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Terahertz (THz) spectroscopy of solids in high magnetic fields can often provide new insight into the microscopic physics behind complex many-body behaviors [1].

Detection of low-intensity light relies on the conversion of photons to photoelectrons, which are then multiplied and detected as an electrical signal. To measure the actual intensity of the light, one must know the factor by which the photoelectrons have been multiplied. To obtain this amplification factor, we have developed a procedure for estimating precisely the signal caused by a single photoelectron. The method utilizes the fact that the photoelectrons conform to a Poisson distribution. The average signal produced by a single photoelectron can then be estimated from the number of noise events, without requiring analysis of the distribution of the signal produced by a single photoelectron. The signal produced by one or more photoelectrons can be estimated experimentally without any assumptions. This technique, and an example of the analysis of a signal from a photomultiplier tube, are described in this study., Comment: 18 pages, 6 figures

Phosphatidylinositol 3-kinase-gamma (PI3Kγ) is highly expressed in leukocytes and is an attractive drug target for immune modulation. Different experimental systems have led to conflicting conclusions regarding inflammatory and anti-inflammatory functions of PI3Kγ. Here, we report a human patient with bi-allelic, loss-of-function mutations in PIK3CG resulting in absence of the p110γ catalytic subunit of PI3Kγ. She has a history of childhood-onset antibody defects, cytopenias, and T lymphocytic pneumonitis and colitis, with reduced peripheral blood memory B, memory CD8+ T, and regulatory T cells and increased CXCR3+ tissue-homing CD4 T cells. PI3Kγ-deficient macrophages and monocytes produce elevated inflammatory IL-12 and IL-23 in a GSK3α/β-dependent manner upon TLR stimulation. Pik3cg-deficient mice recapitulate major features of human disease after exposure to natural microbiota through co-housing with pet-store mice. Together, our results emphasize the physiological importance of PI3Kγ in restraining inflammation and promoting appropriate adaptive immune responses in both humans and mice., Causally linking a mutation to clinical phenotypes in rare hereditary diseases is both challenging and illuminating. Here the authors identify PI3Kɣ mutations in a patient with immune dysregulation, and recapitulate the phenotypes in PI3Kɣ-deficient mice by exposing them to natural microbiota from pet-shop mice.

著者人数: 382名 (JAXA職員: 井上, 芳幸 : 小山, 志勇 : Lee, Shiu-Hang), Accepted: 2017-04-12, 資料番号: SA1170071000

Free volume behavior in polystyrene thin films with thickness ranging from 22 to 1200 nm on silicon substrates was studied by energy variable positron annihilation lifetime spectroscopy (EVPALS). The films were prepared by spincasting from toluene solutions of 0.5–5.0 wt% polystyrene with M w = 1 090 000 g/mol. Distinct deviations from bulk polystyrene in thermal expansion of the free volume holes and the glass transition temperature associated with free volume behavior were observed for the thinnest film with 22 nm thickness, indicating its exclusively high chain mobility. Comparison of the polystyrene concentration in the precursor solution around the overlap concentration suggests that the high chain mobility is due to less entangled chains caused by rapid removal of the solvent from the diluted solution in order to prepare very thin film.

This article presents the development of a two-tractor platooning system on sloping terrain. A reference course for the following tractor was dynamically created from the position points of the leading tractor and subsequently processed by the least squares fitting method to filter out some noise. A path-tracking controller composed of the feedforward and feedback component elements was employed to guide the following tractor along the reference course. Field tests were conducted on an 11° sloping meadow. The results indicated that the following tractor tracked the leading one successfully, with mean and RMS lateral deviations of less than 0.028 and 0.078 m, respectively, at travel speed of 0.5 m s-1 on sloping terrain.

We report on a promising approach for the formation of compound semiconductor two-dimensional photonic crystal slabs utilizing selective-area metal–organic vapor phase epitaxy (SA-MOVPE). The selective-area growth process for the submicron-sized air holes of InP-based semiconductors was investigated on InP(111)A and (111)B substrates with a periodic array of hexagonal SiO2 masks. By optimizing growth conditions, a highly uniform array of hexagonal air holes in InP and InGaAs with a 500 nm pitch was formed on (111)B substrates. We also fabricated air-hole arrays with InP/InGaAs/InP double heterostructures on InP(111)B, and confirmed photoluminescence from an InGaAs quantum well at low temperatures.

