High-Energy Polynitrogen N10 Stabilized on Multi-Walled Carbon Nanotubes.

The synthesis of stable polynitrogen compounds with high-energy density has long been a major challenge. The cyclo-pentazolate anion (cyclo-N5 -) is successfully converted into aromatic and structurally symmetric bipentazole (N10) via electrochemical synthesis using highly conductive multi-walled carbon nanotubes (MWCNTs) as the substrate and sodium pentazolate hydrate ([Na(H2O)(N5)]·2H2O) as the raw material. Attenuated total refraction Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and density functional theory calculations confirmed the structure and homogeneous distribution of N10 in the sidewalls of the MWCNTs (named MWCNT-N10-n m). The MWCNT-N10-2.0 m is further used as a catalyst for electrochemical oxygen reduction to synthesize hydrogen peroxide from oxygen with a two-electron selectivity of up to 95%.

Eckart equations, Maxwellian iteration and relativistic causal theories of divergence type.

We consider a general causal relativistic theory of divergence type in the framework of rational extended thermodynamics (RET) for a compressible, possibly dense, gas. We require that the system converges in the Maxwellian iteration's first step to the parabolic Eckart equations. This requirement implies a constraint between the two coefficients present in the triple tensor evaluated at equilibrium. Moreover, the production tensor is determined for prescript thermal and caloric state equations and given heat conductivity, shear and bulk viscosities. In the second part, we prove that if the original hyperbolic system satisfies the universal principles of RET, as can be put in the symmetric form using the main field, it always satisfies the previous compatibility condition. Therefore, any causal system of divergence type that satisfies the entropy principle with a convex entropy converges to the Eckart system in the Maxwellian iteration also when we have no information at the mesoscopic scale from the kinetic theory. The obtained results are tested on the RET theories of rarefied monatomic and polyatomic gases. This article is part of the theme issue 'Foundational issues, analysis and geometry in continuum mechanics'.

Sparse Machine Learning in Banach Spaces.

The aim of this expository paper is to explain to graduate students and beginning researchers in the field of mathematics, statistics and engineering the fundamental concept of sparse machine learning in Banach spaces. In particular, we use binary classification as an example to explain the essence of learning in a reproducing kernel Hilbert space and sparse learning in a reproducing kernel Banach space (RKBS). We then utilize the Banach space ℓ 1 ( ℕ ) to illustrate the basic concepts of the RKBS in an elementary yet rigorous fashion. This paper reviews existing results in the author's perspectives to reflect the state of the art of the field of sparse learning, and includes new theoretical observations on the RKBS. Several open problems critical to the theory of the RKBS are also discussed at the end of this paper.

The effect of Glibenclamide on somatosensory evoked potentials after cardiac arrest in rats.

BACKGROUND: Science continues to search for a neuroprotective drug therapy to improve outcomes after cardiac arrest (CA). The use of glibenclamide (GBC) has shown promise in preclinical studies, but its effects on neuroprognostication tools are not well understood. We aimed to investigate the effect of GBC on somatosensory evoked potential (SSEP) waveform recovery post CA and how this relates to the early prediction of functional outcome, with close attention to arousal and somatosensory recovery, in a rodent model of CA. METHODS: Sixteen male Wistar rats were subjected to 8-min asphyxia CA and assigned to GBC treatment (n = 8) or control (n = 8) groups. GBC was administered as a loading dose of 10 µg/kg intraperitoneally 10 min after the return of spontaneous circulation, followed by a maintenance dosage of 1.6 µg/kg every 8 h for 24 h. SSEPs were recorded from baseline until 150 min following CA. Coma recovery, arousal, and brainstem function, measured by subsets of the neurological deficit score (NDS), were compared between both groups. SSEP N10 amplitudes were compared between the two groups at 30, 60, 90, and 120 min post CA. RESULTS: Rats treated with GBC had higher sub-NDS scores post CA, with improved arousal and brainstem function recovery (P = 0.007). Both groups showed a gradual improvement of SSEP N10 amplitude over time, from 30 to 120 min post CA. Rats treated with GBC showed significantly better SSEP recovery at every time point (P < 0.001 for 30, 60, and 90 min; P = 0.003 for 120 min). In the GBC group, the N10 amplitude recovered to baseline by 120 min post CA. Quantified Cresyl violet staining revealed a significantly greater percentage of damage in the control group compared with the GBC treatment group (P = 0.004). CONCLUSIONS: Glibenclamide improves coma recovery, arousal, and brainstem function after CA with decreased number of ischemic neurons in a rat model. GBC improves SSEP recovery post CA, with N10 amplitude reaching the baseline value by 120 min, suggesting early electrophysiologic recovery with this treatment. This medication warrants further exploration as a potential drug therapy to improve functional outcomes in patients after CA.

