Valley polarization assisted spin polarization in two dimensions.

Valleytronics is rapidly emerging as an exciting area of basic and applied research. In two-dimensional systems, valley polarization can dramatically modify physical properties through electron-electron interactions as demonstrated by such phenomena as the fractional quantum Hall effect and the metal-insulator transition. Here, we address the electrons' spin alignment in a magnetic field in silicon-on-insulator quantum wells under valley polarization. In stark contrast to expectations from a non-interacting model, we show experimentally that less magnetic field can be required to fully spin polarize a valley-polarized system than a valley-degenerate one. Furthermore, we show that these observations are quantitatively described by parameter-free ab initio quantum Monte Carlo simulations. We interpret the results as a manifestation of the greater stability of the spin- and valley-degenerate system against ferromagnetic instability and Wigner crystalization, which in turn suggests the existence of a new strongly correlated electron liquid at low electron densities.

Metallic behaviour in SOI quantum wells with strong intervalley scattering.

The fundamental properties of valleys are recently attracting growing attention due to electrons in new and topical materials possessing this degree-of-freedom and recent proposals for valleytronics devices. In silicon MOSFETs, the interest has a longer history since the valley degree of freedom had been identified as a key parameter in the observation of the controversial "metallic behaviour" in two dimensions. However, while it has been recently demonstrated that lifting valley degeneracy can destroy the metallic behaviour, little is known about the role of intervalley scattering. Here, we show that the metallic behaviour can be observed in the presence of strong intervalley scattering in silicon on insulator (SOI) quantum wells. Analysis of the conductivity in terms of quantum corrections reveals that interactions are much stronger in SOI than in conventional MOSFETs, leading to the metallic behaviour despite the strong intervalley scattering.

Impact of valley polarization on the resistivity in two dimensions.

We examine the temperature dependence of resistivity in a two-dimensional electron system formed in a silicon-on-insulator quantum well. The device allows us to tune the valley splitting continuously in addition to the electron density. Our data provide a global picture of how the resistivity and its temperature dependence change with valley polarization. At the boundary between valley-polarized and partially polarized regions, we demonstrate that there is an insulating contribution from spin-degenerate electrons occupying the upper valley-subband edge.

Anomalous resistance ridges along filling factor nu=4i.

We report anomalous structure in the magnetoresistance of SiO(2)/Si(100)/SiO(2) quantum wells. When Landau levels of opposite valleys are driven through coincidence at the Fermi level, the longitudinal resistance displays elevations at filling factors that are integer multiples of 4 (nu=4i) accompanied by suppression on either side of nu=4i. This persists when either the magnetic field or the valley splitting is swept, leading to resistance ridges running along nu=4i. The range of field over which they are observed points to the role of spin degeneracy, which is directly confirmed by their disappearance with the addition of an in-plane magnetic field. The data suggest a new type of many-body effect arising from the combined degeneracy due to the valley and the spin degrees of freedom.

Spatial imaging of two-dimensional electronic states in semiconductor quantum wells.

We measure the spatial distribution of the local density of states (LDOS) at cleaved surfaces of InAs/GaSb isolated quantum wells and double quantum wells (DQWs) by low-temperature scanning tunneling spectroscopy. Distinct standing wave patterns of LDOS corresponding to subbands are observed. These LDOS patterns and subband energies agree remarkably well with simple calculations with tip-induced band bending. Furthermore, for the DQWs, coupling of electronic states between the quantum wells is also clearly observed.

Valley polarization in Si(100) at zero magnetic field.

The valley splitting, which lifts the degeneracy of the lowest two valley states in a SiO(2)/Si(100)/SiO(2) quantum well, is examined through transport measurements. We demonstrate that the valley splitting can be observed directly as a step in the conductance defining a boundary between valley-unpolarized and -polarized regions. This persists to well above liquid helium temperature and shows no dependence on magnetic field, indicating that single-particle valley splitting and valley polarization exist in (100) silicon even at zero magnetic field.

Metal-insulator oscillations in a two-dimensional electron-hole system

The electrical transport properties of a bipolar InAs/GaSb system have been studied in a magnetic field. The resistivity oscillates between insulating and metallic behavior while the quantum Hall effect shows a digital character oscillating from 0 to 1 conductance quantum e(2)/h. The insulating behavior is attributed to the formation of a total energy gap in the system. A novel looped edge state picture is proposed associated with the appearance of a voltage between Hall probes which is symmetric on magnetic field reversal.

Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b] quinolin-4-yl)acetoamide on deficits of water maze learning in rats.

The pharmacological properties of MKC-231 (2-(2-oxopyrrolidin-1-yl)-N- (2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl) acetoamide, CAS 135463-81-9) in comparison with an acetylcholinesterase (AChE) inhibitor, tacrine (CAS 1684-40-8) were studied. MKC-231(10(-10)-10(-6) moll) significantly increased high affinity choline uptake (HACU) when it was incubated with the hippocampal synaptosomes of ethylcholine mustard aziridinium ion (AF64A) treated rats, but not of normal rats. MKC-231 did not affect the AChE activity, [3H]- quinuclidinyl benzilate binding, and [3H]-pirenzepine binding. Oral administration of MKC-231 (1-10 mg/kg) significantly improved the learning deficits in the Morris' water maze of AF64A-treated rats, but it did not produce any significant side effects, like tremor, salivation or hypothermia, which were observed in rats treated with high doses of tacrine. Tacrine (0.1-3 mg/kg p.o.) failed to ameliorate the learning deficits in AF64A-treated rats. These results suggest that MKC-231 is a novel and quite unique compound, which improves the memory impairment induced by AF64A through the enhancement of HACU without any side effects at the effective doses.

Preferential impairment of avoidance performances in amygdala-lesioned mice.

To clarify the role of the amygdala in the fulfillment of memory and/or learning, amygdala-lesioned mice were tested in passive and active avoidance performances and also in spatial learning tasks. Although the lesioned animals showed deteriorated performances in both passive and active avoidance tests, they executed the spatial learning tasks as well as the control mice. The learning deficit was prominent in the process of memory acquisition of passive and active avoidance tasks, suggesting that the amygdala might be involved in the acquisition processes of these avoidance tests. The locomotor activities of the lesioned animals were slightly increased, but there was no significant difference compared with the control mice. These findings indicate that the amygdala plays a crucial role preferentially in the avoidance learning rather than the spatial learning.

Prolongation of life span and improved learning in the senescence accelerated mouse produced by aged garlic extract.

The effects of aged garlic extract (AGE) on longevity and learning and memory performances were studied in the senescence accelerated mouse (SAM). A solid diet containing 2% (w/w) AGE was given to SAM from 2 months of age. The survival ratio of SAM P8, senescence accelerated animals, treated with AGE was significantly higher than that of untreated controls. AGE, however, did not affect the life span of SAM R1, a senescence-resistant strain. AGE had no effect on body weight and motor activity. In the passive and conditioned avoidance tests, AGE markably improved a memory acquisition process in the step-down and shuttle-box tests, and also a retention process in the step-through and step-down tests in SAM P8. The beneficial effects of AGE were observed in a memory retention process in the step-down test and in an acquisition stage in lever-press test in SAM R1. These results suggest the possibility that AGE might be useful for treating physiological aging and age-related memory deficits in humans.

Effects of DX-9386, a traditional Chinese preparation, on passive and active avoidance performances in mice.

The acute effects of DX-9386, a traditional Chinese medicinal preparation (ginseng, polygala, acorus and hoelen), were studied on learning and memory performances in passive and active avoidance tests in normal, as well as in learning-impaired, mice. A single oral administration of the prescription had no effect on memory registration, consolidation or retrieval or on motor activity in normal mice. DX-9386 reduced the ethanol-induced impairment of memory registration in the step-down test and also tended to ameliorate the scopolamine-induced memory registration deficit in the same test. The preparation reduced the number of spontaneous responses in the active avoidance test. The preparation also prolonged the disappearance of righting reflex induced by pentobarbital. These results suggest that DX-9386 ameliorates the impairment effect of ethanol on learning and memory processes and also exhibits a sedative effect.

Anti-aging effect of DX-9386 in senescence accelerated mouse.

The effects of DX-9386, a traditional Chinese prescription (ginseng, acorus, polygala and hoelen) were studied on life span, the degree of senescence, motor activity and the antibody production response in senescence accelerated mouse (SAM). DX-9386-containing food was given to SAM for 13 consecutive months from 2 months of age. DX-9386 significantly prolonged the life span of SAM, prevented body weight decrease with aging and tended to improve the senile syndrome. The motor activity of SAMP8 was higher than that of SAMR1, and DX-9386 tended to increase the activity in SAMP8. The in vivo antibody production was markedly decreased in SAMP8 and DX-9386 showed no ameliorating effect on that. These results suggest that DX-9386 has anti-aging impact.