A magnetic levitation system using a magnetic shielding effect of a HTS bulk is numerically studied. The system is constructed by permanent magnets, zero-fleld-cooled superconducting bulks and ferromagnetic rails. And lift-force stability is obtained from magnetic field that is generated by the permanent magnet and is shaped by the superconducting bulks. In our previous studies, we showed the characteristics of the lift force and stability on a basic configuration which had a small permanent magnet made of ferrite, the YBCO bulk superconductors and a short ferromagnetic bar. In this study, extending the basic configuration, we propose some new configurations which have better characteristics of the lift force than the basic configuration by numerical analysis using the 3D Integral Element Method. The first configuration is that a ferromagnetic plate is inserted between the superconductors and the permanent magnet. The second configuration is that more than two basic configurations are placed parallel. The third configuration is a combination of the first and second configurations. The paper presents the details of the basic and three configurations, the numerical analysis for the evaluation of the levitation characteristic and those results.

It is shown that the photonic crystal slab (PCS) with hexagonal air holes has band gaps in the guided mode spectrum, which can be compared to that of the PCS with circular air holes, thus it is also a good candidate to be used for the PC devices. The PC with hexagonal air holes and a = 0.5 μm and r = 0.15 μm was fabricated successfully by selective area metal organic vapor phase epitaxy (SA-MOVPE). The vertical and smooth sidewalls are formed and the uniformity is very good. The same process was also used to fabricate a hexagonal air hole array with the width of 0.1 μm successfully. The air-bridge PCS with hexagonal air holes and a = 0.3 μm and r = 0.09 μm was also fabricated successfully by SA-MOVPE. Further optimization of the growth conditions for the sacrificial layer and the selective etching of the GaAs cap layer is also needed. Our experimental results indicate that SA-MOVPE is a promising method for fabricating PC devices and photonic nanostructures.

A magnetic levitation system using magnetic shielding effect of HTS bulk is studied. The system is constructed by permanent magnets, zero-field-cooled superconducting bulks and ferromagnetic rails, and lift force stability is obtained from magnetic field that is generated by the permanent magnet and is shaped by the superconducting bulks. In previous studies, we showed characteristics of lift force and stability about a basic model which had a small ferrite permanent magnet, three YBCO bulk superconductors and a short ferromagnetic bar. Now, improving the basic model, we found new models which have better characteristics of lift force by numerical analysis using 3D Integral Element Method (IEM). The new models are reported

We have prepared DPP-hematin (DPP=2, 3, 5, 7, 8, 10, 12, 13, 15, 17, 18, 20-dodecaphenylporphyrin), and characterized it by Mossbauer and magnetic measurements. It is concluded that DPP-hematin is most likely a monomer, as is expected from the distorted nonplanar structure of the porphyrin, in contrast to usual hematins: hematins derived from usual porphyrins are μ-oxo dimers.

In situ analyses of high-resolution medium energy ion scattering (MEIS) combined with photoelectron spectroscopy clarify the initial growth processes of Ni on Si(1 1 1) as-grown and post-annealed. For as-deposition at room temperature, a thin NiSi 2 -like layer is initially formed at the interface. With increasing Ni-coverage the surface becomes Ni-rich silicides and finally a Ni-layer stacks on the silicide layer for Ni-coverage more than 10 ML. Present MEIS and Si 2p core level analyses reveal the fact that a small amount of Si(∼0.7 ML) is incorporated in the Ni-layer and partly segregated to the surface. For the samples with Ni-coverage more than 3 ML, annealing at 500 °C leads to formation of a NiSi 2 epitaxial layer, onto which a small amount (∼0.2 ML) of Si adatoms are located. Three components observed in the Si 2p spectra with binding energies of 98.8, 99.3 and 99.9 eV scaled from the Fermi level are assigned, respectively to (1) the 1st-layer Si atoms bonded to the Si adatoms, (2) the Si adatoms together with the 1st- (non-bonded to the Si adatoms) and 3rd-layer Si atoms and (3) the bulk NiSi 2 (4th- and deeper-layers Si atoms). Furthermore, angle-resolved photoemission analysis has derived the bulk band structure along the Γ – L direction and also found a surface state with a strong p z character, corresponding to the p orbitals of a Si dangling bond.

