Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time （Bowen and Atwood, 2004; Grady, 2012）. Aging-related...Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time （Bowen and Atwood, 2004; Grady, 2012）. Aging-related changes are typically accompanied by decline in cognitive function, urinary control, sensory-motor function, and gait ability （Bradley et al., 1991; Bowen and Atwood, 2004; Hedden and Gabrieli, 2004; Grady, 2012; Moran et al., 2012）. In addition, a number of studies have suggested changes in brain structure with normal aging, such as decrease in cortical thickness or increase in ventricular width （Blatter et al., 1995; Tang et al., 1997; Uylings and de Brabander, 2002; Preul et al., 2006; Apostolova et al., 2012）. In particular, ventricular enlargement has been suggested as a structural biomarker for normal aging and progression of some illnesses, such as Alzheimer＇s disease （Blatter et al., 1995; Tang et al.,展开更多
The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis,...The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord （SC）, where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis （mSOD1） and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging （DTI） has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy evaluate axonal structural changes at early stages of the disease in a preclinical model of ALS.展开更多
Objective: Cell structural changes are one of the main features observed during the development of amyotrophic lateral sclerosis(ALS). In this work, we propose the use of diffusion tensor imaging(DTI) metrics to asses...Objective: Cell structural changes are one of the main features observed during the development of amyotrophic lateral sclerosis(ALS). In this work, we propose the use of diffusion tensor imaging(DTI) metrics to assess specific ultrastructural changes in the central nervous system during the early neurodegenerative stages of ALS.Methods: Ultra-high field MRI and DTI data at 17.6 T were obtained from fixed, excised mouse brains, and spinal cords from ALS(G93 A-SOD1) mice.Results: Changes in fractional anisotropy(FA) and linear, planar, and spherical anisotropy ratios(C_L, C_P, and C_S, respectively) of the diffusion eigenvalues were measured in white matter(WM) and gray matter(GM) areas associated with early axonal degenerative processes(in both the brain and the spinal cord). Specifically, in WM structures(corpus callosum, corticospinal tract, and spinal cord funiculi) as the disease progressed, FA, C_L, and C_P values decreased, whereas C_S values increased. In GM structures(prefrontal cortex, hippocampus, and central spinal cord) FA and C_P decreased, whereas the C_L and C_S values were unchanged or slightly smaller. Histological studies of a fluorescent mice model(YFP, G93 A-SOD1 mouse) corroborated the early alterations in neuronal morphology and axonal connectivity measured by DTI.Conclusions: Changes in diffusion tensor shape were observed in this animal model at the early, nonsymptomatic stages of ALS. Further studies of C_L, C_P, and C_S as imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALS.展开更多
A novel super-junction lateral double-diffused metal-oxide semiconductor （SJ-LDMOS） with a partial lightly doped P pillar （PD） is proposed. Firstly, the reduction in the partial P pillar charges ensures the charge...A novel super-junction lateral double-diffused metal-oxide semiconductor （SJ-LDMOS） with a partial lightly doped P pillar （PD） is proposed. Firstly, the reduction in the partial P pillar charges ensures the charge balance and suppresses the substrate-assisted depletion effect. Secondly, the new electric field peak produced by the P/P junction modulates the surface electric field distribution. Both of these result in a high breakdown voltage （BV）. In addition, due to the same conduction paths, the specific on-resistance （Ron,sp） of the PD SJ-LDMOS is approximately identical to the conventional SJ-LDMOS. Simulation results indicate that the average value of the surface lateral electric field of the PD SJ-LDMOS reaches 20 V/μm at a 15 μm drift length, resulting in a BV of 300 V.展开更多
A novel low specific on-resistance （Ron,sp） lateral double-diffused metal oxide semiconductor （LDMOS） with a buried improved super-junction （BISJ） layer is proposed. A super-junction layer is buried in the drift...A novel low specific on-resistance （Ron,sp） lateral double-diffused metal oxide semiconductor （LDMOS） with a buried improved super-junction （BISJ） layer is proposed. A super-junction layer is buried in the drift region and the P pillar is split into two parts with different doping concentrations. Firstly, the buried super-junction layer causes the multiple-direction assisted depletion effect. The drift region doping concentration of the BISJ LDMOS is therefore much higher than that of the conventional LDMOS. Secondly, the buried super-junction layer provides a bulk low on-resistance path. Both of them reduce Ron,sp greatly. Thirdly, the electric field modulation effect of the new electric field peak introduced by the step doped P pillar improves the breakdown voltage （BV）. The BISJ LDMOS exhibits a BV of 300 V and Ron,sp of 8.08 mΩ·cm2 which increases BV by 35% and reduces Ron,sp by 60% compared with those of a conventional LDMOS with a drift length of 15 μm, respectively.展开更多
