Niemann-Pick type C (NPC) disease is a fatal inherited neurodegenerative disorder caused by loss-of-function mutations in the NPC1 or NPC2 gene. There is no effective way to treat NPC disease. In ...this study, we used adeno-associated virus (AAV) serotype 9 (AAV9) to deliver a functional NPC1 gene systemically into NPC1−/− mice at postnatal day 4. One single AAV9-NPC1 injection resulted in robust NPC1 expression in various tissues, including brain, heart, and lung. Strikingly, AAV9-mediated NPC1 delivery significantly promoted Purkinje cell survival, restored locomotor activity and coordination, and increased the lifespan of NPC1−/− mice. Our work suggests that AAV-based gene therapy is a promising means to treat NPC disease.
In the present study, 15 concrete mixes with dry density between 300 and 500 kg/m3 were tested for developing reliable mixing proportions, and establishing the significance of sustainable application ...of alkali-activated (AA) foamed concrete as a thermal insulation material in floor heating systems of buildings. Ground granulated blast-furnace slag (GGBS) was activated using the following three types of alkali activators: 10% Ca(OH)2 and 4% Mg(NO3)2, 5% Ca(OH)2 and 6.5% Na2SiO3, and 2.5% Ca(OH)2 and 6.5% Na2SiO3. The unit binder content varied in the concrete mixes corresponding to each type of activator. All mixes were produced using the pre-formed foam procedure with no aggregate or filler. The test results revealed that AA GGBS foamed concrete has considerable potential for practical applications when the unit binder content is close to 400 kg/m3, achieving the minimum quality requirements specified in the KS F 4039 as well as ensuring economic efficiency. Furthermore, the tested AA GGBS foamed concrete developed higher compressive strength than ordinary Portland cement (OPC) foamed concrete with the same dry density. In particular, a lifecycle assessment demonstrated a reduction in the environmental impact profiles of all specimens relative to typical OPC foamed concrete as follows: 99% for photochemical oxidation potential, 85–93% for global warming potential, 73–85% for abiotic depletion, and 68–85% for both acidification potential and human toxicity. Overall, the developed AA GGBS foamed concrete can be enlarged to sustainable varieties of cast-in-place structural fill and precast masonry materials.
•This study developed AA GGBS foamed concrete with density less than 500 kg/m3.•Prediction equations for the various properties of such concrete were proposed.•The economic efficiency the developed concrete was ascertained.•Beneficial environmental impacts of the concrete were assessed based on LCA.
The development, survival, and fecundity data of Conogethes punctiferalis (Guenée) (Lepidoptera: Crambidae) reared on chestnut (Castanea mollissima Blume), maize (Zea mays L.), sunflower (Helianthus ...annuus L.), hawthorn (Crataegus pinnatifida Bunge), and apple (Malus domestica Miller) were collected at 25 ± 1°C and 70 ± 5% RH. Raw data were analyzed and compared by using the age-stage, two-sex life table. The mean fecundity (F) was the highest (282.3 eggs per female) when larvae were reared on chestnut. The lowest mean fecundity (19.2 eggs per female) occurred on apple. The net reproductive rates (R0) were 134.52, 106.77, 30.29, 27.61, and 8.63 offspring on chestnut, maize, sunflower, hawthorn, and apple, respectively. The intrinsic rates of increase (r) were 0.1359, 0.1326, 0.0807, 0.0811, and 0.0448 d-1 on chestnut, maize, sunflower, hawthorn, and apple, respectively. Computer projections based on the age-stage, two-sex life table revealed the stage structure and variability of the population growth of C. punctiferalis. Our results demonstrated that although chestnut and maize were the most suitable host plants for C. punctiferalis, the moths were also able to develop and reproduce on sunflower, hawthorn, and apple.
Genetic predisposition to oxidative stress (OS) may influence the risk of Painful Diabetic Peripheral Neuropathy (PDPN). This study employed a Mendelian Randomization (MR) approach to investigate the ...causal relationship between genetic predisposition to OS and PDPN. Genetic instruments associated with OS biomarkers were selected as exposures. Summary-level data on PDPN was obtained from the largest available genome-wide association study (GWAS). MR analyses were conducted using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the MR-Egger, weighted median, and MR-PRESSO approaches. Genetic predisposition to increased glutathione S-transferase (GST) activity was associated with a reduced risk of PDPN (OR=0.66, 95%CI: 0.49-0.89, P=0.006). Higher ascorbate levels conferred a protective effect against PDPN (OR=0.83, 95%CI: 0.71-0.97, P=0.018). No significant association was observed between genetic predisposition to OS biomarkers and PDPN severity. Genetic predisposition to increased GST activity and higher ascorbate levels protect against the development of PDPN, suggesting a causal relationship.
