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Fermionic superfluidity with a nontrivial Cooper-pairing, beyond the conventional Bardeen-Cooper-Schrieffer state, is a captivating field of study in quantum many-body systems. In particular, the search for superconducting states with finite-momentum pairs has long been a challenge, but establishing its existence has long suffered from the lack of an appropriate probe to reveal its momentum. Recently, it has been proposed that the nonreciprocal electron transport is the most powerful probe for the finite-momentum pairs, because it directly couples to the supercurrents. Here we reveal such a pairing state by the non-reciprocal transport on tricolor superlattices with strong spin-orbit coupling combined with broken inversion-symmetry consisting of atomically thin d-wave superconductor CeCoIn5. We find that while the second-harmonic resistance exhibits a distinct dip anomaly at the low-temperature (T)/high-magnetic field (H) corner in the HT-plane for H applied to the antinodal direction of the d-wave gap, such an anomaly is absent for H along the nodal direction. By carefully isolating extrinsic effects due to vortex dynamics, we reveal the presence of a non-reciprocal response originating from intrinsic superconducting properties characterized by finite-momentum pairs. We attribute the high-field state to the helical superconducting state, wherein the phase of the order parameter is spontaneously spatially modulated.

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OBJECTIVES: siRNA-induced gene silencing in the salivary gland using microbubble-enhanced sonoporation was used to develop an in vivo gene knockdown technique. METHODS: siRNA targeting rat glyceraldehyde-3-phosphate dehydrogenas (GAPDH) was mixed with echo-enhanced microbubbles and reverse-injected into rat parotid glands using transdermal ultrasound. To compare direct and transdermal ultrasound efficiencies, an incision was made on the lateral neck to expose the parotid glands for direct application. The efficiency of gene suppression was determined using quantitative reverse transcription-polymerase chain reaction 24-72 h after siRNA delivery. Cytotoxicity was assessed using histological analysis. RESULTS: Expression of rat GAPDH in the parotid glands was silenced 48 h after siRNA was delivered by ultrasound (frequency: 1 MHz; intensity: 2 W cm(-2); exposure time: 2 min). High-intensity ultrasound induced tissue damage and apoptotic change. Echo-enhanced microbubbles significantly improved siRNA-induced gene silencing by 10-50%. Compared with transdermal application, direct-exposure ultrasound was only slightly effective, and no significant difference in gene expression was observed. CONCLUSION: The results indicate that microbubble-enhanced sonoporation can yield in vivo siRNA gene silencing in the rat parotid gland. This technique could be applied to provide gene knockdown organs for functional genomic analyses and to develop siRNA-based gene therapy.

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We have assessed amyloid beta protein (Abeta)-induced neurotoxicity, with and without added tunicamycin (TM), an inhibitor of N-glycosylation in the endoplasmic reticulum (ER), in rat organotypic hippocampal slice cultures (OHCs). In the rat OHCs cultured for 3 weeks, there was little neurotoxicity after treatment with Abeta(25-35) (25 microM) alone for 48 h. However, with TM alone, concentration-dependent neuronal death was observed at concentrations between 20 and 80 microg/mL. When amyloid-beta protein was combined with tunicamycin (Abeta+TM), cell death was more acute than with TM alone. Western blot analysis revealed that calpain activity and the active forms of caspase-12 and caspase-3 was increased after exposure to Abeta+TM as compared with exposure to TM alone. In contrast, the levels of glucose regulated protein (GRP)94, GRP78 and C/EBP homologous protein (CHOP) were not changed in the presence of Abeta. Abeta potentiation of TM neurotoxicity was reversibly blocked by S-allyl-L-cysteine (SAC), an organosulfur compound purified from aged garlic extract, and the L-type calcium channel blocker, nifedipine, in a restricted neuronal area of the OHCs. Simultaneously applied SAC also reversed the increases in calpain activity and the active forms of caspase-12 and caspase-3 by Abeta+TM with no change in the increased levels of GRP94, GRP78 and CHOP. These data indicate that Abeta facilitates the calpain-caspase-12-caspase-3 pathway, thus potentiating TM-induced neuronal death in the hippocampus.

