Sensor Data Prediction in Missile Flight Tests.

Sensor data from missile flights are highly valuable, as a test requires considerable resources, but some sensors may be detached or fail to collect data. Remotely acquired missile sensor data are incomplete, and the correlations between the missile data are complex, which results in the prediction of sensor data being difficult. This article proposes a deep learning-based prediction network combined with the wavelet analysis method. The proposed network includes an imputer network and a prediction network. In the imputer network, the data are decomposed using wavelet transform, and the generative adversarial networks assist the decomposed data in reproducing the detailed information. The prediction network consists of long short-term memory with an attention and dilation network for accurate prediction. In the test, the actual sensor data from missile flights were used. For the performance evaluation, the test was conducted from the data with no missing values to the data with five different missing rates. The test results showed that the proposed system predicts the missile sensor most accurately in all cases. In the frequency analysis, the proposed system has similar frequency responses to the actual sensors and showed that the proposed system accurately predicted the sensors in both tendency and frequency aspects.

V2X-Communication-Aided Autonomous Driving: System Design and Experimental Validation.

In recent years, research concerning autonomous driving has gained momentum to enhance road safety and traffic efficiency. Relevant concepts are being applied to the fields of perception, planning, and control of automated vehicles to leverage the advantages offered by the vehicle-to-everything (V2X) communication technology. This paper presents a V2X communication-aided autonomous driving system for vehicles. It is comprised of three subsystems: beyond line-of-sight (BLOS) perception, extended planning, and control. Specifically, the BLOS perception subsystem facilitates unlimited LOS environmental perception through data fusion between local perception using on-board sensors and communication perception via V2X. In the extended planning subsystem, various algorithms are presented regarding the route, velocity, and behavior planning to reflect real-time traffic information obtained utilizing V2X communication. To verify the results, the proposed system was integrated into a full-scale vehicle that participated in the 2019 Hyundai Autonomous Vehicle Competition held in K-city with the V2X infrastructure. Using the proposed system, the authors demonstrated successful completion of all assigned real-life-based missions, including emergency braking caused by a jaywalker, detouring around a construction site ahead, complying with traffic signals, collision avoidance, and yielding the ego-lane for an emergency vehicle. The findings of this study demonstrated the possibility of several potential applications of V2X communication with regard to autonomous driving systems.

Defective feedback regulation of NF-kappaB underlies Sjogren's syndrome in mice with mutated kappaB enhancers of the IkappaBalpha promoter.

Feedback regulation of transcription factor NF-kappaB by its inhibitor IkappaBalpha plays an essential role in control of NF-kappaB activity. To understand the biological significance of IkappaBalpha-mediated feedback regulation of NF-kappaB, we generated mice harboring mutated kappaB enhancers in the promoter of the IkappaBalpha gene (IkappaBalpha(M/M)) to inhibit NF-kappaB-regulated IkappaBalpha expression. Here, we report that these mutant mice are defective in NF-kappaB-induced expression of IkappaBalpha. This defective feedback regulation of NF-kappaB by IkappaBalpha not only altered activity of NF-kappaB, but also the expression of NF-kappaB-regulated genes. As a result, IkappaBalpha(M/M), the homozygous knock-in mice with mutated kappaB enhancers in the IkappaBalpha promoter, acquire shorten life span, hypersensitivity to septic shock, abnormal T-cell development and activation, and Sjögren's Syndrome. These findings therefore demonstrate that the IkappaBalpha-mediated feedback regulation of NF-kappaB has an essential role in controlling T-cell development and functions, provide mechanistic insight into the development of Sjögren's Syndrome, and suggest the potential of NF-kappaB signaling as a therapeutic target for Sjögren's Syndrome and other autoimmune diseases.

An Unexpected Pacemaker Response to Catheter Ablation: Failure of Pacing Pulse Delivery During Asynchronous Pacing Mode.

Radiofrequency (RF) ablation can be a source of electromagnetic interference (EMI) for cardiovascular implantable electronic devices (CIEDs). The response of CIEDs to this type of EMI can be variable and unpredictable. We report a case with an uncommon response where there was a failure to deliver pacing pulses to both atrial and ventricular pacing leads during RF ablation close to the atrial lead even when the pacemaker was set to pace asynchronously. We also explain the mechanism behind this unusual pacemaker response.

