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We have developed a state-of-the-art apparatus for laser-based spin- and angle-resolved photoemission spectroscopy with micrometer spatial resolution (µ-SARPES). This equipment is realized by the combination of a high-resolution photoelectron spectrometer, a 6 eV laser with high photon flux that is focused down to a few micrometers, a high-precision sample stage control system, and a double very-low-energy-electron-diffraction spin detector. The setup achieves an energy resolution of 1.5 (5.5) meV without (with) the spin detection mode, compatible with a spatial resolution better than 10 µm. This enables us to probe both spatially-resolved electronic structures and vector information of spin polarization in three dimensions. The performance of µ-SARPES apparatus is demonstrated by presenting ARPES and SARPES results from topological insulators and Au photolithography patterns on a Si (001) substrate.

We study ultrafast population dynamics in the topological surface state of Sb 2 Te 3 in two-dimensional momentum space with time- and angle-resolved two-photon photoemission spectroscopy. Linearly polarized mid-infrared pump pulses are used to permit a direct optical excitation across the Dirac point. We show that this resonant excitation is strongly enhanced within the Dirac cone along three of the six Γ ¯ – M ¯ directions and results in a macroscopic photocurrent when the plane of incidence is aligned along a Γ ¯ – K ¯ direction. Our experimental approach makes it possible to disentangle the decay of transiently excited population and photocurent by elastic and inelastic electron scattering within the full Dirac cone in unprecedented detail. This is utilized to show that doping of Sb 2 Te 3 by vanadium atoms strongly enhances inelastic electron scattering to lower energies, but only scarcely affects elastic scattering around the Dirac cone.

Quantum anomalous Hall effect (QAHE) is a key phenomenon for low power-consumption device applications owing to its dissipationless spin-polarized and quantized current in the absence of an external magnetic field. However, the recorded working temperature of the QAHE is still very low. Here we systematically investigate the magnetic dopants induced modifications from the view points of magnetic, structural and electronic properties and the ultrafast carrier dynamics in a series of V-doped Sb2Te3 samples of composition Sb2−xVxTe3 with x = 0, 0.015 and 0.03. Element specific x-ray magnetic circular dichroism signifies that the ferromagnetism of V-doped Sb2Te3 is governed by the p-d hybridization between the host carrier and the magnetic dopant. Time- and angle-resolved photoemission spectroscopy excited with mid-infrared pulses has revealed that the V impurity induced states underlying the topological surface state (TSS) add scattering channels that significantly shorten the duration of transient surface electrons down to the 100 fs scale. This is in a sharp contrast to the prolonged duration reported for pristine samples though the TSS is located inside the bulk energy gap of the host in either magnetic or non-magnetic cases. It implies the presence of a mobility gap in the bulk energy gap region of the host material that would work toward the robust QAHE. Our findings shed light on the material design for low-energy-consuming device applications.

We have previously reported that genetically increased angiotensin-converting enzyme levels, or absence of the bradykinin B2 receptor, increase kidney damage in diabetic mice. We demonstrate here that this is part of a more general phenomenon - diabetes and, to a lesser degree, absence of the B2 receptor, independently but also largely additively when combined, enhance senescence-associated phenotypes in multiple tissues. Thus, at 12 months of age, indicators of senescence (alopecia, skin atrophy, kyphosis, osteoporosis, testicular atrophy, lipofuscin accumulation in renal proximal tubule and testicular Leydig cells, and apoptosis in the testis and intestine) are virtually absent in WT mice, detectable in B2 receptor-null mice, clearly apparent in mice diabetic because of a dominant mutation (Akita) in the Ins2 gene, and most obvious in Akita diabetic plus B2 receptor-null mice. Renal expression of several genes that encode proteins associated with senescence and/or apoptosis (TGF-beta1, connective tissue growth factor, p53, alpha-synuclein, and forkhead box O1) increases in the same progression. Concomitant increases occur in 8-hydroxy-2'-deoxyguanosine, point mutations and deletions in kidney mitochondrial DNA, and thiobarbituric acid-reactive substances in plasma, together with decreases in the reduced form of glutathione in erythrocytes. Thus, absence of the bradykinin B2 receptor increases the oxidative stress, mitochondrial DNA damage, and many senescence-associated phenotypes already present in untreated Akita diabetic mice.

Quantum anomalous Hall effect (QAHE) is a key phenomenon for low power-consumption device applications owing to its dissipationless spin-polarized and quantized current in the absence of an external magnetic field. However, the recorded working temperature of the QAHE is still very low. Here we systematically investigate the magnetic dopants induced modifications from the view points of magnetic, structural and electronic properties and the ultrafast carrier dynamics in a series of V-doped Sb 2 Te 3 samples of composition Sb 2− x V x Te 3 with x  = 0, 0.015 and 0.03. Element specific x-ray magnetic circular dichroism signifies that the ferromagnetism of V-doped Sb 2 Te 3 is governed by the p – d hybridization between the host carrier and the magnetic dopant. Time- and angle-resolved photoemission spectroscopy excited with mid-infrared pulses has revealed that the V impurity induced states underlying the topological surface state (TSS) add scattering channels that significantly shorten the duration of transient surface electrons down to the 100 fs scale. This is in a sharp contrast to the prolonged duration reported for pristine samples though the TSS is located inside the bulk energy gap of the host in either magnetic or non-magnetic cases. It implies the presence of a mobility gap in the bulk energy gap region of the host material that would work toward the robust QAHE. Our findings shed light on the material design for low-energy-consuming device applications.