Metallurgical features and mechanical properties of friction stir welded (FS-welded) joints under the combination of 5083, 6N01 and 7N01 alloys of 3 mm thick parent materials by two or three fabricators and four ways of procedures and also difference in these characteristics due to dissimilarities were studied. Shapes and structures of FS-welded zone, and their hardness distribution, etc., were clarified and these profiles were put in order according to these combinations. Some convenient means such as a measure to estimate these profiles were examined. The dissimilarities were clearly reflected in the hardness distributions, and the distributions to be considered suitable were obtained under their specified combinations. Joint efficiencies were obtained of about 100 % in 5083 joints, about 85 % in 6N01 joints except in some joint and about 96 % in 7N01 joints. All of 5083 joints bent till the minimum former diameter of 12 mm. Almost all of 6N01 joints bent till 32 mm but only the specified joint bent till 20 mm. Almost all of 7N01 joints bent till 20 mm but still only the specified joint was no less than 32 mm. Difference due to dissimilarities was recognized partly in the tensile properties and limitedly in the bendability.

GaAs hexagonal air-hole arrays fabricated by selective-area metal-organic vapour phase epitaxy (SA-MOVPE) on patterned GaAs(111)B substrates are promising for applications to hexagonal air-hole-type two-dimensional photonic crystal (2D-PhC) slabs, because the grown structures exhibit smooth flat surfaces surrounded by crystal facets. In this paper, we describe SA-MOVPE carried out under various gas-flow sequences in order to reduce the growth temperature, and to obtain uniform air-hole arrays without lateral over-growth (LOG). We found that the growth rate in the pattern region and LOG were closely related to the effective As coverage and the desorption rate of the source materials. By optimizing SA-MOVPE, we obtained uniform hexagonal air-hole arrays with almost no LOG for arrays with 500?400?nm periodicity using alternate supply of the source materials (flow-rate modulation epitaxy mode). Finally, we successfully fabricated air-bridge-type hole arrays using selective etching of a sacrificial layer for vertical confinement of light in 2D-PhCs.

We report on a catalyst-free approach for the growth of semiconductor nanowires which is attracting interest as building blocks for nanoscale electronics and circuits. Our approach is based on selective-area MOVPE and nanowires are grown from small circular openings of SiO 2 mask defined on (1 1 1)B-oriented substrates. At optimized conditions, extremely uniform array of GaAs and InGaAs nanowires with diameter of about 200 nm was grown on GaAs and InP substrates, respectively. The nanowires have hexagonal cross-section and are perpendicular to the substrates, indicating that they are surrounded by {1 1 0} facet sidewalls. By reducing the mask opening size, nanowires with diameter down to 50 nm and length more than 5 μm were successfully formed. Photoluminescence and transmission electron microscopy characterization was also carried out.

We report on the selective-area metal-organic vapor-phase epitaxial (SA-MOVPE) growth of GaAs-based periodic air-hole arrays on partially masked GaAs (1 1 1)A substrates for application to two-dimensional photonic crystals (2D PhCs). We obtained uniform 1-μm-pitch GaAs 2D air-hole arrays on GaAs (1 1 1)A substrates with vertical side walls under high AsH 3 partial pressure and low-growth-rate conditions. However, under these growth conditions, lateral over-growth (LOG) occurs at three corners of hexagonal air-hole, and the hole shape change to triangle. We clarified the mechanism of selective area growth on a GaAs (1 1 1)A substrates. We also tried shorter pitch (400 nm) GaAs air-hole arrays and AlGaAs SA-MOVPE on GaAs (1 1 1)A.

We report on the growth of GaAs and GaAs/AlGaAs heterostructured hexagonal pillar structures using selective area (SA) metalorganic vapor phase epitaxy (MOVPE). By performing growth on SiO2-masked (1 1 1)B GaAs substrates with circular or hexagonal hole openings, extremely uniform array of hexagonal GaAs/AlGaAs pillars consisting {1 1 0} vertical facets with their diameter of order of 100 nm were obtained. Unexpectedly, strong intense light emission was observed for the room temperature photoluminescence measurement of the pillar arrays in triangular lattice, which is promising for the application to the photonic crystals to enhance the light extraction efficiency from the materials with high refractive index. Furthermore, it was also found that hexagonal pillars with size 60 nm and large aspect ratio (>100) by reducing the size of initial hole size of mask, opening a possibility to grow nanowires using epitaxial growth.

