Search

Vincristine-induced peripheral neuropathy is a common side effect of vincristine treatment, which is accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced pain are not well understood. We have established an animal model to investigate pathophysiological mechanisms of vincristine-induced pain. Our previous studies have shown that the tetrodotoxin-sensitive voltage-gated sodium channel Nav1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes to the maintenance of vincristine-induced allodynia. In this study, we investigated the effects of vincristine administration on excitability in small-diameter DRG neurons and whether the tetrodotoxin-resistant (TTX-R) Nav1.8 channels contribute to mechanical allodynia. Current-clamp recordings demonstrated that small DRG neurons become hyper-excitable following vincristine treatment, with both reduced current threshold and increased firing frequency. Using voltage-clamp recordings in small DRG neurons, we now show an increase in TTX-R current density and a −7.3 mV hyperpolarizing shift in the half-maximal potential (V1/2) of activation of Nav1.8 channels in vincristine-treated animals, which likely contributes to the hyperexcitability that we observed in these neurons. Notably, vincristine treatment did not enhance excitability of small DRG neurons from Nav1.8 knockout mice, and the development of mechanical allodynia was delayed but not abrogated in these mice. Together, our data suggest that sodium channel Nav1.8 in small DRG neurons contributes to the development of vincristine-induced mechanical allodynia. [ABSTRACT FROM AUTHOR]

This paper describes a study on speaker recognition using the ECAPA-TDNN architecture, which stands for Extended Context-Aware Parallel Aggregations Time-Delay Neural Network. It utilizes X-vectors, a method for extracting speaker features by converting speech into fixed-length vectors, and introduces a squeeze-and-excitation block to model dependencies between channels. In order to better explore temporal relationships in the context of speaker recognition and improve the algorithm's generalization performance in complex acoustic scenarios, this study adds input gates and forget gates to the ECAPA-TDNN architecture, combining them with CIFG (Convolutional LSTM with Input and Forget Gates) modules. These are embedded into a residual structure of multi-layer aggregated features. A sub-center Arcface, an improved loss function based on Arcface, is used for selecting sub-centers for subclass discrimination, retaining advantageous sub-centers to enhance intra-class compactness and strengthen the robustness of the network. Experimental results demonstrate that the improved ECAPA-TDNN-CIFG in this study outperforms the baseline model, yielding more accurate and efficient recognition results. [ABSTRACT FROM AUTHOR]

Proton exchange membrane fuel cells (PEMFCs) and alkaline membrane fuel cells (AEMFCs) have received great attention as energy devices of the next generation. Accelerating oxygen reduction reaction (ORR) kinetics is the key to improve PEMFC and AEMFC performance. Platinum‐based catalysts are the most widely used catalysts for the ORR, but their high price and low abundance limit the commercialization of fuel cells. Non‐noble metal‐nitrogen‐carbon (M−N−C) is considered to be the most likely material class to replace Pt‐based catalysts, among which Fe−N−C and Co−N−C have been widely studied due to their excellent intrinsic ORR performance and have made great progress in the past decades. With the improvement of synthesis technology and a deeper understanding of the ORR mechanism, some reported Fe−N−C and Co−N−C catalysts have shown excellent ORR activity close to that of commercial Pt/C catalysts. Inspired by the progress, regulation strategies for Fe−N−C and Co−N−C catalysts are summarized in this Review from 5 perspectives: (1) coordinated atoms, (2) environmental heteroatoms and defects, (3) dual‐metal active sites, (4) metal‐based particle promoters, and (5) curved carbon layers. We also make suggestions on some challenges facing Fe−N−C and Co−N−C research. [ABSTRACT FROM AUTHOR]

The single‐atom Fe−N−C is a prominent material with exceptional reactivity in areas of sustainable energy and catalysis research. It is challenging to obtain the dense Fe‐N4 site without the Fe nanoparticles (NPs) sintering during the Fe−N−C synthesis via high‐temperature pyrolysis. Thus, a novel approach is devised for the Fe−N−C synthesis at low temperatures. Taking FeCl2 as Fe source, a hydrogen environment can facilitate oxygen removal and dichlorination processes in the synthesis, efficiently favouring Fe‐N4 site formation without Fe NPs clustering at as low as 360 °C. We shed light on the reaction mechanism about hydrogen promoting Fe‐N4 formation in the synthesis. By adjusting the temperature and duration, the Fe‐N4 structural evolution and site density can be precisely tuned to directly influence the catalytic behaviour of the Fe−N−C material. The FeNC‐H2‐360 catalyst demonstrates a remarkable Fe dispersion (8.3 wt %) and superior acid ORR activity with a half‐wave potential of 0.85 V and a peak power density of 1.21 W cm−2 in fuel cell. This method also generally facilitates the synthesis of various high‐performance M−N−C materials (M=Fe, Co, Mn, Ni, Zn, Ru) with elevated single‐atom loadings. [ABSTRACT FROM AUTHOR]

