Cationic Geminoid Peptide Amphiphiles Inhibit DENV2 Protease,Furin, and Viral Replication

Dengue is an important arboviral infectious disease for which there is currently no specific cure. We report gemini-like (geminoid) alkylated amphiphilic peptides containing lysines in combination with glycines or alanines (C₁₅H₃₁C(O)-Lys-(Gly or Ala)_nLys-NHC₁₆H₃₃, shorthand notation C₁₆-KX_nK-C₁₆ with X = A or G, and n = 0–2). The representatives with 1 or 2 Ala inhibit dengue protease and human furin, two serine proteases involved in dengue virus infection that have peptides with cationic amino acids as their preferred substrates, with IC₅₀ values in the lower µM range. The geminoid C₁₆-KAK-C₁₆ combined inhibition of DENV2 protease (IC₅₀ 2.3 µM) with efficacy against replication of wildtype DENV2 in LLC-MK2 cells (EC₅₀ 4.1 µM) and an absence of toxicity. We conclude that the lysine-based geminoids have activity against dengue virus infection, which is based on their inhibition of the proteases involved in viral replication and are therefore promising leads to further developing antiviral therapeutics, not limited to dengue.     

Adaptive wave field synthesis for active sound field reproduction: experimental results

Sound field reproduction has applications in music reproduction, spatial audio, sound environment reproduction, and experimental acoustics. Sound field reproduction can be used to artificially reproduce the spatial character of natural hearing. The objective is then to reproduce a sound field in a real reproduction environment. Wave field synthesis (WFS) is a known open-loop technology which assumes that the reproduction environment is anechoic. The room response thus reduces the quality of the physical sound field reproduction by WFS. In recent research papers, adaptive wave field synthesis (AWFS) was defined as a potential solution to compensate for these quality reductions from which WFS objective performance suffers. In this paper, AWFS is experimentally investigated as an active sound field reproduction system with a limited number of reproduction error sensors to compensate for the response of the listening environment. Two digital signal processing algorithms for AWFS are used for comparison purposes, one of which is based on independent radiation mode control. AWFS performed propagating sound field reproduction better than WFS in three tested reproduction spaces (hemianechoic chamber, standard laboratory space, and reverberation chamber).     

MR spectroscopic imaging of glutathione in the white and gray matter at 7 T with an application to multiple sclerosis

Detection of glutathione (GSH) is technically challenging at clinical field strengths of 1.5 or 3 T due to its low concentration in the human brain coupled with the fact that conventional single-echo acquisitions, typically used for magnetic resonance (MR) spectroscopy acquisitions, cannot be used to resolve GSH given its overlap with other resonances. In this study, an MR spectral editing scheme was used to generate an unobstructed detection of GSH at 7 T. This technique was used to obtain normative white (WM) and gray matter (GM) GSH concentrations over a two-dimensional region. Results indicated that GSH was significantly higher (P<.001) in GM relative to WM in normal subjects. This finding is consistent with previous radionuclide experiments and histochemical staining and validates this 7 T MR spectroscopy technique. To our knowledge, this is the first study to report normative differences in WM and GM glutathione concentrations in the human brain. Glutathione is a biomarker for oxidative status and this non-invasive in vivo measurement of GSH was used to explore its sensitivity to oxidative state in multiple sclerosis (MS) patients. There was a significant reduction (P<.001) of GSH between the GM in MS patients and normal controls. No statistically significant GSH differences were found between the WM in controls and MS patients. Reduced GSH was also observed in a MS WM lesion. This preliminary investigation demonstrates the potential of this marker to probe oxidative state in MS.     

Measurement of cluster–cluster interaction in liquids by deposition and AFM of silicon clusters onto HOPG surfaces

Experimental studies have been performed on unisize tungsten clusters constructed on a graphite surface by means of the scanning tunneling microscopy. It was found that the geometry of the clusters changes instantaneously from a monatomic-layer tungsten disk to a diatomic-layer structure between the cluster size of 10 and 11. We concluded that this transition is driven by a change in the dominant interaction from the attractive electrostatic interaction between the cluster and the surface to intracluster cohesive metallic interaction.     