An autonomous tractor guidance system for vehicle navigation on sloping ground was developed by extending a previous study in which navigation was limited to a specific gradient. A previously developed neural network vehicle model was trained along the contour lines of 0, 5, 11 and 15° sloping terrain. Using the trained models and a cost function, optimal steering angles for different ranges of deviations were sought by genetic algorithm and the optimal values were arranged in separate matrix-form reference table for each slope. The optimal steering values of the four reference tables were expressed by a third-order polynomial equation so that the equation can provide an optimal steering value for any inclination. The coefficients of the equations were tabulated in a matrix form, which is designated as a ‘general reference table’. If the slope inclination and vehicle attitude can be determined, real-time navigation of the tractor is possible using this table. An autonomous travel test was conducted on inclined surface. It was found that the developed guidance system could precisely navigate the tractor along a rectilinear contour path on 20° sloping terrain, where the mean offset was 0·05 m and its standard deviation was 0·044 m.

We report on the selective area metal–organic vapour phase epitaxial growth of an InGaAs nano-pillar array on a partially masked InP(111)B substrate. This technique is very promising as a way to form semiconductor two-dimensional photonic crystals (2DPCs) suitable for infrared optical fibre communication. We successfully formed uniform hexagonal 2DPCs having vertical (110) facet sidewalls on 400 nm-pitch masked substrates. We observed vertical growth enhancement as well as the lateral overgrowth suppression for high aspect ratio InGaAs nano-pillar array formation under high growth-rate, long growth-time, and narrow window-opening conditions. We verified infrared emission from the InGaAs nano-pillar array by low-temperature photoluminescence measurement.

A two-dimensional (2D) periodic array having air/semiconductor interfaces can be applied to photonic crystals (PCs), which are expected to control spontaneous emission and optical transports in the next-generation devices. In this paper, we report on the selective area metal-organic vapor phase epitaxial (SA-MOVPE) growth of a Al x Ga 1− x As 2D periodic array on a GaAs (1 1 1)B substrate for application to 2DPCs having GaAs/AlGaAs heterostructures. Al x Ga 1− x As ( x =0, 0.25 and 0.50) growth was carried out on triangular lattice array of hexagonal GaAs openings and hexagonal SiN x masks. A uniform Al 0.50 Ga 0.50 As hexagonal pillar array and a GaAs hexagonal air-hole array with a 1 μm-period were successfully obtained. The important growth parameter for uniform 2DPC structure formation by SA-MOVPE was clarified. Furthermore, we describe the successful demonstration of a 400 nm-period pillar array and an air-hole array, which corresponds to the optical communication wavelength λ =1.3–1.55 μm. The results indicate that SA-MOVPE method is very promising for the formation of uniform semiconductor 2DPCs without the occurrence of process-induced damages.

We describe a novel fabrication method of two-dimensional photonic crystals (2DPCs) by using selective area metal-organic vapor-phase epitaxial (SA-MOVPE) growth on (1 1 1) B masked substrates and its application to air-bridge-type structures with selective wet-chemical etching. This method is very promising as a way to form semiconductor 2DPCs because a PC membrane without process-induced damages can be obtained. To form uniform PC membranes having an air-hole array, we investigated the properties of SA-MOVPE regrowth on sub-micron-pitch masked substrates. We found that the optimum growth conditions strongly depend on the width of the GaAs opening as well as the pitch of the 2DPCs. An air-bridge structure having 250-nm-pitch 2DPC was also demonstrated by using a combination of SA-MOVPE regrowth and selective wet-chemical undercut etching.

Sumo wrestling is one of Japan's national sports, with a history dating back 1500 years. Although the professional sumo wrestler (rikishi) is one of the largest athletes in the world, knowledge of sumo and sumo wrestlers remains quite limited. In many ways, sumo is unique among sports; matches last only a short period of time, frequently less than 15 s, and the wrestlers must maintain their muscle power and volume through an intensive training daily regimen in order to remain competitive. In this article, we will give a brief overview of the history and rules of sumo, and report several cases involving sumo rikishi that we have encountered over the past 10 years.