A stacked lateral double-diffused metal–oxide–semiconductor field-effect transistor(LDMOS) with enhanced depletion effect by surface substrate is proposed(ST-LDMOS), which is compatible with the traditional CMOS pro...A stacked lateral double-diffused metal–oxide–semiconductor field-effect transistor(LDMOS) with enhanced depletion effect by surface substrate is proposed(ST-LDMOS), which is compatible with the traditional CMOS processes. The new stacked structure is characterized by double substrates and surface dielectric trenches(SDT). The drift region is separated by the P-buried layer to form two vertically parallel devices. The doping concentration of the drift region is increased benefiting from the enhanced auxiliary depletion effect of the double substrates, leading to a lower specific on-resistance(Ron,sp). Multiple electric field peaks appear at the corners of the SDT, which improves the lateral electric field distribution and the breakdown voltage(BV). Compared to a conventional LDMOS(C-LDMOS), the BV in the ST-LDMOS increases from 259 V to 459 V, an improvement of 77.22%. The Ron,sp decreases from 39.62 m?·cm^2 to 23.24 m?·cm^2 and the Baliga's figure of merit(FOM) of is 9.07 MW/cm^2.展开更多
Spin injection, spin diffusion, and spin detection are investigated in Co/Ag/Co lateral spin valves at room temperature.Clear spin accumulation signals are detected by the non-local measurement. By fitting the results...Spin injection, spin diffusion, and spin detection are investigated in Co/Ag/Co lateral spin valves at room temperature.Clear spin accumulation signals are detected by the non-local measurement. By fitting the results to the one-dimensional diffusion equation,8.6% spin polarization of the Co/Ag interface and -180 nm spin diffusion length in Ag are obtained.Thermal treatment results show that the spin accumulation signal drastically decreases after 100℃ annealing, and disappears under 200℃ annealing. Our results demonstrate that, compared to the spin diffusion length, the decrease and the disappearance of the spin accumulation signal are mainly dominated by the variation of the interfacial spin polarization of the Co/Ag interface.展开更多
The spin transport was investigated in permally （Py）/MgO/Ag junction with lateral spin valve structure. Non-local lateral spin valves measurement was carried out to determin, the apin accumulignal in Ag strip, and t...The spin transport was investigated in permally （Py）/MgO/Ag junction with lateral spin valve structure. Non-local lateral spin valves measurement was carried out to determin, the apin accumulignal in Ag strip, and the spin dif u^sion - length in Ag of the lateral spin valves was extracted from devices with the different distances between injector and detector. The experimental results are found that spin accumulation and spin diffusion length （2s） could be significantly enhanced in Ag strip with MgO capping layer, and those effects may be attributed to the low-surface spin scattering rate in Ag with an MgO cap- ping layer.展开更多
In silicon photonics, the carrier depletion scheme has been the most commonly used mechanism for demonstrating high-speed electro-optic modulation. However, in terms of phase modulation efficiency, carrieraccumulation...In silicon photonics, the carrier depletion scheme has been the most commonly used mechanism for demonstrating high-speed electro-optic modulation. However, in terms of phase modulation efficiency, carrieraccumulation-based devices potentially offer almost an order of magnitude improvement over those based on carrier depletion. Previously reported accumulation modulator designs only considered vertical metal-oxidesemiconductor(MOS) capacitors, which imposes serious restrictions on the design flexibility and integratability with other photonic components. In this work, for the first time to our knowledge, we report experimental demonstration of an all-silicon accumulation phase modulator based on a lateral MOS capacitor. Using a Mach–Zehnder interferometer modulator with a 500-μm-long phase shifter, we demonstrate high-speed modulation up to 25 Gbit∕s with a modulation efficiency(V_πL_π) of 1.53 V·cm.展开更多
基金supported by Basic Science Research Program through the National Research Foundation of Korea (NRF)funded by the Ministry of Education, Science and Technology, No. 2012R1A1B4003477
文摘Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time （Bowen and Atwood, 2004; Grady, 2012）. Aging-related changes are typically accompanied by decline in cognitive function, urinary control, sensory-motor function, and gait ability （Bradley et al., 1991; Bowen and Atwood, 2004; Hedden and Gabrieli, 2004; Grady, 2012; Moran et al., 2012）. In addition, a number of studies have suggested changes in brain structure with normal aging, such as decrease in cortical thickness or increase in ventricular width （Blatter et al., 1995; Tang et al., 1997; Uylings and de Brabander, 2002; Preul et al., 2006; Apostolova et al., 2012）. In particular, ventricular enlargement has been suggested as a structural biomarker for normal aging and progression of some illnesses, such as Alzheimer＇s disease （Blatter et al., 1995; Tang et al.,
基金provided by the Chicago Biomedical Consortium’s Postdoctoral Research Award,No.085740
文摘The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord （SC）, where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis （mSOD1） and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging （DTI） has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy evaluate axonal structural changes at early stages of the disease in a preclinical model of ALS.
