109 research outputs found
An FGO-based Unified Initial Alignment Method of Strapdown Inertial Navigation System
The initial alignment process can provide an accurate initial attitude of
strapdown inertial navigation system. The conventional two-procedure method
usually includes coarse and fine alignment processes. Coarse alignment
converges fast because of its batch estimating characteristics and the initial
attitude does not influence the results. But coarse alignment is low accuracy
without considering the IMU's bias. The fine alignment is more accurate by
applying a recursive Bayesian filter to estimate the IMU's bias, but the
attitude converges slowly as the initial value influence the convergence speed
of the recursive filter. Researchers have proposed the unified initial
alignment to achieve initial alignment in one procedure, existing unified
methods make improvements on the basics of recursive Bayesian filter and those
methods are still slow to converge. In this paper, a unified method based on
batch estimator FGO (factor graph optimization) is raised, which is converge
fast like coarse alignment and accurate than the existing method. We redefine
the state and rederivation the state dynamic model first. Then, the optimal
attitude and the IMU's bias are estimated simultaneously through FGO. The fast
convergence and high accuracy of this method are verified by simulation and
physical experiments on a rotation SINS.Comment: 9 pages, Journal Paper
Mechanism of Thioesterase-Catalyzed Chain Release in the Biosynthesis of the Polyether Antibiotic Nanchangmycin
SummaryThe polyketide backbone of the polyether ionophore antibiotic nanchangmycin (1) is assembled by a modular polyketide synthase in Streptomyces nanchangensis NS3226. The ACP-bound polyketide is thought to undergo a cascade of oxidative cyclizations to generate the characteristic polyether. Deletion of the glycosyl transferase gene nanG5 resulted in accumulation of the corresponding nanchangmycin aglycone (6). The discrete thioesterase NanE exhibited a nearly 17-fold preference for hydrolysis of 4, the N-acetylcysteamine (SNAC) thioester of nanchangmycin, over 7, the corresponding SNAC derivative of the aglycone, consistent with NanE-catalyzed hydrolysis of ACP-bound nanchangmycin being the final step in the biosynthetic pathway. Site-directed mutagenesis established that Ser96, His261, and Asp120, the proposed components of the NanE catalytic triad, were all essential for thioesterase activity, while Trp97 was shown to influence the preference for polyether over polyketide substrates
DNA modification by sulfur: analysis of the sequence recognition specificity surrounding the modification sites
The Dnd (DNA degradation) phenotype, reflecting a novel DNA modification by sulfur in Streptomyces lividans 1326, was strongly aggravated when one (dndB) of the five genes (dndABCDE) controlling it was mutated. Electrophoretic banding patterns of a plasmid (pHZ209), reflecting DNA degradation, displayed a clear change from a preferential modification site in strain 1326 to more random modifications in the mutant. Fourteen randomly modifiable sites on pHZ209 were localized, and each seemed to be able to be modified only once. Residues in a region (5ā²-cācGGCCgccg-3ā²) including a highly conserved 4-bp central core (5ā²-GGCC-3ā²) in a well-documented preferential modification site were assessed for their necessity by site-directed mutagenesis. While the central core (GGCC) was found to be stringently required in 1326 and in the mutant, āgccgā flanking its right could either abolish or reduce the modification frequency only in the mutant, and two separate nucleotides to the left had no dramatic effect. The lack of essentiality of DndB for S-modification suggests that it might only be required for enhancing or stabilizing the activity of a protein complex at the required preferential modification site, or resolving secondary structures flanking the modifiable site(s), known to constitute an obstacle for efficient modification
Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment
Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL patients over three consecutive days. The patients received 10Ā mg arsenic trioxide each day via intravenous infusion. The saliva samples were analyzed using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. Monomethylarsonous acid and monomethylmonothioarsonic acid were identified along with arsenite, dimethylarsinic acid, monomethylarsonic acid, and arsenate. Arsenite was the predominant arsenic species, accounting for 71.8Ā % of total arsenic in the saliva. Following the arsenic infusion each day, the percentage of methylated arsenicals significantly decreased, possibly suggesting that the arsenic methylation process was saturated by the high doses immediately after the arsenic infusion. The temporal profiles of arsenic species in saliva following each arsenic infusion over 3Ā days have provided information on arsenic exposure, metabolism, and excretion. These results suggest that saliva can be used as an appropriate clinical biomarker for monitoring arsenic species in APL patients. [Figure: see text
Based on Atmospheric Physics and Ecological Principle to Assess the Accuracies of Field CO2 /H2O Measurements From Infrared Gas Analyzers in Closed-Path Eddy-Covariance Systems
Field CO2 /H2O measurements from infrared gas analyzers in closed-path eddy-covariance systems have wide applications in earth sciences. Knowledge about exactness of these measurements is required to assess measurement applicability. Although the analyzers are specified with uncertainty components (zero drift, gain drift, cross-sensitivities, and precision), exactness for individual measurements is unavailable due to an absence of methodology to comprehend the components as an overall uncertainty. Adopting an advanced definition of accuracy as a range of all measurement uncertainty sources, the specified components are composited into a model formulated for studying analyzersā CO2 /H2O accuracy equations. Based on atmospheric physics and environmental parameters, the analyzers are evaluated using the equations for CO2 accuracy (Ā±0.78 ĀµmolCO2 molā1, relatively Ā±0.18%) and H2O accuracy (Ā±0.15 mmolH2 O molā1). Evaluation shows that precision and cross-sensitivity are minor uncertainties while zero and gain drifts are major uncertainties. Both drifts need adjusting through zero/span procedures during field maintenance. The equations provide rationales to guide and assess the procedures. H2O span needs more attentions under humid conditions. Under freezing conditions while H2O span is impractical, this span is fortunately unnecessary. Under the same conditions, H2O zero drift dominates H2O measurement uncertainty. Therefore, automatic zero becomes a more applicable and necessary tactic. In general cases of atmospheric CO2 background, automatic CO2 zero/ span procedures can narrow CO2 accuracy by 36% (Ā±0.74 to Ā± 0.47 ĀµmolCO2 molā1). Automatic/manual H2 O zero/span procedures can narrow H2O accuracy by 27% (Ā±0.15 to Ā±0.11 mmolH2O molā1). While ensuring system specifications, the procedures guided by equations improve measurement accuracies