Stat3, a member of STAT, is activated by a variety of cytokines such as IL-6 family of cytokines, granulocyte CSF, epidermal growth factor, and leptin. A recent study with mice genetically deficient in the Stat3 gene has revealed its important role in the early embryogenesis. To assess the function of Stat3 in adult tissues, we disrupted the Stat3 gene specifically in T cells by conditional gene targeting using Cre-loxP system. In Stat3-deficient T cells, IL-6-induced proliferation was severely impaired. IL-6 did not enhance cell cycle progression, but prevented apoptosis of normal T cells. In contrast, IL-6 did not prevent apoptosis of Stat3-deficient T cells. Antiapoptotic protein, Bcl-2, was normally up-regulated in response to IL-6 even in Stat3-deficient T cells. These results demonstrate that Stat3 activation is involved in IL-6-dependent T cell proliferation through prevention of apoptosis independently of Bcl-2.

The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. We have cloned the second human proteolipid of the V-ATPase (designated hATP6F), a homologue of the Saccharomyces cerevisiae proteolipid VMA16, which is an essential subunit of yeast V-ATPase. hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. The gene for hATP6F (gene symbol, ATP6F), which consists of eight exons and spans approximately 3.5 kb, was isolated and mapped to human chromosome band 1p32.3 and the region 10.81 cR centromeric of the STS marker SHGC36789 (LOD = 6.75) by fluorescence in situ hybridization and radiation hybrid mapping, respectively. This is the first evidence in human of the existence of a second gene encoding a distinct V-ATPase proteolipid.

OBJECTIVE : We attempt to determine whether changes in messenger ribonucleic acid (mRNA) for nitric oxide synthase (NOS) and soluble guanylate cyclase, enzymes that mediate endothelium-dependent vasodilation in cerebral arteries, occur after subarachnoid hemorrhage (SAH) in monkeys. METHODS : Baseline cerebral angiograms were obtained, and right-sided SAH was induced by microsurgically placing autologous blood clot against the right anterior circle of Willis in seven monkeys. Seven days later, angiographic studies were repeated and the animals were killed. Right (vasospastic) and left (control) middle cerebral arteries and underlying cortex were removed. The competitive reverse transcriptase polymerase chain reaction was used to quantify mRNA for soluble guanylate cyclase and two isoforms of constitutive NOS in these tissues. RESULTS : Comparison of angiograms at baseline and after 7 days showed a 41 ± 7% (mean ± standard error of the mean, P < 0.05, Wilcoxon test) decrease in diameter of the right middle cerebral artery. After the animals were killed, comparison of right and left middle cerebral arteries showed a 56 ± 11% decrease (P < 0.005, paired t test) in endothelial NOS mRNA. There was a 142 ± 39% (P < 0.05) increase in right cortex endothelial NOS mRNA compared to the left cortex. There were no significant differences between right and left sides in mRNAs for soluble guanylate cyclase or brain NOS. CONCLUSION : Decreased endothelial NOS mRNA in cerebral arteries 7 days after SAH may be caused by endothelial cell damage and could contribute to vasospasm after SAH. Increased endothelial NOS in brain tissue may reflect a compensatory vasodilator mechanism of the brain against the cerebral ischemia associated with vasospasm and SAH.

The expansion of trinucleotide repeats has been associated with late-onset neurodegenerative disorders. Although the genes harbouring the triplet expansions may be widely expressed, the pathological expression of these diseases is restricted to specific tissues. Non-insulin-dependent diabetes mellitus (NIDDM) shares several features with diseases resulting from such dynamic mutations including late-onset and specific but limited sites of tissue pathology-muscle, fat, liver and insulin-secreting pancreatic beta cells. In order to examine the contribution of genes containing polymorphic CAG/CTG repeats to the development of NIDDM, we screened an adult human skeletal muscle cDNA library for expressed sequences containing tandem repeats of CAG and/ or CTG. Ten different loci with polymorphic CAG/ CTG repeats were identified, of which seven had a heterozygosity greater than 0.20. There was no evidence for linkage between these seven loci and NIDDM in a group of affected Mexican-American sib pairs. Nor was there a significant difference in the distribution of alleles between Caucasian patients with NIDDM and normal healthy control subjects or evidence for repeat expansion in diabetic subjects. Thus, muscle genes with polymorphic CAG/CTG repeats do not appear to play a significant role in the development of NIDDM.