The single‐atom Fe−N−C is a prominent material with exceptional reactivity in areas of sustainable energy and catalysis research. It is challenging to obtain the dense Fe‐N4 site without the Fe nanoparticles (NPs) sintering during the Fe−N−C synthesis via high‐temperature pyrolysis. Thus, a novel approach is devised for the Fe−N−C synthesis at low temperatures. Taking FeCl2 as Fe source, a hydrogen environment can facilitate oxygen removal and dichlorination processes in the synthesis, efficiently favouring Fe‐N4 site formation without Fe NPs clustering at as low as 360 °C. We shed light on the reaction mechanism about hydrogen promoting Fe‐N4 formation in the synthesis. By adjusting the temperature and duration, the Fe‐N4 structural evolution and site density can be precisely tuned to directly influence the catalytic behaviour of the Fe−N−C material. The FeNC‐H2‐360 catalyst demonstrates a remarkable Fe dispersion (8.3 wt %) and superior acid ORR activity with a half‐wave potential of 0.85 V and a peak power density of 1.21 W cm−2 in fuel cell. This method also generally facilitates the synthesis of various high‐performance M−N−C materials (M=Fe, Co, Mn, Ni, Zn, Ru) with elevated single‐atom loadings. [ABSTRACT FROM AUTHOR]

Iron‐nitrogen‐carbon (Fe‐N‐C) catalysts for the oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs) have seriously been hindered by their poor ORR performance of Fe‐N‐C due to the low active site density (SD) and site utilization. Herein, we reported a melamine‐assisted vapor deposition approach to overcome these hindrances. The melamine not only compensates for the loss of nitrogen caused by high‐temperature pyrolysis but also effectively etches the carbon substrate, increasing the external surface area and mesoporous porosity of the carbon substrate. These can provide more useful area for subsequent vapor deposition on active sites. The prepared 0.20Mela‐FeNC catalyst shows a fourfold higher SD value and site utilization than the FeNC without the treatment of melamine. As a result, 0.20Mela‐FeNC catalyst exhibits a high ORR activity with a half‐wave potential (E1/2) of 0.861 V and 12‐fold higher ORR mass activity than the FeNC in acidic media. As the cathode in a H2‐O2 PEMFCs, 0.20Mela‐FeNC catalyst demonstrates a high peak power density of 1.30 W cm−2, outstripping most of the reported Fe‐N‐C catalysts. The developed melamine‐assisted vapor deposition approach for boosting the SD and utilization of Fe‐N‐C catalysts offers a new insight into high‐performance ORR electrocatalysts. [ABSTRACT FROM AUTHOR]

Soft rock has the properties of low strength, poor integrity, and difficulty in core extraction. In order to study the deformation and failure of soft rock, this study used fine river sand as aggregate, cement and gypsum as bonding materials, and borax as a retarder to produce cylindrical rock-like samples (RLS) with a sand cement ratio of 1:1. Uniaxial compression tests were conducted on RLS under DIT (different immersion times) (0, 4, 8, 12, 24, and 48 h) in the laboratory. The mechanical and energy properties of RLS under water-stress coupling were analyzed. The results showed that the longer the IT of the RLS, the higher their water content (WC). As the moisture time increases, the uniaxial compressive strength, elastic modulus (EM), and softening coefficient (SC) of the sample gradually decrease, while the rate of change of EM is the opposite. The fitted sample SC exhibits a good logarithmic function relationship with WC. During the loading process of the sample, more than 60% of the U (total energy absorbed) during the loading process of the sample is accumulated in the form of Ue (releasable elastic energy), while less than 40% of U is dissipated by the newly formed micro cracks during the compaction, sliding, and yield stages of the internal pores and cracks of the sample. The U before the peak and the Ue of the RLS decrease exponentially with the moisture content; the relationship curves of Ue/U (released elastic energy ratio) and Ud/U (dissipated energy ratio) of RLS during uniaxial compression with the σ1/σmax (axial stress ratio) can be divided into three stages of change, namely the stage of primary fissure compaction and closure (σ1/σmax < 0.25), continuously absorbing energy stage (0.25 < σ1/σmax < 0.8), and energy dissipation stage (σ1/σmax > 0.8); the D (damage variable) was defined by the ratio of Ud (dissipated energy) to the Udmax (maximum dissipated energy) at failure time of RLS, the fitting of the relationship between the damage variable and axial strain conforms to the logistic equation. [ABSTRACT FROM AUTHOR]

