PredRNN (improved self-attention PredRNN) for precipitation nowcasting based on radar echoes on the basis of the advanced PredRNN-V2. We introduce the self-attention mechanism and the long-term memory state into the model and design a new set of gating mechanisms. To better capture different intensities of precipitation, the loss function with weights was designed. We further train the model using a combination of reverse scheduled sampling and scheduled sampling to learn the long-term dynamics from the radar echo sequences. Experimental results show that the new model (ISA-PredRNN) can effectively extract the spatiotemporal features of radar echo maps and obtain radar echo prediction results with a small gap from the ground truths. From the comparison with the other six models, the new ISA-PredRNN model has the most accurate prediction results with a critical success index (CSI) of 0.7001, 0.5812 and 0.3052 under the radar echo thresholds of 10 dBZ, 20 dBZ and 30 dBZ, respectively.
We investigate the color–magnitude diagram (CMD) of the Carina dwarf spheroidal galaxy using data of Stetson et al. and synthetic CMDs based on isochrones of Dotter et al., in terms of the parameters [Fe/H], age, and [ α /Fe], for the cases when (i) [ α /Fe] is held constant and (ii) [ α /Fe] is varied. The data are well described by four basic epochs of star formation, having [Fe/H] = −1.85, −1.5, −1.2, and ∼−1.15 and ages ∼13, 7, ∼3.5, and ∼1.5 Gyr, respectively (for [ α /Fe] = 0.1, constant [ α /Fe], and [ α /Fe] = 0.2, 0.1, −0.2, −0.2, variable [ α /Fe]), with small spreads in [Fe/H] and age of order 0.1 dex and 1–3 Gyr. Within an elliptical radius 13.′1, the mass fractions of the populations, at their times of formation, were (in decreasing age order) 0.34, 0.39, 0.23, and 0.04. This formalism reproduces five observed CMD features (two distinct subgiant branches of old and intermediate-age populations, two younger, main-sequence components, and the small color dispersion on the red giant branch (RGB). The parameters of the youngest population are less certain than those of the others, and given it is less centrally concentrated, it may not be directly related to them. High-resolution spectroscopically analyzed RGB samples appear statistically incomplete compared with those selected using radial velocity, which contain bluer stars comprising ∼5%–10% of the samples. We conjecture these objects may, at least in part, be members of the youngest population. We use the CMD simulations to obtain insight into the population structure of Carina's upper RGB.
Three distinctive types of basalt terrains can be recognized on earth on the basis of surface morphology: flood basalts, shield basalts, and plains basalts, each of which reflects unique styles of eruption and modes of emplacement. Two of these, flood basalts and plains basalts, appear to be important in the emplacement of mare basalts on the moon. Using surface features as identifying criteria, mare units in the Orientale Basin were examined and the following emplacement sequence was derived: (1) initial emplacement of impact melt in the basin center, (2) eruption of flood-type basalts in the basin center and approximately concurrent emplacement of plains type basalts in Lacus Veris, and (3) emplacement of plains type basalts in Lacus Autumni
A pulse generator for NMR application is described. Eighteen output channels are provided to allow use in single and double resonance experiments. Complex pulse sequences may be generated by loading instructions into a 256-word by 16-bit program memory. Features of the pulse generator include programmable time delays from 0.5 micros to 1000 s, branching and looping instructions, and the ability to be loaded and operated either manually or from a PDP-11/10 computer.
Images from the Voyager north/south mapping sequences were searched for waves. A remarkable class of mesoscale waves was identified, with the following features: (1) the wavetrains are usually aligned zonally, i.e., wavecrests are north-south; (2) the average wavelength is 300 km with a standard deviation of only 20%; (3) the wavetrains are long; (4) the waves occur within 25 degrees of the equator, the bulk being at the equator itself; (5) the waves are centered at the extrema (in latitude) of the zonal flow; and (6) the meridional extent of the waves is typically 1 degree of latitude. These observations are interpreted as evidence of gravity waves propagating vertically within a leaky duct. A three-level model is assumed composed of a stable duct which extends up to the base of the NH3 cloud deck near 600 mb. Above this is a thin wave-trapping region characterized by a Richardson number Ri less than 1/4 and containing a critical level, where the local value of the zonal flow velocity equals the phase speed of the wave. This in turn is overlain by a stable region, representing the tropopause region and stratosphere.
The Environment for Application Software Integration and Execution (EASIE) provides both a methodology and a set of software utility programs to ease the task of coordinating engineering design and analysis codes. This document provides necessary information for installing the EASIE software on a host computer system. The target host is a DEX VAX running VMS version 4; host dependencies are noted when appropriate. Relevant directories and individual files are identified, and compile/load/execute sequences are specified. In the case of the data management utilities, database management system (DBMS) specific features are described in an effort to assist the maintenance programmer in converting to a new DBMS. The document also describes a sample EASIE program directory structure to guide the program implementer in establishing his/her application dependent environment.
The results of an analysis of several reboost scenarios for nominal and contingency SS operations during the Phase I assembly sequence are presented. Space Station program requirements on assembly and operational altitudes are outlined, and essential features of the SS reaction control system are described. A nominal reboost strategy designed to meet the current program requirements is presented. In addition, reboost strategies are developed for several contingency scenarios, including one missed STS mission, and an extended STS outage. It is shown that the time-averaged propellant 'cost' of maintaining altitude is greatest for equivalent continuous-thrusting altitude maintenance; it decreases with increasing reboost/rendezvous time interval to an asymptotic minimum value.