A novel host-specific restriction system associated with DNA backbone S-modification in Salmonella
A novel, site-specific, DNA backbone S-modification (phosphorothioation) has been discovered, but its in vivo function(s) have remained obscure. Here, we report that the enteropathogenic Salmonella enterica serovar Cerro 87, which possesses S-modified DNA, restricts DNA isolated from Escherichia coli, while protecting its own DNA by site-specific phosphorothioation. A cloned 15-kb gene cluster from S. enterica conferred both host-specific restriction and DNA S-modification on E. coli. Mutational analysis of the gene cluster proved unambiguously that the S-modification prevented host-specific restriction specified by the same gene cluster. Restriction activity required three genes in addition to at least four contiguous genes necessary for DNA S-modification. This functional overlap ensures that restriction of heterologous DNA occurs only when the host DNA is protected by phosphorothioation. Meanwhile, this novel type of host-specific restriction and modification system was identified in many diverse bacteria. As in the case of methylation-specific restriction systems, targeted inactivation of this gene cluster should facilitate genetic manipulation of these bacteria, as we demonstrate in Salmonella
Predicting the rupture status of small middle cerebral artery aneurysms using random forest modeling
ObjectiveSmall intracranial aneurysms are increasingly being detected; however, a prediction model for their rupture is rare. Random forest modeling was used to predict the rupture status of small middle cerebral artery (MCA) aneurysms with morphological features.MethodsFrom January 2009 to June 2020, we retrospectively reviewed patients with small MCA aneurysms (<7 mm). The aneurysms were randomly split into training (70%) and internal validation (30%) cohorts. Additional independent datasets were used for the external validation of 78 small MCA aneurysms from another four hospitals. Aneurysm morphology was determined using computed tomography angiography (CTA). Prediction models were developed using the random forest and multivariate logistic regression.ResultsA total of 426 consecutive patients with 454 small MCA aneurysms (<7 mm) were included. A multivariate logistic regression analysis showed that size ratio (SR), aspect ratio (AR), and daughter dome were associated with aneurysm rupture, whereas aneurysm angle and multiplicity were inversely associated with aneurysm rupture. The areas under the receiver operating characteristic (ROC) curves (AUCs) of random forest models using the five independent risk factors in the training, internal validation, and external validation cohorts were 0.922, 0.889, and 0.92, respectively. The random forest model outperformed the logistic regression model (p = 0.048). A nomogram was developed to assess the rupture of small MCA aneurysms.ConclusionRandom forest modeling is a good tool for evaluating the rupture status of small MCA aneurysms and may be considered for the management of small aneurysms
Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences
Bacterial phosphorothioate (PT) DNA modifications are incorporated by Dnd proteins A-E and often function with DndF-H as a restriction-modification (R-M) system, as in Escherichia coli B7A. However, bacteria such as Vibrio cyclitrophicus FF75 lack dndF-H, which points to other PT functions. Here we report two novel, orthogonal technologies to map PTs across the genomes of B7A and FF75 with >90% agreement: single molecule, real-time sequencing and deep sequencing of iodine-induced cleavage at PT (ICDS). In B7A, we detect PT on both strands of G[subscript ps]AAC/G[subscript ps]TTC motifs, but with only 12% of 40,701 possible sites modified. In contrast, PT in FF75 occurs as a single-strand modification at C[subscript ps]CA, again with only 14% of 160,541 sites modified. Single-molecule analysis indicates that modification could be partial at any particular genomic site even with active restriction by DndF-H, with direct interaction of modification proteins with GAAC/GTTC sites demonstrated with oligonucleotides. These results point to highly unusual target selection by PT-modification proteins and rule out known R-M mechanisms.National Natural Science Foundation (China)Ministry of Science and Technology of the People's Republic of China (973 and 863 Programs)Shanghai Municipal Council of Science and Technology. Shanghai Pujiang ProgramNational Science Foundation (U.S.) (CHE-1019990)National Institute of Environmental Health Sciences (ES002109)Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology
Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's Sarcoma-Associated Herpesvirus Reactivation from Latency
Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent
infection in the host following an acute infection. Reactivation from latency
contributes to the development of KSHV-induced malignancies, which include
Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients,
primary effusion lymphoma and multicentric Castleman's disease. However,
the physiological cues that trigger KSHV reactivation remain unclear. Here, we
show that the reactive oxygen species (ROS) hydrogen peroxide
(H2O2) induces KSHV reactivation from latency through
both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic
replication, and KSHV reactivation from latency induced by oxidative stress,
hypoxia, and proinflammatory and proangiogenic cytokines are mediated by
H2O2. Mechanistically, H2O2
induction of KSHV reactivation depends on the activation of mitogen-activated
protein kinase ERK1/2, JNK, and p38 pathways. Significantly,
H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase
and glutathione inhibit KSHV lytic replication in culture. In a mouse model of
KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and
significantly prolongs the lifespan of the mice. These results directly relate
KSHV reactivation to oxidative stress and inflammation, which are physiological
hallmarks of KS patients. The discovery of this novel mechanism of KSHV
reactivation indicates that antioxidants and anti-inflammation drugs could be
promising preventive and therapeutic agents for effectively targeting KSHV
replication and KSHV-related malignancies
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