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S-allyl-L-cysteine (SAC), one of the organosulfur compounds found in aged garlic extract, has been shown to possess various biological effects including neurotrophic activity. In our previous experiments, we found that SAC could protect against amyloid beta-protein (Abeta)- and tunicamycin-induced cell death in differentiated PC12 cells. In the study described here, we characterized the neuronal death induced by Abeta, 4-hydroxynonenal (HNE), tunicamycin, and trophic factor deprivation, and investigated whether and how SAC could prevent this in cultured rat hippocampal neurons. Treatment with SAC protected these cells against Abeta- and tunicamycin-induced neuronal death, which is mediated predominantly through caspase-12-dependent pathway in a concentration-dependent manner. In contrast, it afforded no protection against HNE- and trophic factor-deprivation-induced cell death, which has been shown to be mediated by caspase-3-dependent pathway. SAC also attenuated the Abeta-induced increase of intracellular reactive oxygen species in hippocampal neurons. SAC had no effect on Abeta-induced cell death in cultured cerebellar granule neurons, which was prevented by a caspase-3 inhibitor. These results suggest that SAC could protect against the neuronal cell death that is triggered by ER dysfunction in the hippocampus, and that it has no effect on neuronal cell death that is dependent upon the caspase-3 mediated pathway.

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Multigated equilibrium radionuclide ventriculography from best septal position (LAO view) was performed in 17 patients with cardiac disease with a single detector Anger-type gamma camera (GCA 602A, Toshiba), then immediately imaged with a solid-state, multi-crystal gamma camera (Digirad 2020tc Imager). Acquisition times were the same of 10 minutes. The solid-state gamma camera uses CsI(Tl) as the scintillation material and a Si photodiode. CsI(Tl) has a higher density and higher atomic number than NaI(Tl), so that its efficiency for detecting gamma rays is higher. To confirm this, total acquisition counts in 17 patients obtained from the 2020tc Imager were significantly higher than those obtained from the Anger-type camera (7847 +/- 2061 K vs. 4427 +/- 1162 K counts, p < 0.0001). In comparing left ventricular ejection fractions obtained from the Anger-type camera and the 2020tc Imager data, an excellent correlation was revealed with a correlation coefficient of 0.97 (p < 0.0001). Again, peak ejection rate and peak filling rate obtained from the 2020tc Imager data correlated well with those obtained from the Anger-type camera data (r = 0.93, p < 0.0001 and r = 0.80, p < 0.001, respectively). These data reveal that the 2020tc Imager has an excellent data collection efficiency and a high reliability in assessment of left ventricular function. Thus, the solid-state gamma camera was thought to be a useful hardware in nuclear cardiology.

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A fragment of the starch-binding domain (SBDF) of Aspergillus niger glucoamylase was prepared using recombinant DNA techniques, and its thermal unfolding was investigated by high-sensitivity differential scanning calorimetry (DSC). Thermal unfolding of SBDF was found to be reversible at pH 7 as expected from a DSC study of the whole enzyme molecule [Tanaka A. et al., J. Biochem., 117, 1024-1028 (1995)] but not reversible at acidic region. Numerical analysis of the DSC curves showed that the denaturation was two-state, and some of the SBDF molecules were oligomeric (average degree of oligomerization was 1.2) at pH 7. It was suggested that the denaturation temperature of SBDF was lower than that of the starch-binding domain in the whole enzyme molecule by about 4.5 degrees (decrease in the Gibbs energy change was 5.3 kJ mol-1) indicating a possibility that the starch-binding domain is stabilized by glycosylation of the domain itself, or by the highly glycosylated linker region.

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Nine analogues of methyl acarviosin (1), the core structure of acarbose and its homologues, the 6-hydroxy-(2), 6-azido-(3), 6-amino- (4), 6-acetamido-(5), 6-methoxy-(6), 6-hydroxy-2-O-methyl-(8), and 6-hydroxy-3-O-methyl derivatives (9), including the 5-methoxycarbonyl analogue (7) and 3,6-anhydro derivative (10) of 2, were synthesized by chemical modification of the sugar part of 2 derived by condensation of methyl 3,4-anhydro-alpha-D-galactopyranoside (17) and 4,7:5,6-di-O-isopropylidenevalienamine (26) or by direct coupling between 26 and the 6-substituted methyl 3,4-anhydro-alpha-D-galactopyranoside derivatives. Compounds 2 and 8 show notable inhibitory activity against yeast alpha-D-glucosidase almost comparable to that of 1. Introduction of a polar substituent at C-6 of 1 decreases the inhibitory activity. Interestingly, inversion of the conformation of the sugar part of 1 by introduction of the 3,6-anhydro bridge elicits almost no effect on the inhibitory activity.

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Methyl oligobiosaminide (1) the core structure of oligostatin C, and five analogues, the 6-hydroxy-(2), 2-deoxy- (3), 2-deoxy-6-hydroxy- (4), 3-deoxy- (5), and 3-deoxy-6-hydroxy derivatives (6), were synthesized by coupling the protected pseudo-sugar epoxide 46 with suitable methyl 4-amino-4-deoxy-alpha-D-hexopyranoside derivatives. Compounds 3 and 6 showed notable inhibitory activity against alpha-D-glucosidase and alpha-D-mannosidase, respectively, whereas compound 1 had almost no activity.

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