Three-dimensional maps and subgroup growth.

In this paper we derive a generating series for the number of cellular complexes known as pavings or three-dimensional maps, on n darts, thus solving an analogue of Tutte's problem in dimension three. The generating series we derive also counts free subgroups of index n in Δ + = Z 2 ∗ Z 2 ∗ Z 2 via a simple bijection between pavings and finite index subgroups which can be deduced from the action of Δ + on the cosets of a given subgroup. We then show that this generating series is non-holonomic. Furthermore, we provide and study the generating series for isomorphism classes of pavings, which correspond to conjugacy classes of free subgroups of finite index in Δ + . Computational experiments performed with software designed by the authors provide some statistics about the topology and combinatorics of pavings on n ≤ 16 darts.

Effects of soil amendments on the growth response and phytoextraction capability of a willow variety (S. viminalis × S. schwerinii × S. dasyclados) grown in contaminated soils.

This study was conducted to evaluate the effects of lime and bisphosphonates (BPs) such as N10O chelate amendment on the growth, physiological and biochemical parameters, and phytoextraction potential of the willow variety Klara (Salix viminalis × S. schwerinii × S. dasyclados) grown in soils heavily contaminated with copper (Cu), nickel (Ni) and zinc (Zn). The plants were irrigated with tap or processed water (mine wastewater). The results suggest that the combined effects of the contaminated soil and processed water inhibited growth parameters, gas exchange parameters and chlorophyll fluorescence (Fv/Fm) values. In contrast, malondialdehyde (MDA) content, organic acids, total phenolic and total flavonoid contents, and the accumulation of metals/metalloids in the plant tissues were increased compared to the control. When the soil was supplemented with lime and N10O; growth, physiological, biochemical parameters, and resistance capacity were significantly higher compared to unamended soil treatments, especially in the contaminated soil treatments. The combined lime‒ and N10O‒amended soil treatment produced higher growth rates, resistance capacity, photosynthesis rates and phytoextraction efficiency levels relative to either the lime‒amended or the N10O‒amended soil treatments. This study provides practical evidence of the efficient chelate‒assisted phytoextraction capability of Klara and highlights its potential as a viable and inexpensive novel approach for in situ remediation of Cu‒, Ni‒ and Zn‒contaminated soils and mine wastewaters.

Generalizing Koopman Theory to Allow for Inputs and Control.

We develop a new generalization of Koopman operator theory that incorporates the e ects of inputs and control. Koopman spectral analysis is a theoretical tool for the analysis of nonlinear dynamical systems. Moreover, Koopman is intimately connected to dynamic mode decomposition (DMD), a method that discovers coherent, spatio-temporal modes from data, connects local-linear analysis to nonlinear operator theory, and importantly creates an equation-free architecture for the study of complex systems. For actuated systems, standard Koopman analysis and DMD are incapable of producing input-output models; moreover, the dynamics and the modes will be corrupted by external forcing. Our new theoretical developments extend Koopman operator theory to allow for systems with nonlinear input-output characteristics. We show how this generalization is rigorously connected to a recent development called dynamic mode decomposition with control. We demonstrate this new theory on nonlinear dynamical systems, including a standard susceptible-infectious-recovered model with relevance to the analysis of infectious disease data with mass vaccination (actuation).

Molecular architecture of an N-formyltransferase from Salmonella enterica O60.