Enhanced tumor localization of monoclonal antibody by treatment with kininase II inhibitor and angiotensin II.

The effect of kininase II inhibitor, enalapril, on the delivery of monoclonal antibody A7 to the targeted tumor was investigated using athymic mice bearing human colon cancer, SW1116. Enalapril alone, which enhances tumor vascular permeability through the kinin-generating cascade, did not increase the uptake of 125I-labeled A7 (125I-A7) in SW1116 due to the systemic hypotension induced by its inhibitory effect on angiotensin converting enzyme. However, with combined angiotensin II (AT-II) and enalapril treatment, a 2-fold increase in the accumulation of 125I-A7 was seen when compared to A7 alone. This marked increase was presumably due to increased tumor vascular permeability induced by enalapril combined with the absence of hypotension due to the actions of AT-II. This approach might be useful in radioimmunodetection and immunotargeting chemotherapy using monoclonal antibody.

Comparative pharmacokinetic properties of murine monoclonal antibody A7 modified with neocarzinostatin, dextran and polyethylene glycol.

The murine monoclonal antibody A7 (Mab A7) was chemically modified with several macromolecules: dextran, polyethylene glycol and the anti-cancer polypeptide neocarzinostatin. The pharmacokinetic properties of the combinations were subsequently examined. Radioimmunoassay revealed that all preparations retained their antigen-binding activities. The Mab A7-neocarzinostatin conjugate was cleared from the blood circulation with a kinetic pattern almost identical to that of the parent Mab A7. Of the three preparations, Mab A7-dextran (A7-Dx) was removed the most rapidly from the circulation. Mab A7-polyethylene glycol (A7-PEG) exhibited the slowest blood clearance curve, with twice the half life of the parent Mab A7 in the circulation. In normal organ distributions, A7-Dx exhibited the highest liver, spleen and kidney uptake, and A7-PEG showed the lowest uptake, when expressed as tissue:blood ratio. Although A7-Dx exhibited lower tumor uptake, there was no significant difference among the three conjugates in tumor-bearing nude mice. A7-PEG seems to be a good candidate for targeted cancer therapy using antibody due to its high blood retention but low normal organ uptake.

Chemical engineering of the monoclonal antibody A7 by polyethylene glycol for targeting cancer chemotherapy.

The murine monoclonal antibody A7 (Mab A7) against human colon cancer was chemically modified with methoxypolyethylene glycol (PEG) (Mr 5000). A high substitution of PEG molecules on Mab A7 produced a progressive reduction in antibody-binding activity. The pharmacokinetic and immunological properties of PEG-modified monoclonal antibody A7 (Mab A7) and the PEG-modified F(ab')2 fragment, which retained their antibody-binding activity, were assessed and compared with the parent Mab A7 and the parent F(ab')2 fragment. Blood clearance of PEG-modified antibodies appeared to be diminished by PEG modification and was fitted by a two-compartment model. Low PEG-substituted Mab A7 showed less organ uptake in the liver and spleen and similar uptake in the lung and kidney, compared with the parent Mab A7. PEG-F(ab')2 showed less uptake in the liver and kidney. Both preparations exhibited less tissue:blood ratios in all resected organs as compared with parent antibodies. Tumor localization was enhanced by PEG modification for the F(ab')2 fragment, but not by PEG modification for the whole Mab A7. Multiple i.v. administration of PEG-modified antibody to rabbit did not appear to elicit a measurable immune response to the antibody portion of the conjugate. In conclusion, PEG-modified antibodies are promising reagents as drug carriers to the target tumor.

Pharmacokinetic analysis of the monoclonal antibody A7-neocarzinostatin conjugate administered to nude mice.

The pharmacokinetics of a disulfide linked conjugate of a murine monoclonal antibody A7 with neocarzinostatin (A7-NCS) was studied following its intravenous administration to nude mice. Disappearance of the conjugate from the circulation was biphasic: an early rapid phase was followed by a much slower phase. The conjugate was removed from the blood circulation with a half-life of 12 hr, showing nearly the same kinetics as the free antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the disulfide linkage in A7-NCS was stable at least for 48 hr after administration of the conjugate to nude mice. The conjugate concentration in a human colon cancer SW1116 derived tumor reached maximum at 24 hr after injection and remained high for an additional 24 hr. The passive hemagglutination inhibition assay revealed that NCS in the conjugated form can be efficiently delivered to the target tissue. The present report indicates that A7-NCS was sufficiently stable in circulation to reach the target tumor without releasing NCS.