Background and Aims: Voltage‐gated sodium channel Nav1.7, encoded by the SCN9A gene, has been linked to diverse painful peripheral neuropathies, represented by the inherited erythromelalgia (EM) and paroxysmal extreme pain disorder (PEPD). The aim of this study was to determine the genetic etiology of patients experiencing neuropathic pain, and shed light on the underlying pathogenesis. Methods: We enrolled eight patients presenting with early‐onset painful peripheral neuropathies, consisting of six cases exhibiting EM/EM‐like disorders and two cases clinically diagnosed with PEPD. We conducted a gene‐panel sequencing targeting 18 genes associated with hereditary sensory and/or autonomic neuropathy. We introduced novel SCN9A mutation (F1624S) into a GFP‐2A‐Nav1.7rNS plasmid, and the constructs were then transiently transfected into HEK293 cells. We characterized both wild‐type and F1624S Nav1.7 channels using an automated high‐throughput patch‐clamp system. Results: From two patients displaying EM‐like/EM phenotypes, we identified two SCN9A mutations, I136V and P1308L. Among two patients diagnosed with PEPD, we found two additional mutations in SCN9A, F1624S (novel) and A1632E. Patch‐clamp analysis of Nav1.7‐F1624S revealed depolarizing shifts in both steady‐state fast inactivation (17.4 mV, p <.001) and slow inactivation (5.5 mV, p <.001), but no effect on channel activation was observed. Interpretation: Clinical features observed in our patients broaden the phenotypic spectrum of SCN9A‐related pain disorders, and the electrophysiological analysis enriches the understanding of genotype–phenotype association caused by Nav1.7 gain‐of‐function mutations. [ABSTRACT FROM AUTHOR]

Naja atra bite is one of the most common severe snakebites in emergency departments. Unfortunately, the pathophysiological changes caused by Naja atra bite are unclear due to the lack of good animal models. In this study, an animal model of Naja atra bite in Guangxi Bama miniature pigs was established by intramuscular injection at 2 mg/kg of Naja atra venom, and serum metabolites were systematically analyzed using untargeted metabolomic and targeted metabolomic approaches. Untargeted metabolomic analysis revealed that 5045 chromatographic peaks were obtained in ESI+ and 3871 chromatographic peaks were obtained in ESI-. Screening in ESI+ modes and ESI- modes identified 22 and 36 differential metabolites compared to controls. The presence of 8 core metabolites of glutamine, arginine, proline, leucine, phenylalanine, inosine, thymidine and hippuric acid in the process of Naja atra bite was verified by targeted metabolomics significant difference (P<0.05). At the same time, during the verification process of the serum clinical samples with Naja atra bite, we found that the contents of three metabolites of proline, phenylalanine and inosine in the serum of the patients were significantly different from those of the normal human serum (P<0.05). By conducting functional analysis of core and metabolic pathway analysis, we revealed a potential correlation between changes in key metabolites after the Naja atra bite and the resulting pathophysiological alterations, and our research aims to establish a theoretical foundation for the prompt diagnosis and treatment of Naja atra bite. Author summary: Naja atra bite is one of the most serious tropical and subtropical diseases, and the pathophysiological mechanism of injury caused by Naja atra bite is still not clear, meanwhile, large animal models of Naja atra bite are rarely reported. In this study, a Naja atra bite Bama miniature pig model was constructed and evaluated. In addition, 22 and 36 metabolites were found to be significantly altered in ESI+ and ESI- mode by untargeted metabolomics assay, respectively. More interestingly, 8 of them co-occurred in both ESI+ and ESI- modes. We quantified these 8 metabolites absolutely by targeted metabolomics and validated them in the serum of Naja atra bite patients, which showed the same trend as the untargeted metabolomics results. We also compared the differences in the levels of these 8 metabolites in the serum of the Naja atra bite patient group and the normal human group, we found decreased expression of inosine, proline and phenylalanine. Based on this, we compared the blood metabolic profiles with those of Bungarus multicinctus and Trimeresurus stejnegeri, and finally we confirmed that inosine, proline and phenylalanine are likely to be the key metabolites in Naja atra bite. [ABSTRACT FROM AUTHOR]

To achieve the Fe−N−C materials with both high activity and durability in proton exchange membrane fuel cells, the attack of free radicals on Fe−N4 sites must be overcome. Herein, we report a strategy to effectively eliminate radicals at the source to mitigate the degradation by anchoring CeO2 nanoparticles as radicals scavengers adjacent (Scaad‐CeO2) to the Fe−N4 sites. Radicals such as ⋅OH and HO2⋅ that form at Fe−N4 sites can be instantaneously eliminated by adjacent CeO2, which shortens the survival time of radicals and the regional space of their damage. As a result, the CeO2 scavengers in Fe−NC/Scaad‐CeO2 achieved ∼80 % elimination of the radicals generated at the Fe−N4 sites. A fuel cell prepared with the Fe−NC/Scaad‐CeO2 showed a smaller peak power density decay after 30,000 cycles determined with US DOE PGM‐relevant AST, increasing the decay of Fe−NCPhen from 69 % to 28 % decay. [ABSTRACT FROM AUTHOR]

To achieve the Fe−N−C materials with both high activity and durability in proton exchange membrane fuel cells, the attack of free radicals on Fe−N4 sites must be overcome. Herein, we report a strategy to effectively eliminate radicals at the source to mitigate the degradation by anchoring CeO2 nanoparticles as radicals scavengers adjacent (Scaad‐CeO2) to the Fe−N4 sites. Radicals such as ⋅OH and HO2⋅ that form at Fe−N4 sites can be instantaneously eliminated by adjacent CeO2, which shortens the survival time of radicals and the regional space of their damage. As a result, the CeO2 scavengers in Fe−NC/Scaad‐CeO2 achieved ~80 % elimination of the radicals generated at the Fe−N4 sites. A fuel cell prepared with the Fe−NC/Scaad‐CeO2 showed a smaller peak power density decay after 30,000 cycles determined with US DOE PGM‐relevant AST, increasing the decay of Fe−NCPhen from 69 % to 28 % decay. [ABSTRACT FROM AUTHOR]