Feasibility and safety of same-day discharge and shortened bedrest after atrial fibrillation ablation.

BACKGROUND: While initial studies suggest that same-day discharge or shortened bedrest may be feasible for some patients following atrial fibrillation (AF) ablation, the risks and benefits of this approach remain unclear for patients undergoing hemostasis with figure-of-eight (FO8) suture technique. METHODS: We prospectively evaluated access site bleeding, length of hospitalization, urinary catheterization, and other clinical outcomes in patients undergoing AF ablation with 3 hours of bedrest between April and May 2021, and compared them to a control group that had undergone AF ablation with 6 hours of bedrest from April to July 2019. FO8 sutures were used for hemostasis in all patients. Independent risk factors for bleeding and urinary catheterization were determined using multiple logistic regression. RESULTS: Same-day discharge was achieved in 74% of patients in the 3-hour bedrest group compared to 7% of patients in the 6-hour bedrest group (p < 0.001). There were no differences between 3-hour and 6-hour bedrest groups in the rates of serious adverse events (2% vs. 1%, p = 0.45) or rehospitalizations or ED visits (1% vs. 3%, p = 0.45) within 30 days of ablation. The 3-hour bedrest group showed a non-significant trend toward more access site bleeding (15% vs. 8%, p = 0.10), but had a significant reduction in urinary catheterization (27% vs. 64%, p < 0.001) and opioid analgesia use (20% vs. 33%, p = 0.04). CONCLUSIONS: Same-day discharge after 3 hours of bedrest is safe and feasible following AF ablation and is not associated with higher rates of complications or rehospitalizations at 30 days. Reduced bedrest resulted in decreased opioid analgesia and urinary catheterization.

Lead-associated Superior Vena Cava Syndrome.

Superior vena cava (SVC) syndrome is a rare complication associated with transvenous cardiac implantable electronic devices that may present with a variety of manifestations. Various strategies such as transvenous lead extraction, anticoagulation, venoplasty, and stenting have been used to treat this condition, but the optimal management protocols have yet to be defined. Subcutaneous implantable cardioverter-defibrillator (ICD) (S-ICD) therapy can be an alternative option to a transvenous system for those who require future ICD surveillance. We present a case of lead-associated SVC syndrome where thoracic venous congestion due to SVC obstruction influenced preimplant S-ICD QRS vector screening. Following treatment of venous obstruction, QRS amplitude may change and patients who were not initially S-ICD candidates may later become eligible.

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

IMPORTANCE: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. OBJECTIVE: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURES: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

Pulsed Field Ablation Using a Lattice Electrode for Focal Energy Delivery: Biophysical Characterization, Lesion Durability, and Safety Evaluation.

BACKGROUND: Pulsed field ablation (PFA) is a nonthermal energy that may provide safety advantages over radiofrequency ablation (RFA). One-shot PFA catheters have been developed for pulmonary vein isolation, but they do not permit flexible lesion sets. This study investigated a novel lattice-tip catheter designed for focal RFA or PFA ablation. METHODS: The effects of PFA (biphasic, 24 amperes) were investigated in 25 swine using a lattice-tip catheter and system (Affera Inc). Step 1 (n=14) examined the feasibility to create atrial line of block and described its acute effects on the phrenic nerve and esophagus. Step 2 (n=7) examined the subacute effects of PFA on block durability, phrenic nerve, and esophagus ≥2 weeks. Step 3 compared the effects of PFA and RFA on the esophagus using a mechanical deviation model approximating the esophagus to the right atrium (n=4) and by direct ablation within its lumen (n=4). The effects of endocardial PFA and RFA on the phrenic nerve were also compared (n=10). Histological analysis was performed. RESULTS: PFA produced acute block in 100% of lines, achieved with 2.1 (1.3-3.2) applications/cm line. Histological analysis following (35 [18-37]) days showed 100% transmurality (thickness range 0.4-3.4 mm) with a lesion width of 19.4 (10.9-27.4 mm). PFA selectively affected cardiomyocytes but spared blood vessels and nervous tissue. PFA applied from the posterior atria (23 [21-25] applications) to the approximated esophagus (6 [4.5-14] mm) produced transmural lesions without esophageal injury. PFA (16.5 [15-18] applications) applied inside the esophageal lumen produced mild edema compared with RFA (13 [12-14] applications) which produced epithelial ulcerations. PFA resulted in no or transient stunning of the phrenic nerve (<5 minutes) without histological changes while RFA produced paralysis. CONCLUSIONS: PFA using a lattice-tip ablation catheter for focal ablation produced durable atrial lesions and showed lower vulnerability to esophageal or phrenic nerve damage compared with RFA.

