In malaria pathophysiology, divergent hypotheses on the inhibition of hematin crystallization posit that drugs act either by the sequestration of soluble hematin or their interaction with crystal surfaces. We use physiologically relevant, time-resolved in situ surface observations and show that quinoline antimalarials inhibit β-hematin crystal surfaces by three distinct modes of action: step pinning, kink blocking, and step bunch induction. Detailed experimental evidence of kink blocking validates classical theory and demonstrates that this mechanism is not the most effective inhibition pathway. Quinolines also form various complexes with soluble hematin, but complexation is insufficient to suppress heme detoxification and is a poor indicator of drug specificity. Collectively, our findings reveal the significance of drug-crystal interactions and open avenues for rationally designing antimalarial compounds.
A two-dimensional (r, z) numerical simulation of the discharge characteristics of an atmospheric pressure plasma jet (APPJ), with coaxial shielding gas, was performed. The helium working gas flowed in a central capillary tube, engulfing a needle electrode powered by 13.7 MHz radio frequency sinusoidal voltage. The N2 shielding gas flowed in the annular space of a coaxial tube. These gases emerged, in laminar flow, in a 78%N2-21%O2-1%Ar dry air ambient. The characteristics of the APPJ with shielding gas were compared to those of the APPJ without shielding gas. The nitrogen shielding gas hindered the diffusion of oxygen and argon from the ambient air into the helium jet. With the shielding gas present, more nitrogen penetrated into the helium core, causing a shorter plasma ‘plume’. The flow rates of the working and shielding gas, critically affected the gas temperature, and in turn the discharge characteristics. For a He flow of 2 standard liters per minute (slm), switching on the nitrogen shielding gas flow (at 4.5 slm) reduced the on-axis O2 and Ar mole fractions from 3.9 × 10 − 4 to 6.8 × 10 − 5 and from 1.9 × 10 − 5 to 3.3 × 10 − 6 , respectively, at an axial distance of 3 mm downstream of the nozzle. The radial profiles of the mole fractions of the ambient gases were monotonically and strongly decreasing towards the system axis, for short axial distances from the nozzle (∼1 mm), but became progressively flatter at longer distances from the nozzle (3 mm and 5 mm). Simulation predictions captured the salient features of experimental data of ambient species mole fractions in the plasma jet, and the 706 nm optical emission intensity profiles of the He 33S excited state.
The prevalence of untreated oral diseases is very high and the need for dental care extensive among the residents of government-administered long-term care facilities in Ho Chi Minh City.
A versatile approach to control crystallization involves the use of modifiers, which are additives that interact with crystal surfaces and alter their growth rates. Elucidating a modifier's binding specificity to anisotropic crystal surfaces is a ubiquitous challenge that is critical to their design. In this study, we select hematin, a byproduct of malaria parasites, as a model system to examine the complementarity of modifiers (i.e., antimalarial drugs) to β-hematin crystal surfaces. We divide two antimalarials, chloroquine and amodiaquine, into segments consisting of a quinoline base, common to both drugs, and side chains that differentiate their modes of action. Using a combination of scanning probe microscopy, bulk crystallization, and analytical techniques, we show that the base and side chain work synergistically to reduce the rate of hematin crystallization. In contrast to general observations that modifiers retain their function upon segmentation, we show that the constituents do not act as modifiers. A systematic study of quinoline isomers and analogues shows how subtle rearrangement and removal of functional moieties can create effective constituents from previously ineffective modifiers, along with tuning their inhibitory modes of action. These findings highlight the importance of specific functional moieties in drug compounds, leading to an improved understanding of modifier-crystal interactions that could prove to be applicable to the design of new antimalarials.
Optical emission spectroscopy was used to measure the radial distribution of the mole fraction of ambient air species (Ar, O 2 and N 2 ) diffusing into a radio frequency (13.7 MHz) helium (2.0 standard liters per min (slm)), atmospheric pressure plasma jet (APPJ). Line-integrated emissions recorded as a function of lateral position (at fixed axial positions), perpendicular to the jet axis, were magnified and fed into a spectrometer. Selected emission intensities were then Abel inverted to obtain radial emission profiles. The latter were converted into absolute mole fraction profiles, using a 'self-actinometry' method, in which known small amounts of Ar, O 2 , or N 2 were added to the He feed gas to produce a small change in emission intensity. Without shielding gas, the on-axis air mole fraction increased from zero at 1 mm, to 10 −3 at 3 mm and 10 −2 at 5 mm from the nozzle. The radial distribution was center-low near the nozzle, and flattened further downstream. N 2 shielding gas (4.5 slm) flow in an annular jet coaxial with the He jet, reduced air diffusion by 2-3 times. Simulation of air diffusion into the plasma jet showed similar axial number densities of air species, as well as similar effectiveness of the shielding gas, compared to experimental data. The shielding effectiveness in this study was lower than that in published works because of the higher gas temperature in the present APPJ.
Species excitation mechanisms were studied, using optical emission spectroscopy, in a helium 200 kHz radio frequency (RF) plasma jet, emerging into the open air at 1 atm. The jet impinged on a dielectric substrate of either MgF2 or quartz. Optical emissions between 115 and 950 nm were recorded through the substrate either along the jet axis or at a steep angle to isolate emissions originating from the region near the substrate surface. Time-resolved emission was observed close to the substrate surface only during a brief period near the positive peak of the applied RF voltage. No emission close to the substrate was observed during the negative voltage with the exception of a weak emission from N2 (C3Πu → B3Πg) just prior to the peak negative voltage. N2+, H, O, OH, and NO emissions along the discharge axis, from impurities in the He feed, or air diffusing into the He jet just downstream of the end of the tube (nozzle), were dominated by Penning ionization of N2 and dissociative excitation of water and O2 by He metastables (He*). Unlike the fully modulated electron-impact excited emission from N2 and He, emissions produced by collisions with He* were weakly modulated during the RF period and were shifted in phase with respect to the peak positive or peak negative voltage. This was attributed to vacuum ultraviolet emissions, in the radiation-trapped environment of atmospheric pressure, that produced He* outside the discharge tube even during the period when the plasma was confined inside the tube. N2 emission revealed a weak ionization wave propagating during the positive voltage period, well before the peak positive voltage. At peak positive voltage, ionization and excitation in the gap between the nozzle and the substrate maximized. The plasma positively charged the substrate, resulting in the brief N2 emission observed during the negative voltage period, as electrons drifted toward the substrate to neutralize the positive charge.
The aim of study is to research the factors affecting customers’ intention to online shopping in Vietnam emerging economy. The study integrates TAM and TPB in that it added the reliability- law factor as a formative factor. The study’s results demonstrate that reliability –law factor greatly affects to the online shoppers’ behavioral intention. The study’s results indicate that the proposed model is applicable to measure the intention for online shopping of consumers in Vietnam, and finally it is concluded in this research that extending TPB and TAM with a reliability – law factor may be useful to know online shopping behavior and the intention of Vietnam’s consumers. Some recommendations are also suggested to the relevant state offices of Vietnam and the companies doing business in online shopping sector.
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