This paper aims to study the law of pressure behavior and the characteristics of mutual influence in the process of steeply inclined coal seam mining. Based on the geological and engineering conditions of the B8 coal seam in Nanshan coal mine, this paper explores the law of mine pressure behavior in the process of steeply inclined coal seam mining by means of theoretical analysis and FLAC3D numerical simulation. Based on this, this paper also examines the influence of the interaction range between coal seams, the reasonable setting size of the section coal pillar, and the mining distance of the working face on the return air roadway. The results suggest as follows: (1) With an increase in the coal seam dip angle, the difference in the abutment pressure plastic zone between upper and lower coal pillars increases, and when mining in steeply inclined coal seams, the stress concentration in the lower and upper part of the working face deviates to the roof and floor respectively, which is obviously different from that of gently inclined coal seams. (2) The vertical stress above the section coal pillar changes in three stages with an increase in the width of the coal pillar, and the width of the coal pillar in the second stage can be taken as the reasonable size of the width of the coal pillar. The numerical simulation results are consistent with the theoretical calculation results, which indicate the high reliability of this method in determining the reasonable coal pillar size. (3) With an increase in the mining distance in steeply inclined coal seams, the maximum pressure around the working face and above the return air roadway has gone through three stages. When the distance between the working face and the adjacent return air roadway is close, the pressure above the return air roadway increases sharply, and disturbance is stronger. [ABSTRACT FROM AUTHOR]

Voltage-gated sodium (NaV) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived NaV channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at NaV channels, and that co-expression of TMEM233 modulates the gating properties of NaV1.7. These findings identify TMEM233 as a previously unknown NaV1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons. Voltage-gated sodium channels function as multiprotein signaling complexes. Here, authors show that the dispanin TMEM233 is essential for activity of stinging nettle toxins and that co-expression of TMEM233 modulates the gating properties of NaV1.7. [ABSTRACT FROM AUTHOR]

This paper aims to complement current knowledge about performance of deep foundations in residual soils by presenting the results of a new experimental field-testing program on steel driven piles (with hollow circular and square cross sections) subjected to cyclic lateral loading at controlled displacement amplitudes. The results show that the maximum mobilized lateral load (at the maximum applied displacement) decreases with the number of cycles to reach a constant final value maintained up to 100 cycles. The amount of load degradation is dependent on the displacement amplitude of the cyclic loading. It is also observed that the ultimate lateral load pile capacity is unaffected (if not slightly enhanced) by the application of cyclic loading. Combined 3-D finite element and pile test analysis revealed that the progressive degradation of maximum mobilized cyclic loading can be related to the progressive plastic displacement accumulation and not only to cement bonding degradation of the residual soil. [ABSTRACT FROM AUTHOR]

Water disaster is one of the major disasters threatening the safety production of coal mine, which is rank only second to gas disaster. And Meisbluke Coal Mine is seriously affected by water disasters. In order to find out the scope and location of water-bearing areas in Meisbluke Coal Mine. The comprehensive geophysical exploration method combining transient electromagnetic method (TEM) and high-density resistivity method (HDRM) is used to carry out this research. Firstly, the measuring area is determined and the relevant measuring points are arranged, and 73 TEM survey lines and 10 HDRM survey lines were arranged according to the requirements. Then, the principle, data processing method and main parameters of TEM and HDRM are introduced. The TEM detection results show that the thickness of Quaternary inferred by TEM is consistent with the geological conditions revealed by boreholes, and the thickness is about 50–80 m. And the water enrichment of the bedrock is obviously recharged by the Quaternary aquifer. Besides, the water-enriched areas in each elevation are marked and the water inrush runoff channel is deduced based on the 3D scenario inverted by TEM. And the detection results of the water-bearing areas by the two methods are in good agreement with each other, which can confirm and complement each other, and the interpretation of the data is scientific and reasonable with high reliability. Besides, the detection depth of HDRM is larger than that of TEM. [ABSTRACT FROM AUTHOR]

In order to improve the efficiency of gas extraction in coal mines, a data-driven fine-management and control method for gas extraction is proposed. Firstly, the accurate prediction of coal seam thickness and gas content was used to evaluate the gas reserves. Based on the time relationship between mining activities and gas extraction, the calculation model of borehole distance in different extraction units is established, and the differential borehole design is realized. Then, a drilling video-surveillance system and drilling trajectory measurement device are used to control the drilling process and the construction effect. Finally, the model of extraction data-correction and the identification of failed boreholes is established, then the failed boreholes are repaired. The technology method provided in the paper has realized the fine control of gas-extraction borehole design, construction, measurement, and repair, and formed a more scientific gas-extraction borehole control technology system, which provides new thought for efficient gas extraction. [ABSTRACT FROM AUTHOR]