Discordance in Scar Detection Between Electroanatomical Mapping and Cardiac MRI in an Infarct Swine Model.

OBJECTIVES: This study sought to investigate the sensitivity of electroanatomical mapping (EAM) to detect scar as identified by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR). BACKGROUND: Previous studies have shown correlation between low voltage electrogram amplitude and myocardial scar. However, voltage amplitude is influenced by the distance between the scar and the mapping surface and its extent. The aim of this study is to examine the reliability of low voltage EAM as a surrogate for myocardial scar using LGE-derived scar as the reference. METHODS: Twelve swine underwent anterior wall infarction by occlusion of the left anterior descending artery (LAD) (n = 6) or inferior wall infarction by occlusion of the left circumflex artery (LCx) (n = 6). Subsequently, animals underwent CMR and EAM using a multielectrode mapping catheter. CMR characteristics, including wall thickness, LGE location and extent, and EAM maps, were independently analyzed, and concordance between voltage maps and CMR characteristics was assessed. RESULTS: LGE volume was similar between the LCx and LAD groups (8.5 ± 2.2 ml vs. 8.3 ± 2.5 ml, respectively; p = 0.852). LGE scarring in the LAD group was more subendocardial, affected a larger surface area, and resulted in significant wall thinning (4.88 ± 0.43 mm). LGE scarring in the LCx group extended from the endocardium to the epicardium with minimal reduction in wall thickness (scarred: 5.4 ± 0.67 mm vs. remote: 6.75 ± 0.38 mm). In all the animals in the LAD group, areas of low voltage corresponded with LGE and wall thinning, whereas only 2 of 6 animals in the LCx group had low voltage areas on EAM. Bipolar and unipolar voltage amplitudes were higher in thick inferior walls in the LCx group than in thin anterior walls in the LAD group, despite a similar LGE volume. CONCLUSIONS: Discordances between LGE-detected scar areas and low voltage areas by EAM highlighted the limitations of the current EAM system to detect scar in thick myocardial wall regions.

Nicotine regulates multiple synaptic proteins by inhibiting proteasomal activity.

Ubiquitination regulates the degradation, membrane trafficking, and transcription of proteins. At mammalian synapses, the ubiquitin-proteasome system (UPS) influences synaptic transmission and plasticity. Nicotine also has the ability to affect synaptic function via mechanisms that remain partially unknown. We found that nicotine, at concentrations achieved by smokers, reduced proteasomal activity, produced accumulation of ubiquitinated synaptic proteins, and increased total protein levels. In particular, a 24 h exposure to nicotine decreased proteasome-dependent degradation of the alpha7 nicotinic acetylcholine receptor (nAChR) subunit, as indicated by the accumulation of ubiquitinated alpha7. The same nicotine treatment increased the levels of the AMPA glutamate receptor subunit GluR1, the NMDA receptor subunit NR2A, the metabotropic receptor mGluR1alpha, the plasticity factor Homer-1A, and the scaffolding postsynaptic density protein PSD-95, whereas the levels of another scaffolding protein, Shank, were reduced. These changes were associated with an inhibition of proteasomal chymotrypsin-like activity by nicotine. The nAChR antagonist mecamylamine was only partially able to block the effects of nicotine on the UPS, indicating that nAChR activation does not completely explain nicotine-induced inhibition of proteasomal catalytic activity. A competition binding assay suggested a direct interaction between nicotine and the 20S proteasome. These results suggest that the UPS might participate in nicotine-dependent synaptic plasticity.

NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease.

Abnormal NFκB activation has been implicated in Alzheimer's disease (AD). However, the signaling pathways governing NFκB regulation and function in the brain are poorly understood. We identify complement protein C3 as an astroglial target of NFκB and show that C3 release acts through neuronal C3aR to disrupt dendritic morphology and network function. Exposure to Aß activates astroglial NFκB and C3 release, consistent with the high levels of C3 expression in brain tissue from AD patients and APP transgenic mice, where C3aR antagonist treatment rescues cognitive impairment. Therefore, dysregulation of neuron-glia interaction through NFκB/C3/C3aR signaling may contribute to synaptic dysfunction in AD, and C3aR antagonists may be therapeutically beneficial.