N-formylated sugars are found on the lipopolysaccharides of various pathogenic Gram negative bacteria including Campylobacter jejuni 81116, Francisella tularensis, Providencia alcalifaciens O30, and Providencia alcalifaciens O40. The last step in the biosynthetic pathways for these unusual sugars is catalyzed by N-formyltransferases that utilize N10-formyltetrahydrofolate as the carbon source. The substrates are dTDP-linked amino sugars with the functional groups installed at either the C-3' or C-4' positions of the pyranosyl rings. Here we describe a structural and enzymological investigation of the putative N-formyltransferase, FdtF, from Salmonella enterica O60. In keeping with its proposed role in the organism, the kinetic data reveal that the enzyme is more active with dTDP-3-amino-3,6-dideoxy-d-galactose than with dTDP-3-amino-3,6-dideoxy-d-glucose. The structural data demonstrate that the enzyme contains, in addition to the canonical N-formyltransferase fold, an ankyrin repeat moiety that houses a second dTDP-sugar binding pocket. This is only the second time an ankyrin repeat has been shown to be involved in small molecule binding. The research described herein represents the first structural analysis of a sugar N-formyltransferase that specifically functions on dTDP-3-amino-3,6-dideoxy-d-galactose in vivo and thus adds to our understanding of these intriguing enzymes.

One-Pot Synthesis of Cyclopropane-Fused Cyclic Amidines: An Oxidative Carbanion Cyclization.

A novel and efficient one-pot method has been developed for the synthesis of cyclopropane-fused bicyclic amidines on the basis of a CuBr2 -mediated oxidative cyclization of carbanions. The usefulness of this unique multicomponent strategy has been demonstrated by the use of a wide variety of substrates to furnish novel cyclopropane-containing amidines with a quaternary center in very good yields. This ketenimine-based approach provides straightforward access to biologically active and pharmaceutically important 3-azabicyclo[n.1.0]alkane frameworks under mild conditions. The synthetic power of this methodology is exemplified in the concise synthesis of the pharmaceutically important antidepressant drug candidate GSK1360707 and key intermediates for the synthesis of amitifadine, bicifadine, and narlaprevir.

Synthesis of Bicyclo[n.1.0]alkanes by a Cobalt-Catalyzed Multiple C(sp3 )-H Activation Strategy.

A cobalt-catalyzed dual C(sp3 )-H activation strategy has been developed and it provides a novel strategy for the synthesis of bicyclo[4.1.0]heptanes and bicyclo[3.1.0]hexanes. A key to the success of this reaction is the conformation-induced methylene C(sp3 )-H activation of the resulting cobaltabicyclo[4.n.1] intermediate. In addition, the synthesis of bicyclo[3.1.0]hexane from pivalamide, by a triple C(sp3 )-H activation, has also been demonstrated.

Investigating in-vitro functionality and in-vivo taste assessment of eco-friendly Tadalafil Pastilles.

Tadalafil (TDL) has poor bioavailability due to the less aqueous solubility and bitter taste. Oral solid dosage forms, especially tablets, have a broad market worldwide. Constraints of tablets are a long process, pollution, high processing cost, and requiring more excipient. The research was performed to optimize an eco-friendly immediate-acting pastille of TDL to put forward an alternate formulation to a tablet using advanced data mining tools. Another objective is to assess the taste masking of TDL using the Brief Access Taste Aversion (BATA) model. The amount of PEG-4000, Polyox N-10, and Kyron T-314 were chosen as critical material attributes from failure mode effect analysis. Box-Behnken design (BBD) was utilized to optimize the pastilles and ascertained the significant impact of chosen variables on disintegration time and % CDR at 10 min. The control strategy and optimal region were located using an overlay plot. The pastilles were able to release the drug within 15 min due to faster disintegration. The formulated pastilles were of uniform size, shape, and mechanical strength. The bitter taste of TDL was masked and confirmed by the BATA model. The newer formulation may be helpful in the industry due to its eco-friendly, single-step, and economical process. It unlocks a new direction in the field of oral solid dosage form as an alternative to tablets.

Reverse Genetics of Bat Influenza A Viruses.

New World fruit bats were recently found to harbor two distinct and previously unknown influenza A viruses (IAVs) of the subtypes H17N10 and H18N11. Although viral genome sequences were detected in the liver, intestine, lung, and kidney of infected bats and the complete genome sequences have been isolated from their rectal swab samples, all attempts to isolate an infectious virus from bats in nature have failed. The lack of an infectious bat IAV isolate was overcome by reverse genetic approaches that led to the generation of an infectious virus in vitro. Using such synthetic bat IAVs enabled the identification of their unconventional cell entry via major histocompatibility complex II (MCH-II) molecules and their ability to replicate in mice, ferrets, and bats. Importantly, we also showed that these synthetic recombinant bat IAVs are not able to reassort with conventional IAVs, preventing the acquisition of enhanced transmission properties in non-bat species by reassortment with conventional IAVs. As authentic viruses are key for understanding the molecular biology of bat IAVs, in this chapter, we describe our recently established reverse genetics protocol for generating H17N10 and H18N11 in vitro. This step-by-step protocol starts with cloning of cDNA copies of the viral RNA segments into reverse genetics plasmids, followed by the generation of a highly concentrated stock and finally a method to determine viral titers.