基金Magnetic Laboratory Visiting Scientist Program,Grant/Award Number 327Chicago Biomedical Consortium,Grant/Award Number 085740National Science Foundation,Grant/Award Number DMR-1157490。
文摘Objective: Cell structural changes are one of the main features observed during the development of amyotrophic lateral sclerosis(ALS). In this work, we propose the use of diffusion tensor imaging(DTI) metrics to assess specific ultrastructural changes in the central nervous system during the early neurodegenerative stages of ALS.Methods: Ultra-high field MRI and DTI data at 17.6 T were obtained from fixed, excised mouse brains, and spinal cords from ALS(G93 A-SOD1) mice.Results: Changes in fractional anisotropy(FA) and linear, planar, and spherical anisotropy ratios(C_L, C_P, and C_S, respectively) of the diffusion eigenvalues were measured in white matter(WM) and gray matter(GM) areas associated with early axonal degenerative processes(in both the brain and the spinal cord). Specifically, in WM structures(corpus callosum, corticospinal tract, and spinal cord funiculi) as the disease progressed, FA, C_L, and C_P values decreased, whereas C_S values increased. In GM structures(prefrontal cortex, hippocampus, and central spinal cord) FA and C_P decreased, whereas the C_L and C_S values were unchanged or slightly smaller. Histological studies of a fluorescent mice model(YFP, G93 A-SOD1 mouse) corroborated the early alterations in neuronal morphology and axonal connectivity measured by DTI.Conclusions: Changes in diffusion tensor shape were observed in this animal model at the early, nonsymptomatic stages of ALS. Further studies of C_L, C_P, and C_S as imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALS.
基金supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China (Grant No. 2010ZX02201)the National Natural Science Foundation of China (Grant No. 61176069)the National Defense Pre-Research of China (Grant No. 51308020304)
文摘A novel super-junction lateral double-diffused metal-oxide semiconductor （SJ-LDMOS） with a partial lightly doped P pillar （PD） is proposed. Firstly, the reduction in the partial P pillar charges ensures the charge balance and suppresses the substrate-assisted depletion effect. Secondly, the new electric field peak produced by the P/P junction modulates the surface electric field distribution. Both of these result in a high breakdown voltage （BV）. In addition, due to the same conduction paths, the specific on-resistance （Ron,sp） of the PD SJ-LDMOS is approximately identical to the conventional SJ-LDMOS. Simulation results indicate that the average value of the surface lateral electric field of the PD SJ-LDMOS reaches 20 V/μm at a 15 μm drift length, resulting in a BV of 300 V.
基金Project supported by the National Science and Technology Project of the Ministry of Science and Technology of China(Grant No.2010ZX02201)the National Natural Science Foundation of China(Grant No.61176069)the National Defense Pre-Research of China(Grant No.51308020304)
文摘A novel low specific on-resistance （Ron,sp） lateral double-diffused metal oxide semiconductor （LDMOS） with a buried improved super-junction （BISJ） layer is proposed. A super-junction layer is buried in the drift region and the P pillar is split into two parts with different doping concentrations. Firstly, the buried super-junction layer causes the multiple-direction assisted depletion effect. The drift region doping concentration of the BISJ LDMOS is therefore much higher than that of the conventional LDMOS. Secondly, the buried super-junction layer provides a bulk low on-resistance path. Both of them reduce Ron,sp greatly. Thirdly, the electric field modulation effect of the new electric field peak introduced by the step doped P pillar improves the breakdown voltage （BV）. The BISJ LDMOS exhibits a BV of 300 V and Ron,sp of 8.08 mΩ·cm2 which increases BV by 35% and reduces Ron,sp by 60% compared with those of a conventional LDMOS with a drift length of 15 μm, respectively.