In this work, the role of chitosan (CS) in improving the properties of bioactive glass (BG) paste for wound healing was studied. Based on in vitro evaluation, it was found that the addition of CS neutralizes the pH value from 11.0 to 7.5, which did not lead to decreasing the bioactivity of BG paste in vitro. The rheological properties showed that the composite paste had higher bio-adhesion and better affinity with the skin surface than either CS or the BG paste. The antibacterial property evaluation showed that the composite paste had stronger antibacterial activity than either CS or BG paste and promoted the proliferation of HUVECs (human umbilical vein endothelial cells) and HaCat (human immortalized keratinocyte cells). Comparatively, the effect of promoting the proliferation of HUVECs is more significant than that of HaCat. The burn-wound model of rat was developed for evaluating in vivo activity, and the addition of CS effectively promoted wound healing without obvious inflammation according to the IL-1β and IL-6 staining. This novel paste is expected to provide a promising alternative for wound healing. [ABSTRACT FROM AUTHOR]

The change of coal temperature has been confirmed by many tests during gas adsorption and desorption in coal, but the thermal-dynamic process and its influence factors for gas adsorption and desorption have not been quantitatively studied. In this study, gas adsorption and desorption tests on different coal samples were performed to investigate the effects of various factors (particle size, gas pressure and metamorphic degrees) on the temperature variation law of coal during adsorption and desorption process. In the initial stage of gas adsorption process, the coal temperature will increase sharply to an extremely low value, then slowly decrease to the previous ambient temperature. The temperature change value is positively correlated to the gas pressure and negatively correlated with particle size. The metamorphic degree has a certain influence on the temperature variation of coal during gas adsorption process. But the temperature change mainly depends on gas adsorption capacity. To some extent, the gas adsorption and desorption process can be regarded as reversible. The temperature variation with time in the gas desorption process of coal samples under different conditions is analyzed quantitatively, and its fitting parameters are analyzed. The relation between the maximum temperature change value and the distance from the central point of coal sample tank is studied, and the fitting formula is obtained according to the experimental data. This study has an important practical significance to reveal the evolution mechanism of coal and gas outburst and predict outburst with temperature change as an index. [ABSTRACT FROM AUTHOR]

The similarities and differences between nervous systems of various species result from developmental constraints and specific adaptations1–4. Comparative analyses of the prefrontal cortex (PFC), a cerebral cortex region involved in higher-order cognition and complex social behaviours, have identified true and potential human-specific structural and molecular specializations4–8, such as an exaggerated PFC-enriched anterior–posterior dendritic spine density gradient5. These changes are probably mediated by divergence in spatiotemporal gene regulation9–17, which is particularly prominent in the midfetal human cortex15,18–20. Here we analysed human and macaque transcriptomic data15,20 and identified a transient PFC-enriched and laminar-specific upregulation of cerebellin 2 (CBLN2), a neurexin (NRXN) and glutamate receptor-δ GRID/GluD-associated synaptic organizer21–27, during midfetal development that coincided with the initiation of synaptogenesis. Moreover, we found that species differences in level of expression and laminar distribution of CBLN2 are, at least in part, due to Hominini-specific deletions containing SOX5-binding sites within a retinoic acid-responsive CBLN2 enhancer. In situ genetic humanization of the mouse Cbln2 enhancer drives increased and ectopic laminar Cbln2 expression and promotes PFC dendritic spine formation. These findings suggest a genetic and molecular basis for the anterior-posterior cortical gradient and disproportionate increase in the Hominini PFC of dendritic spines and a developmental mechanism that may link dysfunction of the NRXN–GRID–CBLN2 complex to the pathogenesis of neuropsychiatric disorders.The authors identify deletions in a retinoic acid signalling responsive genetic element that leads to disproportionate increase of dendritic spines on neurons of the human prefrontal cortex. [ABSTRACT FROM AUTHOR]

For deep coal mines, geological disturbances or mining activities can cause damage to coal and rock masses, easily inducing dynamic disasters such as rock bursts or coal and gas outbursts, which seriously threaten the safety production of coal mine. In this paper, first, the Liyazhuang Coal Mine introduced the SOS MS (Sensor Observation Service Microseismic) monitoring system from the Polish Research Institute and verified the accuracy of its positioning. Then, to study the characteristics of MS signals induced by different mining activities, based on the field monitoring results, the waveform and frequency spectrum characteristics of MS signals at different energy levels induced by different mining activities are analyzed, and the energy levels of MS signals caused by different mining activities are classified. Studies have shown that there are large differences in the waveform and spectral characteristics of MS signals at different energy levels. High-level energy seismic signals are characterized by large amplitudes, low frequencies, relatively concentrated distribution, long vibration duration, and slow attenuation. In addition, the relationship between mining activities and MS events is also statistically analyzed based on the spatial and temporal distribution of MS events with the advancement of working face, and the results show that the increase of vibration frequency and energy can be precursor information for roof pressure. With the advance of the working face, the MS energy has the characteristic of periodic distribution, which is consistent with the periodic weighting revealed by the working resistance of the support. This study provides a reference for further revealing the energy release mechanism of rock burst. [ABSTRACT FROM AUTHOR]