To uncover the potential cardiovascular effects of human polymorphisms influencing transforming growth factor β1 (TGFβ1) expression, we generated mice with Tgfb1 mRNA expression graded in five steps from 10% to 300% normal. Adrenal expression of the genes for mineralocorticoid-producing enzymes ranged from 50% normal in the hypermorphs at age 12 wk to 400% normal in the hypomorphs accompanied with proportionate changes in plasma aldosterone levels, whereas plasma volumes ranged from 50% to 150% normal accompanied by marked compensatory changes in plasma angiotensin II and renin levels. The aldosterone/renin ratio ranged from 0.3 times normal in the 300% hypermorphs to six times in the 10% hypomorphs, which have elevated blood pressure. Urinary output of water and electrolytes are markedly decreased in the 10% hypomorphs without significant change in the glomerular filtration rate. Renal activities for the Na ⁺, K ⁺-ATPase, and epithelial sodium channel are markedly increased in the 10% hypomorphs. The hypertension in the 10% hypomorphs is corrected by spironolactone or amiloride at doses that do not change blood pressure in wild-type mice. Thus, changes in Tgfb1 expression cause marked progressive changes in multiple systems that regulate blood pressure and fluid homeostasis, with the major effects being mediated by changes in adrenocortical function.

Type I human diabetics and streptozotocin-induced diabetic mice with higher genetically determined levels of angiotensin-converting enzyme have an increased risk of developing nephropathy. However, previous experiments in mice and computer simulations indicate that modest increases in angiotensin-converting enzyme have minimal effects on blood pressure and angiotensin II levels, although bradykinin decreases significantly, inferring that bradykinin is critical for protecting the kidney in diabetics. Here, we confirm this inference by demonstrating that Akita diabetic mice lacking the bradykinin B2 receptor develop overt albuminuria, excreting the equivalent of >550 mg/day albumin in humans, which contrasts with the microalbuminuria (equivalent to <150 mg/day) seen in their simply diabetic littermates. The overt albuminuria is accompanied by a marked increase in glomerular mesangial sclerosis. The importance of bradykinin demonstrated here bears strongly on how current drugs reduce diabetic nephropathy and suggests that B2 receptor-specific agonists merit consideration in this context.

The low-density lipoprotein receptor (LDLR) plays a pivotal role in cholesterol homeostasis. However, the role of genetic variations in the 3'UTR of the LDLR in relation to plasma cholesterol has been largely understudied. Six SNPs, G44243A, G44332A, C44506G, G44695A, C44857T and A44964G, within the 5' region of the 3'UTR fall into three common haplotypes, GGCGCA, AGCACG, and GGCGTA, occurring at frequencies of 0.45, 0.31 and 0.17, respectively, in Caucasians (n = 29) and 0.13, 0.13 and 0.38, respectively, in African Americans (n = 32), with three other haplotypes occurring at lesser frequencies. In a tissue culture based system, expression of a reporter gene carrying a 3'UTR that includes the 1 kb nucleotide sequences corresponding to the AGCACG or GGCGTA was 70 or 63%, respectively, of the same sequence with GGCGCA. Genotyping of two \"haplotype tagging\" SNPs, C44857T and A44964G, in the Atherosclerosis Risk in Communities (ARIC) study population showed that in Caucasians, but not in African Americans, the inferred TA haplotype had a significant LDL-cholesterol lowering effect. The adjusted LDL-cholesterol levels in the TA/TA diplotypes were lower by 6.10 mg/dl in men (P < 0.001) and by 4.63 mg/dl in women (P < 0.01) than in individuals with other diplotypes. Caucasian men homozygous for CA, in contrast, showed significantly higher LDL-cholesterol (P < 0.04), lower HDL-cholesterol (P < 0.02) and higher LDL/HDL ratios (P < 0.001). Thus our data shows that 3'UTR sequences that cause higher reporter gene expression in vitro are associated in Caucasians with plasma lipid profiles indicative of higher cardiovascular risk, suggesting that further studies of quantitative variants in the LDLR gene will be valuable.

We have developed a state-of-the-art apparatus for laser-based spin- and angle-resolved photoemission spectroscopy with micrometer spatial resolution (micro-SARPES). This equipment is achieved through the combination of a high-resolution photoelectron spectrometer, a 6-eV laser with high photon flux that is focused down to a few micrometers, a high-precision sample stage control system, and a double very-low-energy-electron-diffraction spin detector. The setup achieves an energy resolution of 1.5 (5.5) meV without (with) the spin detection mode, compatible with a spatial resolution better than 10 micrometers. This enables us to probe both spatially-resolved electronic structures and vector information of spin polarization in three dimensions. The performance of micro-SARPES apparatus is demonstrated by presenting ARPES and SARPES results from topological insulators and Au photolithography patterns on a Si (001) substrate.

We study ultrafast population dynamics in the topological surface state of Sb\\(_2\\)Te\\(_3\\) in two-dimensional momentum space with time- and angle-resolved two-photon photoemission. Linear polarized mid-infrared pump pulses are used to permit a direct optical excitation across the Dirac point. We show that this resonant excitation is strongly enhanced within the Dirac cone along three of the six \\(\\bar{\\Gamma}\\)-\\(\\bar{M}\\) directions and results in a macroscopic photocurrent when the plane of incidence is aligned along a \\(\\bar{\\Gamma}\\)-\\(\\bar{K}\\) direction. Our experimental approach makes it possible to disentangle the decay of transiently excited population and photocurent by elastic and inelastic electron scattering within the full Dirac cone in unprecedented detail. This is utilized to show that doping of Sb\\(_2\\)Te\\(_3\\) by vanadium atoms strongly enhances inelastic electron scattering to lower energies, but only scarcely affects elastic scattering around the Dirac cone.