IκBα deficiency in brain leads to elevated basal neuroinflammation and attenuated response following traumatic brain injury: implications for functional recovery.

BACKGROUND: The transcription factor NFκB is an important mediator of cell survival and inflammation in the immune system. In the central nervous system (CNS), NFκB signaling has been implicated in regulating neuronal survival following acute pathologic damage such as traumatic brain injury (TBI) and stroke. NFκB is normally bound by the principal inhibitory protein, IκBα, and sequestered in the cytoplasm. Activation of NFκB requires the degradation of IκBα, thereby freeing NFκB to translocate to the nucleus and activate the target genes. Mice deficient in IκBα display deregulated and sustained NFκB activation and early postnatal lethality, highlighting a critical role of IκBα in NFκB regulation. RESULTS: We investigated the role of IκBα in regulating NFκB activity in the brain and the effects of the NFκB/IκBα pathway in mediating neuroinflammation under both physiological and brain injury conditions. We report that astrocytes, but not neurons, exhibit prominent NFκB activity, and that basal NFκB activity in astrocytes is elevated in the absence of IκBα. By generating mice with brain-specific deletion of IκBα, we show that IκBα deficiency does not compromise normal brain development. However, basal neuroinflammation detected by GFAP and Iba1 immunoreactivity is elevated. This leads to impaired inflammatory responses following TBI and worsened brain damage including higher blood brain barrier permeability, increased injury volumes and enlarged ventricle volumes. CONCLUSIONS: We conclude that, in the CNS, astrocyte is the primary cell type subject to NFκB regulation. We further demonstrate that IκBα plays an important role in regulating NFκB activity in the brain and a robust NFκB/IκBα-mediated neuroinflammatory response immediately following TBI is beneficial.

Disruption of the NF-κB/IκBα Autoinhibitory Loop Improves Cognitive Performance and Promotes Hyperexcitability of Hippocampal Neurons.

BACKGROUND: Though originally discovered in the immune system as an important mediator of inflammation, NF-κB has recently been shown to play key roles in the central nervous system, such as synaptogenesis, synaptic plasticity, and cognition. NF-κB activity is normally tightly regulated by its primary inhibitor, IκBα, through a unique autoinhibitory loop. In this study, we tested the hypothesis that the IκBα autoinhibitory loop ensures optimal levels of NF-κB activity to promote proper brain development and function. To do so, we utilized knock-in mice which possess mutations in the IκBα promoter to disrupt the autoinhibitory loop (IκBαM/M KI mice). RESULTS: Here, we show that these mutations delay IκBα resynthesis and enhance NF-κB activation in neurons following acute activating stimuli. This leads to improved cognitive ability on tests of hippocampal-dependent learning and memory but no change in hippocampal synaptic plasticity. Instead, hippocampal neurons from IκBαM/M KI mice form more excitatory and less inhibitory synapses in dissociated cultures and are hyperexcitable. This leads to increased burst firing of action potentials and the development of abnormal hypersynchronous discharges in vivo. CONCLUSIONS: These results demonstrate that the IκBα autoinhibitory loop is critical for titrating appropriate levels of endogenous NF-κB activity to maintain proper neuronal function.

Activity of DNA vaccines encoding self or heterologous Her-2/neu in Her-2 or neu transgenic mice.

To assess the efficacy of self versus heterologous ErbB-2 vaccines, the reactivity to human and rat ErbB-2 (Her-2 and neu, respectively) DNA vaccines were tested in normal, Her-2 or neu transgenic mice. When immunized with either Her-2 or neu DNA, normal BALB/c and C57BL/6 mice produced cross-reactive T cells, but only antigen specific antibodies. In Her-2 Tg mice, weak to no anti-Her-2 response was induced by either self Her-2 or heterologous neu DNA, demonstrating profound tolerance to Her-2 and the inability to induce anti-Her-2 immunity with either vaccine. In NeuT mice, vaccination with self neu but not heterologous Her-2 DNA induced anti-neu antibodies and delayed spontaneous tumorigenesis. Both neu and Her-2 DNA induced anti-neu T cell response, but depletion of CD8 T cells did not change the delay in tumorigenesis. Therefore, in NeuT mice, both self and heterologous DNA activated anti-neu T cells, although T cell response did not reach sufficient level to suppress spontaneous tumorigenesis. Rather, induction of anti-neu antibodies by self neu DNA is associated with the delay in spontaneous tumor growth. Overall, NeuT mice were more responsive to DNA vaccination than Her-2 Tg mice and this may be associated with the continuous production of neu by the 10 mammary glands undergoing tumor progression.