Coal seam permeability is one of the key factors influencing the gas extraction efficiency, which is of great significance to reduce coal and gas dynamic disasters in gassy coal mines. Hydraulic slotting technique is an effective method to stimulate the coal reservoir, but the selection of slotting key parameters has great impact on gas extraction efficiency. For this reason, the hydraulic slotting model was established by using FLAC3D software to analyze the stress distribution before and after slotting. Then, the influence of borehole diameter, slotting width, and slotting length on coal seam stress relief is also discussed. The results show that the slotting width has a great influence on the stress relief of the coal seam, while the borehole diameter and slotting length have no obvious influence on that. Based on the results of numerical simulation, field tests were carried out in Sangshuping NO.2 coal mine. The results show that the coal seam stress can be fully released, resulting in the improvement of coal seam permeability. The gas extraction efficiency can be highly enhanced by hydraulic slotting. This research achievement provides the guidance basis for high-stress water jet slotting technology with adaptive selection of slotting parameters in different geological conditions. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive smart photosensitizer (PS) nanoassemblies that allow enhanced delivery and controlled release of PSs are promising for imaging‐guided photodynamic therapy (PDT) of tumors. However, the lack of high‐sensitivity and spatial‐resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo. Herein, we report tumor targeting, redox‐responsive magnetic and fluorogenic PS nanoassemblies (NP‐RGD) synthesized via self‐assembly of a cRGD‐ and disulfide‐containing fluorogenic and paramagnetic small molecule (1‐RGD) for fluorescence/magnetic resonance bimodal imaging‐guided tumor PDT. NP‐RGD show high r1 relaxivity but quenched fluorescence and PDT activity; disulfide reduction by glutathione (GSH) promotes efficient disassembly into a small‐molecule probe (2‐RGD) and an organic PS (PPa‐SH), which could further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive smart photosensitizer (PS) nanoassemblies that allow enhanced delivery and controlled release of PSs are promising for imaging‐guided photodynamic therapy (PDT) of tumors. However, the lack of high‐sensitivity and spatial‐resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo. Herein, we report tumor targeting, redox‐responsive magnetic and fluorogenic PS nanoassemblies (NP‐RGD) synthesized via self‐assembly of a cRGD‐ and disulfide‐containing fluorogenic and paramagnetic small molecule (1‐RGD) for fluorescence/magnetic resonance bimodal imaging‐guided tumor PDT. NP‐RGD show high r1 relaxivity but quenched fluorescence and PDT activity; disulfide reduction by glutathione (GSH) promotes efficient disassembly into a small‐molecule probe (2‐RGD) and an organic PS (PPa‐SH), which could further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors. [ABSTRACT FROM AUTHOR]

Understanding the stress‐cracks‐permeability evolution law inside coal body under cyclic loading is significant to optimize the gas extraction technology and gas disasters prevention technology. In order to explore the influence of mining cyclic stress on the mechanical behavior and permeability variation of gas‐bearing seams, the experiments on permeability evolution, deformation law, and acoustic emission (AE) characteristics of coal samples under cyclic loading with different loading stress level and different loading frequency were carried out. These results indicate that the higher loading stress level, the shorter the fatigue life of coal sample. With the increase of the loading stress level, the change rate of permeability became higher and the relation curves between permeability and loading cycles developed from "U" to "V," which can be defined and divided into three stages, for example, decrease stage, stable stage, and increase stage. And the permeability in the decrease stage can be modeled as a power function of the loading cycles, while the permeability in the increase stage can be modeled as an exponential function of the loading cycles. Besides, the loading stress level has a significant on the permeability, while the loading frequency has little impact on the permeability evolution. In the process of coal deformation under cyclic loading, the strain development of strain coal samples was in the shape of inverted "S," while the variation of the peak values of corresponding AE ring counts presented "U" type. In addition, there was a good correlation between the permeability and the AE parameters of coal samples, which provide a new sight into the dynamic variation process of the stress‐cracks‐permeability evolution inside coal body under cyclic loading. [ABSTRACT FROM AUTHOR]

