A large number of statistics indicate that water inrush has a direct relationship with geological structures such as fault and karst collapse columns. Understanding the mechanism of water inrushes ...controlled by geologic structures is of vital importance for adopting effective measures to prevent their occurrence. The work begins with formulization of a damage-based hydromechanical model based on elastic damage theory. Next, the model is numerically implemented with finite element method by employing a finite element package called COMSOL Multiphysics, and is also validated against some existing experimental observations. Finally, the model is used to simulate the mining-induced groundwater inrushes when the effect of faults and karst collapse columns is considered in the numerical simulation, and some suggestive conclusions for preventing water inrushes and optimizing underground mining operations are drawn.
Extensive insecticide use has led to the resistance of mosquitoes to these insecticides, posing a major barrier to mosquito control. Previous Solexa high-throughput sequencing of Culex pipiens ...pallens in the laboratory has revealed that the abundance of a novel microRNA (miRNA), miR-13664, was higher in a deltamethrin-sensitive (DS) strain than a deltamethrin-resistant (DR) strain. Real-time quantitative PCR revealed that the miR-13664 transcript level was lower in the DR strain than in the DS strain. MiR-13664 oversupply in the DR strain increased the susceptibility of these mosquitoes to deltamethrin, whereas inhibition of miR-13664 made the DS strain more resistant to deltamethrin. Results of bioinformatic analysis, quantitative reverse-transcriptase polymerase chain reaction, luciferase assay and miR mimic/inhibitor microinjection revealed CpCYP314A1 to be a target of miR-13664. In addition, downregulation of CpCYP314A1 expression in the DR strain reduced the resistance of mosquitoes to deltamethrin. Taken together, our results indicate that miR-13664 could regulate deltamethrin resistance by interacting with CpCYP314A1, providing new insights into mosquito resistance mechanisms.
This paper is concerned with competitive Lotka–Volterra model in random environments. It uses regime-switching diffusion to model the dynamic of population sizes of
n different species in a ecosystem ...subject to the random changes of the external environment. We show that the positive solution of the associated stochastic differential equation does not explode in finite time with probability 1. Moreover, we demonstrate that the solution is stochastically bounded, continuous, and has finite moments. Furthermore, we obtain certain asymptotic results regarding large time behavior and present some numerical experimental results.
The dynamic disturbance, which is termed as the time-dependent loading such as explosion, vibration, stress impact from neighboring rockbursts, earthquakes, may trigger the rockbursts around the ...underground opening at depth. A numerical model capable of studying the dynamic failure process of rock under coupled static geo-stress and dynamic disturbance is proposed, and it is implemented into the Rock Failure Process Analysis (RFPA), a general finite element package to analyze the damage and failure process of engineering materials such as rock and concrete. Based on the consideration of the static geo-stress, the RFPA-Dynamics is used to simulate the rockburst that is deemed to be triggered by dynamic disturbance around the deep underground opening. The effect of lateral pressure coefficient and dynamic disturbance waveform on the development of failure zone around the underground opening is numerically simulated. The numerical results indicate that the dynamic disturbance is one of the most important mechanisms that trigger the rockbursts around underground opening. Therefore, it is of theoretical and practical significance to investigate the effect of dynamic disturbance on the rockbursts of underground opening, especially for the underground excavation at depth where the surrounding rockmass is highly stressed. The numerical results also reveal that the contribution of the dynamic disturbances is closely pertinent to both the static geo-stress condition and the waveforms of the dynamic disturbance. In general, dynamic disturbance brings about the greater influences on the stability of underground opening with its increasing magnitude and prolonged duration. However, with regard to the specific static geo-stress condition and characteristics of dynamic disturbance, the contribution of dynamic disturbance to trigger the rockbursts must be examined based on numerical analysis according to the specific geo-stress conditions and characteristics of the dynamic disturbance.
Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques ...consisting of amyloid-beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aβ-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy.
Increasing evidence has shown the aberrant expression of inflammasome-related proteins in Alzheimer's disease (AD) brain; these proteins, including NLRP1 inflammasome, are implicated in the execution ...of inflammatory response and pyroptotic death. Although current data are associated NLRP1 genetic variants with AD, the involvement of NLRP1 inflammasome in AD pathogenesis is still unknown. Using APPswe/PS1dE9 transgenic mice, we found that cerebral NLRP1 levels were upregulated. Our in vitro studies further showed that increased NLRP1-mediated caspase-1-dependent 'pyroptosis' in cultured cortical neurons in response to amyloid-β. Moreover, we employed direct in vivo infusion of non-viral small-interfering RNA to knockdown NLRP1 or caspase-1 in APPswe/PS1dE9 brain, and discovered that these NLRP1 or caspase-1 deficiency mice resulted in significantly reduced neuronal pyroptosis and reversed cognitive impairments. Taken together, our findings indicate an important role for NLRP1/caspase-1 signaling in AD progression, and point to the modulation of NLRP1 inflammasome as a promising strategy for AD therapy.
Lower midlife physical activity is associated with higher risk of neurodegenerative disease in late life. However, it remains unknown whether physical exercise and fitness are associated with brain ...structural integrity during midlife. The purpose of this study was to compare brain structures between middle-aged aerobically trained adults (MA), middle-aged sedentary (MS), and young sedentary (YS) adults. Thirty MA (54±4 years), 30 MS (54±4 years), and 30 YS (32±6 years) participants (50% women) underwent measurements of brain volume, cortical thickness, and white matter (WM) fiber integrity using MRI. MA participants had aerobic training for 24.8±9.6 years and the highest cardiorespiratory fitness level (i.e., peak oxygen uptake: VO2peak) among all groups. Global WM integrity, as assessed with fractional anisotropy (FA) from diffusion tensor imaging, was lower in the MS compared with the YS group. However, global FA in the MA group was significantly higher than that in the MS group (P<0.05) and at a similar level to the YS group. Furthermore, tract-based spatial statistical analysis demonstrated that FA in the anterior, superior, and limbic WM tracts (e.g., the genu of the corpus callosum, superior longitudinal fasciculus, uncinate fasciculus) was higher in the MA compared with MS groups, and positively associated with VO2peak, independently from age and sex. From cortical thickness analysis, MS and MA participants showed thinner prefrontal and parieto-temporal areas than the YS group. On the other hand, the MA group exhibited thicker precentral, postcentral, pericalcarine, and lateral occipital cortices than the MS and YS groups. But, the insula and right superior frontal gyrus showed thinner cortical thickness in the MA compared with the MS groups. Collectively, these findings suggest that midlife aerobic exercise is associated with higher WM integrity and greater primary motor and somatosensory cortical thickness.
Photodynamic
therapy
(PDT) is an
emerging treatment modality that employs the photochemical interaction of three components: light,
photosensitizer, and oxygen. Tremendous progress has been made in ...the last 2 decades in
new technical development of all components as well as understanding of the biophysical
mechanism of PDT.
The authors will review the current state of art in PDT research, with an emphasis
in PDT physics.
They foresee a merge of current separate areas of research in light production and
delivery,
PDT
dosimetry,
multimodality imaging, new photosensitizer development, and PDT biology into
interdisciplinary combination of two to three areas. Ultimately, they strongly believe
that all these categories of research will be linked to develop an integrated model for
real-time dosimetry and treatment planning based on biological response.