Polyethylene glycol modification of the monoclonal antibody A7 enhances its tumor localization.

The F(ab')2 fragment of murine monoclonal antibody A7 was covalently bonded to polyethylene glycol (PEG, molecular weight: 5000) and the conjugate was compared to the parent F(ab')2 fragment by in vitro and in vivo studies. PEG-conjugated antibody fragment retained its antigen-binding activity in a competitive radioimmunoassay. The conjugate had a longer half-life and showed increased accumulation in tumors. Although the tumor: blood ratio for parent F(ab')2 fragment was higher than that for the conjugate, it showed higher value than whole MAb A7. The tissue: blood ratios were kept low with the conjugate, indicating that the conjugate was uptaken to normal organ with lesser extent, as compared with parent F(ab')2 fragment. Our findings indicate that this PEG-conjugated F(ab')2 fragment could be a promising carrier for use in targeting cancer chemotherapy.

Binding, internalization and the cytotoxicity of monoclonal antibody A7-neocarzinostatin conjugates (A7-NCS) in target cells.

To study the mechanism of action of the monoclonal antibody A7-neocarzinostatin conjugates (A7-NCS), the internalization of the antibody and its conjugate into target cells was examined. The incubation of radiolabeled A7 and A7-NCS with target cells revealed that both were taken up by target cells in a time dependent fashion. The immunocytochemical study using anti-NCS also revealed the intracellular localization of the conjugates. The cytotoxicity of the conjugate was markedly reduced when the binding sites were occupied by an excess of antibody on the cell surface. These results showed that A7-NCS was internalized into target cells and that its cytotoxicity was mediated through specific binding and internalization.

Formation of hydroxynorspermidine from exogenously added 1,3-diaminopropan-2-ol in Vibrio species.

When Vibrio parahaemolyticus AQ 3627 was grown in the presence of 1,3-diaminopropan-2-ol (OH-Dap), a new compound accumulated in the cells. This was identified as hydroxynorspermidine (OH-Nspd), N-(3-aminopropyl)-1,3-diaminopropan-2-ol, by gas chromatography-mass spectrometry and thin-layer chromatography. It was also synthesized enzymatically from OH-Dap by a cell-free preparation from this strain. All other Vibrio strains examined also showed the ability to synthesize this compound, but none of the non-vibrio organisms did, indicating that OH-Dap is an in vivo substrate for the enzyme responsible for biosynthesis of norspermidine characteristically present in vibrios. These results suggest that the ability to synthesize OH-Nspd from OH-Dap present in the growth medium may be useful as an additional identifying factor for the genus Vibrio.

Characterization of putrescine production in nongrowing Vibrio parahaemolyticus cells in response to external osmolality.

Nongrowing Vibrio parahaemolyticus cells rapidly produced putrescine (Put) from added arginine when subjected to a low osmotic stress. This phenomenon was characterized in connection with a regulatory mechanism of the responsible enzymes, arginine decarboxylase (ADC) and agmatine ureohydrolase (AUH). NaCl, KCl, LiCl, sucrose, and glycerol were used as solutes to prepare the resuspending media with various osmolalities. Regardless of whether the solutes were electrolytes or non-electrolytes, exposure of cells to low osmolality brought about instantaneous increases in both intra- and extracellular Put contents without significant changes in the contents of other polyamines. This acceleration in Put production was accompanied by no increases in the specific activities of ADC and AUH. On the other hand, when cells were exposed to the osmolality equivalent to 2 or 5% NaCl, all solutes except for glycerol did not cause a remarkable variation in the intracellular Put content, while the amount of Put in the medium varied depending on the solute used; sucrose and glycerol still greatly prompted Put production, as judged by high Put contents in the media, even at the osmolality equivalent to 5% NaCl. The cation efflux from cells, measured as the K+ release, was observed whenever the increase in Put production occurred. Furthermore, in vitro experiments showed that NaCl and KCl inhibited ADC to a similar extent, about 70% inhibition being observed at 200 mM. However, AUH was not affected by these compounds. These results suggest that the reduction in the concentrations of Na+ and K+ predominantly present in cells may cause the increase in activity of the preexisting ADC, which leads to the enhancement of Put production.