Ultraviolet (UV) light emission diode (LED), which is mercury free and theoretically more energy efficient, has now become an alternative to conventional UV lamps in water disinfection industry. In ...this research, the disinfection performance of a novel sequential process, UVA365nm LED followed by UVC265nm LED (UVA-UVC), was evaluated. The results revealed that the responses of different bacterial strains to UVA-UVC varied. Coupled with appropriate dosages of UVC, a 20 min UVA pre-radiation provided higher inactivations (log inactivation) of E. coli ATCC 11229, 15597 and 700891 by 1.2, 1.4 and 1.2 times, respectively than the sum of inactivations by UVA alone and UVC alone. On the contrary, the inactivation of E. coli ATCC 25922, the most UVC sensitive strain, decreased from 3 log to 1.8 log after UVA pre-radiation. A 30 min UVA pre-radiation did not affect the photo repair capacity of the four strains (n = 23, p > 0.1), but their dark repair ability was significantly inhibited (n = 14, p < 0.05). Mechanism study was conducted for two representative strains, E. coli ATCC 15597 and 25922 to understand the observed effect. The hypothesis that UVA pre-radiation promoted the yield of reactive oxygen species (ROS) was rejected. ELISA results indicated that 18% more cyclobutane pyrimidine dimers (CPD) were formed in E. coli ATCC 15597 with UVA pre-radiation (n = 3, p < 0.01), however, the CPD levels of E. coli ATCC 25922 was the same with or without UVA pre-radiation (n = 3, p > 0.01). Considering the results of both dark repair and CPD formation, it was concluded that the increased UV sensitivity of E. coli 15597 was originated from the increased CPD. For E. coli ATCC 25922, the enhanced UV resistance was attributed to the strain's adoption of a survival strategy, translesion DNA synthesis (TLS), when triggered by UVA pre-radiation. The study on UmuD protein, which is a key protein during TLS, confirmed this hypothesis.
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•Disinfection performance of a novel sequential UVA-UVC LED process was evaluated.•Coupled with UVC, a UVA pre-radiation provided higher inactivations for bacteria.•E. coli ATCC 25922 removal decreased 1.2 log after UVA pre-radiation.•Other E. coli strains removal increased by ∼1.3 log than the sum of UVA and UVC.•Sequential UVA-UVC also inhibited the dark repair of the four E. coli strains.
Intracellular concentrations of drugs and metabolites are often important determinants of efficacy, toxicity, and drug interactions. Hepatic drug distribution can be affected by many factors, ...including physicochemical properties, uptake/efflux transporters, protein binding, organelle sequestration, and metabolism. This white paper highlights determinants of hepatocyte drug/metabolite concentrations and provides an update on model systems, methods, and modeling/simulation approaches used to quantitatively assess hepatocellular concentrations of molecules. The critical scientific gaps and future research directions in this field are discussed.
Clinical Pharmacology & Therapeutics (2013); 94 1, 126–141. doi:10.1038/clpt.2013.78
CC chemokine receptor 2 (CCR2) plays important roles in extravasation and transmigration of monocytes under inflammatory conditions. CCR2 and its ligands have been extensively studied in a range of ...inflammatory diseases in the central nervous system (CNS), including multiple sclerosis, Alzheimer's disease and ischemic stroke. This brief review summarizes our current understanding of the physiologic and pathologic roles of CCR2, focusing on its involvement in CNS inflammatory diseases. There appears to be a rationale for exploring therapies involving CCR2 inhibition in multiple sclerosis and ischemic stroke, but there is also evidence for immunomodulatory and protective effects of CCR2 activity during CNS inflammation. The critical balance between protective and detrimental roles of CCR2-dependent recruitment of leukocytes must therefore be carefully examined to guide safe and effective development of any therapies involving CCR2 modulation.
Research the current situation of Vietnam's environment. Researching the real situation of the law on environmental protection: the achievements of the law on environmental protection; Current issues ...raised in the regulation of environmental protection legislation. Proposing and proposing major solutions to perfect the environmental protection legislation in the coming time: perfecting the environmental protection legislation; complete the national standards and technical regulations on environment; complete the regulations on environmental impact assessment; complete the regulations on waste management, especially those in urban and industrial areas; complete the regulations on environmental protection of soil, water and air; issue documents specifying the process of publication and democratization of environmental protection activities.
A plasma density model of the inner magnetosphere is important for a variety of applications including the study of wave‐particle interactions, and wave excitation and propagation. Previous empirical ...models have been developed under many limiting assumptions and do not resolve short‐term variations, which are especially important during storms. We present a three‐dimensional dynamic electron density (DEN3D) model developed using a feedforward neural network with electron densities obtained from four satellite missions. The DEN3D model takes spacecraft location and time series of solar and geomagnetic indices (F10.7, SYM‐H, and AL) as inputs. It can reproduce the observed density with a correlation coefficient of 0.95 and predict test data set with error less than a factor of 2. Its predictive ability on out‐of‐sample data is tested on field‐aligned density profiles from the IMAGE satellite. DEN3D's predictive ability provides unprecedented opportunities to gain insight into the 3‐D behavior of the inner magnetospheric plasma density at any time and location. As an example, we apply DEN3D to a storm that occurred on 1 June 2013. It successfully reproduces various well‐known dynamic features in three dimensions, such as plasmaspheric erosion and recovery, as well as plume formation. Storm time long‐term density variations are consistent with expectations; short‐term variations appear to be modulated by substorm activity or enhanced convection, an effect that requires further study together with multispacecraft in situ or imaging measurements. Investigating plasmaspheric refilling with the model, we find that it is not monotonic in time and is more complex than expected from previous studies, deserving further attention.