Serological evidence of virus infection in Eidolon helvum fruit bats: implications for bushmeat consumption in Nigeria.

Introduction: The Eidolon helvum fruit bat is one of the most widely distributed fruit bats in Africa and known to be a reservoir for several pathogenic viruses that can cause disease in animals and humans. To assess the risk of zoonotic spillover, we conducted a serological survey of 304 serum samples from E. helvum bats that were captured for human consumption in Makurdi, Nigeria. Methods: Using pseudotyped viruses, we screened 304 serum samples for neutralizing antibodies against viruses from the Coronaviridae, Filoviridae, Orthomyxoviridae and Paramyxoviridae families. Results: We report the presence of neutralizing antibodies against henipavirus lineage GH-M74a virus (odds ratio 6.23; p < 0.001), Nipah virus (odds ratio 4.04; p = 0.00031), bat influenza H17N10 virus (odds ratio 7.25; p < 0.001) and no significant association with Ebola virus (odds ratio 0.56; p = 0.375) in this bat cohort. Conclusion: The data suggest a potential risk of zoonotic spillover including the possible circulation of highly pathogenic viruses in E. helvum populations. These findings highlight the importance of maintaining sero-surveillance of E. helvum, and the necessity for further, more comprehensive investigations to monitor changes in virus prevalence, distribution over time, and across different geographic locations.

Identification of Neural Mechanisms in First Single-Sweep Analysis in oVEMPs and Novel Normative Data.

BACKGROUND: Bone-conducted (BC) VEMPs provide important tools for measuring otolith function. However, two major drawbacks of this method are encountered in clinical practice-small n10 amplitude and averaging technique. In this study, we present the results of a new VEMP setup measuring technique combined with a novel single-sweep analysis. METHODS: The study included BC oVEMP data from 92 participants for the evaluation of normative data using a novel analysis technique. For evaluating test-retest reliability, the intraclass correlation coefficient (ICC) was used. RESULTS: We found significant n10 amplitude differences in single-sweep analyses after the first and second measurements. Thereby, mathematical analyses of the head movement did not show any differences in the first or second measurements. The normative n10 amplitude was 20.66 µV with an asymmetric ratio (AR) of 7%. The new value of late shift difference (LSD) was 0.01 ms. The test retest-reliability showed good to excellent ICC results in 9 out of 10 measurements. CONCLUSIONS: Our results support a phenomenon in single-sweep analysis of the first stimuli independent of head movement and signal morphology. Furthermore, the values obtained with the new measurement method appear to be more sensitive and may allow an extended diagnostic range due to the new parameter LSD.

Biosynthetic Pathway Construction and Production Enhancement of 1-Hydroxyphenazine Derivatives in Pseudomonas chlororaphis H18.

1-Hydroxyphenazine derivatives are phenazine family chemicals with broad-spectrum antibacterial and potential biological activities. However, the lack of variety and low titer hinder their applications. In this research, three enzymes PhzS (monooxygenase), NaphzNO1 (N-monooxygenase), and LaphzM (methyltransferase) were heterologously expressed in a phenazine-1-carboxylic acid generating strain Pseudomonas chlororaphis H18. Four phenazines, 1-hydroxyphenazine, 1-methoxyphenazine, 1-hydroxyphenazine N' 10-oxide, and a novel phenazine derivative 1-methoxyphenazine N' 10-oxide, were isolated, characterized in the genetically modified strains, and exhibited excellent antimicrobial activities. Next, we verified the hydroxyl methylation activity of LaphzM and elucidated the biosynthetic pathway of 1-methoxyphenazine N' 10-oxide in vitro. Moreover, the titer of 1-hydroxyphenazine derivatives was engineered. The three compounds 1-methoxyphenazine, 1-hydroxyphenazine N' 10-oxide, and 1-methoxyphenazine N' 10-oxide all reach the highest titer reported to date. This work provides a promising platform for phenazine derivatives' combinatorial biosynthesis and engineering.