One hundred novel cDNAs from a human pancreatic islet library have been mapped using PCR and DNA from a human-rodent somatic cell hybrid mapping panel and/or fluorescence in situ hybridization. In addition, the pattern of expression of 54 of these cDNAs has been determined by RNA blotting.

Various transport quantities have been measured for La1.92Sr0.08Cu1-xMxO4 (M=Ni and Zn) and Nd2-yCeyCuO4 over a wide temperature region to study the crossover-like change of the electronic state previously found in high-Tc oxides. The change shows a formation process of the anomalous low carrier concentration state near the Mott metal-insulator phase boundary. The Zn doping produces only a weak change of the T-dependence of the transport properties, except for electron localization effects at very low temperatures, while the Ni doping introduces a rather significant change of their T-dependence. Results of the measurements on Nd2-yCeyCuO4 have revealed that a rough relation of the electron-hole symmetry with respect to the “half-filled” Mott-insulating phase holds in the transport behaviors.

The acute insulin response (AIR), a measure of pancreatic beta-cell function, aggregates in families and is a predictor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in insulin-resistant Pima Indians. To assess the genetic components of AIR and NIDDM, polymorphic dinucleotide repeat regions in two candidate genes, the liver/islet glucose transporter gene (GLUT2) and the glucokinase gene, were evaluated. Sib-pair linkage analyses were performed to determine if linkage exists between these marker loci and measurements of AIR and NIDDM. No linkage was found between glucokinase and either AIR or NIDDM. Robust sib-pair linkage analyses suggest linkage between GLUT2 and acute insulin response (P = 0.04), but no linkage was observed with NIDDM. The coding region of the GLUT2 gene was screened for mutations using polymerase chain reaction-single-strand conformation polymorphism analysis. A single base change was identified in exon 3 in approximately 5% of the study population, and it constitutes the first reported mutation in the human GLUT2 gene. This base change resulted in an amino acid substitution (Thr110-->Ile110) in the second membrane-spanning region of the GLUT2 protein. No significant association was noted between AIR and the presence or absence of the mutation. Thus, this mutation in GLUT2 is unlikely the cause of a low AIR in Pima Indians.

Pancreatic beta-cell function was studied in six subjects with mutations in the enzyme glucokinase (GCK) who were found to have elevated fasting and postprandial glucose levels in comparison to six normoglycemic controls. Insulin secretion rates (ISRs) were estimated by deconvolution of peripheral C-peptide values using a two-compartment model and individual C-peptide kinetics obtained after bolus intravenous injections of biosynthetic human C-peptide. First-phase insulin secretory responses to intravenous glucose and insulin secretion rates over a 24-h period on a weight maintenance diet were not different in subjects with GCK mutations and controls. However, the dose-response curve relating glucose and ISR obtained during graded intravenous glucose infusions was shifted to the right in the subjects with GCK mutations and average ISRs over a glucose range between 5 and 9 mM were 61% lower than those in controls. In the controls, the beta cell was most sensitive to an increase in glucose at concentrations between 5.5 and 6.0 mM, whereas in the patients with GCK mutations the point of maximal responsiveness was increased to between 6.5 and 7.5 mM. Even mutations that resulted in mild impairment of in vitro enzyme activity were associated with a > 50% reduction in ISR. The responsiveness of the beta cell to glucose was increased by 45% in the subjects with mutations after a 42-h intravenous glucose infusion at a rate of 4-6 mg/kg per min. During oscillatory glucose infusion with a period of 144 min, profiles from the subjects with mutations revealed reduced spectral power at 144 min for glucose and ISR compared with controls, indicating decreased ability to entrain the beta cell with exogenous glucose. In conclusion, subjects with mutations in GCK demonstrate decreased responsiveness of the beta cell to glucose manifest by a shift in the glucose ISR dose-response curve to the right and reduced ability to entrain the ultradian oscillations of insulin secretion with exogenous glucose. These results support a key role for the enzyme GCK in determining the in vivo glucose/ISR dose-response relationships and define the alterations in beta-cell responsiveness that occur in subjects with GCK mutations.

The ferroelectric soft mode in a SrTiO(3) thin film was impulsively driven to a large amplitude using intense picosecond terahertz pulses. As the terahertz electric field increased, the soft-mode absorption peak exhibited blueshifting and spectral narrowing. A classical anharmonic oscillator model suggests that the induced displacement is comparable to that of the ferroelectric phase transition. The spectral narrowing indicates that the displacement exceeds that induced by any inhomogeneities in the film, demonstrating that the method can be used to explore intrinsic quartic anharmonicity.