Key Points
A neural‐network‐based 3‐D dynamic electron density model is developed in the inner magnetosphere
The DEN3D model successfully reproduced the quiet time structure, plasmaspheric erosion, and refilling and plume formation
Long‐term density variations are consistent with expectations, while short‐term variations are modulated by substorm activity or enhanced convection
This white paper provides a critical analysis of methods for estimating transporter kinetics and recommendations on proper parameter calculation in various experimental systems. Rational ...interpretation of transporter‐knockout animal findings and application of static and dynamic physiologically based modeling approaches for prediction of human transporter‐mediated pharmacokinetics and drug–drug interactions (DDIs) are presented. The objective is to provide appropriate guidance for the use of in vitro, in vivo, and modeling tools in translational transporter science.
Clinical Pharmacology & Therapeutics (2013); 94 1, 64–79. doi:10.1038/clpt.2013.45
Abstract Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. They are highly expressed in the striatum, where medium spiny neurons ...(MSNs) are a major population. Given that the properties of ASICs in MSNs are unknown, in this study, we characterized ASICs in MSNs of the mouse striatum. A rapid drop in extracellular pH induced transient inward currents in all MSNs. The pH value for half-maximal activation was 6.25, close to that obtained in homomeric ASIC1a channels. Based on psalmotoxin 1 and zinc sensitivity, ASIC1a (70.5% of neurons) and heteromeric ASIC1a-2 channels (29.5% of neurons) appeared responsible for the acid-induced currents in MSNs. ASIC currents were diminished in MSNs from ASIC1, but not ASIC2, null mice. Furthermore, a drop in pH induced calcium influx by activating homomeric ASIC1a channels. Activation of ASICs increased the membrane excitability of MSNs and lowering extracellular Ca2+ potentiated ASIC currents. Our data suggest that the homomeric ASIC1a channel represents a majority of the ASIC isoform in MSNs. The potential function of ASICs in the striatum requires further investigation.
We report an event study of STEVE on 17 July 2018, with focus on the optical spectra and emission altitudes of STEVE. We find that the STEVE comprises two traces, one at a higher elevation angle and ...the other at a lower elevation angle. The two traces merge into one when viewed near the zenith. Spectrograph measurements show that both STEVE traces are characterized by enhancements over broadband wavelengths, that is, an airglow continuum, but they differ in their red‐line (630 nm) component: The higher‐elevation STEVE contains substantial red‐line enhancement over background, while the lower‐elevation STEVE does not. Based upon triangulation analyses using multiple optical instruments, we evaluate that the two STEVE traces are likely emitted from distinctly different altitudes: The higher‐elevation STEVE comes from ~250‐km altitude, while the lower‐elevation one is from ≤150‐km altitude. Our results impose implications and constraints on the possible underlying mechanisms of STEVE.
Plain Language Summary
The recently discovered STEVE nightglow is active at times of auroral activity but does not seem to be an aurora. It is located at lower latitudes than the usual aurora, and as photographed on the citizen science cameras which played a large role in drawing attention to it, it has a different color. In this study, using a combination of scientific optical instruments, especially the spectrograph recently deployed at Lucky Lake, Canada, by the University of Calgary, we investigate the optical spectral properties of STEVE and their emission altitudes. Two major spectral (color) components of STEVE are identified. One is characterized by a broadband enhancement over the entire visible wavelength range, contributing to the apparently “whitish” color of the STEVE, and the other is contributed by oxygen airglow concentrated at 630 nm, adding a “reddish” tint to the STEVE. In the event occurring on 17 July 2018, the STEVE is found to comprise two emission structures originating from different altitudes, one at ~250 km and the other at ≤150‐km altitude. Both STEVE structures contain the white component but only the higher‐altitude one shows a substantial red component. That red color is the same red as seen in auroras that come from high altitudes in the atmosphere, while the mechanism of the white component remains to be explored.
Key Points
The STEVE comprises two traces, one at higher elevation and the other at lower elevation angle, due to their difference in emission height
Both STEVE traces contain airglow continuum enhancement, but only the higher‐elevation STEVE contains substantial red‐line intensification
We evaluate that the higher-elevation STEVE centers at ~250‐km height, while the lower-elevation STEVE centers at ≤150‐km altitude
An analytical expression for arbitrary moments of the cosh-Gaussian–Shell beam in turbulent atmosphere is derived. As a special case, kurtosis parameters of collimated and focused cosh-Gaussian beam ...with and without turbulent atmosphere are studied in detail. It can be seen from the study that the kurtosis parameters of Gaussian beam do not remain constant in turbulent atmosphere. Similar to the kurtosis parameters of a cosh-Gaussian beam at source plane, the kurtosis parameters at focal plane without turbulent atmosphere are independent of the propagation distance and vary with the parameters of the beam. But the variation of the kurtosis parameters at focal plane is different from that at source plane. However, the kurtosis parameters of collimated and focused cosh-Gaussian beam both vary with the propagation distance and gradually converge to 3 along the
z
-axis in turbulent atmosphere. Compared with a collimated beam, the kurtosis parameters of a focused beam converge more quickly.
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