On the rank-deficient canonical correlation technique solved by analytic spectral decomposition.

Regularization is a well-known and used statistical approach covering individual points or limit approximations. In this study, the canonical correlation analysis (CCA) process of the paths is discussed with partial least squares (PLS) as the other boundary covering transformation to a symmetric eigenvalue (or singular value) problem dependent on a parameter. Two regularizations of the original criterion in the parameterization domain are compared, i.e. using projection and by identity matrix. We discuss the existence and uniqueness of the analytic path for eigenvalues and corresponding elements of eigenvectors. Specifically, canonical analysis is applied to an ill-conditioned case of singular within-sets input matrices encompassing tourism accommodation data.

Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L).

Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state.

Efficient iterative solutions to complex-valued nonlinear least-squares problems with mixed linear and antilinear operators.

We consider a setting in which it is desired to find an optimal complex vector x ∈ C N that satisfies A (x) ≈ b in a least-squares sense, where b ∈ C M is a data vector (possibly noise-corrupted), and A (·) : C N → C M is a measurement operator. If A (·) were linear, this reduces to the classical linear least-squares problem, which has a well-known analytic solution as well as powerful iterative solution algorithms. However, instead of linear least-squares, this work considers the more complicated scenario where A (·) is nonlinear, but can be represented as the summation and/or composition of some operators that are linear and some operators that are antilinear. Some common nonlinear operations that have this structure include complex conjugation or taking the real-part or imaginary-part of a complex vector. Previous literature has shown that this kind of mixed linear/antilinear least-squares problem can be mapped into a linear least-squares problem by considering x as a vector in R 2N instead of C N . While this approach is valid, the replacement of the original complex-valued optimization problem with a real-valued optimization problem can be complicated to implement, and can also be associated with increased computational complexity. In this work, we describe theory and computational methods that enable mixed linear/antilinear least-squares problems to be solved iteratively using standard linear least-squares tools, while retaining all of the complex-valued structure of the original inverse problem. An illustration is providedtodemonstratethatthisapproachcansimplifytheimplementationandreduce the computational complexity of iterative solution algorithms.

Novel All-Nitrogen Molecular Crystals of Aromatic N10.

Nitrogen has unique bonding ability to form single, double, and triple bonds, similar to that of carbon. However, a molecular crystal formed by an aromatic polynitrogen similar to a carbon system has not been found yet. Herein, a new form of stable all-nitrogen molecular crystals consisting of only bispentazole N10 molecules with exceedingly high energy density is predicted. The crystal structures and the conformation of N10 molecules are strongly correlated, both depending on the applied external pressure. These molecular crystals can be recovered upon the release of the pressure. The first-principles molecular dynamics simulations reveal that these all-nitrogen materials decompose at temperatures much higher than room temperature. The decompositions always start from breaking off N2 molecules from the nitrogen ring and can release a large amount of energy. These new polynitrogens are aromatic and are more stable than all the other polynitrogen crystals reported previously, providing a new green strategy to get all-nitrogen, nonpolluting high energy density materials without introducing any metal or other guest stabilizer.

Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Mitigate Trained Immunity in the Brain.

Trained immunity was recently discovered in innate immune cells and shown to facilitate the clearance of pathogens at the time of occurrence of the second insult. However, it exacerbates several aspects of neuropathologies, and proper therapy is needed to rectify this abnormal immune reaction. Mesenchymal-stem cells (MSCs) exhibit a distinct capability for brain repair but are associated with safety concerns. Extracellular vesicles derived from MSCs are a promising alternative therapy. In this study, we used lipopolysaccharides to activate trained immunity in the brain and examined the therapeutic potential of MSC-derived extracellular vesicles in mitigating the trained-immunity-induced exacerbated neuropathology. We found that MSC-derived extracellular vesicles showed comparable effects to those of MSCs in the mitigation of trained immunity in the brain. Moreover, the administration of MCS-derived extracellular vesicles mitigated the aggregated inflammatory responses in the acute stage of stroke and alleviated the trained-immunity-induced increased load of amyloid-ß in APP/PS1 mice. We further investigated the molecular machinery of MSC-derived extracellular vesicles and found that IL-10 is important for the mediation of the therapeutic potential of MSC-derived extracellular vesicles toward the alleviation of trained immunity. Our study indicates that extracellular-vesicle-based regenerative strategies might be useful to mitigate trained immunity in the brain.