Recent studies have shown that two different voltage-dependent Ca2+ channels are expressed in pancreatic islets, the β-cell/neuroendocrine-brain and the cardiac subtypes. The effects of chronic hyperglycemia on the levels in pancreatic islets of the mRNAs encoding the α1-subunits of the β-cell and cardiac subtype Ca2+ channels were studied in rats made hyperglycemic by infusion of glucose for 48 h. A competitive reverse transcriptase-polymerase chain reaction procedure was used to obtain quantitative data on the levels of these two transcripts in islets obtained from individual rats. The quantitative polymerase chain reaction data indicate that the levels of mRNA encoding the α 1-subunit of the β-cell Ca2+ channel are 2.5-fold > those for the cardiac subtype. The levels of β-cell Ca2+ channel mRNA were 72.9% lower in the glucose-infused animals when compared with the saline-infused animals (P < 0.005) and those of the cardiac channel were 72.1% lower in the animals infused with glucose (P < 0.02). In contrast, glucose infusion resulted in a twofold increase in insulin mRNA levels and did not significantly alter levels of β-actin mRNA. In situ hybridization studies revealed that the mRNAs for these two Ca2+ channels are expressed at higher levels in normal rat islets than in the surrounding acinar tissue, which suggests that the observed changes in mRNA levels occur within cells of the pancreatic islet. To assess the possible functional consequences of this reduction in expression of mRNA for the Ca2+ channels, the insulin secretory responses of perfused pancreases to the Ca2+ channel agonist Bay K8644 were studied. In pancreases from glucose-infused animals, the relative incremental insulin secretory response to Bay K8644 was reduced, and a similar blunting of the acute response to glucose also was seen. In summary, the predominant voltage-dependent Ca2+ channels subtype expressed in islets under basal conditions and after glucose infusion is the β-cell form with lower levels of the cardiac subtype. Glucose infusion for 48 h results in a significant reduction in the mRNA levels for both the β-cell and cardiac subtypes, and this is associated with enhanced basal secretion but reduced responses to glucose and the Ca2+ channel agonist Bay K8644.

Glucokinase plays a key role in the regulation of glucose metabolism in insulin-secreting pancreatic beta-cells and in the liver. Recent studies have shown that mutations in this enzyme can lead to the development of a form of non-insulin-dependent diabetes mellitus that is characterized by an autosomal dominant mode of inheritance and onset during childhood. Here, we report the catalytic properties of five additional missense mutations associated with diabetes (Glu70-->Lys, Ser131-->Pro, Ala188-->Thr, Trp257-->Arg and Lys414-->Glu), one polymorphism present in both normal and diabetic subjects (Asp4-->Asn), and three site-directed mutations (Glu177-->Lys, Glu256-->Ala, and Lys414-->Ala). The Trp257-->Arg mutation generated an enzyme that had an activity that was less than 0.5% of that for native human beta-cell glucokinase. By contrast, the Glu70-->Lys, Ser131-->Pro, Ala188-->Thr, and Lys414-->Glu mutations had a Vmax that was 20-100% of normal but a Km for glucose that was 8-14-fold greater than the native enzyme. There was no effect of the Asp4-->Asn polymorphism or the Glu177-->Lys substitution on glucokinase activity. The Lys414-->Ala substitution had no effect on Vmax but increased the Km for glucose 2-fold and the Glu256-->Ala substitution caused a approximately 200-fold decrease in Vmax. These studies have led to the identification of additional residues involved in glucokinase catalysis and substrate binding.

The gene encoding the predominant facilitative glucose transporter expressed in pancreatic β-cells and hepatocytes, termed GLUT2, has been cloned and characterized. The human GLUT2 gene is composed of 11 exons spanning ∼30 kilobases. The sequence of the promoter region and all exons and adjacent intron regions has been determined and deposited in the GenBank database. Two highly polymorphic simple tandem repeat DNA polymorphisms useful for linkage studies were localized in introns 1 and 4a. In addition, a 168-base pair insertion/deletion polymorphism was identified in intron 3. The characterization of the human GLUT2 gene will facilitate studies of its role in the development of diabetes mellitus.