Thin layers deposited from V2O5 gels: II. An optical absorption study

Absorption spectra of V₂O₅ layers deposited from gels of various V⁴⁺ contents C were studied from near UV down to near IR. The high absorption region due to the charge transfer transition extends above ≈ 2 eV. Whatever C the optical gap is ≈ 2.25 eV. On the low energy side an Urbach tail is observed whose slope increases with C. In the near infrared absorption is related to the V⁴⁺ ions and increases linearly with C. The absorption band due to the optically induced polaron hopping is detected. The corresponding maximum E_max suffers a red shift when C increases. The experimental E_max data are very close to the values predicted from the polaron and disorder energies as deduced from the conductivity study in an earlier paper. The slight difference between the two sets of data allowed us to estimate the transfer integral J ≈ 0.015 eV.     

Optimal hedging when the underlying asset follows a regime-switching Markov process

We develop a flexible discrete-time hedging methodology that minimizes the expected value of any desired penalty function of the hedging error within a general regime-switching framework. A numerical algorithm based on backward recursion allows for the sequential construction of an optimal hedging strategy. Numerical experiments comparing this and other methodologies show a relative expected penalty reduction ranging between 0.9%$0.9\%$ and 12.6%$12.6\%$ with respect to the best benchmark.     

Extremal harmonic active control of power for a monocylinder hybrid powertrain

This article presents a real-life application for the extremal harmonic active control of power [1] applied on a hybrid engine setup. The active control was adapted for a hybrid powertrain constituted of a one-cylinder diesel engine coupled with a permanent magnet synchronous machine. The problem was formulated in the harmonic domain and the control objective was to extremalize energetic criterions. Three criterions were considered: minimizing the speed ripple of the engine, maximizing the mechanical reactive power (mechanical impedance adaptation) and maximizing the active electric power for energy harvesting. The results show that, for the first and second orders of the ripple, speed oscillations can be completely cancelled and reactive power and active power can be optimized on-line. The implicit extremal controller converged rapidly, remaining stable even when the mean engine speed changed abruptly. These results confirm the robustness and the applicability of the extremal harmonic active control for industrial applications.     

Experimental investigation into the interference aerodynamics of two slender bodies in close proximity

Aerodynamic interference between high-speed slender bodies can detrimentally affect the force and moment characteristics. This is investigated through a wind tunnel study using pressure sensitive paint and force measurements on a receiver body placed adjacent to a generator body. The aim of this paper is to understand both the force and moment changes as well as the underlying aerodynamics of the interference loads which are induced by the disturbance flowfield. The impact of receiver incidence and the strength of the disturbance field are also assessed. The observed interference loads primarily depend on a complex balance of static pressure footprints and tend to be bespoke to each configuration. As a result, overall trends are difficult to extract, but in general the magnitude of the interference loads increases when the receiver is at incidence and also when the strength of the imposed disturbance flowfield increases.     

Alkaloidal variation in cissampelos capensis (Menispermaceae)

Cissampelos capensis, commonly known by the Afrikaans name "dawidjies" or "dawidjieswortel", is the most important and best known medicinal plant of the family Menispermaceae used by the Khoisan and other rural people in the western region of South Africa. The main alkaloids in the leaves, stems and rhizomes were isolated and identified. Several of the main compounds were previously found in species of the related genus Antizoma and this similarity indicates that the two genera are closely related if not congeneric. Bulbocapnine (an aporphine alkaloid), dicentrine (an aporphine alkaloid) and salutaridine (a morphinane alkaloid) were the main alkaloids in the leaves, while bulbocapnine, cissacapine, cycleanine and insularine (the last three are bisbenzyltetrahydro-isoquinoline alkaloids) are the major compounds in the stems. The rhizome contains mostly bisbenzyltetrahydroisoquinoline alkaloids, with 12-O-methylcurine, cissacapine and cycleanine as the main ones. Alkaloids appear to be quite variable within different plant parts and different provenances, as confirmed by the difference in alkaloid patterns between coastal and inland forms of Cissampelos capensis (the morphinane alkaloid salutaridine, for example, is the major leaf alkaloid along the coast but is practically absent from the inland form of the species). The variety of alkaloids identified may contribute to the medicinal value of this species. The data on alkaloidal variation in the species has potential value and practical applications in chemotaxonomy, toxicology and pharmacognosy.