The transfer matrix method (TMM) is an analytical method for investigating the vibrations in many structures such as beams, pipes, sheets, and shells. For long-span pipeline systems conveying fluid, ...the vibration solution method based on the TMM suffers from numerical instability when calculating in high frequency. In this paper, the hybrid energy transfer matrix method (HETMM) is built to analyze the vibration of pipeline system while avoiding the numerical instability problem. It can be directly and easily derived from the proven TMM. The calculation matrix dimension and form do not change with subunits number. The calculation program hardly varies, and the calculation time is short. So, the trial calculation can be carried out with little to no cost to determine the appropriate subunits number.
Planar branched pipes of arbitrary shapes are prevalent in pipeline systems. The HETMM for fluid-filled pipeline system with any branched pipes is proposed in this paper, too. A dominant chain of the pipeline system is selected, and the influence of branched pipes at the junction will be “absorbed” by the dominant chain. Several numerical examples are presented to illustrate the application and stability of the proposed method. Results from the present approach are validated by measured and numerical data. Finally, the first-order natural frequency of a double-branch pipeline system is optimized combining the HETMM and the complex method. Through these examples, it is shown that the HETMM is efficient, stable in high frequency and can be used to calculate and optimize branched pipes of any shape.
•The smaller and constant number of subunits and shorter period of calculation time.•Good agreement with the FEM and the ATMM.•Good agreement the experimental results.•The proposed method is efficient, stable and can be used to calculate and optimize branched pipes of any shape.
Abstract
Color coding of the graphical user interface (GUI) is effective in cognitive tasks, especially searching and identifying target stimuli from a crowded GUI. The perceived color depth on a ...flat GUI is a critical feature in mapping the stratification of information. In color science, the visual phenomena of advancing and receding colors provide the perceived depth needed for GUI design. The experiment used a series of color pairs as experimental samples to observe the phenomenon of depth perception caused by colors and obtain the judgment of the perception of color depth. This study developed a best‐fit regression model to predict the perceived color depth. The study found that the higher the lightness, the higher the chroma, and the closer the hue is to 33° (reddish color), the colors tend to be the advancing colors; the lower the lightness, the lower the chroma, and the closer the hue is to 213° (blue‐greenish color), the colors tend to be the receding colors.
When the drill and blast technique is used to excavate a roadway in underground coal mines, the relationship between the carriage and roadway space affects the automated hole positioning of a ...computer-controlled drill jumbo. This leads to low efficiency in hole positioning and high safety risks. This study analyzes the effects of deviations in carriage positioning, left-stacked stones, and inappropriate hole-position design and proposes solutions. This method builds a functional relationship between the size of the drill-bit coverage area and the hole-position parameters based on the drill-arm workspace and its projection. Based on the real-time carriage positioning results, the program checks the alignment between the hole positions and drill-bit coverage area. The crucial angle parameters were adjusted based on the extent to which the blast holes exceeded the coverage area. The analysis showed that the carriage deviation from the midline of the roadway and the height of the remaining stacked stones should not exceed 35–45 cm. Hole drilling and blasting tests demonstrate that this strategy ensures continuous high operational efficiency of the jumbo, thereby safeguarding the blasting efficiency.
Until now, there is not yet antitumor drug with dramatically improved efficacy on non-small cell lung cancer (NSCLC). Marine organisms are rich source of novel compounds with various activities. We ...isolated stellettin B (Stel B) from marine sponge Jaspis stellifera, and demonstrated that it induced G1 arrest, apoptosis and autophagy at low concentrations in human NSCLC A549 cells. G1 arrest by Stel B might be attributed to the reduction of cyclin D1 and enhancement of p27 expression. The apoptosis induction might be related to the cleavage of PARP and increase of ROS generation. Moreover, we demonstrated that Stel B induced autophagy in A549 cells by use of various assays including monodansylcadaverine (MDC) staining, transmission electron microscopy (TEM), tandem mRFP-GFP-LC3 fluorescence microscopy, and western blot detection of the autophagy markers of LC3B, p62 and Atg5. Meanwhile, Stel B inhibited the expression of PI3K-p110, and the phosphorylation of PDK1, Akt, mTOR, p70S6K as well as GSK-3β, suggesting the correlation of blocking PI3K/Akt/mTOR pathway with the above antitumor activities. Together, our findings indicate the antitumor potential of Stel B for NSCLC by targeting PI3K/Akt/mTOR pathway.
This article is concerned with the initial-value problem of a Schrödinger–Hartree equation in the presence of anisotropic partial/whole harmonic confinement. First, we get a sharp threshold for ...global existence and finite time blow-up on the ground state mass in the L2-critical case. Then, some new cross-invariant manifolds and variational problems are constructed to study blow-up versus global well-posedness criterion in the L2-critical and L2-supercritical cases. Finally, we research the mass concentration phenomenon of blow-up solutions and the dynamics of the L2-minimal blow-up solutions in the L2-critical case. The main ingredients of the proofs are the variational characterisation of the ground state, a suitably refined compactness lemma, and scaling techniques. Our conclusions extend and compensate for some previous results.
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