Kawasaki Disease: Current Therapeutic Perspectives.

Kawasaki disease is an acute systemic vasculitis of unknown etiology that has become the most common form of acquired heart disease in young children in developing countries. The most serious threat from Kawasaki disease is the development of coronary vasculitis, with subsequent development of aneurysms, thrombosis, and coronary compromise. Standard treatment during the acute phase of Kawasaki disease now consists of intravenous gamma globulin, 2 g/kg, given as a single dose, and high-dose aspirin therapy, 80 to 100 mg/kg daily. When instituted within 10 days of the onset of illness, this approach has reduced the incidence of coronary artery abnormalities from 20% to 25% to approximately 5% at 6 to 8 weeks after initiation of treatment. Despite these therapeutic successes, the optimal management of certain patient groups with Kawasaki disease remains unclear or controversial. This includes patients with persistent or recrudescent fever and inflammation despite prompt initiation of standard therapy, and patients developing coronary arterial aneurysms. For patients with persistent or recrudescent fever, there are increasing reports suggesting that corticosteroid therapy, in addition to retreatment with intravenous gamma globulin, may be useful. Newer antiplatelet agents are being introduced that may improve outcome in children who develop acute coronary artery lesions. Long-term therapy of patients with coronary artery aneurysms typically consists of long-term aspirin therapy; the use of additional antiplatelet agents and anticoagulants is often used in clinical practice, but not universally accepted.

Role of lysine-256 in Citrobacter freundii tyrosine phenol-lyase in monovalent cation activation.

Tyrosine phenol-lyase (TPL) from Citrobacter freundii is dependent on monovalent cations, K(+) or NH(4)(+), for high activity. We have shown previously that Glu-69, which is a ligand to the bound cation, is important in monovalent cation binding and activation [Sundararaju, B., Chen, H., Shillcutt, S., and Phillips, R. S. (2000) Biochemistry 39, 8546-8555]. Lys-256 is located in the monovalent cation binding site of TPL, where it forms a hydrogen bond with a structural water bound to the cation. This lysine residue is highly conserved in sequences of TPL and the paralogue, tryptophan indole-lyase. We have now prepared K256A, K256H, K256R, and E69D/K256R mutant TPLs to probe the role of Lys-256 in monovalent cation binding and activation. K256A and K256H TPLs have low activity (k(cat)/K(m) values of 0.01-0.1%), are not activated by monovalent cations, and do not exhibit fluorescence emission at 500 nm from the PLP cofactor. In contrast, K256R TPL has higher activity (k(cat)/K(m) about 10% of wild-type TPL), is activated by K(+), and exhibits fluorescence emission from the PLP cofactor. K256A, K256H, and K256R TPLs bind PLP somewhat weaker than wild-type TPL. E69D/K256R TPL was prepared to determine if the guanidine side chain could substitute for the monovalent cation. This mutant TPL has wild-type activity with S-Et-L-Cys or S-(o-nitrophenyl)-L-Cys but has no detectable activity with L-Tyr. E69D/K256R TPL is not activated by monovalent cations and does not show PLP fluorescence. In contrast to wild-type and other mutant TPLs, PLP binding to E69D/K256R is very slow, requiring several hours of incubation to obtain 1 mol of PLP per subunit. Thus, E69D/K256R TPL appears to have altered dynamics. All of the mutant TPLs react with inhibitors, L-Ala, L-Met, and L-Phe, to form equilibrating mixtures of external aldimine and quinonoid intermediates. Thus, Lys-256 is not the base which removes the alpha-proton during catalysis. The results show that the function of Lys-256 in TPL is in monovalent cation binding and activation.