Key points Paramyotonia congenita is a hereditary channelopathy caused by missense mutations in the SCN4A gene, which encodes the α subunit of the human skeletal muscle voltage-gated sodium channel NaV1.4., Affected individuals suffered from myotonia and paralysis of muscles, which were aggravated by exposure to cold., We report a three-generation Chinese family with patients presenting paramyotonia congenita and identify a novel N1366S mutation of NaV1.4., Whole-cell electrophysiological recordings of the N1366S channel reveal a gain-of-function change of gating in response to cold. Modelling and molecular dynamic simulation data suggest that an arginine-to-serine substitution at position 1366 increases the distance from N1366 to R1454 and disrupts the hydrogen bond formed between them at low temperature., We demonstrate that N1366S is a disease-causing mutation and that the temperature-sensitive alteration of N1366S channel activity may be responsible for the pronounced paramyotonia congenita symptoms of these patients., Abstract Paramyotonia congenita is an autosomal dominant skeletal muscle channelopathy caused by missense mutations in SCN4A, the gene encoding the α subunit of the human skeletal muscle voltage-gated sodium channel NaV1.4. We report a three-generation family in which six members present clinical symptoms of paramyotonia congenita characterized by a marked worsening of myotonia by cold and by the presence of clear episodes of paralysis. We identified a novel mutation in SCN4A (Asn1366Ser, N1366S) in all patients in the family but not in healthy relatives or in 500 normal control subjects. Functional analysis of the channel protein expressed in HEK293 cells by whole-cell patch clamp recording revealed that the N1366S mutation led to significant alterations in the gating process of the NaV1.4 channel. The N1366S mutant displayed a cold-induced hyperpolarizing shift in the voltage dependence of activation and a depolarizing shift in fast inactivation, as well as a reduced rate of fast inactivation and accelerated recovery from fast inactivation. In addition, homology modelling and molecular dynamic simulation of N1366S and wild-type NaV1.4 channels indicated that the arginine-to-serine substitution disrupted the hydrogen bond formed between N1366 and R1454. Together, our results suggest that N1366S is a gain-of-function mutation of NaV1.4 at low temperature and the mutation may be responsible for the clinical symptoms of paramyotonia congenita in the affected family and constitute a basis for studies into its pathogenesis. [ABSTRACT FROM AUTHOR]

Summary The regulation and mechanisms underlying itch sensation are complex. Here, we report a role for acid-sensing ion channel 3 (ASIC3) in mediating itch evoked by certain pruritogens during tissue acidosis. Co-administration of acid with Ser-Leu-Ile-Gly-Arg-Leu-NH 2 (SL-NH 2 ) increased scratching behavior in wild-type, but not ASIC3-null, mice, implicating the channel in coincident detection of acidosis and pruritogens. Mechanistically, SL-NH 2 slowed desensitization of proton-evoked currents by targeting the previously identified nonproton ligand-sensing domain located in the extracellular region of ASIC3 channels in primary sensory neurons. Ablation of the ASIC3 gene reduced dry-skin-induced scratching behavior and pathological changes under conditions with concomitant inflammation. Taken together, our data suggest that ASIC3 mediates itch sensation via coincident detection of acidosis and nonproton ligands that act at the nonproton ligand-sensing domain of the channel. [ABSTRACT FROM AUTHOR]

Objective: Cerebellar dysfunction in multiple sclerosis (MS) contributes significantly to disability, is relatively refractory to symptomatic therapy, and often progresses despite treatment with disease-modifying agents. We previously observed that sodium channel Nav1.8, whose expression is normally restricted to the peripheral nervous system, is present in cerebellar Purkinje neurons in a mouse model of MS (experimental autoimmune encephalomyelitis [EAE]) and in humans with MS. Here, we tested the hypothesis that upregulation of Nav1.8 in cerebellum in MS and EAE has functional consequences contributing to symptom burden. Methods: Electrophysiology and behavioral assessment were performed in a new transgenic mouse model overexpressing Nav1.8 in Purkinje neurons. We also measured EAE symptom progression in mice lacking Nav1.8 compared to wild-type littermates. Finally, we administered the Nav1.8-selective blocker A803467 in the context of previously established EAE to determine reversibility of MS-like deficits. Results: We report that, in the context of an otherwise healthy nervous system, ectopic expression of Nav1.8 in Purkinje neurons alters their electrophysiological properties, and disrupts coordinated motor behaviors. Additionally, we show that Nav1.8 expression contributes to symptom development in EAE. Finally, we demonstrate that abnormal patterns of Purkinje neuron firing and MS-like deficits in EAE can be partially reversed by pharmacotherapy using a Nav1.8-selective blocker. Interpretation: Our results add to the evidence that a channelopathy contributes to cerebellar dysfunction in MS. Our data suggest that Nav1.8-specific blockers, when available for humans, merit study in MS. Ann Neurol 2012;71:186-194 [ABSTRACT FROM AUTHOR]

Objective: Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I-SFN). We sought to identify a genetic basis for I-SFN by screening patients with biopsy-confirmed idiopathic SFN for mutations in the SCN9A gene, encoding voltage-gated sodium channel NaV1.7, which is preferentially expressed in small diameter peripheral axons. Methods: Patients referred with possible I-SFN, who met the criteria of ≥2 SFN-related symptoms, normal strength, tendon reflexes, vibration sense, and nerve conduction studies, and reduced intraepidermal nerve fiber density (IENFD) plus abnormal quantitative sensory testing (QST) and no underlying etiology for SFN, were assessed clinically and by screening of SCN9A for mutations and functional analyses. Results: Twenty-eight patients who met stringent criteria for I-SFN including abnormal IENFD and QST underwent SCN9A gene analyses. Of these 28 patients with biopsy-confirmed I-SFN, 8 were found to carry novel mutations in SCN9A. Functional analysis revealed multiple gain of function changes in the mutant channels; each of the mutations rendered dorsal root ganglion neurons hyperexcitable. Interpretation: We show for the first time that gain of function mutations in sodium channel NaV1.7, which render dorsal root ganglion neurons hyperexcitable, are present in a substantial proportion (28.6%; 8 of 28) of patients meeting strict criteria for I-SFN. These results point to a broader role of NaV1.7 mutations in neurological disease than previously considered from studies on rare genetic syndromes, and suggest an etiological basis for I-SFN, whereby expression of gain of function mutant sodium channels in small diameter peripheral axons may cause these fibers to degenerate. ANN NEUROL 2012;71:26-39 [ABSTRACT FROM AUTHOR]