基金supported by the National Natural Science Foundation of China(Grant No.61464003)the Guangxi Natural Science Foundation,China(Grant Nos.2015GXNSFAA139300 and 2018JJA170010)
文摘A stacked lateral double-diffused metal–oxide–semiconductor field-effect transistor(LDMOS) with enhanced depletion effect by surface substrate is proposed(ST-LDMOS), which is compatible with the traditional CMOS processes. The new stacked structure is characterized by double substrates and surface dielectric trenches(SDT). The drift region is separated by the P-buried layer to form two vertically parallel devices. The doping concentration of the drift region is increased benefiting from the enhanced auxiliary depletion effect of the double substrates, leading to a lower specific on-resistance(Ron,sp). Multiple electric field peaks appear at the corners of the SDT, which improves the lateral electric field distribution and the breakdown voltage(BV). Compared to a conventional LDMOS(C-LDMOS), the BV in the ST-LDMOS increases from 259 V to 459 V, an improvement of 77.22%. The Ron,sp decreases from 39.62 m?·cm^2 to 23.24 m?·cm^2 and the Baliga's figure of merit(FOM) of is 9.07 MW/cm^2.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11304381 and 11374244)the Research Funds of Renmin University of China(Grant No.17XNLF02)+1 种基金the Foundation for the Author of National Excellent Doctoral Dissertation of China(Grant No.201443)the Natural Science Foundation of Fujian Province of China(Grant No.2015J06016)
文摘Spin injection, spin diffusion, and spin detection are investigated in Co/Ag/Co lateral spin valves at room temperature.Clear spin accumulation signals are detected by the non-local measurement. By fitting the results to the one-dimensional diffusion equation,8.6% spin polarization of the Co/Ag interface and -180 nm spin diffusion length in Ag are obtained.Thermal treatment results show that the spin accumulation signal drastically decreases after 100℃ annealing, and disappears under 200℃ annealing. Our results demonstrate that, compared to the spin diffusion length, the decrease and the disappearance of the spin accumulation signal are mainly dominated by the variation of the interfacial spin polarization of the Co/Ag interface.
基金financially supported by the National Natural Science Foundation of China(Nos.11304381 and 11174366)the Research Funds of Renmin University of China(No.13XNLF02)
文摘The spin transport was investigated in permally （Py）/MgO/Ag junction with lateral spin valve structure. Non-local lateral spin valves measurement was carried out to determin, the apin accumulignal in Ag strip, and the spin dif u^sion - length in Ag of the lateral spin valves was extracted from devices with the different distances between injector and detector. The experimental results are found that spin accumulation and spin diffusion length （2s） could be significantly enhanced in Ag strip with MgO capping layer, and those effects may be attributed to the low-surface spin scattering rate in Ag with an MgO cap- ping layer.
基金Engineering and Physical Sciences Research Council(EPSRC)(EP/M008975/1,EP/M009416/1,EP/N013247/1,EP/R003076/1)EU Seventh Framework Programme(FP7)Marie-Curie Carrier-Integration-Grant(PCIG13-GA-2013-618116)
文摘In silicon photonics, the carrier depletion scheme has been the most commonly used mechanism for demonstrating high-speed electro-optic modulation. However, in terms of phase modulation efficiency, carrieraccumulation-based devices potentially offer almost an order of magnitude improvement over those based on carrier depletion. Previously reported accumulation modulator designs only considered vertical metal-oxidesemiconductor(MOS) capacitors, which imposes serious restrictions on the design flexibility and integratability with other photonic components. In this work, for the first time to our knowledge, we report experimental demonstration of an all-silicon accumulation phase modulator based on a lateral MOS capacitor. Using a Mach–Zehnder interferometer modulator with a 500-μm-long phase shifter, we demonstrate high-speed modulation up to 25 Gbit∕s with a modulation efficiency(V_πL_π) of 1.53 V·cm.