Gain-of-function missense mutations of voltage-gated sodium channel NaV1.7 have been linked to the painful disorder inherited erythromelalgia. These mutations hyperpolarize activation, slow deactivation and enhance currents evoked by slow ramp stimuli (ramp currents). A correlation has recently been suggested between the age of onset of inherited erythromelalgia and the extent of hyperpolarizing shifts in mutant NaV1.7 channel activation; mutations causing large activation shifts have been linked to early age of onset inherited erythromelalgia, while mutations causing small activation shifts have been linked to age of onset within the second decade of life. Here, we report a family with inherited erythromelalgia with an in-frame deletion of a single residue—leucine 955 (Del-L955) in DII/S6. The proband did not show symptoms until the age of 15 years, and her affected mother only experienced mild symptoms during adolescence, which disappeared at the age of 38 years. Del-L955 shows no effect on NaV1.7 current density and fast inactivation, but causes an approximately −24 mV shift in activation, together with increases in amplitude of persistent currents and ramp currents. The mutation also produces an approximately −40 mV shift in slow inactivation, which reduces channel availability. Comparison of the effects of the Del-L955 mutation on dorsal root ganglion neuron hyperexcitability with those produced by another inherited erythromelalgia mutation (L858F) that does not enhance slow inactivation suggests that a delayed age of onset and milder symptoms in association with a large shift of channel activation, enhanced persistent and enhanced ramp currents may be related to the approximately −40 mV shift in slow inactivation for Del-L955, the largest shift thus far demonstrated in mutant NaV1.7 channels. Our results suggest that despite the pivotal role of activation shift in inherited erythromelalgia development, slow inactivation may regulate clinical phenotype by altering channel availability. [ABSTRACT FROM AUTHOR]

Based on advanced 3D finite element modelling, this paper analyses the stress paths experienced by soil elements in the vicinity of a monopile foundation for offshore wind turbines subjected to cyclic loading with the aim of informing soil laboratory testing in support of monopile foundation design. It is shown that the soil elements in front of the laterally loaded monopile are subjected to complex stress variations, which gradually evolve towards steady stress cycles as the cyclic lateral pile loading proceeds. The amplitude, direction and average value of such steady stress cycles are dependent on the depth and radial distance from the pile of the soil element, but it also invariably involves the cyclic rotation of principal stress axes. Complementary laboratory testing using the hollow-cylinder torsional apparatus was carried out on granular soil samples imposing cyclic stress paths (with up to about 3 × 104 cycles) which resemble those determined after 3D finite element analysis. The importance of considering the cyclic rotation of principal stress axes when investigating the response of soil elements under stress conditions mimicking those around a monopile foundation subjected to cyclic lateral loading is emphasised. [ABSTRACT FROM AUTHOR]

Semiconducting nanowires provide routes for realizing high-performance electronic devices, but for many applications of such devices low-cost manufacturing techniques are needed. The authors demonstrate here top-gated zinc oxide nanowire field effect transistors (NW-FETs) fabricated by ink-jet printing. High resolution submicrometer gold gaps between source and drain electrodes were defined by a self-aligned ink-jet printing technique, and the nanowires were deposited from solution onto these electrode arrays and gated from the top using a spin-coated poly(methyl methacrylate) gate dielectric. The typical NW-FETs exhibited a mobility of 2–4 cm2/V s, a current on/off ratio of 104, and a transconductance of 20.5 nS. The process provides a pathway for fabrication of NW-FETs by low-cost, large-area solution processing and direct printing techniques. [ABSTRACT FROM AUTHOR]

A novel hardware design and preliminary experimental results for photoacoustic imaging are reported in this paper. This imaging system makes use of an infrared-transparent capacitive micromachined ultrasonic transducer (CMUT) chip for ultrasound reception and illuminates the image target through the CMUT array. The cascaded arrangement between the light source and transducer array allows for a more compact imager head and results in more uniform illumination. Taking advantage of the low optical absorption coefficient of silicon in the near infrared spectrum as well as the broad acoustic bandwidth that CMUTs provide, an infrared-transparent CMUT array has been developed for ultrasound reception. The center frequency of the polysilicon-membrane CMUT devices used in this photoacoustic system is 3.5 MHz, with a fractional bandwidth of 118% in reception mode. The silicon substrate of the CMUT array has been thinned to 100 ?m and an antireflection dielectric layer is coated on the back side to improve the infrared-transmission rate. Initial results show that the transmission rate of a 1.06-μm Nd:Yag laser through this CMUT chip is 12%. This transmission rate can be improved if the thickness of silicon substrate and the thin-film dielectrics in the CMUT structure are properly tailored. Imaging of a metal wire phantom using this cascaded photoacoustic imager is demonstrated. [ABSTRACT FROM PUBLISHER]